Redefining Bradykinesia.

The value of neurofilament light chain (NfL) levels as a biomarker for the diagnosis and differential diagnosis in patients with Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) remains controversial. Furthermore, few studies have directly compared NfL levels among specific APS categories. This study aimed to compare cerebrospinal fluid (CSF) and blood NfL levels among PD, APS, other PD-related disorders, and controls, as well as rank NfL levels across these groups. PubMed, Embase, Web of Science, and the Cochrane Library were searched from the inception up to November 1st, 2024, to identify eligible studies reporting CSF or blood NfL concentrations in PD, PD dementia (PDD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS), vascular parkinsonism (VP), essential tremor (ET), idiopathic rapid eye movement sleep behavior disorder (iRBD), and controls. The Bayesian approach was utilized to estimate the standardized mean difference (SMD) and the associated 95% credible intervals (CrIs) of NfL levels. The surface under the cumulative ranking curve (SUCRA) was employed to evaluate the ranking probabilities of NfL levels. Subgroup analysis and meta-regression were conducted to explore the sources of heterogeneity. The present network meta-analysis (NMA) included 78 studies with 13,120 participants (4050 controls, 5021 PD, 191 PDD, 1173 MSA, 887 PSP, 1254 DLB, 319 CBS, 160 ET, 65 iRBD, and 0 VP). Of these, the NMA of CSF NfL included 34 studies with 6,013 participants, while the NMA of blood NfL included 49 studies with 7,787 participants. Both CSF and blood NfL levels were significantly elevated in patients with PD and APS compared to controls. Compared to PD patients, CSF NfL levels were significantly elevated in MSA (SMD 1.85; 95% CrI 1.55-2.15), CBS (1.42; 1.08-1.75), PSP (1.35; 1.06-1.64), and DLB 0.52; 0.20-0.85) patients. Similarly, blood NfL levels were significantly higher in patients with MSA (1.36; 1.02-1.71), PDD (1.19; 0.65-1.72), PSP (1.15; 0.77-1.54), CBS (0.92; 0.11-1.72), and DLB (0.63; 0.14-1.12) compared to PD. Among APS, CSF NfL levels in MSA patients were significantly higher than those in PSP, DLB, and CBS patients, while blood NfL levels in MSA patients were significantly higher only compared to DLB. In both CSF and blood NfL, MSA patients exhibited the highest probability of ranking first for NfL level elevations (CSF: SUCRA = 0.998; blood: SUCRA = 0.925). Age significantly influenced the SMD of the comparison between MSA and PD in CSF NfL (β = -0.15; p = 0.016). CSF and blood NfL levels in PD and APS are higher than those in controls, and all APS categories show higher levels than PD, suggesting that NfL levels may serve as a potential biomarker for the differential diagnosis between PD and APS. However, caution is warranted when using NfL as a diagnostic biomarker for PD. Significant differences in NfL levels are also observed between certain APS categories. Patients with MSA exhibit the highest NfL levels among PD and related disorders.

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

Parkinsonian disorders consist mostly of Parkinson’s disease (PD); other forms are relatively rare, although dementia with Lewy bodies (DLB) seems to be, after Alzheimer’s disease, one of the most common causes of dementia. Atypical parkinsonisms (other than idiopathic PD) include progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD) and DLB. In addition to parkinsonism symptoms the most characteristic features of these disorders, sometimes called parkinsonism-plus syndromes, are cerebellar ataxia in MSA, apraxia in CBD, gaze palsy in PSP or early in the course of dementia in DLB, and minimal, sometimes moderate (in MSA or PSP) or complete lack (in CBD) of response to L-dopa therapy. When appraising the condition, it is vital to separate it from those conditions that mimic the appearance of PD, but that are caused by another underlying pathology. Because of the lack of biological markers, differential diagnosis has to be based mostly on clinical findings. Nevertheless, neuroimaging studies, utilizing MRI, SPECT and PET examinations, seem to be helpful in establishing diagnosis. Nuclear medicine uses different tracers, specific for the dopamine transporting system or dopamine receptor ligands, which makes it possible to differentiate presynaptic dopaminergic system involvement (seen in PD) from pre- and postsynaptic involvement in MSA or PSP. Highly asymmetric tracer uptake reflects the asymmetry of cortical-subcortical atrophy and is characteristic for CBD. All of these conditions are accompanied by different psychiatric problems. In PD, depression is the most common, followed by dementia and psychosis at late stages. In PSP, subcortical dementia is typical with frontal behavior. Dementia is less frequent and late in CBD, but usually is the first or early symptom in DLB, followed by parkinsonian features. Functional neuroimaging may be useful for assessment of the preclinical period of PD (with potential early neuroprotective therapy), the rate of progression (evaluation of the influence of drugs and stereotaxic surgery on disease progression), the role of different structures in late complications (dyskinesias, fluctuations), and differential diagnosis of PD with essential tremor and atypical parkinsonian disorders. These techniques may also be helpful for investigation of pathogenesis and pathology underlying the non-motor symptoms of PD and atypical parkinsonisms as depression, dementia and psychosis. This review summarizes recent applications of SPECT, PET, but also MRI in the study of parkinsonian disorders, in terms of differential diagnosis and understanding concomitant neuropsychiatric phenomena.

