title: Paradoxical reaction in tuberculous meningitis: presentation, predictors and impact on prognosis.
abstract: Awareness about paradoxical reactions in tuberculous meningitis is crucial as a paradoxical reaction may lead to certain wrong conclusions (for example, an erroneous diagnosis, and a possibility of treatment failure, mycobacterial drug-resistance, drug toxicity, or presence of a malignancy). The present study was planned to evaluate the incidence and predictive factors of paradoxical reactions in light of clinical, cerebrospinal fluid, and neuroimaging characteristics.
  
  
  
  In this prospective cohort study, consecutive patients fulfilling the International Consensus criteria of tuberculous meningitis were included. Patients were subjected to clinical evaluation, cerebrospinal fluid evaluation, and neuroimaging. Patients were treated with anti-tuberculosis drugs along with corticosteroids. Patients were regularly followed up at 3 monthly intervals. At each follow up patients were evaluated clinically and repeat cerebrospinal fluid analysis was performed along with repeat neuroimaging. Disability assessment was done using Barthel index.
  
  
  
  We enrolled 141 patients of tuberculous meningitis. Approximately one-third of patients (44/141; 31.2 %) developed a paradoxical reaction. Twenty-seven patients developed hydrocephalus, 26 developed tuberculomas, 12 developed optochiasmatic arachnoiditis and 4 patients had spinal arachnoiditis. In 41 patients (out of 44) cerebrospinal fluid paradoxically worsened (increase in cells and/or protein); 2 demonstrated a decrease in cells with polymorph predominance while in one it was normal. In 3 patients, paradoxical cerebrospinal fluid changes were not associated with neuroimaging changes. On multivariate analysis, predictors of paradoxical reaction were female gender (p = 0.013), HIV positivity (p = 0.01) and a shorter duration of illness (p = 0.049). Development of paradoxical reactions did not predict the disability status of the patients.
  
  
  
  Paradoxical reaction occurs in approximately one-third of patients with tuberculous meningitis. Female gender, concomitant HIV infection, and a shorter duration of illness were significant predictors. Paradoxical reactions did not adversely affect the outcome.
authors.affiliation: Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, PIN-226003, India.
authors.forename: Anurag Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, PIN-226003, India.
authors.forename: Hardeep Singh
authors.initials: HS
authors.lastname: Malhotra
authors.affiliation: Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, PIN-226003, India. garg50@yahoo.com.
authors.forename: Ravindra Kumar
authors.initials: RK
authors.lastname: Garg
authors.affiliation: Department of Microbiology, King George Medical University, Uttar Pradesh, Lucknow, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, PIN-226003, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Radiodiagnosis, King George Medical University, Uttar Pradesh, Lucknow, India.
authors.forename: Neera
authors.initials: N
authors.lastname: Kohli
authors.affiliation: Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, PIN-226003, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Verma
authors.affiliation: Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, PIN-226003, India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001100:Arachnoiditis / Q000453:epidemiology*; D015331:Cohort Studies; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000453:epidemiology; D006801:Humans; D006849:Hydrocephalus / Q000453:epidemiology*; D015994:Incidence; D007194:India / Q000453:epidemiology; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D012737:Sex Factors; D013997:Time Factors; D014375:Tuberculoma / Q000453:epidemiology*; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: Cerebrospinal fluid; Hydrocephalus; Immune reconstitution inflammatory syndrome; Optochiasmatic arachnoiditis; Tuberculoma