Vigabatrin aggravates absences and absence status

Panayiotopoulos, C. P.; Agathonikou, A.; Sharoqi, Isa Ahmed; Parker, Alasdair

doi:10.1212/wnl.49.5.1467

Cited by 38 publications

(22 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…161 Elevated GABA concentrations may increase neuronal synchronization, particularly of thalamic neurons in absence epilepsy, and there have been several reports of vigabatrin worsening absence seizures or precipitating absence status epilepticus. 162 …”

Section: Vigabatrinmentioning

confidence: 99%

Molecular mechanisms of antiseizure drug activity at GABAA receptors

Greenfield

2013

Seizure

166

129

View full text Add to dashboard Cite

The GABAA receptor (GABAAR) is a major target of antiseizure drugs (ASDs). A variety of agents that act at GABAARs s are used to terminate or prevent seizures. Many act at distinct receptor sites determined by the subunit composition of the holoreceptor. For the benzodiazepines, barbiturates, and loreclezole, actions at the GABAAR are the primary or only known mechanism of antiseizure action. For topiramate, felbamate, retigabine, losigamone and stiripentol, GABAAR modulation is one of several possible antiseizure mechanisms. Allopregnanolone, a progesterone metabolite that enhances GABAAR function, led to the development of ganaxolone. Other agents modulate GABAergic “tone” by regulating the synthesis, transport or breakdown of GABA. GABAAR efficacy is also affected by the transmembrane chloride gradient, which changes during development and in chronic epilepsy. This may provide an additional target for “GABAergic” ASDs. GABAAR subunit changes occur both acutely during status epilepticus and in chronic epilepsy, which alter both intrinsic GABAAR function and the response to GABAAR-acting ASDs. Manipulation of subunit expression patterns or novel ASDs targeting the altered receptors may provide a novel approach for seizure prevention.

show abstract

Section: Vigabatrinmentioning

confidence: 99%

Molecular mechanisms of antiseizure drug activity at GABAA receptors

Greenfield

2013

Seizure

166

129

View full text Add to dashboard Cite

show abstract

“…Vigabatrin and tiagabine are contraindicated, even in symptomatic absences, because of their proabsence effect. [9,156] Topiramate, effective in some, [157] but not other animal models of absence seizures, [47] may have a limited beneficial effect in humans. [157] Levetiracetam suppresses generalised spike and slow waves in animal models and may be potentially useful in the treatment of absence seizures.…”

Section: Newer Drugs (Other Than Lamotrigine)mentioning

confidence: 99%

“…Carbamazepine [9,10,159,160] vigabatrin [9,156] and tiagabine [25,161,162] are contraindicated in the treatment of absence seizures, irrespective of cause and severity. This is based on clinical and experimental evidence.…”

Section: Contraindicated Drugsmentioning

confidence: 99%

Treatment of Typical Absence Seizures and Related Epileptic Syndromes

Panayiotopoulos

2001

Paediatric Drugs

296

View full text Add to dashboard Cite

Typical absences are brief (seconds) generalised seizures of sudden onset and termination. They have 2 essential components: clinically, the impairment of consciousness (absence) and, generalised 3 to 4Hz spike/polyspike and slow wave discharges on electroencephalogram (EEG). They differ fundamentally from other seizures and are pharmacologically unique. Their clinical and EEG manifestations are syndrome-related. Impairment of consciousness may be severe, moderate, mild or inconspicuous. This is often associated with motor manifestations, automatisms and autonomic disturbances. Clonic, tonic and atonic components alone or in combination are motor symptoms; myoclonia, mainly of facial muscles, is the most common. The ictal EEG discharge may be consistently brief (2 to 5 seconds) or long (15 to 30 seconds), continuous or fragmented, with single or multiple spikes associated with the slow wave. The intradischarge frequency may be constant or may vary (2.5 to 5Hz). Typical absences are easily precipitated by hyperventilation in about 90% of untreated patients. They are usually spontaneous, but can be triggered by photic, pattern, video games stimuli, and mental or emotional factors. Typical absences usually start in childhood or adolescence. They occur in around 10 to 15% of adults with epilepsies, often combined with other generalised seizures. They may remit with age or be lifelong. Syndromic diagnosis is important for treatment strategies and prognosis. Absences may be severe and the only seizure type, as in childhood absence epilepsy. They may predominate in other syndromes or be mild and nonpredominant in syndromes such as juvenile myoclonic epilepsy where myoclonic jerks and generalised tonic clonic seizures are the main concern. Typical absence status epilepticus occurs in about 30% of patients and is more common in certain syndromes, e.g. idiopathic generalised epilepsy with perioral myoclonia or phantom absences. Typical absence seizures are often easy to diagnose and treat. Valproic acid, ethosuximide and lamotrigine, alone or in combination, are first-line therapy. Valproic acid controls absences in 75% of patients and also GTCS (70%) and myoclonic jerks (75%); however, it may be undesirable for some women. Similarly, lamotrigine may control absences and GTCS in possibly 50 to 60% of patients, but may worsen myoclonic jerks; skin rashes are common. Ethosuximide controls 70% of absences, but it is unsuitable as monotherapy if other generalised seizures coexist. A combination of any of these 3 drugs may be needed for resistant cases. Low dosages of lamotrigine added to valproic acid may have a dramatic beneficial effect. Clonazepam, particularly in absences with myoclonic components, and acetazolamide may be useful adjunctive drugs.

show abstract

“…Carbamazepine,7 vigabatrin,13 and tiagabine14 are contraindicated in the treatment of absence seizures, irrespective of cause and severity. This is based on clinical and experimental evidence 7…”

Section: Treatmentmentioning

confidence: 99%