PMID- 9109744
OWN - NLM
STAT- MEDLINE
DCOM- 19970508
LR  - 20190717
IS  - 0003-9942 (Print)
IS  - 0003-9942 (Linking)
VI  - 54
IP  - 4
DP  - 1997 Apr
TI  - Cerebellar atrophy decreases the threshold of carbamazepine toxicity in patients 
      with chronic focal epilepsy.
PG  - 427-31
AB  - 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.
FAU - Specht, U
AU  - Specht U
AD  - Klinik Mara 1, Bethel Epilepsy Center, Bielefeld, Germany.
FAU - May, T W
AU  - May TW
FAU - Rohde, M
AU  - Rohde M
FAU - Wagner, V
AU  - Wagner V
FAU - Schmidt, R C
AU  - Schmidt RC
FAU - Schutz, M
AU  - Schutz M
FAU - Wolf, P
AU  - Wolf P
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arch Neurol
JT  - Archives of neurology
JID - 0372436
RN  - 0 (Anticonvulsants)
RN  - 33CM23913M (Carbamazepine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anticonvulsants/*adverse effects/blood/*therapeutic use
MH  - Ataxia/chemically induced
MH  - Atrophy
MH  - Carbamazepine/*adverse effects/blood/*therapeutic use
MH  - Cerebellar Ataxia/chemically induced
MH  - Cerebellum/*pathology
MH  - Epilepsies, Partial/*drug therapy/pathology
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Nystagmus, Pathologic/chemically induced
MH  - Prospective Studies
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1001/archneur.1997.00550160063017 [doi]
PST - ppublish
SO  - Arch Neurol. 1997 Apr;54(4):427-31. doi: 10.1001/archneur.1997.00550160063017.