Paradoxical manifestations during tuberculous meningitis treatment among HIV-negative patients: a retrospective descriptive study and literature review

• Published in: Neurological sciences 2022-04, Vol.43 (4), p.2699-2708
• Main Authors: Domínguez-Moreno, Rogelio, García-Grimshaw, Miguel, Medina-Julio, David, Cantú-Brito, Carlos, González-Duarte, Alejandra
• Format: Article
• Language: English
• Subjects: Adult; Antitubercular Agents - therapeutic use; Central nervous system; Cerebrospinal fluid; Corticosteroids; Cyclophosphamide; Female; HIV; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Hydrocephalus; Intravenous administration; Literature reviews; Male; Medicine; Medicine & Public Health; Meningitis; Middle Aged; Mycobacterium tuberculosis; Neurology; Neuroradiology; Neurosciences; Neurosurgery; Original Article; Patients; Psychiatry; Retrospective Studies; Steroid hormones; Steroids; Tuberculoma; Tuberculosis; Tuberculosis, Meningeal - cerebrospinal fluid; Tuberculosis, Meningeal - complications; Tuberculosis, Meningeal - drug therapy; Vascular diseases; Young Adult
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-021-05693-2

Background Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. Methods Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. Results We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19–49 years old), developed a paradoxical manifestation within 4–14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. Conclusions This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed.