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J B M Kuks and J W Snoek (Eds.), Textbook of Clinical Neurology, https://doi.org/10.1007/978-90-368-2142-1_16

Disorders of the cranial nerves

Abstract

Diseases of the cranial nerves result in sensory function loss and/or the loss of facial

motor control Hearing and sight may be lost, for example, double vision or vertigo may

occur, swallowing and speech may become difficult, and the face may become paralysed

or hypersensitive Cranial nerve problems can usually be traced and resolved That is the

case, for example, with viral infections, compression due to intracranial hypertension,

drug poisoning, autoimmune disorders and meningitis

16

Electronic supplementary material

The online version of this chapter ( 7 https://doi.org/10.1007/978-90-368-2142-1_16 ) contains supplementary

material, which is available to authorized users.

16.2 Clinical presentation – 196

16.2.1 Olfactory nerve (I) – 196

16.2.2 Optic nerve (II) – 197

16.2.3 Oculomotor nerve (III) – 198

16.2.4 Trochlear nerve (IV) – 200

16.2.5 Trigeminal nerve (V) – 200

16.2.6 Abducens nerve (VI) – 200

16.2.7 Facial nerve (VII) – 200

16.2.8 Vestibulocochlear nerve (VIII) – 202

16.2.9 Glossopharyngeal nerve (IX) and vagus nerve (X) – 204

16.2.10 Accessory nerve (XI) and hypoglossal nerve (XII) – 205

16.3 Failure of multiple cranial nerves – 205

Case 16.1

A sixty-year-old man has sometimes been seeing double

for the last three months When it happens, the images are

displaced diagonally The double vision is present when

the man wakes up in the morning, but after an hour or so

it disappears, and for the rest of the morning he is fine

However, the double vision usually returns in the course

of the afternoon, especially if the man drives or has been

reading a lot For the last week, the man’s right upper eyelid

has been drooping, particularly in the evening However,

when the eyelid droops, the man no longer has double

vision He has no other symptoms.

During a morning examination, no abnormalities are initially

observed However, when the man directs his gaze upward

for about fifteen seconds, the double vision starts and his

left eye is observed to be lower than his right When he

directs his gaze to the right, he experiences uncrossed

double vision and he cannot keep his right eye directed to

the side; it gradually drifts back towards his nose The upper

eyelid also droops to partially cover the pupil.

Question 1: Which muscles are affected?

Question 2: What needs to be tested in order to establish

whether the patient has an eye muscle disorder or a cranial

nerve disorder?

Question 3: What is the most likely diagnosis?

Online: 7Answers to case study questions 16.1

Case 16.2

A fifty-five-year-old woman has experienced five acute

vertigo attacks in the last year, each lasting several hours

During the attacks, she has the sense that everything

around her is spinning Sometimes she is also nauseous;

indeed, during the last attack, she had to vomit According

to her husband, her eye movements were jerky Prior to the

attacks, she has often had the sensation that her right ear

was blocked The attacks are also accompanied by tinnitus

Onset appears unrelated to the woman’s posture or the

time of day, and there is no apparent trigger Between

attacks, the woman’s balance is good, but her hearing on

the right remains affected.

When examined twenty-four hours after an attack, the

hearing in her right ear is found to be impaired The

result of Rinne’s test is abnormal and Weber’s test reveals

lateralization to the left.

Question 1: What disorder does the patient probably have?

Question 2: How should the results of the tuning fork tests be

Their location makes them vulnerable to traumatic injury (especially nerves I, II, IV and VII) and to intracranial hyper-tension, whether or not accompanied by compression (nerves III and VI) Furthermore, all of them can be affected by basal meningitis (bacterial, granulomatous in sarcoidosis) and by leptomeningeal metastases

Local compression can be caused by cranial base processes (chondroma, metastases) and nasopharyngeal tumours, men-ingiomas (mainly nerves II, V, VI, VII and X) and aneurysms (nerve III, sometimes nerve II) The tumours that originate in cranial nerves are olfactory meningioma (nerve I), optic glioma (nerve II) and neurinoma (mainly in nerve VIII, but also nerve

V and occasionally nerves VII, X and XII)

Almost all cranial nerves (except XI and XII) can be affected by herpes virus infection Some cranial nerves are involved in MS (nerves II, V, VI, sometimes nerve VII, occa-sionally nerves III, X and XII) Diabetes mellitus can affect nerves II, III and VI and sometimes nerves VII and X Collagen disease and vasculitis can affect nerves II, III, V, VI and some-times nerve VII However, it is by no means always possible to identify a cause for the impairment of cranial nerve function.The clinical examination undertaken in cases of cranial nerve disorder is described in 7 sect 6.3 This chapter discusses the clinical presentations of cranial nerve disorders

16.2 Clinical presentation16.2.1 Olfactory nerve (I)

The connections between the receptors in the olfactory mucous membrane and the olfactory bulb (7 sect 6.2) are vulnerable Consequently, the sense of smell may remain impaired after a relatively minor traumatic brain injury, e.g contrecoup phe-nomenon or fall-related impact injury to the occipital region (7 sects 20.3.2 and 20.6.5) Loss of smell is a common resi-dual symptom of ‘influenza’ Finally, loss of smell is sometimes

attributable to a frontal process, particularly olfactory oma Olfactory sensations can be triggered by partial epilepsy (uncinate fits; 7 sect 18.2.1), but may also originate from the nasal sinuses

197

Loss of smell

Olfactory nerve dysfunction

5 traumatic brain injury

5 tumour in anterior cranial fossa (olfactory meningioma)

5 sarcoidosis

5 status after meningitis

5 Parkinson’s disease

5 following ‘influenza’ or other viral infection

5 congenital defect (atrophy of the olfactory bulb)

Other causes

5 acute or chronic nasal infection, heavy smoking

5 familial

5 unknown cause

16.2.2 Optic nerve (II)

Impaired visual acuity of one eye often requires

ophthalmologi-cal investigation, but sometimes a neurologist is involved on

a secondary basis A partial visual field disorder of both eyes

is nearly always a matter for a neurologist The anatomy of the

visual system and the associated examination and testing

pro-cedures are described in 7 chap 9

In cases of neuropathy of the optic nerve, distinction is made

between disorders characterized by observable abnormalities of

the papilla and other disorders Disorders that do not involve

papillary abnormalities are referred to as posterior or

retrobul-bar disorders, or as retrobulretrobul-bar neuritis; where such

abnormali-ties are present, the disorder is known as anterior optic neuritis

About 3 % of the population has a ‘lazy eye’ (amblyopia)

with vision of between 1/10 and 1/60, without experiencing a

specific visual field disorder and without any other

ophthalmo-logical or neuroophthalmo-logical abnormalities being detectable

Causes of vision impairment

Vascular

5 ischemia of the retina

5 ischemia of the optic nerve

Infection of the optic nerve

5 demyelinating optic neuritis (e.g in MS)

5 viral infection (children)

Optic neuropathy

5 toxic

5 metabolic

5 hereditary (mitochondrial, SCA, 7 sect 25.3 )

Mechanical injury to optic nerve

5 infiltration in basal meningitis

5 infiltration in leptomeningeal metastasis

5 compression

5 trauma

Primary eye disorders

5 retinopathy, macular degeneration

5 glaucoma and other primarily ophthalmological causes

Other

5 amblyopia

Vascular causes of impaired vision

Distinction may be made between ischemia of the retina

(amaurosis fugax, retinal infarct) and ischemia of the optic nerve papilla (anterior ischemic optic neuropathy, (AION) or posterior ischemic optic neuropathy (PION)) Ischemic optic

neuropathy involves acute painless impairment to the vision

of one eye, often followed by further deterioration in the lowing hours or days If abnormalities are visible in fundo, the disorder is referred to as AION, and otherwise as PION Con-sideration should always be given to temporal arteritis, but the cause may also be generalized vascular pathology Such optic ischemia is attributable to local occlusion of minor blood ves-sels and not to a thromboembolic disorder; hence, neither examination of the heart nor examination of the blood vessels

fol-of the neck is indicated

It is a different matter in cases of ischemia of the retina The retina is supplied with blood by the central retinal artery, which branches off the ophthalmic artery, itself a branch of the internal carotid artery ( fig 11.3) In a case of ischemia of the

retina, whether temporary (amaurosis fugax) or permanent (retinal infarct), examination and testing should be the same as

in a case of cerebral TIA or infarction (7 chap 17)

Migraine can sometimes cause temporary visual field impairment affecting one eye However, if migraine is the cause, the impairment is not sudden, but progresses gradu-ally, often starting peripherally and migrating inward, and the impairment soon disappears (retinal migraine) The latter disorder mainly affects young adults It is not clear whether migraine-related visual field impairment is a vascular pheno-menon (7 sect 21.1.3)

Neuritis of the optic nerve

Optic neuritis can occur in demyelinating disorders Usually,

no abnormalities of the optic nerve are observable in the acute

stage and the condition is referred to as retrobulbar neuritis;

sometimes, however, oedema of the optic nerve papilla is diately visible Within hours or a few days, an impairment will develop at the centre of the field of vision of one eye (central scotoma), resulting in visual acuity declining to between 1/10 and 1/60 The peripheries of the fields of vision remain largely unaffected The eye will also be painful, particularly when moved or subject to external pressure The impaired vision is often accompanied by impaired colour perception Examination should reveal an afferent pupil defect (7 sect 6.3.2)

imme-The prognosis is generally good; a gradual improvement starts after a week or so, and most patients regain normal vision after three to six weeks Relapse can occur, however, and the same disorder may develop in the other eye Generally

16.2 · Clinical presentation

speaking, more than 50 % of patients with optical neuritis

sub-sequently develop MS The extent to which one should

antici-pate that possibility by additionally testing for MS and the

circumstances under which one should treat optic neuritis

resulting from demyelination are matters of debate

Neuropathy of the optic nerve

Toxic neuropathy of the optic nerve can be caused by methanol,

excessive nicotine, drugs such as chloroquine, quinine,

strepto-mycin, chloramphenicol, lead, arsenic and certain insecticides

A deficiency of vitamin B12 or vitamin B1 can lead to vision

impairment

Mitochondrial disorders

Hereditary mitochondrial optic neuropathy (Leber’s hereditary

optic neuropathy) usually develops gradually over the course of

weeks or months and is characterized by central vision

impair-ment affecting both eyes Sometimes, however, it starts with acute

retrobulbar neuritis The disorder occurs mainly in men aged

between eighteen and thirty-five, but it can also become

mani-fest later in life and is occasionally found in women It is

associ-ated with various mutations in the mitochondrial DNA However,

none of the mutations can fully explain the disorder’s

manifesta-tion, because the same DNA abnormalities can be found in family

members with unimpaired vision The prognosis is relatively poor:

although improvement sometimes occurs, significant permanent

impairment ( < 0.1) accompanied by opticusatrophy is common

Some families in which Leber’s disease is present are additionally

affected by other central nervous system (CNS) disorders

Compression and infiltration

Compression or infiltration causes progressive vision

impair-ment within weeks or months If the primary problem is a

disorder of the chiasma, impairment begins with temporal

hemianopsia (7 sect 9.1.3) In such cases, the cause is usually a

tumour of the pituitary gland (7 sect 22.3.6), optic glioma (e.g

in Von Recklinghausen’s neurofibromatosis, 7 sect 28.5.2), or a

tumour in the anterior cranial fossa (meningioma, neurinoma

of the olfactory nerve) Other possible causes are

leptomenin-geal dissemination, sarcoidosis, lymphoma and granulomatosis

accompanied by polyangiitis (Wegener’s disease)

16.2.3 Oculomotor nerve (III)

The oculomotor nerve has a three-fold function (7 sect 6.2)

Hence, a disorder of this nerve can have various symptoms and

differential diagnosis is a complex process

If the nerve is completely damaged, the patient exhibits

pto-sis, a dilated pupil that does not respond to light, and

conver-gence accompanied by impaired oculomotor control, such that

the eye tends to point outwards (due to activity of nerve VI)

and slightly downwards (due to activity of nerve IV) The

struc-ture of the nerve is such that the parasympathetic fibres

respon-sible for pupil constriction are peripherally located Hence, in

the event of external compression – as particularly associated

with an aneurysm of the posterior communicating artery or

of the carotid artery; 7 sect 11.3.2 – the pupillary responses will be affected first Conversely, internal infarction (as asso-ciated mainly with diabetes mellitus) will not affect pupillary responses As a patient recovers from a total loss of oculomo-tor nerve function, the ptosis disappears first, and vertical eye movement is the last function to return to normal

Causes of failure of the oculomotor nerve (nerve III)

5 vascular (diabetes, hypertension)

5 compression by an aneurysm

5 transtentorial compression ( 7 sect 19.3 )

5 orbital process

5 infarction or haemorrhage in the midbrain

5 ophthalmic herpes zoster

ent sizes is referred to as anisocoria Dilation is induced by the

sympathetic system, and constriction by the parasympathetic system (7 sects 6.2.2 and 7.5.1) A case of anisocoria should be described in terms of which pupil is larger, not in terms of a left

or right-sided impairment

Various medications influence pupil size Pupil tion can be induced by, amongst other things, barbiturates, opi-ates, pilocarpine (for the treatment of glaucoma); pupil dilators include various anticholinergic agents (antidepressants, atro-pine) and cocaine

constric-A patient’s pupillary response to light may be poor, while its response to convergence is normal, since the two responses are controlled by different mechanisms That is the case, for example, in Adie’s syndrome and diabetic neuropathy, with brainstem abnormalities (pretectal) and with Argyll-Robertson pupils, as associated with syphilis

Adie’s syndrome involves acquired neuropathy of the

post-ganglionic fibres of the ciliary ganglion The pupil is initially dilated and does not respond to light; at a later stage, how-ever, delayed constriction occurs following convergence, and

the pupil is subsequently slow to normalize (pupillotonia)

Ultimately, the pupil becomes permanently constricted and unresponsive to light Adie’s syndrome may be unilateral or bilateral The abnormal pupillary response is usually accompa-nied by impairment or loss of muscular extension reflexes in the legs

If a patient has a constricted, imperfectly rounded pupil that does not respond to light but responds strongly to conver-

gence, one should consider the possibility of Argyll-Robertson pupil, attributable to a disorder of the dorsal midbrain associ-

ated with syphilis

5 oculomotor nerve palsy

5 bilateral optic nerve damage

5 pressure on the midbrain (pinealoma)

5 Adie’s syndrome (end stage)

5 intoxication (alcohol, opiates)

5 (partial) Horner’s syndrome ( 7 sect 7.5.3 )

5 neuropathy of the sympathetic fibres in diabetes

( 7 sect 13.7.2 )

Ptosis

Drooping eyelids are common: many people have a droop on

one or both sides It is usually interpreted as an inconsequential

personal characteristic, both by the person in question and by

people close to them Drooping is sometimes due to a

connec-tive tissue abnormality; the prolonged use of hard contact lenses

can also play a role Alternatively, ptosis may be attributable to a

muscular disorder Where neurological disorders are concerned,

failure of the oculomotor nerve leads to marked ptosis, usually

sufficient to have sight implications, while in Horner’s syndrome

failure of the sympathetic mechanism causes only slight

pto-sis apparent to the patient only when looking in the mirror It

should be borne in mind that other causal mechanisms can lead

to a patient without ptosis exhibiting abnormal narrowing of the

palpebral fissure, making his eyes seem smaller

Causes of palpebral fissure narrowing (ptosis) and

related symptoms

5 oculomotor nerve palsy (ipsilateral pupil dilation)

5 Horner’s syndrome (ipsilateral pupil contraction;

7 sect 7.5.3 )

5 myasthenia ( 7 sect 12.6.2 )

5 myotonic dystrophy ( 7 sect 12.4.3 )

5 mitochondrial myopathy ( 7 sect 12.4.6 )

5 familial (myopathy?)

