Epileptic syndromes

Dr Muhammed Arshad

• Infantile-onset epilepsies.• Childhood-onset epilepsies.• Adolescent-onset epilepsies.• Important Genetic and Metabolic Causes.

Infantile-onset epilepsies

• West Syndrome• Dravet Syndrome• Genetic Epilepsy With Febrile Seizures Plus

West syndrome

• The most common epileptic encephalopathy with an incidence of 3 to 4.5 per 10,000 live births.

• Clinical features:TRIAD : -epileptic spasms -hypsarrhythmia -arrest or regression of psychomotor development

Epileptic spasms

• flexion, extension, or mixed flexion-extension movements that last 1 to 2 seconds in the proximal and truncal muscles and occur in clusters that last several minutes often shortly after waking.

• clusters are seen several times per day.• Focal seizures may precede or follow spasms

and should suggest an underlying focal pathology.

Hypsarrhythmia

• high-amplitude asynchronous slow waves, multifocal spikes, and polyspikes.

• most prominent during quiet sleep, often attenuated during wakefulness

Treatment

• ACTH• Vegabatrine

Dravet Syndrome

• previously called severe myoclonic epilepsy of infancy.

• relatively rare intractable childhood epilepsy syndrome with an estimated prevalence of 1 in 40,900 live births.

Clinical features

• Epilepsy onset is before age 18 months.• prolonged hemiconvulsive seizures (with or

without secondary generalization)• triggered by fever or hyperthermia.• Classically, seizures switch sides, starting on

the right with some events and the left with others

• Seizures may be falsely generalized.• In the early preschool years, other seizure

types emerge, including myoclonic, atypical absence, and focal seizures.

• Obtundation status, in which the child appears poorly responsive for several hours.

• erratic myoclonus predominantly affecting the fingers and orobuccal muscles, and discrete interspersed massive myoclonic jerks that may interfere with sleep.

• Development is normal at epilepsy onset but slows around the time of onset of myoclonus and nonconvulsive seizures.

Investigations

• SCN1A mutations are found in 80% of patients.

• EEG findings in Dravet syndrome are not specific.

Treatment

• extremely pharmacoresistant.• Sodium channel blocking agents, including

carbamazepine, oxcarbazepine, lamotrigine, and phenytoin, should be avoided as they exacerbate seizures.

• valproic acid or clobazam, although topiramate, levetiracetam, and possibly zonisamide may also have efficacy.

Genetic Epilepsy With Febrile Seizures Plus

• GEFS+ is a common familial electroclinical syndrome in which two or more family members have symptoms consistent with this diagnosis.

• Age at onset is between 6 months and 6 years, and boys and girls are equally affected.

Clinical features

• The mild phenotype are children with febrile seizures alone.

• may be recurrent, prolonged, focal, or clustered.

• Other children have febrile seizures plus, in which febrile seizures either continue beyond the age of 6 years or afebrile seizures coexist with febrile seizures.

• At the severe end of the spectrum are individuals with either myoclonic-atonic epilepsy or Dravet syndrome.

• Some individuals may also present with temporal lobe epilepsy with or without hippocampal sclerosis.

• With the exception of rare cases on the severe end of the phenotypic spectrum, children with GEFS+ are typically neurologically and developmentally normal. Antecedent birth and developmental histories are unremarkable.

Investigations

• GEFS+ is usually inherited in an autosomal dominant manner with incomplete penetrance.

• SCN1A, SCN1B, SCN2A, GABRG2, and GABRD

• EEG not spesefic.

Treatment

• Prophylactic AEDs are not indicated for simple febrile seizures.

• If they are prolonged or clustered, a home dose of rescue benzodiazepine therapy could be administered.

Prognosis

• Generally, most seizures in GEFS+ are pharmacoresponsive and self-limited, in most cases resolving before puberty. Development remains normal.

