16 Neurological disease
The brain, spinal cord and peripheral nerves constitute an organ responsible for perception of the environment, a person’s behaviour within it, and the maintenance of the body’s internal milieu in readiness for this behaviour. In the UK some 10% of the population consult their GP each year with a neurological symptom, and neurological disorders account for about one-fifth of acute medical admissions and a large proportion of chronic physical disability.
PRESENTING PROBLEMS
HEADACHE
Headache is a frequently encountered neurological symptom but is seldom associated with significant neurological disease unless accompanied by other symptoms or neurological signs.
ACUTE HEADACHE
Serious acute neurological disease should always be considered in patients with headaches of very sudden onset. Subarachnoid haemorrhage causes a very sudden headache, followed by vomiting and neck stiffness which may take hours to develop. The main differential diagnosis is between subarachnoid haemorrhage and a migraine variant.
SUBACUTE HEADACHE
Headache coming on over the course of hours is likely to be migraine, unless accompanied by other symptoms or signs. Migraine headaches may be accompanied or preceded by vomiting and focal neurological symptoms. Patients with bacterial meningitis are usually pyrexial and exhibit meningism (p. 664). Patients with viral meningitis may present with a pyrexia and quite sudden and severe headache, but may not have meningism.
CLINICAL EXAMINATION OF THE NERVOUS SYSTEM
INTERMITTENT HEADACHE
When headaches are intermittent rather than continuous over days or weeks, they are most likely to be migrainous. The headache of raised intracranial pressure is present on waking and often improves as the patient becomes upright or takes simple analgesia. It is unusual for a patient with an intracranial mass to present with such a headache alone since it is usually not sufficiently severe to cause alarm; seizure or other focal signs are more common presenting features. The exceptions to this are patients with acute hydrocephalus who present with a more severe headache.
CHRONIC HEADACHE
Headaches that persist for weeks, are present all day and are poorly responsive to simple analgesia are very likely to be tension-type headaches. Headaches so well localised by the patient that a finger is used to locate the exact spot on the skull are never associated with significant disease. In a patient >60 yrs with head pain localised to one or both temples, giant cell arteritis should be considered.
TENSION-TYPE HEADACHE
MIGRAINE
Clinical assessment
Migraine is a triad of paroxysmal headache, nausea and/or vomiting, and an ‘aura’ of focal neurological events. Patients with all three features have migraine with aura (‘classical’ migraine). Migraine without aura, with or without vomiting, is called ‘common’ migraine. A classical migraine attack starts with a prodrome of malaise and irritability followed by the ‘aura’ of a focal neurological event, and then a severe, throbbing, hemicranial headache with photophobia and vomiting. The headache may persist for several days.
The ‘aura’ typically lasts 20–30 mins, and usually takes the form of ‘fortification spectra’: shimmering zigzag lines which march across the visual fields. Some patients experience a sensory aura: tingling then numbness moving from one part of the body to another. Patients may also experience transient aphasia. True weakness is distinctly unusual, so ‘hemiplegic migraine’ should be diagnosed with caution.
The aetiology of migraine is largely unknown.
Management
Acute attack: Simple analgesia with aspirin or paracetamol, often with an antiemetic. Severe attacks can be treated with one of the ‘triptans’ (e.g. sumatriptan), 5-HT agonists that are potent vasoconstrictors of the extracranial arteries.
Prevention: Identification and avoidance of precipitants or exacerbating factors. If frequent, try propranolol (80–160 mg daily, sustained-release), amitriptyline (10–50 mg at night), sodium valproate (300–600 mg/day) or pizotifen (1.5–3.0 mg daily). Women should be warned that the small risk of ischaemic stroke attributable to taking oral contraception is increased if they have migraine, especially if they also smoke.
CLUSTER HEADACHE (MIGRAINOUS NEURALGIA)
Clinical assessment
This is much less common than migraine. There is a predominance of males and onset is usually in the third decade. The syndrome comprises periodic, severe, unilateral periorbital pain accompanied by unilateral lacrimation, nasal congestion and conjunctival injection. The pain is characteristically brief (30–90 mins). The syndrome may occur repeatedly for a number of weeks, followed by months of respite before another cluster occurs.
FACIAL PAIN
Pain in and around the eye not caused by ocular disease should be considered as a headache. Most patients with persisting pain in the face have trigeminal neuralgia (see below), atypical facial pain or post-herpetic neuralgia. Atypical facial pain is continuous and unremitting, and is centred over the maxilla, usually on the left side. Post-herpetic neuralgia is a continuous burning pain throughout the affected territory, often very sensitive to light touch. The cause is usually obvious from a history of ‘shingles’ in the ophthalmic division of the trigeminal nerve.
TRIGEMINAL NEURALGIA
Clinical assessment
DIZZINESS, BLACKOUTS AND ‘FUNNY TURNS’
Episodes of lost or altered consciousness are frequent. After a careful history from the patient, supplemented by a witness account, it should be clear whether the patient is describing loss of consciousness, altered consciousness, vertigo, transient amnesia or something else. The diagnostic approach is shown in Figure 16.1.
VERTIGO
Abnormal perception of movement of the environment occurs as a result of a mismatch between the information about a person’s position reaching the brain from the eyes, limb proprioception and the vestibular system. Vertigo arising from inappropriate input from the labyrinthine apparatus is usually short-lived, though it may recur, whilst vertigo arising from central (brain-stem) disorders is often persistent and accompanied by other signs of brain-stem dysfunction.
VERTIGO CAUSED BY LABYRINTHINE DISTURBANCES
Labyrinthitis (‘vestibular neuronitis’): Usually presents in the 3rd or 4th decade as severe vertigo, with vomiting and ataxia but no tinnitus or deafness. The vertigo is most severe at onset and settles down over the next few days. Nystagmus is present during the attack but does not persist for long.
Benign paroxysmal positional vertigo: Paroxysms of vertigo occurring with certain head movements may be due to degenerative material affecting endolymph flow in the labyrinth. Each attack lasts seconds but patients may become reluctant to move their head, producing a muscle tension-type headache. The diagnosis can be confirmed by using the ‘Hallpike manoeuvre’ in which the head is swung briskly back to demonstrate positional nystagmus. The vertigo fatigues with repetitive positioning of the head and can be treated with vestibular exercises.
Ménière’s disease: Patients usually present with tinnitus and distorted hearing, and then develop paroxysmal vertigo preceded by a sense of fullness in the ear. Examination shows sensorineural hearing loss on the affected side.
Drug treatment of labyrinthine vertigo: Symptomatic relief can be achieved with ‘vestibular sedatives’ (e.g. cinnarizine, prochlorperazine, betahistine). Patients with intractable symptoms should be referred to an ENT specialist for assessment.
CENTRAL CAUSES OF VERTIGO
Any disease that affects the vestibular nucleus in the brain stem or its connections can cause vertigo. Positionally induced central vertigo persists for as long as the position is maintained, unlike peripheral positional vertigo that fatigues if the inducing position is maintained. Causes such as brain-stem ischaemia may be associated with dysarthria or diplopia. If deafness is present, consider compression of the 8th cranial nerve.
EPISODIC LOSS OF CONSCIOUSNESS
Transient loss of consciousness occurs because of a recoverable loss of adequate blood supply to the brain (syncope), or from sudden electrical dysfunction of the brain during a seizure (epileptic fit). Many patients have psychogenic blackouts or non-epileptic seizures which may confuse this distinction. No amount of investigation can replace a clear history in these circumstances. Features in the history useful in distinguishing a seizure from a faint are shown in Box 16.1.
16.1 FEATURES HELPFUL IN DISTINGUISHING SEIZURES FROM FAINTS 
| Seizure | Faint | |
|---|---|---|
| Aura (e.g. olfactory) | + | – |
| Cyanosis | + | – |
| Tongue-biting | + | – |
| Post-ictal confusion | + | – |
| Post-ictal amnesia | + | – |
| Post-ictal headache | + | – |
| Rapid recovery | – | + |
SYNCOPE
A brief feeling of ‘lightheadedness’ often precedes a faint; vision then darkens and there may be a ringing in the ears. Vasovagal syncope (p. 211) may be provoked by some emotionally charged event (e.g. venepuncture) and usually occurs while standing. Cardiac syncope, caused by a sudden decline in cardiac output and hence cerebral perfusion, may be exertional (e.g. with severe aortic stenosis) or may occur completely ‘out of the blue’ (as in heart block). During a syncopal attack, incontinence of urine can occur and there is often stiffening and brief twitching of the limbs, but tongue-biting never occurs. Recovery is rapid and without confusion.
SEIZURES
A seizure is any clinical event caused by an abnormal electrical discharge in the brain, whilst epilepsy is the tendency to have recurrent seizures. The division of seizure types on physiological grounds is between partial (focal) seizures in which paroxysmal neuronal activity is limited to one part of the cortex, and generalised seizures where the electrophysiological abnormality involves both hemispheres simultaneously.
Clinical assessment
Tonic clonic seizures: These may be preceded by a partial seizure (the ‘aura’). The patient then goes rigid, stops breathing, becomes unconscious and cyanosed, and may fall. After a few moments, the rigidity is periodically relaxed, producing clonic jerks. Urinary incontinence or tongue-biting may occur. The patient then gradually regains consciousness, but is drowsy or confused for some hours.
Complex partial seizures: Partial seizures cause episodes of altered consciousness without the patient collapsing to the ground. The patient stares blankly, often making rhythmic smacking movements of the lips or other automatisms. After a few minutes the patient returns to consciousness but may be muddled or drowsy. Immediately before the attack there may be alterations of mood, memory and perception. If these occur without subsequent alteration in awareness, the seizure is a simple partial seizure.
Absence seizures: These are generalised seizures which always start in childhood. The child goes blank and stares for a few seconds only. The attacks resemble complex partial seizures but are usually shorter, more frequent and not associated with post-ictal confusion.
Partial motor seizures: Epileptic activity in the pre-central gyrus causes partial motor seizures affecting the contralateral face, arm, trunk or leg. There is rhythmical jerking or sustained spasm of the affected parts. They may remain localised to one part, or may spread to involve the whole side. Some attacks begin in one part and spread gradually (‘Jacksonian epilepsy’). Prolonged episodes may leave paresis of the involved limb lasting for several hours (Todd’s palsy).
Partial sensory seizures: Seizures arising in the sensory cortex cause unpleasant tingling or ‘electric’ sensations in the contralateral face and limbs. A spreading pattern like a Jacksonian seizure may occur, but is much faster (in seconds) than the ‘march’ of a migrainous focal sensory attack (10–15 mins).
EPILEPSY
Epilepsy is a tendency to have seizures and is a symptom of brain disease rather than a disease itself. A single seizure is not epilepsy but is an indication for investigation. The recurrence rate after a first seizure approaches 70% during the first year. The lifetime risk of having a single seizure is ∼5%, whilst the prevalence of epilepsy is ∼0.5%.
Types of epilepsy
Primary generalised epilepsy: This makes up 10% of all epilepsies, including 40% of those with tonic clonic seizures. Onset is usually in childhood or adolescence. No structural abnormality is present and there is often a substantial genetic predisposition. Some varieties, like childhood absence epilepsy, are relatively uncommon, whilst others, like juvenile myoclonic epilepsy, are common (5–10% of all patients with epilepsy).
Secondary generalised epilepsy: Generalised epilepsy may arise from spread of partial seizures due to structural disease, or may be secondary to drugs or metabolic disorders. Epilepsy presenting in adult life is almost always secondary generalised, even if there is no clear history of a partial seizure before the onset of a major attack.
Partial epilepsy: Partial seizures may arise from any disease of the cerebral cortex, congenital or acquired, and frequently generalise. With the exception of a few idiopathic partial epilepsies of benign outcome in childhood, the presence of partial seizures signifies the presence of focal cerebral pathology.
Investigations
No cause is found in most patients. However, investigations are necessary to confirm the diagnosis, characterise the type of epilepsy, and identify any underlying cause.
Cerebral imaging: After a single seizure, head CT or MRI is advisable, although the yield of structural lesions is low unless there are focal features.
EEG: May be more helpful in showing focal features if performed very soon after a seizure than after an interval. It can also help establish the type of epilepsy and guide therapy.
Other investigations: These should identify any metabolic, infective, inflammatory or toxic causes. They include FBC, ESR, CRP, U&Es, glucose, LFTs, CXR, syphilis serology, HIV, collagen disease, CSF examination.
Management
Immediate care of seizures: Little can or need be done for a person whilst a major seizure is occurring except first aid and common-sense manoeuvres (Box 16.2).
16.2 IMMEDIATE CARE OF SEIZURES 
First aid (by relatives and witnesses)
Restrictions: Patients should be made aware of the riskiness of activities where loss of awareness would be dangerous, until good control of seizures has been established. This includes work or recreational activities involving exposure to heights, dangerous machinery, open fires or water. In the UK and many other countries, legal restrictions regarding vehicle driving apply to patients with epilepsy.
Anticonvulsant drug therapy (see also p. 781): Drug treatment should be considered after more than one seizure has occurred. Of patients whose epilepsy is controllable, only a single drug is necessary in 80%. Dose regimens should be kept as simple as possible to promote compliance. The first line of treatment should be one of the established drugs (Box 16.3), with more recently introduced drugs as second choice. Try up to three agents singly before resorting to combinations; beware drug interactions. Phenytoin and carbamazepine induce liver enzymes and therefore are not ideal for women wishing to use oral contraception. Occasional phenytoin and carbamazepine blood levels can be checked to confirm appropriate dose and to check compliance. There is no relationship between drug levels of sodium valproate and anticonvulsant efficacy.
16.3 GUIDELINES FOR CHOICE OF ANTI-EPILEPTIC DRUGS 
| Epilepsy type | First-line | Second-line |
|---|---|---|
| Partial and/or secondary GTCS | Carbamazepine | |
| Primary GTCS | Sodium valproate | |
| Absence | Ethosuximide | Sodium valproate |
| Myoclonic | Sodium valproate | Clonazepam |
N.B. Preferably one and no more than two drugs should be used at one time. (GTCS = generalised tonic clonic seizure.)
Prognosis
Generalised seizures are more readily controlled than partial seizures. A structural lesion makes complete control less likely. After 20 yrs:
There is a 40-fold increased risk of sudden unexplained death in epilepsy and patients may need to be made aware of this to help them rearrange their lifestyle and comply with treatment.
Withdrawal of anticonvulsant therapy: After complete control of seizures for 2–4 yrs, withdrawal of medication may be considered. Childhood-onset epilepsy carries the best prognosis for successful drug withdrawal. Overall, the recurrence rate of seizures after drug withdrawal is ∼40%. Withdrawal should be undertaken slowly, reducing the drug dose gradually over 6–12 mths.
STATUS EPILEPTICUS
Status epilepticus exists when a series of seizures occurs over 30 mins without the patient regaining awareness between attacks. This usually refers to recurrent tonic clonic seizures and is a medical emergency. Status is never the presenting feature of idiopathic epilepsy but may be precipitated by abrupt withdrawal of anticonvulsant drugs, a major structural lesion or acute metabolic disturbance. Management is summarised in Box 16.4.
16.4 MANAGEMENT OF STATUS EPILEPTICUS 
Pharmacological
If seizures continue after 30 mins
If seizures still continue after 30–60 mins
NON-EPILEPTIC ATTACK DISORDER (‘PSYCHOGENIC ATTACKS’, ‘PSEUDO-SEIZURES’)
Patients may present with attacks that superficially resemble epileptic seizures but which are caused by psychological phenomena and not associated with abnormal epileptic discharges in the brain. Clues pointing towards non-epileptic attacks include elaborate arching of the back, pelvic thrusting and/or wild flailing of limbs. Cyanosis and severe biting of the tongue are rare, but urinary incontinence can occur. Treatment is often difficult and usually requires psychotherapy and/or counselling rather than drug therapy.
SLEEP DISORDERS
Disturbances of sleep are common. Apart from insomnia, patients may complain of:
NARCOLEPSY
In this disorder recurrent bouts of irresistible sleep are experienced. Patients will report at least one other of the ‘narcolepsy tetrad’:
Narcoleptic attacks can be treated with modafinil (200–400 mg per day). Cataplexy responds to clomipramine (25–50 mg 8-hourly) or fluoxetine (20 mg per day).
RESTLESS LEG SYNDROME
This is a common disorder, also known as Ekbom’s syndrome. Unpleasant sensations in the legs that are ameliorated by moving the legs occur when the patient is tired and at the onset of sleep. Restless legs can also be symptomatic of an underlying peripheral neuropathy or iron deficiency, or of general medical conditions (e.g. uraemia). Treatment is with clonazepam (0.5–2.0 mg), levodopa (100–200 mg) or dopamine agonists at night.
DISORDERS OF MOVEMENT
Lesions in various parts of the motor system produce distinctive patterns of motor deficit. These can be ‘negative’ symptoms (weakness, lack of coordination, lack of stability and stiffness) or ‘positive’ symptoms (tremor, dystonia, chorea, athetosis, hemiballismus, tics and myoclonus). When the lower limbs are affected, characteristic patterns of gait disorder may result.
THE MOTOR SYSTEM
A programme of movement formulated by the pre-motor cortex is converted into a series of muscle movements in the motor cortex and then transmitted to the spinal cord in the pyramidal tract (Fig. 16.2).
Fig. 16.2 The motor system. Neurons from the motor cortex descend as the pyramidal tract in the internal capsule and cerebral peduncle to the ventral brain stem, where most cross low in the medulla (A). In the spinal cord the upper motor neurons form the cortico-spinal tract in the lateral column before synapsing with the lower motor neurons in the anterior horns. The activity in the motor cortex is modulated by influences from the basal ganglia and cerebellum. Pathways descending from these structures control posture and balance (B).
Lower motor neuron lesions: Loss of function of lower motor neurons causes loss of contraction in their units’ muscle fibres and the muscle will be weak and flaccid. Denervated muscle fibres atrophy, causing wasting. Re-innervation from neighbouring motor neurons occurs but the neuromuscular junctions are unstable, causing fasciculations (visible to the naked eye because the motor units are larger than normal).
Upper motor neuron (pyramidal) lesions: When the spinal cord is disconnected from the higher motor hierarchies, the anterior horn motor neurons are under the uninhibited influence of the spinal reflex mechanisms. An upper motor neuron lesion therefore manifests clinically with brisk tendon stretch reflexes, ‘spastic’ increase in tone, and extensor plantar responses. Spasticity takes time to develop and may not be present for weeks.
Extrapyramidal lesions: There is an increase in tone, which is continuous throughout the range of movement at any speed of stretch (‘lead-pipe’ rigidity). Involuntary movements are present, and a tremor combined with rigidity produces typical ‘cogwheel’ rigidity. Rapid movements are slowed (bradykinesia). Extrapyramidal lesions also cause postural instability, precipitating falls.
Cerebellar lesions: These cause lack of coordination on the same side of the body. The initial movement is normal but accuracy deteriorates as the target is approached, producing an ‘intention tremor’. The distances of targets are misjudged (dysmetria), resulting in ‘past-pointing’. The ability to produce rapid, regularly alternating movements is impaired (dysdiadochokinesis). Disorders of the central vermis of the cerebellum produce a characteristic ataxic gait.
A DIAGNOSTIC APPROACH TO LIMB WEAKNESS (Box 16.5, Fig. 16.3)
16.6 LIMB WEAKNESS: ASSESSING THE CAUSE 
GAIT DISORDERS
Patterns of weakness, loss of coordination and proprioceptive sensory loss produce a range of abnormal gaits. Neurogenic disorders need to be distinguished from skeletal abnormalities, usually characterised by pain producing an antalgic gait, or limp.
Pyramidal gait: Upper motor neuron (pyramidal) lesions cause a gait in which the upper limb is held in flexion and the lower limb is kept relatively extended. In a hemiplegia, the asymmetry between the affected and normal sides is obvious. In a paraparesis, both lower limbs move slowly, swung from the hips and dragged on the ground in extension.
Foot drop: Weakness of ankle dorsiflexion disrupts the normal gait cycle. Descent of the foot is less controlled, making a slapping noise, and the foot may be lifted higher, producing a high-stepping gait.
Waddling gait of proximal muscle weakness: In proximal muscle weakness, usually caused by muscle disease, the hips are not properly fixed and trunk movements are exaggerated, producing a rolling or waddling gait.
Cerebellar ataxia: Patients with lesions of the central parts of the cerebellum (the vermis) walk with a characteristic broad-based gait, ‘like a drunken sailor’.
Gait apraxia: There is normal power in the legs and no abnormal cerebellar signs or proprioception loss, yet the patient cannot formulate the motor act of walking. This higher cerebral dysfunction occurs in bilateral hemisphere disease, such as normal pressure hydrocephalus and diffuse frontal lobe disease.
Sensory ataxia: Loss of joint position sense makes walking unreliable. The feet tend to be placed on the ground with greater emphasis, resulting in a ‘stamping’ gait.
Extrapyramidal gait: Patients have difficulty initiating walking and controlling the pace of their gait. This produces the festinant gait: initial stuttering steps that quickly increase in frequency while decreasing in length.
INVOLUNTARY MOVEMENTS
Abnormal movements usually imply a disorder in the basal ganglia, in which there is disinhibition of intrinsic rhythm generators or a disorder of postural control.
Rest tremor: A tremor is a rhythmic oscillating movement of a limb or part of a limb, or of the head. Rest tremor is pathognomonic of Parkinson’s disease. It is characteristically ‘pill-rolling’ and asymmetrical. Tremor of the head in the upright position (‘titubation’) is not a rest tremor since this is a postural tremor, disappearing when the head is supported.
Action tremor: More common than rest tremor. The potential causes are numerous:
Chorea: Jerky, small-amplitude, purposeless involuntary movements. There are numerous potential causes:
Ballism: More dramatic than chorea, ballistic movements of the limbs usually occur unilaterally (hemiballismus) in vascular lesions of the subthalamic nucleus.
Athetosis: Slower writhing movements of the limbs. These are often combined with chorea and are then termed ‘choreo-athetoid’ movements.
Dystonia: A movement disorder in which a limb (or the head) involuntarily takes up an abnormal posture. This may be generalised in basal ganglia disease, or may be focal or segmental, as in spasmodic torticollis when the head involuntarily turns to one side. Other segmental dystonias may cause abnormal disabling postures during specific actions (e.g. writer’s cramp) and can be treated with botulinum toxin to the responsible muscles.
Myoclonus: Brief, isolated, random, non-purposeful jerks of muscle groups in the limbs. They occur normally at the onset of sleep (hypnic jerks). Myoclonus can occur in epilepsy, from subcortical structures or from diseased segments of the spinal cord.
Tics: Repetitive semi-purposeful movements such as blinking, winking, grinning or screwing up of the eyes. Unlike with other involuntary movements, patients can suppress tics, at least for a short time.
SENSORY DISTURBANCE
Sensory symptoms are very common but do not always denote nervous system disorder. For example, tingling in the fingers of both hands and around the mouth commonly suggests hyperventilation. Damage to the afferent nervous pathways conveying touch and pain produces either the negative sensation of numbness, or positive symptoms such as paraesthesia and pain.
A DIAGNOSTIC APPROACH TO SENSORY SYMPTOMS
In the history, the most useful features are:
Certain patterns can be recognised. For example, in migraine the aura may consist of a front of paraesthesia followed by numbness which takes 20–30 mins to spread over one half of the body. Sensory loss due to a vascular lesion, on the other hand, will occur more or less instantaneously. The numbness and paraesthesia of spinal cord lesions often ascend one or both lower limbs to a level on the trunk over hours or days.
PATTERNS OF SENSORY DISTURBANCE (Fig. 16.4)
Peripheral nerve lesions
In peripheral nerve lesions, the symptoms are usually of sensory loss and simple paraesthesia (pins and needles). Single peripheral nerve lesions will cause disturbance in the sensory distribution of that nerve. In diffuse neuropathies the longest neurons are affected first, giving the characteristic ‘glove and stocking’ distribution.
Fig. 16.4 Patterns of sensory loss. 
Generalised peripheral neuropathy. 
Sensory roots. 
Single dorsal column lesion (proprioception and some touch loss). 
Transverse thoracic spinal cord lesion. 
Unilateral cord lesion (Brown-Séquard): ipsilateral dorsal column (and motor) deficit and contralateral spinothalamic deficit. 
Central cord lesion: ‘cape’ distribution of spinothalamic loss. 
Mid brain stem lesion: ipsilateral facial sensory loss and contralateral loss on body. 
Hemisphere (thalamic) lesion: contralateral loss on one side of face and body.
Nerve root lesions
Pain is more often a feature of lesions of nerve roots within the spine or of the limb plexuses. It is often felt in the muscles innervated by a root. The site of nerve root lesions may be deduced from the dermatomal pattern of sensory loss.
Spinal cord lesions
Sensory information ascends the nervous system in two anatomically discrete systems, differential involvement of which is often of diagnostic assistance (Fig. 16.5).
Transverse spinal cord lesions: There is loss of all modalities below that segmental level. Often a band of paraesthesia or hyperaesthesia is found at the top of the area of loss. If vascular in origin (e.g. due to anterior spinal artery thrombosis), the posterior one-third of the spinal cord (dorsal column modalities) may be spared.
Unilateral spinal cord lesions: There is loss for spinothalamic modalities (pain and temperature) on the opposite side of the lesion. There is also loss for dorsal column modalities (joint position and vibration) on the same side as the lesion (e.g. Brown-Séquard syndrome).
Central spinal cord lesions (e.g. syringomyelia): These spare the dorsal columns but affect spinothalamic fibres from both sides over the length of the lesion. The sensory loss is therefore dissociated (in terms of the modalities affected) and suspended (segments above and below the lesion are spared).
Single dorsal column lesion (e.g. MS): The patient experiences an unpleasant tight feeling over the limb involved. There is loss of proprioception without any loss of pin-prick or temperature sensation.
Brain-stem lesions
Brain-stem lesions can cause sensory loss affecting all modalities on the contralateral side of the body.
Hemisphere lesions
These may affect all modalities of sensation. In the thalamus, discrete lesions (e.g. small lacunar strokes) can cause loss of sensation over the whole contralateral half of the body. With substantial lesions of the parietal cortex (as with large strokes) there is severe loss of proprioception and even loss of conscious awareness of the existence of the affected limb(s).
Neuropathic pain
Pain is of two main types: nociceptive pain, arising from a pathological process in a body part, and neuropathic pain, caused by dysfunction of the pain perception apparatus itself. Neuropathic pain is a very unpleasant persistent burning sensation, often with increased sensitivity to touch. The most common syndromes include partial damage to peripheral nerves (‘causalgia’), the trigeminal nerve (post-herpetic neuralgia) or the thalamus. Drugs (carbamazepine, tricyclics or phenothiazines) may help but usually only partially. Neurosurgical attempts to interrupt pain pathways sometimes succeed. Implantation of electrical stimulators has occasionally proved successful.
COMA AND BRAIN DEATH
COMA
Persistent loss of consciousness or coma indicates disorder of the arousal mechanisms in the brain stem and diencephalon. There are many causes of coma (Box 16.7). The history is crucial to establishing the cause and should be obtained from any witnesses. Neurological examination may reveal important findings, e.g. evidence of head injury, papilloedema, meningism or eye movement disorder.
| Metabolic disturbance | Drug overdose, diabetes mellitus (hypoglycaemia, ketoacidosis, hyperosmolar coma), hyponatraemia, uraemia, liver failure, respiratory failure, hypothermia, hypothyroidism |
| Trauma | Cerebral contusion, extradural haematoma, subdural haematoma |
| Cerebrovascular disease | Subarachnoid haemorrhage, intracerebral haemorrhage, brain-stem infarction/haemorrhage, cerebral venous sinus thrombosis |
| Infections | Meningitis, encephalitis, cerebral abscess, general sepsis |
| Others | Epilepsy, brain tumour, thiamine deficiency |
Assessment of conscious level
Systematic assessment using the Glasgow Coma Scale provides a grading of coma which allows serial comparison and may provide prognostic information, particularly in traumatic coma (Box 16.8).
BRAIN DEATH
The availability of mechanical ventilators has resulted in the survival of patients with severe irreversible brain damage but functioning cardiovascular systems. Diagnostic criteria for brain death have been established in order that those patients without functioning brains who have no chance of recovery may be identified, organ donation options considered, and ventilation discontinued.
ACUTE CONFUSIONAL STATE (DELIRIUM)
This is much more common than dementia. Unlike in dementia, there is a disturbance of arousal that accompanies the global impairment of mental function. There is drowsiness with disorientation, perceptual disturbances and muddled thinking. Patients typically fluctuate, confusion being worse at night, and there may be associated emotional disturbance or psychomotor changes. There are many possible causes (Box 16.9).
16.9 CAUSES OF ACUTE CONFUSIONAL STATE 
| Type | Common | Unusual |
|---|---|---|
| Infective | ||
| Metabolic/endocrine | ||
| Vascular | ||
| Toxic | ||
| Neoplastic | Secondary deposits | |
| Trauma | Cerebral contusion, subdural haematoma | |
| Other |
Diagnosis
It is vital to take a history from a witness. Examination may yield other clues. It is important to distinguish confusion from a fluent aphasia. Often, however, the cause is not immediately obvious and a wide screen of tests must be performed (Box 16.10).
16.10 INVESTIGATION OF ACUTE CONFUSIONAL STATE 
| First-line | Other useful tests | |
|---|---|---|
| Blood tests | ||
| CNS tests | Head imaging (CT and/or MRI) | Lumbar puncture, EEG |
| Other |
DISTURBANCE OF MEMORY
It is important to determine for how long the problem has existed, and exactly which aspects of memory are affected. Disturbance of episodic memory (‘short-term memory’) must be distinguished from semantic memory. The former can be selectively impaired in Korsakoff’s syndrome (often secondary to alcohol) or bilateral temporal lobe damage.
TRANSIENT AMNESIA
Loss of memory for a period of time may be due to:
These are usually distinguished from the history. Transient global amnesia is a syndrome affecting middle-aged patients in which there is an abrupt, discrete and reversible loss of short-term memory function. After 4–6 hrs, memory functions and behaviour return to normal. There are none of the phenomena associated with seizures, and transient global amnesia tends not to recur. The patient has no physical signs and further investigation may not be needed if epilepsy can be excluded.
DEMENTIA
Progressive memory deterioration over months suggests an underlying dementia, which is characterised by a loss of previously acquired intellectual function in the absence of impairment of arousal. There are many causes but Alzheimer’s disease and diffuse vascular disease are the most common. Rarer causes should be sought in younger patients and those with short histories. Many primary degenerative diseases have characteristic features that may help diagnosis:
Investigations
The aim is to discover a treatable cause, if present, and to try to give an idea of prognosis. Standard investigations include:
CHANGES IN PERSONALITY AND BEHAVIOUR
Organic conditions can result in altered personality and behaviour. This particularly applies to disorders affecting the frontal lobes, which control executive function, movement and behaviour. The frontal lobes may be damaged structurally (e.g. trauma, strokes, hydrocephalus or tumour) or functionally (e.g. metabolic disturbances). Personality can be affected in three broad directions:
SPEECH AND LANGUAGE DISTURBANCE
Speech is the process whereby vocal sounds are used to convey meaning between individuals. A large volume of the cerebral cortex is involved in this complex process, mostly in the dominant hemisphere. The temporal speech comprehension region is referred to as Wernicke’s area. The language information then passes to Broca’s area. The motor commands generated here pass to the lips, tongue, palate, pharynx, larynx and respiratory muscles via the facial nerve and cranial nerves 9, 10 and 12, resulting in speech.
DYSPHONIA AND DYSARTHRIA
The vocal cords may fail to generate sounds properly in speech, resulting in hoarse or whispered speech (dysphonia). This may be due to a local problem affecting the cords or a higher-level problem (dystonia) of vocal cord operation. If the muscles or nerves controlling the mouth, tongue, pharynx and lips are not functioning correctly, poorly articulated speech will result (dysarthria). Cerebellar or brain-stem disease, lower cranial nerve lesions, myasthenia or muscle disease may all result in dysarthria.
APHASIA
Aphasia (or dysphasia) is a disorder of the language content of speech. It can occur with lesions over a wide area of the dominant hemisphere. Aphasia is detected by the patient’s inability to produce the correct word. If a patient has difficulty with speech comprehension there is likely to be a lesion in Wernicke’s area. Patients with large lesions over much of the speech area have no language production and have ‘global aphasia’.
DISORDERS OF PERCEPTION
The temporal, parietal and occipital lobes receive sensory information including touch, vision, hearing and balance. Damage to any of these areas will result in loss of the ability to perceive that particular modality. Abnormal excitation (e.g. epilepsy, migraine) results in an apparent perception not based in physical reality. This can be visual (flashing lights), so-matosensory (tingling, burning or pain), auditory (noises) or vestibular (vertigo).
The parietal lobes are also involved in the higher processing and integration of primary sensory information. Damage here gives rise to sensory (including visual) inattention and apraxia. Apraxia is the inability to perform complex, organised activity in the presence of a normal basic motor, sensory and cerebellar system (e.g. dressing, using cutlery and finding one’s way around geographically).
PROBLEMS WITH BRAIN-STEM FUNCTION
Many different functional areas are tightly packed into the brain stem. Damage to even a small area potentially causes major disturbance of several systems. An example would be upper motor neuron features affecting the right face, arm and leg in association with a left 3rd nerve palsy. The lesion would have to be in the left cerebral peduncle in the brain stem (‘Weber’s syndrome’). The lower cranial nerves, 9, 10, 11 and 12, are frequently affected bilaterally (by vascular, degenerative, infective/inflammatory or neoplastic conditions), producing dysphagia and dysarthria:
SWALLOWING DIFFICULTIES
Swallowing is a complex activity involving the coordinated action of lips, tongue, soft palate, pharynx and larynx, which are innervated by the facial nerve and cranial nerves 9, 10, 11 and 12.
DISORDERS OF BALANCE
Disorders of balance can arise from a number of different abnormalities affecting:
Loss of joint position sense or cerebellar function may result in a sensation of ‘unsteadiness’, while damage to the vestibular nuclei or labyrinth may cause an illusory sensation of movement, i.e. ‘vertigo’. Sensory abnormalities may be manifest as altered visual acuities or visual fields, altered eye movements, impaired vestibular function or lack of joint position sense. Disturbance of cerebellar function may be manifest as nystagmus, dysarthria or ataxia.
VISUAL DISTURBANCE
VISUAL LOSS
The visual pathway from the retina to the occipital cortex is topographically organised, so the pattern of visual field loss allows localisation of the site of the lesion (Fig. 16.6, Box 16.11). Patients often present with transient visual loss.
Fig. 16.6 Visual pathways and visual field defects. Schematic representation of eyes and brain in transverse section.
EYE MOVEMENT DISORDERS
The control of eye movements begins in the cerebral hemispheres, and the pathway then descends to the brain stem with input from the visual cortex and cerebellum. Horizontal and vertical gaze centres in the pons and mid-brain coordinate output to the ocular motor nerve nuclei (3, 4 and 6). These are connected to each other by the medial longitudinal fasciculus (MLF). The extraocular muscles are then supplied by the oculomotor (3rd), trochlear (4th) and abducens (6th) nerves.
Diplopia (‘double vision’)
The pattern of double vision and associated features allow localisation of the lesion, whilst the mode of onset and subsequent behaviour suggest the aetiology. The trochlear (4th) nerve innervates the superior oblique muscle, and the abducens (6th) nerve innervates the lateral rectus. The oculomotor (3rd) nerve innervates the remainder of the extraocular muscles along with the levator palpebrae superioris and the ciliary body (pupil constriction and accommodation). Causes of ocular motor nerve palsies are given in Box 16.12.
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