5 fatigue

5 weakening of the connective tissue of the eyelid

(dermatochalasis, in the elderly)

5 posterior displacement of the eyeball within the

orbit (enophthalmos; possibly accompanied by

exophthalmos on the other side)

5 injury to the tendon of the superior tarsal muscle caused

by prolonged use of hard contact lenses

5 oedema of the eyelid (also present on the underside)

5 blepharospasm (active tight closure of the orbicularis oculi muscle; 7 sect 26.3.3 )

5 pseudoptosis (due to tonus loss in the frontalis muscle

or the orbicularis oculi muscle associated with facial nerve paralysis; 7 sect 16.2.7 )

Binocular double vision

The first step in evaluation of double vision is to establish whether it disappears when one eye is covered If not, the

patient has monocular double vision, which usually has an

ophthalmological cause (e.g early-stage cataract), although

no cause is identified in many cases Oculomotor nerve palsy causes crossed double vision (7 sect 6.2.2) The main causes of binocular double vision are listed in tab 16.1

Vascular disorder

The cause of acute double vision is often a vascular disorder, especially in elderly people with diabetes or hypertension In such cases, pupillary response is unaffected, because the fibres responsible are located peripherally within the nerve and there-fore, due to external vascularization, remain functional in the event of central artery failure The prognosis is favourable Examination using imaging techniques is not strictly neces-sary in the absence of a pupil disorder, but is nevertheless car-ried out in many cases If the patient exhibits pupil dilation, it

is important to investigate the possibility of compression by an aneurysm, originating in the posterior communicating artery

or the carotid artery, or by a space-occupying process in the middle cranial fossa

16.2 · Clinical presentation

. Table 16.1 Causes of double vision

eye abnormality – monocular double vision eye muscle abnormality – non-neurological esophoria

(‘squinting’) or exophoria (‘wall eyes’)

– intermittent in myasthenia gravis ( 7 sect 12.6.2 ) – very occasionally myositis orbital process – often a degree of exophthalmos

(‘bulging’ eye), e.g bilateral in myopathy

– thyroid disorder orbital fracture

nerve III palsy – crossed double vision, often

also ptosis and anisocoria nerve IV palsy – diagonal double vision during

downward convergence nerve VI palsy – horizontal uncrossed double

vision in the distance brainstem injury – the eyes often differ in height

(skew deviation) and/or

internu-clear ophthalmoplegia is present

16.2.4 Trochlear nerve (IV)

The core symptom of trochlear nerve palsy (7 sect 6.2.3) is

double vision that is greatest when the gaze is downwards and

towards the healthy eye (towards the tip of the nose); when

looking in that direction, the images are not parallel Typically,

therefore, the patient experiences double vision when going

down stairs The image from the affected eye is lower than that

from the good eye The double vision disappears when the head

is inclined towards the shoulder on the side of the healthy eye;

hence, the patient may present with torticollis

The main cause of isolated trochlear nerve palsy is a

trau-matic brain injury (e.g birth trauma) In most cases, however,

no cause is found

Causes of the trochlear nerve palsy (IV)

5 traumatic brain injury

5 vascular disorder (diabetes)

5 orbital pathology

5 ethmoiditis

5 pathology of the cavernous sinus ( 7 sect 16.3 )

5 cranial base abnormalities

5 brainstem syndrome

Causes of sensation disorders of the face and oral

cavity

5 postherpetic neuralgia ( 7 sect 23.4.5 ), (mainly of the

upper ramus of nerve V: 1st ramus)

5 dental extraction (nerve V: 2nd and 3rd rami)

5 facial trauma (nerve V: 2nd and 3rd rami)

5 sinusitis (nerve V: 2nd and 3rd rami)

5 pathology of the cavernous sinus ( 7 sect 16.3 )

5 cranial base process

5 leptomeningeal metastases

5 collagen disease

5 nasopharyngeal carcinoma

5 pressure caused by dental prosthesis

5 subjective in cases of muscle weakness

5 psychogenic

16.2.5 Trigeminal nerve (V)

A disorder of the trigeminal nerve (7 sects 6.2.4 and 6.3.4) can

result in loss of function (neuropathy) or irritation (neuralgia;

7 sect 21.3.1), or sometimes both In neuropathy without other

neurological abnormalities, the first possibility to consider is

mixed connective tissue disease or tumour metastasis (bone or

leptomeningeal); the patient will typically experience gradually increasing numbness of the chin and adjacent half of the lower

lip (numb chin).

A trigeminal nerve disorder will rarely cause masseter weakness, but that is possible in the event of compression and trauma, mainly as associated with traumatic injury due to ther-mocoagulation in trigeminal neuralgia, 7 sect 21.3.1

Causes of abducens nerve palsy (nerve VI)

5 vascular

5 intracranial hypertension

5 CSF hypotension ( 7 sect 10.8.4 )

5 toxic

5 traumatic brain injury

5 basal meningitis, syphilis

5 polyradiculoneuritis ( 7 sect 13.3.2 )

5 leptomeningeal metastases ( 7 sect 22.5 )

5 acute vitamin B1 deficiency ( 7 sect 8.7.3 )

5 injury to the pons (vascular, MS, tumour; fig 16.1 )

5 orbital or periorbital process ( 7 sect 16.3 )

16.2.6 Abducens nerve (VI)

Abducens nerve palsy will often cause double vision when looking into the distance; the image misalignment is purely horizontal, without vertical displacement or crossing (7 sect 6.2.3)

Although less common than infarction of the oculomotor nerve, infarction of the abducens nerve does occur The length

of its pathway from the pons to the orbit makes the abducens nerve very vulnerable to intracranial hypertension; double vision in the distance can be the first sign of such a disorder,

along with headaches Hypotension (CSF hypotension drome, e.g following lumbar puncture) can also lead to nerve

syn-VI palsy (7 sect 10.8.4) Furthermore, the use of vincristine, chloroquine or streptomycin can bring about (often rever-sible) abducens nerve palsy Palsy can occur in MS as well ( fig 16.1) In 30 to 50 % of patients who experience acute palsy, the cause remains unexplained and spontaneous recovery follows

16.2.7 Facial nerve (VII)

In addition to its primary motor function (7 sect 6.2.6), the facial nerve has sensory (7 sect 6.2.5) and autonomic functions (7 sect 7.1.2) If a patient presents with facial weakness, the pri-ority is to establish whether the disorder is central (corticobul-bar tract) or peripheral (facial nerve or nucleus) (7 sect 6.2.6)

5 basilar skull fracture

5 forceps delivery injury

5 nuclear aplasia (Moebius syndrome)

Acute facial palsy

Acute facial palsy without immediately apparent cause was

for-merly referred to as Bell’s palsy, but is now generally known as idiopathic peripheral facial palsy (IPFP) The incidence of the

disorder is 20 to 30 cases per 100,000 of the population per year; it is the most common form of acute peripheral facial palsy The disorder can occur at any age, but is most common between the ages of fifteen and forty-five

A diagnosis of IPFP cannot be made until other possible causes, principally otitis, have been excluded Systemic condi-tions such as sarcoidosis, polyradiculoneuritis and infection (neuroborreliosis) often lead to bilateral palsy In a child, neu-roborreliosis must also be considered in the event of unilateral palsy

In 70 % of cases, the patient exhibits total paralysis; in the remaining cases, the disorder manifests itself as weakness About 10 % of patients suffer relapse The symptoms begin suddenly or develop over a period of hours or days, often pre-ceded and initially accompanied by pain behind the ear One patient in three exhibits a gustatory disorder affecting the front two-thirds of the tongue on the same side (7 sect 6.3.5) In the affected eye, lacrimal secretion is sometimes impaired How-ever, it may seem as if over-secretion is occurring, but that is actually due to the tear duct opening no longer being the lowest drainage point and tears consequently running over the droop-ing lower eyelid

The pathophysiology of IPFP is unclear The activation of

a latent herpes simplex virus may be involved In some cases, the trigeminal nerve is also affected, in which case the varicella zoster virus is responsible and the condition is referred to as

herpes zoster oticus or Ramsay-Hunt syndrome.

Following recovery without significant residual ment, there may be mild residual symptoms in the form of slight palsy or contracture, and blinking may be delayed on the affected side Where recovery is incomplete, the patient may continue to exhibit significant palsy and subsequent con-tracture, ‘crocodile tears’ (unilateral hyperlacrimation while

impair-eating) and involuntary coordinated movement (synkinesia),

due to the fibres of the oral ramus innervating the muscles of the optic ramus and vice versa IPFP usually (in 85 % of cases) heals completely or almost completely within six to eight weeks However, functional recovery takes at least six months The prognosis is less favourable following complete paraly-sis (61 %, compared with 94 % in cases of paresis), if signs of recovery are not apparent within three weeks, in patients over the age of sixty, and in cases of comorbidity (hypertension, dia-betes mellitus) The prognosis for the recovery of facial nerve

. Figure 16.1 Pontine lesion associated with MS in a 35-year-old woman

exhibiting right abducens nerve palsy

16.2 · Clinical presentation

function in Ramsay-Hunt syndrome is significantly worse The

House-Brackmann Scale (I-VI) for the grading of facial palsy

can be used for progress monitoring

Therapy initially consists of protecting the cornea against

drying by means of eye ointment or eye drops, and

cover-ing the eye with a dresscover-ing overnight If the patient presents

within seventy-two hours following a major failure (inability

to close the eye), administration of oral prednisone for seven

to ten days is indicated There is evidence to suggest that, in a

case of serious nerve damage (House-Brackmann score of V or

VI), the addition of an antiviral agent (valaciclovir/famciclovir)

improves the prognosis for full recovery An antiviral agent is

also indicated in Ramsay-Hunt syndrome

In the convalescent phase following permanent serious

nerve damage, it is desirable to involve a speech therapist with

a view to establishing whether mime therapy may be beneficial

Speech exercise therapy can also help with swallowing

prob-lems, which sometimes develop following facial nerve palsy

Irritation

Irritation of the facial nerve can induce spasms: series of

mas-sive contractions of one half of the face lasting between a

few seconds and a minute or so (hemifacial spasm) In about

10 % of cases, the spasms are a residual symptom of injury,

as described above; in the other cases, they may be due to

compression of the nerve by the anterior inferior cerebellar

artery or posterior inferior cerebellar artery (AICA or PICA;

figs 16.2 and 11.1) or by a branch of one of those arteries In

rare cases, a local tumour is the cause Surgical decompression

of the nerve is often effective (Jannetta procedure) Another

option is botulin toxin therapy Various other medications

(car-bamazepine and other anti-epileptics, baclofen, clonazepam)

have little effect

Hemifacial spasm is nearly always a unilateral disorder,

unlike blepharospasm, a form of dystonia (7 sect 26.3.3)

Facial myokymia are subtle muscle contractions

affect-ing part of the face, sometimes unnoticed by the patient

They are benign and may be triggered by emotions or fatigue

Sometimes, however, an intrapontine process is present (tumour, MS) Involuntary contractions of the facial muscles

are usually attributable to tics (7 sects 5.1.2 and 26.3.7)

16.2.8 Vestibulocochlear nerve (VIII)

Neurogenic deafness

If perception deafness is observed, an ENT specialist can erally establish by audiometric testing whether the deafness is attributable to a cochlear or retrocochlear disorder; the latter is usually due to a problem with the acoustic nerve

gen-The most common cause of acute unilateral perception deafness (idiopathic sudden sensory-neural hearing loss) is

unknown The incidence is estimated to be 8 in 100,000 per year There is often a temporary vestibular disorder and tinnitus

is almost always present In 30 % of cases, the patient has fered a respiratory infection in the previous month About half

suf-of patients experience spontaneous recovery, with the ness of recovery correlating to the mildness of the initial failure The problem is likely to be located in the auditory organ itself.Drugs that can induce perception deafness and disorders

complete-of the vestibular nerve are: aminoglycosides (streptomycin and related substances), quinine derivatives, acetylsalicylic acid, cytostatics and some diuretics Tumours of the cerebellopon-tine angle (neurinoma, usually originating in the vestibular nerve) are dealt with in 7 chap 22 (7 sect 22.3.5, fig 22.5)

Causes of neurogenic deafness

5 acoustic trauma

5 tumour of the cerebellopontine angle ( 7 sect 22.3.5 )

5 congenital dysplasia

5 drugs

5 herpes zoster oticus, measles, mumps

5 intoxication, e.g by a solvent

severe vertigo with nausea and vomiting, which diminishes

over a period of weeks due to adaptation by central nisms Examination should reveal vestibular nystagmus (7 sect 6.2.8) If both vestibular organs are affected (e.g by intoxication), the patient will experience disorientation and

mecha-oscillopsia Oscillopsia involves the environment seeming to

move whenever the head is moved Normally, the sensation is prevented by the vestibulo-ocular reflexes

. Figure 16.2 MRI scan of the cerebellopontine angle A loop of the right

anterior inferior cerebellar artery (AICA; top left of the image) is

compres-sing the facial nerve, leading to hemifacial spasm

203

over when lying (even while sleeping), and by rapidly ing the head backwards or to the side An attack can there-fore be provoked by getting the patient to move from sitting

tilt-to lying within a few seconds, with his head turned, and then supporting the patient’s head and lowering it through about

30 degrees (Hallpike manoeuvre) Typically, the spinning

sensa-tion develops after a latency period of five to ten seconds, and disappears quite quickly (within ten to thirty seconds) if the patient keeps still After being repeated several times, the pro-voking manoeuvre ceases to be effective The condition involves horizontal rotatory nystagmus towards the affected ear, which

is therefore hypersensitive In practice, however, the nystagmus

is not always observed, because it is suppression by fixation

The disorder is observed following cranial trauma, viral ronitis, during or after prolonged bed rest and in periods of stress However, in more than half of patients, no cause can be identi-fied Patients in whom no cause can be found are usually elderly and two thirds of them are women The disorder is very common.The pathophysiology involves abnormal stimulation of the sensory organ in the posterior canal of the labyrinth due to

neu-an accumulation of debris impeding the flow of endolymph

(canalolithiasis) Another, less common cause is the attachment

of debris to the cupula

After giving the patient reassurance and explanation, the

Epley manoeuvre (a variation on the Hallpike manoeuvre)

can be performed with a view to immediately resolving the problem If the patient has residual problems, daily positional change exercises can be prescribed, whereby the patient repeat-edly moves quickly from sitting to lying on his side, then sits

up again after thirty seconds During the exercises, the head should be turned so that the patient lies with the ipsilateral side

of the occipital region on the bed The patient should lie first to the left and then to the right Improvement often occurs after one to four weeks, after which the exercises may be gradually phased out Even without exercises, the attacks usually cease after a few weeks or months Medicinal therapy is not desirable

Vestibular neuritis

In vestibular neuritis or neuronitis, the patient experiences fairly sudden, continuous vertigo accompanied by vegeta-tive symptoms Horizontal rotatory nystagmus away from the affected ear (slow phase towards the affected ear) is observable, and the patient is liable to fall and point off-centre, towards the affected side There is no hearing loss or tinnitus The vertigo remains severe only for a few days (three to five), during which time it is best for the patient to remain in bed It then gradually diminishes over a period of four to six weeks, although oscil-lopsia (see above) following rapid head movements may per-sist About half of patients have residual symptoms, which are sometimes manifest only under particular circumstances (e.g

on fairground rides and boats)

The affected labyrinth is usually insensitive to stimuli ing the acute phase and subsequently exhibits reduced sen-sitivity for a prolonged period The nystagmus is second or third degree in the acute phase and subsequently present only when the patient looks to the healthy side The disorder occurs mainly in middle age, particularly in the autumn and winter It

dur-As a result of adaptation, gradual unilateral loss of function

of the labyrinth or vestibular nerve (nerve VIII) creates few

problems in everyday life The same is true of central disorders

that cause vertigo and sensations of movement

Migraine patients often suffer vestibular attacks that are not

necessarily followed by the usual headaches Such attacks do not

involve hearing loss or tinnitus They are therefore described as

benign recurrent vertigo Young children (one to four years old)

can experience vertigo attacks lasting seconds to minutes, in

which the children go pale The children concerned are typically

from families in which migraine occurs, and some of them go on

to develop typical migraine Finally, the disorder known as

basi-lar migraine (7 sect 21.2.3) is sometimes accompanied by vertigo

Ménière’s disease

Ménière’s disease is characterized by spontaneous vertigo

attacks, usually accompanied by vegetative symptoms, such as

nausea, vomiting, perspiration and, very occasionally, syncope,

in combination with auditory abnormalities (impaired

hear-ing and tinnitus) Ménière’s disease may be diagnosed only if

the patient exhibits vertigo attacks, impaired hearing and

tin-nitus, and no other cause can be found Before and during

the attack, the patient has the sensation that the affected ear is

blocked, often followed by hearing impairment and/or

tinni-tus (7 sect 6.2.8) During the attack, nystagmus is present, the

direction of which is a matter of debate There is good reason to

assume that the labyrinth is hyperstimulated in the acute phase

– causing nystagmus towards the affected ear, 7 sect 6.2.8 –

and subsequently suppressed – causing nystagmus towards

the healthy ear Attacks last for a few hours only, and are

fol-lowed by symptoms that gradually diminish over a few days

The frequency and seriousness of the attacks varies However,

they peak in the first two years, and 80 % of patients

experi-ence spontaneous remission within five to ten years Ultimately,

patients are liable to experience Tumarkin attacks, which

involve falling and the sense of being pushed over Progressive

loss of the ability to hear high-frequency sound almost always

occurs, which is usually unilateral but is bilateral in about a

third of patients The disorder mainly affects people between

the ages of thirty and fifty The annual incidence is 40 to 50

cases per 100,000, while the prevalence is 300 per 100,000

The pathophysiological mechanism responsible is

uncer-tain However, it is believed that the flow of endolymph from

the cochlea to the vestibular organ is intermittently excessive

As a result, the utriculus becomes over-full and the

semicir-cular canals are hyperstimulated There is no therapy that

addresses the cause Betahistidine can reduce the frequency of

the attacks, however Numerous other therapies, including

sur-gery to disable the cochlea, have proved largely ineffective In

therapy-resistant cases, local treatment with aminoglycosides

appears to be beneficial However, caution should be exercised,

because aminoglycosides are ototoxic

Benign paroxysmal positional vertigo

The patient presents with an acute, extreme sensation of

spin-ning triggered by changing position, e.g going from standing

to lying or from lying to sitting, and sometimes by turning

16.2 · Clinical presentation

Semi-solid non-fibrous food usually gives rise to est problems, while watery fluids are particularly difficult for patients to swallow Dairy products are undesirable, due to their influence on mucous production Patients can often sense (and therefore swallow) cold foodstuffs much better than hot foodstuffs (particularly in ALS and myasthenia) In cases of unilateral function loss, it helps to turn the head, usually to the affected side In acute dysphagia, e.g after a stroke, it is often necessary to temporarily stop oral intake and to instigate saliva suction and temporary nasogastric or parenteral feeding In chronic cases (ALS), percutaneous gastrostomy followed by gastric tube feeding is often the best solution

few-Causes of neurological swallowing disorders

– diminished level of consciousness – pseudobulbar

disorders ( 7 sect 6.6 )

– bilateral cerebral infarction in the acute phase of unilateral cerebral infarction

– MS ( 7 sect 24.2 ) – ALS ( 7 sect 13.2.3 ) – acute phase following

stroke

– ( 7 sects 6.6 and 17.5.1 )

– extrapyramidal disorders

– Parkinson’s disease ( 7 sect 26.1.2 ) – dystonia ( 7 sect 26.3.3 ) – disorders of the

medulla oblongata

– Wallenberg’s syndrome ( 7 sects 6.7.3 and 17.4.6 ) – ALS ( 7 sect 13.2.3 ) – poliomyelitis ( 7 sect 23.4.4 ) – cranial nerves VII, IX, X

and XII

– skull base tumour – polyradiculoneuritis ( 7 sect 13.3.2 ) – diphtheria – leptomeningeal metastases ( 7 sect 22.5 )

– neuromuscular transmission

– myasthenia gravis ( 7 sect 12.6.2 ) – botulism ( 7 sect 12.6.4 ) – botulin toxin therapy – muscular disorders – oculopharyngeal dystrophy

– polymyositis ( 7 sect 12.5.1 ) – myotonic dystrophy ( 7 sect 12.4.3 ) – autonomic plexopathy

is assumed to be a viral disorder, but the responsible pathogen

has not been identified and not all patients have experienced a

prior infection Nor is it clear whether it is the vestibular nerve

or the labyrinth that becomes infected The same vertigo

syn-drome can develop in the event of infection by herpes zoster

oticus (7 sects 16.2.7 and 23.4.5) Therapy consists of rest and

possibly anti-emetics in the first days, followed by mobilization

as soon as possible Antivertiginous medication may help to

mitigate the symptoms in the early stages Antiviral agents do

not appear to help, but corticosteroids can expedite recovery

Non-vestibular vertigo

The presence of vertigo does not necessarily imply a problem

with the vestibular organ Many other problems are referred

to as vertigo well Thorough history taking is the main way of

differentiating between other forms of ‘vertigo’ and vestibular

vertigo Vestibular vertigo is accompanied by a sensation of

movement, whereas other forms involve light-headedness or

blackness in front of the eyes, and sometimes ringing in the

ears A lack of sensory information (tactile, visual or auditory)

can induce a sense of disorientation; the problem accumulates

if multiple sensory problems are present (multi sensory deficit).

