Pellagra and Alcohol Dependence Syndrome: Findings From a Tertiary Care Addiction Treatment Centre in India.

AIM: To define the prevalence and clinical presentation of pellagra, a multi-systemic disease caused by the deficiency of niacin, in patients admitted to a tertiary addiction treatment centre in southern India, with alcohol dependence syndrome (ADS)-(ICD10). METHODS: Review of the health records of 2947 patients who received inpatient care for ADS between 2015 and 2017. RESULTS: Out of 2947, 31 (1%) were diagnosed with pellagra. Nearly two-thirds (64.5%) of those with pellagra were from a low-income group. Of the clinical-triad of pellagra, all patients had dermatitis, more than half (58%) had delirium, a minority (19%) had diarrhoea. Nearly two-thirds (61%) had presented in a complicated-withdrawal state. Associated conditions included peripheral neuropathy (32%); Wernicke's encephalopathy (26%); seizures (16%).Seventeen (54%) had BMI <18.5 kg/m2. Treatment was a high dose of parenteral vitamins including niacin (mean dose: 1500 mg/day) for an average of 7.5 days followed by oral multivitamin supplements. All had complete resolution of pellagrous symptoms by the end of the three weeks of inpatient care. CONCLUSIONS: Pellagra is an acute medical condition, frequently encountered in the context of alcohol dependence and poverty. It often presents with other disabling and life-threatening comorbidities like delirium tremens and Wernicke's encephalopathy. The classical triad of pellagra is only seen in a minority of cases. Thus a high index of suspicion is required lest pellagra may remain undiagnosed. Prompt identification and treatment with a high dose of niacin in combination with other vitamins result in complete recovery.

Delirium tremens in an AUD patient after an intrathecal baclofen pump induced total alcohol abstinence.

OBJECTIVE: Delirium Tremens (DT) is the most severe complication of alcohol withdrawal syndrome (AWS), and has a mortality rate of 1-5%. Baclofen is recommended for spasticity treatment, but it has recently been used for alcohol withdrawal symptoms reduction and alcohol abstinence. CASE REPORT: A cervical spinal cord injury patient was treated for two years with oral baclofen 80 mg/day for spasticity. He is alcohol-dependent and a cannabis user and required an intrathecal baclofen (ITB) pump implant. A week after the implant, he stopped drinking, as "he didn't felt the urge anymore". The AWS appeared five days after the last alcohol intake and DT at 7 days. Diazepam 20 mg was used up to three times per day, but didn't seem to improve or reduce the anxiety, agitation, visual or auditory hallucinations. Two years later the patient remains alcohol abstinent and still on intrathecal baclofen. CONCLUSIONS: Alcohol-dependent patients can abruptly stop their alcohol intake, while in continuous infusion of intrathecal baclofen. Baclofen can be useful in the acute treatment of AWS as it seems to reduce diazepam requirements and in long-term alcohol abstinence. In the presence of AWS, while on chronic baclofen, no dose reduction should be attempted, as it can worsen the AWS or trigger baclofen withdrawal.

An open prospective pilot study of a herbal combination "Relief" as a supportive dietetic measure during alcohol withdrawal.

OBJECTIVE: A herbal combination (saffron extract, passion flower herb extract, cocoa seed extract, radish extract and black cumin extract) called "Relief" was designed as a supportive therapy of alcohol withdrawal syndrome (AWS). This combination was based on the scientific evidence of each constituent effect on AWS-like symptoms. In addition, our preclinical studies have shown the effectiveness of Relief on AWS detoxification. The rationale of the study was to document whether the oral intake of the designed content of Relief could have a positive effect on the course of alcohol detoxification by reducing some of the AWS in hospitalized patients. METHODS: This pilot study was performed as non-interventional, open, single-armed, prospective on 32 hospitalized patients entered for detoxification of alcohol withdrawal syndrome. Each patient received daily three capsules of Relief for 15 days, and AWS parameters were monitored, in addition to serum liver enzymes and quality of life which was evaluated using the Befindlichkeits-Skala (Bf-SR) scaling system. RESULTS: Relief administration significantly reduced the percentage of patients with hyperhidrosis (r=0.815, p<0.001), reduced serum liver enzymes by ~50-80% (p<0.05), and increased normalization of appetite (r=0.777, p<0.001). Besides, before the treatment began the Bf-SR scale was 28.3±4.3, which was typical for neurological syndromes such as depression or insomnia, and during Relief administration the Bf-SR scale significantly dropped to 15.6±2.4 (p<0.001). As for the safety, four, but not serious, adverse events were observed; two of them may be product related. Finally, 84.4% of patients' assessed Relief treatment as good to excellent and 87.5% of the patients declared an interest in reusing Relief for the next detoxification period. CONCLUSIONS: Despite the limitations of the present study, the findings showed the potential of Relief for the improvement of the clinical situation of patients with symptoms of alcohol withdrawal and therefore, justify a full-scale well-controlled study design to be implemented.

