Manifestations and outcomes of intracerebral hemorrhage during COVID‐19 pandemic in China: a multicenter, longitudinal cohort study (preprint)

Background: We just right were carrying out a multicenter cohort study about ICH when COVID-19 broke out in Wuhan，and we wondered whether COVID-19 pandemic was associated with the manifestations and outcomes of intracerebral hemorrhage (ICH). Methods: : Acute ICH patients before (1/12/2018-30/11/2019) and during COVID-19(1/12/2019-30/11/2020) pandemic at 31 centers in China, were entered into the analysis. Demographic information, clinical manifestations and outcomes were collected and compared between the two groups. Results: : From December 1, 2018 to November 30, 2020, a total of 3460 patients with ICH were enrolled and eventually analyzed. Results showed that patients with ICH were more likely to be older, have higher systolic blood pressure (BP) (P<0.001), diastolic-BP (P=0.002), higher admission NIHSS score (P=0.039) and higher fasting blood glucose (P=0.003) during COVID-19 pandemic compared with before. After adjusting age, gender, COVID-19 pandemic was associated with 3-month poor outcome (OR = 1.206, 95%CI: 1.043-1.395) and 3-month mortality (OR = 1.711, 95%CI: 1.428-2.050) after ICH onset. Conclusions: : COVID-19 pandemic deteriorated the manifestations and outcomes of ICH.

Poor Hemorrhagic Stroke Outcomes During the COVID-19 Pandemic Are Driven by Socioeconomic Disparities (preprint)

Background Nationally representative data demonstrating the impact of the COVID-19 pandemic on hemorrhagic stroke outcomes are lacking. Methods In this pooled cross-sectional analysis, we used the National Inpatient Sample (2016-2020) to identify adults (>=18 years) with primary intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). We fit segmented logistic regression models to evaluate the differences in the rates of in-hospital outcomes (in-hospital mortality, home discharge, and receiving neurosurgical procedures) between the pre-pandemic (January 2016-February 2020) and pandemic periods (March 2020-December 2020). We used multivariable logistic regression models to evaluate the differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted during a similar period in 2019. Stratified analyses were conducted among patients residing in low and high-income zip codes and among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF). Results Overall, 309,965 ICH patients (mean age [SD]: 68[14.8], 47% female, 56% low-income) and 112,210 SAH patients (mean age [SD]: 60.2[15.4], 62% female, 55% low-income) were analyzed. Pre-pandemic, ICH mortality was decreasing by {approx}1% per month (adjusted odds ratio, 95% confidence interval: 0.99, 0.99-1.00). However, during the pandemic, the overall ICH mortality rate increased by {approx}2% per month (1.02, 1.00-1.02) and {approx}4% per month among low-income patients (1.04, 1.01-1.07). However, there was no change in trend among high-income ICH patients during the pandemic (1.00, 0.97-1.03). Patients with comorbid COVID-19 in 2020 had significantly higher odds of mortality compared to the 2019 comparison cohort, overall (ICH: 1.83, 1.33-2.51; SAH: 2.76, 1.68-4.54), and among patients with MM-LoF (ICH: 2.15, 1.12-4.16; SAH: 5.77, 1.57-21.17). However, patients with E-LoF and comorbid COVID-19 had similar mortality rates with the 2019 cohort. Conclusion Sustained efforts are needed to address socioeconomic disparities in healthcare access, quality, and outcomes during public health emergencies.

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.

Cerebral small vessel disease (CSVD) is the leading cause of vascular cognitive impairment and is associated with COVID-19. However, contributing factors that often accompany CSVD pathology in COVID-19 patients may influence the incidence of cerebrovascular complications. Thus, a mechanism linking COVID-19 and CSVD has yet to be uncovered and differentiated from age-related comorbidities (i.e., hypertension), and medical interventions during acute infection. We aimed to evaluate CSVD in acute and recovered COVID-19 patients and to differentiate COVID-19-related cerebrovascular pathology from the above-mentioned contributing factors by assessing the localization of microbleeds and ischemic lesions/infarctions in the cerebrum, cerebellum, and brainstem. A systematic search was performed in December 2022 on PubMed, Web of Science, and Embase using a pre-established search criterion related to history of, or active COVID-19 with CSVD pathology in adults. From a pool of 161 studies, 59 met eligibility criteria and were included. Microbleeds and ischemic lesions had a strong predilection for the corpus callosum and subcortical/deep white matter in COVID-19 patients, suggesting a distinct CSVD pathology. These findings have important implications for clinical practice and biomedical research as COVID-19 may independently, and through exacerbation of age-related mechanisms, contribute to increased incidence of CSVD.

