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.
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.
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.
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.
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.
ClinicalTrials.gov NCT02112812.
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.
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.
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;
< 0.001), longer disease duration 8.71 (SD 6.23) vs. 6.60 (SD 5.39) years;
< 0.001, and longer hospital stay 7.70 (SD 5.89) vs. 6.42 (SD 7.63) days;
= 0.020. Non-PD admissions were associated with more comorbidities (97.3%;
= 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;
= 0.001) and respiratory-related causes (
< 0.001) were predictors of unfavorable hospital admission outcomes (death and complications).
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.
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
> 0.75) to excellent (ICC
> 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
> 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.
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.
Background
Spinocerebellar ataxia type 3 (SCA3) is a complex cerebrocerebellar disease primarily characterized by ataxia symptoms alongside motor and cognitive impairments. The heterogeneous clinical ...presentation of SCA3 necessitates correlations between magnetic resonance imaging (MRI) and clinical findings in reflecting progressive disease changes. At present, an attempt to systematically examine the brain-behavior relationship in SCA3, specifically, the correlation between MRI and clinical findings, is lacking.
Objective
We investigated the association strength between MRI abnormality and each clinical symptom to understand the brain-behavior relationship in SCA3.
Methods
We conducted a systematic review on Medline and Scopus to review studies evaluating the brain MRI profile of SCA3 using structural MRI (volumetric, voxel-based morphometry, surface analysis), magnetic resonance spectroscopy, and diffusion tensor imaging, including their correlations with clinical outcomes.
Results
Of 1,767 articles identified, 29 articles met the eligibility criteria. According to the National Institutes of Health quality assessment tool for case-control studies, all articles were of excellent quality. This systematic review found that SCA3 neuropathology contributes to widespread brain degeneration, affecting the cerebellum and brainstem. The disease gradually impedes the cerebral cortex and basal ganglia in the late stages of SCA3. Most findings reported moderate correlations (
r
= 0.30–0.49) between MRI features in several regions and clinical findings. Regardless of the MRI techniques, most studies focused on the brainstem and cerebellum.
Conclusions
Clinical findings suggest that rather than individual brain regions, the connectivity between different brain regions in distributed networks (i.e., cerebellar-cerebral network) may be responsible for motor and neurocognitive function in SCA3. This review highlights the importance of evaluating the progressive changes of the cerebellar-cerebral networks in SCA3 patients, specifically the functional connectivity. Given the relative lack of knowledge about functional connectivity on SCA3, future studies should investigate possible functional connectivity abnormalities in SCA3 using fMRI.
Background & Objectives: Post-stroke pain (PSP) is a common complication that is often overlooked. It leads to depression, impaired quality of life (QoL) and increased economic burden. In this study, ...we aimed to determine the prevalence and risk factors of PSP in a Malaysian stroke centre.
Methods: This is a single-centered, cross-sectional study of 175 post-stroke patients attending the neurology clinic. Their demographic data and clinical variables were collected. They were interviewed using the Brief Pain Inventory (BPI), Geriatric Depression Scale (GDS), Barthel Score (BI) and EuroQol-5D (EQ-5D) questionnaires.
Results: The prevalence of PSP was 26.3%, with most of them aged 51-70 years (52.2%). The types of pain included headache (30.4%), pain secondary to spasticity (32.6%), central post-stroke pain (26.1%) and shoulder joint pain (19.6%), in which they first experienced the pain between a week to three months post-index stroke. Our study showed that a high NIHSS, prolonged hospital stay for index stroke, poor modified Rankin Scale (mRS) and no post-discharge rehabilitation increased the probability of developing PSP. This resulted in depression, regression of functional status and poor QoL. There was no correlation between older age, gender, ethnicity, and pre-existing medical conditions with the development of PSP.
Conclusion: PSP should be diligently screened and treated in every stroke survivor to improve quality of life.
Background
Neurological involvement associated with SARS‐CoV‐2 infection has been reported from different regions of the world. However, data from South East Asia are scarce. We described the ...neurological manifestations and their associated factors among the hospitalized COVID‐19 patients from an academic tertiary hospital in Malaysia.
Methods
A cross‐sectional observational study of hospitalized COVID‐19 patients was conducted. The neurological manifestations were divided into the self‐reported central nervous system (CNS) symptoms, stroke associated symptoms, symptoms of encephalitis or encephalopathy and specific neurological complications. Multiple logistic regression was performed using demographic and clinical variables to determine the factors associated with outcome.
Results
Of 156 hospitalized COVID‐19 patients with mean age of 55.88 ± 6.11 (SD) years, 23.7% developed neurological complications, which included stroke, encephalitis and encephalopathy. Patients with neurological complications were more likely to have diabetes mellitus (p = 0.033), symptoms of stroke limb weakness (p < 0.001), slurred speech (p < 0.001); and encephalitis or encephalopathy confusion (p < 0.001), forgetfulness (p = 0.006) and seizure (p = 0.019). Unvaccinated patients had a 4.25‐fold increased risk of having neurological complications (adjusted OR = 4.25; 95% CI: 1.02, 17.71, p = 0.047). Anosmia and dysgeusia were less associated with neurological complications (adjusted OR = 0.22; 95% CI: 0.05, 0.96, p = 0.044). The odds of neurological complications were increased by 18% in patients with leukocytosis (adjusted OR = 1.18, 95% CI: 1.003, p = 0.0460).
Conclusions
Stroke, encephalitis and encephalopathy were the common neurological complications from our study. Diabetes mellitus, presence of symptoms of stroke, symptoms of encephalitis or encephalopathy, leukocytosis, and being unvaccinated against COVID‐19 were the associated risk factors of developing neurological complications.
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.
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