La psiquiatría de enlace y el diagnóstico del delirium tremens / Liaison psychiatry in diagnosing delirium tremens

La manifestación clínica más grave y potencialmente fatal de la abstinencia de alcohol es el delirium tremens (DT), cuadro observado en aproximadamente el 5% al 10% de los pacientes con trastorno por consumo de alcohol que requieren hospitalización. El diagnóstico adecuado del DT requiere conocer los factores de riesgo, el cuadro clínico típico y la evolución y la gravedad de los síntomas de abstinencia. Las benzodiazepinas son el tratamiento farmacológico de elección para los pacientes con DT. Su eficacia fue confirmada mediante numerosos estudios. Si bien hay drogas alternativas que también pueden ser efectivas, las benzodiazepinas son elegidas debido a su perfil farmacocinético y de seguridad favorable. Las drogas alternativas son utilizadas como complemento de las benzodiazepinas para el tratamiento de los pacientes con cuadros de abstinencia complicados o resistentes. Los esquemas que incluyen dosis de carga administradas por vía oral o intravenosa son los preferidos para los pacientes con DT. El aumento rápido de la dosis de benzodiazepinas de acuerdo con la gravedad de los síntomas evaluados mediante escalas estructuradas y el empleo de drogas adyuvantes alternativas permiten el control oportuno del DT. Cerca del 10% de los pacientes que presentan resistencia a las benzodiazepinas requieren tratamiento en unidades de terapia intensiva con dosis intravenosas elevadas de benzodiazepinas y otras drogas, evaluación minuciosa y, de ser necesario, ventilación mecánica. La suplementación vitamínica y la atención adecuada por parte del personal de enfermería también son componentes esenciales del tratamiento. Los psiquiatras de enlace deberían integrar equipos multidisciplinarios destinados al tratamiento agudo de los pacientes con DT. No obstante, solo los psiquiatras de enlace con capacidades y conocimiento que se desempeñan de acuerdo con los protocolos estandarizados pueden lograr que determinados pacientes con DT reciban tratamiento adecuado. El psiquiatra de enlace también debe procurar un periodo de abstinencia seguro que proteja la dignidad del paciente y lo prepare para resolver la dependencia

The most serious and potentially life-threatening manifestation of alcohol withdrawal is delirium tremens (DT) or alcohol withdrawal delirium, which occurs in about 5% to 10% of hospitalized patients with alcohol problems. A consideration of risk factors, the typical clinical picture, evolution of withdrawal-symptoms and their severity aid in the proper recognition of DT. Benzodiazepines are the mainstay of medication treatment of DT. Their efficacy has been established by a large body of evidence. Although alternative medications might be equally effective, benzodiazepines are preferred because of their favourable pharmacokinetic and safety. Alternative medications are used as adjuncts to benzodiazepines in the treatment of complicated and refractory withdrawal states. Oral or intravenous loading-dose regimens are preferred for treatment of DT. Rapidly escalating doses of benzodiazepines titrated to symptom-severity on structured scales and the use of adjunctive alternative medications ensures prompt control of DT. About 10% of patients who are benzodiazepine-resistant require treatment in intensive care units with massive intravenous doses of benzodiazepines and additional medications, careful monitoring and mechanical ventilation if necessary. Vitamin supplementation and adequate medical, nursing and supportive care are other essential components of management. Liaison psychiatrists are expected to form an integral part of the multidisciplinary team, which manages patients with DT in acute-care settings. Only skilled and knowledgeable liaison psychiatrists relying on standardized treatment protocols can make certain that patients with DT receive adequate care. The liaison psychiatrist also needs to ensure a safe and humane withdrawal that protects the patient's dignity and prepares the patient for on-going treatment of dependence.

Influence of microelement concentration on the intensity of alcohol withdrawal syndrome.