Dysarthria and dysphagia are known to occur in parkinsonian syndromes such as Parkinson disease (PD), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Differences in the evolution of these symptoms have not been studied systematically in postmortem-confirmed cases. To study differences in the evolution of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. Eighty-three pathologically confirmed cases (PD, n = 17; MSA, n = 15; DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis for a multicenter clinicopathological study organized by the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Cases with enough clinicopathological documentation for the purpose of the study were selected from research and neuropathological files of 7 medical centers in 4 countries (Austria, France, England, and the United States). Median dysarthria latencies were short in PSP and MSA (24 months each), intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months). Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months), and long in PD (130 months). Dysarthria or dysphagia within 1 year of disease onset was a distinguishing feature for atypical parkinsonian disorders (APDs) (specificity, 100%) but failed to further distinguish among the APDs. Survival time after onset of a complaint of dysphagia was similar in PD, MSA, and PSP (15 to 24 months, P =.7) and latency to a complaint of dysphagia was highly correlated with total survival time (rho = 0.88; P<.001) in all disorders. Latency to onset of dysarthria and dysphagia clearly differentiated PD from the APDs, but did not help distinguish different APDs. Survival after onset of dysphagia was similarly poor among all parkinsonian disorders. Evaluation and adequate treatment of patients with PD who complain of dysphagia might prevent or delay complications such as aspiration pneumonia, which in turn may improve quality of life and increase survival time.

Phosphorylated α-synuclein and phosphorylated tau-protein in sural nerves may contribute to differentiate Parkinson’s disease from multiple system atrophy and progressive supranuclear paralysis

Clinical diagnosis of multiple system atrophy is challenging and many patients with Lewy body disease (i.e. Parkinson's disease or dementia with Lewy bodies) or progressive supranuclear palsy are misdiagnosed as having multiple system atrophy in life. The clinical records of 203 patients with a clinical diagnosis of multiple system atrophy were reviewed to identify diagnostic pitfalls. We also examined 12 features supporting a diagnosis of multiple system atrophy (red flag features: orofacial dystonia, disproportionate antecollis, camptocormia and/or Pisa syndrome, contractures of hands or feet, inspiratory sighs, severe dysphonia, severe dysarthria, snoring, cold hands and feet, pathological laughter and crying, jerky myoclonic postural/action tremor and polyminimyoclonus) and seven disability milestones (frequent falls, use of urinary catheters, wheelchair dependent, unintelligible speech, cognitive impairment, severe dysphagia, residential care). Of 203 cases, 160 (78.8%) were correctly diagnosed in life and had pathologically confirmed multiple system atrophy. The remaining 21.2% (43/203) had alternative pathological diagnoses including Lewy body disease (12.8%; n = 26), progressive supranuclear palsy (6.4%; n = 13), cerebrovascular diseases (1%; n = 2), amyotrophic lateral sclerosis (0.5%; n = 1) and cerebellar degeneration (0.5%; n = 1). More patients with multiple system atrophy developed ataxia, stridor, dysphagia and falls than patients with Lewy body disease; resting tremor, pill-rolling tremor and hallucinations were more frequent in Lewy body disease. Although patients with multiple system atrophy and progressive supranuclear palsy shared several symptoms and signs, ataxia and stridor were more common in multiple system atrophy. Multiple logistic regression analysis revealed increased likelihood of multiple system atrophy versus Lewy body disease and progressive supranuclear palsy if a patient developed orthostatic hypotension or urinary incontinence with the requirement for urinary catheters [multiple system atrophy versus Lewy body disease: odds ratio (OR): 2.0, 95% confidence interval (CI): 1.1-3.7, P = 0.021; multiple system atrophy versus progressive supranuclear palsy: OR: 11.2, 95% CI: 3.2-39.2, P < 0.01]. Furthermore, autonomic dysfunction within the first 3 years from onset can differentiate multiple system atrophy from progressive supranuclear palsy (multiple system atrophy versus progressive supranuclear palsy: OR: 3.4, 95% CI: 1.2-9.7, P = 0.023). Multiple system atrophy patients with predominant parkinsonian signs had a higher number of red flag features than patients with Lewy body disease (OR: 8.8, 95% CI: 3.2-24.2, P < 0.01) and progressive supranuclear palsy (OR: 4.8, 95% CI: 1.7-13.6, P < 0.01). The number of red flag features in multiple system atrophy with predominant cerebellar signs was also higher than in Lewy body disease (OR: 7.0, 95% CI: 2.5-19.5, P < 0.01) and progressive supranuclear palsy (OR: 3.1, 95% CI: 1.1-8.9, P = 0.032). Patients with multiple system atrophy had shorter latency to reach use of urinary catheter and longer latency to residential care than progressive supranuclear palsy patients, whereas patients with Lewy body disease took longer to reach multiple milestones than patients with multiple system atrophy. The present study has highlighted features which should improve the ante-mortem diagnostic accuracy of multiple system atrophy.

