Delirium tremens and related clilnical states:| Psychopathology, cerebral pathophysiology and psychochemistry: A two‐component hypothesis concerning etiology and pathogenesis

Abstract

Clinically patients with Delirium Tremens (DT) and acute alcohol hallucinosis (impending DT) appear excited with vivid false perception. Cerebral blood flow and eeg correspondingly point to hyperexcitability in the CNS during these conditions. Clinical trials with barbital treatment in alcohol withdrawal shows that the amount of drug and the drug plasma concentration is the same no matter whether the physical signs of withdrawal are accompanied by halluciations and clouding of consciousness. The psychotic signs in DT and acute alcoholic hallucinosis develops after many years of alcoholism as dose seizures. We hypothesize that physical withdrawal ils determined by the degree of physica dependence developed during the most recent drilnking period whereas the psychotic silgns and sizures are due to a cumulated CNS hyperactivity developed over many years of repeated alcohol intoxication and withdrawal. Changes of electrolyte concentrations in plasma or CSF do not play an important role in the pathogenesis of DT and realted clilnical states except that changes in calcium and inorganic phosphate metabolism indirectly point to changes in membrane excitability. A new model for a study of rapidly repeated intoxication and withdrawal episodes in rats has shown that repetition of episodes augments the convulsive component of withdrawal whereas the non‐convulsive signs are dependent on the most recent episode only. The augmentation of the convulsive component correlates with regional difference in brain glucose consumption. Furthermaore, synaptic proteins and acidic phospholipids may be involved in the development of CNS hyperexcitability during alcohol withdrawal. In conclusion both clinical and experimental studies indicate that severe alcohol withdrawal reactions may consist of two components: 1) Physical withdrawal signs determined by recent phsical dependence. 2) A long term cumulated CNS hyperexcitability relating to seizures and psychotic signs during withdrawal. This state is elicited by alcohol withdrawal but it represents a cumulated and permanent or long lasting CNS dysfunction in alcholilcs. This precise biochemical/pathophysiological mechanisms for the development of the two‐comoponent dysfuction stiil remain to be clarified in detail.

Differential Patterns of Serum Brain-Derived Neurotrophic Factor Levels in Alcoholic Patients With and Without Delirium Tremens During Acute Withdrawal

“…A rather noteworthy finding is that our data suggest more deficient BDNF levels could be related to the incidence of DTs. DTs has been hypothesized to be the consequence of cumulative and permanent central nervous system (CNS) dysfunction following years of heavy drinking (Hemmingsen and Kramp, 1988) and linked to higher levels of alcohol dependence or higher relapse rates (Wright et al., 2006). It is plausible that the more inadequate BDNF expression to act against addiction is associated with more severe alcohol dependence and withdrawal.…”

“…Hence, a subdivision of AWS is of clinical importance for prompt identification and management. Among the heterogeneous phenomena of AWS, DTs develops more slowly and independently of other symptoms (Hemmingsen and Kramp, 1988; Segal et al., 2009). Involvement of genetic factors could explain the variations in the AWS spectrum (van Munster et al., 2007), for example, BDNF gene polymorphism was suggested to be associated with a history of DTs (Matsushita et al., 2004).…”

“…With an effect on neurotransmitter modulation (Goggi et al., 2002; Guillin et al., 2001; Swanwick et al., 2006; Thoenen, 1995), BDNF is implicated in the pertinent neuroadaptation of AWS, and thus mediates various clinical exhibitions such as DTs. DTs, a severe form of AWS, has even been considered as an independent clinical entity (Hemmingsen and Kramp, 1988). The reason an individual develops DTs is still unknown.…”

Comparison of OxidativeDNADamage Between Alcohol‐Dependent Patients With and Without Delirium Tremens

“…NMDA‐induced excitotoxic damage is mediated by the high Ca 2+ permeability evoked generation of ROS as well as a concurrent increase in nitric oxide by up‐regulating nitric oxide synthase (Gunasekar et al., ; Uzbay et al., ) and thereby enhances the oxidative stress in alcohol‐dependent patients. Existing evidence indicates that DTs usually develops more slowly and independently compared to other AWS symptoms (Hemmingsen and Kramp, ; Segal et al., ) and might be a clinically distinct phenotype within the AWS spectrum. It is believed to occur as a result of more cumulative and permanent central nervous system dysfunction following years of heavy drinking (Hemmingsen and Kramp, ) and is linked to higher levels of alcohol dependence or relapse rates (Wright et al., ).…”

“…Existing evidence indicates that DTs usually develops more slowly and independently compared to other AWS symptoms (Hemmingsen and Kramp, ; Segal et al., ) and might be a clinically distinct phenotype within the AWS spectrum. It is believed to occur as a result of more cumulative and permanent central nervous system dysfunction following years of heavy drinking (Hemmingsen and Kramp, ) and is linked to higher levels of alcohol dependence or relapse rates (Wright et al., ). This suggests that those with more elevated oxidative stress and ensuing central nervous system toxicity may be susceptible to developing a more severe phenotype of alcohol dependence.…”