Abstract Details

Title Clinical and Pathological Characterization of VPS16 Dystonia

Topic Movement Disorders

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-005

Objective To expand the clinical, radiologic and pathologic understanding of VPS16 related dystonia.

Background

Variants in VPS16 have been associated with isolated dystonia in 35 cases from Chinese and European cohorts, including report of brainstem signal change on MRI.

Design/Methods We describe clinical features in 10 additional individuals with isolated dystonia and VPS16 variants, including neuroimaging on a subset and pathology in one, and perform pooled analysis with published cases.

Results 80% were men, mean age onset was 14.1 years (range 5-30), and mean age at exam was 35.89 years (range 11-73). Four began with arm, 3 with leg, and 3 with neck dystonia. Only one remained focal (arm); others became generalized (7), multifocal (1) or segmental (1). Brachial involvement was present in 90%, with 80% crural, 70% cranial/bulbar, and 50% cervical involvement. Two individuals underwent deep brain stimulation and one thalamotomy. Four cases were related, and five others had family history. MRI was available in two cases and demonstrated red nucleus and cerebral peduncle T2 hypointensity. Neuropathologic evaluation in one case (post bilateral GPi DBS) demonstrated asymmetric severe gliosis and marked neuronal loss of the left subthalamic nucleus with optically empty vacuoles and much less right-sided involvement. Pooled analysis with 34 additional published cases showed 62.22% male and average onset of 14.53 years (range 3-50). Onset site was 20.45% cranial/bulbar, 54.55% limb, and 36.36% axial (cervical or trunk); 75% of cases exhibited cranial/bulbar symptoms, 90.9% limb and 81.82% axial involvement.

Conclusions Expansion of known cases of VPS16 dystonia further support that it is a childhood- or adolescent-onset disorder, typically with limb or cervical onset that often spreads to the arm and leg. Additional histopathologic and metabolomic evaluation is underway to better understand the lysosomal and endolysosomal pathophysiology that may contribute to both vacuolization in the subthalamic nucleus as well as T2 brainstem hypointensities.

Authors/Disclosures
Mariel Pullman, MD (Mount Sinai Beth Israel) PRESENTER	The institution of Dr. Pullman has received research support from Empire Clinical Research Investigator Program.
Deborah Raymond (Beth Isreal Medical Center)	The institution of Ms. Raymond has received research support from NIH.
Walter J. Molofsky, MD (Mount Sinai Hospital)	Dr. Molofsky has nothing to disclose.
Naomi Lubarr, MD (Mount Sinai Beth Israel Medical Center)	Dr. Lubarr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for applied therapeutics.
Katherine E. Leaver, MD	Dr. Leaver has nothing to disclose.
Roberto P. Ortega, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Fedor Panov	Fedor Panov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for neuropace. Fedor Panov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for zimmer biomet.
	No disclosure on file
Laurie J. Ozelius, PhD	The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care.
Rachel J. Saunders-Pullman, MD (Mount Sinai Beth Israel, Neurology, Downtown Union Square)	The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program.
Susan B. Bressman, MD, FAAN (Mount Sinai Health System)	The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH .

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