(BQ) Part 1 book Textbook of clinical neurology has contents: A brief history of neurology, the neurological consultation, an overview over nervous system and muscles. technical investigations in neurology, strength and sensation, motor control,... and other contents.
Trang 1Textbook of
Clinical Neurology
editors: J.B.M Kuks J.W Snoek
Trang 3Textbook of Clinical Neurology
Trang 4© Bohn Stafleu van Loghum is een imprint van Springer Media B.V., onderdeel van Springer Nature 2018
This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.
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Trang 5This edition of the Textbook of Clinical Neurology is
a translation of the original Dutch textbook edited
back in the day by Prof H.J.G.H Oosterhuis It has
proved highly useful over the years and we therefore
decided to produce an English-language edition
The textbook is intended for medical and
paramedi-cal students, clerks and registrars Cliniparamedi-cal
neurol-ogy builds on the foundation of basic sciences,
hence in the first eleven chapters we have devoted
attention to basic concepts and only referred to
clin-ical pictures occasionally From Chapter 12 onwards
we deal with the various areas of clinical neurology,
referring back wherever necessary to the first eleven
chapters
The Dutch textbook has been constantly revised to
reflect new developments and in response to
com-ments by users – both teachers and students – thus
keeping it up to date both neurologically and
peda-gogically
We are aware that the book will be many readers’
first encounter with clinical neurology and have
therefore ensured that neurological terms and
con-cepts are introduced in such a way that, as far as
possible, readers with as yet limited medical
knowl-edge do not need to have access to other reference
works in order to continue reading without losing
the thread Having both been active practitioners of
general clinical neurology and lecturers and deans
of education for many years, we trust we have
suc-ceeded in this
The textbook is supported by a website where test questions for each chapter are provided It also includes some up-to-date references to reviews in the neurological literature
We hope that this book will prove useful as a ence work for both students and medical practition-ers in the broadest sense
refer-We welcome any questions and comments and will endeavour to respond swiftly
J.B.M Kuks, MD PhD J.W Snoek, MD PhD
Clinical Neurology ConsultantsUniversity Medical Center GroningenThe Netherlands
j.b.m.kuks@umcg.nl
Trang 61 A brief history of neurology 1
1.1 Images from antiquity 2
1.2 The middle ages 2
1.3 The development of present-day knowledge 2
1.4 Research into the nervous system 3
1.5 Clinical neurology and related medical specialisms 3
2 The neurological consultation 5
2.1 History-taking 6
2.1.1 The seven dimensions of the problem 6
2.1.2 Heteroanamnesis 7
2.1.3 Family history 7
2.1.4 Other diseases, intoxications 7
2.1.5 Social history 7
2.1.6 What does the patient think it could be? 7
2.2 Physical neurological examination: often carried out only where indicated 7
2.3 Diagnostic tests 8
2.3.1 A priori considerations 8
2.3.2 Diagnostic value 9
2.4 Organizing information 9
2.5 Diagnostic follow-up 9
3 An overview over nervous system and muscles Technical investigations in neurology 11
3.1 Structure of the nervous system 13
3.2 Visualizing the peripheral nervous system 14
3.2.1 Computed tomography (CT) 14
3.2.2 Magnetic resonance imaging (MRI) 14
3.2.3 Radioisotope scanning 15
3.2.4 Ultrasound 15
3.3 The nerve 16
3.3.1 Functional structure 16
3.3.2 Histology and metabolism 16
3.3.3 Physiology at rest 17
3.3.4 Nerve action potential 17
3.3.5 Interneuronal communication 18
3.3.6 Abnormal nerve activity 18
3.4 The muscle 18
3.4.1 Functional structure 18
3.4.2 Microscopic anatomy 19
3.4.3 Neuromuscular transmission 19
3.4.4 The muscle in action 19
3.4.5 Symptoms of muscular disorders 20
3.5 The motor unit 21
3.6 Electromyography 21
3.6.1 Needle EMG 21
3.6.2 Measuring nerve conduction 21
3.7 Physiological measurements of the central nervous system 23
3.7.1 Electroencephalography 23
3.7.2 The indications for EEG 23
3.7.3 Magnetoencephalography 24
3.8 Other diagnostic tests 25
3.8.1 Causes of neurological diseases 25
3.8.2 Blood tests 25
3.8.3 Neuropathological tests 25
Trang 74.1 Physiological background 28
4.1.1 The spinal reflex 28
4.1.2 Several types of spinal reflexes 28
4.1.3 Central control of spinal reflexes 28
4.1.4 Increased and depressed reflexes 29
4.1.5 Central paresis 30
4.1.6 Sensory feeling 30
4.1.7 Central sensory pathways 30
4.1.8 Somatotopy of the sensory system 32
4.1.9 Segmental distribution 32
4.2 Examination of the motor and sensory system 32
4.2.1 Examination of muscle function 33
4.2.2 Examination of reflexes 39
4.2.3 Testing sensation 41
4.3 Central hemiplegia 44
4.4 Non-Organic disorders 45
4.5 Measurement of central motor and sensory disturbances 46
5 Motor control 47
5.1 Central motor control 48
5.1.1 The parietal sensory cortex plays an important role in movement initiation 48
5.1.2 The basal ganglia 49
5.1.3 The cerebellum 53
5.1.4 The examination of central motor function 54
5.1.5 Inspection and observation 54
5.1.6 Eye movements 54
5.1.7 Dysarthria 55
5.1.8 Upper limb ataxia 55
5.1.9 Lower limb ataxia 55
5.1.10 Truncal movements 56
5.1.11 Muscle tone 56
5.1.12 Muscle stretch reflexes 56
5.2 Gait and stance 56
5.2.1 Postural reflexes 56
5.2.2 Examination 56
6 Brainstem and cranial nerves 59
6.1 Functional arrangement of the brainstem 61
6.1.1 Overview 61
6.1.2 Functions of the brainstem 61
6.1.3 Motor control in the event of brainstem disorder 64
6.2 The cranial nerves 64
6.2.1 Smell 65
6.2.2 Pupillary responses and eyelid movement 66
6.2.3 Eye movements 67
6.2.4 Facial sensation 70
6.2.5 Taste 70
6.2.6 Facial movement 71
6.2.7 Hearing 71
6.2.8 Balance 72
6.2.9 Chewing, speaking and swallowing 73
6.2.10 The special characteristics of the accessory nerve 73
6.3 Examination of the cranial nerves 73
6.3.1 Testing smell 73
6.3.2 Resting-state eye examination and pupillary response testing 73
6.3.3 Examination of eye movements 74
Trang 86.3.4 Examination of facial sensation 75
6.3.5 Examination of taste sensation 75
6.3.6 Facial motor control 75
6.3.7 Hearing examination 75
6.3.8 Examination of the balance organ 76
6.3.9 Examination of the tongue and throat musculature 76
6.3.10 Examination of the accessory nerve 77
6.4 Examination of a comatose patient 77
6.5 Abnormal respiration associated with brainstem problems 79
6.6 Bulbar or pseudobulbar disorder? 79
6.7 Brainstem syndromes 80
6.7.1 Occlusion of the basilar artery 80
6.7.2 Locked-in syndrome 80
6.7.3 Wallenberg’s syndrome 80
6.7.4 Foville’s syndrome 81
7 Autonomic nervous system, hypothalamus and pituitary gland 83
7.1 The sympathetic and parasympathetic systems 85
7.1.1 The sympathetic system 85
7.1.2 The parasympathetic system 85
7.1.3 Afferent fibres of the autonomic nervous system 85
7.2 The hypothalamus 86
7.2.1 Temperature regulation 86
7.2.2 Regulation of blood osmolarity 86
7.2.3 Growth and sexual maturation 87
7.2.4 Sleep regulation 87
7.3 Pituitary gland 87
7.4 Autonomic regulation of blood pressure and heart action 88
7.5 Autonomic control of the eye 88
7.5.1 Regulation of pupil diameter 88
7.5.2 Sympathetic elevation of the eyelid 89
7.5.3 Horner’s syndrome 89
7.6 Micturition and defecation 89
7.6.1 Micturition 89
7.6.2 Neurogenic bladder disorders 90
7.6.3 Myogenic bladder disorders 91
7.6.4 Defecation 91
7.7 Sexual function disorder 91
8 The higher cerebral functions 93
8.1 The functions of the cerebellar cortex 95
8.1.1 Diffuse and local cortical disorders 95
8.1.2 Anatomical arrangement 95
8.1.3 Language dominance 96
8.1.4 Emotion and memory 96
8.1.5 Cortical functions are more or less localized 97
8.2 Aphasia 97
8.2.1 Language and speech 97
8.2.2 Fluent and non-fluent language disorders 97
8.2.3 Categorization of aphasia 97
8.2.4 The impact of aphasia 98
8.2.5 Reading, writing and arithmetic 98
8.3 Apraxia 98
8.4 Agnosia 99
8.4.1 Klüver-bucy syndrome 99
8.5 Aprosody 99
8.6 Spatial disorders 100
Trang 98.7.1 Short-term and long-term memory disorders 100
8.7.2 Amnestic syndrome 100
8.7.3 Wernicke’s encephalopathy 101
8.7.4 Transient global amnesia 101
8.8 Physical causes of psychological dysregulation 102
8.8.1 Organic psychosyndrome 102
8.8.2 The two forms of frontal psychosyndrome 102
8.8.3 Psychological phenomena associated with the posterior cortex 102
8.9 Delusions and hallucinations 102
8.10 Ill-defined symptoms 102
8.11 Testing of higher functions 103
9 The visual system 105
9.1 Vision and visual fields 106
9.1.1 From eye to cortex 106
9.1.2 Central visual information processing 106
9.1.3 Visual field defects 106
9.2 Higher visual disorders 108
9.2.1 Visual agnosia 108
9.2.2 Losing sight of things 109
9.2.3 Positive visual phenomena 109
9.3 Examination and testing of the visual system 110
9.3.1 Vision 110
9.3.2 Visual field test 110
9.3.3 Fundoscopy 111
10 Cerebral meninges and the cerebrospinal fluid system 113
10.1 Cerebral meninges 114
10.2 Production and drainage of fluid 114
10.3 Lumbar puncture 114
10.4 Measuring cerebrospinal fluid pressure 115
10.5 Cerebrospinal fluid analysis 115
10.6 Cerebrospinal fluid abnormalities 117
10.7 Cerebrospinal fluid circulation disorders 117
10.7.1 Hydrocephalus 117
10.7.2 Obstructive and communicating hydrocephalus 117
10.7.3 Acute and chronic hydrocephalus 119
10.7.4 Diagnosis of hydrocephalus 119
10.8 Clinical problems associated with fluid circulation disorders 119
10.8.1 Obstructive hydrocephalus 119
10.8.2 Communicating hydrocephalus 120
10.8.3 Idiopathic intracranial hypertension 120
10.8.4 Cerebrospinal fluid hypotension 121
11 The cerebrovascular system 123
11.1 The blood supply to the CNS 124
11.1.1 Arterial blood supply to the brain 124
11.1.2 Venous drainage 124
11.1.3 The blood-brain barrier 126
11.2 The cerebral blood flow 126
11.2.1 Physiology 126
11.2.2 Cerebral infarction 127
11.2.3 Relative hypoxia 127
11.2.4 Vasogenic cerebral oedema 128
11.2.5 Venous cerebral thrombosis 128
Trang 1011.3 Pathological vascular changes 128
11.3.1 Atherosclerosis 128
11.3.2 Aneurysm 128
11.3.3 Arteriovenous malformation 129
11.3.4 Dissection of an artery 129
11.4 Cerebrovascular diagnostics 130
11.4.1 Angiography 130
11.4.2 Ultrasonography 130
11.4.3 Perfusion and diffusion measurement 131
12 Diseases of the muscle and neuromuscular junction 133
12.1 Classification of neuromuscular disorders 135
12.2 Acquired and congenital disorders 135
12.3 Diagnostic tests 136
12.3.1 Strategy 136
12.3.2 Muscle biopsy 136
12.4 Congenital muscular diseases 137
12.4.1 Dystrophinopathy 137
12.4.2 Facioscapulohumeral muscular dystrophy 138
12.4.3 Myotonic dystrophy 139
12.4.4 Limb-girdle dystrophy 140
12.4.5 Channelopathies 140
12.4.6 Metabolic myopathies 140
12.5 Acquired myopathies 141
12.5.1 Inflammatory myopathies 141
12.5.2 Inclusion body myositis 142
12.5.3 Polymyalgia rheumatica 142
12.5.4 Non-inflammatory acquired muscular diseases 142
12.6 Diseases of the neuromuscular junction 142
12.6.1 Clinical signs 142
12.6.2 Myasthenia gravis 142
12.6.3 Lambert-Eaton myasthenic syndrome 144
12.6.4 Differential diagnosis of fluctuating muscle weakness 145
12.7 Causes of muscle cramp 145
12.8 Chronic tiredness without muscular disease 145
