Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2

Abstract

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the occurrence of bilateral vestibular schwannomas, various brain and spinal tumours as well as peripheral nerve tumours, cutaneous tumours and juvenile posterior lenticular opacity. NF2 is caused by mutations in both alleles of a tumour suppressor gene coding for a protein called schwannomin or merlin. It is suggested that the development of NF2 tumours is caused by complete inactivation of the merlin/schwannomin gene. Interestingly, in a NF2 mouse model, peripheral nerve pathology was more frequently described than schwannomas. However, review of the literature shows that patients suffering from NF2 seldom have unexplained clinical features of peripheral nerve lesion unrelated to tumour masses. Single case reports describe sural nerve biopsies, which histologically show onion-bulb-like formations, seemingly originating from Schwann cells. We have conducted a systematic investigation to determine the occurrence and aetiology of peripheral nerve involvement in NF2 patients. We investigated 15 patients with definite NF2 and in 10 of these found electrophysiological evidence of neuropathy. In this study we present the classification of neuropathy, correlation to clinical findings, and histological findings of a sural nerve biopsy. We conclude that peripheral neuropathy, mostly of axonal type, is a common clinical finding in NF2. We hypothesize that the aetiology of this frequent peripheral neuropathy syndrome in NF2 is caused by compression effects of multiple tumourlets, originating along the length of the peripheral nerves on adjacent nerve fibres, by local influences of the endoneurial pathological cells on adjacent nerve fibres and/or the inability of these cells to properly adhere to, or ensheath, the axon.

Tumor Suppressor Schwannomin/Merlin Is Critical for the Organization of Schwann Cell Contacts in Peripheral Nerves

“…It is also possible that a gene dosage effect occurs, especially taking into account the long lifespan of humans compared with mice. Neuropathies have been reported in NF2 patients that may not be all accounted for by microcompressions (Sperfeld et al, 2002). Our results suggest that primary alterations in Schwann cell biology may also play a role in these neuropathies and provide an incentive for further exploring this issue, which may have diagnostic and therapeutic implications.…”

Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]

“…1,44 Further evidence for the mononeuropathy of childhood and the polyneuropathy of adulthood has come from sural nerve biopsies. 45 4 Evans et al 1 Parry et al 33 Mautner et al 34 No …”

Multiple central nervous system tumors, neurofibromatosis type 2, a case report

“…However, low-grade gliomas and ependymomas have also been observed. NF-2 patients represent 2.5% of all patients with intramedullary spinal tumors and intramedullary tumors of the spinal cord, such as ependymoma, occur in 5 to 33% of individuals with NF-2 [4]. Patients with spinal cord involvement can have multiple tumors.…”

“…Spinal cord tumors typically remain quiescent for lengthy periods with a potential lag time of 3 to 4 years between onset of symptoms and the diagnosis. Imaging of the brain and spine at yearly intervals is usually recommended in patients who have been known to have brain and spinal tumors or sooner if symptoms develop [4,5].…”