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Objective To assess the efficacy, safety, and outcomes of sacral nerve stimulation (SNS) for Parkinson's disease (PD) patients with overactive bladder symptoms. Methods We retrospectively reviewed PD patients who underwent Stage I SNS. Demographics, urodynamic data, and baseline voiding function were analyzed. Efficacy and safety of treatment were determined by rate of progression to Stage II, explantation, and surgical revision. Long-term outcomes were assessed using voiding diaries and/or clinic notes. Results Sixty percent (9/15) experienced ≥50% improvement in urinary parameters and proceeded to Stage II. There was no significant difference in age, body mass index, comorbidities, PD disease duration, or levodopa equivalent daily dose between successful and nonsuccessful Stage I patients. However, 100% of female patients experienced Stage I success compared to 44% of male PD patients (P = .04). Individuals with >12-month follow-up experienced an average reduction of 6 voids/day. No patients required revision or explantation of their device at latest clinic follow-up (22.2 ± 7.8 months). Higher maximal urethral closure pressures, detrusor pressure at maximum flow rate (PdetQmax), post-void residual volume, and mean bladder outlet obstruction index were observed in the Stage I trial failures. Conclusion At our institution, PD patients have a similar rate of progression to Stage II compared to the general population. SNS is an effective therapy that should be considered among the treatment options for PD patients with overactive bladder symptoms. Urodynamic parameters associated with obstruction may be predictive of SNS failure in PD patients and may help guide patient selection, however further studies are needed.

Increasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting.We compared 16,994 neurology (9.4%) and 163,714 non-neurology comparison trials registered to ClinicalTrials.gov. Trials therapeutic focus within neurology was assigned via combination programmatic and manual review. We performed descriptive analyses of trial characteristics, cox regression of early discontinuation, and multivariable logistic regression for results reporting within 3 years of completion.Most neurology trials were academic-funded (58.5%) followed by industry (31.9%) and US-government (9.6%). Neurology trials focused more on treatment than prevention compared to non-neurology studies. Of neurology trials, 11.3% discontinued early, and 32.2% of completed trials reported results by April 30, 2018. In multivariable analysis accounting for time-to-event, neurology trials were at lower risk of discontinuation than non-neurology trials (adjusted hazard 0.83, p 0.0001). Both academic and government-funded trials had greater risk of discontinuation than industry (adjusted hazard 0.57 and 0.46, respectively). Among completed trials, government-funded studies (adjusted odds ratio 2.12, p 0.0001) had highest odds of results reporting while academic trials reported less (adjusted odds ratio 0.51, p 0.0001).Funding source is associated with trial characteristics and outcomes in neurology. Improvements in trial completion and timely dissemination of results remain urgent goals for the field.

ObjectiveTo determine whether NeuroBytes is a helpful e-Learning tool in neurology through usage, viewer type, estimated time and cost of development, and postcourse survey responses.BackgroundA sustainable Continuing Professional Development (CPD) system is vital in neurology due to the field's expanding therapeutic options and vulnerable patient populations. In an effort to offer concise, evidence-based updates to a wide range of neurology professionals, the American Academy of Neurology (AAN) launched NeuroBytes in 2018. NeuroBytes are brief (MethodsNeuroBytes was beta tested from August 2018 to December 2018 and launched for pilot circulation from January 2019 to April 2019. Usage was assessed by quantifying course enrollment and completion rates; feasibility by cost and time required to design and release a module; appeal by user satisfaction; and effect by self-reported change in practice.ResultsA total of 5,130 NeuroBytes enrollments (1,026 ± 551/mo) occurred from January 11, 2019, to May 28, 2019, with a median of 588 enrollments per module (interquartile range, 194–922) and 37% course completion. The majority of viewers were neurologists (54%), neurologists in training (26%), and students (8%). NeuroBytes took 59 hours to develop at an estimated $77.94/h. Of the 1,895 users who completed the survey, 82% were “extremely” or “very likely” to recommend NeuroBytes to a colleague and 60% agreed that the depth of educational content was “just right.”ConclusionsNeuroBytes is a user-friendly, easily accessible CPD product that delivers concise updates to a broad range of neurology practitioners and trainees. Future efforts will explore models where NeuroBytes combines with other CPD programs to affect quality of training and clinical practice.

The decline of skeletal muscle mass and strength that leads to sarcopenia is a pathology that might represent an emergency healthcare issue in future years. Decreased muscle mass is also a condition that mainly affects master athletes involved in endurance physical activities. Skeletal muscles respond to exercise by reshaping the biochemical, morphological, and physiological state of myofibrils. Adaptive responses involve the activation of intracellular signaling pathways and genetic reprogramming, causing alterations in contractile properties, metabolic status, and muscle mass. One of the mechanisms leading to sarcopenia is an increase in reactive oxygen and nitrogen species levels and a reduction in enzymatic antioxidant protection. The present review shows the recent experimental models of sarcopenia that explore molecular mechanisms. Furthermore, the clinical aspect of sport sarcopenia will be highlighted, and new strategies based on nutritional supplements, which may contribute to reducing indices of oxidative stress by reinforcing natural endogenous protection, will be suggested.