AIMS: To establish a nutritional and constitutional profile concerning the micronutrient plasma concentration of patients who suffer from AWS. METHOD: Observational case control study to determine whether patients who exhibited symptoms of AWS (N = 60) had micronutrient plasmatic concentration deficiencies when compared with healthy controls (N = 34). RESULTS: There were statistically significant differences between the concentrations of nutrients that are correlated with glutamate hyperactivity (zinc, magnesium and folate/vitamin B12/homocysteine). CONCLUSION: Evidence from literature and our experiment suggests that brain activity, especially the glutamatergic system, might be directly involved in micronutrient concentrations. Therefore, their supplementation to the AWS patient might improve symptom evolution.

A 'symptom-triggered' approach to alcohol withdrawal management.

In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms.

Fusion of psychiatric and medical high fidelity patient simulation scenarios: effect on nursing student knowledge, retention of knowledge, and perception.

High fidelity patient simulation (HFPS) has become an increasingly popular teaching methodology in nursing education. To date, there have not been any published studies investigating HFPS scenarios incorporating medical and psychiatric nursing content. This study utilized a quasi-experimental design to assess if HFPS improved student knowledge and retention of knowledge utilizing three parallel 30-item Elsevier HESI(TM) Custom Exams. A convenience sample of 37 senior level nursing students participated in the study. The results of the study revealed the mean HESI test scores decreased following the simulation intervention although an analysis of variance (ANOVA) determined the difference was not statistically significant (p = .297). Although this study did not reveal improved student knowledge following the HFPS experiences, the findings did provide preliminary evidence that HFPS may improve knowledge in students who are identified as "at-risk." Additionally, students responded favorably to the simulations and viewed them as a positive learning experience.

Agrypnia excitata.

Agrypnia (from the Greek: to chase sleep) excitata (AE) is a syndrome characterized by loss of sleep and permanent motor and autonomic hyperactivation (excitata). Disruption of the sleep-wake rhythm consists in the disappearance of spindle-delta activities, and the persistence of stage 1 non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep persists but fails to stabilize, appearing in short recurrent episodes, isolated, or mixed with stage 1 NREM sleep. Diurnal and nocturnal motor, autonomic and hormonal overactivity is the second hallmark of AE. Of particular interest is the finding that norepinephrine secretion is extremely elevated at all hours of the day and night whereas the nocturnal melatonin peak is lacking. Oneiric stupor is probably an exclusive sign of AE and consists in the recurrence of stereotyped gestures mimicking simple daily life activities. Agrypnia excitata aptly defines 3 different clinical conditions, fatal familial insomnia (FFI), an autosomal dominant prion disease, Morvan syndrome (MS), an autoimmune encephalitis, and delirium tremens (DT), the alcohol withdrawal syndrome. Agrypnia excitata is due to an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. This pathogenetic mechanism is visceral thalamus degeneration in FI, whereas it may depend on autoantibodies blocking voltage-gated potassium (VGK) channels within the limbic system in MS, and in the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in DT.

Pellagrous encephalopathy presenting as alcohol withdrawal delirium: a case series and literature review.

BACKGROUND: Alcohol withdrawal delirium (AWD) is associated with significant morbidity and mortality. Pellagra (niacin deficiency) can be a cause of delirium during alcohol withdrawal that may often be overlooked. OBJECTIVES: We present a three-patient case series of pellagrous encephalopathy (delirium due to pellagra) presenting as AWD. METHODS: We provide a brief review of pellagra's history, data on pellagra's epidemiology, and discuss pellagra's various manifestations, particularly as related to alcohol withdrawal. We conclude by providing a review of existing guidelines on the management of alcohol withdrawal, highlighting that they do not include pellagrous encephalopathy in the differential diagnosis for AWD. RESULTS: Though pellagra has been historically described as the triad of dementia, dermatitis, and diarrhea, it seldom presents with all three findings. The neurocognitive disturbance associated with pellagra is better characterized by delirium rather than dementia, and pellagra may present as an isolated delirium without any other aspects of the triad. DISCUSSION: Although endemic pellagra is virtually eradicated in Western countries, it continues to present as pellagrous encephalopathy in patients with risk factors for malnutrition such as chronic alcohol intake, homelessness, or AIDS. It may often be mistaken for AWD. Whenever pellagra is suspected, treatment with oral nicotinamide (100 mg three times daily for 3-4 weeks) prior to laboratory confirmation is recommended as an inexpensive, safe, and potentially life-saving intervention.

