Authors :
Presenting Author: Sunanjay Bajaj, MD – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Tobias Bruenger, PhD – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Alison Merket, MSc – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Anu Cherukara, MSc – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Chandler Sargent, MD – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Emile Moura Coelho da Silva, MS, CGC – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Althea Smith, MS/CGC – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Costin Leu, PhD – McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Christiane Hsu, MS – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Sarah Wilson, MD – McGovern Medical School, The University of Texas Health Science Center at Houston
Sara E. McMahan, PT – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Samden Lhatoo, MD – UTHealth Houston
Gretchen Von Allmen, MD – Division of Child and Adolescent Neurology, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Nivedita Thakur, MD – Division of Child Neurology, Department of Pediatrics, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA
Dennis Lal, PhD – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Rationale:
Sodium channelopathies such as SCN2A- and SCN8A-related disorders present with diverse multisystem symptoms. Beyond seizures, movement disorders contribute significantly to disease burden and limit activities of daily life. However, movement-based trial endpoints remain underdeveloped due to lack of standardized assessment measures. We aimed to delineate the movement disorder spectrum in sodium channelopathies using complementary clinical and wearable assessments to identify scalable outcome measures.Methods:
We conducted a prospective, multi-setting study involving 44 individuals (16 controls, 24 with SCN2A and 4 with SCN8A variants) recruited through a multidisciplinary clinic and advocacy events. Affected individuals carried (likely) pathogenic variants per ACMG guidelines. Functional effects were classified as gain (GoF), loss-of-function (LoF), or missense based on published data, clinical presentation, and in silico predictions. Participants underwent standardized, video-recorded neurological exams, scored by trained raters using three validated scales: Modified Ashworth Scale (MAS) for spasticity, Fahn-Marsden Scale (FMS) for dystonia, and the Scale for the Assessment and Rating of Ataxia (SARA). Video recordings were scored post-hoc. Participants also wore the Empatica Embrace Plus wrist-worn accelerometer for 24-72 hours to capture continuous motor activity. Wearable-derived metrics included acceleration variance, mean jerk and autocorrelation, and were analyzed in relation to genotype and clinical severity.Results:
The neurological exam differentiated affected individuals from controls by both prevalence (p< 0.001; Fisher’s test) and severity (p< 0.001; Kolmogorov- Smirnov test (KS)). SCN2A LoF carriers had milder symptoms (mean: MAS=0.10, FMS=0.39, SARA=1.05) compared to other genotypes (p< 0.05, KS) but exhibited notable speech/communication impairments. GoF carriers exhibited significantly higher scores for spasticity than LoF (p< 0.05, KS).