title: Paradoxical Manifestation is Common in HIV-negative Tuberculous Meningitis.
abstract: Paradoxical manifestation is worsening of pre-existing tuberculous lesion or appearance of new lesions in patients whose condition initially improved with antituberculous treatment. Our hypothesis was that paradoxical manifestation in non-HIV tuberculous meningitis (TBM) patients was underestimated and this could contribute to patients' prognosis. This was the first systemic study of paradoxical manifestation in HIV-negative TBM patients. Between 2009 and 2014, TBM patients were studied prospectively in 2 hospitals. Clinical features, cerebrospinal fluid, and radiological findings were monitored. Paradoxical manifestation was divided into definite (4 weeks or more) and probable (between 14 and 27 d) after commencement of antituberculous treatment. Forty-one non-HIV TBM patients were recruited. Definite paradoxical manifestation occurred in 23/41 (56%) of the patients. Time to onset of paradoxical manifestation was between 28 days and 9 months, and majority was between 28 and 50 days. Neuroimaging manifestation in the brain (22/41 patients, 54%) and clinical manifestation (22/41 patients, 54%) were most commonly seen, followed by cerebrospinal fluid manifestation (7/41 patients, 17%). Neuroimaging changes most commonly seen were worsening of leptomeningeal enhancement, new infarcts, new tuberculomas, and enlargement of tuberculoma. Initial Computed Tomography Angiography/magnetic resonance angiography brain showed vasculitis in 14 patients, with 2 (12.5%) showing paradoxical vasculitis during follow-up. Recurrence of the paradoxical manifestation was seen in 7/23 (30%) of the patients. More than half (14/23, 61%) of the patients improved, 6 (26%) patients died, and 3 (13%) patients had persistent neurological deficit. Paradoxical manifestation was very common in non-HIV TBM patients. Neuroimaging paradoxical manifestation of 2-4 weeks may not be paradoxical manifestation but could be delayed treatment response.
authors.affiliation: From the Division of Neurology, Department of Medicine (M-LST, CTT); Department of Biomedical Imaging, Faculty of Medicine, University Malaya, Kuala Lumpur (HMN, KAAK, KR); Department of Neurology (SV, MHR); Department of Radiology, Hospital Kuala Lumpur (NRMZ); and Department of Rehabilitation Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia (KGO).
authors.forename: Mei-Ling Sharon
authors.initials: MS
authors.lastname: Tai
authors.forename: Hazman Mohd
authors.initials: HM
authors.lastname: Nor
authors.forename: Khairul Azmi Abdul
authors.initials: KAA
authors.lastname: Kadir
authors.forename: Shanthi
authors.initials: S
authors.lastname: Viswanathan
authors.forename: Kartini
authors.initials: K
authors.lastname: Rahmat
authors.forename: Norzaini Rose Mohd
authors.initials: NRM
authors.lastname: Zain
authors.forename: Kuo Ghee
authors.initials: KG
authors.lastname: Ong
authors.forename: Mohd Hanip
authors.initials: MH
authors.lastname: Rafia
authors.forename: Chong Tin
authors.initials: CT
authors.lastname: Tan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging; D002533:Cerebral Angiography; D018450:Disease Progression; D005260:Female; D018023:HIV Seronegativity; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000995:Antitubercular Agents