Course Of Intravenous Immunoglobulin Research Articles

Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. Diagnosis and treatment of Hu-PNS. This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

INTRAVENOUS IMMUNOGLOBULINS LEAD TO FUNCTIONAL VASCULAR AMELIORATION IN LONG-COVID

Objective: The Long-COVID syndrome constitutes a major physical and psychological challenge for many patients after the recovery from COVID-19. We have previously shown positive effects of intravenous immunoglobulins (IVIG) on multiple symptoms. The effect of this therapeutical approach on vascular function and different levels of disease burden remains elusive. Design and method: We performed a prospective study, enrolling 21 patients with diagnosed Long-COVID, who received 3 monthly courses of IVIG (0.5 g/kg Privigen, CSL Behring, Austria) alongside supportive therapy (group 1). The control group (group 2; n=29) was addressed by supportive therapy, only. The study population was homogeneous for age, comorbidities and time since SARS-CoV-2 infection. We assessed vascular endothelial function by flow mediated dilation (FMD). Long-COVID associated fatigue intensity, related disability and quality of life were assessed by Short Form Health Survey-36, Chalder and Bell scale. Neuropsychological assessments utilized the German version of the ’Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery’ (CERAD-Plus). Results: The median FMD at baseline in group 1 was 5.0% (interquartile range [IQR] 4.2-6.1%). We saw a substantial amelioration (+27%) of FMD after IVIG, reaching a median of 6.6% (IQR 4.5-9.4%; p=0.039). Baseline FMD in the comparison group was 5.2% (IQR 3.5-7.6%), supportive treatment resulting in unsignificant increase (FMD 6.1% [IQR 4.6-7.7%; p=0.177). Baseline CERAD-Plus scores were comparable between groups (p=0.280). Only treatment with IVIG resulted in a relevant amelioration of neurocognition (p=0.05; group 2 p=0.430). Furthermore, less Fatigue (Chalder Fatigue scale bimodal and Likert p=0.002, each) and disability was seen after 3 months of IVIG (Bell Score, p=0.008), supportive treatment did not ameliorate this burden (Chalder Fatigue Scale bimodal p=0.086 and Likert p=0.952; Bell Score p=0.121). Health related quality of life (SF-36) increased for both groups (group 1 p=0.003, group 2 p=0.017). Conclusions: Using a broad test battery, addressing neuropsychological function, fatigue, related disability and health related quality of life as well as vascular function, we were able to confirm the potential beneficial effect of IVIG in Long-COVID. IVIG might be a candidate approach in this context, that requires further evaluation in randomized controlled trials.

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome

Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis. We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers included in the modified Erasmus GBS Outcome Score (mEGOS). NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR=1.74, 95% CI=1.27-2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR=2.79, 95% CI=1.72-4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of predictors included in the mEGOS. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p=0.0048) and week 2 (p<0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo. Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment. Prinses Beatrix Spierfonds W.OR19-24.

Effectiveness of two same-manufacturer intravenous immunoglobulin for Kawasaki disease

BackgroundTo investigate whether two brands of intravenous immunoglobulin (IVIG) from the same manufacturer lead to varied effects when administered to patients with Kawasaki disease. (KD) MethodsClinical characteristics, laboratory data, IVIG response, and coronary arteries change were analyzed between two groups. ResultsWe included 158 KD cases. The mean age at KD diagnosis was 23 ± 1.39 (range, 2–95) months. In the first IVIG course, 18 (11.4 %) patients were unresponsive. TBSF (brand T) and Privigen (brand P) were administered to 94 and 64 patients, respectively. The brand P group had a significantly longer fever (P < 0.001) and hospitalization (P = 0.007) durations after the therapy and a higher number of IVIG unresponsiveness (P = 0.016) than the brand T group. In the multivariate logistic regression analysis, a high Formosa score (≥3, Odds ratio [OR], 4.939; 95 % confidence interval [CI], 1.199–20.337; P = 0.027), high levels of CRP (≥12 mg/L, OR: 4.257,95 % CI,1.265–14.322; P = 0.019), and treatment with brand P (OR, 3.621; 95 % CI, 1.029–12.677; P = 0.045) were independent risk factors for IVIG unresponsiveness. ConclusionsCompared with brand T, brand P prolonged the fever and hospitalization durations after IVIG treatment and increased the proportion of IVIG treatment unresponsiveness, but it did not infer the coronary arteries sequelae.

European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.

European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.

Efficacy and Safety of Intravenous Immunoglobulin Treatment in Selected Neurological Diseases-One Centre's Experience Based on the Therapy of 141 Patients.

Intravenous immunoglobulins (IVIg) are the first-choice drugs for the treatment of certain neuroimmune diseases. The aim of this study was to evaluate the efficacy and safety of IVIg in patients with selected nervous system diseases. The study enrolled patients who received IVIg in programmes financed by the National Health Fund in Poland. The status of patients upon inclusion and during treatment was assessed using scales dedicated to specific neurological diseases. The study enrolled 141 patients aged 56.28 ± 14.72 (51.77% female): 21 patients with myasthenia gravis (MG), 65 with chronic inflammatory demyelinating polyneuropathy (CIDP), 30 with Guillain-Barré syndrome (GBS), 12 with neuromyelitis optica spectrum disorder (NMOSD) and 13 patients with autoimmune encephalitis (AE). Neurological improvement was found in 14 (66.66%) MG patients (with a reduction of at least three points on the Quantitative Myasthenia Gravis Score (QMGS) within 14 days from the completion of the cycle), and in 34 (52.3%) GBS patients (with a reduction of at least one point on the Medical Research Council Scale within 14 days from the completion of the cycle). The parameters with the strongest effect on clinical improvement in MG patients were age [OR 1.033, CI 95% [0.09-1.09], p = 0.049] and baseline QMGS [OR 0.505; CI 95% [0.24-0.87], p = 0.038]. In the majority of CIDP patients (27, 97%) and NMOSD patients (6, 50%), neurological stabilisation was observed (without clinical improvement, defined for CIDP patients as an increase of at least two points on the Lovett Scale after three courses of IVIg were administered, and for NMOSD patients as an increase of at least one point on the Medical Research Council Scale and/or a shift of at least 0.3 logMAR after three courses of treatment). Deep-vein thrombosis was only one serious adverse event in the total group of patients treated with IVIg. The use of IVIg in patients with MG and GBS mostly results in neurological improvement, while in patients with NMOSD and CIDP, it mostly results in disease stabilisation. This could indicate the predominant anti-idiotypic antibody activity of IVIg in acute neuroimmune diseases or during exacerbations in chronic autoimmune diseases. The therapy of AE in comorbid neoplastic disease is burdened with an elevated risk of failure for IVIg. The results of our study confirm the improved safety of IVIg for selected neurological diseases.

Respiratory pathogen trends in patients with Kawasaki disease during the COVID-19 pandemic and respiratory syncytial virus epidemic in Japan.

Although the etiology of Kawasaki disease (KD) remains unknown, the most common view is that an infectious agent triggers the activation of the inflammatory cascade in predisposed children. The coronavirus disease 2019 (COVID-19) pandemic has led to the establishment of infection control measures, which reduced the overall incidence of respiratory infections; however, a resurgence of respiratory syncytial virus (RSV) infection occurred in the summer of 2021. This study aimed to examine the relationship between respiratory pathogens and KD during the COVID-19 pandemic and the RSV epidemic in Japan between 2020 and 2021. We retrospectively reviewed the medical charts of pediatric patients with KD or respiratory tract infection (RTI) admitted to National Hospital Organization Okayama Medical Center between December 1, 2020, and August 31, 2021. All patients with KD and RTI underwent multiplex polymerase chain reaction testing upon admission. We classified patients with KD into the three subgroups-pathogen-negative, single pathogen-positive, and multi-pathogen-positive-and compared their laboratory data and clinical features. This study enrolled 48 patients with KD and 269 with RTI. Rhinovirus and enterovirus were the most prevalent pathogens in both patients with KD and RTI (13 [27.1%] and 132 patients [49.1%], respectively). The clinical characteristics of the pathogen-negative KD group and the pathogen-positive KD group at diagnosis were similar; however, the pathogen-negative group tended to receive additional treatment, such as multiple courses of intravenous immunoglobulin, intravenous methylprednisolone, infliximab, cyclosporine A, and plasmapheresis, more frequently. The number of patients with KD remained stable when RTI was not prevalent but increased following the surge in RTI with RSV. An epidemic of respiratory infections led to an increase in the incidence of KD. Patients with respiratory pathogen-negative KD could have greater recalcitrance to intravenous immunoglobulin than those with respiratory pathogen-positive KD.

Intravenous Immunoglobulin for Autoimmune Bullous Diseases: A Case Series from a Central European Referral Center.

Background and Objectives: Autoimmune bullous diseases (AIBDs) may be treated with intravenous immunoglobulin (IVIG) infusions. This study aimed to evaluate the benefits and safety profiles of high-dose IVIG therapy in AIBD patients, as determined by clinical remission, the glucocorticosteroid-sparing effect, and adverse events at 12 months follow-up in a Central European university dermatology department setting. Materials and Methods: Our case series included 10 patients: five patients with pemphigus vulgaris, one with pemphigus herpetiformis, one with pemphigus foliaceus, one with bullous pemphigoid, two with epidermolysis bullosa acquisita. They underwent 4-12 monthly cycles of IVIG therapy at a dose of 2 g/kg per cycle. Results: The prednisone dosage reduction after 2, 6, and 12 months following the final IVIG course was 65.45%, 70.91%, and 76.37%, respectively. During the 12-month observation period, disease relapse was observed in 20% of patients, while others achieved complete or partial remission without or with minimal therapy. Side effects were seen in 80% of patients; they were transient and did not necessitate discontinuation of IVIG. Conclusions: IVIG demonstrates effectiveness as a treatment with a favorable safety profile. Nevertheless, its high cost remains a significant drawback, particularly in low-income countries. IVIG should be considered, especially in patients opposed to standard therapies or with contraindications to their use.

Complications and outcomes of pregnancy in patients with antiphospholipid antibodies during various treatment methods

Introduction. Antiphospholipid antibodies (APAs) exert multifaceted effects on the course of pregnancy by disrupting microcirculation, affecting the hemostasis, as well as damaging the endothelial membranes, leading to early reproductive loss and development of placenta-associated complications depending on the affected gestation stage. Planning and management of pregnancy in women in the absence of criteria for complete antiphospholipid syndrome (APS) currently remains unresolved issue. The absence of generally accepted treatment standards for this category of patients and inability to substantiate the diagnosis according to the APS classification criteria complicate selection of therapeutic tactics.Aim: to conduct a comparative analysis of therapy-based complications and outcomes of pregnancy in APA carriers.Materials and Methods. During the period 2019–2021 a prospective study of 150 patients who entered pregnancy with aggravated obstetric and gynecological history, serum APA level was examined. Considering the risks of developing obstetric and thrombotic complications, all patients were prescribed prophylactic doses of low molecular weight heparins (LMWHs) and low doses of acetylsalicylic acid (ASA). The patients were divided into 3 groups using a random number generator. Group 1 (n = 50), in addition to the prescribed LMWH (enoxaparin sodium 40 mg 1 time per day) and ASA (150 mg 1 time per day), also underwent plasmapheresis (PF) 4 sessions per 1 course in 6–8, 12–14 and 22–24 weeks of pregnancy; group 2 (n = 50) received courses of intravenous immunoglobulins (IVIG) at a course dose of 300 ml (15 g) simultaneously; group 3 (n = 50) received no additional therapies. Rate of pregnancy complications was comparatively assessed – development of fetal growth retardation (FGR), low birth weight fetus, gestational arterial hypertension (AH), moderate and severe preeclampsia (PE), anemia and delivery outcomes.Results. It was found that in group 3 there was a higher incidence of gestational hypertension (p2,3 &lt; 0.0001), moderate PE (p 1,3 =0.071; p 2,3 = 0.0019), low weight fetus for gestational age (p2,3 = 0.0002) and FGR (p2,3 = 0.003). In group 1, compared with group 2, there were more often observed small weight for gestational age fetus (p1,2 = 0.018) and FGR (p1,2 = 0.024), gestational hypertension (p1,2 = 0.0008), anemia (p1,2 &lt; 0.0001) and latent iron deficiency (p1,2 &lt; 0.0001). Also, groups 2 and 3 vs. group 1 were more likely to have intrahepatic cholestasis during pregnancy (p1,2 = 0.013; p1,3 = 0.003).Conclusion. In the group of patients receiving complex therapy consisting of LMWHs prophylactic doses, low ASA doses and IVIG courses, the risks of developing placenta-associated complications and iron deficiency were reduced compared to other groups indicating about a higher efficiency of this therapy regimen. However, the development of intrahepatic cholestasis during pregnancy was less common in the group of patients receiving PF courses, in contrast to using IVIG courses, which can be accounted for by additional effect of efferent therapeutic methods and should be taken into account in a differentiated approach for management of patients with liver and gallbladder pathology.

