Neurological Emergencies - part 4 doc

In this study mania was associated withtemporal basal polar lesions; no links were established withseverity of brain-injury or previous personal or family historyof psychiatric disorder.

Monoamine oxidase inhibitors (phenelzine, tranylcypromine)are also effective in depressive illness They are used by somepsychiatrists as the preferred drug when depression isaccompanied by anxiety, phobic symptoms, weight gain,hypersomnia, and fatigue For many years they have beenunderused because of fears of their interaction with tyramine-containing foods, potentially resulting in a catastrophic rise

in blood pressure Various foods, alcoholic drinks, and drugshave had to be avoided by patients taking monoamine oxidaseinhibitors This problem has been overcome by the introduction

of reversible and selective inhibitors of monoamine oxidasesubtype A, such as moclobemide

All antidepressants take up to 2–3 weeks to produce clinicaleffect In some clinical situations this delay may beunacceptable and a speedier response to treatment is required.Electroconvulsive therapy (ECT) is the preferred treatment inthese situations, particularly when the risk of suicide is high,

or when the patient is stuporose and is not maintainingadequate nutrition or fluid intake ECT may have to be givenunder the terms of the Mental Health Act (1983) if the patient

is incapable of giving informed consent to treatment; inEngland and Wales this involves obtaining a second opinionfrom a psychiatrist appointed by the Mental Health Actcommission Box 5.3 shows the main indications for ECT indepressive disorder

There are no absolute contraindications to ECT A decisionshould be taken after careful consideration of the risks of thevarious treatment options weighed against the risk ofcontinuation of the depressive disorder Box 5.4 lists theconditions in which ECT should be avoided whenever possible

In severe forms of mania, the inflated self-esteem maydevelop into delusions Genetic and anatomical factors areimportant in the development of mania secondary toneurological disease.33A study of mania following closed headinjury reported that six of 66 patients (9%) had features ofmania at some stage during a 12 month follow-up period, thisfigure being higher than has been reported in other brain-injured people In this study mania was associated withtemporal basal polar lesions; no links were established withseverity of brain-injury or previous personal or family history

of psychiatric disorder.34

Management of acute mania

Treatment is best carried out in hospital; if the patient isalready in a neurology ward, transfer to a psychiatric ward isdesirable Because of the lack of insight which is characteristic

of mania, compulsory admission may have to be arranged.The two groups of drugs which are regularly used in acutemania are: (i) antipsychotics (such as chlorpromazine or

Box 5.3 Indications for electroconvulsive therapy in

depressive disorder

Severe depression with high risk of suicide

Depressive stupor

Depressive disorder with psychotic symptoms

Failure to respond to an adequate course of an antidepressant Inability to tolerate side effects of antidepressants

If physical illness makes antidepressants less safe than ECT

Box 5.4 Relative contraindications to ECT

Raised intracranial pressure

Instability of cer vical spine

Cerebral aneur ysm

Recent histor y of cerebral haemorrhage

Myocardial infarction within previous three months

Aor tic aneur ysm

Acute respirator y infection

haloperidol and the newer so-called atypical antipsychoticsolanzapine and risperidone) and (ii) benzodiazepines (such asdiazepam) Chlorpromazine can be given orally starting at adose of 25–50 mg eight hourly, increasing to a maximum dailydose of 1500 mg according to the clinical response When oraltreatment is not accepted, an intramuscular injection of up to

150 mg can be given but this should not be repeated because

of its irritant effect on muscle tissue Haloperidol can bestarted at an oral dose of 5 mg eight hourly increasing to amaximum daily dose of 40 mg When speedier control ofsymptoms is required, an intramuscular injection of 10–20 mgcan be given

The older antipsychotic drugs are likely to produce a variety

of extrapyramidal side effects, especially in patients withexisting brain damage Akathisia, Parkinsonism, acutedystonia, and tardive dyskinesia are well establishedcomplications Akathisia, a subjective sense of motorrestlessness, leads to hyperactivity and an inability to relax Itcan be wrongly attributed to a worsening of the maniccondition, so an inexperienced clinician may increase thedose of antipsychotic rather than reduce it and consequentlythe akathisia symptoms worsen A beta-adrenergic blockingdrug such as propranolol is an effective remedy once thecondition is diagnosed Acute dystonias can also give rise todiagnostic confusion They can present with tongueprotrusion, torticollis, oculogyric crisis, or opisthotonus, andthese are often wrongly diagnosed as dissociative (hysterical)reactions Rapid relief of symptoms can be achieved by anintravenous dose of 5–10 mg of procyclidine Suddencardiorespiratory collapse is a potentially fatal complication ofantipsychotic treatment, especially when the patient showsevidence of extreme physiological arousal and overactivity.Drug doses should be kept as low as possible and thetreatment regimen monitored regularly Pulse and bloodpressure should be checked before each intramuscularinjection and at regular intervals during oral treatment In thelight of these problems attention is turning to the newerantipsychotics Olanzapine appears effective in the treatment

