Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathies.

BACKGROUND: Low levels of serum urate are associated with a higher risk of Parkinson's disease (PD). Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA). AIMS: To compare CSF and blood urate levels in healthy controls, patients with synucleinopathies and with tauopathies. METHODS: We investigated urate levels in serum and CSF from 18 healthy controls, 19 patients with synucleinopathies (six patients with PD and 13 with MSA), and 24 patients with tauopathies (18 with progressive supranuclear palsy and six with corticobasal degeneration). None of the patients were treated with dopaminergic medications. RESULTS: No significant differences were seen when comparing serum and CSF urate levels from controls across the parkinsonian diagnostic groups. However, in men, serum urate levels were significantly lower in the synucleinopathy group compared with the tauopathy group (P = 0.046), although with a broad overlap. CONCLUSION: Our study suggests that urate levels might provide new insights into the potential pathophysiological mechanisms underlying Parkinsonism and thereby contribute to the future management of these disorders.

Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease.

BACKGROUND: This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (HRQoL) effects in routine care. METHODS: Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, ≥3 months after surgery, and then every 3 months. RESULTS: Twenty-seven treatment-naïve subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean ± SD), baseline = 52.1 ± 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 ± 16.7, N = 27, P = 0.003; month 12 = 42.5 ± 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean ± SD), baseline = 33.6 ± 10.8, N = 27, month 0 = 27.1 ± 11.8, N = 27, P = 0.001; 12 months = 28.8 ± 12.8, n = 23, P = 0.126. CONCLUSIONS: LCIG provides functional improvement beginning at first visit that is sustained for 12 months.

Anal sphincter electromyography in patients with newly diagnosed idiopathic parkinsonism.

OBJECTIVES: The differential diagnosis of patients with idiopathic parkinsonism is difficult, especially early in the course of the disease. External anal sphincter electromyography (EAS-EMG) has been reported to be of value in the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA). Patients with MSA are reported to have pathological EAS-EMG and patients with PD are reported to have significantly less pathological EAS-EMG results. Comparisons between patients with parkinsonian disorders have usually been made many years into the disease, and thus it is largely unknown if the results of EAS-EMG can be used to distinguish the different diagnoses in the early phase of the disease. MATERIALS AND METHODS: We investigated 148 newly diagnosed patients with idiopathic parkinsonism from a population-based incidence cohort (100 definite PD, 21 probable PD, 16 MSA, 11 progressive supranuclear palsy, and 40 controls) with EAS-EMG within 3 months of their first visit and, in the majority of patients, before start of treatment with dopaminergic drugs. The clinical diagnoses were made using established clinical diagnostic criteria after a median follow-up of 3 years. RESULTS: All patient groups had more pathological EAS-EMG results than controls. No EAS-EMG differences were found between the patient groups, especially not between PD and MSA. CONCLUSIONS: External anal sphincter electromyography examination cannot separate the different parkinsonian subgroups from each other in early course of the diseases.

A new automated implementation of the Posturo-Locomotion-Manual (PLM) method for movement analysis in patients with parkinson's disease.

OBJECTIVE: The Posturo-Locomotion-Manual (PLM) test, which uses an optoelectronic laboratory system, has here been further developed into an automated, more user-friendly, standardized tool for movement analysis named the QbTestMotus. This paper compares the accuracy of QbTestMotus to the PLM test, in particular the automated data analysis. METHODS: Both QbTestMotus and the PLM recorded data simultaneously from the same 61 patients. The correlation coefficients of movement time (MT), postural time (P), locomotion time (L), and manual time (M) were calculated between the systems. The absolute differences between the result parameters for each patient were also studied. Finally, the differences in MT between the systems were compared with the positive responses in the levodopa (L-dopa) challenges as measured in the PLM test for 11 patients. RESULTS: The comparisons in all the 61 patients showed high correlation coefficients for all four parameters. The absolute differences between the parameters were small and had small standard deviations, and the decreases in MT because of L-dopa in the positive L-dopa responders were much larger than the absolute difference between the systems. CONCLUSION: The PLM test and QbTestMotus are equivalent along all parameters, thus indicating that the test quality is equivalent between the PLM test and the automated QbTestMotus system.

