Automated Pupillometry for Assessment of Treatment Success in Nonconvulsive Status Epilepticus

Abstract

Altered pupillary function may reflect nonconvulsive status epilepticus (NCSE). Neurological pupil index (NPi) assessed by automated pupillometry is a surrogate marker of global pupillary function. We aimed to assess NPi changes in relation to NCSE treatment response. In this prospective observational study, serial automated pupillometry was performed in 68 NCSE episodes. In accordance with local standards, patients were treated with clonazepam (1–2 mg), levetiracetam (40 mg/kg), and lacosamide (5 mg/kg) in a stepwise approach under continuous electroencephalography monitoring until NCSE was terminated. Patients with refractory NCSE received individualized regimens. NPi was assessed bilaterally before and after each treatment step. For statistical analysis, the lower NPi of both sides (minNPi) was used. Nonparametric testing for matched samples and Cohen’s d to estimate effect size were performed. Principal component analysis was applied to assess the contribution of baseline minNPi, age, sex, and NCSE duration to treatment outcome. In 97.1% of 68 episodes, NCSE could be terminated; in 16.2%, NCSE was refractory. In 85.3% of episodes, an abnormal baseline minNPi\u2009≤\u20094.0 was obtained. After NCSE termination, minNPi increased significantly (p\u2009<\u20090.001). Cohen’s d showed a strong effect size of 1.24 (95% confidence interval 0.88–1.61). Baseline minNPi was higher in clonazepam nonresponders vs. responders (p\u2009=\u20090.008), minNPi increased in responders (p\u2009<\u20090.001) but not in nonresponders. NCSE refractivity was associated with normal baseline minNPi (principal component analysis, component 1, 32.6% of variance, r\u2009=\u20090.78), male sex, and longer NCSE duration (component 2, 27.1% of variance, r\u2009=\u20090.62 and r\u2009=\u20090.78, respectively). Automated pupillometry may be a helpful noninvasive neuromonitoring tool for the assessment of patients with NCSE and response to treatment.