of acute mania, with a low incidence of side effects,35so it mayreplace the more established drugs

If manic symptoms do not respond to medication, ECT canprove to be a quick and effective treatment

Anxiety and stress-related disorders

Patients with anxiety and allied conditions may present

to neurologists if their symptoms are intermittent and ofsudden onset

Generalised anxiety disorder

There are a wide variety of physical complaints produced by:

• increased motor tension (restless fidgeting, tensionheadaches, trembling, and an inability to relax)

• apprehension (feeling “on edge”, worries about futuremisfortunes, and difficulty in concentrating)

• autonomic overactivity (lightheadedness, sweating,tachycardia or tachypnoea, epigastric discomfort, dizziness,and dry mouth)

This disorder is more common in women and often related tochronic environmental stress Its course is variable but tends

to be fluctuating and chronic

Phobic anxiety disorders

A phobia is an abnormal, disproportionate fear of an object orsituation that leads to avoidance of the object or situationwhich precipitates it Agoraphobia is the commonest phobiaencountered clinically and symptoms attributed to neurologicaldisease are particularly prominent; these include headache,impaired concentration, dizziness, and a fear of falling The clue

to the diagnosis comes from eliciting a link between symptomsand specific situations which invariably precipitate them In thecase of agoraphobia the commonest triggers are open spaces,crowded streets, supermarkets, and public transport

Panic disorder

The characteristic features are recurrent episodes ofoverwhelming anxiety which are unpredictable and notconfined to a particular situation The somatic symptoms ofanxiety, notably palpitations, chest pain, hyperventilation,and dizziness, usually dominate the picture but there is alsointense psychological anxiety, often involving a fear of going

mad or dying from heart attack or brain tumour This may beaccompanied by depersonalisation which patients describe as

an altered sensation in their bodies which feel lifeless orunreal as if they have lost their feelings and are observingthemselves from the outside Panic attacks may be mistakenfor the aura of temporal lobe epilepsy, vestibular disease, orthe early manifestation of multiple sclerosis Non-neurologicalconditions that need to be considered in the differentialdiagnoses are hyperthyroidism, phaeochromocytoma,hypoglycaemia, and supraventricular tachycardias

A typical attack lasts only a few minutes but tends to recur.Patients become apprehensive of recurrent episodes and somelearn to avoid certain places where an attack would beparticularly embarrassing, such as a public place far fromhome from which there is no easy escape route Thus panicattacks come to be associated with agoraphobic behaviour insome patients

Post-traumatic stress disorder

This syndrome is a delayed response following exposure to astressful experience of an exceptionally threatening naturewhich is quite outside the range of everyday experienceand which is likely to cause distress to almost everyone There

is a perceived danger of death or severe physical trauma but theinjuries actually sustained may be quite trivial The experiencesthat evoke the response include natural disaster, road trafficaccidents, military or terrorist activity, and being the victim oftorture or rape The disorder has been estimated to occur in up

to one third of patients involved in road traffic accidents.36,37

There may be a delay between the traumatic event and theonset of symptoms which ranges from a few weeks up to sixmonths The typical symptoms include recurrent intrusivememories of the event (“flashbacks”), disturbed sleep,nightmares of the event, emotional blunting, avoidance ofcues that evoke memories of the original trauma, depression,irritability, and autonomic arousal

Acute stress reaction

A transient disorder which develops in response toexceptional physical and/or mental stress and which usually

subsides within hours or days The stressor may be anoverwhelming traumatic experience such as a war, a naturalcatastrophe, rape, multiple bereavement, or fire The symptomsshow great variation but typically include an initial “daze” statewith some constriction of the field of consciousness andnarrowing of attention, inability to comprehend stimuli, anddisorientation Autonomic signs of panic may also be present.The symptoms usually subside within minutes, but can lasthours or up to two or three days No treatment is usuallynecessary.

