28 pubs · 214 cites · h-index 9
Objectives To characterize real‐world barriers to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) management in the Philippines and identify pragmatic patient‐centered solutions aligned with international guidance and local health‐system realities. Methods We conducted a survey‐informed qualitative expert‐panel study involving six Philippine neurologists from public and private tertiary centers. Data sources included review of EAN/PNS‐2021 CIDP guidelines, contemporary literature, and pre‐meeting survey results on local clinical practice followed by structured discussions. Findings were organized using a patient‐journey framework and analyzed thematically across clinical, operational, policy, and economic domains. Results Real‐world challenges were identified across three domains. Clinical: clinical mimics, variability in electrodiagnostic interpretation, limited test availability, and delayed referral; Operational: partial or variable treatment response, corticosteroid side‐effects, inpatient infusion logistics, and difficulties maintaining therapy; and Policy/economic: high out‐of‐pocket costs, limited reimbursement, procurement delays, and regional inequities. Experts described several key components of patient‐centered CIDP care, including the use of standardized diagnostic pathways, improved access to neurophysiological testing, increased disease awareness, and structured monitoring using disability and impairment scales. Additional elements included the incorporation of patient‐reported outcomes, shared decision‐making, and individualized infusion and weaning strategies, and generation of local real‐world, cost‐effectiveness, budget‐impact, and patient‐reported outcome data. Conclusions This study identifies neurologist‐perceived clinical and system barriers affecting CIDP care across the patient journey in the Philippines. Findings support implementation of an evidence‐based patient‐centered framework aligned with international guidelines but adapted for the Philippine healthcare system. Such a framework may improve diagnosis, streamline treatment, and enhance equitable access.
This retrospective study reveals a significant increase in methamphetamine-associated intracerebral hemorrhage, suggesting urgent public health action is necessary.
Background Clinical frailty is a multifaceted biological phenomenon that arises from a cumulative multisystem decline, resulting in a state of increased vulnerability to stressor events. Here, we investigated the impact of premorbid clinical frailty on outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Methods This retrospective cohort study included 103 patients (≥70 years) treated with IVT for AIS. Frailty was assessed using the Clinical Frailty Scale (CFS). Primary and secondary endpoints were favorable functional outcomes (defined as a modified Rankin Scale (mRS) score of 0-2) at 30 and 90 days, respectively. Other endpoints included National Institutes of Health Stroke Scale (NIHSS) improvement at 24 h post-IVT, 30-day all-cause mortality, and symptomatic intracerebral hemorrhage (sICH). Results Frailty was independently associated with lower odds of achieving favorable functional outcomes at both 30 (adjusted OR 0.01 [95% CI 0.003-0.11], P < .001) and 90 days (adjusted OR 0.03 [95% CI 0.01-0.36], P < .001), and with increased 30-day all-cause mortality (adjusted OR 1.95 [95% CI 1.12-3.96], P < .001). Early neurologic improvement was likewise attenuated among frail patients, with each one-point increase in CFS found to be independently associated with a 1.871-point decrease in NIHSS improvement at 24 h post-IVT ( P < .001). Frailty was not independently associated with sICH (adjusted OR 1.36 [95% CI 0.87-3.06], P = .857). Conclusion Our findings suggest that premorbid clinical frailty is independently associated with worse outcomes among patients receiving IVT for AIS, without significantly increasing the risk of sICH.
Introduction Despite the rapidly increasing prevalence of electronic cigarette (EC) use, its effects on cerebrovascular health remain unclear. This study is the first to explore the impact of chronic EC vaping on human cerebral vascular function. Methods This cross‐sectional study included 60 participants: 30 long‐term EC users, and 30 age‐ and sex‐matched controls with no history of EC use. Cerebrovascular function was assessed using the breath‐holding index (BHI), a transcranial Doppler‐based measure of cerebral vasomotor reactivity, and a preclinical marker associated with increased risk of cerebrovascular disease, neurocognitive decline, and mortality. Cumulative EC exposure was quantified using “EC burden,” a composite measure derived from the product of average daily puffs and duration of use. Results Long‐term EC vapers exhibited significantly lower BHI values compared to controls ( p < 0.001), with long‐term EC use found to be independently associated with impaired BHI {adjusted odds ratio (OR) 1.21 [95% CI 1.03–3.21]; p = 0.039}. Subjects with impaired BHI had significantly greater EC burden ( p < 0.001) and longer duration of EC use (minimum 4 years; p < 0.001) compared to long‐term EC users with normal BHI. EC burden was independently associated with impaired BHI (adjusted OR 1.35 [95% CI 1.02–2.41]; p = 0.022), demonstrating a strong inverse linear relationship ( R 2 = 0.78; p < 0.001). Conclusions Our findings provide preliminary evidence suggesting an association between long‐term EC vaping and impaired cerebrovascular function, as assessed by BHI. Confirmation through larger prospective studies using more definitive measures of cerebral vasomotor reactivity is warranted.
