Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic a
cid (5-HIAA) in cerebrospinal fluid (CSF) of patients with progressive
myoclonus epilepsy (PME) suggest hypofunctional serotonergic neurotra
nsmission. To study this hypothesis, we enrolled 6 patients with PME [
Unverricht-Lundborg disease (U-L), mitochondrial encephalomyopathy, or
Lafora disease] in a controlled, double-blinded, dose-ranging, cross-
over add-on pilot clinical trial of 5-hydroxy-L-tryptophan (L-5-HTP) p
lus carbidopa after 2 other patients had received open-label L-5-HTP f
or compassionate use. Prestudy CSF 5-HIAA concentrations were low (<20
ng/ml) in 6 patients regardless of the etiology of PME. One patient w
ith U-L disease showed clinical improvement and a fivefold increase in
CSF 5-HIAA, and 1 with Lafora disease showed a twofold increase in CS
F 5-HIAA without improvement. A patient with Lafora disease reported e
nough improvement in myoclonus-evoked convulsions to continue chronic
use of the drug. One patient with mitochondrial encephalomyopathy deve
loped status epilepticus during treatment with L-5-HTP. As a group, pa
tients had no statistically significant changes in myoclonus evaluatio
n scale scores, subjective and objective measures of ataxia, seizure f
requency, antiepileptic drug (AED) levels, or routine blood tests. The
se data suggest a serotonergic abnormality regardless of the underlyin
g etiology of PME, but one that seldom responds to acute treatment wit
h L-5-HTP.