Pain processing in atypical Parkinsonisms and Parkinson disease: A comparative neurophysiological study

Objective

Pain is a frequent non-motor feature in Parkinsonism but mechanistic data on the alteration of pain processing are insufficient to understand the possible causes and to define specifically-targeted treatments.

An magnetic resonance imaging T2*‐weighted sequence at short echo time to detect putaminal hypointensity in Parkinsonisms

At 1.5 T, T2*‐weighted gradient echo (GE) sequences are more sensitive in revealing mineral deposition in the basal ganglia than standard T2 weighted sequences. T2*‐weighted GE sequences, however, may detect putaminal hypointensities either in patients affected by parkinsonian syndromes or in healthy subjects. The aim of this study was to identify the magnetic resonance imaging (MRI) T2*‐weighted sequence which more specifically detected putaminal hypointensities differentiating atypical parkinsonian syndromes from Parkinson's disease (PD) and control subjects. In a sample of 38 healthy subjects, we performed three T2*‐weighted GE sequences at increasing time echo (TE; TE = 15 millisecond, TE = 25 millisecond, and echoplanar at TE = 40 millisecond; T2* sequences study). The sequence not showing any putaminal abnormality in the healthy subjects was then used to assess putaminal signal intensity in 189 patients with PD, 20 patients with multiple system atrophy (MSA), 41 patients with progressive supranuclear palsy (PSP), and in 150 age and sex‐matched control subjects. In the T2* sequences study, the T2*‐weighted TE = 15 (T2*/15) did not show any putaminal abnormalities in the healthy subjects. This sequence detected putaminal hypointensities in a significantly higher proportion of patients with MSA (35%, P < 0.05) and PSP (24.4%, P < 0.05) than in patients with PD (5.3%), but in none of the controls. The sensitivity of putaminal hypointensity in T2*/15 sequence was 25.4% for PD, 43.9% for PSP, and 55% for MSA versus controls whereas the specificity was 93.2% for all groups. Despite the suboptimal sensitivity, the high specificity of the T2*/15 sequence performed on routine MRI suggests its usefulness in clinical practice for identifying putaminal hypointensities associated with parkinsonian disorders. © 2010 Movement Disorder Society     

Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy.

Our objective was to examine whether rapid eye movement (REM) sleep behavior disorder occurs in disproportionally greater frequency in multiple system atrophy (MSA), Parkinson's disease (PD), and dementia with Lewy bodies (DLB), collectively known as the synucleinopathies, compared to other nonsynucleinopathy neurodegenerative disorders. In study 1, we reviewed the clinical records of 398 consecutive patients evaluated at Mayo Clinic Rochester for parkinsonism and/or cognitive impairment. The frequency of suspected and polysomnogram (PSG)-confirmed REM sleep behavior disorder (RBD) among subjects with the synucleinopathies MSA, PD, or DLB was compared to the frequency among subjects with the nonsynucleinopathies Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), mild cognitive impairment (MCI), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). In study 2, we reviewed the clinical records of 360 consecutive patients evaluated at Mayo Clinic Jacksonville for parkinsonism and/or cognitive impairment. The frequency of probable RBD among patients with PD and DLB was compared to the frequency among patients with AD and MCI. In study 3, we reviewed the brain biopsy or postmortem autopsy diagnoses of 23 Mayo Clinic Rochester patients who had been clinically examined for possible RBD and a neurodegenerative disorder. In study 1, patients with MSA, PD, or DLB were more likely to have probable and PSG-confirmed RBD compared to subjects with the nonsynucleinopathies (probable RBD 77/120=64% vs. 7/278=3%, p < 0.01; PSG-confirmed RBD 47/120=39% vs. 1/278=0%, p < 0.01). In study 2, patients with PD and DLB were more likely to have probable RBD compared to those with AD and MCI (56% vs. 2%, p < 0.01). In study 3, of the 23 autopsied patients who had been questioned about possible RBD, 10 were clinically diagnosed with RBD. The neuropathologic diagnoses in these 10 included Lewy body disease in nine, and MSA in one. Of the other 13 cases, 12 did not have a history suggesting RBD, and the one case who did had normal electromyographic atonia during REM sleep on PSG and autopsy findings of PSP. Only one of these 13 had a synucleinopathy. The positive predictive values for RBD indicating a synucleinopathy for studies 1-3 were 91.7%, 94.3%, and 100.0%, respectively. Clinically suspected and PSG-proven RBD occurs with disproportionally greater frequency in MSA, PD, and DLB compared to other neurodegenerative disorders. In the setting of degenerative dementia and/or parkinsonism, we hypothesize that RBD is a manifestation of an evolving synucleinopathy.     

