According to the National Institute for Health and Care Excellence (NICE), it is difficult to determine the true prevalence of epilepsy because identifying people who may have epilepsy is challenging. However, the World Health Organization (WHO), estimates that approximately 50 million people worldwide have epilepsy and a further 100 million will have at least one seizure at some time in their lives.

The WHO further estimates that the prevalence rates of epilepsy in Africa ranges from 2.2 to 58 per 1000 population. The lowest rate was reported in SA. In addition, the WHO found that up to 90% of people with epilepsy in Africa do not receive adequate care because of the ‘grave social stigma’ attached to the condition. People in Africa believe that epilepsy is contagious and hesitate to help or touch the person who has fallen during a seizure.

In their new guideline, NICE defines epilepsy as a common neurological disorder characterised by recurring seizures. According to the updated (2016) the International League Against Epilepsy (ILAE) definition, epilepsy is a disease of the brain defined by any of the following conditions:

  • At least two unprovoked (or reflex) seizures occurring more than 24 hours apart.
  • One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years.
  • Diagnosis of an epilepsy syndrome

Diagnosis

In terms of diagnosis, NICE recommends that children, young people and adults with a recent onset suspected seizure should be seen urgently by a specialist physician in order to ensure precise and early diagnosis and initiation of appropriate therapy.

NICE recommends the following diagnostic tests:

Electroencephalogram (EEG)

An EEG should be performed only to support a diagnosis of epilepsy in adults in whom the clinical history suggests that the seizure is likely to be epileptic in origin and to support a diagnosis of epilepsy in children and young people. If an EEG is considered necessary, it should be performed after the second epileptic seizure but may, in certain circumstances, as evaluated by the specialist, be considered after a first epileptic seizure. Repeated standard EEGs may be helpful when the diagnosis of the epilepsy or the syndrome is unclear. However, if the diagnosis has been established, repeat EEGs are not likely to be helpful.

Neuroimaging

Magnetic resonance imaging (MRI) should be the imaging investigation of choice in children, young people and adults with epilepsy. Computed tomography (CT) should be used to identify underlying gross pathology if MRI is not available or is contraindicated, and for children or young people in whom a general anaesthetic or sedation would be required for MRI but not CT. In addition, should be used to identify structural abnormalities that cause certain epilepsies. MRI is particularly important in those who develop epilepsy before the age of two years or in adulthood or if there is any suggestion of a focal onset on history, examination or EEG (unless clear evidence of benign focal epilepsy) in whom seizures continue in spite of first-line medication.

Other tests

Appropriate blood tests (for example, plasma electrolytes, glucose, calcium) to identify potential causes and/or to identify any significant comorbidity should be considered in adults. In children and young people, other investigations, including blood and urine biochemistry, should be undertaken at the discretion of the specialist to exclude other diagnoses, and to determine an underlying cause of the epilepsy. A 12-lead electrocardiogram (ECG) should be performed in adults with suspected epilepsy and in children and young people, it should be considered in cases of diagnostic uncertainty. If uncertain, refer to a cardiologist.

Neuropsychological assessment

NICE recommends neuropsychological assessment in children, young people and adults in whom it is important to evaluate learning disabilities and cognitive dysfunction, particularly in regard to language and memory.

NICE treatment recommendations

According to the new NICE guideline, patient’s needs and preferences should be taken into account when developing a treatment approach. Patients should be allowed to make informed decisions about their treatment in partnership with the healthcare team.  Good communication between healthcare professionals and people with epilepsy is therefore essential.

The guideline also recommends that treatment and care as well as the information provided to patients and their caregivers should be culturally appropriate and should be accessible to people with special needs.

The anti-epileptic drug (AED) treatment strategy should be individualised taking into account the seizure type (see Figure 1), epilepsy syndrome (see information box), comedication and comorbidity, the patient’s lifestyle (age), his/her preference and that of their caregivers.

First seizure

A patient who present to the emergency department (ED) following a suspected seizure should be screened initially by a physician and then referred to a specialist if an epileptic seizure is suspected or if the diagnosis is unclear.