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease.

OBJECTIVES: Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non-specific marker of neuronal damage, are normal in Parkinson's disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF-NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. MATERIALS AND METHODS: CSF-NFL levels were measured consecutively in eight patients with PD before and after STN-DBS treatment. RESULTS: CSF-NFL levels were normal prior to STN-DBS and increased sharply during the first 2 weeks post-operatively, but normalized after 12 months or more. CONCLUSION: The STN-DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF-NFL levels at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term STN-DBS stimulation.

Autonomic innervation in multiple system atrophy and pure autonomic failure.

BACKGROUND: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are both characterised by chronic dysautonomia although presenting different disability and prognosis. Skin autonomic function evaluation by indirect tests has revealed conflicting results in these disorders. Here, the authors report the first direct analysis of skin sympathetic fibres including structure and function in PAF and MSA to ascertain different underlying autonomic lesion sites which may help differentiate between the two conditions. METHODS: The authors studied eight patients with probable MSA (mean age 60±5 years) and nine patients fulfilling diagnostic criteria for PAF (64±8 years). They underwent head-up tilt test (HUTT), extensive microneurographic search for muscle and skin sympathetic nerve activities from peroneal nerve and punch skin biopsies from finger, thigh and leg to evaluate cholinergic and adrenergic autonomic dermal annexes innervation graded by a semiquantitative score presenting a high level of reliability. RESULTS: MSA and PAF patients presented a comparable neurogenic orthostatic hypotension during HUTT and high failure rate of microneurographic trials to record sympathetic nerve activity, suggesting a similar extent of chronic dysautonomia. In contrast, they presented different skin autonomic innervation in the immunofluorescence analysis. MSA patients showed a generally preserved skin autonomic innervation with a significantly higher score than PAF patients showing a marked postganglionic sympathetic denervation. In MSA patients with a long disease duration, morphological abnormalities and/or a slightly decreased autonomic score could be found in the leg reflecting a mild postganglionic involvement. CONCLUSION: Autonomic innervation study of skin annexes is a reliable method which may help differentiate MSA from PAF.

Short-term effects of repetitive transcranial magnetic stimulation on speech and voice in individuals with Parkinson's disease.

The main characteristics of dysarthria in Parkinson's disease (PD) are monotony of pitch and loudness, reduced stress, variable speech rate, imprecise consonants, and breathy and harsh voice. Earlier treatment studies have shown that dysarthria is less responsive to both pharmacological and surgical treatments than other gross motor symptoms. Recent findings have suggested that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect on vocal function in PD. In the present study, 10 individuals with mild PD and no or minimal dysarthria were treated with rTMS as well as placebo stimulation in a blinded experiment. Stimulation was delivered using a frequency of 10 Hz and a stimulation intensity of 90% of the motor threshold. The site of stimulation was the cortical area corresponding to the hand, on the hemisphere contralateral to the patient's most affected side. The participants were audio-recorded before and after both rTMS and sham stimulation. Acoustic analysis was performed on 3 sustained /a:/ for each of the 4 conditions, and analyzed both for the whole group as well as for men and women separately. Results showed that there were no significant differences between any of the conditions regarding duration of sustained fricative or sustained vowel phonation, diadochokinetic rates or intelligibility. Above all, the results of acoustic analyses showed an effect of placebo; there was a significant reduction in fundamental frequency (F(0)) variation, pitch period perturbation, amplitude period perturbation, noise-to-harmonics ratio and coefficient of variation in F(0) between the recordings performed before compared to after sham stimulation.

Cytochrome P450 2E1 gene polymorphisms/haplotypes and Parkinson's disease in a Swedish population.

