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Introduction: Movement Disorder Society (MDS) new diagnostic criteria for Progressive Supranuclear palsy (PSP) identifying different disease phenotypes were recently released. The aim of the present study is to report on the cognitive and behavioral features of the different phenotypes diagnosed according to the MDS criteria. Methods: Forty-nine PSP patients underwent an extensive battery of clinical assessments. Differences between PSP subtypes were computed with χ2 or ANOVA tests. Using the z scores, subjects were classified as having normal cognition, mild cognitive impairment, single or multiple domain, and dementia. A logistic regression model was implemented to investigate the major determinants of PSP non-Richardson’s syndrome phenotype. Results: Half of the cohort presented Richardson’s syndrome (46.9%), followed by PSP with parkinsonism and corticobasal syndrome (22.4% and 14.2%, respectively). Richardson’s syndrome and PSP with corticobasal syndrome presented a similar burden of disease. The only cognitive testing differentiating the phenotypes weresemantic fluency and ideomotor apraxia. The majority of our cohort was either affected by dementia or presented normal cognition. Richardson’s syndrome presented the highest rate of dementia. The only marker of PSP non-Richardson’s syndrome phenotype was better performance in visuo-spatial testing, implying worse visuo-spatial abilities in PSP Richardson’s syndrome. Conclusion: Available clinical assessments hardly capture differences between PSP phenotypes. The cognitive testing differentiating the PSP phenotypes were semantic fluency and ideomotor apraxia. In PSP, mild cognitive impairment likely represents an intermediate step from normal cognition to dementia. The only marker of PSP non-Richardson’s syndrome phenotype was better performance in visuo-spatial testing.

Author(s): Stankovic, Iva; Fanciulli, Alessandra; Kostic, Vladimir S; Krismer, Florian; Meissner, Wassilios G; Palma, Jose Alberto; Panicker, Jalesh N; Seppi, Klaus; Wenning, Gregor K; MoDiMSA Study Group | Abstract: Background: Neuroimaging has been used to support a diagnosis of possible multiple system atrophy (MSA). Only blood pressure changes upon standing are included in the second consensus criteria but other autonomic function tests (AFT) are also useful to diagnose widespread and progressive autonomic failure typical of MSA. Additional diagnostic tools are of interest to improve accuracy of MSA diagnosis. Objectives: To assess the utility of diagnostic tools beyond brain imaging and AFT in enhancing a laboratory-supported diagnosis of MSA to support the upcoming revision of the consensus criteria. Methods: The International Parkinson and Movement Disorders Society MSA Study Group (MoDiMSA) performed a systematic review of original papers on biomarkers, sleep studies, genetic, neuroendocrine, neurophysiological, neuropsychological and other tests including olfactory testing and acute levodopa challenge test published before August 2019. Results: Evaluation of history of levodopa responsiveness and olfaction is useful in patients in whom MSA-parkinsonian subtype is suspected. Neuropsychological testing is useful to exclude dementia at time of diagnosis. Applicability of sphincter EMG is limited. When MSA-cerebellar subtype is suspected, a screening for the common causes of adult-onset progressive ataxia is useful, including spinocerebellar ataxias in selected patients. Diagnosing stridor and REM sleep behavior disorder is useful in both MSA subtypes. However, none of these tools are validated in large longitudinal cohorts of postmortem confirmed MSA cases. Conclusions: Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy.

BACKGROUND Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity. CONCLUSIONS GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.

Insulin-like growth factors (IGF-I and IGF-II) have been shown to have several neurotrophic actions and IGF sys-tem may be impaired in neurodegenerative disorders. The aim of this study was to investigate the IGF system in patients with MSA and to evaluate correlations between this endocrine sys-tem and clinical features of the disease. Serum levels of IGF-I, IGF-II, insulin, IGF-binding protein 1 (BP1), and IGF-binding protein 3 (BP3) were measured in 25 patients with probable MSA and 25 age, sex and BMI-matched healthy controls. Clin-ical status of each patient was evaluated with the Unified Mul-tiple System Atrophy Rating Scale (UMSARS) Part II and the Hoehn and Yahr rating scale. IGF-I levels were significantly higher in MSA (164.1 1 66.2 lg/L) than in healthy controls (111.7 1 60.3 lg/L; p 5 0.001). Insulin levels were signifi-cantly higher in MSA patients (21.9 6 14.4 lU/mL) than in healthy controls (13.3 6 5.1 lU/mL, p 5 0.048). No signifi-cant difference was found in serum IGF-II, IGF-BP1, and IGF-BP3 levels between patients with MSA an d healthy controls. There was a trend toward significantly higher IGF-II levels in MSA patients with UMSARS score < 2 6 (1026 .3 6 442.6 l g/L) than MSA patients with UMSARS score > 26 (796.1 6 234 l g/L , p 5 0.055). The results of this study d emonstrated that IGF system is altered in MSA. The d eg enerative process in MSA could lead to a c ompensatory increase in IGF-I and insulin in an attempt to provide additional su pport to degenerating neuro ns.

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 microg/L) than in both PD (8.74 +/- 0.98 microg/L) and PSP (6.64 +/- 0.82 microg/L) patients, and controls (8.59 +/- 0.44 microg/L). Growth hormone peaked later in PSP patients than in PD patients and controls. At a cut-off level of 4 microg/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

To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD.