Fighting Against the Clock: Circadian Disruption and Parkinson's Disease.

Circadian disruption is being increasingly recognized as a critical factor in the development and progression of Parkinson's disease (PD). This review aims to provide an in-depth overview of the relationship between circadian disruption and PD by exploring the molecular, cellular, and behavioral aspects of this interaction. This review will include a comprehensive understanding of how the clock gene system and transcription-translation feedback loops function and how they are diminished in PD. The article also discusses the role of clock genes in the regulation of circadian rhythms, as well as the impact of clock gene dysregulation on mitochondrial function, oxidative stress, and neuroinflammation, including the microbiota-gut-brain axis, which have all been proposed as being crucial mechanisms in the pathophysiology of PD. Finally, this review highlights potential therapeutic strategies targeting the clock gene system and circadian rhythm for the treatment of PD.

Epigenetic regulation of Parkinson's disease risk variant GPNMB cg17274742 methylation by sex and exercise from Taiwan Biobank.

Background: Parkinson's disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals. Methods: We analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension. Results: Our results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (ß = -0.00242; p = 0.0026), but not in females (ß = -0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (ß = -0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078). Conclusion: This study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies.

Case report: Steroid-responsive acute chorea as first presentation of the coexistence of Moyamoya and Graves' disease.

Background: Chorea is a movement disorder characterized by abrupt, rapid, and uncontrollable, random movements from one part of the body to another with motor impersistence. Sporadic chorea is rarely caused by either thyrotoxicosis or Moyamoya disease (MMD). Methods and results: In this case report, we describe a female patient with chorea with the rare coexistence of Graves' disease and Moyamoya disease. Tc-99m ethyl cysteinate dimer (ECD) brain perfusion single-photon emission computed tomography (SPECT) showed mild to moderate hypoperfusion in bilateral frontal and left temporal regions. After administering dexamethasone 20 mg for 5 days, her choreic movement symptoms recovered rapidly. Conclusion: Although uncommon, thyrotoxicosis and Moyamoya disease can co-occur, especially in Asian female adults. Excessive thyroid hormones contribute to the dysregulation of neurotransmitters in basal ganglia-thalamocortical circuits. Moyamoya disease is responsible for ischemic changes affecting the excitatory-inhibitory circuits between the basal ganglia and the neocortex. Under a state of coexistence, thyrotoxicosis exaggerates cerebral metabolism, aggravating the impaired cerebral perfusion induced by Moyamoya disease. Moreover, inflammatory reactions caused by thyroid autoantibodies may also promote the progression of Moyamoya disease. In our experience, treatment with steroids may not only synergize the anti-thyroid effect but may also be a way to modulate the neurotransmitters within the basal ganglia or restore cerebral perfusion. We suggest that evaluation of the thyroid function status in Moyamoya disease is essential.

Sustained response in early responders to safinamide in patients with Parkinson's disease and motor fluctuations: A post hoc analysis of the SETTLE study.

Safinamide is a selective, reversible, monoamine oxidase B inhibitor for the treatment of patients with Parkinson's disease (PD) and motor fluctuations. This was a post hoc analysis of the SETTLE study, in which patients with PD and motor fluctuations were randomly assigned to 24-week treatment with safinamide (50 mg/day for 2 weeks, increased to 100 mg/day if tolerated) or placebo. In the present analysis, responders were defined according to their treatment responses at Week 2 and Week 24 based on changes in ON-time without troublesome dyskinesia from baseline with cutoffs of 1 hour. It was found that 81% (103/127) of the responders at Week 2 maintained the response through Week 24 in the safinamide group. Other outcomes did not necessarily coincide with the ON-time response; however, "Early" responders who showed a treatment response at both Week 2 and Week 24 had substantial improvements from baseline in OFF-time, UPDRS Part II and III scores, and PDQ-39 summary index scores through Week 24. The safinamide group had a higher proportion of early responders than the placebo group (39% vs 20%, p < 0.0001). At baseline, early responders in the safinamide group had significantly higher UPDRS Part II and III scores, shorter ON-time, and longer OFF-time than the other responder populations. In conclusion, the results of the present post hoc analysis suggest that patients with a short ON-time, severe motor symptoms, and highly compromised activities of daily living can benefit from safinamide early in treatment and over the long term.

Safinamide as an Adjunct to Levodopa in Asian and Caucasian Patients With Parkinson's Disease and Motor Fluctuations: A Post Hoc Analysis of the SETTLE Study.

