Neighbourhood social participation and women's use of anxiolytic-hypnotic drugs: a multilevel analysis.

STUDY OBJECTIVES: To identify and quantify a hypothesised collective effect of the neighbourhood on individual use of anxiolytic-hypnotic drugs (AHD). To analyse the general impact of neighbourhood social participation on use of AHD, adjusting for individual characteristics. DESIGN: Cross sectional analysis performed by multilevel logistic regression with women at the first level and neighbourhoods at the second level. SETTING: Malmö (250 000 inhabitants), Sweden. PARTICIPANTS: 15 456 women aged 45 to 73, residing in 95 neighbourhoods in Malmö, who took part in the Malmö diet and cancer study (1991-1996). MAIN RESULTS: The prevalence of AHD use was 5.5% in the study sample. Overall, 1.7% of the total individual differences in the propensity for using AHD were explained by the neighbourhood level. This percentage, however, differed between different individuals. Low level of social participation in the neighbourhood was associated with higher probability of AHD use (OR = 3.10 (95% CI 1.51 to 6.41)), independently of individual age, low social participation, low educational level, and living alone. This association was reduced (OR = 2.01 (95% CI 0.97 to 4.14)) after the additional accounting for individual disability pension, low self rated health, stress, and medication for somatic disorders. CONCLUSIONS: The neighbourhood level of social participation seems to affect individual use of AHD, possibly through individual characteristics. However, neighbourhood boundaries play a minor part in understanding individual AHD use in the city of Malmö.

Amplitude-integrated encephalography in pyridoxine-dependent seizures and pyridoxine-responsive seizures.

UNLABELLED: Pyridoxine-dependent seizures are rare in newborn infants, although recent data suggest that the prevalence probably is underestimated. In all newborn infants with recurrent epileptic seizures the general recommendation is to administer pyridoxine and simultaneously record an electroencephalogram (EEG). CONCLUSION: One infant with pyridoxine-responsive seizures and another with pyridoxine-dependent seizures had different electroclinical responses on amplitude-integrated EEG monitoring (aEEG) when pyridoxine was administered.

The N400 component in parents of children with specific language impairment.

Children with specific language impairment (SLI) often have a family history of language disorder. In this study, ERPs in response to a visual semantic priming task were recorded in parents of children with SLI. Despite equal performance, the ERPs displayed differences in language processing: larger N400 amplitudes indicated that the parents, especially the fathers, were less primed by the preceding context. Difference waveforms showed that the fathers of SLI children, contrary to controls, had less differentiated responses to congruent versus incongruent sentences. We propose that the N400 observations may be residual markers of past language deficiencies in the fathers. No differences in the N400 effect were found in the mothers of SLI children.

[Buprenorphine as a new alternative for detoxification of heroin addicts. It causes only mild withdrawal problems, abating quickly]. / Buprenorfin nytt alternativ för avgiftning av heroinister. Ger lindrigare abstinensbesvär, som klingar av snabbare.

Buprenorphine might be an alternative drug to be used in opiate detoxification. Its main advantage is that it carries a low risk for respiratory depression, it gives less euphoria and limited withdrawal effects. In a pilot detoxification project ten heroin addicts were given buprenorphine; seven completed the course. Before detoxification seven patients showed five or more signs on the Himmelsbach scale [6]. After the second day four patients showed no signs, four patients displayed one sign, two patients two signs. Buprenorphine may be a valuable alternative to clonidine, dextropropoxiphene and methadone in the detoxification of opiate addicts.

Mortality in elderly men with low psychosocial coping resources using anxiolytic-hypnotic drugs.

OBJECTIVE: Insufficient coping with stress may lead to increased susceptibility for disease and death. Use of anxiolytic-hypnotic drugs has been suggested as a coping strategy, and some opinions have proposed their use as preventive medication. The aim of this study was to estimate if use of anxiolytic-hypnotic drugs counters the increased mortality observed in individuals lacking other coping strategies such as emotional support and social participation. METHODS: A population based cohort study with 10-year (1982/83-1993) survival analysis was performed in 491 men born in 1914, living in the Swedish city of Malmö. RESULTS: Compared with men with a high level of psychosocial coping resources who did not use anxiolytic-hypnotic drugs, men with a low level of psychosocial coping resources had a higher risk of death irrespective whether they used anxiolytic-hypnotic drugs, RR = 1.7 (95% CI 1.1-2.6) or not RR = 1.8 (95%: 1.3-2.5). CONCLUSION: Anxiolytic-hypnotic drugs do not seem to counter increased mortality in elderly men with low psychosocial coping resources.

Antiepileptic drug-related cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation.

The cognitive complaints reported by children and their parents, as subjectively associated with antiepileptic drug (AED) treatment, were evaluated in seizure-free children before and after drug discontinuation. The aim of the design was to isolate the cognitive side effects of AEDs from other factors, such as the effect of seizures. Our inventory explored the following areas: "alertness," "concentration," "activation/ tiredness," "memory," "drowsiness," "depression," "aggressiveness," and "hyperactivity," using a 5-point Likert scaling procedure. One hundred two eligible patients were selected, each matched with a healthy control and assessed when still on antiepileptic medication. All children were seizure free for at least 1 year. The medication was then discontinued gradually over a 3-month period. Four months after the children were completely medication free, a second assessment was carried out, but only in the 83 children who remained seizure free and in their matched controls. The results of the reports made by the children themselves did not show differences with the matched controls, and only showed improvement after drug discontinuation for complaints about "tiredness." Parents of the children with epilepsy reported significant improvement in all areas related to "alertness and activation" after discontinuation of the drugs. The finding that only a limited number of children have cognitive complaints, both when still on AEDs and after discontinuation, may be in line with the reports that the major factor contributing to quality of life is whether patients are seizure free or still have seizures. All patients in this study were seizure free for a period >1 year, which may have caused the favorable pattern of response in our patient group.

Vagus nerve stimulation in 16 children with refractory epilepsy.

PURPOSE: Vagus nerve stimulation (VNS) has been reported to produce >90% reduction in the number of seizures in children with intractable epilepsy. These encouraging results need confirmation. METHODS: Sixteen children, 10 boys and 6 girls aged 4-19 years, were treated with VNS (Cyberonics, Webster, TX, U.S.A.) for 12-24 months. Seizure frequency, seizure severity, changes in quality of life (QOL: visual analogue scale), and side effects were recorded. Eight children had partial and 8 had generalized seizures; 4 of the latter had Lennox-Gastaut syndrome (LGS). RESULTS: During the tenth to twelfth month of VNS, 6 of 16 children experienced > or =50% reduction in seizure frequency. One girl became seizure-free. Seizure severity showed an average decrease in the score from 15 to 11. After 10 months of treatment, QOL was estimated to have improved > or =50% in 6 of 16 children. Reduction in seizure frequency, decreased seizure severity, and reported improvement in QOL did not entirely coincide. Six children experienced hoarseness, 1 had neck pain, 2 had hypersalivation, 2 experienced tiredness, 2 had aspiration episodes during liquid intake, and 6 had electrical transmission problems; in 4 the problem has been surgically corrected. Five stimulators were turned off due to lack of efficacy. CONCLUSIONS: Six of 16 children with refractory epilepsy treated with VNS improved, with a reduction not only in seizure frequency but also in seizure severity and in QOL.

Adrenoleukodystrophy--unusual CT and MR findings in two siblings. Case reports.

PURPOSE: To describe the unusual appearance of adrenoleukodystrophy (ALD) in MR imaging. MATERIAL AND METHODS: An analysis was made of MR findings, histopathology and clinical course in the cases of two brothers with ALD. RESULTS: The older brother presented with frontal contrast-enhanced lesions, including a cyst. These were initially misinterpreted as a tumour at both radiology and pathology. The correct diagnosis was made after the discovery of very-long-chain fatty acids in the blood. The younger brother presented initially with involvement of various segments of the corticospinal tract. CONCLUSION: It is important that the radiologist be aware of the variants of ALD in MR imaging so as to avoid diagnostic mistakes.

Long-term melatonin treatment in blind children and young adults with circadian sleep-wake disturbances.

Oral melatonin therapy was used to treat-severe circadian sleep-wake disturbances in eight children and young adults in an open study. All patients were functionally blind, six of them because of defects in the anterior visual pathway. All were mentally retarded. Baseline sleep diaries kept by the caregivers before treatment showed non-24-hour sleep-wake syndrome. Diurnal variations in serum and urinary melatonin were examined. Melatonin secretion peak time was delayed in seven patients. Body temperature variation was out of phase relative to sleep and melatonin in five patients, and thus they had signs of internal desynchronisation. Melatonin given in the evening dramatically improved the sleep-wake pattern in all patients. The effect was maintained during long-term therapy for between 1 and 6 years in six patients. One patient fell back into the earlier sleep pattern after 6 to 8 months, and another had increasing sleep disturbance because of reflux oesophagitis, although the improvement regarding the circadian component remained. No side effects have been noted during the therapy. Oral melatonin is promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances.

