sodium-oxybate and Dementia

Varying degrees of metabolic arrest are used by many living species to survive in a harsh environment. For example, in hibernating mammals, neuronal activity and cerebral metabolism are profoundly depressed in most regions of the brain and limited energy resources are deployed to maintain vital cell functions. Gathering evidence suggests that energy resources are also limited in both Alzheimer's and Parkinson's diseases, and that this promotes metabolic stress and the degenerative process. Key steps in this process are energy requiring, and this further compromises cell energy reserves. It may be possible to slow the progress of these diseases by inducing slow-wave sleep (SWS) at night with gammahydroxybutyrate. Patients with these diseases sleep poorly and generate little SWS. SWS and hibernation are thought to be on a continuum of energy conservation. Thus, the induction of SWS may retard the degenerative process by depressing cell metabolism and by directing energy utilization to vital cell functions. In this way, GHB-induced SWS may duplicate the effects of hibernation and extend biologic time.

Topics: Alzheimer Disease; Animals; Brain; Dementia; Energy Metabolism; Humans; Nerve Degeneration; Parkinson Disease; Sleep Stages; Sodium Oxybate

Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Brain; Cognition; Dementia; Electroencephalography; Electrophysiology; Epilepsy, Absence; Evoked Potentials; gamma-Aminobutyric Acid; Humans; Motor Skills; Norepinephrine; Prognosis; Sensation; Sodium Oxybate; Valproic Acid

Topics: 3-Hydroxybutyric Acid; Cerebrovascular Circulation; Dementia; Drug Therapy; Electric Impedance; Electroencephalography; Geriatrics; Humans; Hydroxybutyrates; Intracranial Arteriosclerosis; Niacin; Nicotinic Acids; Plethysmography; Plethysmography, Impedance; Psychotic Disorders; Sodium; Sodium Oxybate; Vasodilator Agents