- •Paradoxical deterioration occurred in 25% (3/12) of our patients with TB meningitis.
- •In 2 patients this was successfully managed with high dose corticosteroids alone.
- •1 patient deteriorated in spite of corticosteroids and cyclosporine was used.
- •Cyclosporine has a T cell suppressive effect, which may explain its efficacy.
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.
Retrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005–2016) with laboratory and/or radiologically confirmed TBM.
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.
Our case series highlights the seriousness of paradoxical deterioration in TBM and the potential role of adjuvant cyclosporine in patients refractory to corticosteroids.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of the Neurological Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- National Tuberculosis Advisory Committee, for the Communicable Diseases Network Australia, and the Australian Mycobacterium Reference Laboratory Network. Tuberculosis notifications in Australia, 2012 and 2013.Comm. Dis. Intell Q. Rep. 2015; 39: E217-E235
- Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2010. A report of the Australian Mycobacterium Reference laboratory Network.Comm. Dis. Intell Q. Rep. 2013; 37: E40-E46
- EpiReview: tuberculosis in NSW, 2009–2011.NSW Public Health Bull. 2013; 24: 3-9
- Risk factors for development of paradoxical response during antituberculosis therapy in HIV-negative patients.Eur. J. Clin. Microbiol. Infect. Dis. 2003; 22: 597-602
- Meta-analysis: the association between HIV infection and extrapulmonary tuberculosis.Lung. 2013; 191: 27-34
- Prognostic models for 9-month mortality in tuberculous meningitis.Clin. Infect. Dis. 2018; 66: 523-532
- Tuberculous meningitis in Denmark: a review of 50 cases.BMC Infect. Dis. 2011; 11: 47
- Paradoxical manifestation is common in HIV-negative tuberculous meningitis.Medicine (Baltimore). 2016; 95e1997
- Corticosteroids for managing tuberculous meningitis.Cochrane Database Syst. Rev. 2016; 4: CD002244
- Recent advances in the diagnosis and management of tuberculous meningitis.Curr. Opin. Infect. Dis. 2017; 30: 123-128
- The Th2 biased immune response in cases with active Mycobacterium tuberculosis infection and tuberculin anergy.FEMS Immunol. Med. Microbiol. 1998; 22: 199-204
- Tuberculosis-immune reconstitution inflammatory syndrome.J. Clin. Tuberc. Other Mycobact. Dis. 2016; 3: 6-9
- Paradoxical response in patients with CNS tuberculosis.J. Assoc. Physicians India. 2003; 51: 257-260
- Paradoxical reaction in HIV negative tuberculous meningitis.J. Neurol. Sci. 2014; 340: 26-36
- Paradoxical reaction in tuberculous meningitis: presentation, predictors and impact on prognosis.BMC Infect. Dis. 2016; 16: 306
- Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.N. Engl. J. Med. 2004; 351: 1741-1751
- Infliximab therapy in two cases of severe neurotuberculosis paradoxical reaction.Med. J. Aust. 2015; 202: 156-157
- A paradoxical treatment for a paradoxical condition: infliximab use in three cases of mycobacterial IRIS.Clin. Infect. Dis. 2016; 62: 258-261
- Adalimumab treatment may replace or enhance the activity of steroids in steroid-refractory tuberculous meningitis.J. Clin. Rheumatol. 2012; 18: 189-191
- Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study.J. Child Neurol. 2004; 19: 250-257
- The use of thalidomide in the treatment of intracranial tuberculomas in adults: two case reports.J. Inf. Secur. 2003; 47: 251-255
- Tuberculosis –associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings.Lancet Infect. Dis. 2018; 8: 516-523
- Clinical spectrum of paradoxical deterioration during antituberculous therapy in non-HIV-infected patients.Eur. J. Clin. Microbiol. Infect. Dis. 2002; 21: 803-809
- Mechanism of action of cyclosporine.Immunopharmacology. 2000; 47: 119-125
- The mechanisms of action of cyclosporin a in the treatment of psoriasis.Immunol. Today. 1993; 14: 69-74
- Divergent effect of cyclosporine on Th1/Th2 type cytokines in patients with severe, refractory rheumatoid arthritis.J. Rheumatol. 2000; 27: 324-331
- Pharmacokinetic interactions with rifampicin: clinical relevance.Clin. Pharmacokinet. 2003; 42: 819-850
- Cyclosporine A for induction of remission in severe ulcerative colitis.Cochrane Database Syst. Rev. 2005; CD004277
- Oral cyclosporin in psoriasis: a systematic review on treatment modailities, risk ofkidney toxicity and evidence for use in non-plaque psoriasis.J. Eur. Acad. Dermatol. Venereol. 2011; 25S2: 19-27
Published online: July 13, 2019
Accepted: July 8, 2019
Received in revised form: June 9, 2019
Received: June 10, 2018
© 2019 Elsevier B.V. All rights reserved.