12.9 Muscular diseases in medical practice 146
13 Disorders of the motor neurons, nerve roots and peripheral nerves 147
13.1 Classification of nerve disorders 149
13.1.1 Symptoms and signs 149
13.1.2 Involuntary movements and neuropathic symptoms 149
13.1.3 Autonomic symptoms 149
13.1.4 Electromyography 150
13.1.5 Further tests for neuropathies 151
13.2 Diseases of the nerve cell body: neuronopathy 151
13.2.1 Symptoms 151
13.2.2 Spinal muscular atrophy 151
13.2.3 Amyotrophic lateral sclerosis 152
13.2.4 Less severe motor neuron diseases 153
13.3 Disorders of the nerve root: radiculopathy 153
13.3.1 Radiculopathy is often accompanied by radiating pain 153
13.3.2 Guillain-Barré syndrome 153
13.4 Mononeuropathy 154
13.4.1 Damage to a peripheral nerve 154
13.4.2 Causes 154
13.4.3 Surgery for peripheral nerve lesions 155
Trang 1113.5.1 Brachial plexus injuries 155
13.5.2 Arm nerve injuries 155
13.5.3 Carpal tunnel syndrome 158
13.6 Mononeuropathies of the leg 159
13.6.1 Lumbosacral plexus injury 159
13.6.2 Nerve injury 159
13.7 Polyneuropathies 160
13.7.1 Symptoms 160
13.7.2 Causes 160
13.7.3 Hereditary neuropathies 165
13.7.4 Further investigation 166
13.7.5 Treating polyneuropathy 166
14 Neurological pain syndromes 167
14.1 Pain is a subjective phenomenon 169
14.2 Classification of pain 169
14.2.1 Nociceptive pain 169
14.2.2 Neuropathic pain 169
14.2.3 Functional neurological pain disorders 170
14.2.4 Basic principles of pain management 170
14.3 Pain in the neck and arm 170
14.3.1 Cervicobrachial syndrome 170
14.3.2 Cervical radicular syndrome 171
14.3.3 Thoracic outlet syndrome 171
14.4 Pain in back and leg 172
14.4.1 Back pain, acute low back strain and ischialgia 172
14.4.2 Lumbar herniated nucleus pulposus (HNP) 172
14.4.3 Lumbar stenosis 176
14.5 Pain in the trunk 176
14.6 Complex regional pain syndrome 177
15 Diseases of the spinal cord 179
15.1 Anatomy of the spinal column and spinal cord 181
15.1.1 Location of the spinal cord 181
15.1.2 Loss of function due to spinal cord injury 181
15.2 Radiological diagnosis 182
15.2.1 Conventional X-ray examination 182
15.2.2 MRI scan 183
15.3 Traumatic spinal cord injuries 183
15.3.1 Transient and permanent loss of function 183
15.3.2 Traumatic spinal cord syndromes 184
15.3.3 The value of surgical intervention in traumatic spinal cord injuries 187
15.3.4 Late effects of cervical trauma 187
15.4 Non-traumatic spinal cord injuries 188
15.4.1 Clinical approach 188
15.4.2 Imaging tests for myelopathy 188
15.4.3 General supplementary tests 188
15.4.4 Examination of CSF 188
15.5 Spinal cord compression due to non-traumatic causes 188
15.5.1 Clinical differences between extramedullary and intramedullary compression 188
15.5.2 Cervical spinal stenosis 189
15.5.3 Syringomyelia 190
15.5.4 Ventral transdural spinal cord herniation 190
15.5.5 Chiari malformation 191
15.5.6 Treatment of non-traumatic spinal cord compression 191
Trang 1215.6 Myelopathy without compression 192
15.6.1 Vascular disorders of the spinal cord 192
15.6.2 Transverse myelitis 193
15.6.3 Combined degeneration of the spinal cord 193
15.6.4 Vacuolar myelopathy in AIDS 194
15.6.5 Tropical spastic paraparesis 194
16 Disorders of the cranial nerves 195
16.1 General causes 196
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
17 Cerebral infarction and cerebral haemorrhage 207
17.1 Classification of cerebrovascular disorders 209
17.2 Causes and effects 209
17.2.1 Epidemiology and prognosis 209
17.2.2 Risk factors 209
17.3 Diagnosis 210
17.3.1 Clinical approach 210
17.3.2 Imaging 211
17.4 Clinical aspects of cerebral vascular occlusions 211
17.4.1 TIAs 211
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
17.5.1 Acute treatment 216
17.5.2 Stroke unit 216
17.5.3 Surgical decompression if there is a risk of cerebral herniation 217
17.5.4 Primary and secondary prevention 217
17.5.5 Carotid endarterectomy 218
17.5.6 Rehabilitation following a stroke 218
17.6 Intracranial haemorrhages 218
17.6.1 Primary hypertensive intracerebral haemorrhage 218
17.6.2 Lobar haematomas 219
17.6.3 Surgical removal of an intracerebral haematoma 219
17.7 Subarachnoid haemorrhage 219
17.7.1 Traumatic and non-traumatic SAHs 219
17.7.2 Clinical signs 220
17.7.3 Diagnosis 220
17.7.4 Monitoring and treatment 221
17.7.5 Residual symptoms 222
17.7.6 Subsequent bleeds 222
17.7.7 Aneurysms discovered by chance 222
Trang 1317.7.9 Perimesencephalic haemorrhage 222
17.7.10 Thunderclap headache 222
17.8 Cerebral venous sinus thrombosis 223
17.8.1 Clinical signs and diagnosis 223
17.8.2 Treatment 223
17.9 Primary and secondary cerebral vasculitis 224
17.10 Hypertensive encephalopathy 224
18 Epilepsy and other paroxysmal disorders 225
18.1 Seizures 226
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
18.2.5 Treatment 233
18.3 Non-epileptic seizures 236
18.3.1 Syncope 236
18.3.2 Sleep disorders 237
18.3.3 Psychogenic seizures 238
18.3.4 Drop attacks 239
18.3.5 Unconsciousness due to a reticular formation disorder 239
18.3.6 Hyperventilation 239
18.3.7 TIAs 239
18.3.8 Other non-epileptic seizures 239
19 Altered consciousness 241
19.1 Impaired consciousness 242
19.2 Treating comatose patients 242
19.3 Herniation syndromes 243
19.4 Metabolic coma 245
19.4.1 Causes and symptoms 245
19.4.2 Intoxication 246
19.4.3 Postanoxic coma 246
19.5 Non-convulsive status epilepticus 246
19.6 Altered but not lowered consciousness 247
19.6.1 Attention disorder 247
19.6.2 Twilight state 247
19.6.3 Delirium 247
19.6.4 Abulia 247
19.7 Vegetative state 247
19.8 Brain death 248
20 Head and brain injuries 249
20.1 Initial assessment and care for head traumas 251
20.2 Skull fractures and intracranial injuries 251
20.3 Severity of brain injuries 251
20.3.1 Clinical signs 251
20.3.2 Diffuse and focal injuries 252
20.3.3 Primary and secondary brain damage 252
20.3.4 Increased intracranial pressure following trauma 253
20.4 Initial assessment and treatment 254
20.4.1 Initial assessment 254
20.4.2 Mild head and brain injuries and intracranial abnormalities 254
20.4.3 Treatment of mild head and brain injuries 255
20.4.4 Treatment of more severe brain injuries 255
Trang 1420.4.5 The donor procedure 256
20.4.6 Vegetative state 256
20.5 Skull fractures 256
20.6 Post-traumatic intracranial complications 257
20.6.1 Epidural bleeding 257
20.6.2 Secondary deterioration in children 258
20.6.3 Subdural haematoma 258
20.6.4 Liquorrhoea 259
20.6.5 Cranial nerve damage 260
20.7 The prognosis after head injury 260
20.7.1 Physical sequelae 260
20.7.2 Cognitive and mental sequelae 260
20.7.3 Post-traumatic epilepsy 261
20.7.4 Chronic traumatic encephalopathy 261
21 Headache and facial pain 263
21.1 Headache: frequency and causes 264
21.2 Diagnosing migraine 264
21.2.1 The course of a migraine attack 264
21.2.2 The pathophysiology of migraine attacks 265
21.2.3 Unusual types of migraine 265
21.2.4 Treatment for migraine 266
21.3 Facial pain 266
21.3.1 Trigeminal neuralgia 266
21.3.2 Glossopharyngeal neuralgia 267
21.3.3 Trigeminal neuropathy 267
21.3.4 Temporomandibular disorder 267
21.3.5 Atypical chronic facial pain 267
21.4 Cluster headache 267
21.5 Temporal arteritis 268
21.6 Tension-type headache 268
21.7 Acute headache 268
21.8 Warning symptoms in cases of headache 269
22 Neurological tumours and neurological complications of malignant conditions 271
22.1 Neuro-oncology 273
22.2 Clinical symptoms and signs 273
22.2.1 General clinical symptoms 273
22.2.2 Local neurological symptoms 274
22.3 Primary tumours of the nervous system 274
22.3.1 Classification 274
22.3.2 Gliomas 275
22.3.3 Primitive neuroectodermal tumours 276
22.3.4 Meningiomas 276
22.3.5 Neuromas 277
22.3.6 Pituitary tumours 277
22.3.7 Craniopharyngiomas 277
22.3.8 Primary intracerebral lymphomas 278
22.4 Cerebral metastases 278
22.5 Leptomeningeal metastases 278
22.6 Vertebral metastases 280
22.7 Paraneoplastic symptoms 281
22.8 Complications of oncological treatment 282
22.8.1 Radiotherapy 282
22.8.2 Chemotherapy 282
Trang 1523.1 Intracranial infections 285
23.2 Bacterial meningitis 285
23.2.1 Clinical presentation 285
23.2.2 Diagnosing meningitis 285
23.2.3 Epidemiology and treatment 286
23.3 Brain abscess 287
23.3.1 Mechanism 287
23.3.2 Clinical presentation 287
23.3.3 Treatment 288
23.4 Viral and postviral diseases of the nervous system 288
23.4.1 Viral meningitis 288
23.4.2 Viral encephalitis 288
23.4.3 Herpes simplex encephalitis 289
23.4.4 Anterior poliomyelitis 289
23.4.5 Herpes zoster neuritis 290
23.4.6 Rabies 290
23.5 Neurological complications of HIV infections 290
23.5.1 Incidence 290
23.5.2 Cerebral toxoplasmosis 290
23.5.3 Progressive multifocal leukoencephalopathy 290
23.5.4 Cryptococcal meningitis 291
23.5.5 Primary central nervous system lymphoma 291
23.6 Tuberculosis of the central nervous system 291
23.7 Tetanus 291
23.8 Syphilis 292
23.9 Neuroborreliosis 292
24 Multiple sclerosis and related disorders 295
24.1 Pathophysiology 297
24.2 Clinical symptoms 297
24.3 Progression 298
24.4 Genetic and exogenous factors 299
24.5 Diagnosing MS 299
24.6 Treatment 300
24.6.1 Lifestyle recommendations 300
24.6.2 Shortening an exacerbation 300
24.6.3 Influencing the course of the disease 300
24.6.4 Treating the symptoms 301
24.6.5 Supporting the patient and family 302
24.7 Other diseases involving CNS demyelination 302
24.7.1 Acute disseminated encephalomyelitis 302
24.7.2 Transverse myelitis 302
24.7.3 Neuromyelitis optica 302
24.8 Disorders resembling multiple sclerosis 303
24.8.1 Neurosarcoidosis 303
24.8.2 Neurological complications of systemic lupus erythematosus 303
24.8.3 Neurological abnormalities in Sjögren’s syndrome 303
25 Spinocerebellar disorders 305
25.1 Classification of spinocerebellar disorders 306
25.2 Neurodegenerative disorders 307
25.2.1 Course 307
25.2.2 Selective loss of function 307
25.2.3 Hereditary and sporadic occurrence 307
Trang 1625.3 Spinocerebellar ataxia 308
25.3.1 Symptoms 308
25.3.2 Autosomal dominant ataxia 308
25.3.3 Autosomal recessive ataxia: friedreich’s ataxia 309
25.3.4 Non-hereditary ataxia 309
25.4 Hereditary spastic paraplegia and lateral sclerosis 310
26 Diseases of the basal ganglia 311
26.1 Parkinson’s disease 312
26.1.1 Causes 312
26.1.2 Motor symptoms and signs 312
26.1.3 Non-motor symptoms 313
26.1.4 Prevalence 314
26.1.5 Pathophysiology 315
26.1.6 Clinical diagnosis 315
26.1.7 Treatment 315
26.2 Atypical forms of parkinsonism 318
26.2.1 Vascular parkinsonism 318
26.2.2 Drug-induced parkinsonism 318
26.2.3 Parkinson-plus syndromes 318
26.3 Other movement disorders 319
26.3.1 Tremor 319
26.3.2 Chorea 321
26.3.3 Dystonia and dyskinesia 322
26.3.4 Myoclonus 323
26.3.5 Ballism 323
26.3.6 Excessive startle reactions 324
26.3.7 Tics 324
27 Dementia 325
27.1 The dementia spectrum 326
27.2 Epidemiology 326
27.3 Early symptoms and signs 326
27.4 History-taking and heteroanamnesis for suspected dementia 327
27.5 Alzheimer’s disease 327
27.5.1 Diagnostic criteria 327
27.5.2 Neuropathological substrate 328
27.5.3 Hereditary factors 328
27.5.4 Progression 328
27.5.5 Drug treatment 329
27.6 Vascular dementia 329
27.6.1 Dementia due to large cerebral infarctions 330
27.6.2 Dementia due to small vessel disease 330
27.7 Frontotemporal dementia 330
27.7.1 Subtypes 330
27.8 Dementia with Lewy bodies 331
27.9 Creutzfeldt-Jakob disease 332
27.10 Dementia due to AIDS 332
27.11 Paralytic dementia 333
