IgG4-Related Neurological Disease: A Single Center Ambispective Study from South India.

IgG4-related disease (IgG4-RD) is an immune-mediated multi-system disorder. The nervous system (IgG4-RND) is rarely affected. We describe a short case series. We performed an ambispective analysis of IgG4-RND patients admitted at our centre between January 2016 and December 2022. Eight patients (M: F-2:6) were included with a mean age at presentation of 40.63 ± 17.88 years and disease duration of 5.16 ± 4.08 years. The common diseased sites were pachymeninges (7), orbits (4), paranasal sinuses (3), frontal lobe (1), hypophysis (1), leptomeninges (1), and middle ear (1). Common symptoms were headache and cranial neuropathy. The common nerves involved were the optic nerve, followed by the third, fifth, sixth, and seventh. Cerebrospinal fluid showed lymphocytic pleocytosis. Histopathology showed lymphoplasmacytic infiltrate (8), fibrosis (5), >10 IgG4 + cells (7), and IgG4/IgG >40% (6). Six had a relapsing course. The rituximab-based treatment regimen showed a favourable response.

Comparison of Muscle Biopsy Features with Myositis Autoantibodies in Inflammatory Myopathies: A Pilot Experience.

Background: Idiopathic inflammatory myopathies (IIM), also called autoimmune myositis, are heterogeneous. These include dermatomyositis (DM), inclusion body myositis, immune mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASS), and overlap polymyositis. Classification of IIM has evolved from clinical to clinico-pathologic to the recent clinico-sero-pathologic with the discovery of myositis-specific antibodies (MSA) and myositis-associated antibodies. The various antibodies have shown association with specific phenotypes. Objective: To analyze muscle biopsy features with respect to each MSA and MAA to understand the frequency of findings in each entity. Materials and Methods: Biopsy-proven cases of IIM where myositis profile was available were included in the study after obtaining Institutional Ethics Committee (IEC) approval. In addition to the stains and enzyme histochemistry, immunohistochemistry with MHC class I and II and MxA was performed. Features like perifascicular atrophy, perifascicular necrosis, scattered necrosis, inflammation, etc. were analyzed. Myositis profile was performed by line-blot technique using a 16-antigen panel. Cases were divided into different autoantibody subgroups. Various clinical, demographic, and muscle biopsy features were studied with respect to each MSA and MAA. Results: There were a total of 64 cases. Mi2 (N = 18) was the most common autoantibody. Some of the salient observations included PFA with perivascular inflammation in Mi2; pediatric cases and microinfarcts in NXP2; no PFA or inflammation in MDA5; perifascicular necrosis in JO1; extensive necrosis with sparse inflammation in SRP; more inflammation in overlap myositis; MxA positivity in DM; and absent in ASS. Conclusion: This is a pilot study documenting differences in biopsy phenotype with each MSA and MAA which is comparable to the literature. These findings can be used to characterize IIM in seronegative biopsies.

Diagnosis and Severity Evaluation of Ulnar Neuropathy at the Elbow by Ultrasonography: A Case-Control Study.

Background: Traditional diagnostic techniques such as clinical examination and electrodiagnosis are less sensitive in diagnosing ulnar neuropathy at the elbow (UNE). Ultrasonography (USG) is increasingly being used to diagnose UNE. However, clinical applicability is limited by the lack of uniformity in the previous studies. Therefore, we aimed to study in the Indian patients the diagnostic utility of the ulnar nerve cross-sectional area (CSA) and a novel parameter-entrapment index (EI) in UNE measured by USG and to find if both these parameters correlate with the electrodiagnostic severity. Methods: This retrospective casecontrol study included 28 patients (36 nerves) of UNE and 12 (24 nerves) age- and gender-matched healthy controls. Electrodiagnostic severity was graded using the Padua classification. USG was performed in both groups, and CSA was measured at the medial epicondyle (ME) and 5 cm proximally and distally. EI was calculated by multiplying the ratio of CSA above ME over CSA at ME by 100. Best cutoffs were derived by the receiver operating characteristic curve analysis. Results: UNE group had significantly higher CSA at all three locations and lower EI than the control group. CSA at ME ≥9.7 mm2 and EI ≤61.5 has sensitivity and specificity of 88.9%/87.5% and 72.2%/79.2%, respectively. There was no significant difference in CSA and EI between nonsevere and severe UNE groups. Conclusion: CSA at ME and EI have good sensitivity and specificity in diagnosing UNE. However, they cannot differentiate nonsevere from severe UNE.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. METHODS: A multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. RESULTS: During the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16-1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. CONCLUSIONS: Natalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

Decoding "guitar pick sign" in COVID-19-associated mucormycosis: A case series.

"Guitar pick sign," also referred to as posterior globe tenting, is a radiological surrogate marker of tense orbit and profound vision loss. It is seen commonly in traumatic retrobulbar hemorrhage and carotico-cavernous fistula and less frequently in orbital cellulitis, subperiosteal abscess, and invasive fungal infections. We report a case series of Coronavirus disease-19-associated rhino-orbito-cerebral mucormycosis with guitar pick sign, of which none survived, and discuss the causative pathomechanisms, severity grade, and the clinical relevance of this unique radiological finding.