Introduction Parkinsonian syndromes of different nature feature autonomic nervous system dysfunction (ANSd) which may herald or follow motor symptoms (MS) in Parkinson disease (PD), but anticipate by years and progress more rapidly in multiple system atrophy (MSA). Abnormal Heart Rate Variability (HRV) has been reported in both PD and MSA. Purpose This study aimed to evaluating if HRV analysis (HRVa) could contribute to differentiate PD from MSA and to guide early and more appropriate treatment and prognostic assessment. Methods 66 consecutive parkinsonian patients (pts) (48 males, 18 females) (mean age 63.8±10 y) were enrolled between 2010 and 2020. Initial clinical diagnosis was MSA (19), PD (20), PD with autonomic impairment (PD-AI) (10), Lewy body disease (2), supranuclear palsy (3), undefined Parkinsonism (UP) (12). The severity of MS was quantified with UPDRS and Hoehn/Yahr scales. HRV was analyzed with linear (TD and FD) and non-linear (NL) methods (Kubios Premium 3.4.1), during daily activity and NREM sleep (2-minutes intervals) and during REM sleep (1-minute Interval). 44/66 underwent also ASN functional evaluation with the Ewing protocol. Data of 52 age-matched healthy subjects (HS) were used for comparison. For statistical analysis, SPSS software (version 21) was used. Discriminant Analysis (DA) was applied to identify the more relevant parameters differentiating PD from MSA and classifying “undefined” cases. Prolonged follow-up (f-up) provided clinical diagnostic certainty, as goldstandard for validation of HRVa classification accuracy. Results UPDRS and Hoehn/Yahr scores were higher in MSA than in PD (p&amp;lt;0.0001). Along 10-years of f-up, 16/66 pts died (56,2% MSA), 5/66 had new diagnostic definition, and 15/66 were lost to f-up. Most of HRV parameters of 34 pts with certain diagnosis (17 MSA and 17 PD) whose f-up was completed, were significantly different from those of HS. VLFpower and recurrence plot parameters calculated during active wakefulness were different (p&amp;lt;0.05) between MSA and PD, and correctly classified them with 88,2% predictive accuracy (PA) at DA, according to the formula: F1 = (vlfpw%ar* − 0,087) + (rprec* − 0,319) + (rpshen*10.81) + (−20,53) Comparative classification accuracy of HRVa, Ewing score, UPDRS and Hoehn/Yahr scales is shown in Table 1. Attempting prognostic risk assessment by applying F1 to HRV data of pts with PD-AI and of pts with UP, those classified as MSA according to F1 showed the worst clinical outcome during the f-up. Conclusions This study confirms that a higher degree of prevailing sympathetic ASNd in MSA compared to PD can be identified by a combination of Linear and NL HRV parameters, and correctly differentiate with high (88,2%) predictive accuracy all pts with certain diagnosis verified during prolonged f-up. Moreover, HRVa might be useful for earlier prognostic stratification of pts with parkinsonian symptoms of uncertain nature and to improve clinical and pharmacological management. Funding Acknowledgement Type of funding sources: None.

Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD. This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer disease (CBS-AD), and CBS-non-AD. Data were analyzed from February 1, through May 1, 2019. Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures. A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n = 76) and patients with PD (n = 1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS-non-AD group (AUC, 0.80-0.87; P < .05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P < .05). These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.

Rhythmic auditory cueing (RAC) can improve gait parameters in neurological disorders such as Parkinson's disease and stroke. However, there is a lack of research on the effects of RAC in patients with atypical parkinsonian disorders (APD). Using a smartphone metronome application, we aimed to investigate the immediate effects of RAC in patients with clinically diagnosed APD, namely Progressive Supranuclear Palsy (PSP-Richardson Syndrome and other variants, PSP-nonRS), Corticobasal Syndrome (CBS), Multiple System Atrophy (MSA), and Dementia with Lewy Bodies (DLB). A total of 46 APD participants (25 PSP, 9 CBS, 8 MSA and 4 DLB; age: mean = 70.17, standard deviation = 7.15) walked at their preferred pace for 2 min without any rhythmic auditory cueing (RAC). Participants then walked the same path for another 2 min with RAC set at a tempo 10% faster than the baseline cadence of each participant. After a 10–15-min break, participants walked the same path for another 2 min without RAC to observe for carryover effects. Gait parameters [cadence (steps/minute), gait velocity (meters/minute), and stride length (centimeters)] were collected at baseline, during RAC, and post-RAC. There was a significant improvement in cadence in all participants from baseline to during RAC and post-RAC (corrected p-values = 0.009 for both). Gait velocity also improved from baseline to during RAC and post-RAC in all participants, although this improvement was not significant after correcting for multiple comparisons. The changes in cadence and gait velocity were most pronounced in PSP. In addition, our exploratory analysis showed that the cadence in the suspected TAU group (PSP+CBS) showed a significant improvement from baseline to during RAC and post-RAC (corr. p-value = 0.004 for both). This pilot study using short-term RAC in APD patients demonstrated improvements in cadence and velocity. There is an urgent need for effective gait rehabilitation modalities for patients with APD, and rhythmic cueing can be a practical and useful intervention to improve their gait pattern.

Somatoform disorders have only recently been described in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Of 1,210 patients with neurodegenerative diseases referred to our institutions from 1999, 488 were diagnosed with PD, 415 with Alzheimer’s disease, 162 with DLB, 48 with progressive supranuclear palsy, 48 with multiple system atrophy, and 49 with frontotemporal dementia. Rates of somatoform disorder were considerably higher in DLB (18%) and PD (7.5%) than in any other group (0–2%). Somatoform disorders in PD and DLB were characterized by motor and non-motor patterns with bizarre presentations, and were often accompanied by catatonic signs (41%). In 77%, they preceded PD motor signs by 6–120 months, and in 86%, they were recurrent at follow-up. In 91%, there was preceding or concomitant hypochondriasis. Global cognitive decline was greater in PD with somatoform disorder than without (p < 0.001), comparable to that observed in the DLB group. The phenomenology suggests a blurred boundary between somatoform disorder and psychosis (somatic delusions). The presence of somatoform disorder may identify a subgroup of PD patients with distinctive clinical symptoms, including catatonic features and a poor cognitive outcome.