Pharmacological treatment

  • Patients should be treated with a single AED (monotherapy) wherever possible. If the initial treatment is unsuccessful, then monotherapy using another drug can be tried. Caution is needed during the changeover period.
  • If an AED has failed because of adverse effects or continued seizures, a second drug should be started (which may be an alternative first-line or second-line drug) and built up to an adequate or maximum tolerated dose and then the first drug should be tapered off slowly.
  • If the second drug is unhelpful, either the first or second drug may be tapered, depending on relative efficacy, side effects and how well the drugs are tolerated before starting another drug.
  • It is recommended that combination therapy (adjunctive or ‘add-on’ therapy) should only be considered when attempts at monotherapy with AEDs have not resulted in seizure freedom. If trials of combination therapy do not bring about worthwhile benefits, treatment should revert to the regimen (monotherapy or combination therapy) that has proved most acceptable to the child, young person or adult, in terms of providing the best balance between effectiveness in reducing seizure frequency and tolerability of side effects.
  • If using carbamazepine, offer controlled-release carbamazepine preparations.
  • When prescribing sodium valproate to women and girls of present and future childbearing potential, discuss the possible risk of malformation and neurodevelopmental impairments in an unborn child, particularly with high doses of this AED or when using as part of

Initiation of pharmacological treatment

  • AED therapy should only be started once the diagnosis of epilepsy is confirmed, except in exceptional circumstances that require discussion and agreement between the prescriber, the specialist and the child, young person or adult and their family and/or carers as appropriate.
  • AED therapy should be initiated in adults on the recommendation of a specialist.
  • AED therapy in children and young people should be initiated by a specialist.
  • The decision to initiate AED therapy should be taken between the child, young person or adult, their family and/or carers (as appropriate) and the specialist after a full discussion of the risks and benefits of treatment. This discussion should take into account details of the person’s epilepsy syndrome, prognosis and lifestyle.
  • Treatment with AED therapy is generally recommended after a second epileptic seizure.
  • When possible, choose which AED to offer on the basis of the presenting epilepsy syndrome. If the epilepsy syndrome is not clear at presentation, base the decision on the presenting seizure type(s).
  • AED therapy should be considered and discussed with the patient and his/her family and/or caregivers as appropriate after a first unprovoked seizure if the patient has a neurological deficit and the EEG shows unequivocal epileptic activity or if the patient and/or his/her family and/or caregivers consider the risk of having a further seizure unacceptable brain imaging shows a structural abnormality.
  • It should be recognised that some patients (through their families and/or carers, in some instances) may choose not to take AED therapy following a full discussion of the risks and benefits.

Pharmacological treatment of focal seizures

First-line treatment

  • Carbamazepine or lamotrigine.
  • Offer levetiracetam, oxcarbazepine or sodium valproate if carbamazepine and lamotrigine are unsuitable or not tolerated. Be aware of the teratogenic risks of sodium valproate.
  • If the first AED tried is ineffective, offer an alternative AED.
  • Consider adjunctive treatment if a second well-tolerated AED is ineffective.

Adjunctive treatment in patients with refractory focal seizures

  • Offer carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist. Other AEDs that may be considered are eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin and zonisamide. Carefully consider the risk–benefit ratio when using vigabatrin because of the risk of an irreversible effect on visual fields.

Pharmacological treatment of newly diagnosed generalised tonic–clonic (GTC) seizures

First-line treatment

  • Sodium valproate.
  • Offer lamotrigine if sodium valproate is unsuitable. If the person has myoclonic seizures or is suspected of having juvenile myoclonic epilepsy (JME), be aware that lamotrigine may exacerbate myoclonic seizures.
  • Consider carbamazepine and oxcarbazepine but be aware of the risk of exacerbating myoclonic or absence seizures.

Adjunctive treatment

  • Offer clobazam, lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.
  • If there are absence or myoclonic seizures, or if JME is suspected, do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of absence seizures

First-line

  • Ethosuximide or sodium valproate. If there is a high risk of GTC seizures, offer sodium valproate first, unless it is unsuitable.
  • Offer lamotrigine if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated.

Adjunctive treatment

  • If two first-line AEDs are ineffective consider a combination of two of these three AEDs as adjunctive treatment: Ethosuximide, lamotrigine or sodium valproate.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam, levetiracetam, topiramate or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of myoclonic seizures

First-line treatment

  • Sodium valproate unless it is unsuitable.
  • Consider levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. Be aware that topiramate has a less favourable side-effect profile than levetiracetam and sodium valproate.