Managing patient interactions in the age of the Internet can be particularly difficult due to the vast amount of information available. Dermatologists should be able to identify relevant patient concerns to adequately address them. We discuss the ethical issues involved in interacting with patients who use the Internet for medical knowledge, and we suggest a method, using the "three Rs" (reassure, redirect, refer), to conduct these interactions. Appropriate evaluation and categorization of patients with regard to their concerns and needs can help guide physicians on how to use the three Rs in managing patient care and expectations.

Cognitive impairment in older adults is a rapidly growing public health concern as the elderly population dramatically grows worldwide. While it is generally assumed that cognitive deficits in older adults are associated with reduced brain flexibility, quantitative evidence has been lacking. Here, we investigate brain flexibility in healthy older adults (ages 60–85) using a novel Bayesian switching dynamical system algorithm and ultrafast temporal resolution (TR = 490 ms) whole-brain fMRI data during performance of a Sternberg working memory task. We identify latent brain states and characterize their dynamic temporal properties, including state transitions, associated with encoding, maintenance, and retrieval. Crucially, we demonstrate that brain inflexibility is associated with slower and more fragmented transitions between latent brain states, and that brain inflexibility mediates the relation between age and cognitive inflexibility. Our study provides a novel neurocomputational framework for investigating latent dynamic circuit processes underlying brain flexibility and cognition in the context of aging.

Background Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options. Methods Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques. Results Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery. Conclusions Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society

Kleine-Levin syndrome (KLS) is a rare disorder characterized by recurrent episodic hypersomnia, cognitive changes, and neuropsychiatric symptoms between months of interictal normality (table). Triggers include infection, sleep deprivation, or alcohol intake, and diagnosis requires exclusion of other medical etiologies.1 Urea cycle disorders are most commonly diagnosed via newborn screening or during workup of early, life-threatening hyperammonemia. We describe a young man with a late-onset urea cycle disorder who initially presented with phenomenology akin to KLS.

ObjectivesTo better understand the reasons medical students select or avoid a career in neurology by using a qualitative methodology to explore these factors, with the long-term objective of attracting more graduates to the field.MethodsIn 2017, 27 medical students and 15 residents participated in 5 focus groups, and 33 fourth-year medical students participated in semistructured individual interviews. Participants were asked predefined open-ended questions about specialty choice, experiences in their basic neuroscience course and neurology clerkship, and perceptions about the field. Interviews were audio recorded and transcribed. We used a flexible coding methodology to generate themes across groups and interviews.ResultsFour main analytical themes emerged: (1) early and broad clinical exposure allows students to “try on” neurology and experience the variety of career options; (2) preclerkship experiences and a strong neuroscience curriculum lay the foundation for interest in the field; (3) personal interactions with neurology providers may attract or deter students from considering the specialty; and (4) persistent stereotypes about neurologists, neurology patients, and treatment options harm student perceptions of neurology.ConclusionEfforts to draw more students to neurology may benefit from focusing on clinical correlations during preclerkship neuroscience courses and offering earlier and more diverse clinical experiences, including hands-on responsibilities whenever possible. Finally, optimizing student interactions with faculty and residents and reinforcing the many positive aspects of neurology are likely to favorably affect student perceptions.

ObjectiveTo test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.MethodsOutcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.ResultsMeasured scores remained improved from baseline to 36 months (allp< 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2,p= 0.0098) and disability (95% CI 1–4,p= 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.ConclusionsResults at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

ObjectivesTo identify factors associated with medical students becoming neurologists because, despite the increasing burden of neurologic disorders, there is a growing neurologist shortage.MethodsDeidentified data from the Association of American Medical Colleges Matriculating Student Questionnaire (MSQ) and Graduation Questionnaire (GQ) were obtained for the graduation years 2013 to 2014 through 2016 to 2017. Logistic regression was used to assess demographic characteristics and responses to training and career-related questions in association with specialty choice (intent to enter neurology).ResultsOf the 51,816 students with complete data, 1,456 (2.8%) indicated an intent to enter a neurology residency. Factors associated with an increased likelihood of entering neurology were a student's rating of excellent for their basic neuroscience course and neurology clerkship, participation in an MD/PhD program, majoring in neuroscience or psychology as an undergraduate, a selection response of “content of the specialty was a strong influence on career choice,” and indicating interest in neurology on the MSQ. Factors associated with a decreased likelihood of entering neurology were a higher-priority response on the GQ for salary, work/life balance, and personal fit of the specialty.ConclusionData from surveys at the entry into and graduation from medical school suggest several approaches to increase the number of medical students entering neurology, including a focus on the student-reported quality of the basic neuroscience course and neurology clerkships, targeted engagement with MD/PhD students, and mentoring programs for students interested in neurology. Efforts to improve salaries for neurologists, to reduce medical school debt, and to improve work/life balance may also help to attract more students.

Introduction Reading difficulties are common in Parkinson's disease (PD) but not well studied. We report a case of reading difficulties in a 40-year-old man with 6-year history of PD on dopamine replacement therapy. Methods We performed detailed neuro-ophthalmic examination and assessment of reading with and without infrared oculography. Results Clinical examination revealed visual acuity of 20/20, no evidence of vision loss, and normal eye movement and ocular alignment with normal saccades, pursuit, and normal convergence. During King-Devick test, a rapid number reading task performed on a book, patient had normal number reading speed. More detailed study of number and word reading using infrared oculography revealed that while this patient had normal speed and eye movement behavior during number reading, he had dramatic slowing and eye movement abnormality during word reading. The slower reading speed during word reading was due to increased number of progressive saccades, smaller saccade amplitudes, increased number of regressive saccades, and longer fixation durations. Conclusions This case nicely illustrated the importance of comprehensive neuro-ophthalmic evaluations in Parkinson's disease and shows that reading difficulties can arise even when there is good visual acuity, ocular motor abilities necessary to read, and accommodation. In this case, reading difficulty was due to higher order ocular motor planning or cognitive abilities involved in word reading since the patient had no difficulty with ocular motor planning while reading numbers. These findings may have important implications towards our understanding of PD and can serve to spark further research in this important area.

The introduction of three-dimensional echography (3D echo) in vascular field is not recent, but it still remains a seldom-used technique because of the costs of ultrasound probe and the need of dedicated laboratories. Therefore, despite significant prognostic implications, the high diagnostic accuracy in plaque definition, and the relative ease of use, 3D echo in vascular field is a niche technique. The purpose of this review is mainly clinical and intends to demonstrate the potential strength of a 3D approach, including technical aspects, in order to present to clinicians and imagers the appealing aspects of a noninvasive and radiation-free methodology with relevant diagnostic and prognostic correlates in the assessment of carotid atherosclerosis. A comprehensive literature search (since 1990s to date) using the PubMed, MEDLINE, and Cochrane libraries databases has been conducted. Articles written in English have been assessed, including reviews, clinical trials, meta-analyses, and interventional/observational studies. Manual cross-referencing was also performed, and relevant references from selected articles were reviewed. The search was limited to studies conducted in humans. Search terms, retrieved also with PubMed Advanced search and AND/OR Boolean operators (mainly in title and abstract), included three-dimensional, echo, stroke/transient ischemic attack, predictors, carotid, imaging, and biomarkers.

Background Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor. Purpose/Hypothesis To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor. Study Type Retrospective. Population/Subjects/Phantom/Specimen/Animal Model Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T. Field Strength/Sequence T2-weighted images were acquired immediately and at 1 year posttreatment at 3T. Assessment An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year. Statistical Tests Statistical significance was assessed using the Wilcoxon two-tailed rank test. Results The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure – posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure. Data Conclusion In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS. Level of Evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.

Haiti is a country rich in revolutionaries and visionaries. It has faced countless hardships, most recently the devastating earthquake of 2010. In 2011, the population was estimated at approximately 10 million people. WHO estimates show a stark difference in the health of Haitians compared to other inhabitants of the region (table 1).1

Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 ± 13 years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction

Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.

The United States faced an estimated deficit of 1,800 neurologists in 2012 and could face a shortfall of more than 3,000 neurologists by 2025.1 This situation raises the question of what strategies medical educators could use to recruit medical students into neurology. One approach has included increasing student exposure to neurology through required clerkships.2 While important, exposure is simply not enough. Medical students must come to identify themselves with the community of neurologists in order to feel the desire to join our specialty.

The Clock Drawing Test (CDT) is a common neuropsychological measure sensitive to cognitive changes and functional skills (e.g., driving test performance) among older adults. However, normative data have not been adequately developed. We report the distribution of CDT scores using three common scoring systems [Mendez, M. F., Ala, T., & Underwood, K. L. (1992). Development of scoring criteria for the Clock Drawing Task in Alzheimer's Disease. Journal of the American Geriatrics Society, 40, 1095-1099; Cahn, D. A., Salmon, D. P., Monsch, A. U., Butters, N., Wiederholt, W. C., & Corey-Bloom, J. (1996). Screening for dementia of the Alzheimer type in the community: The utility of the Clock Drawing Test. Archives of Clinical Neuropsychology, 1](6), 529-5391, among 207 cognitively normal elderly. The systems were well correlated, took little time to use, and had high inter-rater reliability. We found statistically significant differences in CDT scores based on age and WRAT-3 Reading score, a marker of education quality. We present means, standard deviations, and t- and z-scores based on these subgroups. We found that "normal" CDT performance includes a wider distribution of scores than previously reported. Our results may serve as useful comparisons for clinicians wishing to know whether their patients perform in the general range of cognitively normal elderly. (C) 2007 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved.