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Objective: To determine a suitable outcome measure for assessing muscle strength in neurofibromatosis (NF) type 1 and NF2 clinical trials, we evaluated the intraobserver reliability of handheld dynamometry (HHD) and developed consensus recommendations for its use in NF clinical trials., Methods: Patients ≥5 years of age with weakness in at least 1 muscle group by manual muscle testing (MMT) were eligible. Maximal isometric muscle strength of a weak muscle group and the biceps of the dominant arm was measured by HHD. An average of 3 repetitions per session was used as an observation, and 3 sessions with rest period between each were performed on the same day by a single observer. Intrasession and intersession intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) were calculated to assess reliability and measurement error., Results: Twenty patients with NF1 and 13 with NF2 were enrolled; median age was 12 years (interquartile range [IQR] 9-17 years) and 29 years (IQR 22-38 years), respectively. By MMT, weak muscle strength ranged from 2-/5 to 4+/5. Biceps strength was 5/5 in all patients. Intersession ICCs for the weak muscles were 0.98 and 0.99 in the NF1 and NF2 cohorts, respectively, and for biceps were 0.97 and 0.97, respectively. The median CVs for average session strength were 5.4% (IQR 2.6%-7.3%) and 2.9% (IQR 2.0%-6.2%) for weak muscles and biceps, respectively., Conclusion: HHD performed by a trained examiner with a well-defined protocol is a reliable technique to measure muscle strength in NF1 and NF2. Recommendations for strength testing in NF1 and NF2 trials are provided., (© 2021 American Academy of Neurology.)

Objective: Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN., Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials., Results: For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows., Conclusions: These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs., (© 2016 American Academy of Neurology.)