Asymmetric anhidrosis in MSA.
Explore the source record for details and available documents.
Denervation↗
Biomedical subjects
H Przuntek
Publications and source records attributed to H Przuntek.
Neurophysiological findings in SPG4 patients differ from other types of spastic paraplegia.
The authors examined 12 families with autosomal dominant hereditary spastic paraplegia for phenotypic characteristics predicting the underlying genotype. They found no clinical differences between patients with or without mutations in the spastin gene (SPG4). Motor evoked potentials and nerve conduction studies were almost normal in those with SPG4. In contrast, non-SPG4 families had prolonged central motor conduction times or marked peripheral neuropathy, or both.
Adenosine Triphosphatases↗
Repeated rating improves value of diagnostic dopaminergic challenge tests in Parkinson's disease.
Clinicians use acute challenges with levodopa (LD) and/or apomorphine (A) for diagnostic dopaminergic response tests in Parkinson's disease (PD) patients. We consecutively compared the value of both drugs with performance of repeated ratings and adverse effect recording. Oral administration of 200 mg LD was superior to subcutaneous injection of 4 mg A in terms of tolerability and onset of temporary UPDRS motor score decline ([previously untreated PD patients] LD: 4.02 [mean] +/- 2.45 [SD] [significant decrease: p = 1.42 E-07] vs. A: 1.58 +/- 3.38 [not significant decrease: p = 0.14], p = 0.0009; [treated PD patients] LD: 7.71 +/- 4.35 [significant decrease: p = 2.48 E-06] vs. A: 5.19 +/- 4.32 [significant decrease: p = 7.83 E-05], p = 0.07). We suggest diagnostic acute challenge test performance with LD as first- and A as second choice due to better tolerability and valuation in combination with repeated scoring procedures to improve sensitivity and specifity.
Administration, Oral↗
Modulation of disease risk according to a cathepsin D / apolipoprotein E genotype in Parkinson's disease.
Aspartyl protease Cathepsin D (CTSD) has been suggested to play a role in the pathogenesis of sporadic Alzheimer's disease (AD) due to interference with protein degradation mechanisms. A C224T (A38V) polymorphism in exon 2 of the CTSD gene is reported to be associated with an increased risk for AD. The partially overlapping pathology between AD and Parkinson's disease (PD) led us to investigate the role of this polymorphism in PD. Using association studies in 457 German PD patients and 340 controls we found no evidence for direct association between the CTSD genotype and PD. However, stratification for the apolipoprotein E (APOE) epsilon4 allele suggests a protective effect of the CTSD T-allele in PD (OR = 0.24, p = 0.002). Our findings suggest interference of CTSD and APOE polymorphisms in the pathogenesis of PD, in the sense of modulating disease risk.
Aged↗
Facial expression recognition in people with medicated and unmedicated Parkinson's disease.
Recognition of facial expressions of emotion was investigated in people with medicated and unmedicated Parkinson's disease (PD) and matched controls (unmedicated PD, n=16; medicated PD, n=20; controls, n=40). Participants in the medicated group showed some visual impairment (impaired contrast sensitivity) and performed less well on perception of unfamiliar face identity, but did not show significant deficits in the perception of sex, gaze direction, or familiar identity from the face. For both Parkinson's disease groups, there was evidence of impaired recognition of facial expressions in comparison to controls. These deficits were more consistently noted in the unmedicated group, who were also found to perform worse than the medicated group at recognising disgust from prototypical facial expressions, and at recognising anger and disgust in computer-manipulated images. Although both Parkinson's disease groups showed impairments of facial expression recognition, the consistently worse recognition of disgust in the unmedicated group is consistent with the hypothesis from previous studies that brain regions modulated by dopaminergic neurons are involved in the recognition of disgust.
Aged↗
Depressed mood and executive dysfunction in early Parkinson's disease.
OBJECTIVES: Studies on neuropsychological functions in early Parkinson's disease (PD) have reported changes with respect to memory and executive control related to dysfunction of fronto-striatal circuitry. The question has been raised, however, whether these findings are at least partly influenced by depression, which as such can also lead to cognitive impairments that depend on the functional integrity of the prefrontal cortex. MATERIAL AND METHODS: In the present investigation early non-depressed PD patients (NPD), early PD patients with mild depressive symptoms (DPD), patients with primary depression (DEP) and healthy controls (HC) completed a range of neuropsychological tests. RESULTS: Group comparisons revealed impairments of DPD patients in comparison with HC with respect to verbal fluency, short-term memory and concept formation. In addition they showed mild working-memory deficits. CONCLUSIONS: In summary the present results indicate that depressed mood in early PD may exacerbate cognitive impairments. Thus careful assessment of affective variables in PD should be an integral part of the treatment of PD.