Effect of COVID-19 pandemic on outcomes in intracerebral hemorrhage.

OBJECTIVES: Patients with severe intracerebral hemorrhage (ICH) often suffer from impaired capacity and rely on surrogates for decision-making. Restrictions on visitors within healthcare facilities during the pandemic may have impacted care and disposition for patient with ICH. We investigated outcomes of ICH patients during the COVID-19 pandemic compared to a pre-pandemic period. MATERIALS AND METHODS: We conducted a retrospective review of ICH patients from two sources: (1) University of Rochester Get With the Guidelines database and (2) the California State Inpatient Database (SID). Patients were divided into 2019-2020 pre-pandemic and 2020 pandemic groups. We compared mortality, discharge, and comfort care/hospice. Using single-center data, we compared 30-day readmissions and follow-up functional status. RESULTS: The single-center cohort included 230 patients (n = 122 pre-pandemic, n = 108 pandemic group), and the California SID included 17,534 patients (n = 10,537 pre-pandemic, n = 6,997 pandemic group). Inpatient mortality was no different before or during the pandemic in either cohort. Length of stay was unchanged. During the pandemic, more patients were discharged to hospice in the California SID (8.4% vs. 5.9%, p<0.001). Use of comfort care was similar before and during the pandemic in the single center data. Survivors in both datasets were more likely to be discharged home vs. facility during the pandemic. Thirty-day readmissions and follow-up functional status in the single-center cohort were similar between groups. CONCLUSIONS: Using a large database, we identified more ICH patients discharged to hospice during the COVID-19 pandemic and, among survivors, more patients were discharged home rather than healthcare facility discharge during the pandemic.

COVID-19 Infection Is Associated with Poor Outcomes in Patients with Intracerebral Hemorrhage (preprint)

Background: Patients with ischemic stroke and concomitant coronavirus 2019 (COVID-19) infection have worse outcomes than those without this infection. However, research on the impact of COVID-19 infection on outcomes following hemorrhagic stroke remains limited. We aim to study whether concomitant COVID-19 infection leads to worse outcomes in spontaneous intracerebral hemorrhage (ICH).Design: We conducted an observational study using data from Get With The Guidelines Stroke, an ongoing, multi-center, nationwide quality assurance registry. Methods: We implemented a two-stage design: first, we compared outcomes of ICH patients with and without COVID-19 infection admitted during the pandemic (from March 2020 to February 2021). Second, we compared the same outcomes between ICH patients admitted before (March 2019 to February 2020) and during (March 2020 and February 2021) the pandemic. Main outcomes were poor functional outcome (defined as a modified Rankin Scale of 4 to 6 [mRS] at discharge), mortality and discharge to skilled nursing facility (SNF) or hospice. Results: The first stage included 60,091 COVID-19-negative and 1,326 COVID-19-positive ICH patients. In multivariable analyses, ICH patients with versus without COVID-19 infection had 68% higher odds of poor outcome (OR 1.68, 95%CI 1.41-2.01), 51% higher odds of mortality (OR 1.51, CI 1.33-1.71) and 66% higher odds of being discharged to a SNF/hospice (OR 1.66, 95%CI 1.43-1.93). The second stage included 62,743 pre-pandemic and 64,681 intra-pandemic ICH cases. In multivariable analyses, ICH patients admitted during versus before the COVID-19 pandemic had a 10% higher odds of poor outcome (OR 1.10, 95%CI 1.07-1.14), 5% higher mortality (OR 1.05, 95%CI 1.02-1.08) and no significant difference in the risk of being discharged to SNF/hospice (OR 0.93, 95%CI 0.90-0.95). Conclusions: The pathophysiology of the COVID-19 infection and changes in healthcare delivery during the pandemic played a role in worsening outcomes in this patient population. Further research is needed to identify these factors and understand their effect on the long-term outcome.

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Stroke After SARS-CoV-2 mRNA Vaccine: A Nationwide Registry Study.