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA‐P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA‐P in order to evaluate its differential diagnostic value in vivo. Twenty‐eight patients with PSP (14 with possible‐PSP and 14 with probable‐PSP), 15 PD, 15 MSA‐P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 × 10^?3mm²/s) than patients with PD (median 0.79 × 10^?3 mm²/s, P < 0.001), MSA‐P (median 0.79 × 10^?3 mm²/s, P < 0.001), and healthy controls (median 0.80 × 10^?3 mm²/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA‐P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. © 2008 Movement Disorder Society     

Applause sign in parkinsonian disorders and Huntington's disease

The applause sign has been previously reported to be indicative of neurodegenerative disorders, such as progressive supranuclear palsy (PSP). In order to determine the sensitivity, specificity, and positive predictive value, we tested it in patients with PSP, Parkinson's disease (PD), multiple system atrophy (MSA), corticobasal degeneration (CBD), and Huntington's disease (HD). Subjects were asked to clap three times after demonstration by the examiner. The performance was scored as follows: 3 = claps only three times; 2 = claps four times; 1 = claps 5 to 10 times; 0 = claps >10 times. The clap test was videotaped and rated. Patients with CBD, MSA, and PSP showed significant differences in clap scores compared with normal controls. The test differentiated patients with CBD from those with PD (P < 0.005) and HD (P < 0.005), but failed to discriminate patients with PSP from other parkinsonian groups. The specificity of the applause sign is 100% in distinguishing parkinsonian patients from normal subjects with the highest sensitivity in CBD patients. We concluded that the applause sign is highly specific for parkinsonian disorders but it is not a specific sign for PSP; it appears to be most sensitive for CBD. © 2008 Movement Disorder Society     

快速眼动期睡眠行为障碍与突触核蛋白病的关系

目的 研究快速眼动(REM)期睡眠行为障碍(RBD)在突触核蛋白病中的出现率、出现时间、电生理特点,探讨RBD与突触核蛋白病之间的关系以及电生理诊断指标.方法 通过对患者的睡眠状况调查以及夜间多导睡眠监测(NPSG),研究本组疾病的睡眠障碍特征:(1)主观睡眠调查:帕金森病(PD)患者66例,多系统萎缩(MSA)患者30例,性别、年龄匹配的健康对照组65名,询问睡眠史,了解RBD出现的比例及出现时间.(2)NPSG:PD组8例、MSA组13例,健康对照组15名,所有受试者行连续两夜NPSG监测.分析伴发RBD的突触核蛋白病患者的NPSG特点.结果 PD和MSA合并RBD比例分别是59.1%(39/66)和86.6%(26/30),明显高于对照组(4.6%,3/65),其中RBD早于两种变性病临床发病的患者比例分别是46.2%(18/39)和84.6%(22/26).PD和MSA合并RBD最主要的NPSG特点是:REM期肌肉弛缓现象消失(RWA)和运动增多.RWA比例和位相性肌电活动密度可能成为神经变性病合并RBD的NPSG诊断指标.结论 RBD在PD和MSA患者中出现率明显增高,部分RBD发生先于变性病,提示RBD与突触核蛋白病关系密切,RBD有可能是突触核蛋白病的早期表现.NPSG特征应作为RBD的主要诊断标准,RWA比例和位相性肌电活动密度可能成为神经变性病合并RBD的NPSG诊断指标.     

Joint and skeletal deformities in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

The objective of this study is to characterize clinical features of joint and skeletal deformities in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Clinical information including age, gender, presence of deformity, initial symptom side, neuropsychological and motor features, family history, and treatment with levodopa/dopamine agonists was collected on consecutive patients with PD, MSA, and PSP evaluated at the Movement Disorders Clinic at Baylor College of Medicine. In this series of 202 patients, 36.1% had deformities of the limbs, neck, or trunk, including 33.5% of PD, 68.4% of MSA, and 26.3% of PSP patients. "Striatal" hand and foot deformities were present in 13.4%, involuntary trunk flexion in 12.9%, anterocollis in 9.4%, and scoliosis in 8.4% of all patients. Patients with these joint and skeletal deformities had higher mean Unified Parkinson's Disease Rating Scale scores (57.4 vs. 46.6; P < 0.01) and were more often treated with levodopa (69.9% vs. 50.4%; P < 0.01) than patients without deformity, independent of disease duration. Patients with striatal deformity were younger than patients without deformity (mean 60.4 vs. 68.6 years; P < 0.01), and they tended to have an earlier age of onset of initial parkinsonian symptoms (mean 54.7 vs. 62.5 years; P < 0.01). Furthermore, the side of striatal deformity correlated with the side of initial parkinsonian symptoms in all patients (100%) with striatal hand and in 83.3% of patients with striatal foot. Joint and skeletal deformities are common and frequently under-recognized features of PD, MSA, and PSP that often cause marked functional disability independent of other motor symptoms.     

