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.

ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG mimic?

BACKGROUND AND PURPOSE: Defects of coenzyme Q10 (CoQ10) metabolism cause a variety of disorders ranging from isolated myopathy to multisystem involvement. ADCK3 is one of several genes associated with CoQ10 deficiency that presents with progressive cerebellar ataxia, epilepsy, migraine and psychiatric disorders. Diagnosis is challenging due to the wide clinical spectrum and overlap with other mitochondrial disorders. METHODS: A detailed description of three new patients and one previously reported patient from three Norwegian families with novel and known ADCK3 mutations is provided focusing on the epileptic semiology and response to treatment. Mutations were identified by whole exome sequencing and in two measurement of skeletal muscle CoQ10 was performed. RESULTS: All four patients presented with childhood-onset epilepsy and progressive cerebellar ataxia. Three patients had epilepsia partialis continua and stroke-like episodes affecting the posterior brain. Electroencephalography showed focal epileptic activity in the occipital and temporal lobes. Genetic investigation revealed ADCK3 mutations in all patients including a novel change in exon 15: c.T1732G, p.F578V. There was no apparent genotype-phenotype correlation. CONCLUSION: ADCK3 mutations can cause a combination of progressive ataxia and acute epileptic encephalopathy with stroke-like episodes. The clinical, radiological and electrophysiological features of this disorder mimic the phenotype of polymerase gamma (POLG) related encephalopathy and it is therefore suggested that ADCK3 mutations be considered in the differential diagnosis of mitochondrial encephalopathy with POLG-like features.

Common imitators of epilepsy.

Many episodic phenomena involving motor, sensory, autonomic, and behavioral functions may imitate epilepsy. The aim of this article is to focus on the various manifestations and the diagnostic and therapeutic challenges of the most common of these disorders, as well as their relationship to emotional aspects. Syncope is caused by reduced global cerebral perfusion. Convulsive movements are sometimes released from subcortical structures, but do not follow the characteristic sequence of tonic-clonic seizures, and postictal symptoms are minimal. Hyperventilation attacks are caused by the metabolic consequences of hypocapnia. Altered blood pH and cerebral vasoconstriction may cause a range of peripheral and central nervous system symptoms. Psychogenic non-epileptic seizures (PNES) are attacks of reduced self-control associated with various behavioral phenomena, usually beyond voluntary control. A detailed clinical history is the most important tool in the differential diagnosis. Various emotional factors may act as immediate triggers in reflex syncope and hyperventilation attacks, whereas in PNES, emotional traumas may be remote and suppressed. Patient education with appropriate explanation of the underlying mechanisms is a fundamental part of the management of these disorders.

Comparison of carbamazepine rash in multiple sclerosis and epilepsy.

OBJECTIVES: Studies on the comorbidity of multiple sclerosis (MS) and allergic disorders have shown conflicting results. Carbamazepine (CBZ) is widely used in MS to control pain. We have compared the incidence of rash from CBZ use in MS and epilepsy. MATERIALS AND METHODS: Consecutive adult patients with MS and epilepsy were studied retrospectively. A detailed survey of medical records concerning CBZ treatment was performed. RESULTS: A total of 495 patients with epilepsy and 442 patients with MS were included. Sixty-five per cent of patients with epilepsy and 20% of patients with MS had used CBZ. In CBZ-exposed patients, rash occurred in 15/89 (17%) in MS and in 43/323 (13%) in epilepsy, a difference which was not significant. Women below 50 years experienced more skin reactions than older women and men. The unadjusted odds ratio (OR) for rash in the MS vs epilepsy group was 1.32 (CI 0.70-2.51, P = 0.40). Adjusting groups for gender and age reduced the OR to 1.11 (CI 0.56-2.19, P = 0.76). CONCLUSION: Compared with epilepsy, which is only rarely caused by immunological mechanisms, the autoimmune disorder MS was not associated with a different occurrence of CBZ skin reactions. The trend towards an increased occurrence of rashes in MS can partly be explained by a higher predisposition to CBZ rash in women of fertile age.

Comorbidity of migraine and epilepsy in a Norwegian community.

