Date of Award

January 2013

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Tore Eid

Subject Area(s)

Medicine

Abstract

About two-thirds of patients with one of the most common forms of epilepsy - mesial temporal lobe epilepsy (MTLE) - cannot control their seizures with current antiepileptic drugs. More efficacious therapies for this disorder are therefore needed. A low carbohydrate, high fat - i.e. ketogenic - diet (KD) is a highly effective treatment for many types of epilepsies; however, whether the diet is effective in reducing seizures in MTLE is relatively unexplored. As a first step towards understanding the role of the KD in MTLE, we investigated whether the diet reduces the frequency and severity of seizures in a novel rat model of this disorder.

Thirty-eight male Sprague Dawley rats were implanted with an osmotic pump injecting the glutamine synthetase inhibitor methionine sulfoximine (MSO) into the polymorphic layer of the right hippocampus. Beginning immediately after surgery, the rats were continuously monitored with intracranial EEG and simultaneous video recordings. One week post-surgery, rats were assigned to either a KD with 20% caloric restriction or a standard chow (SC) fed ad libitum and further monitored for another two to four weeks. EEG analysis was correlated with video recordings to determine the frequency and severity of seizures according to a modified Racine scale.

There was no significant difference in the weekly frequency of seizures in rats treated with the KD versus SC. Neither was there any difference in the severity of seizures between rats treated with the KD and rats fed SC. These data should be interpreted with caution because animal models of MTLE may respond differently to the KD than humans with the disorder. Also, a lack of significant difference does not rule out the presence of a real, but small difference that cannot be detected due to the statistical power of the present study. Nevertheless, the data suggest that the KD may not be an effective treatment for MTLE.

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