Childhood-onset epilepsies

• Panayiotopoulos Syndrome (Early-Onset Benign Occipital Epilepsy)

• Benign Epilepsy With Centrotemporal Spikes (Benign Rolandic Epilepsy)

• Electrical Status Epilepticus in Slow Sleep• Myoclonic-Atonic Epilepsy (Doose Syndrome)• Lennox-Gastaut Syndrome

Panayiotopoulos Syndrome (Early-Onset Benign Occipital Epilepsy)

• Panayiotopoulos syndrome accounts for 1% to 2% of pediatric focal epilepsy cases with a peak age at onset of 5 years.

• The condition is slightly more common in girls and affects neurologically normal children.

Clinical features

• Seizures are characterized by prominent autonomic features (eg, nausea, retching, and vomiting).

• usually occur at night• Tonic eye deviation is common• visual hallucinations are rare

• Seizures often become dyscognitive and may evolve to hemiconvulsions or generalized convulsions.

• Duration can be prolonged; up to one-third develop focal status epilepticus.

• seizure frequency is low with 33% of patients having only a single seizure.

Investigations

• EEG show: high-amplitude, frequent, focal, or multifocal

spikes that typically increase in sleep.

Location is often, but not always, in the occipital region

Treatment

• prophylactic AED treatment may not be needed if seizures are infrequent.

Prognosis

• Remission of active epilepsy typically occurs within 1 or 2 years from onset, and children can then discontinue prophylactic medications. Cognitive and social outcome is excellent.

Benign Epilepsy With Centrotemporal Spikes (Benign Rolandic Epilepsy)

• Benign epilepsy with centrotemporal spikes accounts for 6% to 10% of all childhood epilepsies

• peak age at onset of 7 to 8 years.• resolving by age 16. • Boys are more commonly affected.

Clinical features

• Focal seizures with clonic or tonic activity of one side of the lower face or tongue.

• paresthesia of the tongue, lips, gum, and cheek.

• drooling; and dysarthria are classic features of the condition.

• Hemiconvulsions are more common in young children.

• evolution to bilateral convulsive activity is frequent in sleep.

• Seizures typically occur shortly after falling asleep or before awakening.

• 15% of patients have seizures in both sleep and wakefulness and

• 20% to 30% in the waking state alone.• Seizures are typically brief and often occur in

clusters .

• Frequent seizures are seen in only 6%, while 13% to 21% will have only a single event.

• Postictal Todd paresis is seen in 7% to 16% and may suggest focal onset.

Investigations

• EEG shows:• high-amplitude, diphasic, unilateral or

bilateral, centrotemporal spikes or sharp waves, which have a characteristic horizontal dipole.

Treatment

• Prophylactic medication may not be required for children with infrequent nocturnal focal seizures.

• What is the best choice if you want to give treatment ?

Prognosis

• remission occurs in essentially all children: 50% by age 6 years, 92% by age 12 years, and 99.8% by age 18 years.

• long-term psychosocial outcome is excellent with no increase in psychiatric or personality problems and excellent occupational status.

• Rarely, this syndrome evolves atypically to electrical status epilepticus in slow sleep (ESES)

Electrical Status Epilepticus in Slow Sleep

• ESES comprises two similar but distinct syndromes:

-Continuous spike and wave in slow sleep (CSWS).

-Landau-Kleffner syndrome

Clinical features

• In both CSWS and Landau-Kleffner syndrome, marked activation of epileptiform discharges occurs during non-REM sleep to the point that they become nearly continuous.

• Children experience developmental regression, which is more global in CSWS and predominantly affects receptive language in Landau-Kleffner syndrome.

Investigations

• GRIN2Amutations have been identified to play a role in a significant minority of epilepsy-aphasia spectrum disorders.

• EEG

Treatment

• Medications that can exacerbate such activity, including oxcarbazepine and carbamazepine, should be discontinued.

• Selected AEDs, including valproate, ethosuximide, levetiracetam, lamotrigine.

• High-dose benzodiazepines or steroids are often used as first-line agents.

