Generalized Epilepsies

Question 1

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)
Demographics:

Answer 1

Approximately 1 to 2% of all childhood epilepsies. Two thirds are boys.

Question 2

Childhood absence epilepsy (CAE, pyknolepsy)

Demographics:

Answer 2

Two-thirds are girls. Prevalence is about 10%.

Question 3

Epilepsy with myoclonic absences (MAE)

Demographics:

Answer 3

Boys predominate. MAE is very rare.

Question 4

Juvenile absence epilepsy

Demographics:

Answer 4

Both genders are equally affected. The prevalence is not completely known. It may account to 2 or 3% of all epilepsies in adults.

Question 5

Juvenile myoclonic epilepsy (JME, Janz syndrome)

Demographics:

Answer 5

Both sexes are equally affected. Prevalence is 8–10% among adult and adolescent patients with epilepsies.

Question 6

Epilepsy with GTCS only (includes epilepsy with generalized tonic clonic seizures on awakening - EGTCSA)
Demographics:

Answer 6

Men slightly predominate over women possibly due to alcohol consumption and sleep habits. Prevalence is unknown.

Question 7

AED treatment of Idiopathic generalized epilepsies

Answer 7

Clonazepam is the best choice of drug for myoclonic jerks, but is ineffective in primarily GTCSs.

Lamotrigine is effective in primarily GTCSs and absences, but may exacerbate myoclonic jerks.

Vigabatrin is the drug of first choice in the treatment of West syndrome, but its use is contra-indicated in IGE.

Tiagabine and vigabatrin are major pro-absence agents.

Zonisimide is effective for myoclonia jerks and GTCS, but weakly effective against Absences.

The only effective medications against photosensitivity are VPA and LVT.

Gabapentin exacerbates myoclonic jerks and absences.

Pregabalin is strongly pro-myoclonic.

Question 8

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)
Age range of onset

Answer 8

Onset is between seven months and six years (peak 2–4 years).

Question 9

Childhood absence epilepsy (CAE, pyknolepsy)

Age range of onset

Answer 9

Onset is between 4 and 10 years of age (peak at 5–7 years).

Question 10

Epilepsy with myoclonic absences (MAE)

Age range of onset

Answer 10

From the first months of life to the early teens (peak at seven years).

Question 11

Juvenile absence epilepsy

Age range of onset

Answer 11

The age of onset is 9–13 years, but may range from 5 to 20 years.

Question 12

Juvenile myoclonic epilepsy (JME, Janz syndrome)

Age range of onset

Answer 12

Absences, when a feature, begin between the ages of 5 and 16 years. Myoclonic jerks follow 1–9 years later, usually about the age of 14 or 15 years. GTCSs normally appear a few months later than the myoclonic jerks.

Question 13

Epilepsy with GTCS only (includes epilepsy with generalized tonic clonic seizures on awakening - EGTCSA)
Age range of onset

Answer 13

Varies from 6 to 50 years with a peek at 16–17 years.

Question 14

Autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME)
Age range of onset

Answer 14

Onset varies from 11 to 15 years

Question 15

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)
Semiology

Answer 15

Febrile or afebrile generalized tonic clonic seizures may precede the myoclonic seizures by several months

Myoclonic astatic seizures are the defining symptoms (100% of the cases).

Isolated atonic seizures and absences seizures also occur frequently, sometimes many times per day.

Tonic seizures are an exclusion criterion.

Non-convulsive status epilepticus is common, affecting one third of the patients.

Question 16

Childhood absence epilepsy (CAE, pyknolepsy)

Semiology

Answer 16

Absences are severe and frequent.

The hallmark of the absence is abrupt, brief and severe impairment of consciousness with unresponsiveness and interruption of the ongoing voluntary activity.

Automatisms occur in two thirds of the seizures, the most common being mild myoclonic elements of the eyes, eyebrows and eyelids.

Other seizures are not compatible with CAE. The only exception is febrile convulsions prior to the onset of absences. Absence seizures are commonly brought on by hyperventilation.

Exclusion criteria for CAE:
other types of seizures; truncal myoclonia (however mild myoclonic elements maybe be present); mild or no impairment of consciousness during 3 Hz discharges; poly spikes – more than three; visual (photic) precipitation of seizures.

Question 17

Epilepsy with myoclonic absences (MAE)

Semiology

Answer 17

Impairment of consciousness and rhythmic myoclonic jerks of the shoulders, arms and legs. Seizures occur many times a day.

Question 18

Juvenile absence epilepsy

Semiology

Answer 18

Frequent and severe typical absences are the characteristic and defining seizure type.

The absences are triggered by hyperventilation.

Nearly all patients also develop generalized tonic clonic seizures, mainly after awakening.

A fifth may also suffer from mild myoclonic jerks, which occur in the afternoon when the patient is tired, rather than in the morning after awakening.

Mental and psychological arousal is the main precipitating factor for absences. Conversely, sleep the preservation, fatigue, alcohol, excitement and lights are the precipitating factor for tonic clonic seizures.

In JME, absences are usually brief and mild, but in JAE they tend to be more severe. Photo sensitivity and other sensory precipitation of absences is not compatible with the diagnosis of JAE.

Question 19

Juvenile myoclonic epilepsy (JME, Janz syndrome)

Semiology

Answer 19

JME is characterized by: myoclonic jerks on awakening; GTCSs in nearly all patients; typical absences in more than a third of the patients.

Myoclonic jerks occurring after awakening are the most prominent and characteristic seizure type. Absences are brief with subtle impairment of consciousness - they are different from the absence seizures of CAE or JAE. Seizures, principally myoclonic jerks, occur within 30 min to 1 hour of awakening.

Sleep deprivation and fatigue, particularly after excessive alcohol intake, are the most powerful precipitants of jerks and GTCSs in JME.

Photosensitivity is confirmed with EEG in more than 30% of patients but this may be of no clinical significance.

Question 20

Epilepsy with GTCS only (includes epilepsy with generalized tonic clonic seizures on awakening - EGTCSA)
Semiology

Answer 20

GTCS typically occur 1 to 2 hours after awakening. Sleep deprivation, fatigue and excessive alcohol consumption are the main seizure precipitants.

Question 21

Autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME)

Answer 21

Adult onset cortical tremor and myoclonus are the defining symptoms. Cortical tremors resemble fine shivering of the fingers and hands intensified by posture. The myoclonus are typically on hands and fingers. 80% of patients also have GTCS.

Question 22

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)
Etiology

Answer 22

Genetically determined with a multifactorial polygenic fashion with variable penetrance.

Question 23

Childhood absence epilepsy (CAE, pyknolepsy)

Etiology

Answer 23

Genetically determined but the precise mode of inheritance remains unidentified.

In monozygotic twins 84% had 3 Hz GSWD.

Current evidence suggests that mutations in genes encoding GABA receptors or voltage dependent calcium channels underlie CAE.

Recent evidence suggests that CAE is caused by abnormalities in the T type Ca channels in the thalamus.

Question 24

Epilepsy with myoclonic absences (MAE)

Etiology

Answer 24

This is an idiopathic form of epilepsy.

Question 25

Juvenile absence epilepsy

Etiology

Answer 25

Genetically determined, but the mode of inheritance is not yet defined.

Question 26

Juvenile myoclonic epilepsy (JME, Janz syndrome)

Etiology

Answer 26

JME is a genetically determined syndrome. Inheritance is complex.
Molecular studies favor a susceptibility locus for JME in chromosome 6p11–12 (EJM1) or 15q14 (EJM2). A gene, C6orf33, in the EJM1 region has been identified.

Question 27

Epilepsy with GTCS only (includes epilepsy with generalized tonic clonic seizures on awakening - EGTCSA)
Etiology

Answer 27

There’s a high incidence of epilepsy in the family and a link to EJM1 locus has been reported.

ClCN2 (Cl channel) mutations also implicated.

Question 28

Autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME)
Etiology

Answer 28

The genes for ADCME have been mapped to 8q24 in Japanese and 2p11.1-q12.2 in European families. Conversely, none of these loci were found in a large French family with ADCME linked to chromosone 16pl3.

Question 29

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)

EEG

Answer 29

In the initial stages, rhythmic theta activity in the midline may be the only significant finding.

When myoclonic – atonic seizures appear, there are frequent clusters of Irregular 2-3 Hz GPSWD.

Atonia is usually concurrent with the slow wave of a single or polyspike–wave complex.

The myoclonus of EM-AS appears to be a primarily generalized epileptic phenomenon, which differs from that of Lennox–Gastaut syndrome, which originates from the frontal cortex spreading to contralateral and ipsilateral cortical areas.

Question 30

Childhood absence epilepsy (CAE, pyknolepsy)

EEG

Answer 30

Of note – in typical cases, only EEG is needed. Normal background. 3 Hz GSWD. Spikes representing fragments are common.

The myoclonic jerk coincides with the spike component of the discharge.

Question 31

Epilepsy with myoclonic absences (MAE)

EEG

Answer 31

Background is usually normal at onset but may deteriorate. Interictal 3 Hz GPSWD.

Question 32

Juvenile absence epilepsy

EEG

Answer 32

Bursts of generalized spikes – poli spikes are common.

3–4 Hz GPSWD. Usually well formed, with regular spikes and polispikes (differently than JME).

Question 33

Juvenile myoclonic epilepsy (JME, Janz syndrome)

EEG

Answer 33

3–6 Hz GPSWD, and with intradischarge fragmentations and unstable intradischarge frequency.

The ictal discharges of absences in JME are distinctly different from those in CAE and JAE. They consist of spike/double/treble or polyspikes usually preceding or superimposed on the slow waves. The typical EEG discharge of a myoclonic jerk is a generalized burst of polyspikes of 0.5–2 s duration.

Question 34

Epilepsy with GTCS only (includes epilepsy with generalized tonic clonic seizures on awakening - EGTCSA)

EEG

Answer 34

GPSWD. Photoparoxysmal responses are reported in approximately 10 to 20% of cases.

Question 35

Autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME)

EEG

Answer 35

Generalize polispikes and waves and photoparoxysmal responses.

Question 36

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)

Diagnostic Criteria

Answer 36

Inclusion criteria:
Normal development prior to the onset of seizures
Normal MRI
Onset of myoclonic, myoclonic – atonic or atonic seizures between seven months and six years of age.
Normal background EEG with 2–3 Hz GPSWD without focal spikes.

Exclusion criteria:
Dravet syndrome, Lennox – Gastaut syndrome, myoclonic epilepsy in infancy.
Tonic seizures

The differential diagnosis is mainly with benign myoclonic epilepsy in infancy , Dravet syndrome, Lennox–Gastaut syndrome and late-onset West syndrome. In general, children with EM-AS are normal prior to the development of seizures, have a strong family history of IGE, and the background EEG and brain imaging are normal.

A similar, but reversible, clinico-EEG condition may be induced by carbamazepine, oxcarbazepine and lamotrigine in a few children with rolandic sei zures or Panayiotopoulos syndrome. This possibility should be considered in children with benign focal seizures and dramatic deterioration after treatment with these drugs.

Question 37

Epilepsy with myoclonic astatic seizures (EM-AS; Doose syndrome)

Prognosis

Answer 37

Half of patients achieve a seizure-free state and normal or near-normal development. These may correspond to the idiopathic form of EM-AS.

Question 38

Childhood absence epilepsy (CAE, pyknolepsy)

Prognosis

Answer 38

Excellent. 60% chance of remission in the absence of GTCS or myoclonia.

Question 39

Epilepsy with myoclonic absences (MAE)

Prognosis

Answer 39

Nearly half of the children having paired cognitive functioning prior to the onset of absences but these are probably symptomatic cases. Half of the idiopathic children develop cognitive and behavioral impairment.

The seizures are often resistant to treatment. The three meant usually requires high doses of valproate often in combination with ethosuximide.

Question 40

Juvenile absence epilepsy

Prognosis

Answer 40

Lifelong disorder although seizures can be controlled in 70–80% of patients.

Question 41

Juvenile myoclonic epilepsy (JME, Janz syndrome)

Prognosis

Answer 41

All seizures are probably life-long, although improving after the fourth decade of life. Seizures are well-controlled in approximately 90% of patients.

Question 42

Epilepsy with GTCS only (includes epilepsy with generalized tonic clonic seizures on awakening - EGTCSA)

Prognosis

Answer 42

It is a lifelong disease. Seizures are typically well-controlled with antiepileptic medications.

Question 43

Autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME)

Prognosis

Answer 43

It is a nonprogressive disorder.