Non-vestibular vertigo

5 blood pressure regulation disorders

5 hyperventilation/panic attacks

5 disorders of central control regulation

5 gnostic sensory disorders of the legs

The functions of the glossopharyngeal nerve and vagus nerve

(7 sect 6.2.9) are closely connected in a swallowing action

Swal-lowing disorders are not always spontaneously reported,

par-ticularly by the elderly Eating more slowly, eating less, weight

loss, increased salivation, coughing after drinking, food or

drink getting up the back of the nose and repeated respiratory

infections are important indicators and the patient should be

asked specifically about such symptoms Coughing or a ‘watery

voice’ after drinking and fluid getting up the back of the nose

suggest choking due to palatal weakness Such weakness is

read-ily observable by asking the patient to drink a glass of water

Problems such as a sensation of thickness in the throat and

the sensation that something is stuck in the throat (globus

sen-sation without choking) are not true indicators of a neurogenic

disorder

Swallowing problems require a multidisciplinary approach

involving an ENT specialist, dietitian, gastroenterologist and

speech therapist Mild swallowing disorders can often be

pre-vented by advising the patient to take his time eating and not

to talk while eating Head posture can also be relevant

205

Furthermore, ‘patchy’ multiple cranial nerve failure can occur in neuropathies associated with infections (diphthe-ria, syphilis, herpes zoster, HIV), granulomatous disorders and vasculitis (sarcoidosis, SLE, Sjögren’s syndrome and other disorders), in response to medication (nitrofurantoin, cyto-statics, tuberculostatics), in lymphoreticular disorders and in paraproteinemia

16.2.10 Accessory nerve (XI) and hypoglossal

nerve (XII)

Damage to the accessory nerve leads to loss of strength in the

trapezius muscle and the sternocleidomastoid muscle and

thus to shoulder weakness and weakness during rotation of

the head Hypoglossal nerve palsy affects contralateral tongue

movements Tongue atrophy is also common The cause can be

iatrogenic injury suffered during surgery in the neck region,

traumatic injury, tumours of the skull base and local

compres-sion by a tumour, or dissection of the carotid artery

Causes of tongue atrophy

5 motor neuron disease (particularly ALS; 7 sect 13.2 )

5 syringobulbia (anterior horn; 7 sect 15.5.3 )

5 skull base processes

5 MS ( 7 sect 24.2 )

5 traumatic nerve lesion (including surgical trauma)

5 polyradiculitis (Guillain-Barré syndrome; 7 sect 13.3.2 )

5 nasopharyngeal carcinoma

5 brainstem process

5 dissection of the carotid artery ( 7 sects 11.3.4 and

17.4.2 )

16.3 Failure of multiple cranial nerves

Because the cranial nerve nuclei are adjacent to each other in

the brainstem and the cranial nerves are located close together

at the base of the brain, it is not uncommon to lose the

func-tion of multiple nerves ( fig 16.3) The identification of a

syn-drome can facilitate causal determination The main synsyn-dromes

associated with cranial nerve failure are listed in tab 16.2

The table is not exhaustive There are also various vascular

syn-dromes that can involve multiple cranial nerve palsies, due not

only to brainstem infarction from the basilar artery, but also to

cranial nerve infarction from branches of the internal carotid

artery, as in a carotid dissection

sphenoid sinus

pituitary gland

carotid artery

III IV VI V1 V2 II

. Figure 16.3 Cavernous sinus with nerves III, IV and V (1st and 2nd rami)

and nerve VI ( fig 11.4 ) Pathological processes such as venous

thrombo-sis, vascular malformations and granulomatous infections can occur in this

region, potentially leading to multiple cranial nerve palsies

. Table 16.2 Main syndromes involving multiple cranial nerve

palsies

location/syndrome nerves main causes

cavernous sinus III to VI to

varying degrees

– thrombosis – tumours in the pituitary gland region

– metastasis – aneurysm in the carotid artery

superior orbital fissure

III, IV, V (1st ramus), VI

– space-occupying lesion behind orbit

– granulomatous infection (Tolosa-Hunt syndrome)

cerebellopontine angle syndrome

V, VI, VII, VIII

– neurinoma in nerve VIII – other tumours lateral medulla

oblongata (Wallenberg’s syndrome)

V (sensory dissocia- tion), IX, X

– infarction of the solateral region of the medulla oblongata

dor-jugular foramen IX, X, XI – trauma

– tumour – thrombosis in the jugular vein apex of petrous

temporal bone

V, VI, horner’s syndrome

– mastoiditis – meningitis

parapharyngeal space

IX, X, XII – malignant tumours

– abscess adjacent to the pharynx

unilateral cranial nerve failure

V to XII (variable)

– malignant process – skull base infection (mucormycosis in diabetes mellitus) herpes zoster oticus V, VII (IX) – 7 section 23.4.5

16.3 · Failure of multiple cranial nerves

© Bohn Stafleu van Loghum is een imprint van Springer Media B.V., onderdeel van Springer Nature 2018

J B M Kuks and J W Snoek (Eds.), Textbook of Clinical Neurology, https://doi.org/10.1007/978-90-368-2142-1_17

Cerebral infarction and cerebral

haemorrhage

Abstract

Cerebral infarctions and cerebral haemorrhages are cerebrovascular disorders (strokes)

Strokes are a major cause of mortality and disability Imaging is required to make the

correct diagnosis Cerebral infarctions are caused primarily by atherosclerosis, but there

are cardiac and other – albeit rare – causes A TIA is in fact an impending cerebral

infarc-tion and needs to be diagnosed quickly The possibility of thrombolysis during the acute

phase means that a cerebral infarction is a medical emergency Hypertension, amyloid

angiopathy and vascular malformations can cause intracranial bleeding Subarachnoid

haemorrhages are usually caused by a ruptured aneurysm Rare cerebrovascular

dis-orders are cerebral venous sinus thrombosis and cerebral vasculitis The treatment of

stroke patients requires a multidisciplinary approach If residual symptoms are present

after a cerebral infarction or cerebral haemorrhage the success of rehabilitation is

affected by cognition and mood

Electronic supplementary material

The online version of this chapter ( 7 https://doi.org/10.1007/978-90-368-2142-1_17 ) contains supplementary

material, which is available to authorized users.

17.1 Classification of cerebrovascular disorders – 209

17.2.1 Epidemiology and prognosis – 209

17.4.2 Carotid artery occlusion – 212

17.4.3 Cerebral infarct in the area supplied by the middle cerebral artery – 214

17.4.4 Cerebral infarct in the area supplied by the anterior cerebral artery – 214

17.4.5 Posterior cerebral artery occlusion – 214

17.4.6 Cerebral infarct in the area supplied by the vertebrobasilar artery – 215

17.4.7 Lacunar infarcts – 215

17.5 Treatment for cerebral infarction – 216

17.8.1 Clinical signs and diagnosis – 223

17.8.2 Treatment – 223

17.9 Primary and secondary cerebral vasculitis – 224

chapter we include subarachnoid haemorrhages under strokes (in line with American practice), which is not always the case The primary cause of most epidural and subdural haemor-rhages is trauma: these disorders are beyond the scope of this chapter and are discussed in 7 chap 20.

Strokes are common In a small country as the Netherlands for instance, some 40,000 people a year have a first stroke There is

a marked increase in incidence with age A stroke is a serious event, with a high risk of mortality and dependency on care In two out of three cases death is due to cardiovascular disease, in

45 % of cases to a subsequent stroke Since 1980, particularly in men, there has been a decline in mortality following cerebral infarction and subarachnoid haemorrhage, but not following intracerebral haemorrhage

Epidemiology and prognosis

incidence of first stroke

– highly dependent on age; the average is approximately 200 per 100,000 head of population per year

mortality following stroke

Cerebral infarction causes and risk factors

Risk factors for atherosclerosis-related cerebral infarction

5 smoking

5 diabetes

5 hypertension

5 hyperlipidaemia

5 family history of cardiovascular disease under the age of 60

5 overweight and lack of exercise

Case 17.1

A 62-year-old right-handed man is suddenly unable to find

the right words while giving a talk After about five minutes

his speech returns to normal, and during the event he

was able to understand everything that was said to him

He has never had a language disorder of this kind before,

but during the past few weeks he has had two brief bouts

of blindness in one eye (lasting five and fifteen minutes

respectively), which cleared up spontaneously For the

past two years he has been on oral anticoagulant therapy

following replacement of the mitral valve.

Question 1: What are these episodes called, and what is the

likely cause in this patient’s case?

Question 2: What is the explanation for the bouts of blindness?

Which eye is most likely to have gone blind?

Question 3: What diagnostic tests are indicated?

Question 4: What other cause of this episodic loss of function

should be considered in patients who do not have heart

defects?

Online: 7Answers to case study questions 17.1

Case 17.2

A 45-year-old woman suddenly develops severe pain in the

occiput and neck around midday while gardening She goes

indoors to lie down and then vomits During the afternoon

she becomes agitated, her speech is confused and she

complains of headache and back pain She can move her

arms and legs normally Examination at 5 pm: confused

woman Temperature: 37.6 °C No symptoms of meningeal

irritation No neurological symptoms.

Question 1: What is the most likely diagnosis?

Question 2: Why is the information on meningeal irritation

relevant here, and what can we conclude from the fact that

there is none?

Online: 7Answers to case study questions 17.2

If there is sudden loss of function in the central nervous system

which does not improve rapidly it is very likely to be a stroke

Stroke (or cerebrovascular accident, CVA) is an umbrella term

for a variety of disorders ( tab 17.1) Broadly speaking, strokes

can be divided into cerebral infarctions (80 %) and cerebral

haemorrhages (20 %).

There can be a combination of the two when a secondary

haemorrhage occurs in the soft infarcted area: haemorrhagic

infarction.

If the symptoms of a cerebral infarction rapidly improve it

is referred to as a transient ischaemic attack (TIA) By

defini-tion the neurological symptoms last no longer than 24 hours (a

fairly arbitrary period) and usually clear up within 30 minutes

Spontaneous subarachnoid haemorrhage (SAH) and cere­

bral venous sinus thrombosis (CVST) are relatively rare types

of stroke ( < 5 %), more common in younger people In this

210 Chapter 17 · Cerebral infarction and cerebral haemorrhage

Cerebral haemorrhage causes and risk factors

5 hypertension

5 use of anticoagulants

5 coagulation disorders

5 cerebral amyloid angiopathy (CAA)

5 vascular malformation ( 7 sect 11.3.3 )

5 bleeding in a tumour or metastasis

In later life amyloid is a rather frequent cause: in many

older patients amyloid beta 40, an insoluble protein,

accumu-lates in cortical and leptomeningeal vessels, making them

brittle and thus causing cerebral amyloid angiopathy (CAA)

In a small proportion of patients this causes a lobar rhage (which often recurs) These patients are also often found

haemor-to have asymphaemor-tomatic microbleeds in the brain parenchyma

These can be clearly seen using certain MRI techniques (gradi­ ent echo or susceptibility-weighted imaging, SWI) Severe CAA

can cause dementia CAA is found to a greater or lesser extent

in over half of over-70s; there is also a hereditary variant

17.3.1 Clinical approach

The aim of history-taking and physical examination in the acute stage is first and foremost to check whether the symp-toms are indeed a manifestation of stroke or whether they are due to some other condition (epilepsy, hypoglycaemia, migraine, a vestibular disorder or a functional disorder) Other relevant conditions and risk factors that impact on treatment and secondary prevention can be investigated at the same time

A clinical diagnosis of stroke is based mainly on the nature

of the neurological symptoms and the sudden onset (within minutes or hours) Whether a haemorrhage or an infarction

is involved is difficult to determine on clinical grounds In the case of an infarction the symptoms and signs will usually be consistent with loss of function in an area supplied by a single artery (7 sect 17.4) In 10–15 % of cases there will already have been one or more TIAs

Vomiting, headache and rapid decrease in the level of sciousness are more common with cerebral haemorrhage than cerebral infarction These symptoms can also occur in the case

con-of a cerebral infarction, however, so they are non-specific and

do not help with the differential diagnosis With a view to sequent treatment, therefore, imaging should be carried out on all stroke patients during the acute phase

sub-Cardiac causes of cerebral infarction

5 atrial fibrillation

5 recent myocardial infarction

5 heart valve defect/endocarditis

5 cardiac myxoma

Other (often rare) causes of cerebral infarction

5 dissection of a neck artery

5 Moyamoya disease (a vascular disease with stenosis or

occlusion of the carotid artery and extensive collateral circulation)

5 vasculitis

5 coagulation disorders

5 migraine

5 polycythaemia, thrombocytosis

5 polyglobulia (Waldenström’s macroglobulinaemia)

5 syphilis, borreliosis (vasculitis)

5 drug use

5 antiphospholipid syndrome

5 RCVS ( 7 sect 17.9 )

5 rare hereditary forms (e.g CADASIL: 7 sect 17.4.7 )

Where the patient is relatively young (under the age of 50) the

term young stroke is used The cause in this group is usually

dif-ferent from that in older stroke patients, so it is important to

look for rare causes as well in these young patients

. Table 17.1 Terminology

stroke cerebrovascular accident, CVA (cerebral

infarction/haemorrhage) haemorrhagic

loss of function increasing in severity

completed stroke cerebral infarction where the loss of

function stops increasing

‘silent’ infarctions cerebral infarctions without loss of

func-tion, only detectable using imaging lacunar infarct small (less than 15 mm) subcortical

infarct caused by blood vessel occlusion due to arteriolosclerosis (small vessel disease: 7 sect 17.4.7 )

leukoaraiosis periventricular or subcortical white

mat-ter abnormalities (this is a radiological description; leukoaraiosis can also be a manifestation of small vessel disease:

7 sect 11.3.1 ) microbleeds small dot-like bleeds on an MRI, often

asymptomatic

17.4 Clinical aspects of cerebral vascular occlusions

17.4.1 TIAs

The most common symptoms of TIA are as follows (or a bination thereof):

com-5 complete or partial blindness in one eye (amaurosis fugax)

5 unilateral impaired sensation

5 paresis of one half of the body (or part thereof)

verte-Amaurosis fugax is transient field-of-vision loss in one eye

Loss of the entire field of vision or a horizontally bounded upper or lower field in one eye is caused by a temporary inter-ruption in the peripheral retinal circulation

TIAs can recur, often causing the same symptoms and signs (e.g paresis in one arm), with varying severity and duration

If the perfusion areas in which the TIAs occur keep changing, cardiac (or aortic) embolisms should be considered

In a small number of cases (1 %) symptoms and signs lar to those of a TIA can be caused by something other than ischaemia, e.g a bleed or tumour Imaging (a CT or MRI scan)

simi-is therefore indicated even for transient symptoms such as those of a TIA It can be difficult to diagnose TIA; the diagnosis

17.3.2 Imaging

A CT scan of the brain at the acute stage can distinguish

between an infarction and a haemorrhage with great certainty

In such cases CT is preferable to MRI because it is quicker –

important with a view to acute intervention (7 sect 17.5.1) –,

the patient can be monitored more effectively and there are

fewer contraindications Immediately after a haemorrhage the

CT scan will show a hyperdense area ( fig 17.1 a), whereas an

infarct may not be visible during the acute phase Any infarct

will not usually be fully visible for the first one to three days

( fig 17.1 b)

An MRI, on the other hand, is more sensitive to early

changes indicative of an infarction, especially during the

acute phase: diffusion-weighted images can show cytotoxic

oedema caused by an infarction at an early stage, enabling it

to be detected reliably while the CT scan is not yet showing

any abnormality (7 sect 11.4.3) The diffusion-weighted image

shows a fresh infarct as an area of increased signal ( figs 17.2 b,

17.3 a, 17.4 c), whereas the corresponding apparent diffusion

coefficient (ADC) images show a reduced signal in this area

( fig 17.3 b) These techniques enable the size of any infarct

and surrounding tissue that is not yet permanently damaged

(the penumbra, 7 sect 11.2.3) to be estimated

The size of an infarct can also be measured using a perfu­

sion CT ( fig 17.5), a CT scan with intravenous contrast fluid

showing blood flow and volume in brain tissue

The cerebral images enable conclusions to be drawn on

localization and extensiveness that help to determine the

prob-able cause ( tab 17.2)

. Figure 17.1 CT scans of a haemorrhage (a) and an infarct (b) in the area supplied by the deep branches (lenticulostriate arteries) of the right middle

cerebral artery

212 Chapter 17 · Cerebral infarction and cerebral haemorrhage

initiated as soon as possible The risk of infarction following a TIA can be estimated fairly reliably based on a validated score known

as the ‘ABCD 2 score’ Advanced age, raised blood pressure,

particu-lar clinical signs, duration of symptoms and diabetes all increase the score, which means a higher risk of cerebral infarction

17.4.2 Carotid artery occlusion

Acute occlusion of a carotid artery can be asymptomatic if the other cerebropetal arteries and the Circle of Willis are intact Infarction can occur, however, depending on how quickly the

is based mainly on careful history-taking Research shows that

GPs generally diagnose TIA correctly in two-thirds of cases;

neurologists too differ on the interpretation of symptoms and

signs in 10 % of cases The differential diagnosis list includes

such things as syncope, migraine with aura and focal epilepsy

Patients who have had a recent TIA are at highly increased

risk of cerebral infarction, and the risk is highest immediately after

the TIA Ultimately an average of 25 % of TIA patients have a

cere-bral infarction within five years, but the risk of having one within

one week of a TIA is already 5–10 % Rapid diagnosis is therefore

required after a TIA, and secondary drug prophylaxis (platelet

inhibitors, a statin and if necessary an antihypertensive) should be

. Figure 17.2 MRI scan of a 60-year-old man who had a cerebral infarction two years ago in the posterior area supplied by the right middle cerebral

artery Residual symptoms: incomplete hemianopia and mild functional impairment of the left hand Now acute minimal increase in loss of function in

the left arm and left-sided central facial palsy a Fluid-attenuated inversion recovery (FLAIR) MRI showing an old infarct, unchanged from the CT scan two years ago b Diffusion-weighted MRI scan showing a fresh infarct, visible as an area of increased signal intensity in the anterior area supplied by the middle

cerebral artery

. Figure 17.3 a Diffusion MRI b ADC (apparent diffusion coefficient) and c FLAIR images of a very small, recent-onset (less than 24 hours ago) infarct in

the right precentral sulcus (cortical hand area) Male 65 year Very minor loss of strength, only in left hand, not noticed acutely Initial doubt as to central

cause The diffusion image (a) shows a high signal which is low in the corresponding area on the ADC image (b) and hyperintense on the FLAIR image (c)

impairment of the sympathetic fibres around the carotid artery, due to ischaemia or compression, it leads to Horner’s syndrome (7 sect 7.5.3).

