Guillain barre syndrome and its association with covid-19 infection – A clinical case series

A novel coronavirus (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2). This pandemic has been globally alarming in the current period. Several neurological manifestations are reported occurring with the infection. Guillain barre syndrome (GBS) or acute onset inflammatory polyradiculoneuropathy has been among the frequent manifestations observed among them. To know the pattern and outcome of GBS in COVID-19 affected individuals. We have taken six individuals admitted with flaccid quadriparesis in the last two months. All were affected recently by COVID 19 infection, which RT PCR of the nasopharyngeal swab confirmed. The study participants have undergone nerve conduction studies and have been diagnosed with Guillain Barre syndrome using Brighton criteria. We did cerebrospinal fluid (CSF) analysis after admission. We initiated all patients on Intravenous immunoglobulin according to body weight (2g/kg divided over five days). We used the Barthel index score to assess the outcome of the individuals. We observed a mean duration of 18.25 days between the COVID-19 infection and the onset of symptoms. Apart from motor quadriparesis and sensory symptoms being in common, we also noticed cranial nerves and autonomic involvement. We made the diagnosis using the nerve conduction studies and Brighton criteria. After initiating intravenous immunoglobulin, all patients had a good outcome, and quality of life was better after two months of follow up. Guillain Barre syndrome is one of the neurological manifestations of COVID-19 and has a dramatic response with intravenous immunoglobulin and better outcome with treatment.

Subamniotic haemorrhage, a possible new presentation of fetal and neonatal alloimmune thrombocytopenia

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare fetal disease in which maternal antibodies directed towards fetal human platelet antigens (HPA) are formed during pregnancy and cause fetal thrombocytopenia. The diagnosis FNAIT is suspected when a fetus or neonate presents with signs of bleeding. Case: We describe a pregnancy complicated by a placental hematoma in the 20th week of gestation as the first manifestation of FNAIT. Further evaluation showed signs of germinal matrix haemorrhage and HPA-5b allo-antibodies. After the diagnosis, intravenous immunoglobulin was administered weekly and a healthy daughter was born at 37 weeks. Histopathological analysis revealed that the hematoma was caused by a subamniotic haemorrhage of fetal origin. Conclusion: A subamniotic hematoma appears to be the first manifestation of FNAIT.

A Simple Scoring Model Based on Machine Learning Predicts Intravenous Immunoglobulin Resistance in Kawasaki Disease

In Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions. To establish a simple and accurate scoring model predicting IVIG resistance, we conducted a retrospective cohort study of 996 KD patients that were diagnosed at 11 facilities for 10 years, in which 108 cases (23.5%) were resistant to initial IVIG treatment. We performed machine learning with random forest model using 30 clinical variables at diagnosis in 796 and 200 cases for training and test datasets, respectively. Random forest model accurately predicted IVIG resistance (AUC; 0.75, sensitivity; 0.54, specificity; 0.80). Next, using top five influential features (days of illness at initial therapy, serum levels of C-reactive protein, sodium, total bilirubin, and total cholesterol) in the random forest model, we designed a simple scoring system. In spite of its simplicity, the scoring system predicted IVIG resistance (AUC; 0.73, sensitivity; 0.55, specificity; 0.83) as accurately as the random forest model itself. Moreover, accuracy of our scoring system with five clinical features was almost identical to that of Gunma score with seven clinical features (AUC; 0.73, sensitivity; 0.53, specificity; 0.83), a well-known logistic regression scoring model, and superior to that of two widely used scores (Kurume score; 0.67, 0.46 and 0.76, respectively, and Osaka score; 0.69, 0.33 and 0.84, respectively). Conclusions: Our simple scoring system based on the findings in machine learning, as well as machine learning itself, seems to be useful to accurately predict IVIG resistance in KD patients.

Splenectomy Outcomes in Relapsed or Refractory Immune Thrombocytopenia According to First-Line Intravenous Immunoglobulin Response

Introduction: Although splenectomy has long been second-line option for immune thrombocytopenia (ITP) patients, an indicator that reliably predicts the efficacy of splenectomy is still being explored. We investigated the treatment outcomes of splenectomy as a second-line therapy for relapsed/refractory ITP according to first-line intravenous immunoglobulin (IVIG) responses. Methods: Fifty-two adult patients treated with splenectomy as second-line therapy for ITP between 2009 and 2019 were included, and they were classified according to first-line IVIG responses (no response to IVIG: non-responders; only transient IVIG response shorter than 4 weeks: poor responders; IVIG response for a longer period; stable responders). The efficacy of splenectomy was analyzed in the three subgroups. Results: Of the 52 patients, 10 were IVIG non-responders, 34 were poor responders, and the remaining eight were stable responders. Response to splenectomy was observed in 50.0% of IVIG non-responders, 94.1% of poor responders, and 100% of stable responders (p = 0.0030). Among the 45 patients who responded to splenectomy, 51.1% relapsed subsequently, and a significantly lower relapse rate was noted in the stable IVIG responders (12.5%, p = 0.0220) than in non-responders (60.0%) and poor responders (59.4%). Conclusions: First-line IVIG response is indicated as a useful predictive factor for response to splenectomy.

Rituximab and intravenous immunoglobulin treatment in PM/Scl antibody-associated disease: case-based review

Autoantibodies to the 75-kDa and 100-kDa subunits of the PM/Scl nucleolar protein complex are associated with an overlap syndrome, manifesting with clinical features of systemic sclerosis and idiopathic inflammatory myopathy. We describe the diverse clinical features in a series of 4 cases with anti-PM/Scl-75 and/or anti-PM/Scl-100 antibodies, including severe proximal muscle weakness, oesophageal dysfunction, respiratory weakness requiring mechanical ventilation, Raynaud’s, calcinosis cutis, sclerodactyly and critical digital ischaemia. Despite the severity of striated and oesophageal muscle weakness, all patients responded very well to immune suppression, and calcinosis cutis in one case regressed substantially. We highlight the efficacy of Rituximab and intravenous immunoglobulin therapy (IVIg) in these cases, enabling return to normal muscle function within six months. Rituximab was preferentially chosen for cases with hyper-gammaglobulinemia and multiple autoantibodies in addition to anti-PM/Scl, and IVIg was utilised for cases where a rapid onset of effect was required, such as severe ventilator-dependent respiratory muscle weakness and oesophageal dysfunction.

Efficacy of High-Dose Polyclonal Intravenous Immunoglobulin in COVID-19: A Systematic Review

Background: Although several therapeutic strategies have been investigated, the optimal treatment approach for patients with coronavirus disease (COVID-19) remains to be elucidated. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of polyclonal intravenous immunoglobulin (IVIG) therapy in COVID-19. Methods: A systematic literature search using appropriate medical subject heading (MeSH) terms was performed through Medline (PubMed), EMBASE, SCOPUS, OVID and Cochrane Library electronic databases. The main outcomes considered were mortality and safety of IVIG versus placebo/standard of care. This review was carried out in accordance with Cochrane methodology including the risk bias assessment and grading of the quality of evidence. Measures of treatment effect were mean differences (MD) together with 95% confidence intervals (CIs) for continuous outcome measures and risk ratio (RR) or MD for binary outcomes. Two reviewers independently extracted data from individual studies, and disagreements were resolved by a third reviewer. Results: A total of 2401 COVID-19 patients from 10 studies (four randomized controlled trials (RCT) and six non-randomized controlled trials (non-RCTs)) were included in the analysis. Participants received IVIG or placebo/standard of care. The use of IVIG was not associated with a significantly reduced risk of death (RR 0.50, 95% CIs 0.18–1.36, p = 0.17 for RCTs; RR 0.95, 95% CIs 0.61–1.58, p = 0.94 for non-RCTs; low certainty of evidence). IVIG significantly reduced the length of hospital stay (MD −2.24, 95% CIs −3.20/−1.27; p = 0.00001; low certainty of evidence), although this difference was significant only for studies evaluating moderate COVID-19 patients. No significant difference was observed in the incidence of overall and serious adverse events between IVIG recipients and controls (very low certainty of evidence). Conclusions: The current evidence from the literature does not support the use of IVIG in COVID-19 patients.