A KMT2B Frameshift Variant Causing Focal Dystonia Restricted to the Oromandibular Region After Long-Term Follow-up

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.

Historical and More Common Nongenetic Movement Disorders From Asia

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.

Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution

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.

Gastrointestinal Dysfunction in Parkinson’s Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem

Patients with Parkinson’s disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.

Fecal Calprotectin in Parkinson’s Disease and Multiple System Atrophy

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.

Glucocerebrosidase genetic variants in Malays with early and late-onset Parkinson’s disease

@#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.

Hyperglycemia-Associated Hemichorea-Hemiballismus with Predominant Ipsilateral Putaminal Abnormality on Neuroimaging

No abstract available.

Alternating Hemiplegia of Childhood in a Person of Malay Ethnicity with Diffusion Tensor Imaging Abnormalities

No abstract available.

Chorea in Sporadic Creutzfeldt-Jakob Disease

No abstract available.

Purposeless Groaning in Parkinson's Disease

Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson's disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).

A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy

We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient's disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.

Bilateral thalamic internal medullary lamina involvement in a case of dengue encephalitis

There are 50-100 million dengue infections each year, but dengue encephalitis is relatively uncommon. The aetiology of neuronal injury is proposed to be due to direct viral neurotropism or host immune response-mediated inflammation causing neuronal damage. We report a case of severe dengue encephalitis, presenting during the acute viraemic phase of the disease. This was associated with inflammation and haemorrhage of the internal medullary lamina of both thalami which, to our knowledge, has not yet been reported in other infections of the central nervous system.

Lack of association between the LRRK2 A419V variant and Asian Parkinson's disease

<p><b>INTRODUCTION</b>The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.</p><p><b>MATERIALS AND METHODS</b>Eight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine.</p><p><b>RESULTS</b>The heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624).</p><p><b>CONCLUSION</b>A419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.</p>

Karaoke, power failure and carbon monoxide poisoning

Accidental carbon monoxide poisoning in countries with cold climates is commonly related to indoor heating. This condition appears to be relatively uncommon in tropical Asian countries and therefore the diagnosis may be unsuspected. We report a case of a Malaysian patient who presented with a severe, and ultimately fatal, delayed (biphasic) neuropsychiatric syndrome due to carbon monoxide poisoning. The diagnosis was made only when a history compatible with carbon monoxide poisoning subsequently surfaced, and neuroimaging demonstrated the typical pallidal lesions, associated with marked leukoencephalopathy, seen in this condition. Our case is unique because the poisoning occurred in the setting of indoor operation of a portable electricity generator in a karaoke centre because of power failure. Karaoke is a highly popular form of entertainment in many parts of Asia and we suggest that a high index of suspicion of carbon monoxide poisoning is required in this setting.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: A series of ten cases from a university hospital in Malaysia

Objective: To report on the incidence, and the clinical and laboratory features of patients seen at the University of Malaya Medical Centre with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: The charts of all patients admitted to the adult neurology ward with encephalitis over an 18- month period from January 2010 to June 2011 were reviewed. Diagnosis of anti-NMDAR encephalitis was based on the presence of encephalitis plus antibody against the NMDAR. Two other paediatric patients with anti-NMDAR encephalitis seen over the same period were also included in this report. Results: There was a total of 10 patients with anti-NMDAR encephalitis seen over the study period. The mean age was 18.1 years (range 9-29 years). Eight patients were female, two male. Five were Malay and fi ve were Chinese. All patients had prominent psychiatric symptoms, followed by epileptic seizures. Nine patients had a movement disorder, orofacial dyskinesia being the commonest, and all had autonomic involvement. None had an underlying tumour. Treatments consisted of corticosteroid, plasma exchange and intravenous immunoglobulin (IVIG). The clinical outcome was variable, with full recovery (2), substantial recovery (3), partial recovery (4), and mortality (1) seen. Remarkably, the eight adult cases of anti-NMDAR encephalitis accounted for 50% of the 16 cases of encephalitis seen during the study period. Conclusion: Anti-NMDAR encephalitis may be a relatively common cause of adult encephalitis among certain Asian groups. None of our cases was paraneoplastic in origin.

Diffusion-weighted magnetic resonance imaging in a case of osmotic demyelination syndrome with fatal outcome

Hyponatraemia with rapid correction of serum sodium may cause an osmotic demyelination syndrome (ODS) with damage to pontine and/or extrapontine areas of the brain. The prognosis of ODS can range from complete recovery to death; at present, our ability to predict clinical outcome is very limited. We describe here a patient with ODS and increased signal intensity in the striatum on diffusion-weighted MRI, with corresponding low apparent diffusion coeffi cient values (indicating restricted water diffusion). This case provides a further example of the typical MRI appearance of extrapontine ODS and suggests the potential value of diffusion-weighted MRI in predicting prognosis in ODS.

Development of marked striatal hand with antiparkinsonian medication withdrawal during traditional (Ayurvedic) medicine treatment for Parkinson’s disease

Ayurveda is a traditional medical system used widely in India and increasingly worldwide. Here, we report on a patient with Parkinson’s disease (PD) who developed marked striatal hand with antiparkinsonian medication withdrawal during Ayurvedic medicine treatment for her PD. Although a direct role for the Ayurvedic medicines in inducing the hand deformity cannot be excluded, we propose that severe dopaminergic defi ciency (due to prolonged withdrawal of antiparkinsonian medications in the context of long-standing PD) was probably the main culprit in our patient.