[Anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated cortical encephalitis with low signal in subcortical white matter on MRI FLAIR imaging].

A 32-year-old male presented with unilateral orbital-temporal pulsatile headache, followed by fever in the 38°C range and nausea. The patient experienced two episodes of transient dysarthria and tinnitus, each lasting several minutes. MRI revealed swelling of the left cerebral cortex, enhancement of the leptomeninges, dilation of the left middle cerebral artery, and subcortical FLAIR hypointensity. The clinical presentation and MRI findings raised suspicions of myelin oligodendrocyte glycoprotein (MOG) antibody-associated cortical encephalitis. After two courses of steroid pulse therapy, the patient's headache subsided, and there was a significant improvement in the swelling of the left cerebral cortex. Subsequently, serum MOG antibody positivity was confirmed. While unilateral cortical FLAIR hyperintensity and increased blood flow can be observed in various diseases, MOG antibody-associated cortical encephalitis is notably characterized by subcortical FLAIR hypointensity, a finding more frequently observed in this condition compared to other diseases. In this case, the findings were useful for early diagnosis and intervention.

Prehospital Pulse-Dose Glucocorticoid in ST-Segment Elevation Myocardial Infarction: The PULSE-MI Randomized Clinical Trial.

Importance: In patients with ST-segment elevation myocardial infarction (STEMI), acute inflammation is related to the extent of myocardial damage and may increase infarct size. Thus, administration of pulse-dose glucocorticoid in the very early phase of infarction may reduce infarct size. Objective: To determine the cardioprotective effect of prehospital pulse-dose glucocorticoid in patients with STEMI. Design, Setting, and Participants: This was a 1:1 investigator-initiated, blinded, placebo-controlled, randomized clinical trial conducted between November 14, 2022, and October 17, 2023, with last follow-up on January 17, 2024. Patients 18 years and older with less than 12 hours of acute chest pain and STEMI were included in the prehospital setting throughout the Region Zealand and Capital Region of Denmark and transferred to Rigshospitalet, Denmark. Intervention: Patients were randomly allocated to intravenous glucocorticoid (methylprednisolone, 250 mg) or placebo in the prehospital setting. Main Outcomes and Measures: The primary outcome was final infarct size on cardiac magnetic resonance (CMR) at 3 months. The power calculation was based on an anticipated final infarct size of 13%. Secondary outcomes included CMR outcomes on acute scan and at 3 months, peak of cardiac biomarkers, clinical end points at 3 months, and adverse events. Results: Of 530 included patients (median [IQR] age, 65 [56-75] years; 418 male [78.9%]) with STEMI, 401 (76%) were assessed for the primary outcome, with 198 patients treated with glucocorticoid and 203 with placebo. Median final infarct size was similar in the treatment groups (glucocorticoid, 5%; IQR, 2%-11% vs placebo, 6%; IQR, 2%-13%; P = .24). Compared with placebo, the glucocorticoid group had smaller acute infarct size (odds ratio, 0.78; 95% CI, 0.61-1.00), less microvascular obstruction (relative risk ratio, 0.83; 95% CI, 0.71-0.99), and greater acute left ventricular ejection fraction (mean difference, 4.44%; 95% CI, 2.01%-6.87%). Other secondary outcomes were similar in both groups. Conclusions and Relevance: In patients with STEMI, treatment with prehospital pulse-dose glucocorticoid did not reduce final infarct size after 3 months. However, the trial was likely underpowered as the final infarct size was smaller than anticipated. The glucocorticoid group had improved acute parameters compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT05462730.

Herpes simplex encephalomyeloradiculitis initially presents with urinary retention.

Herpes simplex virus (HSV) infections necessitate careful management of urinary dysfunction and retention, which are underestimated conditions. Here, we present a rare case of HSV encephalomyeloradiculitis in a 76-year-old man, whose initial symptoms included urinary dysfunction and retention that alone lasted for approximately 1 week. Unlike in meningoencephalitis, high fever and headache were absent; however, the patient subsequently developed cauda equina syndrome and consciousness disturbance. Gadolinium-enhanced spinal MRI suggested enhanced cauda equina at the L2/3 level. Upon admission, he was treated for meningoencephalitis with acyclovir and steroid pulse therapy. Subsequent cerebrospinal fluid analysis result was positive for HSV DNA. A |brain MRI conducted 1 week after admission displayed high-intensity lesions in the white matter of the right temporal lobe, confirming HSV encephalomyeloradiculitis. These treatments were highly effective and gradually improved the patient's condition. He was discharged 1 month after hospitalization, and the urinary catheter was removed 2 weeks later. HSV infections can cause life-threatening encephalomyeloradiculitis. Therefore, both neurologists and urologists must pay attention to their occurrence and characteristics in clinical settings.

