Maya Katz

Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease.

Increased oxidative stress is implicated in the pathogenesis of Alzheimers disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-β (Aβ) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntingtons disease and Parkinsons disease, and reduces plaque burden in AβPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Aβ42-specific antibody. Brain Aβ42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-β protein precursor (AβPP) β-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.

Longitudinal Impedance Variability in Patients with Chronically Implanted DBS Devices

BACKGROUND Deep brain stimulation (DBS) is an effective therapy for advanced movement disorders, but its optimal use is still controversial. One factor that could play a role in the proper delivery of therapeutic stimulation by current DBS devices is the variability of the impedance at the interface between the electrode surface and surrounding tissue. OBJECTIVE To analyze variability and trends in the impedance of chronically-implanted DBS electrodes in subjects with movement disorders. METHODS We reviewed impedance values from medical records of DBS patients at an academic tertiary-care movement disorders center. The standard deviation of data recorded within individual subjects and single contacts were used as measures of longitudinal impedance variability. A generalized linear mixed model (GLMM) determined if a number of effects had significant influences on impedance. RESULTS We analyzed 2863 impedance measurements from 94 subjects. Median variability, for subjects with follow-up from 6 months to 5 years (n = 77), was 194 Ω for individual subjects and 141 Ω for individual contacts, with a range spanning from 18 to over 600 Ω. The GLMM, incorporating all subjects (n = 94), identified time, electrical activity, implanted target, contact position on the electrode and side of implantation as significant predictors of impedance. Age and disease duration at surgery, gender or ethnicity were not significant predictors. CONCLUSIONS Our analysis suggests that a significant amount of impedance variability can be expected in chronically implanted DBS electrodes and indicates a number of factors with possible predictive value. Further studies are needed to link impedance characteristics to clinical outcomes.

Referring Patients for Deep Brain Stimulation: An Improving Practice

BACKGROUND Deep brain stimulation (DBS) is a recent treatment modality. Few studies have examined referral practices for DBS. OBJECTIVE To review referral patterns to a large movement disorders center to investigate the current level of knowledge surrounding DBS candidacy. DESIGN Retrospective analysis. SETTING Tertiary care medical center. PATIENTS Reviewed were 197 medical records of patients referred for DBS between December 1, 2005, and November 30, 2009. MAIN OUTCOME MEASURES Standardized criteria for DBS patient selection were used to categorize referred DBS candidates as the following: good candidates, possible future candidates, poor candidates because of neurological contraindications, or poor candidates because of medical contraindications. Yearly percentages were computed. Referral sources were categorized as movement disorder specialists vs non-movement disorder physicians and self-referred. RESULTS In total, 165 referrals (83.8%) had ailments for which DBS was indicated, and 100 referrals (50.8%) were good candidates (62 with idiopathic Parkinson disease, 35 with dystonia, and 3 with essential tremor). Referrals by movement disorder specialists vs other sources differed significantly in their percentages of good candidates (66.7% vs 40.4%, P = .002) and possible future candidates (14.7% vs 32.7%, P = .02) but not poor candidates (18.7% vs 25.0%, P = .60). Over the observed period of referrals, the yearly percentages significantly decreased for good candidates and increased for possible future candidates and poor candidates. CONCLUSIONS Compared with findings in prior studies, the quality of DBS referrals has improved. The increase in referral of possible future candidates and poor candidates may reflect greater confidence in the procedure.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinsons disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets.

Focal task-specific lower extremity dystonia associated with intense repetitive exercise: A case series

BACKGROUND Focal task-specific dystonia of the lower extremity associated with intense repetitive exercise has recently been recognized. The clinical course, treatment response and prognosis remain poorly understood. METHODS Individuals with lower extremity task-specific dystonia evaluated at UCSFs Movement Disorders Center (2004-2012) were eligible for this descriptive case study series if he/she had a history of strenuous and prolonged exercise involving the lower extremity and had no abnormal neurological or medical conditions to explain the involuntary movements. Data was gathered from the medical history and a self-report questionnaire. The findings were compared to 14 cases previously reported in the literature. RESULTS Seven cases (4M/3F) were identified with a diverse set of exercise triggers (cycling, hiking, long-distance running, drumming). The mean age of symptom onset was 53.7 ± 6.1 years. The median symptom duration prior to diagnosis was 4 (9.5) years. Several patients underwent unnecessary procedures prior to being appropriately diagnosed. Over a median of 2 (3.5) years, signs and symptoms progressed to impair walking. Seven patients had improvement in gait with treatment (e.g. botulinum toxin injections, benzodiazepines, physical therapy, bracing, body weight supported gait training and/or functional electrical stimulation of the peroneal nerve) and six returned to a reduced intensity exercise routine. CONCLUSIONS Isolated lower extremity dystonia associated with strenuous, repetitive exercise is relatively uncommon, but disabling and challenging to treat. The pathophysiology may be similar to task-specific focal dystonias of the upper limb. Prompt recognition of leg dystonia associated with extreme exercise could minimize unnecessary testing and procedures, and facilitate earlier treatment.

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers

BACKGROUND Delivering specialty care remotely directly into peoples homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinsons disease in the community with usual care augmented by virtual house calls with a Parkinsons disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinsons disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS During recruitment, 11,734 individuals visited the studys Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinsons disease specialist within the previous year. CONCLUSIONS Among individuals with Parkinsons disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

Palliative care and Parkinson's disease: Meeting summary and recommendations for clinical research

INTRODUCTION Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinsons disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. METHODS An International Working Group Meeting on PD and Palliative Care supported by the Parkinsons Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. RESULTS Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. CONCLUSIONS Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers.

Bilateral Ventral Intermediate Nucleus Thalamic Deep Brain Stimulation in Orthostatic Tremor

Background: Orthostatic tremor (OT) is characterized by high-frequency leg tremor when standing still, resulting in a sense of imbalance, with limited treatment options. Ventral intermediate (Vim) nucleus thalamic deep brain stimulation (DBS) has been reported as beneficial in a few cases. Objective: To report clinical outcomes, lead locations, and stimulation parameters in 2 patients with severe medication-refractory OT treated with Vim DBS. Methods: The patients underwent surface electromyography (EMG) to confirm the OT diagnosis. Outcomes were measured as change in tolerated standing time at the last follow-up. Lead locations were quantified using postoperative MRI. Results: Vim DBS was well tolerated and resulted in improvement in standing time (patient 1: 50 s at baseline to 15 min 16 months after surgery; patient 2: 34 s at baseline to 4.2 min 7 months after surgery). Postoperative surface EMG for patient 1 demonstrated a delayed onset of tremor, lower-amplitude tremor, and periods of quiescence, but an unchanged tremor frequency. Conclusion: These cases provide further support for Vim DBS to improve standing time in severe medication-refractory OT. The location of the effective thalamic target for OT does not differ from the effective target for essential tremor.

Rocuronium as muscle relaxant for electroconvulsive therapy in a patient with adult-onset muscular dystrophy.

Abstract Adult-onset muscular dystrophy is an inherited myopathy characterized by a variable degree of progressive muscle weakness and degeneration. Although not usually fatal, significant muscle weakness results in an up-regulation of acetylcholine receptors on the less responsive postjunctional muscles. The resulting profound potassium release when these receptors are stimulated by the depolarizing muscle relaxant succinylcholine can result in potentially fatal cardiac arrhythmias. We report a case of electroconvulsive therapy safely administered in a 61-year-old man with adult-onset muscular dystrophy requiring muscle relaxation with rocuronium.

CEREBROVASCULAR DISEASE AND PREGNANCY

Approximately 12%–27% of cerebrovascular disease in women of childbearing age is associated with pregnancy. The reported incidence of stroke in pregnancy ranges from 0.01%–0.05%. While these events are uncommon, they are often clinically devastating. The Center for Disease Controls (CDC) review of death certificates in all 50 states and the District of Columbia found that neurologic or neurovascular problems are one of the leading causes of mortality in pregnancy.