The actual dissection can be seen on a CT or MRI scan, and

a bleed in the wall of the damaged blood vessel will often be seen on the MRI ( fig 17.6) In the case of an infarction due

occlusion developed and whether thromboembolisms and

col-lateral circulation (7 sect 11.1.1) develop

One of the causes of acute occlusion is dissection, which

is likely if the infarction was preceded by a neck trauma

(sometimes even trivial) and when there is pain in the neck

or around the eye (7 sect 11.3.4) If the dissection causes

. Figure 17.4 Wallenberg syndrome MRI scan of an infarct in the right dorsolateral medulla oblongata (on the left of the image) of an 80-year-old

woman with vertigo, right-sided Horner’s syndrome, impaired sensation in the right half of the face, mildly impaired sensation in the left arm and leg and

tendency to fall to the right a and b FLAIR image c Diffusion-weighted image

. Figure 17.5 Example of a perfusion CT during the acute phase of a cerebral infarction During the acute phase the actual infarct is not yet visible on a normal CT; at most it will show subtle early signs, such as a slightly less visible pattern of gyri and sulci in the left hemisphere (on the right of image a) The perfusion CT scan carried out at the same time already shows a large area of severely restricted perfusion (dark grey area image b) and a small area of good

or even increased perfusion (light grey area: penumbra, brain tissue that could theoretically still be saved) A few days later this patient’s normal CT scan

(c) showed a large cerebral infarct, already with some space-occupying effect and displacement of the central structures The entire area supplied by the

middle cerebral artery is infarcted

. Table 17.2 Infarcts on a CT or MRI scan

cause thromboembolism thromboembolism arteriolosclerosis perfusion impairment

location area supplied by large

214 Chapter 17 · Cerebral infarction and cerebral haemorrhage

17.4.4 Cerebral infarct in the area supplied by the anterior cerebral artery

An infarct in the area supplied by the anterior cerebral artery

causes mainly paresis of the contralateral leg and clumsiness in the corresponding arm It can also cause cognitive problems, with frontal symptomatology, but this is not usually the case unless there is also contralateral damage

17.4.5 Posterior cerebral artery occlusion

The key symptom here is hemianopia Memory and behaviour can also be impaired, as the posterior limbic system is also sup-plied by the posterior cerebral artery

The occlusion of the posterior cerebral artery is sometimes bilateral ( fig 17.7), as both arteries branch off side by side from the junction between the basilar artery and the Circle of Willis

The clinical presentation is thus bilateral complete or incomplete loss of visual field, often with retention of cen-tral vision (7 sect 9.1.3, see G) The patient is sometimes not primarily aware of this (cortical blindness) There can also be

confusion, complex visual gnostic disorders, such as problems

to dissection, intravenous thrombolysis treatment during the

acute phase is still safe and indicated, despite the damage to the

wall of the blood vessel

17.4.3 Cerebral infarct in the area supplied by the

middle cerebral artery

Most common is hemiparesis, with the arm and lower half of

the face (central facial palsy) affected more than the leg and for

a longer period, since the cortical representation of the leg is

also supplied by the anterior cerebral artery In most cases the

paresis is initially hypotonic, but within days or weeks it takes

on all the characteristics of loss of central motor neuron

func-tion; Babinski’s sign (extensor plantar reflex) is usually

pre-sent from the outset The condition is characterized mainly

by spasticity, especially if frontal or deep areas of the brain are

damaged If the weakness is global and more or less equally

pronounced in the arm and leg, this is likely to be due not to

infarction of the middle cerebral artery but to an infarction or

small bleed in the posterior crus of the internal capsule

Hemihypaesthesia usually affects epicritic more than

proto-pathic sensation; in the case of parietal lesions it is mainly

ste-reognosis that is impaired and there is often hemianopia due to

interruption of the optic radiation In the acute stage, deviation

of the head and eyes towards the side of the lesion is quite

com-mon, as loss of function in the frontal gaze centre causes the

eyes to be ‘pushed away’ by the contralateral gaze centre (‘the

patient looks at the site accusingly’)

Further loss of function depends on which side is affected

Infarcts in the language-dominant hemisphere (7 sect 8.1.3)

cause aphasia In the non-dominant hemisphere there will be

impairment of emotion and spatial orientation/construction

(7 sect 8.6)

Large parietal lesions in the non-dominant hemisphere

cause denial of the left-sided loss of function (visual neglect, or

as part of anosognosia: 7 sect 8.4) during the acute stage

. Figure 17.6 Dissection of the left vertebral artery The bleed in the

arterial wall can be seen on this transverse T 2 W section of the MRI, on the

right of the image

. Figure 17.7 Bilateral occipital infarct in a 62-year-old man Symptoms:

initially cortical blindness for two days, followed by tunnel vision, absence

of colour vision (achromatopsia), visual agnosia (e.g inability to distinguish between different types of shoes and coats)

The prognosis for lacunar syndromes is better than for larger cortical infarcts Lacunar infarcts often remain asymp-tomatic and are found on a scan by chance A lacunar syn-drome can sometimes start with intermittent loss of function

that becomes permanent later on: this is referred to as cap­ sular warning syndrome The precise cause is not known; it is

assumed that a small vessel becomes permanently occluded If many small blood vessels at various locations are occluded, a progressive syndrome with gait disorders, parkinsonism, uri-nary incontinence and dementia can develop Lacunar infarcts will then be seen on a scan, as well as more diffuse white matter

abnormalities (leukoaraiosis) (7 sect 27.6.2, fig 27.3)

Subcortical lacunar infarcts can develop at a young age in

patients with the rare hereditary disease CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) The condition starts in 30 % of patients

with migraine headache All the patients have typical white matter abnormalities ( fig 17.8) Small subcortical or lacunar infarcts develop from the age of 30 to 50, eventually causing vascular dementia in the majority of patients (7 sect 27.6.2)

DNA analysis is possible (mutation of Notch 3 gene on

chromo-some 19)

with facial recognition (7 sect 9.2), or visual hallucinations

Clinicians often pay insufficient attention to these latter

symp-toms and signs and therefore give inadequate explanations,

and patients (along with their nearest and dearest) are left with

symptoms that they do not understand

17.4.6 Cerebral infarct in the area supplied by the

vertebrobasilar artery

A circulatory disorder in the area supplied by the basilar artery

causes impairments in functioning in the brainstem, and

pos-sibly in the occipital lobes and cerebellum The symptoms and

signs vary (7 sect 6.7), for one thing because of the

anasto-moses and variations in the configuration of the arteries The

occlusion may be located in the basilar artery itself or one of

the vertebral arteries, e.g due to dissection ( fig 17.6)

Isolated vertebral thrombosis does not necessarily cause

symptoms if the other vertebral arteries are properly developed,

but occlusion can cause a cerebellar infarction (pica) or

brain-stem (medullary) infarction

Total occlusion of the basilar artery causes tetraparesis and

pseudobulbar palsy This is usually accompanied by

horizon-tal gaze palsy and cerebellar symptoms Damage to the reticular

formation can cause unconsciousness and irregular breathing In

the case of lower infarctions consciousness may be retained or

mildly impaired, sometimes fluctuating Cases where complete

tetraplegia is combined with palsy of the face and throat muscles,

with vertical eye movements, vision, hearing, sensation and

con-sciousness remaining intact, is referred to as ‘locked-in syndrome’

This is usually caused by infarction of the pons with interruption

of the corticobulbar and corticospinal tracts (7 sect 6.7.2)

The prognosis for a complete infarction in the area supplied

by the basilar artery varies – the loss of function may be

rever-sible if there is adequate collateral circulation – but permanent

loss of function is often not compatible with life as a result of

complications

Many syndromes due to occlusion of a smaller artery in

the area supplied by the basilar artery or vertebral arteries have

been described (7 sect 6.7) Wallenberg syndrome (described

in 7 sect 6.7.3) is the most common one, though it is not often

found in its complete form

17.4.7 Lacunar infarcts

Lacunar infarcts are small infarcts (smaller than 15 mm) deep

in the brain parenchyma (internal capsule, basal ganglia) or

brainstem, caused by the occlusion of small perforating

arte-ries They are easier to see on an MRI scan than a CT scan

Lacunar infarcts account for approximately 20 % of

symp-tomatic infarcts Whereas cortical infarcts have a thrombotic or

thromboembolic cause, the mechanism responsible for lacunar

infarcts is far less well known They may be caused by changes

in the walls of the small perforating blood vessels due to

long-standing hypertension Risk factors other than hypertension

are diabetes and smoking

. Figure 17.8 T2 -weighted MRI scan of a man (aged 48) with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoen- cephalopathy (CADASIL) It shows extensive ischaemic abnormalities of the white matter (particularly in the external capsule) and some lacunar infarcts

in the basal ganglia (including in the left caudate nucleus, on the right of the image)

216 Chapter 17 · Cerebral infarction and cerebral haemorrhage

The percentage of patients actually undergoing this treatment

is relatively low, because of various contraindications and above all the short length of time for which it can be given: it

is appropriate for 25 % of cerebral infarction patients, but only 10–15 % actually receive it The triage and treatment of this group of patients falls under acute medicine, as they need to be treated as soon as possible

Intra-arterial thrombectomy (IAT) – removing a thrombus

by means of a catheter inserted through the groin – has proved effective, and this acute treatment too will improve the func-tional outcome for a substantial proportion of patients Intra-arterial thrombectomy must be carried out within six hours

of the onset of the symptoms, and it is given to patients who fail to recover (or do not recover sufficiently) following IVT, or patients who have a contraindication for IVT such as use of an oral anticoagulant This treatment should only be given if an occlusion of a cerebral artery has been found on a CT angio-gram and it is accessible

17.5.2 Stroke unit

As regards treatment in the acute stage, following any IVT, it

has been proven that rapid admission to a stroke unit, where

stroke patients are treated right from the outset by a ciplinary team, improves the prognosis A stroke unit should

multidis-ideally be part of a stroke service, a regional system of care

pro-viders A stroke service typically provides coordinated,

joined-up care for stroke patients with good information transfer.Causal factors such as cardiac disorders, hypertension, blood disorders and diabetes can be recognized and treated immediately at a stroke unit, thus reducing the risk of a poor outcome Factors associated with poor outcome, such as elec-trolytic disorders, hyperglycaemia and fever, can also be corrected

In many cases −25 % of patients with hemiparesis – there are transient swallowing problems with the risk of aspiration pneumonia A water-swallowing test should be carried out before giving a stroke patient anything to drink or solid food

A feeding tube may be required temporarily In cases of brain stem infarction swallowing problems are often prolonged or

even permanent, so it is advisable to consider percutaneous endoscopic gastrostomy (PEG) (inserting a feeding tube through

the abdominal wall) at an early stage

Stroke patients (even those with minor loss of function) are always at increased risk of infections such as pneumonia or uri-nary tract infection Patients will have difficulty swallowing and urinary retention, but aside from this they are likely to suffer temporary depression of the immune system soon after the brain damage occurs Any infection is a strong predictor of poor out-come and therefore needs to be recognized and treated quickly.Problems such as decubitus ulcers, joint problems in the weakened extremities and pressure on the peroneal or ulnar nerve due to lying in the wrong position can be prevented or treated better by paying particular attention to them A good position and passive movement therapy for the weakened limbs, avoiding contractures (shoulder, feet), are very important

brainstem, internal capsule

dysarthria-clumsy hand syndrome (approx

10 %)

brainstem, basal ganglia

17.5.1 Acute treatment

The blood supply to an area with acute ischaemia can in

prin-ciple be restored (reperfusion) This involves the intravenous

administration of thrombolytics such as recombinant

tissue-plasminogen activator (rt-PA): intravenous thrombolysis (IVT)

If the treatment is started in time it can produce a better

out-come in a large group of patients Generally speaking, the

results are as follows: 40 %: no change in prognosis; 30 %: death

and dependency prevented; the remaining 30 % would already

be independent anyway, but without treatment they might have

had more impairments On the other hand there is a slight

increase in the risk of bleeding in the cerebral infarct

It goes without saying that an intracranial haemorrhage or

haemorrhagic transformation of a cerebral infarct (7 sect 17.1)

needs to be ruled out by an urgent CT scan before any

treat-ment is given If there are no other contraindications, cerebral

infarction is treated as soon as possible using intravenous

thrombolysis with rt-PA This treatment can be given up to

4.5 hours after the onset of the symptoms, but the sooner it is

started the more effective it is: ‘time is brain’.

Contraindications for intravenous thrombolysis

5 recent bleeding in the gastrointestinal or urinary tract

5 moderately severe head or brain injury in the past two

months

5 coagulation disorder

5 elevated INR ( > 1.7) in a patient on oral anticoagulants

5 use of DOACs ( 7 sect 17.5.2 ) less than four hours

previously

5 abnormal coagulation parameters in a patient on

DOACs

5 cerebral infarction in the past two months

5 intracranial haemorrhage in the past three months

5 coma

5 systolic blood pressure > 185 mmHg

5 blood glucose < 2.7 mmol/L

17.5.4 Primary and secondary prevention

A number of risk-increasing factors, such as hypertension, overweight, lack of exercise, cigarette-smoking and vascular disease in the family, are found to be already present at a young age Precise dosing of any diabetes medication is required to regulate blood glucose levels The patient should be advised (and assisted) to stop smoking Proper control of hyperten-sion reduces the risk of a recurrent stroke (haemorrhagic or non-haemorrhagic) The only exception is the small group of patients with very severe carotid stenosis or occlusion and cli-nical signs that could be consistent with a haemodynamic dis-order, in whom the neurological symptoms could be caused by low blood pressure: these patients are at increased risk of dys-function when standing up There are indications that it is bet-ter not to reduce blood pressure in these patients

Anticoagulant therapy (a vitamin K antagonist or DOAC)

is indicated to prevent cerebral embolism in patients with a proven cardiac source of embolism such as atrial fibrillation If there is no cardiac source, the treatment is to prescribe plate-let aggregation inhibitors The drug of choice is clopidogrel, followed by acetylsalicylic acid combined with dipyramidol as second choice, and aspirin on its own as third choice It goes without saying that a patient on an oral anticoagulant who needs to undergo surgery has an increased bleeding tendency, but discontinuing the medication increases the risk of a sub-sequent infarction, so the situation is always risky Fortunately

it is usually not necessary to discontinue platelet aggregation inhibitors before surgery

To prevent deep vein thrombosis and pulmonary

embo-lism, a low dose of low-molecular-weight heparin is

adminis-tered subcutaneously from the first day onwards During the

acute phase it is advisable not to mobilize the patient

imme-diately, as he may not be sufficiently cooperative yet, and

autoregulation of the cerebral circulation may still be impaired

(7 sect 11.2.1)

As blood pressure is often reactively elevated soon after the

infarction, antihypertensive drugs should only be given

dur-ing the acute phase if the levels are extremely high Elevated

blood pressure often falls spontaneously after a few days, and

the harmful effect of a sharp fall in blood pressure if cerebral

autoregulation fails is then a matter for concern Very high

blood pressures (systolic pressure > 185 mmHg) should be

low-ered, however (with caution) It is also clear that after the acute

stage (the first five to seven days) blood pressure needs to be

regulated in order to reduce the risk of further cerebral

infarc-tions (and cerebral haemorrhages)

Anticoagulants and platelet aggregation inhibitors only

have a preventive effect and cannot remove the obstruction

from a blood vessel, but they should nevertheless be given as

soon as possible to prevent recurrent stroke A proven cardiac

source of embolism and cerebral venous sinus thrombosis

(7 sect 17.8) are indications for oral anticoagulants, namely

vitamin K antagonists or the newer direct thrombin inhibitors

and factor Xa inhibitors (direct oral anticoagulants, DOACs)

