Disinhibited-Like Behavior Correlates With Frontal Cortex Damage in Alcohol-Induced Wernicke-Korsakoff Syndrome

Wernicke-Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated to impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, isolate or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation; TDD), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior, which appears to be dependent on TDD. Also, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS.

Alcohol and the Brain

Alcohol works on the brain to produce its desired effects, e.g., sociability and intoxication, and hence the brain is an important organ for exploring subsequent harms. These come in many different forms such as the consequences of damage during intoxication, e.g., from falls and fights, damage from withdrawal, damage from the toxicity of alcohol and its metabolites and altered brain structure and function with implications for behavioral processes such as craving and addiction. On top of that are peripheral factors that compound brain damage such as poor diet, vitamin deficiencies leading to Wernicke-Korsakoff syndrome. Prenatal alcohol exposure can also have a profound impact on brain development and lead to irremediable changes of fetal alcohol syndrome. This chapter briefly reviews aspects of these with a particular focus on recent brain imaging results. Cardiovascular effects of alcohol that lead to brain pathology are not covered as they are dealt with elsewhere in the volume.

Alcohol-Related Dementia: Rethink How Much You Drink

People have consumed alcohol for centuries. Most clinicians who work with people who have dementia acknowledge that alcohol may cause or exacerbate dementia's symptoms. Alcohol-related dementia (ARD) has been recognized since the 1960s, but clinicians rarely use this diagnosis. Regardless, it is common and develops pursuant to long-term excessive alcohol consumption. It may, in some cases, evolve into Wernicke-Korsakoff syndrome. Diagnosis can be obscured if patients are not truthful about their alcohol consumption. Often, friends or family provide a better picture of the patient's alcohol history than patients do themselves. Thiamine treatment may prevent or improve symptoms. Abstinence from alcohol is critical, but it is difficult for older people with long histories of heavy drinking. Consultant pharmacists can help the heath care team develop nuanced care plans for patients who have ARD.

Alcohol-Related Dementia: Rethink How Much You Drink

People have consumed alcohol for centuries. Most clinicians who work with people who have dementia acknowledge that alcohol may cause or exacerbate dementia’s symptoms. Alcohol-related dementia (ARD) has been recognized since the 1960s, but clinicians rarely use this diagnosis. Regardless, it is common and develops pursuant to long-term excessive alcohol consumption. It may, in some cases, evolve into Wernicke-Korsakoff syndrome. Diagnosis can be obscured if patients are not truthful about their alcohol consumption. Often, friends or family provide a better picture of the patient’s alcohol history than patients do themselves. Thiamine treatment may prevent or improve symptoms. Abstinence from alcohol is critical, but it is difficult for older people with long histories of heavy drinking. Consultant pharmacists can help the heath care team develop nuanced care plans for patients who have ARD.

Music Therapy in People Suffering from Korsakoff Syndrome: A Case Report

This article reports about two different cases of persons with Korsakoff syndrome (KS) who benefit greatly from music therapy while they are struggling with behavioral and emotional problems, caused by their chronic alcohol abuse which led to developing KS. Typical characteristics of persons suffering from KS are memory impairment, confabulation and problems with executive functions. Music therapy is a non-pharmacological intervention which has the potential to improve communication skills, reducing behavioral problems and thus leading to a better quality of life in KS-patients. An empathic yet directive approach has been proven beneficial when working with KS-clients. There is still little knowledge on how music therapy may contribute to improving these skills or reducing these impairments. The two case reports that follow provide greater insight into how to treat patients with KS through music therapy, specifically in patients who are residing in a long-term care facility specialized in KS.

Case Report: Intensive Inpatient Neurorehabilitation Achieves Sustained Real-World Benefits in Severe Alcohol-Related Wernicke-Korsakoff Syndrome: A Case Study With 7-Years Follow-Up

About 85% of survivors of acute Wernicke's Encephalopathy (WE), a frequent and serious consequence of thiamine deficiency and alcohol misuse, sustain chronic neurocognitive deficits also known as chronic Wernicke-Korsakoff syndrome (WKS). If alcoholism is combined with smoking, tobacco alcohol optic neuropathy (TAON) may occur which leads to visual impairment. In contrast to WKS, TAON may be treated successfully by early vitamin substitution and detoxification. Little research has been conducted on WKS longterm outcomes. Existing literature suggests poor prognosis. Symptoms remaining beyond the acute treatment with thiamine are thought to be irreversible. Whether neurorehabilitation may be an effective route to help recovery of those persistent symptoms is an open question. At our neurorehabilitation center, which specializes in the treatment of severe chronic deficits after brain injury, the opportunity arose to treat a 35 year old male with WKS, and to conduct follow-up assessments 3- and 7-years post discharge, respectively. Initially MK was admitted to emergency care with suspected postconcussive syndrome, alcohol-related thiamine deficiency, and TAON. Thiamin, cobalamin, and folate substituion improved TAON but major cognitive deficits remained. When admitted to our center 4 months later, he was fully reliant on care staff for all activities of daily living (ADL). Through intensive neurocognive training and psychological treatment he improved gradually and, after 26 months, was well enough to be discharged into the community and pursue work in a sheltered setting. Neuropsychological tests, as well as patient reports obtained at the follow-ups showed that the benefits apparent at discharge had been sustained, and for some scores, improved further. This was particularly evident in the Rey-Osterrieth Complex Figure Test which improved from percentage ranges <1 for immediate recognition and recall at discharge to rank 16 for immediate recognition and rank 5 for recall at the 7-year follow-up. This case study illustrates the immense benefits neurorehabilitation can have for WKS induced by alcohol misuse. It further demonstrates how skills and strategies, learned in the inpatient setting, translate into living well and independently, and how the latter promotes further improvement long after discharge.