Epilepsy

EPILEPSY

Essentials of Diagnosis

• Recurrent seizures.

• Characteristic

electroencephalographic

changes accompany seizures.

• Mental status abnormalities or

focal neurologic symptoms may

persist for hours postictally.

General ConsiderationsThe term "epilepsy" denotes any

disorder characterized by recurrent

unprovoked seizures. A seizure is a transient disturbance

of cerebral function due to an

abnormal paroxysmal neuronal

discharge in the brain. Epilepsy is common, affecting

approximately 0.5% of the population

in the United States

Etiology

Genetic EpilepsyThis category encompasses a broad

range of disorders, for which the age at onset ranges from the neonatal period to adolescence or even later in life. Monogenic disorders tend to exhibit an

autosomal dominant pattern of inheritance, and where the mutation is known, the responsible gene often encodes a neuronal ion channel.

Structural/Metabolic EpilepsyThere are many causes for recurrent seizures

Metabolic disordersWithdrawal from alcohol or drugs. Uremia andHypoglycemia or hyperglycemiaSince these seizures are provoked by a readily reversible cause, this would not be considered epilepsy

TraumaAn important cause of seizures at any age especially in young adults. Posttraumatic epilepsy is more likely to develop if the dura mater was penetrated and generally becomes manifest within 2 years following the injury. However, seizures developing in the first week after head injury do not necessarily imply that future attacks will occur. There is no clear evidence that prophylactic anticonvulsant drug treatment reduces the incidence of posttraumatic epilepsy.

Tumors and other space-occupying lesionsNeoplasms may lead to seizures at any ageEspecially important cause of seizures in middle and later lifeSeizures are commonly the initial symptoms of the tumoroften are focal in character. They are most likely to occur with structural lesions involving the frontal, parietal, or temporal regions. Tumors must be excluded by imaging studies (MRI preferred over CT) in all patients with onset of seizures after 30 years of age, focal seizures or signs, or a progressive seizure disorder.

Vascular diseases

Become increasingly frequent causes of seizures with advancing ageAre the most common cause of seizures with onset at age 60 years or older

Degenerative disordersAlzheimer disease and other degenerative disorders are a cause of seizures in later life.

Infectious diseasesMust be considered in all age groups potentially reversible causes of seizures.Seizures may occur with an acute infective or inflammatory illnessBacterial meningitis or herpes encephalitis or in patients with more longstanding or chronic disorders, such as neurosyphilis or cerebral cysticercosis. In patients with AIDS, they may result from central nervous system toxoplasmosis, cryptococcal meningitis, secondary viral encephalitis, or other infective complications.Seizures are a common sequela of supratentorial brain abscess, developing most frequently in the first year after treatment.

UnknownIn many cases, the cause of epilepsycannot be determined.

Pediatric age groupsCongenital abnormalities and perinatal injuries may result in seizures presenting in infancy or childhood.

Classification of SeizuresThe International League Against Epilepsydistinguishes seizures affecting only part of the brain (focal seizures) from those that are generalized.

Seizure classification.

Seizure Type Key Features Other Associated Features

Focal seizures Involvement of only a restricted

part of brain; may evolve to a

bilateral, convulsive seizure

Without

impairment of

consciousness

Observable focal motor or autonomic

symptoms, or subjective sensory or

psychic symptoms may occur

With impairment

of consciousness

Above symptoms may precede,

accompany, or follow the period of

altered responsiveness

Generalized

seizures

Diffuse involvement of brain at

onset

Absence (petit

mal)

Consciousness impaired briefly;

patient often unaware of attacks

May have clonic, tonic, or atonic (ie,

loss of postural tone) components;

autonomic components (eg, enuresis);

or accompanying automatisms

Almost always begin in childhood and

frequently cease by age 20

Atypical absences May be more gradual in onset

and termination than typical

absence

More marked changes in tone may

occur

Myoclonic Single or multiple myoclonic

jerks

Tonic-clonic

(grand mal)