In all other cases platelet aggregation inhibitors (7 sect 17.5.4)

and a statin are given It goes without saying that

anticoagu-lant therapy should not be started until the risk of intracranial

haemorrhage has been minimized In many cases a repeat CT

scan will be carried out, and if the infarct is large the treatment

will not start for one or two weeks, as the risk of secondary

haemorrhagic transformation of a cerebral infarct is initially

increased

17.5.3 Surgical decompression if there is a risk

of cerebral herniation

The main cause of death in the first week in cerebral infarction

patients is transtentorial herniation A large, complete media

infarction can cause a life-threatening situation during the

first 24 hours (up to 5 days) as a result of swelling and oedema,

which can cause herniation This is referred to as malignant

middle cerebral artery infarction The older the patient the

lower the risk, as atrophy and hence space for a swelling infarct

increases with age This can be treated using hemicraniectomy

( fig 17.9), which involves removing a large part of the skull

on the side of the infarct to create space Research has shown

that this treatment manifestly reduces the risk of mortality, but

it does not affect the degree of invalidity The very high risk of

surviving with a severe disability should be discussed,

espe-cially in the case of older patients (over the age of 60)

. Figure 17.9 CT scan of a patient who has undergone hemicraniectomy

for a large cerebral infarction in the left hemisphere causing substantial pressure on surrounding tissues (malignant media infarction) The patient

is the same as in fig 17.5

218 Chapter 17 · Cerebral infarction and cerebral haemorrhage

botulinum toxin treatment) as well as adaptation of utensils and the home environment provide a host of options Approxi-mately 5 % of patients develop epilepsy in the first year after

a stroke and 1–2 % in the second year The seizures usually respond well to anti-epileptics

At least half of stroke patients admitted to hospital are found to have cognitive impairments, which can be in orienta-tion, attention, communication, memory and spatial and execu-tive functions Depression is common and may be due to the actual brain damage or a psychological reaction to the radical change that a stroke represents in a person’s life It may be nec-essary to prescribe antidepressants

17.6.1 Primary hypertensive intracerebral haemorrhage

Half of intracerebral haemorrhages are caused by hypertension

(primary hypertensive intracerebral haemorrhage) This type of

haemorrhage is found mainly in the internal capsule and basal ganglia ( fig 17.10) Patients usually complain of very severe rapid-onset headache, often with vomiting A patient who has a severe haemorrhage with a space-occupying effect can quickly become comatose

There is often hypotonic paresis of one half of the body:

in an unconscious patient this is noticeable from reduced response to pain stimuli and difference in muscle tone An

Lastly, all cerebral infarction patients are in principle

pre-scribed a statin, except for those with a proven cardiac cause of

embolism or dissection

17.5.5 Carotid endarterectomy

Large randomized studies have shown that carotid endarter­

ectomy is worthwhile in patients with severe stenosis of the

internal carotid artery that has caused a TIA or non-disabling

cerebral infarction Surgery of this kind is worthwhile not only

for patients with 70–99 % carotid stenosis but also in men with

ipsilateral hemisphere symptoms and only 50–69 % stenosis

The treatment yields most benefit if it is carried out quickly,

ideally within two weeks Successful carotid endarterectomy

reduces the risk of a recurrent TIA or infarction of the affected

side within five years by 16 % This means that six patients

with symptomatic carotid stenosis need to be operated upon

to prevent one stroke during the next five years The operation

is not without risk (it has perioperative morbidity and

mor-tality of 3–6 %) and it needs to be carried out at a centre with

proven expertise The expectation is that MRI imaging of the

plaque will in future play a role in deciding whether surgery is

worthwhile or whether optimum drug treatment will suffice,

but these techniques are still being investigated For the time

being it would seem that the benefits of carotid endarterectomy

for severe asymptomatic stenosis, even in highly experienced

hands, do not outweigh the risks of the procedure

Signifi-cant stenosis of the carotid artery can in principle be treated

by means of a stent, but it has been shown that the results of

this treatment cannot currently compete with those of carotid

endarterectomy surgery Stents have also been shown to be less

effective than optimum drug treatment for symptomatic

intra-cranial stenosis, e.g of the middle cerebral artery

17.5.6 Rehabilitation following a stroke

The main aims of rehabilitation for stroke patients are to

improve function by reducing impairments and enabling them

to return home and reintegrate in society The rehabilitation

process already starts at the stroke unit and is managed by a

multidisciplinary team (specialist nurses, a physiotherapist, an

occupational therapist, a speech and language therapist; a

reha-bilitation specialist and neuropsychologist are brought in on a

consultative basis) To reduce the risk of complications such as

pneumonia stroke patients should be mobilized as soon as it is

safe to do so (7 sect 17.5.2) The neurologist is responsible for

coordination in the acute and sub-acute phases Input from the

rehabilitation specialist, the nursing home doctor and the GP

is required when deciding on follow-up If there is permanent

loss of function, the aim of the rehabilitation treatment will be

to teach the patient to use compensatory mechanisms or

alter-native strategies to perform activities

It takes at least two years to reach the end-state, but most

recovery takes place during the first six weeks

Orthopae-dic aids (orthoses), treatment for spasticity (spasmolytics,

. Figure 17.10 CT scan of a 78-year-old acutely unwell man with a deep

intracerebral haemorrhage Comatose on admission, left-sided hemiplegia; died after four days Haemorrhage in right basal ganglia extending into the ventricular system

The cause of a non-traumatic subarachnoid haemorrhage

is usually (85 %) rupture of a saccular aneurysm arising from

a basal cerebral artery (7 sect 11.3.2, fig 17.11) 10 % of

suba-rachnoid haemorrhages involve a – probably venous – perimes­ encephalic haemorrhage (7 sect 17.7.9) and in the remaining

5 % some other cause, e.g arteriovenous malformation or haemorrhage due to vasculitis If the SAH is due to rupture of

an arteriovenous malformation there will almost always be an intracerebral haematoma as well

Statistics for SAHs and aneurysms can be found in the tables in the subsections below Women are more likely to have

an SAH than men but are also more likely to survive the first one The frequency of aneurysms increases with age, and ulti-mately 2 % of the population will develop one or more of these vascular abnormalities Aneurysms gradually grow, and the risk

of rupture increases with increasing size The majority of rysms are small (smaller than 1 cm) Fortunately only a small proportion of aneurysms rupture The risk of bleeding from

aneu-an aneu-aneurysm is 0.05–1 % per year The risk of rupture depends not only on the size of the aneurysm but also on the site, age and risk factors (previous bleeding from an aneurysm, positive family history, hypertension and smoking)

Aneurysms sometimes run in families, in which case the following applies First-degree relatives are at a more than 1.5 times higher risk of aneurysm but over five times higher risk of

an SAH from it: familial aneurysms are apparently more likely

to rupture Also, in patients with a familial SAH it occurs at a younger age and is 1.5 times more likely to have a poor out-come than in patients with a sporadic SAH

increase in the volume of the bleed can raise the intracerebral

pressure to such a high level that tentorial herniation (7 sect.

19.3) occurs The prognosis is usually poor: it is determined

by the severity of the loss of consciousness, the volume of the

bleed and the extent to which it extends into the ventricles

Approximately 10 % of primary intracerebral haemorrhages

are located in the cerebellum or brainstem, and here again the

natural progression is usually poor Rapid surgical removal

of a cerebellar haematoma can be life-saving in these cases,

however, as it can prevent tonsillar herniation or obstructive

hydrocephalus

17.6.2 Lobar haematomas

An intracerebral haematoma that is more superficially sited

below the cortex may remain confined to a single lobe and not

extend into the ventricular system The natural progression

can be surprisingly good if there is little damaged brain

paren-chyma following resorption These haematomas are often sited

in the temporal lobe Lobar haematomas frequently occur in

patients with no history of hypertension; they are more

com-monly a manifestation of a generalized cerebral vascular

disor-der, cerebral amyloid angiopathy (CAA: 7 sect 17.2), in which

case there is a chance of recurrence

17.6.3 Surgical removal of an intracerebral

haematoma

Surgical removal is usually not worthwhile in the case of a

deeply sited bleed in an older patient with hypertension, as it

will be inaccessible and the benefits are outweighed by the

risks Surgical removal of an intracerebral haematoma is an

option in younger patients, however A CT angiogram or

con-ventional angiogram should be carried out first to detect or

rule out an underlying vascular malformation The likelihood

of improvement from a neurosurgical procedure is much

greater if the haematoma is close to the cortex Evacuation of

an infratentorial haematoma should be considered if the

neu-rological deterioration is progressive or the initial neuneu-rological

state is poor The decision needs to be made on a

patient-by-patient basis in the acute phase in consultation with the

neurosurgeon

A subarachnoid haemorrhage (SAH) occurs in the

subarach-noid CSF-filled space between the brain parenchyma and the

arachnoid mater (sometimes in the spinal subarachnoid space)

The most common cause is a head or brain injury, in which

case it is referred to as a traumatic SAH.

. Figure 17.11 MR angiography Large aneurysm arising from the right

posterior communicating artery

220 Chapter 17 · Cerebral infarction and cerebral haemorrhage

prognosis – mortality from first bleed:

– mortality/severe residual symptoms after subsequent bleed:

– subsequent bleed (without intervention):

– residual symptoms:

50 % (10–15 % before arrival)

80 %

15 % within

24 hours

40 % in the first month

3 % per year after the first month

75 %

Aneurysm

frequency – healthy population – occurrence of more than one aneurysm

2.3 %

20 %

risk factors – predisposition

– hypertension – alcohol abuse – smoking risk of aneurysm given

familial problems

– one family member with SAH: 4 % – two family members with SAH: 8 % – polycystic kidney disease: 10 %

17.7.3 Diagnosis

An urgent CT scan should be carried out if there is the est suspicion of a subarachnoid haemorrhage Occasionally a patient with an SAH will have unsuccessfully sought help for a severe headache a few days before and had a second bleed that might have been prevented

slight-On the first day of the bleed 95 % of patients are found to have blood in the subarachnoid space ( fig 17.12 a), but over the next few days the sensitivity of CT declines rapidly, as the blood soon clears from the subarachnoid space The site of the aneurysm can often be surmised based on the largest amount

of blood, but it is only possible to determine the site reliably

in the case of an intracerebral haematoma If the CT scan is carried out within six hours of the attack and assessed by an experienced neuroradiologist, an SAH can be ruled out with adequate certainty After six hours an MRI or lumbar puncture

to examine blood pigments in the CSF can provide additional certainty in finally ruling out an SAH

The problem with carrying out a lumbar puncture (LP) in the case of a suspected SAH is that the blood does not reach the lumbar space for a while after the bleed, and an LP can also yield bloody CSF as a result of puncturing a blood ves-sel If the bleed is fresh no breakdown products will be visible for a few hours, so at least twelve hours should be allowed to elapse before LP The CSF pressure should then be measured,

as a sharp rise is an indication of venous sinus thrombosis

17.7.2 Clinical signs

The symptoms of a subarachnoid haemorrhage are very severe

headache that is peracute (developing within a fraction of a

second or a few seconds in three-quarters of patients) and

usually followed by nausea with or without vomiting Some

patients describe a feeling of ‘something snapping in my head’

In a proportion of patients (20 %) physical exertion (sport,

coitus) is found to have immediately preceded the

haemor-rhage, but most bleeds occur at rest or during non-strenuous

activities

Half of patients briefly lose consciousness and are

disorien-tated or confused when they come round In a third of patients

the only symptom is unusually severe acute headache (thunder­

clap headache) Conversely, in general practice only just over

10 % of patients with acute headache of this kind as an

iso-lated symptom are found to have a subarachnoid haemorrhage

(7 sect 17.7.10) The headache caused by an SAH is usually

dif-fuse, and most patients describe it as the worst headache they

have ever had It usually persists for one or two weeks

There are no symptoms of meningeal irritation, such as

stiff neck, for the first few hours after the bleed It usually takes

3–12 hours for meningeal irritation to become manifest, often

accompanied by mild reactive fever Symptoms of

menin-geal irritation can be completely absent in coma patients and

those with a minor bleed Neurological symptoms are found in

about a quarter of patients, due to the haemorrhage extending

into the brain parenchyma, the aneurysm pressing on a cranial

nerve (usually the oculomotor nerve in the case of an aneurysm

in the posterior communicating artery) or secondary

cere-bral ischaemia developing soon after the bleed (7 sect 17.7.4)

Epileptic seizures occur in 7 % of patients during the acute

stage General symptoms of SAH are hypertension,

hypoxae-mia and ECG abnormalities Cardiac arrest occurs in 3 % of

patients during the acute phase, in which case resuscitation is

worthwhile, as half of patients have a fair to good prognosis

In 20 % of patients ophthalmoscopy shows relatively large flat

haemorrhages in front of the retina (Terson’s syndrome) These

are due to an increase in CSF pressure obstructing the central

retinal artery

Non-traumatic subarachnoid haemorrhage

incidence female:male ratio peak incidence

6–7 per 100,000 1.6:1

35 to 65 years stroke percentage

main cause

5 % aneurysm (85 %) symptoms

diagnosis is virtually certain to be SAH Smaller concentrations

of blood breakdown products can be found using tometry (7 sect 10.5) This test remains reliable for two weeks after the ictus

spectropho-If a patient with thunderclap headache has a normal CT scan, a diagnosis of SAH can be ruled out if no blood pigments are found in the CSF from twelve hours to two weeks after the onset of the headache

If the diagnosis of SAH is based on blood found on the

CT scan or the presence of blood pigments in the CSF, the next step is to find the aneurysm or other source of the bleed

Nowadays this is usually done using CT angiography (CTA)

If CTA does not yield sufficient information to determine the optimum treatment, additional angiography is carried out

(digital subtraction angiography, DSA) If neither CTA nor DSA

shows an aneurysm, the DSA should be repeated after two

or three weeks If there is a perimesencephalic haemorrhage (7 sect 17.7.9) and the CTA is negative, no further diagnostic tests are needed

Complications of subarachnoid haemorrhage

A subarachnoid haemorrhage is a life-threatening condition Patients with an SAH run a high risk of complications, some of which respond well to treatment

Patients diagnosed with spontaneous SAH need to be transferred to a neurological medium or intensive care unit at

a neurovascular centre as a matter of urgency Pending further diagnostic tests they should be given absolute bed rest, pain relief (and if necessary sedation), laxatives to avoid pushing, nimodi-pine and adequate fluids SAH patients in a good clinical condi-tion (GCS > 12) should have their ruptured aneurysm treated as soon as possible after admission, ideally within 24 hours

If the patient has a large haemorrhage and a decrease in the level of consciousness, removal of the bleed (ideally combined

with closure of the aneurysm) can be life-saving A second bleed

occurs during the first few hours in 15 % of patients; during the next four weeks the risk (equally distributed) is 40 %, and 3 % per year after that The prognosis following a second bleed is extremely poor: 80 % of patients die or remain severely dis-abled It is therefore vitally important to repair a symptomatic aneurysm as soon as possible

(7 sects 11.2.5 and 17.8), which can be a cause – albeit rare – of

thunderclap headache A moderate rise will also be caused by

an SAH or meningitis If the CSF is yellow (xanthochromic), the

. Figure 17.12 a CT scan of a 46-year-old women with a

subarach-noid haemorrhage from an aneurysm of the left middle cerebral artery

(on the right of the image) The basal CSF spaces are filled with blood b

Hydrocephalus a month after a subarachnoid haemorrhage from an

aneu-rysm of the posterior communicating artery in a 68-year-old woman which

has been clipped The lateral ventricles and third ventricle are dilated

Hypodense areas can be seen around the anterior horns of the lateral

ventricles, indicating recent hydrocephalus

222 Chapter 17 · Cerebral infarction and cerebral haemorrhage

If cerebral imaging for some other reason happens to reveal an aneurysm, the question is whether it is advisable to repair it, as most aneurysms never bleed A risk estimate can be made based

on patient characteristics such as age, hypertension, ing and family history, and aneurysm characteristics such as site, size and any growth since previous imaging It can then be decided whether preventive treatment is worthwhile The emo-tionally charged phrase ‘time bomb in the head’ should always

smok-be avoided Elective clipping of an unruptured aneurysm has an average mortality of 2.5 % and an average morbidity of 10 %, so it should be used with great caution The risks of coiling are lower

17.7.8 Screening

Screening and treating people who have a family member with

an SAH is not generally regarded as worthwhile The gain in life expectancy is limited and outweighed by the risks of pre-ventive surgery The gain does appear to outweigh the risks of repairing the aneurysm where more than one first-degree rela-tive has an SAH and in patients with polycystic kidney disease, however Screening for familial aneurysms should be carried out on at regular intervals (every five years), as fresh aneurysms can develop Anyone with an affected family member should be advised not to smoke or to stop smoking and have his or her blood pressure checked regularly and treated if necessary

sud-If the CTA is negative, DSA is not needed, unlike in the case

of a non-perimesencephalic haemorrhage (7 sect 17.7.3) The prognosis for a perimesencephalic haemorrhage is very good This benign variant accounts for 10 % of subarachnoid haem-orrhages Although 20 % of patients show acute hydrocephalus

on the first CT scan for which drainage is sometimes necessary, there is no secondary cerebral ischaemia and the condition has not been found to recur

Of all patients with acute headache of the thunderclap variety a quarter were indeed found to have an aneurysmatic SAH This includes those patients who had neurological abnormalities Not including these, only 12 % of patients whose headache was iso-lated had an SAH, whereas over 10 % were found to have some

