Color Atlas of Neurology (Thieme 2004)

Central Nervous System

Epilepsy: Seizure Types

An epileptic seizure (convulsion, fit) is a sign of brain dysfunction (p. 198). Seizures generally last no more than 2 minutes; the postictal period may be marked by impairment of consciousness or focal neurological signs. The type and extent of motor, sensory, autonomic and/or psychological disturbance during the seizure (seizure semiology) reflects the location and extent (localized/generalized) of brain dysfunction. Seizure classification, including the differentiation of true epileptic from nonepileptic seizures (pseudoseizures or psychogenic seizures, p. 202), is essential for effective treatment.

! Partial (Focal) Seizures

Focal or partial seizures reflect paroxysmal discharges restricted to a part of the affected hemisphere. By definition, simple partial seizures are those in which consciousness is not impaired, while complex partial seizures (psychomotor seizures) are those in which consciousness is impaired. A sensory or behavioral disturbance preceding a focal or generalized seizure with motor manifestations is called a seizure aura. Some features of partial seizures are listed in the table below.

The semiology of simple and complex partial seizures depends on their site of origin (focus) and the brain areas to which they spread (see table, p. 194). They may become secondarily generalized, evolving into generalized paroxysmal attacks or tonic-clonic seizures. The initial symptoms and signs vary depending on the location of the epileptic focus.

		Feature	Simple Partial Seizures	Complex Partial Seizures
		Consciousness	Unaffected	Impaired
		Duration	Seconds to minutes	Minutes
		Symptoms and signs	Depend on site of origin; no postictal	Depend on site of origin; postictal
			confusion	confusion
		Age group	Any age	Any age
192		Ictal EEG	Contralateral epileptiform discharges;	Unilateral or bilateral epileptiform
			in many cases, no interictal abnormali-	discharges, diffuse or focal
			ties are detected
	(Adapted from Gram, 1990)

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Epilepsy: Seizure Types

Ictal EEG: Focal activity on

left (frontoprecentral spike Clonus on right side waves)

of face

Clonus in right arm
	50 V
Simple partial seizure				1s

Ictal EEG: Bilateral frontotemporal activity Oral automatisms (rhythmic ε waves)

(licking, chewing, lip smacking)

Oral automatisms
(snorting, throat				50 V
clearing, chewing)					1s
Complex partial seizure
		Partial seizures (focal epilepsy)
Interictal	Prodromal	Tonic	Clonic			Postictal phase
phase	phase	phase	phase

Normal EEG	Focal or	Ictal ` and _	Rhythmic	Extinction	Irregular and
	generalized	spike waves	slowing with	phase	high β and
	dysrhythmia		occasional		sub-β wave
	and slowing		spikes		activity

Generalized seizures (schematic representation of ictal EEG in grand mal seizure)

Central Nervous System

193

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Central Nervous System

Epilepsy: Seizure Types

Site of focus	Seizure type	Symptoms and signs

Frontal lobe	Simple or complex par-
	tial seizures with or
	without secondary
	generalization (hypermo-
	tor frontal lobe seizures)

Adversive head movement and other complex motor phenomena (mainly in legs), e. g., pelvic movements, ambulatory automatisms, swimming movements, fencing posture, staring, laughing, outcries, genital fumbling, autonomic dysfunction, speech arrest. Mood changes may also occur. Seizures occur several times a day with an abrupt onset. The unvarying course of the seizures may suggest hysteria. Brief postictal confusion

Temporal lobe	Complex partial seizures	Ascending epigastric sensations (nausea, heat sensa-
	with or without second-	tion); olfactory/gustatory hallucinations; compulsive
	ary generalization	thoughts, feeling of detachment, déjà-vu, jamais-vu;
		oral and other automatisms (psychomotor attacks);
		dyspnea, urinary urgency, palpitations; macropsia,
		micropsia; postictal confusion
Parietal lobe	Simple partial seizures	Sensory and/or motor phenomena (jacksonian
	with or without second-	seizures); pain (rare)
	ary generalization

Occipital lobe	Simple partial seizure
	with or without second-
	ary generalization
(Adapted from Gram, 1990)

! Generalized Seizures

Generalized epilepsy reflects paroxysmal discharges occurring in both hemispheres. The seizures may be either convulsive (e. g., general-

Unformed visual hallucinations (sparks, flashes)

ized tonic-clonic seizure GTCS) or nonconvulsive (myoclonic, tonic, or atonic seizures; absence seizures). Generalized seizures are classified by their clinical features.

