The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment

The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson's disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment

Cognitive and Neurophysiological Effects of Non-invasive Brain Stimulation in Stroke Patients after Motor Rehabilitation.

The primary aim of this study was to evaluate and compare the effectiveness of two specific Non-Invasive Brain Stimulation (NIBS) paradigms, the repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial Direct Current Stimulation (tDCS), in the upper limb rehabilitation of patients with stroke. Short and long term outcomes (after 3 and 6 months, respectively) were evaluated. We measured, at multiple time points, the manual dexterity using a validated clinical scale (ARAT), electroencephalography auditory event related potentials, and neuropsychological performances in patients with chronic stroke of middle severity. Thirty four patients were enrolled and randomized. The intervention group was treated with a NIBS protocol longer than usual, applying a second cycle of stimulation, after a washout period, using different techniques in the two cycles (rTMS/tDCS). We compared the results with a control group treated with sham stimulation. We split the data analysis into three studies. In this first study we examined if a cumulative effect was clinically visible. In the second study we compared the effects of the two techniques. In the third study we explored if patients with minor cognitive impairment have most benefit from the treatment and if cognitive and motor outcomes were correlated. We found that the impairment in some cognitive domains cannot be considered an exclusion criterion for rehabilitation with NIBS. ERP improved, related to cognitive and attentional processes after stimulation on the motor cortex, but transitorily. This effect could be linked to the restoration of hemispheric balance or by the effects of distant connections. In our study the effects of the two NIBS were comparable, with some advantages using tDCS vs. rTMS in stroke rehabilitation. Finally we found that more than one cycle (2-4 weeks), spaced out by washout periods, should be used, only in responder patients, to obtain clinical relevant results

Instrumented Gait Analysis for an Objective Pre-/Postassessment of Tap Test in Normal Pressure Hydrocephalus

Objective: To present an objective method to evaluate gait improvements after tap test in idiopathic normal pressure hydrocephalus (iNPH). Tap test is often used to prognosticate shunt responsiveness, although test accuracy is limited by the lack of quantitative outcome measures. Design: Retrospective analysis of gait data. Setting: Public tertiary care center, day hospital. Gait analysis was performed before and 2-4 hours after tap test. Participants: 60 iNPH patients and 50 age and sex matched controls (used to obtain reference intervals). From an initial referred sample of 79 patients, we excluded those unable to walk without walking aids (n = 9) or with incomplete (pre/post tap test) gait data (n=10). Thirteen out of 60 patients were shunted and then reappraised after 6 months. Intervention: Not applicable. Main Outcome Measures: Mahalanobis distance from controls, before and after tap test. Eleven gait parameters were combined in a single quantitative score. Walking velocity was also evaluated, since it is frequently used in tap test assessment. Results: Patients were classified as: (A) tap test responders (n=22 patients, 9 of them were shunted), or (B) not suitable for shunt (n=38 patients, 4 of them were shunted). In group A, 9 out of 9 patients improved after shunt. In group B, 3 out of 4 patients did not improve. Gait velocity increased after tap test in 53% of responders and in 37% of patients not suitable for shunt. Conclusions: The new method is applicable to the clinical practice and allows for selecting tap test responders in an objective way, quantifying the improvements. Our results suggest that gait velocity alone is not sufficient to reliably assess tap test effect