Biomedical subjects

K Bürk

Publications and source records attributed to K Bürk.

At least 37 records · Page 2Linked to original sources

PubMed2001

Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3.

To identify the prevalence and determinants of restless legs syndrome (RLS) in spinocerebellar ataxia (SCA) we studied 58 patients with a molecular diagnosis of SCA1, SCA2 and SCA3. Data on the symptoms of RLS were collected by a standardized questionnaire, and RLS was diagnosed when patients met the four minimal criteria of the syndrome as recently defined by an international study group. In addition, we studied the relationship between RLS and age, age at ataxia onset, CAG repeat length, and nerve conduction and evoked potentials data. RLS was significantly more frequent in SCA patients than in controls (28% vs. 10%). Age at RLS onset in SCA was 49.0 +/- 10.9 years. There were no significant differences in nerve conduction or evoked potentials between RLS and non-RLS SCA patients. The probability of developing RLS increased with age but not with CAG repeat length or higher age of ataxia onset. The data provide evidence that patients with SCA1, SCA2 and SCA3 are per se more susceptible to RLS than non-affected individuals. The probability of developing RLS is related principally to the period over which the CAG repeat mutation exerts its effect and not to CAG repeat length or age of ataxia onset.

Adult↗

PubMed2001

Sporadic cerebellar ataxia associated with gluten sensitivity.

A total of 104 patients with sporadic cerebellar ataxia were tested for antigliadin and antiendomysium antibodies. Twelve individuals (11.5%) with gluten sensitivity underwent duodenal biopsy and extensive clinical, electrophysiological, neuropsychological, radiological and laboratory investigations including human leucocyte antigen (HLA) typing. Two patients showed typical changes of gluten-sensitive enteropathy with crypt hyperplasia and mucosal flattening. In five patients, the intraepithelial lymphocyte count was elevated. Sporadic ataxia with gluten sensitivity was found to be tightly linked to the HLA DQB1*0201 haplotype (70%). Neurological symptoms were not related to hypovitaminosis or inflammatory CSF changes. The clinical syndrome was dominated by progressive cerebellar ataxia with ataxia of stance and gait (100%), dysarthria (100%) and limb ataxia (97%). Oculomotor abnormalities were gaze-evoked nystagmus (66.7%), spontaneous nystagmus (33.3%), saccade slowing (25%) and upward gaze palsy (16.7%). Extracerebellar features also included deep sensory loss (58.3%), bladder dysfunction (33.3%) and reduced ankle reflexes (33.3%). In accordance with clinical findings, electrophysiological investigations revealed prominent axonal neuropathy with reduced amplitudes (50%) and abnormal evoked potentials (58.3%). On neuropsychological testing, patients presented with moderate verbal memory and executive dysfunction. All patients had evidence of cerebellar atrophy on MRI. We conclude that sporadic ataxia may be associated with positive antibodies against gliadin. Nevertheless, mucosal pathology does not represent an obligatory condition of ataxia with gluten sensitivity. The fact that the disease is strongly associated with the same HLA haplotypes found in coeliac disease not only demonstrates coeliac disease and ataxia with gluten sensitivity to be part of the same disease entity but supports the hypothesis of an immunological pathogenesis of cerebellar degeneration.

Adult↗

PubMed2001

Executive dysfunction in spinocerebellar ataxia type 1.

Fourteen patients with spinocerebellar ataxia 1 (SCA1) and 11 controls with similar mean age and IQ estimates were submitted to a neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory as well as executive functions. Neuropsychological assessment yielded verbal memory and executive dysfunction while tests of visuospatial memory and attention were not significantly impaired in SCA1 as compared to controls. Test performance was neither related to the repeat length, the age of onset nor the disease duration. The profile of cognitive impairment in SCA1 with prominent executive dysfunction corresponds to the concept of "frontal-subcortical" dementia that is likely to be contingent upon disruption of a cerebrocerebellar circuitry that consists of afferent and efferent connections between the prefrontal cortex and the cerebellum.

Adult↗

PubMed2000

Oxidative stress in patients with Friedreich ataxia.

Increased generation of reactive oxygen species may underlie the pathophysiology of Friedreich ataxia (FRDA). The authors measured concentrations of 8-hydroxy-2'-deoxyguanosine (8OH2'dG), a marker of oxidative DNA damage, in urine and of dihydroxybenzoic acid (DHBA), a marker of hydroxyl radical attack, in plasma of 33 patients with FRDA. They found a 2.6-fold increase in normalized urinary 8OH2'dG but no change in plasma DHBA as compared with controls. Oral treatment with 5 mg/kg/day of the antioxidant idebenone for 8 weeks significantly decreased urinary 8OH2'dG concentrations, indicating that 8OH2'dG may be useful in monitoring therapeutic interventions in patients with FRDA.-1721

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Evoked potentials in multiple system atrophy (MSA).

OBJECTIVES: To study the involvement of pyramidal tracts and sensory pathways in multiple system atrophy (MSA). MATERIALS AND METHODS: Evoked potential studies were performed in 45 MSA patients suffering from either MSA of cerebellar type (MSA-C) or MSA of parkinsonian type (MSA-P). RESULTS: Motor evoked potentials were normal in all MSA patients, whereas visual and somatosensory evoked potential abnormalities were found in about 40% of the MSA patients with no significant difference between the cerebellar (MSA-C) and parkinsonian (MSA-P) subgroup. Abnormal latencies of wave III in brainstem auditory evoked potentials were significantly more frequent in MSA-C. CONCLUSIONS: Abnormalities of somatosensory, visual and auditory evoked potentials are frequent findings in MSA, whereas abnormal motor evoked potentials are not a characteristic feature of the disease.

Adult↗

PubMed2000

Nerve conduction studies in multiple system atrophy.

To study the frequency and severity of peripheral neuropathy in multiple system atrophy (MSA), we performed nerve conduction studies in 42 MSA patients suffering from either cerebellar MSA (MSA-C) or parkinsonian MSA (MSA-P). Abnormal nerve conduction was present in 24% of the patients. Abnormalities were significantly more frequent in MSA-P (43%) compared to MSA-C (14%). Motor nerve conduction velocities were reduced in 4% of the MSA-C and in 7% of the MSA-P patients. Abnormal compound muscle action potentials were more frequent in MSA-P (29% versus 7% in MSA-C) pointing to a more pronounced loss of motor axons in this subgroup. Sensory nerve conduction velocities were abnormal in 4% of the MSA-C and 14% of the MSA-P patients, and mean sensory nerve action potentials were normal in all MSA-C and reduced in 7% of the MSA-P patients. The data provide evidence that the peripheral nervous system is differentially affected in MSA-C and MSA-P.

Action Potentials↗

PubMed1999

Spinocerebellar ataxia type 6: evidence for a strong founder effect among German families.

The authors found a strong geographic cluster of spinocerebellar ataxia type 6 (SCA6) families in the Northrhine-Westfalia area, suggesting a founder effect in the German SCA6 population. Genotyping with DNA markers linked to the CACNL1A4 gene on chromosome 19p13 revealed a common haplotype and shared allelic characteristics in the majority of German families. The observed founder effect may be related to the relative meiotic stability of CAG repeats in this type of autosomal dominant cerebellar ataxia.

Alleles↗

PubMed1999

Cerebellar ataxia with glutamic acid decarboxylase autoantibodies.

Degenerative cerebellar ataxia with autoantibodies against glutamic acid decarboxylase (GAD) is a rare disorder and may represent a subset of ataxias previously classified as idiopathic. The authors report a patient with progressive cerebellar ataxia, insulin-dependent diabetes mellitus, and GAD antibodies who responded to i.v. immunoglobulins.

Aged↗

PubMed1999

[New insights in the molecular genetics and pathophysiology of hereditary ataxias].

The hereditary ataxias are a heterogeneous group of inherited neurodegenerative disorders characterised by progressive ataxia that results from degeneration of the cerebellum and its afferent and efferent connections. With respect to the pathogenic mechanisms, the hereditary ataxias may be tentatively divided into three groups: (1) The recessive ataxias are induced by the functional impairment of a protein that is essential for the survival of specific neurons while the autosomal dominant ataxias are either caused by (2) mutations of genes coding for ion channels thus resulting in a channelopathy or by (3) a novel deleterious function of a extended polyglutamine sequence within the proteins encoded by the respective genes.

Adolescent↗

PubMed1999

Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3.

Forty-six patients suffering from autosomal dominant cerebellar ataxia type I (ADCA I) underwent to a genotype-phenotype correlation analysis by molecular genetic assignment to the spinocerebellar ataxia type 1, 2, or 3 (SCA1, SCA2, SCA3) genetic locus and electro-oculography. Oculomotor deficits that are attributed to dysfunction of cerebellar structures occurred in all three mutations without major differences between the groups. Gaze-evoked nystagmus, however, was not found to be associated with SCA2. Square wave jerks were exclusively observed in SCA3. The gain in vestibulo-ocular reflex was significantly impaired in SCA3 and SCA1. In SCA3 the severity of vestibular impairment increased with CAG repeat length. Severe saccade slowing was a highly characteristic feature of SCA2. In SCA3 saccade velocity was normal to mildly reduced while SCA1 fell into an intermediate range. The present data show that each mutation is associated with a distinct syndrome of oculomotor deficits. Reduced saccade velocity and the absence of both square-wave jerks and gaze-evoked nystagmus allow one SCA2 to be distinguished from SCA3 patients in almost all cases. The eye movement disorder of SCA1 patients, however, overlaps with both SCA2 and SCA3.

Adult↗

PubMed1999

Cognitive deficits in spinocerebellar ataxia 2.

This is one of the first studies assessing the pattern of cognitive impairment in spinocerebellar ataxia 2 (SCA2). Cognitive function was studied in 17 patients with genetically confirmed SCA2 and 15 age- and IQ- matched controls using a neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory, as well as executive functions. Twenty-five percent of the SCA2 subjects showed evidence of dementia. Even in non-demented SCA2 subjects, there was evidence of verbal memory and executive dysfunction. Tests of visuospatial memory and attention were not significantly impaired in the non-demented group compared with controls. There was no relationship between test performance and motor disability, repeat length or age of onset, while disease duration was shown to be inversely correlated with two tests reflecting the progression of cognitive deficits during the course of the disease. Intellectual impairment should therefore not be interpreted as a secondary effect of progressive motor disability, but represents an important and independent part of the SCA2 phenotype.

Adult↗

PubMed1999

Age related axonal neuropathy in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD).

To identify determinants of peripheral involvement in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) the influence of CAG repeat length, age of onset, disease duration and age on the results of nerve conduction studies was analysed in 58 patients with SCA3/MJD. Patients with SCA3/MJD showed marked reduction of compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes indicating axonal neuropathy of both motor and sensory fibres. In addition, there was moderate slowing of nerve conduction suggestive of mild peripheral demyelination. Multivariate regression showed that CMAP and SNAP amplitudes decreased with age, but were not affected by CAG repeat length, age of onset, or disease duration. The age related decline of CMAP and SNAP amplitudes in SCA3/MJD was greater than in normal subjects. The data suggest that the degree of peripheral damage in SCA3/MJD does not depend on CAG repeat length, age of onset, or disease duration, but is mainly related to the time period over which the SCA3/MJD mutation exerts its effect.

Adult↗

PubMed1999

Linkage disequilibrium at the SCA2 locus.

Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.

Ataxins↗

PubMed1998

Risk factors for idiopathic cerebellar ataxia of late onset.

In an attempt to identify risk factors for the development of idiopathic cerebellar ataxia (IDCA) we performed a case-control study of 59 IDCA patients. Hypertension and medicine intake were less frequent in IDCA than in neurological controls. Multiple logistic regression yielded an odds ratio (OR) for hypertension of 0.13 (95% confidence interval: 0.00-1.02, P=0.0527) and medicine intake of 0.10 (95% confidence interval: 0.00-0.72, P=0.0157). In contrast, we did not identify an association of IDCA with a number of medical diseases, head trauma, smoking, alcohol intake, rural living and well-water drinking. Some of these factors have been previously shown to be associated with other neurodegenerative diseases. In addition, serum antibody titers against neurotropic viruses were not elevated in IDCA.

Age Factors↗

PubMed1998

A new semiautomated, three-dimensional technique allowing precise quantification of total and regional cerebellar volume using MRI.

A new method was developed to measure total and regional cerebellar volumes using MRI. Previously, the volumes of the cerebellum and its substructure had been studied planimetrically. The new method uses three-dimensional semiautomated volumetry with focus on reliability and performance. The method consists of a manual presegmentation using landmark-adjusted planes followed by region-growing segmentation and calculation of volume. The cerebellum is partitioned into 11 regions defined by planes, which are adjusted for internal cerebellar landmarks (three radial regions inside the vermis that extend into the medial hemisphere (one-fourth of the transverse diameter of the hemisphere); one region in the lateral hemisphere (remaining three-fourths)). Forty-six healthy volunteers were examined and the effects of age, gender, and symmetry were estimated. Shrinkage in the vermis (especially anterior superior compartment) was marked. Age effects diminished laterally and were not observed in the lateral hemisphere. Age effects on the total cerebellar volume were marginal. Effects of gender and symmetry were nonsignificant. Technique and results are discussed and related to methods and findings of others.