Objectives To assess the value of external anal sphincter electromyography (EASEMG) in evaluating the related autonomic dysfunction in Parkinson's disease ( PD), parkinsonism dominant multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP). Methods From the records of EAS-EMG collected in our lab (total 562 cases), 60 PD (male 41, female 19), 68 MSA-P (male 35,female 33) and 13 PSP (male 10, female 3) were included in the analysis in this study. Mean duration,polyphasic ratio and satellite potential occurrence rate were comparable among the groups. Mean duration prolongation were graded as normal ( ＜ 10.0 ms), mild ( 10.0-11.9 ms), moderate ( 12.0-13.9 ms)and severe ( ≥ 14.0 ms). Results Among all related autonomic symptoms, the occurrence rate of constipation, urinary incontinence, urgency and frequency in patients with MSA-P(95.8% (23/24) ,94.6% (53/56) ,87.7% ( 50/57 ), 85.7% (42/49), 76.5% ( 39/51 ) ) were higher than that of PD ( 61.5%(16/26), 62.3% (33/53), 30.6% (15/49), 46.2% (24/52), 45.7% (21/46)) and PSP (75.0%(3/4) , 62.5% (5/8), 50.0% (4/8), 42.9% (3/7), 42.9% (3/7)). The abnormal rate of EAS-EMG in PD, MSA-P and PSP were 60.0%, 94.2% and 84.6%, accordingly. Mean duration ( PD ( 12.0 ± 1.6)ms, MSA-P (15.4±3.0) ms, PSP (13.8±1.8) ms), polyphasic ratio (PD 46.2% ±19.2%, MSA-P 63.9% ± 15.8%, PSP 51.5% ± 12.1% ) and satellite potential occurrence rate ( PD 9.5% ± 8.3%,MSA-P 26.5% ± 15.9%, PSP 19.2% ± 12.5% ) varied significantly different among the groups ( F =31.724, F = 17.412, x2 =45. 335, all P ＜0.01 ). Severe mean duration prolongation was overwhelming in MSA-P (66.2% ) , compared with mild 10.3% and moderate 23.5%. The predominant prolongation degree was moderate in PSP (61.5%, mild 7.7%, severe 30.8% ), and mild in PD (36.7%, moderate 36.7% ,severe 11.7%, normal 15.0% ). Conclusions EAS-EMG could play a role in evaluating the related autonomic dysfunctions in PD, MSA-P and PSP. The EAS-EMG impairment was severe and frequent in MSA-P, mild and infrequent in PD, moderate in PSP. The spectrum of mean duration prolongation suggested the possibility of Onuf's nucleus involvement in these diseases. Key words: Parkinson disease; Multiple system atrophy; Supranuelear palsy progressive; Anal canal; Electromyography; Autonomic nervous system

Enteric glial cells (EGCs) are in many respects similar to astrocytes of the central nervous system and express similar proteins including glial fibrillary acidic protein (GFAP). Changes in GFAP expression and/or phosphorylation have been reported during brain damage or central nervous system degeneration. As in Parkinson's disease (PD) the enteric neurons accumulate α-synuclein, and thus are showing PD-specific pathological features, we undertook the present survey to study whether the enteric glia in PD become reactive by assessing the expression and phosphorylation levels of GFAP in colonic biopsies. Twenty-four PD, six progressive supranuclear palsy (PSP), six multiple system atrophy (MSA) patients, and 21 age-matched healthy controls were included. The expression levels and the phosphorylation state of GFAP were analyzed in colonic biopsies by western blot. Additional experiments were performed using real-time PCR for a more precise analysis of the GFAP isoforms expressed by EGCs. We showed that GFAPκ was the main isoform expressed in EGCs. As compared to control subjects, patients with PD, but not PSP and MSA, had significant higher GFAP expression levels in their colonic biopsies. The phosphorylation level of GFAP at serine 13 was significantly lower in PD patients compared to control subjects. By contrast, no change in GFAP phosphorylation was observed between PSP, MSA and controls. Our findings provide evidence that enteric glial reaction occurs in PD and further reinforce the role of the enteric nervous system in the initiation and/or the progression of the disease. We showed that GFAP is over-expressed and hypophosphorylated in the enteric glial cells (EGCs) of Parkinson's disease (PD) patients as compared to healthy subjects and patients with atypical parkinsonism (MSA, multiple system atrophy and PSP, progressive supranuclear palsy). Our findings provide evidence that enteric glial reaction occurs in PD but not in PSP and MSA and further reinforce the role of the enteric nervous system in the pathophysiology of PD.

Hashimoto's encephalopathy with serum anti-NH2-terminal of α-enolase (NAE) antibodies occasionally displays clinical symptoms such as cerebellar ataxia and parkinsonism. We studied the frequency of anti-NAE antibodies in patients with Parkinson-plus syndrome. We examined the positive rates of anti-NAE antibodies in 47 patients with multiple system atrophy (MSA), 29 patients with Parkinson's disease (PD), eight patients with corticobasal syndrome (CBS), and 18 patients with progressive supranuclear palsy (PSP) using conventional immunoblot analysis. Positive anti-NAE antibody rates of 31.9%, 10.3%, 50.0%, and 11.1% were reported in the MSA, PD, CBS, and PSP patients, respectively. The duration from onset to a wheelchair-bound state in seropositive MSA patients tended to be shorter than that in seronegative MSA patients. Anti-NAE antibodies are detected in some patients clinically diagnosed with MSA and CBS. Although its pathophysiological significance remains uncertain, serum anti-NAE antibodies might represent a prognostic marker in the clinical course of MSA.

Differential patterns of central synucleinopathy and catecholaminergic abnormalities in Lewy body diseases and multiple system atrophy.

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer's disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antibody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.