Delirium y delirium subsindrómico: prevalencia de un espectro de enfermedad / Subsyndromal delirium: prevalence of a disease spectrum

Introducción: El delirium subsindrómico (DSS) es una entidad en debate, que supone un espectro de enfermedad más allá de la dicotomía diagnóstica del delirium según los criterios actuales. Material y métodos: Para cuantificar y objetivar la prevalencia del DSS se ha realizado un estudio transversal multicéntrico con carácter posteriormente prospectivo a todos los pacientes ingresados en 3 Servicios de Geriatría de hospitales terciarios. Los criterios diagnósticos de DSS utilizados se basaron en los de Marcantonio, y también se utilizó la escala DRS-R-98 como variable continua del grado de delirium. Resultados: Se estudiaron 85 pacientes, 56% mujeres, Barthel 62 (DE: 32), edad 87 años (DE: 6), CIRS-G 24 (DE: 6,85). El 75,3% de los pacientes tenía al menos un criterio CAM positivo, y la mitad al menos 13 puntos en el DRS-R-98. La prevalencia de delirium fue del 53%, y la de DSS del 22,3%. El grado de delirium-DSS aparece asociado con los diferentes síndromes geriátricos, nivel de desnutrición, y grado de deterioro funcional y cognitivo con una tendencia lineal significativa entre grupos. Los pacientes sin delirium tienen niveles más altos que los que presentan delirium subsindrómico, y estos a su vez más altos que aquellos sin diagnóstico de delirium. También hay tendencia en el grado de delirium medido mediante el DRS-R-98. Conclusión: Más allá del concepto dicotómico sobre la presencia o ausencia de delirium, este trabajo sugiere la probable continuidad del proceso cognitivo y la posibilidad de establecer medidas diagnósticoterapéuticas más eficaces en un momento cronológico más precoz(AU)

Introduction: Subsyndromal delirium (SSD) is a developing concept of disease with a spectrum beyond the diagnostic dichotomy of delirium with standard criteria. Material and methods: To study the prevalence and significance of SSD we have conducted a crosssectional prospective multicenter study of all patients admitted to three Geriatric Departments in tertiary hospitals. The SSD diagnostic criteria used were based on Marcantonio¢§©¥s criteria, and the DRS-R-98 scale was also used as a continuous variable of the degree of delirium. Results: We studied 85 patients, 56% women, Barthel 62 (SD: 32), age 87 (SD: 6), CIRS-G 24 (SD: 6.85). Three quarters (75.3%) of patients had at least one CAM positive item, and half of them with at least 13 points in the DRS-R-98 scale. The prevalence of delirium was 53% and 22.3% for SSD. The degree of delirium-DSS was associated with different geriatric syndromes, levels of malnutrition, and degree of functional and cognitive impairment, with a significant linear trend between groups. Patients without delirium have higher levels than those with subsyndromal delirium, and these in turn are higher than those without diagnosed delirium. There is also a tendency in the degree of delirium measured by the DRS-R-98(AU)

Treatments for alcohol-related disorders in China: a developing story.

AIMS: Alcohol-related disorders (ARDs) have become an increasing mental health and social challenge in China. Research from China may provide important clinical information for researchers and clinicians around the world. However, most of the Chinese research on ARDs has only been published in Chinese language journals. This article summarizes publications related to treatments for ARDs found in the Chinese literature. METHODS: A descriptive study based on literature identified from searches of the China National Knowledge Infrastructure (1979-2012), Pubmed databases and hand-picked references with emphasis on traditional Chinese medicine (TCM). RESULTS: More than 1500 Chinese language papers on treatment for ARDs were found and ~110 were selected. Many medications used in the Western countries (e.g. disulfiram and acamprosate) are not available in China, and no drugs have been officially approved for alcohol dependence. TCM approaches (including acupuncture, electroacupunture and herbals) have played a role in treatment for ARDs with some positive results. These unique methods are reviewed and the need for additional controlled studies is noted. CONCLUSION: Currently, very limited facilities, medications or programs are available for patients with ARDs in China, thus much improvement is needed in the field, including setting up intervention/treatment programs.

Disrupted thalamic T-type Ca2+ channel expression and function during ethanol exposure and withdrawal.

