The effects of intravascular photobiomodulation on sleep disturbance caused by Guillain-Barré syndrome after Astrazeneca vaccine inoculation: Case report and literature review.

RATIONALE: Sleep disturbance is commonly noted after Guillain-Barré syndrome (GBS) and is often caused by persistent discomfort after disease survival. Intravascular laser irradiation of blood (ILIB) has been shown to be effective in pain modulation owing to the influence of nociceptive signals in the peripheral nervous system. We investigated the application of ILIB on post-Oxford -AstraZeneca vaccination GBS and evaluated its effect on sleep quality. PATIENT CONCERNS: A 48-year-old woman was subsequently diagnosed with GBS after Oxford-AstraZeneca vaccination. The patient was discharged after a 5-day course of intravenous immunoglobulin administration. However, 1 week after discharge, the previously relieved symptoms flared with accompanying sleep disturbance. DIAGNOSIS AND INTERVENTIONS: The patient was diagnosed with post-vaccination GBS, and persistent pain and sleep disturbances persisted after disease survival. ILIB was performed. OUTCOMES: We used the Pittsburgh Sleep Quality Index before and after intravascular laser irradiation. There was a marked improvement in the sleep duration, efficiency, and overall sleep quality. The initial score was 12 out of 21 and the final score was 7 out of 21. LESSONS: We found that ILIB was effective in pain modulation in post-vaccination GBS and significantly improved sleep quality.

High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

BACKGROUND: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. METHODS: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. RESULTS: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. CONCLUSIONS: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.

COVID-19 and abdominal pain: a pediatric case report and a point of view in pediatric emergency medicine.

COVID-19 is to date a global pandemic that can affect all age groups; gastrointestinal symptoms are quite common in patients with COVID-19 and a new clinical entity defined as Multisystem Inflammatory Syndrome in Children (MIS-C) has been described in children and adolescents previously affected by COVID-19. Presenting symptoms of this new disease include high fever and severe abdominal pain that can mimic more common causes of abdominal pain; patients can rapidly deteriorate presenting severe cardiac dysfunction and multiorgan failure. Some fatalities due to this serious illness have been reported. We describe the case of a ten-year-old patient presenting with persistent high fever associated with continuous and worsening abdominal pain. Various hypotheses were performed during his diagnostic workup and an initial appendectomy was performed in the suspect of acute appendicitis. As his clinical picture deteriorated, the child was subsequently diagnosed and successfully treated as a case of MIS-C. The objective of this case report and brief review of abdominal pain in children throughout the age groups is to provide the emergency pediatrician with updated suggestions in diagnosing abdominal pain in children during the COVID-19 pandemic.

Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy.

In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the "common cold"-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients' sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a "forever necessary therapy" for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.

Cardiogenic shock complicating multisystem inflammatory syndrome following COVID-19 infection: a case report.

BACKGROUND: With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION: A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS: MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.

Pediatric Multisystemic Inflammatory Syndrome Temporarily associated with COVID-19: Clinical characteristics and management in a Pediatric Critical Care Unit. / Síndrome Inflamatorio Multisistémico Pediátrico asociado a COVID-19: Características clínicas y manejo en una Unidad de Paciente Crítico Pediátrico.

INTRODUCTION: In April 2020, the pediatric multisystem inflammatory syndrome temporarily associated with COVID-19 (MIS-C) was described for the first time. MIS-C could have a severe course and may require critical care support. OBJECTIVE: To describe the clinical, laboratory, and management characteristics of hospitalized children who meet MIS-C criteria with severe presentation in a pediatric critical pa tient unit. PATIENTS AND METHOD: Descriptive prospective study of children with severe MIS-C mana ged by treatment phases with immunoglobulin and methylprednisolone, according to their clinical response. Epidemiological, clinical, laboratory and imaging data were obtained. Phenotypes were classified into Kawasaki and not Kawasaki, comparing their findings. RESULTS: 20 patients were analy zed, the median age was 6 years, 60% were female, and 40% presented comorbidity. SARS-CoV-2 was detected in 90% of the patients. They presented fever as the first symptom, followed by brief and early gastrointestinal symptoms (70%). 75% presented the Kawasaki phenotype. They evolved with lymphopenia, hypoalbuminemia, coagulation alterations, and elevated systemic and cardiac in flammatory parameters. 80% of the cases presented echocardiographic alterations and 90% shock that required critical care support. All the patients had a short and favorable evolution. All patients responded to the established therapy, but 40% required a second phase of treatment. There were no differences when comparing phenotypes. No deaths were reported. CONCLUSION: MIS-C is a new childhood disease whose presentation could be life-threatening. It requires early suspicion, immuno modulatory management, critical care support, and a multidisciplinary approach to obtain the best results and optimize its prognosis.

SARS-CoV-2 infection triggering recurrence of Kawasaki disease in a 10-year-old child.

SARS-CoV-2 infection has recently been related to a spectrum of hyper-inflammatory states in children. There is a striking similarity between these hyper-inflammatory states and Kawasaki disease (KD). We present an interesting case of KD recurrence in a 10-year-old child, who had previously developed KD at 4 years of age. His symptoms included fever, maculopapular rash and altered sensorium. Investigations showed noticeably elevated inflammatory markers, and an echocardiography revealed dilated coronary arteries. SARS-CoV-2 IgG antibodies were positive. The child responded dramatically to intravenous immunoglobulin and intravenous methylprednisolone. It is possible that SARS-CoV-2 infection triggered the recurrence of KD in this child who might have been genetically predisposed to KD.

Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review.

