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Abstract Details

Prevalence of Elevated Intracranial Pressure in Alexander Disease
Child Neurology and Developmental Neurology
S2 - Child Neurology and Developmental Neurology 1 (1:48 PM-2:00 PM)
005

AxD is caused by a gain of function mutation in GFAP and formation of Rosenthal fibers. With a predilection for perivascular, subpial, and subependymal astrocytes, Rosenthal fibers are hypothesized to impair CSF circulation, resulting in increased ICP.

To determine the prevalence of elevated intracranial pressure (ICP) in subjects with Alexander disease (AxD).
Subjects with AxD, confirmed by GFAP testing and enrolled in a natural history study, were included. Study procedures included neurologic exam, LP with opening pressure (OP), and brain MRI. OP was conservatively defined as elevated if >28 cm H2O. MRIs were reviewed by a neuroradiologist (masked to clinical data and OP) for imaging signs of elevated ICP (e.g., flattened sclerae, enlarged optic nerve sheaths, empty sella, and sinus venous stenoses). Linear mixed effects regression was used to explore OP as a function of age. Random forest analysis was used to predict OP from imaging variables.

Sixty-one LPs were performed in 40 subjects; 20 (50%) had elevated OP on at least one LP. Eighteen subjects had longitudinal LPs; 9 demonstrated an increase in OP compared to baseline, while the others were stable (N=2) or decreased (N=5, all asymptomatic and untreated). The remaining 2 subjects received acetazolamide for headache and vomiting with symptom benefit and reduced OP. There was no association between age and OP (p=0.19). Anesthesia (N=35) and procedures were well tolerated without complications.

Twenty-one subjects (totaling 28 LPs) had an undilated fundus exam ≤1 day prior to the LP; none had papilledema. MRI features of elevated ICP predicted high OP (R2=0.637). 

Elevated OP and MRI features of elevated ICP occur frequently in AxD, even in the absence of clinical signs. The implications of elevated ICP on patients’ outcomes and whether elevated ICP requires treatment need to be determined in patients with AxD.

Authors/Disclosures
Joshua Joung, Other (Children's Hospital of Philadelphia)
PRESENTER
The institution of Mr. Joung has received research support from Ionis Pharmaceuticals.
John Rainer Sollee (Sidney Kimmel Medical College At Thomas Jefferson University) Mr. Sollee has nothing to disclose.
Kathryn Gallison, Other (The Children's Hospital of Philadelphia) The institution of Miss Gallison has received research support from Ionis Pharmaceuticals.
Geraldine *Use 388658 Liu An immediate family member of Geraldine Liu has received publishing royalties from a publication relating to health care.
Hannah Rose Cooper (Children'S Hospital of Philadelphia) Ms. Cooper has nothing to disclose.
Walter Faig, PhD Mr. Faig has nothing to disclose.
Heather McClung, MD (Children's Hospital of Philadelphia) Dr. McClung has nothing to disclose.
Elizabeth Drum, MD (Children's Hospital of Philadelphia) The institution of Dr. Drum has received research support from American Society of Anesthesiologists.
Sona Narula, MD (CHOP) Dr. Narula has received personal compensation in the range of $0-$499 for serving as a Consultant for Medscape .
Grant Liu, MD, FAAN (Div. of Neuro-Ophthalmology) Dr. Liu has received publishing royalties from a publication relating to health care.
Robert Avery, DO, MSCE (Children's Hospital of Philadelphia ) Dr. Avery has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ovid. Dr. Avery has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. The institution of Dr. Avery has received research support from NIH. Dr. Avery has received intellectual property interests from a discovery or technology relating to health care.
Arastoo Vossough, MD (University of Pennsylvania - Children'S Hospital of Philadelphia) Dr. Vossough has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Syneos Health. Dr. Vossough has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for DeepSight. Dr. Vossough has received publishing royalties from a publication relating to health care.
Amy T. Waldman, MD (Children's Hospital of Philadelphia) Dr. Waldman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio. An immediate family member of Dr. Waldman has stock in Pfizer. The institution of Dr. Waldman has received research support from Ionis Pharmaceuticals. Dr. Waldman has received publishing royalties from a publication relating to health care.