[Differential diagnosis in epilepsy. Anamnesis is still the most important guide]. / Differentialdiagnostik vid epilepsi. Anamnesen fortfarande viktigast.

Epilepsy is defined by the WHO as "a chronic brain disorder of various aetiologies characterised by recurrent seizures due to excessive discharge of cerebral neurones." There are many other episodic conditions including systemic, neurological and psychiatric disorders, which may be confused with epileptic seizures but are not the result of epileptic neuronal discharge. The principal differential diagnoses in cases of episodic seizures in adults and children are outlined in this review, and the importance of adequate history taking is stressed. Correct interpretation of the history is dependent upon the physician's recognition of the clinical features typical of epileptic seizures. Both the importance and the limitations of electroencephalography (EEG) are discussed. The contribution of EEG in cases where a diagnosis of therapy-resistant epilepsy has been questioned is exemplified in case studies of 42 patients, of whom 43 per cent were found to have psychiatric disease only, 26 per cent to have epilepsy only, 12 per cent to have both epileptic seizures and episodic symptoms of psychiatric origin, and the remaining 19 per cent to have episodic disorders of non-epileptic and non-psychiatric origin. The importance of adequate history taking before making a diagnosis of epilepsy is emphasised, as is the conclusion that an incorrect diagnosis of epilepsy often causes more harm than postponing the diagnosis until it becomes more clear.

Fine mapping of the gene for carbohydrate-deficient glycoprotein syndrome, type I (CDG1): linkage disequilibrium and founder effect in Scandinavian families.

Carbohydrate-deficient glycoprotein syndrome type I (CDG I) is characterized clinically by severe nervous system involvement and biochemically by defects in the carbohydrate residues in a number of serum glycoproteins. The CDG1 gene was recently localized by us to a 13-cM interval in chromosome region 16p13. In this study 44 CDG I families from nine countries were analyzed with available markers in a region ranging from marker D16S495 to D16S497, and haplotype and linkage disequilibrium analyses were performed. One specific haplotype was found to be markedly overrepresented in CDG I patients from a geographically distinct region in Scandinavia, strongly indicating that CDG I families in this region share the same ancestral CDG1 mutation. furthermore, analysis of the extent of the common haplotype in these families indicates that the CDG1 gene is located in the region defined by markers D16S513-AFMa284wd5-D16S768-D16S406-D16S502 . The critical CDG1 region, in strong linkage disequilibrium with markers AFMa284wd5, D16S768, and D16S406, thus constitutes less than 1 Mb of DNA and less than 1 cM in the very distal part of the CDG1 region defined by us previously.

Disorders of the cerebral white matter in children. The spectrum of lesions.

The use of magnetic resonance imaging (MRI) has resulted in the detection of an increasing number of children with an apparently leukodystrophic white matter. Laboratory tests and the clinical presentation, however, often do not correspond to any known entity and the course is sometimes not progressively deteriorating. Such children with white-matter changes and no known diagnosis were the subject of this Swedish multicentre study, in which MRI findings and clinical data from 100 children considered to have white-matter abnormalities were assessed during the period 1992-1995. At re-evaluation of MR images by an established "white-matter group" of neuroradiologists, paediatric neurologists, neurologists and neurochemists, the MRI signal of the white matter was considered normal in eleven children and eleven had mainly a grey matter affection. Of the remaining 78 children with white matter abnormalities, a diagnosis was found in 32, but in 46 children no diagnosis could be established. A progressive downhill course characterised 17, probably representing hitherto undefined types of leukodystrophies. Five children had a relapsing-remitting course, and in 11 it was difficult to establish whether the course was progressive or stationary. The disease was non-progressive in 13. This group of non-leukodystrophic white-matter changes obviously represents maldevelopments of myelin formation, thus dys- or hypomyelination rather than demyelination.

Wakefulness and arousal in neonates born to women with schizophrenia: diminished arousal and its association with neurological deviations.

Arousal at 3-4 days of age was blindly assessed during the course of a standardized neurological examination of offspring born to index women with schizophrenic (n = 20), schizo-affective (n = 12), affective (n = 19) and unspecified functional (n = 4) psychoses, as well as 70 offspring born to control women with no history of psychosis. The offspring of women with schizophrenia was the only index group to differ from controls in showing significantly reduced arousal. Among the offspring of schizophrenics, reduced arousal was associated with neurological abnormality and deviant sensitivity to stimulation but not with obstetric complications. Only a subgroup of schizophrenics' offspring showed these characteristics. Deviations in arousal, neurological status and sensitivity may be part of a more generalized pattern representing a possibly genetically based neurodevelopmental disorder evident within this particular group at heightened risk for schizophrenia.

Low risk of seizure recurrence after early withdrawal of antiepileptic treatment in the neonatal period.

The risk of seizure recurrence within the first year of life was evaluated in infants with neonatal seizures diagnosed with a combination of clinical signs, amplitude-integrated electroencephalogram (EEG) monitoring, and standard EEG. Fifty eight of 283 (4.5%) neonates in tertiary level neonatal intensive care had seizures. The mortality in the infants with neonatal seizures was 36.2%. In 31 surviving infants antiepileptic treatment was discontinued after one to 65 days (median 4.5 days). Three infants received no antiepileptic treatment, two continued with prophylactic antiepileptic treatment. Seizure recurrence was present in only three cases (8.3%)--one infant receiving prophylaxis, one treated for 65 days, and in one infant treated for six days. Owing to the small number of infants with seizure recurrence, no clinical features could be specifically related to an increased risk of subsequent seizures. When administering antiepileptic treatment, one aim was to abolish both clinical and electrographical seizures. Another goal was to minimise the duration of treatment and to keep the treatment as short as possible. It is suggested that treating neonatal seizures in this way may not only reduce the risk of subsequent seizure recurrence, but may also minimise unnecessary non-specific prophylactic treatment for epilepsy.

The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): compiled data from 10 pedigrees.

The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, severely impaired mental and motor development, and extrapyramidal dyskinesia is a distinct system degeneration, previously designated pontocerebellar hypoplasia type 2 (PCH-2). To further characterize its clinical and neuroimaging features, we compiled data from 10 nonrelated pedigrees. Six pedigrees were Dutch, two Swedish, and two German. All 16 patients showed an identical profile of virtually absent developmental milestones, early-onset severe chorea, and microcephaly together with pontocerebellar hypoplasia. Family distribution supports autosomal recessive transmission. The present data support the PCH-2 phenotype as a distinct neurogenetic entity.

Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p, and linkage disequilibrium to microsatellite marker D16S406.

Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as an autosomal recessive trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to localize the gene (CDG1) with linkage techniques. We analyzed individuals from 25 CDG1 pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta max = 0.00) for several markers in this region. In order to further localize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406 indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us. The positions of cytogenetically localized flanking markers suggest that the location of the CDG1 gene is in chromosome region 16p13.3-p13.12.

Withdrawal of antiepileptic medication in children. Correlation of cognitive function and plasma concentration--the multicentre 'Holmfrid' study.

Eighty-three patients with epilepsy and 83 matched controls completed 12 computerized cognitive tests while on antiepileptic drugs and six months later when they had been medication-free for three to four months. All patients had been seizure-free for more than one year and were on monotherapy with carbamazepine (CBZ, n = 56), valproate (VPA, n = 17), or phenytoin (PHT, n = 10). The tests and plasma concentration collection were done at noon. The mean peak plasma concentrations in the CBZ patients were as follows: 31% below 30 mumol/l, 48% between 30 and 42 mumol/l and 21% above 42 mumol/l. No difference in performance could be detected between the groups. One significant correlation between plasma concentration and test results was found. The mean VPA concentration was 625 mumol/l (S.D. 189). A tendency towards a weak negative correlation between test results and plasma concentration was present. The PHT patients' therapeutic range had a mean concentration of 32.0 mumol/l (S.D. 18.5). One significant correlation between a memory test and plasma concentration could be detected. Overall, the patients in the different antiepileptic groups performed less good than the control group and in a few cases the differences were statistically significant when compared either before or after withdrawal. A comparison of the changes after withdrawal showed improvement in the majority of tests, but these changes were also present in the matched control group.