Deep phenotyping in ataxia: The Massachusetts General Hospital (MGH) Ataxia Center: A three-decade retrospective (P9-11.007)

Abstract

<h3>Objective:</h3> We reviewed the ~3-decade experience of the MGH Ataxia Center to identify the diagnoses in patients presenting with ataxia, and to determine the success rate of diagnosis. <h3>Background:</h3> Exponential increase in the range of diagnoses in patients with cerebellar ataxia represents a challenge to the clinician. Genetic testing facilitated this advance and heightened the need for meticulous phenotyping to determine who needs gene testing, and which results are meaningful. <h3>Design/Methods:</h3> Our Patient List is an IRB-approved ongoing catalog of patients seen in the MGH Ataxia Center since its establishment in 1994, including patients followed by the Principal Investigator since 1989. We reviewed medical records of each patient: clinical evaluations, pertinent imaging, and laboratory data. When indicated we contacted gene testing labs to update information, and in some we sought re-evaluation of gene data or autopsy findings because of new genetic developments. <h3>Results:</h3> The Patient List includes 1,690 Ataxia Center patients. The diagnoses were “non-genetic” in 969, “genetic” in 679, and ongoing workup or lost to follow-up in 42. Non-genetic included acquired and degenerative cerebellar disorders such as multiple system atrophy, and non-cerebellar disorders with a gait impairment, such as normal pressure hydrocephalus and functional neurological disorder. Genetic cases were categorized as molecularly confirmed, molecularly probable, candidate diagnosis, negative work-up with genetic tests available at the time, inconclusive, or at-risk due to positive family history. Idiopathic late onset cerebellar ataxia was designated only after exhaustive negative investigation including exome analysis. Using the clinically driven method the diagnostic success was 85.5 % for all patients, and 70.8% in those with clinically suspected genetic diagnoses. <h3>Conclusions:</h3> Diagnostic success in the MGH Ataxia Center provides support for the precision medicine approach of deep clinical phenotyping as the precursor to targeted testing and underscores the need for specialized expertise in Ataxia Centers of Excellence. <b>Disclosure:</b> The institution of Dr. Crotty has received research support from Parkinson’s Foundation. Ms. Chen has nothing to disclose. Ms. Mize has nothing to disclose. Dr. Gupta has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Biogen. The institution of Dr. Gupta has received research support from Biogen. Dr. Stephen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio Therapeutics. The institution of Dr. Stephen has received research support from Sanofi. Dr. Stephen has received research support from National Institutes of Health. Jason MacMore has nothing to disclose. Dr. Schmahmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medavante. Dr. Schmahmann has stock in Cadent. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care.