Cytochrome P450 2E1 (CYP2E1), which inter alia is located in dopamine containing neurons in the substantia nigra, has been hypothesized to be of importance for the pathophysiology of Parkinson's disease (PD), either by its production of reactive oxygen species (ROS) or by its capability to detoxify putative neurotoxins. Numerous polymorphisms in the coding and non-coding regions of the gene for this enzyme have been reported. Different variants may account for inter-individual differences in the activity of the enzyme or production of ROS. In this study, the CYP2E1 gene was examined in a control population (n = 272) and a population with PD (n = 347), using a tag-single nucleotide polymorphism (tSNP) approach founded on HapMap Data. Six tSNPs were used in the analysis and haplotype block data were obtained. In case of significance, the SNP was further examined regarding early/late age of disease onset and presence of relatives with PD. We found an association between allele and genotype frequencies of the C/G polymorphism at intron 7 (rs2070676) of this gene and PD (P value of 0.026 and 0.027, respectively). Furthermore, analysis of the rs2070676 polymorphism in subgroups of patients with age of disease onset higher than 50 years and those not having a relative with PD also demonstrated a significant difference with controls. This was seen in both genotype (corresponding to P value = 0.039 and 0.032) and allele (P = 0.027 and 0.017 respectively) frequency. As a representative of many polymorphisms or in possible linkage disequilibrium with other functional variants, it is possible that rs2070676 could influence the regulation of the enzyme. In conclusion, our results display an association between the rs2070676 polymorphism and PD. Additional investigations are needed to elucidate the importance of this polymorphism for the activity of CYP2E1 and PD susceptibility.

Comparison of apomorphine and levodopa infusions in four patients with Parkinson's disease with symptom fluctuations.

BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. AIMS OF THE STUDY: We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. METHODS: The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. RESULTS: Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS: Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

Minimized weight gain between hemodialysis contributes to a reduced risk of death.

UNLABELLED: The risk of death is higher in dialysis patients compared to age matched healthy subjects, the main reason being cardiovascular. This prospective study investigated if the extent of ultrafiltration was of importance for the outcome. MATERIAL AND METHODS: 88 hemodialysis patients were included and followed prospectively. The outcome was registered in regard to death, acute myocardial infarction or coronary vascular intervention. The extent of ultrafiltration needed at dialysis was calculated as a mean during the observation period as were other variables. The mean extent of ultrafiltration was compared for patients who had survived without end-points (group 1, n=53) versus those who reached any end-point during the period (group 2, n=35). RESULTS: In total, 40% of the patients reached end-point during the observation period. There was no difference at baseline between the groups in regard to age, prevalence of diabetes mellitus or history of previous cardiovascular disease, KT/V, residual renal function ultrafiltration need, C-reactive protein, s-albumin, cholesterol, LDL-cholesterol, HDL-cholesterol, appetite or wellbeing, while triglyceride was lower in group 2 (p=0.035). The observation period for group 1 was at a mean 24.7 months (SD13.1) and for those in group 2 at a mean 13.8 (+/-11.7 months, p<0.001). Patients representing group 1 at 24 and 30 months had less need of ultrafiltration than those in group 2. Thus, the need of ultrafiltration was about 27% lower at 24 months (for 29 persons in group 1: 3.63+/-1.93 weight% versus 4.97+/-1.70 weight% for 9 patients from group 2, p=0.046) and 46% at 30 months (for 18 from group 1: 3.48+/-1.95 versus 6.45+/-1.55 for 3 from group 2, p=0.030). C-reactive protein did not differ significantly between the groups during the period. CONCLUSION: After a prolonged period of 24 months the extent of ultrafiltration need seems to be important for the outcome of the patients. Thereby those with higher need of ultrafiltration had worse prognosis. It seems important to motivate patients to reduce the extent of fluid intake between dialysis to prolong survival.

Development of an spFRET method to measure structure changes in ion exchange proteins.

