Enteric GFAP expression and phosphorylation in Parkinson's disease.

Redefining Bradykinesia.

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

Magnetic resonance imaging (MRI) paired with appropriate disease-specific machine learning holds promise for the clinical differentiation of Parkinson disease (PD), multiple system atrophy (MSA) parkinsonian variant, and progressive supranuclear palsy (PSP). A prospective study is needed to test whether the approach meets primary end points to be considered in a diagnostic workup. To assess the discriminative performance of Automated Imaging Differentiation for Parkinsonism (AIDP) using 3-T diffusion MRI and support vector machine (SVM) learning. This was a prospective, multicenter cohort study conducted from July 2021 to January 2024 across 21 Parkinson Study Group sites (US/Canada). Included were patients with PD, MSA, and PSP with established criteria and unanimous agreement in the clinical diagnosis among 3 independent, blinded neurologists who specialize in movement disorders. Patients were assigned to a training set or an independent testing set. MRI. Area under the receiver operating characteristic curve (AUROC) in the testing set for primary model end points of PD vs atypical parkinsonism, MSA vs PSP, PD vs MSA, and PD vs PSP. AIDP was also paired with antemortem MRI to test against postmortem neuropathology in a subset of autopsy cases. A total of 316 patients were screened and 249 patients (mean [SD] age, 67.8 [7.7] years; 155 male [62.2%]) met inclusion criteria. Of these patients, 99 had PD, 53 had MSA, and 97 had PSP. A retrospective cohort of 396 patients (mean [SD] age, 65.8 [8.9] years; 234 male [59.1%]) was also included. Of these patients, 211 had PD, 98 had MSA, and 87 had PSP. Patients were assigned to the training set (78%; 104 prospective, 396 retrospective) or independent testing set, which included 145 (22%; 60 PD, 27 MSA, 58 PSP) prospective patients (mean age, 67.4 [SD 7.7] years; 95 male [65.5%]). The model was robust in differentiating PD vs atypical parkinsonism (AUROC, 0.96; 95% CI, 0.93-0.99; positive predictive value [PPV], 0.91; negative predictive value [NPV], 0.83), MSA vs PSP (AUROC, 0.98; 95% CI, 0.96-1.00; PPV, 0.98; NPV, 0.81), PD vs MSA (AUROC, 0.98; 95% CI, 0.96-1.00; PPV, 0.97; NPV, 0.97), and PD vs PSP (AUROC, 0.98; 95% CI, 0.96-1.00; PPV, 0.92; NPV, 0.98). AIDP predictions were confirmed neuropathologically in 46 of 49 brains (93.9%). This prospective multicenter cohort study of AIDP met its primary end points. Results suggest using AIDP in the diagnostic workup for common parkinsonian syndromes.

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.

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

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.

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.

The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P < 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-β42 in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-β42 in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia.

The early pathogenesis of Parkinson's disease (PD) and the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) is poorly understood, but presynaptic and axonal dysfunction are hypothesized to play a prominent role. To identify synapse- and/or axonal dysfunction as indicated by cerebrospinal fluid (CSF) biomarker profiles and their clinical correlates in early-stage PD, MSA, and PSP. Liquid chromatography mass spectrometry and enzyme-linked immunosorbent assay analyses of CSF samples from patients with early-stage PD (n=38), MSA (n=21), or PSP (n=19), and age-matched, neurologically healthy controls (n=30). Compared to controls, patients with early parkinsonian disorders had significantly reduced CSF levels of the synapse-associated proteins neuronal pentraxin-1 (NPTX1), amyloid precursor protein, and β-amyloid 42 (Aβ42), as well as the neurosecretory granin-derived proteins secretogranin-II, chromogranin-A, and secretogranin-VII. Among these, synapse-associated proteins correlated with non-motor features, while none correlated with age. CSF levels of the predominantly axonal proteins neurofilament light (NfL) and tau were elevated in patients with MSA or PSP. Reduced NPTX1 and Aβ42 distinguished PD from PSP, while elevated NfL and tau distinguished PSP and/or MSA from PD. Low CSF levels of biomarkers associated with synaptic and neurosecretory function (e.g., NPTX1) implicate age-independent synaptic dysfunction as a shared, early feature in the pathogenesis of PD, MSA, and PSP. Such biomarkers may be particularly sensitive correlates of early non-motor dysfunction. Early axonal dysfunction is more pronounced in PSP and MSA than in PD.

