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O Bandmann

Publications and source records attributed to O Bandmann.

At least 19 recordsLinked to original sources
PubMed2002

Steele-Richardson-Olszewski-syndrome: the relation of dopamine D2 receptor binding and subcortical lesions in MRI.

We compared (123)I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) for imaging of striatal dopamine D(2) receptors in vivo, and MRI in 32 patients with the clinical diagnosis of progressive supranuclear palsy (PSP). We found a significant inter-dependence of reduction of specific striatal IBZM binding indicative of striatal degeneration and of the absence of multiple signal hyperintensities in MRI; age had no influence neither on IBZM binding nor on signal hyperintensities. We conclude that the presence of multiple signal hyperintensities should raise doubt on the correct clinical diagnosis.

Aged↗
PubMed2002

Dopa-responsive dystonia -- the story so far.

Dopa-responsive dystonia (DRD) is an eminently treatable condition and its recognition is therefore of crucial importance. In classical cases, the disease manifests in early childhood with walking problems due to dystonia of the lower limbs. The dystonia is frequently accompanied by "parkinsonian" features such as reduced facial expression or slowing of fine finger movements. Biochemically, the disorder is typically characterized by low levels of the neurotransmitter metabolite homovanillic acid and reduced levels of neopterin and tetrahydrobiopterin (BH4) in the cerebrospinal fluid. This is due to heterozygote mutations of the GTP cyclohydrolase I gene, which is the rate-limiting enzyme in the synthesis of BH4. BH4 is an essential co-factor for tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine. Reduced levels of BH4 lead to the dopamine-deficit syndrome DRD because of reduced TH activity. Other genes implicated in the pathogenesis of this disorder are the TH gene itself and the parkin gene. This article summarizes all relevant aspects of DRD including recent advances in the genetics of this disorder and the widening phenotype. Particular emphasis is given to clinically relevant aspects such as diagnostic difficulties and atypical presentations in infancy and early childhood.

Child, Preschool↗
PubMed2000

Detailed genotyping demonstrates association between the slow acetylator genotype for N-acetyltransferase 2 (NAT2) and familial Parkinson's disease.

In a preliminary report we demonstrated an association between the slow acetylator genotype of N-acetyltransferase 2 (NAT2) and familial cases of Parkinson's disease (FPD). Using a considerably more precise NAT2 typing method, which detects all mutant NAT2 alleles with a frequency of >1% in the white population, we have now retyped all the original patients and control subjects to investigate the reliability of our initial findings. The slow acetylator genotype remained considerably more common among FPD (73%) than normal control subjects (NPC, 43%) or the disease (Huntington's disease [HD]) control group (52%) with an odds ratio (OR) of 3.58 (95% confidence interval (CI): 1.96-6.56; p = 0.00003) for FPD versus NPC and an OR of 2.50 (95% CI: 1.37-4.56, p = 0.003) for FPD versus HD. Furthermore, the wild-type allele 4 conferred a protective effect with an OR of 0.39 (95% CI: 0.23-0.64; p = 0.0025) for FPD versus NPC and an OR of 0.50 (95% CI: 0.30-0.85, p = 0.01) for FPD versus HD. The results of this study support an association between the NAT2 slow acetylator genotype and FPD in our population.

Acetylation↗
PubMed1999

Multiple system atrophy.

Multiple system atrophy (MSA) is a degenerative central nervous system disease of unclear origin. Patients affected typically show symptoms attributable to the combined involvement of the extrapyramidal, pyramidal, cerebellar and autonomic nervous systems. At onset patients mostly see a doctor because of extrapyramidal or--more rarely--cerebellar symptoms. Evidence of autonomic nervous system involvement is often not apparent, at least to the neurologist, before the history is taken. In later stages, by contrast, involvement of all of the above systems is clinically detectable.

Humans↗
PubMed1999

Different postural reaction patterns for expected and unexpected perturbations in patients with idiopathic Parkinson's disease and other parkinsonian syndromes.

Different postural reaction patterns after predictable and unpredictable perturbations during free stance were studied in 8 patients with idiopathic Parkinson's disease (iPD), in 4 patients with other parkinsonian syndromes (PS) and in 5 healthy controls. First, the amplitude of leaning maximally backward and forward was measured (condition I). Secondly, the body equilibrium was disturbed by self-paced, predictable, rapid arm elevations (condition II) and by sudden unpredictable toe-down and toe-up rotations of a supporting platform (condition III). Patients with PS particularly had difficulties in regaining body equilibrium after unexpected perturbations. In controls and patients with PS, unpredictable disturbances were better compensated in toe-down than in toe-up direction, whereas the opposite was true for patients with iPD. These results correspond to the fact that patients with PS had a specific leaning-backward impairment and patients with iPD, a leaning-forward impairment. The authors conclude that the differences in postural stability between patients with iPD and PS are caused by different pathophysiological mechanisms. These differences in postural stability could serve as an additional tool for differential diagnosis.

Aged↗
PubMed1999

GTP cyclohydrolase deficiency; intrafamilial variation in clinical phenotype, including levodopa responsiveness.

A family with a dominant form of partial GTP cyclohydrolase deficiency is described. Clinical severity varied from mild involvement with complete responsiveness to levodopa to severe dystonia precluding any voluntary activity including talking, progressive contractures, and only partial responsiveness to levodopa. Although there are several possible reasons for intrafamilial variability, any patient with dystonia, the cause of which is not clearly identified, should receive a trial of levodopa.

Antiparkinson Agents↗
PubMed1999

The tau gene A0 polymorphism in progressive supranuclear palsy and related neurodegenerative diseases.

Progressive supranuclear palsy is characterised pathologically by the deposition of neurofibrillary tangles consisting of tau protein. Patients with the disease have been reported to have a more frequent occurrence of one allele of an intronic polymorphism of the tau gene. Other diseases which may involve tau deposition include frontotemporal dementia and corticobasal degeneration. This polymorphism has been studied in a series of subjects with progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia, idiopathic Parkinson's disease, and normal controls to (1) confirm this association in a large series and (2) to investigate a possible role for this association in other disorders which involve tau deposition. The results confirm the finding of an overrepresentation of the A0 allele and the A0/A0 genotype in patients with progressive supranuclear palsy, in the largest series reported to date. The A0 allele was found in 91% of patients with progressive supranuclear palsy as opposed to 73% of controls (p<0.001) and the A0/A0 genotype was seen in 84% of patients as compared with 53% of controls (p<0.01). There was no significant difference between patients with Parkinson's disease, frontotemporal dementia, or corticobasal degeneration, and controls. The A0 allele may have a direct effect on tau isoform expression in progressive supranuclear palsy or it may be in linkage disequilibrium with an adjacent determinant of tau gene expression. The explanation for this difference between a predisposition factor to progressive supranuclear palsy and the other conditions may lie in the molecular pathology of these diseases.

Alleles↗
PubMed1998

The alpha-synuclein Ala53Thr mutation is not a common cause of familial Parkinson's disease: a study of 230 European cases. European Consortium on Genetic Susceptibility in Parkinson's Disease.

We report the results of a screen of 230 European familial index cases of Parkinson's disease for the recently described Ala53Thr mutation in the alpha-synuclein gene in an autosomal dominant Parkinson's disease kindred. No mutations were found from this broad white population, and we therefore conclude that although of great interest, this mutation is a very rare cause of familial Parkinson's disease.

Adult↗
PubMed1998

Dopa-responsive dystonia: a clinical and molecular genetic study.

We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa-responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH-1 deficiency. A large number of new heterozygote mutations (seven point mutations, two splice site mutations, and one deletion) as well as a new homozygote mutation in the child with atypical phenylketonuria were detected. In addition, two previously described mutations were found in two other cases. We further extended our investigation of GCH-1 to the 5' and 3' regulatory regions and report the first detection of point mutations in the 5' untranslated region. Demethylation of CpG islands does not appear to be an important causative factor for the GCH-1 mutations in DRD. In addition, we have extended the clinical phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing and remitting course, and DRD with onset in the first week of life. None of our DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.

5' Untranslated Regions↗
PubMed1997

Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson's disease.

BACKGROUND: Epidemiological studies have identified positive family history and exposure to environmental toxins as risk factors for Parkinson's disease (PD). An inherited defect of xenobiotic metabolism could result in increased susceptibility to such toxins. We investigated the frequency of functionally relevant polymorphisms in six detoxification enzymes among patients with PD to elucidate the relation between these polymorphisms and the disease. METHODS: We obtained brain-tissue samples from 100 patients with apparently sporadic PD and blood samples from 100 living patients with familial PD. For the control group, we extracted DNA from the tissue of 100 pathologically normal brains. The six enzymes analysed in these three groups were: CYP2D6, CYP2E1, NAD(P)H-menadione reductase, glutathione transferases M1 and T1, and N-acetyltransferase 2. We also investigated N-acetyltransferase 2 in 100 blood samples from patients with genetically proven Huntington's disease. We used PCR-based methods and restriction-enzyme analysis to detect polymorphisms. FINDINGS: The slow acetylator genotype for N-acetyltransferase 2 was more common in the familial PD group (69%) than in all controls (37%). Even after correction for multiple comparisons, this result remained highly significant (p = 0.002) for familial PD compared with normal controls (odds ratio 3.79 [95% CI 2.08-6.90]) and compared with Huntington's disease (2.45 [1.37-4.38], p = 0.004). The slow acetylator frequency for N-acetyltransferase 2 for sporadic PD was between that for Huntington's disease and familial PD. The frequencies of all the other polymorphisms were similar in the two study groups and the normal control group. INTERPRETATION: We found an association between the slow acetylator genotype for N-acetyltransferase 2 and familial PD. Further studies are needed to investigate the biological relevance of these findings, but slow acetylation could lead to impaired ability of patients with familial PD to handle neurotoxic substances.

Acetylation↗
PubMed1997

Mitochondrial DNA polymorphisms in pathologically proven Parkinson's disease.

To date, five single base pair changes of the mitochondrial DNA have been reported to occur either exclusively or with increased frequency in Caucasian patients with Parkinson's disease (PD) and it has been postulated that these mutations might be casually related to the observed inhibition of mitochondrial respiratory chain function in PD. To evaluate these findings, we analysed the frequency of all five polymorphisms in 100 cases of pathologically proven cases of PD. We were either unable to detect the previously described polymorphisms in our series or found them to be present with the same frequency among controls. Our data do not support the hypothesis of an involvement of the mitochondrial DNA in the pathogenesis of PD.

Adult↗
PubMed1997

GTP cyclohydrolase I mutations in patients with dystonia responsive to anticholinergic drugs.

OBJECTIVES: To investigate the hypothesis that GTP cyclohydrolase I (GCH1) mutations are responsible for the phenotype of highly anticholinergic responsive dystonia in patients with apparent primary torsion dystonia. METHODS: From 107 British patients with clinically diagnosed primary torsion dystonia, seven patients were identified with an excellent response to anticholinergic drugs. All six exons of the GCH1 gene were sequenced in these patients to identify mutations. RESULTS: Three novel GCH1 mutations were identified in two patients. One patient was a compound heterozygote with asymptomatic carrier parents. The clinical phenotype of patients with and without GCH1 mutations was similar. CONCLUSIONS: These findings show that a proportion of patients with apparent primary torsion dystonia and a good response to anticholinergic drugs have GCH1 mutations and therefore have a variant of dopa responsive dystonia. The difficulty in distinguishing clinically between patients with and without mutations underscores the importance of considering the diagnosis of a levodopa responsive dystonia in all such patients.

Adult↗
PubMed1997

Multiple-system atrophy is genetically distinct from identified inherited causes of spinocerebellar degeneration.

Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown cause. The only case-control study conducted in MSA patients to date suggested a possible contributory genetic component in the pathogenesis of this disorder. The aim of this study was to evaluate a possible overlap between clinically or pathologically well-defined MSA and other conditions with an identified genetic defect causing spinocerebellar degeneration in humans or mutant mice strains. The spinocerebellar ataxia type 1 and 3 genes (SCA1 and SCA3) were analyzed for a pathologic expansion in 80 patients with MSA to evaluate a possible overlap between MSA and SCA1 or SCA3. Weaver mice and lurcher mice are animal models for spinocerebellar degeneration; both share pathologic features with MSA. We sequenced the H5 pore region of the human homologue of the weaver mouse gene, hiGIRK2, in all our patients. In lurcher mice, previous biochemical studies have shown a decreased intracellular response to insulin-like growth factor 1 (IGF-1) in the cerebellar cortex, and we thus investigated the possibility of an allelic association between MSA and the receptor for IGF-1. In addition, we evaluated a possible involvement of the ciliary neurotrophic factor gene (CNTF) and examined the role of HLA-A32 to clarify the conflicting data from previous studies. No changes were detected in any of the analyzed genes. Our studies strongly suggest that MSA is an autonomous syndrome distinct from identified genetic causes for spinocerebellar degeneration.

Alleles↗