Methylprednisolone pulse and prednisolone for intensification of primary treatment in Kawasaki disease patients at high risk of treatment resistance: a multicenter prospective cohort study.

The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospective, observational study was conducted at 28 hospitals in Japan from October 2016 to June 2020. For patients predicted to be resistant to treatment based on a Kobayashi score ≥ 5 and total bilirubin ≥ 1.0 mg/dL, each hospital independently decided to add IVMP followed by prednisolone, prednisolone alone, or nothing to the primary IVIG therapy. In total, 2856 consecutive KD patients were enrolled; of these, 399 (14.0%) were predicted to be treatment resistant. Patients who were resistant to the primary treatment and required additional treatment comprised 59%, 20%, and 26% of the IVIG-alone group, IVIG-plus-prednisolone group, and IVIG-plus-IVMP group, respectively (P < .0001). The CAA incidence (Z score ≥ 2.5) at month 1 was similar among the treatment groups (6.7%, 4.8%, and 7.3%, respectively; P = .66). CAA occurred more frequently in patients who needed third- or later-line therapy.Conclusions: Primary adjunctive corticosteroid therapy improved the treatment response and suppressed inflammation. However, the study found no benefit of adding IVMP to prednisolone therapy. Patients receiving IVIG alone achieved coronary outcomes comparable to those of patients receiving primary adjunctive corticosteroid therapy although they were more likely to require additional rescue treatment. KD inflammation should be resolved no later than the third line of additional treatment to reduce the risk of CAA.Trial registration: University Hospital Medical Information Network Clinical Trials Registry in Japan ( https://www.umin.ac.jp/ctr/index.htm ) under code UMIN000024937.

[A case of a young woman with bilateral medial medullary infarcts caused by varicella-zoster virus vasculopathy without skin rash].

The patient, a 36-year-old female, had no previous history of shingles. She was admitted to the hospital due to nausea and lightheadedness. Upon admission, she was diagnosed with bilateral medial medullary infarcts. She received treatment with intravenous edaravone and argatroban, as well as antiplatelet therapy with aspirin and clopidogrel. However, her dysphagia, dysarthria, and paraplegia worsened. Due to changes in the lesion of the basilar artery on brain |MRA, we suspected the possibility of basilar artery dissection, and discontinued antiplatelet therapy. Subsequent imaging studies suggested vasculitis. After examining the cerebrospinal fluid, we diagnosed varicella-zoster virus (VZV) vasculopathy. Based on this diagnosis, we administered steroid pulse therapy for three days, started intravenous acyclovir, and resumed antithrombotic therapy with clopidogrel. Prednisone was administered for five days. Biochemical tests revealed an elevated D-dimer level. Due to the presence of lower extremity venous thrombus, clopidogrel was replaced with apixaban. The acyclovir infusion was discontinued due to observed acyclovir-induced neutropenia. These treatments improved neurological symptoms, circumflex thickening of the basilar artery, and contrast effects in the same area. On the 70th day, the patient was transferred to the hospital for rehabilitation. It is important to consider VZV angiopathy as a potential cause of juvenile cerebral infarction accompanying progressive basilar artery stenosis, regardless of the presence or absence of a skin rash.

Cancer-associated neuromyelitis optica spectrum disorder: a case report with literature review.

Neuromyelitis optica spectrum disorders (NMOSD) is one of autoimmune inflammatory diseases and is characterized by area postrema syndrome, brainstem syndrome, optic neuritis, and/or myelitis. Typical myelitis is longitudinally extended transverse myelitis (LETM) which extends over three vertebral bodies. Several previous case reports have suggested association between cancer and NMOSD. A 50-year-old woman had breast cancer and underwent mastectomy and, 10 months later, she had developed acutely progressive dysbasia. Spine MRI showed LETM in 13 vertebrae length and blood test revealed positive anti-aquaporin 4 (anti-AQP4) antibody based on enzyme-linked immunosorbent assay with index of over 40. She was treated by intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin, followed by oral prednisolone. The condition had mostly recovered after the treatment. A small population of NMOSD has the aspect of paraneoplastic neurological syndrome. The age of onset in patients with cancer-associated NMOSD tends to be higher than that in individuals with NMOSD due to any causes of NMOSD.

Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

[Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report].

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 |IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively. CONCLUSION: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Methylprednisolone Pulses and Prolonged Remission in Systemic Lupus Erythematosus: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort.

OBJECTIVE: The objective of this study was to analyze the effect of methylprednisolone pulses (MP), given during the first year after the diagnosis of systemic lupus erythematosus (SLE), in achieving prolonged remission according to the degree of lupus activity at presentation. METHODS: We conducted an observational study of routine clinical care data from the Lupus-Cruces-Bordeaux cohort. The end point was prolonged remission (ie, during five consecutive yearly visits). The effect of MP on remission during the first year was analyzed in the whole cohort and according to the baseline Systemic Lupus Erythematosus Disease Activity Index 2000 score: <6, 6 to 12, and >12, reflecting mild, moderate, and severe activity, respectively. For adjustment, logistic regression with propensity score (PS) and other therapeutic covariates was performed. RESULTS: Two hundred thirty-three patients were included. Prolonged remission was achieved by 132 patients (57%). MP were associated with prolonged remission (PS-adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.04-623, P = 0.042). A strong clinical effect was seen among patients with moderate (adjusted OR 5.28, 95% CI 1.27-21.97, P = 0.022) and moderate-severe SLE activity (adjusted OR 4.07, 95% CI 1.11-14.82, P = 0.033). The administration of MP resulted in reduced average dosages of prednisone during the first year among patient with moderate (mean 6.6 vs 10.2 mg/day, P = 0.017) and severe activity (mean 14 vs 28 mg/day, P = 0.015). The odds of prolonged remission were increased by longer-term use of hydroxychloroquine (HCQ) and decreased by higher initial doses of prednisone. CONCLUSION: This study supports the use of MP to induce prolonged remission in patients with SLE, particularly in those with moderate and severe activity. The extended use of HCQ also contributes to achieve prolonged remission.

Topical Betamethasone Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis with Ocular Involvement in the Acute Phase.

PURPOSE: To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular involvement in the acute phase. DESIGN: Retrospective case series. METHODS: Using the medical records of acute SJS/TEN patients treated at the Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan, between July 2006 and July 2017, the ocular findings, topical steroid dosage, systemic steroid dosage, and ocular sequelae were retrospectively examined. The level of cytokines in tear fluid and serum samples was also analyzed. RESULTS: This study involved 13 cases. In 10 cases in whom the clinical courses were recorded before the start of steroid therapy, the mean acute ocular severity score (AOSS: 3 = very severe; 2 = severe; 1 = mild; 0 = none) was 2.8 ± 0.4 points in the severest phase. The mean systemic steroid dose after steroid pulse therapy was 694 ± 386 mg and the mean topical steroid (0.1% betamethasone eye drop and ointment) dose was 13.4 ± 3.3 times daily in the severest phase. Analysis of cytokine levels of 4 cases showed that a cytokine storm occurred in the tear fluid after the steroid pulse therapy. At final follow-up, 16 eyes of 8 patients had a logMAR visual acuity of ≤0, and no serious ocular sequelae were observed. CONCLUSIONS: In patients with SJS/TEN, ocular surface inflammation remains strong even after systemic inflammation has improved post steroid pulse therapy, thus suggesting that both systemic and topical steroid therapy should be administered appropriately.

Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial.

Objective: To study the efficacy of pulse methylprednisolone (MPS) therapy in patients with malaria-associated acute respiratory distress syndrome (ARDS). Materials and methods: The study was a randomized, single-blind, placebo-controlled trial with a total sample size of 44 patients. The total random number table was used on a computer for randomization. The sample size was divided into either the study group that received pulse MPS therapy along with the standard therapy to manage acute lung injury (ALI)/ARDS or the control group that received a placebo in the form of 100 mL of normal saline with the standard therapy to manage ALI/ARDS. The primary outcome was defined as either death of the patient or discharge from the hospital. The sequential organ failure assessment (SOFA) score, the lung injury score (LIS), duration of stay in the medical intensive care unit (MICU), number of days for which mechanical ventilation was required, and the rate of secondary infections between the study and the control groups were also calculated. Statistically significant differences among continuous variables were analyzed by t-test, and differences between categorical variables were assessed by Chi-squared test. Results: A total of 30 patients passed initial screening, out of which 60% were males and 40% were females. About 73.3% of the patients fell between the age groups of 36-45 years. A total of 20 patients (66.7%) were discharged from the hospital, while the remaining 10 patients succumbed to death in the intensive care unit (ICU) (33.3%). The outcome of death or discharge was found to be independent of the use of pulse MPS therapy (p = 0.44). No statistically significant difference was found between the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, SOFA score, and LIS between the two groups. Furthermore, the differences between the mean duration of stay in the MICU, the mean duration for the provision of mechanical ventilation (p = 0.41), and the rate of secondary infections (p = 0.46) remained unaffected with the use of pulse MPS therapy. Conclusion: Pulse MPS therapy has not shown any clear-cut benefit in the management of malaria-associated ARDS, and in fact, the continuous use of this treatment in hospitals may lead to worsened outcomes. A novel, effective therapy for this grave complication needs to be developed to reduce the morbidity and mortality in such patients, which is frequently encountered. The development of a robust surveillance system is required for adequate monitoring and early diagnosis of this complication, along with larger multicentric randomized clinical trials. Disclosures: Approval was granted by the Institutional Ethics Committee (IEC). All participants were only selected after taking their written informed consent. The authors have no conflicts of interest or acknowledgments to report. How to cite this article: Tiwari S, Kursange S, Goyal A, et al. Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial. J Assoc Physicians India 2023;71(11):36-39.

