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.

Mortality of subjects with alcohol-related seizures increased after alcohol cheapening.

OBJECTIVE: To investigate whether the reduction of alcohol prices in Finland (March 1, 2004) associated with an increase in mortality of subjects with alcohol-related seizures. PATIENTS AND METHODS: All subjects with head trauma in Oulu University Hospital during 1999 (n = 827) were identified and thereafter followed up until death or the end of 2009. We used National Hospital Discharge Register, hospital charts, and death records from Official Cause-of-Death Statistics to identify seizure visits and alcohol-related deaths. Kaplan-Meier survival curves were used to characterize the effect of alcohol price reduction on risk of death. Cox proportional hazards model was used to identify independent predictors of death. RESULTS: Twenty-five subjects had alcohol-related seizures before the alcohol price reduction. Their cumulative mortality rate was significantly higher (P = 0.015) than that of other head trauma subjects during the follow-up and it clearly increased after the price reduction. Age (HR 1.06 per year, 95% CI 1.05-1.07, P < 0.001), moderate-to-severe traumatic brain injury (HR 2.04 95% CI 1.37-3.04, P < 0.001), and alcohol-related seizure (HR 3.02, 95% CI 1.48-6.16, P = 0.002) were independent predictors of death after adjustment for confounding factors. CONCLUSION: We conclude that the political decision to lower alcohol price associated with a significant increase in the mortality rate of subjects with alcohol-related seizures.

Head trauma sustained under the influence of alcohol is a predictor for future traumatic brain injury: a long-term follow-up study.

BACKGROUND AND PURPOSE: Hazardous drinking may result in recurrent head trauma. It was investigated whether head trauma sustained under the influence of alcohol is a predictor of future traumatic brain injury (TBI). METHODS: All subjects with head trauma (n = 827) brought to the emergency room at Oulu University Hospital during 1999 were identified and followed up until death or the end of 2009. The National Hospital Discharge Register and hospital charts were used to identify TBIs during the follow-up and Kaplan-Meier curves and the Cox proportional hazards model were used to characterize predictors of TBI. RESULTS: During the total follow-up of 7386 person-years, 52/827 subjects sustained a new head trauma with TBI and the risk of TBI was significantly (P = 0.005) higher amongst subjects who had been under the influence of alcohol at the time of the index trauma in 1999. New TBI occurred under the influence of alcohol in 30/52 cases (57.7%). An alcohol-related index trauma [adjusted hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.38-4.56, P < 0.01] and history of TBI (HR 3.39, 95% CI 1.32-8.72, P < 0.05) were independent risk factors for subsequent TBI after adjustment for sex and age. A history of harmful drinking was also a significant risk factor (adjusted HR 10.37, 95% CI 5.53-19.43, P < 0.001). In the subset of 396 patients having an index head trauma without TBI, this being alcohol related was also a significant risk factor for subsequent TBI after adjustment for sex, age and history of TBI (HR 3.54, 95% CI 1.36-9.18, P = 0.009). CONCLUSIONS: Even head trauma without TBI under the influence of alcohol implies an elevated risk of subsequent TBI. A brief intervention to reduce hazardous drinking is needed to prevent TBI.

Incidence of moderate-to-severe traumatic brain injuries after reduction in alcohol prices.

OBJECTIVE: Alcohol may be involved in 40-50% of traumatic brain injuries (TBI). In Finland, the cutting of alcohol taxes by one third in 2004 resulted in a marked increase in per capita alcohol consumption. We investigated the consequences of increased alcohol consumption on the incidence of moderate-to-severe traumatic brain injury among a defined population. MATERIAL AND METHODS: We identified all residents of Northern Ostrobothia with acute moderate-to-severe TBI admitted to Oulu University Hospital in 1999 and in 2007 as well as those who died on the scene without being admitted to the hospital. Alcohol involvement was recorded by similar methods and equally often during both years. Incidence rates were calculated as number of subjects per 100,000 population. Logistic regression was performed to determine which factors predicted fatal TBI and associated with alcohol-related TBI. RESULTS: No significant increase from 1999 to 2007 occurred in the incidence of alcohol-related moderate-to-severe TBIs among the population of Northern Ostrobothnia. The total number of alcohol-related TBIs were 61/135 (45.2%) in 2007 and 52/126 (41.3%) 1999. Fall-related TBIs were more frequent in 2007 than in 1999. Alcohol and older age predicted fatal outcome. Alcohol was significantly (P < 0.001) more often present in fatal TBIs (83/156, 53.2%) than in non-fatal TBIs (30/105, 28.6%). Male sex, fall, suicide, and assault significantly associated with alcohol-related TBI. CONCLUSIONS: The reduction in alcohol prices and the concomitant increase in alcohol consumption did not increase the incidence of alcohol-related moderate-to-severe TBI.

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).

Better than expected survival after primary intracerebral hemorrhage in patients with untreated hypertension despite high admission blood pressures.

BACKGROUND: Hypertension is the most important modifiable risk factor for primary intracerebral hemorrhage (ICH), but little is known of the effect of preceding hypertension on outcome. Because high mean arterial blood pressure (MABP) at admission is an independent predictor of early death in patients with ICH, we explored its role on survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension. METHODS: We assessed clinical data and the 3-month outcome of patients with spontaneous ICH (n = 453) admitted to the stroke unit of Oulu University Hospital between 1993 and 2004. Standard medical treatment was used to lower MABP from levels >127 mmHg to <120 mmHg. RESULTS: Overall mortality within 3 months was 28%. Patients with untreated hypertension had significantly lower mortality (6%) than those with treated hypertension (36%, P < 0.001) or those without hypertension (25%, P < 0.01). High admission MABP associated with early death in normotensive subjects (P < 0.05) and those on medication for hypertension (P < 0.01) but not in those with untreated hypertension. Patients with untreated hypertension were younger and had less frequently cardiac disease, diabetes, and/or warfarin or aspirin medications, but they showed the highest blood pressures (BPs) at admission. Amongst patients with high admission MABP, favorable outcome was seen most frequently in those who had untreated hypertension. Hematoma growth did not associate with high MABP amongst them. CONCLUSION: Despite their higher BP values at admission, subjects with untreated hypertension showed better survival and more frequently favorable outcome after BP-lowering therapy than other patients.

Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury.

OBJECTIVES: Severe head injury (HI) and the apolipoprotein E (ApoE) epsilon4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE epsilon4 is not known. MATERIALS AND METHODS: Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored > or =26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable. RESULTS: Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE epsilon4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE epsilon4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02-7.16). CONCLUSIONS: According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE epsilon4 allele is associated with subsequent dementia among older adults.

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.

Fall-related brain injuries and the risk of dementia in elderly people: a population-based study.

Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini-Mental State Examination (MMSE) test score of > or =26 (n = 325) were followed-up for 9 years to record all their fall-related head injuries resulting in traumatic brain injury (TBI). At the end of the follow-up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM-IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age-specific hazard ratio (95% confidence interval) 2.80 (1.35-5.81). In a population scoring > or =28 points in the baseline MMSE an apolipoprotein E (ApoE) epsilon4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35-9.34), and the effect of brain injury and ApoE epsilon4 phenotype was synergistic; 7.68 (2.32-25.3). We conclude that fall-related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE epsilon4 allele.

Early predictors of post-concussion symptoms in patients with mild head injury.

A small proportion of patients with mild head injury (MHI) develop post-concussion symptoms (PCSs). We searched simple measures for the early detection of patients who are probable to develop PCSs. We recorded signs and symptoms, history of previous diseases, medications, and lifestyle factors and measured serum protein S-100B on admission in a series of 172 consecutive MHI patients admitted into the emergency room of a general hospital. A modified Rivermead Post-Concussion Symptoms Questionnaire was used to identify the patients with and without PCSs 1 month after the injury. We identified 37 patients with MHI who developed PCSs (22%). Odds ratios (OR) and 95% confidence intervals (CI) after adjustment for possible confounding variables were calculated by logistic regression. Independent early risk factors for PCSs in the MHI patients were skull fracture (OR 8.0, 95% CI 2.6-24.6), serum protein S-100B >/= 0.50 microg/l (OR 5.5, 95% CI 1.6-18.6), dizziness (OR 3.1, 95% CI 1.2-8.0), and headache (OR 2.6, 95% CI 1.0-6.5). Serum protein S-100B proved to be a specific, but not sensitive predictor of PCSs. The presence of skull fracture, elevated serum protein S-100B, dizziness, and headache may help the emergency room physician to identify patients at risk of PCSs and to refer them for further examination and follow-up.

Risk factors for cryptogenic ischaemic stroke.

This case-control study was designed to identify risk factors for cryptogenic brain infarction. We assessed the frequency of prothrombotic states, homocysteine, lipoprotein (a) [Lp(a)] and other lipids and the apolipoprotein E phenotype together with conventional risk factors in 46 patients (19 women and 27 men) with cryptogenic brain infarction aged from 15 to 60 years and in 104 community-based controls. Multivariate odds ratios (ORs) for risk factors and 95% CIs were calculated by logistic regression. Hypertension (OR 4.5; 95% CI, 1.5-13.2; P = 0.006), current smoking (OR 2.9; 95% CI, 1.2-6.8; P = 0.012), low HDL cholesterol (HDL-C) (OR 5.4; 95% CI, 1.1-25.5; P = 0.035) and high clotting factor VIII activity (OR 3.6; 95% CI, 1.1-12.2; P = 0.041) were variables associated with cryptogenic brain infarction. These risk factors were not equally frequent in women and men. Low HDL-C and high factor VIII activity in the women, and hypertension, current smoking and a low level of plasma folate in the men were risk factors for cryptogenic stroke. Several of the observed risk factors for cryptogenic brain infarction were lifestyle-associated, which emphasizes the role of health education in addition to pharmacological treatment in the prevention of stroke.

Could automated template based quantification of benzodiazepine receptors in brain single photon emission tomography with 123I NNC 13-8241 be used to demonstrate neuronal damage in traumatic brain injury?

Automated methods are required for the analysis of brain single photon emission tomography images. We applied an automated method to assess the benzodiazepine receptor distribution in the brain. Images of 19 patients with mild traumatic brain injury who had received I NNC 13-8241 were compared with a mean brain template accumulated from 18 healthy volunteers. To obtain more information, we calculated the neuronal benzodiazepine receptor binding in the brain by using pre-defined anatomical regions and a voxel-by-voxel technique. The group of patients with mild traumatic brain injury differed significantly (P =0.015) from the group of healthy volunteers in the distribution of benzodiazepine receptors. This methodological work suggests that a reference based template and a three-dimensional brain model help in regional analysis and quantification and could be useful in demonstrating permanent neuronal damage after head injury.

Enoxaparin vs heparin for prevention of deep-vein thrombosis in acute ischaemic stroke: a randomized, double-blind study.

OBJECTIVES: To compare the efficacy, safety, and overall risk-benefit profile of enoxaparin and unfractionated heparin (UFH) prophylaxis of venous thromboembolic complications in patients with acute ischaemic stroke. METHODS: Patients with ischaemic stroke resulting in lower-limb paralysis lasting for at least 24 h and necessitating bedrest, were randomized within 48 h of the onset of stroke, and treated with enoxaparin (40 mg subcutaneously once daily) or UFH (5000 IU subcutaneously thrice daily) for 10 +/- 2 days. Main outcome measures were deep-vein thrombosis, pulmonary embolism (PE), death from any cause, intracranial haemorrhage including haemorrhagic infarction, or any other major bleeding. RESULTS: Outcome events occurred within 3 months of stroke in 40/106 patients treated with enoxaparin (37.7%) and 52/106 patients treated with UFH (49.1%, P=0.127). Fewer patients treated with enoxaparin (14, 13.2%) than with UFH (20, 18.9%) had evidence of haemorrhagic transformation of ischaemic stroke. CONCLUSIONS: Enoxaparin administered subcutaneously once daily was as safe and effective as subcutaneous UFH given thrice daily in the prevention of thromboembolic events in patients with lower limb paralysis caused by acute ischaemic stroke.

Use of aspirin, epistaxis, and untreated hypertension as risk factors for primary intracerebral hemorrhage in middle-aged and elderly people.

BACKGROUND AND PURPOSE: The incidence of primary intracerebral hemorrhage (ICH) increases exponentially with age, but the risk factors are not well known. We investigated lifestyle factors, previous diseases, and medications as risk factors for ICH in middle-aged and elderly people. METHODS: We compared 98 consecutive patients with primary ICH between 36 and 90 years of age with 206 community-based control subjects matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for possible confounding variables were calculated by logistic regression. RESULTS: The independent risk factors for ICH were untreated hypertension (OR, 6.95; 95% CI, 3.06 to 15.8), previous ischemic stroke (OR, 3.83; 95% CI, 1.70 to 8.63), epilepsy (OR, 13.8; 95% CI, 2.49 to 76.6), recent strenuous physical exertion (OR, 3.97; 95% CI, 1.95 to 8.10), and a history of epistaxis (OR, 2.92; 95% CI, 1.28 to 6.62). In men, treated hypertension (OR, 2.67; 95% CI, 1.03 to 6.93) was also a significant risk factor. Patients with a history of epistaxis who had used nonsteroidal anti-inflammatory drugs, especially aspirin in high doses, had an increased risk for ICH (adjusted OR of epistaxis, 2.75; 95% CI, 1.11 to 6.81; adjusted OR of aspirin use, 14.7; 95% CI, 2.03 to 106). In addition, there was a significant (P:<0.01) positive interaction between the history of epistaxis and the use of aspirin on the risk for ICH. CONCLUSIONS: Epistaxis is a risk factor for ICH in middle-aged and elderly people, both independently and combined with the use of aspirin. Other independent risk factors are untreated hypertension, previous ischemic stroke, epilepsy, and recent strenuous physical exertion. Epistaxis may be a warning sign of an increased risk for ICH in subjects using aspirin.

Ear oximetry: a noninvasive method for detection of patent foramen ovale: a study comparing dye dilution method and oximetry with contrast transesophageal echocardiography.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) may play an important role as a risk factor for ischemic stroke and some other neurological conditions. There is a need for low-cost and noninvasive methods for the detection of PFO. This study evaluates the accuracy of two simple bedside tests, the dye dilution method and ear oximetry, in the detection of PFO. METHODS: Dye dilution curves and ear oximetry recordings with a noninvasive ear densitometer were obtained from consecutive cryptogenic stroke patients referred for contrast transesophageal echocardiography (TEE). All test results were blindly assessed for the presence of PFO. Sensitivity and specificity were calculated with TEE used as a reference method. kappa statistics were used to measure interrater agreement. RESULTS: Dye dilution curves were obtained from 67 patients. Dye dilution correctly diagnosed 35 of the 46 patients who had PFO in TEE and all the 21 patients without PFO. Thus, the sensitivity (95% CI) of the dye dilution method was 76% (61% to 87%) and its specificity 100% (84% to 100%). Ear oximetry was done on 83 patients. Oximetry correctly diagnosed 45 of the 53 patients who had PFO in TEE and all of the 30 patients without PFO. Thus, the sensitivity of ear oximetry was 85% (72% to 93%) and its specificity 100% (88% to 100%). The interrater agreement was excellent (kappa value 0.94 for dye dilution and 0.90 for oximetry). CONCLUSIONS: Dye dilution and oximetry are both sensitive and specific methods for the detection of PFO. Oximetry has the following primary advantages over the currently available diagnostic methods: it is noninvasive, safe, and inexpensive and causes no discomfort for the patient. We suggest that oximetry could be used as a first-line screening method for PFO in patients with cryptogenic stroke. Ear oximetry also has potential use in epidemiological studies.

Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids.

Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled conditions on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether the subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willebrand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcohol. Excretion of the platelet thromboxane A(2) metabolites 11-dehydrothromboxane B(2) and 2,3-dinorthromboxane B(2), as well as the endothelial prostacyclin metabolite 2, 3-dinor-6-ketoprostaglandin F(1)alpha, into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.