Characteristics:	Associated features:
– generalised. – aggravated by bending or coughing. – worse in the morning on awakening; may awaken patient from sleep. – the severity of the headache gradually progresses.

– vomiting in later stages.

– transient loss of vision (obscuration) with sudden change in posture.

– eventual impairment of conscious level

Management:

further investigations are essential – CT or MRI

Low pressure headache

Low pressure headache occurs most commonly after lumbar puncture but can arise spontaneously (Spontaneous intracranial hypotension). Headache is worse on standing and improves lying flat. After LP no investigation is needed. If no cause is apparent MRI will show downward displacement cerebellar tonsils and meningeal enhancement with contrast (Gd). Spontaneous improvement is usual. Occasionally a dural ‘blood patch’ at the site of CSF leak (post LP or epidural anaesthesia) is necessary.

NON-NEUROLOGICAL CAUSES OF HEADACHE

Local causes:

Sinuses: Well localised. Worse in morning. Affected by posture, e.g. bending.

X-ray – sinus opacified. Treatment – decongestants or drainage.

Ocular: Refraction errors may result in ‘muscle contraction’ headaches

– resolves when corrected with glasses.

Acute glaucoma can produce headache but is accompanied by other symptoms, e.g. misting of vision, ‘haloes’.

Dental disease: Discomfort localised to teeth. Check for malocclusion.

Check temporomandibular joints.

Systemic causes:

Headache may accompany any febrile illness or may be the presenting feature of accelerated hypertension or metabolic disease, e.g. hypoglycaemia, hypercalcaemia.

Many drugs produce headache

– through vasodilatation, e.g. bronchodilators, antihistamines

– on withdrawal, e.g. amphetamines, benzodiazepines, caffeine.

MENINGISM

Evidence of meningeal irritation caused by infection or subarachnoid haemorrhage results in characteristic clinical features (though not all will necessarily be present):

RAISED INTRACRANIAL PRESSURE

The skull is basically a rigid structure. Since its contents – brain, blood and cerebrospinal fluid (CSF) – are incompressible, an increase in one constituent or an expanding mass within the skull results in an increase in intracranial pressure (ICP) – the ‘Monro-Kellie doctrine’.

Compensatory mechanisms for an expanding intracranial mass lesion:

CEREBROSPINAL FLUID (CSF)

Secreted at a rate of 500 ml per day from the choroid plexus, CSF flows through the ventricular system and enters the subarachnoid space via the 4th ventricular foramina of Magendie and Luschka.

Under normal conditions, CSF flows freely through the subarachnoid space and is absorbed into the venous system through the arachnoid villi. If flow is obstructed at any point in the pathway, hydrocephalus with an associated rise in intracranial pressure develops, as a result of continued CSF production. With an expanding intracranial mass lesion, normal pressure is initially maintained by CSF expulsion to the expandable lumbar theca. Further expansion and subsequent brain shift may obstruct the free flow of CSF not only to the lumbar theca but also to the arachnoid villi, causing an acute rise in intracranial pressure.

BRAIN WATER/OEDEMA

Cerebral oedema – an excess of brain water – may develop around an intrinsic lesion within the brain tissue, e.g. tumour or abscess or in relation to traumatic or ischaemic brain damage, and contribute to the space-occupying effect.

Different forms of cerebral oedema exist:

Vasogenic: excess fluid (protein rich) passes through damaged vessel walls to the extracellular space – especially in the white matter. The extracellular fluid gradually infiltrates throughout normal brain tissue towards the ventricular CSF and this drainage route may aid clearance. e.g. adjacent to tumour.

Cytotoxic: fluid accumulates within cells – neurons and glia i.e. intracellular, e.g. toxic or metabolic states.

Interstitial: when obstructive hydrocephalus develops, CSF is forced through to the extracellular space especially in the periventricular white matter.

With ischaemic damage, as cell metabolism fails, intracellular Na⁺ and Ca²⁺ increase and the cells swell i.e. cytotoxic oedema. Capillary damage follows and vasogenic oedema supervenes.

CEREBRAL BLOOD FLOW (CBF)/CEREBRAL BLOOD VOLUME (CBV)

Blood flow is dependent on blood pressure and the vascular resistance:

Inside the skull, intracranial pressure must be taken into account:

Under normal conditions the cerebral blood flow is coupled to the energy requirements of brain tissue. Various regulatory mechanisms acting on the arterioles maintain a cerebral blood flow sufficient to meet the metabolic demands.

FACTORS AFFECTING THE CEREBRAL VASCULATURE

Chemoregulation

– Change in extracellular pH or an accumulation of metabolic by-products directly affects the vessel calibre.

– Any change in arteriolar PCO₂ has a direct effect on cerebral vessels, but only a reduction of PO₂ to < 50 mmHg has a significant effect.

Autoregulation

– A change in the cerebral perfusion pressure results in a compensatory change in vessel calibre.

Any change in blood vessel diameter results in considerable variation in cerebral blood volume and this, in turn, directly affects intracranial pressure.

Energy requirements differ in different parts of the brain. To meet such needs in the white matter, flow is 20 ml/100 g/min, whereas in the grey matter flow is as high as 100ml/100g/min.

Autoregulation is a compensatory mechanism which permits fluctuation in the cerebral perfusion pressure within certain limits without significantly altering cerebral blood flow.

A drop in cerebral perfusion pressure produces vasodilation (probably due to a direct ‘myogenic’ effect on the vascular smooth muscle) thereby maintaining flow; a rise in the cerebral perfusion pressure causes vasoconstriction.

Neurogenic influences appear to have little direct effect on the cerebral vessels but they may alter the range of pressure changes over which autoregulation acts.

Autoregulation fails when the cerebral perfusion pressure falls below 60 mmHg or rises above 160 mmHg. At these extremes, cerebral blood flow is more directly related to the perfusion pressure.

In damaged brain (e.g. after head injury or subarachnoid haemorrhage), autoregulation is impaired; a drop in cerebral perfusion pressure is more likely to reduce cerebral blood flow and cause ischaemia. Conversely, a high cerebral perfusion may increase the cerebral blood flow, break down the blood–brain barrier and produce cerebral oedema as in hypertensive encephalopathy.

INTRACRANIAL PRESSURE (ICP)

Intracranial pressure, measured relative to the foramen of Monro, under normal conditions ranges from 0–135 mm CSF (0–10 mmHg) although very high pressure, e.g. 1000 mm CSF may occur transiently during coughing or straining.

When intracranial pressure is monitored with a ventricular catheter, regular waves due to pulse and respiratory effects are recorded (page 53). As an intracranial mass expands and as the compensatory reserves diminish, transient pressure elevations (pressure waves) are superimposed. These become more frequent and more prominent as the mean pressure rises.

Eventually the rise in intracranial pressure and resultant fall in cerebral perfusion pressure reach a critical level and a significant reduction in cerebral blood flow occurs. Electrical activity in the cortex fails at flow rates about 20 ml/100 g/min. If autoregulation is already impaired these effects develop even earlier. When intracranial pressure reaches the mean arterial blood pressure, cerebral blood flow ceases.

INTERRELATIONSHIPS

Many factors affect intracranial pressure and these should not be considered in isolation. Inter-relationships are complex and feedback pathways may merely serve to compound the brain damage.

CLINICAL EFFECTS OF RAISED INTRACRANIAL PRESSURE

A raised ICP will produce symptoms and signs but does not cause neuronal damage provided cerebral blood flow is maintained. Damage does, however, result from brain shift – tentorial or tonsillar herniation.

Clinical features due to ↑ICP:

1. Headache – worse in the mornings, aggravated by stooping and bending.

2. Vomiting – occurs with an acute rise in ICP.

3. Papilloedema – occurs in a proportion of patients with ICP. It is related to CSF obstruction and does not necessarily occur with brain shift alone. Increased CSF pressure in the optic nerve sheath impedes venous drainage and axoplasmic flow in optic neurons. Swelling of the optic disc and retinal and disc haemorrhages result. Vision is only at risk when papilloedema is both severe and prolonged.

BRAIN SHIFT – TYPES

Unchecked lateral tentorial herniation leads to central tentorial and tonsillar herniation, associated with progressive brain stem dysfunction from midbrain to medulla.

CLINICAL EFFECTS OF BRAIN SHIFT

An injudicious lumbar puncture in the presence of a subtentorial mass may create a pressure gradient sufficient to induce tonsillar herniation.

N.B. Harvey Cushing described cardiovascular changes – an increase in blood pressure and a fall in pulse rate, associated with an expanding intracranial mass, and probably resulting from direct medullary compression. The clinical value of these observations is often overemphasised. They are often absent; when present they are invariably preceded by a deterioration in conscious level.

INVESTIGATIONS

Patients with suspected raised intracranial pressure require an urgent CT/MRI scan. Intracranial pressure monitoring where appropriate (see page 53).

TREATMENT OF RAISED INTRACRANIAL PRESSURE

When a rising intracranial pressure is caused by an expanding mass, or is compounded by respiratory problems, treatment is clear-cut; the mass must be removed and blood gases restored to normal levels – by ventilation if necessary.

In some patients, despite the above measures, cerebral swelling may produce a marked increase in intracranial pressure. This may follow removal of a tumour or haematoma or may complicate a diffuse head injury. Artificial methods of lowering intracranial pressure may prevent brain damage and death from brain shift, but some methods lead to reduced cerebral blood flow, which in itself may cause brain damage (see page 84).

Intracranial pressure is monitored with a ventricular catheter or surface pressure recording device (see page 52). Treatment may be instituted when the mean ICP is > 25 mmHg. Ensure cause is not due to constriction of neck veins.

Methods of reducing intracranial pressure

Mannitol infusion: An i.v. bolus of 100 ml of 20% mannitol infused over 15 minutes reduces intracranial pressure by establishing an osmotic gradient between the plasma and brain tissue. This method ‘buys’ time prior to craniotomy in a patient deteriorating from a mass lesion. Mannitol is also used 6 hourly for a 24–48 hour period in an attempt to reduce raised ICP. Repeated infusions, however, lead to equilibration and a high intracellular osmotic pressure, thus counteracting further treatment. In addition, repeated doses may precipitate lethal rises in arterial blood pressure and acute tubular necrosis. Its use is therefore best reserved for emergency situations.