AIM: Understanding the mechanism of tightly coupled ion exchange proteins, important effectors of cell volume regulation and other physiologically important transport processes requires means to observe dynamic changes in structure during the transport cycle. As a step towards this goal, we have applied single-pair fluorescence resonance energy transfer to a monomeric bacterial oxalate-formate exchanger (OxlT). METHODS: A His-9 tagged OxlT mutant containing two cysteines at positions 17 and 224 was labelled with cyanine dye maleimides (Cy3 donor and Cy5 acceptor) and attached to glass coverslips for measurements of donor and acceptor emission from single molecules, as described (P. Pal et al. Biophys J89, L11, 2005). RESULTS: Time-series data from 20 spots containing donor and acceptor provided evidence for single-pair energy transfer. From the efficiency of energy transfer, the mean donor-acceptor distance was determined to be 44.2 A. Considering the size of the probes, this is in good agreement with the Calpha distance of 39.6 A for the corresponding sites found in the OxlT structural (homology) model (Q. Yang et al. Proc Natl Acad Sci102, 8513, 2005). CONCLUSION: These results demonstrate the feasibility of single-pair fluorescence resonance energy transfer to measure distances between known sites in single OxlT molecules. This technique provides a potential means to test models for transport-related conformational changes, as well as to detect real-time structure alterations during the catalytic transport cycle.

Inadvertent malposition of a transvenous pacing lead in the left ventricle.

We report the case of inadvertent malpositioning of a pacemaker lead in the left ventricle. The lead went through an open foramen ovale from the right to the left atrium and through the mitral valve into the left ventricle. After a review of the literature, we decided to anticoagulate the patient and leave the electrode in place. During a follow-up period of 16 months, there were no clinical complications.

Safety and efficacy of atorvastatin in patients with severe renal dysfunction.

OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. CONCLUSION: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease.

OBJECTIVES: To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). METHODS: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/carbidopa gel for 3 + 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from -3 to 0 to +3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. RESULTS: Median percentage of ratings in a functional "on" interval (-1 to +1) was increased from 81 to 100% by infusion therapy (p < 0.01). This improvement was accompanied by a decrease in "off" state (p < 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p < 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p < 0.01). Adverse events were similar for both treatment strategies. CONCLUSIONS: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study.

OBJECTIVE: There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min). MATERIAL AND METHODS: The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat. RESULTS: Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was 20%. Atorvastatin was withdrawn in 20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months. CONCLUSIONS: Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.

Association between the estrogen receptor beta gene and age of onset of Parkinson's disease.

The purpose of this study was to investigate the potential contribution of genetic variants in the estrogen receptor beta gene to the aetiology of Parkinson's disease (PD). Several lines of evidence from human and animal studies suggest a protective role for estrogen in PD. Recently the estrogen receptor beta subtype was reported to be an important mediator of estrogen actions in the nigrostriatal dopamine system. Two single nucleotide polymorphisms at position 1730 and 1082 in the ER beta gene were genotyped, using pyrosequencing, in 260 patients with PD and 308 controls recruited from the Swedish population. Neither of the two estrogen receptor beta polymorphisms was associated with an increased risk for PD. However, the G allele of the A1730G polymorphism was more frequent in patients with an early age of onset than in patients with a late age of onset of PD (P = 0.006). Patients carrying the GG genotype had an odds ratio of 2.2 for having an early onset of PD compared to non-carriers. In conclusion, our results indicate that genetic variation in the estrogen receptor beta gene may influence the age of onset of PD.

Endocrine responses of ovariectomized ewes to i.c.v. infusion of urocortin.