OBJECTIVE: Safinamide is a selective, reversible monoamine oxidase B inhibitor with demonstrated efficacy and tolerability in placebo-controlled studies and is clinically useful for patients with motor fluctuations. This study evaluated the efficacy and safety of safinamide as a levodopa adjunct therapy in Asian patients with Parkinson's disease. METHODS: Data from 173 Asian and 371 Caucasian patients from the international Phase III SETTLE study were included in this post hoc analysis. The safinamide dose was increased from 50 mg/day to 100 mg/day if no tolerability issues occurred at week 2. The primary outcome was the change from baseline to week 24 in daily ON-time without troublesome dyskinesia (i.e., ON-time). Key secondary outcomes included changes in Unified Parkinson's Disease Rating Scale (UPDRS) scores. RESULTS: Safinamide significantly increased daily ON-time relative to placebo in both groups (least-squares mean: 0.83 hours, p = 0.011 [Asians]; 1.05 hours, p < 0.0001 [Caucasians]). Motor function relative to placebo (UPDRS Part III) improved significantly in Asians (-2.65 points, p = 0.012) but not Caucasians (-1.44 points, p = 0.0576). Safinamide did not worsen Dyskinesia Rating Scale scores in either subgroup, regardless of the presence or absence of dyskinesia at baseline. Dyskinesia was largely mild for Asians and moderate for Caucasians. None of the Asian patients experienced adverse events leading to treatment discontinuation. CONCLUSION: Safinamide as a levodopa adjunct is well tolerated and effective in reducing motor fluctuations in both Asian and Caucasian patients. Further studies to investigate the real-world effectiveness and safety of safinamide in Asia are warranted.

Walking Exercise Reduces Postprandial Lipemia but Does Not Influence Postprandial Hemorheological Properties and Oxidative Stress.

A higher postprandial triglycerides response and hemorheological abnormalities may increase the incidence of metabolic disorders and negatively interfere with the aging process. A single session of preprandial endurance exercise was found to be effective in reducing triglyceride levels after a high-fat diet. However, whether the exercise-induced reduction in postprandial triglyceride levels influences hemorheological indicators remains unknown. This study aims to investigate the effects of postprandial lipemia on hemorheological properties and oxidative stress. Eight healthy young male participants completed two experimental trials. On day 1, the participants were randomly assigned to walk for 1 h at 50% VO2max (EE trial) or rest (CON trial). On day 2, participants rested and consumed a high-fat meal in the morning. Results: The postprandial area under the curve (AUC) of plasma TG concentration was significantly lower in EE compared to CON (EE: 9.2 ± 1.9; CON: 10.9 ± 1.7 mmol/L·h−1; p = 0.013; Cohen's d = 0.036). No significant difference was observed in hemorheological properties and MDA (p > 0.05). Endurance exercise effectively decreased postprandial TG concentration but did not influence the postprandial hemorheological properties and oxidative stress indicators.

Effects of modern technology (exergame and virtual reality) assisted rehabilitation vs conventional rehabilitation in patients with Parkinson's disease: a network meta-analysis of randomised controlled trials.

BACKGROUND: Modern technological applications, including exergames and virtual technology-assisted rehabilitation (VTAR) programmes, are promising for Parkinson's disease (PD) rehabilitation. However, evidence regarding their efficacy for rehabilitation is inconclusive. OBJECTIVES: This network meta-analysis (NMA) investigated the efficacy of exergames and VTAR on gait and balance outcomes and acceptability for patients with PD. DATA SOURCES: ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science and ClinicalTrials.gov. STUDY SELECTION: Randomised controlled trials (RCTs) investigating changes in gait or balance parameters were included in this study. STUDY APPRAISAL AND SYNTHESIS METHODS: In the NMA, standardised mean differences with 95% confidence intervals were calculated using a frequentist model. GRADE ratings were used to evaluate the quality of evidence in this study. RESULTS: Twenty-three RCTs with 949 participants were included. Exergames and VTAR were associated with significantly better improvements in balance and gait outcomes than usual treatment and other active control interventions. However, exergames were not associated with changes in depressive symptoms. The evaluation of acceptability results indicated that all exergames and VTAR were adequately tolerated, as indicated by the low drop-out rates. LIMITATIONS: Small sample sizes and heterogeneity were the key limitations of this study. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: This NMA confirmed that exergames are associated with more favourable gait and balance outcomes in patients with PD compared with usual treatment and other active control interventions. GRADE ratings revealed that most direct, indirect and overall network evidence was of low to medium quality. Larger-scale studies with longer follow-up periods are warranted.

Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5-53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable.

Neurological Sequela of Acute Pesticide Poisoning Among Adults in Central Taiwan.

Background and Purpose: Cases of acute pesticide poisoning account for significant morbidity and mortality in developing countries; however, its burden in Taiwan remains unknown. The study examined acute pesticide poisoning (APP) involving adults in the central region of Taiwan, which is a mainly agricultural sub-urban area. Methods: The retrospective study evaluated the outcome and neurological sequelae of patients with APP in a Taiwanese cohort between April 2002 and February 2019. The pesticides were classified according to the Insecticide Resistance Action Committee Mode of Action (MoA) classification. The clinical characteristics, duration of hospitalization (days), follow-up duration (years), in-hospital mortality, neurological sequela, and imaging findings were recorded. Furthermore, multivariate logistic regression analyses were performed. Results: We identified 299 patients with APP comprising 206 (68.9%) adult men with a mean exposure age of 56.4 ± 16.8 years. Paraquat, organophosphates, pyrethroids, carmabates, and phosphinic acid were the most commonly known reported poisoning agents. The mortality rate was highest in users with paraquat (77.1%), followed by phosphinic acid (22.2%), carbamates (16.7%), and organophosphates (15.8%). After a mean follows up of 3.69 ± 2.26 years, the most common neurological sequela was a cognitive decline (56 among 225 survivors, 24.89%), peripheral neuropathy (11 among 225 survivors, 4.89%), tremor (10 among 225 survivors, 4.44%), ataxia (3/225, 1.33%), and parkinsonism feature (2/225, 0.89%). Brain imaging studies revealed basal ganglion lesions on CT or hyperintensity on T2-weighted MRI images in 26 among 46 patients (56.5%). The basal ganglion lesions on brain imaging had a positive correlation with neurological sequelae. Conclusion: Acute pesticide poisoning (APP)-related mortality is high especially paraquat intoxication, and cognitive decline, as well as peripheral neuropathy, were the most common neurological sequelae among survivors, which is highly correlated with basal ganglia lesions on brain imaging.

Motor Dysfunction Questionnaire and Dopamine Transporter Imaging Composite Scale Improve Differentiating Dementia With Lewy Bodies From Alzheimer's Disease With Motor Dysfunction.

Objective: Characteristic parkinsonism is the major comorbidity of dementia with Lewy bodies (DLB). We aimed to differentiate DLB from Alzheimer's disease (AD) with motor dysfunction using a composite scale with a characteristic motor dysfunction questionnaire (MDQ) and dopamine transporter (DAT) imaging. It could help detect DLB easily in healthcare settings without movement disorder specialists. Methods: This is a two-phase study. In the design phase, seven questions were selected and composed of a novel MDQ. In the test phase, all participants with DLB, AD, or non-dementia (ND) control completed dementia and parkinsonism survey, the novel designed questionnaire, DAT imaging, and composite scales of MDQ and DAT. The cutoff scores of the MDQ, semiquantitative analysis of the striatal-background ratio (SBR) and visual rating of DAT, and the composite scale of MDQ and DAT for discriminating DLB from AD or ND were derived and compared. Results: A total of 277 participants were included in this study (126 with DLB, 86 with AD, and 65 with ND). Compared with the AD or ND groups, the DLB group showed a significantly higher frequency in all seven items in the MDQ and a significantly lower SBR. For discrimination of DLB from non-DLB with MDQ, SBR, and composite scale, the cutoff scores of 3/2, 1.37/1.38, and 6/5 were suggested for the diagnosis of DLB with the sensitivities/specificities of 0.91/0.72, 0.91/0.80, and 0.87/0.93, respectively. The composite scale significantly improved the accuracy of discrimination compared with either the MDQ or SBR. Conclusion: This study showed that the novel designed simple questionnaire was a practical screening tool and had similar power to DAT scanning to detect DLB. The questionnaire can be applied in clinical practice and population studies for screening DLB. In addition, the composite scale of MDQ and DAT imaging further improved the diagnostic accuracy, indicating the superiority of the dual-model diagnostic tool.

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF. Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF. Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25-0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21-0.79 for severe DWMLs]. Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

Effects of home-based exercise on motor, non-motor symptoms and health-related quality of life in Parkinson's disease patients: A randomized controlled trial.

