Eye rolling as a manifestation of clobazam toxicity in a child with epilepsy.
A four-year-old male with symptomatic generalized epilepsy presented with ataxia, eye rolling, and episodes of back arching which were of non-epileptic origin following the introduction of clobazam at 0.75mg/kg/day. Concurrent antiepileptic medication was lamotrigine at 13mg/kg/day. Clobazam plasma levels were within the normal range, while N-desmethylclobazam (DCLB) concentrations were between five and seven times above the upper limit of the normal range. The plasma elimination half-life for DCLB was prolonged, suggesting a genetic variability in DCLB metabolism leading to toxicity. Reduction in the dose of clobazam to 0.3mg/kg/day was associated with resolution of the non-epileptic neurological symptoms, reduction in DCLB plasma levels, and maintenance of seizure control.
Aylett
Sarah E
SE
Great Ormond Street Hospital NHS Trust, London, UK. saylett@ncype.org.uk
Cross
Helen
H
Berry
Dave
D
D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D002675:Child, Preschool; D000078306:Clobazam; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D015835:Ocular Motility Disorders / Q000097:blood / Q000139:chemically induced*; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use
D000927:Anticonvulsants; D014227:Triazines; D001569:Benzodiazepines; D000078306:Clobazam; C024581:N-desmethylclobazam; D000077213:Lamotrigine