28 Neurological abnormalities in children 335
28.1 History-taking and examination in children 337
28.1.1 History-taking 337
28.1.2 Examination 337
28.2 Neurological disorders in children 338
Trang 1728.3.1 Development of the central nervous system 338
28.3.2 Spina bifida 338
28.3.3 Impaired neuron proliferation and migration of neurons 340
28.3.4 Congenital disorders due to chromosomal aberrations 340
28.3.5 Abnormal skull shape and/or size 341
28.3.6 Teratogenic effects 341
28.3.7 Intrauterine infections 341
28.3.8 Porencephaly 342
28.3.9 Perinatal damage 342
28.3.10 Traumatic plexus injuries 342
28.4 Hereditary metabolic disorders 343
28.4.1 Intoxication diseases 343
28.4.2 Storage diseases 343
28.4.3 Diseases of energy regulation 344
28.5 Neurocutaneous disorders 344
28.5.1 Tuberous sclerosis 345
28.5.2 Neurofibromatosis 345
28.5.3 Encephalotrigeminal angiomatosis (Sturge-Weber Syndrome) 345
28.5.4 Von Hippel–Lindau disease 346
28.6 Childhood ataxia 346
28.6.1 Dandy-Walker malformation 346
28.6.2 Chiari malformation 347
28.6.3 Tumours in the cerebellum 347
28.6.4 Neurodegenerative disorders 347
28.6.5 Acute ataxia 347
28.7 Learning and behavioural problems 348
28.7.1 ADHD 348
28.7.2 Autism 348
28.7.3 Learning disorders 348
29 Neurological complications of non-neurological disorders and as adverse effects of therapy 349
29.1 Cardiovascular disorders 350
29.2 Endocrine disorders 350
29.3 Systemic disorders 351
29.4 Water and electrolyte balance disorders 351
29.5 Metabolic disorders and deficiencies 351
29.6 Haematological abnormalities 352
29.7 Drugs 352
29.8 Consequences of alcohol abuse 352
Supplementary Information 355
Appendix 1 356
Appendix 2 358
Register 359
Trang 18Professor J.B.M Kuks
Consultant Neurologist, University Medical Center Groningen,
Groningen, The Netherlands
Professor J.W Snoek
Consultant Neurologist, University Medical Center Groningen,
Groningen, The Netherlands
Authors
Dr M.C Brouwer (Chapter 23)
Consultant Neurologist, Amsterdam University Medical Center,
Amsterdam, The Netherlands
Professor O.F Brouwer (Chapter 18 and 28)
Consultant Pediatric Neurologist, University Medical Center Groningen,
Groningen, The Netherlands
Professor P Cras (Chapter 26 and 27)
Consultant Neurologist, Born Bunge Institute, Antwerp University
Hospital, Edegem, Belgium
Dr C.A van Donselaar (Chapter 18)
Consultant Neurologist, Clara Division, Rijnmond Medical Center
Rotterdam, Rotterdam, The Netherlands
Professor P.A van Doorn (Chapter 13)
Consultant Neurologist, Erasmus Medical Center Rotterdam, Rotterdam,
The Netherlands
Professor M.D Ferrari (Chapter 21)
Consultant Neurologist, Leiden University Medical Center, Leiden, The
Netherlands
Professor R.J.M Groen (Chapter 14 and 15)
Consultant Neurosurgeon, University Medical Center Groningen,
Groningen, The Netherlands
Dr J Haan (Chapter 21)
Consultant Neurologist, Rijnland Hospital Leiderdorp and Leiden
University Medical Center, Leiden, The Netherlands
Professor J.J Heimans (Chapter 22)
Consultant Neurologist, Amsterdam University Medical Center,
Amsterdam, The Netherlands
Dr B Jacobs (Chapter 20)
Consultant Neurologist, University Medical Center Groningen,
Groningen, The Netherlands
Professor H.P.H Kremer (Chapter 25)
Consultant Neurologist, University Medical Center Groningen, Groningen, The Netherlands
Professor T van Laar (Chapter 26)
Consultant Neurologist, University Medical Center Groningen, Groningen, The Netherlands
Dr P.J Nederkoorn (Chapter 17)
Consultant Neurologist, Amsterdam University Medical Center, Amsterdam, The Netherlands
Dr B.W van Oosten (Chapter 24)
Consultant Neurologist, Amsterdam University Medical Center, Amsterdam, The Netherlands
Professor P Scheltens (Chapter 27)
Consultant Neurologist, Amsterdam University Medical Center, Amsterdam, The Netherlands
Dr M Uyttenboogaart (Chapter 11 and 17)
Consultant Neurologist, University Medical Center Groningen, Groningen, The Netherlands
Professor M.A.A.P Willemsen (Chapter 28)
Consultant Pediatric Neurologist, St Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
Trang 19© 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_1
A brief history of neurology
Abstract
It took some time for our awareness of the nervous system to evolve: it was only after
the Middle Ages that the current concepts accepted in regular Western medicine were
developed Important foundations for neurological theory were laid down in the 19th
century These were corroborated using scientific techniques in the 20th and 21st
cen-turies, and many of these methods have become normal features of clinical practice The
substantial expansion of knowledge and understanding has given rise to more and more
specialist fields of neurology
1.5 Clinical neurology and related medical specialisms – 3
Trang 201 function began to become clearer in the 17th century Increas-The relationship between anatomical structure and brain
ing importance was attached to the cerebral cortex, compared with the fluid-filled ventricles Thomas Willis, Professor of Natural Philosophy at Oxford, divided the brain into functional areas, with the folds and grooves of the cerebral cortex con-taining memory and will, and the involuntary processes being directed by the cerebellum Another 17th century philosopher, Descartes, put forward the idea that the soul must be located in the pineal gland, because it was an unpaired organ right in the middle of the brain
knowledge
It became clear around 1760 that damage to the brainstem could cause respiratory arrest Theories on the locations of par-ticular functions in the cerebral cortex continued to be devel-oped in the 18th century (Swedenborg) Motor and sensory nerves were identified throughout the body in the early 19th century (Bell, Magendie) This made it clear that sensory infor-mation was processed in the dorsal part of the spinal cord and motor function was produced by the ventral part
The first notions of the locations of specific functions in the brain date back to the end of the 18th century, when the Austrian scientist Gall developed theories on the subject, link-ing psychological functions, character and temperament to physical characteristics He supported his theories with obser-vations of patients with limited brain injuries, but he saw what
he wanted to see Substantial reservations were expressed about Gall’s phrenology in the first half of the 19th century, along with serious doubts about his brain localization theories The French scientist Paul Broca, for instance, did not agree that mental functions were linked to certain parts of the cortex, until he found abnormalities in the frontal lobe of a patient with motor aphasia He explained that speech must emanate from this part of the brain in a classic article in 1861 In 1874 Wernicke discovered that there were good arguments for say-ing that language comprehension must take place towards the rear of the temporal lobe and made the ground-breaking pro-nouncement that speech disorders could be caused not only by loss of function in certain parts of the cortex but also by prob-lems with the connections between them
Later, in the second half of the 19th century, there were increasing attempts to link clinical symptoms and signs to findings from pathological examination of the brain (Hughlings Jackson), and electrical stimulation experiments were carried out on the brains of laboratory animals (Fritsch and Hitzig) Good arguments were thus found for saying that the cortex must be organized along somatotopic lines Motor func-tions were localized in the anterior areas of the brain, sensory functions in the posterior areas At the same time, however, it became clearer that intellect and memory could not be linked
to specific parts of the brain
Through the ages we very gradually developed some
under-standing of the processes going on in the nervous system
In various parts of the world remnants of skulls dating back
millennia (to 10,000 BCE) have been found displaying carefully
drilled holes: from the shape of the holes we can deduce that
at least a proportion of the people who underwent these
tre-panning operations must have survived for some considerable
time We can only guess at the reasons for carrying out these
operations, but evidently people must have come up with the
idea that there was something important inside the head a long
time ago
The ancient Egyptians have left us writings describing head
wounds and their effects on the victims’ functioning, but they
thought that the soul was located somewhere in the thorax
When mummifying bodies the Egyptians accordingly dealt
with the brains of the deceased rather unceremoniously, while
treating the heart and liver so as to preserve them The notion
that feeling and intellect resided in the chest persisted for a
long time throughout the world The ancient Greek word ϕρην
(phrèn) can be translated as midriff, heart, psyche, soul, mind,
disposition, feeling, reason or thoughts, depending on the
con-text Even now English speakers do not learn a text ‘by head’
but ‘by heart’, to mention just one of the sayings left over from
these old theories
The Greeks, then, regarded the heart and diaphragm as the
seat of thought and emotion, whereas they saw the cerebrum
as a somewhat undifferentiated mass in the head (which might
exit through the nose if the person had a cold) Hippocrates
(5th century BCE) was far in advance of his contemporaries
in assuming that states of mind and epileptic seizures must
emanate from the brain In the 4th century BCE Plato
pro-claimed that intellectual functions were produced by the head,
whereas moods emanated from the heart and the lower urges
were caused by the liver His pupil Aristotle regarded the brain
rather as a cooling system for the feelings from the heart, and
it was because humans were more warm-blooded (and hot-
tempered?) than most other species that they had a relatively
large brain volume
Galen (2nd century CE) rejected these cooling theories as
nonsense, as it would make sense for the brain to be nearer
the heart in that case For him the brain played a pivotal role
in feeling and motor function He saw perceiving signals from
the outside world as a function of the soft cerebrum, whereas
motor function was controlled by the firm, elastic cerebellum
For Galen mental functions were also produced by the brain, in
particular the ventricles, where the spirits thought to emanate
from the left ventricle of the heart resided From there they
were able to enter the nerves and thus travel throughout the
body This notion persisted throughout the Middle Ages and
Renaissance
Trang 21Electrical brain activity was first measured at the end of the 19th century, and electroencephalography has been in use since the end of the 1920s Sceptics initially claimed that the electric currents were caused by movements of the hairs, but these the-ories were refuted on the basis of increased neurophysiological knowledge and measurements during brain surgery EEGs have long been carried out as a matter of routine to examine brain function – and brain anatomy – as gross anatomical abnormali-ties cause local disturbances in the EEG signal It was virtually inconceivable in the mid-20th century for a neurological con-sultation to be concluded without doing an EEG, and bizarre conclusions have been drawn from the results of such tests.
