Progressive multifocal leukoencephalopathy in a patient with B-cell chronic lymphocytic leukemia after COVID-19 vaccination, complicated with COVID-19 and mucormycosis: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. CASE PRESENTATION: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. CONCLUSION: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis.

SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group.

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Coexistence of myasthenia gravis and lichen planus: A case report and systematic review of related case reports from 1971 to 2024.

Key Clinical Message: The co-occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases. Abstract: Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co-occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co-occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67-year-old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti-AchR-Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late-onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x-ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co-occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.

The Effect of Easily Implementable Changes to the "D's of Stroke Care" in Reducing Sex Disparity in Door-to-Needle Time.

BACKGROUND: Door-to-needle (DTN) is the duration between patient's arrival at the hospital and receiving intravenous thrombolysis in ischemic stroke settings, for which studies have reported delays in women. The "D's of stroke care" describes 8 steps (D1 to D8) in patients' time tracker. We implemented simple modifications to the "D's of stroke care" by splitting D4 and D6 steps into these substeps: patients' arrival to the emergency room (D4-A), early assessment by a neurologist (D4-B), neurologist decision on patient's eligibility to receive recombinant tissue plasminogen activator (D6-A), and patient's transfer to the stroke unit (D6-B). We evaluated the effect of these changes on reducing DTN time disparity between men and women. METHODS: This study was conducted from September 2019 to August 2021, at a comprehensive stroke center. Patients were analyzed in 2 groups: group 1, before, and group 2, after using the modifications. Sex as the main variable of interest along with other covariates was regressed toward the DTN time. RESULTS: In groups 1 and 2, 47 and 56 patients received intravenous thrombolysis, respectively. Although there was a significant difference in DTN≤1 hour between women and men in group 1 (36% vs. 52%, P =0.019), it was not significantly different in group 2 ( P =0.97). Regression analysis showed being female was a significant predictor of DTN>1 hour in group 1 (adjusted odds ratio=6.65, P =0.02), whereas after using the modifications, sex was not a significant predictor for delayed DTN. CONCLUSIONS: Implementing these substeps reduced sex disparity in DTN time in our center.

Effects of Botulinum Toxin Injection on Reducing Myogenic Artifacts during Video-EEG Monitoring: A Longitudinal Study.

Medically refractory seizures affect one-third of patients with epilepsy (PwE), for whom epilepsy surgery is considered. Video electroencephalography (vEEG) monitoring is a fundamental tool for pre-operative seizure localization. Facial and cranial myogenic artifacts can obscure vEEG findings, thus interfering with seizure localization. Studies have shown the beneficial effects of botulinum toxin type A (BTX-A) injection into cranial muscles for reducing myogenic artifacts. This longitudinal study aimed to assess the effects of BTX-A injection on these artifacts. Twenty-two patients with medically refractory hypermotor seizures with daily seizure frequency and undetermined epilepsy localization were included in this study and underwent Dysport® injection (200 units) into the frontotemporal region. vEEG recordings were performed at baseline (one week before the injection), and at three days and six days post-injection. Before and after the injection, the amplitudes of myogenic artifacts were compared during various states (ictal, blinking, chewing, bruxism, head lateralization, scowling, talking, and yawning). BTX-A injection significantly reduced the amplitudes of EEG myogenic artifacts, except during blinking (day three) and talking (days three and six). On day six, significant reduction in EEG myogenic artifacts were noted during blinking, chewing, and bruxism for the greatest number of patients (95.5%, 90.9%, 81.8%), while significant reductions in EEG myogenic artifacts during talking, head lateralization, and ictal phase were associated with the least number of patients (22.7%, 36.3%, and 40.9%). Therefore, BTX-A injection could be a convenient method for filtering myogenic contamination, improving EEG interpretation, and facilitating seizure localization in patients with medically refractory seizures.

SARS-CoV-2 Is a Culprit for Some, but Not All Acute Ischemic Strokes: A Report from the Multinational COVID-19 Stroke Study Group.

BACKGROUND: SARS-CoV-2 infected patients are suggested to have a higher incidence of thrombotic events such as acute ischemic strokes (AIS). This study aimed at exploring vascular comorbidity patterns among SARS-CoV-2 infected patients with subsequent stroke. We also investigated whether the comorbidities and their frequencies under each subclass of TOAST criteria were similar to the AIS population studies prior to the pandemic. METHODS: This is a report from the Multinational COVID-19 Stroke Study Group. We present an original dataset of SASR-CoV-2 infected patients who had a subsequent stroke recorded through our multicenter prospective study. In addition, we built a dataset of previously reported patients by conducting a systematic literature review. We demonstrated distinct subgroups by clinical risk scoring models and unsupervised machine learning algorithms, including hierarchical K-Means (ML-K) and Spectral clustering (ML-S). RESULTS: This study included 323 AIS patients from 71 centers in 17 countries from the original dataset and 145 patients reported in the literature. The unsupervised clustering methods suggest a distinct cohort of patients (ML-K: 36% and ML-S: 42%) with no or few comorbidities. These patients were more than 6 years younger than other subgroups and more likely were men (ML-K: 59% and ML-S: 60%). The majority of patients in this subgroup suffered from an embolic-appearing stroke on imaging (ML-K: 83% and ML-S: 85%) and had about 50% risk of large vessel occlusions (ML-K: 50% and ML-S: 53%). In addition, there were two cohorts of patients with large-artery atherosclerosis (ML-K: 30% and ML-S: 43% of patients) and cardioembolic strokes (ML-K: 34% and ML-S: 15%) with consistent comorbidity and imaging patterns. Binominal logistic regression demonstrated that ischemic heart disease (odds ratio (OR), 4.9; 95% confidence interval (CI), 1.6-14.7), atrial fibrillation (OR, 14.0; 95% CI, 4.8-40.8), and active neoplasm (OR, 7.1; 95% CI, 1.4-36.2) were associated with cardioembolic stroke. CONCLUSIONS: Although a cohort of young and healthy men with cardioembolic and large vessel occlusions can be distinguished using both clinical sub-grouping and unsupervised clustering, stroke in other patients may be explained based on the existing comorbidities.

COVID-19: Neuroimaging Features of a Pandemic.

BACKGROUND AND PURPOSE: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is occasionally associated with manifold diseases of the central nervous system (CNS). We sought to present the neuroimaging features of such CNS involvement. In addition, we sought to identify typical neuroimaging patterns that could indicate possible COVID-19-associated neurological manifestations. METHODS: In this systematic literature review, typical neuroimaging features of cerebrovascular diseases and inflammatory processes associated with COVID-19 were analyzed. Reports presenting individual patient data were included in further quantitative analysis with descriptive statistics. RESULTS: We identified 115 studies reporting a total of 954 COVID-19 patients with associated neurological manifestations and neuroimaging alterations. A total of 95 (82.6%) of the identified studies were single case reports or case series, whereas 660 (69.2%) of the reported cases included individual information and were thus included in descriptive statistical analysis. Ischemia with neuroimaging patterns of large vessel occlusion event was revealed in 59.9% of ischemic stroke patients, whereas 69.2% of patients with intracerebral hemorrhage exhibited bleeding in a location that was not associated with hypertension. Callosal and/or juxtacortical location was identified in 58.7% of cerebral microbleed positive images. Features of hemorrhagic necrotizing encephalitis were detected in 28.8% of patients with meningo-/encephalitis. CONCLUSIONS: Manifold CNS involvement is increasingly reported in COVID-19 patients. Typical and atypical neuroimaging features have been observed in some disease entities, so that familiarity with these imaging patterns appears reasonable and may assist clinicians in the differential diagnosis of COVID-19 CNS manifestations.

Nitric oxide and TNF-α are correlates of diabetic retinopathy independent of hs-CRP and HbA1c.

PURPOSE: Regarding the role of inflammation in progression of diabetes this study was conducted to investigate the association between inflammatory biomarkers such as nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) with the chance of existence of diabetic retinopathy and its progression in patients with diabetes. METHODS: A total of 83 patients with T2DM (Type 2 diabetes mellitus) were divided into three groups of patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy (NPDR) and patients without diabetic retinopathy (NDR) based on ophthalmologic funduscopic examination. Twenty six healthy controls were also enrolled. Blood samples were taken after 12 h of overnight fasting, NO, TNF-α, and hs-CRP were measured. Association of the level of these biomarkers with retinopathy was analyzed. RESULTS: The levels of TNF-α, NO and hs-CRP were higher among patients with diabetic retinopathy. Multinomial Logistic Regression model showed that TNF-α and NO could predict the presence of retinopathy among patients with diabetes when adjusted for hs-CRP, HbA1c, FBS, gender, total cholesterol, triglyceride, HDL, LDL, BMI, and age (respectively OR = 1.76, CI 95% = 1.01-3.02, p = 0.046 and OR = 1.12, CI 95% = 1.05-1.18, p < 0.001); however they could not predict the severity of retinopathy. In ROC analysis AUC for TNFα was 0.849 (p < 0.001) and for NO was 0.907 (p < 0.001). Serum TNF-α level of 7.10 pmol/L could be suggestive of the presence of retinopathy (sensitivity = 92.2% and specificity = 66.0%), also serum NO level of 45.96 µmol/L could be suggestive of the presence of retinopathy (sensitivity = 96.1% and specificity = 86%). CONCLUSIONS: Our results suggest elevated levels of NO and TNF-α can be suggestive of diabetic retinopathy.

Cerebral venous sinus thrombosis associated with SARS-CoV-2; a multinational case series.

BACKGROUND: SARS-CoV-2 induced coagulopathy can lead to thrombotic complications such as stroke. Cerebral venous sinus thrombosis (CVST) is a less common type of stroke which might be triggered by COVID-19. We present a series of CVST cases with SARS-CoV-2 infection. METHODS: In a multinational retrospective study, we collected all cases of CVST in SARS-CoV-2 infected patients admitted to nine tertiary stroke centers from the beginning of the pandemic to June 30th, 2020. We compared the demographics, clinical and radiological characteristics, risk factors, and outcome of these patients with a control group of non-SARS-CoV-2 infected CVST patients in the same seasonal period of the years 2012-2016 from the country where the majority of cases were recruited. RESULTS: A total of 13 patients fulfilled the inclusion criteria (62% women, mean age 50.9 ± 11.2 years). Six patients were discharged with good outcomes (mRS ≤ 2) and three patients died in hospital. Compared to the control group, the SARS-CoV-2 infected patients were significantly older (50.9 versus 36.7 years, p < 0.001), had a lower rate of identified CVST risk factors (23.1% versus 84.2%, p < 0.001), had more frequent cortical vein involvement (38.5% versus 10.5%, p: 0.025), and a non-significant higher rate of in-hospital mortality (23.1% versus 5.3%, p: 0.073). CONCLUSION: CVST should be considered as potential comorbidity in SARS-CoV-2 infected patients presenting with neurological symptoms. Our data suggest that compared to non-SARS-CoV-2 infected patients, CVST occurs in older patients, with lower rates of known CVST risk factors and might lead to a poorer outcome in the SARS-CoV-2 infected group.

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.

BACKGROUND: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. METHODS: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. FINDINGS: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. INTERPRETATION: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. FUNDING: None.

Absence of a positive correlation between CRP and leptin in rheumatoid arthritis.

AIMS: Rheumatoid Arthritis (RA) is a model of chronic inflammatory disease. In this study we evaluated the correlation of leptin and CRP in patients with RA and normal controls. MAIN METHODS: A total of 75 patients with RA and 40 healthy adults were recruited in this case-control study. RA patients were categorized into high (DAS-28 > 3.2) and low activity (DAS ≤ 3.2) group according to their DAS-28 score. KEY FINDINGS: Leptin level was significantly correlated with CRP in healthy controls (r = 0.365; p < 0.05), but this correlation was lost in RA patients (r = 0.095, p = 0.41). Patients with RA had higher serum leptin levels compared to healthy controls (P < 0.01). No difference in serum leptin level was observed between patients with high and low activity disease. Also leptin was correlated with BMI in healthy controls (r = 0.326, p = 0.037). This correlation was not present in RA patients (r = 0.039, p = 0.756). SIGNIFICANCE: We observed that the physiologic correlation between leptin and CRP and BMI and CRP was not present RA patients. This is a new study reporting the lost correlation between leptin and CRP in RA patients.