Independent Risk Factors and Mortality Implications of De Novo Central Nervous System Involvement in Patients Hospitalized with Severe COVID-19: A Retrospective Cohort Study.

Background/Objectives: Central nervous system (CNS) involvement is a complication of COVID-19, adding to disease burden. The aim of this study is to identify the risk factors independently associated with CNS involvement in a cohort of patients hospitalized with severe forms of COVID-19 and the risk factors associated with all causes of in-hospital mortality and assess the impact of CNS involvement on in-hospital mortality of the severe COVID-19 patients. Methods: We performed a retrospective observational cohort study including adult patients with severe or critical forms of COVID-19 with and without new-onset CNS manifestations between March 2020 and December 2022. Results: We included 162 patients, 50 of which presented with CNS involvement. Independent risk factors for CNS involvement were female sex (p = 0.04, OR 3.67, 95%CI 1.05-12.85), diabetes mellitus (p = 0.008, OR 5.08, 95%CI 1.519-17.04)), lymphocyte count (0.04, OR 0.23, 95%CI 0.05-0.97), platelets count (p = 0.001, OR 0.98, 95%CI 0.98-0.99) CRP value (p = 0.04, OR 1.007, 95%CI 1.000-1.015), and CK value (p = 0.004, OR 1.003, 95%CI 1.001-1.005). Obesity was a protective factor (p < 0.001, OR 0.57, 95%CI 0.016-0.20). New-onset CNS manifestations (p = 0.002, OR 14.48, 95%CI 2.58-81.23) were independent risk factors for in-hospital mortality. In-hospital mortality was higher in the new-onset CNS involvement group compared to patients without neurological involvement, 44% versus 7.1% (p < 0.001). Conclusions: CNS involvement in severe COVID-19 patients contributes to all causes of in-hospital mortality. There are several risk factors associated with new-onset CNS manifestations and preventing and controlling them could have an important impact on patients' outcome.

Long-term follow up of alemtuzumab-treated patients: a retrospective study in a Belgian tertiary care center.

BACKGROUND: Pivotal studies have reported a significant proportion of patients achieving no evidence of disease activity (NEDA) after 2 cycles of treatment with alemtuzumab (ATZ), that can be maintained for several years. Long-term real-world evidence regarding ATZ as well as subsequent treatment trajectories is still scarce. OBJECTIVE: To analyze the effectiveness and safety of ATZ-treated patients in a tertiary care Belgian center. METHODS: A retrospective cohort study including 32 patients treated with ATZ between 2015 and 2021 was performed. RESULTS: 32 patients received 2 ATZ courses with a mean follow-up (FU) duration of 5.6 years (range: 2.25-8.2). 21.75% patients were treatment naïve. 40.5% were previously treated with natalizumab or fingolimod. NEDA-3 was achieved in 61.3-85% of patients, with failure mostly attributed to recurrence of radiological disease activity. During FU, annualized relapse rates remained very low (0.06-0.14), disability improvement occurred in up to 40.5%, whereas disability worsening occurred in up to 13.5%. Retreatment risk was associated with younger age (< 45 years old, Odds Ratio 8.0, p = 0.02) and a higher number of previous DMTs (Hazard ratio 2.7, 95%CI 1.3-7.4, p = 0.02). Safety in our cohort was consistent with the known profile of ATZ. At the end of FU, 65.6% patients remained untreated after 2 or 3 courses of ATZ, while the remaining switched to anti-CD20 therapy or cladribine. CONCLUSION: ATZ is a high efficacy therapy for active MS, providing long-term remission in a significant proportion of patients. Retreatment was more frequent in younger patients or patients having failed a higher number of previous DMTs.

Peripheral nervous system involvement associated with COVID-19. A systematic review of literature.

There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate the characteristics, management and outcomes of patients with PNS, including the types and severity of cranial nerves (CN) involvement. We systematically searched on PubMed for studies reporting adult patients diagnosed with COVID-19 and PNS involvement until July 2021. From 1670 records, 225 articles matched the inclusion criteria, with a total of 1320 neurological events, in 1004 patients. There were 805 (61%) CN, 350 (26.5%) PNS, and 165 (12.5%) PNS plus CN events. The most frequently involved CN were the facial, vestibulo-cochlear and olfactory nerve in 27.3%, 25.4% and 16.1%, respectively. Guillain-Barre syndrome spectrum was identified in 84.2% of PNS events. We analysed 328 patients reported in 225 articles with CN, PNS, and PNS plus CN involvement. The patients with CN involvement were younger (mean age 46.2±17.1, p = .003), and were more frequently treated as outpatients (p < .001), mostly with glucocorticoids (p < .001). Patients that had PNS with or without CN involvement were more likely to be hospitalized (p < .001), and to receive intravenous immunoglobulins (p = .002) or plasma exchange (p = .002). Patients with CN, PNS, and PNS plus CN had severe COVID -19 disease in 24.8%, 37.3%, 34.9% respectively. The most common neurological outcome was mild/moderate sequelae in patients with CN, PNS, and PNS plus CN in 54.7%, 67.5% and 67.8% respectively (p = .1) and no significant difference was found between the three categories regarding death, disease severity, time from disease onset to neurological symptoms, lack of improvement and complete recovery. CN involvement was the most frequent PNS finding. All three categories of PNS involvement were rather associated to non-severe COVID-19 but it may be an important cause of hospitalization and post COVID-19 sequelae.

The outcome and risk factors associated with central and peripheral nervous system involvement in hospitalized COVID-19 patients: a retrospective cohort study.

Introduction: SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the outcome and risk factors associated with the involvement of either CNS or PNS in a cohort of hospitalized COVID-19 patients. Methods: We performed a retrospective observational cohort study of hospitalized adult patients with COVID-19, between May 2020 and December 2022, presenting with new onset neurological disabilities any time after admission. Results: We included 115 patients, 72 with CNS manifestations and 43 with PNS involvement. The CNS manifestations were COVID-19-associated encephalopathy, headache, neurovascular events, and seizures in 80.5, 43, 31.9, and 11.1% of patients, respectively. The neurovascular events were ischemic stroke in 17 (23.6%) patients, hemorrhagic stroke in 6 (8.3%) patients, venous thrombosis in 1 (1.4%) patient, and subarachnoid hemorrhage in 1 (1.4%) patient. Cranial nerve involvement was the most frequent PNS manifestation in 34 (79%) cases, followed by mononeuritis in 5 (11.6%) patients and polyneuropathy in 4 (9.3%) patients. The affected cranial nerves were the vestibulocochlear nerve in 26 (60.5%) patients, the olfactory nerve in 24 (55.8%) patients, the oculomotor nerves in 5 (11.6%) patients, and the facial nerve in 1 (2.3%) patient. Two patients (9.3%) presented with polyneuritis cranialis. Older age (HR = 1.02, 95% CI: 1.003-1.037, p = 0.01), COVID severity (HR = 2.53, 95% CI: 1.42-4.5, p = 0.002), ischemic cardiac disease (HR = 2.42, 95% CI: 1.05-5.6, p = 0.03), and increased D-dimers (HR = 1.00, 95% CI: 1.00-1.00, p = 0.02) were independently associated with the development of CNS manifestations. The factors associated with in-hospital mortality were age (HR = 1.059, 95% CI: 1.024-1.096, p = 0.001), C-reactive protein (HR = 1.006, 95% CI: 1.00-1.011, p = 0.03), CNS involvement (HR = 9.155, 95% CI: 1.185-70.74, p = 0.03), and leucocyte number (HR = 1.053, 95% CI: 1.026-1.081, p < 0.001). Conclusion: COVID-19-associated encephalopathy was the most common CNS manifestation in our study, but neurovascular events are also important considering the overlap between inflammatory and prothrombotic pathways, especially in severe cases. CNS involvement was associated with in-hospital all-cause mortality. PNS findings were various, involving mostly the cranial nerves, especially the vestibulocochlear nerve.

Factors Associated with Newly Developed Postoperative Neurological Complications in Patients with Emergency Surgery for Acute Type A Aortic Dissection.

Background and Objectives: Postoperative neurological complications (NCs) are an important cause of mortality in patients with acute type A aortic dissection (ATAAD). The aim of the study was to determine the association between intraoperative risk factors and newly developed postoperative NCs in patients after emergency surgery for ATAAD. Materials and Methods: A total of 203 patients requiring emergency surgery were included in the study. Patients with preoperative neurological dysfunction, deceased on the operating table or within the first 48 h after intensive care admission, with uncertain postoperative neurologic status or with incomplete records were excluded. Results: Mean age was 57.61 ± 12.27 years. Hyperlipidemia was the most frequent comorbidity (69%). A bicuspid aortic valve was present in 12.8% of cases, severe acute aortic regurgitation was present in 29.1% of patients, and cardiac tamponade was present in 27.1% of cases. The innominate artery was the most frequently dissected supra-aortic artery in 27.1% of cases. In 65% of cases, the primary entry tear was at the level of the ascending aorta. The incidence of newly developed postoperative NCs was 39.4%. The most common surgical technique performed was supra-coronary ascending aorta and hemiarch replacement, in 53.2% of patients. Using logistic regression, cardiopulmonary bypass time (OR = 1.01; 95% CI = 1.01-1.02; p < 0.001), aortic cross-clamp time over 3 h (OR = 2.71, 95% CI = 1.43-5.14, p = 0.002) and cerebral perfusion time (OR = 1.02; 95% CI = 1.002-1.03; p = 0.027) were independently associated with newly developed postoperative NCs. Conclusions: Based on the results of the study, all efforts should be made to reduce operative times. Using a simple surgical technique, like the supra-coronary ascending aorta and hemiarch technique, whenever possible, and using a simpler technique for cerebral perfusion like unilateral cerebral perfusion via the right axillary artery, could reduce operating times.

Relevance of Nerve Biopsy in the Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy-A Systematic Review.

Chronic Inflammatory Demyelinating Polyneuropathy is an immune-mediated pathology of the peripheral nerves and nerve roots that leads to weakness and sensory symptoms. Given its clinical heterogeneity, often times diagnosis is challenging. Even though nerve conduction studies and clinical features are the main criteria used for diagnosis, supplementary investigations, such as nerve biopsies, cerebral spinal fluid examination and magnetic resonance studies, may be used in order to confirm the diagnosis. Given the fact that the hallmark in CIDP physiopathology is the demyelination process, nerve biopsies are used to demonstrate and assess the magnitude of the phenomenon. The question and the main interest of this review is whether histopathological findings are relevant for the diagnosis and can be useful in disease assessment.