Ganglioside complex antibodies in an Indian cohort of Guillain-Barré syndrome.

BACKGROUND: Antibodies against ganglioside complexes (GSCs) are associated with various clinical features and subtypes of Guillain-Barré syndrome (GBS). METHODS: One-hundred patients were evaluated for antibodies to GSCs formed by combination of GM1, GM2, GD1a, GD1b, GT1b, and GQ1b using manual enzyme linked immuno-sorbent assay (ELISA). RESULTS: Twenty-six patients were GSC antibody-positive, most frequent being against GM1-containing GSC (76.9%). Gender distribution, mean age, symptom-duration, antecedent events, electrophysiological subtypes, requirement for mechanical ventilation, and median duration of hospital stay were comparable between the GSC antibody-positive and negative groups. There was no association between specific GSC antibody and electrophysiological subtypes or clinical variants. After controlling for false discovery rate (FDR) using the Benjamini-Hochberg method, the number of subjects who improved in overall disability sum score, modified Erasmus GBS outcome score, and neuropathy symptom score at discharge was significantly higher in the GSC antibody-positive group. Improvements in Medical Research Council sum scores and Hughes Disability Scale during the hospital stay between the GSC antibody-positive and negative groups were not significantly different after controlling for FDR. CONCLUSIONS: The GSC antibody-positive group had better outcome at hospital discharge in some of the disability scores. Pathophysiological pathways among patients without GSC antibodies may be different and this requires further evaluation.

Evidence of altered Th17 pathway signatures in the cerebrospinal fluid of patients with Guillain Barré Syndrome.

Data indexing the contribution of various immuno-inflammatory components in the cerebrospinal fluid (CSF) towards the pathophysiology of Guillain Barré Syndrome (GBS) are limited. Th17 pathway plays crucial role in many immune mediated disorders of the nervous system. This study was aimed at exploring the role of Th17 pathway related cytokines in the CSF of patients with GBS. Levels of multiple key cytokines of Th17 pathway in CSF of patients with GBS (N = 37) and controls (N = 37) were examined in this prospective study using Bio-plex Pro Human Th17 cytokine assays in a Multiplex Suspension Array platform. The findings were correlated with clinical features and electrophysiological subtypes. Three key cytokines of Th17 pathway (IL-6, IL-17A and IL-22) were significantly elevated in CSF of patients with GBS as compared to controls. There was a positive correlation between the levels of IL-6 and IL-17A as well as between the levels of IL-17A and IL-22 in the CSF of patients with GBS. The CSF levels of IL-6 and IL-22 were negatively correlated with the duration of symptoms of GBS. None of the studied cytokines correlated with functional disability scores at admission to hospital or with the electrophysiological subtypes. Identification of Th17 pathway signatures in CSF sheds more insights into the pathogenic role of Th17 cells in GBS. These findings complement the contemporary knowledge and tender further support towards the involvement of Th17 pathway in GBS.

Th17 pathway signatures in a large Indian cohort of Guillain Barré syndrome.

The etiopathogenesis of Guillain Barré Syndrome (GBS) is inadequately understood. The role of immuno-inflammatory Th17 pathway was examined in GBS patients by genetic, gene expression and biochemical studies. Genotyping of G197A single nucleotide polymorphism within IL17 gene was carried out by PCR-RFLP method in 220 GBS patients. Quantification of gene expression of STAT3 and RORC and estimation of plasma level of IL-17A were carried out in a subset of patients. Significantly increased STAT3 gene expression in lymphocytes and plasma IL-17A levels were observed in GBS patients. This study adds new dimension and reinforces important implications of Th17 pathway in GBS.

Comprehensive cytokine profiling provides evidence for a multi-lineage Th responses in Guillain Barré Syndrome.

Guillain Barré Syndrome (GBS) is one of the commonest acquired immune-mediated neuropathies, often preceded by infections. Although cellular immune responses are shown to substantially account for the pathophysiology of GBS, the precise mechanistic basis of risk and disease course remains enigmatic till date. Cytokines are best known for their abilities to drive cellular immunity and inflammation through their co-ordinated actions. Data obtained from clinical and animal model studies suggest important implications of some of the cytokines in the progression and recovery of GBS. However, these studies were performed on few cytokines and small set of GBS patients, thereby lacking a complete understanding of the patterns of association of cytokines representing Th1, Th2, and Th17 responses with GBS. We studied 65 well-characterized GBS patients and 73 age- and sex-matched healthy controls. A panel of 15 cytokines representing Th1, Th2 and Th17 pathways was assayed using Multiplex Suspension Array platform. Plasma levels of five cytokines were found to be altered in GBS patients compared to healthy control subjects: (i) IL-1ß exhibited reduced levels, and (ii) IFN-γ, IL-4, IL-21 and IL-33 were elevated in GBS patients. The most important finding of this study was up-regulated expression of IL-21 and IL-33 in patients with GBS. Given the role of IL-33 as an alarmin, the elevated level of this cytokine provides important indication about a much broader role of cytokines in GBS. This study also provides evidence towards a multi-lineage Th cells (Th1, Th2 and Th17) associated cytokine responses in the pathophysiology of GBS.

Hydroxyethyl starch and kidney function: A retrospective study in patients undergoing therapeutic plasma exchange.

PURPOSE: Hydroxyethyl starch (HES) and albumin are used as replacement fluids during therapeutic plasma exchange (TPE). HES solutions are no longer recommended in critically ill patients due to its effect on kidneys and coagulation. In this retrospective study, we tried to look at the association between cumulative HES administration and kidney function in patients undergoing TPE. METHODS: Transfusion medicine department register was scrutinized to identify adult patients who had completed at least 5 cycles of TPE during the period June 2014-May 2015. Patient demographics, indication for TPE, amount of plasma removed, amount of colloid administered, adverse events and vascular access details were collected. Electronic hospital database was scrutinized to retrieve lab parameters, including blood urea and serum creatinine (before and after 5 cycles of TPE) and platelet count. Baseline renal parameters were compared with post TPE values using Wilcoxon signed rank test. A p value <0.05 was kept as significant. RESULTS: Of the 593 patients who received TPE during the study period, 104 patients fulfilled the inclusion criteria. Forty-five patients out of 104 received TPE in the intensive care unit. All patients received 2500 ml of HES during the study period. Blood urea and serum creatinine values, when compared to baseline, significantly decreased after 5 cycles of TPE (p = 0.004, p = 0.001, respectively). CONCLUSION: Blood urea and serum creatinine, used as markers of renal function, improved in patients requiring multiple doses of HES solutions during TPE. Further studies using novel renal biomarkers are required to examine whether HES induces any structural damage to kidneys.

Role of low plasma volume treatment on clinical efficacy of plasmapheresis in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is an autoimmune demyelinating disease preferentially targeting the optic nerves and spinal cord. Plasmapheresis (PP) is an effective adjunct therapy in severe NMO attacks. The recommended minimum plasma volume to be treated per session of PP is equivalent to total plasma volume (TPV) of the patient. AIM: To study the effect of lower plasma volume treated in patients with NMO on clinical efficacy of plasmapheresis in comparison to minimum recommended volume. METHODS: This retrospective study was done on acute NMO patients who were managed with PP at our center. Patients who had 5 sessions of PP, spread over 10 days, were included. Clinical outcome was defined as per predefined criteria. RESULTS: 24 patients who underwent PP for acute NMO met our inclusion criteria. Females (age; mean (SD) 33.7 (11.2) years) were more common (n = 18). The minimum recommended plasma volume (PV) that was supposed to be treated per patient during entire acute therapeutic period was 195.5 (14.6) mL per kilogram-body-weight (kg-bw). We treated lower plasma volume (mean (SD) 112.7 (17.0) mL per kg-bw); the difference was significant (P < 0.05). The volume treated was same across the gender (P > 0.05). Significant clinical improvement was observed in 79% of patients (n = 19) after 6 months. There were no significant differences in volume of plasma treated, between patients who had moderate and marked improvement; also, who did, and did not have significant clinical improvement (P > 0.05; for both). CONCLUSIONS: Plasmapheresis is a safe and efficient add-on therapy in NMO, especially in steroid-resistant cases. Although the volumes of plasma treated during acute plasmapheresis were less than recommended minimum volumes, majority of patients had significant clinical improvement.

Complications related to blood donation: A multicenter study of the prevalence and influencing factors in voluntary blood donation camps in Karnataka, India.

INTRODUCTION: Complications associated with blood donation significantly lower odds of subsequent donations. The aim of the study is to assess the prevalence of complications related to blood donation, identify the influencing factors, and come up with suggestions for minimizing discomfort to donors and making outdoor voluntary blood donation camps safer. MATERIALS AND METHODS: This study covered 181 blood donation camps organized by Sankalp India Foundation where 16 blood banks participated from 01-04-2011 to 01-08-2014 in Karnataka. Uniform protocols for donor selection, predonation preparation, counseling, postdonation care, and refreshments were used. The postdonation complications were recorded on a form immediately, after they were observed. RESULTS: We observed 995 (3.2%) complications in 30,928 whole blood donations. Of these 884 (2.86%) mild, 77 (0.25%) moderate, and 5 (0.02%) severe complications were observed. Local symptoms (blood outside vessels, pain, and allergy) contributed 1.0%, and generalized symptoms (vasovagal reaction) contributed 2.2% to all the complications. CONCLUSION: We observed 322 complications for every 10,000 donations. Since 27 out of every 10000 experience moderate and severe complication, the readiness to manage complications is crucial. Women donors, young donors, and donors with a lower weight are at a significantly greater risk of experiencing complications, highlighting the need for specific guidelines for the management of higher risk donor groups. Complications varied significantly between various blood banks. Predonation hydration was effective in limiting complications with generalized symptoms. We recommend a robust donor hemovigilance program for voluntary blood donation for monitoring complications and enable assessment of effectiveness and implementation of appropriate interventions.

A study of the noncompliance of blood banks on safety and quality parameters in blood donation camps in Bengaluru.

AIMS: The compliance of safety and quality parameters laid out by national and international guidelines in outdoor blood donation camps has not been studied in India. Our study aimed at identifying, monitoring, analyzing, and developing preventive strategies for several key parameters associated with the quality and safety of outdoor voluntary blood donation camps (VBDC). SETTINGS: The study covered a total of 424 VBDCs at various locations in Bengaluru, Karnataka (South India) from 2009 to 2013. Seven government hospitals based blood banks, three private hospitals based blood banks and two voluntary standalone blood banks participated in the VBDCs included in the study. MATERIALS AND METHODS: At the onset, the quality and safety standards to be followed were discussed and agreed upon. During the study, noncompliance (NC) to the agreed upon standards were recorded and shared. Periodic trainings were also organized to help minimize NC. RESULTS: One or more instances of NC in 73% of the VBDCs. Highest NC were observed associated with punctuality (34%), wearing gloves (16%), hemoglobin (Hb) estimation (11%) and donor screening and selection other than Hb check (8-9%). CONCLUSION: For all 16 parameters under study, significant NC was observed. As a whole private hospital based blood banks were more noncompliant. The high degree of NC to matters relating to quality and safety in VBDCs is high and warrants for urgent attention and further study. Our study also shows that regular monitoring and systematic and strategic intervention can decrease the rate of NC.