The cold hand sign in multiple system atrophy: skin perfusion revisited.

The cold hand sign (CHS) is a distinct feature of multiple system atrophy (MSA), but its pathophysiology is poorly understood. We, therefore, conducted a study to examine the skin temperature and the skin blood flow at rest and after local heating in 6 age-matched MSA patients with CHS (MSA + CHS), 18 MSA patients without CHS (MSA - CHS) and 13 patients with idiopathic Parkinson's disease (PD). Basal skin temperature and blood flow were significantly lower in MSA + CHS patients than in MSA - CHS or PD patients. Local heating induced a greater response in terms of amplitude in MSA + CHS compared to MSA - CHS and PD. Considering kinetics, skin blood flow increment per 1 degrees C was higher in MSA + CHS than MSA - CHS but was similar when compared to PD patients. Skin blood flow rate (change per second) did not differ among the groups. Our findings suggest that despite impaired basal skin perfusion, the skin vasomotor response to local heating is intact in MSA + CHS but disturbed in MSA - CHS. By measuring skin temperature and blood flow, the presence of CHS can be diagnosed in MSA patients. Further studies are necessary to understand regulation of skin perfusion in patients with extrapyramidal disease.

Valsalva manoeuvre in patients with different Parkinsonian disorders.

The valsalva manoeuvre (VM), used as an autonomic function test, can detect sympathetic and/or parasympathetic autonomic dysfunction. This study investigated the value of VM in patients with different Parkinsonian syndromes (PS). We continuously recorded blood pressure, ECG and respiration among 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson's disease (PD) and in 27 healthy subjects matched in age and sex (Con). VM was performed in addition to metronomic breathing and tilt-table testing. VM could not be analysed in 26% of the ES patients. Valsalva ratio (VR), as a parameter of cardiovagal function, was pathologically decreased in all patient groups. Valsalva ratio (VR) was not able to discriminate parasympathetic dysfunction between patients and controls as well as E/I ratio of metronomic breathing. As a parameter of sympathetic dysfunction during VM, the physiological increase of blood pressure was more often missing during phase IV than phase II especially in PD and MSA patients. Correlation with orthostatic hypotension during tilt-table testing was only moderate. Although VM can demonstrate sympathetic and parasympathetic autonomic dysfunction, we cannot recommend VM as a first line autonomic test in PS patients. Metronomic breathing and tilt-table test seem more capable as parasympathetic resp. and sympathetic function tests to identify cardiovascular abnormalities in PS patients.

Prevalence of smell loss in Parkinson's disease--a multicenter study.

Previous data on the prevalence of olfactory dysfunction in Parkinson's disease (PD) range from 45% to 90%. The present multicenter study aimed to provide data on the prevalence of smell loss in a large sample of PD patients from three independent populations. Olfactory sensitivity was tested in 400 patients from Australia, Germany, and The Netherlands by means of a psychophysical olfactory test, the "Sniffin' Sticks", which is comprised of 3 subtests of olfactory function. Out of the total number of patients 45.0% presented as functionally anosmic, 51.7% were hyposmic, whereas only 3.3% were normosmic. This indicates that 96.7% of PD patients present with significant olfactory loss when compared to young normosmic subjects. This figure falls to 74.5%, however, when adjusted to age-related norms. Thus, olfactory dysfunction should be considered as a reliable marker of the disease.

Baroreflex sensitivity and power spectral analysis in different extrapyramidal syndromes.

Cardiac autonomic abnormalities have been described in Parkinson's disease and other extrapyramidal syndromes. To investigate baroreflex sensitivity as an important risk marker of cardiovascular mortality in patients with Parkinson's disease and other extrapyramidal syndromes. We recorded continuously blood pressure, ECG and respiration in 35 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 46 patients with idiopathic Parkinson's disease (PD) and in 27 corresponding healthy subjects (Con). Recordings of 2 min at rest were used to calculate baroreflex and spectral analysis of heart rate and systolic blood pressure. Resting baroreflex sensitivity (BRS) was significantly lower in the MSA and the PSP group but not in the PD group in comparison to the Con group. With increasing Hoehn & Yahr stage, BRS significantly decreased in all patient groups. In spectral analysis, all patient groups had a significantly lower relative low frequency (LF)-band power than the healthy controls. Patients with extrapyramidal disorders frequently demonstrate pathologically decreased BRS values and abnormalities of spectral analysis. This may have fundamental impact on the cardiovascular prognosis of patients with extrapyramidal disease.

[Olfactory dysfunction in Parkinson's disease: its role as a new cardinal sign in early and differential diagnosis]. / Riechstörungen bei Morbus Parkinson : Ein neues Kardinalsymptom mit Relevanz für die Früh- und Differenzialdiagnose?

Olfactory dysfunction is a prominent symptom in Parkinson's disease (PD) and found in about 70-100% of patients. In earlier studies significant loss of olfactory function seemed to be unrelated to disease duration, did not correlate with motor function, and was uninfluenced by antiparkinsonian medication. We suggest that the increase of dopaminergic cells in the olfactory bulb is responsible for the hyposmia in PD patients. Interestingly, this olfactory dysfunction is not found in progressive supranuclear palsy or corticobasal degeneration. In multiple system atrophy, the deficit is mild and indistinguishable from cerebellar syndromes of other aetiologies. Intact olfaction has also been reported recently in Parkin disease (PARK 2) and vascular parkinsonism. Olfactory tests may significantly enhance the diagnostic armamentarium in the differential diagnosis of parkinsonian syndromes and indeterminate tremors. Furthermore, olfactory testing may also prove to be a useful aid in the early or "preclinical" detection of PD, once effective disease-modifying therapies are found. Braak and coworkers have confirmed the widespread, extranigral pathology in PD and suggested that pathology in the anterior olfactory region may be one of the earliest appearances of neurodegeneration in PD.

[Miller Fisher syndrome: case report and review with discussion of differential diagnosis and nosology]. / Miller-Fisher-Syndrom: Diskussion der Differenzialdiagnostik und Nosologie anhand einer Kasuistik.

We report a 52-year-old patient with Miller Fisher syndrome and discuss Wernicke's encephalopathy as one important differential diagnosis. This article focuses on diagnostic criteria and possible nosological relations between Miller Fisher syndrome, Guillain-Barré syndrome with ophthalmoplegia, Bickerstaff's brainstem encephalitis, and acute ophthalmoparesis without ataxia.

Analysis of the polymorphic prion protein gene codon 129 in idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Histopathological similarities between IPD and Creutzfeldt-Jakob prion disease (CJD) have been suggested. Homozygosity at polymorphic prion protein gene codon 129 (PRNP129) is a risk factor for developing CJD. Therefore we investigated a putative genetic link between CJD and IPD by studying PRNP129 genotype segregation in 81 patients with IPD. We did not ascertain a different PRNP129 genotype distribution in IPD patients compared to healthy Germans. We found a significant difference in PRNP129 genotype in dependence of the clinical predominance type of IPD. Patients with tremor-dominant IPD presented less frequent a methionine homozygosis at PRNP129 than hypokinetic-rigid IPD patients (30% versus 62.5%; p<0.033). In conclusion, genotype distribution at codon 129 is obviously not essential in determining IPD. But our results may provide first evidence of an association between certain PRNP129 polymorphisms and the clinical presentation of IPD.

Olfactory bulb volumes in patients with idiopathic Parkinson's disease a pilot study.

Olfactory loss is among early signs of idiopathic Parkinson's disease (IPD). The present pilot study aimed to investigate whether this loss would be reflected in a decreased volume of the olfactory bulb (OB) established through magnetic resonance imaging. Eleven consecutive IPD patients were compared to 9 healthy, age-matched controls. Results indicated that there is little or no difference between IPD patients and healthy controls in terms of OB volume. Based upon the relation between loss of olfactory input to the olfactory bulb and consecutive decrease in volume, these data support the idea that olfactory loss in IPD is not a primary consequence of damage to the olfactory epithelium but rather results from central-nervous changes.

Switching and combining dopamine agonists.

Switching from one dopamine agonist to another is common practice in the treatment of patients with Parkinson's disease. This paper describes some ideas on the most practical way to perform switching. In addition, it describes the possibilities of combining various dopamine agonists and discusses pros and cons for doing so.

Differentiation of parkinsonian syndromes according to differences in executive functions.

Groups of patients with Parkinson's disease (PD), striatonigral degeneration-type multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) with motor disability stages II and III according to Hoehn and Yahr, and a healthy control group were compared using neuropsychological tests of executive functions. The results indicate that all three patient groups were impaired in the tests of executive functions. In comparison with healthy subjects, the three patient groups showed impaired performance regarding verbal fluency, problem solving and verbal and figural working memory. Patients with PD differed significantly from healthy subjects in a test of verbal recency, while patients with MSA or PSP were unimpaired. The comparison of patient groups revealed no differences between PD and MSA patients. However, patients with PSP showed greater impairment in both phonemic and semantic fluency than patients with PD or MSA. Using discriminant function analysis, it was found that variables derived from four verbal fluency tasks (simple and alternate semantic and phonemic fluency) discriminated among the three patient groups at a level significantly exceeding chance. Over 90% of patients with PSP were correctly classified. Patients with PD and MSA were correctly classified in over 70% of cases. These results suggest that verbal fluency tasks may be sensitive measures in the differential diagnosis of PD, MSA and PSP.

HLA typing and Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.

[Entacapone for treatment of motor fluctuations in idiopathic Parkinson syndrome]. / Entacapon zur Therapie der motorischen Fluktuationen bei idiopathischem Parkinson-Syndrom.

The treatment of idiopathic Parkinson's disease becomes rather difficult if levodopa-induced late complications such as motor fluctuations or dyskinesias occur. This prospective and open study shows that an add-on therapy with entacapone can significantly lower wearing-off and end-of-dose akinesia. This treatment is well tolerated and easy to perform.

Metabolic patterns in malignant gliomas.

Changes of mitochondrial and cytoplasm tumor metabolism were studied in malignant gliomas and normal cortex probes in vitro. By spectrophotometric methods marker enzymes of different mitochondrial (whole respiratory chain, citrate acid cycle, fatty oxidation) and cytoplasm (glycolysis, pentose phosphate shunt) metabolic energy pathways were analysed. Generally, the activities of intramitochondrial key enzymes were significantly decreased in gliomas when compared with enzyme activities of normal cortex tissue (p < 0.01). Glycolytic enzymes and a representative of the pentose phosphate shunt were unchanged or increased. Ratios of marker enzymes of the glycolytic pathway (lactate dehydrogenase) and glycose-6-P dehydrogenase revealed a significant difference between glioblastomas (p < 0.05) and grade III (p < 0.05) tumors in comparison to normal astrocytic tissue and astrocytomas WHO grade II. Thus, biochemical analyses allow metabolic grading of gliomas in vitro and may be a useful tool for understanding tumor biology.