Adjustment disorder

A varied disorder of distress and emotional disturbanceusually interfering with social functioning and performancearising from a significant life change or a stressful life Thecausal event does not in any way reach the level of thoseleading to an acute stress reaction (see above) Symptomsinclude depressed mood, anxiety, worry (or a mixture of these),

a feeling of inability to cope and plan ahead The individualmay be prone to dramatic behaviour or outbursts of violence.The disorder is usually transient and requires no treatment

Management of anxiety and

stress-related disorders

Behaviour therapy, involving relaxation and gradualexposure to the precipitating situation, is of proven value inphobic disorders and in panic disorder when there is avoidancebehaviour A clinical psychologist should assess the patient andorganise treatment if behaviour and cognitive therapy areconsidered appropriate Phenelzine is a useful adjunct topsychological methods of treatment Drug treatment is moreimportant in spontaneous panic attacks; phenelzine,imipramine, and paroxetine have been shown to be effective.There has been considerable interest in the psychologicaltreatment of victims of accidents or disasters who are at risk ofdeveloping post-traumatic stress and other psychiatricdisorders Early intervention has been advocated but itsefficacy has not been convincingly demonstrated Cognitivetherapy and exposure, preventing the development of

avoidance therapy, are now established components oftreatment.38 If symptoms have become established, eithertricyclic antidepressants or monoamine oxidase inhibitors canprovide symptomatic relief.39

Dissociative (conversion) disorder

This group of disorders is also known as conversion hysteria.The term “hysteria” is a controversial one and is used inseveral different ways; as a result it has been omitted fromboth DSM-IV and ICD-10 but it is still widely used as adiagnostic category in clinical practice

Dissociative disorders are characterised by symptoms thatsuggest lesions in the motor or sensory pathways of thevoluntary nervous system There is loss or distortion ofneurological function which cannot be adequately accountedfor by organic disease.40 Psychiatrists would also want toestablish positive evidence that the symptom is linked topsychological factors,41 either previous severe stress,emotional conflict, or an associated psychiatric disorder It isassumed that the symptoms are not intentionally produced, as

in malingering, but are a result of unconscious motives This,however, is a notoriously difficult distinction to make and itoften appears that the degree of insight into the nature of thedisability varies from time to time

Dissociative disorders are thought to be declining inincidence The commonest symptoms, which are usually ofacute onset, are motor weakness, altered sensation, gaitdisturbance, and pseudo-seizures.42 The neurologicalexamination reveals characteristic abnormalities that enablethe experienced neurologist to make a confident diagnosis inmost cases.43 Weakness usually involves whole movementsrather than muscle groups and it affects the extremities muchmore often than ocular, facial, or cervical movements Variousclinical techniques can be employed to show that weakness of

a limb is associated with simultaneous contraction ofopposing muscle groups There is discontinuous resistanceduring testing of power (“give way weakness”), musclewasting is absent, and reflexes are normal Sensory loss ordistortion is often inconsistent when tested on more than oneoccasion and incompatible with peripheral nerve or root

distribution There may be discrete patches of anaesthesia orhemisensory loss which stops abruptly in the midline Visualsymptoms include monocular diplopia, triplopia, field defects,tunnel vision, and bilateral blindness associated with normalpupillary reflexes Dissociative gait disturbance, astasia-abasia,

is recognised by its bizarre character and intermittent pattern;the patient walks normally if he or she thinks that no one isobserving In some cases, when being observed, the patientactively attempts to fall and this contrasts with the patientwith organic disease who tries to support him- or herself.Pseudo-seizures are more difficult to evaluate because theyare episodic and often coexist with true epilepsy An accountfrom a reliable observer is invaluable but it is essential for theclinician to witness an attack before making a firm diagnosis.The clinical features, which simulate epilepsy to a varyingdegree, have been described in detail.44During an attack there

is marked involvement of the truncal muscles withopisthotonus and lateral rolling or jerking of the head andbody All four limbs may exhibit random thrashingmovements which increase in amplitude if restraint is applied.Cyanosis is rare unless there is deliberate breath holding.Corneal and pupillary reflexes are retained although they may

be difficult to elicit because the eyelids are kept firmly closed.Tongue biting and urinary incontinence are uncommonunless the patient has some degree of medical knowledge andhas learned from experience that they are characteristicfeatures of epilepsy

