Background

Neurological examination is a powerful tool for diagnosing and measuring progression of neurodegenerative diseases. However, examinations are resource intensive and thus not practical for comprehensive measurement of neurological disability in chronic diseases. A remote digital solution may be more practical and particularly relevant now due to the ongoing COVID-19 pandemic.

Objectives

To clinically validate a digital adaptation of the Symbol Digit Modalities Test (SDMT) developed as part of a smartphone test suite replicating aspects of a neurological exam.

Methods

Participants consisted of healthy volunteers (HV; n=39) and multiple sclerosis (MS; n=154) patients, with a longitudinal subcohort that performed tests at home (n=15). During clinic visits, the smartphone test suite was administered alongside a full neurological exam. The smartphone SDMT featured randomization of symbol-digit code and testing sequence. The subjects also underwent written SDMT and brain MRI.

Results

Performance differed significantly between HV and MS cohorts (p<.0001). Performance on smartphone and written SDMT had strong evidence of association (R²=0.71, concordance coefficient CCC=0.69, p<.0001). Smartphone SDMT had higher criterion validity than written SDMT measured by correlation with T2 lesion load and brain atrophy. Correlations with NeurEx subdomains identified neurological functions involved in performance of each of the 3 functional cognitive tests. Correcting for these contributing non-cognitive disabilities generated linear regression models strongly predicting the amount of MS-related brain injury measured by volumetric MRI (R² = 0.75, p < 0.0001 vs R² = 0.62, p < 0.0001). Of the longitudinal cohort, 87% of patients demonstrated practice effects measured by non-linear regression. Averaging multiple sequential post-learning results significantly decreased threshold for identifying true test deteriorations on a patient level.

Conclusions

Smartphone SDMT allows for less resource intensive remote administration. The clinometric properties of smartphone SDMT compare to or outperform written SDMT. This study expands the validation of multiple neurological tests administered via smartphone and bring us closer to a patient-autonomous neurological examination.

Acknowledgments: The research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID).

Notice: This study involved patients and was approved by NIAID IRB.