	Feature	Absence Seizure	Myoclonic	Atonic	Tonic-clonic Seizure
			Seizure	(Astatic)
				Seizure
	Conscious-	Impaired	Unaffected	Impaired	Impaired
	ness
	Duration	A few (!30) seconds	1–5 seconds	A few sec-	1–3 minutes
				onds
	Symptoms	Brief absence, vacant	Sudden, bi-	Sudden loss	Initial cry (occasionally); falls
	and signs	gaze and blinking fol-	laterally syn-	of muscle	(loss of muscle tone); respira-
		lowed by immediate	chronous	tone causing	tory arrest; cyanosis; tonic,
		return of mental clar-	jerks in arms	severe falls	then clonic seizures; muscle re-
		ity; automatisms (lip	and legs;		laxation followed by deep
		smacking, chewing,	often occur in		sleep. Tongue biting, urinary
		fiddling, fumbling)	series		and fecal incontinence
		may occur
	Age group	Children and adoles-	Children and	Infants and	Any age
		cents	adolescents	children
	Ictal EEG	Bilateral regular	Polyspike	Polyspike	Often obscured by muscle arti-
		3 (2–4) Hz spike	waves, spike	waves, flat-	facts
194		waves	waves, or	tening or low-
			sharp and	voltage fast
			slow waves	activity

(Adapted from Gram, 1990)

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Epilepsy: Seizure Types

Fixed stare, blank facial expression

	100 V	1s
		Generalized 3 Hz
		spike-wave activity

Absence

Tonic arm Eyes open, upward gaze position

Mouth open

Leg extension

	100 V		1s	Generalized
			sharp/slow-wave
				activity
				Tonic seizure

(in myoclonic/astatic epilepsy)

Body rigid, limbs extended, head back, grimace

Generalized tonic-clonic seizure

(Grand mal, tonic phase; transition to clonic phase with forceful, rhythmic convulsions)

EEG

EMG (masseter m.)

EMG (biceps brachii m.)

Pupillary diameter

Intravesical pressure

Blood pressure (systolic)

Heart rate

Respiratory rate
Prodromal phase	Ictal phase	Extinction	Recovery phase
	(tonic-clonic)	phase

Tonic-clonic grand mal seizure (temporal course)

Central Nervous System

195

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Central Nervous System

Epilepsy: Classification

The etiology and prognosis of epilepsy depend on its clinical type. All forms of epilepsy (e. g., absence epilepsy of childhood, juvenile myoclonic epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, reflex epilepsy) are characterized by recurrent paroxysmal attacks; thus classification cannot be based on a single seizure. Epileptic syndromes vary in seizure pattern, cause, age at onset, precipitating factors, EEG changes, and prognosis (e. g., neonatal convulsions, infantile spasms and salaam seizures = West syndrome, Lennox–Gastaut syndrome, temporal lobe seizures). Seizures triggered by fever, substance abuse, alcohol, eclampsia, trauma, tumor, sleep deprivation, or medications are designated as isolated nonrecurring seizures or acute epileptic

reactions. Status epilepticus is a single prolonged seizure or a series of seizures without full recovery in between. Any type of seizure (convulsive or nonconvulsive) may appear under the guise of status epilepticus. In grand mal status epilepticus, patients do not regain consciousness between seizures.

Location-related (focal, partial) epilepsy can be differentiated from generalized epilepsies and epileptic syndromes on the basis of the seizure pattern. Seizures that cannot be classified because of inadequate data on focal or generalized seizure development are called unclassified epilepsy or epileptic syndrome. Other terms used in classification refer to seizure etiology (e. g., idiopathic, cryptogenic, symptomatic).

Type of Epilepsy	Features
Location-related	Partial (focal) seizures
Generalized	Generalized convulsive seizures (GCS)
Idiopathic	No known cause other than genetic predisposition. No manifestations
	other than epileptic seizures. Characteristic age of onset
Cryptogenic	Assumed to reflect a CNS disorder of unidentified type. (Once the cause
	is identified, epilepsy is classified as symptomatic.)
Symptomatic	Due to an identified CNS disorder or lesion

	Type of Epilepsy	Etiology	Epilepsy/Epileptic Syndrome
	Location-related	Idiopathic (charac-	Benign epilepsy of childhood with centrotemporal spikes;
	(focal, localized,	teristic age of	epilepsy of childhood with occipital paroxysms
	partial)	onset)
		Cryptogenic or	Variable expression depending on cause and location (e. g., tem-
		symptomatic	poral, frontal, parietal, or occipital lobe epilepsy)
	Generalized	Idiopathic (charac-	Absence epilepsy of childhood (pyknolepsy); juvenile absence
		teristic age of	epilepsy; juvenile myoclonic epilepsy (impulsive petit mal); awak-
		onset)	ening grand mal epilepsy (GTCS); epilepsy with specific triggers
			(reflex epilepsy)
		Cryptogenic or	West syndrome (infantile spasms, salaam seizures); Lennox–
		symptomatic	Gastaut syndrome; myoclonic-astatic epilepsy; epilepsy with
			myoclonic absence
		Symptomatic	Early myoclonic encephalopathy (unspecific etiology); seizures
			secondary to various diseases
	Unsure whether	Idiopathic or symp-	Neonatal convulsions; acquired epileptic aphasia (Landau–
	focal or general-	tomatic	Kleffner syndrome)
	ized
196	Variably focal and	Symptomatic	Febrile convulsions; isolated seizure or isolated status epilepti-
	generalized	(situation-related	cus; acute metabolic or toxic triggers

seizure)

