Acute REM sleep behaviour disorder associated with alcohol withdrawal: A case report and literature review.

INTRODUCTION: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of REM sleep muscle atonia and the enactment of dreams. Acute RBD associated with alcohol withdrawal syndrome is known, but the studies are limited, particularly on its neurobiological underpinnings and management alongside the withdrawal state. This work attempts to address this using a case study and relevant literature review. CASE PRESENTATION: A 40-year-old male with alcohol dependence (for 20 years) reported new-onset terrifying nightmares and violent behaviours in his sleep precipitated by alcohol withdrawal states for the last 18 months. The polysomnographic finding of REM-without-atonia supported the diagnosis of RBD. He was treated with chlordiazepoxide 100 mg/day (gradually tapered and stopped) and thiamine supplements. Post-discharge, he remained abstinent and symptom-free during the three months of follow-up. DISCUSSION: RBD related to alcohol withdrawal syndrome has been previously described in a few anecdotal reports. Sudden withdrawal from central nervous system suppressants like alcohol is hypothesised to cause a homeostatic imbalance in gamma-aminobutyric acid (GABA) pathways and 'REM rebound', resulting in the clinical and polysomnographic picture of RBD. Benzodiazepines have been found to be useful in both RBD and alcohol withdrawal. CONCLUSIONS: Alcohol withdrawal syndrome may present with acute RBD, which can be treated with a short course of benzodiazepine. However, further studies are needed to explore the long-term course of RBD in these patients.

Mast-cell-specific receptor mediates alcohol-withdrawal-associated headache in male mice.

Rehabilitation from alcohol addiction or abuse is hampered by withdrawal symptoms including severe headaches, which often lead to rehabilitation failure. There is no appropriate therapeutic option available for alcohol-withdrawal-induced headaches. Here, we show the role of the mast-cell-specific receptor MrgprB2 in the development of alcohol-withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces headache behaviors, including facial allodynia, facial pain expressions, and reduced movement, which are symptoms often observed in humans. Those behaviors were absent in MrgprB2-deficient mice during alcohol withdrawal. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia (TG) neurons in alcohol-withdrawal WT mice, but not in alcohol-withdrawal MrgprB2-deficient mice. Increased mast cell degranulation by alcohol withdrawal in dura mater was dependent on the presence of MrgprB2. The results indicate that alcohol withdrawal causes headache via MrgprB2 of mast cells in dura mater, suggesting that MrgprB2 is a potential target for treating alcohol-withdrawal-related headaches.

Prevalence, Characteristics, and Reasons for Kratom Use among Psychiatrically Ill Inpatients Who Use Substances.

OBJECTIVE: Despite kratom impacting neurobiological systems involved in psychiatric disorders, little is known about the prevalence of use among patients with severe psychopathologies. Here, we investigated the prevalence of kratom use, motives for use, and the clinical associations among inpatients with severe psychiatric disorders. METHODS: A total of 578 patients, aged 18 to 65, were evaluated by New Hampshire Hospital's Addiction Services from January 1, 2020, to February 28, 2022. The study collected demographic information and used chi-square tests, multivariable logistic regression, and subgroup analyses with 95% confidence intervals to examine trends among kratom users. A receiver operating characteristic curve analysis was also conducted. All statistical tests were performed using IBM SPSS Version 28.0.1. RESULTS: Of the patients assessed, 2.2% (n = 13) reported using kratom. The reasons for kratom use were managing withdrawal symptoms (15.4%), maintaining sobriety and reducing cravings for opioids (53.8%), improving focus and concentration (30.8%), alleviating low moods (38.5%), and managing pain (15.4%). Compared to non-kratom users, the only factor with a fair to good association with kratom use is postsecondary education (Area Under Curve, AUC = 0.77). CONCLUSIONS: Prevalence of kratom use among patients with serious mental illness at our site aligns with that reported in the general population. Users often cite self-management of cravings and sobriety from opioids, as well as treatment of low mood states, as motivations for consumption. While observations suggest a possible association between kratom use and individuals with post-secondary education, multiple substance use, and experience of substance-induced psychosis or mood disorders, it is essential to interpret these links cautiously until further rigorous studies are carried out to substantiate these findings.

Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

Fixed-Dose Phenobarbital Versus As-Needed Benzodiazepines for the Management of Alcohol Withdrawal in Acute Care General Internal Medicine.

