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.