Clinical Research Directory

Investigating the Genetic and Phenotypic Presentation of Ataxia and Nucleotide Repeat Diseases

The purpose of this study is to create a repository for cerebellar ataxia and nucleotide repeat diseases in order to fully investigate the genetic and phenotypic presentations of both.

The Role of Cerebellum in Speech

This study will investigate the how the cerebellum is involved in speech motor learning over time and short-term corrections in patients with cerebellar ataxia and healthy controls. This will be accomplished through three approaches: behavioral studies, magnetic resonance imaging (MRI), and transcranial magnetic stimulation (TMS). During behavioral studies, participants will be asked to speak into a microphone while their voice is played back over earphones, and to do other speaking tasks. MRI will be acquired to perform a detailed analysis on brain function and anatomy related to speech and the cerebellum. In healthy controls, TMS will also be performed to temporarily disrupt the cerebellum before, during, or after the participant performs speaking tasks. Patients with cerebellar ataxia and healthy volunteers will be asked to complete behavioral studies and/or MRI; healthy volunteers may be asked to additionally participate in TMS.

rTMS for Cerebellar Ataxia in Children

Dysfunction of the cerebellum can result in cerebellar ataxia (CA), typically marked by symptoms such as movement incoordination, gait instability, articulation disorder, oculomotor and swallowing difficulties. Children affected by paediatric cerebellar ataxia (PCA) often suffer from an array of motor symptoms, affecting their quality of life and psychosocial well-being. It was estimated that PCA affects 26/100,000 children worldwide for both genetic and acquired causes. Epidemiological data on PCA, however, are absent in the Hong Kong population. PCAs comprise a varied group of cerebellar development disorders, marked by impaired balance and motor coordination (e.g., dysmetria and tremor) when performing voluntary movement. Clinical symptoms in children with PCA are related to lesioned localization - focal disorder of the cerebellar vermis leads to truncal instability, head titubation, and nystagmus; while lesioned cerebellar hemispheres results in ataxia gait (wide-staggering gait, tend to fall towards the affected side). These clinical symptoms result in functional difficulties involving balance and walking, reaching, grasping and manipulation, oculomotor and speech domains. Abnormalities of motor excitability have been reported in patients with cerebellar lesions - the motor threshold was found to be raised in the motor cortex contralateral to a hemi-cerebellar lesion. With no effective pharmacological treatments available, rehabilitation serves as the primary treatment approach. Even though adaptive learning is affected by cerebellar lesion, motor learning is still possible via exercise interventions. Interventions may include compensatory (educate strategies to compensate for impairment) or restorative approaches (improve functions through training). While exercise interventions have been explored as a potential therapeutic approach for paediatric patients with cerebellar lesions or degeneration, the current evidence lacks robust, high-quality randomized controlled trials (RCTs) to substantiate their efficacy. Existing evidence shows that cerebellar outputs project to several cortical areas, including the primary motor cortex (M1). CA patients with lesions in structures of the cerebellar efferent pathway exhibit reduced inhibition in the motor cortex. Selective modulation of the efferent pathways may offer an additional means of modulating cortical activity, thus improve motor coordination abilities in CA patients. With the development of non-invasive brain stimulation (NIBS) techniques, more research has been conducted using NIBS as treatment modalities for patients with CA. The most used NIBS techniques include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Repetitive transcranial magnetic stimulation (rTMS) enables to modulate cortical excitability focally in conscious subjects; low-frequency stimulation (e.g., 1 Hz) is known to suppress cortical excitability, while higher frequencies (\> 5 Hz) induce facilitation. These changes in excitability occur not only at the site of stimulation but also at other distant interconnected sites of a network. Both the excitatory stimulation and inhibitory stimulation approaches were adopted in existing adult studies. Paediatric patients with cerebellar lesions-caused by stroke, tumour, or genetic conditions-are thought to share the same pathophysiological basis as adults. Using contra-lesional inhibitory rTMS, França et al. demonstrated that the intervention is safe and feasible for adult patients with CA, showing a reduction in ataxic symptoms. Despite promising results in the adult population, it is still unclear whether rTMS can relieve ataxic symptoms and improve motor performance in children with CA. To date, no studies have been published on the effects of rTMS on improving ataxic symptoms in children with cerebellar ataxia. However, emerging evidence suggests its potential utility. Using rTMS of 1 Hz to stimulate the cerebellar hemisphere ipsilateral to the ataxic side combined with mirror therapy, Cha et al. demonstrated that there was improvement in functional mobility as measured by 6-minute walk test and the timed up and go test. Supporting the feasibility of rTMS in paediatric motor rehabilitation, our pilot RCT (HKWC UW 23-492) found that contra-lesional inhibitory rTMS over M1 combined with motor training is safe and effective in improving motor performance in children with cerebral palsy. Comparative studies in older adults suggest that cerebellar rTMS was more effective than M1 rTMS for motor learning and the consolidation, likely due to the unique role of cerebellum in the integration and processing of multimodal sensory inputs to refine motor planning. These findings highlight the cerebellum as a promising neuromodulatory target for motor rehabilitation, warranting further investigation in paediatric cerebellar ataxia.

Motor Learning After Cerebellar Damage: The Role of the Primary Motor Cortex

This study will determine (1) whether baseline inhibitory activity in the primary motor cortex can predict motor learning ability in individuals with cerebellar degeneration, and (2) whether modulating primary motor cortex activity with non-invasive brain stimulation alters motor learning ability in this population.

Retraining Reaching in Cerebellar Ataxia

The purpose of this study is to test for benefits of reinforcement based training paradigm versus standard practice over weeks for improving reaching movements in people with ataxia.

Enhancement of Quality of Work And Life

Work participation is essential for quality of life, providing purpose, social interaction, financial security, and shaping social status. Work participation is increasingly compromised in people with slowly progressive chronic disorders (hereafter referred to as progressive disorders). This negatively impacts their quality of life. Early work-related support, focused on sustainable work-retention, has the potential to enhance work participation in people with progressive disorders. Therefore, this study investigates the (cost)effectiveness of the Preventive Participatory Workplace Intervention (PPWI), a personalized work intervention to enhance sustainable work participation. The investigators perform an 18-month randomized controlled trial (RCT). In addition, the investigators perform a process evaluation and an economic evaluation alongside the RCT. 124 Dutch working persons with three types of movement disorders will be included: Parkinson's Disease (PD), cerebellar ataxia (CA) and hereditary spastic paraparesis (HSP) and with slowly progressive neuromuscular and mitochondrial disorders.

Evaluation of Urinary Dysfunction in CANVAS Patients

The investigator wishes to evaluate the prevalence of urinary symptoms in patients diagnosed with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS). As much as one third of patients living with CANVAS experience symptoms of urinary system dysfunction. The primary objective of this study is to evaluate the incidence of urinary symptoms in these patients, as well as the potential complications that might occur at the level of the upper and lower urinary system. The investigator also wishes to analyse the connection between the severity of the neurological deficits, the presence of dysautonomia and the presence of urinary dysfunction. To that end, the data collected in the study will concern : a detailed neurological examination including SARA (Scale for the assessement and rating of ataxia) scale assessement, laboratory tests of the renal function, dysautonomia tests with Sudoscan and research of orthostatic hypotension, urinary function questionnaires, dysautonomia questionnaire, urodynamic tests and urinary system ultrasound.

Home Exercise for Individuals with Neurodegenerative Disease

The primary goal of this study is to address the need for targeted therapeutic interventions for impairments that impact walking in related neurodegenerative diseases.

Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia

Engage-Ataxia will implement a physical activity coaching program for people with cerebellar ataxia at Teachers College, Columbia University. This program expands upon the current Engage program for people with Parkinson's disease (Engage-PD), an exercise coaching program for people with early stage Parkinson's disease to target individuals with early stage cerebellar ataxia. Engage-Ataxia will utilize a physical or occupational therapist to provide up to five one-on-one coaching sessions for individuals newly diagnosed with cerebellar ataxia. Therapists will work with participants to provide individualized structured support to facilitate and optimize exercise uptake as one part of comprehensive disease management. Participants will undertake two assessments three months apart, and will receive coaching interventions via Zoom healthcare platform. The primary objective of this program is to increase physical activity and exercise engagement in individuals with early stage cerebellar ataxia. This feasibility study will provide preliminary data and insight into the benefits of a remote coaching intervention for people with cerebellar ataxia.

A Registered Cohort Study on Cerebellar Ataxia in the Organization in South-East China for Cerebellar Ataxia Research (OSCCAR)

Cerebellar ataxia is a form of ataxia originating in the cerebellum. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms of an inability to coordinate balance, gait, extremity and eye movements. To understand the clinical and genetic characteristics of cerebellar ataxia, we establish a registered cohort to follow up Chinese patients with cerebellar ataxia.