Aneurysms can be treated endovascularly or surgically The

endovascular technique involves inserting platinum coils in the

aneurysm via a catheter, inducing thrombosis of the aneurysm

Surgical treatment involves closing the aneurysm by placing a

tiny clip across the neck of the aneurysm In the case of

aneu-rysms that could be treated either endovascularly or

surgi-cally, coiling is preferable as it is more likely to produce a good

functional outcome than clipping A proportion of aneurysms

(especially of the middle cerebral artery) are inaccessible to

coiling, however, and must be treated with clipping

During the first two weeks after an SAH there can be

sec-ondary deterioration in the patient’s general condition with

additional loss of function: this is due to secondary cerebral

ischaemia The term ‘vasospasm’ is used, but this is

prob-ably not the only pathogenic mechanism Patients with a large

amount of blood in the subarachnoid space run a higher risk

of secondary cerebral ischaemia The duration of any loss of

consciousness when the bleed occurred is also predictive of

the likelihood of cerebral ischaemia A three-week course of

nimodipine (a calcium channel blocker) reduces the risk of

such ischaemia and improves the prognosis

Hydrocephalus can develop soon after the bleed,

espe-cially in patients with blood in the ventricular system or the

basal cisterns ( fig 17.12b) Dilation of the ventricular

sys-tem is already found on the initial CT scan of one in five SAH

patients If an SAH patient’s level of consciousness decreases it

is always necessary to repeat the CT scan, as it could be due to

acute or sub-acute hydrocephalus The treatment usually

con-sists in CSF drainage using an external ventricular drain; if

there is no massive intraventricular haemorrhage, diffuse

cer-ebral oedema or intracercer-ebral haematoma, CSF drainage can

also be carried out safely during the acute phase by means of

lumbar puncture

17.7.5 Residual symptoms

Even if the patient has come through the acute phase unscathed

and the aneurysm has been repaired successfully, this is not the

end of the story, as a proportion (5–7 %) of patients go on to

develop epilepsy Approximately 30 % of patients have

anos-mia Because of the cognitive and psychosocial problems only a

quarter of patients regard themselves as fully recovered

17.7.6 Subsequent bleeds

Subsequent SAHs occur, arising from the originally clipped or

coiled aneurysm, or from an aneurysm that was already present

or developed later The risk of recurrence following clipping

is approximately 2–3 % in the first ten years If the aneurysm

has been coiled, at least one follow-up MR angiogram (MRA)

should be carried out, ideally after six months Routine

follow-up is not normally required for clipped aneurysms, but if it is

indicated (e.g because there is a family history), CT

angiogra-phy is possible if titanium clips have been used

40–50 % and neurological symptoms (hemiparesis) in 35–45 % Decrease in the level of consciousness occurs in 35 % of cases In

20 % of cases the clinical presentation is one of isolated cranial hypertension (7 sect 10.8.3), comprising headache, often papilloedema with or without impaired vision and/or visual field defects The CT scan may be completely normal, or it may show infarction, bleeds or a combination of venous infarctions and bleeds (haemorrhagic infarcts) Sometimes the only abnormality apparent on a plain CT is the actual thrombus, visible as a hyper-dense lesion in one of the large superficial venous sinuses Some-thing more than an ordinary CT will almost always be needed:

intra-CT venography (intra-CTV) or MR venography (MRV) usually allows

for the condition to be diagnosed with high reliability

Causes of venous sinus thrombosis

endovascular thrombolysis or thrombectomy is sometimes carried

out There is as yet insufficient evidence as to its efficacy and the treatment is currently given as part of a randomized trial

other severe cerebral disorder (e.g cerebral venous sinus

throm-bosis or reversible cerebral vasoconstriction syndrome, RCVS:

7 sect 17.9) Further tests found no abnormalities in the

remain-ing patients, who eventually turned out not to have any severe

disorder that could be related to the acute-onset headache In

these cases the cause of the thunderclap headache is likely to

have been vasoconstriction In men in particular the pain can

come on suddenly following strenuous exertion (e.g orgasm)

and generally clears up within minutes or hours A connection

with migraine is found in a proportion of patients (7 sect 21.7)

17.8.1 Clinical signs and diagnosis

Cerebral venous sinus thrombosis (CVST) is rare (accounting

for less than 1 % of strokes), and three-quarters of patients are

women Headache caused by cerebral venous thrombosis is

sometimes impossible to distinguish from that caused by SAH

(thunderclap headache), but it usually develops more

gradu-ally Other symptoms of sinus thrombosis vary greatly, making

diagnosis often difficult (7 sect 11.2.5)

Neurological symptoms may be present, or there may be

none at all The key symptom is headache, in some cases with

diplopia caused by loss of abducens nerve function due to

increased intracranial pressure Epileptic seizures are common,

namely in 35–50 % of patients Impaired vision due to

papil-loedema, which is indicative of increased CSF pressure, occurs in

. Figure 17.13 Perimesencephalic haemorrhage in a 49-year-old patient

(with acute headache and vomiting) Blood can be seen in the

interpedun-cular fossa, ventral to the brainstem A CT angiogram did not find

any aneurysm

224 Chapter 17 · Cerebral infarction and cerebral haemorrhage

In cases of cerebral vasculitis the cerebral MRI scan will usually show multifocal abnormalities that are in themselves non-specific MRI is nevertheless important here, as a com-pletely normal MRI scan rules out a diagnosis of cerebral vas-culitis with reasonable certainty CSF testing will also show non-specific abnormalities (e.g slightly elevated protein and mild pleocytosis), but it is necessary as it sometimes yields an alternative diagnosis such as an infection If primary cerebral vasculitis is suspected, the next step after MRI is MRA angio-graphy, and the final piece of the diagnostic puzzle for this very difficult condition is a brain biopsy (of cortex and leptomenin-ges from an area shown to be abnormal on the MRI scan) In all cases of vasculitis the treatment is immunosuppression, usu-ally by means of corticosteroids and cyclophosphamide There has been a focus recently on ‘vasculitis mimics’, in particular

reversible cerebral vasoconstriction syndrome (RCVS), which

begins with thunderclap headache and displays focal malities and sometimes seizures; unlike vasculitis it is due not

abnor-to inflammation of the vascular wall but abnor-to vasospasms These are often accompanied by bleeds and oedema, and sometimes infarcts, in the brain parenchyma RCVS can have different causes, such as use of medicinal or recreational drugs that have

a vasoconstrictive effect, and it can develop spontaneously in women soon after childbirth The diagnosis is based on angio-graphy and sometimes abnormal CSF test results The prog-nosis is good: most patients recover within a few weeks with no residual symptoms

In hypertensive encephalopathy (7 sect 11.2.4) cerebral auto regulation is impaired There are usually very high blood pres-sures, but in the case of pregnant women (eclampsia) and patients with severely compromised renal function the blood pressures will not necessarily be extremely high The complete clinical presentation comprises headache and vomiting com-bined with impaired consciousness and vision and epileptic seizures The symptoms usually develop in the space of a few hours The visual impairments can comprise cortical blind-ness, but also blurred vision, loss of visual field or visual hal-lucinations Imaging often shows oedema of the white matter, especially in the posterior perfusion area: this is referred to

-as posterior leukoencephalopathy or PRES, posterior reversible encephalopathy syndrome The treatment consists in lowering

blood pressure and discontinuing the immunosuppressant or reducing the dose, and prescribing an antiepileptic if necessary Both the clinical and neuroradiology symptoms are usually reversible

The same clinical and radiological presentation may also be found in normotensive patients with metabolic disorders and those using an immunosuppressant (cyclosporine)

Lastly, if there are symptoms of herniation by a large,

swell-ing venous infarct, hemicraniectomy should be considered

(7 sect 17.5.3) If the patient is in a poor clinical condition in the

acute phase, this treatment should be carried out without

hesita-tion, as the prognosis for venous infarcts is better than that for

arterial infarcts and the patients involved are often young In cases

of coma due to bilateral oedema in the thalamus or basal ganglia

the prognosis is also often relatively good Clinicians should not

be tempted to limit their treatment options in the acute phase of

the disease, even if ventilation in intensive care is required

Various types of systemic vasculitis can cause cerebral vascular

abnormalities: these are referred to as secondary cerebral vascu­

litis There is also a primary vasculitis of the central nervous sys­

tem – albeit very rare – known as primary (or granulomatous)

angiitis of the central nervous system.

Vasculitis in the central nervous system

5 primary cerebral vasculitis

5 secondary cerebral vasculitis

5 disorder of the large arteries

5 arteritis (Takayasu’s disease)

5 giant cell (temporal) arteritis

5 disorder of the medium-sized and small arteries

– polyarteritis nodosa – Churg-Strauss syndrome – Wegener’s granulomatosis

5 disorder of the small arteries

– Henoch-Schönlein purpura

5 hybrid forms

– Behçet’s disease – Kawasaki disease

5 secondary to other diseases

– infection – collagen disease – medication (penicillin, sulphonamides)

Cerebral vasculitis can cause diffuse encephalopathy including

altered or decreased consciousness, signs of increased intracranial

pressure and sometimes seizures There can also be focal

neuro-logical symptoms such as hemiparesis and/or aphasia Headache

is the most common symptom (70 % of cases) but never the only

one Given this wide variety of symptoms there is no specific

neurological presentation, and the condition is thus notoriously

difficult to diagnose It is easier if cerebral vasculitis is

second-ary to systemic vasculitis, when there are often symptoms and

signs such as fever, weight loss and malaise, skin abnormalities

and possibly renal failure, with tests showing elevated C-reactive

protein (CRP), compromised renal function, abnormal urinary

sediment, eosinophilia, and more specific immunological blood

abnormalities, including ANA, ANCA and cardiolipin

anti-bodies Temporal arteritis (giant cell arteritis: 7 sect 21.5) can

cause TIAs and strokes, especially in the posterior circulation

© Bohn Stafleu van Loghum is een imprint van Springer Media B.V., onderdeel van Springer Nature 2018

J B M Kuks and J W Snoek (Eds.), Textbook of Clinical Neurology, https://doi.org/10.1007/978-90-368-2142-1_18

Epilepsy and other paroxysmal

disorders

Abstract

There are many types of seizure, and by no means every seizure is caused by epilepsy

Seizures need to be classified as precisely as possible, as the classification affects the

like-lihood of a symptomatic or hereditary cause and the treatment and prognosis Treatment

for epilepsy needs to be tailored to the patient In addition to drug treatment – and

sometimes surgery – it is important to consider lifestyle and life stage (contraception,

pregnancy, etc.)

Electronic supplementary material

The online version of this chapter ( 7 https://doi.org/10.1007/978-90-368-2142-1_18 ) contains supplementary

material, which is available to authorized users.

18.2 Epileptic seizures – 226

18.2.1 Classification of epileptic seizures – 226

18.2.2 Classification of epilepsy syndromes – 230

18.2.3 Causes and triggers – 231

18.2.4 Epileptic seizures in childhood – 231

226 Chapter 18 · Epilepsy and other paroxysmal disorders

this information plus the findings from an gram (EEG) (7 sect 18.2.2) The final question is what could be the underlying cause (7 sect 18.2.3)

electroencephalo-A precise description of the seizures is essential in order

to distinguish between epileptic and non-epileptic seizures In favour of epilepsy as the cause are the absence of a trigger, the abrupt onset, the decrease in the level of consciousness, active motor symptoms (rigidity or jerking, nystagmus, lateral head and eye deviation), eyes open during the seizure, neurological symptoms after the seizure (e.g postictal hemiparesis or apha-sia) and a stereotypical seizure pattern None of these factors

is an absolute indication, however: some epileptic seizures can

in fact be triggered by certain factors (7 sect 18.2.3) and the symptoms can vary greatly

In order to differentiate correctly between epileptic and non-epileptic events we also need to be familiar with the pat-tern of non-epileptic seizures (7 sect 18.3)

18.2 Epileptic seizures

The prevalence of ‘active’ epilepsy – i.e epilepsy being treated with drugs – in Western Europe is estimated at 1 in 200 There are many different types of epilepsy and a host of causes, so treatment and prognosis vary a good deal, and careful diag-nosis is needed before deciding on treatment As clinicians are rarely able to observe seizures for themselves, it is very help-ful if someone who witnesses them can describe the events or record a video on a mobile phone

The possibility of epilepsy should always be considered

if the episodes have an abrupt onset, following a stereotypical pattern, are short-lived and involve unusual behaviour Perio-dic or episodic symptoms with no impaired consciousness can also be epileptic (‘simple partial’) (7 sect 18.2.1)

There are also epileptic seizures with only autonomic toms (e.g abdominal pain in children), which sometimes go unrecognized Even when such seizures with no loss of con-sciousness are observed in a clinical setting they are some-times difficult to diagnose It is even more difficult in the case

symp-of some patients who have both epileptic seizures and genic pseudoepileptic seizures

psycho-Bouts of headache, dizziness and rage are hardly ever caused by epilepsy and are therefore not an epileptic ‘equiva-lent’ In the case of children with learning difficulties epilepsy is more often suspected than is really likely

18.2.1 Classification of epileptic seizures

An epileptic seizure (fit) is due to the abnormal functioning of

voltage-gated (7 sect 3.3.4) and transmitter-gated (7 sect 3.3.3) ion channels, which can make neurons electrically hyperactive

It is mainly Na+ and Ca2+ channels that are involved When

a large population of neurons ‘switch one another on’, major changes take place locally in the electrical activity in the brain, and these can spread

Case 18.1

A 45-year-old man has been having seizures for six weeks,

with the following pattern: first jerking, then cramp in the

right thumb, followed by cramp in the other fingers of

the right hand; the jerking then creeps up the right arm,

which moves backwards in the shoulder The seizures last

10–15 seconds and usually end of their own accord, but

they can recur a few times, e.g with a ten-minute interval

He once lost consciousness during a seizure but was able

to remember how it began His wife says his other arm

was also jerking that particular time He has never had

incontinence or bitten his tongue during a seizure.

Question 1: What are the arguments for suspecting that

the seizures are epileptic? What other symptoms would be

expected in this kind of seizure?

Question 2: What abnormalities might be found on physical

examination in between seizures?

Question 3: What could be causing the seizures?

Online: 7Answers to case study questions 18.1

Case 18.2

A two-year-old boy has been experiencing episodes of

brief loss of consciousness (lasting one or two minutes)

for a few months Each one is preceded by crying out of

frustration or pain During the crying fit he stops breathing,

turns blue and then loses consciousness He is usually

limp, but occasionally becomes rigid for a short time He

then starts breathing again of his own accord and regains

consciousness.

Question 1: What kind of seizures are these?

Question 2: What are the arguments for and against epilepsy

as the cause?

Question 3: What is the prognosis?

Online: 7Answers to case study questions 18.2

Case 18.3

For the past three years a 30-year-old man has been

having episodes in which his limbs become limp and he

suddenly laughs or starts He sometimes falls down or drops

something He does not lose consciousness, and if he falls

he is able to get up again after a few seconds.

Question 1: What are these seizures called, and what is the

syndrome that causes them?

Question 2: How could this kind of seizure be treated?

Online: 7Answers to case study questions 18.3

18.1 Seizures

If a patient suffers from recurrent seizures, the first question

is whether they are epileptic If this is likely to be the case, the

particular type needs to be identified (7 sect 18.2.1) There can

sometimes be a combination of different types The next step

is to see whether an epilepsy syndrome can be diagnosed from

The actual seizure begins peracutely with loss of ness and tonic contraction of all the muscles for 10–30 seconds, which can be accompanied by an unnatural scream (forced expiration with tensed vocal folds) This is followed by approxi-mately 30–60 seconds of clonic convulsions at increasingly long intervals with increasingly large movements Some types

conscious-of seizure have only a tonic or only a clonic phase During the seizure the face first turns red (due to the straining) and then blue when the breathing stops The eyes are open and the eye-balls are turned upwards During the tonic and clonic phases the pupils are dilated and non-reactive to light, after which they start reacting to light again

Biting the tongue (especially the side) or cheek occurs in approximately 25 % of cases and is fairly specific to an epilep-tic fit The patient salivates copiously, and once breathing starts again (hyperventilation) the patient foams at the mouth The foam will be bloody if the patient has bitten his tongue Half of patients have urinary incontinence during the seizure, but fae-cal incontinence is very rare

There follows a postictal phase, lasting a few minutes or

a quarter of an hour, when the patient is limp and remains drowsy for some time or may even fall asleep

When the patient comes round or wakes up, he will often be somewhat disorientated, but this soon passes In exceptional cases there can be postictal confusion lasting a few hours or even days A proportion of patients are left with

a ‘hangover’ for some time Any focal neurological deficits in the postictal phase are an indication that the seizure had a focal onset

If an epileptic seizure lasts longer than five minutes, or if there is a series of three or more tonic-clonic seizures in the

space of an hour, this is referred to as status epilepticus

Tonic-clonic status epilepticus is life-threatening, as cerebral anoxia and the risk of aspiration pneumonia increase with the length

of the seizure, and there is a risk of cardiac complications, cially in the elderly The standard time limit is five minutes in adults and seven minutes in children, as the risk of the seizure not ending of its own accord increases thereafter, since the natural control mechanism is already failing It also becomes increasingly difficult to stop the seizure

espe-This is not the case with absence status or partial status, which can be allowed to continue longer without risk

If status epilepticus is the first manifestation of epilepsy there is almost certainly an anatomical abnormality in the brain, except in the case of young children In the case of patients being treated for epilepsy a succession of fits can occur when anti-epileptic medication is suddenly omitted or the patient stops taking it Other causes of status epilepticus are intracranial infection, organic brain disease and metabolic dis-orders such as severe hypoglycaemia and hyponatraemia