Sleep disturbances and brain MRI morphometry in Parkinson's disease,multiple system atrophy and progressive supranuclear palsy – a comparative study

Despite common reports in Parkinson's disease (PD), in other parkinsonian syndromes, sleep disturbances have been less frequently described. This study evaluated and compared sleep disturbances in patients with PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and analyzed associations with brain magnetic resonance imaging (MRI) morphometry. This was a cross-sectional study of 16 PD cases, 13 MSA, 14 PSP and 12 control. Sleep disturbances were evaluated by Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), Restless Legs Scale and Berlin questionnaire. Pons area, midbrain area, medial cerebellar peduncle (MCP) width, and superior cerebellar peduncle width were measured using MRI. Poor quality sleep, risk of obstructive sleep apnea (OSA) and restless legs syndrome (RLS) were detected in all groups. Patients with MSA showed higher risk of OSA and less frequent RLS. In MSA, a correlation between PSQI scores and Hoehn and Yahr stage was observed (p < 0.05). In PSP, RLS was frequent (57%) and related with reduced sleep duration and efficiency. In PD, excessive daytime sleepiness was related to atrophy of the MCP (p = 0.01). RLS was more frequent in PD and PSP, and in PSP, was associated with reduced sleep efficiency and sleep duration. Brain morphometry abnormalities were found in connection with excessive daytime sleepiness and risk of OSA in PD and PSP suggesting widespread degeneration of brainstem sleep structures on the basis of sleep abnormalities in these patients.     

Slowing of Frontal β Oscillations in Atypical Parkinsonism

Background

Diagnosis of atypical parkinsonian syndromes (APS) mostly relies on clinical presentation as well as structural and molecular brain imaging. Whether parkinsonian syndromes are distinguishable based on neuronal oscillations has not been investigated so far.

Objective

The aim was to identify spectral properties specific to atypical parkinsonism.

Methods

We measured resting-state magnetoencephalography in 14 patients with corticobasal syndrome (CBS), 16 patients with progressive supranuclear palsy (PSP), 33 patients with idiopathic Parkinson's disease, and 24 healthy controls. We compared spectral power as well as amplitude and frequency of power peaks between groups.

Results

Atypical parkinsonism was associated with spectral slowing, distinguishing both CBS and PSP from Parkinson's disease (PD) and age-matched healthy controls. Patients with atypical parkinsonism showed a shift in β peaks (13–30 Hz) toward lower frequencies in frontal areas bilaterally. A concomitant increase in θ/α power relative to controls was observed in both APS and PD.

Conclusion

Spectral slowing occurs in atypical parkinsonism, affecting frontal β oscillations in particular. Spectral slowing with a different topography has previously been observed in other neurodegenerative disorders, such as Alzheimer's disease, suggesting that spectral slowing might be an electrophysiological marker of neurodegeneration. As such, it might support differential diagnosis of parkinsonian syndromes in the future. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Abnormal metabolic networks in atypical parkinsonism

Spatial covariance analysis has been used with ¹⁸F‐fluorodeoxyglucose (FDG) PET to detect and quantify specific metabolic patterns associated with Parkinson's disease (PD). However, PD‐related patterns cannot necessarily serve as biomarkers of the processes that underlie the atypical parkinsonian syndromes. In this FDG PET study, we used strictly defined statistical criteria to identify disease‐related metabolic patterns in the imaging data from patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the two most common of these atypical conditions. We found that MSA and PSP were each associated with a specific, highly stable metabolic brain network (P < 0.0001, bootstrap estimation). The MSA‐related pattern was characterized by decreased metabolism in the putamen and cerebellum. The PSP‐related pattern was characterized by metabolic decreases in the brainstem and medial frontal cortex. For both conditions, pattern expression was significantly elevated in patients relative to age‐matched healthy control subjects (P < 0.001). For each condition, we validated the associated disease‐related metabolic pattern by computing its expression on an individual scan basis in two independent patient cohorts, and in one subsequent healthy volunteer cohort. We found that for both MSA and PSP, prospective assessments of pattern expression accurately discriminated patients from controls (P < 0.001). These findings suggest that the major atypical parkinsonian syndromes are associated with distinct patterns of abnormal regional metabolic activity. These disease‐related networks can potentially be used in conjunction with functional brain imaging as quantifiable biomarkers for the assessment of these pathological conditions. © 2008 Movement Disorder Society     