Adjunctive treatment

  • Offer levetiracetam, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam, piracetam or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin,
  • pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of tonic or atonic seizures

First-line treatment

  • Sodium valproate.

Adjunctive treatment

  • Offer lamotrigine as adjunctive if first-line treatment with sodium valproate is ineffective or not tolerated.
  • Other AEDs that may be considered are rufinamide and topiramate.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of infantile spasms

First-line treatment

  • Steroid (prednisolone or tetracosactide) or vigabatrin for spasms not due to tuberous sclerosis. Carefully consider the risk–benefit ratio when using vigabatrin or steroids.
  • Offer vigabatrin as first-line treatment for spasms due to tuberous sclerosis. If vigabatrin is ineffective, offer an alternative steroid (prednisolone or tetracosactide).

Pharmacological treatment of Dravet syndrome

First-line treatment

  • Consider sodium valproate or topiramate.

Adjunctive treatment

  • If first-line treatments are ineffective or not tolerated, consider clobazam or stiripentol.
  • Do not offer carbamazepine, gabapentin, lamotrigine, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of Lennox–Gastaut syndrome

First-line treatment

  • Sodium valproate.

Adjunctive treatment

  • Offer lamotrigine as adjunctive treatment to children, young people and adults with Lennox–Gastaut syndrome if first-line treatment with sodium valproate is ineffective or not tolerated.
  • Other AEDs that may be considered are rufinamide and topiramate.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin.
  • Only offer felbamate in centres providing tertiary epilepsy specialist care and when treatment with all AEDs has proved ineffective or not tolerated.

Pharmacological treatment of benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome or late-onset childhood occipital epilepsy (Gastaut type)

First-line treatment

  • Carbamazepine or lamotrigine.
  • Offer levetiracetam, oxcarbazepine or sodium valproate if carbamazepine and lamotrigine are unsuitable or not tolerated.
  • If the first AED tried is ineffective, offer an alternative AEDs. Be aware that carbamazepine and oxcarbazepine may exacerbate or unmask continuous spike and wave during slow sleep, which may occur in some children with benign epilepsy with centrotemporal spikes.
  • Consider adjunctive treatment if a second well-tolerated AED is ineffective.

Adjunctive treatment

  • Offer arbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.
  • Other AEDs that may be considered are eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin and zonisamide. Carefully consider the risk–benefit ratio when using vigabatrin because of the risk of an irreversible effect on visual fields.

Pharmacological treatment of idiopathic generalised epilepsy (IGE)

First-line treatment

  • Offer sodium valproate, particularly if there is a photoparoxysmal response on EEG.
  • Offer lamotrigine if sodium valproate is unsuitable or not tolerated. Be aware that lamotrigine can exacerbate myoclonic seizures.
  • Consider topiramate but be aware that it has a less favourable side-effect profile than sodium valproate and lamotrigine.

Adjunctive treatment

  • Offer lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, consider clobazam, clonazepam or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of JME

First-line treatment

  • Sodium valproate, unless it is unsuitable.
  • Consider lamotrigine, levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. Be aware that topiramate has a less favourable side-effect profile than lamotrigine, levetiracetam and sodium valproate, and that lamotrigine may exacerbate myoclonic seizures.

Adjunctive treatment

  • Offer lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, consider clobazam, clonazepam or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Pharmacological treatment of epilepsy with generalised GTC seizures only

First-line treatment

  • Lamotrigine or sodium valproate. If they have suspected myoclonic seizures, or are suspected of having JME, offer sodium valproate first, unless it is unsuitable.
  • Consider carbamazepine and oxcarbazepine but be aware of the risk of exacerbating myoclonic or absence seizures.

Adjunctive treatment

  • Offer clobazam, lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.

Pharmacological treatment of childhood absence epilepsy, juvenile absence epilepsy or other absence epilepsy syndromes

First-line treatment

  • Ethosuximide or sodium valproate. If there is a high risk of GTC seizures, offer sodium valproate first, unless it is unsuitable.
  • Offer lamotrigine if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated.

