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L Forsgren

Publications and source records attributed to L Forsgren.

At least 37 records · Page 2Linked to original sources
PubMed2000

Melatonin and epileptic seizures in patients with acute intermittent porphyria.

The objective of this study was to assess melatonin production in patients with acute intermittent porphyria (AIP), with and without known epileptic seizures, as a guide to whether melatonin may have anti-convulsive or pro-convulsive effects in AIP. Melatonin concentration in urine, sampled over eight hours on two consecutive nights, was analysed in eight AIP patients with epileptic seizures and in 14 AIP relatives without epilepsy. The AIP patients with epileptic seizures had a significantly lower urinary excretion of melatonin, compared with their AIP relatives without epilepsy, which may indicate that melatonin has a protective effect on seizures.

Adult↗
PubMed1999

[Growing genes cause neurological diseases].

A growing number of hereditary neurodegenerative disorders have been found to be caused by expansion of trinucleotide repeats. A smaller number of diseases such as fragile X syndrome, myotonic dystrophy, and Friedreich's ataxia, have been found to be due to expansions in non-coding DNA. In a large group of diseases, the expansion consists of CAG repeats in the coding region of the gene, producing an expanded polyglutamine sequence in the protein. Nine diseases have so far been identified as belonging to this group: Huntington's disease, spinobulbar muscular atrophy (SBMA), dentatorubral pallidoluysian atrophy (DRPLA), autosomal dominant "pure" spastic paraplegia (ADPSP), and five forms of spinocerebellar ataxia (SCA 1,2,3,6 and 7). Except for SBMA, all of the CAG repeat disorders are characterised by autosomal dominant heredity and anticipation (i.e., earlier onset age and increasing severity in successive generations). The mutated protein causes disease via an as yet unidentified gain-of-function mechanism in specific subsets of neurones. Today, DNA analysis permits the diagnosis of a trinucleotide disease in individual cases.

Anticipation, Genetic↗
PubMed1998

CuZn-superoxide dismutase, extracellular superoxide dismutase, and glutathione peroxidase in blood from individuals homozygous for Asp90Ala CuZu-superoxide dismutase mutation.

The Asp90Ala CuZn-superoxide dismutase mutation is associated with amyotrophic lateral sclerosis (ALS) in both homo- and heterozygous form. We analyzed antioxidant enzymes in blood from 44 individuals homozygous and 114 individuals heterozygous for the Asp90Ala mutation as well as 66 blood relatives carrying the wild-type allele only. Erythrocyte CuZn-superoxide dismutase activity was reduced by 9% in the homozygous individuals, confirming previous findings on a smaller cohort. The specific activity of Asp90Ala mutant CuZn-superoxide dismutase in erythrocytes was equal to that of isolated mutant enzyme and slightly higher than that of isolated wild-type enzyme. There was no evidence for the presence of inactive mutant molecules in erythrocytes, and the lower activity is due to the occurrence of fewer active molecules. There were no significant differences between the groups in plasma extracellular superoxide dismutase content, and the erythrocyte glutathione peroxidase activities were virtually identical. Also, there were no differences in these parameters between homozygous individuals with or without ALS. There was no evidence for any association with ALS of a polymorphic extracellular superoxide dismutase mutation, Arg213Gly. The absence of response of the blood antioxidant enzymes to the Asp90Ala CuZn-superoxide dismutase mutation does not support the theory that the ALS-linked CuZn-superoxide dismutase mutations cause disease by increased oxidant stress.

Alanine↗
PubMed1998

Repeated maximum reciprocal knee movements in patients with minimal overt symptoms after ischaemic stroke: an evaluation of mechanical performance and EMG.

The ability to perform reciprocal knee flexions and knee extensions was investigated in patients with minimal or no overt motor symptoms after stroke. Ten patients and 22 controls performed 10 maximal reciprocal knee extensions and knee flexions without intervening rest period using an isokinetic dynamometer (Cybex II). Peak torque (PT; Nm), signal amplitude (RMS) and mean frequency (fmean) of the electromyography were registered for each extension and flexion separately and as the ratio extension/flexion. The patients exhibited pronounced motor deficit despite no or minimal overt clinical symptoms. The reduced motor capacity in the knee muscles was shown as a decrease in the PT and in a different electromyographic pattern compared with the controls. A bilateral affection was found with the formerly hemiparetic side mostly affected. Repeated reciprocal contractions influenced the motor performance, shown as an increase of the PT ratio in the patients, which was especially pronounced with an increasing number of contractions.

