Peripheral nervous system alterations in infant and adult neurofibromatosis type 2

Neurology ◽  
2019 ◽  
Vol 93 (6) ◽  
pp. e590-e598 ◽  
Author(s):  
Tim Godel ◽  
Philipp Bäumer ◽  
Said Farschtschi ◽  
Isabel Gugel ◽  
Moritz Kronlage ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Healthy Controls ◽  
Magnetic Resonance Neurography ◽  
Nerve Lesions ◽  
Peripheral Nerve Lesions

ObjectiveTo examine the involvement of dorsal root ganglia and peripheral nerves in children with neurofibromatosis type 2 compared to healthy controls and symptomatic adults by in vivo high-resolution magnetic resonance neurography.MethodsIn this prospective multicenter study, the lumbosacral dorsal root ganglia and sciatic, tibial, and peroneal nerves were examined in 9 polyneuropathy-negative children diagnosed with neurofibromatosis type 2 by a standardized magnetic resonance neurography protocol at 3T. Volumes of dorsal root ganglia L3 to S2 and peripheral nerve lesions were assessed and compared to those of 29 healthy children. Moreover, dorsal root ganglia volumes and peripheral nerve lesions were compared to those of 14 adults with neurofibromatosis type 2.ResultsCompared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in children with neurofibromatosis type 2 (L3 +255%, L4 +289%, L5 +250%, S1 +257%, and S2 +218%, p < 0.001) with an excellent diagnostic accuracy. Moreover, peripheral nerve lesions occurred with a high frequency in those children compared to healthy controls (18.89 ± 11.11 vs 0.90 ± 1.08, p < 0.001). Children and adults with neurofibromatosis type 2 showed nonsignificant differences in relative dorsal root ganglia hypertrophy rates (p = 0.85) and peripheral nerve lesions (p = 0.28).ConclusionsAlterations of peripheral nerve segments occur early in the course of neurofibromatosis type 2 and are evident even in children not clinically affected by peripheral polyneuropathy. While those early alterations show similar characteristics compared to adults with neurofibromatosis type 2, the findings of this study suggest that secondary processes might be responsible for the development and severity of associated polyneuropathy.

scholarly journals Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type 2

2021 ◽  
Author(s):  
Tim Godel ◽  
Philipp Bäumer ◽  
Said Farschtschi ◽  
Klaus Püschel ◽  
Barbara Hofstadler ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nerve ◽  
Peripheral Nervous System ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Nerve Lesions ◽  
Peripheral Nerve Lesions

Abstract Purpose To 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. Methods In 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. Results Follow-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. Conclusion Peripheral 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.

scholarly journals Activation of Raf signalling in NF2-null Schwann cells leads to sustained proliferation; an investigation of a new and inducible model for human schwannoma

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv7-iv7
Author(s):  
Charlotte Lespade ◽  
Liyam Laraba ◽  
Evyn Woodhouse ◽  
Marie Srotyr ◽  
Alison C Lloyd ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Mouse Model ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Proliferation Response

Abstract Aims The NF2 gene encodes the tumour suppressor Merlin, which is deleted in 100% of patients with the familial tumour predisposition syndrome neurofibromatosis type 2 but also in 70% of those who develop sporadic schwannomas. The Raf-TR mouse model uses a tamoxifen-inducible Raf-kinase/ oestrogen receptor fusion protein (Raf-TR) expressed in myelinating Schwann cells to mimic a nerve injury response in Schwann cell by activating Raf/MEK/ERK signalling in the absence of peripheral nerve injury. We will assess whether Raf/MEK/ERK activation on an NF2 null background leads to tumourigenesis within the vestibular nerves and dorsal root ganglia (DRGs), two tumour sites identified in the Periostin-Cre mouse model in which schwannoma formation is spontaneous, with a view to generating an inducible NF2 null schwannoma mouse model. Method Mice with a Schwann cell specific loss of Merlin were crossed with mice carrying a tamoxifen-inducible Raf-TR gene to generate Raf-TR+/-; P0-Cre+/-; NF2fl/fl (Cre+) mice which were NF2 null and compared to Raf-TR+/-; P0-Cre-/-; NF2fl/fl (Cre-) littermate controls. Mice were injected with tamoxifen or vehicle for five consecutive days and their vestibular nerves and dorsal root ganglia (DRGs) were analysed at various timepoints . An EdU proliferation assay was used to quantify the proliferation in the vestibular ganglia, as well as the DRGs. Rates of proliferation were compared to Cre- age-matched littermate controls treated with tamoxifen or vehicle. Results In the Periostin-Cre NF2 null schwannoma model, tumours form spontaneously in the DRGs and vestibular ganglia. In our new model, we see a clear increase in proliferation at 21 d post-injection in the NF2 null (Cre+) tamoxifen-treated mice compared to control (Cre-) tamoxifen-treated controls in both DRGs and vestibular ganglia. Cre- tamoxifen-treated mice do not show increased proliferation compared to Cre- vehicle controls. Taken together, this shows that activation of the Raf/MEK/ERK pathway in Schwann cells only causes a sustained proliferation response on an NF2 null background in the DRGs and vestibular ganglia. We are assessing later timepoints to further characterise tumour development in these mice. Conclusion Combining the Raf-TR mouse model to create a demyelinating phenotype with an NF2 null background leads to vastly increased rates of proliferation at the sites of schwannoma tumourigenesis within the peripheral nervous system: the DRGs and the vestibular ganglia. The high proliferation in the vestibular ganglia in particular is similar to the development of vestibular schwannomas in patients with Neurofibromatosis type 2. The new mouse model used in this study shows potential to be very useful as an inducible schwannoma tumour model, in which we can study the early events of tumour formation.

