Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation.

are highly effective anticonvulsants against seizures induced in animals by a variety of mechanisms including kindling. Adenosine receptor antagonists exert proconvulsant actions indicating tonic adenosinergic control of ictal susceptibility. Animal studies have shown a rapid and substantial release of adenosine and its metabolites inosine and hypoxanthine in brain interstitial fluid during experimental seizures.2 The physiological actions and metabolism of adenosine in the human CNS remain to be fully elucidated. We report that acute increases of adenosine metabolites can be detected in lumbar CSF after clinical status epilepticus in humans.Seven patients with new onset status epilepticus were studied. Five patients (aged 12 to 67) developed generalised status epilepticus with three or more clonic or tonic-clonic seizures occurring in less than one hour without regaining consciousness between seizures. Causes included viral encephalitis, cysticercosis, uraemia, benzodiazepine withdrawal, and drug toxicity. One patient (48 years old) with diabetes and chronic renal failure developed epilepsia partialis continua involving repeated clonic seizures of the right face and arm. One patient (82 years old) experienced complex partial status epilepticus documented by electroencephalography due to withdrawal from alprazolam. Eleven patients (aged 22 to 53) evaluated for other neurological conditions (demyelinating neuropathy, headaches, cranial neuropathy, multiple sclerosis) were used as controls.All CSF samples used in this study were discarded specimens from lumbar punctures performed for diagnostic purposes as part of each patient's clinical evaluation. The CSF was refrigerated at less than 4°C. Cell counts ranged from 0-30 white blood cells/mm3 and 0-92 red blood cells/mm.3 Nanomolar concentrations of adenosine were determined by high performance liquid chromatographic-fluorometric assay as described by Zhang et al.3 Micromolar concentrations of nucleosides and purine bases (for example, adenosine, inosine, and hypoxanthine) were determined by high performance liquid chromatographic assay using a Beckman Ultrasphere ODS 4-6 x 250 mm column eluted at 1-0 ml/min at ambient temperature with a gradient of buffer A (20 mM potassium phosphate pH 3 5) and buffer B (acetonitrile) (0-1 min, 0%; 1-18 min, 0-4%; 18-28 min, 4-7%; 28-33 min, 7-80% buffer B) and detection by ultraviolet absorbance at 254 nM.Concentrations of adenosine in CSF obtained from control patients without seizures were in the low nanomolar range whereas concentrations of the adenosine metabolites inosine and hypoxanthine were considerably higher ( hours after termination of their last seizure. No changes in CSF adenosine concentrations were found but inosine and hypoxanthine concentrations were substantially higher than controls (table). The time interval from the last seizure to CSF sampling seemed to be an important factor with the maximum increase of hypoxanthine (greater than sixfold) seen at one hour. Nevertheless, increases in inosine and hypoxanthin...

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