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Fulltext Prospective study of functional recovery of stroke patients at three months post admission: outcomes and implications for post stroke care provision

Ali, M.F., Aziz, N.A., Aznida, F.A.A., Rizal, A.M., Azmin, S.

Medicine & Health, 2013;8(1):19-27.
MyJurnal

Functional recovery in the immediate post stroke period predicts the long-term prognosis of post stroke patients. Despite the advancement in stroke rehabilitation in improving the physical function of survivors, there are other factors that may influence functional recovery. We aimed to assess the functional recovery of ischaemic stroke patients attending a tertiary hospital and its associated factors in order to make recommendations for post stroke care after hospital admission. A three months prospective observational study looking at functional recovery using the Modified Barthel’s Index (MBI) and depression (Patient Heath Questionnaire-9) score of post stroke patients. There were 46 ischaemic stroke patients who were recruited for the study. At three months, only 37 patients were eligible for analysis. The mean age was 67.2 (SD 11) years with the Malays (50%) making up the majority of the patients, followed by Chinese (41.3%) and Indians (8.7%). There was a total of seven (15.2%) deaths. Hypertension was the most common risk factor (89.1%) followed by dyslipidaemia (65.2%) and diabetes mellitus (63.0%). The mean MBI difference was 45.2 (SD 27.0) with a median MBI of 17.0(IQR 33.0) at baseline compared to 85.0(IQR 42.0) at three months (p < 0.001, CI 35.98,55.45). The prevalence of depression (PHQ-9≥10) was 21.6%. Lower functional recovery was found among depressed patients (p
Fulltext Spinocerebellar ataxias in Asia: Prevalence, phenotypes and management

van Prooije T, Ibrahim NM, Azmin S, van de Warrenburg B

Parkinsonism Relat Disord, 2021 11;92:112-118.
PMID: 34711523 DOI: 10.1016/j.parkreldis.2021.10.023

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

Shaibdat NS, Ahmad N, Azmin S, Ibrahim NM

Front Neurol, 2023;14:1136858.
PMID: 36959822 DOI: 10.3389/fneur.2023.1136858

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.
Fulltext Cerebral amyloid angiopathy: an important differential diagnosis of stroke in the elderly

Azmin S, Osman SS, Mukari S, Sahathevan R

Malays J Med Sci, 2015 Jan-Feb;22(1):74-8.
PMID: 25892953

Cerebral amyloid angiopathy (CAA) accounts for approximately 10-20% of spontaneous intracerebral haemorrhage (ICH). This figure is thought to be higher in the elderly population. With the increasing life expectancy of our population, we anticipate that the prevalence of CAA- related ICH will increase in tandem. Although CAA-related ICH and hypertension-related ICH are distinct entities based on histopathology and imaging, the clinical presentation of the two conditions is similar. The use of brain computed tomography (CT) scans remain the ICH imaging modality of choice in Malaysia due to its availability, cost, and sensitivity in detecting acute bleeds. On the other hand, the use of brain magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) sequencing enables the clinician to determine the presence of chronic blood products in the brain, especially clinically silent microbleeds associated with CAA. However, the use of brain MRI scans in our country is limited and leads to a blurring of lines when differentiating between hypertension-related ICH and CAA-related ICH. How this misrepresentation affects the management of these conditions is unclear. In this study, we present two cases of ICH to illustrate this point and to serve as a springboard to question current practice and promote discussion.
Fulltext Post-dengue parkinsonism

Azmin S, Sahathevan R, Suehazlyn Z, Law ZK, Rabani R, Nafisah WY, et al.

BMC Infect Dis, 2013;13:179.
PMID: 23594500 DOI: 10.1186/1471-2334-13-179

BACKGROUND: Dengue is a common illness in the tropics. Equally common are neurological complications that stem from dengue infection. However, to date, parkinsonism following dengue has not been reported in medical literature.
CASE PRESENTATION: A previously well 18-year old man developed parkinsonism, in addition to other neurological symptoms following serologically confirmed dengue fever. Alternative etiologies were excluded by way of imaging and blood investigations.
CONCLUSIONS: The authors detail the first reported case of parkinsonism complicating dengue fever. Keeping rare presentations of common illnesses in mind, it behoves clinicians to consider parkinsonism as a complication following dengue infection. This would prevent injudicious treatment with L-dopa and dopamine agonists. Immunosuppression with steroids has been shown to be helpful in certain cases.
Neurocognitive Changes in Spinocerebellar Ataxia Type 3: A Systematic Review with a Narrative Design

Yap KH, Kessels RPC, Azmin S, van de Warrenburg B, Mohamed Ibrahim N

Cerebellum, 2021 Jul 07.
PMID: 34231180 DOI: 10.1007/s12311-021-01282-3

Spinocerebellar ataxia type 3 (SCA3), the commonest dominantly inherited ataxia worldwide, is characterized by disruption in the cerebellar-cerebral and striatal-cortical networks. Findings on SCA3-associated cognitive impairments are mixed. The classification models, tests and scoring systems used, language, culture, ataxia severity, and depressive symptoms are all potential confounders in neuropsychological assessments and may have contributed to the heterogeneity of the neurocognitive profile of SCA3. We conducted a systematic review of studies evaluating neurocognitive function in SCA3 patients. Of 1304 articles identified, 15 articles met the eligibility criteria. All articles were of excellent quality according to the National Institutes of Health quality assessment tool for case-control studies. In line with the disrupted cerebellar-cerebral and striatal-cortical networks in SCA3, this systematic review found that the neurocognitive profile of SCA3 is characterized by a core impairment of executive function that affects processes such as nonverbal reasoning, executive aspects of language, and recall. Conversely, neurocognitive domains such as general intelligence, verbal reasoning, semantic aspect of language, attention/processing speed, recognition, and visuospatial perception and construction are relatively preserved. This review highlights the importance of evaluating neurocognitive function in SCA3 patients. Considering the negative impact of cognitive and affective impairment on quality of life, this review points to the profound impairments that existing or future treatments should prioritize.
Pharmacological and non-pharmacological management of spinocerebellar ataxia: A systematic review

Yap KH, Azmin S, Che Hamzah J, Ahmad N, van de Warrenburg B, Mohamed Ibrahim N

J Neurol, 2021 Nov 06.
PMID: 34743220 DOI: 10.1007/s00415-021-10874-2

Spinocerebellar ataxias (SCA) comprise a rare, genetic subgroup within the degenerative ataxias and are dominantly inherited, with up to 48 recognized genetic subtypes. While an updated review on the management of degenerative ataxia is published recently, an evidence-based review focussed on the management of SCA is lacking. Here, we reviewed the pharmacological and non-pharmacological management of SCA by conducting a systematic review on Medline Ovid and Scopus. Of 29,284 studies identified, 47 studies (pharmacological: n = 25; non-pharmacological: n = 22) that predominantly involved SCA patients were included. Twenty studies had a high risk of bias based on the Cochrane's Collaboration risk of bias tool. As per the European Federation of Neurological Societies 2004 guideline for therapeutic intervention, the remaining 27 studies were of Class I (n = 4) and Class II (n = 23) evidence. Only two therapies had Level A recommendations for the management of ataxia symptoms: riluzole and immediate in-patient neurorehabilitation. Ten therapies had Level B recommendations for managing ataxia symptoms and require further investigations with better study design. These include high dose valproate acid, branched-chain amino acid, intravenous trehalose; restorative rehabilitation using cycling regimen and videogame; and cerebellar stimulations using transcranial direct current stimulation and transcranial magnetic stimulation. Lithium and coaching on psychological adjustment received Level B recommendation for depressive symptoms and quality of life, respectively. Heterogeneous study designs, different genotypes, and non-standardized clinical measures alongside short duration and small sample sizes may hamper meaningful clinical translation. Therefore, rating of recommendations only serve as points of reference.
Fulltext Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson's disease

Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MR, et al.

PLoS One, 2014;9(11):e112330.
PMID: 25411976 DOI: 10.1371/journal.pone.0112330

BACKGROUND: Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.
METHODS: A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa 'onset' time and ON-duration were recorded.
RESULTS: Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.
CONCLUSIONS: H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02112812.
Fulltext Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases: a systematic review

Yap KH, Azmin S, Makpol S, Damanhuri HA, Mustapha M, Hamzah JC, et al.

Neural Regen Res, 2023 Jun;18(6):1179-1185.
PMID: 36453391 DOI: 10.4103/1673-5374.360164

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.
Fulltext Stroke thrombolysis at 5.5 hours based on computed tomography perfusion

Sahathevan R, Azmin S, Palaniappan S, Nafisah WY, Tan HJ, Norlinah MI, et al.

Malays J Med Sci, 2014 Mar;21(2):78-81.
PMID: 24876813 MyJurnal

A young man was admitted with sudden onset of right-sided weakness. He was assessed in the emergency department, and an immediate computed tomography (CT) perfusion study of the brain was arranged, which showed a left middle cerebral artery territory infarct with occlusion of the M1 segment. There was a significant penumbra measuring approximately 50% of the arterial territory. By the time his assessment was completed, it was 5.5 hours from the onset of symptoms. He was nonetheless administered intravenous recombinant tissue plasminogen activator (rtPA) based on the significant penumbra. He was discharged from the hospital after one week with significant residual deficit. At 2 months clinic follow-up, he showed almost complete recovery with a Modified Rankin Score of 1. We hope to demonstrate that a significant penumbra is an important determinant for good neurological recovery and outcome following stroke thrombolysis, even when patients present outside the 4.5 hours onset-to-treatment time window.
Fulltext Restless legs syndrome and its associated risk factors in Parkinson's disease

Azmin S, Khairul Anuar AM, Nafisah WY, Tan HJ, Raymond AA, Hanita O, et al.

Parkinsons Dis, 2013;2013:535613.
PMID: 24455416 DOI: 10.1155/2013/535613

Introduction. Restless legs syndrome has been shown to negatively impact the quality of life of patients. Studies have shown an association between restless legs syndrome and Parkinson's disease. We attempted to investigate the prevalence of restless legs syndrome in Parkinson's disease patients and to identify associated risk factors. Method. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criterion was a Mini Mental State Examination score of less than 21/30. The International Restless Legs Syndrome Study Group criterion was used to identify patients with restless legs syndrome. Results. A total of 113 patients were recruited. The prevalence rate of restless legs syndrome in our cohort was 9.7% and was significantly associated with a younger onset of Parkinson's disease (P = 0.023), male gender (P = 0.045), higher Mini Mental State Examination score (P = 0.004), and less advanced Hoehn & Yahr stage (P = 0.014). Conclusion. The prevalence rate of restless legs syndrome in our Parkinson's disease population is in keeping with other studies published worldwide. The significance of the association between a younger onset of Parkinson's disease and restless legs syndrome needs to be further investigated.
Fulltext Biochemical aspirin resistance in stroke patients - a cross-sectional single centre study

Azmin S, Sahathevan R, Rabani R, Nafisah WY, Tan HJ, Raymond AA, et al.

EXCLI J, 2013;12:907-15.
PMID: 27092036

BACKGROUND: Aspirin use is known to reduce the recurrence of stroke. However, the clinical response to aspirin has been mixed. The rate of stroke recurrence whilst on aspirin treatment is still unacceptably high. A plausible explanation for this may be resistance to the effects of aspirin. The causes of aspirin resistance are manifold and multi-factorial. We conducted a study to investigate the prevalence rate of biochemical aspirin resistance in a cohort of aspirin-naïve stroke patients. We also sought to determine the inherent factors that may predispose towards the development of aspirin resistance.
METHOD: This was a cross-sectional, observational study conducted on patients admitted to our centre with an acute stroke who were aspirin-naïve. The diagnosis of an acute stroke was confirmed by clinical history and brain imaging. Fifty consecutive patients were prospectively enrolled. Socio-demographic data were collected and baseline blood investigations were performed. Patients were tested for biochemical aspirin resistance using Multiplate platelet analyser (Dynabyte, Munich, Germany) after 5 doses of aspirin, corresponding to a total dose of 900 mg.
RESULTS: The median age of patients was 65.5 years and 54 % of patients were female. There were 11 smokers; of these 10 were male. Twenty-six (52 %) patients were Chinese, 21 (41 %) were Malay and 3 (6.0 %) were Indian. Aspirin resistance was present in 14 % of our patients. There was an inverse relationship between the presence of aspirin resistance and plasma HDL levels (r = -0.394; p = 0.005). There was no relationship observed between aspirin resistance and total cholesterol, triglycerides, LDL, HbA1c, ALT, ALP, urea and creatinine levels. There were no significant differences in demographic profiles or smoking status between the aspirin resistant and non-aspirin resistant groups. We did not find any link between ethnicity and aspirin resistance.
CONCLUSIONS: Our results indicate that a lower HDL level is associated with biochemical aspirin resistance. This may increase platelet aggregation and consequently increase the risk of a recurrent stroke. The clinical implications for aspirin resistance are far reaching. Any evidence that correctable factors may negatively influence the action of aspirin warrants further investigation. The prevalence rate of biochemical aspirin resistance in our study is comparable to the findings in other studies performed in an Asian population. Further research is required to determine how our findings translate into clinical aspirin resistance and stroke recurrence.
KEYWORDS: Asia; antiplatelet therapy; aspirin; aspirin resistance; developing countries; ischaemic stroke; risk factors
An unusual neurological complication from a garden-variety organism: post-melioidosis parkinsonism

Ng CS, Azmin S, Law ZK, Sahathevan R, Wan Yahya WN, Remli R, et al.

Med J Aust, 2015 Apr 06;202(6):333-4.
PMID: 25832163
Fulltext Automated Gait Analysis Based on a Marker-Free Pose Estimation Model

Hii CST, Gan KB, Zainal N, Mohamed Ibrahim N, Azmin S, Mat Desa SH, et al.

Sensors (Basel), 2023 Jul 18;23(14).
PMID: 37514783 DOI: 10.3390/s23146489

Gait analysis is an essential tool for detecting biomechanical irregularities, designing personalized rehabilitation plans, and enhancing athletic performance. Currently, gait assessment depends on either visual observation, which lacks consistency between raters and requires clinical expertise, or instrumented evaluation, which is costly, invasive, time-consuming, and requires specialized equipment and trained personnel. Markerless gait analysis using 2D pose estimation techniques has emerged as a potential solution, but it still requires significant computational resources and human involvement, making it challenging to use. This research proposes an automated method for temporal gait analysis that employs the MediaPipe Pose, a low-computational-resource pose estimation model. The study validated this approach against the Vicon motion capture system to evaluate its reliability. The findings reveal that this approach demonstrates good (ICC(2,1) > 0.75) to excellent (ICC(2,1) > 0.90) agreement in all temporal gait parameters except for double support time (right leg switched to left leg) and swing time (right), which only exhibit a moderate (ICC(2,1) > 0.50) agreement. Additionally, this approach produces temporal gait parameters with low mean absolute error. It will be useful in monitoring changes in gait and evaluating the effectiveness of interventions such as rehabilitation or training programs in the community.
Fulltext Nonmotor symptoms in a malaysian Parkinson's disease population

Azmin S, Khairul Anuar AM, Tan HJ, Nafisah WY, Raymond AA, Hanita O, et al.

Parkinsons Dis, 2014;2014:472157.
PMID: 24800102 DOI: 10.1155/2014/472157

Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson's disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson's disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0-8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (r s : 0.727, P < 0.001). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson's disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study.
Fulltext DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients

Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, et al.

BMC Neurol, 2015;15:59.
PMID: 25896831 DOI: 10.1186/s12883-015-0316-2

Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis.
Lung computed tomography patterns of a cluster of asymptomatic young males with COVID-19 admitted to a teaching hospital in Kuala Lumpur

Ng BH, Nuratiqah NA, Andrea YLB, Faisal AH, Soo CI, Najma K, et al.

Med J Malaysia, 2020 07;75(4):368-371.
PMID: 32723996

BACKGROUND AND OBJECTIVE: Coronavirus Disease 2019 (COVID- 19) was first reported in Malaysia in March 2020. We describe here the clinical characteristics and computed tomography (CT) patterns in asymptomatic young patients who had laboratory-confirmed COVID-19.
METHODS: This is a retrospective observational study where 25 male in-patients with laboratory-confirmed COVID-19 in Hospital Canselor Tuanku Muhriz. Demographics, clinical data and CT images of these patients were reviewed by 2 senior radiologists.
RESULTS: In total there were 25 patients (all males; mean age [±SD], 21.64±2.40 years; range, 18-27 years). Patients with abnormal chest CT showed a relatively low normal absolute lymphocytes count (median: 2.2 x 109/L) and absolute monocyte count (median: 0.5 x 109/L). Lactate dehydrogenase was elevated in 5 (20%) of the patients. The procalcitonin level was normal while elevated levels of alanine aminotransferase, total bilirubin, platelet and C-reactive protein were common. Baseline chest CT showed abnormalities in 6 patients. The distribution of the lesions were; upper lobe 3 (12%) lower lobe 3 (12%) with peripheral distribution 4 (16%). Of the 25 patients included, 4 (16%) had ground glass opacification (GGO), 1 (4%) had a small peripheral subpleural nodule, and 1 (4%) had a dense solitary granuloma. Four patients had typical CT features of COVID-19.
CONCLUSION: We found that the CT imaging showed peripheral GGO in our patients. They remained clinically stable with no deterioration of their respiratory symptoms suggesting stability in lung involvement. We postulate that rapid changes in CT imaging may not be present in young, asymptomatic, non-smoking COVID-19 patients. Thus the use of CT thoraxfor early diagnosis may be reserved for patients in the older agegroups, and not in younger patients.
Randomized double-blind placebo-controlled trial of the effects of oral trehalose in spinocerebellar ataxia type 3: An interim analysis

Yap KH, Azmin S, Abdul Manan H, Yahya N, Ahmad N, Tajurudin FW, et al.

Parkinsonism Relat Disord, 2024 Jul;124:107013.
PMID: 38843619 DOI: 10.1016/j.parkreldis.2024.107013

INTRODUCTION: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients.
METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo).
RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated.
CONCLUSION: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.

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