KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.

Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

Nongenetic movement disorders are common throughout the world. The movement disorders encountered may vary depending on the prevalence of certain disorders across various geographical regions. In this paper, we review historical and more common nongenetic movement disorders in Asia. The underlying causes of these movement disorders are diverse and include, among others, nutritional deficiencies, toxic and metabolic causes, and cultural Latah syndrome, contributed by geographical, economic, and cultural differences across Asia. The industrial revolution in Japan and Korea has led to diseases related to environmental toxin poisoning, such as Minamata disease and β-fluoroethyl acetate-associated cerebellar degeneration, respectively, while religious dietary restriction in the Indian subcontinent has led to infantile tremor syndrome related to vitamin B12 deficiency. In this review, we identify the salient features and key contributing factors in the development of these disorders.

Labrune’s syndrome, or leukoencephalopathy with brain calcifications and cysts (LCC), is a rare genetic syndrome with variable neurological presentations. Psychiatric manifestations and involuntary movements are uncommonly reported. We report the case of a 19-year-old female, initially diagnosed with Fahr’s syndrome, who presented to us with acute psychosis, abnormal behavior and involuntary movements. Her brain computed tomography showed extensive bilateral intracranial calcifications without cysts. Genetic testing detected two compound heterozygous variants, NR_033294.1 n.*9C>T and n.24C>T, in the SNORD118 gene, confirming the diagnosis of LCC. We discuss the expanding phenotypic spectrum of LCC and provide a literature review on the current diagnosis and management of this rare syndrome.

Objective: Converging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson’s disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA. Methods: We recruited 169 subjects (71 PD, 38 MSA, and 60 age-similar nonneurological controls). Clinico-demographic data were collected. PD and MSA were subtyped and the severity assessed using the MDS-UPDRS and UMSARS, respectively. Fecal calprotectin and blood immune markers were analyzed. Results: Compared to controls (median: 35.7 [IQR: 114.2] μg/g), fecal calprotectin was significantly elevated in PD (median: 95.6 [IQR: 162.1] μg/g, p = 0.003) and even higher in MSA (median: 129.5 [IQR: 373.8] μg/g, p = 0.002). A significant interaction effect with age was observed; between-group differences were significant only in older subjects (i.e., ≥ 61 years) and became more apparent with increasing age. A total of 28.9% of MSA and 18.3% of PD patients had highly abnormal fecal calprotectin levels (≥ 250 μg/g); however, this difference was only significant for MSA compared to controls. Fecal calprotectin correlated moderately with selected blood immune markers in PD, but not with clinical features of PD or MSA. Conclusions Elevated fecal calprotectin suggests a role for intestinal inflammation in PD and MSA. A more complete understanding of gut immune alterations could open up new avenues of research and treatment for these debilitating diseases.

Objective: The basal ganglia (BG) are susceptible to fluctuations in blood urea levels, sometimes resulting in movement disorders. We described patients with end-stage kidney disease (ESKD) presenting with movement disorders associated with bilateral BG lesions on imaging. Methods: We report four patients and systematically reviewed all published cases of ESKD presenting with movement disorders and bilateral BG lesions (EBSCOhost and Ovid). Results: Of the 72 patients identified, 55 (76.4%) were on regular dialysis. Parkinsonism was the most common movement disorder (n = 39; 54.2%), followed by chorea (n = 24; 33.3%). Diabetes mellitus (n = 51; 70.8%) and hypertension (n = 16; 22.2%) were the most common risk factors. Forty-three (59.7%) were of Asian ethnicity. Complete clinical resolution was reported in 17 (30.9%) patients, while 38 (69.1%) had incomplete clinical resolution with relapse. Complete radiological resolution occurred in 14 (34.1%) patients. Conclusion Movement disorders associated with BG lesions should be recognized as a rare and potentially reversible metabolic movement disorder in patients with ESKD.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has led to a serious global health crisis. Increasing evidence suggests that elderly individuals with underlying chronic diseases, including Parkinson’s disease (PD), are particularly vulnerable to this infection. Changes in the routine care of PD patients should be implemented carefully without affecting the quality provided. The utilization of telemedicine for clinical consultation, assessment and rehabilitation has also been widely recommended. Therefore, the aim of this review is to provide recommendations in the management of PD during the pandemic as well as in the early phase of vaccination programs to highlight the potential sequelae and future perspectives of vaccination and further research in PD. Even though a year has passed since COVID- 19 emerged, most of us are still facing great challenges in providing a continuum of care to patients with chronic neurological disorders. However, we should regard this health crisis as an opportunity to change our routine approach in managing PD patients and learn more about the impact of SARS-CoV-2. Hopefully, PD patients can be vaccinated promptly, and more detailed research related to PD in COVID-19 can still be carried out.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has led to a serious global health crisis. Increasing evidence suggests that elderly individuals with underlying chronic diseases, including Parkinson’s disease (PD), are particularly vulnerable to this infection. Changes in the routine care of PD patients should be implemented carefully without affecting the quality provided. The utilization of telemedicine for clinical consultation, assessment and rehabilitation has also been widely recommended. Therefore, the aim of this review is to provide recommendations in the management of PD during the pandemic as well as in the early phase of vaccination programs to highlight the potential sequelae and future perspectives of vaccination and further research in PD. Even though a year has passed since COVID- 19 emerged, most of us are still facing great challenges in providing a continuum of care to patients with chronic neurological disorders. However, we should regard this health crisis as an opportunity to change our routine approach in managing PD patients and learn more about the impact of SARS-CoV-2. Hopefully, PD patients can be vaccinated promptly, and more detailed research related to PD in COVID-19 can still be carried out.