CSF withdrawal: Removal of a few ml of CSF from the ventricle immediately reduces the intracranial pressure. Within minutes, however, the pressure will rise and further CSF withdrawal will be required. In practice, this method is of limited value, since CSF outflow to the lumbar theca results in a diminished intracranial CSF volume and the lateral ventricles are often collapsed. Continuous CSF drainage may make most advantage of this method.

Sedatives: If intracranial pressure fails to respond to standard measures then sedation may help under carefully controlled conditions.

Propofol, a short acting anaesthetic agent, reduces intracranial pressure but causes systemic vasodilatation. If this occurs pressor agents may be required to prevent a fall in blood pressure and a reduction in cerebral perfusion. Avoid high doses of Propofol; rhabdomyolysis may result and carries a 70% mortality.

Barbiturates (thiopentone) reduce neuronal activity and depress cerebral metabolism; a fall in energy requirements theoretically protects ischaemic areas. Associated vasoconstriction can reduce cerebral blood volume and intracranial pressure but systemic hypotension and myocardial depression also occur. Clinical trials of barbiturate therapy have not demonstrated any improvement in outcome.

Controlled hyperventilation: Bringing the PCO₂ down to 3.5kPa by hyperventilating the sedated or paralysed patient causes vasoconstriction. Although this reduces intracranial pressure, the resultant reduction in cerebral blood flow may aggravate ischaemic brain damage and do more harm than good (see page 232). Maintaining the blood pressure and the cerebral perfusion pressure (CPP) (>60 mmHg) appears to be as important as lowering intracranial pressure.

Decompressive craniectomy: This technique is gaining renewed interest in treating raised ICP unresponsive to other methods. The principal concern is that although reducing mortality, unacceptable levels of morbidity may result. A randomised trial of decompressive craniectomy in head injury is currently underway.

Hypothermia: Cooling to 34°C lowers ICP. Although hypothermia after cardiac arrest with slow rewarming has been reported to improve outcome, trials in head injured patients have failed to demonstrate significant benefit.

Steroids: By stabilising cell membranes, steroids play an important role in treating patients with oedema surrounding intracranial tumours. Trials have found no evidence of benefit after traumatic or ischaemic damage.

COMA AND IMPAIRED CONSCIOUS LEVEL

Consciousness is regarded as a state of awareness of self and surroundings. Impaired consciousness is due to disturbed arousal or content of mental function.

Many pathological processes may impair conscious level and numerous terms have been employed to describe the various clinical states which result, including obtundation, stupor, semicoma and deep-coma. These terms result in ambiguity and inconsistency when used by different observers. Recording conscious level with the Glasgow coma scale (page 5) avoids these difficulties and clearly describes the level of arousal. With this scale:

COMA = NO SPEECH, NO EYE OPENING, NO MOTOR RESPONSE

In this section we describe conditions which may present with, or lead to, coma. Patients experiencing ‘transient disturbance of conscious level’ require a different approach.

Pathophysiology of coma

A ‘conscious’ state depends on intact cerebral hemispheres, interacting with the ascending reticular activating system in the brain stem, midbrain, hypothalamus and thalamus. Lesions diffusely affecting the cerebral hemispheres, or directly affecting the reticular activating system cause impairment of conscious level:

CAUSES

INTRACRANIAL

Examination of the unconscious patient (see pages 29, 30)

DIAGNOSTIC APPROACH

Questioning friends, relatives or the ambulance team, followed by general and neurological examination all provide important diagnostic information.

General examination

Note the presence of:

Neurological examination

Investigations

The sequence of investigations depends on clinical suspicion:

In addition

CHEST X-RAY – may reveal a bronchial carcinoma.

ELECTROENCEPHALOGRAPHY – may provide evidence of – subclinical epilepsy

– herpes simplex encephalitis

– metabolic encephalopathy.

MRI – has a limited role in the investigation of coma. More sensitive than CT scan in demonstrating small ischaemic changes and early encephalitis.

Prognosis

Although conscious level examination does not aid diagnosis, it plays an essential role in patient management and along with the duration of coma, pupil response and eye movements provides valuable prognostic information. Non-traumatic coma tends to carry a better prognosis (see page 214).

TRANSIENT LOSS OF CONSCIOUSNESS

Many conditions causing coma may also transiently affect a patient’s conscious level. This results from:

Syncope:

Reduction in cerebral arterial oxygen supply can be caused by cardiac arrhythmias, cardiac outflow obstruction or vasovagal attack.

Seizure:

Pseudo-seizure (non-epileptic attack disorder) – see below

Acute toxic or metabolic coma:

– Drug abuse – alcohol, solvents or barbiturates – may cause transient, intermittent confusion.

– Hypoglycaemia

DIAGNOSTIC APPROACH

History

Try to obtain a history from eye-witness as well as from the patient themselves.

History from the patient:

Context: may suggest likely cause – a collapse when having blood taken suggests syncope; an episode arising from sleep suggests a seizure.

Prodrome: a brief sensation of déjà vu before the episode indicates a focal onset seizure; a feeling of lightheadness, sweatiness and visual fading suggests syncope.

Recovery: a rapid recovery suggest syncope; waking in the ambulance suggest seizure.

History from witness (find them; phone them):

How long the patient was out for; – syncope is typically less than 1 minute; seizures usually longer.

What they did; brief asynchronous jerking movements occur in syncope; more prolonged synchronous tonic clonic movements occur in seizures.

Any colour change; ‘ashen’ suggests syncope; cyanosed suggests seizure.

How quickly they recovered; rapid recovery suggest syncope.

Silent witnesses:

Incontinence is common in all forms of loss of consciousness and does not distinguish between a seizure and syncope. Tongue biting strongly suggests a seizure as do other much less common injuries – posterior dislocation of the shoulder or vertebral fracture.

Investigation is directed by the clinical history:

Electroencephalography (EEG) may reveal a focal or generalized disturbance – epilepsy.

Electrocardiography (ECG) and 24 hour ECG may reveal a cardiac arrythmia.

Head up tilt-table testing may reveal neurocardiogenic syncope or orthostatic hypotension.

Echocardiography may reveal cardiomyopathy.

Blood glucose may indicate hypoglycaemia.

EEG telemetry is occassionally needed.

Often attacks of unconsciousness remain unexplained and possibly have a psychological basis. The circumstances of the attack (e.g. during an argument), the non-stereotyped nature of the episode suggest a non-organic explanation. Such attacks are often mistaken for a seizure and are referred to as pseudo-seizures or non-epileptic attacks (see page 99).

CONFUSIONAL STATES AND DELIRIUM

Of all acute medical admissions, 5–10% present with a confused verbal response, i.e. disorientation in time and/or place. Most patients are easily distracted, have slowed thought processes and a limited concentration span. Some may lose interest in the examination to the point of drifting off to sleep.

Perceptual disorders (illusions and hallucinations) may accompany the confused state – delirium. This is often associated with withdrawal and lack of awareness or with restlessness and hyperactivity.

Primary neurological disorders contribute to only 10% of those patients presenting with an acute confusional state. In the elderly, postoperative disorientation is particularly common and multiple factors probably apply; in these patients the prognosis is good.

The Confusion Assessment Method (CAM) is used to confirm delirium.

Feature 1 – Acute onset and fluctuating course.

Feature 2 – Inattention.

Feature 3 – Disorganised thinking.

Feature 4 – Altered level of consciousness.

The presence of features 1 and 2 and either 3 or 4 are diagnostic.

DIAGNOSTIC APPROACH

EPILEPSY

Definitions

A seizure or epileptic attack is the consequence of a paroxysmal uncontrolled discharge of neurons within the central nervous system. The clinical manifestations range from a major motor convulsion to a brief period of lack of awareness.

The prodrome refers to mood or behavioural changes which may precede the attack by some hours.

The aura refers to the symptom immediately before a seizure and will localise the attack to its point of origin within the nervous system.

The ictus refers to the attack or seizure itself.

The postictal period refers to the time immediately after the ictus during which the patient may be confused, disorientated and demonstrate automatic behaviours.

The stereotyped and uncontrollable nature of the attack is characteristic of epilepsy.

A patient is said to have epilepsy when they have had more than one seizure. It is important to remember that epilepsy is not a single condition; epilepsy can be the symptom of other disorders and there are numerous different epilepsy syndromes.

Pathogenesis

Epilepsy has been described since ancient times. The 19th century neurologist Hughlings-Jackson suggested ‘a sudden excessive disorderly discharge of cerebral neurons’ as the causation of the attack. Berger (1929) recorded the first electroencephalogram (EEG) and not long after, it was appreciated that certain seizures were characterised by particular EEG abnormalities.

Recent studies in animal models of focal epilepsy suggest a central role for the excitatory neurotransmitter glutamate. This produces a depolarisation shift by activating receptors which in turn facilitate cellular influx of Na⁺, K⁺ and Ca²⁺. Gamma amino butyric acid (GABA) has an important inhibitory influence in containing abnormal cortical discharges and preventing the development of generalised seizures.

Epilepsies have complex inheritance; molecular genetics studies in rarer syndromes with autosomal dominant features have identified genes that code for ion channel subunits, either ligand or voltage gated (Channelopathies).

Incidence and course

Epilepsy presents most commonly in childhood and adolescence or in those over 65, but may occur for the first time at any age.

5% of the population suffer a single seizure at some time.

Though there is considerable variability depending on seizure type, 6 years after diagnosis 40% of patients have had a substantial remission; after 20 years – 75%.

THE PARTIAL SEIZURES

Partial seizures are classified according to both their:

Severity – simple; complex partial; evolving to tonic/clonic convulsion

Semiology – what happens during the seizure, which reflects the site of origin, in order of frequency: temporal, frontal, parietal and occipital lobes.

FRONTAL LOBE SEIZURES

Adversive seizures

PARIETAL LOBE SEIZURES

These arise in the sensory cortex (parietal lobe), the patient describing paraesthesia or tingling in an extremity or on the face sometimes associated with a sensation of distortion of body image. A ‘march’ similar to the Jacksonian motor seizure may occur. Motor symptoms occur concurrently – the limb appears weak without involuntary movement.

