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The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current study aimed at exploring the relationship between objective disability, illness perceptions, resilience, fear of COVID-19, and psychological distress (i.e., anxiety, depression, and stress) in people with multiple sclerosis (pwMS) during the second wave of the COVID-19 outbreak. A group of 122 pwMS recruited in an Italian university hospital took part in this cross-sectional monocentric study. Hierarchical multiple linear regression analyses were performed to assess the strength of the hypothesized associations. Results indicated that, differently from cognitive impairment, motor disability was positively associated with anxiety. However, accounting for subjective illness perception, such association was no longer significant. Moreover, accounting for both protective and risk factors in the models, even illness perception was no longer significant, highlighting the central role of resilience and fear of COVID-19 in explaining the negative emotional outcomes. Implications for clinical interventions and psychoeducational trainings are discussed., (© 2022. The Author(s).)

Introduction: Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging., Methods: We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models., Results: Of the 243 subjects included in the study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 ± 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41-0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1-2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04-3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1-4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997-0.999, p = 0.01)., Conclusion: In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices., (© 2022. The Author(s).)

Objectives: To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson's disease (PD)., Methods: 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers' and patients' characteristics on the varying aspects of burden., Results: ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases., Discussion: An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient's global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

Background: Safinamide, as a levodopa adjunct, is effective in reducing motor fluctuations in Parkinson's disease (PD) patients; however, scarce evidence is available regarding its use in older PD patients., Aim: To evaluate the safety and tolerability of safinamide as an adjunct therapy in patients aged ≥ 60 years with advanced PD., Methods: A retrospective study including 203 PD patients admitted to a geriatric day hospital, who were evaluated following an extensive clinical protocol. Safinamide use was categorized as never used, ongoing, and withdrawn. Potential correlations of Safinamide withdrawal were investigated in stepwise backward logistic regression models., Results: A total of 44 out of 203 participants were current or former users of Safinamide. Overall, 14 (32%) patients discontinued due to treatment-emergent adverse events (TEAEs). Withdrawal was not associated with older age., Conclusions: Safinamide as an adjunct therapy in patients aged ≥ 60 years with advanced PD was found to be safe and well-tolerated in older patients. There were no specific demographic or clinical characteristics associated with suspension.

Cognitive impairment in Parkinson's disease (PD) is related to the reorganization of brain topology. Although drug challenge studies have proven how levodopa treatment can modulate functional connectivity in brain circuits, the role of chronic dopaminergic therapy on cognitive status and functional connectivity has never been investigated. We sought to characterize brain functional topology in mid-stage PD patients under chronic antiparkinson treatment and explore the presence of correlation between reorganization of brain architecture and specific cognitive deficits. We explored networks topology and functional connectivity in 16 patients with PD and 16 matched controls through a graph theoretical analysis of resting state-functional MRI data, and evaluated the relationships between network metrics and cognitive performance. PD patients showed a preserved small-world network topology but a lower clustering coefficient in comparison with healthy controls. Locally, PD patients showed lower degree of connectivity and local efficiency in many hubs corresponding to functionally relevant areas. Four disconnected subnetworks were also identified in regions responsible for executive control, sensory-motor control and planning, motor coordination and visual elaboration. Executive functions and information processing speed were directly correlated with degree of connectivity and local efficiency in frontal, parietal and occipital areas. While functional reorganization appears in both motor and cognitive areas, the clinical expression of network imbalance seems to be partially compensated by the chronic levodopa treatment with regards to the motor but not to the cognitive performance. In a context of reduced network segregation, the presence of higher local efficiency in hubs regions correlates with a better cognitive performance.

Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. In this review, we (1) provide an overview of the pathological features of PMS, (2) summarize the findings of research and clinical trials conducted in PMS which have applied conventional and advanced magnetic resonance imaging techniques and (3) discuss recent advancements and future perspectives in monitoring PMS with imaging techniques.

Botulinum toxin is considered as first-line therapy for cervical dystonia, but few papers have addressed these issues in the long term. Aim of this study was to investigate the long-term efficacy and safety of abobotulinumtoxin A (A/Abo) in patients with primary cervical dystonia. Consecutive patients who received at least six injections with A/Abo were included. Safety was assessed on patients' self-reports. Efficacy was assessed by recording the total duration of benefit, duration of maximum efficacy, disease severity measured by means of the Tsui score, and pain intensity evaluated by means of the visual analog scale (VAS). Thirty-nine patients with PCD were included. The mean dose injected was 701.5 ± 280.6 U. The mean duration of the clinical improvement was 93.0 ± 30.7 days, while the mean duration of the maximum clinical improvement was 77.1 ± 27.1 days. The mean VAS before and 4 weeks after injection was 4.4 ± 1.8 and 1.8 ± 1.6, respectively. The mean Tsui score before and 4 weeks after treatment was 5.7 ± 1.8 and 3.5 ± 1.5, respectively. Doses of A/Abo and duration of the maximum clinical improvement significantly increased over time, while the Tsui score and VAS displayed a tendency to decrease along time. Side effects occurred in 19.6% of all the treatments but were severe in only four injections. The results of our study confirm the effectiveness and safety profile of A/Abo for the long-term treatment of primary cervical dystonia.