161

9Epilepsy and Its Differential Diagnosis

Types of Epilepsy . . . 161

Episodic Neurological Disturbances of Nonepileptic Origin . . . 169

Types of Epilepsy

An epileptic seizure is produced by a temporally limited, synchronous electrical discharge of neurons in the brain. It presents as a variable combination of motor, somatosensory, special sensory, autonomic, and/or behavioral disturbances, which arises suddenly and may last for a few seconds or a few minutes. On rare occasions, seizure activity persists for more than 20 minutes and may go on for hours, or even longer, without interruption (status epilepticus). The epileptic event may affect a circumscribed area of the brain (partial or focal seizures), or both cerebral hemispheres at the same time (generalized seizures). An impairment of consciousness is found in generalized seizures and in so-called complex focal seizures. In their differential diagnosis, epileptic seizures must be carefully distinguished from other sudden events involving neurological deficits and disturbances of consciousness.

Epidemiology. It has been calculated that 0.5 % of all individuals suffer from epileptic seizures. The child of a parent with idiopathic epilepsy has a 4 % likelihood of suffering from it.

Pathophysiology. Epileptic seizures are due to dysfunction of neurons in the brain, which expresses itself electrophysiologically as an abnormality of the fluctuations of electrical potential that are seen in an electroencephalogram (EEG, p. 54). (If the surface EEG is normal, such abnormalities can be revealed by recording with depth electrodes.) The underlying cause is an imbalance of excitatory and inhibitory potentials, with predominance of excitatory neurotransmitters such as glutamate and aspartate, or diminished activity of inhibitory neurotransmitters such as GABA. The synchronous discharge of neurons in a particular area of the brain is accompanied by a local increase in blood flow.

Etiology. Epileptic seizures can be produced by structural lesions in the brain (so-called epileptic foci: scar, tumor, congenital malformation), by metabolic disturbances (e. g., hypoglycemia), or by toxic influences (e. g., alcohol). These are all types of symptomatic epilepsy. In contrast, the idiopathic epilepsies involve a genetic predisposition to epileptic seizures, in the absence of a structural lesion. The cryptogenic epilepsies are presumed to be of symptomatic origin, although their cause cannot (yet) be demonstrated. Molecular genetic techniques have made it possible to trace certain forms of focal epilepsy back to abnormalities of specific gene loci.

Not uncommonly, more than one etiologic factor is at work: thus, diseases of the brain are more likely to produce epileptic seizures in persons with an inherited predisposition to seizures than in other, normal individuals.

General characteristics of epileptic disorders are the following:

Epileptic seizures are events of sudden onset, which occur with variable frequency (generally in the range of a few seizures per year to several per day).

They often present with motor phenomena (in particular, repetitive, clonic twitching or changes of muscle tone) and sometimes with somatosensory, special sensory, and/or autonomic manifestations.

Depending on their type, they may involve an impairment or loss of consciousness, or consciousness may be preserved during the seizure.

The seizure may be preceded by premonitory symptoms of various kinds (auras, e. g., nausea, ascending warmth, or a feeling or unreality).

In some patients, seizures occur in response to specific provocative and precipitating factors (sleep deprivation, alcohol withdrawal, medications, strobe lighting, hyperventilation, fever).

Classification of the Epilepsies

Epilepsy can be classified according to a number of criteria, including:

Etiology, e. g.:

“genuine/idiopathic,” genetic,

symptomatic,

cryptogenic.

Age of onset, e. g.:

epilepsy of childhood or adolescence,

epilepsy of adulthood,

late epilepsy (age 30 and up; always suspect a primary organic disease).

Setting in which seizures are most frequent, e. g.:

sleep epilepsy,

epilepsy on awakening.

EEG correlate and corresponding topographical localization, e. g.:

generalized epilepsy,

focal (partial) epilepsy.

finally, the clinical manifestations of each seizure.

Clinical classification of seizures. The nomenclature for the different clinical types of epileptic seizure proposed by the International League Against Epilepsy is reproduced in Table 9.1, with the addition of a few further designations that are currently in general use.