Modification of astrocytes in the spinal cord following dorsal root or peripheral nerve lesions

1990 ◽  
Vol 110 (3) ◽  
pp. 248-257 ◽  
Author(s):  
Marion Murray ◽  
Shwun-De Wang ◽  
Michael E. Goldberger ◽  
Pat Levitt
Keyword(s):  
Spinal Cord ◽  
Peripheral Nerve ◽  
Dorsal Root ◽  
Nerve Lesions ◽  
Peripheral Nerve Lesions

Malignant peripheral nerve sheath tumor: Transformation in a patient with neurofibromatosis type 2

2018 ◽  
Vol 66 (2) ◽  
pp. e27520 ◽  
Author(s):  
Laura Agresta ◽  
Ralph Salloum ◽  
Trent R. Hummel ◽  
Nancy Ratner ◽  
Francesco T. Mangano ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Nerve Sheath ◽  
Tumor Transformation

Fascicular Ratio Pilot Study: High-Resolution Neurosonography—A Possible Tool for Quantitative Assessment of Traumatic Peripheral Nerve Lesions Before and After Nerve Surgery

Neurosurgery ◽  
2018 ◽  
Vol 85 (3) ◽  
pp. 415-422 ◽  
Author(s):  
Christian Heinen ◽  
Patrick Dömer ◽  
Thomas Schmidt ◽  
Bettina Kewitz ◽  
Ulrike Janssen-Bienhold ◽  
...  
Keyword(s):  
High Resolution ◽  
Peripheral Nerve ◽  
Quantitative Assessment ◽  
Control Group ◽  
Structural Reorganization ◽  
Magnetic Resonance Neurography ◽  
Nerve Lesions ◽  
Peripheral Nerve Lesions ◽  
Significant Difference ◽  
Nerve Surgery

Abstract BACKGROUND Clinical and electrophysiological assessments prevail in evaluation of traumatic nerve lesions and their regeneration following nerve surgery in humans. Recently, high-resolution neurosonography (HRNS) and magnetic resonance neurography have gained significant importance in peripheral nerve imaging. The use of the grey-scale-based “fascicular ratio” (FR) was established using both modalities allowing for quantitative assessment. OBJECTIVE To find out whether FR using HRNS can assess nerve trauma and structural reorganization in correlation to postoperative clinical development. METHODS Retrospectively, 16 patients with operated traumatic peripheral nerve lesions were included. The control group consisted of 6 healthy volunteers. All imaging was performed with a 15 to 6 MHz ultrasound probe (SonoSite X-Porte; Fujifilm, Tokyo, Japan). FR was calculated using Fiji (兠) on 8-bit-images (“MaxEntropy” using “Auto-Threshold” plug-in). RESULTS Thirteen of 16 patients required autologous nerve grafting and 3 of 16 extra-intraneural neurolysis. There was no statistical difference between the FR of nonaffected patients’ nerve portion with 43.48% and controls with FR 48.12%. The neuromatous nerve portion in grafted patients differed significantly with 85.05%. Postoperatively, FR values returned to normal with a mean of 39.33%. In the neurolyzed patients, FR in the affected portion was 78.54%. After neurolysis, FR returned to healthy values (50.79%). Ten of 16 patients showed clinical reinnervation. CONCLUSION To our best knowledge, this is the first description of FR using HRNS for quantitative assessment of nerve damage and postoperative structural reorganization. Our results show a significant difference in healthy vs lesioned nerves and a change in recovering nerve portions towards a more “physiological” ratio. Further evaluation in larger patient groups is required.

scholarly journals Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2

Brain ◽  
2002 ◽  
Vol 125 (5) ◽  
pp. 996-1004 ◽  
Author(s):  
A. D. Sperfeld ◽  
C. Hein ◽  
J. M. Schröder ◽  
A. C. Ludolph ◽  
C. O. Hanemann
Keyword(s):  
Peripheral Nerve ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Nerve Involvement ◽  
Peripheral Nerve Involvement
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