Abstract BACKGROUND Patients with neurofibromatosis type 1 (NF1) can develop plexiform neurofibromas (PN). PN are peripheral nerve sheath tumors that can cause pain, neurological deficit and can transform into malignant peripheral nerve sheath tumors (MPNST). High-resolution ultrasound (HRUS) is suggested as a quick and cost-effective technique, as compared to whole-body MRI, for screening NF1 patients for PN. Our aim is to describe the variety of HRUS nerve abnormalities in NF1 patients and to study the link between nerve morphology and nerve function. MATERIAL AND METHODS We selected patients with a clinical diagnosis of NF1, with or without symptoms related to the peripheral nervous system (PNS) such as pain, sensory disturbances or loss of strength. Patients were invited for a study visit including neurological examination, nerve conduction studies (NCS) and HRUS. One-sided NCS were performed of the median and ulnar nerve (motor and sensory), peroneal and tibial nerve (motor) and sural nerve according to standard protocol. We visualised the brachial plexus, median-, radial-, ulnar-, peroneal-, tibial-, and sural nerves on both sides using HRUS. The cross-sectional area (CSA) of the nerve was measured at predefined anatomical sites, and additional sites in case of focal nerve enlargement. RESULTS We enrolled 60 NF1 patients, of which 57% had PNS-related symptoms. One third of our patients had neurological deficits during physical examination. We found nerve enlargement with HRUS in 48 out of 60 patients (80%), this was not significantly different between patients with PNS symptoms or without PNS symptoms (82% vs 77% respectively, p=0.602). In 82% of the patients with PNS symptoms, their symptoms were likely to be related to one or more nerve enlargements. Nine of these patients had clinical and neurophysiological signs of carpal tunnel syndrome. Different patterns of nerve enlargement were identified. 46% had isolated nerve enlargements, 25% had diffusely enlarged nerves and 29% had a mixture of diffusely enlarged nerves with isolated nerve enlargements. The majority of the patients with nerve enlargement on HRUS had no abnormalities on NCS (65%). CONCLUSION The majority of NF1 patients have nerve enlargements as seen by HRUS, however we have shown that nerve enlargements can often be asymptomatic and do not always lead to impaired nerve function. To determine whether patients have PN cannot be based solely on clinical evaluation of symptoms. HRUS might have an application as a screening tool for NF1 patients in clinical practice. However, further research is needed to describe growth of nerve enlargements, the impact of intra- and interobserver variability on CSA measurements and to improve our knowledge on the link between nerve morphology and nerve function in NF1.