Importance: The COVID-19 pandemic saw one of the fastest developments of vaccines in an effort to combat an out-of-control pandemic. The 2 most common COVID-19 vaccine platforms currently in use, messenger RNA (mRNA) and adenovirus vector, were developed on the basis of previous research in use of this technology. Postauthorization surveillance of COVID-19 vaccines has identified safety signals, including unusual cases of thrombocytopenia with thrombosis reported in recipients of adenoviral vector vaccines. One of the devastating manifestations of this syndrome, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), is cerebral venous sinus thrombosis (CVST). This review summarizes the current evidence and indications regarding biology, clinical characteristics, and pharmacological management of VITT with CVST. Observations: VITT appears to be similar to heparin-induced thrombocytopenia (HIT), with both disorders associated with thrombocytopenia, thrombosis, and presence of autoantibodies to platelet factor 4 (PF4). Unlike VITT, HIT is triggered by recent exposure to heparin. Owing to similarities between these 2 conditions and lack of high-quality evidence, interim recommendations suggest avoiding heparin and heparin analogues in patients with VITT. Based on initial reports, female sex and age younger than 60 years were identified as possible risk factors for VITT. Treatment consists of therapeutic anticoagulation with nonheparin anticoagulants and prevention of formation of autoantibody-PF4 complexes, the latter being achieved by administration of high-dose intravenous immunoglobin (IVIG). Steroids, which can theoretically inhibit the production of new antibodies, have been used in combination with IVIG. In severe cases, plasma exchange should be used for clearing autoantibodies. Monoclonal antibodies, such as rituximab and eculizumab, can be considered when other therapies fail. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying bleeding risk. Conclusions and Relevance: Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.

[Cerebral vein/venous sinus thrombosis with thrombocytopenia syndrome after COVID-19 vaccination].

Vaccines are important in managing the COVID-19 pandemic caused by SARS-CoV-2. Despite the very low incidence, severe cases of thrombosis with thrombocytopenia after COVID-19 vaccination termed as Thrombosis with Thrombocytopenia Syndrome (TTS) have been reported. TTS clinically resembles autoimmune heparin-induced thrombocytopenia. TTS can cause disability and even death. It usually presents 4-28 days after vaccination characterized by thrombocytopenia and progressive thrombosis, often causing cerebral vein/venous thrombosis (CVT) and splanchnic venous thrombosis. We should avoid all forms of heparin and platelet transfusion. While awaiting further information on the pathophysiological mechanism and treatment of TTS, clinicians should be aware of TTS with CVT in patients receiving COVID-19 vaccinations. This new syndrome of TTS is an active area of investigation globally. Here, we review the available literature.

Guillain-Barré Syndrome Variant Occurring after SARS-CoV-2 Vaccination.

Although SARS-CoV-2 vaccines are very safe, we report 4 cases of the bifacial weakness with paresthesias variant of Guillain-Barré syndrome (GBS) occurring within 3 weeks of vaccination with the Oxford-AstraZeneca SARS-CoV-2 vaccine. This rare neurological syndrome has previously been reported in association with SARS-CoV-2 infection itself. Our cases were given either intravenous immunoglobulin, oral steroids, or no treatment. We suggest vigilance for cases of bifacial weakness with paresthesias variant GBS following vaccination for SARS-CoV-2 and that postvaccination surveillance programs ensure robust data capture of this outcome, to assess for causality. ANN NEUROL 2021;90:315-318.

Miller Fischer and posterior reversible encephalopathy syndromes post COVID-19 infection.

COVID-19 infection displays heterogeneity of clinical manifestations in symptomatic and asymptomatic patients. We report on a child with Miller Fischer syndrome (MFS) and posterior reversible encephalopathy syndrome (PRES) post-COVID-19 infection. An 11-year-old boy presented with vomiting, headache, blurred vision, dysarthria, dysphagia, respiratory failure, muscle weakness, and unsteadiness. He had been exposed to COVID-19 through an asymptomatic elder brother two months prior to his illness. The MRI brain showed findings consistent with PRES and the diagnosis with Miller Fischer variant of the Guillain-Barré syndrome was made. A cerebrospinal fluid analysis revealed cytoalbuminous dissociation, and a nerve conduction velocity study conclusively showed polyneuropathy. A fluoroscopy of the diaphragms found that there was limited movement in both. Although children seem to be less affected by COVID-19 infection, this report highlights on an important neurological complications that can develop in children and its presence should be taken into consideration when diagnosing different forms of Guillain-Barré.

Guillain-Barré syndrome associated with COVID-19 infection: a case from the UK.

Originating from Wuhan, China, COVID-19 has rapidly spread worldwide. Neurological manifestations are more commonly associated with severe COVID-19 infection. Guillain-Barré syndrome (GBS) is a rare immune-mediated postinfectious neuropathy. It has been reported as a possible rare complication of COVID-19. We report a case of GBS associated with COVID-19 in the UK.

A case of multisystem inflammatory syndrome in an African adolescent male: case report.

Since late April 2020, a syndrome now termed Multisystem Inflammatory Syndrome in Children (MIS-C) has been seen in children and adolescents in association with COVID-19 infection. The definition of MIS-C involves fever, organ dysfunction and laboratory confirmation of inflammation in the context of laboratory or epidemiological evidence of SARS-CoV-2 infection in a patient under 21 years of age. Notably, cases are now being identified in adults termed Multisystem Inflammatory syndrome in Adults (MIS-A). Few cases have been reported in sub-Saharan Africa. We report a case of a young African male presenting with a maculopapular rash, persistent fever, elevation in inflammatory markers and a sudden, significant deterioration in cardiac function resulting in cardiogenic shock. The patient responded to intravenous steroids, intravenous immunoglobulin and background inotropic support. The recognition of this disease entity proves even more crucial now amidst the ongoing global wave of COVID-19 infection. It is paramount to identify these patients early, leading to prompt treatment avoiding further morbidity and mortality.