Assessment of the Role of Kindling in the Pathogenesis of Alcohol Withdrawal Seizures and Delirium Tremens

Abstract

The aim of this study was to evaluate the hypothetical role of kindling phenomenon in the development and course of alcohol withdrawal (AW) seizures and delirium tremens (DT). The 2186 medical records of 1179 patients hospitalized in Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire. Investigating the role of kindling, a course of consecutive AW episodes of patients hospitalized several times was analyzed. The relationships of withdrawal seizures with the duration of alcohol abuse, the number of prior detoxification episodes, and other variables were also studied. Increasing severity of AW symptoms was observed during the course of consecutive episodes in 22.5% of patients. The first episode of DT was preceded by withdrawal seizures in 11% of cases. First-ever withdrawal seizures occurred more frequently in patients with head injury in the past and with coexisting symptoms of alcohol liver disease. Occurrence of withdrawal seizures and DTs did not correlate with the number of previous withdrawal episodes or with the length of period of intensive drinking. We concluded that the kindling model could be applied only to some cases in the development of AW seizures and DTs. Kindling should be considered as one of the multiple mechanisms involved in the pathogenesis of AW delirium.

Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics

“…Decreased GABA-Amediated inhibition during alcohol withdrawal has been related to increased glutamate-mediated excitability and both may be critical mechanisms of alcohol withdrawalinduced seizures 38 and the development of delirium tremens, which often occur simultaneously since many alcoholics with delirium tremens also experience epileptic seizures. 39 Glutamate enhances inhibitory GABA neurotransmission. 1 During chronic alcohol consumption, decreased glutamatergic neurotransmission may eventually cause GABA to be low.…”

Alcohol withdrawal syndromes in the intensive care unit

“…In 1978, Ballenger and Post (24) proposed that the increase in central nervous system hyperexcitability that occurs with each successive withdrawal episode was the result of "kindling." This particularly seems to play a role in alcohol withdrawal seizures, and this may explain the clinical observation of increasing severity of alcohol withdrawal among individual subjects, and the development of benzodiazepine-resistant alcohol withdrawal (25)(26)(27). However, although well described in laboratory studies where repeated episodes of alcohol withdrawal lead to persistent and progressive electroencephalographic abnormalities, with further episodes of withdrawal becoming increasingly resistant to benzodiazepines, it is unclear of the clinical relevance in humans (27).…”

Alcohol-induced changes in the brain as assessed by MRI and CT

“…The relationship between delirium tremens and seizures is believed to be due to a kindling phenomenon. According to this theory, delirium tremens is related to an excitotoxic mechanism following alcohol withdrawal that leads to repetitive subconvulsive stimuli that are responsible for the symptoms and can accumulate its activity culminating in a generalised seizure [50]. Clinical presentation of delirium tremens consists of hallucinatory episodes, mostly with micro-zooptic contents, usually preceded by disturbed sleep and irritability and generally takes several days to develop.…”