Chronic ethanol exposure produces profound disruptions in both brain rhythms and diurnal behaviors. The thalamus has been identified as a neural pacemaker of both normal and abnormal rhythms with low-threshold, transient (T-type) Ca(2+) channels participating in this activity. We therefore examined T-type channel gene expression and physiology in the thalamus of C57Bl/6 mice during a 4-wk schedule of chronic intermittent ethanol exposures in a vapor chamber. We found that chronic ethanol disrupts the normal daily variations of both thalamic T-type channel mRNA levels and alters thalamic T-type channel gating properties. The changes measured in channel expression and function were associated with an increase in low-threshold bursts of action potentials during acute withdrawal periods. Additionally, the observed molecular and physiological alterations in the channel properties in wild-type mice occurred in parallel with a progressive disruption in the normal daily variations in theta (4-9 Hz) power recorded in the cortical electroencephalogram. Theta rhythms remained disrupted during a subsequent week of withdrawal but were restored with the T-type channel blocker ethosuximide. Our results demonstrate that a key ion channel underlying the generation of thalamic rhythms is altered during chronic ethanol exposure and withdrawal and may be a novel target in the management of abnormal network activity due to chronic alcoholism.

Improved glucose control associated with i.v. chromium administration in two patients receiving enteral nutrition.

PURPOSE: The effect of i.v. chromium administration on glucose control in two patients receiving enteral nutrition is described. SUMMARY: Chromium supplementation has been hypothesized to potentiate the actions of insulin in facilitating cellular uptake of glucose. We report two cases-one involving a diabetic patient and the other a nondiabetic patient-in which chromium administration appeared to decrease insulin requirements. In case 1, a diabetic patient given a single course of chromic chloride appeared to have a probable response to the drug. Within the first day of chromic chloride administration, insulin requirements declined. When chromic chloride was discontinued, insulin requirements did not rise, suggesting efficacy and sustained effect. The patient's glucose intake and blood glucose levels remained relatively stable, while there was a significant decline in insulin requirements. Serum chromium levels were not assessed, so it is uncertain if the patient experienced chromium deficiency or if it was adequately treated with chromium supplementation, and a dose-response relationship could not be ascertained because the patient received a continuous infusion of chromium. In case 2, the insulin requirements of a nondiabetic patient appeared to decrease in response to multiple courses of chromic chloride. Upon initial discontinuation of chromic chloride, the patient's lower insulin requirements were sustained for a few days, but changes in clinical status and other medications precipitated elevated insulin requirements and the need for subsequent chromic chloride administration. Further research in more controlled settings is necessary to elucidate chromium's effect on insulin requirements. CONCLUSION: Infusion of chromic chloride appeared to reduce insulin requirements in one diabetic patient and one nondiabetic patient.

Ramadan fasting triggering koro-like symptoms during acute alcohol withdrawal: a case report from Oman.

This article describes a case of koro-like symptoms from Oman associated with alcohol withdrawal and illustrates how the socio-cultural practices of Ramadan-fasting affected the patterning and timing of presentation of severe alcohol withdrawal symptoms. The patient was severely distressed by the delusion that his penis had been amputated. The acute anxiety involving this delusion appears to be conceptually and phenomenologically similar to koro.

Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats.

Withania somnifera (WS) or its psychotropic preparation is known to play a critical role in morphine, alcohol and benzodiazepines addiction. This study investigates the role of WS in acute ethanol and withdrawal from chronic ethanol consumption using elevated plus maze paradigm in rats. Acute administration of ethanol (1.5-2 g/kg, ip) triggered anxiolytic effect and withdrawal from prolonged ethanol (9% v/v ethanol, 15 days) consumption elicited enhanced behavioral despair (anxiety). Acute administration of WS (50 mg/kg, oral) potentiated the anxiolytic action of subeffective dose of ethanol (0.5 or 1 g/kg, ip). Moreover, the ethanol withdrawal anxiety was markedly antagonized in dose dependent manner by WS at 200 and 500 mg/kg or higher dose of ethanol (2.5 g/kg). However, co-administration of subeffective doses of WS (50 mg/kg, oral) and ethanol also attenuated withdrawal-induced anxiety due to chronic ethanol (9% v/v ethanol, 15 days) consumption. The results suggest the protective effect of WS in the management of ethanol withdrawal reactions.

Fatal familial insomnia and agrypnia excitata.

This review summarizes the pioneering steps culminating in the identification of a novel disease, fatal familial insomnia (FFI), a hereditary prion disease. Together with Morvan's chorea and delirium tremens, FFI is characterized by an inability to sleep associated with motor and autonomic overactivation. We named this pattern agrypnia excitata, a syndrome caused by a dysfunction in thalamolimbic circuits. This review highlights the strategic role of the limbic thalamus in the central autonomic network running from the limbic cortex to the lower brainstem and regulating sleep and wakefulness.

Increased QT interval variability index in acute alcohol withdrawal.

OBJECTIVE: Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal. METHODS: High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations. RESULTS: Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations. CONCLUSION: Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal.