[Treatment with antiepileptic agents in patients with mental retardation and multiple handicaps].
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Anticonvulsants↗
Biomedical subjects
E Brodtkorb
Publications and source records attributed to E Brodtkorb.
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.
Adult↗
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.
Adult↗
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.
Adult↗
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.
Adult↗
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.
Adolescent↗
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.
Adult↗
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.
Adult↗
Rectal diazepam: pitfalls of excessive use in refractory epilepsy.
INTRODUCTION: The rectal administration of diazepam (DZP) has provided a safer existence to many epilepsy patients and their carers, when prolonged or serial seizures are present. However, in patients with frequent seizures, chronic, intermittent over-administration may occur, particularly in the presence of multihandicaps. METHODS: Six patients who experienced untoward effects from excessive rectal DZP are reported. In two patients, serial plasma levels of DZP and its active metabolites were monitored. RESULTS: Three patients exhibited a pattern of cyclic reappearance of seizures, interrupted by rectal DZP, followed by sedation and gradual awakening. The intervals were approximately 4 days. The three other patients had variable and complex symptoms with serial seizures and alternating states of tension, apathy, and sleepiness. The plasma levels of DZP and desmethyl-DZP showed rapid fluctuations. CONCLUSION: When rectal DZP is prescribed, chronic and excessive administration should be avoided. Fluctuating plasma-levels may probably support a cyclic reappearance of seizures in some patients. The combination of high bolus doses and a rapid drug clearance due to enzyme inducing co-medication may probably increase the risk for rebound reactions. Toxic, withdrawal, and epileptic symptoms may be intermingled and difficult to manage. A replacement strategy in the form of a prophylactic, oral, low dose benzodiaepine regimen may facilitate the discontinuation of this prescription pattern. Adequate counselling and medically appropriate, written directions for the use of rectal DZP is mandatory.
Administration, Rectal↗
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.
Adolescent↗
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.
Adolescent↗
Antiepileptic drug treatment: clinical considerations and concerns.
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Anticonvulsants↗
Focal, continuous spikes suggest cortical developmental abnormalities. Clinical, MRI and neuropathological correlates.
OBJECTIVES: Widespread use of MRI now gives us increased insights into the different expressions of malformations of cortical development (MCD). The heterogeneity of these disorders are reflected by their varied clinical and neuroimaging features. Characteristic and intense scalp EEG abnormalities have been described in some patients. MATERIAL AND METHODS: We report the MRI and clinical findings of 3 adult patients (age 32-36) with a peculiar EEG pattern of distinct, localized, fast, continuous spiking. These patients represent all patients with such EEG findings that have been recognized by the first author during 9 years. RESULTS: MRI showed MCDs in all, respectively hemimegalencephaly, a subcortical heterotopion, and a focal cortical dysgenesis. The EEG findings had been stable since childhood and were posteriorly located. Two patients had fairly well controlled epilepsy in adult age. The third patient was incapacitated by persistent seizures and was treated with surgery. Histologically cortical dysplasia with neuronal clusters was found in this patient. Variable degrees of cognitive dysfunction were present in all. CONCLUSION: Focal, continuous, fast spiking is an unusual scalp EEG pattern. It is not an inevitable sign of severe epilepsy. It may suggest an MCD. It is not yet clear to what extent such findings are predictive of a dysgenetic etiology of epilepsy.
Action Potentials↗
[Organization of epilepsy care for people with mental retardation. A situational analysis after the care reform].
The special care services for the mentally retarded in Norway were closed down by law on 1 January 1991. This implied the termination of centralized care, and integration of these individuals into the local communities. To map the epilepsy service facilities for mentally retarded patients after the care reform, questionnaires were sent to all officially responsible community physicians and to all Departments of Neurology at Norwegian hospitals. 20% of the community physicians expressed the view that mentally retarded patients did not receive adequate specialist service for their epilepsy. There were wide variations within the country. 37% of the responders stated that the community care was inadequately equipped to attend to the special needs of these patients. Firstly, there seems to be a lack of professionals able to transfer their competence concerning epilepsy. Many of the neurological departments felt that the number of referrals of patients with epilepsy and mental retardation had increased since the care reform. 50% of the responders had no opinion about whether the quality of the epilepsy service was not the same for the mentally retarded as for other patients. Many did not realize the need for special measures to provide adequate medical follow-up of this group. It is concluded that education and guidance to personnel and carers should receive high priority in the further development of a comprehensive epilepsy service. The development of multiprofessional epilepsy units at all university hospitals should be facilitated, and the appointment of specially assigned epilepsy nurses at all neurological departments is recommended.
Community Mental Health Services↗
[Treatment with antiepileptics of mentally retarded patients. Experiences from the 1980s a challenge in the 1990s].
Epilepsy is the most frequent additional handicap in mentally retarded persons. Brain injury and mental retardation may predispose to side effects of antiepileptic drugs (AEDs) on the central nervous system. 63 institutionalized mentally retarded patients were treated for epilepsy in the 1980s. AED treatment was carefully monitored, aiming at the lowest effective dose and an optimal balance between seizure control and adverse effects. In 15 patients, AEDs could be withdrawn. Drugs with less cognitive side effects, such as carbamazepine and valproate, were preferred to longer established drugs, such as phenobarbital and phenytoin. A pronounced decrease in the frequency of seizures was achieved during the study. Based on the calculated Defined Daily Doses, the prescription of AEDs was reduced by 18%. Phenobarbital constituted 39% of the AED consumption at the beginning and 7% at the end of the study. The corresponding figures for phenytoin were 20 and 16%. The fraction of carbamazepine increased from 31 to 44% and that of valproate from 6 to 32%. Less sedative side effects were reported. Several factors other than AEDs may have modified control of seizure in this long term study. These issues are discussed. After the reform of the system of care for the mentally retarded in Norway, it is a challenge to the health authorities to provide an adequate comprehensive epilepsy service to this group of patients.
Adolescent↗
The revised classification of non-convulsive status epilepticus.
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Diagnosis, Differential↗
Juvenile myoclonic epilepsy and human leukocyte antigens.
The idiopathic generalized epilepsies (IGE) occur with a high aggregation within families. Juvenile myoclonic epilepsy (JME) is recognized as a commonly occurring form of idiopathic generalized epilepsy. A possible association between JME and HLA antigens was investigated by serological typing of human leukocyte antigens (HLA) class I antigens and by DNA oligotyping of class II antigens. Twenty-four patients and 129 controls, all Caucasians of Scandinavian descent, were tested. Uncorrected there was a significant positive association (Relative risk (RR) = 8.07) to B17 and a significant negative association (RR = 0.13) to B8 as well as DRB1*3. The negative association to DQ alleles DQA1*0501 and DQB1*0201, which are in strong linkage disequilibrium with the alleles B8 and DRB1*3, was weaker and not significant, thus giving no clue as to a primary HLA-DQ association of JME.
Adolescent↗
Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase.
Hereditary tyrosinemia type 1, due to a deficiency of fumarylacetoacetase (FAH), is characterized by progressive liver damage and renal tubular dysfunction and may occur in an acute or a chronic form. An Ala 134 to Asp (GCT to GAT) transition was found in one Turkish and two Norwegian patients with chronic tyrosinemia. SphI digestion of polymerase chain reaction (PCR) amplified genomic DNA identified the mutation and showed that the patients were heterozygous. All these patients had immunoreactive FAH protein in fibroblasts. Another Norwegian patient with chronic disease, without FAH immunoreactive material in fibroblasts, had a Pro 342 to Leu mutation (CCG to CTG). This mutation was identified by MspI digestion of PCR amplified genomic DNA, and the patient was heterozygous. Northern blotting showed FAH mRNA of normal size and amounts in all patients. Site directed mutagenesis and translation in a rabbit reticulocyte lysate demonstrated that both mutations abolished FAH activity.
Amino Acid Metabolism, Inborn Errors↗