Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder.

Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.

Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome).

PURPOSE: To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). METHODS: We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. RESULTS: Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%. CONCLUSIONS: SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions.

Reversal of Alcohol-Induced Dysregulation in Dopamine Network Dynamics May Rescue Maladaptive Decision-making.

Alcohol is the most commonly abused substance among adolescents, promoting the development of substance use disorders and compromised decision-making in adulthood. We have previously demonstrated, with a preclinical model in rodents, that adolescent alcohol use results in adult risk-taking behavior that positively correlates with phasic dopamine transmission in response to risky options, but the underlying mechanisms remain unknown. Here, we show that adolescent alcohol use may produce maladaptive decision-making through a disruption in dopamine network dynamics via increased GABAergic transmission within the ventral tegmental area (VTA). Indeed, we find that increased phasic dopamine signaling after adolescent alcohol use is attributable to a midbrain circuit, including the input from the pedunculopontine tegmentum to the VTA. Moreover, we demonstrate that VTA dopamine neurons from adult rats exhibit enhanced IPSCs after adolescent alcohol exposure corresponding to decreased basal dopamine levels in adulthood that negatively correlate with risk-taking. Building on these findings, we develop a model where increased inhibitory tone on dopamine neurons leads to a persistent decrease in tonic dopamine levels and results in a potentiation of stimulus-evoked phasic dopamine release that may drive risky choice behavior. Based on this model, we take a pharmacological approach to the reversal of risk-taking behavior through normalization of this pattern in dopamine transmission. These results isolate the underlying circuitry involved in alcohol-induced maladaptive decision-making and identify a novel therapeutic target. SIGNIFICANCE STATEMENT: One of the primary problems resulting from chronic alcohol use is persistent, maladaptive decision-making that is associated with ongoing addiction vulnerability and relapse. Indeed, studies with the Iowa Gambling Task, a standard measure of risk-based decision-making, have reliably shown that alcohol-dependent individuals make riskier, more maladaptive choices than nondependent individuals, even after periods of prolonged abstinence. Using a preclinical model, in the current work, we identify a selective disruption in dopamine network dynamics that may promote maladaptive decision-making after chronic adolescent alcohol use and demonstrate its pharmacological reversal in adulthood. Together, these results highlight a novel neural mechanism underlying heightened risk-taking behavior in alcohol-dependent individuals and provide a potential therapeutic target for further investigation.

Protective Effects of Tetramethylpyrazine on Cerebrovascular Regulations in Rats with Chronic Alcoholic Encephalopathy.

Recent studies showed that pathology of alcoholic encephalopathy was associated with cerebral vascular damage. TMP (tetramethyl- pyrazine) is widely used in the treatment of cerebrovascular diseases, however, it has not been reported whether TMP can relieve alcohol-induced cerebral vascular damages. The study was performed to investigate the learning and memory, cerebrovascular pathological changes and the expressions of vascular endothelial growth factor (VEGF) and serum levelsofendothelin-1 (ET-1) in the rat model of chronic alcoholic encephalopathy, and explore the effects of TMP intervention on alcoholic encephalopathy. In the present study, the rat model of chronic alcoholic encephalopathy was established by the gavage administration of alcohol; the learning and memory ability was tested by Morris water maze; the expression of VEGF was measured by RT-PCR and Western blot; and the serum levels of ET-1 was measured by radioimmunoassay. We found that alcohol intoxication impaired learning and memory, induced VEGF overexpression and increased ET 1 concentrations. TMP intervention improved learning abilities, increased the VEGF expression and reduced ET-1 level. These results indicate that TMP exhibits therapeutic effects on chronic alcoholic encephalopathy.

[Cognitive disorders in toxic (mercurial) and alcohol encephalopathy].

To differentiate cognitive disorders in toxic (mercurial) and alcohol encephalopathy, the authors determined peculiarity of mental disorders in patients with toxic encephalopathie of various origins. Discriminant analysis helped to evaluate totality of informative neurophysiologic and psychologic parameters to assign patients to a group with cognitive disorders due to mercurial toxic encephalopathy or to a group with that due to alcohol encephalopathy.

Daño cerebral relacionado con el alcohol. Situación actual y llamada a la acción / Alcohol related brain damage. State of the art and a call for action

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[A woman without speech]. / Een vrouw zonder spraak.

