Parkinson's Disease: Risk Factor Modification and Prevention.

The global burden of Parkinson's disease (PD) has increased from 2.5 to 6.1 million since the 1990s. This is expected to rise as the world population ages and lives longer. With the current consensus on the existence of a prediagnostic phase of PD, which can be divided into a preclinical stage and a prodromal stage, we can better define the risk markers and prodromal markers of PD in the broader context of PD pathogenesis. Here, we review this pathogenetic process, and discuss the evidence behind various heritability factors, exposure to pesticides and farming, high dairy consumption, and traumatic brain injuries that have been known to raise PD risk. Physical activity, early active lifestyle, high serum uric acid, caffeine consumption, exposure to tobacco, nonsteroidal anti-inflammatory drugs, and calcium channel blockers, as well as the Mediterranean and the MIND diets are observed to lower PD risk. This knowledge, when combined with ways to identify at-risk populations and early prodromal PD patients, can help the clinician make practical recommendations. Most importantly, it helps us set the parameters for epidemiological studies and create the paradigms for clinical trials.

GuitarPD: A Randomized Pilot Study on the Impact of Nontraditional Guitar Instruction on Functional Movement and Well-Being in Parkinson's Disease.

Playing musical instruments may have positive effects on motor, emotional, and cognitive deficits in patients with Parkinson's disease (PD). This pilot study examined the feasibility of a six-week nontraditional guitar instruction program for individuals with PD. Twenty-six participants with idiopathic PD (Age: 67.22 ± 8.07; 17 males) were randomly assigned to two groups (intervention first or 6 weeks of usual care control exposure) with stepwise exposure to the guitar intervention condition with cross-over at six weeks. Outcomes were assessed at baseline, 6, 12, and 18 weeks. Twenty-four participants completed the study. Combined analysis of the groups showed significant BDI-II improvement immediately after intervention completion (3.04 points, 95% CI [-5.2, -0.9], p = 0.04). PDQ-39 total quality of life scores improved from baseline to immediately postintervention 5.19 points (95% CI [-9.4, -1.0]) at trend significance (corrected p = 0.07). For Group 1 (exposed to the intervention first), MDS-UPDRS total scores improved by a mean of 8.04 points (95% CI [-12.4, -3.7], p = 0.004) and remained improved at 12 weeks by 10.37 points (95% CI [-14.7, -6.0], p < 0.001). This group also had significant improvements in mood and depression at weeks 6 and 12, remaining significant at week 18 (BDI-II: 3.75, 95% CI [-5.8, -1.7], p = 0.004; NeuroQoL-depression: 10.6, 95% CI [-4.9. -1.4], p = 0.004), and in anxiety at week 6 and week 18 (NeuroQoL; 4.42, 95% CI [-6.8, -2.1], p = 0.004; 3.58, 95% CI [-5.9, -1.2], p = 0.02, respectively). We found clinically and statistically significant improvements in mood/anxiety after 6 weeks of group guitar classes in individuals with PD. Group guitar classes can be a feasible intervention in PD and may improve mood, anxiety, and quality of life.

Movement Disorders Emergencies.

Many acute and potentially life-threatening medical conditions have hyperkinetic or hypokinetic movement disorders as their hallmark. Here we review the clinical phenomenology, and diagnostic principles of neuroleptic malignant syndrome, malignant catatonia, serotonin syndrome, Parkinsonism hyperpyrexia, acute parkinsonism, acute chorea-ballism, drug-induced dystonia, and status dystonicus. In the absence of definitive lab tests and imaging, only a high index of clinical suspicion, awareness of at-risk populations, and variations in clinical presentation can help with diagnosis. We also discuss the principles of management and rationale behind treatment modalities in the light of more recent evidence.

Functional Movement Disorders and Placebo: A Brief Review of the Placebo Effect in Movement Disorders and Ethical Considerations for Placebo Therapy.

BACKGROUND: Functional movement disorders are common and disabling neurologic conditions. Patients with functional neurologic disorders represent a large proportion of neurology clinic referrals, and limited availability of subspecialty care creates a considerable burden for the healthcare system. These conditions are currently treated with a combination of physical therapy and cognitive behavioral therapy, with variable success. METHODS: We searched the Medline database for studies on the epidemiology and physiology of functional movement disorders, as well as those on the placebo effect in movement disorders. We reviewed and summarized the literature on these topics and explored ethical issues concerning the administration of placebos to patients with functional movement disorders. RESULTS: Studies of placebos, particularly in patients with movement disorders, have shown that these "inert" agents can provide demonstrable neurophysiologic benefits, even in open-label studies. Physician surveys have shown that many administer placebos for diagnostic and therapeutic purposes, although there are ethical concerns about this practice. We used a principle-based approach and reviewed ethical arguments for (justice and beneficence) and against (non-maleficence and autonomy) the use of placebos in functional movement disorders. In this context, we argue for the importance of the therapeutic alliance in preserving patient autonomy while exploring the potential benefits of placebo therapy. CONCLUSIONS: An ethical argument is presented in support of nondeceptive clinical placebo use for the treatment of functional movement disorders. Patient and clinician attitudes regarding the use of placebos should be investigated before placebo-therapy trials are conducted.

Clinical and neuroimaging spectrum of hyperglycemia-associated chorea-ballism: systematic review and exploratory analysis of case reports.

