Myositis in H1N1 Infection Compounds to Myasthenic Crisis.

ABSTRACT: Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We report two myasthenia gravis (MG) patients with H1N1 infection, and highlight the reasons for deterioration. Two patients with MG had H1N1 infection. The diagnosis of MG was confirmed by neostigmine, repetitive nerve stimulation, and anti-acetylcholine receptor antibody tests. H1N1 was confirmed by nucleic acid detection study, and myositis by creatinine kinase. The patient with pneumonia and myositis had MC needing mechanical ventilation for 10 days, and the other patient without myositis did not have MC. They were treated with oseltamivir 75 mg twice daily for 5 days, and the patients with MC received ceftriaxone intravenously. Both the patients were on prednisolone and azathioprine, and none received prior H1N1 vaccination. The lady with MC with myositis was discharged on day 27 in wheelchair bound state, and the other one patient without myositis or MC was discharged on 6th day with full recovery. These patients highlight the need for evaluation for myositis along with pneumonia in the MG patients with H1N1 infection. Vaccination in MG patients on immunosuppression may be useful.

mRNA profiling of cytokines to understand paradoxical response in HIV-uninfected tuberculous meningitis.

Paradoxical reaction (PR) in tuberculous meningitis (TBM) is a major management issue. We report mRNA profiling of cytokines to understand PR in HIV-uninfected TBM patients. 72 patients with TBM were included, and their clinical, MRI, and mRNA profiling of tumor necrosis factor (TNF) α, interleukin (IL) 6, IL10 and interferon (IFN) γ genes in the peripheral blood mononuclear cells were done at admission and 6 weeks of antitubercular treatment. Cytokine profiling was done using reverse transcriptase polymerase chain reaction. PR was defined if repeat MRI at 6 weeks revealed new or increase in exudates, tuberculoma, hydrocephalus or infarctions. Outcome was defined at 6 months using modified Rankin Scale (mRS), and categorized as death, poor and good. 44 (61.1 %) patients had PR, and 28 (38.9 %) had paradoxical tuberculoma (PT). The expression of IL6 and TNFα genes were higher in PR and PT groups. Stage of meningitis and hydrocephalus at admission predicted PR. Patients with PR and PT had more frequently poor outcome. About three-fifth HIV-uninfected TBM patients have PR and two-fifth have PT. Paradoxical reaction is associated with higher expression of IL6 and TNFα. Patients with severe meningitis with hydrocephalus develop PR more frequently.

Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial.

BACKGROUND: High dose of corticosteroid has been found beneficial in complex regional pain syndrome type I (CRPS-I). We report the efficacy and safety of prednisolone 20 mg versus 40 mg in CRPS-I in an open label randomized controlled trial. METHODS: The patients with CRPS-I of the shoulder joint with a CRPS score of ≥8 were included. Their demographic details, comorbidities, and underlying etiology were noted. The severity of CRPS was assessed using a 0-14 CRPS scale, the pain using a 0-10 Visual Analogue Scale (VAS), and sleep quality using a 0-10. Daily Sleep Interference Scale (DSIS). Patients were randomized to prednisolone 40 mg/day (group I) or 20 mg/day (group II) for 14 days, then tapered to 10 mg in group I and to 5 mg in group II by 1 month. Thereafter both groups received prednisolone 5 mg/day for 2 months. The primary outcome was a >50% reduction in VAS score, and secondary outcomes were a reduction in CRPS score, DSIS score, and adverse events. RESULTS: Fifty patients were included, and their baseline characteristics were comparable. At one month, all the patients had >50% reduction in the VAS score. The effect size was 0.38 (95% CI 0.93-0.20; p = 0.20). On the Kaplan-Mayer analysis, the improvement in the VAS score (Hazard ratio-1.43, 95 % CI-0.80-2.56, p = 0.22) and the CRPS score (HR-0.79,95 % CI-0.45-1.39; p = 0.41) was insignificant between the two groups. The DSIS score improved in group II (HR-1.85,95 % Cl-1.04-3.31,p = 0.04). Group I patients needed frequent adjustment of antidiabetic drugs (14 vs 6; p = 0.04). CONCLUSION: The efficacy of prednisolone 20 mg is not inferior to 40 mg in CRPS-I, and is safe in diabetic patients. LIMITATIONS: This is an open label randomized controlled trial with small sample size without a placebo arm.

Racemose neurocysticercosis simulating tuberculous meningitis.

We report a patient with racemose neurocysticercosis, highlighting the diagnostic and management issues. A 37-year-old male had headaches, fever, and seizures for 8 months. He had a positive tuberculin test, cerebrospinal fluid pleocytosis, and hydrocephalus and exudates on MRI. His symptoms rapidly resolved following antitubercular and prednisolone treatment. After 2 months, he was readmitted with headache and vomiting, and his brain MRI revealed communicating hydrocephalus with a cyst in the lateral ventricle and subarachnoid space, which was confirmed as neurocysticercosis on the third ventriculostomy. The patient was managed with dexamethasone and a ventriculoperitoneal shunt. This case highlights that meningitis symptoms, CSF pleocytosis, and positive tuberculin tests may not always suggest tubercular etiology.

Paroxysmal spinal hemidystonia in neuromyelitis optica.

Paroxysmal dystonia occurs because of genetic or structural lesion in the basal ganglia or thalamus, and there is paucity of reporting in spinal pathology. We report a patient with paroxysmal hemidystonia admitted to a tertiary care hospital, India, and review the literature on spinal dystonia in neuromyelitis optica (NMO). A 19-year-old woman presented with recurrent visual loss and quadriparesis. She developed paroxysmal hemidystonia after 18 days of a second episode of quadriplegia, during which her muscle power improved to Grade 3. Magnetic resonance imaging (MRI) of her spine showed central T2 hyperintensity extending from C2 to C7 vertebral level, and a cranial MRI was normal. Tibial somatosensory evoked potentials were unrecordable. Aquaporin-4 antibody was positive in serum, confirming the diagnosis of NMO. Paroxysmal hemidystonia responded to carbamazepine 200 mg thrice daily. Paroxysmal dystonia may occur in a patient with myelitis and may respond to carbamazepine.

Balancing between apoptosis and survival biomarkers in the patients with tuberculous meningitis.

BACKGROUND: The balancing factor of apoptosis, survival, inflammatory and oxidative stress biomarkers may determine the clinico-radiological severity and death in the patients with tuberculous meningitis (TBM). AIM: We report the relationship of death [caspase-3, malondialdehyde (MDA), tumor necrosis factor-α (TNFα), interleukin 6 (IL6)] and survival biomarkers [X-linked inhibitory apoptotic protein (XIAP), IL10, glutathione (GSH) and catalase] in TBM, and its role in determining disease severity and death. METHODS: The diagnosis of TBM was based on clinical, MRI and cerebrospinal fluid (CSF) findings. Their clinical and MRI findings were noted. The severity of TBM was categorized as stages I to III. Serum and CSF caspase-3 and XIAP were measured by ELISA, and TNFα, IL6 and IL10 gene expression in peripheral blood mononuclear cells using RT-PCR (reverse-transcriptase polymerase chain reaction). Plasma MDA, GSH and catalase were measured by spectrophotometer. RESULTS: There were 40 patients with TBM whose mean age was 31.6 years and 50% were females. TBM patients had higher expression of death (caspase-3, TNFα, IL6, and MDA) and suppression of survival biomarkers (XIAP, catalase and GSH) compared to the healthy controls. Caspase-3 positively correlated with TNFα, IL6 and MDA, and negatively with XIAP, GSH and catalase. Patients with longer duration of illness and definite TBM had higher expression of caspase-3. Patients who died has higher expression of caspase-3 and suppression of XIAP compared to those who survived. CONCLUSION: It can be concluded from this study that there is up-regulation of death signals and suppression of survival signals in TBM.

Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study.