OBJECTIVES: The management of patients at risk of severe alcohol withdrawal is challenging because conventional treatment with as-needed benzodiazepines may be ineffective. We created a fixed-dose phenobarbital protocol and compared patient outcomes using this protocol with an as-needed benzodiazepine protocol. METHODS: Patients admitted from the emergency department (ED) to General Medicine from January 1 to June 30, 2022 and treated for alcohol withdrawal with a novel phenobarbital protocol were compared with all of the patients admitted from the ED to General Medicine from January 1 to June 30, 2018, and treated with as-needed benzodiazepines. The primary outcome was a composite of intensive care unit (ICU) transfer or mortality. Secondary outcomes included mortality, ICU transfer, seizure, length of stay, excess sedation, delirium, against medical advice discharge, 30-day re-admission, 30-day ED reevaluation, and antipsychotic use. RESULTS: There were 54 patients in the phenobarbital group and 197 in the benzodiazepine group. The phenobarbital group was less medically complex but had more risk factors for severe withdrawal. There was no difference in the primary outcome, although there was a trend toward benefit in the phenobarbital group (3.7 vs 8.1%, P = 0.26), and there was a lower incidence of delirium in the phenobarbital cohort (0 vs 8.6%, P = 0.03). Secondary outcome trends favored phenobarbital, with lower mortality, ICU transfer, seizure, oversedation, against medical advice discharge, and 30-day re-admissions. A subgroup analysis accounting for differences in patient populations in the primary analysis found similar results. CONCLUSIONS: Phenobarbital is as safe and effective as benzodiazepine-based protocols for the treatment of high-risk alcohol withdrawal, with lower rates of delirium.

Closing the Care Gap: Management of Alcohol Use Disorder in Patients with Alcohol-associated Liver Disease.

Alcohol-associated liver disease (ALD)-related morbidity and mortality are rising in the United States. Although effective medications and behavioral interventions are available for the treatment of patients with alcohol use disorder (AUD), patients with ALD are profoundly undertreated for AUD. This article reviews the management of AUD in patients with ALD, with a focus on appropriate screening and diagnosis, management of alcohol withdrawal syndrome, pharmacotherapy for AUD, alcohol biomarkers, and behavioral interventions. Expanding access to AUD treatment is imperative for improving health outcomes in patients with ALD.

Amantadine withdrawal in a patient with spinocerebellar ataxia.

We report a case of a man with spinocerebellar ataxia (SCA) on high-dose amantadine who was admitted for acute on chronic dysphagia secondary to progression of SCA. Four days after oral medications were held due to patient's dysphagia, he developed fever, tachycardia and mild rigidity in extremities and became obtunded. Despite antibiotics treatment, the vitals and mental status changes persisted for 8 days. When amantadine was resumed, the patient's vital signs and encephalopathy improved within 2 days. This is among the first reports of amantadine withdrawal syndrome (AWS) in a patient without Parkinson's disease. Our case reinforces the importance of careful medication review at admission and consideration of pharmacologic side effects with not only medication initiation but also discontinuation.

Neonatal opioid toxicity: opioid withdrawal (abstinence) syndrome with emphasis on pharmacogenomics and respiratory depression.

The increasing use of opioids in pregnant women has led to an alarming rise in the number of cases of neonates with drug-induced withdrawal symptoms known as neonatal opioid withdrawal syndrome (NOWS). NOWS is a toxic heterogeneous condition with many neurologic, autonomic, and gastrointestinal symptoms including poor feeding, irritability, tachycardia, hypertension, respiratory defects, tremors, hyperthermia, and weight loss. Paradoxically, for the management of NOWS, low doses of morphine, methadone, or buprenorphine are administered. NOWS is a polygenic disorder supported by studies of genomic variation in opioid-related genes. Single-nucleotide polymorphisms (SNPs) in CYP2B6 are associated with variations in NOWS infant responses to methadone and SNPs in the OPRM1, ABCB1, and COMT genes are associated with need for treatment and length of hospital stay. Epigenetic gene changes showing higher methylation levels in infants and mothers have been associated with more pharmacologic treatment in the case of newborns, and for mothers, longer infant hospital stays. Respiratory disturbances associated with NOWS are not well characterized. Little is known about the effects of opioids on developing neonatal respiratory control and respiratory distress (RD), a potential problem for survival of the neonate. In a rat model to test the effect of maternal opioids on the developing respiratory network and neonatal breathing, maternal-derived methadone increased apneas and lessened RD in neonates at postnatal (P) days P0 and P1. From P3, breathing normalized with age suggesting reorganization of respiratory rhythm-generating circuits at a time when the preBötC becomes the dominant inspiratory rhythm generator. In medullary slices containing the preBötC, maternal opioid treatment plus exposure to exogenous opioids showed respiratory activity was maintained in younger but not older neonates. Thus, maternal opioids blunt centrally controlled respiratory frequency responses to exogenous opioids in an age-dependent manner. In the absence of maternal opioid treatment, exogenous opioids abolished burst frequencies at all ages. Prenatal opioid exposure in children stunts growth rate and development while studies of behavior and cognitive ability reveal poor performances. In adults, high rates of attention deficit disorder, hyperactivity, substance abuse, and poor performances in intelligence and memory tests have been reported.

Adult hemiconvulsive hemiatrophy syndrome: a novel clinicoradiologic disorder in adults.

The association of focal motor seizures with cerebral hemiatrophy is a recognised rare paediatric syndrome known as 'hemiconvulsion, hemiatrophy and epilepsy' (HHE). To date, HHE has not been reported in adults. We present four adult patients with striking similarities to HHE, following alcohol withdrawal in chronic alcoholics. We document the imaging findings in the acute and subacute phases, discuss the underlying mechanisms and present a hypothesis regarding the pathophysiology.

Somatosensory profiling of patients undergoing alcohol withdrawal: Do neuropathic pain and sensory loss represent a problem?

INTRODUCTION: Chronic heavy alcohol use is known to cause neurological complications such as peripheral neuropathy. Concerning the pathophysiology, few sural nerve and skin biopsy studies showed that small fibers might be selectively vulnerable to degeneration in alcohol-related peripheral neuropathy. Pain has rarely been properly evaluated in this pathology. The present study aims at assessing pain intensity, potential neuropathic characteristics as well as the functionality of both small and large nerve sensitive fibers. METHODS: In this observational study, 27 consecutive adult patients, hospitalized for alcohol withdrawal and 13 healthy controls were recruited. All the participants underwent a quantitative sensory testing (QST) according to the standardized protocol of the German Research Network Neuropathic Pain, a neurological examination and filled standardized questionnaires assessing alcohol consumption and dependence as well as pain characteristics and psychological comorbidities. RESULTS: Nearly half of the patients (13/27) reported pain. Yet, pain intensity was weak, leading to a low interference with daily life, and its characteristics did not support a neuropathic component. A functional impairment of small nerve fibers was frequently described, with thermal hypoesthesia observed in 52% of patients. Patients with a higher alcohol consumption over the last 2 years showed a greater impairment of small fiber function. DISCUSSION: Patients report pain but it is however unlikely to be caused by peripheral neuropathy given the non-length-dependent distribution and the absence of neuropathic pain features. Chronic pain in AUD deserves to be better evaluated and managed as it represents an opportunity to improve long-term clinical outcomes, potentially participating to relapse prevention.

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Risk factors for alcohol withdrawal-related hospital transfer in a correctional setting.

INTRODUCTION: A major health concern among individuals with alcohol use disorder is alcohol withdrawal syndrome (AWS), where individuals with physical dependence on alcohol may experience withdrawal signs and symptoms upon stopping or reducing alcohol use. AWS has a range of severity, with the most severe cases referred to as complicated AWS, presenting as seizure or signs and symptoms indicative of delirium or new onset of hallucinations. In the general community, risk factors or predictors of complicated AWS among hospitalized patients have been described, but there is no literature that examines such risk factors in a correctional population. The Los Angeles County Jail (LACJ) is the nation's largest jail system and manages 10-15 new patients per day for AWS. Here we aim to identify the risk factors associated with alcohol withdrawal-related hospital transfers among incarcerated patients being managed for AWS in the LACJ. METHODS: From January 1, 2019, to December 31, 2020, data were gathered about LACJ patients who required transfer to an acute care facility for alcohol withdrawal-related concerns while on the Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) protocol. Log regression analysis was performed to generate an odds ratio for acute care facility transfer for the following variables: race, sex assigned at birth, age, CIWA-Ar scores, highest systolic blood pressure (SBP), and highest heart rate (HR). RESULTS: Out of 15,658 patients on CIWA-Ar protocol during this 2-year time frame, a total of 269 (1.7%) were transferred to an acute care facility for alcohol withdrawal-related concerns. Of those 269 patients, significant risk factors associated with withdrawal-related hospital transfer included: Other race (OR 2.9, 95% CI 1.5-5.5), male sex assigned at birth (OR 1.6, 95% CI 1.0-2.5), age ≥55 years (OR 2.3, 95% 1.1-4.9), CIWA-Ar score 9-14 (OR 4.1, 95% CI 3.1-5.3), CIWA-Ar score ≥15 (OR 21.0, 95% CI 12.0-36.6), highest SBP ≥150 mmHg (OR 2.3, 95% CI 1.8-3.0), highest HR ≥ 110 bpm (OR 2.8, 95% CI 2.2-3.8). CONCLUSION: Among patients studied, the higher CIWA-Ar score was the most significant risk factor associated with alcohol withdrawal-related hospital transfer. Other significant risk factors identified are race other than Hispanic, white, and African American; male sex assigned at birth; age ≥55 years; highest SBP ≥150 mmHg; and highest HR ≥ 110 bpm.

An innovative inpatient protocol for alcohol withdrawal prevention in a 16-year-old adolescent: a case report.

BACKGROUND: Alcohol cessation in youth with daily drinking poses a risk of severe and life-threatening alcohol withdrawal. If unsupervised, alcohol withdrawal in heavy users can cause severe complications, such as seizures, delirium tremens, and death. We present the case of a teenager admitted at our pediatric center for the prevention of alcohol withdrawal using an innovative protocol, including a fixed-dosage benzodiazepine regimen. CASE DESCRIPTION: A 16-year-old Caucasian male, known to have anxiety and an attention deficit disorder, was electively admitted for medical stabilization and surveillance of alcohol withdrawal. He had been previously diagnosed with alcohol use disorder and had a past history of withdrawal symptoms. He was prescribed a course of thiamine, folic acid, as well as a fixed-dosage benzodiazepine taper over 5 days. His withdrawal symptoms were evaluated using a standardized Clinical Institute Withdrawal Assessment for Alcohol scale. During his stay, he reported minimal symptoms, as well as a score on the Clinical Institute Withdrawal Assessment for Alcohol scale consistently lower than 5. His mood, motivation, eating habits and sleeping patterns significantly improved during his stay. He developed no medical complications and demonstrated pride in his successes. He was successfully transferred to a long-term rehabilitation center. CONCLUSIONS: A withdrawal prevention protocol was developed on the basis of existing literature. It included a soothing environment, basic laboratory work evaluating the medical complications of alcohol use, as well as medication aiming to prevent and reduce potential withdrawal symptoms. The patient responded well to the fixed-dosage taper with minimal symptoms and discomfort. Although alcohol use in adolescents is frequent, alcohol withdrawal in this population is rarely seen in a pediatric hospital setting. Nonetheless, given the lack of existing guidelines regarding alcohol withdrawal in adolescents, standardized protocols could be greatly beneficial for the prevention of this condition in this population.

Differences in clinical features and gut microbiota between individuals with methamphetamine casual use and methamphetamine use disorder.

Background: The transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD. Method: We recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits. Result: Compared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05). Conclusion: Our findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.

Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome.

BACKGROUND: Phenobarbital (PB) has been acknowledged among clinicians as a potential alternative to benzodiazepines (BZD) to decrease the need for hospital length of stay and complications associated with alcohol withdrawal syndrome (AWS). However, the level of evidence, including appropriate dosing, is unclear. We aim to summarize the evidence regarding PB used in AWS and provide future agendas for research. METHODS: Following the PRISMA guidelines, we searched MEDLINE, EMBASE, ClinicalTrials.gov, and WHO ICTRP for all peer-reviewed articles and clinical trials using keywords including"alcohol withdrawal", "delirium tremens", "phenobarbital," and "barbiturate" from their inception to September 18, 2022. RESULTS: We included 20 articles, nine in the emergency department (ED) and 11 in the general floors or intensive care units (ICUs). Studies performed in the ED included two RCTs, although both suffered from a considerably small sample size. Six studies done in the general floors or ICUs compared PB and BZD monotherapy, while four compared the utility of adjunct PB in addition to BZD compared with BZD monotherapy and one was a database study without specific dosing information. Overall, there was considerable heterogeneity in PB dosing, measured outcomes, and AWS severity measurement scales. CONCLUSION: This systematic review summarizes the current evidence related to PB use in AWS. While considerable heterogeneity exists among studies available, PB as monotherapy without BZD may be a safe and effective alternative in AWS treatment. Future prospective studies or trials should focus on the standardization of PB dosing and outcomes.

Does tobacco dependence worsen cannabis withdrawal in people with and without schizophrenia-spectrum disorders?

BACKGROUND AND OBJECTIVES: Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co-use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well-established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD. METHOD: Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT-, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT-, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12-h of cannabis abstinence. RESULTS: There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co-use when treating CUD.

Approach and Management of Alcohol Withdrawal Syndrome in Operative Head and Neck Cancer Patients.

Postoperative head and neck cancer patients are at increased risk for alcohol withdrawal syndrome. Literature has shown that in this patient population, alcohol withdrawal is associated with an increase in postoperative medical and surgical complications, length of hospitalization, and hospital-related costs. Harm reduction and addiction medicine philosophies can reduce morbidity and mortality, but have not been fully validated in perioperative surgical management for head and neck cancer. This commentary synthesizes key principles of addiction medicine and current strategies that Otolaryngology-Head and Neck Surgery surgeons can consider in their perioperative assessment and management of alcohol withdrawal syndrome in their patients.

Substance Withdrawal-Associated Takotsubo Cardiomyopathy: A Review of the Literature.

Objective: To better understand Takotsubo cardiomyopathy, a rare but life-threatening complication of acute substance withdrawal.Data Sources: A PubMed search was conducted to identify relevant case reports through 2021 using the medical subject headings alcohol withdrawal, opioid withdrawal, benzodiazepine withdrawal OR withdrawal AND Takotsubo OR stress cardiomyopathy.Study Selection: Case reports were included in the review if there was a diagnosis of Takotsubo cardiomyopathy in the setting of withdrawal from substances of abuse. Case reports were excluded if patients were withdrawing from other substances, actively intoxicated, or had myocardial ischemia.Data Extraction and Synthesis: Data were manually abstracted for the variables of interest, including demographics, symptoms, medical evaluation, and treatment. Descriptive statistics of the demographics, symptoms, medical evaluation, and treatment of Takotsubo cardiomyopathy were analyzed.Results: The mean (SD) age of patients experiencing withdrawal-associated Takotsubo cardiomyopathy was 50.8 years (15.2), and 64% of patients were female. The most common signs and symptoms were tachycardia (60%), changes in blood pressure (48%), altered mental status (48%), dyspnea (32%), nausea or vomiting (28%), and chest pain (28%). All patients with a reported electrocardiogram (92%) demonstrated ECG abnormalities; 76% had an elevated troponin level, and 24% had an elevated CK-MB level. Medications that could treat withdrawal and α2-agonists were utilized for 60% and 12% of patients, respectively. Ventilator support, cardiopulmonary resuscitation, and intra-aortic balloon pump were needed for 24%, 8%, and 8%, respectively, of patients with withdrawal-associated Takotsubo cardiomyopathy.Conclusions: Withdrawal-associated Takotsubo cardiomyopathy is a rare but potentially life-threatening complication of substance withdrawal. Clinicians should maintain a high degree of clinical suspicion for withdrawal-associated Takotsubo in patients with a history of substance use disorders or physical dependence on benzodiazepines or opioids, as the clinical presentation may be atypical.

A challenging case of lumbar vertebral burst fracture with alcohol withdrawal delirium: A case report.

BACKGROUND: Delirium tremens is a symptom of alcohol withdrawal syndrome that occurs 48 to 96 hours after the last drink in 5% of withdrawing patients. METHODS: This report describes the clinical progression of a case of lumbar vertebral burst fracture with alcohol withdrawal delirium that was difficult to manage. RESULTS: A 47-year-old man was rushed to our hospital complaining of lumbar back pain and numbness in both lower extremities resulting from a 6-m fall during civil engineering work. Computed tomography (CT) revealed a L1 burst fracture with a highly protruding bone fragment in the spinal canal. Magnetic resonance imaging disclosed significant compression of the conus and intramedullary signal changes. We immediately performed posterior spinal fusion and vertebroplasty using instrumentation. On the 4th postoperative day, he became severely agitated, as diagnosed as having delirium tremens related to alcohol withdrawal syndrome, and soon began appropriate medication with diazepam. Although his symptoms persisted until 6 days postoperatively, follow-up CT detected no evidence of screw loosening or breakage. CONCLUSION: We encountered a patient with severe delirium tremens developing several days after thoraco-lumbar fusion surgery. Prompt internal fixation successfully treated the spinal injury and prevented neurological damage. It may also be necessary to consider treatment strategies for patients with a background of heavy alcohol consumption in consideration of delirium tremens and other symptoms of alcohol withdrawal.

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

BACKGROUND: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development. METHODS: We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD). RESULTS: Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice. CONCLUSION: We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.