From the early 1970s facilities for carrying out brain scans using computer technology increased by leaps and bounds, and nowadays many patients are not happy unless they have had a computer scan (CT or preferably MRI) of the brain or parts of the back Neuroradiology techniques are still being refined and developed, and ways of measuring brain functions using ingen-ious isotope techniques have been devised
specialisms
Although neurology could in effect said to have existed as far back as the 17th century (Willis), as a specialist subject it only developed later In days gone by there was a distinction between physicians (theory specialists) and barber-surgeons (surgical specialists) The surgeons were held in lower esteem than the theoreticians, although was turned on its head later
on During the 18th century doctors increasingly focused
on mental illness and specialists arose who would nowadays occupy the middle ground between neurology and psychia-try They developed from general physicians (internists, as
it were) Important founding fathers of neurology included Charcot in France, Romberg in Germany and Jackson in England,
to name but a few famous figures In the Netherlands, Winkler was the first to be awarded a professorship of Neurology and Psychiatry, in 1893, abandoning internal medicine with some reluctance Wertheim Salomonson was appointed Professor of Neurology, Electrotherapy and Radiography in Amsterdam in 1899
During the 20th century neurology and psychiatry ally went their separate ways, but for a long time its students were still trained as ‘nerve specialists’ (specialists for both nerv-ous and mental illnesses.), permitted to practise both special-isms Here too a clear separation developed in the 1970s and students were trained to be neurologists or psychiatrists, rarely to be nerve specialists The specialism was abolished in the Netherlands in the early 1980s Neurology as a specialism moved increasingly close to internal medicine, as various neu-rological disorders were found to be due primarily to internal diseases
gradu-The beginning of the 20th century, especially the World War I period, saw a flowering of neurosurgery, with general surgeons and a few neurologists specializing in the surgical treatment of disorders of the central and peripheral
post-Hughlings Jackson also put forward the theory that the
brain was organized hierarchically: the highest centres (for the
execution of complex ideas) in the evolutionarily younger
fron-tal brain, the lowest centres (for direct control of the muscles)
in the phylogenetically older anterior horn of the spinal cord
Loss of function in the higher centres was thought to cause
disinhibition of the lower ones Damage to the central nervous
system therefore caused loss of control over the lower (more
primitive) distant centres, which could then go their own way
The localization theories were countered by holism, which
regarded the function of the cerebral cortex – or at least
impor-tant parts of it – more as a single entity Advocates of both
theories disputed the issue until the mid-20th century, when
the American neurologist Geschwind and the Russian
neu-ropsychologist Luria made it clear that cognitive functions and
behaviour arise from relationships between various fields in the
cortex, as Wernicke had already argued
Understanding of the way individual nerves and muscles work
grew by leaps and bounds in the second half of the 19th
cen-tury Substantial progress was made in the area of
neurophysi-ology, and microscopy produced more and more information
on the cytoarchitecture of the brain The neuron was
identi-fied as the smallest functional element in the nervous system
(Purkinje) and the sheaths surrounding nerve fibres were
described (Schwann) The fact that the brain is grey on the
out-side and white on the inout-side was found to be due to nerve cell
bodies being situated on the outside and the axons, surrounded
by whitish myelin, more on the inside How neurons
communi-cate with one another via synapses became increasingly clear in
the first half of the 20th century (Sherrington)
These discoveries increasingly gave rise to a need to map
the living brain and measure brain functions In 1919 Dandy
in Baltimore introduced pneumoencephalography This involved
introducing air through a lumbar puncture (which had been
‘invented’ by Quincke 30 years earlier) The air moved around
the spinal cord via the cerebrospinal fluid up into the
sur-rounding CSF spaces and the brain, enabling the cerebral
ventricles to be seen on X-rays, showing whether they were
enlarged or displaced If you didn’t have a headache already this
test would certainly give you one, and the technique entailed
substantial risks Another way of gaining an impression of the
locations of various parts of the brain was to inject contrast
fluid into the arteries and see how it circulated in the head
using X-rays This technique was introduced in 1927 by Moniz
in Lisbon As the contrast fluid quickly became diluted in the
bloodstream, becoming invisible, it was necessary to inject it
into the carotid artery near the brain, causing a not
insubstan-tial number of casualties Brain scans using radioactive
materi-als (brain scintigraphy) were introduced in the 1940s, but these
too gave only a rough impression of the brain anatomy So until
the early 1970s clinicians had to rely on these rather dangerous
imaging techniques, which were of course used with caution
This was not the case with the electroencephalogram (EEG)
Trang 221 nervous system This too developed into a new specialism com-pletely separate from clinical neurology Neurology saw the rise
of clinical neurophysiology, and many neurology centres now have neuropsychologists
Within clinical neurology we have super-specialists ing particularly on neuromuscular diseases, movement disor-ders, neuroimmunology (including multiple sclerosis), vascular disorders, epilepsy, neuro-oncology, neuro-intensive care and imaging techniques There are also radiologists who specialize
focus-in neuroradiology Paediatric neurology is provided by specialist neurologists and paediatricians
super-A neurologist is a doctor who treats diseases such as lepsy, multiple sclerosis, tumours of the nervous system, trau-mas, muscular diseases, nervous diseases, movement disorders, infections and related disorders If there are thought or mood disorders, a psychiatrist is consulted at an early stage; a neu-rosurgeon is brought in if a surgical intervention is required Neurologists are also in close contact with virtually all the other medical specialisms, as many conditions are the result of treat-ment or caused by other diseases
Trang 23epi-© 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_2
The neurological consultation
Abstract
A diagnosis and treatment plan is drawn up following history-taking and clinical
exami-nation at the bedside or in the consulting room These elements of every consultation
are vital to good practice and save a good deal of time, money, problems and
uncer-tainty, provided they are carried out properly Each element of history-taking, clinical
examination and diagnostic testing has a particular diagnostic value, changing the
prior probability into a posterior probability If the prior probability is low it will often
be decided not to carry out any further tests unless diagnosing the condition has major
consequences for the patient
2.1.6 What does the patient think it could be? – 7
2.2 Physical neurological examination: often carried out only
Trang 24to the spinal cord or a peripheral nerve Certain neuromuscular diseases can be identified from the fact that the loss of strength is symmetrical or asymmetrical and mainly proximal or distal
Quality
Here again it is important to probe If the patient says he has
‘difficulty walking’ it could be due to numbness in the feet neuropathy, cervical spinal stenosis), loss of strength in the thighs (muscular disease), pain in the calves (atherosclerosis or lumbar spinal stenosis) or unsteady gait (a cerebellar disorder)
(poly-‘Not being able to see properly’ may be due to diplopia (an eye muscle, brainstem or cranial nerve problem), reduced vision in one or both eyes (an ophthalmic problem, e.g cataract) or par-tial loss of visual field in both eyes (depending on whether the problem is in front of, on or behind the optic chiasm, or some-times due to drooping upper eyelids etc.)
Severity
To select the treatment we need to know how badly the lems affect the patient in his day-to-day life In the case of carpal tunnel syndrome (7 sect 13.5.3), for example, the sever-ity of sleep deprivation could be the decisive factor in opting for surgery; several partial complex epileptic seizures a year (7 sect 18.2.1) are more problematic for a person who uses his car every day than for a non-driver
prob-Ask about activities of daily living: dressing, toileting, ting around in and outside the home, feeding yourself, use
get-of aids, and so on The work history is also important: is the patient able to manage at work or is he ‘off sick’, and if so, how since when? How do his work colleagues and employer react? Lastly, it goes without saying that how the patient likes to spend his time is important, as well as whether there are limitations, for instance on sports activities and travel
Onset and progression
If the patient was fully conscious when a problem – e.g cle weakness – developed suddenly, he will almost always be able to say to the hour when it occurred The onset of pera-cute headache, e.g caused by a subarachnoid haemorrhage (7 sect 17.7), is often indicated even to the minute If the symp-toms developed gradually it is often impossible to say precisely when they started: this can then only be estimated in terms of weeks, months or years
mus-The progression of the symptoms is also important Is the problem constant (chronic) or recurring (episodic)? The treat-ment for episodic headache is completely different from that for chronic headache, for example Is the severity of the prob-lem changing, is the patient developing fresh symptoms?
If the problem is episodic: how long do the episodes last and how frequent are they? Are the symptoms completely absent between episodes? Is the frequency of the episodes changing over time?
Circumstances at onset
What was the person doing, or what had he just done, when the problem arose? Was the back pain radiating to the leg pre-ceded by heavy lifting or a long car journey? Does the episodic
Neurology is a field where simply looking carefully and
lis-tening to the patient can go a long way towards diagnosis and
treatment A whole host of abnormalities in the nervous
sys-tem can be detected using tests, but they are only significant if
they can be linked to clinical symptoms Many people would
‘just like a scan’, but they do not realize that it can reveal many
things that are not significant, and that a scan only has value
if you know precisely what you are looking for The findings
from consultation are therefore vital in making a diagnosis and
deciding on treatment
A neurological consultation, like any other medical
consul-tation, falls into three stages: history-taking, physical
examina-tion and diagnostic tests
While certainly not the most exciting part of a neurological
examination, history-taking is the most important and often
most difficult one It takes time but ultimately saves both time
and money Inadequate history-taking causes many needless
referrals and tests, leading to friction between the patient and
the doctor, and unnecessary procedures
It is best to start by giving the patient an opportunity to
explain what the main problem is in his own words and at his
own pace This not only identifies the problem, but also makes
clear how the patient regards it Next it is useful to summarize
what the patient has said in order to check whether the problem
has been properly understood Ambiguous words and phrases
should be clarified: for instance, what does the patient mean by
‘dizziness’? Does it mean feeling light-headed, everything going
black, unsteady gait, a whirling sensation, or something else?
This provides an opportunity to ask the patient about
things that he has not mentioned spontaneously
An experienced doctor is able to listen at length without
writing anything down and reproduce the patient’s account
later on, which is beneficial to the quality of history-taking
Once the discussion turns to the medication list and the prior
history no-one will manage to avoid writing things down
Avoid technical terms when taking notes on the history, as
it will not be clear later on whether these were the words used
by the patient or the practitioner’s interpretation
2.1.1 The seven dimensions of the problem
Location
When there is pain or some other sensory change there will
often be a difference between the location of the cause and
where the patient indicates that the problem is (7 sect 4.2.3)
Take pain in the dorsal side of the leg down into the calf with
numbness in the big toe, for instance: the problem in fact lies
in the lower lumbar spinal column The area where the loss of
function is found may provide an important clue to the
diagno-sis Loss of function or pain due to a brain dysfunction will
fol-low a different pattern from loss of function caused by damage
Trang 25It is often possible to determine from the case history what type
of inheritance is involved: dominant or recessive, mitochondrial through the maternal line affecting both men and women, or sex-linked through the maternal line affecting mainly men
2.1.4 Other diseases, intoxications
Information on these can make neurological diagnosis much easier Some ‘complications’ or neurological symptoms of non-neurological diseases and side effects of treatments are discussed in 7 chap 29 It is particularly important in older patients to check what medication they are using Quite a few admissions to hospital are the result of unintended side effects
of medicines, intoxications or interactions It is quite common for patients not to take their prescribed medication or not to do
so as prescribed Use of alcohol is often understated
2.1.5 Social history
The main information on the patient’s social situation (marital status, children, nature of work, sickness absences, housing sit-uation) should be included in routine history-taking
If you are considering a non-organic or psychosomatic
dis-ease it is worthwhile to take a biographical history What was
going on when the patient’s symptoms started? How was the patient’s life before then?
2.1.6 What does the patient think it could be?
Asking what the patient thinks he has might seem ioned, but it quite often yields important information Some-times a patient will be thinking in terms of a condition that the doctor considers too unlikely to be worth discussing, while the patient is seriously concerned but dare not talk about it Fears
old-fash-of ‘a blood vessel bursting’ in a patient with chronic headache,
‘being wheelchair-bound’ in one with back pain or ‘risk of a stroke’ in one who has dizziness caused by the organ of balance can easily be dispelled
Lastly, it is important to discuss patients’ expectations and wishes with them before instituting a whole programme of tests whose results may not be worthwhile for them
carried out only where indicated
A complete neurological examination is a fairly extensive cedure and takes a lot of time, so usually only a partial exam-ination is carried out, depending on the situation and the patient’s problem
pro-In effect the examination often begins on meeting the patient, for example when fetching him from the waiting room
An impression of various functions and symptoms can also be gained from the history-taking
headache always follow stress or an emotional upset? Has the
patient’s medication been changed recently? It is not
uncom-mon for a particular doctor to prescribe a medicine and for the
patient to see another doctor about the side effects (headache,
orthostatic dizziness) Most patients are well able to observe
themselves and make connections, and these should not be
ignored On the other hand, patients may draw far-reaching
but completely incorrect conclusions, perhaps suggested by
someone they know or because they have read something
online
Factors
Patients often know what they should and should not do to
influence the symptoms, especially if they are recurring
Neu-rological pain syndromes quite often depend on posture or
degree of activity (e.g neuropathic pain is worse at rest) Pain
along the course of a nerve that is exacerbated by coughing,
sneezing or pushing is indicative of a nerve root problem
Another important point is whether or not certain actions
pre-viously affected the severity of the symptoms
It goes without saying that the patient should also be asked
to provide information on factors that alleviate the symptoms
(e.g avoiding touching or heat in the case of neuropathic pain)
Accompanying symptoms
If a headache attack is preceded by visual symptoms and
accompanied by nausea, the diagnosis is likely to be migraine
If there is severe pain behind one eye and a watering eye and
nasal discharge on the same side it is much more likely to be a
cluster headache
2.1.2 Heteroanamnesis
Impaired consciousness, amnesia, disorientation and aphasia
often make proper history-taking from patients difficult, so
it is always a good idea to ask people in their immediate
cir-cle for information as well Is the unsteadiness that the patient
experiences when walking also apparent to outsiders? Has the
patient’s speech really deteriorated? Does it fluctuate over time?
How clear is the patient’s speech when talking on the phone?
2.1.3 Family history
If the same symptoms are found in family members this gives
some indication of heredity, of course, but the converse is not
true: if a problem is not found elsewhere in the family this does
not rule out a genetic problem It is often impossible to obtain
reliable information (as a result of scattered families, problems
that are not much discussed etc.)
One in three people who have a hereditary disease say that
they are not aware of anyone else in the family with the same
problems This could be due to recessive inheritance or to a
spontaneous mutation Or it may be the case that the penetrance
(the extent to which symptoms manifest themselves) is so low
that the disease has not previously been noticed in the family
Trang 26This book describes the elements of a neurological nation in the context of anatomy and physiology
exami-Descriptions of neurological examination in this book
5 cranial nerves ( 7 sect 6.3 )
5 strength ( 7 sect 4.2.1 )
5 reflexes ( 7 sect 4.2.2 )
5 sensation ( 7 sect 4.2.3 )
5 movement control ( 7 sect 5.2 )
5 cortical functions ( 7 sect 8.11 )
5 visual system ( 7 sect 9.3 )
5 radicular irritation ( 7 sects 14.3 and 14.4 )
5 examination of coma patients ( 7 sect 6.4 )
5 examination of children ( 7 sect 28.1.2 )
2.3 Diagnostic tests2.3.1 A priori considerations
Imaging techniques, function tests and histological and chemical tests can be used to find out more about the location, nature and cause of symptoms Before using these aids it is important to organize your thoughts
bio-Is the cost realistic in proportion to the expected results
of the tests? And the discomfort that the patient is cing? A nerve biopsy usually means losing a nerve for good; its diagnostic value is often limited, but there can sometimes be a major effect on the treatment strategy (if vasculitis is detected)
experien-In other cases (e.g coma) it will not be possible to take a
history, so highly specific tests will need to be carried out
quickly in order to take action If the patient is in a lot of pain
and unable to cooperate properly the physical examination
will sometimes need to be adapted; it is best, therefore, to save
pain provocation for the end In some cases the neurological
examination will be hampered by impaired sensation or
non-physical factors; these may identify apparent loss of strength
(7 sect 4.2.1), sensation (7 sect 4.2.3), movement (7 sect 5.3.2)
or even a complete pseudosyndrome (7 sect 4.4)
The more experienced the examiner is and the stronger the
suspicion of a particular condition, the more targeted the
examina-tion can be On the other hand, if the examiner is less experienced
or less certain about the cause of the symptoms it is advisable to
carry out a complete neurological examination as far as possible In
some training situations, for the sake of efficiency, the emphasis is
placed on targeted physical examination too early, with the result
that students can overlook a lot of information, costing a lot of time
later on If you examine a lot of things, you will get a good overall
impression but you may lose sight of details; if your examination
is too targeted, you may overlook causes and associated diagnoses
Not everything that appears abnormal is indicative of a
dis-ease Table 2.1 is a list of findings from physical examination
that lie within the limits of normality Age is also a factor:
cer-tain symptoms are normal in older people, whereas they could
be indicative of a disease in a younger person These symptoms
are set out in tab 2.2
. Table 2.1 ‘Normal’ symptoms and findings
– transient, sometimes rhythmic muscle contractions (myoclonic
jerks)
– transient muscle cramp (calf, abdominal muscles, anal sphincter)
– leg jerking when falling asleep (nocturnal jerks)
– transient sharp pains, itching for no apparent reason
– tingling ranging to complete anaesthesia on compression of the
peripheral nerves (lying on one arm, crossing the legs, carrying a heavy object)
– headache (tight and throbbing) following strenuous exertion or
emotional upset – mildly impaired imprinting and concentration and difficulty find-
ing words associated with fatigue, chronic pain or lack of sleep – anisocoria (10 % of the population), pupillary hippus (pupil
diameter fluctuations) – upward gaze impairment up to 20 %
– facial asymmetry at rest
– curved uvula
– pseudo-positive Lasègue’s sign (pseudo-positive straight leg
raise test due to tight hamstrings) – absent masseter reflex, absent abdominal skin reflexes (over-
weight people, loose abdominal skin after childbirth) – indifferent plantar reflex
– high symmetrical reflexes with some clonus beats
. Table 2.2 Neurological disorders normally found in older people
– impaired sense of smell and taste – mild ptosis, constricted pupils, convergence insufficiency, impaired upward gaze
– presbyacusis (loss of auditory high-frequency perception) – atrophy and loss of strength in the masticatory muscles – mild atrophy of the small hand muscles without functional impairment
– slightly reduced strength in the trunk muscles and pelvic girdle muscles
– fasciculations (fairly coarse) in the calf muscles – exaggerated physiological tremor
– impaired balance, especially when turning quickly – walking with small steps, slightly reduced arm swinging – general increase in muscle tone
– inability to actively relax – absent ankle reflex (if bilateral) – impaired sense of vibration in the legs – impaired imprinting
– reduced need for sleep
Trang 27If a provisional diagnosis cannot be made from history-taking, examination and tests, the further course of the disease may make it clear If there are symptoms that are not understood, or uncertain, it can often be useful to simply examine the patient
a second time, e.g a few weeks later, instead of immediately requesting tests at the first consultation with nothing specific in mind Meanwhile the patient can try to write down a list of his symptoms or keep a diary
If it is not possible to reach a diagnosis following adequate detective work, it may be useful to ask a fellow clinician for a second opinion A fresh perspective on the case can sometimes produce unexpected ideas
Lastly, it is common in neurology for the explanation of a disorder to take time – possibly months or years of follow-up
What is the diagnostic value of the test for the problem for
which it is being requested?