A 56-year-old woman with a history of alcohol abuse was found at home amidst empty wine bottles with somnolence and severe dysarthria. MRI of the brain revealed selective demyelination of the corpus callosum, consistent with Marchiafava-Bignami disease.

Phenomenology of squalor, hoarding and self-neglect: an Australian aged care perspective.

Aged care health professionals in Australia are increasingly referred patients whose standard of cleanliness and self-care has deteriorated to levels resulting in public health concern. This paper describes three illustrative case studies of people referred to an Australian Aged Care Assessment Service who present with 'Diogenes Syndrome'. The diversity and complexity of these cases reflect variable underlying diagnoses. Symptoms of self-neglect, hoarding and domestic squalor and combinations thereof may provide a more useful classification system of the older person who presents in such circumstances than the frequently used term Diogenes syndrome. Practical guidelines are required for appropriate assessment and management of these conditions.

The psycho-social rehabilitation of patients with alcohol-related brain damage in the community.

AIMS: To describe the clinical presentation, course and psycho-social outcome of patients with alcohol-related brain damage (ARBD) referred from acute general hospital inpatient settings to a newly commissioned community team. METHODS: A follow-up study of a consecutive series of 41 patients subjected to a developing, phased rehabilitation programme in community settings. RESULTS: Patients were followed for an average of 25 months. Thirty-two patients were either abstinent or categorized as 'controlled drinkers' and were placed in appropriate community settings. Acute hospital admissions were reduced by 85%. The various domains of a neuropsychiatric assessment tool, the health of the nation outcome scale-acquired brain damage, improved with the exception of concomitant mental illness and self-directed harmful behaviour. CONCLUSIONS: A community team with experience in working with younger people with cognitive impairment can provide a service for people with ARBD. Such a service is not dependent on pre-designated specialist institutions but relies on person-centred care planning, close follow-up and collaborative work with a variety of community agencies. A structured rehabilitation programme provides a framework for intervention.

Neuroimaging findings in alcohol-related encephalopathies.

OBJECTIVE: Our aim was to review the emergent neuroimaging findings of alcohol-related CNS nontraumatic disorders. Alcohol (ethanol) promotes inflammatory processes, increases DNA damage, and creates oxidative stress. In addition, the accompanying thiamine deficiency may lead to Wernicke encephalopathy. Associated changes in serum osmolarity may lead to acute demyelination. CONCLUSION: Alcohol-related encephalopathies can be life-threatening conditions but can be prevented or treated, if recognized.

Early onset probable linezolid-induced encephalopathy.

Linezolid is increasingly being utilized for the treatment of gram-positive pathogens. While neurological complications with linezolid are rare, long-term exposure can be associated with neurotoxic effects. Patients with pre-existing neurologic sequelae or risk factors, such as alcohol abuse, diabetes, or concomitant administration of chemotherapeutic agents and/or antiretroviral therapy, may be more susceptible to the development of linezolid-induced neurotoxicity. We describe a 41-year-old male who developed early onset encephalopathy after a day and a half of linezolid therapy. Our patient had at least one significant risk factor (alcoholism), making linezolid-induced encephalopathy probable based upon the Naranjo probability scale. Clinicians should be aware of the potential for early onset linezolid-induced neurotoxicity, particularly in patients with concomitant risk factors.

The relationship between alcoholic cerebellar degeneration and cognitive and emotional functioning.

Although it is now widely acknowledged that the cerebellum contributes to the modulation of higher-order cognitive and emotional functions, this relationship has not been extensively explored in perhaps the largest group of individuals with cerebellar damage, chronic alcoholics. Localised damage to the cerebellum has been associated with a specific constellation of deficits and has been termed the 'cerebellar cognitive affective syndrome' (CCAS) [Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome. Brain 121, 561-579]. The CCAS describes a profile of impairments, including deficits in executive functioning and visuospatial skills, language disruption and altered personality and affective behaviour. It is conceivable that the CCAS may also develop in a subgroup of alcoholics with alcoholic cerebellar degeneration and may in part account for a proportion of the cognitive and affective deficits commonly observed with the condition. While evidence has emerged supporting such a relationship, methodological limitations and the lack of theoretically driven investigation of the contribution of cerebellar dysfunction to cognitive and emotional functioning in chronic alcoholics, preclude definitive conclusions being drawn.

[Occupational relevance of alcohol related neurological involvement]. / Comorbilità neurologica dell'alcolismo di rilevanza occupazionale e relazionale.

BACKGROUND AND OBJECTIVES: Accidents and various degrees of impairment in working performances and abilities are strongly correlated to alcohol consumption, either of moderate or of severe degree. Accidents, in particular, have been investigated in population studies that strongly suggest a direct effect of alcohol on attention and executive functions as well as a relevant interference of drinking with the neurological functioning and with eventual subclinical dysfunction of individuals: epilepsy threshold, cardiovascular risk and previous events, sleep disorders; post-traumatic sequelae. DISCUSSION AND CONCLUSIONS: Impairment of cognitive function (and concomitant functional/structural brain damage) is characterized, in particular, by difficulties in abstract problem solving, visuo-spatial and verbal learning, memory function, perceptual and motor skills, related to disruption of frontal, pontocerebellar and cerebellothalamocortical systems. These abilities should therefore be monitored in at-risk working populations in order to prevent work accidents and to address appropriate therapeutic and rehabilitative interventions.

Supporting the long-term residential care needs of older homeless people with severe alcohol-related brain injury in Australia: the Wicking Project.

For years, community service providers have been frustrated with the lack in availability of long-term, specialized supported accommodation for older people, particularly older homeless people, with severe acquired brain injury (ABI) and challenging behaviors. Although the incidence of ABI (particularly alcohol-related brain injury) is far wider than being confined to the homeless population, it is frequently misdiagnosed and very often misunderstood Wintringham is an independent welfare company in Melbourne, Australia, that provides secure, affordable, long-term accommodation and high quality services to older homeless people. The high incidence of alcohol abuse among the resident population has led us to adapt our model ofcare to accommodate a complexity of need. However, there are some individuals with severely affected behaviors that continue to challenge Wintringham's capacity to provide adequate support. The deficiency in highly specialized, long-term supported accommodation for older people with severe alcohol-related brain injury (ARBI) is the driving force behind this project. We aim to further develop and improve the current Wintringham model of residential care to better support people with these complex care needs. We will report on the synthesis of this project which aims to test a specialized model that can be reproduced or adapted by other service providers to improve the life circumstances of these frequently forgotten people.

Sudden bilateral blindness in Wernicke's encephalopathy: case report and review of the literature.

We report on a patient suffering from bilateral sudden blindness as initial symptom of Wernicke's encephalopathy (WE). A 37-year-old male alcoholic was admitted to a psychiatric clinic because of excessive alcohol consumption (3.4 per thousand). 24 h later he developed acute bilateral blindness with no light perception, downbeat nystagmus, bilateral ocular abduction deficits, cerebellar ataxia as well as a slight psychomotor slowing and mild disorientation. MRI including diffusion-weighted imaging and MR-angiography 3 h after symptom onset did not reveal findings suggestive for ischemic stroke. Immediate iv-application of thiamine led to a nearly complete remission of the neuroophthalmologic symptoms within 12 h. Although we critically discuss other potential etiologies, we conclude that the complex clinical picture with initial sudden blindness is an unusual presentation of WE.

Lack of recognition and complexity of foetal alcohol neuroimpairments.

AIMS: To obtain the recorded prevalence of foetal alcohol syndrome (FAS) and foetal alcohol spectrum disorders (FASD) in Norway, and evaluate the effect of a general information program to increase the recognition of FAS/FASD for health care and social workers. METHODS: A questionnaire regarding prevalence of FAS/FASD was sent to all Norwegian paediatric and child psychiatry departments. In the region Hordaland county, an information program was carried out to educate health-care and social workers on symptoms and signs of FAS/FASD, and referral was encouraged for suspected cases. Referred children received a neuropaediatric evaluation, and the effect of the information program on recorded FAS/FASD was recorded. RESULTS: Based on the national survey, a prevalence of 0.3 per 1000 was calculated. After the information program, the estimated prevalence in Hordaland County increased to 1.5 per 1000. In 5 years, 25 children were diagnosed with FAS and 22 with FASD. One-third of all children were mentally retarded. Microcephaly and neuroimpairments were more common among FAS children. Almost all children met the criteria of ADHD. CONCLUSION: The rate of FAS/FASD may be greatly underestimated because of lack of knowledge. An information program aimed at health-care and social workers is effective.