Richard M. Dasheiff

The effects of colchicine in mammalian brain from rodents to rhesus monkeys

The injection of colchicine into rats and monkeys produced two different types of brain damage. At selected doses, intradentate colchicine preferentially destroyed DGC in rats, whereas damage was less selective and more severe in monkeys. Experiments were performed with different tubulin-binding drugs to investigate the structure-function relationship of tubulin binding and DGC death. The tubulin-binding characteristics of these and other drugs reported in the literature did not correlate with their ability to damage DGC. The role of seizure-induced cell death was investigated by recording the EEG in monkeys and in rats treated with phenobarbital. The data suggest that seizures are an infrequent epiphenomenon of colchicines action. We proposed that colchicine is not a selective neurotoxin and that it causes brain damage by inducing a non-specific inflammatory response. This response is both dose- and species-dependent. We concluded by discussing the medical implications of the present and proposed uses of colchicine.

Efficacy of Second Line Antiepileptic Drugs in the Treatment of Patients with Medically Refractive Complex Partial Seizures

Summary: The efficacy of second‐line antiepileptic drugs (AEDs) was evaluated in the treatment of 66 patients with complex partial seizures who had previously failed first‐line AEDs. Methsuximide, valproate, or clorazepate had eliminated seizures in 11% of the patients at the end of the study. However, these good results deteriorated on longer follow‐up and were not expected to be permanent. It is recommended that suitable patients with partial epilepsy be referred for surgical evaluation after failing the first‐line AEDs, and that second‐line AEDs be reserved for nonsurgical candidates.

Epilepsy surgery improves regional glucose metabolism on PET scan - A case report

SummaryA patient with medically intractable complex partial epilepsy was evaluated for epilepsy surgery by electroencephalograph recording with depth electrodes and 18F-fluorodeoxyglucose positron emission tomography (PET). A small calcified arteriovenous malformation was excised from the left parietal lobe, and the patient became seizure free. Baseline and language stimulation PET scans were obtained preoperatively and 10 months postoperatively. There was a significant increase in glucose metabolism of the left temporal lobe postoperatively, which we interpret as evidence of improved neuronal function. We suggest that this case represents evidence for a functional, and reversible, inhibition of neuronal metabolism by epileptic activity.

A new method of monitoring membrane potential in rat hippocampal slices using cyanine voltage-sensitive dyes

A novel application of voltage-sensitive dyes is described. Hippocampal slices in vitro accumulated voltage-sensitive cyanine dyes under conditions presumed to cause depolarization and hyperpolarization. Increasing extracellular potassium caused a depression of dye uptake that correlated linearly with the membrane potential calculated from the Goldman equation. Veratrine depressed dye uptake, and this effect was blocked by addition of tetrodotoxin or removal of extracellular sodium. Ouabain also depressed dye uptake. Conversely, hyperpolarizing conditions using reduced extracellular sodium caused increased dye uptake. These results support a voltage-dependent mechanism for the uptake of cyanine dyes in hippocampal slices. Application of this phenomenon as an alternative to 2-deoxyglucose autoradiography for mapping neuronal activity will be presented.

d-Tubocurarine causes neuronal death when injected directly into rat brain

d-Tubocurarine (d-TC) is a drug commonly used to produce muscle paralysis. Although it has been demonstrated to produce seizures when injected directly into the cerebral ventricles, no lasting neurotoxic effects have been reported. Data presented here suggest that amounts of d-TC as small as 1 microgram injected directly into rat hippocampus resulted in selective damage to dentate granule cells. Larger doses (5 to 10 micrograms) induced limbic and motor seizures with damage to hippocampal pyramidal cells. Other brain regions showed a differential sensitivity to direct injections. Pharmacologic studies suggest a nicotinic mechanism for both actions. The neurotoxic effects could not be elicited if d-TC was administered systemically, even when the blood-brain barrier was disrupted.

Positive Interictal Spikes in Complex Partial Epilepsy: A Case Report

ABSTRACT.Positive interictal epileptiform discharges were recorded from the scalp of a patient with new onset complex partial epilepsy. A follow-up EEG revealed negative and positive spikes. The patient was treated successfully with phenytoin. To our knowledge, this is the first reported case of exclusively surface positive spikes in an EEG of an adult without a skull defect who had epilepsy.