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162 9 Epilepsy and Its Differential Diagnosis

Table 9.1 Classification of epileptic seizures as proposed by the Practical Clinical Management

International League Against Epilepsy

of a Suspected Epileptic Seizure

1.Partial (focal, localized) seizures

1.1Simple partial seizures (without alteration of consciousness)

1.1.1with motor signs

focal motor without Jacksonian march focal motor with Jacksonian march versive

postural

phonatory (vocalization without interruption of speech)

1.1.2with somatosensory or special sensory symptoms (elementary hallucinations)

somatosensory visual

auditory olfactory gustatory vertiginous

1.1.3with autonomic symptoms or signs epigastric sensations, diarrhea pallor

sweating blushing gooseflesh

pupillary dilatation

1.1.4with mental symptoms and/or disturbances of higher cerebral function (almost always involving alteration of consciousness, i. e., more common in complex partial epilepsy)

dysphasia

dysmnesia (e. g., déjà vu)

cognitive (twilight states, altered sense of time)

affective (anxiety, agitation) illusions (e. g., dysmorphopsia) structured hallucinations

1.2Complex partial seizures (with disturbance of consciousness, sometimes beginning with simple manifestations only)

1.2.1simple partial onset, followed by disturbance of consciousness with simple partial features, followed by disturbance of consciousness with automatisms

1.2.2with disturbance of consciousness at onset with isolated disturbance of consciousness with automatisms

1.3Partial seizures with secondary generalization to a tonic− clonic (GTC) seizure (synonymous terms: GTC seizures with partial or focal onset; secondarily generalized partial

seizures)

1.3.1simple partial seizures with secondary generalization

1.3.2complex partial seizures with secondary generalization

1.3.3simple partial seizures that develop into complex partial seizures and then become secondarily generalized

2.Generalized seizures

2.1Absence seizures

with isolated disturbance of consciousness with automatisms

with mild clonic component with atonic component with tonic component

with autonomic component

2.2Atypical absences

altered muscle tone may be more prominent; seizures may begin and end gradually, rather than abruptly

2.3Myoclonic seizures single

multiple

2.4Clonic seizures

2.5Tonic seizures

2.6Tonic−clonic seizures

2.7Atonic seizures

3.Unclassifiable seizures

History and physical examination. A precise history is of the essence for the diagnosis of epilepsy and its differentiation from other, nonepileptic disorders (see below). A description of the seizures should also be obtained from someone other than the patient, if possible, because patients usually suffer amnesia for the seizures. The questions to be asked are summarized in Table 9.2. When performing the physical examination, the examiner should pay special attention to: (1) any physical evidence that a seizure has occurred; and (2) any signs of a neurological or general medical disease that might have caused the seizure (Table 9.3).

General diagnostic aspects. If the clinical findings suggest that an epileptic seizure has occurred, a series of laboratory studies and ancillary tests should be performed. These are indicated as part of the initial evaluation of every case of suspected epilepsy and mainly serve to detect, or exclude, any possible symptomatic cause of the seizure (Table 9.4).

General therapeutic aspects. If the diagnosis of pilepsy can be made securely based on the clinical findings and further testing, an appropriate course of therapy must be decided upon. Any underlying cause of symptomatic epilepsy should be treated (causal treatment); moreover, the predisposition to seizures can be treated symptomatically with one or a combination of medications (antiepileptic drugs, AEDs). Not every epileptic seizure implies a need for treatment. In many patients of a first seizure, it may be best to wait and see whether the event will repeat itself, as long as this presents no special danger and the patient agrees. The decision whether to treat with medications must always be taken on an individual basis, with due consideration of the patient’s personality, life situation, occupation, and so forth. The following situations, however, are generally held to indicate treatment:

two or more epileptic seizures within six months;

seizures in the setting of a known disease of the brain (encephalitis, cerebral hemorrhage, tumor, etc.);

epilepsy-typical potentials on EEG;

initial status epilepticus.

Some general guidelines for the treatment of epilepsy are summarized in Table 9.5. Table 9.6 provides an overview of the major antiepileptic drugs that are currently available and the indications for each.

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Types of Epilepsy 163

Table 9.2 Questions for history-taking in the aftermath of a suspected epileptic seizure

1.About the current seizure:

Premonitory signs?

Amnesia?

Loss of consciousness?

Manner of waking up?

Postictal fatigue?

Injuries?

Tongue biting?

Urinary or fecal incontinence?

Provocative factor?

2.Past history:

Family history of epilepsy?

Past events possibly causing brain damage?

Perinatal injury (left handedness, strabismus, psychomotor retardation)?

Meningitis, encephalitis?

Head trauma?

Prior episodes of loss of consciousness or related disturbances?

Febrile seizure(s) in childhood?

Unconsciousness?

Bedwetting (possibly due to nocturnal grand mal seizures)?

Twilight states? (ask specifically about partial complex seizures and déjà vu)

If epileptic seizures have occurred in the past:

When was the first one?

When was the most recent previous one?

Frequency?

Characteristics of each seizure?

EEG obtained? If so, with what result?

Antiepileptic medications taken, if any: Which medications?

Dosage?

Taken regularly as directed? With what effect on seizures? Any side effects?

Table 9.4 Ancillary tests that may be useful in the aftermath of a suspected epileptic seizure

1.Evidence that a seizure has occurred

laboratory tests: elevation of CK; elevation of serum prolactin level (a few minutes after the seizure)

2.Clues implicating an underlying disease as the cause of the seizure

EEG: if a routine EEG is normal, EEG with special provocative maneuvers may be indicated (e. g., sleep deprivation, hyperventilation)

brain imaging (MRI is more sensitive than CT) to detect, or rule out, a structural lesion of the brain

lumbar puncture if meningitis and/or encephalitis is suspected

further laboratory testing (routine laboratory parameters and additional, specific ones depending on the clinical situation)

Table 9.3 Important points for physical examination in the aftermath of a suspected epileptic seizure

1.Evidence that a seizure has occurred

tongue bite

urinary or fecal incontinence

conjunctival hemorrhage

external injuries

bone fracture

shoulder dislocation

2.Clues implicating an underlying disease as the cause of the seizure

neurological deficits evident on physical examination, and/ or signs of intracranial hypertension (esp. papilledema); both are indications of an underlying organic disease of the brain

abnormal mental status; may indicate an intoxication, or an adverse effect of a medication or illicit drug

general medical conditions (evidence of metabolic or endocrine disturbances, evidence of heart disease that may be causally related to a possible episode of cerebral ischemia)

Table 9.5 General principles of the treatment of epilepsy

thorough patient education

avoidance of precipitating factors (regular sleep habits, no excessive alcohol consumption, avoidance of strobe lights)

treatment of the underlying illness, if any (e. g., resection of a meningioma)

if pharmacotherapy is indicated: choice of a suitable medication for the particular seizure type (cf. Table 9.6)

gradual increase of the dose till seizure control is achieved, or intolerable adverse effects arise. Beware of treatment failure through underdosing: the adverse effect threshold varies greatly from patient to patient and must be crossed, or nearly so, before a medication can be declared ineffective

meticulous follow-up for possible adverse effects, with especially close observation in the initial phase of treatment

checking for compliance, e. g., with serum levels, if medications appear to be ineffective

if therapy with the first agent tried is truly ineffective despite maximal dosing and adequate compliance, change to another agent of first choice, in gradual and overlapping fashion

combination therapy only if monotherapy fails

determination of serum levels when:

poor compliance is suspected

drug toxicity is suspected

drug interactions are suspected, particularly those involving enzyme induction

an already high dose is to be raised even further

medicolegal questions arise, particularly with respect to driving

guidelines for the cessation of pharmacotherapy: the patient should be free of seizures for at least 2 years; the EEG should be free of potentials typical for epilepsy; traditionally, the medication is slowly tapered off over several months (though the need for this has not been fully demonstrated); the patient and family must be explicitly told that seizures may recur during or after the tapering phase

Epilepsy and Its Differential Diagnosis

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164 9 Epilepsy and Its Differential Diagnosis

Table 9.6 Antiepileptic drugs of choice depending on the type of seizure (after Donati, in Hess). Drugs of second and third choice are listed in alphabetical order

	Partial seizures	Absences	Primary gener-	Myoclonic	West syndrome	Lennox−	Rolandic epilepsy
	with or without		alized tonic−	seizures	(salaam	Gastaut	(benign epilepsy
	generalization		clonic seizures		seizures)	syndrome	of childhood and
						(myoclonic−	adolescence, with
						astatic	central spikes on
						seizures)	EEG)
1st	carbamazepine	valproate	valproate	valproate	valproate	valproate	carbamazepine
choice	valproate	ethosuxi-			vigabatrin		sulthiame (not
		mide					available in USA)
2nd	gabapentin	lamotrigine	lamotrigine	clonazepam	ACTH	ACTH	valproate
choice	lamotrigine			ethosuximide		clobazam
	oxcarbazepine			lamotrigine		felbamate
	phenytoin
	tiagabine
	topiramate
	levetiracetam
3rd	vigabatrin	clonazepam	phenobarbital	primidone	clonazepam	carbamazepine	phenytoin
choice	clonazepam		primidone			phenytoin
	phenobarbital
	primidone