The representation of limbs, trunk, etc. in the post-Rolandic sensory cortex is similar to that of the motor cortex.

VISUAL, AUDITORY and AUTONOMIC simple partial seizures occur, but are rare.

Frontal and Parietal seizures indicate structural brain disease, the focal onset localising the lesion. Full investigation is mandatory.

TEMPORAL LOBE SEIZURES

These attacks are characterised by a complex aura (initial symptom) often with some impairment of consciousness.

The nature of the attack

The content of attacks may vary in an individual patient. Commonly encountered symptoms include:

Visceral disturbance: Gustatory (taste) and olfactory (smell) hallucinations, lip smacking, epigastric fullness, choking sensation, nausea, pallor, pupillary changes (dilatation), tachycardia.

Memory disturbance: Déjà vu (‘something has happened before’), jamais vu (‘feeling of unfamiliarity’), depersonalisation, derealisation, flashbacks, formed visual or auditory hallucinations.

Motor disturbance: Fumbling movement, rubbing, chewing, semi-purposeful limb movements.

Affective disturbance: Displeasure, pleasure, depression, elation, fear.

A constellation of these symptoms associated with subtle clouding of consciousness characterises a temporal lobe onset seizure.

AUTOMATISM occurs during the state of clouding of consciousness either during or after the attack (postictal) and takes the form of involuntary, often complicated, motor activity. In ambulatory automatism, subjects may ‘wander off’.

Confusion and headache after an attack are common. The whole episode may last for seconds but occasionally may be prolonged and a rapid succession or cluster of attacks may occur. Attacks show an increased incidence in adolescence and early adult life. A history of birth trauma or febrile convulsions in infancy may be obtained. Lesions in the hippocampus occur as a result of anoxia or from the convulsion itself and act as a source of further epilepsy. When surgery is carried out, hippocampal sclerosis is often found. Occasionally other pathologies are identified, such as dysembryoplastic neuroepithelial tumours (DNET), vascular malformations and low-grade astrocytomas.

OCCIPITAL LOBE SEIZURES

These are uncommon. Typically there is an elementary visual hallucination – a line or flash – prior to a tonic-clonic seizure.

PARTIAL SEIZURES EVOLVING TO TONIC/CLONIC CONVULSION

Seizure discharges have the capacity to spread from their point of origin and excite other structures. When spread occurs to the subcortical structures (thalamus and upper reticular formation) their excitation releases a discharge which spreads back to the cerebral cortex of both hemispheres, resulting in a tonic/clonic seizure. This chain of events is reflected in the electroencephalogram (EEG).

The symptoms before the tonic/clonic convulsion give a clue to the site of the initial discharge (simple partial or complex partial).

An eyewitness account is important because retrograde amnesia may prevent recall of the onset.

TONIC/CLONIC ATTACKS

Loss of consciousness; falls to the ground.

The patient then sleeps with stertorous respiration and cannot be roused. On regaining consciousness, confusion and headache are present. He may feel exhausted for hours or even days afterwards. Muscles may ache as a result of violent movement and muscle damage occurs with elevation of the muscle enzyme creatinine phosphokinase (CPK). Trauma occurs frequently, either as a result of the fall, or as a result of the movements, e.g. posterior dislocation of the shoulder. Very rarely sudden death may occur from inhalation or an associated cardiac arrhythmia.

The differentiation of these attacks from pseudoseizures will be discussed later.

GENERALISED SEIZURES

Generalised seizure attacks arise from subcortical structures and involve both hemispheres. Consciousness may be impaired and motor manifestations are bilateral.

ABSENCES (previously called Petit mal)

The patient (usually a child) stares vacantly, eyes may blink. The absence may occur many times a day with a duration of 5–15 seconds and may be induced by hyperventilation.

The ELECTROENCEPHALOGRAM (EEG) is diagnostic.

ABSENCE STATUS

Long periods of clouding of consciousness with continuing ‘spike and wave’ activity on the EEG.

MYOCLONIC SEIZURES

Sudden, brief, generalised muscle contractions. They often occur in the morning and are occasionally associated with tonic/clonic seizures. The commonest disorder is benign juvenile myoclonic epilepsy (JME) with onset after puberty. Myoclonus on the edge of sleep is normal. Myoclonus also occurs in degenerative and metabolic disease (see page 190).

TONIC SEIZURES

Sudden sustained muscular contraction associated with immediate loss of consciousness.

Tonic episodes occur as frequently as tonic/clonic episodes in children and should alert the physician to a possible anoxic aetiology.

In adults, tonic attacks are rare.

GENERALISED SEIZURES

TONIC/CLONIC SEIZURES (previously called Grand mal)

Primary tonic/clonic seizures occur without warning or aura. The epileptic cry at onset results from tonic contraction of respiratory muscles with partial closure of vocal cords. The tonic phase is associated with rapid neuronal discharge. The clonic phase begins as neuronal discharge slows.

ATONIC SEIZURES

These are rare and almost always occur in patients with other types of seizure. They are characterised by a loss of muscle tone and a sudden fall. Consciousness may only be lost briefly. The EEG shows polyspike activity or low voltage fast activity.

SYMPTOMATIC SEIZURES

Seizures can be symptoms of acute brain pathology. If the patient goes on to develop recurrent seizures this is symptomatic epilepsy (see later).

The age of onset gives a clue to the causation.

Newborn	Infancy and Childhood	Adult
Asphyxia	Febrile convulsions	Trauma
Intracranial haemorrhage	CNS infection	Drugs and alcohol
Hypocalcaemia	Trauma	CNS infection
Hypoglycaemia	Congenital defects	Intracranial haemorrhage
Hyperbilirubinaemia	Inborn errors of metabolism	Tumours
Water intoxication	Tumours	Vascular disease
Inborn errors of metabolism		Hypoglycaemia

Seizures occur in about 5% of patients following stroke and in 5% of patients with multiple sclerosis.

SEIZURES – DIFFERENTIAL DIAGNOSIS

The following should be considered in the differential diagnosis of seizures – SYNCOPE (VASOVAGAL) ATTACKS

Syncope usually occurs when the patient is standing and result from a global reduction of cerebral blood flow.

Prodromal pallor, nausea and sweating occur associated with a feeling of lightheadness and often fading of vision. If the patient sits down, the attack may pass off or proceed to a brief loss of consciousness.

Brief asynchronous jerks are common as is urinary incontinence. Tonic and clonic movements may develop if impaired cerebral blood flow is prolonged (‘anoxic’ seizures).

Mechanism: Peripheral vasodilatation with drop in blood pressure followed by vagal overactivity with fall in heart rate.

Syncopal attacks occur in hot, crowded rooms (e.g. classroom) or in response to pain or emotional disturbance.

‘Reflex’ syncope from cardiac slowing may occur with carotid sinus compression. Similarly, cough syncope may result from vigorous coughing.

CARDIAC ARRHYTHMIAS

Seen in situations such as complete heart block (Adams-Stokes attacks).

Prolonged arrest of cardiac rate or critical reduction will progressively lead to loss of consciousness – tonic jerks – cyanosis/stertorous respiration – fixed pupils and extensor plantar responses.

On recovery of normal cardiac rhythm, the degree of persisting neurological damage depends upon the duration of the episode and the presence of pre-existing cerebrovascular disease. In suspected patients, electrocardiography is mandatory. Continuous (24 hours) ECG monitoring may be necessary.

HYPOGLYCAEMIA

Amongst other neuroglycopenic manifestations, seizures or intermittent behavioural disturbances may occur. A rapid fall of blood sugar is associated with symptoms of catecholamine release, e.g. palpitations, sweating, etc. In ‘atypical’ seizures exclude a metabolic cause by blood sugar estimation when symptomatic.

EPISODIC CONFUSION

Intermittent confusional episodes caused by drugs (e.g. barbiturates) or toxins (e.g. solvents).

PANIC ATTACKS Hyperventilation can induce focal motor and sensory symptoms.

NARCOLEPSY

Inappropriate sudden sleep episodes may easily be confused with epilepsy (see page 107).

DISSOCIATIVE SEIZURES (pseudoseizures, non-epileptic attack disorder, NEAD)

A difficult distinction lies between epileptic seizures and dissociative seizures. The latter are heterogeneous comprising episodes in which shaking/thrashing and apparent loss of consciousness occur. The episodes are often variable (rather than stereotyped), prolonged, with a rapid recovery. Often patients with epilepsy will also manifest such attacks. Patients may have a history of other functional illness and have an increased frequency of preceding sexual or physical trauma (about 30%). Dissociative seizures are usually thought to be a subconscious disorder. Rarely some patients do have insight and the episodes are part of a facticious disorder or malingering. EEG studies, particularly with video telemetry, may help discriminate. Management depends on helping the patient understand and manage the episodes, for example with cognitive behavioural therapy, managing any associated depression or anxiety and stopping unnecessary anticonvulsants.

EPILEPSY – CLASSIFICATION

The classification of epilepsy brings together the seizure semiology and other aspects of the history and investigations. The International League Against Epilepsy classified epilepsies as:

• Idiopathic – thought to be primarily genetic with generalised seizures, sometimes grouped as more specific syndromes (see below). Account for about 10–20% of cases.

• Symptomatic – partial onset seizures associated with a structural lesion, such as tumour, cortical dysplasia, infection, head injury or trauma – about 30–40% of cases. The combination of the site of seizure onset and the underlying pathology leads to the diagnosis: for example ‘post traumatic frontal lobe epilepsy’ or ‘temporal lobe epilepsy due to mesial temporal sclerosis’ or ‘symptomatic occipital lobe epilepsy secondary to an arteriovenous malformation’.

• Cryptogenic – partial onset seizures for which no cause has been found. Account for about 50% of patients.

With developments in understanding, particularly in genetics, limitations with this generally practical classification have arisen – for example familial frontal onset epilepsy (associated with a mutation in the gene encoding the neuronal nicotinic acetylcholine receptor (nAChR) alpha-4 subunit) is an idiopathic yet partial onset epilepsy. Newer proposals under consideration suggest the classification should move to ‘genetic’, ‘structural/metabolic’ or ‘of unknown cause’ rather than the groups given above.

Selected Idiopathic Epilepsy Syndromes (by age of onset)

Childhood absence epilepsy (common)

Absence seizures begin between 4 and 12 years of age. Family history in 40% of patients. The absence may occur many times a day with a duration of 5–15 seconds.

Frequent episodes lead to falling off in scholastic performance.

Attacks rarely present beyond adolescence.

In 30% of children, adolescence may bring tonic/clonic seizures.

Distinction of absences from complex partial seizures is straightforward; the latter are longer – 30 seconds or more – and followed by headache, lethargy, confusion and automatism.

EEG finds 3 Hz spike and wave (page 97)

Juvenile myoclonic epilepsy (common)

Myoclonic jerks begin in teenage years, typically in the morning. Develop tonic/clonic seizures, often with sleep deprivation, in late teens. Occasionally have absence seizures. EEG frequently finds 4-5 polyspike and wave discharges.

West Syndrome (rare)

Infants present with diffusely abnormal EEGs, tonic clonic convulsions, myoclonic jerks and mental retardation following perinatal trauma or asphyxia. The seizures are sometimes called infantile spasms and the abnormal EEG pattern between events – hypsarrhythmia. Mortality or severe disability is high.

Lennox-Gastaut Syndrome (rare)

The REFLEX EPILEPSIES are a rare group of seizure disorders in which tonic/clonic or complex partial seizures are evoked by sensory stimuli. These stimuli can be certain pieces of music (Musicogenic epilepsy), reading (reading epilepsy) or performing calculations (arithmetical epilepsy).

EPILEPSY – INVESTIGATION

Investigations are directed at:

• corroborating the diagnosis of epilepsy

• classifying the type of epilepsy

• looking for an underlying cause

• eliminating alternative diagnoses

The relative emphasis of these elements will depend on the clinical situation.

For most patients the clinical diagnosis of a seizure is secure and the emphasis is to seek the cause and to classify the epilepsy to direct treatment. In others the main concern is whether the episodes are seizures or an alternative diagnosis.

Neuroimaging

All adults and all with focal onset seizures should be scanned. MRI brain imaging is more sensitive than CT and many lesions, for example small tumours, cortical dysplasia or hippocampal sclerosis will be missed on CT.

EEG

Standard interictal EEG is relatively insensitive – though this varies according to the type of epilepsy (it is very sensitive in childhood absence epilepsy). The interpretation of abnormalities requires caution; 0.5% of the normal population have inter-ictal spikes or sharp waves (epileptic discharges) as compared to 30% of patients after their first seizure.

The pattern of abnormalites can point towards a focal or generalised onset and can supplement the clinical classification.

Sleep deprived EEG increases the yield but with the risk of provoking a seizure. EEG shortly after a seizure is more likely to find an abnormality.

Ambulatory EEG recording increases the chance of finding an abnormality and of recording a clinical event. The ‘gold standard’ investigation is simultaneous EEG monitoring and video monitoring (videotelemetry).

Eliminating alternatives

ECG should be done in all patients with seizures. This is a simple cheap test and a small number of epilepsy mimics can be identified this way, e.g. prolonged QT syndrome.

Prolonged ECG may be useful in patients with possible cardiac syncope – especially in patients with sleep associated events. Implantable loop recorders can be used when patients have infrequent events.

Head up tilt table testing is often helpful in the diagnosis of neurocardiogenic syncope.

Metabolic investigation to consider include fasting glucose for insulinoma and synacthen test for Addison’s disease.

Advanced investigation

Volumetric MRI can identify hippocampal sclerosis not apparent on conventional imaging.

Functional imaging, using ictal and inter-ictal SPECT may be helpful in identifying an epileptogenic focus when evaluating patients for surgery.

Advanced EEG techniques for example using sphenoidal electrodes or recording from surgically inserted intracranial grid or depth electrodes can help localise a focus before surgery.

EPILEPSY – TREATMENT

Basic principles: Most patients respond to anticonvulsant drug therapy. Drug treatment should be simple, preferably using one anticonvulsant (monotherapy). Polytherapy should be avoided to minimise adverse effects and drug interactions.

Treatment aims to prevent seizures without side effects though this is not always achieved. Surgery is an option in a small number on non-responders.

Teratogenicity: it is important to consider the teratogenetic risks when starting any anticonvulsant in a woman of childbearing age. Large prospective studies have established rates of major congenital malformations for widely used drugs: those on no medication, carbamazepine or lamotrigine had similar rates of around 3%; in valproate monotherapy the rate was significantly higher at 6%; polytherapy overall was about 6%, and 9% if valproate was one of the drugs.

Interactions: many anticonvulsants (especially carbamazepine, phenytoin, phenobarbitone) induce liver enzymes to increase metabolism of other drugs (notably the oral contraceptive, warfarin and other anticonvulsants); valproate inhibits liver enzymes.

Blood levels: monitoring levels is useful for phenytoin because of the difficult pharmacokinetics. Other blood levels can occasionally be useful to check the patient is taking the medication or for toxicity.