Immunotherapy Provides Electrophysiological Recovery and Excellent Clinical Response in Sjogren's Syndrome-Linked Quite Severe Autonomic Neuropathy.

The autonomic system is frequently affected in Sjogren's syndrome (SS), but presentation with severe autonomic neuropathy is infrequent. Herein, we present a patient with primary SS-linked autonomic neuropathy, which is significantly clinic and electrophysiological responsive to immunotherapy. A 29-year-old female patient was admitted to our neurology department with recurrent syncope, postural light-headedness, and weight loss. Neurological examination revealed tonic pupils. The baseline composite autonomic symptom score-31 was 51 (0 to 75), and baseline functional ability score was 10 (0 to 100%). In the follow-up, syncope episodes that frequently develop during the day required the patient to lie in the supine position in bed all day and were triggered even by coming to a slightly sitting position. Neurophysiologic testing showed evidence of cardiovagal and sudomotor impairment. The patient was diagnosed with SS after detailed investigations. A 5-day course of intravenous immunoglobulin (IVIg) was given, and she continued IVIg once a month. After 6 months, she could walk long distances without support, and gastrointestinal complaints and syncopes had significantly decreased. After ~1.5 years, she had a composite autonomic symptom score-31 score of 11 and a functional ability score of 80%. Control heart rate variability analysis showed a significant improvement in the values of SD of the RR interval and root mean square of successive RR interval differences. In SS-linked severe autonomic neuropathy, immunotherapy can provide electrophysiological recovery in addition to excellent clinical response.

Immune Checkpoint Inhibitors Related New Onset Myasthenia Gravis: Case Series (P4-5.028)

<h3>Objective:</h3> Immune checkpoint inhibitors (ICI), such as cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are treatment for several malignancies. Myasthenia gravis (MG) is a rare but life-threatening adverse event of ICI. <h3>Background:</h3> With ICI single agent use, 42 cases of new-onset MG are reported in literature, among those, 14 patients developed severe respiratory failure and required intubation whereas 10 patients died. Combination ICI-induced MG was reported in 7 cases, with at least 2 cases complicated by respiratory failure and 1 death. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms). <h3>Design/Methods:</h3> Case series and literature review <h3>Results:</h3> <h3>Case 1:</h3> 87-year-old woman with stage IV adenocarcinoma of colon received pembrolizumab. Ten days after second dose she presented with worsening new onset bilateral ptosis (left&gt;right) and dysphagia, seropositive with acetylcholine receptor antibodies. There was no significant improvement after a course of IVIG in combination with high dose steroids. A trial of pyridostigmine could not be completed due to symptomatic bradycardia and hospice care was started thirty-eight days after first dose of pembrolizumab. <h3>Case 2:</h3> 73-year-old man with metastatic melanoma, received 2 doses of combined ipilimumab and nivolumab. Fifteen days after second dose, he presented with worsening dysphagia, dysarthria, fatigable generalized weakness and shortness of breath, seronegative for MG antibodies. Symptoms improved dramatically with IVIG. His course was complicated by rostral brainstem ischemic stroke and discharged to hospice ninety-four days after the first dose of combined ipilimumab and nivolumab <h3>Conclusions:</h3> Evidence is limited and data from a large cohort of patients is needed to recognize and manage this fatal complication. <b>Disclosure:</b> Dr. Habib has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Al-Awwad has nothing to disclose. Sarah Sung, MD has nothing to disclose.

Ataxic variant of Guillain-Barre syndrome, with positive GD1b antibodies in an elderly male: a case report (P10-5.005)

<h3>Objective:</h3> Discuss an atypical presentation of ataxic GBS with positive GD1b antibody. <h3>Background:</h3> The clinical spectrum of Guillain-Barre syndrome (GBS) ranges from asymptomatic to rapidly progressive and fatal. Ataxic GBS is one of the rare presentations. It is characterized by profound ataxia without ophthalmoplegia. We report a case of atypical presentation of GBS with rapidly progressive neurological deficits in an elderly male. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 73-year-old right-handed male with past medical history of hypertension and hyperlipidemia presented with gait imbalance and distal extremity numbness for five days prior to presentation. He noted he was having difficulty walking but denied weakness. He reported “electricity” type pain in his arms and legs and perioral tingling. He denied any other neurological deficits. He denied recent illness or vaccination. Physical exam was remarkable for severe ataxia, areflexia, and mild nystagmus. An MRI of the brain, cervical and thoracic spine showed no pathology. Cerebrospinal fluid (CSF) sampling showed protein of 46 mg/dL and no cells with a negative CSF culture. An electromyogram showed motor-sensory non-length dependant non-axonal loss without demyelination. A diagnosis of variant Guillain-Barre syndrome was suspected, and the patient received a 5-day course of intravenous immunoglobulins (IVIG). Despite this the patient developed neuromuscular respiratory failure necessitating intubation. GD1b antibody titter was found to be elevated at 1:800 (reference &lt;1:100) <h3>Conclusions:</h3> The ataxic variant of GBS is a very uncommon disease pathology. This case highlights the importance of considering different subtypes and presentations of GBS and related disorders. Early diagnosis and treatment with IVIG are important for a good outcome. <b>Disclosure:</b> Dr. Valhuerdi Porto has nothing to disclose. Dr. Shnawa has nothing to disclose. Dr. Joseph has nothing to disclose. Dr. Scott has nothing to disclose.

New-onset Myasthenia Gravis after SARS-CoV-2 infection: case report and literature review.

We report the case of a 19-year-old female patient who developed Myasthenia Gravis 13days after SARS-CoV-2 infection with positive RT-PCR testing. Her symptoms initially involved the oculo-bulbar district, but they gradually worsened in 3months converting into a generalized form of Myasthenia Gravis complicated with a myasthenic crisis. A high level of anti-acetylcholine receptor antibodies was found in the serum, while anti-MuSK antibodies were negative; Repetitive Nerve Stimulation and Single-fiber Electromyography were suggestive of Myasthenia Gravis. Intravenous immunoglobulin courses and specific therapy were able to improve her symptoms, but thymic resection was needed to control the disease. This is a report of new-onset Myasthenia Gravis correlated to COVID-19 in which thymic resection was described and the histologic analysis of the thymus was performed showing thymic hyperplasia despite negative thoracic Magnetic Resonance Imaging. SARS-CoV-2 infection releases inflammatory cytokines that could dysregulate the immune system and lead to Myasthenia Gravis in susceptible subjects.

S3373 Atypical GBS as the Presenting Symptom of Celiac Disease: Recognizing Extra-intestinal Presentations of Celiac Disease

Introduction: Celiac disease (CD) is an immune-mediated enteropathy in response to gluten that occurs in 1% of the population. Classic presenting symptoms include bloating, weight loss, and diarrhea. But, extraintestinal symptoms such as dermatitis herpetiformis, iron deficiency anemia, asymptomatic liver abnormalities, and more rarely, neurologic symptoms can be seen. We present a case of a patient who presented with worsening polyneuropathy and hepatitis leading to a final diagnosis of CD. Case Description/Methods: A 44-year-old male with history of recent left-chest shingles complicated by paralysis of right face and left leg weakness was initially admitted for suspected atypical Guillain Barre Syndrome (GBS) and treated with prednisone and a 5-day course of intravenous immunoglobulin (IVIG). The patient was readmitted a few weeks later with worsening neurologic status. A thorough infectious workup was unremarkable. The patient was also noted to have abnormal liver enzymes on prior admission that initially improved, but were noted to be worse on readmission up to ALP 1103, AST 634 and ALT 689. Given no prior history of liver disease, patient underwent a thorough workup including negative viral hepatitis, normal liver US, abdominopelvic CT showed scattered hypoattenuating lesions in the liver, one measuring up to 2.2 cm. He underwent a liver biopsy which demonstrated acute hepatitis with findings concerning for autoimmune versus drug-induced hepatitis. Autoimmune hepatitis panel was negative, however, he was found to have a tissue transglutaminase IgA >250 U/mL. Finally, he underwent upper endoscopy with biopsies that demonstrated findings consistent with celiac disease. Liver enzymes improved with gluten avoidance, but neurologic impairments persisted. Discussion: Atypical extra-intestinal symptoms at presentation of CD can result in diagnostic delay and permanent neurological disability if not treated. CD has been found in as many as 9% of patients with elevated liver enzymes. It is imperative not only to recognize neurologic presentations of CD but also the spectrum of possible liver impairments. Adherence to a strict gluten-free diet has been shown to improve symptoms of both neuropathy and liver enzyme abnormalities, but must be instituted quickly.

