Abstract Details

Title Neuromuscular Ultrasound for Diaphragm Assessment Following Gene Replacement Therapy in a Canine Model of X-Linked Myotubular Myopathy (XLMTM)

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P05 - (-)

Poster/Presentation
Number 083

Objective

Background BACKGROUND: Ultrasound was used to evaluate the diaphragm in spontaneously breathing, anesthetized dogs (Wild type-WT: n=1; X-Linked Myotubular Myopathy-XLMTM: n=2). XLMTM dogs develop progressively fatal skeletal and respiratory weakness and atrophy of the diaphragm. One XLMTM dog received gene replacement therapy with rAAV8-MTM1 4 weeks prior to assessments.

Design/Methods DESIGN/METHODS: The ACUC approved all experiments in live animals. A 15 MHz linear probe was placed in the lowest intercostal space on either side to assess diaphragm thickness and echogenicity using the B mode through the liver windows. A 4 MHz vascular probe was placed in the right subcostal space in the mid-clavicular line to assess the amplitude of diaphragmatic excursion during spontaneous breathing using the M mode. Doxapram, a respiratory stimulant, was administered and measurements were repeated.

Results RESULTS: The muscular portion of diaphragm was easily identified using ultrasound probes. Quantitative parameters of the diaphragm structure assessed using ultrasound were found to be different among genotypes. The WT diaphragm was noted to be thicker and less echogenic than the XLMTM diaphragm. The dog receiving gene replacement therapy had thickness and echogenicity measurements comparable to the WT dog and significantly different from the untreated XLMTM dog. Velocity of diaphragm contraction was similar among the three animals.

Conclusions CONCLUSIONS: This pilot demonstrates feasibility and utility of using ultrasound for quantitative assessment of diaphragmatic structure and function in a canine model. This non-invasive technique has the potential to replace or supplement invasive measures of diaphragm muscle function in canine models and in the future, could provide a clinically useful method to assess diaphragm function in patients with neuromuscular disorders.

Authors/Disclosures
Aarti Sarwal, MD, FAAN PRESENTER	Dr. Sarwal has received personal compensation in the range of $0-$499 for serving as a Consultant for Stimdia, Inc. Dr. Sarwal has received personal compensation in the range of $0-$499 for serving as a Consultant for Sheinkei. Dr. Sarwal has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Society of Critical Care Medicine . Dr. Sarwal has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Society of Neuroimaging . The institution of Dr. Sarwal has received research support from Butterfly, Inc. The institution of Dr. Sarwal has received research support from Bard. The institution of Dr. Sarwal has received research support from Biogen. The institution of Dr. Sarwal has received research support from Novartis. The institution of Dr. Sarwal has received research support from CVR Global. The institution of Dr. Sarwal has received research support from NIH/NIA R01 AG066910-01 . The institution of Dr. Sarwal has received research support from Image Monitoring. Dr. Sarwal has received personal compensation in the range of $500-$4,999 for serving as a Speaker/Faculty, CME courses with Society of Critical Care Medicine . Dr. Sarwal has received personal compensation in the range of $500-$4,999 for serving as a Speaker at annual congress with Intensive Care Society. Dr. Sarwal has received personal compensation in the range of $500-$4,999 for serving as a Speaker at annual congress with Indian Society of Critical Care. Dr. Sarwal has received personal compensation in the range of $500-$4,999 for serving as a speaker/Faculty for Annual meeting, travel compensation with European Society of Intensive Care Medicine. Dr. Sarwal has received personal compensation in the range of $500-$4,999 for serving as a Speaker with ISICEM. Dr. Sarwal has a non-compensated relationship as a Social Media Editor with Neurocritical Care that is relevant to AAN interests or activities. Dr. Sarwal has a non-compensated relationship as a Secretary with American Society of Neuroimaging that is relevant to AAN interests or activities. Dr. Sarwal has a non-compensated relationship as a President with Association of Indian Neurologists in America that is relevant to AAN interests or activities. Dr. Sarwal has a non-compensated relationship as a Member, Board of Directors with Neurocritical Care Society that is relevant to AAN interests or activities. Dr. Sarwal has a non-compensated relationship as a Section Chair, Neurosciences Section with Society of Critical Care Medicine that is relevant to AAN interests or activities.
	No disclosure on file
Michael Girouard	No disclosure on file
	No disclosure on file
Michael Cartwright, MD (Wake Forest School of Medicine)	Dr. Cartwright has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
Friedemann Paul (Charite Universitatsmedizin in Berlin)	Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann-La Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb GmbH & Co. KGaA (BMS. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for F&U Confirm. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb GesmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MICE Service. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for VINDICO medical education. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Beijing Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sandoz Internation GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Thailand. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology, Neuroimmunology&Neuroinflammation.
Martin K. Childers, DO, PhD (Wake Forest University School of Med)	No disclosure on file

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