The trophic, anti-apoptotic and regenerative effects of bone marrow mesenchymal stromal cells (MSC) may reduce neuronal cell loss in neurodegenerative disorders. We used MSC as a novel candidate therapeutic tool in a pilot phase-I study for patients affected by progressive supranuclear palsy (PSP), a rare, severe and no-option form of Parkinsonism. Five patients received the cells by infusion into the cerebral arteries. Effects were assessed using the best available motor function rating scales (UPDRS, Hoehn and Yahr, PSP rating scale), as well as neuropsychological assessments, gait analysis and brain imaging before and after cell administration. One year after cell infusion, all treated patients were alive, except one, who died 9 months after the infusion for reasons not related to cell administration or to disease progression (accidental fall). In all treated patients motor function rating scales remained stable for at least six-months during the one-year follow-up. We have demonstrated for the first time that MSC administration is feasible in subjects with PSP. In these patients, in whom deterioration of motor function is invariably rapid, we recorded clinical stabilization for at least 6 months. These encouraging results pave the way to the next randomized, placebo-controlled phase-II study that will definitively provide information on the efficacy of this innovative approach. Trial registration ClinicalTrials.gov NCT01824121

Background: An increase in artistic-like production in Parkinson’s disease (PD) has been associated with compulsive and repetitive behaviours after the introduction of dopaminergic treatment (DT). Recent data suggest that it could be due to the emergence of artistic-like skills triggered by DT. Objective: In order to evaluate whether artistic production and creative thinking are influenced by DT or linked to artistic-like skills, we characterize creativity features in PD and healthy controls (HC) including professional artists. Methods: Three groups of PD out-patients were included consecutively: professional artists (PD-A), patients with (PD-C) and without artistic-like production (PD-NC). Twenty-four gender and age-matched HC were included: professional artists (HC-A) and non-artists (HC-NC). All patients were evaluated by means of a) a battery of neuropsychological tests and a semi-structured interview; b) the Abbreviated Torrance Test for Adults (ATTA) for creative thinking; c) the Minnesota Impulsive Disorders Interview (mMIDI) and a screening for impulse control disorders (ICDs) for compulsive behaviour. Results: ATTA total score was significantly higher in HC-A and PD-A than in the other groups. Although PD-NC showed the lowest ATTA total score the difference vs HC-NC was not significant. ATTA scores were not significantly correlated with DT dosage and duration. mMIDI tests were positive only in PD. There were no differences in ICDs among PD groups. Conclusions: Our results do not support a relationship between DT and the emergence of artistic creativity. We believe that DT may increase the drive to create and that further studies in “on” and “off” medication are needed to clarify this issue.

The assessment of cognitive deficits is pivotal for diagnosis and management in patients with parkinsonisms. Low levels of correspondence are observed between evaluations assessed with screening cognitive tests in comparison with those assessed with in-depth neuropsychological batteries. A new tool, we named CoMDA (Cognition in Movement Disorders Assessment), was composed by merging Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery (FAB). In total, 500 patients (400 with Parkinson’s disease, 41 with vascular parkinsonism, 31 with progressive supranuclear palsy, and 28 with multiple system atrophy) underwent CoMDA (level 1–L1) and in-depth neuropsychological battery (level 2–L2). Machine learning was developed to classify the CoMDA score and obtain an accurate prediction of the cognitive profile along three different classes: normal cognition (NC), mild cognitive impairment (MCI), and impaired cognition (IC). The classification accuracy of CoMDA, assessed by ROC analysis, was compared with MMSE, MoCA, and FAB. The area under the curve (AUC) of CoMDA was significantly higher than that of MMSE, MoCA and FAB (p < 0.0001,p = 0.028 andp = 0.0007, respectively). Among 15 different algorithmic methods, the Quadratic Discriminant Analysis algorithm (CoMDA-ML) showed higher overall-metrics performance levels in predictive performance. Considering L2 as a 3-level continuous feature, CoMDA-ML produces accurate and generalizable classifications: micro-average ROC curve, AUC = 0.81; and AUC = 0.85 for NC, 0.67 for MCI, and 0.83 for IC. CoMDA and COMDA-ML are reliable and time-sparing tools, accurate in classifying cognitive profile in parkinsonisms.This study has been registered on ClinicalTrials.gov (NCT04858893).

Background: Creativity is a multidimensional phenomenon and an important component of human capacities. This ability is characterized by the involvement of several cognitive functions particularly linked to the prefrontal cortex (PFC). We compared divergent thinking (DT), a measure of creativity, in patients affected by Progressive Supranuclear Palsy (PSP), other parkinsonian syndromes and healthy controls (HC). Methods: Creativity features were evaluated using the Abbreviated Torrance Test for Adults (ATTA). Consecutive PSP out-patients were screened for inclusion. Then, patients with Multiple System Atrophy (MSA) and Parkinson’s Disease (PD) and a group of HC were studied. All groups have preserved cognitive functions and were matched for gender, education, disease duration, and age at onset with exception of PD patients who were matched by disease severity rather than disease duration. Results: PSP patients were characterized by lower values in total ATTA and all subscales than HC and both MSA and PD patients. No differences were found comparing HC versus both MSA and PD patients. PSP patients were characterized by more impaired frontal functioning (assessed by means of Frontal Assessment Battery-FAB) than HC and both PD and MSA patients. Conclusion: In the present study ATTA was significantly lower in PSP patients than in the other study groups. The worst performance in ATTA-total score and the lower score in FAB in PSP patients support the role of frontal function in creative processes.

Background: The outcome of levodopa/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of GBA1 mutations (GBA‐PD) remains uncertain.Objective: To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on GBA1 variants.Methods: This multicenter, retrospective, longitudinal “real‐world” study included consecutive patients with advanced PD treated with LCIG at 31 Italian centers; data were collected at baseline, 1‐, 5‐year, and last‐available follow‐up.Results: Data from 512 PD patients (59% male, mean age and disease duration at LCIG initiation 67.0 ± 8.0 and 12.9 ± 5.0 years, respectively) were analyzed. GBA1 genotyping was available for 306 patients (60%), of whom 40 (13%) had GBA1 mutations or risk variants. Mean follow‐up on LCIG was 3.9 ± 2.9 years; 5‐year follow‐up data were available for 159 subjects. At baseline, GBA‐PD had a younger age, shorter PD duration, worse cognition, and more hallucinations than noncarriers. At 1‐ and 5‐year follow‐up, LCIG improved motor and non‐motor symptoms, OFF‐time, and dyskinesias in the entire population. In GBA‐PD, MDS‐UPDRS parts I, II, and III scores did not change, while part IV score improved significantly less than in noncarriers; cognition and orthostatic hypotension symptoms worsened more rapidly. Multivariate analysis of predictors for adverse events and LCIG discontinuation found no significant contribution from GBA1 mutation status.Conclusions: GBA1 status does not increase the risk of adverse events or LCIG discontinuation. LCIG is a safe option for advanced GBA‐PD, even in patients with cognitive impairment at baseline. However, GBA‐PD experiences lower efficacy on motor disability and complications and faster cognitive decline than noncarriers.