Diagnosis of atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), rely on clinical criteria that often result in misclassification or delayed confirmation. Cerebrospinal fluid (CSF) metabolomics offers the potential to identify disease-specific biochemical "fingerprints". The aim of the study is to identify CSF metabolomic biomarkers that distinguish PSP and MSA from each other and from non-neurodegenerative controls. Targeted mass spectrometry-based metabolomics was performed on CSF samples from 30 patients with MSA, 41 with PSP, and 30 age- and sex-matched non-neurodegenerative controls. Global metabolomic profiles showed no clear group separation. Both PSP and MSA showed elevated gut-derived metabolites p-cresyl sulfate and deoxycholic acid versus controls. In PSP, decreased cortisone and increased hexosylceramide d18:1/24:1 were observed, whereas in MSA, dihydroxyphenylalanine was elevated alongside homoarginine and creatinine. In the direct comparison of APS, levels of α-aminoadipic acid were increased in PSP compared to MSA. Pathway analysis highlighted disrupted glycerophospholipid metabolism in both APS disorders. Distinct metabolite panels mainly combining membrane-associated lipids, gut-derived and neurotransmitter-related metabolites demonstrated high diagnostic accuracy for distinguishing PSP and MSA from control groups (AUC = 0.95 for PSP and AUC = 0.98 for MSA), while a separate panel showed moderate performance in differentiating PSP from MSA (AUC = 0.85). Distinct but partially overlapping CSF metabolomic profiles characterize PSP and MSA. These metabolomic fingerprints highlight gut-brain axis involvement, alterations in cell membrane-related lipid metabolism, and disease-specific changes in neurotransmitter-related metabolites. Further, a panel of these metabolites showed strong potential as diagnostic biomarkers.

Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.(ABSTRACT TRUNCATED AT 250 WORDS)

IntroductionTo determine an exploratory multimodal approach including serum NFL and MR planimetric measures to discriminate Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). MethodsMR planimetric measurements and NFL serum levels, with a mean time interval of 60 months relative to symptom onset, were assessed in a retrospective cohort of 11 progressive supranuclear palsy (PSP), 22 Parkinson's disease (PD), 16 multiple system atrophy (MSA) patients and 42 healthy controls (HC). A decision tree model to discriminate PD, PSP, and MSA was constructed using receiver operating characteristic curve analysis and Classification and Regression Trees algorithm. ResultsOur multimodal decision tree provided accurate differentiation of PD versus MSA and PSP patients using a serum NFL cut-off of 14.66 ng/L. The pontine-to-midbrain-diameter-ratio (Pd/Md) discriminated MSA from PSP at a cut-off value of 2.06. The combined overall diagnostic yield was an accuracy of 83.7% (95% CI 69.8–90.8%). ConclusionWe provide a clinically feasible decision algorithm which combines serum NFL levels and a planimetric MRI marker to differentiate PD, MSA and PSP with high diagnostic accuracy. Classification of evidenceThis study provides Class III evidence that the combination of serum NFL levels und MR planimetric measurements discriminates between PD, PSP and MSA.

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.

Magnetic resonance imaging (MRI) techniques, such as quantitative susceptibility mapping (QSM) and susceptibility-weighted imaging (SWI), can detect iron deposition in the brain. Iron accumulation in the putamen (PUT) can contribute to the pathogenesis of Parkinson's disease (PD) and atypical Parkinsonian disorders. This systematic review aimed to synthesize evidence on iron deposition in the PUT assessed by MRI susceptibility techniques in PD and Parkinsonism syndromes. The PubMed and Scopus databases were searched for relevant studies. Thirty-four studies from January 2007 to October 2023 that used QSM, SWI, or other MRI susceptibility methods to measure putaminal iron in PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and healthy controls (HCs) were included. Most studies have found increased putaminal iron levels in PD patients versus HCs based on higher quantitative susceptibility. Putaminal iron accumulation correlates with worse motor scores and cognitive decline in patients with PD. Evidence regarding differences in susceptibility between PD and atypical Parkinsonism is emerging, with several studies showing greater putaminal iron deposition in PSP and MSA than in PD patients. Alterations in putaminal iron levels help to distinguish these disorders from PD. Increased putaminal iron levels appear to be associated with increased disease severity and progression. Thus, magnetic susceptibility MRI techniques can detect abnormal iron accumulation in the PUT of patients with Parkinsonism. Moreover, quantifying putaminal susceptibility may serve as an MRI biomarker to monitor motor and cognitive changes in PD and aid in the differential diagnosis of Parkinsonian disorders.

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.