Adult↗
PubMed1998

Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: evidence for a linked protective factor.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase ( SOD1 ), which catalyses the dismutation of the superoxide radical to hydrogen peroxide and oxygen. Experimental evidence suggests mutations act by a toxic gain of function but the mechanism is unknown. There are >60 known SOD1 mutations associated with ALS and all are dominant except for one in exon 4, a D90A substitution which is recessive. D90A pedigrees with dominant inheritance have now been reported and this apparent contradiction needs to be explained. We performed a worldwide haplotype study on 28 D90A pedigrees using six highly polymorphic microsatellite markers. We now show that all 20 recessive families share the same founder (alpha = 0.999), regardless of geographical location, whereas several founders exist for the eight dominant families (alpha = 0.385). This finding confirms that D90A can act in a dominant fashion in keeping with all other SOD1 mutations, but that on one occasion, a new instance of this mutation has been recessive. We propose a tightly linked protective factor which modifies the toxic effect of mutant SOD1 in recessive families.

Amino Acid Substitution↗
PubMed1998

Expanded CAG repeats in Swedish spinocerebellar ataxia type 7 (SCA7) patients: effect of CAG repeat length on the clinical manifestation.

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disorder characterized by degeneration of the cerebellum, brainstem and retina. The gene responsible for SCA7, located on chromosome 3p, recently was cloned and shown to contain a CAG repeat in the coding region of the gene, that is expanded in SCA7 patients of French origin. We examined the SCA7 repeat region in four Swedish SCA7 families as well as in 57 healthy controls. All Swedish SCA7 patients exhibited expanded CAG repeats with a strong negative correlation between repeat size and age of onset. The repeat length in SCA7 patients ranged from 40 to >200 repeats. The largest expansion was observed in a juvenile case with an age of onset of 3 months, and represents the longest polyglutamine stretch ever reported. In patients with 59 repeats or more, visual impairment was the most common initial symptom observed, while ataxia predominates in patients with <59 repeats. Two of the Swedish SCA7 families analysed in this study were shown to be related genealogically. The other two SCA7 families could not be traced back to a common ancestor. All four families shared the same allele on the disease chromosome at a locus closely linked to SCA7, suggesting the possibility of a founder effect in the Swedish population.

Adolescent↗
PubMed1997

[Epidemiology in epilepsy. Epilepsy primarily affects small children and the elderly].

Epilepsy is one of the commonest neurological/disorders, with peak incidences among the elderly and among children in the first year of life. Approximately 60,000 (0.7 per cent) of the Swedish population, 50,000 adults and 10,000 children, have active epilepsy. Stroke is the aetiology most commonly identified. The majority of those with a first-ever unproven seizure suffer no further seizures. Of those who do have further seizures (i.e., who develop epilepsy), 65-85 per cent eventually become free from seizures, and many of them are able to cease antiepileptic medication. Epilepsy is a heterogeneous disorder. The larger proportion of patients who are otherwise healthy, and who respond readily to antiepileptic treatment and manifest no side effects or only mild ones, are characterised by the best prognosis and are able to terminate treatment within 2-5 years without recurrence. At the other extreme is the smaller group of patients with onset of epilepsy very early in life, and characterised by multiple severe neurological defects, severe daily seizures, resistance (more or less) to all available treatment, and high mortality. In many cases of epilepsy, however, severity and prognosis lie somewhere between these two extremes.

Adolescent↗
PubMed1997

A follow-up of an incident case-referent study of febrile convulsions seven years after the onset.

A cohort of 92 children with an initial febrile convulsion (FC), prospectively identified in a community-based study 1985-1987, was compared with a cohort of 185 age- and sex-matched referents from the same study area. The median time of follow-up was 6.7 years (range: 5.7-7.7) and the median age at follow-up was 8.3 years (range 6.5-14). The cases had their first FC at a median age of 18 months (range 5-67 months), their second FC at 24 months (11-108 months) and their third FC at 26 months (13-92 months). FC recurred in 42% of the FC cohort, and 3.8% of the children in the referent cohort experienced FC. Single or recurrent afebrile seizures occurred in 4.3% and epilepsy in 3.3% of the FC cohort, while no afebrile seizures occurred in the referent cohort. The risk of having a sibling with FC was three times (95% confidence interval 1.3-6.2) higher in the FC cohort, while there was no difference between the cohorts in the risk of siblings developing afebrile seizures. There was no difference between the cohorts in the utilization of health services during the follow-up period. Two children in the FC cohort went to a school for the mentally retarded. There was no aetiological relationship between the FC and the mental retardation in these cases. All other children attended normal schools and none needed remedial instruction.

Adolescent↗
PubMed1997

Normal binding and reactivity of copper in mutant superoxide dismutase isolated from amyotrophic lateral sclerosis patients.

In some families with amyotrophic lateral sclerosis (ALS), the disease is linked to mutations in the gene encoding CuZn-superoxide dismutase. The mutant CuZn-superoxide dismutases appear to cause motor neuron degeneration by a toxic property, suggested to be linked to an altered reactivity of the active-site Cu ions. Asp90Ala mutant CuZn-superoxide dismutase was isolated from six patients with ALS, allowing properties of the mutant enzyme synthesized and conditioned in patients with ALS to be examined. The molecular mass of the Asp90Ala mutant CuZn-superoxide dismutase was 45 Da lower than that of the wild-type enzyme, as expected from the amino acid exchange. The mobility after sodium dodecyl sulfate-polyacrylamide gel electrophoresis was markedly increased, however, suggesting altered properties of the polypeptide. The mutant CuZn-superoxide dismutase showed a minimal reduction in stability but did not differ significantly from the wild-type enzyme in enzymic activity, in content and affinity for active-site Cu ions and in the propensity to catalyze formation of hydroxyl radicals. Our findings suggest that the deleterious effect of mutant CuZn-superoxide dismutases on motor neurons in ALS is not related to altered reactivity of active-site Cu ions, resulting in increased oxidant stress. Attention should therefore also be directed at other mechanisms and properties of the mutant polypeptides and their degradation products.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia.

Four-hundred and fifty-one blood samples from Scandinavian patients with motor neuron disease were analysed for mutations in the CuZn-superoxide dismutase gene. Forty-one (9.6%) of the 427 patients with the amyotrophic lateral sclerosis (ALS) form of the disease were found to have a disease-associated mutation, and 14 of these patients were apparently sporadic cases. A mutation was found in 12 of the 51 families with recognized familial ALS. The five different mutations found (Ala4Val, Val14Gly, Asp76Tyr, Asp90Ala, Gly127insTGGG) have different genetic characteristics and are associated with very variable phenotypes spanning from rapidly progressing disease with only lower motor neuron signs to very slowly progressing disease with both the upper and lower motor neuron systems affected. The patients showed different sites of onset, though the progressive bulbar palsy form of the disease appears to be rare among patients with a CuZn-superoxide dismutase mutation. The progression of motor signs and symptoms followed the same basic pattern in patients with different mutations. Extra-motor system symptoms were frequent among patients with a CuZn-superoxide dismutase mutation. The results suggest that patients with mutations in the CuZn-superoxide dismutase gene constitute one disease entity. The Val14Gly and Asp76Tyr mutations have not been reported before, and the latter is the first mutation to be found in exon 3 of the CuZn-superoxide dismutase gene.

Adult↗
PubMed1997

Incidence of epilepsy in rural central Ethiopia.

