Second edition

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262 Other major syndromes
After each of these groups is discussed, attention is then
turned to a suggested diagnostic work-up.
IDIOPATHIC GENERALIZED EPILEPSIES
The idiopathic generalized epilepsies (IGEs) are genetically
determined syndromes characterized by generalized seizures
(petit mal, myoclonic, or grand mal) which usually first
appear in childhood or adolescence, and which are usually,
although not always, readily controlled by appropriate antiepileptic
drugs (AEDs), such as divalproex. Although there
is some controversy as to how many, and what types, of
IGE exist, most authorities describe the following: childhood
absence epilepsy; juvenile absence epilepsy; juvenile
myoclonic epilepsy; and, idiopathic generalized epilepsy
with tonic–clonic seizures only. This is a very important
group, accounting for approximately one-third of all
epilepsies seen among adults.
Childhood absence epilepsy and juvenile absence
epilepsy are similar in that in both disorders all patients
have petit mal seizures, and most will also have grand mal
seizures. These disorders differ in their age of onset, with
childhood absence epilepsy appearing between the ages of
4 and 8 years, and juvenile absence epilepsy between the
ages of 9 and 13 years. In all cases, the EEG shows typical
interictal generalized spike and dome discharges, especially
evident during hyperventilation.
Juvenile myoclonic epilepsy is characterized by generalized
myoclonic seizures, and, in most, by either grand mal
or petit mal seizures; onset is typically between the ages of
12 and 18 years. The EEG typically shows interictal generalized
spike, polyspike, or polyspike and wave discharges.
Idiopathic generalized epilepsy with tonic–clonic seizures
only is characterized, as the name suggests, by only grand mal
seizures. Another name for this disorder is epilepsy with generalized
tonic–clonic seizures on awakening, a synonym that
calls attention to the fact that in this disorder the grand mal
seizures, although able to occur at any time of the day, are
most often seen early in the morning, soon after awakening.
This disorder usually has an onset in adolescence or early
adult years. As with juvenile myoclonic epilepsy, the EEG in
this disorder typically shows interictal generalized spike,
polyspike, or polyspike and wave discharges.
There is some evidence that all of these IGEs share a common
genetic background, differing largely in their age of
onset (Marini et al. 2004; Yenjun et al. 2003). From a general
clinical point of view, the diagnosis should be suspected in
all cases characterized by petit mal seizures or by non-focal
grand mal seizures with onset between childhood and early
adult years, and in any case when the EEG shows generalized
interictal discharges of the spike and dome, spike, polyspike,
or polyspike and wave types (Betting et al. 2006).
METABOLIC
Of the metabolic causes of seizures, hypoglycemia is perhaps
most common, and although such seizures may be
accompanied by autonomic signs (e.g., tremor) or delirium,
it must be borne in mind that a seizure can be the presenting
manifestation of hypoglycemia (Hoefer et al. 1946;
Malouf and Brust 1985).
Hyperglycemia, occurring in the syndrome of non-ketotic
hyperosmolar hyperglycemia, has been strongly associated
with simple partial seizures with either sensory (Maccario
et al. 1965) or, more commonly, motor symptoms (Grant
and Warlow 1985; Hennis et al. 1992b): in some cases, these
simple partial seizures with motor symptoms display a reflex
character, being induced by motion (Brick et al. 1989).
Occasionally, simple partial status epilepticus with motor
symptoms (epilepsia partialis continua) may occur (Singh
et al. 1973; Singh and Strobos 1980). Rarely, simple partial
seizures may occur with hyperglycemia during diabetic
ketoacidosis (Placidi et al. 2001).
Hyponatremia, with levels at 120 mEq/L or below may
cause seizures, often in the context of a delirium (Swanson
and Iseri 1958); seizures secondary to hypernatremia are
very rare, and generally occur only with levels of
160 mEq/L or higher (Moder and Hurley 1990).
Hypocalcemia may provoke seizures that may or may
not be accompanied by other signs, such as tetany (Glaser
and Levy 1960). In cases of chronic hypocalcemia secondary
to hypoparathyroidism, seizures may be the presenting
sign (Berger and Ross 1981) or may be preceded by other
signs, for example cataracts or parkinsonism (Eraut 1974).
Hypomagnesemia, in addition to causing delirium and
myoclonus, may also lead to seizures (Hall and Joffe 1973).
Uremia may be accompanied by seizures (Tyler 1968),
with one study finding this to be the case in approximately
one-third of uremic patients (Locke et al. 1961). Rarely,
seizures in uremia may be caused not so much by the uremia
per se, but by aluminum intoxication, as occurred in
some patients with renal failure who had chronically taken
antacids (Russo et al. 1992).
TOXIC
Toxic seizures may occur secondary to medications, such as
clozapine, intoxicants, such as cocaine, and miscellaneous
toxins, such as iodinated contrast dye.
Medications
Of the medications capable of causing seizures perhaps the
most notorious is clozapine. Clozapine, an atypical antipsychotic,
causes seizures overall in 1.3 percent of patients
(Pacia and Devinsky 1994), with a higher incidence found
in patients with a history of seizures (Wilson and Claussen
1994): the risk increases with rapid dose titration (Baker
and Conley 1991; Devinsky et al. 1991) and with high doses,
rising to approximately 10 percent in those taking more
than 600 mg daily (Haller and Binder 1990). Phenothiazine
antipsychotics may also cause seizures (Olivier et al. 1982),
especially with higher doses (Logothetis 1967). Of the antidepressants,
bupropion is most likely to cause seizures:
among patients treated with 600 mg or more daily, some