Bilateral scapular winging is a rare and atypical manifestation of Arnold-Chiari malformation type 1 (ACM1). We report a case of ACM with extensive syrinx formation, presenting with progressive bilateral proximal upper extremity weakness, bilateral scapular winging, and segmental hypesthesia and reduced thermesthesia over the bilateral C2-C8 dermatomal levels. The patient was successfully treated with surgical decompression and syringosubarachnoid shunting. This unusual presentation of ACM1 emphasizes the need to consider central nervous system pathologies in the differential diagnosis for bilateral scapular winging.
There is increasing evidence that establishes a connection between fluctuations in glucose metabolism and the onset of Alzheimer's disease (AD). Current research supports the notion that this metabolic imbalance significantly affects cognitive health. However, the specific mechanisms through which these fluctuations influence neurodegeneration, eventually leading to AD, require further exploration. This study aims to determine the risk of AD among individuals with fluctuations in blood glucose levels, with or without type 2 diabetes mellitus (T2DM), further providing the most recent and thorough overview of the evidence in this area. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a thorough search was carried out utilizing particular phrases in the PubMed, Elsevier, Research Gate, and Cochrane databases: ("glucose variability" or "glycemic variability" or "glucose fluctuation" or "glucose instability" or "glycemic fluctuation") and ("Alzheimer's disease" or "Alzheimer disease" or "Alzheimer dementia" or "Alzheimer"). Studies published between January 2014 to January 2024, written in English, and examining the relationship between glucose variability and AD, were included. The outcomes measured were risk of cognitive impairment and AD, cognitive performance, and risk of AD. The results of the literature search produced 142 records, with six studies meeting the eligibility criteria. Parameters for glycemic variability included fasting plasma glucose (FPG) variability, glycated hemoglobin (HbA1c) variability, FPG variability independent of the mean (VIM), FPG coefficient of variation (CV), and FPG standard deviation (SD). The studies revealed a positive correlation between glycemic variability and the risk of AD over time, and the findings indicated that maintaining stable glycemic levels may reduce the risk of cognitive decline among individuals with or without T2DM. Due to the small number of studies that are currently available, despite a calculated relative risk of 2.65 indicating a higher risk of AD among subjects with glycemic variability, the inclusion of the null value in the confidence interval (0.61-11.45) renders these findings not statistically significant. This comprehensive review demonstrated that, in people with or without diabetes, glycemic variability influences cognitive decline and the risk of AD. The studies demonstrated a correlation between higher fluctuations in glucose levels and an increased risk of AD, highlighting the importance of managing blood sugar levels to mitigate dementia risks. Despite these strong associations, the actual incidence rates of AD in the studied populations remained relatively low. Overall, the results were not statistically significant. Further research is recommended to explore the risk of AD among individuals with fluctuations in blood glucose levels.
Diagnostic evaluation demonstrates clinical criteria identify predominant vascular pathology in cognitive impairment, indicating effective differentiation from mixed amyloid disease.
It is estimated that 45% of individuals with cognitive impairment experience sleep disturbances prior to the onset of cognitive symptoms. Assessing sleeping problems and enhancing sleep quality are critical first steps to reduce the risk of cognitive impairment. Objective: To review existing literature based on predefined eligibility criteria to understand the connection between sleep disturbance and Alzheimer's disease. Methods: A thorough and systematic evaluation of numerous studies was carried out to assess one or more of the following epidemiological factors: (1) sleep disorders, (2) cognitive impairment, and (3) risk estimates for cognitive impairment due to sleep. Results: Studies suggest that individuals who experience memory loss may encounter sleep disturbances before noticing other symptoms. Numerous sleep disorders, such as excessive and inadequate sleep duration, poor sleep quality, circadian rhythm abnormalities, insomnia, and obstructive sleep apnea were found to increase the risk of cognitive dysfunction and dementia. Additionally, lower sleep quality and shorter sleep duration have been linked to higher cerebral-β-amyloid levels. Objective evidence for the development of cognitive impairment is provided by the architecture of sleep stages. Patients experiencing sleep problems may benefit from specific types of sleep medicine as a preventative measure against cognitive decline. Conclusion: Sleep disorders can have adverse effects on cognitive health. The duration and quality of sleep are fundamental factors for maintaining a healthy brain as we age. Proper sleep can aid prevent cognitive impairment, particularly Alzheimer's disease and dementia.
