Possible Roles of Extracellular Vesicles in the Pathogenesis and Interventions of Immune-Mediated Central Demyelinating Diseases.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two of the most devastating immune-mediated central demyelinating disorders. NMOSD was once considered as a variant of MS until the discovery of an antibody specific to the condition. Despite both MS and NMOSD being considered central demyelinating disorders, their pathogenesis and clinical manifestations are distinct, however the exact mechanisms associated with each disease remain unclear. Extracellular vesicles (EVs) are nano-sized vesicles originating in various cells which serve as intercellular communicators. There is a large body of evidence to show the possible roles of EVs in the pathogenesis of several diseases, including the immune-mediated central demyelinating disorders. Various types of EVs are found across disease stages and could potentially be used as a surrogate marker, as well as acting by carrying a cargo of biochemical molecules. The possibility for EVs to be used as a next-generation targeted treatment for the immune-mediated central demyelinating disorders has been investigated. The aim of this review was to comprehensively identify, compile and discuss key findings from in vitro, in vivo and clinical studies. A summary of all findings shows that: 1) the EV profiles of MS and NMOSD differ from those of healthy individuals, 2) the use of EV markers as liquid biopsy diagnostic tools appears to be promising biomarkers for both MS and NMOSD, and 3) EVs are being studied as a potential targeted therapy for MS and NMOSD. Any controversial findings are also discussed in this review.

Coexistence of IgLON5-IgG and SOX1-IgG in a Patient with Progressive Brainstem Dysfunction.

PURPOSE: The coexistence of IgLON5-IgG and SOX1-IgG is rare. Previous reports have shown that patients with IgLON5-IgG spectrum disease present with sleep disorders, bulbar involvement, and autonomic abnormality, while SOX1-IgG positive patients present with peripheral nervous system symptoms such as the Lambert-Eaton Myasthenic Syndrome (LEMS). CASE REPORT: We report a patient who presented with progressive ophthalmoplegia, ptosis, oropharyngeal dysphagia, gait instability, and sleep disorders. The paraneoplastic antibody screening tested doublepositive for IgLON5-IgG and SOX1-IgG. However, there was no clinical sign of LEMS in this patient. After extensive cancer screening, only lung nodules with hilar adenopathy were noted. CONCLUSION: The coexistence of IgLON5-IgG with onconeuronal SOX1-IgG would suggest an underlying immune-mediated paraneoplastic process rather than secondary autoimmunity because of neurodegeneration. This is the first IgLON5-IgG case reported in Thailand, with a case of doublepositive IgLON5-IgG and SOX1-IgG as well. Keyword: IgLON5-IgG, SOX1-IgG, Paraneoplastic process, case report.

Serum NT-proBNP level for predicting functional outcomes after acute ischemic stroke.

N-terminus pro-brain natriuretic peptide (NT-proBNP) has been studied and recognized as a biomarker of cardiac thrombogenicity and stroke risk. However, the association between NT-proBNP and functional outcomes following acute ischemic stroke is still debated. This study aimed to investigate whether serum NT-proBNP level is associated with functional outcomes in acute ischemic stroke individuals. This prospective cohort study included patients diagnosed with acute ischemic stroke, and serum NT-proBNP levels were measured within 72 h. At 3 months, all patients were followed up for a modified Rankin Scale (mRS), and logistic regression models were used to evaluate the association of NT-proBNP on the primary outcome, in which a score of 3-6 was classified as an unfavorable functional outcome. Sixty-seven patients were enrolled in the study, and 23 (34.3%) patients were identified with an unfavorable functional outcome. Elevated serum NT-proBNP levels (> 100 pg/mL) were observed in 57 (85.1%) patients, and the Youden index demonstrated a cutpoint estimation of poor outcomes at 476 pg/mL with 74% sensitivity and 63% specificity. Multivariate regression analysis showed an elevation of NT-proBNP above the cutpoint level was an independent predictor for unfavorable functional outcomes, odds ratio 3.77, 95% confidence interval (1.04-13.62), P = 0.04. The present study demonstrated that elevated serum NT-proBNP levels were expected among acute ischemic stroke patients and represented the risk of unfavorable functional outcomes, suggesting that NT-proBNP might be a useful biomarker for predicting prognosis after ischemic stroke.