In contrast to true epilepsy, pseudo-seizures usually occur inthe presence of other people and not when the patient is alone

or asleep Some episodes simulate partial motor seizures orsimple faints Others occur in rapid succession withoutrecovery of consciousness and they may be accompanied bydeliberate tongue biting or incontinence so the clinical picturemimics status epilepticus In addition to the clinical features

of the attacks, certain demographic characteristics help todistinguish pseudo-seizures from true epilepsy Patients withpseudo-seizures are more likely to have a family history ofpsychiatric illness, a personal history of psychiatric illness,previous suicide attempts, sexual maladjustment, and currentaffective disorder.45

Dissociative, or psychogenic, amnesia can also creatediagnostic problems.46 There is a sudden loss of memory,

usually in relation to a markedly stressful event The amnesia

is selective and predominantly involves the inability to recallemotionally charged memories The ability to learn newinformation is relatively preserved, as are cognitive skills such

as reading and writing A characteristic feature is a loss ofpersonal identity; the patient is unable to recall his or hername, age, address, occupation, and family details, and mayfail to recognise relatives when they visit Recovery is usuallyrapid and complete In some cases, however, dissociativeamnesia lasts for several days or weeks and is accompanied by

an apparently purposeful wandering away from the home orplace of work During this condition, known as a dissociativefugue, a new name and identity may be assumed Self-care ismaintained and the patient’s behaviour may appearcompletely normal to people who do not know him or her.Recovery occurs abruptly and there is amnesia for the period

of the fugue Organic conditions that need to be considered inthe differential diagnosis of dissociative amnesia include headinjury, delirium, epileptic fit, Wernicke’s encephalopathy,alcoholic blackout, and transient global amnesia

Any patient suspected of having dissociative symptomsshould be examined carefully by a neurologist andpsychiatrist Special investigations, such as MRI and EEGtelemetry, are required in some cases before a confidentdiagnosis can be made and, in a few, a decision has to bedeferred until the symptoms can be reviewed after a suitabletime interval The presence of organic disease does not ruleout a diagnosis of dissociative disorder Indeed it is nowrecognised that neurological lesions and dissociativesymptoms occur together more frequently than can beexplained by chance Although the neurological lesion cannotexplain the presenting symptom, coexisting disease of thenervous system may facilitate the emergence of dissociativemechanisms and provide a model for the symptom.40 Thismay explain the frequent occurrence of pseudo-seizures inpatients who also have genuine epilepsy

Management of dissociative disorder

Once the diagnosis of dissociative disorder has beenestablished, the results of the clinical examination and special

investigations should be discussed with the patient togetherwith reasons for considering the symptoms to have apsychological basis This should not be conducted in aconfrontational manner It is best to explain that thesymptoms are due to stress, that they are familiar to theclinician, that serious disease has been excluded, and that fullrecovery can be expected Requests for further investigationsshould be resisted A reassuring and encouraging approach isbeneficial Any associated psychiatric disorder such asdepression should be treated appropriately and interpersonalconflicts discussed with the patient and key relatives Thesepatients are often highly suggestible so they respond well

to predictions of recovery Given that they are preoccupiedwith physical complaints, their recovery can be assisted

by providing a physical framework for improvement.Physiotherapy is particularly effective in restoring the power

to a paralysed or weakened limb Using such an approach withpatients with hysterical gait disorders, about half recovercompletely during a three to four day hospital stay.47

In resistant cases an abreaction interview under intravenoussedation is useful Several drugs can be used to provide therequired level of sedation but benzodiazepines such asdiazepam are probably the safest During the interview thepatient is encouraged to explore and ventilate any emotionalproblems that have hitherto not been discussed This can have

a cathartic effect and is often followed by dramaticimprovement, which is facilitated if the interviewer predictsrecovery before and during the interview An interview canalso be useful to clarify the diagnosis and gain access toundisclosed psychopathology It appears particularly useful fordissociative amnesia and should be used if the memoryimpairment does not begin to improve within a few days of itsonset Hypnosis can be employed as an alternative procedure

if the clinician has sufficient experience of the technique

Somatoform disorders and neurasthenia

These disorders tend to be chronic and are associated withrepeated consultations for physical symptoms and requests formedical investigations despite previous negative findings

