Abstracts

RATIONALE: Following reports of a reversible valproate-induced extrapyramidal syndrome with cognitive impairment, we wanted to ascertain the incidence of such a syndrome amongst patients receiving sodium valproate (VPA) in the Greater Manchester area.
VPA is a widely used antiepileptic drug (AED) efficacious in both primary generalised and localisation related epilepsies. In recent years there have been case reports suggesting the existence of a reversible extrapyramidal syndrome induced by exposure to VPA. These studies recruited patients attnding University hospital based epilepsy clinics, and did not exclude patients with previous exposure to neuroleptic, antidepresant or anti-emetic drugs. In the present study, patients attending their family practitioner, a community-based epilepsy clinic attended by individuals with well-controlled epilepsy, and a University hospital epilepsy clinic were assessed for the presence of extrapyramidal signs and symptoms.
METHODS: 40 consecutive patients receiving VPA monotherapy, none of whom had been exposed to neuroleptic, anti-depressant or anti-emetic drugs, were recruited. All patients had received VPA monotherapy for a minimum of 12 months before recruitment. A control group of 16 patients taking carbamazepine (CBZ) subject to the same inclusion and exclusion criteria as the VPA monotherapy group were recruited. All patients underwent a full neurological examination, completed the mini-mental state (MMS), and had their posture, gait, fine finger movements, and tremor, if present, videoed. Those considered to have extrapyramidal signs underwent the Unified Parkinson[ssquote]s Disease Rating Scale (UPDRS) parts 1-3. The videos were reviewed [dsquote]blind[dsquote] to patient therapy by MK and those considered to exhibit extrapyramidal features were invited to clinic for further examination by him.
RESULTS: 56 patients were examined, 40 taking VPA (24 male, 16 female) and 16 taking CBZ (4 male, 12 female). No significant differences existed in mean age, duration of therapy, or duration of epilepsy, between control and study groups.
3 (7.5%) of the VPA monotherapy patients were found to have extrapyramidal signs (rigidity, tremor, gait disturbance, bradykinesia). Mean UPDRS score was 2.95. None of the CBZ group exhibited extrapyramidal signs. There were no significant differences in MMS scores between the two groups. There was no correlation between UPDRS score and dose of VPA or duration of therapy. There was a correlation between UPDRS score and age (p=0.01, r=0.405).
CONCLUSIONS: In conclusion, there was a higher incidence of extrapyramidal signs in patients receiving VPA monotherapy in this study (7.5%) than would be expected in the general population (0.5%), although the presence and severity of these signs were not correlated with either the dose or duration of therapy with VPA. This suggests that certain patients may be more susceptible to such a syndrome. It should be noted that the method of recruitmet may also confound results, and so further large scale studies are needed to elucidate the extent of this phenomenon in people exposed to VPA.
[Supported by: Miss Easterford[ssquote]s travel expenses were covered by educational grants from Sanofi-Synthelabo Pharmaceuticals and the Wigan and Leigh Epilepsy Fund. Drs Kellett, Clough and Duncan are National Health Service employees and received no grants or honoraria during their envolvement with this study.]; (Disclosure: Salary - nil, Grant - nil, Equity - nil, Consulting - nil, Ownership - nil, Materials - nil, Stock - nil, Royalties - nil, Honoraria - Dr Duncan has received honoraria from Novartis, Janssen and Sanofi Pharmaceuticals, Other - nil)