A Simplified Risk Score to Predict In-Hospital Newly-Diagnosed Atrial Fibrillation in Acute Ischemic Stroke Patients.

Purpose: Atrial fibrillation (AF) is a significant cause of stroke, and newly diagnosed AF (NDAF) is typically detected in the early period of stroke onset. We aimed to identify the factors associated with in-hospital NDAF in acute ischemic stroke patients and developed a simplified clinical prediction model. Methods: Patients with cryptogenic stroke aged 18 years or older who were admitted between January 2017 and December 2021 were recruited. NDAF was determined by inpatient cardiac telemetry. Univariable and multivariable regression analyses were used to evaluate the factors associated with in-hospital NDAF. The predictive model was developed using regression coefficients. Results: The study enrolled 244 eligible participants, of which 52 NDAFs were documented (21.31%), and the median time to detection was two days (1-3.5). After multivariable regression analysis, parameters significantly associated with in-hospital NDAF were elderly (>75 years) (adjusted Odds ratio, 2.99; 95% confident interval, 1.51-5.91; P = 0.002), female sex (2.08; 1.04-4.14; P = 0.04), higher admission national institute of health stroke scale (1.04; 1.00-1.09; P = 0.05), and presence of hyperdense middle cerebral artery sign (2.33; 1.13-4.79; P = 0.02). The area under the receiver operating characteristic curve resulted in 0.74 (95% CI 0.65-0.80), and the cut-point of 2 showed 87% sensitivity and 42% specificity. Conclusion: The validated and simplified risk scores for predicting in-hospital NDAF primarily rely on simplified parameters and high sensitivity. It might be used as a screening tool for in-hospital NDAF in stroke patients who initially presumed cryptogenic stroke.

Cryptococcal Meningitis: Differences between Patients with and without HIV-Infection.

Background: Cryptococcal meningitis is one of the most devastating infections, particularly in HIV-infected individuals. The increased use of immunosuppressants led to an increase in the incidence of cryptococcosis in HIV-uninfected individuals. This study aimed to compare the characteristics between groups. Methods: This retrospective cohort study was conducted from 2011 to 2021 in northern Thailand. Individuals diagnosed with cryptococcal meningitis aged ≥15 years were enrolled onto the study. Results: Out of 147 patients, 101 were individuals infected with HIV and 46 were non-infected. Factors associated with being infected with HIV included age < 45 years (OR 8.70, 95% CI 1.78-42.62), white blood cells < 5000 cells/cu.mm. (OR 7.18, 95% CI 1.45-35.61), and presence of fungemia (OR 5.86, 95% CI 1.17-42.62). Overall, the mortality rate was 24% (18% in HIV-infected vs. 37% in HIV-uninfected individuals, p-value = 0.020). Factors associated with mortality included concurrent pneumocystis pneumonia (HR 5.44, 95% CI 1.55-19.15), presence of alteration of consciousness (HR 2.94, 95% CI 1.42-6.10), infection caused by members of C. gattii species complex (HR 4.19, 95% CI 1.39-12.62), and anemia (HR 3.17, 95% CI 1.17-8.59). Conclusions: Clinical manifestations of cryptococcal meningitis differed between patients with and without HIV-infection in some aspects. Increasing awareness in physicians of this disease in HIV-uninfected individuals may prompt earlier diagnosis and timely treatment.

Preseptal and Pretarsal Botulinum Toxin Injection in Hemifacial Spasm and Blepharospasm: A 10-Year Comparative Study.