Depressive Disorder↗
Recanalization of acute symptomatic occlusions of the internal carotid artery.
BACKGROUND: Little is known about the natural course of internal carotid artery (ICA) occlusion and its possible recanalization. The present study was designed to evaluate recanalization rates of extracranial ICA occlusions in acute stroke patients by means of color-coded duplex sonography (CCDS). METHODS: 305 patients with acute ischemia in the territory of the middle cerebral artery were included in this study. All patients had a neurological examination on admission and on discharge and were rated by means of the European Stroke Scale (ESS). Extracranial color-coded duplexsonography, transcranial Doppler sonography and cranial computed tomography were immediately performed after admission and within 7 days. RESULTS: 254 patients showed no sign of hemodynamic relevant stenosis greater than 70% of the ICA. 21 patients had symptomatic high grade ICA stenosis. 20 patients had an acute occlusion and 10 patients an old ICA occlusion as judged by duplex sonographic criteria. Six patients (5 male, 1 female; age range 57 to 77 years) with an acute atherothrombotic or cardioembolic occlusion showed a recanalization of the ICA in the follow-up ultrasonography. Two patients with cardiogenic embolic occlusion of the ICA had the most favorable outcome and these patients showed no residual stenosis. 4 patients who had ultrasound findings consistent with atherosclerosis on follow-up examination (2 high-grade stenosis, 2 with carotid plaques) did not show a notable improvement of their ESS-score. Patients with carotid plaques developed complete MCA infarctions; the other 4 patients had partial anterior circulation infarction on follow-up CT. CONCLUSIONS: The present study showed that recanalization of the occluded ICA in acute stroke patients is more frequent than generally presumed. CCDS should be routinely performed in the follow-up of stroke patients as spontaneous recanalization may influence clinical outcome.
Aged↗
Practical importance of neuroprotection in Parkinson's disease.
Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term clinical neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed.
Amantadine↗
Mutation analysis and association studies of nuclear factor-kappaB1 in sporadic Parkinson's disease patients.
Biochemical and morphological studies revealed that oxidative stress and apoptosis play a role in neurodegeneration in Parkinson's disease (PD). Reactive oxygen species may be directly involved in apoptosis or via upregulation of toxic cytokines, i.e. tumor necrosis factor alpha (TNFalpha). We recently demonstrated that the TNFalpha pathway contributes to the pathogenesis of sporadic PD using a genetic approach. These signalling pathways converge to the transcription factor nuclear factor kappaB (NF-kappaB), which has been found activated in affected neurons in PD. We performed a detailed mutation analysis of the p50 subunit of NF-kappaB (NFKB1 gene) in 96 sporadic PD patients. Previously, positive association was demonstrated in this cohort to chromosome 4q21-23 containing the NFKB1 gene. We identified three base exchanges not affecting the amino acid sequence, which were found at similar frequencies in controls. Our study does not support a genetically definable role of NFKB1 in the pathogenesis of sporadic PD.
Amino Acid Sequence↗
Progress of visual dysfunction in Parkinson's disease.
Studies on progression of Parkinson's disease (PD) mainly focus on the nigrostriatal dopaminergic decline, but not on the visual system. We determined progression of (i) disturbed color vision, assessed with the Farnsworth-Munsell 100 Hue test (FMT) and (ii) intensity of PD in 18 patients. Significant differences occurred between (i) initial FMT error scores and follow-up results 3 years later (P=0.002) and analogously (ii) scored intensity of PD (P=0.002). A relation between computed differences of FMT error scores and rated activities of daily living appeared. Deterioration of color vision progresses in PD.
Color Perception↗
A null mutation within the ciliary neurotrophic factor (CNTF)-gene: implications for susceptibility and disease severity in patients with multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Impaired remyelination and axonal degeneration may account for progressive disability in MS patients. As ciliary neurotrophic factor (CNTF) takes part in myelogenesis, we examined the frequency of a CNTF-null mutation in 349 MS patients with respect to their clinical presentation and in comparison with 434 healthy controls. Similar genotype frequencies for the CNTF mutation were obtained in MS patients (genotype 0101=74.8%, 0102=22.3%, 0202=2.9%) and controls (genotype 0101=71.7%, 0102=26.5%, 0202=1.8%) even after stratification for the HLA-DRB1*15 allele. In addition, there was no significant correlation of CNTF genotypes to age at onset, course or severity of the disease. We therefore conclude, that the requirement for CNTF in myelogenesis or cell survival may be bypassed by a second ligand or redundancy of functional activity of other neurotrophic factors.
Ciliary Neurotrophic Factor↗
Autonomic nervous system function in Huntington's disease.
OBJECTIVE: To investigate whether Huntington's disease (HD) affects autonomic nervous system (ANS) functioning. METHODS: Twenty patients with HD who had positive genetic test results underwent standardised ANS function tests including sympathetic skin responses (SSRs) of the hands and feet, measurements of heart rate variability (HRV), both during five minutes of resting and deep respiration, and an orthostatic blood pressure test. Patients were classified according to the motor subscale of the unified Huntington's disease rating scale (UHDRS; mean (SD) score 26.4 (13.6)) and divided into two subgroups: UHDRS <25 points (early stages, E-HD) and UHDRS > or =25 points (mid stages, M-HD). Autonomic indices were compared with those obtained for a group of well matched healthy controls (n=60). RESULTS: Overall, patients showed lower HRV indices than controls. Multivariate analysis with the independent factor of "group" (controls, E-HD, M-HD) showed a significant group effect on both the high frequency power (F=4.32, p=0.017) and the coefficient of variation (F=4.23, p=0.018), indicating a significant reduction in vagal modulation in the M-HD group. There was a shift in autonomic neurocardiac balance towards sympathetic predominance in the M-HD group compared with controls (F=2.89, p=0.062). Moreover, we found an inverse correlation between the severity of clinical HD symptoms (assessed by the UHDRS) and the modulation of cardiovagal activity (p=0.028). Vagal dysregulation was present in two patients; one of them also showed a pathological blood pressure test and a latency prolongation in the SSRs of the hands. Two other patients had pathologically reduced SSR amplitudes. Only patients of the M-HD group were affected. CONCLUSION: Autonomic dysfunction is present even in the middle stages of HD and affects both the sympathetic and parasympathetic branch of the ANS.
Adult↗
Attentive and preattentive processing in narcolepsy as revealed by event-related potentials (ERPs).
Narcolepsy is a neurological disorder, characterised by excessive daytime sleepiness, sleep attacks, cataplexy and abnormal manifestations of rapid eye movement sleep. Recent studies suggest that neuropsychological impairments in narcolepsy may include memory and attention deficits due to a monoaminergic or cholinergic transmitter dysfunction. To explore the nature of cognitive problems, the P300 and mismatch negativity (MMN) event-related potentials were investigated in narcoleptic patients and matched controls. Narcoleptics showed significantly increased P300 amplitudes relative to controls, especially at frontal recording sites. While control subjects exhibited typically larger MMN over the right than the left hemisphere, in particular at frontal and central electrodes, narcoleptics did not show this asymmetry. These results are interpreted as possible alterations in cognitive preattentive and attentive processing associated with altered functioning of the prefrontal cortex in narcolepsy.
Acoustic Stimulation↗
Evaluation of the gamma-synuclein gene in German Parkinson's disease patients.
Mutations in the alpha-synuclein gene are responsible for an autosomal-dominantly inherited form of Parkinson's disease (PD) and alpha-synuclein was found to be the major component of Lewy bodies in PD. Because of the high homology to alpha-synuclein and the abundance in neuronal tissues, we investigated the gamma-synuclein gene in PD. We analyzed 262 German PD patients and 179 healthy German controls via two polymorphisms in the gamma-synuclein gene. No significant differences in the allelic or genotypic distributions of the investigated polymorphisms were observed between patients and controls. In addition no evidence for an increased risk of combined genotypes of polymorphisms in the gamma-synuclein and the alpha-synuclein gene was found. Therefore, our results do not support a major role of the gamma-synuclein gene in PD.
Aged↗
Familial parkinsonism with synuclein pathology: clinical and PET studies of A30P mutation carriers.
