Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson’s disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson’s Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs.Electronic supplementary materialThe online version of this article (doi:10.1007/s11481-012-9402-z) contains supplementary material, which is available to authorized users.

Parkinson's disease (PD) is a neurodegenerative disorder associated with debilitating motor, posture, and gait abnormalities. Human studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchronization throughout the cortical–basal ganglia motor network in PD. Suppression of such pathological beta synchronization has been associated with improved motor function, which may explain the effectiveness of deep-brain stimulation. We used magnetoencephalography (MEG) to investigate neural population-level beta responses, and other oscillatory activity, during a motor task in unmedicated patients with PD and a matched group of healthy adults. MEG is a noninvasive neurophysiological technique that permits the recording of oscillatory activity during movement planning, execution, and termination phases. Each of these phases was independently examined using beamforming to distinguish the brain areas and movement phases, where pathological oscillations exist during motor control. Patients with PD exhibited significantly diminished beta desynchronization compared with controls prior to and during movement, which paralleled reduced alpha desynchronization. This study is the first to systematically investigate neural oscillatory responses in PD during distinct stages of motor control (e.g. planning, execution, and termination) and indicates that these patients have significant difficulty suppressing cortical beta synchronization during movement planning, which may contribute to their diminished movement capacities.

CEA can be performed in patients at high risk, with stroke and death rates well within accepted standards. These data question the use of CAS as an alternative to CEA, even in patients at high risk.

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions.

The use of intramuscular injections of Botulinum neurotoxin A (BoNT-A) is common in the treatment of hypertonicity and movement disorders. While most side effects are mild, systemic effects, manifested by generalized weakness distant from the site of injection, have been reported. Previously reported occurrences are discussed, and three new cases of patients who developed systemic weakness following administration of BoNT-A (Botox®), despite having tolerated similar injections on several prior occasions, are presented. A review of the literature and reported cases indicate that risk of developing systemic effects does not appear to be related to dose based on body weight. It may be more likely that risk for systemic effects is related to total injection dose and injection frequency. The results of our three patients would indicate that injections of greater than 600 units of Botox with follow-up injections occurring every three months may lead to an increased risk. We would recommend careful consideration of re-injection frequency if injections of greater than 600 units of Botox are given. Reduction in systemic side effects may occur if re-injection frequency occurs in intervals of four months or greater in these individuals.

Evaluation of people with Parkinson's disease (PD) is often complex due to heterogeneity of symptoms and disease course, including the variability of motor fluctuations and dyskinesia. Routine clinical evaluations may be incomplete, may not accurately capture important symptoms, and may not reflect day-to-day variability. While significant advances have been made in wearable ambulatory continuous objective monitoring (COM) technologies, many clinicians remain uncertain of how to incorporate them in clinical practice, including the value to clinical decision-making. The Personal KinetiGraph™ (PKG) has FDA clearance in the United States, and has recently been used in several clinical studies. Areas covered: An expert group of movement disorders neurologists convened to discuss the clinical utility of the PKG in the routine assessment of people with PD. Based on their experience, the group identified clinical scenarios where objective information gained from review of PKG reports can provide useful information to improve clinical management. Expert commentary: PKG provides clinically meaningful data in patients with PD that can aid the clinician in evaluating patients and optimizing their pharmacologic therapy. Early clinical experience and expert opinion suggest that utilization of COM technologies such as the PKG have the potential to improve medical care in people with PD.

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Background Orthostatic Tremor (OT) is characterized by the presence of a sensation of instability while standing, associated with high frequency (13–18 Hz) lower extremity tremor. Diagnosis is confirmed with surface electromyography (EMG). An accurate screening tool that could be used in the routine clinical setting, without any specialized equipment, would be useful in earlier detection of OT and judicial use of additional testing. Objective The objective of this study was to evaluate OT diagnostic test characteristics at bedside using iPhone's built‐in accelerometer and available applications for tremor recordings. Methods We obtained recordings using iPhones (Model 5, 5s, and 6) and free Applications (“LiftPulse” by LiftLabs [App1] and “iSeismometer” by ObjectGraph LLC [App2]) at default settings. Results 24 EMG‐confirmed OT subjects (mostly females, 22/24) and 15 age‐matched controls (mostly males, 11/15) were evaluated. App1 detected OT range tremor in 22/24 patients and none of the controls. (Sensitivity = 92%, Specificity = 100%, NPV = 88%). App2 detected OT range tremor in 21/24 patients and in 1/13 controls (Sensitivity = 88%, Specificity = 92%, NPV = 80%). When combined, 24/24 patients and 1/13 controls had OT range tremor (Sensitivity = 100%, Specificity = 92%, NPV = 100%). Conclusions Smartphone apps that use the built‐in accelerometer provide a simple, accurate and inexpensive bedside screening diagnostic tool for patients with OT.