Adjunctive treatment

  • If two first-line AEDs are ineffective or not tolerated, consider a combination of two of these three AEDs as adjunctive treatment: Ethosuximide, lamotrigine or sodium valproate.
  • If adjunctive treatment is ineffective or not tolerated, consider clobazam, clonazepam, levetiracetam, topiramate or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

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Epilepsy syndromes

Epilepsy syndromes have a typical age of seizure onset, specific seizure types and EEG characteristics and other features. According to the ILAE, the identification of an epilepsy syndrome is useful because it provides information on which underlying etiologies should be considered and which anti-seizure medication(s) might be most useful.

Epilepsy syndromes include:

Neonatal/infantile

Self-limited neonatal seizures and self-limited familial neonatal epilepsy

Have similar clinical and electrical features. Can be distinguished on the basis of family history. Seizures start in the neonate between day four and seven and are often recurring unilateral clonic events. May alternate sides from seizure to seizure. Seizures can be repetitive over hours to days, but remit between four and six months.

Self-limited familial and non-familial infantile epilepsy

Onset of seizures is typically between three and 20 months (peak at six months). Seizures may be frequent at onset but usually remit within one year from the onset.

Early myoclonic encephalopathy

Onset of seizures is in the first two month of life (more than half of cases have onset of seizures by 10 days of life). Both sexes are affected equally.

Ohtahara syndrome

Considered an ‘epileptic encephalopathy’. This syndrome has onset in the first month of life (range one and three months). Both sexes are affected equally.

West syndrome

Onset of epileptic spasms is between three and 12 months of age. Later onset may occur. Infants may have had no antecedent history, or the antecedent history may reflect the underlying cause e.g. acquired structural brain abnormality.

Dravet syndrome

Previously known as severe myoclonic epilepsy of infancy, typically presents in the first year of life in a normal child with prolonged, febrile and afebrile, focal (usually hemiclonic) or generalised convulsive seizures.

Myoclonic epilepsy in infancy

Uncommon. Onset of myoclonic seizures is between the ages of six months and two years, in some cases earlier (four months) or later (two to four years). May be induced by photic stimulation in some patients, or by sudden noise or touch in others. Infrequent febrile seizures seen in approximately 10% of patients. Seizures remit within six months to five years from onset. Generalised convulsions may be seen in teenage years in 10%-20% of patients.

Epilepsy of infancy with migrating focal seizures

Onset of refractory focal seizures is in the first year of life, with associated severe encephalopathy.

Atypical childhood epilepsy with centrotemporal spikes

Previously known as pseudo-lennox syndrome. Atypical benign partial epilepsy of childhood and atonic-benign childhood epilepsy with centrotemporal spikes) is recognized as an atypical evolution of childhood epilepsy with centrotemporal spikes. Characterized by frequent seizures of multiple types, including nocturnal focal motor and fronto-parietal opercular seizures, negative myoclonus and atypical absence seizures.

Myoclonic encephalopathy in non-progressive disorders

Characterised by repeated episodes of myoclonic status epilepticus that occur over prolonged periods (days). The majority of patients have an underlying chromosomal disorder, others have developmental or acquired structural brain abnormalities. The cause is unknown in one fifth of cases.

Febrile seizures plus, genetic epilepsy with febrile seizures plus

Characterised by the presence of febrile seizures in an individual that may continue past the usual age where these are expected to resolve and/or be accompanied by afebrile seizures that may be generalised or focal.

Childhood

Epilepsy with myoclonic-atonic seizures

Characterised by seizures that have onset between six months and six years of age (peak two to four years). In approximately 66% of children, febrile seizures and generalised convulsive seizures precede the onset of myoclonic-atonic and atonic seizures. Both sexes are affected, with a male predominance (ratio 2:1).

Epilepsy with eyelid myoclonias

Previously known as Jeavons syndrome. Characterised by daily eyelid myoclonias with or without absences induced by eye closure and visual stimulation, seen in an otherwise normal child. Onset of seizures is between two and 14 years (peak six to eight years). Both sexes are affected with a female predominance (2F:M).

Lennox Gastaut syndrome

Characterised by the presence multiple types of intractable seizures (in particular tonic seizures in sleep, but atonic and atypical absence seizures also occur), cognitive and behavioural impairments and diffuse slow spike-and-wave and paroxysms of fast activity on EEG. Onset of seizures from age one to seven years (peak three to five years). Both sexes are affected.

