Thomas R. Browne

We conducted a 10-center, double-blind trial to compare the efficacy and toxicity of four antiepileptic drugs in the treatment of partial and secondarily generalized tonic-clonic seizures in 622 adults. Patients were randomly assigned to treatment with carbamazepine, phenobarbital, phenytoin, or primidone and were followed for two years or until the drug failed to control seizures or caused unacceptable side effects. Overall treatment success was highest with carbamazepine or phenytoin, intermediate with phenobarbital, and lowest with primidone (P less than 0.002). Differences in failure rates of the drugs were explained primarily by the fact that primidone caused more intolerable acute toxic effects, such as nausea, vomiting, dizziness, and sedation. Decreased libido and impotence were more common in patients given primidone. Phenytoin caused more dysmorphic effects and hypersensitivity. Control of tonic-clonic seizures did not differ significantly with the various drugs. Carbamazepine provided complete control of partial seizures more often than primidone or phenobarbital (P less than 0.03). Overall, carbamazepine and phenytoin are recommended drugs of first choice for single-drug therapy of adults with partial or generalized tonic-clonic seizures or with both.

SUMMARY The anticonvulsant effect of benzodiazepines is reviewed, both on experimentally produced seizures and on epilepsy in man, including aspects of clinical pharmacology and toxicology. The drugs are chlordiazepoxide (Librium®), diazepam (Valium®), oxazepam (Serax®), nitrazepam (Mogadon®) and clonazepam. Flurazepam (Dal‐mane®) has not been tested extensively. The benzodiazepines suppress generalized EEG discharges but not focal ones. They are highly effective in stopping absence (petit mal), infantile and other myoclonic seizures, akinetic, photosensitive and alcohol withdrawal attacks. They are the drugs of choice to arrest status epilepticus of all kinds and eclamptic convulsions. Grand mal, focal and partial (psychomotor, temporal lobe) seizures are less often controlled and grand mal may be aggravated. Because tolerance may develop, the benzodiazepines are most effective when given parenterally and less effective when given continuously by mouth. Toxicity, usually drowsiness or ataxia, is less apt to be troublesome when the dose is increased gradually. RESUME On a revu ľeffet anticonvulsant des benzodiazepines à la fois sur les crises produites expérimentalement et sur ľépilepsie chez ľhomme, en tenant compte des aspects de pharmacologic clinique et de toxicologic Les drogues étudiées sont le chlordiazepoxide (Librium®), le diazepam (Valium®), ľoxazepam (Serax®), le nitrazepam (Mogadon®) et le clonazepam (Rivotril®). Le flurazepam (Dalmane®) n'a pas été testé de façon étendue. Les benzodiazepines suppriment les décharges EEG généralisées mais non les décharges focales. Elles sont très efficaces pour arrêter les absences (petit mal), les crises infantiles et les autres crises myocloniques, les crises akinétiques et les crises photosensibles et les crises après sevrage alcoolique. Les benzodiazepines sont les drogues de choix pour arrêter les états de mal de toute sorte et les crises eclamptiques. Les crises grand mal, focales et partielles (psychomotrices, temporales) sont moins bien contrôlées et le grand mal peut être aggravé. Parce que la tolérance peut se développer, les benzodiazepines sont plus efficacies quand elles sont données par voie parenterale et moins efficaces quand elles sont donnees de façon continue per os. La toxicité, généralement somnolence ou ataxie est moins fréquente quand le traitement est augmenté progressivement. ZUSAMMENFASSUNG Überblick über die antikonvulsive Wirkung der Benzodiazepine auf experimentell erzeugte Krämpfe und auf die Epilepsie beim Menschen; klinisch pharmakologische und toxikologische Aspekte. Folgende Präparate werden berücksichtigt: Chlor‐diazepoxyd (Librium®), Diazepam (Valium®), Oxazepam (Serax®), Nitrazepam (Mogadon®) und Clonazepam. Flurazepam (Dalmane®) wurde nicht ausführlich getestet. Die Benzodiazepine unterdrücken generalisierte EEG Entladungen, nicht aber fokale. Ihre anfallverhütende Wirkung erstreckt sich vorwiegend auf Absencen (Petit Mai), infantile und andere myoklonische Anfälle, akinetische, photosensible Anfälle und solche bei Alkoholentzug. Es handelt sich um Präparate der ersten Wahl zur Behandlung jedes Status Epilepticus und eklamptischer Krämpfe. Die Wirkung auf Grand Mai‐, fokale‐ und Partialanfälle (psychomotorische‐, Temporallappen‐anfalle) ist geringer, ein Grand Mai kann verstärkt werden. Da sich eine Gewöhnung gegenüber den Präparaten entwickeln kann, ist die Wirkung der Benzodiazepine am größten, wenn sie parenteral gegeben werden, geringer bei oraler Applikation über einen längeren Zeitraum. Toxische Nebenwirkungen, gewöhnlich Schläfrigkeit oder Ataxie, sind weniger zu befürchten, wenn die Dosierung allmählich erhöht wird. RESUME El efecto anticonvulsivo de las benzodiacepinas es revisado tanto desde el punto de vista experimental como en la epilepsia del hombre, incluyendo aspectos de farma‐cologia clinica toxicología. Las drogas estudiadas son clorodiacepoxido (Librium®), diacepam (Valium®), oxacepam (Serax®), nitracepam (Mogadon®) y clonacepam. El flurazepam (Dalmane®) no ha sido estudiado. Las benzodiacepinas suprimen las descargas EEG generalizadas, pero no las focales. Son extraordinariamente eficaces en las ausencias (petit mal), en los espas‐mos infantiles y otras crisis mioclonicas, y en las crisis aquinéticas fotosensibles o debidas a la supresión de alcohol. Constituyen el medicamento de electión para detener el status epiléptico y las convulsiones eclám ticas. Las crisis de gran mal, focales y parciales (psicomotoras, lóbulo temporal) son ineficazmente controladas y el gran mal puede incluso verse agravado. Las benzodiacepinas son más activas cuando se administran por via parenteral y menos eficaces “per os” debido a que en estas condiciones su efecto puede ser tran‐sitorio. La somnolencia y la ataxia constituyen los principales efectos secundarios, que pueden evitarse, mediante una administration progresiva.

Approximately 2 million persons in the United States have epilepsy,1,2 making the prevalence of this disorder similar to that of type 1 diabetes mellitus.3 Each year, 100,000 new cases of epilepsy are diagnosed in the United States.1,4 Both the prevalence and the incidence of epilepsy are dramatically higher among elderly persons than among those who are younger.1 Thus, many primary care physicians care for a substantial number of patients with epilepsy.EvaluationDiagnosis of a Seizure DisorderThe first step in the evaluation of a patient with possible epilepsy is to determine whether the patient does or does . . .

Eighty-five cases of hemangioblastoma of the spinal cord are reviewed, including five new ones. While current views of the incidence, histology, and cytogenesis are presented, the main purpose of this article is to call attention to the identifying clinical and radiological characteristics of these spinal tumors. Median age at onset of symptoms was 30 years. The ratio of men to women was 1.1:1. Presenting symptoms were usually radicular pain or posterior column sensory loss or both. The lesions were most often single (79%), intramedullary (60%), and located in the cervical or thoracic spinal cord. There was associated syringomyelia in 67% of intramedullary cases and meningeal varicosities in 48% of all cases. Lindau disease and hemangioblastomas in other central nervous system locations were present in 33% of cases. The characteristic roentgenographic picture is a densely vascular tumor in association with a larger avascular syrinx and meningeal varicosities. Surgery is the only definitive treatment.

Clonazepam is a new benzodiazepine anticonvulsant recently approved by the Food and Drug Administration for the treatment of typical absence, infantile myoclonic, atypical absence, myoclonic, and akinetic seizures. It is rapidly absorbed by the oral route and appears to pass quickly from blood to brain. Preliminary results indicate a biological half-life of 22 to 32 hours and a therapeutic serum concentration of 5 to 50 ng/ml. Many studies report tolerance to the anticonvulsant effects with chronic administration. Major side effects of the drug are drowsiness, ataxia, and behavior changes. They tend to be dose related, occur early in the course of therapy, and may subside with chronic administration. Accordingly, the dosage is begun at a low level and increased slowly.