Factors associated with poor outcome in tuberculous meningitis; study from a tertiary care referral Centre from South India

Introduction: Tuberculosis (TB) remains a worldwide burden with a large majority of new active cases occurring in underdeveloped and developing countries. This study is an attempt to look into various aspects of the disease that can be associated with the outcome, to promote a timely referral to an appropriate centre. Purpose: To identify various clinical, lab, CSF and radiological variables associated with poor outcome of TBM at the time of discharge. Material & Methods: Demographic data, duration of symptoms before diagnosis, clinical presentation, staging of the disease at the time of admission of all the TBM patients who presented to our centre between December, 2015 and May 2018 were noted. Results of biochemical investigations and brain and spine imaging were retrieved. Outcome at the time of discharge as measured by MRC and mRS grades was correlated to clinical profile, lab, CSF and radiological findings. Results: A total of 100 patients were included. 15 patients died. Subjects with MRC and mRS grades of 2 or more at admission constituted 65% and 93% respectively. At discharge, MRC and mRS grades of 2 or more were found in 29.63% and 39% respectively. Multivariable analysis showed a significant positive association of MRC stage at discharge with MRC stage (p = 0.001) and mRS score (p = 0.001) at admission and Vellore hydrocephalus grade (p < 0.001) when hydrocephalus first identified. Similarly, mRS score at discharge had an independent positive association with the MRC stage (p < 0.001) and the mRS score (p=0.002) at admission. Conclusion: Stage of the disease (MRC) and functional status of the patient (mRS) at admission are the two most important independent factors determining the outcome of TBM patients at the time of discharge

Longitudinally extensive transverse myelitis due to toxoplasma: An autopsy study

Toxoplasma is an obligate intracellular parasite that remains asymptomatic in humans but, at times, can cause devastating disease. Here, we describe an autopsy study of a young immunocompetent gentleman with no comorbidities whose presentation was acute transverse myelitis. Magnetic resonance imaging spine showed longitudinally extensive spinal cord lesion (LESCL) that mimicked neuromyelitis optica with normal brain imaging at presentation. Investigations showed albuminocytological dissociation which prompted a course of parenteral steroid. However, the lesion relentlessly progressed to involve the brain stem and cerebrum leading to toxoplasmic encephalitis that terminated fatally. This report highlights that toxoplasma can present as LESCL and needs to be considered in the differential diagnosis of atypical myelitis

Aceruloplasminemia with novel mutation, with IgG4 related pachymeningitis – occam's razor or hickam's dictum?

To report a patient with concomitant aceruloplasminemia (with a novel mutation) and IgG4-related pachymeningitis and to hypothesize on the possible relation between the two diseases. Clinical, radiological, and laboratory features of a 56-year-old lady with chronic headache, bifacial palsy, and cerebellar signs are described. Pathophysiology of aceruloplasminemia leading to hyperferritinemia and consequent immune activation is elucidated. A coherent explanation of IgG4-related pachymeningitis resulting from aceruloplasminemia and hyperferritinemia is given. The patient has aceruloplasminemia with a novel nonsense mutation. She also suffers from biopsy-proven IgG4 related pachymeningitis as per standard criteria. These two seemingly unrelated illnesses are linked by hyperferritinemia. This case is a fine example of Occam's razor. Immune dysfunction and autoimmune disorders in aceruloplasminemia need to be explored through further studies to look for causal associations

A series of biopsy-proven patients with immunoglobulin G4-related neurological disease

Aim: To study the clinical presentation, radiological findings, and therapy responsiveness of patients with biopsy-proven immunoglobulin G4 (IgG4)-related neurological disease. Methods: The study was conducted between January 2016 and March 2018 from the Department of Neurology and Pathology of Nizam's Institute of Medical Sciences. Patients with neurological symptoms and biopsy suggestive of IgG4-related disease (IgG4-RD) were included. These patients were studied for their demographic pattern and clinical presentation. The presence of serological markers such as vasculitic profile and IgG4 levels was analyzed. Radiological findings were studied in detail. Therapeutic agents used and the response to therapy were assessed. Results: There were six cases with IgG4-related neurological disease which were all hypertrophic pachymeningitis. The age ranged from 35 to 64 (mean = 46) years. The clinical presentation was acute in one, subacute in two, and chronic in three patients. The most common presenting symptom was headache (4), followed by gait and/or urinary disturbances (2), paraparesis (1), and diplopia (1). IgG4 levels were elevated in 50% of them. Pseudotumor-like mass and sinovenous thrombosis, not described previously, were seen in one patient. All the patients were treated with oral or intravenous steroid. Rituximab was given in three patients; azathioprine was the steroid-sparing agent in one patient. Those with acute/subacute onset of presentation had an excellent response to steroids. All the patients with a chronic duration of their symptoms received empirical anti-tuberculous therapy before a definitive diagnosis of Ig G4-RD was made. Conclusions: The characterization of patients with IgG4-related neurological disease based on the understanding of the clinical spectrum increases the confidence in the clinician to resort to early immunosuppression, thereby having prognostic implications