• Surgery can also be considered, particularly in children with CSWS with neuroimaging abnormalities.

Prognosis

• Seizures ultimately resolve or markedly decrease in frequency by puberty.

• The electrographic pattern of ESES also resolves in puberty.

• the neuropsychological prognosis is more worrisome with less than half of children achieving normal intelligence and language function.

Myoclonic-Atonic Epilepsy (Doose Syndrome)

• Doose syndrome, is a rare syndrome (1% to 2% of childhood epilepsy).

• Onset between 2 and 5 years of age and has a male preponderance.

• Most children are developmentally normal prior to the onset of seizures.

• Family history is frequently positive for either epilepsy (15% to 37%) or febrile seizures (50%)

Clinical features

• Febrile or afebrile generalized tonic-clonic seizures, followed by other generalized seizures after weeks to months.

• The myoclonic-atonic seizure is characteristic, seen in nearly all cases, consists of a brief generalized myoclonic jerk affecting proximal muscles, and is followed by an atonic component that can be very subtle (head nod) or more prominent (abrupt fall).

• Myoclonic, atonic, atypical absences, and, rarely, tonic seizures may also occur.

• One or more periods of nonconvulsive status epilepticus can be seen in 40% of patients and may be induced by inappropriate AEDs such as carbamazepine.

Investigations

• EEG: -Centroparietal theta rhythms. -Amplitude increases, and a 2-Hz to 3-Hz

generalized spike, polyspike, and wave discharge

- Photosensitivity is common.

Treatment

• valproic acid, ethosuximide, lamotrigine, topiramate, levetiracetam, zonisamide, and, in refractory cases, ACTH.

• seizures are frequently pharmacoresistant, and the ketogenic diet is one of the most efficacious therapies.

Prognosis

• Seizures remit in 54% to 89% of cases.• half of children have normal development

long term or only mild cognitive delay.

Lennox-Gastaut Syndrome

• Lennox-Gastaut syndrome is a relatively rare epilepsy syndrome with an incidence of 1.9 to 2.1 per 100,000 children.

• Accounts for approximately 6% to 7% of children with intractable epilepsy.

• Onset is typically in the preschool years, and males are preferentially affected.

• Two-thirds of cases occur in children with preexistent brain abnormalities, one-third of whom have a history of West syndrome.

Clinical features

• Triad of : -Multiple generalized seizure types, including

tonic, atonic, myoclonic, and atypical absence.

-Interictal EEG pattern of diffuse slow spike-wave complexes.

-Cognitive dysfunction.

• Nocturnal tonic events are most characteristic of Lennox-Gastaut syndrome.

• Daytime tonic and atonic seizures often lead to problematic falls.

• Nonconvulsive status epilepticus is also common but often difficult to detect in a timely manner

Investigations

• EEG: -Interictally high-amplitude 1.5-Hz to 2.5-Hz

generalized and multifocal polyspike and spike-wave discharges.

-Low-voltage frontally predominant greater than 10-Hz generalized paroxysmal fast activity is seen in slow-wave sleep

Treatment

• Seizures in Lennox-Gastaut syndrome are pharmacoresistant.

• Valproic acid and its derivatives are commonly used.

• Carbamazepine may lessen tonic seizures but worsen atypical absences.

• Ethosuximide may be helpful for refractory atypical absences.

• Given the poor response to AEDs, the ketogenic diet should be considered early in the course of Lennox-Gastaut syndrome.

• Corpus callosotomy is a possible treatment for intractable drop seizures.

• Vagus nerve stimulation reduce seizures by approximately 50% in nearly half of children

Adolescent-onset epilepsies.

Juvenile Absence Epilepsy

Juvenile Myoclonic Epilepsy

Progressive Myoclonic Epilepsy

• Progressive myoclonic epilepsies are most commonly due to neurometabolic or neurodegenerative disorders.

• Present with cognitive regression, progressive medically intractable myoclonus, and slowing of the EEG background

Genetically important syndromes

• Thanks