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n₁ = 51, n₂ = 101), corticobasal degeneration (CBD) (n₁ = 11, n₂ = 3), progressive supranuclear palsy (PSP) (n₁ = 22, n₂ = 21), multiple system atrophy (MSA) (n₁ = 31, n₂ = 26), and healthy control (HC) (n₁ = 48, n₂ = 30) participants, as well as Alzheimer's disease (AD) (n₂ = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

123I]beta-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration.

Differentiation between Parkinson's disease (PD) and other neurodegenerative disorders with parkinsonian features, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), is difficult on clinical grounds. We studied the pattern of dopaminergic degeneration in 18 patients with probable MSA, 8 patients with PSP, 4 patients with CBD, 48 patients with PD and a similar degree of disability, and 14 control subjects performing single photon emission computed tomography (SPECT) 20 hours after injection of [123I]beta-CIT. Overall striatal binding was significantly reduced in MSA (-51% of normal mean), PSP (-60%), CBD (-35%), and PD (-58%), without overlap with control values. Asymmetry of striatal beta-CIT binding was significantly increased in patients with CBD and PD, as compared with control subjects. Although asymmetry seemed to be less pronounced in MSA and PSP than in PD, this was not statistically significant. Putamen-caudate nucleus ratios in patients with PD, MSA, and PSP, but not with CBD, were significantly reduced, as compared with control subjects. In conclusion, [123I]beta-CIT SPECT reliably enables the visualization of the presynaptic dopaminergic lesion in patients with MSA, PSP, and CBD. In most patients, however, it does not seem to be possible to differentiate these disorders from PD with this method.     

Whole-Brain Magnetic Resonance Spectroscopy Reveals Distinct Alterations in Neurometabolic Profile in Progressive Supranuclear Palsy

Background

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized by supranuclear gaze palsy, early postural instability, and a frontal dysexecutive syndrome. Contrary to normal brain magnetic resonance imaging in Parkinson's disease (PD), PSP shows specific cerebral atrophy patterns and alterations, but these findings are not present in every patient, and it is still unclear if these signs are also detectable in early disease stages.

Objective

The aim of the present study was to analyze the metabolic profile of patients with clinically diagnosed PSP in comparison with matched healthy volunteers and PD patients using whole-brain magnetic resonance spectroscopic imaging (wbMRSI).

Methods

Thirty-nine healthy controls (HCs), 29 PD, and 22 PSP patients underwent wbMRSI. PSP and PD patients were matched for age and handedness with HCs. Clinical characterization was performed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, PSP rating scale, and DemTect (test for cognitive assessment).

Results

In PSP patients a significant reduction in N-acetyl-aspartate (NAA) was detected in all brain lobes. Fractional volume of the cerebrospinal fluid significantly increased in PSP patients compared to PD and healthy volunteers.

Conclusions

In PSP much more neuronal degeneration and cerebral atrophy have been detected compared with PD. The most relevant alteration is the decrease in NAA in all lobes of the brain, which also showed a partial correlation with clinical symptoms. However, more studies are needed to confirm the additional value of wbMRSI in clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

The arginine growth hormone stimulation test in bradykinetic‐rigid parkinsonisms

The arginine growth hormone (GH) stimulation test differentiates the Parkinsonian variant of multiple system atrophy (MSA‐P) from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine GH stimulation test in distinguishing between PSP, MSA‐P, and PD. We measured the GH response to arginine in serum samples of 26 MSA‐P, 23 PSP, and 26 PD patients, and in 80 healthy controls. We used ANOVA followed by the Bonferroni test to compare GH values and peaks among groups. We used receiver operating characteristic curve analysis to establish the arginine cut‐off level that best differentiated between MSA‐P, PSP, and PD. The GH peak was significantly lower (P < 0.01) in MSA‐P (1.46 ± 0.29 μg/L) than in both PD (8.74 ± 0.98 μg/L) and PSP (6.64 ± 0.82 μg/L) patients, and controls (8.59 ± 0.44 μg/L). Growth hormone peaked later in PSP patients than in PD patients and controls. At a cut‐off level of 4 μg/L, arginine test distinguished MSA‐P from PD with a sensitivity of 92% and a specificity of 96%, and MSA‐P from PSP with a sensitivity of 78% and a specificity of 96%. The GH response to arginine differentiates MSA‐P from PD and PSP with a good diagnostic accuracy. The neuroendocrine response to arginine of PSP patients differed from that of MSA‐P patients, but was not identical to that of normal controls and PD patients. Our results suggest that the impairment of the central mechanisms modulating GH release differs between PSP and MSA‐P. © 2007 Movement Disorder Society     

Incidence of Parkinson's disease and parkinsonism in northern Sweden: A population‐based study

The differential diagnosis of parkinsonian disorders is difficult, especially early in the course of the diseases. The clinical subtypes of Parkinson's disease (PD) have not so far been described in newly diagnosed patients. We present a prospective incidence cohort study of patients with idiopathic parkinsonian syndromes in the Umeå region in northern Sweden identified over a 4‐year period. The clinical diagnoses were re‐evaluated at follow‐up visits at 12 months. We found 138 patients with parkinsonism: 112 PD, 12 multiple system atrophy with predominant parkinsonism (MSA‐P), six progressive supranuclear palsy (PSP) and eight unclassifiable patients. The crude incidences for all age ranges per 100,000 were: PD 19.7 (95% confidence interval 16.1–23.3); MSA‐P 2.1 (1.1–3.7); PSP 1.1 (0.4–2.4); idiopathic parkinsonism 24.3 (20.2–28.4). Age‐standardized to the average Swedish population 2004–2007: PD 22.5 (18.3–26.7); MSA‐P 2.4 (1.2–4.2); PSP 1.2 (0.4–2.6); idiopathic parkinsonism 27.5 (22.9–32.1). The crude annual incidence rate for PD, with exclusion of patients with normal dopamine receptor uptake (FP‐CIT‐SPECT), was 18.8 per 100,000 (95% confidence interval 15.2–22.4), age‐adjusted to the average Swedish population 2004 to 2007: 21.5 (17.4–25.6). The incidence rates did not differ significantly between men and women. The cumulative incidence of PD up to 89 years of age was for men 3.4%, for women 2.6%, and for both sexes combined 2.9%. The annual incidence rates found for PD, idiopathic parkinsonism, MSA‐P and PSP are among the highest reported. © 2010 Movement Disorder Society     

Effects of safinamide on REM sleep behavior disorder in Parkinson disease: A randomized,longitudinal, cross-over pilot study

BackgroundRapid Eye Movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during REM-sleep. RBD as a premotor feature occurred souvent in patients who develop Parkinson’s disease. The glutamatergic, glycinergic, and GABA-ergic systems appear to play a crucial role in the pathogenesis of RBD.MethodsThe present exploratory longitudinal cross-over study aimed to observe the effect of safinamide on RBD symptoms. Thirty patients with PD and RBD were randomized into two groups (15 subjects each), those that received for a period of 3-months safinamide (50 mg/die) in addition (Group A + ) or in absence (Group B − ) to the usual antiparkinsonian therapy. Patients exploring the clinical and video-polysomnographic changes occurred during this pharmacological therapy.ResultsTwenty-two of 30 patients reported clear improvement in symptoms during safinamide treatment, and 16 were absolutely free from clinical RBD-symptoms at the end of the treatment. Eight patients reported slight improvement in RBD-symptoms. In 6/30 patients no substantial improvement was recorded about clinical RBD-symptoms had frightening dreams or from the bed after 1-week of treatment. In addition, after safinamide, the mean UPDRS-II and III scores decreased, while PDSS-2 score indicating an improvement in both motor symptoms and nocturnal sleep features. A significant reduction of sleep behavior disorder by questionnaire-Hong Kong-score (RBDQ-HS), mainly for two individual RBDQ-HK-items (dream related movements and failing out of bed) was registered.ConclusionsThis pilot study indicated that safinamide is well tolerated and improves RBD-symptom in parkinsonian.     

Differentiation of parkinsonian syndromes according to differences in executive functions

Summary. Groups of patients with Parkinsons 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.Received November 5, 2002; accepted March 27, 2003 Published online June 30, 2003     

Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: A case-control study

BackgroundRestless Legs Syndrome (RLS) is associated with impaired central dopaminergic neurotransmission. Though a link between RLS and parkinsonism has been proposed, the prevalence of RLS in parkinsonian disorders is poorly documented.ObjectiveTo determine the prevalence of RLS in patients with Parkinson's Disease (PD), Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB).MethodsWe evaluated 187 consecutive patients with parkinsonian disorders (PD = 134, PSP = 27, MSA = 21, DLB = 5) and 172 healthy controls. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria and the severity of RLS was assessed in patients with definite RLS. Quality of sleep was evaluated with established scales.ResultsThe prevalence of RLS was higher in patients compared to controls (9.6% vs. 2.9%; p = 0.009) and was highest in PD (11.9%). RLS was present in only one patient each with MSA and PSP and none with DLB. The mean IRLSSG severity score of patients was 16.2 ± 6.5. The global Pittsburgh Sleep Quality Index score and Epworth Sleepiness Scale score were significantly higher in patients compared to controls (p < 0.001). PD patients with RLS had lower Parkinson's Disease Sleep Scale (PDSS) score compared to patients without RLS (p = 0.023). There was no significant difference in gender, age, duration and severity of PD between the two groups.ConclusionsOur study found a higher prevalence of RLS in PD compared to healthy controls or other parkinsonian disorders. Apart from PDSS score, there was no significant difference in the clinical characteristics of PD patients with and without RLS.     

Reproducible network and regional topographies of abnormal glucose metabolism associated with progressive supranuclear palsy: Multivariate and univariate analyses in American and Chinese patient cohorts

Progressive supranuclear palsy (PSP) is a rare movement disorder and often difficult to distinguish clinically from Parkinson's disease (PD) and multiple system atrophy (MSA) in early phases. In this study, we report reproducible disease‐related topographies of brain network and regional glucose metabolism associated with PSP in clinically‐confirmed independent cohorts of PSP, MSA, and PD patients and healthy controls in the USA and China. Using ¹⁸F‐FDG PET images from PSP and healthy subjects, we applied spatial covariance analysis with bootstrapping to identify a PSP‐related pattern (PSPRP) and estimate its reliability, and evaluated the ability of network scores for differential diagnosis. We also detected regional metabolic differences using statistical parametric mapping analysis. We produced a highly reliable PSPRP characterized by relative metabolic decreases in the middle prefrontal cortex/cingulate, ventrolateral prefrontal cortex, striatum, thalamus and midbrain, covarying with relative metabolic increases in the hippocampus, insula and parieto‐temporal regions. PSPRP network scores correlated positively with PSP duration and accurately discriminated between healthy, PSP, MSA and PD groups in two separate cohorts of parkinsonian patients at both early and advanced stages. Moreover, PSP patients shared many overlapping areas with abnormal metabolism in the same cortical and subcortical regions as in the PSPRP. With rigorous cross‐validation, this study demonstrated highly comparable and reproducible PSP‐related metabolic topographies at network and regional levels across different patient populations and PET scanners. Metabolic brain network activity may serve as a reliable and objective marker of PSP, although cross‐validation applying recent diagnostic criteria and classification is warranted.     

Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy

Objectives: To compare subjective sleep perception, sleep architecture, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (PSP) to patients with Parkinson’s disease (PD).Methods: A comparative sleep study using the Parkinson’s Disease Sleep Scale (PDSS), the Mini-Mental State Examination (MMSE), and cardiorespiratory polysomnography on two consecutive nights with synchronized video recording. The study was undertaken in a sleep laboratory in a movement disorder center. Forty patients matched for age and cognition with probable PSP (n = 20, aged 71 ± 8 years, MMSE ? 24 in n = 7) and PD (n = 20, aged 69 ± 5 years, MMSE ? 24 in n = 8).Results: PDSS sum scores showed no difference between PSP and PD. PSP patients had significantly lower sleep efficiency (43.0 ± 15.0%) compared to PD patients (62.8 ± 19.1%) (p < 0.0008). Seventeen PSP patients and 19 PD patients had REM without atonia (RWA). Seven PSP patients and 13 PD patients had clinical RBD. The amount of RWA was lower in PSP (14.5 ± 17.3%) than in PD (44.6 ± 31.3%) (p < 0.0007). Eleven PSP and 11 PD patients were newly identified with sleep-disordered breathing (SDB).Conclusions: Polysomnographically recorded sleep is more severely impaired in PSP than in PD. PDSS ratings do not reflect the poorer sleep quality in PSP, possibly pointing to a specific neuropsychological profile. RWA and RBD are present in both neurodegenerative diseases. So far undetected SDB affects more than half of all patients in this study.