Participation of cAMP/PKA-Mediated Signaling Pathways in Functional Activity of Regeneration-Competent Cells in the Nervous Tissue under Conditions of Ethanol-Induced Neurodegeneration.

We studied the involvement of cAMP/PKA signaling in the realization of the growth potential of neural progenitors and secretion of neurotrophic growth factors by glial elements under conditions of ethanol-induced neurodegeneration in vitro and in vivo. The stimulating role of cAMP and PKA in cell cycle progression of the neural progenitor cells and in production of neurotrophins by the cells in nervous tissue under the optimal conditions to vital activity was demonstrated. Ethanol inverted the role of cAMP/PKA signaling pathways in determination of the proliferation-differentiation status of neural stem cells. Selective blockade of adenylate cyclase or PKA in neural stem cells increased the rate of their division against the background of relative decrease in differentiation rate. In addition, cAMP/PKA signaling does not longer participate in neurotrophin production by glial cells in neurodegeneration. These findings suggest that inhibitors of activity/expression of adenylate cyclase and PKA can be considered as possible drugs with regenerative activity for the treatment of nervous system pathologies provoked by alcohol.

[The possibilities of neurostimulation (sympathetic correction) in the treatment of amnestic (Korsakoff's) psychosis]. / Vozmozhnosti neirostimuliatsii (simpatokorrektsii) v terapii amnesticheskogo (korsakovskogo) psikhoza.

AIM: To evaluate the efficacy of non-invasive multichannel electrical stimulation (sympathetic correction) in patients with alcohol amnesic (Korsakoff's) psychosis. MATERIAL AND METHODS: Thirty-seven men, aged 33-48 years, with Korsakoff's (amnestic) psychosis were studied. The duration of disease varied from 12 to 24 month. The device of electrical stimulation of neck nerve structures was used for neuroelectrostimulation. Treatment included 15 sessions within 3 weeks. During this period, patients did not receive pharmacological therapy. The Frontal Assessment Battery (FAB), the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) were used to determine changes in cognitive state of patients. Electroencephalography with qEEG analysis and spectral analysis of heart rate variability (HRV) were carried out as well. RESULTS AND CONCLUSION: Positive effects of treatment were observed in all patients that suggested the high therapeutic potential of the neuroelectrostimulation method.

Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation.

The transient period of memory instability that can be triggered when memories are retrieved under certain conditions offers an opportunity to modify the maladaptive memories at the heart of substance use disorders (SUDs). However, very well-learned memories (such as those in excessive drinking and alcohol use disorders) are resistant to destabilisation when retrieved or may not destabilise at all. Memory retrieval and intervention procedures that reliably destabilise and update maladaptive motivational memories may help to improve the long-term treatment of SUDs. In 59 hazardous drinkers, we tested a novel retrieval procedure for destabilising well-learned cue-drinking memory networks that maximises prediction error (PE) via guided expectancy violation during retrieval of these memories. This was compared with a retrieval procedure without PE and no-retrieval controls. We subsequently counterconditioned alcohol cues with disgusting tastes and images in all groups and assessed responding to alcohol stimuli 1 week later. Counterconditioning following PE retrieval produced generalised reductions in oculomotor attentional bias, explicit valuation and outcome expectancies in response to alcohol cues 1 week after intervention, evidence of updating of distributed motivational drinking memory networks. These findings demonstrate that well-learned cue-drinking memories can be destabilised and that learning history need not constrain memory destabilisation if PE is maximised at retrieval. Broad rewriting of diverse aspects of maladaptive memory by counterconditioning is achievable following this procedure. The procedure described may provide a platform for the development of novel memory-modifying interventions for SUDs.

Alcohol: use, abuse and dependence.

As a drug, alcohol has grave bio-psychosocial effects on patients, their families and society in general. It is very important that clinicians be able to recognise, admit and thoroughly treat alcoholism. Subsequent to the indicated treatment of intoxication and withdrawal, the clinician should outline sound incentives (external initially, becoming internal in time) for rehabilitation and continued sobriety. A variety of alcohol-induced medical and psychiatric disorders should be recognised by doctors, and should be treated or referred appropriately. The multidisciplinary team should be involved, and doctors should not hesitate to seek help and advice. Alcoholism is potentially quite treatable.

[Alcohol-related amnesia ("blackout") in broader perspective]. / Alkoholové "okénko" v sirsích souvislostech.

Alcohol-related amnesia ("blackout") is a common even in people who are not alcohol dependent. The average duration of simple alcohol-induced amnesia in our alcohol dependent male patients was almost 8 hours (7.96, SD=23.96). Alcohol-induced amnesia is considered to be a risk factor for long-term impairment of cognitive functions, if alcohol abuse continues. On the other hand cognitive functions in alcohol dependent persons who abstain from alcohol often improve remarkably because of reorganisation and restoration of neuronal networks. This process can be enhanced by vitamin B1, appropriate treatment of withdrawal syndrome, memory training, coping with stress and depression (relaxation techniques can be used), balanced life-style, and nootropic drugs. Alcohol-related amnesia often motivates alcohol dependent patients to overcome their problem, especially if it is appropriately used in psychotherapy.

[Alcoholism in the elderly. A review of diagnosis, therapy and psychological effects]. / Alkoholismus im Alter. Ein Uberblick über Diagnostik, Therapie und psychische Folgeschäden.

Alcohol abuse and alcohol dependence are frequent disorders in the elderly. The disorders often develop as a response to burdensome life events which have to be treated specifically. Old alcoholics often respond well to age-specific interventions, if co-existing depressive symptoms are also treated. Because of the non-specific nature of the initial symptoms, the majority of the elderly alcoholics remain unrecognised during the diagnostic process. This review, therefore, gives a synopsis of clinical clues to alcoholism and associated psychic complications in elderly patients. Psychic complications in persistent alcoholism include Wernicke-Korsakow's syndrome, symptom patterns of delusions and hallucinations and specific types of organic brain syndromes.

B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse.

Alcohol misuse and alcohol withdrawal are associated with a variety of neuropsychiatric syndromes, some of which are associated with significant morbidity and mortality. B vitamin deficiency is known to contribute to the aetiology of a number of these syndromes, and B vitamin supplementation thus plays a significant part in prophylaxis and treatment. In particular, the Wernicke Korsakoff syndrome (WKS). due to thiamine deficiency, is a common condition in association with alcohol misuse, and is associated with high morbidity and mortality. Nicotinamide deficiency may result in a rarer condition, alcoholic pellagra encephalopathy, which often has a similar clinical presentation to WKS. This review considers the role of B vitamins in the aetiology and treatment of neuropsychiatric syndromes associated with alcohol misuse, with particular emphasis on WKS.

Wernicke-Korsakoff syndrome.

Alcohol abuse is one of the most serious problems in public health and the Wernicke-Korsakoff syndrome is one of the gravest consequences of alcoholism. The pathology is often undiagnosed in its less evident presentations, therefore an accurate diagnostic approach is a critical step in treatment planning. Treatment is based on restoration of thiamine, although this is insufficient to prevent the psychological decline of a great number of patients. The cognitive impact of the pathology is derived from the interaction of alcoholic neurotoxicity, thiamine deficiency and personal susceptibility. In this article, the literature concerning Wernicke-Korsakoff syndrome is reviewed.

Treatment of alcohol withdrawal in hospitalized patients.

Alcoholism can be encountered in many aspects of medicine. Frequently, primary-care physicians are asked to treat patients who are experiencing various stages of alcohol withdrawal while hospitalized for intercurrent illness. A thorough assessment of the patient is important because the symptoms and signs of alcohol withdrawal are nonspecific. Recognizing the patient who is at risk for alcohol withdrawal and initiating appropriate treatment can prevent progression to more serious symptoms and complications. Benzodiazepines are the drugs of choice for pharmacologic treatment of alcohol withdrawal. Their application by means of a symptom-triggered approach based on frequent, objective assessment of the patient is recommended. Adjunctive therapy for specific complications of alcohol withdrawal is discussed. After the acute withdrawal symptoms have been controlled, psychiatric or chemical dependence assessment (or both) is strongly encouraged.

[Main involvement of the central nervous system in alcoholism]. / Principales atteintes du système nerveux central dans l'alcoolisme.

The effects of alcohol on the central nervous system can be subdivided into three main categories: the effects of acute intoxication (drunkenness, acute encephalopathy, stroke), the effects of tolerance and ethanol withdrawal (delirium tremens, seizures) and the delayed manifestations of chronic alcohol consumption (cerebellar degeneration, Wernicke's encephalopathy, dementia).

Prevalence of the Korsakoff syndrome in The Hague, The Netherlands.

An epidemiological survey of the Korsakoff syndrome was made in The Hague, The Netherlands, by interviewing workers of all relevant health care organisations in that city. A prevalence of 4.8 per 10,000 inhabitants was found. The mean age of patients was 62 years. Seventy-five percent of all patients had already been hospitalised for several years. Physical and mental health, as judged by other medical diagnoses, was poor.

A psychobiologic analysis of cognitive failures. Structure and mechanisms.

Impairments in memory, learning, and related cognitive functions can vary in most psychiatric or neuropsychiatric disorders. Although many methods have been used to measure the presence and severity of cognitive symptoms, little progress has been made in defining and contrasting possible determinants of cognitive dysfunction. We propose a theoretical framework that describes impairments of higher mental functions in terms of both "extrinsic" noncognitive processes and "intrinsic" cognitive processes. The latter include effort (capacity) demanding processes; automatic processes; episodic (recent biographical) memory; and processes involved in accessing previously acquired knowledge. Noncognitive processes include sensitivity to reinforcement, activation, sensorimotor function, and mood. Each of these processes can be expressed at the time of information acquisition or retrieval from memory. Findings from clinical studies of patients suffering amnestic disorders, progressive dementias, and mood disorders illustrate the utility of such a model for understanding some of the determinants of cognitive dysfunction, for developing diagnostic tools, and for considering therapeutic strategies that may be useful in treating cognitive dysfunctions.