Generalized Seizures

Generalized seizures involve both cerebral hemispheres, either from the outset of seizure activity, or when an initially focal seizure becomes secondarily generalized (see below). They typically involve an obvious impairment of consciousness. Abnormalities of muscle tone are always present and there are often involuntary, repetitive motor phenomena involving both sides of the body (clonic or myoclonic activity; see also Table 9.1).

The more common types of generalized seizure are described in this section.

Tonic−Clonic Seizures (Grand Mal Epilepsy)

Pathogenesis and etiology. A grand mal seizure may be idiopathic; in such patients, it is usually primarily generalized (“centrencephalic”). It may also be due to a circumscribed brain lesion (secondary generalization). The cause can sometimes be inferred from the findings of the clinical history, imaging studies, and EEG, though it often remains obscure.

Clinical manifestations. Grand mal seizures are the most common and most impressive type of epileptic seizure and also the most familiar to nonprofessionals. Such seizures are sometimes heralded by an aura (see above) and a loud cry or shout. Next, the patient acutely loses consciousness and falls to the ground, and the muscles are tonically contracted: the limbs are extended, and the trunk and neck are hyperextended. About 10 seconds later, there follows a rhythmic, clonic, generalized twitching of all muscles of the body, accompanied by cyanosis of the face, frothing at the mouth, and possibly by a tongue bite and urinary or fecal incontinence. The

Fig. 9.1 Tongue bite incurred during a grand mal seizure.

twitching persists for a minute or a little longer and is followed by a period of initially deep unconsciousness. Within a few minutes, a gradual transition begins to a phase of confusion and somnolence (postictal twilight state) and then to the return of normal consciousness.

The entire seizure typically lasts about 10 minutes. The patient may remember the aura but is otherwise entirely amnestic for the seizure event. Afterward, the patient is tired and may complain of myalgia. A tongue bite (Fig. 9.1), urinary or fecal incontinence, and fallrelated injuries may be evident. Shoulder dislocation and vertebral or other fractures are rare.

Diagnostic evaluation. Even in the interictal period, the electroencephalogram may reveal the typical picture of synchronous, generalized spikes and waves in all electrodes (Fig. 9.2).

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Types of Epilepsy

Treatment . The medication of first choice for the treatment of grand mal epilepsy is valproate (Table 9.6).

Absences (Petit Mal)

Absences are very brief seizures involving a momentary diminution of consciousness, rather than a complete loss of consciousness. They most commonly occur in children and adolescents.

Etiology. Like other types of childhood epilepsy, absences are idiopathic.

Clinical manifestations. Motor phenomena are not always seen; if present, they are only mild (blinking, automatisms, loss of muscle tone, brief clonus). In the simplest type of absence epilepsy, petit mal epilepsy of

school-aged children, the seizures often seem to be no more than brief periods of “absent-mindedness”: the child stares fixedly with eyes turned upward, blinks, and may make movements of the tongue or mouth, or pick at his or her clothes. These types of movements are called petit mal automatisms. The entire event lasts no more than a few seconds. Absences usually occur multiple times per day. The examining physician may be able to provoke an absence by having the patient hyperventilate.

Diagnostic evaluation. The electroencephalogram reveals a pathognomonic pattern of bursts of synchronous, generalized spike-and-wave activity at a frequency of about 3 Hz. These can be provoked by hyperventilation (Fig. 9.3).

1s

50μV

Fp1	Fp2
F3	F4
C3	C4
P3	P4
O1	O2

Fig. 9.2 Interictal EEG in a patient with grand mal seizures, showing a synchronous paroxysm of generalized, partly atypical spikes and waves.

			1s
F8
	C4					50μV
F0	C0
	C3

F7

T4

P4

C0

P3

T3

Fig. 9.3 EEG in a patient with absence seizures, showing generalized spikes and waves at 3−4 Hz, induced by hyperventilation.

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Epilepsy and Its Differential Diagnosis

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