Pathogenetic factors fanning the flames of COVID-19 to cause rhino-orbito-cerebral mucormycosis: An observational study.

BACKGROUND AND AIMS: Published studies on coronavirus disease 19 (COVID-19) associated rhino-orbito-cerebral mucormycosis (CAROCM) were primarily descriptive. Therefore, we aimed to identify features of COVID-19 that could predispose to CAROCM and explore the pathogenic pathways. PATIENTS AND METHODS: This retrospective hospital-based study was done during the first (March 2020 - January 2021) and the second (February 2021 - June 2021) waves of the COVID-19 pandemic. Subjects were grouped into four categories: first-wave CAROCM (n-4); second-wave CAROCM (n-27); first-wave non-mucor COVID (n-75), and second-wave non-mucor COVID (n-50). Data elements included age, gender, comorbidities, COVID-19 severity, steroid therapy, peak values of interleukin-6 (IL-6), serum ferritin and D-dimer, nadir values of absolute lymphocyte count (ALC), absolute neutrophil count (ANC) and platelet count (Pl. C). RESULTS: Thirty-one patients of CAROCM were included. The mean (SD) age was 51.26 (11.48) years. 27 (87.1%) were aged ≥ 40 years and males. Severe COVID-19 was seen more often in the second wave than the first wave (P-0.001). CAROCM group was significantly younger (P-0.008) and showed a higher incidence of uncontrolled diabetes (P-0.001) and renal dysfunction (P-0.004) than non-mucor COVID. While IL-6, ferritin and D-dimer were significantly elevated in CAROCM than non-mucor COVID, clinical severity, ANC, ALC and Pl. C showed no significant difference. CONCLUSION: CAROCM is seen often in middle-aged diabetic males with uncontrolled hyperglycaemia, diabetic ketoacidosis, renal dysfunction and those infected by more transmissible delta variants and treated with steroids. IL-6, D-dimer, serum ferritin are more often elevated in CAROCM and might play a pathogenic role.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Apical pleural aspergillosis with pancoast's syndrome and posterior circulation stroke: a case report.

Pancoast's syndrome and subclavian arteritis are rarely caused by Aspergillus sp. . Here we report a case of a 22-yr-old, immunocompetent male who presented with fever, weight loss, right-sided facial anhidrosis and hand weakness of six months duration. Neurological examination confirmed right Horner's syndrome and weakness of small muscles of right hand. Contrast MRI of neck and chest revealed a pleural-based right apical mass abutting subclavian artery and C8-T1 root and multiple enlarged lymph nodes. He developed right hemiataxia due to cerebellar infarct before the planned excision of mass. Surgical exploration showed abscess encasing subclavian artery. Biopsy of the mass resulted in accidental injury of subclavian artery which was repaired. He developed bleeding from suture site postoperatively due pseudo-aneurysm of the subclavian artery which was stented. Histopathology of mass was suggestive of Aspergillus sp. . He was successfully treated with voriconazole. This is probably the first report of Pancoast's syndrome and large vessel angiitis caused by Aspergillus fumigatus which has been successfully managed.

Comparative clinical and radiographic evaluation of mineralized cancellous bone allograft (puros®) and autogenous bone in the treatment of human periodontal intraosseous defects: 6-months follow-up study.

AIMS: Several materials have been introduced as bone grafts, i.e., autografts, allograft, xenografts, and alloplastic grafts, and studies have shown them to produce greater clinical bone defect fill than open flap debridement alone. The aim of this clinical and radiological 6-month study was to compare and evaluate the clinical outcome of deep intraosseous defects following reconstructive surgery with the use of mineralized cancellous bone allograft (Puros®) or autogenous bone. MATERIALS AND METHODS: Ten patients with 12 sites exhibiting signs of moderate generalized chronic periodontitis were enrolled in the study. The investigations were confined to two and three-walled intra bony defects with a preoperative probing depth of ≥5 mm. Six of these defects were treated with Puros® (group A) the remaining six were treated with autogenous bone graft (group B). Allocation to the two groups was randomized. The clinical parameters, plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL), and bone fill, were recorded at different time intervals at the baseline, 1 month, 3 months, and 6 months. Intraoral radiographs were taken using standardized paralleling cone technique at baseline, 1, 3, and 6 months. Statistical analysis was done by using the one-way analysis of variance (ANOVA) followed by Tukey highly significant difference. RESULTS: Both groups resulted in decrease in probing depth (group A, 3.0 mm; group B, 2.83 mm) and gain in clinical attachment level (group A, 3.33 mm; group B, 3.0 mm) over a period of 6 months, which was statistically insignificant. CONCLUSION: Within the limitations of the present study, it can be concluded that both mineralized cancellous bone allograft (Puros®) or autogenous bone result in significant clinical improvements.