Childhood absence epilepsy

A genetic generalised epilepsy that should be considered in an otherwise normal child with multiple daily absence seizures associated with 2.5 – 3.5 Hz generalized spike-and-wave. Absence seizures are provoked by hyperventilation. Characterized by onset of frequent absence seizures between the ages of two to 12 years (peak five to six years). Both sexes are equally affected.

Epilepsy with myoclonic absences

Should be considered in a child who presents with frequent daily myoclonic absence seizures. At presentation approximately half the children are developmentally and neurologically normal, learning disability is eventually seen in 70% of cases. Onset of seizures between one to 12 years of age (peak seven years). Seizures are often difficult to treat and may continue into adulthood. Both sexes are affected, with a male predominance (70%).

Panayiotopoulos syndrome

Onset of seizures is between one and 14 years of age (majority between three and six years). Seizures are infrequent in most patients, with 25% having a single seizure (which may be autonomic status epilepticus) and 50% having six seizures or less. Frequent seizures can occur in some patients. Seizures usually resolve by age 11-13 years. The EEG commonly shows high amplitude focal spikes and may be activated by sleep.

Childhood occipital epilepsy (Gastaut type)

Onset of seizures between 15 months and 19 years of age (peak eight to nine years). Remission occurs in 50-60% of patients within two to four years after onset. A dramatic response to carbamazepine is seen in more than 90% of patients. Both sexes are equally affected.

Photosensitive occipital lobe epilepsy

Onset of seizures usually between four and 12 years of age (although younger and older ages of onset are reported). Both sexes are affected.  Seizures are usually easily controlled and remission of seizures occurs within two to four years from onset.

Childhood epilepsy with centrotemporal spikes

Previously known as benign childhood epilepsy with centrotemporal spikes or Rolandic epilepsy. Onset of seizures is between three and 14 years (peak eight to nine years). Seizures usually resolve by age 13 years. Can occasionally occur up to age 18 years of age. Both sexes are affected. The seizures are brief, hemifacial seizures that may secondarily generalise if they occur nocturnally.

Atypical childhood epilepsy with centrotemporal spikes

Previously known as pseudo-Lennox syndrome. Recognized as an atypical evolution of childhood epilepsy with centrotemporal spikes. Onset of seizures between two to eight years (peak five to six years). Both sexes are affected.

Epileptic encephalopathy with continuous spike-and-wave during sleep

Onset of seizures between two and 12 years (peak four to five years), with epileptic encephalopathy with continuous spike-and-wave during sleep developing one to two years after seizure onset. Both sexes are affected.  Characterised by continuous spike-and-wave during sleep, seizures and progressive decline in cognitive, behavioural and psychiatric functioning.

Landau Kleffner syndrome

Initial presentation may be with progressive aphasia (40%), seizures or both. Onset is between two and eight years (peak five to seven years) – rarely later. Both sexes are affected.

Autosomal dominant nocturnal frontal lobe epilepsy

Onset of seizures is at a mean age of nine years (ranges from infancy to the sixth decade of life). Approximately 85% of cases have onset of seizures by 20 years of age. Both sexes are equally affected. This is a familial epilepsy with focal seizures. Cognitive decline has been reported with time in rare individuals. Treatment with low dose carbamazepine is effective, however 30% of cases are resistant to treatment.

Adolescents/adults

Juvenile absence epilepsy

Characterised by absence seizures that have onset from age eight to 20 years of age (peak 9-13 years). Less commonly, adolescents may present with generalised convulsive seizures prior to onset of absences. Treatment is usually required for life. Both males and females are affected. A previous history of febrile seizures is seen occasionally.

Juvenile myoclonic epilepsy

One of the most common genetic generalized epilepsies. Characterised by myoclonic and generalised convulsive seizures in an otherwise normal adolescent or adult. Onset is usually between eight to 25 years of age. The EEG shows generalized spike-and-wave and polyspike-and-wave. Photosensitivity is common. A small number (approximately 5%) of cases evolve into this syndrome from childhood absence epilepsy. Both males and females are equally affected. A history of febrile seizures is seen in 5%-10%.