The symptoms depend on the location, spread and intensity

of the electrical changes If they occur in the reticular

forma-tion they cause a decrease in the level of consciousness If a

seizure starts with a general bilateral disorder of electrical

func-tion in both cerebral hemispheres it is referred to as a general­

ized epileptic seizure If the electrical changes remain confined

to part of one hemisphere they cause symptoms related to the

function of that area of the brain, a partial (or focal) epileptic

seizure During a partial epileptic seizure consciousness may

remain normal (simple partial) or there may be a decrease in

the level of consciousness or a kind of twilight state (complex

partial) A partial seizure can also spread (secondary generali­

zation): the abnormal electrical activity spreads throughout the

cerebrum, often leading to loss of consciousness Table 18.1

shows a simplified classification of seizure types that is used

internationally

We should not be too hasty to diagnose a case as epilepsy:

a single epileptic seizure on its own does not justify this

diag-nosis If there is no clear cause, epilepsy is only diagnosed once

the patient has had at least two epileptic seizures that were not

triggered by e.g lack of sleep or fever Even after an epileptic

seizure that has a temporary cause (e.g a head trauma) it is not

standard practice to diagnose epilepsy immediately

Generalized tonic-clonic seizures

A tonic-clonic seizure is a dramatic event, and this kind of

sei-zure is what most people are thinking of when talking about

epilepsy The pattern is fairly typical

In approximately 10 % of patients generalized tonic-clonic

seizures are preceded by slight moodiness for hours or even

days There is a feeling of tension or being different; sometimes

there are already short-lived muscle spasms

A tonic-clonic seizure may be preceded by an aura

last-ing seconds or minutes: this is actually a partial seizure, which

then becomes generalized and is therefore referred to as a

‘secondary generalized tonic-clonic seizure’ An aura can be a

strange unwell sensation, which often starts in the stomach and

rises to the head (epigastric rising sensation) or other sensory

(sounds, flashes of light, strange odours) or mental

manifesta-tions (anxiety, derealization) Here again the pattern is usually

stereotypical

. Table 18.1 Classification of epileptic seizures

partial seizures – simple partial (motor, sensory,

autonomic, higher functions) – complex partial

– partial developing into generalized generalized seizures – clonic, tonic or tonic-clonic seizures

– absence seizures – seizures with myoclonic jerks with

no loss of consciousness – atonic or drop seizures unclassifiable seizures

prevalence – 1 in 12.500 cause – genetic (idiopathic) seizure pattern – acute decrease in level of

consciousness – blinking – empty gaze postictal confusion – absent length of seizure – brief, usually 5–10 seconds frequency – high

effect of hyperventilation

– strong EEG – 3 Hz generalized spike-wave activity

Myoclonic seizures

Myoclonic seizures take the form of the sudden occurrence

of one or more violent muscle spasms, especially in the arms, causing the patient to drop things These seizures are found in juvenile myoclonic epilepsy (7 sect 18.2.2)

Simple partial seizures

In simple partial seizures the patient’s consciousness remains normal The symptoms and signs depend on the initial focus.Motor seizures start in the areas in front of the central sul-cus They can then gradually spread to the adjacent cortex,

when they are referred to as Jackson’s seizures The seizure often

starts in part of the body with a relatively large cortical sentation, e.g the thumb or mouth If it starts in the thumb it spreads to adjacent areas of the cortex, i.e the hand, arm, face, trunk and possibly leg This takes only a short time, generally 20–30 seconds

repre-Seizures with jerky rotation of the head, eyes and trunk, usually away from the focus, often followed by secondary

generalization, are referred to as adversive seizures: these start

in the supplementary motor cortex ( fig 5.1) If the seizure occurs in the area that controls the muscles involved in speech

there may be speech arrest, possibly accompanied by tonic or

clonic jaw movements

A focal motor seizure may be followed by temporary

weak-ness (postictal or Todd’s paralysis), but this rarely lasts longer

than one day

Seizures starting in the frontal cortex are quite often accompanied by automatisms of the lower extremities with violent motor agitation (e.g cycling movements) or rota-tional movements of the entire body Frontal seizures of this kind occur mainly at night while the patient is asleep They sometimes appear so bizarre that the clinician suspects a non-organic cause Surprisingly, a unilateral epileptic focus in the frontal secondary motor cortex can cause motor phenomena in

both sides of the body.

Tonic-clonic seizures

cause – genetic or primary generalized

epilepsy – partial (focal) epilepsy (secondary generalized seizures)

– physiological, due to lack of sleep etc.

seizure pattern – sometimes partial onset, then

tonic and/or clonic symptoms, finally postictal coma postictal confusion – present

length of seizure – tonic-clonic phase usually a few

minutes – then postictal coma frequency – in the case of primary generalized

epilepsy: usually between a few times a year and one seizure every few years

effect of hyperventilation

– trigger for primary generalized epilepsy

– no effect on partial epilepsy EEG – generalized paroxysms, with or

without focal onset

Absence seizures

Absence seizures are short-lived (usually 5–10 seconds)

epi-sodes of decreased level of consciousness found particularly in

children The child stops doing what he was doing, has a glazed

look in the eyes or turns them upwards; there is often

rhyth-mic jerking (myoclonic jerks) of the eyelids or mouth

Some-times he drops something, or briefly buckles at the knees

(though this is rare) The seizure ends abruptly and the child

resumes whatever he was doing as if nothing had happened

These minor seizures often occur without the child being aware

of them

They can be very frequent (dozens per day), usually every

day Absence seizures can be triggered by hyperventilation

An EEG – even in between clinically perceptible seizures –

will show series of three-second spike-wave activity on all

leads Absence seizures can occur in such quick succession

that absence status develops: the clinical presentation is a

twi-light state that can last for hours or days Absence epilepsy is

found mainly in children and young people, but absence status

can also occur in adults: this should be considered if there is an

unexplained twilight state (7 sect 19.2)

get derailed (e.g putting the kettle on with no water in it) At the start of the seizure there may be a variety of mental, sensory

or vegetative manifestations that the patient may sometimes remember The seizures sometimes remain confined to these,

or the patient can prevent them from getting worse e.g by engaging in physical or mental activity They typically start with focal mental symptoms such as those described above, which is

why they are often referred to as ‘temporal seizures’ or ‘psycho­ motor seizures’.

Patients with complex partial seizures also often have ondary generalized seizures, particularly while asleep

sec-Complex partial seizures

cause – genetic (idiopathic)

– symptomatic (structural, metabolic)

– unknown seizure pattern – aura

– narrowed consciousness – automatisms

postictal confusion – present length of seizure – between a few minutes and one

hour, sometimes longer frequency – variable, often in clusters effect of

do not have epilepsy Better results can be obtained by ing an EEG during sleep after depriving the patient of sleep the previous night, or by doing a repeat EEG If the seizures are fairly frequent and short-lived and their nature is unclear,

record-a combinrecord-ation of video monitoring record-and telemetric EEG crecord-an provide useful information If the patient is aware of having seizures, it can be helpful to record a 24-hour EEG on a port-able recorder The patient will need to note the time of the sei-zure to enable the correct part of the EEG trace to be found The heart rate should also be recorded, as seizures of unknown cause, especially in the elderly, are not infrequently due to car-diac arrhythmia It should be realized that an EEG recorded

during a seizure (ictal EEG) that does not show any

epilepti-form abnormalities does not necessary rule out an epileptic

If the focus is behind the central sulcus there will be

sen-sory manifestations, e.g paraesthesia if the focus is parietal

These too can spread (as in a Jackson’s motor seizure),

pos-sibly followed by the motor symptoms These symptoms are

sometimes reminiscent of the aura symptoms that can occur in

migraine (7 sect 21.2.1), but the spread (march) is much more

rapid in epilepsy Occipital foci cause optic stimulation in the

contralateral field of view (the patient sees fiery balls, geometric

figures) Temporal foci can cause elementary sound

manifesta-tions, and an epileptic source deep in the temporal cortex can

cause odour or taste sensations (uncinate fits) More complex

hallucinations, such as hearing music, visual manifestations

or spoken language, usually originate in the

temporoparieto-occipital association cortex

Focal autonomic symptoms are pallor, perspiration,

palpi-tations, changes in blood pressure and even changes in pupil

diameter (pupillary hippus); epigastric rising sensation is also

included under this heading These autonomic symptoms

pro-bably originate in the deep frontal and temporal regions

Cognitive symptoms are micropsia or macropsia (seeing the

world as unnaturally small or large), memory phenomena such

as déjà vu or déjà vécu (‘I’ve somehow seen/experienced this

before’) and jamais vu (‘Where am I?’, ‘What is all this around

me?’), short bouts of anxiety or depression, feelings of

deper-sonalization and aphasia These seizures originate mainly in the

deep temporal cortex and the limbic system, and they can be

accompanied by other focal symptoms such as those described

above The same symptoms are reported by patients who have

migraine with aura

Simple partial seizures

cause – genetic (idiopathic)

– symptomatic (structural, metabolic) – unknown

seizure pattern – depending on the location

postictal confusion – absent

length of seizure – variable

frequency – variable

effect of

hyperventilation

– little or none EEG – focal unilateral paroxysms

Complex partial seizures

Complex partial seizures involve a partial decline in

conscious-ness (‘narrowed consciousconscious-ness’), with the result that the patient

sometimes knows that he has had a seizure and how it started

but cannot describe its course precisely or at all The patient

may be staring straight ahead and not responding when spoken

to The seizures are often accompanied by gesticulation,

chew-ing, lip-smacking or simple routine actions (getting something

from a cupboard, dusting, undressing, urinating) which often

230 Chapter 18 · Epilepsy and other paroxysmal disorders

seizures the EEG may be completely normal, but sluggish or spiky activity is often found These symptoms can be induced

by hyperventilation or photic stimulation Otherwise no malities at all are found in these patients The natural pro-gression and frequency of seizures differ widely This type of epilepsy generally responds well to drug treatment Seizures occur in 10–15 % of cases in one or more first-degree relatives, and EEGs with epileptic abnormalities even in 25–30 % of those under the age of 30: this is a polygenic disorder

abnor-Absence epilepsy

Childhood absence epilepsy usually starts between the third

and tenth year of life, and the seizures are very frequent The absence seizures clear up spontaneously after puberty in three-quarters of these patients Generalized tonic-clonic seizures occur in approximately 10–20 % of these patients The risk increases with the age at which the absence seizures first mani-fest themselves These seizures often start in puberty, but can also begin in later life

Juvenile absence epilepsy starts after the tenth year of life,

and this type is much rarer than the childhood form These absence seizures are far less frequent, last longer and have less effect on consciousness Approximately 15 % of these patients also have myoclonic jerks, and tonic-clonic seizures can occur

in no less than 80 % These major seizures occur particularly while the patient is waking up This type of epilepsy in effect lies in the spectrum between childhood absence epilepsy and juvenile myoclonic epilepsy as described below Given the spe-cial treatment required (7 sect 18.2.5) it is important to recog-nise absence epilepsy, and especially to distinguish it from partial complex seizures in patients with partial epilepsy

cause In the case of nocturnal frontal lobe epilepsy in

particu-lar a substantial proportion of patients do not show ictal EEG

abnormalities The diagnosis is then based on the clinical signs

(semiology) of the observed seizures.

Uncritical use of EEG can result in incorrectly diagnosing

epilepsy and hence subjecting the patient to years of incorrect

medication ‘Having epilepsy’ can moreover have major social

consequences (driving licence eligibility, job applications), so it

is important for every diagnose to be carefully considered

18.2.2 Classification of epilepsy syndromes

So far we have considered the symptoms and signs of epilepsy

We shall now look at combinations of symptoms that occur in

particular types: epilepsy syndromes ( tab 18.2) Recognising

epilepsy syndromes is important for their correct treatment

Information on the type of seizure and the EEG findings are

considered in conjunction with the age at which the seizures

occur Causes are classified internationally into symptomatic

(genetic, structural or metabolic) and unknown (cryptogenic)

The genetic types used to be referred to as ‘idiopathic epilepsy’,

but that caused confusion; for the time being we use the terms

‘genetic’ and ‘idiopathic’ interchangeably in this chapter for the

sake of completeness

Primary generalized epilepsy with tonic-clonic

seizures

Primary generalized epilepsy with tonic­clonic seizures

gener-ally starts between the third and 25th year of life During the

seizure the EEG shows generalized spikes occurring at

pre-cisely the same time in both cerebral hemispheres In between

. Table 18.2 Classification of epilepsy syndromes

partial (focal) – genetic (idiopathic), e.g benign Rolandic epilepsy ( 7 sect 18.2.4 ) 6–12 years

– symptomatic (structural, metabolic) ( 7 sect 18.2.3 ) – unknown

generalized – genetic (idiopathic) (age-related):

a childhood absence epilepsy ( 7 sect 18.2.2 ) 4–10 years

b juvenile absence epilepsy( 7 sect 18.2.2 ) 10–18 years

c juvenile myoclonic epilepsy ( 7 sect 18.2.2 ) 10–18 years

d primary generalized tonic-clonic epilepsy ( 7 sect 18.2.2 ) 12–25 years – symptomatic/unknown:

a West syndrome ( 7 sect 18.2.4 ) 3–12 months

b Lennox-Gastaut syndrome ( 7 sect 18.2.4 ) 2–5 years – symptomatic (structural, metabolic)

a symptomatic generalized epilepsy: ( 7 sect 18.2.3 ) unclassifiable syndromes

special syndromes – febrile convulsions ( 7 sect 18.2.4 ) 6 months to 6 years

Surprisingly, the first epileptic manifestation may occur only years after an accident or the development of an abnor-mality Generally speaking, the risk of recurrence is high in the case of symptomatic localization-related epilepsy of this kind, and patients therefore remain dependent on medication.

Triggers

Certain factors can trigger a seizure in patients with epilepsy: lack of sleep (particularly in the case of juvenile myoclonic epi-lepsy), alcohol abuse (especially the abstinence phase), a head

or brain injury, an infection with rapidly rising body ature, hyperventilation, intoxication and certain medicinal drugs (e.g high doses of antidepressants) Mental stress can also be a contributory factor There is sometimes an association with menstruation

temper-If the epileptic seizure is triggered by simple external stimuli, e.g a change in lighting conditions, a particular sound, a touch or the start of a movement, this is referred to

as reflex epilepsy The most common form is photosensitive epi­ lepsy: these seizures can be caused by suddenly moving from

dark into light surroundings (e.g driving out of a tunnel) or

by intermittent stimuli (television interference, driving along a sunny tree-lined avenue, a disco with flashing lights) This type

of provocation is used with EEG (stroboscopy) Photosensiti

-vity of this kind is found mainly in primary generalized lepsy (50 %)

epi-Seizures that only occur under provocative conditions are

referred to as provoked seizures An estimated 5 % of the

popu-lation will have a provoked seizure at least once in their lives: they are likely to have a relatively low ‘seizure threshold’ An epileptic seizure following severe lack of sleep is an example of

or extremities or autonomic (cardiovascular) paroxysms There are also phenomena such as irritability and tremor-like move-ments that should not be regarded as epileptic, however

Causes of neonatal convulsions are withdrawal of the cation that the mother was taking during the pregnancy, which the baby no longer receives after birth, hypoglycaemia, electro-lytic disorders, pyridoxine dependency, medication or biliru-bin encephalopathy Here too, epilepsy can be a manifestation

medi-of cerebral damage due to haemorrhage, infection, hypoxia, congenital cerebral disorders or congenital metabolic disease Not all seizures in neonates are a cause for alarm: there are also benign syndromes with no underlying abnormalities that can run in the family

In both types of epilepsy, medication renders 80 % of

patients seizure-free, but the risk of the seizures returning if the

anti-epileptic is discontinued after a few years of being

seizure-free is far greater in the case of the juvenile form than in that of

absence epilepsy that starts in childhood

Juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy usually comes to light around the

14th year of life (between the ages of eight and 23) in the form

of a generalized tonic-clonic seizure soon after waking up This

is often preceded by stress, lack of sleep or alcohol

consump-tion the previous evening Most patients will already have

expe-rienced sudden jerks in the arms or legs for some time within

one or two hours after waking and sometimes also at the end

of the afternoon The jerks usually occur in the arms, causing

the patient to drop things, and patients sometimes suddenly fall

down when their legs give way These myoclonic seizures

some-times occur in clusters; there is never a decrease in the level of

consciousness As a result, epilepsy is not usually diagnosed

until after the first tonic-clonic seizure, which occurs sooner or

later in 90 % of these patients Accompanying absence seizures

occur in 30 % of these patients

Juvenile myoclonic epilepsy is another type of primary

(genetic/idiopathic) generalized epilepsy with typical EEG

abnormalities There is an association with both absence

sei-zures (20 %) and sensitivity to flashes of light (photoconvulsive

epilepsy, 10 %) These patients respond well to medication,

pro-vided the correct type is selected (7 sect 18.2.5): it renders over

90 % of patients seizure-free, but discontinuing the

medica-tion usually causes the seizures to return, unfortunately Rather

than go on lifelong anti-epileptic medication, a proportion of

patients opt to change their lifestyle, using medication only as

a temporary measure when special circumstances occur that

could easily cause a seizure

18.2.3 Causes and triggers

Causes of epilepsy

As regards the causes of epilepsy, it is helpful to distinguish

between acute symptomatic and late symptomatic forms Acute

symptomatic seizures are caused by acute metabolic

dysregula-tion or intoxicadysregula-tion, or occur in the acute phase (one week) of

neurological disorders such as head or brain injury and

menin-gitis Late symptomatic seizures are due to an underlying

con-dition that has persisted for more than a week, which can be

genetic, structural or metabolic ( tab 18.3)

Any kind of brain damage (encephalitis, brain injury,

tumour, infarction or haemorrhage) can cause partial (focal)

epilepsy and possibly secondary generalization

Epileptic seizures in young children are often due to the

residual effects of problems in the prenatal or perinatal period

or early childhood (7 chap 28) The seizures often start in the

first year of life and are difficult to treat (7 sect 18.2.4)

232 Chapter 18 · Epilepsy and other paroxysmal disorders

children stagnates, often with loss of eye contact and a cal EEG with multifocal spikes and high-voltage sharp waves,

typi-known as hypsarrhythmia.

The triad of infantile spasms, arrested development and the

typical EEG is referred to as West syndrome The prognosis for both

the epilepsy and general neurological state is poor; approximately

80 % of patients with West syndrome are found to have an ing neurological disorder (e.g tuberous sclerosis: 7 sect 28.5.1)

underly-Lennox-Gastaut syndrome

A type of epilepsy can occur in the second to sixth year of life that is accompanied by a mixture of three different types of

seizure in the same patient This is known as Lennox­Gastaut

The nervous system in young children has not yet matured

to the point where typical epileptic seizures can occur; any fully

generalized tonic-clonic seizure will not occur until the first

year of life

West syndrome

There is a particular type of seizure in the first year of life that is

accompanied by what are known as infantile spasms or salaam

spasms This type peaks between four and six months The child

is seen to bend the head and trunk forward abruptly (or raises

the extended legs if it is lying down), while flexing or

extend-ing the arms, for a fraction of a second These cramps usually

occur in series, several times a day The development of these

. Table 18.3 Causes of epilepsy

a Mainly symptomatic generalized seizures.

late symptomatic

following atypical febrile convulsions (mesial temporal sclerosis) 7 section 18.2.4 , in particular temporal seizures ( 7 sect 18.2.1 )

cerebral tumour or metastasis 10 % of epilepsies with onset in later life, first symptom in 40 %

arteriovenous malformations incidence 40 % in the case of major malformations

stroke rarely acute after ischaemic stroke, but acute in the case of haemorrhage

autoimmune-mediated epilepsy immunological aberration due to infection or malignancy with the

forma-tion of auto-antibodies (e.g anti-NMDA receptor, anti-AMPA receptor, anti-voltage-gated potassium channels)

head or brain injury in 15–50 % of penetrating brain injuries, following closed brain injuries,

higher risk in the case of long-standing post-traumatic amnesia (20×)

birth trauma

cerebral infection meningitis, encephalitis, abscess, vaccination (rare)

other neurological disorders virtually all diseases of the cortex, in rare cases also diseases of the white

matter such as MS congenital abnormalities congenital disorders of the cerebral cortex (migration disorders

7 sect 28.3.3 ), neurocutaneous syndromes ( 7 sect 28.5 ) degenerative disorders especially Alzheimer’s disease and other cortical syndromes

genetic types of generalized epilepsy, e.g absence epilepsy ( 7 sect 18.2.2 ),

juve-nile myoclonic epilepsy ( 7 sect 18.2.2 ), primary generalized epilepsy with tonic-clonic seizures ( 7 sect 18.2.2 ), types of partial epilepsy, e.g benign Rolandic epilepsy ( 7 sect 18.2.4 )

acute symptomatic

various medicinal drugs a cardiac arrhythmics, most antidepressants (in higher doses),

anti-malarial drugs, various central anaesthetics, phenothiazines, clozapine, cyclosporine, penicillin, theophylline, cocaine, amphetamine

withdrawal a alcohol, barbiturates, benzodiazepines, anti-epileptics, opiates

metabolic dysregulation a e.g hypoglycaemia, hypoparathyroidism, rapid changes in osmotic state,

in particular Na + , K + , Ca 2+ , Mg 2+

arrest (due to dysarthria) and hypersalivation It can then spread to one side of the body, or secondary generalization can occur.

There can also be pure sensory seizures Consciousness remains intact unless there is secondary generalization The sei-zures originate in the primary motor or sensory cortex (around the central sulcus of Rolando: fig 5.1) Characteristic EEG abnormalities may be recorded over this area in between sei-zures No structural abnormalities are found in the brain The seizures by no means always require treatment; they clear up spontaneously during puberty If they are frequent or cause excessive concern to the parents or child, anti-epileptics are a fast and effective remedy

18.2.5 Treatment

First aid for epileptic seizures

A tonic-clonic seizure is always alarming: anyone experiencing

it for the first time will think that the patient is dying The only thing that can be done is to protect the patient against injuries

to the head and extremities during the convulsions There is

no point in trying to prevent the patient biting his tongue or cheek, e.g by placing a handkerchief between the teeth, as a tongue bite heals much faster than a tendon injury to the help-er’s hand After the clonic phase the patient should be placed

in a stable recovery position to avoid aspiration The fit almost always ends of its own accord, so it is rarely necessary (or pos-sible) to stop it

If a fit lasts longer than five minutes (status epilepticus), midazolam is administered before taking the patient to hos-pital (adults: 10 mg, children: 0.2 mg/kg) as a nasal spray or drops inside the cheek An alternative is rectal diazepam (chil-dren under 3 years 5 mg, children over 3 years 10 mg, adults 10–20 mg) Clonazepam (1–2 mg) can alternatively be mas-saged into the buccal mucosa Once one of these drugs has been administered the patient should be admitted to hospital urgently It should be remembered that benzodiazepines have only a temporary effect (e.g diazepam only 30–45 minutes), after which another seizure can occur

Quick action is called for in cases of status epilepticus, and it is important for someone with appropriate expertise to remain with the patient to keep the airway clear and administer another dose of seizure medication if necessary Another dose

of benzodiazepine will need to be administered if necessary in the ambulance (or in hospital), followed if appropriate in Acci-dent and Emergency by an anti-epileptic such as phenytoin, valproate or levetiracetam IV The next step is to determine the cause of the status epilepticus

If the seizures cannot be stopped, intubation and ment with midazolam or thiopental or pentothal (a barbiturate anaesthetic) or propofol will eventually be required with EEG monitoring The mortality rate for convulsive status epilepticus itself is 1–2 %; the prognosis depends mainly on the underlying cause

treat-syndrome It is particularly characterized by tonic seizures in

which the child briefly goes completely rigid and falls over as

stiff as a board These seizures can cause substantial injuries,

and the only protection is a helmet There can also be

atypi-cal absence seizures, myoclonic jerks and atonic seizures with

abrupt loss of muscle tone The latter cause the child to collapse

into a heap and then get up again The EEG shows

characteris-tic abnormalities The child may have developed normally until

the epilepsy started, but this type of epilepsy is often

accompa-nied by cerebral abnormalities or developmental retardation

The causes are many and varied; in a substantial proportion of

patients the cause remains unclear, however This type of

epi-lepsy is very intractable

Febrile convulsions

Febrile convulsions (febrile seizures) are generalized

epilep-tic seizures that often occur in the early stage of a feverish

disease They are almost entirely confined to the age range of

six months to six years, and they run in the family

Approxi-mately 4 % of children have a febrile convulsion at one time or

another The seizure hardly ever recurs during the same fever

episode In typical cases the seizures are generalized tonic

or tonic-clonic and last no more than 15 minutes The risk of

recurrence is approximately 30 %; it is higher the earlier the age

at which the first febrile seizure occurred Only a small

propor-tion of patients (2–5 %) go on to develop epilepsy, also outside

the fever episodes, partly due to genetic predisposition, partly

due to a minor cerebral injury during the anoxia caused by a

long febrile seizure The risk of this is greater if the febrile

con-vulsion is atypical, i.e longer, asymmetrical, occurring during

the first year of life or recurring several times within 24 hours

Some of the later partial epilepsies are probably due to the

inju-ries the convulsion causes in the interior of the temporal lobe

and hippocampus (mesial temporal sclerosis).

Neurologically abnormal children with cerebral palsy are

more likely to have convulsions during a fever than healthy

children In this group the existing neurological symptoms

usu-ally get worse after the seizure The term ‘febrile convulsion’ is

not applicable to this group: here we prefer to use the term con­

vulsion due to fever.

If a young child has a febrile convulsion there is always

some risk of meningitis, but the a priori probability in general

practice is low (1–2 %), and if there are no other symptoms or

signs, e.g meningeal irritation, petechiae or abnormal

progres-sion of the seizures, no further investigation in that direction is

needed

It is not usually necessary to treat febrile convulsions

Long-term treatment with anti-epileptics is not generally indicated,

nor is it effective The value of prophylactic treatment with

paracetamol during fever episodes is also unproven

Intermit-tent treatment with diazepam during fever episodes does seem

to reduce the risk of recurrence, but it has the drawback that it

can make children drowsy

Benign Rolandic epilepsy

This type of epilepsy causes tonic or clonic convulsions in the

muscles of one side of the face, mouth and throat with speech

234 Chapter 18 · Epilepsy and other paroxysmal disorders

be counterproductive in generalized types of epilepsy There

is hardly any scientific proof that particular anti-epileptics are generally more effective than others, but they do have different adverse effects and interactions It is beyond the scope of this book to list all the drugs and their characteristics

We shall confine ourselves here to a few general practical comments

5 Carbamazepine is a drug of choice for focal epileptic

seizures It has the drawback that it needs to be phased in gradually to avoid dizziness It can also reduce the effective-ness of other drugs such as oral contraceptives and antico-agulants as a result of enzyme induction If carbamazepine proves effective but has unwanted side effects, such as an

allergic skin reaction, oxcarbazepine is a good alternative

(causing cross allergy in ‘only’ 25 % of cases) Both these drugs can cause hyponatraemia, although this does not require treatment

5 Lamotrigine is a broad-spectrum anti-epileptic whose main

drawback is that it has to be phased in very gradually to reduce the risk of a hypersensitivity reaction It can cause

an increase in myoclonic jerks

5 Levetiracetam is a broad-spectrum anti-epileptic that can

be phased in quickly and does not interact with other medication It can also be administered intravenously It

is excreted via the kidneys A problem is that it can cause aggressiveness

5 Sodium valproate is a broad-spectrum anti-epileptic that is

used mainly for absence seizures and juvenile myoclonic epilepsy, where it is far more effective than most of the other drugs, even in low doses The main adverse effects are weight gain and tremor, and there can be hair loss at the start of the treatment Of all the anti-epileptics, sodium valproate has the highest risk of teratogenic side effects and should therefore be avoided as far as possible in the case of women of child-bearing age Lastly, it is absolutely con-traindicated in the case of a rare mitochondrial metabolic disorder (POLG1 mutation)

5 The oldest drug still in use, phenobarbital, is nowadays used

almost exclusively for neonatal epilepsy, as it has an adverse effect on cognitive development when used at a later age; there is also a high risk of withdrawal seizures, so it needs

to be phased out very gradually compared with all the other drugs

5 Phenytoin is a powerful anti-epileptic, which has the major

advantage of being able to be administered rapidly enterally Its therapeutic range is small, however, as it can quickly accumulate if the dose is increased only slightly above a certain limit (the enzyme system becomes satu-rated and breaks down) Other problems when it is used over a long period are gum growths, osteoporosis, risk of cerebellar ataxia, polyneuropathy and coarsening of the facial features Some drugs are known to increase the risk of phenytoin intoxication Phenytoin is virtually the only anti-epileptic where blood levels need to be monitored (espe-cially after adding another drug that could affect phenytoin excretion)

par-Anti-epileptics

Treatment with anti-epileptics is usually initiated and

moni-tored by a neurologist or paediatrician There must be adequate

certainty as to the diagnosis before this treatment is prescribed

Anti-epileptics prevent seizures but have no effect on the

prog-nosis for the epilepsy

The average risk of recurrence after a one-off seizure is

50 % It is not the case that every patient should be treated with

anti-epileptics after the first seizure If the EEG shows signs of

epilepsy there is a particular reason to prescribe them, as the

risk of recurrence is higher in these cases, also if the seizures

are nocturnal If there is an underlying structural cerebral

dis-order the risk is much higher and treatment will usually start

immediately If the seizures are highly sporadic the question

is whether the benefits of daily use of anti-epileptics are

out-weighed by the disadvantages, given all the possible adverse

effects and the fact that this is not certain to make the patient

seizure-free If there are two or more seizures within a year or

status epilepticus develops, anti-epileptic medication is usually

prescribed (depending on factors including the severity of the

seizures and expected patient compliance)

Once treatment has started it is usually possible to check

after two years of freedom from seizures whether the

medi-cation can be discontinued In the case of some types of

epi-lepsy (e.g juvenile myoclonic epiepi-lepsy, 7 sect 18.2.2) this needs

to be approached with great caution, as the risk of recurrence

remains very high In the case of other types of epilepsy the

risk of recurrence after discontinuing the medication is still

approximately 30–40 %, higher if the epilepsy is symptomatic

It is lower if no underlying structural cause of the epilepsy has

been found and the patient is immediately rendered

seizure-free after starting to take anti-epileptics Factors such as fear

of recurrence and needing to have a driving licence can play

a major role in the decision With a few exceptions EEG has

a low predictive value as regards risk of recurrence It

prob-ably makes little or no difference whether the anti-epileptic

medication is phased out quickly (over weeks) or slowly (over

months)

Choosing the right anti-epileptic

The decision to prescribe a particular anti-epileptic is based

on the type of epilepsy or epileptic seizures, particular patient

characteristics such as comorbidity, co-medication and desire

for pregnancy, and practical considerations such as the need to

act quickly

The various anti-epileptics act in different ways Most of

them act on the Na+ and/or Ca2+ channels, others

(pheno-barbital, benzodiazepines, vigabatrin) on GABA receptors or

K+ channels (retigabine) Various drugs have a mechanism of

action which is largely unknown

For focal seizures or types of epilepsy carbamazepine,

lamotrigine, levetiracetam, oxcarbazepine or sodium valproate

is preferred For generalized seizures or primary

general-ized types of epilepsy valproate, lamotrigine or levetiracetam

is the drug of choice; this is also the case if the seizure

classi-fication is unclear, as carbamazepine and oxcarbazepine can

carba-to avoid using these drugs, or alternatively prescribe an OC with a higher oestrogen content Provided there is no break-through bleeding, OCs are fairly reliable, but less reliable than

in women who are not using anti-epileptics Instead of the OC the clinician can recommend an IUD that contains progesto-gen, with a local hormone application, as this is not affected

by enzyme induction Use of an OC reduces the blood level of lamotrigine by 50 %, which rises proportionately during the pill-free week Levetiracetam does not reduce the effectiveness

of oral contraceptives

If the patient wishes to try for a baby, various subjects need

to be discussed with her:

5 Which anti-epileptic to use before and during the pregnancy

5 Folic acid treatment during the period prior to conception

5 The increased risk of congenital foetal abnormalities and the possibilities and limitations of diagnosing them prenatally

5 The course of the epilepsy during the pregnancy

5 The risks associated with labour and puerperium

It is best to use a single drug to treat the epilepsy during nancy To avoid peaks a number of doses should preferably be administered spread over the day or a slow-release version It is inadvisable, however, to discontinue anti-epileptics just before

preg-or during pregnancy

The least teratogenic anti-epileptics are carbamazepine, lamotrigine and levetiracetam When using lamotrigine and levetiracetam it is advisable to monitor blood levels before and during the pregnancy, as they can fall sharply (lamotrigine

by 40 %) during pregnancy, making it necessary to adjust the dosage (which should be returned to the old level in the first week after birth) Use of sodium valproate is associated with a large increase in the risk of neural tube defect (from 0.07 % to 1–2 %), and – especially at doses over 1,000 milligrams per day – other congenital abnormalities It may also have an adverse effect on children’s long-term development

All pregnant women are recommended to take 0.4 (or 0.5) milligrams of folic acid per day from deciding to try for

a baby up to and including the eighth week after conception

If a previous child had a neural tube defect the dose should be increased to 5 milligrams per day Carbamazepine and other anti-epileptics that induce the cytochrome P450 liver enzyme system can cause oxidative breakdown of vitamin K, leading

to coagulopathy When using drugs of this kind, 10 milligrams

of vitamin K per day should therefore be taken during the last four weeks of pregnancy to avoid neonatal haemorrhages

The fact that the mother uses anti-epileptics is not a traindication for breast-feeding Seizure frequency rises in

con-5 Benzodiazepines (clonazepam, clobazam, nitrazepam,

diazepam) are not drugs of choice for chronic treatment

because of their sedative effect and the risk of withdrawal

symptoms Clonazepam and clobazam are useful drugs

for intermittent administration, e.g to patients who have

only occasional seizures that may be triggered by lack of

sleep Clobazam is used over longer periods as an add­on to

another anti-epileptic, however

5 Ethosuximide is used nowadays as the drug of choice for

childhood absence seizures It is just as effective as sodium

valproate but has a slightly less adverse effect on reaction

speed

A variety of second-choice drugs are available, e.g (in

alpha-betical order) gabapentin, lacosamide, perampanel, pregabalin,

topiramate and zonisamide These are only used if the drugs of

choice prove ineffective Vigabatrin is suitable for treating West

syndrome (7 sect 18.2.4), but a major disadvantage is the high

risk of visual field defects

Except in the case of phenytoin, it is only necessary to

moni-tor blood levels if there is doubt as to patient compliance, and

in the case of lamotrigine, oxcarbazepine and levetiracetam to

maintain therapeutic levels during pregnancy (7 sect 18.2.5)

Blood level monitoring can also be worthwhile in patients

admitted with an acute condition and those on dialysis

Rou-tine monitoring of the blood panel and liver functions during

treatment is not regarded as necessary nowadays Patients do

need to know, however, that some anti-epileptics (e.g

carba-mazepine) can very occasionally cause severe haematological

abnormalities, and others (e.g sodium valproate) severe

hepa-totoxicity Use of anti-epileptics often causes a slight rise in

liver enzyme levels, but this is not clinically significant

A single drug can produce good results in approximately

70–80 % of patients, but this does not always equate to

com-plete freedom from seizures If the results are inadequate, the

first option is to prescribe an alternative anti-epileptic, initially

while leaving the first drug in place If adding the second drug

has a beneficial effect, the first drug can be gradually phased

out If the first add-on proves ineffective, a second add-on will

need to be tried Some add-ons affect the blood level of the first

drug, making it necessary to adjust the dosages

When it comes to treatment it is often necessary to

bal-ance the efficacy of the medication against its adverse effects

It is important to question patients actively about side effects

such as loss of concentration, reduced alertness, memory

prob-lems, skin reactions, behavioural problems and weight gain/

loss, as patients and those around them do not always make

the connection between these problems and medication

Anti-epileptics must not be discontinued suddenly, as this can

trig-ger seizures If the patient has to undergo surtrig-gery, for example,

some anti-epileptics can be administered intravenously as a

temporary measure

Treating epilepsy is not just a question of suppressing the

seizures Developing or having epilepsy often has far-reaching

social consequences