2.3.2 Diagnostic value
The concepts of sensitivity (the percentage of people with the
disease in whom the test detects abnormalities) and specificity
(the percentage of people without the disease in whom the test
does not detect abnormalities) are used here
Factors that confound the diagnostic value of a test are false
positives (abnormalities found in people who do not have the
disease) and false negatives (failure to find abnormalities where
the disease is present)
The diagnostic value of a test is determined by the
combina-tion of its sensitivity and specificity The higher they both are,
the more powerful the test is They are combined in the like
lihood ratio (sensitivity/(100 − specificity)) There is a prior
probability (a priori probability) from the information known
prior to the test, and a posterior probability (a posteriori prob
ability) that can be estimated from the test data If the
likeli-hood ratio is 1, the a posteriori probability is always equal to
the a priori probability, so a test of this kind provides no
infor-mation If the likelihood ratio is less than 1, an abnormality
found in the test is indicative of the contrary of the provisional
diagnosis A likelihood ratio of more than 1 contributes to the
diagnostic process, and the higher a test’s likelihood ratio, the
greater the likelihood of diagnosing the disease correctly
If the a priori probability is low, the a posteriori
probabil-ity will rarely be very high, so it is generally inadvisable to test
for diseases that are very unlikely to be found An exception is
diseases that are very rare but respond well to treatment and
where non-treatment can have major consequences
Diagnostic value applies not only to tests but equally to
history-taking questions and elements of the physical
examina-tion Detection of abnormal plantar reflexes has a high
diagnos-tic value if we are looking for cervical spinal stenosis to explain
numbness in the lower legs In other words, the likelihood that
cervical spinal stenosis is the correct explanation for the
numb-ness in the feet is greater if abnormal plantar reflexes are found
If we are considering compression of lumbosacral nerve roots
as the explanation for the numbness in the feet, testing the
plantar reflexes has a negative likelihood ratio If an abnormal
plantar reflex is found, it makes sense to check whether nerve
root compression is actually the explanation for the problem
The diagnostic value of the plantar reflex to identify a
neu-romuscular junction disorder as an explanation for fluctuating,
fatigue-dependent drooping of the eyelids is zero: the
likeli-hood ratio is 1 If abnormal plantar reflexes are found there
may be something else going on, but this finding does not help
to reject or confirm the original hypothesis of myasthenia
Trang 28© 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_3
An overview over nervous
system and muscles Technical
investigations in neurology
Abstract
The nervous system can be divided into two parts, the central and the peripheral
nerv-ous system The central nervnerv-ous system is a hierarchical structure, with higher centres
modulating lower ones The peripheral nervous system originates in the motor anterior
horn of the spinal cord and terminates in the dorsal ganglion, near the spinal cord
At rest, nerves and muscles are in electrical equilibrium When they are stimulated,
action potentials develop: these follow particular paths and produce an effect remotely
through nerve-to-nerve and nerve-to-muscle communication, which is mediated
chemi-cally by transmitters In pathological situations nerves or muscles fail to respond when
stimulated Electromyography provides a lot of information by measuring nerve
conduc-tion velocity or abnormal muscle acconduc-tion An EEG measures brain activity The indicaconduc-tions
for EEG are epilepsy, sleep and coma To enable readers to understand the opportunities
afforded by supplementary tests in the case of neurological disorders this chapter gives
a brief recapitulation of neuroanatomy and neurophysiology A broad outline of anato my
is given in 7sect 3.1, and 3.2 gives information on imaging 7Sections 3.3, 3.4 and 3.5
recapitulate the physiology of nerves, muscles and motor units respectively, which is
required for the explanation of electromyography in 7sect 3.6 The measurement of
sig-nals in and from the central nervous system is explained in 7sect 3.7, and 3.8 discusses
other laboratory techniques
3.2 Visualizing the peripheral nervous system – 14
Trang 293.4 The muscle – 18
Trang 30bulbo-) Just as in the spinal cord, automatic processes take
place here, but they are far more complex than those in the nal cord: for example breathing, coordinating eye movements, changing pupil size and automatic body movements The brain-stem could be called the ‘cruise control’ of the CNS While the brainstem keeps us alive, the brain can do its thinking
spi-The brainstem is divided from bottom (caudal) to top (cra nial) ( fig 3.1) into the medulla oblongata (extension of the spinal cord), the pons (the bridge crossed by various neural pathways), and the mesencephalon (midbrain); this is discussed
in detail in 7 chap 6 The cerebellum (‘little brain’), which
plays a role in certain aspects of movement control, forms an embryological unit with the pons (an important point that we shall encounter later on when discussing the crossing of neu-
ral pathways) Further forward (rostral) is the diencephalon (‘tweenbrain’), containing the thalamus (‘inner chamber’ or
‘bedroom’), the hypothalamus (‘lower chamber’) and the hypo physis (‘undergrowth’) The hypothalamus is the coordination point for the autonomic (involuntary) nervous system and the endocrine (hormonal) system; the thalamus is a hub for the
cerebral cortex which passes on virtually all the information needed for perception and movement
Lastly we have the most refined part of the nervous system, which is more highly developed the higher the species is in the
phylogenetic ranking: the telencephalon (‘endbrain’) This part comprises the cortex (cerebral cortex), the limbic system (the
‘inner edge’ of the brain) and the basal ganglia The cortex plays
an important role in conscious perception and action, the bic system in episodic memory and emotion (7 chap 8) and the basal ganglia in procedural activities such as automatic and conscious and unconscious motor function (7 chap 5)
lim-The CNS is entirely surrounded by three membranes
Inside the brain there are spaces (ventricles) where fluid (cere brospinal fluid, fig 10.3) is formed The CSF enters the space between the meninges (membranes) around the brain and spinal cord, where it is discharged into the venous system (7 chap 10)
There is a functional hierarchy in the CNS: higher tres modulate the activity of lower centres One would intui-tively expect this to be stimulation, but in the nervous system
cen-it is more a question of inhibcen-iting reflex activcen-ity When higher systems fail, lower centres become ‘disinhibited’ and therefore hyperactive: for example, behaviour is disinhibited when parts
of the frontal cortex fail, or there is increased muscle tension in the arms and legs when motor control by the cortex fails (spas-ticity) Another example is the primitive motor reflexes that occur (the lower M scores on the GCS, 7 sect 6.4) when higher parts of the CNS are disabled, e.g by a trauma
Parts of the CNS are interconnected by neural pathways
(tracts) Two important main groups of tracts are the ascending tracts, which run up from the spinal cord, and the descending tracts, which run down from the brain to the spinal cord These
are discussed in 7 chap 4
A living organism can reproduce and actively change its
envi-ronment and adapt to it In simple terms this is all done by
secreting substances and making movements The big
differ-ence between flora and fauna is that plants can generally only
move on the spot, mainly by growing, whereas almost all
ani-mals are capable of moving independently (through motor
function), either away from a place that needs to be abandoned
or avoided or towards an attractive target
Additionally, an animal organism, unlike a plant, is
capa-ble of changing or communicating with its environment This
is done by secreting substances (marking territory) or emitting
signals in the form of sounds, gestures and facial features
For all this to happen there first needs to be good
infor-mation and good perception of the environment Perceiving
and then acting is the function of the nervous system, which
explores the environment using receivers (sensory receptors) –
sensitive to light, sound, smell, taste, pain, temperature,
struc-ture and position – and influences it using two types of
effec-tors – glands and muscles These three systems – glands,
muscles and nerves – are recognizable in embryonic
develop-ment from the outset, as they are represented in the three germ
layers: the muscle system in the mesoderm and the nervous
system with its sense organs in the ectoderm, while gland tissue
originates in all three germ layers, including the endoderm
Muscles are present throughout the body, and there is an
extensive network of nerves to control them, running from
top to toe through the head, trunk and extremities (limbs)
( figs 13.2 and 13.8) This network is the peripheral nervous
system The peripheral nervous system originates in the cell
bodies of the motor nerves in the spinal cord and the brainstem
( fig 4.1, No 1), and terminates in the cell bodies of the
sen-sory nerves in the ganglia next to the spinal cord and the
brain-stem ( fig 3.1, No 4; fig 4.1, No 3)
The spinal cord (medulla spinalis) and higher parts – the
brainstem, diencephalon and cerebral cortex – together form
the central nervous system (CNS) In very primitive animal
spe-cies the higher parts are undeveloped or underdeveloped and
the spinal cord performs an important function in controlling
motor function; in this case various motor programmes are
stored in the spinal cord itself In highly developed species the
programmes are stored higher up and the majority of
move-ments instigated by the spinal cord are automatic reflexes
The spinal cord is divided into 30 vertical segments: eight
cervical, twelve thoracic, five lumbar and five sacral Each
seg-ment has a ventral root, which sends information from the
spinal cord to muscles, and a dorsal root connected to a
gan-glion, which transmits sensory information to the spinal cord
( fig 4.1 and 7 sect 15.1)
The cranial extension of the spinal cord is the brainstem
Because of its shape the brainstem often used to be referred to
as the bulb, as reflected in composite terms (bulbar, bulbaris,
Trang 31white (hyperdense), as are structures stained after the
adminis-tration of intravenous contrast fluid Extra fluid (oedema), e.g
around a tumour, is of lower density (hypodense) and therefore
shows up darker on the scan CT scanning still plays an tant role in the acute diagnosis of brain trauma (7 chap 20) and stroke (7 chap 17), where we need to know as soon as possible whether there is a bleed CT is also the most suitable method for examining the bone system surrounding nerve tissue Gen-erally, however, magnetic resonance imaging (MRI) provides more information on the central nervous system
impor-3.2.2 Magnetic resonance imaging (MRI)
MRI ‘kicks’ dipoles of atomic nuclei ‘out of balance’ by means
of a pulse: they change direction and become aligned After the pulse the dipoles revert to their original direction (relaxa-tion), emitting a radio-frequency signal (resonance), which is recorded As every tissue has its own relaxation pattern over time, different pulse sequences generate various contrasts Examples of these sequences are T1-weighted and T2-weighted
images, within which there are various options T 1 -weighted MRI images show the anatomy of the brain and small anoma-
lies best, e.g small tumours in the pituitary gland region or the vestibule and cavities in the spinal cord Fatty tissue pro-
duces a clear signal (hyperintense), CSF is black (hypointense),
and brain tissue is dark grey ( fig 3.2) Blood and blood products are clearly visible, and if the membranes between blood and brain tissue are impaired (the blood-brain barrier,
7 sect 11.1.3), brain tissue becomes stained when intravenous
In earlier days it was not possible to gain a picture of the CNS
without surgery or an autopsy; the optic nerve is in fact the
only nerve that can be inspected directly (using an
ophthal-moscope) It was possible to gain an indirect impression of
the space that the nervous system had at its disposal by
view-ing X-rays of the surroundview-ing bone structures (nerve tissue is
not visible on normal X-rays) Information on any
displace-ment of brain structures could be obtained by injecting air into
the CSF space or contrast fluid into blood vessels These tests
were a last resort because of the burden on and risks to the
patient; the nervous system was assessed almost entirely using
the observant eye, the attentive ear and the skilful hand of the
neurologist, i.e the information that emerged during a
con-sultation Highly developed angiography techniques involving
the intravenous administration of contrast fluid are still in use
(7 sect 11.4.1) We now also have CT, MRI, radioisotope
scan-ning and ultrasound to image the brain
3.2.1 Computed tomography (CT)
It has been possible to view the living brain using computed
tomography (CT scanning) since about 1970 A rotating X-ray
tube and detectors are used to collect data at high speed on
the flat plane lying in the circle of rotation Computation
pro-duces an image of each plane in black and white and all the
intervening shades of grey, with bone shown as white, CSF as
black and the brain tissue as shades of grey A fresh bleed is
dorsal
ventral
coronal section
13 14
anterior
posterior
transverse section
13 15
dorsal ventral
dorsal ventral
9 11 10
8
5
3 4 1
2
sagittal section
. Figure 3.1 Overview of the nervous system, with the terminology used for planes and directions, where a is the sagittal section, b the coronal section,
and c the transverse section The peripheral nervous system is shown in blue 1 muscle, 2 skin with sensory receptors, 3 peripheral motor neuron with cell
body in the spinal cord, 4 peripheral sensory neuron with cell body next to the spinal cord, 5 spinal cord, 6 medulla oblongata, 7 pons, 8 cerebellum,
9 mesencephalon, 10 hypothalamus, 11 hypophysis (pituitary gland), 12 cortex, 13 basal ganglia, 14 limbic system, 15 thalamus
Trang 323.2.3 Radioisotope scanning
Brain-imaging techniques always involve making concessions
to place or time These brain scans provide precise information
on the anatomy, but the nervous system is a dynamic entity
in which fractions of a second count It is equally important, therefore, to have information on what is happening over time MRI and CT scans have good spatial but poor temporal resolu-tion An EEG (7 sect 3.7) provides unsurpassed temporal reso-lution, but at the cost of fairly poor spatial resolution
Positron emission tomography (PET) and singlephoton emis sion computed tomography (SPECT) provide a happy medium
to some extent Both these techniques rely on radioactive gamma radiation generated by isotopes If isotopes are injected into the bloodstream they spread throughout the body but will
be attracted to a particular site (e.g 18F-fluorodopa or 123CIT in the basal ganglia) or will be found particularly in certain well-perfused areas (e.g 18F-fluorodeoxyglucose or 99mtechne-tium) These types of test can provide an impression of regional brain function during certain actions or thought processes that involve increased oxygen or glucose consumption This
I-β-is particularly valuable in research, but these techniques are increasingly being used in the diagnosis of dementia, epilepsy and brain tumours as well Both methods are used to exam-ine the availability of certain types of receptors in the CNS Administering certain radiopharmaceuticals known to act on
a certain point in the CNS (ligands) enables binding to those receptors to be visualized and therefore to find out, for exam-ple, whether there is a disease due to a shortage of receptors or (if there are enough receptors) a shortage of neurotransmitters (7 sect 3.3.4) This can be useful when diagnosing and treating movement disorders (7 sect 26.1.6) or psychiatric disorders
PET scanning uses positron-emitting isotopes with a cal half-life ranging from minutes to hours, so a local cyclotron
physi-is needed to produce them Thphysi-is physi-is not necessary for SPECT scanning using gamma-radiating isotopes that have a shorter half-life Just as with MRI and CT scanning a ring of detectors
is used to measure the directions and amounts of radiation, so
a fairly good topography can be obtained CT and MRI still provide much higher spatial resolution, however
A local increase in cortical activity when certain tive tasks are performed can also be detected by measuring the regional blood flow using MRI and contrast agents that are natu-rally present in the form of blood products This type of test
cogni-(functional MRI) measures the ratio between oxygen-depleted
and oxygen-rich haemoglobin Functional MRI has two tages: the spatial resolution is better than that of PET and SPECT and no radioactive substances are used
space-occupy-contrast fluid is administered T 2 -weighted MRI images (as in
fig 24.2 a) show anomalies in tissue composition more clearly,
e.g those found in multiple sclerosis (MS, 7 sect 24.1) or
minor cerebral infarctions (7 chap 17) CSF is white, and brain
tissue (parenchyma) is also fairly dense In T2-weighted images
the clear CSF signal can be suppressed (darkened) using the
fluidattenuated inversion recovery (FLAIR) technique to make
dense anomalies in the brain parenchyma show up more clearly
( fig 24.2 b)
To date no adverse effects of MRI have been found, so this
technique is more attractive than conventional X-rays,
espe-cially for children Other advantages of MRI compared with CT
scanning are the possibility of generating images in the sagittal
plane ( fig 3.2 a) and the absence of interference from cranial
bone, especially when examining the posterior cranial fossa
In practice MRI is limited to some extent in that the patient
needs to be able to lie still for quite a long time If there are any
ferrous metal objects present (in particular pacemakers and
other stimulators and wiring) they can be heated or damaged
by the strong magnetic field, making MRI impossible or
limit-ing its scope Claustrophobia can also be a problem because of
the narrow space in which the patient has to lie
. Figure 3.2 MRI scan M aged 40 T1 -weighted images (sagittal) and T 1
IR transverse a Sagittal sect in the midline: visible features include the
median side of the right cerebral hemisphere, the corpus callosum, the
brainstem, the pons, the fourth ventricle, the cerebellum, and the spinal
cord b Transverse section (with the front at the top): visible are the gyri
and sulci of the cerebral cortex, the white matter, the anterior and posterior
part of the lateral ventricles, the caudate nucleus (1), the putamen (2), and
the internal capsule (3) c Transverse section (lower than b.): also visible
are the globus pallidus (4), the thalamus (5), and the third ventricle (6)
d Transverse section (lower than c.): visible are the optic chiasm (7), the
mesencephalon (8), and the cerebellar vermis (9)
Trang 333.3.2 Histology and metabolism
As well as large numbers of axons, a peripheral nerve contains Schwann cells, which form myelin around the nerve fibres (7 sect 3.3.4) All of this is held together by connective tissue:
the epineurium, which surrounds the entire nerve, the perineu rium, which keeps groups of fibres together within the nerve, and the endoneurium, which covers separate nerve fibres.
The cell body is the metabolic centre of the nerve cell: from it organelles and products (including neurotransmitters,
7 sect 3.3.3) are transported to the nerve ends at a rate of up to
400 millimetres per day (anterograde transport) The packaging
material and breakdown products return for re-use along the
same route (retrograde transport).
brain parenchyma and CSF outflow blockage (hydrocephalus,
7 chap 10): this is possible as long as the cranial bone is still
thin and the fontanelle open
Ultrasound is also used to examine the substantia nigra
in the brainstem to enhance a diagnosis of Parkinson’s disease
(7 chap 26), and ultrasound is very useful for examining blood
vessels, as we shall see in detail later on (7 sect 11.4.2)
Ultra-sound scanning of nerves and muscles has also become
estab-lished alongside conventional electromyography
3.3.1 Functional structure
The nervous system, like other body tissues, is made up of
sep-arate cells joined together in networks
Nerve cells (neurons) differ from most other body cells
in several respects Their long processes give them a different
shape, they are responsive to electrical stimuli, and they do not
generally divide once fully grown
The centre of a nerve cell is the cell body (perikaryon or
soma, sometimes referred to as a ‘neuron’) The cell nucleus is
surrounded by cytoplasm, containing organelles such as the
Golgi apparatus, mitochondria and lysosomes As protein
syn-thesis is abundant in a nerve cell there is a highly developed
endoplasmic reticulum with ribosomes (known as ‘Nissl
sub-stance’) Almost all neuron cell bodies are found within the
CNS; only those of the peripheral sensory nerves and
auto-nomic nerves (7 chap 7) are found in nerve cell clusters
(gan-glia) outside the spinal cord and brainstem: for example, the
dorsal sensory ganglion ( fig 4.1) and the ganglia of the
auto-nomic nervous system (7 sect 7.1)
Neuron cell bodies vary greatly in size (from 5 to
150 micrometres) Their numerous processes are known as
‘dendrites’, as they resemble tree branches ( fig 3.3) Neurons
in the cerebral cortex that are connected with the spinal cord
and neurons in the spinal cord itself that communicate with
muscles have one process that is very long (depending on the
length of the owner), referred to as an ‘axon’ ( fig 3.3) Other
neurons, especially in the sensory ganglia, have two such
pro-cesses (one to the periphery, e.g the skin, and one into the
cen-tral nervous system, connecting to the next neuron) and are
therefore referred to as ‘bipolar’ Yet other neurons do not have
a long axon but only dendrites Nerve cells with fibres have
only one function, sensory, motor or autonomic Impulse
con-duction within a single nerve under physiological conditions is
always in the same direction
Axons are grouped together in tracts (in the CNS) or in
peripheral nerves (outside the CNS) A peripheral nerve is
made up of a collection of sensory fibres running to the CNS
and both motor and autonomic fibres running from the CNS to
the target organ (muscle, gland)
. Figure 3.3 Neuron with axon and dendrites
Trang 343.3.4 Nerve action potential
The depolarization can be large enough to exceed a certain threshold potential (usually approx −50 mV) ( fig 3.5) At this potential the Na+ influx is greater than the K+ efflux and still more voltage-gated Na+ channels open up, sharply increas-ing the Na+ influx In this way the inside of the cell membrane can even briefly become positive (up to 30 mV) in relation to the outside Once this action potential develops, its magnitude
is always the same It either occurs or does not occur; there is
no middle way, it is an all-or-nothing effect Once an action potential has reached its peak the potential difference rapidly
falls (repolarization) as a result of efflux of K+ ions and tivation of Na+ channels This effect is such that the potential difference across the membrane becomes even higher than it
inac-was in the resting situation (hyperpolarization) As long as Na+
channels are inactivated the neuron is less responsive to stimuli
(the refractory period).
The Na+/K+ pump restores the old equilibrium that caused the resting potential This return to equilibrium only cancels out the discharging effect locally; further along the nerve the action potential is constantly regenerated, as the large change
in potential opens voltage-gated Na+ channels there, thus ducting an action potential along the nerve membrane
con-3.3.3 Physiology at rest
All body cells have a potential difference across the cell
mem-brane between the internal environment of the cell and the
outside world In nerve cells this potential difference is caused
principally by the fact that in the resting situation there are
mainly K+ ions in the cell and mainly Na+ outside it: this is
referred to as the ‘resting membrane potential’ As a result the
inside of the cell is approximately 70 millivolts negative in
rela-tion to the outside This difference is caused by passive
dif-fusion of these ions through the membrane and also active
transport by a Na+/K+ pump in the cell membrane There are
also channels on the cell membrane that can be permeable to
ions under certain conditions The potential difference can
change rapidly as a result of external stimuli, as nerve cells can
be stimulated by neurotransmitters – signal substances from a
neighbouring nerve cell The neurotransmitter from another
cell contacts a specialized protein on the nerve cell membrane,
the receptor Generally speaking, a receptor is a protein in a cell
membrane that can bind to a specific transmitter molecule and
thus receive external signals to produce a response in the cell
Nerve and muscle cell receptors often have an ion channel that
opens when this molecule, the neurotransmitter, binds to it
(transmitter-gated channels), generating an electric current
In the case of receptors with cation channels (Na+, K+)
the potential difference across the cell membrane will become
slightly less negative (depolarization): this is referred to as an
‘excitatory postsynaptic potential’ (EPSP) The converse is also
true: activation of anion channels (Cl−) makes the potential
difference slightly more negative (hyperpolarization): this is
referred to as an ‘inhibitory postsynaptic potential’ (IPSP) A
single nerve cell is influenced by synaptic contacts with
sev-eral nerve cells ( fig 3.4) When the total effect of the EPSPs
exceeds that of the IPSPs, the net effect is a reduction in the
potential difference (depolarization).
membrane potential
resting potential
1 msec
refractory period
depolarization repolarization
threshold potential
. Figure 3.5 Nerve action potential Stimulation by neighbouring nerves
generates a series of excitatory postsynaptic potentials (EPSPs) that raise the membrane potential above a certain threshold This sharply increases
Na + conductance, causing further depolarization K + conductance then increases and repolarization occurs Finally the membrane potential falls below the resting potential and the cell is temporarily hyperpolarized and thus refractory to a fresh stimulus
Trang 35A muscle is made up of large numbers of muscle fibres (skeletal muscle cells) These cells are fairly large (diameter 10–100 µm) and elongated (length 1 mm–30 cm) They develop
at the embryonic stage from the fusion of various precursor
cells (myoblasts) and contain a number of nuclei as a result.
Between the fibres in a muscle there are connective tissue and blood vessels ( fig 3.6) Lastly, between the fibres there are
‘muscle spindles’, which register muscle tension and changes in
it They provide the CNS with information on the state of the muscle so that appropriate action can be taken The muscle
plex myelin Myelin is formed by cells other than the nerve cell:
oligodendrocytes in the CNS and Schwann cells in the peripheral
nervous system It could be referred to as ‘insulating material’
by analogy with electrical wire, but with the difference that the
insulation is not continuous from end to end but interrupted
every 1–2 millimetres, exposing the nerve fibre membrane in
the gaps These gaps are known as ‘nodes of Ranvier’ The nerve
action potential jumps from gap to gap (saltatory conduction of
impulses), making conduction in myelinated fibres many times
faster than in unmyelinated fibres Diseases of myelin
(multi-ple sclerosis in the CNS, demyelinating polyneuropathy in the
peripheral nervous system) provide a dramatic demonstration
of the importance of the conduction function that myelin
per-forms Unmyelinated fibres are also surrounded by Schwann
cells (albeit sparsely), but they do not have nodes of Ranvier
and no saltatory conduction takes place
3.3.5 Interneuronal communication
If the action potential reaches the end of a nerve process,
com-munication takes place with other neurons or effect organs
(gland cells, muscle cells) This communication is not direct:
the cells keep their distance and communicate in one-way
traffic via a chemical substance, the neurotransmitter already
mentioned There are different kinds of neurotransmitters,
including acetylcholine, serotonin, dopamine, glutamine and
gamma-hydroxybutyric acid (GABA) Some neurotransmitters
have a stimulatory (excitatory) effect, others an inhibitory effect;
some are inhibitory or excitatory, depending on which receptor
they reach ( fig 3.4)
The contact between a nerve fibre end and the next cell
is known as a ‘synapse’ A synapse is made up of part of the
nerve cell process (the presynaptic membrane), the part of
the next cell targeted by the communication (the postsynap
tic membrane) and the intervening space through which the
neurotransmitter has to diffuse Communication of this kind,
mediated by a neurotransmitter, can result in an EPSP or IPSP,
depending on the receptor on the other side (7 sect 3.3.3)
3.3.6 Abnormal nerve activity
When the function of a nerve cell is impaired, for example due
to mechanical damage or metabolic disorders, this can lead to
(a) failure (loss of strength or sensation) or (b) abnormal
acti-vity, e.g excessive muscle contraction (cramp) or abnormal
sensations (tingling, pain) Disorders such as epilepsy, migraine
and neuropathy are examples of such impairments
muscle fibres
cell nuclei capillary
mitochondrion
. Figure 3.6 Cross-section of a skeletal muscle with twenty muscle
cells (fibres), each with a number of nuclei The fibre is largely filled with myofibrils containing actin and myosin and contains an extensive T-tubule system as well as a few mitochondria (enlargement)
Trang 36and myofibrils Shortage of these cytoskeletal proteins (dystro phins, dysferlins and sarcoglycans) can cause catastrophic mus-
This binding and releasing process is highly
energy-dependent Adenosine triphosphate (ATP) is required to release
the myosin heads and ‘tense’ (reach towards the actin) It is only to be expected, then, that the skeletal muscle fibre contains large numbers of mitochondria scattered throughout the cell The formation of ATP is one of the vital steps in this process,
involving the enzyme creatine phosphokinase (CK) An elevated
serum CK level is indicative of muscle damage, information that is used for neurological diagnosis A myocardial infarction releases troponin into the serum, information that is used for early diagnosis
3.4.3 Neuromuscular transmission
The stimulus that causes a muscle fibre to contract usually comes from a nerve impulse Each muscle fibre is stimulated
(innervated) by one of the many processes of an axon.
The point where a nerve fibre and a muscle fibre meet (the
neuromuscular junction) is also referred to as a ‘synapse’, and
a muscle fibre, like a nerve fibre, is excitable, with a resting membrane potential that can change when a neurotransmit-ter arrives This change is always depolarization, never hyper-polarization When a nerve impulse arrives at the presynaptic membrane of the neuromuscular synapse, extracellular Ca2+
flows into the nerve cell This influx causes the
neurotransmit-ter acetylcholine to be released from the nerve end The
neuro-muscular synapse contains large numbers of receptors on the muscle fibre, and a nerve impulse releases a large quantity of acetylcholine Not all of the neurotransmitter released binds to the receptor, and not all receptors are occupied, but if binding occurs in many transmitter receptors a substantial change in
potential develops, the end plate potential (EPP, fig 3.9)
3.4.4 The muscle in action
If this causes the muscle’s threshold potential to be reached – which is always the case after one nerve impulse under physio-logical conditions – an action potential develops here too This muscle action potential spreads not only over the muscle fibre membrane but also over the T-tubules and the sarcoplasmic reticulum ( fig 3.8), influencing the internal structures in the muscle fibre When they are activated Ca2+ is released at the site of the contraction proteins, causing the troponin’s structure
to change and the process of actin-myosin binding to begin
The spatial arrangement of the troponin-tropomyosin complex causes the binding sites for the myosin heads to be released Now cross-bridges between actin and myosin can be
spindles themselves are kept in tension by the CNS to enable
them to function to the full This is done by ‘gamma motor neu
rons’, whose cell bodies are in the spinal cord ( fig 3.7)
3.4.2 Microscopic anatomy
A muscle cell or muscle fibre is surrounded by an excitable
muscle fibre membrane, the sarcolemma The largest space
in a muscle fibre is occupied by elongated proteins, actin and
myosin, which are organized alongside one another lengthwise
in myofibrils and can form cross-bridges with one another
Because of the organization of these proteins a muscle fibre
appears striated under the microscope ( fig 3.8)
The muscle fibre also has a muscular protein ‘skeleton’,
which provides stability between the muscle cell membrane
. Figure 3.7 Muscle spindle between two ordinary muscle fibres (only
partly shown) The muscle spindle is kept in tension by motor nerves
(gamma motor neurons) and provides information on the tension and
changes in tension in a muscle
Trang 373.4.5 Symptoms of muscular disorders
It is only to be expected that a malfunction of a muscle cell, e.g due to a metabolic disorder or inflammation, will have conse-quences These could take the form of weakness, but the muscle
formed; the myosin heads rotate, with actin and myosin
pro-teins sliding past each other The actin-myosin compounds
then detach again This detaching, rebinding and rotating is
repeated until the desired shortening is achieved ( fig 3.10)
which in turn has a connection with the muscle fibre membrane (sarcolemma)
1
2
3
4 5
6
nerve
acetylcholine vesicle acetylcholin acetylcholin receptor
muscle fibre membrane action potential
end plate potential threshold potential
actin-myosin complex Figure 3.9 Muscle action potential A nerve action potential (1) releases a quantity of acetylcholine into the synaptic cleft (2) After the acetylcholine
binds to the acetylcholine receptors a small change in potential develops across the membrane (3) The total effect is the end plate potential (4) If this exceeds the threshold potential (5) a muscle action potential develops, eventually followed by muscle fibre contraction (6)
Trang 38large, however ( fig 3.11 c), as many muscle fibres that are no longer innervated by a functioning nerve – and are therefore denervated – are ‘adopted’ by neighbouring functioning nerve
fibres (reinnervated) The number of functioning nerve fibres
has gone down and they form large motor units, making the resulting potential on activation abnormally large These are
referred to as neurogenic EMG artefacts.
mal spontaneous muscle or nerve activity as sometimes found
in neuromuscular diseases If special needles are used it is even possible to assess the activity of separate muscle fibres in rela-
tion to others in the same motor unit (singlefibre EMG) If one
fibre lags behind another in the same motor unit it could mean that nerve-muscle communication is impaired (as in myasthe-nia, 7 sect 12.6) Surface myography is also used in specialist
centres: this can measure the conduction of electrical activity across the muscle fibre membrane, which is impaired in certain muscle diseases
3.6.2 Measuring nerve conduction
In addition to needle EMG, an EMG can be used to measure the conduction velocity of peripheral nerves This involves stimulating a nerve at various points and measuring the effect
at the end of the nerve This can be done by measuring the
fibre could alternatively become unstable and start acting
inde-pendently due to overstimulation, causing fine muscle
move-ments (myokymia) or painful cramps.
A single muscle fibre is connected to a single terminal branch
of a nerve fibre, by which it is controlled (innervated) An axon
branches off into large numbers of terminal fibres, so a single
nerve fibre has a large number of muscle fibres under its care
The entire nerve cell (i.e the cell body and axon) with all the
terminal branches of the nerve fibre, the innervated muscle
fibres, and the associated synapses are together known as a
‘motor unit’ When a single motor nerve cell in the spinal cord
discharges, all the associated muscle fibres contract The many
muscle action potentials generated together form a single large
potential, the motor unit action potential (MUAP) This can
be measured by inserting a needle into a muscle, a procedure
known as ‘electromyography’ (EMG) Thus an EMG measures
an extracellular potential that is the sum of many muscle action
potentials in a single motor unit Individual motor unit action
potentials can be assessed by slightly contracting a muscle
( fig 3.11 a); when it is strongly contracted the action
poten-tials of the many active motor units cut across one another,
cre-ating an interference pattern.
In neuromuscular diseases the motor unit action
poten-tials are usually smaller than usual because some muscle fibres
in a particular motor unit have failed Even when the patient
is asked to apply slight force all the nerve cells need to be
recruited and a rapid-interference pattern occurs ( fig 3.11 b)
These are myogenic EMG artefacts.
In the case of nerve disorders, on the other hand, the
con-traction pattern is poor Many nerve fibres have failed, and few
motor units remain The potentials that occur are abnormally
H band
Z disc M
Ca 2+
. Figure 3.10 Schematic representation of contractile muscle proteins
Trang 392 2
2
2 2 1 1 1
1 1 1 1 1 3
3 3
3
4 4 4 4
4
4 4
1 2 3 4
1 2 3 4
1 2
3 4
1 2 3 4
2 2
2 2 2
3 3
3
4
4 4
2 2
2
2 2
2 2
1 1
1 1 1 1
3 3 3 3
3 3
3
4
4 4 4
4 4 4 4
atrophic fibres
original motor unit
1 2 3 4
a
b
c
. Figure 3.11 The activity of motor units 1–4 measured using EMG The patient is repeatedly asked to slightly tense the muscle under observation
a shows the normal situation In b the nerve segment of the motor unit is intact, but due to a muscular disorder various fibres are inactive, resulting in
small potentials and an EMG that, despite the slight contraction, is full because as many motor units as possible are recruited (rapid interference) In
c motor units 2 and 4 are affected by a neuromuscular disease: the processes of the axons of motor units 1 and 3 adopt muscle fibres that previously
belonged to 2 and 4, creating a poor pattern with few motor unit action potentials, which have however become very large because of the ‘adoption procedure’
Trang 40which can be measured: this is the H-reflex This too provides
information on conduction velocity in the proximal nerve ments and any blockages there
nervous system
An EMG provides information on the functioning of the peripheral nervous system The electrophysiological proper-ties of the CNS can also be measured The conduction veloc-ity of pathways in the CNS can be measured by administering a suitable stimulus (in the example, a light stimulus) at a suitable site (e.g the retina of the eye) and detecting the response in the
brain (in this case, the visual cortex): evoked potentials (For
more on this subject see 7 chap 4.) The spontaneous activity of the CNS can also be measured second by second, namely with
electroencephalography (EEG).
3.7.1 Electroencephalography
An electroencephalogram (EEG) shows the constantly changing potential differences in nerve cell groups These can be detected using electrodes in, on or near the brain A routine EEG uses 21 electrodes placed on the scalp in a particular configuration
Special amplification equipment is required, as the potential differences are of the order of only 20–100 microvolts The EEG records not only brain activity, but also the electrical activity of extracranial sources generated by eye movements, muscles and the heart, causing interference signals that need to be distin-guished from brain activity Monitoring usually takes 30 min-utes after the electrodes have been placed, and it is not stressful for the patient
The normal structure of the EEG depends on both the waking state and age of the patient In an adult a normal EEG shows activity with a rhythm predominantly between 8 and 30 waves per second If the patient closes his/her eyes and remains
awake an alpha rhythm will be found over the posterior half of
the skull (8–13 waves per second, fig 3.12 a) During sleep the EEG changes in various respects ( fig 3.12 d) The EEG data can show the patient’s sleep state, and long-term monitoring can give an impression of sleep quality Compared with adults, children have a much slower basic pattern made up of a mix-ture of waves of different frequencies (e.g a one-year-old child mainly has waves at 4 to 5 per second), so the limits of norma-lity in children are less clear than in adults ( fig 3.12 b and c) Older persons also have somewhat slower activity
3.7.2 The indications for EEG
The role of EEG as a diagnostic tool has changed radically in recent decades with the advent of brain-scanning techniques Patients and doctors not working in the field of neurology are
response of the associated muscle (usually by means of skin
electrodes over the muscle) or measuring the electrical activity
of the nerve further along In the muscle the activity of many
motor units causes many simultaneous motor unit actions,
hence a mechanical effect This can be measured on the outside
of the muscle: the compound muscle action potential (CMAP)
A CMAP is thus the result of many MUAPs In the nerve
stimulation causes an electrical effect, the sensory nerve action
potential (SNAP) An SNAP is thus the combined result of
many nerve action potentials
Note that a muscle fibre action potential and a nerve fibre
action potential always have the same size An MUAP can be
large or small, depending on how many muscle fibres are active
in the motor unit A CMAP can be large or small, depending
on the number of motor units that are active An SNAP can be
large or small, depending on the number of nerve fibres that
are active in the nerve
A CMAP or SNAP can be late due to conduction delay and
both lowered and broadened due to its distribution As the
nerve consists of many fibres, we need to gain an idea of both
the maximum velocity and the distribution when conducted by
the various fibres
Measuring along various pathways (e.g the median nerve:
lead on the thenar eminence, stimulation at the wrist, elbow
and armpit, provides information on possible entrapment of
the nerve along its course (e.g in the carpal tunnel)
Prolonged motor conduction time is caused not only by
entrapment but also by intrinsic disorders of the myelin sheath
around the nerve (demyelinating polyneuropathy).
When axons decay (axonal neuropathy) the conduction
velocity of the nerve as a whole remains fairly normal for a long
time In such cases most abnormalities are detected by needle
EMG, as the motor unit action potentials are abnormal due to
reinnervation (a neurogenic pattern)
If both the nerve and the muscle are functioning normally,
the neuromuscular junction can be further tested by subjecting
the nerve, and thus the muscle, to repeated electrical
stimula-tion and checking whether the muscle’s response to the various
stimuli (measured using surface electrodes) diminishes rapidly
These measurements are made from proximal (the
stimu-lation site) to distal (the measuring site) and provide
informa-tion on distal conducinforma-tion If a nerve is artificially stimulated,
however, there is not only an impulse to distal but also to
proximal, and the stimulus thus goes to the spinal cord This
is an unphysiological situation, where nerve conduction in a
nerve can go both ways Stimulating a motor nerve then
elic-its a response in the motor cell body in the spinal cord, which
in turn generates an action potential in the cell body back to
peripheral: the F response The time between the stimulus and
the F response can be measured, indicating whether there
could be a proximal conduction disorder along the line
Arti-ficial stimulation of sensory nerves also produces a response
in the spinal cord, but this enters at the rear (7 sect 4.1.1) The
motor anterior horn cell is activated by the central part of the
spinal cord, and again a muscle action potential is generated