Epilepsy with generalized tonic-clonic seizures alone

Previously known as epilepsy with grand mal seizures on awakening is a common genetic generalised epilepsy. Individuals have infrequent generalised convulsive seizures from the second decade of life, typically provoked by sleep deprivation. Onset of generalized convulsive seizures usually between the ages of 5 to 40 years (peak 11-23 years, 80% of cases have their first convulsion in the second decade). Seizures may be frequent, with one fifth of cases having more than one seizure per month prior to treatment. Treatment is required for life. Sleep deprivation, fatigue and alcohol lower threshold for seizures.

Autosomal dominant epilepsy with auditory features

Typical onset is in adolescence or early adulthood (four to 40 years). Hereditary, with focal seizures with auditory features seen in family members. Seizures often comprise such mild symptoms that they are undiagnosed.  Both sexes are affected equally.

Other familial temporal lobe

Seizure onset is >10 years of age, commonly in adolescent or adult years (median 25 years). Seizures are mild phenomena and easily controlled by medication. Both males and females are affected. Family history of similar seizures is present.

Variable age

Familial focal epilepsy with variable foci

Age of seizure onset is highly variable (from infancy to adulthood, mean age 13 years). Hereditary epilepsy, with focal seizures arising in different focal regions in different family members but with each individual in a family having a single focal seizure type. Both males and females are affected.

Reflex epilepsies

Characterised by the presence of reflex seizures and the absence of spontaneous seizures. A number reflex epilepsies are recognised e.g. reading epilepsy (seizures start between 12 and 19 years of age, male predominance [1.8 M:F], are elicited by reading [aloud or silently], prognosis is good as seizures are usually minor and can be avoided through reducing exposure to the stimulus) and startle epilepsy (characterised by seizures that may start in childhood or early adolescence [one to 16 years], affect both sexes, most patients have underlying structural brain abnormality with neurological [e.g. hemiplegia] and intellectual disability, often difficult to control).

Progressive myoclonus epilepsies

Progressive myoclonus epilepsy should considered in a patient with myoclonic seizures, with or without generalized convulsive seizures in the following settings:

  • Progressive cognitive decline.
  • Myoclonus resulting in progressive motor impairment.
  • Cerebellar signs.
  • Background slowing on EEG (particularly if increasing over time).
  • Myoclonus that is refractory to trials of appropriate anti-seizure medication.

Causes that are recognised include:

  • Neurodegenerative conditions:
    • Unverricht-Lundborg disease: Commonest cause of progressive myoclonus epilepsy, presenting with seizures before 18 years. Most cases originate from the Scandanavian or Baltic regions of Europe. Linked to mutations in the Cystatin B (EMP1) gene. Phenytoin use aggravates the seizure disorder.
    • Lafora disease: Typically presents with seizures before 20 years of age and is rapidly progressive, with death in 10 years. The disorder has been linked to mutations in the EPM2A and EPM2B genes. Lafora bodies are found in cells in most organs (neurons, liver).
  • Less commonly: Dentatorubo-pallidoluysian atrophy, juvenile Huntingtons, action-myoclonus-renal failure syndrome, juvenile neuroaxonal dystrophy, pantothenate-kinase associated neurodegeneration, neuroserpin inclusion body disease, leukoencephalopathy with vanishing white matter, early-onset Alzheimers and GOSR2 mutations.
  • Metabolic etiologies: Mitochondrial disorders (MERRF), neuronal ceroid lipofuscinosis, sialidosis.
  • Less commonly: Mitochondrial disorders (POLG1, MELAS, others), GM2 gangliosidoses, tetrahydrobiopterin deficiency, non-infantile neuronopathic Gaucher’s disease and Niemann Pick type C.
  • Immune etiologies: Celiac disease (uncommon).

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References:
  • Belhocine M, de Boer HM, Mandlhate C. Epilepsy in the WHO African region: Bridging the Gap. WHO publication, 2004.
  • Fisher RS, Cross JH, French JA et al. Operational Classification of Seizure Types by the International League Against Epilepsy. Epilepsia, 2016.
  • National Clinical Guideline Centre. The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. NICE clinical guideline 137, 2015.
  • International League Against Epilepsy. Epilepsy syndromes. https://www.epilepsydiagnosis.org/syndrome/epilepsy-syndrome-groupoverview.html, 2016.