P 967. IRIS—A Dreaded Complication of Tuberculous Meningitis
30 October 2018 (online)
Background: Even with adequate treatment, tuberculous meningitis (TBM) can be complicated by a life-threatening, progressive vasculitis as part of an immune reconstitution inflammatory syndrome (IRIS). In addition to the standard anti-inflammatory therapy with steroids, there is an increasing use of the immune-modulatory effect of thalidomide.1
Data of the Robert-Koch Institute2 show that there is an increasing incidence of tuberculosis in Germany in recent years. It was 7.1 and 7.2/100.000 in 2015 and 2016, respectively, which is an increase of ∼30% compared with 2014. In children and adolescents, the peak incidence is under 5 years of age and there were ∼19% more infected children in 2016 than the year before. In 2015, four and in 2016, three children with predominant central nervous system symptoms were registered. All of them were younger than 5 years—one girl (4 years old) died. Specific treatment recommendations for complicated courses of tuberculosis are still missing—even after introduction of the Concensus-Based Guidelines for Tuberculosis in Children and Adolescents.3
Goals: We aim to increase awareness of complicated courses of tuberculosis, such as IRIS. We want to suggest a diagnostic and therapeutic approach for TBM in childhood, which has to be evaluated by adequate trials.
Question: Which diagnostic approach is able to recognize progression to IRIS or a cerebral vasculitis as a complicated course of tuberculosis at an early stage? What are the therapeutic options in these cases?
Methods: We describe two boys (5 years and 3 years 5 months), who suffered from TBM with IRIS while receiving adequate tuberculostatic therapy in 2014 and 2016. They were monitored by serial transcranial Doppler and duplex sonography and cerebral MRI/MRA including vasculitis sensitive sequences (spectral presaturation with inversion recovery [SPIR]). After screening of the literature, we added thalidomide to the steroid-based anti-inflammatory therapy.
Results: A 5-year-old boy with TBM, distinctive basal arachnoiditis, and open tuberculosis clinically improved on tuberculostatic therapy. Neuroimaging showed progression of the vasculitis and basal arachnoiditis in spite of dexamethasone therapy. Recurring ischemic strokes lead to the use of thalidomide. He survived with severe neurologic and neurosurgical (shunting procedures for hydrocephalus) sequelae.
A 3-year-old boy with TBM and ischemic complications was treated with thalidomide and was regularly screened by transcranial Doppler sonography and stabilized with normalization of his cerebral vasculature.
Conclusion: Patients with TBM should be monitored thoroughly for development of cerebral vascular disease. Therefore, the noninvasive transcranial Doppler and duplex sonography performed once a week is suitable as an addition to the MRI (with MR angiography and SPIR sequences), which then can be performed in a frequency of every 3 months.
In the case of basal arachnoiditis and tuberculomas, thalidomide is a therapeutic option. Clinical experience has shown that thalidomide may influence the severity of TBC-associated cerebral vasculitis in a positive way (van Toorn, personal communication). At the same time, existing data yielded conflicting results,4 so that a confirmation of the above-mentioned therapeutic effect of thalidomide by randomized, controlled trials is still missing.
There is a scarcity of evidence considering the benefit of other immunomodulatory therapies such as cyclophosphamide. Due to the potential fatal course and dreaded neurological sequelae of TBM, we suggest considering the use of thalidomide at an early stage of the disease process.
van Toorn R, du Plessis AM, Schaaf HS, Buys H, Hewlett RH, Schoeman JF. Clinicoradiologic response of neurologic tuberculous mass lesions in children treated with thalidomide. Pediatr Infect Dis J 2015;34(2):214–218
Bericht zur Epidemiologie der Tuberkulose in Deutschland für 2016 Robert Koch-Institut, Berlin 2017. DOI: 10.17886/rkipubl-2017-004
Feiterna-Sperling C, Brinkmann F, Adamczick C, et al. [Consensus-based guidelines for diagnosis, prevention and treatment of tuberculosis in children and adolescents - a guideline on behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. Pneumologie 2017;71(10):629–680
Schoeman JF, Springer P, van Rensburg AJ, et al. Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J Child Neurol 2004;19(4):250–257