Tonic phase: Sudden loss of

consciousness, with rigidity and

arrest of respiration, lasting < 1

minute

Clonic phase: Jerking occurs,

usually for < 2–3 minutes

Flaccid coma: Variable duration

May be accompanied by tongue biting,

incontinence, or aspiration; commonly

followed by postictal confusion

variable in duration

Status epilepticus Repeated seizures without

recovery between them; a fixed

and enduring epileptic condition

lasting ≥ 30 minutes

Focal SeizuresThe initial clinical and EEG manifestations of partial seizures indicate that only a restricted part of one cerebral hemisphere has been activated.The ictal manifestations depend on the area of the brain involved Focal seizures sometimes involve impairment of consciousness and may evolve to convulsive seizures, in a process previously called secondary generalization.

Without impairment of consciousness Seizures may be manifested by focal motor symptoms

(convulsive jerking) Somatosensory symptoms (eg, paresthesias or tingling) that

spread (or “march”) to different parts of the limb or body depending on their cortical representation

Were previously described as “simple partial” seizures In other instances, special sensory symptoms (eg, light

flashes or buzzing) indicate involvement of visual, auditory, olfactory, or gustatory regions of the brain

There may be autonomic symptoms or signs (eg, abnormal epigastric sensations, sweating, flushing, pupillary dilation).

The sole manifestations of some seizures are phenomena such as dysphasia, dysmnesic symptoms (eg, déjà vu, jamaisvu), affective disturbances, illusions, or structured hallucinations, but such symptoms are usually accompanied by impairment of consciousness.

With impairment of consciousness Impaired consciousness or responsiveness

may be preceded, accompanied, or followed by the various symptoms mentioned above

Automatisms may occur. Such dyscognitive seizures were previously

called "complex partial" seizures.

Generalized Seizures There are several different varieties of

generalized seizures In some circumstances, seizures cannot

be classified because of incomplete information or because they do not fit into any category.

Absence seizures These are characterized by impairment of consciousness, sometimes

with mild clonic, tonic, or atonic components (ie, reduction or loss of postural tone), autonomic components (eg, enuresis)

Or accompanying automatisms Onset and termination of attacks are abrupt If attacks occur during conversation, the patient may miss a few words

or may break off in midsentence for a few seconds The impairment of external awareness is so brief that the patient is

unaware of it Absence ("petit mal") seizures almost always begin in childhood and

frequently cease by the age of 20 years or are then replaced by other forms of generalized seizure

Electroencephalographically, such attacks are associated with bursts of bilaterally synchronous and symmetric 3-Hz spike-and-wave activity

A normal background in the electroencephalogram and normal or above-normal intelligence imply a good prognosis for the ultimate cessation of these seizures.

Atypical absence seizures There may be more marked changes in tone, or attacks may

have a more gradual onset and termination than in typical absence seizures.

They commonly occur in patients with multiple seizure types May be accompanied by developmental delay or mental

retardation Are associated with slower spike-wave discharges than those in

typical absence attacks.

Myoclonic seizuresMyoclonic seizures consist of single or multiple myoclonic jerks.

Tonic-clonic ("grand mal") seizuresIn these seizures, which are characterized by sudden loss of consciousnessthe patient becomes rigid and falls to the groundrespiration is arrested.This tonic phase, which usually lasts for < 1 minute, is followed by a clonic phase in which

there is jerking of the body musculature that may last for 2 or 3 minutes followed by a stage of flaccid comaDuring the seizure, the tongue or lips may be bitten, urinary or fecal incontinence may occurthe patient may be injured.Immediately after the seizure, the patient may recover consciousness, drift into sleep, have a

further convulsion without recovery of consciousness between the attacks (status epilepticus), or after recovering consciousness have a further convulsion (serial seizures).In other cases, patients will behave in an abnormal fashion in the immediate postictal

period, without subsequent awareness or memory of events (postepileptic automatism).Headache, disorientation, confusion, drowsiness, nausea, soreness of the muscles, or some

combination of these symptoms commonly occurs postictally.

Tonic, clonic, or atonic seizuresLoss of consciousness may occur with either the tonic or clonic accompaniments

described above, especially in children.Atonic seizures (epileptic drop attacks) have also been described.

Clinical Findings Symptoms and Signs Nonspecific changes such as headache, mood alterations, lethargy, and myoclonic jerking alert

some patients to an impending seizure hours before it occurs. These prodromal symptoms are distinct from the aura; the aura that may precede a generalized

seizure by a few seconds or minutes is itself a part of the attack and it arises locally from a restricted part of the brain

In most patients, seizures occur unpredictably at any time and without any relationship to posture or ongoing activities

Occasionally, however, they occur at a particular time (eg, during sleep) or in relation to external precipitants such as lack of sleep, missed meals, emotional stress, menstruation, alcohol ingestion (or alcohol withdrawalbelow), or use of certain drugs

Fever and nonspecific infections may also precipitate seizures in epileptic patients. In a few patients, seizures are provoked by specific stimuli such as flashing lights or a flickering

television set (photosensitive epilepsy), music, or reading.

Clinical examination No abnormality between seizures in patients with idiopathic epilepsy In the immediate postictal period, extensor plantar responses may be seen The presence of lateralized or focal signs postictally suggests that seizures may have a focal origin In patients with symptomatic epilepsy, the findings on examination will reflect the underlying

cause.

Imaging MRI is indicated for patients with focal neurologic symptoms or signs,

focal seizures, or electroencephalographic findings of a focal disturbance some clinicians routinely order MRI for all patients with new-onset

seizure disorders. CT is generally less sensitive than MRI to small structural brain

abnormalities but may be used when MRI is contraindicated (eg, in a patient with a metallic implant).

Such studies should be performed in patients with clinical evidence of a progressive disorder and in those with new onset of seizures after the age of 20 years because of the possibility of an underlying neoplasm.

Laboratory and Other Studies Initial investigations should include complete blood count serum glucose, electrolytes, creatinine, calcium, magnesium liver function tests to exclude various causes of seizures and to

provide a baseline for subsequent monitoring of long-term effects of treatment

A lumbar puncture may be necessary when any sign of infection is present or in the evaluation of new-onset seizures in the acute setting

Electroencephalography may support the clinical diagnosis of epilepsy(by demonstrating paroxysmal abnormalities containing spikes or sharp waves), provide a guide to prognosis, and help classify the seizure disorder.

Classification of the disorder is important for determining the most appropriate anticonvulsant drug with which to start treatment

For example, absence and focal seizures with impairment of consciousness may be difficult to distinguish clinically, but the electroencephalographic findings and treatment of choice differ in these two conditions.

Finally, by localizing the epileptogenic source, the electroencephalographic findings are important in evaluating candidates for surgical treatment.

Differential Diagnosis The distinction between the various disorders

likely to be confused with generalized seizures is usually made on the basis of the history.

The importance of obtaining an eyewitness account of the attacks cannot be overemphasized.

Differential Diagnosis of Focal Seizures Transient ischemic attacks These attacks are distinguished from seizures by their longer

duration, lack of spread, and symptoms Level of consciousness, which is unaltered, does not distinguish

them There is a loss of motor or sensory function (eg, weakness or

numbness) with transient ischemic attacks, whereas positive symptoms (eg, convulsive jerking or paresthesias) characterizes seizures.

Rage attacks Rage attacks are usually situational lead to goal-directed aggressive

behavior

Panic attacks These may be hard to distinguish from focal

seizures unless there is evidence of an anxiety disorder between attacks

attacks have a clear relationship to external circumstances.

Differential Diagnosis of Generalized Seizures Syncope Syncopal episodes usually occur in relation to postural change,

emotional stress, instrumentation, pain, or strainingThey are typically preceded by pallor, sweating, nausea, and

malaise and lead to loss of consciousness accompanied by flaccidity; recovery occurs rapidly with recumbency, and there is no postictal headache or confusion

In some instances, however, motor accompaniments and urinary incontinence may simulate a seizure.

Cardiac disease Cerebral hypoperfusion due to a disturbance of cardiac

rhythm should be suspected in patients with known cardiac or vascular disease or in elderly patients who present with episodic loss of consciousness

Prodromal symptoms are typically absent Repeated Holter monitoring may be necessary to

establish the diagnosis Monitoring initiated by the patient ("event monitor")

may be valuable if the disturbances of consciousness are rare

A relationship of attacks to physical activity and the finding of a systolic murmur are suggestive of aortic stenosis

Brainstem ischemia Loss of consciousness is preceded or accompanied

by other brainstem signs Basilar artery migraine and vertebrobasilar vascular

disease are discussed elsewhere in this chapter

Psychogenic nonepileptic seizure (PNES) Simulates an epileptic seizure PNES may occur due to a conversion disorder or malingering Many patients also have true seizures or a family history of epilepsy. Although a PNES tends to occur at times of emotional stress, this may also be the case

with true seizures. Clinically, the attacks superficially resemble tonic-clonic seizures, but there may be

obvious preparation before a PNES. Moreover, there is usually no tonic phase; instead, there may be an asynchronous

thrashing of the limbs, which increases if restraints are imposed and rarely leads to injury. Consciousness may be normal or “lost,” but in the latter context the occurrence of goal-directed behavior or of shouting, swearing, etc, indicates that it is feigned. Postictally, there are no changes in behavior or neurologic findings.

Often, clinical observation is insufficient to discriminate epileptic from nonepilepticseizures. Video electroencephalographic monitoring may be helpful: epileptic seizures, especially those involving altered consciousness, commonly involve scalp electroencephalographic signs that coincide with a behavioral spell, whereas a PNES does not

The serum level of prolactin has been found to increase dramatically between 15 and 30 minutes after a tonic-clonic convulsion in most patients, whereas it is unchanged after a PNES. Serum creatine kinase levels also increase after a convulsion but not a PNES.

TreatmentGeneral Measures

For patients with epilepsy, drug treatment is prescribed with the goal of preventing further attacks and is usually continued until there have been no seizures for at least 2 yearsEpileptic patients should be advised to avoid situations

that could be dangerous or life-threatening if further seizures should occur. Legislation may require clinicians to report to the state

authorities any patients with seizures or other episodic disturbances of consciousness; driving cessation for 6 months or as legislated is appropriate following an unprovoked seizure.

Choice of medication Drug selection depends on seizure type The dose of the selected drug is gradually increased until seizures are controlled or side

effects prevent further increases If seizures continue despite treatment at the maximal tolerated dose, a second drug is added

and the dose increased depending on tolerance; the first drug is then gradually withdrawn In treatment of focal seizures, the success rate is higher with carbamazepine, phenytoin, or

valproic acid than with phenobarbital or primidone. Gabapentin, topiramate, lamotrigine, oxcarbazepine, levetiracetam, zonisamide, lacosamide, ezogabine, vigabatrin, and tiagabineare newer antiepileptic drugs used to treat focal seizures. Felbamate is also effective for such seizures but, because it may cause aplastic anemia or fulminant hepatic failure, should be used only in selected patients unresponsive to other measures. Rufinamide is currently approved only for seizures in patients with Lennox-Gastaut syndrome, but it may be effective against seizures in a broader range of refractory patients. For generalized or unclassified seizures, valproate is better tolerated than topiramate and more efficacious than lamotrigineand is thus preferred for many patients; however, the teratogenic potential of valproatemakes its use undesirable in women of childbearing age. All antiepileptics are potentially teratogenic, although the teratogenicity of the newer antiseizure medications is less clear. Nevertheless, antiepileptic medication must be given to pregnant women with epilepsy to prevent seizures, which can pose serious risk to the fetus from trauma, hypoxia, or other factors. In most patients with seizures of a single type, satisfactory control can be achieved with a single anticonvulsant drug. Treatment with two drugs may further reduce seizure frequency or severity but usually only at the cost of greater toxicity. Treatment with more than two drugs is almost always unhelpful unless the patient is having seizures of different types.