Alcohol withdrawal syndrome: mechanisms, manifestations, and management.

The alcohol withdrawal syndrome is a well-known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.

Facial Dystonia with Facial Grimacing and Vertical Gaze Palsy with "Round the Houses" Sign in a 29-Year-Old Woman.

A 29-year-old woman developed progressive dysarthria and coordination problems from the age of 15. Examination showed dysarthria, facial dystonia, bibrachial dystonia, hyperreflexia, ataxia, and emotional incontinence. Downward supranuclear gaze palsy was prominent with a "Round the Houses" sign. Magnetic resonance imaging of the brain and medulla, electroneurography, and cerebrospinal fluid were normal. A computed tomography scan showed hepatosplenomegaly. This combination of progressive neurological symptoms together with hepatosplenomegaly was suggestive of inborn error of metabolism. A bone marrow biopsy showed an increased number of macrophages with foamy content, highly suggestive of lysosomal disease. Plasmatic chitotriosidase activity and CCL18 were increased. Genetic testing showed heterozygosis for the variation c.1070C→T (p.Ser357Leu) and c.1843→T (Arg615Cys), confirming the diagnosis of Niemann-Pick type C (NPC). The "Round the Houses" sign has only been described in patients with progressive supranuclear palsy (PSP). This sign is described as an inability to produce pure vertical saccades along the midline and instead moving the eyes in a lateral arc to accomplish the movement. The observation of this sign in a patient with NPC indicates that this bedside finding is not specific for PSP, but a sign of medial longitudinal fasciculus dysfunction. The presence of facial dystonia with facial grimacing together with supranuclear gaze palsy is highly characteristic and useful for the diagnosis of NPC. NPC is an important underdiagnosed condition, given the availability of treatment and a mean diagnostic delay of 6 years.

EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy.

BACKGROUND: Although Wernicke encephalopathy (WE) is a preventable and treatable disease it still often remains undiagnosed during life. OBJECTIVES: To create practical guidelines for diagnosis, management and prevention of the disease. METHODS: We searched MEDLINE, EMBASE, LILACS, Cochrane Library. CONCLUSIONS AND RECOMMENDATIONS: 1 The clinical diagnosis of WE should take into account the different presentations of clinical signs between alcoholics and non alcoholics (Recommendation Level C); although prevalence is higher in alcoholics, WE should be suspected in all clinical conditions which could lead to thiamine deficiency (good practice point - GPP). 2 The clinical diagnosis of WE in alcoholics requires two of the following four signs; (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment (Level B). 3 Total thiamine in blood sample should be measured immediately before its administration (GPP). 4 MRI should be used to support the diagnosis of acute WE both in alcoholics and non alcoholics (Level B). 5 Thiamine is indicated for the treatment of suspected or manifest WE. It should be given, before any carbohydrate, 200 mg thrice daily, preferably intravenously (Level C). 6 The overall safety of thiamine is very good (Level B). 7 After bariatric surgery we recommend follow-up of thiamine status for at least 6 months (Level B) and parenteral thiamine supplementation (GPP). 8 Parenteral thiamine should be given to all at-risk subjects admitted to the Emergency Room (GPP). 9 Patients dying from symptoms suggesting WE should have an autopsy (GPP).

Headache prevalence related to smoking and alcohol use. The Head-HUNT Study.

The aim of this study was to examine a possible association between smoking, alcohol and headache in a large population-based cross-sectional study. A total of 51,383 subjects completed a headache questionnaire and constituted the 'Head-HUNT' Study. Questionnaire-based information on smoking was available in 95% and on alcohol in 89% of the individuals. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI). Prevalence rates for headache were higher amongst smokers compared with never smokers, most evident for those under 40 years smoking more than 10 cigarettes per day (OR 1.5, 95% CI 1.3-1.6). Passive smoking was also associated with higher headache prevalence. For alcohol use, there was a tendency of decreasing prevalence of migraine with increasing amounts of alcohol consumption compared with alcohol abstinence. Only with regard to symptoms indicating alcohol overuse, a positive association with frequent headache was found. The association between headache and smoking found in the present study raises questions about a causal relationship, e.g. that smoking causes headache or that it allays stress induced by headache. The observed negative association between migraine and alcohol consumption is probably explained by the headache precipitating properties of alcohol.

EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task force.

Despite being a considerable problem in neurological practice and responsible for one-third of seizure-related admissions, there is little consensus as to the optimal investigation and management of alcohol-related seizures. The final literature search was undertaken in September 2004. Consensus recommendations are given graded according to the EFNS guidance regulations. To support the history taking, use of a structured questionnaire is recommended. When the drinking history is inconclusive, elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can support a clinical suspicion. A first epileptic seizure should prompt neuroimaging (CT or MRI). Before starting any carbohydrate containing fluids or food, patients presenting with suspected alcohol overuse should be given prophylactic thiamine parenterally. After an alcohol withdrawal seizure (AWS), the patient should be observed in hospital for at least 24 h and the severity of withdrawal symptoms needs to be followed. For patients with no history of withdrawal seizures and mild to moderate withdrawal symptoms, routine seizure preventive treatment is not necessary. Generally, benzodiazepines are efficacious and safe for primary and secondary seizure prevention; diazepam or, if available, lorazepam, is recommended. The efficacy of other drugs is insufficiently documented. Concerning long-term recommendations for non-alcohol dependent patients with partial epilepsy and controlled seizures, small amounts of alcohol may be safe. Alcohol-related seizures require particular attention both in the diagnostic work-up and treatment. Benzodiazepines should be chosen for the treatment and prevention of recurrent AWS.

Clinical utility of EEG in alcohol-related seizures.

OBJECTIVE: To study if electroencephalogram (EEG) can discriminate between alcohol-related seizures (ARS) and seizures unrelated to alcohol use. MATERIAL AND METHODS: Alcohol-related seizures was defined as a seizure in a patient with score > or = 8 in the Alcohol Use Disorders Identification Test (AUDIT). Twenty-seven patients with ARS (22 without epilepsy: ARSwE), 21 AUDIT-negative epileptic patients with seizures (ES), and 30 other AUDIT negative patients with seizures (OS) were studied. Thirty-seven epilepsy outpatients and 79 sciatica inpatients were controls. RESULTS: Epileptiform and slow activity were less frequent in the ARSwE than in the ES group. Alpha amplitude was lower in the ARSwE than the other groups. Photoparoxysmal activity was not observed. EEG was associated with a larger negative predictive value (78% probability of non-ARS if EEG was abnormal) than a positive predictive value (55% probability of ARS if EEG was normal). CONCLUSION: A definitely abnormal EEG suggests epilepsy or symptomatic seizures unrelated to alcohol. The predictive value of a normal EEG is limited, but the typical post-ictal finding in ARS is nevertheless a normal low-amplitude EEG record.

Detection of alcohol abuse in neurological patients: variables of clinical relevance to the accuracy of the %CDT-TIA and CDTect methods.

OBJECTIVES: Alcohol-related neurological diseases are encountered frequently. Early diagnosis is essential, because minimal intervention effectively reduces hazardous alcohol consumption and may prevent permanent neurological damage. Carbohydrate-deficient transferrin (CDT) is a valuable tool for the identification of alcohol abuse, but for unselected patient populations, reduced test accuracy has been reported. Recently, factors other than alcohol use have been shown to influence CDT levels. Our aim was to identify clinically relevant factors that might reduce test accuracy. MATERIAL AND METHODS: We included 397 neurological patients consecutively hospitalized for seizures, ischemic stroke, or sciatica and 87 patients who attended routine outpatient controls for epilepsy. Blood samples were analyzed for CDT by using two commercially available tests, %CDT-TIA and CDTect. All patients underwent a semistructured clinical interview that included a record of the reported ethanol consumption during the last 8 days, and all completed the Alcohol Use Disorders Identification Test (AUDIT). Current medication, medical history, and demographic information also were obtained. RESULTS: Both tests were elevated in female antiepileptic drug users, compared with others who reported no recent ethanol intake. A higher number of false-positive cases was seen for CDTect than for %CDT. Various combinations of CDT and gamma-glutamyltransferase improved sensitivity, but at the cost of reduced specificity. Variables that predicted the variation of CDT included antiepileptic drug use, sex, body mass index, and smoking. Total transferrin levels were reduced significantly in postmenopausal women, whereas a falling trend was seen for CDTect. Transferrin alterations caused a higher number of false-positive results for CDTect than for %CDT. The area under the receiver operating characteristics curve for women was higher for CDTect than for %CDT, and for %CDT, the area under the receiver operating characteristics curve was higher for men than for women. CONCLUSION: The accuracy of CDT for detection of alcohol abuse in neurological patients was generally low, particularly for women. Combination variables of CDT and gamma-glutamyltransferase did not increase test accuracy. Variables that were associated with higher CDT levels included female sex, antiepileptic drug use, transferrin alterations, and possibly low body mass index. When factors known to cause poor accuracy in particular patient groups are appreciated, CDT may be a good adjunct to the clinical examination.

Weekday distribution of alcohol consumption in Norway: influence on the occurrence of epileptic seizures and stroke?

Binge drinking at weekends is considered to be a predominant feature of alcohol consumption in the Nordic countries. Neurological diseases, such as seizures and stroke, have been reported to occur in temporal relation to alcohol intoxication and withdrawal. We wanted to investigate weekday variances in alcohol consumption in relation to the onset of neurological symptoms in these disorders. Consecutive patients admitted for epileptic seizures (n = 142) and ischemic strokes (n = 91) were included in the study. Control groups were consecutively hospitalized sciatica patients (n = 181), outpatients with epilepsy (n = 91), and healthy subjects (n = 254). The day-by-day alcohol intake during the 8 days prior to hospital admission was recorded. Seizures occurring in subjects with hazardous alcohol consumption, operationally defined by a score > or =8 in the Alcohol Use Disorders Identification Test (AUDIT-positive) were considered to be related to alcohol use. Binge drinkers were identified by an alcohol intake, on at least 1 of the last 3 days, of > or =6 standard units in men, or > or =4 standard units in women. Thirty-five percent of seizure patients were AUDIT-positive, in contrast to 18% and 16% of stroke and sciatica patients, and 12% and 13% of epilepsy outpatients and healthy controls. Twenty-three percent of seizure patients were binge drinkers whereas in the other groups, this proportion did not exceed 10%. In all groups, alcohol consumption peaked on Saturdays. More seizures occurred on Mondays compared to Saturdays, with a diminishing trend through the week. However, AUDIT-negative seizure patients, of which binge drinking occurred in only 5%, caused this difference. AUDIT-positive seizure patients had a higher and more evenly distributed alcohol intake through the week, and the occurrence of seizures in this group did not differ significantly between days of the week. Alcohol consumption peaked 2 days prior to the onset of withdrawal seizures. The weekend drinking pattern was confirmed for all the study groups. Hazardous alcohol consumption preceded every third acute seizure, but was found in only one of eight outpatients with epilepsy. AUDIT-negative patients caused a peak of seizure admissions on Mondays, compared to Saturdays, with a diminishing trend through the week.

Validity of carbohydrate deficient transferrin and other markers as diagnostic aids in the detection of alcohol related seizures.

OBJECTIVE: The role of alcohol misuse in the genesis of seizures is probably often undetected. The aim was to investigate the utility of carbohydrate deficient transferrin (CDT) compared with other biomarkers and clinical examination in the diagnosis of alcohol related seizures. METHODS: The study included consecutively 158 seizure patients-83 men and 75 women-with mean age 45 (16-79) years. Seizures related to alcohol use were identified by a score > or =8 in the alcohol use disorders identification test (AUDIT positive). AUDIT was applied as the gold standard to which sensitivity and specificity of the various markers were related. Blood samples were obtained from 150 patients on admission and analysed for ethanol, liver enzymes, and CDT, using AXIS Biochemicals' %CDT-TIA kit. RESULTS: 53 patients (34%) were AUDIT positive. Using the commonly applied decision value for %CDT of 5.0%, a sensitivity of 41% and a specificity of 84% were obtained. Analysis of receiver operator characteristics (ROC) curves disclosed an optimal cut off value for %CDT of 5.4%, which yielded a sensitivity of 39% and a specificity of 88%. At a specificity of 80%, the sensitivity was 43% for %CDT and 26% for GGT. The %CDT sensitivity was markedly higher for men than for women. Compared with GGT, ASAT, ALAT, and ASAT/ALAT ratio, CDT was the best single biomarker for alcohol related seizures. However, even in the subgroup of withdrawal seizures, the sensitivity level barely exceeded 50%. Clinicians scored alcohol as the main cause of the seizure in only 19 cases (12%). In 38 (24%) cases, clinicians suspected that alcohol had a role (sensitivity of 62% at a specificity of 89%). Their ability to identify AUDIT positive patients was better than that of any biomarker, but many cases were missed. Agreement of clinicians' scores to CDT was only fair (kappa=0.28). CDT concentrations were significantly increased among alcohol abstaining patients on enzyme-inducing antiepileptic drugs. Six out of 16 patients with false positive CDT results were exposed to such drugs. CONCLUSIONS: CDT is not recommended as a stand alone marker for alcohol related seizures, but may provide a useful contribution to the overall diagnostic investigation of seizures. Confirmatory studies are needed as to the apparent vulnerability of CDT to antiepileptic drugs.

[Acute headache--diagnostic considerations]. / Akutt hodepine--diagnostiske overveielser.

Acute headache may be the presenting symptom of several conditions. Sometimes, a headache with an abrupt onset and unusual severity may occur, experienced by the patient as the worst headache ever. The diagnostic evaluation primarily aims at ruling out subarachnoid haemorrhage (SAH), as well as other serious causes of acute headache, such as meningitis or stroke. The clinical examination should immediately be followed by cerebral computed tomography (CT). A CT scan will reveal 95% of SAHs, provided that it is performed within the first 24 hours after headache onset. If the CT scan is normal, a lumbar puncture should follow, preferably 12 hours after the onset of headache, unless infectious meningitis is suspected. If infectious meningitis is strongly suspected, lumbar puncture should be performed without delay. The spinal fluid should be investigated by spectrophotometry, in order to obtain optimal diagnostic accuracy for SAH. This article briefly reviews the various conditions that may present with an acute headache.

The diversity of seizures related to alcohol use. A study of consecutive patients.

The aim of this study was to investigate the influence of hazardous alcohol drinking on the occurrence of epileptic seizures, the semiology of such seizures, and the extent of the problem. A consecutive sample of 142 acute seizure patients (78 male and 64 female, mean age 46 (16-79) years) was studied. Control groups were 185 consecutive sciatica patients and 254 healthy individuals. Subjects with a hazardous alcohol drinking level were identified by a score >8 in the Alcohol Use Disorders Identification Test (AUDIT). Seizures in AUDIT-positive individuals occurring within 72 h of the last drink were considered to be related to alcohol withdrawal. Generalized or partial onset seizures were classified on the basis of history, electroencephalographic (EEG) and neuroradiological findings. Thirty-five percent of seizure patients were AUDIT-positive, whereas conversely 27% were abstainers. Two-thirds of AUDIT-positive seizure patients met the criteria for withdrawal seizures. Indications of partial onset seizures were found in 25 (51%) of AUDIT-positive patients, all secondarily generalized seizures. Sixty percent of generalized onset seizure patients were AUDIT-positive. In conclusion, seizure patients included significantly more AUDIT-positive subjects, as well as abstainers, than healthy Norwegian controls and consecutive sciatica patients from our hospital. Partial onset seizures are more frequent among hazardous drinkers than hitherto recognized. A generalized onset seizure in adults warrants a high suspicion of alcohol as a provoking factor. Routine screening of acute seizure admissions with the Alcohol Use Disorders Identification Test is recommended.