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Epilepsy: Classification

Clonus (left)

Partial seizure, EEG

(right temporoparietal β-wave activity)

Benign neonatal convulsions

1	5	10	15	20
Age of onset			Grand mal epilepsy

Prenatal lesions/disturbances

Metabolic diseases

Congenital anomalies

Encephalitis

Genetic disorders

Head trauma

Brain tumor

Cerebrovascular disorders

Absence

Generalized seizure, EEG

(generalized 3 Hz spike-wave pattern)

Febrile convulsions Lennox-Gastaut syndrome

Epilepsy with myoclonic-astatic seizures

Benign focal epilepsy of childhood Epilepsy with spike waves during sleep Pyknolepsy

Juvenile absence epilepsy Impulsive petit mal Awakening grand mal epilepsy Benign juvenile focal epilepsy

2 3 4 5 10 20 30 50 70

Etiology and age of onset	Age (years)

Central Nervous System

197

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Central Nervous System

198

Epilepsy: Pathogenesis and Treatment

Causes. Some patients have a genetic predisposition to epilepsy, particularly those with generalized epilepsies. Some hereditary diseases are associated with epilepsy (e. g., tuberous sclerosis, Sturge–Weber syndrome, mitochondrial encephalopathies, sphingolipidoses). Acquired forms of epilepsy may be focal (possibly with secondary generalization), bilateral, or diffuse (primary generalized epilepsies). The causes include developmental disorders, pyridoxine deficiency, hippocampal sclerosis, brain tumors, head trauma, cerebrovascular disturbances, alcohol, drug abuse, medications, and CNS infections.

Pathophysiology. Seizure activity in the brain is thought to be initiated by a preponderance of excitatory over inhibitory postsynaptic potentials (EPSP, IPSP), resulting in depolarization of nerve cell membranes. Such a depolarization may appear on the EEG as an interictal spike, an initial spike component, or an abrupt depolarization with superimposed high-frequency action potentials (paroxysmal depolarization shift, PDS). The synchronous discharges of large numbers of neurons result in an epileptic seizure. Seizure activity is terminated by active processes such as transmembrane ion transport via sodium–potassium pumps, adenosine release, and the liberation of endogenous opiates, whose combined effect is membrane hyperpolarization, manifested as slow-wave activity in the EEG. Factors favoring the development of seizures include changes in the concentration of electrolytes (Na+, K+, Ca2+), excitatory amino acids (glutamic acid), and inhibitory amino acids (GABA), irregular interneuron connections, and abnormal afferent connections from subcortical structures ( diencephalon, thalamus, brain stem). In focal epilepsy, the epileptic focus is surrounded by an “inhibitory margin”, while the paroxysmal activity of generalized epilepsy is spread throughout the brain.

General treatment measures. Lifestyle changes

(sleep–wake rhythm, avoidance of seizure triggers); chronic use of anticonvulsant medication. Patients with partial seizures preceded by long auras may be able to abort their seizures while still in the aura phase by various concentration techniques (seizure interruption methods).

Antiepileptic drugs (AEDs). AEDs work by a variety of mechanisms, e. g., inhibition of vol-

tage-gated sodium channels (carbamazepine, oxcarbazepine, lamotrigine, phenytoin, valproic acid) or thalamic calcium channels (ethosuximide), or interaction with inhibitory GABA receptors (benzodiazepines, phenobarbital, gabapentin, tiagabine, levetiracetam) or excitatory glutamate receptors (phenobarbital, felbamate, topiramate). Antiepileptic therapy is generally started in patients who have had a single seizure and are thought to be at risk of recurrence, in those with an epileptic syndrome, and in those who have had two or more seizures within 6 months. AEDs used to treat focal, unclassified, and symptomatic tonic-clonic seizures include carbamazepine, gabapentin, lamotrigine, oxcarbazepine, topiramate, levetiracetam, phenytoin, phenobarbital, and primidone; those used to treat generalized seizures include valproic acid, ethosuximide (absences), primidone, phenobarbital (epilepsy associated with myoclonic seizures, tonic-clonic seizures), and lamotrigine. Treatment is always begun with a single drug (monotherapy); if this ineffective, another drug is used instead of or in addition to the first (combination therapy). Antiepileptic therapy can be discontinued in some cases if the risk of seizure recurrence is judged to be low.

Other measures. Surgery (indicated in patients with drug-resistant focal epilepsy and/or resectable lesions, such as brain tumors or unilateral mesial temporal sclerosis). Vagus nerve stimulation by means of an implanted neurocybernetic prosthesis (NCP) is a form of treatment whose efficacy remains controversial.

Prognosis (Table 24, p. 373). Antiepileptic drugs prevent seizure recurrence in roughly 70% of patients, reduce the frequency of seizures in 25%, and are ineffective in 5% (drug resistance), especially those with Lennox–Gastaut syndrome, symptomatic myoclonic epilepsy, and cryptogenic syndromes.

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			Epilepsy: Pathogenesis and Treatment
Initial spike component
	Slow fluctuations		Prodromal phase
				Postictal
				phase
	Interictal
	EEG	Silent period	Tonic phase	Clonic
EEG	changes			phase
					System
			Epileptic seizure (GTCS)
	Interictal spikes
	500 ms				Nervous
Extracellular					Central
recording
	PDS		Membrane hyperpolarization
Intracellular	Neurophysiological changes during epileptic seizure
recording	(data from animal experiments)
			Eyes open
			Hypersalivation, tongue biting
Symmetric clonic
limb movements
			Enuresis, encopresis
			Grand mal (GTCS, clonic phase)		199

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Central Nervous System

Nonepileptic Seizures

The differentiation of epileptic from nonepileptic seizures is of major prognostic and therapeutic importance. Nonepileptic seizures may or may not involve loss of consciousness. Pseudoseizures resemble epileptic seizures (p. 192 ff), but are of nonepileptic origin. This broad category includes syncope, psychogenic seizures, and simulated seizures. “Pseudoseizure,” in the narrower sense, is a synonym for “psychogenic seizure.”

Nonepileptic seizures are misdiagnosed as epileptic seizures in nearly 20% of patients, roughly 15% of whom are unnecessarily treated with antiepileptic drugs; conversely, some 10% of all epileptic seizures are misdiagnosed as nonepileptic seizures; 20–30% of patients have both epileptic and nonepileptic seizures. In case of doubt, the patient should be referred to a specialist or specialized epilepsy center.

! Syncope

Syncope is defined as a brief loss of consciousness, often involving a fall, due to transient cerebral ischemia or hypoxia (see Table 25, p. 374 for potential causes). In 45% of cases, the cause can be determined from the history and physical examination. Important anamnestic clues include triggers such as excitement or anxiety, precipitating situations (blood drawing, prolonged standing, urination, coughing fits, pain), heart disease, mental illness (generalized anxiety disorder, depression, somatization disorders), and medications. The patient should be evaluated for possible blood pressure abnormalities and for cardiac or neurological disorders (p. 148). EEG yields the diagnosis in only about 2% of cases. Only rare cases of syncope are due to TIA (p. 166). Syncope clinically resembles an epileptic seizure in some ways, but differs in others (see table, below).

		Clinical Feature	Syncope	Epileptic Seizure
		Triggers	Common	No
		Time of day	Mostly diurnal; does not awaken	Day or night; awakens patient from
			patient from sleep	sleep
		Skin coloration	Pale	Cyanotic or normal
		Premonitory symptoms	Tinnitus, visual blurring or blackout,	None or aura
			feeling faint, lightheadedness
		Type of fall	Collapse or fall over stiffly (often back-	Fall over stiffly
			wards)
		Duration	Usually ! 30 seconds	1–3 minutes or longer
		Abnormal movements	Frequent, arrhythmic, multifocal to	Always generalized, 1–2 minutes
		(myoclonus)	generalized, last ! 30 seconds
		Eyes	Open	Closed
		Urinary incontinence	Occasional	Common
		Postictal confusion	Brief or absent	Longer-lasting
		Tongue-biting	Occasional	Common
		Prolactin, creatine kinase	Normal	Elevated
200		Typical EEG changes	Absent	Common
		Focal neurological deficit	Absent	Occasional

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	Nonepileptic Seizures
Vertigo, light-	Sweating, yawning, tinnitus,
headedness,	unsteadiness, pallor, visual disturbances
malaise	(blurred, gray, black)

Central Nervous System

Warning signs

Fall (by collapsing or falling over stiffly; may cause injury)

Brief unconsciousness (myoclonus possibly accompanied by tonic convulsions)

Brief reorientation phase

201

Syncope

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