Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study

Background: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. Methods: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. Results: The patients’ mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18–4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48–5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). Conclusions: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

Eculizumab Use in a Temporarily Dialysis-Dependent Patient With Shiga Toxin–Producing Escherichia Coli Hemolytic Uremic Syndrome With Neurological Complications

Shiga toxin–producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the most common cause of acute renal failure in children, and it is associated with thrombocytopenia and hemolytic anemia. Although this disease primarily affects the kidney, it can also contribute to cellular damage in other organ systems, such as the CNS. Eculizumab is a monoclonal antibody that binds to complement proteins to prevent complement-mediated intravascular hemolysis in atypical HUS. In STEC-HUS, complement activation also occurs by Shiga toxin, and previous cases of eculizumab use in the setting of neurological involvement have been shown to be successful. We report the successful use of eculizumab in the setting of typical STEC-HUS–induced neurological symptoms including seizure, altered mental status, and left arm weakness. The patient also experienced concomitant renal failure requiring dose adjustment for hemodialysis. Following 2 doses of eculizumab, our patient was discharged to an inpatient rehabilitation facility with resolution of her renal injury, seizures, and altered mentation without adverse effects from eculizumab throughout the admission. Based on our case study, it appears that eculizumab may be given during or between hemodialysis without dose adjustment.

Relapsing Neurological Complications in a Child With ATP1A3 Gene Mutation and Influenza Infection: A Case Report

Mutations in the ATP1A3 gene encoding the α3 subunit of Na+/K+-ATPase are associated with different neurological manifestations that may be elicited by febrile episodes. A recently described phenotype, linked to the p.Arg756Cys mutation, is clinically characterized by Relapsing Encephalopathy with Cerebellar Ataxia (RECA). In our case, a diagnosis of RECA has been established, and despite an alternative, reasonable cause had been already identified.We describe the case of a child with two recurrent episodes, 2 years apart, of hypotonia and ataxia. In both episodes, a laboratory-confirmed influenza virus infection suggested the diagnosis of influenza-associated encephalopathy. After the second episode, a search for genetic mutations was performed, and ATP1A3 mutation associated to RECA was found. After both episodes, the child was discharged after partial improvement of neurological conditions.The diagnosis of encephalopathy in children is often challenging. A genetic predisposition to neurological decompensation should be suspected in case of recurrent episodes, even if an alternative diagnosis has been established. Indeed, febrile infections may only represent the trigger of neurological involvement. In these patients, the knowledge of a genetic predisposing factors may help in the prevention of neurological episodes by the prompt use of anti-pyrectics and preventive measures as appropriate vaccination.

Instrumental Evaluation of COVID-19 Related Dysautonomia in Non-Critically-Ill Patients: An Observational, Cross-Sectional Study

Coronavirus disease-19 (COVID-19) is a predominantly respiratory syndrome. Growing reports about a SARS-CoV-2 neurological involvement, including autonomic dysfunction (AD), have been reported, mostly in critically-ill patients, or in the long-COVID syndrome. In this observational, cross-sectional study, we investigated the prevalence of AD in 20 non-critically-ill COVID-19 patients (COVID+ group) in the acute phase of the disease through a composite instrumental evaluation consisting of Sudoscan, automated pupillometry, heart rate variability (HRV), and pulse transit time (PTT). All the parameters were compared to a control group of 20 healthy volunteers (COVID− group). COVID+ group presented higher values of pupillary dilatation velocities, and baseline pupil diameter than COVID− subjects. Moreover, COVID+ patients presented a higher incidence of feet sudomotor dysfunction than COVID− group. No significant differences emerged in HRV and PTT parameters between groups. In this study we observed the occurrence of autonomic dysfunction in the early stage of the disease.

Neurological Involvement in COVID-19

The respiratory system is the most common target of COVID-19, however, various experimental studies and case reports have shown its affinity for neural tissues. In this chapter, we described pathogenesis and propagation of SARS-CoV-2 virus in the nervous system, potential routes of the SARS-CoV-2 invasion in the brain, as well as indirect effects of COVID-19 on multiorgan disorders. We have also presented all of the reported neurological manifestations in COVID-19 with an explanation of possible underlying pathways. Among patients who tested positive on SARS-CoV-2, various neurological irregularities have been described, affecting both the central and peripheral nervous systems. In general, neurological complications in COVID-19 patients occur within 1 and 14 days, in most cases on average on the 5th day of the incubation period. We have demonstrated all of the reported neurological findings, whereas the most commonly reported were headache, dizziness, myalgia, hypogeusia, hyposmia, and impaired consciousness. More serious neurological conditions in COVID-19 included meningitis, encephalitis, and ischemic or hemorrhagic stroke.

Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What’s behind Neuro-RACopathies

Rho family guanosine triphosphatases (GTPases) regulate cellular signaling and cytoskeletal dynamics, playing a pivotal role in cell adhesion, migration, and cell cycle progression. The Rac subfamily of Rho GTPases consists of three highly homologous proteins, Rac 1–3. The proper function of Rac1 and Rac3, and their correct interaction with guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs) are crucial for neural development. Pathogenic variants affecting these delicate biological processes are implicated in different medical conditions in humans, primarily neurodevelopmental disorders (NDDs). In addition to a direct deleterious effect produced by genetic variants in the RAC genes, a dysregulated GTPase activity resulting from an abnormal function of GEFs and GAPs has been involved in the pathogenesis of distinctive emerging conditions. In this study, we reviewed the current pertinent literature on Rac-related disorders with a primary neurological involvement, providing an overview of the current knowledge on the pathophysiological mechanisms involved in the neuro-RACopathies.

Clinical Features and Predictors for Mortality in Neurolisteriosis: An Administrative Data-Based Study

Listeriosis is an uncommon and potentially severe zoonotic bacterial infection that usually occurs in outbreaks instead of isolated cases. In recent years, there has been an increase in the incidence of this disease. One of the most severe of its complications involves the central nervous system (CNS) in a condition known as neurolisteriosis. Here, we describe the demographic and clinical features of patients presenting with neurolisteriosis between 2001 and 2015 using administrative data and attempt to identify potential predictors for mortality. We used the Spanish Minimum Basic Data Set at Hospitalization, a compulsory registry that collects data from clinical discharge reports. Up to 2015, data were coded based on the International Classification of Diseases, 9th Revision, so we used diagnoses and clinical conditions based on these codes. Age, sex, clinical presentation, mortality, and involvement of the CNS were identified. Using algorithms to aggregate data, variables such as immunosuppression and malignant disease were obtained. We analyzed correlations among clinical features and identified risk factors for morbidity and mortality. Between 2001 and 2015 we identified 5180 individuals, with a hospitalization rate of 0.76 per 100,000 population. Most (94%) were adults, and only 5.4% were pregnant women. The average age was 66 years. Neurological involvement was present in 2313 patients (44.7%), mostly meningitis (90.4%). Global mortality was 17%, but mortality in CNS infections was 19.2%. Age, severe sepsis, chronic liver disease, chronic kidney disease, and malignancy were the main risk factors for mortality in patients with CNS infections by Listeria monocytogenes. Although it is uncommon, neurolisteriosis can be a severe condition, associated with a high rate of mortality. Health care providers should be aware of potential sources of infection so that appropriate measures can be taken to prevent it.

Clinical features of respiratory syncytial virus bronchiolitis in an infant: rapid and fatal brain involvement

Background Respiratory Syncytial Virus (RSV) infection is a significant cause of bronchiolitis and pneumonia, mostly responsible for hospitalization and infant death worldwide. However, in recent years the importance of extrapulmonary RSV manifestations, especially at neurological level, have become evident. Seizures, lethargy, ataxia and status epilepticus are suggestive of brain involvement, but also in their absence a direct neurological damage RSV-related need to be evaluated. Case presentation A 40-day old male infant was admitted to the Emergency Department with severe bronchiolitis and dyspnea. The patient was reported to be coughing for a week with a vomiting episode in the previous two days. The nasopharyngeal swab confirmed the diagnosis of RSV infection and blood gas test showed hypoxemia and respiratory acidosis. For these reasons, the patient was provided with oxygen therapy. A few hours later, after an initial improvement in clinical parameters, a worsening of respiratory dynamics occurred and the patient was prepared for endotracheal intubation, but in the meantime death occurred. During all the observation period in the Emergency Room, no signs of neuropathological damage were evident. Post mortem examination showed lungs congestion with alveolar atelectasis and white matter degradation with severe edema at brain level. Microbiological analysis performed on autoptic samples confirmed the presence of RSV genome in tracheobronchial aspirate, meningeal swabs, pericardic and abdominal fluids, lung and brain biopsies. Conclusions RSV is usually associated with respiratory diseases, however, as reported by an increasingly number of studies, the systemic dissemination of virus during severe disease can lead to a sudden infant death. The clinical picture herein reported showed a severe bronchiolitis resulting in a fatal and underestimated cerebral involvement due to RSV neurotropic behaviour and underline the need for clinicians to pay more attention to neurological involvement of RSV infection, even in absence of cerebral damage evidence.