The ExTINGUISH Modified Rankin Scale: A Comprehensive Functional Outcome Measure for NMDAR Encephalitis
Ka-Ho Wong1, Gregory Day2, Christopher Coffey3, Ursula Utz4, David Clifford5, Eric Klawiter6, J. Singleton7, Dixie Ecklund3, David Klements6, Michele Costigan8, Erin Steinhart6, Brenda Pearson3, Christina Desir6, Josep Dalmau9, Maarten Titulaer10, Stacey Clardy11
1U of U Neurology Clinic, 2Mayo Clinic, 3University of Iowa, 4NINDS, 5Washington University School of Med, 6Massachusetts General Hospital, 7University of Utah Department of Neurology, 8University of Iowa College of Public Health, 9Institut d'Investigacions Biomèdiques August Pi i Sunyer, 10Erasmus Medical Center, 11University of Utah
Objective:
To refine the modified Rankin Scale(mRS) to reflect the impact of psychiatric and cognitive deficits on daily functioning in patients with N-methyl-D-aspartate receptor encephalitis(NMDARE).
Background:
The mRS is a 7-point scale validated for poststroke motor outcomes and widely used to assess functional recovery in neurologic disorders. At the time of ExTINGUISH trial’s initiation, no prospectively validated measure captured the full spectrum of disability in NMDAR encephalitis. Given the disease’s prominent cognitive, behavioral, and psychiatric manifestations, adapting the mRS to include nonmotor domains was essential to reflect meaningful change in treated patients.
Design/Methods:
ExTINGUISHmRS was developed collaboratively by protocol co-investigators and the NeuroNEXT Coordinating Centers to expand the standard mRS to include domains assessing cognitive, behavioral, and psychiatric disability. Site investigators completed standardized online training and testing to ensure scoring accuracy and adherence to protocol guidelines. Scoring consistency was maintained through algorithmic support, centralized adjudication, and ongoing rater calibration. The ExTINGUISHmRS serves as the trial’s primary outcome, analyzed as a ranked composite endpoint based on change from baseline to 16 weeks, use of rescue therapy, and time to recovery.
Results:
Implementation of ExTINGUISHmRS standardized functional outcome assessment across trial sites. Of 94 trained investigators, 86(91.5%) passed initial certification, and 8(8.5%) required retraining before passing on a second attempt. Structured training, centralized adjudication, and real-time quality monitoring minimized scoring discrepancies and supported consistent scoring across sites. The adapted scale successfully operationalized both motor and nonmotor contributors to disability, enabling comprehensive assessment of functional outcomes in NMDAR encephalitis.
Conclusions:
ExTINGUISHmRS provides a comprehensive, standardized tool for evaluating functional outcomes in NMDAR encephalitis by integrating psychiatric, cognitive, and motor domains. Successful rater certification across sites demonstrates the feasibility of implementing a structured, multidimensional outcome measure in a multicenter trial. This adaptation enables standardized assessment of clinically meaningful disability in autoimmune encephalitis and lays foundation for future validation studies.
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