Objective:We sought to determine whether MRI-based Cerebral Small Vessel Disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous Intracerebral Hemorrhage (ICH).Methods:We analyzed data from ICH survivors enrolled in a single-center prospective study. We employed three validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)-specific, hypertensive arteriopathy (HTNA)-specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status (TICS-m) test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores’ cut-offs to maximize predictive performance for dementia diagnosis.Results:We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (Inter-Quartile Range: 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (Coeff -0.25, Standard Error [SE] 0.02) and dementia risk (Sub-Hazard Ratio 1.35, 95% CI 1.10-1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all p<0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (Area Under the Curve [AUC] 0.89, SE 0.02 vs. AUC 0.81, SE 0.03, p = 0.008 for comparison). Global CSVD scores ≥ 2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis.Conclusions:A validated MRI-based CSVD score is associated with cognitive performance after ICH, and improved diagnostic accuracy for predicting new onset of dementia.

Background and purposes: Hematoma location within the cerebellum may help identify the dominant small vessel disease (SVD) type (cerebral amyloid angiopathy [CAA] vs. non-amyloid SVD). However, it is unknown whether this holds true for cerebellar microbleeds (CMBs). We tested the hypothesis that cerebellar CMBs restricted to the cortex and vermis (defined as superficial regions) are associated with clinically diagnosed and pathology-verified CAA. Methods: Three hundred and seven consecutive spontaneous intracerebral hemorrhage (ICH) patients with a baseline MRI that included susceptibility-weighted imaging or angiography were enrolled. Using a topographical template, cerebellar CMBs patterns were defined as strictly superficial vs. deep (cerebellar grey nuclei and white matter) or mixed (both regions involved). Thirty-six ICH patients with cerebellar CMBs and neuropathology data available were evaluated for presence of CAA. Results: One hundred and thirty-five (44%) ICH patients had CMBs in the cerebellum. In the patient group with cerebellar CMBs, 85 (63%) showed a superficial pattern and 50 (37%) had a deep/mixed pattern. Strictly superficial cerebellar CMBs were independently associated with a supratentorial pattern of probable CAA-ICH according to the Boston criteria (OR: 1.6, CI: 1.03-2.5) and deep/mixed cerebellar CMBs with a pattern of deep/mixed-ICH (OR: 1.8, CI: 1.2-2.7).

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ObjectiveTo investigate the prevalence, predictors, and clinical relevance of cortical superficial siderosis (cSS) progression in cerebral amyloid angiopathy (CAA).MethodsConsecutive patients with symptomatic CAA meeting Boston criteria in a prospective cohort underwent baseline and follow-up MRI within 1 year. cSS progression was evaluated on an ordinal scale and categorized into mild (score 1–2 = cSS extension within an already present cSS focus or appearance of 1 new cSS focus) and severe progression (score 3–4 = appearance of ≥2 new cSS foci). Binominal and ordinal multivariable logistic regression were used to determine cSS progression predictors. We investigated future lobar intracerebral hemorrhage (ICH) risk in survival analysis models.ResultsWe included 79 patients with CAA (mean age, 69.2 years), 56 (71%) with lobar ICH at baseline. cSS progression was detected in 23 (29%) patients: 15 (19%) patients had mild and 8 (10%) severe progression. In binominal multivariable logistic regression, ICH presence (odds ratio [OR], 7.54; 95% confidence interval [CI], 1.75–53.52; p = 0.016) and baseline cSS (OR, 10.41; 95% CI, 2.84–52.83; p = 0.001) were independent predictors of cSS progression. In similar models, presence of disseminated (but not focal) cSS at baseline (OR, 5.58; 95% CI, 1.81–19.41; p = 0.004) was an independent predictor of cSS progression. Results were similar in ordinal multivariable logistic regression models. In multivariable Cox regression analysis, severe cSS progression was independently associated with increased future ICH risk (HR, 5.90; 95% CI, 1.30–26.68; p = 0.021).ConclusionscSS evolution on MRI is common in patients with symptomatic CAA and might be a potential biomarker for assessing disease severity and future ICH risk. External validation of these findings is warranted.

Background We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. Case presentation A 29-year-old woman recently immunized with inactivated viral vaccine—BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. Conclusions ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood–brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

Active learning is an important shift in pedagogical paradigms in recent decades. Previous studies establish many benefits from this learning strategy. However, an implementation is challenging. This study aimed to clarify an explanation of the benefits and challenges of active learning from various educational field students’ perspectives. This study was conducted in a general education course at Chulalongkorn University. Underpinning with a mixed-method study, 22 undergraduates were interviewed in a focus group study. Results were analyzed with deductive thematic analysis and contributed to 23 items in close-ended questionnaires for a cross-sectional quantitative survey study. Notably, 222 undergraduates revealed their attitude toward active learning including benefits and challenges. Quantitative data were analyzed with analytical statistics including the Mann-Whitney U test, and these results are supported by thick descriptions derived from the qualitative data. This study revealed students’ attitude in benefits of active learning dividing into cognitive domain, student efficacy, and 21st century skills, and also challenges of active learning in teachers, students, and pedagogical aspects. Health science undergraduates tended to agree that active learning exposure enhances effective active learning than non-health science undergraduates (U = 2843, p = 0.029). An educational theory is also discussed with these results, and an educational implication to achieve an effective learning strategy is presented in this study.

COVID-19 infection often results in an excessive inflammatory response with a spectrum of neurological manifestations. Here, we describe an 81-year-old female with severe COVID-19 pneumonia and subsequent alteration of consciousness after high-dose intravenous dexamethasone and remdesivir. A non-contrast head computed tomography (CT) demonstrated bilateral hypodensities involving bilateral cerebellar hemispheres, thalami, cerebral peduncles and medial parieto-occipital areas. There was no improvement and repeat CT showed progression with findings suggestive of acute necrotizing encephalopathy. Interleukin-6 levels were initially normal; however, subsequent levels were found to be markedly elevated. Acute necrotizing encephalopathy associated with COVID-19 may occur in the setting of severe pneumonia and may represent an immune-mediated process involving inflammatory cytokines such as interleukin-6.

Background Fluorouracil-induced leukoencephalopathy is a rare complication and has been reported to present as confusion, oculomotor abnormality, ataxia, and parkinsonism; however, there is no previous report of a presentation mimicking neuroleptic malignant syndrome. Acute cerebellar syndrome may occur, which can be explained by the extremely high accumulation of the drug in the cerebellum. However, presentation mimicking neuroleptic malignant syndrome similar to our case has never been reported. Case presentation Here, we describe a 68-year-old Thai male presenting with advanced-stage cecal adenocarcinoma, as well as symptoms and signs indicative of neuroleptic malignant syndrome. He received two doses of intravenous metoclopramide 10 mg 6 hours before his symptoms occurred. Magnetic resonance imaging scan revealed signal hyperintensity within the bilateral white matter. Further evaluation showed that his thiamine level was extremely low. Thus, he was diagnosed with fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome. The concomitant fluorouracil-induced thiamine deficiency eventually leads to rapid depletion of thiamine and was considered a risk factor for fluorouracil-induced leukoencephalopathy. Conclusion Fluorouracil-induced leukoencephalopathy is believed to be caused by insult causing mitochondrial dysfunction. However, the exact mechanism remains unknown, but our finding suggests that thiamine deficiency plays a crucial role in fluorouracil-induced leukoencephalopathy. Diagnosis is usually delayed due to a lack of clinical suspicion and results in significant morbidity requiring unnecessary investigations.