Adult↗

PubMed1998

The natural history of degenerative ataxia: a retrospective study in 466 patients.

The aim of the present study was (i) to compare disease progression and survival in different types of degenerative ataxia, and (ii) to identify variables that may modify the rate of disease progression. We included patients suffering from Friedreich's ataxia (FRDA, n = 83), early onset cerebellar ataxia (EOCA, n = 30), autosomal dominant cerebellar ataxia (ADCA) type I (ADCA-I, n = 273), ADCA-III (n = 13) and multiple system atrophy (MSA, n = 67). Molecular genetic testing allowed us to assign 202 ADCA-I patients to one of the following subgroups: spinocerebellar ataxia type I (SCAI, n = 36), SCA2 (n = 56) and SCA3 (n = 110). To assess disease progression we defined the following disease stages: stage 0 = no gait difficulties; stage 1 = disease onset, as defined by onset of gait difficulties; stage 2 = loss of independent gait; stage 3 = confinement to wheelchair; stage 4 = death. Disease progression was most rapid in MSA, intermediate in FRDA, ADCA-I and ADCA-III and slowest in EOCA. The rate of progression was similar in SCA1, SCA2 and SCA3. The CAG repeat length was a significant risk factor for faster progression in SCA2 and SCA3, but not in SCA1. In FRDA, the time until confinement to wheelchair was shorter in patients with earlier disease onset, suggesting that patients with long GAA repeats and early disease onset have a poor prognosis. Female gender increased the risk of becoming dependent on walking aids or a wheelchair, but it did not influence survival in FRDA, SCA3 and MSA. In SCA2, female gender was associated with shortened survival. In MSA, later age of onset increased the risk of rapid progression and death.

Adolescent↗

PubMed1998

Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3.

Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3 (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and basal ganglia nuclei. There was significant atrophy of the cerebellum and brainstem in all three SCA mutations compared with a group of 31 age- and sex-matched controls. Comparison between the SCA groups showed that cerebellar and brainstem atrophy was more severe in SCA2 than in SCA1 and SCA3. Putaminal and caudate volume was reduced only in SCA3, but not in SCA1 and SCA2. A set of three morphological criteria was defined that enabled us to assign all SCA2 and SCA3 patients correctly to the underlying genotype. In contrast, these criteria did not distinguish SCA1 from SCA2 and SCA3. Regression analysis failed to reveal a significant association between CAG repeat length and the volumes of the respective brain structures in any of the SCA mutant types. The present data provide in vivo evidence that SCA2 and SCA3 lead to distinct patterns of brain atrophy, while the atrophy changes in SCA1 overlap with both SCA2 and SCA3.

Adult↗

PubMed1997

Clinical and genetic analysis of three German kindreds with autosomal dominant cerebellar ataxia type I linked to the SCA2 locus.

The detailed clinical, electrophysiological and imaging data of three German autosomal dominant cerebellar ataxia (ADCA) families are reported. Linkage to SCA2 was established using microsatellite markers D12S105, D12S1339(1328), D12S1304(1329) yielding a lod score exceeding +3.0 for the combined data. Analysis of the pedigree data provided evidence of anticipation as observed in other neurodegenerative disorders due to polyglutamine expansion encoded by a CAG repeat. This hypothesis was confirmed by the detection of the SCA2-specific pathological protein using the 1C2 monoclonal antibody which selectively recognizes large polyglutamine expansions and the characterization of a CAG expansion in the patients. Clinically, the families were characterized by progressive ataxia of stance, gait and limbs. Saccade velocity was markedly reduced in SCA2. Further oculomotor findings were gaze palsy, impaired smooth pursuit and reduced optokinetic reflex. Dementia and pyramidal tract signs were rather rare, while peripheral involvement (reduced or absent ankle reflexes, fasciculation-like movements, amyotrophy) was a prominent feature. Electrophysiological investigations provided evidence of sensory neuropathy of the axonal type and degeneration of the posterior columns. Imaging studies demonstrated severe shrinkage of brain-stem structures even in early stages of the disease.

Adult↗