The role of somatosensory afferences in Parkinson's disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world. The primary motor symptom of PD is bradykinesia, a slowing and reduction in amplitude of voluntary movement. Here, I aim to test some neurophysiological aspects of PD. Furthermore, I explored the possibility to develop non-invasive treatment for this group of patients. The first two studies tested the contribution of a specific phenomenon labelled sensory attenuation or sensory gating in the motor symptoms of PD, especially bradykinesia. I found that the sensory attenuation is abnormal in this group of patients. Especially, PD patients OFF medications showed a reduced sensory attenuation measured as the amplitude of the somatosensory evoked potentials. Interestingly, I found that the sensory attenuation was equal to the healthy age matched controls when the patients were tested in ON pharmacological state. Additionally, this research tested a theory of the functional role of sensorimotor beta oscillations that could explain beta power modulations in healthy subjects and the increase in beta power observed in PD patients. My results were in line with the previous data presented in the literature. Indeed, I found the increase beta power in both my two cohorts of PD patients. Finally, I tested a potential correlation between the abnormalities of these two phenomena in PD: reduced sensory attenuation and increased beta oscillations. I did not find any significant correlation between the two phenomena. They might be two different neurophysiological mechanisms 5 underlying this disease. However, further studies are necessary to investigate this hypothesis. Having tested the influence of the somatosensory signal in some motor symptoms, the second part of the thesis was focused on the development of non-invasive treatments of bradykinesia in PD. I tested the impact of vibratory stimuli to improve these motor signs. In particular, several frequencies of vibration have been tested through different devices applied to the wrist. The device was called “Emma watch” and I found that the application of vibration with the modulation of 60 bpm improved the bradykinesia in PD patients Finally, I presented a case study regarding the benefit of vibratory stimulation on the freezing of gait thought shoe insoles generating vibration. The tested patient showed an improvement of the frequency of the freezing episodes after a week wearing the insoles, which generated vibration at 200 Hz

Dual target deep brain stimulation for complex essential and dystonic tremor - A 5-year follow up.

BackgroundEssential tremor (ET) is characterized by action tremor of the upper limbs, head tremor and voice tremor. Dystonic tremor (DT) is produced by muscle contractions in a body affected by dystonia. Deep brain stimulation (DBS) of ventral intermediate nucleus of the thalamus (VIM) is the most well-known advanced treatment for medication-refractory tremor. However, decline in efficacy overtime has led to explore other targets. This study aimed to measure the efficacy of bilateral dual targeting ViM/caudal Zona Incerta (cZI) stimulation on tremor control. A secondary aim was to evaluate if there was a difference in the efficacy between ET and DT.Methods36 patients were retrospectively recruited at the Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and then at 1-year, 3-years, and 5-years post-operatively with the following scales: Fahn-Tolosa-Marin tremor rating (FTMTR) scale, EuroQol-5D, and Hospital Anxiety and Depression Scale.ResultsBilateral ViM-cZI DBS significantly improved overall tremor score by 45.1% from baseline to 3-years post-operatively (p  0.001).ConclusionsOur study found that bilateral ViM-cZI DBS treatment had a favourable effect on motor symptoms sustained over the 5-years in tremor patients, especially in ET group. There was limited effect on mood and QoL with similar trends in outcomes for both tremor types

Subthalamic nucleus deep brain stimulation for Parkinson's disease: current trends and future directions

Over the last three decades, extensive basic and clinical research has been performed on the use of subthalamic nucleus (STN) as the preferred deep brain stimulation (DBS) target for the treatment of Parkinson's disease (PD). The mechanism underlying the benefit for the motor symptoms in PD is related to the modulation of firing patterns within the hyperdirect projections from motor cortical areas, as well as within the afferent and efferent fibers to the motor STN. Advancements in neuroimaging techniques allow us to identify precisely the STN optimizing surgical targeting. In this review, we provide an update on the current uses of STN-DBS as a routine therapy as well as its experimental indications in PD, the critical aspects associated with its successful implementation and recent advances in DBS technology

Genetic and Environmental Contributors to Neurodegeneration: An Exploration of the Effects of Alcohol on Clinical Features of Huntington's Disease Using the Enroll-HD Global Platform

Huntington’s disease (HD) is a neurodegenerative dementia with a well recognised genetic cause. Alcohol misuse is a major environmental factor relevant to numerous neurological presentations, including HD. We explored the effects of alcohol intake on clinical features of HD by means of data from the Enroll-HD, which is a global registry study. A retrospective observational study making use of the Enroll-HD periodic dataset up to 2020 (in accordance with the Enroll-HD guidelines, encompassing 16,120 subjects with the HD gene (CAG expansion > 36), was carried out. This included 180 sites in 21 countries. The study looked at the association of alcohol use with the clinical presentation of HD, specifically looking into the age of first symptoms and HD severity. We also describe a specific case with manifest HD, a participant in the Enroll-HD study, whereby the patient’s obsessionality was central to her pattern of high alcohol intake and to her successful avoidance of alcohol thereafter. A record of past problems with high alcohol intake was more common in the group with manifest HD (9.0%, n = 1121) when compared with the pre-manifest carriers of the HD genetic abnormality (2.3%, n = 339). Age at onset of symptoms was not significantly influenced by current alcohol misuse, or past misuse. The severity of clinical impairments in HD was influenced by alcohol. Patients who reported high alcohol intake in the past had a statistically significant increase in motor impairments, by the Unified Huntington’s Disease Rating Scale total motor score (Kruskal–Wallis, post hoc Dunn’s, p < 0.001), and a significantly higher burden of psychiatric symptoms by the Problem Behaviours Assessment score (Kruskal–Wallis, post hoc Dunn’s, p < 0.01) compared with those not reporting high alcohol use. However, the past alcohol group did not have a lower Mini Mental State Examination score (Kruskal–Wallis, post hoc Dunn’s, p > 0.05) The first symptom of HD, as determined by the assessing clinician, was more likely to be psychiatric disturbance in patients currently misusing alcohol or those with prior history of alcohol misuse (55% and 31% respectively) when compared with controls (5%). Individual case experience, such as that presented in this study, shows that HD and alcohol, two major genetic and environmental contributors to neurodegeneration, interact in producing clinical problems. However, the complexities of these interactions are difficult to define, and may require larger studies dedicated to exploring the various factors in this interaction

Abnormal beta power is a hallmark of explicit movement control in functional movement disorders.

OBJECTIVE: To determine whether sensorimotor beta-frequency oscillatory power is raised during motor preparation in patients with functional movement disorders (FMD) and could therefore be a marker of abnormal "body-focused" attention. METHODS: We analyzed motor performance and beta-frequency cortical oscillations during a precued choice reaction time (RT) task with varying cue validity (50% or 95% congruence between preparation and go cues). We compared 21 patients with FMD with 13 healthy controls (HCs). RESULTS: In HCs, highly predictive cues were associated with faster RT and beta desynchronization in the contralateral hemisphere (contralateral slope -0.045 [95% confidence interval (CI) -0.057 to -0.033] vs ipsilateral -0.033 [95% CI -0.046 to -0.021], p < 0.001) and with a tendency for reaching lower contralateral end-of-preparation beta power (contralateral -0.482 [95% CI -0.827 to -0.137] vs ipsilateral -0.328 [95% CI -0.673 to 0.016], p = 0.069). In contrast, patients with FMD had no improvement in RTs with highly predictive cues and showed an impairment of beta desynchronization and lateralization before movement. CONCLUSIONS: Persistent beta synchronization during motor preparation could reflect abnormal explicit control of movement in FMD. Excessive attention to movement itself rather than the goal might maintain beta synchronization and impair performance

The effects of rivastigmine on neuropsychiatric symptoms in the early stages of Parkinson's disease: A systematic review.

Neuropsychiatric symptoms including depression, apathy and psychosis occur frequently in patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia, but whether the use of rivastigmine is effective earlier in the disease course is unclear. The aim of this systematic review was to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia. Embase, Medline, PsychINFO, Cochrane CENTRAL, NGLC, National Institute for Health and Care Excellence Evidence and medRxiv.org were searched for studies with terms relating to population (Parkinson's disease) and intervention (rivastigmine). Of 1922 references identified, 358 were duplications. Following title and abstract review, 1331 articles were excluded. After full-text review, nine articles remained. Outcomes were heterogenous, therefore, the results are presented in narrative form. The articles included six randomized controlled trials, two open-label trials and one case series. Outcome measures included: time to develop psychosis; frequency of rapid eye movement sleep behaviour disorder (RBD) episodes; apathy; gait variability; falls; cognitive ability; Neuropsychiatric Inventory score; and regional spontaneous brain activity. There is evidence that rivastigmine is beneficial for RBD and apathy in Parkinson's disease patients without dementia. There is high level evidence that rivastigmine reduces falls, which may be due to improved attention. The impact of rivastigmine on psychotic symptoms is less clear, but is supported by current theoretical models which involve acetylcholine dysfunction in the generation of visual hallucinations in Parkinson's disease

Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study.

IntroductionParkinson's disease (PD) is an idiopathic disease of the central nervous system characterized by both motor and non-motor symptoms. It is the second most common neurodegenerative disease. Magnetic resonance imaging (MRI) can reveal underlying brain changes associated with PD.ObjectiveIn this study, structural connectivity and white matter networks were analyzed by diffusion MRI and graph theory in a cohort of patients with PD and a cohort of healthy controls (HC) obtained from the Parkinson's Progression Markers Initiative (PPMI) database in a cross-sectional analysis. Furthermore, we investigated longitudinal changes in the PD cohort over 36 months.ResultCompared with the control group, participants with PD showed lower structural connectivity in several brain areas, including the corpus callosum, fornix, and uncinate fasciculus, which were also confirmed by a large effect-size. Additionally, altered connectivity between baseline and after 36 months was found in different network paths inside the white matter with a medium effect-size. Network analysis showed trends toward lower network density in PD compared with HC at baseline and after 36 months, though not significant after correction. Significant differences were observed in nodal degree and strength in several nodes.ConclusionIn conclusion, altered structural and network metrics in several brain regions, such as corpus callosum, fornix, and cingulum were found in PD, compared to HC. We also report altered connectivity in the PD group after 36 months, reflecting the impact of both PD pathology and aging processes. These results indicate that structural and network metrics might yield insight into network reorganization that occurs in PD

COVID-19 and Clinically Isolated Syndrome: Coincidence or Causative Link? A 12-Month Follow-Up Case Report

A 35-year-old female with positive anamnesis of COVID-19 infection presented with a seven-day history of headache along with tingling and numbness involving the right lower limb and visual disturbance on the right side of her vision. Magnetic resonance imaging (MRI) of the brain and C-spine were consistent with acute demyelinating lesions. However, the MAGNIMS criteria for a multiple sclerosis diagnosis were not met, and, subsequently, a diagnosis of clinically isolated syndrome (CIS) was made. At 12 months, the patient showed new inflammatory lesions in the right frontal lobe and at the septocallosal interface, a lesion of the right hemi-cord at C3, and subsequent development of vertigo and unsteadiness and signs consistent with a brainstem/cerebellar relapse. On the basis of clinical and radiological criteria in the 2017 McDonald criteria, a diagnosis of relapsing remitting multiple sclerosis was made.</jats:p