BACKGROUND: Central nervous system (CNS) has a different immune surveillance system; therefore, fever at admission and timeline of fever response after antitubercular treatment (ATT) may follow a different course in CNS infection. We report the predictors of fever response in tuberculous meningitis (TBM) including the effect of tumour necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs). METHODS: Fifty-seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF-α gene in PBMCs was quantified by real-time polymerase chain reaction and TNF-α concentration in CSF by cytokine bead array both in the patients and 14 matched controls. RESULTS: All the patients had history of fever for a median duration of 75 days. The admission temperature ranged between 37.2°C and 40°C and correlated with CSF cell counts (p < 0.05). Cranial MRI was abnormal in 54 (94.7%) and revealed exudates in 33(57.9%), hydrocephalus in 27(47.4%), infarction in 27(47.4%) and tuberculoma in 33(57.9%) patients. Fever subsided after a median duration of 18 (2 60) days of treatment. Twelve (21.8%) patients only became afebrile within 10 days. The expression of TNF-α gene correlated with CSF concentration of TNF-α (p = 0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00-1.04; p = 0.01). CONCLUSION: In the patients with TBM, defervescence takes longer time, and TNF-α gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF-α-modifying drugs in TBM.

Feasibility and usefulness of tele-follow-up in the patients with tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and these patients need close follow-up because of a high frequency of complications. The coronavirus disease 2019 pandemic and lockdown resulted in an interruption in physical follow-up. In this situation, tele-follow-up may be helpful. We report the feasibility and usefulness of a telephonic follow-up in patients with TBM. METHODS: Patients with TBM managed by us from January 2017 to March 2020 were included from the TBM registry. Their presenting symptoms, and clinical and investigation findings were noted. We contacted these patients telephonically and their clinical status was obtained using a questionnaire. Based on the telephonic information, outcomes were categorized as death, poor or good. Patients with the new medical problems were advised as to relevant investigations and the reports were obtained through WhatsApp for prescribing treatment. RESULTS: The telephone numbers of 103 of 144 (71.5%) patients were viable. Twenty-seven (26.2%) patients died, 15 (19.7%) had a poor outcome and 61 (80.2%) had a good outcome. Twenty-five (32.9%) patients had new medical problems: 18 TBM related and 7 TBM unrelated. The medical problems of 23 patients could be managed telephonically and only 3 (4%) patients needed a physical visit. Sixty-five (85.5%) patients happily answered the questionnaire and willing responders needed a treatment modification more frequently than the reluctant responders (p=0.008). Patients on active antitubercular treatment needed treatment modification more frequently (80% vs 21.3%). CONCLUSIONS: Tele-follow-up is feasible in 96% of TBM patients and is beneficial, cost effective and overcomes the barrier of distance.

Inclusion of Mechanical Ventilation in Severity Staging of Tuberculous Meningitis Improves Outcome Prediction.

Patients with tuberculous meningitis (TBM) in any stage of the British Medical Research Council (BMRC) scale, if requiring mechanical ventilation (MV), are likely to have a poor outcome. We report the usefulness of BMRC, BMRC-MV, and BMRC-hydrocephalus (BMRC-HC) staging, and Haydarpasa Meningitis Severity Index (HAMSI) scoring in predicting the outcome of TBM. One hundred ninety-seven TBM patients were analyzed from a prospectively maintained TBM registry. The severity of meningitis was categorized using BMRC (stages I-III), BMRC-MV (I-IV [MV patients were grouped as stage IV]), and BMRC-HC (I-IV [BMRC stage III patients with hydrocephalus were grouped as stage IV]). Haydarpasa Meningitis Severity Index scoring was categorized as < 6 and ≥ 6. The outcome was defined at 6 months using the modified Rankin Scale (mRS) as death, poor (mRS score > 2), or good (mRS score ≤ 2). Forty-nine (25%) patients died. BMRC-mechanical ventilation stage IV had the highest predictive value for defining death, with a sensitivity of 88% and a specificity of 86%. About 81.7% of surviving patients had a good outcome at 6 months. BMRC-mechanical ventilation stages I-III had the highest predictive value for defining good outcome, with a sensitivity of 93% and a specificity of 61%. In TBM, BMRC-MV staging has the best predictive value for defining death and disability.