Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type\xa02

Tim Godel,Mathias Gelderblom,Christian Hagel,Said Farschtschi,Martin Bendszus,Philipp Bäumer,Sabine Heiland,Klaus Püschel,Victor-Felix Mautner,Barbara Hofstadler

doi:10.1007/s00062-021-01102-5

Abstract

PurposeTo examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology.MethodsIn this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3–S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14–100 months. In one patient, imaging findings were further correlated to histology.ResultsFollow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm2 vs. 2.15 mm2, p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified.ConclusionPeripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.

Highlights

Neurofibromatosis type 2 (NF2) is an autosomal dominant inherited tumor syndrome characterized by the development of schwannomas as the predominant tumor entity [1]
A subsequent magnetic resonance neurography (MRN) study that investigated children with NF2 revealed that both dorsal root ganglia (DRG) hyperplasia and peripheral nerve microlesions occur to a similar extent compared to adults with severe PNP
Volumes of DRG L3–S2 as well as peripheral nerve lesion diameters and counts per category were quantitatively assessed for a total of 6 NF2 patients by initial and follow-up examinations 70.0 ± 37.7 months later (Fig. 2, Table 1)

Summary

Introduction

Neurofibromatosis type 2 (NF2) is an autosomal dominant inherited tumor syndrome characterized by the development of schwannomas as the predominant tumor entity [1]. More recent studies considered multiple Schwann cell tumorlets along peripheral nerves, radiological classified as peripheral nerve lesions, to be responsible for the development of PNP, with a close correlation between the number of noncompressive lesions and the severity of associated symptoms [3,4,5,6]. A subsequent MRN study that investigated children with NF2 revealed that both DRG hyperplasia and peripheral nerve microlesions occur to a similar extent compared to adults with severe PNP. These observations suggest that alterations of the peripheral nervous system (PNS) occur very early in the time course of NF2, show a limited instead of a linear or continuous growth, and additional longterm processes might be responsible for development of neuropathic symptoms

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