BACKGROUND: The authors identified the second known mutation in the alpha-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one German family with autosomal dominantly inherited parkinsonism (ADP). The authors studied carriers of the A30P mutation to compare the phenotype of this mutation with idiopathic PD (IPD) and to assess nigrostriatal dopaminergic function in symptomatic and preclinical mutation carriers. METHODS: The pedigree of the A30P family spans five generations with five affected individuals. The authors performed detailed neurologic examinations followed by mutation analysis in 11 living individuals. In three mutation carriers, two individuals with definite PD and one person at risk for PD, they used L-[18]F-fluoro-3,4-dihydroxyphenylalanine (F-DOPA), [11]C-raclopride (RAC), and [18]F-fluorodeoxyglucose (FDG) PET to investigate presynaptic dopaminergic function, dopamine D2 receptors, and cerebral energy metabolism. The authors studied the cognitive functions of carriers of the A30P mutation using neuropsychological screening. RESULTS: PET studies revealed striatal presynaptic dopaminergic alterations consistent with sporadic IPD in two affected family members and no evidence for nigrostriatal dopaminergic dysfunction in one presymptomatic mutation carrier. Neuropsychological testing in four mutation carriers provided evidence for cognitive impairment as a frequent and early symptom of the A30P mutation; this is also supported by regional cerebral energy metabolism alterations in the clinically presymptomatic subject. CONCLUSIONS: The phenotype of the A30P mutation in the SNCA gene is similar to that of sporadic IPD, including a high variability of the age at disease onset, ranging from 54 to 76 years. The follow-up of presymptomatic carriers of the A30P mutation may give insight into preclinical disease stages and early manifestations of PD.
Aged↗
Integrity of the blood-cerebrospinal fluid barrier in early Parkinson's disease.
Dysfunction of the blood-cerebrospinal fluid barrier (BCB) has been implicated in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. Therefore, we assayed serum and cerebrospinal fluid (CSF) from 30 parkinsonian patients and 30 controls for concentrations of albumin and IgG. The CSF/serum ratio for albumin (AQ), IgG (GQ), IgG-index as well as determination of oligoclonal bands were used to evaluate BCB function and to quantify humoral immune response within the central nervous system (CNS). Levels of AQ, GQ and IgG-index did not significantly differ in both groups. We found no dysfunction of the blood-CSF barrier or signs of local synthesis of IgG in the central nervous system of parkinsonian patients. Our data do not support the hypothesis of a dysfunctional BCB that contributes to pathophysiological mechanisms underlying PD.
Adult↗
Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease.
OBJECTIVE: To evaluate the efficiency of a combination of trimethoprim and sulfamethoxazole in patients with spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). DESIGN: Placebo-controlled, double-blind crossover trial in 22 patients with genetically confirmed SCA3/MJD. Study phases of 6 months were separated by a washout period of 4 weeks. Dosages were a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim, 80 mg, and sulfamethoxazole, 400 mg, twice daily for 5.5 months. SETTING: Outpatient department of the Neurological Clinic, Ruhr-University, Bochum, Germany. MAIN OUTCOME MEASURES: Ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing. Effects on the visual system were studied using the achromatic Vision Contrast Test System and the Farnsworth-Munsell 100-hue test for color discrimination. Physical and mental health were documented using the Medical Outcomes Study 36-Item Short-Form Health Survey. Subgroup analyses assessed the influence of age, sex, age at onset, duration of the disease, phenotype, and CAG repeat length on test performance. RESULTS: Twenty of 22 patients completed the study. Dropouts were due to a rash (placebo phase) and an attempted suicide in a family conflict. Trimethoprim-sulfamethoxazole therapy had no significant effect in SCA3/MJD patients in the short-term analysis (2 weeks) or in the long-term interval (6 months). CONCLUSIONS: In contrast to previous reports that studied smaller groups of patients, treatment with trimethoprim-sulfamethoxazole did not improve the diverse and complex movement disorders caused by SCA3/MJD. Trimethoprim-sulfamethoxazole had no effect on the visual system and cannot be recommended as a continuous treatment for SCA3/MJD patients.
Adult↗
Multiple sclerosis: modulation of apoptosis susceptibility by glatiramer acetate.
OBJECTIVES: We investigated whether therapy of multiple sclerosis (MS) with glatiramer acetate (GA) involves the modulation of programmed cell death (apoptosis) in disease-relevant T-helper lymphocytes. MATERIAL AND METHODS: Blood was drawn from 15 relapsing-remitting MS patients both before (baseline) as well as 6, 12, and 18 weeks after GA therapy and from 15 healthy controls. Detection of apoptosis was performed in response to in vitro stimulation with GA, myelin basic protein or medium alone. RESULTS: T-helper lymphocytes from untreated MS patients displayed an overall increased apoptosis susceptibility in vitro, compared to controls. During subsequent GA therapy, apoptosis vulnerability of these T cells in MS patients significantly declined under the initial baseline before treatment, and was finally equal in treated patients and controls. GA itself had no direct apoptosis-modulatory properties in vitro. CONCLUSION: Our findings indicate that therapy of multiple sclerosis with glatiramer acetate presumably involves the compensation of altered apoptosis in T-helper lymphocytes.
Adult↗