Urocortin is a novel corticotropin-releasing factor-like peptide, first isolated from the rat midbrain, which has anorexigenic properties, possibly associated with its involvement in the stress axis. Urocortin has been implicated in blood pressure regulation, ACTH release and feed intake, but its role as an integral component of the reproduction-nutrition axis has not been examined. The present experiment was designed to determine the effects of i.c.v. infusion of urocortin on feed intake and endocrine profiles of LH, GH, IGF-I, cortisol and leptin in ovariectomized ewes. Ewes were fitted with two laterocerebroventricular cannulae and urocortin was continuously infused in a linearly increasing manner from 0.001 microg/h on day 0, to a maximum of 31.6 microg/h on day 5. Blood samples were collected via jugular catheters at 10 min intervals for 4 h on day 1, 3 and 5, and assayed by RIA for LH, GH, IGF-I, cortisol and leptin. All ewes were allowed free access to feed and water, and feed intake was recorded daily. Urocortin-infused ewes responded with a significant decrease in feed intake beginning on day 1 (P<0.02) and were aphagic for the remainder of the experiment. Serum concentrations of LH were elevated in individual samples from urocortin-treated compared with saline-treated ewes on day 3 (treatment x day x sample, P=0.05), but were not different on day 1 or 5. Mean serum concentrations of GH increased (P<0.04) over days with urocortin treatment, although concentrations of IGF-I were not influenced by treatment (P>0.5). Serum concentrations of cortisol were markedly increased by urocortin treatment (P<0.001). Leptin tended to be influenced by treatment and day (P=0.08), with leptin levels tending to be elevated in urocortin-treated vs saline-treated ewes on day 5 (P=0.08). The ability of urocortin to decrease feed intake while increasing LH, GH, cortisol and leptin provides evidence that urocortin is not only an integral component of the stress axis, but possibly of the nutrition-reproduction axis in sheep.

CSF-neurofilament and levodopa tests combined with discriminant analysis may contribute to the differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is important for prognostic and therapeutic purposes. In order to evaluate the diagnostic capability of two tests reflecting these items, patients fulfilling strict clinical criteria for PD (n=35), MSA (n=36) and PSP (n=14), were consecutively included. An analysis of neurofilament protein (NFL), a marker of axonal degeneration in the cerebrospinal fluid (CSF) and a levodopa test, recorded with optoelectronic technique were performed. Using discriminant analyses, the test's abilities to predict the clinical PD or non-PD (MSA and PSP) diagnoses were compared. Whereas the CSF-NFL and levodopa tests predicted 79 and 85% correct diagnoses respectively, the combined test predicted 90% correct diagnoses. We conclude that the CSF-NFL and levodopa tests provide detailed information of clinical variables on which the clinical diagnostic criteria are based. As they are pathologically unrelated, the diagnostic precision increases compared to clinical diagnoses when they are combined.

Cardiovascular reflex testing contributes to clinical evaluation and differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) may be difficult but is important for prognostic and therapeutic purposes. Varying degrees of autonomic failure have been described in PD and MSA, whereas its involvement in PSP remains controversial. The aim of this study was to investigate autonomic function in patients fulfilling strict clinical diagnostic criteria for the disorders above, to evaluate the diagnostic capacity of laboratory autonomic tests. The study group was consecutively recruited among patients referred to a movement disorder unit. Thirty-four patients with PD, 15 patients with PSP, and 47 patients with MSA were compared with 18 healthy age-matched controls. Autonomic tests included analysis of heart rate variability (HRV) in temporal domain, at rest and during forced respiration, as well as blood pressure (BP) changes during 75 degrees head-up tilt. HRV did not differ between groups during quiet breathing but was significantly reduced during forced respiration in MSA (P < 0.01), while PD and PSP groups did not differ from controls. Hypotensive responses during orthostatic provocation were seen in PD (P < 0.01) and MSA (P < 0.001), whereas BP remained stable in most PSP patients, not differing from the healthy control group. On an individual basis, decreased HRV and severe hypotensive responses were seen in MSA patients regardless of age and disease duration, whereas PD patients showed this combination only at high age and long duration. In PSP, only a few cases with decreased HRV and limited hypotensive responses were found. We conclude that cardiovascular reflex tests can supplement the clinical differentiation of Parkinsonian syndromes.