BACKGROUND AND OBJECTIVES:Pain is an important non-motor symptom in Parkinson's disease (PD) and is often under-recognized. Pain is also a symptom frequently reported by non-PD elderly subjects. The King's Parkinson's Disease Pain Scale (KPPS) is a valid tool to characterize and quantify pain in PD and has been translated into several languages. METHODS:We translated KPPS to Malayalam for native patients with PD and examined the pain characteristics in consecutive patients. Correlations with comprehensive disease-specific rating scales, including the Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS), were explored. A group of age- and gender-matched subjects without PD were interviewed using KPPS to examine how the pain reported by the non-PD aging population is different from that in PD. RESULTS:In this study, 82% of patients with PD reported at least one type of pain, compared to 31.3% of age- and gender-matched control subjects ( P < 0.001). KPPS total scores (18.2 ± 14.0 vs. 1.8 ± 3.2; P < 0.001) and all the individual domain scores were significantly higher in patients. Pain scores correlated with age in control subjects (R = 0.46, P < 0.001), but not in patients; females reported more pain in both groups. Patients' pain scores were higher in the postural instability and gait difficulty subtype and showed significant correlations with MDS-UPDRS and NMSS scores. CONCLUSIONS:Pain is a prevalent symptom in PD and differs from the pain reported by a non-PD aging population. The Malayalam version of KPPS is a valid tool to characterize pain in native, Malayalam-speaking patients.

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. 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). 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. 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). 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.

Dear Sir, Deep brain stimulation (DBS) is currently the standard of care for patients with Parkinson’s disease (PD) experiencing motor complications.[1] The subthalamic nucleus (STN) is the most widely used target for DBS in PD.[2] We present an interesting case of successful bilateral STN-DBS surgery for PD, in a patient in whom a brain lesion was incidentally detected close to the trajectory. A 51-year-old gentleman with advanced PD of 11 years duration, with motor fluctuations and dyskinesias, was referred to us for considering DBS. The symptoms had started on the left side and became bilateral over the years. He was found suitable and was selected for bilateral STN DBS. In the preoperative magnetic resonance imaging (MRI), an incidental well-defined rounded non-enhancing lesion which was isointense in T1 and hyperintense in T2 and FLAIR sequences was detected in the left globus pallidus (GP) [Figure 1a and b]. The lesion did not show restricted diffusion or blooming in susceptibility-weighted sequences. The lesion was abutting the planned lead trajectory [Figure 1c and d]. The distance between the initial planned trajectory and the GP lesion margin was 1.2 mm with trajectory traversing the mid sagittal plane at 26° and the axial plane at 50°. It was decided to go ahead with surgery, after modifying the trajectory, considering the benign appearance of the lesion on MR imaging.Figure 1: (a) Hyperintense lesion in axial and (b) coronal pre-DBS T2-MRI at left GP. (c) Planned trajectory abutting the lesion (d) planned trajectory in probe’s eye view, (e) Post-operative MRI showing, STN tip in the subthalamic area (f) 2-year follow-up scan highlighting trajectory of the DBS lead (white arrow) and the lesion (yellow arrow) (g) T2-sag MRI at 2-year follow-up highlighting stable lesion size and lead trajectory, (h) sagittal plane showing the distance between the final lead trajectory and GP lesion marginA different trajectory was planned, avoiding the lesion at a distance of 5.8 mm and the trajectory traversing the mid-sagittal plane at 30° and the axial plane at 57.7°. He underwent bilateral STN-DBS under MR-based stereotactic guidance, 5-channel microelectrode recording, and macrostimulation with clinical monitoring for benefits and adverse effects. There were no perioperative complications, and the patient reported improvement in his symptoms following programming. Post-operative MRI brain showed satisfactory placement of the DBS lead tips bilaterally in the STN [Figure 1e], with the left-sided lead traversing close to the lesion [Video 1]. Serial MR imaging studies done at 6 months and 2-year follow-up visits did not show any interval increase in the size of the lesion [Figure 1f and g]. The patient continues to have benefits in motor symptoms. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Clip 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_yk114oga"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} STN is a lens-shaped diencephalic structure located ventral to the thalamus, playing a fundamental role in the basal ganglia circuits. STN is located approximately 10 to 12 mm lateral, 1–4 mm posterior, and 4–5 mm inferior to the mid-commissural point. It is obliquely located in the subthalamic area, and therefore, the trajectory should ideally have a mediolateral angle of around 15 degrees from the sagittal plane and an anteroposterior angle of 60 degrees from the anterior commissure-posterior commissure plane for getting the longest track of microelectrode recording and optimal placement of lead contacts in the motor part of the nucleus. At the same time, the sulci, blood vessels, and ventricles should also be avoided. Trajectory planning based on MRI fusion is a safe technique for lead placement.[3] The GP lesion in the present case was abutting the ideal trajectory, and hence, it had to be modified to ensure an adequate safe margin from the lesion. The radiological features including the well-rounded appearance, non-enhancement, and absence of restricted diffusion or blooming suggested a low-grade neoplasm. The patient had a 11-year history of typical levodopa-responsive Parkinsonism with the left-sided onset and bilateral signs, motor fluctuations, and dyskinesias at the time of presentation to us, clearly indicating that the left pallidal lesion was an incidentally detected one. This is a rare situation, and hence, there are no specific guidelines as to whether a patient can be taken up for DBS surgery in such a scenario, with an incidental lesion close to trajectory. The increasing size of the lesion later can lead to impingement on the lead, traction, or displacement from the target. However, given the benign radiological characteristics, we felt that the chances for these were low and we did not consider the presence of this lesion as a contraindication for DBS. We proceeded with surgery with a slightly modified target keeping a safe margin of 5.8 mm from the lesion [Figure 1g and h]. Our patient had significant motor improvement which persisted at his last follow-up, 2 years after surgery. We kept him under radiological follow-up with imaging studies every 6 months as usually recommended for such incidentally detected lesions.[4] No increase in size or change in signal characteristics was noted during the follow-up scans in our patient confirming that the lesion was benign. There are reports of successful DBS in challenging medical co-morbidities like hemophilia, increasing the surgical risks.[5] However, we did not find any other reports of incidentally detected tumors or other lesions close to the lead trajectory, interfering with the surgical technique. With the increasing number of DBS surgeries done globally, such unexpected encounters are likely to be happening occasionally and decisions in an individual case should depend on the neurological diagnosis, location, and radiological characteristics of the lesion. Incidental low-grade neoplasms near lead trajectory are not a contraindication for DBS planned for neurological indications and the patients should not be denied the benefit of surgery. Declaration of patient consent The authors confirm that the approval of the institutional review board was not required for this work. Written informed consent was taken from the patient. We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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.

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.

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.