Hyperglycemia-associated chorea-ballism (HCB) is an infrequent neurological syndrome occurring predominantly in elderly females and in the setting of non-ketotic hyperglycemia (NKH). A systematic review was conducted in accordance with the PRISMA statement. Studies published between 1980 and 2018 that reported demographic, clinical, laboratory and imaging features from patients with HCB were screened. 136 studies describing 286 patients were included in the analysis. The patients included had a median age of 72 years; those with ketotic hyperglycemia (KH) were older (p<0.001). Women and NKH patients were the most frequently affected (63% and 92%, respectively). The median glucose level at admission was 420 mg/dL (IQR 328-535), and was significantly higher in KH (p=0.009). Moreover, the absence of a clear lesion on imaging studies and the finding of bilateral imaging evidence of lesions were each more frequent in the KH group (p=0.036 and p=0.008, respectively). 48 cases (19.4%) presented with bilateral CT/MRI lesions, having higher values of plasma osmolarity compared with the patients with unilateral lesions (p=0.011). Every patient received hypoglycemic treatment, but only 174 (60.84%) were prescribed neuroleptics. 213 patients (84.86%) showed a total recovery, after a median of 14 days (IQR 3-31). Bilateral chorea-ballism was supported by bilateral imaging evidence of involvement in only 60% of the cases (positive predictive value). Patients not prescribed neuroleptics, with negative lentiform nucleus involvement, and age within the third tertile (≥ 78 years) had an odds ratio of 6.6 (CI 95% 1.18-141.10) for a complete clinical recovery. Significant differences were identified between types of hyperglycemia and regarding the clinical and imaging laterality features. Furthermore, the predictor variables evaluated showed potential utility for assessing the prognosis of HCB patients.

Midbrain Infarction Resulting in Bilateral Pseudoabducens Palsies.

INTRODUCTION: Pseudoabducens palsy refers to abduction paresis in the absence of a pontine or peripheral nerve process. This finding has been described with mesodiencephalic lesions, and likely has a common mechanism with thalamic esotropia. CASE REPORT: We describe the case of a 55-year-old man who presented with near-complete ophthalmoparesis, sparing only adduction of the left eye. Magnetic resonance imaging of the brain demonstrated midbrain infarction. CONCLUSIONS: Pseudoabducens palsy is likely underrecognized, but can be highly localizing when identified. Possible pathophysiologic mechanisms for this finding are discussed.

Brachial plexitis preceding encephalomyelitis in a patient with West Nile virus infection.

We describe the case of a 54-year-old woman with West Nile virus infection presenting with painful brachial plexitis and radiculitis that preceded the more typically associated symptoms of meningoencephalitis. Physicians should be aware that West Nile virus infection can present with painful brachial plexitis.

Spectrum and prevalence of vasculopathy in pediatric neurofibromatosis type 1.

To describe the spectrum and associated clinical features of peripheral and cerebral vasculopathy in pediatric patients with neurofibromatosis type 1, children seen at a single center from 2000 to 2010 with appropriate imaging studies were identified. Scans were assessed for vascular disease by 2 pediatric neuroradiologists. Of 181 children, 80 had pertinent imaging studies: 77 had brain imaging, 6 had peripheral imaging, and 3 had both. Vasculopathy was identified in 14/80 children (18%, minimum prevalence of 14/181; 8%). Of those with vascular abnormalities, 2/14 had peripheral vasculopathy (1% minimum prevalence) and 12/14 had cerebrovascular abnormalities (7% minimum prevalence). No associations were found between vasculopathy and common clinical features of neurofibromatosis type 1, including optic pathway glioma, plexiform neurofibroma, skeletal abnormalities, attention-deficit hyperactivity disorder (ADHD), or suspected learning disability. Both peripheral and cerebral vasculopathy are important complications of pediatric neurofibromatosis type 1 and should be considered in the management of this complex disease.

Technical report: exploring the basis of congenital myasthenic syndromes in an undergraduate course, using the model organism, Caenorhabditis elegans.

Mutations affecting acetylcholine receptors have been causally linked to the development of congenital myasthenic syndromes (CMS) in humans resulting from neuromuscular transmission defects. In an undergraduate Molecular Neurobiology course, the molecular basis of CMS was explored through study of a Caenorhabditis elegans model of the disease. The nicotinic acetylcholine receptor (nAChR), located on the postsynaptic muscle cell membrane, contains a pentameric ring structure comprised of five homologous subunits. In the nematode C. elegans, unc-63 encodes an α subunit of nAChR. UNC-63 is required for the function of nAChR at the neuromuscular junction. Mutations in unc-63 result in defects in locomotion and egg-laying and may be used as models for CMS. Here, we describe the responses of four unc-63 mutants to the cholinesterase inhibitor pyridostigmine bromide (range 0.9-15.6 mM in this study), a treatment for CMS that mitigates deficiencies in cholinergic transmission by elevating synaptic ACh levels. Our results show that 15.6 mM pyridostigmine bromide enhanced mobility in two alleles, depressed mobility in one allele and in N2, while having no effect on the fourth allele. This indicates that while pyridostigmine bromide may be effective at ameliorating symptoms of CMS in certain cases, it may not be a suitable treatment for all individuals due to the diverse etiology of this disease. Students in the Molecular Neurobiology course enhanced their experience in scientific research by conducting an experiment designed to increase understanding of genetic defects of neurological function.