Oral-diadochokinesis between Parkinson's disease and neurotypical elderly among Malaysian-Malay speakers.

BACKGROUND: Parkinson's disease (PD) has an impact on speech production, manifesting in various ways including alterations in voice quality, challenges in articulating sounds and a decrease in speech rate. Numerous investigations have been conducted to ascertain the oral-diadochokinesis (O-DDK) rate in individuals with PD. However, the existing literature lacks exploration of such O-DDK rates in Malaysia and does not provide consistent evidence regarding the advantage of real-word repetition. AIMS: To explore the effect of gender, stimuli type and PD status and their interactions on the O-DDK rates among Malaysian-Malay speakers. METHODS & PROCEDURES: O-DDK performance of 62 participants (29 individuals with PD and 33 healthy elderly) using a non-word ('pataka'), a Malay real-word ('patahkan') and an English real-word ('buttercake') was audio recorded. The number of syllables produced in 8 s was counted. A hierarchical linear modelling was performed to investigate the effects of stimuli type (non-word, Malay real-word, English real-word), PD status (yes, no), gender (male, female) and their interactions on the O-DDK rate. The model accounted for participants' age as well as the nesting of repeated measurements within participants, thereby providing unbiased estimates of the effects. OUTCOMES & RESULTS: The stimuli effect was significant (p < 0.0001). Malay real-word showed the lowest O-DDK rate (5.03 ± 0.11 syllables/s), followed by English real-word (5.25 ± 0.11 syllables/s) and non-word (5.42 ± 0.11 syllables/s). Individuals with PD showed a significantly lower O-DDK rate compared to healthy elderly (4.73 ± 0.15 syllables/s vs. 5.74 ± 0.14 syllables/s, adjusted p < 0.001). A subsequent analysis indicated that the O-DDK rate declined in a quadratic pattern. However, neither gender nor age effects were observed. Additionally, no significant two-way interactions were found between stimuli type, PD status and gender (all p > 0.05). Therefore, the choice of stimuli type has no or only limited effect considering the use of O-DDK tests in clinical practice for diagnostic purposes. CONCLUSIONS & IMPLICATIONS: The observed slowness in O-DDK among individuals with PD can be attributed to the impact of the movement disorder, specifically bradykinesia, on the physiological aspects of speech production. Speech-language pathologists can gain insights into the impact of PD on speech production and tailor appropriate intervention strategies to address the specific needs of individuals with PD according to disease stages. WHAT THIS PAPER ADDS: What is already known on this subject The observed slowness in O-DDK rates among individuals with PD may stem from the movement disorder's effects on the physiological aspects of speech production, particularly bradykinesia. However, there is a lack of consistent evidence regarding the influence of real-word repetition and how O-DDK rates vary across different PD stages. What this study adds to existing knowledge The O-DDK rates decline in a quadratic pattern as the PD progresses. The research provides insights into the advantage of real-word repetition in assessing O-DDK rates, with Malay real-word showing the lowest O-DDK rate, followed by English real-word and non-word. What are the potential or actual clinical implications of this work? Speech-language pathologists can better understand the evolving nature of speech motor impairments as PD progresses. This insight enables them to design targeted intervention strategies that are sensitive to the specific needs and challenges associated with each PD stage. This finding can guide clinicians in selecting appropriate assessment tools for evaluating speech motor function in PD patients.

Stroke Riskometer Application (SRA™) influence on lifestyle changes of home bound familial Malaysian stroke caregivers: a randomised controlled trial in a primary care based longer term stroke care facility.

BACKGROUND: In countries where access to Specialist stroke care services are limited, primary care physicians often manage stroke patients and the caregiving family members. This study aimed to evaluate the impact of Stroke Riskometer Application (SRA™) on promoting healthier lifestyles among familial stroke caregivers for primary prevention. METHODS: A parallel, open-label, 2-arm prospective, pilot randomised controlled trial was conducted at a long-term stroke service at a university based primary care clinic. All stroke caregivers aged ≥ 18 years, proficient in English or Malay and smartphone operation were invited. From 147 eligible caregivers, 76 participants were randomised to either SRA™ intervention or conventional care group (CCG) after receiving standard health counselling. The intervention group had additional SRA™ installed on their smartphones, which enabled self-monitoring of modifiable and non-modifiable stroke risk factors. The Stroke Riskometer app (SRATM) and Life's Simple 7 (LS7) questionnaires assessed stroke risk and lifestyle practices. Changes in clinical profile, lifestyle practices and calculated stroke risk were analysed at baseline and 3 months. The trial was registered in the Australia-New Zealand Clinical Trial Registry, ACTRN12618002050235. RESULTS: The demographic and clinical characteristics of the intervention and control group study participants were comparable. Better improvement in LS7 scores were noted in the SRA™ arm compared to CCG at 3 months: Median difference (95% CI) = 0.88 (1.68-0.08), p = 0.03. However, both groups did not show significant changes in median stroke risk and relative risk scores at 5-, 10-years (Stroke risk 5-years: Median difference (95% CI) = 0.53 (0.15-1.21), p = 0.13, 10-years: Median difference (95% CI) = 0.81 (0.53-2.15), p = 0.23; Relative risk 5-years: Median difference (95% CI) = 0.84 (0.29-1.97), p = 0.14, Relative risk 10-years: Median difference (95% CI) = 0.58 (0.36-1.52), p = 0.23). CONCLUSION: SRA™ is a useful tool for familial stroke caregivers to make lifestyle changes, although it did not reduce personal or relative stroke risk after 3 months usage. TRIAL REGISTRATION: No: ACTRN12618002050235 (Registration Date: 21st December 2018).

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 ß-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.

Movement disorders in Indochina: Resource challenges and future solutions.

Movement disorders are a major cause of disability worldwide and their increasing prevalence predicts a substantial future burden of care. Impactful patient care requires availability of, and accessibility to, effective medications, knowledge, and disease awareness among both medical professionals and patients, driven by skilled personnel to harness and manage resources. The highest burden of movement disorders is in low-to-middle income countries where resources are often limited and infrastructure is insufficient to meet growing demands. This article focuses on the specific challenges faced in the management and delivery of care for movement disorders in Indochina, the mainland region of Southeast Asia comprising the neighboring countries of Cambodia, Laos, Malaysia, Myanmar, Thailand, and Vietnam. The first Indochina Movement Disorders Conference was held in August 2022 in Ho Chi Minh City, Vietnam, to provide a platform to better understand the situation in the region. Future management of movement disorders in Indochina will require progressive adaptation of existing practices to reflect modern approaches to care delivery. Digital technologies offer an opportunity to strengthen these processes and address the challenges identified in the region. Ultimately, a long-term collaborative approach by regional healthcare providers is key.

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.

Causes, factors, and complications associated with hospital admissions among patients with Parkinson's disease.

Introduction: Patients with Parkinson's disease (PD) are at a higher risk of hospital admissions compared to the general population. We studied the causes and factors associated with admissions among patients with PD over 6 years. Methods: We included all PD admissions between 1 January 2016 and 31 December 2021. Other causes of parkinsonism were excluded. Causes of admissions were divided into PD-related (direct or indirect) or non-PD-related. The type of admission was categorized into emergency or elective. Results: We identified 605 hospital admissions (259 patients with PD); 345 (57.0%) were PD-related and 260 (43%) were non-PD-related. Emergency PD admissions contributed to 50.4% of all admissions, most commonly from respiratory infection (23%). PD admissions in comparison to non-PD admissions were associated with worse disease severity (HY ≥ 3; p < 0.001), longer disease duration [8.71 (SD 6.23) vs. 6.60 (SD 5.39) years; p < 0.001], and longer hospital stay [7.70 (SD 5.89) vs. 6.42 (SD 7.63) days; p = 0.020]. Non-PD admissions were associated with more comorbidities (97.3%; p = 0.013). There were 124 (20.5%) complications and 31 deaths (5.1%). A total of 29 deaths were due to respiratory infection and 3 deaths were due to COVID-19 pneumonia. Emergency admission (PD- and non-PD-related; p = 0.001) and respiratory-related causes (p < 0.001) were predictors of unfavorable hospital admission outcomes (death and complications). Conclusion: Respiratory infection was the leading cause of hospital admission and a significant independent predictor of unfavorable hospital admission outcomes (death and complications). PD-related admissions were associated with disease severity and led to more complications and longer hospital stays. Non-PD-related admissions were associated with comorbidities.

Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases: a systematic review.

Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.

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.

Movement Disorders Resulting From Bilateral Basal Ganglia Lesions in End-Stage Kidney Disease: A Systematic Review.

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.

Labrune's Syndrome Presenting With Stereotypy-Like Movements and Psychosis: A Case Report and Review.

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.

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. CONCLUSION: s 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.

Spinocerebellar ataxias in Asia: Prevalence, phenotypes and management.

This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively reviewed. Overall, the most common subtypes include SCA1, SCA2, SCA3, and SCA6, but there are large differences in the relative prevalence of these and other SCA subtypes between Asian countries. Some subtypes such as SCA12 and SCA31 are rather specific to certain Asian populations. Second, we summarized distinctive phenotypic manifestations of SCA patients of Asian origin, for example a frequent co-occurrence of parkinsonism in some SCA subtypes. Lastly, we have conducted an exploratory survey study to map SCA-specific expertise, resources, and management in various Asian countries. This showed large differences in accessibility, genetic testing facilities, and treatment options between lower and higher income Asian countries. Currently, many Asian SCA patients remain without a final genetic diagnosis. Lack of prevalence data on SCA, lack of patient registries, and insufficient access to genetic testing facilities hamper a wider understanding of these diseases in several (particularly lower income) Asian countries.

Clinical and genetic profile in index patients with spinocerebellar ataxia type 3 in Indonesia: case report.

Spinocerebellar ataxia (SCA) is an autosomal dominant hereditary disease with progressive course, and no causal therapy. Diagnostics are still challenging, due to facility and protocols, and so as in Indonesia. As a national referral center, Dr. Hasan Sadikin Central General Hospital has received a lot of patients from all over Indonesia, particularly from Western Java. Study related to SCA (including clinical and genetic profile) is still limited in Indonesia. We identified index patients from three families with ataxia, hence intend to determine their clinical and genetic pattern. The hereditary pattern is autosomal dominant. Scale for the assessment and rating of ataxia (SARA) shows mild and moderate ataxia. Inventory of non-ataxia signs (INAS) scores of the patients were 3, 5 and 6. Montreal cognitive assessment-Indonesian version (MOCA-INA) shows only one patient has mild cognitive impairment, despite young age. Barthel index shows 1 subject has moderate dependency. Mutation in Ataxin3 polyQ repeats shows pathologically long CAG repeats, 72,10; 72,10; and 72,23 respectively in mutant and wild type allele. We diagnosed the index patients with spinocerebellar ataxia type 3. This study is the first case series study in Indonesia. The hereditary pattern is clearly shown as an autosomal dominant ataxia. The clinical and genetic profile was varied, and the symptom is progressive and deteriorates overtime, including wide based gait, speech problem, motor and sensor complaint, and cognitive decline complaint. Despite the same polyQ stretch length, the onset and clinical characteristics of patients are diverse.

Management of Parkinson's Disease in the COVID-19 Pandemic and Future Perspectives in the Era of Vaccination.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-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.

Voice therapy for Parkinson's disease via smartphone videoconference in Malaysia: A preliminary study.

INTRODUCTION: Intensive voice therapy is one of the best evidence-based treatments to improve speech and voice difficulties to individuals with Parkinson's disease (PD). However, accessibility to intensive voice therapy is highly challenging in Malaysia due to the lack of voice specialised speech-language therapists. This study examined the feasibility of using smartphone videoconference to deliver intensive voice therapy to individuals with PD in Malaysia. METHODS: Intensive voice therapy was delivered to 11 adults with PD using a smartphone videoconference method via WhatsApp Messenger freeware. The therapy consisted of 12 sessions over four weeks and focused on increasing vocal loudness. Outcomes were assessed using objective, perceptual and quality-of-life measures pre and post treatment. Participant satisfaction with the telerehabilitation method was obtained via the Smartphone-Based Therapy Satisfaction Questionnaire. RESULTS: Significant gains were reported for sound pressure level in sustained vowels and monologue. Perceptual ratings showed significant improvements in overall mean severity and loudness after treatment. Mean scores of speech intelligibility and Voice Handicap Index-10 were significantly better post treatment. Overall, participants were highly satisfied with the smartphone videoconference method. DISCUSSION: Present results suggest that the smartphone videoconference method is feasible to deliver intensive voice therapy to individuals with PD to gain better speech and voice functions. Future studies need to address the standardisation of the system protocol to optimise this novel service delivery method in Malaysia.

Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson's disease: A randomised controlled trial.

OBJECTIVE: We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation. METHODS: PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS). RESULTS: Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects. CONCLUSION: This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

Factors Associated With Length of Stay for Patients With Stroke in Malaysia.

Introduction: Globally, stroke continues to become a significant public health issue contributing to one of the significant causes of morbidity and mortality. The study aimed to describe the characteristics of patients with stroke who were admitted to a teaching hospital in Malaysia and to determine the factors associated with length of stay (LOS). Methods: This is a single-center, cross-sectional study using in-patient data maintained by the Case-Mix Unit of a teaching hospital in Malaysia from 2016 to 2017. The study included all patients with International Classification of Disease (ICD) code 164 (stroke, not specified as hemorrhage or infarct). The significance of association was determined using nonparametric tests in the form of the Mann-Whitney U test and the Kruskal-Wallis test. Results: A total of 162 stroke patients from 2016 to 2017 from Case-Mix database were included in the study. The age ranged from 31 to 97 years old. The minimum and maximum LOS for patients with stroke ranged from 1 to 17 days. The severity of illness was found to be significantly associated with longer LOS (p < 0.001); however, age, sex, and presence of co-morbidities did not show any significant association. Conclusion: Despite its limitations, this study is an essential first step to examine the characteristics of patients with stroke and to determine the factors associated with LOS.