Biomedical subjects

Peter H Kraus

Publications and source records attributed to Peter H Kraus.

11 recordsLinked to original sources

PubMed2006

No association between polymorphisms in the BDNF gene and age at onset in Huntington disease.

BACKGROUND: Recent evidence suggests that brain-derived neurotrophic factor (BDNF) is an attractive candidate for modifying age at onset (AO) in Huntington disease (HD). In particular, the functional Val66Met polymorphism appeared to exert a significant effect. Here we evaluate BDNF variability with respect to AO of HD using markers that represent the entire locus. METHODS: Five selected tagging polymorphisms were genotyped across a 65 kb region comprising the BDNF gene in a well established cohort of 250 unrelated German HD patients. RESULTS: Addition of BDNF genotype variations or one of the marker haplotypes to the effect of CAG repeat lengths did not affect the variance of the AO. CONCLUSION: We were unable to verify a recently reported association between the functional Val66Met polymorphism in the BDNF gene and AO in HD. From our findings, we conclude that neither sequence variations in nor near the gene contribute significantly to the variance of AO.

Adult↗

PubMed2006

Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series.

BACKGROUND: Chorea in Huntington's Disease (HD) is usually treated with antidopaminergic neuroleptics like haloperidol, olanzapine and tiaprid or dopamine depleting drugs like tetrabenazine. Some patients with hyperkinesia, however, react to treatment with antidopaminergic drugs by developing extrapyramidal side effects. In earlier studies valproic acid showed no beneficial effect on involuntary choreatic movements. Myoclonus is rare in HD and is often overseen or misdiagnosed as chorea. METHODS: In this report, we present eight patients whose main symptom is myoclonic hyperkinesia. All patients were treated with valproic acid and scored by using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before and after treatment. In addition to this, two patients agreed to be videotaped. RESULTS: In seven patients myoclonus and, therefore the UHDRS motor score improved in a dose dependent manner. In three of these patients antidopaminergic medication could be reduced. CONCLUSION: In the rare subgroup of HD patients suffering from myoclonic hyperkinesia, valproic acid is a possible alternative treatment.

Adult↗

PubMed2005

Age at onset of Huntington disease is not modulated by the R72P variation in TP53 and the R196K variation in the gene coding for the human caspase activated DNase (hCAD).

BACKGROUND: TP53 is an attractive candidate for modifying age of onset (AO) in Huntington disease (HD): The amino-terminus of the mutated huntingtin (htt) exon 1 translation product has functional properties which may affect critically the TP53 pathway in HD neurons. The pathogenic domain of mutant htt interacts with nuclear transcription factors, and it potentially modulates TP53-induced transcriptional events. A single nucleotide polymorphism (SNP) resulting in the R72P exchange in TP53 protein might modulate the variation in AO. In addition, also the R196K replacement in human caspase activated DNase (hCAD) may theoretically affect the AO. METHODS: We have genotyped the polymorphisms R72P and R196K in a well established cohort of 167 unrelated HD patients. RESULTS: The expanded CAG repeat explained 30.8% of the variance in AO. Adding the genotypes of the SNPs investigated did not affect the variance of the AO variance explained. CONCLUSION: In this replication study, no association was found explaining a significant amount of the variability in AO of HD thus contradicting a recent report.

Age of Onset↗

PubMed2005

Analysis of the course of Parkinson's disease under dopaminergic therapy: performance of "fast tapping" is not a suitable parameter.

In addition to clinical rating scales, instrumental methods are employed frequently for assessment of performance or motor deficits in Parkinson's disease (PD). Many studies have analyzed such parameters in cross-sectional studies. We employed a battery of tests to investigate fine motor performance over a period of 4 years in 411 de novo parkinsonian patients from the Prado study. Specifically, tapping and pegboard testing ("plugging") were evaluated and performance on these tests compared with clinical ratings. Plugging scores correlated well with tapping scores and clinical rating at each assessment timepoint. Both tests also showed significant differences to healthy controls. Nevertheless "fast tapping" was found to be less impaired than was plugging in de novo patients. Over time, it was observed that plugging scores, but not tapping scores, exhibited changes that paralleled movements in clinical score. Plugging scores exhibited a marked response to dopaminergic therapy whereas fast tapping showed no therapeutic response. Fast tapping is certainly not suitable for assessment of bradykinesia or hypokinesia, and does not respond to dopaminergic therapy.

Bromocriptine↗

PubMed2005

Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease.

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT-15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age- and gender-matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD.

Adenosine Triphosphate↗

PubMed2005

[Amisulpride in Huntington's disease].

OBJECTIVES: Amisulpride is a substituted benzamide derivative with atypical antipsychotic properties and low side effects. METHOD: We report four cases of patients with clinically and genetically established Huntington's disease and signs of psychosis who were treated with Amisulpride. RESULTS: Two patients developed extrapyramidal side effects due to the treatment. The antipsychotic therapy of all patients was effective. DISCUSSION: Due to degeneration of striatal neurons patients suffering from Huntington's disease react early with development of extrapyramidal side effects after therapy with amisulpride.

Aged↗

PubMed2005

Anhedonia, depression, and motor functioning in Parkinson's disease during treatment with pramipexole.

Anhedonia, a core symptom of depression, correlates with motor alterations in major depressive disorder and has been assumed to be frequent in depressed patients with Parkinson's disease (PD). In the present study, the authors assessed for the first time frequency of anhedonia in patients with idiopathic Parkinson's disease (N = 657) and the relationship of anhedonia and parkinsonian motor deficits during treatment with pramipexole. Mild depression was present in 47% of the patients and moderate to severe depression in 22%. Anhedonic individuals included 45.7% of all patients and 79.7% of depressed Parkinson's disease patients. Anhedonic Parkinson's disease patients had greater motor deficits, restrictions in activities of daily living, and depression compared to nonanhedonic patients. Frequency of anhedonia and depression was significantly reduced during treatment with pramipexole. Future studies should further investigate antianhedonic efficacy of dopamine agonists including pramipexole in depressed patients with Parkinson's disease.

Activities of Daily Living↗

PubMed2004

NR2A and NR2B receptor gene variations modify age at onset in Huntington disease.

N -Methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity has been proposed to play a role in the pathogenesis of Huntington disease (HD), an autosomal dominantly inherited disorder associated with defined expansions in a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of CAG repeat units is highly predictive for the age at onset (AO) in HD. However, AO is only modestly correlated with repeat length when the HD expansion range is in the high 30s or low 40s. Therefore, we investigated whether the genes for the different subunits composing the multimeric complexes of NMDA receptors (GRIN glutamate receptor, ionotropic, N-methyl-d-aspartate) represent candidates for modulating the AO of HD. In the studied cohort of 167 HD patients, the repeat range from 41 to 45 CAG units accounted for 30.8% of the variance in AO; 12.3% additional variance could be attributed to GRIN2B genotype variation and 4.5% to GRIN2A genotype variation. We conclude that these two genes, coding for NR2B and NR2A subtypes mainly expressed in the striatum, may influence the variability in AO of HD. Neuroprotective strategies for HD patients and persons at risk should be reconsidered in the light of these findings.

Adult↗

PubMed2004

Hyperhomocysteinaemia in treated patients with Huntington's disease homocysteine in HD.

Significantly increased plasma total homocysteine levels (t-Hcys) appeared in treated Huntington disease (HD) patients compared to controls and untreated HD subjects. Because the protein Huntingtin interacts with the homocysteine metabolism modulating enzyme cystathionine beta-synthase, we hypothesize that homocysteine promotes neurodegeneration in HD.

Adult↗

PubMed2003

Pramipexole in routine clinical practice: a prospective observational trial in Parkinson's disease.

OBJECTIVE: The mixed dopamine D2/D3 receptor agonist pramipexole is effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease. Clinical trials suggest that the benefits of pramipexole may extend beyond the relief of motor symptoms (akinesia, rigidity and tremor at rest) to amelioration of depressive symptoms in Parkinson's disease. The aim of this study was to confirm the beneficial effects of pramipexole on the core symptoms of Parkinson's disease (with a focus on tremor), as well as to assess its antidepressant activity, during routine clinical practice. The study also aimed to demonstrate the practicability of the Snaith-Hamilton Pleasure Scale (SHAPS-D), the Tremor Impact Scale (TIS) and the Short Parkinson's Evaluation Scale (SPES) under conditions of routine clinical practice. STUDY DESIGN: This was a prospective observational study. PATIENTS: Data for 657 outpatients with Parkinson's disease were collected from German hospitals and specialist practices. The majority of patients were in Hoehn & Yahr stage II or III and were receiving levodopa. METHODS: Pramipexole (Sifrol) was initiated at a dosage of 0.375 mg/day (using a three-times-daily schedule) and titrated upwards, as required, at weekly intervals over a 4-week period to a maximum dosage of 4.5 mg/day (three times daily). Clinical evaluation was performed at baseline, at the end of the titration phase and at the end of maintenance therapy. Patients were assessed via the German questionnaire versions of the physician-assessed SPES, the self-evaluated TIS and the SHAPS-D. Changes in scale scores were evaluated nonparametrically, using the Wilcoxon-matched pairs test. Cronbach's alpha was used as a measure for item consistency. RESULTS: Pramipexole significantly improved SPES subscores for motor symptoms, complications of therapy, psychological status and activities of daily living. Pramipexole also reduced the detrimental effect of tremor on activities of daily living and social interactions, as assessed by patients via the TIS. As indicated by the results of the SHAPS-D questionnaire, pramipexole significantly reduced anhedonia in patients who had associated depression. Internal consistency of SPES subscales was found to be unaltered between the initial evaluation and follow-up. Likewise, internal consistency for TIS and SHAPS-D was demonstrated. Pramipexole was well tolerated and accepted by the vast majority of physicians and patients. CONCLUSION: In addition to ameliorating the core symptoms of akinesia and rigidity in Parkinson's disease, pramipexole improves tremor and depressive symptoms in routine clinical practice. The SPES, TIS and SHAPS-D were found to be useful instruments with validity in this study.

Activities of Daily Living↗

PubMedDate not supplied

Activity-based diary for Parkinson's disease.

The objective of this study was to develop a Parkinson's disease diary that evaluates a patient's difficulties in performing activities as a substitute for the amount of "on"- and "off"-time and to assess its clinimetric qualities. In this study, 84 patients with Parkinson's disease kept a diary for 2 or 3 periods of 5 days. Daily, five items were recorded across 11 time periods. Patients simultaneously recorded "on-off" in the traditional way. The diary was easily understood, and median recording time was 5-10 minutes a day. Clinimetric analysis showed that the diary could be reduced successfully to 3 days, in which five items (walking, transfers, manual activities, dyskinesias, and sleep) with four response options (no, slight, moderate, and severe difficulty) were assessed seven times daily. Sumscores of the first three items accurately predicted being "on" or "off" in 93% of the cases, making separate scoring of "on" and "off" unnecessary. The diary was internally consistent and showed good reproducibility. Construct validity with external measures was adequate, and comparisons between patients grouped by disease severity and by degree of fluctuations revealed significant differences in the expected directions. Taken together, this Parkinson's disease diary has a sound clinimetric basis, provides information on the extent of perceived disability, and thereby accurately reflects the severity of "off"-periods and the variability of motor fluctuations.

Activities of Daily Living↗