Purpose: is a parasite that is widely distributed around the globe and can cause brain inflammation, particularly in immunosuppressed patients such as those diagnosed with human immunodeficiency virus (HIV). This paper reviews the efficacy of azithromycin and pyrimethamine combination therapy for cerebral toxoplasmosis in patients with HIV. Methods: The scope of the studies included in this review was limited from 1992 to 2022, with studies primarily being randomized, controlled clinical trials available on online scientific journal databases. The authors screened eligible records for review, removing those that did not fit the inclusion and exclusion criteria. The risk of bias of the extracted data was analyzed through the Cochrane risk-of-bias tool for randomized trials. Results: A broad search of major online databases such as PubMed, Medline, Google Scholar, and Cochrane using keywords, limit fields, and Boolean operators yielded 3,130 articles. After thoroughly screening the search results, two studies were included in this review. Results from the studies included in the review demonstrate that the combination therapy of azithromycin and pyrimethamine is favorable for cerebral toxoplasmosis. However, the net response is less effective than the standard treatment regimen (pyrimethamine and sulfadiazine). Conclusion: The combination therapy of azithromycin and pyrimethamine is less effective than the standard treatment regimen for maintenance therapy for cerebral toxoplasmosis; thus, administering these medications for this indication must be met with caution.
Background The underlying cause of cognitive decline in individuals who are positive for biomarkers of neurodegeneration (N) but negative for biomarkers of amyloid‐beta (A), designated as Suspected non‐Alzheimer's pathophysiology (SNAP), remains unclear. We evaluate whether cerebrovascular disease (CeVD) is more prevalent in those with SNAP compared to A−N− and A+N+ individuals and whether CeVD is associated with cognitive decline over time in SNAP patients. Methods A total of 216 individuals from a prospective memory clinic cohort (mean [SD] age, 72.7 [7.3] years, 100 women [56.5%]) were included and were diagnosed as no cognitive impairment (NCI), cognitive impairment no dementia (CIND), Alzheimer's dementia (AD) or vascular dementia (VaD). All individuals underwent clinical evaluation and neuropsychological assessment annually for up to 5 years. Carbon 11‐labeled Pittsburgh Compound B ([ 11 C]‐PiB) or [ 18 F]‐flutafuranol‐positron emission spectrometry imaging was performed to ascertain amyloid‐beta status. Magnetic resonance imaging was performed to assess neurodegeneration as measured by medial temporal atrophy ≥2, as well as significant CeVD (sCeVD) burden, defined by cortical infarct count ≥1, Fazekas score ≥2, lacune count ≥2 or cerebral microbleed count ≥2. Results Of the 216 individuals, 50 (23.1%) A−N+ were (SNAP), 93 (43.1%) A−N−, 36 (16.7%) A+N− and 37 (17.1%) A+N+. A+N+ individuals were significantly older, while A+N+ and SNAP individuals were more likely to have dementia. The SNAP group had a higher prevalence of sCeVD (90.0%) compared to A−N−. Moreover, SNAP individuals with sCeVD had significantly steeper decline in global cognition compared to A−N− over 5 years ( p = 0.042). Conclusions These findings suggest that CeVD is a contributing factor to cognitive decline in SNAP. Therefore, SNAP individuals should be carefully assessed and treated for CeVD.
OBJECTIVES: Preclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression. DESIGN: Randomized double-blind placebo-controlled delayed-start study. SETTING AND PARTICIPANT: Patients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials.gov, NCT03038035). METHODS: The primary outcome measure was occurrence of serious adverse events (SAEs) at 6 months. Secondary outcomes included the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and other assessment scales. RESULTS: There was no significant difference in the risk of SAEs between early and delayed starters at month (M) 6 (22.6% vs 27.0%, risk difference -4.4%, 90% CI -16.9% to 8.3%). Similarly, there was no significant difference in the risk of adverse events and the occurrence of stroke or vascular events between early and delayed starters throughout the 12-month study period. Early starters did not differ significantly on ADAS-Cog from delayed starters at M6 [mean difference (MD) -1.0, 95% CI -3.3 to 1.3] and M12 (MD -2.35, 95% CI -5.45 to 0.74) on intention-to-treat analysis. Other cognitive assessment scales did not show significant differences. CONCLUSIONS AND IMPLICATIONS: This study of 125 persons with dementia found no evidence of a significant increase in adverse events between MLC901 and placebo, thus providing support for further studies on both efficacy and safety. Analyses suggest the potential of MLC901 in slowing down AD progression, but this requires further confirmation in larger and longer studies using biomarkers for AD.
CURATE.AI shows promise as an artificial intelligence platform to predict antihypertensive treatment responses and optimize personalized dosing in hypertension patients.
The CURATE.AI platform shows potential for personalized, N-of-1 dose optimization in hypertension management without requiring extensive additional data collection.
Introduction The SINGER pilot randomized controlled trial aims to examine the feasibility and acceptability of the Finnish Geriatric Intervention Study (FINGER) multi‐domain lifestyle interventions compared to Singaporean adaptations. Methods Seventy elderly participants were recruited and randomized into FINGER (n = 36) or SINGER (n = 34) interventions; involving physical exercise, cognitive training, diet, and vascular risk factors management, for 6 months. Results Both intervention groups were equally feasible and acceptable with participants completing at least 80% of the interventions. Body strength improved in both groups ( P upper body = .04, P lower body = .06, P core = .05). More participants in the SINGER group attained good blood pressure control at month‐6 compared to FINGER (41% vs 19%; P = .06). Discussion This study is the first to compare the feasibility of multi‐domain interventions adapted to local culture with the FINGER interventions. The findings will be utilized for a larger study to provide evidence for the efficacy of multi‐domain lifestyle interventions in preventing cognitive decline.
Objective To evaluate the association between brain amyloid β (Aβ) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition, in a memory clinic study. Methods A total of 186 individuals visiting a memory clinic, diagnosed with no cognitive impairment, cognitive impairment no dementia (CIND), Alzheimer dementia (AD), or vascular dementia were included. Brain Aβ was measured by [¹¹C] Pittsburgh compound B–PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing. Results An increase in global SUVR is associated with a decrease in Mini-Mental State Examination (MMSE) in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume, and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND (P for interaction: 0.009), with an increase of the effect size of Aβ (β = −6.57 [−9.62 to −3.54], p < 0.001) compared to the model without the interaction term (β = −2.91 [−4.54 to −1.29], p = 0.001). Conclusion Higher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH only in CIND. This suggests that Aβ and CSVD are independent processes with a possible synergistic effect between Aβ and WMH in individuals with CIND. There was no interaction effect between Aβ and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction.
INTRODUCTION: Disproportionately Enlarged Subarachnoid space Hydrocephalus (DESH) is considered as an important imaging feature of idiopathic normal pressure hydrocephalus (iNPH). METHOD: Subjects aged 60 and over in a memory clinic and a community-based cohort were assessed for the presence of ventriculomegaly, Sylvian dilatation, and high convexity tightness by neuroimaging, and a clinical triad of iNPH symptoms, i.e. cognitive, gait and urinary symptoms. RESULTS: In the memory clinic-based study (548 subjects), the prevalence of DESH was 1.1% and increased with age. The clinical triad was significantly more frequent in subjects with DESH (50%) compared to those with normal images (none), Sylvian dilatation (7%), and ventriculomegaly (12%). Gait disturbance was also significantly more frequent in DESH (83%) compared to those with normal images (2%), Sylvian dilatation (14%), and ventriculomegaly (26%). In the community-based cohort (946 subjects), the prevalence of DESH was 1.0% and increased with age. The clinical triad (11%) was significantly more common in subjects with DESH compared to those with normal images (none), Sylvian dilatation (2%), and ventriculomegaly (7%). Gait disturbance was also significantly more common in DESH (33%) compared to those with normal images (1%), Sylvian dilatation (4%), and ventriculomegaly (10%). CONCLUSION: The reported prevalence of DESH was approximately 1%, and increased with age. DESH and high convexity tightness were specifically associated with the clinical triad of iNPH. Of the triad, gait disturbance was associated to DESH and high convexity tightness.