Adjuvant immunosuppression for paradoxical deterioration in tuberculous meningitis including one case responsive to cyclosporine. A tertiary referral hospital experience

D Ledingham; S El-Wahsh; D Sebire; C Cappelen-Smith; S J Hodgkinson; A J McDougall; M Maley; D J Cordato

doi:10.1016/j.jns.2019.07.002

Adjuvant immunosuppression for paradoxical deterioration in tuberculous meningitis including one case responsive to cyclosporine. A tertiary referral hospital experience

J Neurol Sci. 2019 Sep 15:404:58-62. doi: 10.1016/j.jns.2019.07.002. Epub 2019 Jul 13.

Authors

D Ledingham¹, S El-Wahsh¹, D Sebire¹, C Cappelen-Smith², S J Hodgkinson², A J McDougall², M Maley³, D J Cordato⁴

Affiliations

¹ Department of Neurology and Neurophysiology, Liverpool Hospital, Sydney, Australia.
² Department of Neurology and Neurophysiology, Liverpool Hospital, Sydney, Australia; Ingham Institute for Applied Medical Research, Sydney, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia.
³ South Western Sydney Clinical School, University of New South Wales, Sydney, Australia; Department of Microbiology and Infectious Diseases, NSW Health Pathology Liverpool, Sydney, Australia.
⁴ Department of Neurology and Neurophysiology, Liverpool Hospital, Sydney, Australia; Ingham Institute for Applied Medical Research, Sydney, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia. Electronic address: dennis.cordato@health.nsw.gov.au.

PMID: 31330455
DOI: 10.1016/j.jns.2019.07.002

Abstract

Background: Tuberculous meningitis (TBM) accounts for 1-4% of all tuberculosis (TB) presentations. Paradoxical deterioration in non-HIV patients is a common manifestation of anti-tuberculosis therapy, characterised by clinico-radiological deterioration. We report a case series of TBM admissions to our institution including one case with paradoxical deterioration refractory to corticosteroids who responded to adjuvant cyclosporine.

Methods: Retrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005-2016) with laboratory and/or radiologically confirmed TBM.

Results: Median patient age was 40 (range 22-81 years), M:F = 7:5. Eleven patients (92%) were of Asia-Pacific origin. Eleven initially presented with central nervous system manifestations and one had preceding miliary TB. Nine patients had extra-cranial TB involvement including eight with past or current pulmonary disease. Cerebrospinal fluid (CSF) TB PCR/culture was positive in 10 patients. Paradoxical deterioration developed in three patients despite concomitant corticosteroids in two. One patient with paradoxical deterioration was refractory to corticosteroids: A 22-year-old Vietnamese male with TBM developed worsening headaches and altered mentation after seven weeks concomitant anti-TB and corticosteroid treatment. Interval MRI brain demonstrated increased size and number of tuberculomas as well as hydrocephalus. Cyclosporine was added with gradual improvement and ultimately good outcome.

Conclusion: Our case series highlights the seriousness of paradoxical deterioration in TBM and the potential role of adjuvant cyclosporine in patients refractory to corticosteroids.

Keywords: Cyclosporine; Paradoxical deterioration; Paradoxical reaction; Tuberculous meningitis.

MeSH terms

Adrenal Cortex Hormones / therapeutic use*
Adult
Aged
Aged, 80 and over
Antitubercular Agents / therapeutic use*
Brain / diagnostic imaging
Cyclosporine / therapeutic use*
Female
Humans
Immunosuppressive Agents / therapeutic use*
Magnetic Resonance Imaging
Male
Middle Aged
Tertiary Care Centers
Tuberculosis, Meningeal / diagnostic imaging
Tuberculosis, Meningeal / drug therapy*
Young Adult

Substances

Adrenal Cortex Hormones
Antitubercular Agents
Immunosuppressive Agents
Cyclosporine