Prevalence of Elevated Opening Pressure Measurements in Alexander Disease

Alexander disease (AxD) is caused by a gain-of-function mutation in GFAP resulting in the formation of Rosenthal fibers, which are hypothesized to impair cerebrospinal fluid circulation, potentially resulting in increased ICP. We explored the prevalence of elevated intracranial pressure (ICP) in AxD.

Patients with AxD underwent a neurological examination, lumbar puncture (LP) with opening pressure (OP) with legs flexed, and brain magnetic resonance imaging (MRI). Elevated OP was defined as >28 cm H₂O. A neuroradiologist (masked to clinical data and OP) reviewed MRIs for imaging signs of elevated ICP (flattened posterior sclerae, enlarged optic nerve sheaths, partially empty sella, and dural sinus venous stenoses). Descriptive statistics included proportions of patients with elevated OP and MRI findings. Mixed effects logistic regression was used to explore associations with elevated OP.

Sixty-nine LPs were performed in 43 patients; 21 (49%) patients had an elevated OP on at least one LP. Papilledema was not present among those with a concurrent undilated funduscopic examination. Although most patients were asymptomatic, two patients received acetazolamide for headache and vomiting with symptom benefit and reduced OP. There was no association between age and OP (P = 0.11). MRI features of increased ICP were primarily observed in those with elevated OP.

Elevated OP with legs flexed and MRI features of increased ICP occur frequently in AxD, even in the absence of overt clinical signs. The implications of increased ICP on patient outcomes and whether asymptomatic elevated OP requires treatment need to be determined in AxD.