Aims While behavior-based pelvic floor muscle exercise therapy is an effective treatment for overactive bladder in Parkinson's disease (PD) patients, cognitive function may be a predictor of rehabilitation outcomes. Methods In a planned exploratory analysis, participants who had a Montreal Cognitive Assessment (MoCA) with a score >= 18 who were randomized in a clinical trial to behavioral treatment were classified by perceived improvement (Benefit vs. No Benefit) as reported on a validated Satisfaction and Benefit Questionnaire. General cognition (MoCA), motor procedural learning (Serial reaction time task), verbal memory (Buschke delayed recall), spatial memory (Nonverbal/Spatial selective reminding test), and working memory (Wisconsin card sorting task) were compared between the two groups using Wilcoxon rank-sum test. Results Of the 26 participants randomized to behavioral treatment (70% male, mean age 71 +/- 6.1 years), 22 participants (85%) reported Benefit and four reported No Benefit. General cognition, motor procedural learning, verbal memory, spatial memory, and working memory did not differ between these groups. While the difference between the time to complete the final practiced series and the random series of the Serial Reaction Time Task (SRTT) was statistically similar between the groups, the Benefit group performed the random sequence more quickly (567.0 +/- 136.5 ms) compared to the No Benefit group (959.4 +/- 443.0 ms; p = 0.03) and trended toward faster performance in the final practiced series. Conclusions Perceived benefit from behavioral treatment for overactive bladder was not associated with measures of baseline cognition other than faster completion of the SRTT. This is noteworthy because many behavior-based therapy studies exclude participants with mild cognitive impairment. Additional studies may evaluate if domain-specific cognitive function, particularly the assessment of implicit memory, could lead to individualized behavioral therapy recommendations.

Background: Age-gender-specific prevalence rates for parkinsonism and Parkinson’s disease (PD) are important to guide research, clinical practice and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine its risk factors in a cohort of elderly individuals from LatAm.Methods: Data from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and who lived in six LatAm countries were analyzed to estimate Parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson’s Disease Society Brain Bank’s clinical criteria.Findings: In this cohort, the prevalence of Parkinsonism was 8.0% (95% CI 7.6%-8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%-2.3%). PD prevalence increased with age from 1.0 to 3.5 (65-69 vs. 80 years or older, p<0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40-3.01, I2=56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I2=0.0%) and educational level (aPR 1.14, 95% CI 1.01- 1.29, I2=58.6%).Interpretation: The reported prevalence of PD in LatAm is similar to the prevalence in HIC. A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations that are currently undergoing rapid demographic aging and epidemiological transition.Funding: The 10/66 Dementia Research Group’s research has been funded by the Wellcome Trust Health Consequences of Population Change Program (GR066133 – Prevalence phase in Cuba and Brazil; GR080002- Incidence phase in Peru, Mexico, Argentina, Cuba, Dominican Republic, Venezuela, and China).Declaration of Interest: None to declare. Ethical Approval: This project was approved by local institutional review boards and the King’s College London Research Ethics Committee.

Ocular oscillations often have critical role in diagnostic algorithm of neurodegenerative disorders. Nystagmus, if present in parkinsonian syndrome, suggests cerebellar involvement that is typical of multiple system atrophy. We found vertical jerky oscillations of the eyes during oculographic assessments using head-fixed corneal curvature trackers in six patients with progressive supranuclear palsy. The oscillations were eliminated by adequate head stabilization of the patients. Although this phenomenon gave the initial impression of "downbeat nystagmus", the oscillations were phase locked and frequency matched with subtle jerky head oscillations. We interpreted such jerky eye oscillations as "pseudonystagmus" representing the vestibulo-ocular reflex in response to involuntary subtle jerky head oscillations in our patients. This study further emphasizes the importance of head stabilization during instrumented or clinical assessment of gaze holding.

Significance Expansion of 55-200 CGG repeats in the 5′ untranslated region of FMR1 predisposes carriers to fragile X–associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. FXTAS demonstrates incomplete penetrance, which strongly suggests the presence of genetic modifiers. We performed whole-genome sequencing (WGS) on male premutation carriers (CGG 55–200 ) followed by a functional screen in Drosophila and identified PSMB5 as a strong suppressor of CGG-associated neurodegeneration, thereby presenting a therapeutic strategy for FXTAS.

Functional neurological disorder (FND) is a complex neuropsychiatric syndrome with many phenotypes that are commonly encountered in clinical practice. Despite the heterogeneity of FND, the rate of misidentification is consistently low. For the more common motor subtypes, there are clear positive clinical, electrophysiological, and rarely imaging criteria that can establish the diagnosis in the traditional sense. For nonmotor subtypes, the characterization may be less clear. Here, we argue that the current diagnostic criteria are not reflective of the current shared neuropsychiatric understanding of FND, and, as a result, provide an incomplete picture of the diagnosis. We propose a three-step diagnostic triad for FND, in which the traditional neurological diagnosis is only the first element. Other steps include psychiatric/psychological formulation, integration, and follow-up. We advocate that this diagnostic approach should be the shared responsibility of neurology and mental health professionals. Finally, a research agenda is proposed to address the missing factors in the field.

Basal ganglia are particularly vulnerable to mitochondrial dysfunction leading to a wide range of movement disorders of which dystonia and parkinsonism are the most common. Management of these conditions remains a challenge, because their response to all available treatments is poor. MEGDEL syndrome (3-MEthylGlutaconic aciduria, Deafness, Encephalopathy, and Leigh-like syndrome) is one such rare mitochondriopathy that presents in early childhood. We report a patient with novel mutations in SERAC1 gene who presented with secondary dystonia and had a meaningful and sustained improvement in her condition with bilateral deep brain stimulation (DBS) therapy of the globus pallidus interna (GPi).

OBJECTIVE:A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS:We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. RESULTS:We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS:Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.

AIM:Determine the efficacy of behavioral therapy for urinary symptoms in Parkinson's disease. METHODS:Randomized trial of behavioral therapy compared with control condition among adults (aged 54-85 years, 74% male, 10% Black/ 83% White) with Parkinson's and greater than or equal to 4 incontinence episodes weekly. Behavioral therapy included pelvic floor muscle exercises, bladder training, fluid and constipation management. Both groups completed bladder diary self-monitoring. Outcomes included diary-derived incontinence and ICIQ-overactive bladder (OAB) score (range, 0-16) with bother and quality of life questionnaires (higher scores = worse outcomes). RESULTS:Fifty-three participants randomized and 47 reported 8-week outcomes including 26 behavioral therapy and 21 control. Behavioral vs control participants were similar with respect to age (71.0 ± 6.1 vs 69.7 ± 8.2 years), sex (70% vs 78% male), motor score, cognition, mean weekly incontinence episodes (13.9 ± 9.6 vs 15.1 ± 11.1) and OAB symptoms (8.9 ± 2.4 vs 8.3 ± 2.2). Weekly incontinence reduction was similar between behavioral (-6.2 ± 8.7) and control participants (-6.5 ± 13.8) (P = 0.89). After multiple imputation analysis, behavioral therapy participants reported statistically similar reduction in OAB symptoms compared to control (-3.1 ± 2.8 vs -1.9 ± 2.2, P = 0.19); however quality of life (-22.6 ± 19.1 vs -7.0 ± 18.4, P = 0.048) and bother (-12.6 ± 17.2 vs - 6.7 ± 8.8, P = 0.037) improved significantly more with behavioral therapy. CONCLUSION:Self-monitoring resulted in fewer urinary symptoms; however, only multicomponent behavioral therapy was associated with reduced bother and improved quality of life. Providers should consider behavioral therapy as initial treatment for urinary symptoms in Parkinson's disease.

Correspondence George Araklitis, Department of Urogynaecology, King’s College Hospital, London, SE5 9RS, UK. Email: george.araklitis@nhs.net Abstract Aims: To test the different formulae to calculate the bladder volume using ultrasound; the accuracy of patients hearing/feeling “bubbles” at the end of urodynamics testing as a measure of being empty; and how good we are at estimating PVR using X‐ray at the end of video urodynamics testing. Methods: This was a prospective cohort study. Using Sonosite 180 plus, bladder volumes were calculated as, height × width × depth × proportionality constant (0.52, 0.625, 0.65, and 0.7) Patients were asked whether the patient heard or felt “bubbles” at the end of the investigation. Each patient was fluoroscopically screened and the clinician estimated the volume and compared with single‐use catheter volume. Results: A total of 85 patients were assessed. All four formulae were significantly correlated. The PC, 0.52, correlated best (r= 0.938, P< 0.001) with no significant difference with the actual volumes (P= 0.275). The “bubbles test” had a positive predictive value of 93%. A video postvoid residual (PVR) estimation significantly correlated with catheterised bladder volume (r= 0.842, P< 0.001). There was no significant difference between the estimated and actual bladder volumes (P= 0.579). Conclusion: This study showed that although all four formulae correlated significantly, the PC of 0.52 was the only formula without a significant difference from the actual volume. More work is needed to produce patient individualised PC. Our clinicians were able to accurately estimate the PVR on X‐ray. This study has identified the best formula to accurately estimate bladder volume and that video estimation along with the “bubbles” test can avoid unnecessary intervention.

We present two cases that highlight the importance of non-motor symptoms in the management of tics in Tourette syndrome (TS). Attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are frequent comorbidities in TS. Their presentation in TS can be significantly different from that in the general population. Failure to recognize these differences can lead to missed opportunities for effective management and to unnecessary suffering on the part of TS patients. In children, tic severity is influenced by developmental issues that may be more subtle in adults. In children and adults, tic severity is highly variable but heavily influenced by the above and other possible comorbidities of TS. These include anxiety, mood disorders, learning disabilities, and acquired maladaptive behaviors used to cope with the stress brought on by TS. Tics are also heavily influenced by external factors such as self esteem issues stemming from being repeatedly taunted by peers early on and by well-meant disciplinary strategies used by parents and teachers that may end up enabling tics over time (e.g., blaming everything on the tics, using tics to avoid expectations and responsibilities, and in school, placing unrealistic expectations and little support with tic control). We hope these cases and the suggested reading allow the reader to better recognize, prioritize, and orchestrate the various treatment paths to controlling tics in TS.

Background: The epidemiologic evidence of whether hypertension is associated with Progressive Supranuclear Palsy (PSP) is inconsistent. The ENGENE-PSP case-control study determined various PSP risk factors including whether hypertension preceded PSP onset. Methods: Incident PSP cases per NINDS-PSP criteria and age-, sex-, race- matched controls were recruited from similar North American geographic areas. All study participants were administered standardized interviews to obtain data on demographics, medical history and medications. Statistics: We used univariate and multivariate conditional logistic regression models to measure the associations between PSP and the following predictor variables: education level, hypertension, comorbid vascular conditions (diabetes mellitus and hyperlipidemia), and classes of anti-hypertensive medications using odds ratios and 95% confidence intervals. Results: There were significant associations seen between PSP and hypertension (OR: 1.569; 95% CI 1.129-2.181; p-value = 0.007), education level (OR: 0.733; 95% CI 0.637-0.843; p-value < 0.001) and beta-blocker use (OR: 2.000; 95% CI 1.053-3.799; p-value = 0.034). However, in the multi-variate analysis hypertension (OR: 1.492; 95% CI 1.045-2.129; p-value = 0.027) and education level (OR: 0.730; 95% CI 0.633-0.841; p-value < 0.001) were the only significant associations. Conclusion These results suggest that there is a modest, yet significant association between hypertension and PSP. Further studies will be needed to better understand the pathophysiological basis for this finding.

The International Parkinson Disease and Movement Disorder Society PSP study group (IPMDS-PSP) recently published new clinical diagnostic criteria for progressive supranuclear palsy (PSP). Currently, there is no data regarding the accuracy of these sets of criteria for differentiating various PSP phenotypes. We discuss the accuracy of the IPMDS-PSP criteria for differentiation of patients with the PSP- Richardson phenotype (PSP-RS) from those with the PSP-Parkinsonism (PSP-P) using data from a sample of 274 clinically diagnosed PSP patients participating in the Environmental Genetic PSP (ENGENE-PSP) case control study. Using National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) criteria and the Williams criteria we categorized 259 of these patients as probable PSP-RS and 15 as PSP-P. The IPD-MDS PSP-RS and PSP-P criteria were unable to distinguish the PSP-RS from the PSP-P phenotypes in this sample. Nearly all (92.6%; 240 out of 259) the PSP-RS patients and over half (60%; 9 out of 15) of the PSP-P patients fulfilled both the IPMDS criteria for PSP-RS and PSP-P. Applying the newly proposed multiple allocation extinction rules decreased the number of overlapping diagnoses among the NINDS-SPSP PSP-RS patients, however problems remained in the PSP-P group. Diagnostic accuracy might be improved by modification of timelines for development of falls and other parkinsonian features.

Background: Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome. Methods: Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of >= 20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales. Results: Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo). Conclusions: Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. (c) 2018 International Parkinson and Movement Disorder Society

We will use video presentations and discussions to familiarize psychiatrists and other mental health professionals with common movement disorders in children with developmental and neuropsychiatric conditions and help them identify various phenotypes and differentials of these conditions, such hyperactivity, stereotypies, repetitive and self-injurious behaviors, tics, chorea, and myoclonus. We will examine and expand on the motor phenotypes of the developmental conditions, such as Tourette's disorder and ASD, using the neurological examination and clinical metrics to assess the severity of the symptoms. We will also examine drug-induced movements in the children. Although they can be best avoided by limiting and controlling the exposure to these agents, the side effects can be managed through early recognition and/or treatment as appropriate. In these age groups, the probable etiologies for these movements are underlying developmental, genetic, metabolic, or infectious conditions, as well as exposure to psychotropic drugs and substance use.

An Online First version of this article was made available online at http://link.springer.com/journal/40263/onlineFirst/page/1 on 12 March 2018. An error was subsequently identified in the article, and the following correction should be noted.

Background: Slowed and curved rapid eye movements, saccades, are the well-known features of progressive supranuclear palsy (PSP). The authors hypothesized that the saccades in PSP not only are slow and curved but also are irregular and have timing deficits. Methods: This hypothesis was tested in 12 patients with PSP by measuring vertical and horizontal visually guided saccades using a limbus tracker. Results: Both horizontal and vertical saccades were slow and had irregular trajectory and velocity profiles, but deficits were much more robust in vertical saccades. The irregularity in the saccade velocity was due to premature interruptions that either completely stopped the eyes or moved the eyes at much slower velocity along or in the opposite direction of the ongoing saccade. The direction of the eye's trajectory was often changed after the interruption. A conductance-based, single-compartment model of the burst neurons embedded in local feedback circuit for saccade generation was simulated. This model mimicked anatomic and physiologic realism while allowing the liberty to selectively change the activation of individual burst neurons or pause neurons. The PSP saccades were comparable to the simulations during reduced activity of the inhibitory and excitatory burst neurons. Conclusion: PSP saccades are due to the paucity in burst generation at the excitatory burst neurons and imprecise timing signal from the inhibitory burst neurons. Premature discharge of the inhibitory burst neuron further leads to breaks in the saccade trajectory and maladaptive superior colliculus activity, leading to aberrant saccades that change the intended trajectory of the ongoing saccade.

BACKGROUND:Anti-inflammatory drug use, particularly ibuprofen, has been associated with a lower risk of Parkinson's disease. Microglial activation and inflammatory cytokine expression have been shown to be pathological features of progressive supranuclear palsy. We examined the association between NSAID use and risk of PSP, disease severity and age at onset.METHODS:The ENGENE-PSP multicenter case-control study recruited incident PSP cases who met the NINDS-PSP Society diagnostic criteria and age-, sex- and race-matched controls primarily from the same geographical areas. All subjects underwent standardized interviews to obtain data on demographics, residential history, medication history and lifetime occupational history. NSAID use was specifically queried by telephone interview using a standardized questionnaire.RESULTS:Information was obtained on anti-inflammatory drug exposure in 276 cases and 278 controls. No association was found between NSAID exposure and risk of PSP, age at onset or rate of change of UPDRS motor subscale, PSP Rating Scale or Mattis Dementia Rating Scale scores. This lack of association persisted when NSAID exposure was measured considering any NSAIDs, ibuprofen only, ASA only or non-ibuprofen, non-aspirin NSAIDs.CONCLUSIONS:These results do not suggest an important association between NSAID use and PSP occurrence or expression. Despite the large size of our study, confidence intervals were wide. To rule out small associations, very large sample sizes will be required.

We report on the first group of patients selected for Emory Special Diagnostic Clinic evaluation, with an emphasis on those referred to neurology and psychiatry with unknown diagnoses after extensive workups.

Studies of saccadic eye movements in subjects with Tourette syndrome (TS) have provided additional evidence that there is a link between TS symptoms and deficits in fronto-striato-thalamic networks. These studies revealed impaired timing and inhibition of saccades. We compared fixational eye movements, such as microsaccades and ocular drifts, in subjects with TS and healthy controls.We measured horizontal and vertical eye positions with video-oculography in 14 subjects with Tourette syndrome. We found reduced microsaccade amplitude but increased time between adjacent microsaccades (intersaccadic interval). Hence, the rate of microsaccades was reduced in subjects with TS compared to controls. Measure of ocular stability during intersaccadic intervals revealed increased drift velocity and increased variance in eye position. We hypothesize that increased activity of the direct fronto-striatal pathway and the resulting reduction in basal ganglia outflow targeting the superior colliculus fixation zone affect the rate and amplitude of microsaccades in subjects with TS. The resulting impairment in frontal eye field fixation leads to increased drifts during intersaccadic interval in subjects with TS. Possible clinical implication for these results is that fixational eye movements can be objective biological markers of TS.

April 20, 2016April 5, 2016Free AccessPredictors of Cognitive Decline in FXTAS (P5.386)Joash Lazarus, Lisa Shubeck, Emily Allen, Debra Hamilton, Jennifer Choi, Stephanie Sherman, and Jorge JuncosAuthors Info & AffiliationsApril 5, 2016 issue86 (16_supplement)https://doi.org/10.1212/WNL.86.16_supplement.P5.386 Letters to the Editor