Drug choice:

Idiopathic generalised epilepsy: sodium valproate*; lamotrigine*; topiramate; levetiracetam; phenytoin.

Partial (focal) epilepsy: lamotrigine*; carbamazepine*; sodium valproate*; Phenytoin*; Phenobarbitone; Levetiracetam; Topiramate; Tiagabine; Zonisamide; Oxcarbazepine; Gabapentin; pregabalin; lacosamide.

Those drugs asterisked are typically used for monotherapy others as ‘add-on’ therapy when control sub-optimal. The choice of anticonvulsant will be a balance between efficacy, adverse effects, teratogenicity and drug interactions and the patient should be involved in this decision.

Lifestyle issues: Generally there should be as few restrictions as possible (see driving regulations). Patient should be made aware of potential triggers to avoid – sleep deprivation, excess alcohol, and, where relevant flashing lights (though most patients are not photosensitive). Sensible precautions – showering rather than taking a bath, avoiding heights – should be suggested.

EPILEPSY – SURGICAL TREATMENT

In some patients, particularly those with complex partial epilepsy, seizures remain intractable despite adequate drug administration and prevent a normal lifestyle; of those, a proportion will benefit from surgery.

Operation is contraindicated in patients with severe mental retardation or with an underlying psychiatric problem.

Investigations: Videotelemetry (24–48 hr EEG), in some after electrode grid or depth electrode insertion and imaging with MRI, SPECT or PET scanning help identify the primary focus. Coronal MRI may show ‘mesial temporal sclosis’ or a structural abnormality (e.g. tumour, AVM, hamartoma or a neuronal migration disorder). The presence of such a lesion improves the chance of a good result with resective surgery.

Operative techniques

Vagal nerve stimulation (VNS): involves periodic stimulation of the left vagus nerve by an implanted stimulator. Considered in patients with intractable epilepsy not suited to the resective procedures. VNS appears to reduce neuronal excitability, but the exact mechanism remains obscure. About 30% of patients show a 50% seizure reduction within two years.

EPILEPSY – SPECIFIC ISSUES

WITHDRAWAL OF DRUG TREATMENT

Withdrawal of medication can be considered when the patient has been seizure free for 2 or more years. The decision to come off medication rests with the patient. There is a risk of recurrence (about 40% on average) with a temporary loss of driving licence (and risk of loss if seizures recur). The benefit depends on circumstances but will be greatest where there are drug side effects or in a woman planning pregnancy.

Several factors increase the likelihood of relapse of epilepsy after drug withdrawal:

– epilepsy associated with known cerebral disease

– response to starting treatment

– seizure type

– early childhood onset

EPILEPSY AND PREGNANCY

Seizures developing during pregnancy: The patient may present with the first seizure during pregnancy (when investigation is limited) or during the puerperium. Tumours and arteriovenous malformations can enlarge in pregnancy and produce such seizures; however, these causes are rare and most attacks are idiopathic. In late pregnancy seizures occur in association with hypertension and proteinuria as eclampsia. This is an emergency which needs to be managed in association with obsteticians. Intravenous magnesium sulphate and delivery is the recommended management.

When seizures present post-partum consider cortical venous thrombosis.

In patients with established epilepsy folic acid is recommended, preferably preconceptually, to reduce congenital malfomations (on little evidence). The risks of teratogenicity should be discussed with all women of childbearing ages before they become pregnant. Patients should be offered early detailed scans. Over 90% of pregnant women with epilepsy will deliver a normal child.

Strategies to best minimise the risk when nursing the baby need to be discussed, including any potential problems with breast feeding.

FEBRILE CONVULSIONS

Febrile convulsions occur in the immature brain as a response to high fever, probably as a result of water and electrolyte disturbance.

Usually occurs between 6 months and 3 years of age.

Long-term follow up suggests a liability to develop seizures in later life (unassociated with fever) especially in males, when seizures are prolonged and have focal features.

Treatment is aimed at preventing a prolonged seizure by sponging the patient and using rectal diazepam. The role of prophylaxis after one seizures is debatable.

SUDDEN UNEXPLAINED DEATH IN EPILEPSY (SUDEP)

The Standardised Mortality Ratio (SMR) compares mortality in a group with a specific illness to age and sex matched controls. The SMR is increased 2–3 times in epilepsy. When accidental death and suicide are excluded it appears that some persons with epilepsy die abruptly of no clear cause. Such deaths could be seizure related (cardiac arrhythmias/suffocation); autopsy is usually uninformative. A community-based study suggests 1 SUDEP/year/370 persons with epilepsy. Patients and carers should be compassionately informed of this small risk.

DRIVING AND EPILEPSY (DVLA UK regulations for type 1 licence (cars))

Off treatment	Isolated (single) seizure: 1 year off driving; if MRI and EEG are normal DVLA will consider reducing this to 6 months.
	Withdrawal of treatment: 6 months off driving (excluding period of drug withdrawal)
On treatment	Patients must be free of attacks (whilst awake) for 1 year
	Patients must be free of attacks whilst asleep for 1 year unless they have a 3 year history of sleep related attacks alone.