Purpose: Preseptal and pretarsal botulinum toxin injections are approved for treatment of hemifacial spasm and blepharospasm. However, the long-term data is limited. We compared the efficacy, safety, and costs between preseptal and pretarsal injection in hemifacial spasm and blepharospasm. Patients and Methods: The data were retrieved between 2011 and 2021. Consecutive hemifacial spasm and blepharospasm botulinum toxin patients were categorized as preseptal or pretarsal. Study outcomes were the difference in pre-and post-treatment modified Jankovic scale, self-reporting scales, time-related treatment, safety, and cost. Results: Of 152 botulinum toxin-injected patients, 117 (77.0%) patients had hemifacial spasm and 35 (33.0%) patients had blepharospasm. Analysis included data pertinent to 1665 injections in hemifacial spasm (920 preseptal and 745 pretarsal) and 527 injections in blepharospasm (210 preseptal and 317 pretarsal). The difference between pre-and post-treatment modified Jankovic scale was lower in the preseptal group than in the pretarsal group in both hemifacial spasm and blepharospasm (1.5±0.8 vs 1.8±0.6, P-value <0.001 and 1.8±0.8 vs 3.1±0.9, P-value <0.001). There was no difference in duration of maximum response in hemifacial spasm between groups, while the blepharospasm with preseptal had a longer duration than blepharospasm with pretarsal. The preseptal injection was associated with more adverse events overall than the pretarsal (9.4% vs 5.2%, P-value <0.001). The total dose and cost per session in the preseptal group is lower for onabotulinum toxin but higher for abobotulinum toxin. Conclusion: Pretarsal injections reduced symptom severity with fewer side effects. Further studies on the pharmacoeconomics of both techniques are required.

Outcomes of asymptomatic recombinant tissue plasminogen activator associated intracranial hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) is the most devastating complication of recombinant tissue plasminogen activator (rtPA) treatment in acute ischemic stroke patients. Data on rtPA-associated asymptomatic ICH (aICH) are limited. OBJECTIVES: To determine the incidence, risk factors, characteristics, management, and clinical outcome of rtPA-associated aICH. METHODS: The data were retrieved from the Chiang Mai University Hospital Stroke Registry between 1995 and 2019. Consecutive ischemic stroke patients were included if they were 18 or older and received rtPA. Study outcomes were the incidence and characteristics of aICH, management, 90-day modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS), Barthel index, and all-cause mortality. RESULTS: Of 725 rtPA treated patients, 166 (16.0%, 95% confidence interval [CI] 13.4-18.9) had aICH, 50 (6.9%, 95% CI 5.2-9.0) had symptomatic ICH (sICH). Patients with aICH had more hemorrhagic infarctions (HI) compared to sICH (81.9% vs 2.0%, P-value < 0.001). Fresh Frozen Plasma and cryoprecipitate were the most common blood products used to reverse the anticoagulant effect in sICH. Craniotomy was performed in 1% and 60% of patients who had aICH and sICH. At 90 days, patients who had aICH had poorer clinical outcomes (mRS, NIHSS and Barthel index) as compared to those without ICH. Compared to non-ICH patients, aICH patients were associated with increased risk of 90-day mortality, the hazard ratio (HR), 3.7, 95% CI 1.6-8.9. CONCLUSIONS: The rtPA-associated aICH increased the risk of morbidity and mortality outcomes. Further treatment consensus, guideline generation, or clinical trials focusing on the treatment of rtPA-associated aICH may be required.

Cerebral venous sinus thrombosis in immune thrombocytopenia patients treated with thrombopoietin receptor agonist: Case reports and literature review.

Introduction and importance: Cerebral venous sinus thrombosis is an uncommon adverse event in immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (TPO-RAs). Case presentation: We reported two cases of cerebral venous sinus thrombosis after eltrombopag administration. The first case is a 29-year-old ITP woman who recently initiated eltrombopag one month before admission. She presented with progressive headache, visual disturbance, and nausea for six days with unremarkable physical examination except for bilateral optic disc edema. She was treated with enoxaparin and switched to edoxaban when discharged. The second case is a 75-year-old man with a history of vaccine-induced ITP. He was initially treated with dexamethasone and eltrombopag. One month later, he developed acute cerebral venous thrombosis with hemorrhagic infarction in the bilateral frontal lobes. Even though he was treated with intravenous heparin, his status was not improved. He received the best supportive care. Discussion: The pathophysiology of TPO-RAs-associated cerebral venous sinus thrombosis remained unclear but might associate with platelet activation. Most cases of cerebral venous sinus thrombosis occur within two months, thus closed platelet monitoring is important. Conclusion: Careful use and closed monitoring might prevent this event. Indications of initiation and tapering must be considered before TPO-RAs administration. Off-label use may enhance TPO-RA side effects.