AIM: To explore the effect of home-based exercise on motor symptoms (MS), non-motor symptoms (NMS), and health-related quality of life (HRQOL) in Parkinson's disease (PD) patients. METHODS: This study was a randomized control trial with a convenience sample of 98 PD patients. Data were collected at baseline and interventions after 4 and 8 weeks. The exercise group was instructed to perform 150 min/week of exercise at home; the control group maintained their regular lifestyle. Questionnaires measured MS, NMS, and HRQOL. We also compare compliance and non-compliance subgroups of the exercise group. The generalized estimating equation (GEE) was used to determine the exercise effect of 120 and 150 min per week after testing for exercise times was at six time points (90-140 min). RESULTS: The exercise (n = 49) and control groups (n = 49) were homogeneous except for disease stage at baseline. Significant differences were found for depression, HRQOL, motor ability, activity of daily living, and fatigue (p < .000) between the exercise and control groups, and also between the compliance and non-compliance subgroups (p < .05). The GEE revealed that exercising 150 min/week significantly improved HRQOL, depression, motor ability, ADL, fatigue, and sleep quality (p < .05), though not anxiety, and exercising 120 min/week was also effective. CONCLUSIONS: This home-based exercise was effective in improving MS, NMS, and HRQOL. We recommend PD patients to exercise 30-50 min at least three times a week, or 10-15 min per session daily, to accumulate 120-150 min per week.

EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia.

OBJECTIVE: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia. METHODS: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients. RESULTS: We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) gene, segregating with early onset isolated generalized dystonia in 5 patients of a Taiwanese family. EIF2AK2 sequencing in 191 unrelated patients with unexplained dystonia yielded 2 unrelated Caucasian patients with an identical heterozygous c.388G>A, p.Gly130Arg variant, occurring de novo in one case, another patient carrying a different heterozygous variant, c.413G>C, p.Gly138Ala, and one last patient, born from consanguineous parents, carrying a third, homozygous variant c.95A>C, p.Asn32Thr. These 3 missense variants are absent from gnomAD, and are located in functional domains of the encoded protein. In 3 patients, additional neurological manifestations were present, including intellectual disability and spasticity. EIF2AK2 encodes a kinase (protein kinase R [PKR]) that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), which orchestrates the cellular stress response. Our expression studies showed abnormally enhanced activation of the cellular stress response, monitored by PKR-mediated phosphorylation of eIF2α, in fibroblasts from patients with EIF2AK2 variants. Intriguingly, PKR can also be regulated by PRKRA (protein interferon-inducible double-stranded RNA-dependent protein kinase activator A), the product of another gene causing monogenic dystonia. INTERPRETATION: We identified EIF2AK2 variants implicated in early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. Our findings provide direct evidence for a key role of a dysfunctional eIF2α pathway in the pathogenesis of dystonia. ANN NEUROL 2021;89:485-497.

Retinal arterial occlusion with multiple retinal emboli and carotid artery occlusion disease. Haemodynamic changes and pathways of embolism.

OBJECTIVE: To introduce a special subgroup, retinal artery occlusion (RAO) with multiple emboli, which is highly associated with ipsilateral carotid artery occlusion disease (CAOD). METHODS AND ANALYSIS: This is a cohort study. Cases of RAO with multiple retinal emboli were consecutively enrolled. All patients underwent at least one of the carotid/cerebral evaluations: carotid arteriography, orbital/carotid colour Doppler ultrasonography and CT angiography to demonstrate haemodynamic changes and to discuss possible mechanisms and pathways of the emboli. RESULTS: Among 208 RAO eyes, 12 eyes (5.7%) in 11 patients had multiple emboli were recruited in this study. Eleven eyes (91.6%) had ipsilateral carotid plaques and atherosclerosis with high-grade stenosis; among them, five were total carotid occlusion. Haemodynamic changes were found in nine patients with RAO (81.8%) with carotid stenosis 60% or greater. Most compensatory intracranial circulations were re-established via the circle of Willi with antegrade ophthalmic flows, but the direction of ophthalmic flow reversed in three eyes indicating the recruitment of external collaterals. Two cases underwent carotid stent successfully. CONCLUSION: RAOs with multiple emboli are rare but highly associated with severe CAOD with haemodynamic flow changes, warning critical condition in carotid/cerebral circulations. Either direct embolism from the carotid or cardiac lesions or indirect embolism via the collateral pathways is the mechanism of pathogenesis. Immediate action should start to manage these patients to prevent further deterioration.

Antidiabetic Agents for Treatment of Parkinson's Disease: A Meta-Analysis.

Background: Clinical and epidemiological studies suggest that two of the most common geriatric diseases, type 2 diabetes and Parkinson's disease (PD), are linked. These studies notably suggest that treatment of insulin resistance in type 2 diabetes may beneficially modify the pathophysiology of PD and help to maintain motor and nonmotor function. In this meta-analysis, we evaluate the efficacy of new antidiabetic agents in the treatment of PD. Methods: We systematically searched PubMed, Medline, ProQuest, ScienceDirect, ClinicalKey, and Cochrane Library from the date of their inception until 15 March 2020. Multiple efficacy parameters were compared between treatment groups. The results are expressed as mean differences with 95% confidence intervals (CIs) in a random-effects model. Results: A meta-analysis of the data extracted from three randomized control trials revealed that treatment with exenatide yielded significant improvements in scores on the Unified Parkinson's Disease Rating Scale Part I (UPDRS-I) (-0.438, 95% CI, -0.828 to -0.048, p = 0.028), UPDRS Part IV (UPDRS-IV) (-0.421, 95% CI, -0.811 to -0.032, p = 0.034) and the Mattis Dementia Rating Scale (MDRS) (-0.595, 95% CI, -1.038 to -0.151, p = 0.009). At the 12-month follow-up, the UPDRS Part III (UPDRS-III) scores in the off-medication phase revealed significant improvements in patients using exenatide (-0.729; 95% CI, -1.233 to -0.225, p = 0.005). Treatment with pioglitazone did not yield significant improvements in UPDRS, MDRS, or Parkinson's Disease Questionnaire scores. Conclusion: This meta-analysis suggests that exenatide use is associated with the alleviation of cognitive, motor and nonmotor symptoms. However, long-term studies with a large sample size of patients with PD of varying severity are required.

Dysphagia with fatal choking in oculopharyngeal muscular dystrophy: Case report.

RATIONALE: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late-onset progressive muscle disorder typically characterized by ptosis, difficulty in swallowing, and proximal limb weakness. Underdiagnosis of OPMD is common in Asian countries and results in delayed diagnoses and fatal events. PATIENT CONCERNS: Here, we report the case of a 53-year-old female who suffered from progressive dysphagia and experienced several choking events involving solid material. An extensive family history of dysphagia was noted, and 2 family members had died as a result of aspiration. DIAGNOSES: PABPN1 genotyping and DNA sequence analysis revealed a heterozygous (GCG)10(GCA)3GCG mutation that led to the diagnosis of OPMD. INTERVENTIONS: Rehabilitation exercises, namely, the Shaker exercise and the Masako maneuver, were suggested. OUTCOMES: Improved swallowing ability with safe food intake was noted after 2 months of training. Surgical intervention will be considered when progression of the disease is noted. LESSONS: Underdiagnosis and a lack of awareness of OPMD may lead to choking, aspiration pneumonia, and death in multiple members of affected families. Currently, there is no definitive treatment for OPMD, but rehabilitation exercises and surgical intervention are helpful in relieving dysphagia.

The professional practice and training of neurology in the Asian and Oceanian Region: A cross-sectional survey by the Asian and Oceanian Association of Neurology (AOAN).

OBJECTIVE: To survey AOAN member countries regarding their organizational structure, postgraduate neurology training program, and resources for neurological care provision. METHODOLOGY: A cross-sectional survey using a 36-item questionnaire was conducted among country representatives to AOAN from August 2015 to August 2016. RESULTS: A total of 18/20 AOAN member countries participated in the survey. All the countries have organized association with regular meetings, election of officers and neurology training program. In 9/18 countries, professionals other than neurologists were eligible for affiliation. In 11/18 countries, prior Internal medicine training (or equivalent postgraduate housemanship) is prerequisite to neurology program. Recertification examination is not a practice, but submission of CME is required in 7/18 countries to maintain membership. 12/18 countries publish peer-reviewed journals with at least 1 issue per year. Subspecialty training is offered in 14/18 countries. The ratio of neurologist to population ranges from 1:14,000 to as low as 1:32 million with 9/18 having <1 neurologist per 100,000 population. 6/18 countries have at least 1 specialized center solely for neurological diseases. In government-funded hospitals, the lag time to be seen by a neurologist and/or obtain neuroimaging scan ranges from 1day to 3months. All except one country have several medical- and lay- advocacy or support groups for different neurological conditions. IMPLICATIONS: The data generated can be used for benchmarking to improve neurological care, training, collaborative work and research in the field of neurosciences among the AOAN member countries. The paper presented several strategies used by the different organizations to increase their number of neurologists and improve the quality of training. Sharing of best practices, academic networking, exchange programs and use of telemedicine have been suggested.