They are unlikely to present as emergencies but as part of

a lengthy history, at times exceeding 30 years, of chronicill-health and contact with medical services

Acute psychotic disorders

Psychotic symptoms are common complications ofneurological and other medical illnesses In most cases theyare due to delirium and represent the acute effects on mentalfunctioning of intracranial lesions, or metabolic or toxicdisturbance elsewhere in the body The characteristic features

of delirium are alterations of consciousness, muddledthinking, mood change, psychomotor abnormalities – eitherretardation or excitability – and perceptual disturbances in thevisual or tactile senses In severe cases there are florid visualand tactile hallucinations The aetiology and management ofdelirium have already been reviewed in this series.48

Psychotic symptoms arising during treatment of Parkinson’sdisease can often lead to diagnostic problems becausepsychological symptoms may be due to the disease itself or toprescribed drugs Anticholinergic drugs such as benzhexol,procyclidine, and orphenadrine can precipitate acute deliriumwhich resolves when the drug is withdrawn Quickerresolution can be achieved by parenteral administration of theanticholinesterase physostigmine Psychotic symptoms alsooccur during treatment with levodopa but other acutepsychological reactions can develop with this drug includingdepression, hypomania, and hypersexuality Antipsychoticsmay exacerbate the neurological symptoms of Parkinson’sdisease Clozapine, which has low D2 receptor affinity, hasbeen recommended as an effective treatment for psychoticdisorders associated with levodopa therapy.49 The drug iscurrently available for the treatment of resistant schizophrenia:its use is restricted because of the appreciable risk ofagranulocytosis which occurs in at least 1% of cases Other sideeffects of clozapine include convulsions and hypersalivation

In the light of these complications, the more recentlyintroduced atypical antipsychotics such as risperidone andolanzapine may be preferred to clozapine

Psychotic symptoms without features of delirium ordementia can occur in association with a wide range of cerebral

disorders, notably epileptic foci, cerebral tumour, cerebraltrauma, Wilson’s disease, and Huntington’s disease Thepsychosis can take the form of a schizophrenic or affectivedisorder The site of the lesion has been considered to influencethe pattern of symptoms A schizophrenic presentation hasbeen particularly associated with temporal lobe lesions in thedominant hemisphere, whereas affective disorders have beenlinked with lesions in the non-dominant hemisphere Not allstudies have demonstrated such an association with laterality.50

Occasionally transient psychotic disorders develop in clearconsciousness in the absence of evidence of structural braindamage The most striking clinical symptom is a welldeveloped delusional system, nearly always of a paranoidnature These psychotic disorders are seen most commonly inpatients who have been admitted acutely to hospital and whohave been treated in intensive care or coronary care unitswhich they perceive as bewildering and threatening Thedelusions typically involve members of the nursing or medicalstaff whom the patient may accuse of trying to poison or evenkill him or her In response to these delusions there may besudden outbursts of aggression towards members of staff orattempts to leave hospital against medical advice Psychoses ofthis nature are probably precipitated by the emotional impact

of the illness and by the disruption it causes to the patient’sfamiliar environment

Management of acute psychoses

When the psychosis is believed to be triggered by theperceived stress of the treatment environment, it is advisable totransfer the patient as soon as possible to a less intimidatingenvironment, for example from an intensive care unit to ageneral ward or from a general ward to the patient’s home, ifadequate care is available there Rapid tranquillisation may beneeded if there is aggressive or disruptive behaviour.Chlorpromazine or haloperidol may be given in doses similar

to those used in acute mania If very rapid control of symptoms

is required, diazepam can be given intravenously in a dose of5–10 mg as Diazemuls Intravenous therapy ensures nearimmediate delivery of the drug to its site of action andeffectively avoids the danger of inadvertent accumulation of

slowly absorbed intramuscular doses Note also thatintravenous doses can be repeated after only 5–10 minutes if

no effect is observed.51A recent review of rapid tranquillisationhas recommended that the mainstay of pharmacologicaltreatment should be parenteral benzodiazepines used with duecare.52In an emergency, and if the patient is considered to lackcapacity to give or withhold consent to treatment, medicationcan be administered under common law if it is thought to be

in the person’s best interest, for example to reduce the risk ofviolence or self-harm until a Mental Health Act assessment isarranged.53,54 A patient’s capacity to consent may betemporarily affected by many factors, including confusion,panic, shock, pain, fatigue, or drugs

These antipsychotic drugs are well recognised as havingunpleasant extrapyramidal side effects The most dangerous ofthese, but fortunately the least frequent, is the neurolepticmalignant syndrome in which extrapyramidal rigidity andakathisia develop abruptly or within a few days.55 Pyrexia isalways present, together with autonomic disturbances includingprofuse sweating, increased salivation, hyperventilation,tachycardia, and labile blood pressure Laboratory investigationsshow a leucocytosis and a raised creatinine kinase The incidence

of the condition is not known but is probably well under 1% ofcases treated with antipsychotics if strict diagnostic criteria areapplied Antipsychotics should be stopped immediately once thecondition is diagnosed Rapid improvement is seen if adopamine agonist such as bromocriptine is administered, andthe mortality rate has been considerably reduced by thistreatment The newer “atypical” antipsychotics should be used

in the treatment of psychotic disorders associated with organicbrain lesions If antipsychotic drugs are ineffective orcontraindicated, lorazepam 2–4 mg can be given orally orintramuscularly every two hours, with a maximum daily dose

of 10 mg

Personality change due to cerebral disease

A change in personality is likely to follow diffuse, severedamage to the brain of the sort that is commonly seen aftermajor head injury, but which can also occur in association

with cerebral tumours, cerebrovascular disease, dementias,and encephalitis The changes in behaviour are persistent andoften develop gradually, but they may lead to suddenoutbursts of impulsivity which create acute problems Asurvey of patients who had survived a severe head injuryreported that the prevalence of personality change increasedwith time; at five years after the injury, 74% of patients weredescribed by their relatives as having undergone a personalitychange Threats or gestures of violence had occurred in 54%while there had been an actual assault on a relative in 20% ofcases Other problems which had occurred included troublewith the law (31%), childishness (38%), and being upset byminor changes in routine (38%).56

Brain injury can produce an exaggeration of premorbidpersonality traits so that a person with an obsessionalpersonality becomes even more meticulous and preoccupiedwith detail, whereas someone with an antisocial personalitybecomes more impulsive, irresponsible, and aggressive Among

a group of patients with Wilson’s disease, psychopathicpersonality traits were significantly related to the severity ofneurological symptoms, particularly dysarthria, bradykinesia,and rigidity.57If the damage is localised to particular parts ofthe brain, the personality changes tend to be more specific.58,59

Frontal lobe damage is associated with apathy, lack ofinitiative, tactlessness, irritability, euphoria, and disinhibition.Although the patient’s demeanour is predominantly listlessthere may be unpredictable outbursts of aggression or sexuallydisinhibited behaviour Social skills tend to be lost with afailure to consider the feelings of other people and the impact

of tactless remarks The ability to plan ahead is impaired, withthe result that irresponsible decisions may be taken with littleconcern about their outcome

Irritability and aggressive outbursts are especially associatedwith temporal lobe pathology Herpes simplex encephalitishas an affinity for the temporal lobes, so behaviouralmanifestations are common during the acute stages of theillness and after recovery if there is residual brain damage.Patients who survive temporal lobe damage may manifest thefeatures of the Klüver–Bucy syndrome which includehypersexuality, aggressive outbursts, excessive oral behaviour,and visual agnosia

Management of aggressive behaviour

Box 5.5 summarises the conditions in which unpredictableoutbursts of aggression may occur

Patients who are potentially violent should not beinterviewed in an isolated room; when the risk is particularlyhigh the doctor should not be alone with such patients.Adequate staff should be available nearby The immediateaims are to control the risk of violence, to diagnose theunderlying disorder, and to administer specific treatment Adetailed history and full physical and mental state assessmentare rarely possible; immediate treatment has to be arrangeduntil complete information is available

Every effort should be made to calm patients bysympathetic understanding and reassurance Violence is often

a response to paranoid experiences and patients can bepacified if they believe that the doctor appreciates the reasonsfor their behaviour If this can be achieved medication may beaccepted voluntarily; otherwise compulsory treatmentbecomes unavoidable if patients are endangering themselves

or others Physical restraint should be applied with theassistance of security staff; the safety of all involved is bestensured by having more than a sufficient number of staffavailable At least one person should restrain each limb whileanother administers medication.60,61 Haloperidol 10–20 mgintramuscularly is the preferred drug, except for cases ofalcohol or drug misuse or patients with serious physicalillness Benzodiazepines should then be given instead; forexample diazepam 10 mg by slow intravenous injection orlorazepam 2 mg intramuscularly Once the risk of aggression

Box 5.5 Neurological and psychiatric disorders associatedwith aggression

has been controlled it is nearly always necessary to arrangeadmission to an appropriate inpatient unit to begin adiagnostic evaluation and specific treatment for theunderlying condition when the diagnosis has been clarified.

Management of acute behaviour disturbances

• Acute behaviour disturbances are commonly encountered in neurological practice Psychiatric disorders may accompany neurological disease or may present with somatic symptoms that suggest neurological lesions but for which no organic pathology can be detected.

• Evidence of intellectual impairment, particularly reduced level of consciousness, disorientation, and memor y deficits, enables conditions such as delirium, which are due to over t physical disease, to be distinguished from affective, anxiety, and acute psychotic disorders The psychotic disorders are not usually associated with over t physical disease although in a few patients they may be the presenting manifestations of an occult lesion in the central ner vous system or elsewhere The likelihood of this increases with advancing age and if there is no previous personal

or family histor y of psychiatric illness or no apparent psychosocial precipitating factor.

• Successful management requires close collaboration between neurologists and psychiatrists It is essential to be familiar with the psychotropic drugs that are most appropriately used for patients with neurological disorders Tricyclic antidepressants and selective serotonin re-uptake inhibitors are both used for treating depression, but the latter group of drugs may prove more acceptable because of their lower incidence of side effects.

• Acute psychotic disorders require treatment with neuroleptic drugs, the main groups being the phenothiazines and butyrophenones Rapid control of acute psychosis is essential when it is associated with aggressive behaviour and it is important that clinicians are familiar with regimens of parenteral neuroleptic administration and indications for compulsory treatment.

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epilepticus

SIMON SHORVON, MATTHEW WALKER

Tonic-clonic status epilepticus can be defined as a condition inwhich prolonged or recurrent tonic-clonic seizures persist for

30 minutes or more.1 Most tonic-clonic seizures last less thantwo minutes; nevertheless many seizures that continue for lessthan 30 minutes self-terminate.2,3Treatment of the premonitorystages is likely to be more successful than treatment in the laterstages and so treatment should commence as soon as it isapparent that the seizure is persisting (a tonic-clonic seizure ofmore than five minutes duration) or there is a significantworsening of a patient’s normal seizure pattern

The annual incidence of tonic-clonic status epilepticus variesconsiderably from study to study depending on the populationanalysed; estimates have ranged from 4 to 28 cases per 100 000persons (2000–14 000 new cases each year in the UnitedKingdom).4–7It is most frequent in the young, in whom it alsotends to be longer lasting Status epilepticus is also commoner inepileptic patients with mental handicap, or with structuralcerebral pathology (especially in the frontal lobes) In establishedepilepsy, status epilepticus can be precipitated by drugwithdrawal, intercurrent illness, or metabolic disturbance, or theprogression of the underlying disease, and is more common insymptomatic than in idiopathic epilepsy About 5% of allepileptic adult clinic patients will have at least one episode ofstatus epilepticus in the course of their epilepsy,1and in childrenthe proportion is higher (10–25%).1,8 Most status epilepticusepisodes, however, do not develop in known epileptic patients,and in such cases are almost always due to acute cerebraldisturbances; common causes are cerebral infection, trauma,cerebrovascular disease, cerebral tumour, acute toxic (usuallyalcohol related) or metabolic disturbance, or febrile illness (in

children) Studies have shown status epilepticus to account forabout 4% of admissions to neurological intensive care, and 5%

of all visits to a university hospital casualty department.9 Themortality of status epilepticus is about 20% Most patients die

of the underlying condition, rather than the status epilepticusitself or its treatment.1,5,10 Permanent neurological and mentaldeterioration may result from status epilepticus, particularly inyoung children, the risks of morbidity being greatly increasedthe longer the duration of the status epilepticus episode.1

Furthermore status epilepticus can result in chronic epilepsy, andindeed 43% of those with acute symptomatic status epilepticushave a subsequent unprovoked seizure compared to 13% ofthose with acute symptomatic seizures Tonic-clonic statusepilepticus is only one of the forms of status epilepticus (Box 6.1),and indeed is not the most common Nevertheless, unlike mostother types, it is a medical emergency Treatment is urgentbecause the longer seizures continue, the more difficult they

Box 6.1 Classification of status epilepticus

Confined to the neonatal period

Neonatal status

Status in neonatal epilepsy syndromes

Confined to infancy and childhood

Infantile spasm (West’s syndrome)

Febrile status epilepticus

Status in childhood myoclonic syndromes

Status in benign childhood par tial epilepsy syndromes

Electrical status during slow wave sleep (ESES)

Syndrome of acquired epileptic aphasia

Occurring in childhood and adult life

Absence status

Epilepsia par tialis continua (EPC)

Myoclonic status in coma

Specific forms of status in mental handicap

Myoclonic status in other epilepsy syndromes

Non-convulsive simple par tial non-convulsive status

Complex par tial status

Boundar y syndromes

Confined to adult life

De novo absence status of late onset

Derived from Shor von 1

become to treat, and the worse the outcome Successfulmanagement is a balance between the often conflictingrequirements of controlling seizure activity as quickly aspossible, and minimising physiological changes and medicalcomplications.

Tonic-clonic status epilepticus as a staged

phenomenon

Although the original WHO definition referred to statusepilepticus as an “unvarying and enduring epilepticcondition”, it is, on the contrary, an evolving state.1Indeed, itcan be staged by clinical and electrographic criteria,physiological compromise, occurrence of excitotoxicity, andresponse to treatment

Clinical and electrographic stages

The pattern of seizures in tonic-clonic status epilepticusevolves over time There is often a premonitory stage ofminutes or hours, during which epileptic activity increases infrequency or severity from its habitual level This clinicaldeterioration is an augury, often stereotypical, of impendingstatus epilepticus, and urgent therapy may well prevent its fulldevelopment At the onset of status epilepticus, the attackstypically take the form of discrete grand mal seizures As timepasses, however, the convulsive motor activity often evolves,first to become continuous, and then clonic jerking becomesless pronounced and less severe, and finally ceases altogether.This is the stage of “subtle status epilepticus”, by which timethe patient will be deeply unconscious, and the prognosis ispoor These stages are not seen in all patients; they can bemodified by concomitant medication, and there is often avarying time period between each stage In parallel to thisclinical evolution, a progressive change in the EEG has alsobeen reported in animal models.11 The initial stage is that ofdiscrete seizures; then there is waxing and waning of ictaldischarges which progresses to continuous ictal discharges.The final stages are continuous ictal discharges punctuated byflat periods, and then periodic epileptiform discharges on aflat background These electrographic and clinical stages

importantly relate to underlying neuronal damage, and also toprogressive difficulty in treating the status epilepticus (seebelow) The extent to which this EEG progression occurs inhumans is less certain.11–12

Physiological stages

The physiological changes in status epilepticus are oftendivided into two phases, the transition from phase 1 to 2occurring after about 30–60 minutes of continuousseizures.1,13–15 Although this is a generally useful concept, itmust be recognised that there is great variation Both the rateand extent of physiological change are dependent on manyother factors, including the anatomical site of the epilepticfocus, the severity of the seizures, the underlying aetiology,and the treatment employed Nevertheless, this staging ofchanges is helpful in devising a rational plan for therapy Phase 1

From the onset of status epilepticus, seizure activity greatlyincreases cerebral metabolism Physiological mechanisms areinitially sufficient largely to compensate for this perturbation.Cerebral blood flow is increased, and initially the delivery ofglucose to the active cerebral tissue is maintained Latersystemic and cerebral lactate levels rise, and a profound lacticacidosis may develop.16 There are massive cardiovascular andautonomic changes Blood pressure rises, as does cardiacoutput and rate The autonomic changes result in sweating,hyperpyrexia, bronchial secretion, salivation, vomiting, andepinephrine (adrenaline) and noradrenaline release Endocrineand autonomic changes also cause an early rise in sugar levels Phase 2

As the seizure activity progresses, the compensatoryphysiological mechanisms begin to fail Cerebral autoregulationbreaks down progressively, and thus cerebral blood flowbecomes increasingly dependent on systemic blood pressure.13–15

Hypotension develops due to seizure-related autonomic andcardiorespiratory changes and drug treatment, and in terminalstages may be severe The falling blood pressure results infailing cerebral blood flow and cerebral metabolism The high