Illusory Responses across the Lewy Body Disease Spectrum.

OBJECTIVE: This study was undertaken to study pareidolias, or perceived meaningful objects in a meaningless stimulus, in patients across the Lewy body (LB) disease spectrum, where most do not report hallucinations or delusions. METHODS: We studied illusory responses on the Noise Pareidolia Task in 300 participants (38 cognitively impaired LB, 65 cognitively unimpaired LB, 51 Alzheimer disease spectrum [AD-s], 146 controls). Pairwise between-group comparisons examined how diagnosis impacts the number of illusory responses. Ordinal regression analysis compared the number of illusory responses across diagnosis groups, adjusting for age, sex, and education. Analyses were repeated after removing participants with reported hallucinations or delusions. RESULTS: Cognitively impaired LB participants were 12.3, 4.9, and 4.6 times more likely than control, cognitively unimpaired LB, and AD-s participants, respectively, to endorse illusory responses. After adjusting for age, sex, and education, the probability of endorsing 1 or more illusory responses was 61% in the cognitively impaired LB group, compared to 26% in AD-s, 25% in cognitively unimpaired LB, and 12% in control participants. All results were similar after repeated analysis only in participants without hallucinations or delusions. In LB without hallucinations or delusions, 52% with mild cognitive impairment and 66.7% with dementia endorsed at least 1 illusory response. INTERPRETATION: We found illusory responses are common in cognitively impaired LB patients, including those without any reported psychosis. Our data suggest that, prior to the onset of hallucinations and delusions, the Noise Pareidolia Task can easily be used to screen for unobtrusive pareidolias in all LB patients. ANN NEUROL 2023;93:702-714.

Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.

OBJECTIVE: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial. METHODS: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. All adverse events (AEs) were reported. RESULTS: Forty-five and 40 patients completed the 4- and 5-year follow-ups, respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment, respectively (both p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each respective time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). All previously reported AEs remained mild or moderate, and no new AEs were reported. CONCLUSIONS: Unilateral MRgFUS thalamotomy demonstrates sustained and significant tremor improvement at 5 years with an overall improvement in quality-of-life measures and without any progressive or delayed complications. Clinical trial registration no.: NCT01827904 (ClinicalTrials.gov).

Neurology trial registrations on ClinicalTrials.gov between 2007 and 2018: A cross-sectional analysis of characteristics, early discontinuation, and results reporting.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Sacral Nerve Stimulation in Parkinson's Disease Patients With Overactive Bladder Symptoms.

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.

Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation.

Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.

Attracting neurology's next generation: A qualitative study of specialty choice and perceptions.

OBJECTIVES: To 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. METHODS: In 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. RESULTS: Four 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. CONCLUSION: Efforts 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.

"But doctor, I googled it!": The "three Rs" of managing patients in the age of information overload.

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.

Neurology Residents as Comprehensive Educators (Neuro RACE).

Residents are expected to be educators often without any formal schooling, and many continue a career in academic medicine where they play a pivotal role in education. However, few resident curricula have been published to include instruction in teaching, particularly in the field of Neurology. To guide Neurology residents as they take on their role as a clinician-educator, we developed a 1-year curriculum (Neurology Residents as Comprehensive Educators "Neuro RACE") with monthly sessions divided into didactics, small group discussions, and interactive kinetic learning. A postcurriculum survey was used to evaluate the residents' response to this curriculum. Residents reported an overall improvement in their comfort and confidence in their teaching abilities. As an integral part of academic training, residents-as-teachers curricula should take a prominent role in Neurology training programs.

Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor.

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.

Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.

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.