The Clinical Spectrum of ANO3-Report of a New Family and Literature Review.

BACKGROUND: Mutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood. CASES: We extensively characterize a new, large ANO3 family with six affected carriers. The proband is a young girl who had suffered from tremor and painful dystonic movements in her right arm since the age of 11 years. She later developed a diffuse dystonic tremor and mild extrapyramidal signs (ie, rigidity and hypodiadochokinesis) in her right arm. She also suffered from psychomotor delay and learning difficulties. Repeated structural and functional neuroimaging were unremarkable. A dystonic tremor was also present in her two sisters. Her paternal aunt, father, and a third older sister presented episodic postural tremor in the arms. The father and one sister also presented learning difficulties. The heterozygous p.G6V variant in ANO3 was identified in all affected subjects. LITERATURE REVIEW: Stratification by age at onset divided ANO3 cases into two major groups, where younger patients displayed a more severe phenotype, probably due to variants near the scrambling domain. CONCLUSIONS: We describe the phenotype of a new ANO3 family and highlight the need for functional studies to explore the impact of ANO3 variants on its phospholipid scrambling activity.

Can we add whey protein supplementation in patients with Parkinson's disease without interfering with levodopa response?

OBJECTIVE: The main endpoint of the study was to evaluate if a daily intake of whey protein-based dietary supplement causes a worse response to levodopa in people with Parkinson's Disease (PWPD). BACKGROUND: In PWPD, the competition between large neutral aminoacids and levodopa at intestinal absorption level may interfere with dopaminergic therapy's (DRT) effect; therefore, protein redistribution dietary regimen has been suggested. Many dietary supplementations are available to help people in balancing the protein intake and overcoming muscle mass loss. However, most of the products contain protein and could potentially affect levodopa action in PWPD. METHODS: We performed a randomised single blind monocentric study on PWPD admitted in the rehabilitative unit for a 4-week multidisciplined intensive aerobic rehabilitation treatment. All patients received a standard protein redistribution dietary regimen plus a whey protein-based oral formula (N = 26) or Magnesium (N = 25) twice daily for 28 days. Neurological assessment and physical evaluation were conducted before (T0) and after (T1) rehabilitative treatment; DRT was recorded T0 and T1 as well. The delta of changes within groups in neurological (UPDRS III) and physical (TUG, 6 MW) evaluation scales was compared between groups. RESULTS: Groups were comparable at baseline in clinical and demographic data; at T1, both groups showed a decrease in UPDRS III, TUG and 6 MWT and no differences between deltas were found. DRT remained stable in both groups. CONCLUSIONS: Our results show that whey protein supplementation does not interfere with DRT's efficacy and can be used in PWPD who need a protein supplementation without restrictions in intake hours.

Safety and Effectiveness of Cell Therapy in Neurodegenerative Diseases: Take-Home Messages From a Pilot Feasibility Phase I Study of Progressive Supranuclear Palsy.

Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field.

Hypomania, Depression, Euthymia: New Evidence in Parkinson's Disease.

The field related to mood disorders in Parkinson's disease (PD) is fragmented. The aim of this cohort observational study was to evaluate whether the episodes of mood alteration could appear in different disease stages and to verify how nonmotor symptoms were led off into different stages. We enrolled 93 PD outpatients (three groups: drug naive-DN; not exhibiting motor fluctuations-n-MF; and exhibiting motor fluctuations-MF) and 50 healthy controls. Mood state was assessed through the Internal State Scale (ISS) while depressive symptoms were evaluated through the Beck Depression Inventory-II (BDI-II), nonmotor symptoms by means of the Non-Motor Symptoms Scale (NMSS), and the presence of impulse control disorders (ICDs) with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Clinical and pharmacological data have also been recorded. No significant differences in mood state distribution between groups were observed. Nevertheless, as regards the mood state distribution within groups, in n-MF (47.6%) and MF patients (50%), (hypo)mania presence was significantly higher than other symptoms. In DN patients, hypomania showed a prevalence of 38.1% although it was not significant. At least one ICD was reported in 29.3% of n-MF and 50% of MF patients. In the MF group, a moderate positive correlation between ISS ACTivation subscale scores and the presence of ICDs and compulsive medication use emerged. Finally, MF patients reported higher BDI-II total scores than DN. Our results show that mood alterations in PD, considering both depressive symptoms and mood elevation, are related to the advanced stages of the disease as well as the presence of ICDs, and dopaminergic therapy would not always be able to restore a normal mood condition.

Divergent Thinking in Parkinsonism: A Case-Control Study.

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. We compared divergent thinking, a measure of creativity, in patients affected by progressive supranuclear palsy (PSP), other parkinsonian syndromes, and healthy controls (HCs). METHODS: Creativity features were evaluated using the Abbreviated Torrance Test for Adults (ATTA). Consecutive PSP outpatients 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.

Creative Thinking, Professional Artists, and Parkinson's Disease.

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.