Color Atlas of Neurology

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

! 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.

Fixed stare, blank facial expression

Absence

Tonic arm Eyes open, upward gaze position

Mouth open

Leg extension

(in myoclonic/astatic epilepsy)

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).

Partial seizure, EEG

(right temporoparietal β-wave activity)

Benign neonatal convulsions

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

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.

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).