BACKGROUND: Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain. METHODS: In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident. RESULTS: The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85-1.00) and 0.89 (0.73-1.08) for ischemic stroke, 0.81 (0.67-0.98) and 1.05 (0.64-1.71) for intracerebral hemorrhage, and 0.64 (0.46-0.87) and 1.12 (0.57-2.19) for subarachnoid hemorrhage, respectively. CONCLUSIONS: We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

Neurological and (neuro)psychological sequelae in intensive care and general ward COVID-19 survivors.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) affects the brain, leading to long-term complaints. Studies combining brain abnormalities with objective and subjective consequences are lacking. Long-term structural brain abnormalities, neurological and (neuro)psychological consequences in COVID-19 patients admitted to the intensive care unit (ICU) or general ward were investigated. The aim was to create a multidisciplinary view on the impact of severe COVID-19 on functioning and to compare long-term consequences between ICU and general ward patients. METHODS: This multicentre prospective cohort study assessed brain abnormalities (3 T magnetic resonance imaging), cognitive dysfunction (neuropsychological test battery), neurological symptoms, cognitive complaints, emotional distress and wellbeing (self-report questionnaires) in ICU and general ward (non-ICU) survivors. RESULTS: In al, 101 ICU and 104 non-ICU patients participated 8-10 months post-hospital discharge. Significantly more ICU patients exhibited cerebral microbleeds (61% vs. 32%, p < 0.001) and had higher numbers of microbleeds (p < 0.001). No group differences were found in cognitive dysfunction, neurological symptoms, cognitive complaints, emotional distress or wellbeing. The number of microbleeds did not predict cognitive dysfunction. In the complete sample, cognitive screening suggested cognitive dysfunction in 41%, and standard neuropsychological testing showed cognitive dysfunction in 12%; 62% reported ≥3 cognitive complaints. Clinically relevant scores of depression, anxiety and post-traumatic stress were found in 15%, 19% and 12%, respectively; 28% experienced insomnia and 51% severe fatigue. CONCLUSION: Coronavirus disease 2019 ICU survivors had a higher prevalence for microbleeds but not for cognitive dysfunction compared to general ward survivors. Self-reported symptoms exceeded cognitive dysfunction. Cognitive complaints, neurological symptoms and severe fatigue were frequently reported in both groups, fitting the post-COVID-19 syndrome.

Tailoring Two White Chromatographic Platforms for Simultaneous Estimation of Ritonavir-Boosted Nirmatrelvir in Their Novel Pills: Degradation, Validation, and Environmental Impact Studies (preprint)

As long as the COVID-19 pandemic is not over, Pfizer had launched the novel pills Paxlovid® (Nirmatrelvir (NMV) co-packaged with Ritonavir (RIT)) as an effective medication for hospitalized and non-hospitalized patients. Making pharmaceutical analysis greener and more sustainable is lately the main direction of the research community. In these contexts, two fast, green and stability indicating chromatographic methods were designed for the neat quantitative determination of NMV and RIT in their bulk and dosage forms. Method I is deemed as the first electro-driven attempt for the assay of Paxlovid®. Herein, the optimized conditions of the Micellar Electrokinetic Chromatographic (MEKC) method was 50 mM borate buffer at pH 9.2  with 25 mM sodium lauryl sulfate (SDS) being used as the back ground electrolyte (BGE) on a deactivated fused silica capillary (50 cm effective length × 50 μm id). Method II was an isocratic reversed phase HPLC separation method using Zorbax-Eclipse C18 (4.6 × 250 mm, 5 μm particle size) column and 50 mM ammonium acetate buffer at pH 5 and acetonitrile as mobile phase constituents at flow rate 1 mL/min. For sake of simplicity and increasing the sensitivity, single wavelength 210 nm was used for the two methods to assay both drugs.  Linear correlations between peak areas and concentration were observed in the ranges of 10–200 μg/mL for NMV and 5–100 μg/mL RIT in both methods. The impact of versatile stress conditions such as hydrolysis, oxidation and photolysis on the stability of NMV and RIT were studied. Fortunately, both methodologies were capable to separate both drugs from their degradants. Thus, the stability indicating power of the methods were proved. The derived methods were statistically validated in agreement with the ICH guidelines. Furthermore, the environmental friendliness and sustainability of these methods were investigated and compared with the cited methods using the holistic multicriteria evaluation tools namely Hexagon, AGREE and RGB12 Methods. Conclusively, the proposed methods offered reliable, feasible, economic, white and stability-indicating alternatives to the cited chromatographic methods.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review.

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

Acute Neurological Complications of Coronavirus Disease.

The coronavirus disease (COVID-19) pandemic has impacted many lives globally. Neurologic manifestations have been observed among individuals at various stages and severity of the disease, the most common being stroke. Prompt identification of these neurologic diagnoses can affect patient management and prognosis. This article discusses the acute neuroradiological features typical of COVID-19, including cerebrovascular disease, intracerebral hemorrhage, leukoencephalopathy, and sensory neuropathies.

Prevalence of acute neurological complications and pathological neuroimaging findings in critically ill COVID-19 patients with and without VV-ECMO treatment.

Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital's databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.

Pathophysiology of reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder being recognized during the past two decades. It is characterized by multiple abrupt severe headaches and widespread cerebral vasoconstrictions, with potential complications such as ischemic stroke, convexity subarachnoid hemorrhage, intracerebral hemorrhage and posterior reversible encephalopathy syndrome. The clinical features, imaging findings, and dynamic disease course have been delineated. However, the pathophysiology of RCVS remains elusive. Recent studies have had substantial progress in elucidating its pathogenesis. It is now believed that dysfunction of cerebral vascular tone and impairment of blood-brain barrier may play key roles in the pathophysiology of RCVS, which explains some of the clinical and radiological manifestations of RCVS. Some other potentially important elements include genetic predisposition, sympathetic overactivity, endothelial dysfunction, and oxidative stress, although the detailed molecular mechanisms are yet to be identified. In this review, we will summarize what have been revealed in the literature and elaborate how these factors could contribute to the pathophysiology of RCVS.

Fatal intracerebral haemorrhage associated with thrombosis with thrombocytopenia syndrome after ChAdOx1-S vaccine. / Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient's neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.

TITLE: Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.Introducción. La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico. Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones. El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

The Challenges in Neurosurgery during the COVID-19 pandemic: a systematic review (preprint)

Background The coronavirus disease-2019 (COVID-19) pandemic has created a global crisis unique to the health care system around the world. It also had a profound impact on the management of neurosurgical patients. In our research, we intended to investigate the effect of COVID-19 pandemic on neurosurgery, particular including vascular and oncological neurosurgery.Method Two investigators independently and systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant studies respecting the criteria for inclusion and exclusion published up to June 30th, 2022. The outcomes of our research including mortality rate, length of stay, modified Rankin Score, delay in care, Glasgow outcome scale and major complications.Results Two investigators independently and systematically searched 1270 results from PubMed, Embase, Cochrane database, and extracted the detailed data from 13 articles assessed for eligibility, including 2 intracerebral hemorrhage, five subarachnoid hemorrhage, two neuro-oncology and 2 unspecified neurosurgery. A total of 25,864 patients were included in our research.Conclusion Some of our included studies suggested that pandemic caused negative effect on the outcomes of neurosurgery while others suggested that the pandemic didn't cause significant effect on the neurosurgery. Meanwhile, the effect of pandemic on neurosurgery may differ from different region.

Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Observation on the Nursing Effect of the Whole Process in Patients with Severe Intracranial Hemorrhage.

Objective: The goal of this study was to look at the clinical impact of the entire process of nursing care for patients with severe cerebral hemorrhage. Method: From January 2018 to December 2019, the clinical data of 160 patients with severe cerebral hemorrhage who were hospitalized to our hospital were reviewed retrospectively. They were separated into two groups based on their admission: routine and complete procedure. The routine group used routine emergency care, the whole process group was provided first aid care with whole process nursing. The diagnosis and treatment time, the success rate of emergency care, the incidence of adverse events, and the complaint rate were compared between the two groups. Results: The treatment time, emergency examination time, and preoperative rescue time of emergency patients in the whole process group were significantly shorter than those in the conventional group, with statistically significant differences (all P < 0.05). The rescue success rate of emergency patients in the whole process group was 95.00% (76/80), and the rescue success rate of emergency patients in the routine group was 83.75% (67/80); the difference was statistically significant (χ 2 = 4.378, P = 0.034). The complaint rate of emergency patients in the whole process group was 2.50% (2/80), while that in the routine group was 8.75% (7/80), with statistically significant difference (χ 2 = 4.732, P = 0.024). The incidence of total nursing adverse events was 6.25% (5/80) in the whole process group and 17.50% (14/80) in the routine group; the difference was statistically significant (χ 2 = 5.011, P = 0.027). Conclusion: The implementation of whole process nursing care for patients with severe intracranial hemorrhage can shorten the time-consuming first aid for patients with intracranial hemorrhage. And it also can improve the rescue success rate of patients and reduce the incidence of adverse events and complaints, which represents a significant clinical application effect.