BACKGROUND AND PURPOSE: Studies on the comorbidity of migraine and epilepsy have shown conflicting results. We wanted to explore the epidemiological association between migraine and seizure disorders in a population-based material where case ascertainment was enhanced by individual specialist assessments. METHODS: Information concerning migraine and seizure disorders was collected from 1793 participants in an interview-based survey in a circumscribed community. Mixed headache, with features both of migraine without aura and tension-type headache, was excluded from further analyses because of its ambiguous character (n = 137). Thus, data from 1656 participants were included in the study. RESULTS: The number of subjects with epilepsy was small, and a statistically significant association between migraine and the diagnosis of epilepsy was not found. There was a tendency to more active epilepsy in subjects with migraine (1.0%, 5/524), particularly for migraine with aura (1.8%, 3/168), compared with subjects without migraine (0.5%, 6/1132). Migraine was present in five of 11 subjects with active epilepsy (45%) and in four of 28 (14%) with epilepsy in remission (P = 0.09). CONCLUSIONS: An overall association between migraine and seizure disorders could not be demonstrated, but there was a tendency to more migraine in individuals with active epilepsy.

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study.

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR alpha4 or beta2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since alpha4beta2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the alpha4beta2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal.

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.

LGI1: a gene involved in epileptogenesis and glioma progression?

The leucine-rich, glioma inactivated gene 1 (LGI1) gene on human chromosome 10q24 was first identified as a candidate tumor suppressor gene for glioma. Surprisingly, mutations in LGI1 were also shown to cause an idiopathic epilepsy syndrome, autosomal dominant lateral temporal lobe epilepsy (ADLTE). LGI1 is one of the only two currently known non-ion channel genes whose mutations cause idiopathic epilepsy in humans. In this review we summarize the current data on structure and function of the LGI1 protein and discuss clinical aspects of ADLTE and their correlation with LGI1. We also propose that the evidence supporting the tumor suppressor role of LGI1 in malignant gliomas is weak and that further work is necessary to establish LGI1 role in glial cells.

Tyrosinaemia type I--de novo mutation in liver tissue suppressing an inborn splicing defect.

Many patients with tyrosinaemia type 1 have a mosaic pattern of fumarylacetoacetase (FAH) immunopositive or immunonegative nodules in liver tissue. This phenomenon has been explained by a spontaneous reversion of the mutation in one allele to a normal genotype, but only a few nodules have been examined. We now report on a Norwegian patient, compound heterozygous for the mutations IVS12g(+5)-->a and G(1009-->)A, with liver mosaicism, but with an immunopositive nodule in which both primary mutations were intact. In the immunopositive hepatocytes of this nodule, genetic analyses showed a new mutation, C(1061-->)A, 6 bp upstream of the primary mutation IVS12g(+5)-->a in the FAH gene. The splicing defect caused by the primary mutation is most likely suppressed by the new mutation due to improvement of the splicing site. In the same liver we demonstrate another nodule of regenerating immunopositive tissue due to reversion of one of the primary mutations to a normal genotype. Together with the original cells this makes a triple mosaicism of hepatocytes with one, two or three point mutations in the FAH gene.

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.

Visual field defects in patients taking vigabatrin.

PURPOSE: To investigate visual field loss in patients on long-term treatment with the antiepileptic drug vigabatrin, recently reported to cause visual disturbances. METHODS: Eighteen patients taking vigabatrin for 0.5-9.5 years were examined with automated perimetry up to 60 degrees from fixation using the Humphrey Field Analyser. Five patients with epilepsy receiving other medications served as controls. Patients found to have a visual field defect underwent ophthalmologic examination. RESULTS: Among the 18 patients in the vigabatrin group, visual field defects categorised as mild were revealed in 6 right eyes (33%) and 8 left eyes (44.4%), while defects categorised as severe were found in 9 right eyes (50%) and 8 left eyes (44.4%). The majority of the defects (66.7% in the right eye) were peripheral constriction with nasal predominance. The location of the defects was confirmed in 8 patients also tested with Kowa AP340 perimetry. CONCLUSION: According to our results, visual field defects among the patients on vigabatrin therapy may occur more frequently than previously recognised.

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.

Is monochorionic twinning a risk factor for focal cortical dysgenesis?

OBJECTIVES: Various genetic and acquired factors have been proposed as being etiologically important in cortical dysgenesis. It has been suggested that fetal, developmental abnormalities may be induced by transient, circulatory instability in monochorionic twinning due to feto-fetal transfusions. We report the discordant occurrence of a malformation of cortical development in monozygotic, monochorionic twins, and discuss the findings and possible pathogenetic mechanisms. MATERIAL AND METHODS: The twins were females, 30 years of age, one of them suffering from uncontrolled localization-related epilepsy. Neurological deficits or mental retardation were not present. Genetic analysis, brain MRI, and a neuropsychological test battery were carried out. RESULTS: DNA analysis verified monozygocity. MRI showed a unilateral grey matter heterotopion and a contralateral temporal arachnoid cyst in the affected twin. Neuro-psychological assessment revealed no corresponding focal cognitive deficits, but an overall slightly lowered performance in the affected twin. CONCLUSION: Discordant affection of focal, cortical dysgenesis in monozygotic twins creates a particular opportunity to assess the consequences of such a disorder. The fact that only a mild generalized influence on cognitive functioning was demonstrated in this case, is possibly due to the plasticity of the fetal brain. According to current, obstetrical literature, the unique embryology of monochorionic twinning may predispose to vascular events in early fetal life. As ultrasound studies now indicate that a large proportion of pregnancies start out as twin products, we hypothesize that the "vanishing twin" syndrome and its potential hemodynamic hazard to the surviving fetus may be an etiological factor in malformations of cortical development, even in singletons.

Independent occurrence of the CHRNA4 Ser248Phe mutation in a Norwegian family with nocturnal frontal lobe epilepsy.

PURPOSE: To describe the clinical features of a family from Northern Norway in which autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is associated with a Ser248Phe amino acid exchange in the second transmembrane domain of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4). We also tested for evidence of a de novo mutation or founder effect by comparing haplotypes with the original Australian family where the Ser248Phe mutation was first described. METHODS: Clinical details were obtained from 19 family members. Personal interviews and genetic analysis were carried out in 17. Parts of the coding region of CHRNA4 were sequenced, and two known polymorphisms (bp555/FokI, bp594/CfoI) were typed by restriction analysis. RESULTS: Eleven individuals had ADNFLE. The haplotypes of the mutation-carrying alleles of affected individuals from the Northern Norwegian and the Australian ADNFLE family are different. The phenotypic expressions are remarkably similar. CONCLUSIONS: The Ser248Phe mutation occurred independently in both families. Given the rarity of the disease, this suggests that not only the position of a mutation in the coding sequence but also the type of an amino acid exchange is important for the etiology of ADNFLE. The phenotypic similarity of these two families with different genetic backgrounds suggests that the Ser248Phe mutation largely determines the phenotype, with relatively little influence of other background genes.

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.

Familial mydriasis, cardiac arrhythmia, respiratory failure, muscular weakness and hypohidrosis.

OBJECTIVES: To describe a family with some sort of progressive autonomic failure in one generation (2 affected of a sibship of 7 sisters). The main features were: mydriasis, cardiac arrhythmia, cardiomegaly, hypohidrosis, respiratory failure, and muscular weakness. METHODS: Pupillometry, evaporimetry, and isokinetic power measurements were carried out. RESULTS: The autonomic dysfunction pattern (mainly cardiac abnormalities, mydriasis) seems to differ somewhat from that of progressive autonomic failure (Shy-Drager syndrome). "Lewy body-like" inclusions were present, in particular in substantia nigra, but also in locus ceruleus and raphe nuclei (cell loss only in locus ceruleus). There were no oligodendroglial, cytoplasmatic inclusions, apparently a marker in multiple system atrophy. Proper Lewy bodies were also present. Differences seemed to prevail vs the Shy-Drager syndrome. Various traits: muscular weakness pattern (e.g. preferential peroneal distribution), minor elbow contractures, and arrhythmia were reminiscent of Emery-Dreifuss muscle dystrophy (E-D). Distinguishing features included: hereditary pattern, mydriasis, and hypohidrosis. CONCLUSION: Conceivably, this disorder is close to, but still not identical with E-D.

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.

Applications of neural network analyses to in vivo 1H magnetic resonance spectroscopy of epilepsy patients.

A total of 67 in vivo water-suppressed proton magnetic resonance spectra of the temporal lobes were recorded from 15 patients with long standing temporal lobe epilepsy and 13 healthy volunteers. Conventional data analysis indicated slightly lower N-acetyl aspartate levels in epileptic patients compared with controls. For further analysis of data, a spectral region (4.0-1.5 ppm) was used as input for artificial neural network analysis. Correct classification of spectra was obtained in 66 out of 67 cases, disregarding from which side of the brain the spectra were recorded. The ability of the trained network to recognize spectra recorded both contalaterally and ipsilaterally to the epileptic focus strongly indicates bilateral metabolic changes. Artificial neural networks could also be trained to recognize whether the spectra were recorded from the ipsilateral or contralateral side of the epileptic focus, indicating that neural network analysis of in vivo proton MR spectra can be used as an additional tool for pre-surgical lateralization of seizure foci.