PURPOSE: To study the incidence of epilepsy in a rural area of Ethiopia. METHODS: A community-based study was performed in a random sample of villages with 61,686 inhabitants in a rural area of central Ethiopia. In a door-to-door survey, all inhabitants in the study area were interviewed about seizures. A standardized protocol was used. All new cases with epilepsy that had occurred since a previous study was made 3.5 years earlier were included. Fifty-three of the subjects were investigated with EEG. RESULTS: One-hundred thirty-nine incident cases were identified, corresponding to an annual incidence of 64 in 100,000 inhabitants [95% confidence interval (CI) 44-84]. The corresponding rate for males was 72 (CI 42-102); for females, it was 57 (CI 31-84). The highest age-specific incidence occurred in the youngest age groups (0-9 years); the next highest was in the group aged 10-19 years. Generalized convulsive seizures occurred in 69%, partial seizures occurred in 20%, and unclassifiable seizures occurred in 11%. Seizures occurred daily in 10% and weekly in another 14%; 33% had monthly seizures. Twenty-two percent had a family history of epilepsy. A history of head trauma was ascertained in 5.7% and was the most common possible etiologic factor identified. Thirteen percent were treated with antiepileptic drugs (AEDs). CONCLUSIONS: The incidence of epilepsy in Ethiopia is high. A high incidence in combination with a prevalence of epilepsy in the study area comparable to that in the rest of the world may be explained by a high degree of spontaneous remission of epilepsy and/or a high mortality due to epilepsy. Despite health education on epilepsy given to the community, a minority of subjects were treated with AEDs, which may reflect the inadequacies of the health services and transportation difficulties faced by the patients.

Adolescent↗
PubMed1997

Autoimmunity and ALS: studies on antibodies to acetylcholinesterase in sera.

The involvement of the immune system in the pathogenesis of amyotrophic lateral sclerosis is controversial. It has been suggested that ALS patients develop specific antibodies against acetylcholinesterase (AChE) and that these antibodies by retrograde axonal transport may be the cause of death of the spinal motor neurons. It has also been argued that these antibodies elicit hemolysis of erythrocytes. However, using recombinant human AChE as antigen in ELISA and Western blot analysis, we have been unable to find any evidence for the existence of specific AChE antibodies in ALS patients.

Acetylcholinesterase↗
PubMed1996

Muscle morphology and mitochondrial investigations of a family with autosomal dominant cerebellar ataxia and retinal degeneration mapped to chromosome 3p12-p21.1.

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders with ataxia and dysarthria as early and dominant signs. In ADCA type II, retinal degeneration causes severe visual impairment. ADCA type II has recently been mapped to chromosome 3p by three independent groups. In the family with ADCA type II studied here, the disease has been mapped to chromosome 3p12-p21.1. Histochemical examination of muscle biopsies in 5 cases showed slight neurogenic atrophy and irregular lobulated appearance or focal decreases of enzyme activity when staining for NADH dehydrogenase, succinic dehydrogenase and cytochrome oxidase. Ragged-red fibres were scarce. Electron microscopic examination showed uneven distribution of mitochondria with large fibre areas devoid of mitochondria and/or large subsarcolemmal accumulations of small rounded mitochondria, and frequent autophagic vacuoles. These vacuoles contained remnants of multiple small rounded organelles, possibly mitochondria, and had a remarkably consistent ultrastructural appearance. Biochemical investigation of mitochondrial function showed reduced activity of complex IV and slightly reduced activity of complex I in the respiratory chain in a severely affected child while no abnormalities were found in his affected uncle.

Adult↗
PubMed1996

Prevalence and characteristics of epilepsy in children in northern Sweden.

Active epilepsy was assessed in all children aged 0-16 years in an area of northern Sweden with about 250,000 inhabitants and around 50,000 children in the age group. One hundred and fifty-five children fulfilled the criteria of active epilepsy giving a prevalence rate of 4.2/1000. The proportion of boys to girls was 1:1.1. This dominance of girls had also been seen in a prospective study of incidence of epilepsy in the same area. Partial seizures were more common than generalized. Among the syndromes benign childhood epilepsy with centrotemporal spikes occurred in 17.4%, absence epilepsy in 6.5% and Lennox-Gastaut syndrome in 5.8%. Children with neurodeficit (ND) more often had generalized epileptic syndromes while the non-ND groups more often had localisation related syndromes. The aetiology was regarded to be remote symptomatic in 42%, idiopathic in 28% and cryptogenic in 30% of the children. Almost all children were on antiepileptic treatment, three quarters of them on monotherapy. Neurodeficit was noted in 42%. The prevalence of epilepsy and mental retardation was 1.7/1000. Relatively few children with neurodeficit had been seizure free during the last year, 43% had more than one seizures per month compared to 19% in the non-ND group.

Adolescent↗