3.1.2 Management Considerations
Management of our patient presented a challenge due to disease location and high recurrence rate of meningitis. Upon the identification of the area of CSF leak, interventional closure of the dura mater defect is ideal in order to prevent life-threatening meningitis events as well as to improve symptoms. However, in our patient, surgical closure was not an option given the location and size of the dura matter defect. Thus, medical therapy targeted towards GSD management became the priority.
The risk of using systemic sirolimus was initially considered too high due to its immunosuppressive effects in the setting of our patient’s recent life-threatening infections. Weekly subcutaneous pegylated interferon alpha 2b was initiated given its reported beneficial effect in GSD [20]. Interferon alpha 2b, only available in injectable form, became less preferentially used as first line therapy when sirolimus demonstrated efficacy in treating GSD. Interferon alpha 2b has a black box warning for potential development of spastic diplegia in patients younger than 3 years (our patient was older) and can cause flu-like symptoms such as myalgia, headaches, fatigue, and low-grade fever within 24 hours after administration.
In order to inhibit osteoclastic activity and try to prevent further bone destruction, our patient also received bisphosphonate therapy with zoledronic acid. The combination of mTOR inhibitor and bisphosphonates has been described to have good effect in complex lymphatic anomalies with bone lytic lesions [21].
Our patient’s headaches resolved on interferon alpha 2b and bisphosphonate therapy. Repeat cysternogram showed improved intracranial hypotension and substantially smaller dura mater defect, although not completely closed. After two years without any new episodes of meningitis, we transitioned to sirolimus and zoledronic acid. Some of his lytic bone lesions have improved, while the remainder are stable. Although non-curative, his treatment regimen has not only stopped the disease progression but also lessened his CSF leak and intracranial hypotension, resolved his headaches and improved his QOL.