Cerebellar atrophy decreases the threshold of carbamazepine toxicity in patients with chronic focal epilepsy
U. Specht, T. W. May, M. Rohde, V. Wagner, R. C. Schmidt, M. Schutz and P. Wolf
Klinik Mara 1, Bethel Epilepsy Center, Bielefeld, Germany.
BACKGROUND: Cerebellar atrophy (CA) is a frequent finding in patients with
chronic epilepsy. Since gaze-evoked nystagmus, dizziness, and ataxia are
some of the typical adverse effects (AEs) of the dose-dependent toxicity of
carbamazepine, preexisting CA could possible explain in part the
interindividual variation in the tolerance of high serum concentrations of
carbamazepine. OBJECTIVE: To determine whether CA reduces the threshold for
overdose symptoms with carbamazepine in patients with chronic focal
epilepsy in a prospective study. DESIGN: Cohort study. SETTING: A
fourth-level epilepsy center to which patients were referred. PATIENTS:
Twenty-six consecutive patients with chronic focal epilepsy were
prospectively studied while they were receiving high-dose monotherapy with
carbamazepine. Patients were slowly titrated to doses at which the first
toxic AEs of carbamazepine occurred. The determination of multiple serum
levels was carried out, together with an evaluation of toxicity that
comprised a standardized neurologic examination, a questionnaire for AEs,
and posturography. MAIN OUTCOME MEASURES: Serum concentrations of
carbamazepine at the occurrence of the first dose-dependent AEs were
related to the presence or absence of CA in magnetic resonance imaging
studies as rated by 2 independent and blinded neuroradiologists. RESULTS:
In 9 patients (35%), magnetic resonance imaging scans revealed moderate (n
= 7) or severe (n = 2) CA. In these patients, gaze-evoked nystagmus (P =
.001, log rank test), dizziness (P = .008), and ataxia of stance as
measured by posturography (P = .02) occurred at significantly lower serum
concentrations of carbamazepine compared with patients without CA. This was
also found for the first individually observed AE (P = .03). CONCLUSION:
Cerebellar atrophy occurs in a considerable percentage of patients with
chronic focal epilepsy and obviously increases the susceptibility for
cerebellar AEs of carbamazepine.