Epilepsy syndrome

TABLE 27-1. International League Against Epilepsy Classification Scheme for Epilepsies and Epilepsy Syndromes... 

Classification of epilepsies and epilepsy syndromes is helpful in determining appropriate pharmacotherapy. This classification scheme is based on the type of seizures a patient has and an attempt to identify the etiology of the epilepsy or epilepsy syndrome. 

Juvenile myoclonic epilepsy (JME) A primary generalized epilepsy syndrome that usually starts in the early to middle teenage years and has a strong familial component. Patients have myoclonic jerks and tonic-clonic seizures and may also have absence seizures. 

Once it is concluded that the patient has seizures, the type of seizure and epilepsy syndrome, if any, must be determined. Proper identification and classification of the seizure type is most helpful in selecting appropriate pharmacotherapy. Without an accurate classification of the seizure type, it is possible to select a medication that is ineffective or even harmful to the patient. 

Rufinamide is a new triazole derivative with little similarity to other antiseizure drugs. It is approved for use in Lennox-Gastaut syndrome and preliminary evidence suggests that it may also be useful in other difficult-to-treat epilepsy syndromes. 

Crosby AH (2004) Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet 36 1225-1229... 

Agent (Initial Availability) Seizure Type or Epilepsy Syndrome ... 

The CASR has been further implicated in neurological functions since an idiopathic epilepsy locus was mapped to the CASR locus and novel, rare missense CASR variants were identified in idiopathic generalized epilepsy [58, 59]. Mutations involved in the idiopathic epilepsy syndrome disrupt an arginine-rich retention motif in the proximal part of the CASR cytoplasmic tail promoting greater cell-surface expression and activity of the CASR than normal [59]. 

Kapoor A, Satishchandra P, Ratnapriya R et al (2008) An idiopathic epilepsy syndrome linked to 3ql3.3-q21 and missense mutations in the extracellular calcium-sensing receptor gene. Ann Neurol 64 158-167... 

Stepanchick A, McKenna J, McGovern O et al (2010) Calcium-sensing receptor mutations implicated in pancreatitis and idiopathic epilepsy syndrome disrupt an arginine-rich retention motif. Cell Physiol Biochem 26 363-374... 

Seizure type KD is effective in models employing a wide variety of seizure paradigms KD is effective in a wide variety of seizure types and epilepsy syndromes... 

The International League Against Epilepsy (ILAE) has proposed two major schemes for the classification of seizmes and epilepsies the International Classification of Epileptic Seizmes and the International Classification of the Epilepsies and Epilepsy Syndromes. ... 

Epilepsy syndrome—The combination of seizure type with other components of the patient history such as age of onset, intellectual development, findings on neurologic examination, and results of neuroimaging. 

Valproic acid is the drug of choice for myoclonic seizures in juvenile myoclonic epilepsy, in which myoclonic seizures often coexist with tonic-clonic and absence seizures. No trials have examined any of the newly introduced drugs for patients with juvenile myoclonic epilepsy or other idiopathic generalized epilepsy syndromes. 

Both forms of absence seizure often occur as part of one of the recognized epilepsy syndromes. Typical absence seizures respond fairly well to AEDs ethosuximide and valproate are first-choice drugs. Clonazepam is effective but sedating, and tolerance to the antiabsence effects may develop. Lamotrigine may be useful. Treatment of atypical absence seizures with AEDs Is less successful. 

The incidence of phenytoin toxicity may be increased in the eideriy, or in those patients with hepatic or renal impairment, because of alterations in its pharmacokinetics. Plasma level determinations may be indicated in these cases. Although a role for P-glycoprotein transporter alleles in the development of phenytoin toxicity remains controversial, phenytoin is a robust substrate for the non-ABC efflux transporter RLIP76. Because RLIP76 has been found to be overexpressed in excised human epileptic foci, its action may account for treatment failures conversely, inhibition of transport may cause toxicity (34). There is a 2 to 3% increase in the risk of fetal epilepsy syndrome if the mother is taking phenytoin. Phenytoin is contraindicated in cardiac patients with bradyarrhythmias. Induction of CYP2C19 by ginkgo biloba may increase phenytoin clearance and precipitate serious seizures (35). 

Because of its propensity for causing liver damage, valproate therapy should be avoided in persons with liver disease. It should be used with caution before surgery, because it can produce thrombocytopenia and inhibition of platelet aggregation. In pregnancy, it has been associated with an increased risk of fetal epilepsy syndrome and spina bifida. 

Epilepsy is commonly categorised as idiopathic, symptomatic, probable symptomatic (previously known as cryptogenic) and reactive. Idiopathic epilepsies are presumed to have an underlying genetic canse indeed ion channelopathies have been identified in several human idiopathic epilepsy syndromes (Gardiner, 2(X)5). Symptomatic epilepsies, which are thought to account for up to 50% of all epilepsy cases (Delorenzo et al., 2005), arise secondary to an underlying identifiable brain insult or lesion such as stroke, intracranial neoplasia or encephalitis. Probable... 

In a retrospective analysis of rufinamide in 77 children with refractory epilepsy syndromes the median starting dose was 8.8 mg/kg/day and the median maintenance dose was 34 mg/kg/day [275. Adverse reactions were reported by 23 patients and included drowsiness in 10, rashes in 5, dizziness in 4, nausea and vomiting in 3, anorexia in 2, headache in 1, and visual disturbance in 1. Ten patients withdrew because of adverse reactions drowsiness (n = 5), rash (n = 3), headache (n = l), and loss of vision ( = ) ... 

In a retrospective analysis of all data from patients taking rufinamide in Germany and Austria, 45 children and 15 adults were identified with various severe and inadequately controlled epilepsy syndromes. The response rate (at least a 50%... 

Bromfield EB, Dworetzky BA, Wyszynski DF, Smith CR, Baldwin EJ, Holmes LB. Valproate teratogenicity and epilepsy syndrome. Epilepsia 2008 49 (12) 2122-4. 

Tsairis P, Engel WK, Kark AP. (1973) Familial myoclonic epilepsy syndrome associated with skeletal muscle mitochondrial abnormalities. Neurology 23, 408. 

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