Intravenous Immunoglobulins Tapering and Withdrawal in Systemic Capillary Leak Syndrome (Clarkson Disease)

The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown. We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS. We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal. Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W- group). Cumulative probabilities of 10-year survival in W+ versus W- groups were 50% and 83% (log rank test, P= .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W- groups were 72% versus 58% (P= 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P= .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model. The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients.

Population Pharmacokinetic Modelling of Intravenous Immunoglobulin Treatment in Patients with Guillain-Barré Syndrome.

Background and ObjectiveIntravenous immunoglobulin (IVIg) at a standard dosage is the treatment of choice for Guillain–Barré syndrome. The pharmacokinetics, however, is highly variable between patients, and a rapid clearance of IVIg is associated with poor recovery. We aimed to develop a model to predict the pharmacokinetics of a standard 5-day IVIg course (0.4 g/kg/day) in patients with Guillain–Barré syndrome.MethodsNon-linear mixed-effects modelling software (NONMEM®) was used to construct a pharmacokinetic model based on a model-building cohort of 177 patients with Guillain–Barré syndrome, with a total of 589 sequential serum samples tested for total immunoglobulin G (IgG) levels, and evaluated on an independent validation cohort that consisted of 177 patients with Guillain–Barré syndrome with 689 sequential serum samples.ResultsThe final two-compartment model accurately described the daily increment in serum IgG levels during a standard IVIg course; the initial rapid fall and then a gradual decline to steady-state levels thereafter. The covariates that increased IgG clearance were a more severe disease (as indicated by the Guillain–Barré syndrome disability score) and concomitant methylprednisolone treatment. When the current dosing regimen was simulated, the percentage of patients who reached a target ∆IgG > 7.3 g/L at 2 weeks decreased from 74% in mildly affected patients to only 33% in the most severely affected and mechanically ventilated patients (Guillain–Barré syndrome disability score of 5).ConclusionsThis is the first population-pharmacokinetic model for standard IVIg treatment in Guillain–Barré syndrome. The model provides a new tool to predict the pharmacokinetics of alternative regimens of IVIg in Guillain–Barré syndrome to design future trials and personalise treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-022-01136-z.

Meloxicam-associated immune thrombocytopenia

A 71 year old man presented with a 24 hour history of a pruritic rash on his bilateral lower extremities, petechiae and purpura. 3 days prior he saw an Ophthalmologist for eye dryness and pain. He was prescribed eye drops and Meloxicam. After taking Meloxicam, he developed petechiae and purpura in both lower extremities (Figure 1) prompting him to seek medical care. Admission complete blood count revealed a platelet count of 3,000 (reference range, 142,000-424,000 per microliter). He was started on empiric intravenous immunoglobulin (IVIG) therapy and methylprednisolone for suspected immune thrombocytopenic purpura (ITP). Evaluation for hidden secondary causes of ITP was unremarkable: comprehensive metabolic panel, antinuclear antibody, cytoplasmic antineutrophil cytoplasmic antibodies, perinuclear anti neutrophil cytoplasmic antibodies, Hepatitis panel, HIV 1 &amp; 2, Helicobacter pylori, urinary toxicology test, Vitamin B12 level, rheumatoid factor, double stranded DNA, Epstein Barr virus (EBV) PCR, Varicella Zoster virus (VZV) PCR, Cytomegalovirus PCR, CD5, CD19, CD20, CD23 and antiphospholipid antibodies. Computed tomography with contrast of the abdomen/pelvis, chest and brain were all unremarkable. Hematology consultant recommended a five day course of IVIG 400 mg/kg and methylprednisolone 125 mg IV before discharge. Upon discharge, the platelet count had risen to 15,000. He was prescribed prednisone and instructed to follow-up with hematology.

Differential Treatment Effects for Renal Transplant Recipients With DSA-Positive or DSA-Negative Antibody-Mediated Rejection.

BackgroundAntibody-mediated rejection (ABMR) is the main cause of renal allograft loss. The most common treatment strategy is based on plasmapheresis plus the subsequent administration of intravenous immunoglobulin (IVIG). Unfortunately, no approved long-term therapy is available for ABMR. The current study was designed to analyze the effect of various ABMR treatment approaches on allograft survival and to compare treatment effects in the presence or absence of donor-specific antibodies (DSAs).MethodsThis single-center study retrospectively analyzed 102 renal allograft recipients who had biopsy-proven ABMR after transplant. DSA was detectable in 61 of the 102 patients. Initial standard treatment of ABMR consisted of plasmapheresis (PS) or immunoadsorption (IA), followed by a single course of IVIG. In case of nonresponse or recurrence, additional immunosuppressive medications, such as rituximab, bortezomib, thymoglobulin, or eculizumab, were administered. In a second step, persistent ABMR was treated with increased maintenance immunosuppression, long-term therapy with IVIG (more than 1 year), or both.ResultsOverall graft survival among transplant patients with ABMR was <50% after 3 years of follow-up. Compared to the use of PS/IA and IVIG alone, the use of additional immunosuppressive medications had no beneficial effect on allograft survival (p = 0.83). Remarkably, allografts survival rates were comparable between patients treated with the combination of PS/IA and IVIG and those treated with a single administration of IVIG (p = 0.18). Renal transplant patients with ABMR but without DSAs benefited more from increased maintenance immunosuppression than did DSA-positive patients with ABMR (p = 0.01). Recipients with DSA-positive ABMR exhibited significantly better allograft survival after long-term application of IVIG for more than 1 year than did recipients with DSA-negative ABMR (p = 0.02).ConclusionsThe results of our single-center cohort study involving kidney transplant recipients with ABMR suggest that long-term application of IVIG is more favorable for DSA-positive recipients, whereas intensification of maintenance immunosuppression is more effective for recipients with DSA-negative ABMR.

Baseline Characteristics and Predictive Factors of Intravenous Immunoglobulin Response in Drug and Device Refractory Gastroparesis Symptoms.

Intravenous immunoglobulin (IVIG) has been shown in a small pilot series to be helpful for some patients with gastroparesis that is refractory to drugs, devices, and surgical therapies. Many but not all patients have serologic neuromuscular markers. We hypothesize that those patients with serologic markers and/or longer duration of therapy would have better responses to IVIG. We studied 47 patients with a diagnosis of gastroparesis and gastroparesis-like syndrome that had all failed previous therapies including available and investigational drugs, devices, and/or pyloric therapies. Patients had a standardized 12-week course of IVIG, dosed as 400 mg/kg per week intravenously. Symptom assessment was done with Food and Drug Administration (FDA) compliant traditional patient-reported outcomes. Success to IVIG was defined as 20% or greater reduction in average symptom scores from baseline to the latest evaluation. Fourteen patients (30%) had a response, and 33 (70%) had no response per our definition. Patients responding had a higher glutamic acid decarboxylase 65 positivity (64% vs. 30%, P =0.049, missing=3) and longer duration of therapy (>12 wk/continuous: 86% vs. 48%, P =0.09). In this moderately sized open-label series of refractory patients with gastroparesis symptoms treated with IVIG, 30% of patients responded. While serologic markers and extended therapies show a trend to greater response, neither was statistically significant, except for glutamic acid decarboxylase 65 which showed a higher positivity rate in responders. We conclude that a clinical trial of IVIG may be warranted in severely refractory patients with gastroparesis symptoms.