Short-term Side Effects of Pulse Steroid Treatment in Children.

This study is aimed to evaluate pediatric patients, who were hospitalised in the Department of Pediatrics, University of Health Sciences, Adana City Training and Research Hospital, Turkey, between January, 2019 and January, 2020, and treated with pulse steroid therapy and the early side effects of their treatment. The fasting blood glucose levels of the patients during treatment were statistically significantly higher than those prior to the treatment. The most common side effects observed in the patients were dermatological (48.5%), psychiatric (31.4%), and gastrointestinal (31.4%). Hypertension was detected in seven patients (20%) after treatment; and continued in three, who subsequently underwent antihypertensive treatment. Pulse steroid treatment was administered for a median of five days (3-11 days). It was found that 24 patients responded to treatment, 11 patients did not respond, and one patient died. There is a shortage of studies in literature on pulse steroid therapy and its side effects, especially focusing on children. Multicentre and randomised controlled studies are needed comprising different patient groups to evaluate the efficacy and complications associated with its use. Key Words: Children, Side effect, Pulse steroid treatment.

Treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy.

BACKGROUND: IgA nephropathy is a typical chronic glomerulonephritis that tends to occur in childhood. METHOD: We reviewed the report on pathogenesis, treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy to clarify the pathophysiology and treatment of IgA nephropathy in childhood. RESULTS: In recent years, it has been found that the pathogenesis at onset is associated with aberrant glycosylation at the IgA1 hinge. Given this genetic background, the aberrantly glycosylated IgA1immune complex produced by antigen-stimulated T cells and B cells is deposited in the glomeruli. Inflammation is induced via activation of the complement, macrophages and mesangial cells, and glomerular damage progresses thereafter. Treatment is selected according to the severity of IgA nephropathy. In order to prevent the development of renal damage, it is important to control the associated immune responses. For severe IgA nephropathy, in particular, multidrug therapy with prednisolone, immunosuppressants, and angiotensin enzyme synthesis inhibitors and tonsillectomy methylprednisolone pulse therapy are now performed- and, as a result, the number of renal deaths has decreased and the long-term prognosis has improved. CONCLUSION: The prognosis of IgA nephropathy is improving. In the future, it will be important to develop a treatment method that takes into consideration the fact that children are in their growth and development stage and, therefore, seeks to minimizes side effects.

Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature.

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed. CRS events were confirmed by 2 independent reviewers and graded using the Lee et al. scale. The median duration of CRS was 15.0 days (Q1; Q3 6.3; 29.8) and 10 (40.0%) had multiple episodes of CRS flares. Comparing the clinical factors and biomarkers in Grades 1-2 and 3-5 CRS, we found that patients with Grades 3-5 CRS had following: (i) had longer time to fever onset [25.0 days (Q1; Q3 13.0; 136.5) vs. 3.0 days (Q1; Q3 0.0; 18.0), p=0.027]; (ii) more cardiovascular (p=0.002), neurologic (p=0.001), pulmonary (p=0.044) and rheumatic (p=0.037) involvement; (iii) lower platelet count (p=0.041) and higher urea (p=0.041) at presentation compared to patients with Grades 1-2 CRS. 7 patients (28.0%) with Grades 1-2 CRS were rechallenged using ICIs without event. 9 patients (36.0%) were treated with pulse methylprednisolone and 6 patients (24.0%) were treated with tocilizumab. Despite this, 3 patients (50%) who received tocilizumab had fatal (Grade 5) outcomes from ICI-induced CRS. Longer time to fever onset, lower platelet count and higher urea at presentation were associated with Grade 3-5 CRS. These parameters may be used to predict which patients are likely to develop severe CRS.