Quantifying abnormal writing kinematics in writer's cramp using a novel software platform.

BACKGROUND: Writer's cramp is a task-specific focal hand dystonia, which is diagnosed clinically. Quantification of defect in WC is done using clinical scales, while digitized platforms are lacking. OBJECTIVE: To design and test a platform that can differentiate and quantify the abnormal kinematics of writing using a software interface and to validate it in adult-onset isolated writer's cramp (WC). METHODS: A native platform was designed using Java and Wacom Intuos pro tablet and the data analyzed using a MATLAB-based platform called Large Data-Based Evaluation of Kinematics in Handwriting (LEKH). We standardized this new platform by comparing the handwriting between patients with WC and age, and gender and education-matched healthy controls, using standard tasks to assess the kinematics. RESULTS: Comparison of the writing of right-handed WC patients (N = 21) and 39 healthy controls (N = 39) showed that patients differed from controls in the frequency of strokes (P < 0.001), number of inversions of velocity (P < 0.001), number of breaks (P = 0.02), air time and paper time (P < 0.001). CONCLUSIONS: Using the LEKH platform, the kinematic profile of patients with WC could be differentiated from healthy controls. Studies in larger samples will be needed to derive statistical models that can differentiate the flexion and extension types of WC which can help in muscle selection and to quantify the effects of treatment.

Unravelling the Parkinson's puzzle, from medications and surgery to stem cells and genes: a comprehensive review of current and future management strategies.

Parkinson's disease (PD) is a neurodegenerative disorder, prevalent in the elderly population. Neuropathological hallmarks of PD include loss of dopaminergic cells in the nigro-striatal pathway and deposition of alpha-synuclein protein in the neurons and synaptic terminals, which lead to a complex presentation of motor and non-motor symptoms. This review focuses on various aspects of PD, from clinical diagnosis to currently accepted treatment options, such as pharmacological management through dopamine replacement and surgical techniques such as deep brain stimulation (DBS). The review discusses in detail the potential of emerging stem cell-based therapies and gene therapies to be adopted as a cure, in contrast to the present symptomatic treatment in PD. The potential sources of stem cells for autologous and allogeneic stem cell therapy have been discussed, along with the progress evaluation of pre-clinical and clinical trials. Even though recent techniques hold great potential to improve the lives of PD patients, we present the importance of addressing the safety, efficacy, ethical, cost, and regulatory concerns before scaling them to clinical use.

Quantitative susceptibility mapping from basal ganglia and related structures: correlation with disease severity in progressive supranuclear palsy.

OBJECTIVE: We examined whether mean magnetic susceptibility values from deep gray matter structures in patients with progressive supranuclear palsy (PSP) differed from those in patients with Parkinson's disease (PD) and healthy volunteers, and correlated with the PSP rating scale. METHODS: Head of caudate nucleus, putamen, globus pallidus, substantia nigra and red nucleus were the regions of interest. Mean susceptibility values from these regions in PSP patients were estimated using quantitative susceptibility mapping. Correlations with clinical severity of disease as measured by the PSP rating scale were examined. The mean susceptibility values were also compared with those from healthy volunteers and age- and disease duration-matched patients with PD. RESULTS: Data from 26 healthy volunteers, 26 patients with PD and 27 patients with PSP, were analysed. Patients with PSP had higher mean susceptibility values from all regions of interest when compared to both the other groups. The PSP rating scale scores correlated strongly with mean susceptibility values from the red nucleus and moderately with those from the putamen and substantia nigra. The scores did not correlate with mean susceptibility values from the caudate nucleus or globus pallidus. In patients with PD, the motor deficits correlated moderately with mean susceptibility values from substantia nigra. CONCLUSIONS: In patients with PSP, mean susceptibility values indicating the severity of mineralization of basal ganglia and related structures correlate with disease severity, the correlation of red nucleus being the strongest. Further studies are warranted to explore whether mean susceptibility values could serve as biomarkers for PSP.

Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning.

Introduction: The cerebellum and basal ganglia were initially considered anatomically distinct regions, each connected via thalamic relays which project to the same cerebral cortical targets, such as the motor cortex. In the last two decades, transneuronal viral transport studies in non-human primates showed bidirectional connections between the cerebellum and basal ganglia at the subcortical level, without involving the cerebral cortical motor areas. These findings have significant implications for our understanding of neurodevelopmental and neurodegenerative diseases. While these subcortical connections were established in smaller studies on humans, their evolution with natural aging is less understood. Methods: In this study, we validated and expanded the previous findings of the structural connectivity within the cerebellum-basal ganglia subcortical network, in a larger dataset of 64 subjects, across different age ranges. Tractography and fixel-based analysis were performed on the 3 T diffusion-weighted dataset using Mrtrix3 software, considering fiber density and cross-section as indicators of axonal integrity. Tractography of the well-established cerebello-thalamo-cortical tract was conducted as a control. We tested the relationship between the structural white matter integrity of these connections with aging and with the performance in different domains of Addenbrooke's Cognitive Examination. Results: Tractography analysis isolated connections from the dentate nucleus to the contralateral putamen via the thalamus, and reciprocal tracts from the subthalamic nucleus to the contralateral cerebellar cortex via the pontine nuclei. Control tracts of cerebello-thalamo-cortical tracts were also isolated, including associative cerebello-prefrontal tracts. A negative linear relationship was found between the fiber density of both the ascending and descending cerebellum-basal ganglia tracts and age. Considering the cognitive assessments, the fiber density values of cerebello-thalamo-putaminal tracts correlated with the registration/learning domain scores. In addition, the fiber density values of cerebello-frontal and subthalamo-cerebellar (Crus II) tracts correlated with the cognitive assessment scores from the memory domain. Conclusion: We validated the structural connectivity within the cerebellum-basal ganglia reciprocal network, in a larger dataset of human subjects, across wider age range. The structural features of the subcortical cerebello-basal ganglia tracts in human subjects display age-related neurodegeneration. Individual morphological variability of cerebellar tracts to the striatum and prefrontal cortex was associated with different cognitive functions, suggesting a functional contribution of cerebellar tracts to cognitive decline with aging. This study offers new perspectives to consider the functional role of these pathways in motor learning and the pathophysiology of movement disorders involving the cerebellum and striatum.