Background: Mutations in glucocerebrosidase (GBA) have been associated with the risk of developing Parkinson’s disease (PD) in different ethnic populations. The prevalence of GBA mutations among Malay PD patients is unknown. Thus, the aim of this study was to determine the frequency of GBA mutations among Malay PD patients, focusing on early (EOPD) and late-onset (LOPD) patients. Methods:EOPD (n = 50) and LOPD (n = 50) patients along with 50 ethnically and age-matched control wererecruited. The GBA exons of these patients were sequenced using the Ion Torrent PGMTM System. Results: Five heterozygous mutations exclusive to EOPD patients were identified; c.-203A>G,p.S146L, p.R159Q, p.L483P and p.L483R+c.-145G>A. In LOPD patients, c.543C>T(p.(F181=)), c.28-10C>A and p.R202Q were identified in which this p.R202Q was also present in a control subject. In addition, c.259C>A(p.(R87=)) and c.-145G>A were identified in two control subjects. In summary, we observed GBA mutations in 8% and 6% of Malay PD cases and control subject, respectively. The prevalence of GBA mutations was higher in EOPD (10%) than LOPD (6%). However, these differences were not statistically significant; [PD vs. controls: OR = 1.36, 95%CI 0.35-5.38, p = 0.752] and [EOPD vs. LOPD: OR = 1.74, 95%CI 0.39-7.71, p = 0.715]. Conclusion: We identified five exclusive heterozygous GBA mutations in EOPD patients which might predict the increase susceptibility of Malays to develop PD at young age. These findings could add knowledge into the existing evidences linking genetic alterations in GBA and PD.

Background & Objective: Circulating microRNAs (miRNAs) expressions have been suggested as potential biomarkers for Parkinson’s Disease (PD). Identification of early biomarkers for PD is important and crucial as PD symptoms occur at a late stage. Hence, these biomarkers could be used in molecular diagnosis for early detection. We therefore examined and compared the expression of circulating miRNAs between PD patients and controls. We also compared the miRNAs expression between early-onset PD (EOPD) and late-onset PD (LOPD). Methods: RNA was extracted from the plasma of EOPD (onset age <50 years; n=14), LOPD (onset age < 60 years; n=14) and healthy controls (n=11). The miRNAs expression was determined using the Affymetrix GeneChip microarray. Differential analysis was performed using the R software. Significantly differentiated miRNAs were subsequently analyzed for functional enrichment and biological pathway using the FunRich v1.3 software based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Omics.net was used to determine the predicted target mRNAs of these miRNAs, and their interactions, based on the five most differentially expressed miRNAs. Results: In total, 273 miRNAs were upregulated in PD patients compared to controls. The most significant miRNAs were hsa-miR-301a-3p, 100-5p, 140-5p, 486-3p, 143-3p (fold change ranging from 11.2 – 32.0). A total of 140 circulating miRNAs were differentially expressed in EOPD compared to LOPD. Five of these miRNAs (one upregulated miRNA (hsa-miR-29b-3p) and four downregulated miRNAs (hsa-miR-297, 4462, 1909-5p and 346) belonged exclusively to the EOPD patients. The predicted gene targets of these miRNAs involved in dopaminergic synapse regulation, crucial to the pathogenesis of PD. Conclusion: Circulating miRNAs differ between PD patients and controls, and between EOPD and LOPD patients. A validation study with a larger and more diverse multi-ethnic population should be conducted to confirm our results.