Distinctive low epidermal nerve fiber density in schwannomatosis patients provides a major parameter for diagnosis and differential diagnosis

Farschtschi, Said; Schön, Gerhard; Friedrich, Reinhard E; Matschke, Jakob; Glatzel, Markus; Weis, Joachim; Hagel, Christian; Mautner, Victor‐Felix

doi:10.1111/bpa.12780

Cited by 5 publications

(8 citation statements)

References 15 publications

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“…In our study, all schwannomatosis patients showed considerable reduction of the intraepidermal nerve fiber density, indicative of chronic small-fiber neuropathy as cause for the neuropathic pain experienced by schwannomatosis patients. Moreover, we found strong evidence that this reduction of intraepidermal nerve fiber density is pathognomonic for schwannomatosis in the spectrum of similar disorders especially in contrast to neurofibromatosis type 2 [13]. In analogy to other small-fiber entities [31,32], the combination of clinical pain pattern and the observed LEP abnormalities strongly suggests the presence of small-fiber neuropathy as an intrinsic disease feature of schwannomatosis.…”

Section: Discussionsupporting

confidence: 54%

“…Regarding LEP amplitudes, no differences were detected in the patient group compared to matched controls (N2: exhibited a significant reduction of intraepidermal nerve fiber density (1.85 ± 0.92/mm) in comparison to age-adjusted reference-values (1.7-5.7/mm) [12] with a mean deviation from the age-dependent reference value of 1.84 ± 1.24/mm (Figure 4). Please note that the skin biopsy results presented here are a subset of data published in 2020 [13]. Interestingly, the observed reduction in intraepidermal nerve fiber density (IENFD) was neither associated with lesion burden as assessed by MR neurography (MRN), nor did it show any significant correlation with laser-evoked potentials (LEP) parameters.…”

Section: Laser Evoked Potentialsmentioning

confidence: 73%

“…The raw IEND data were plotted against age, separately for male and female patients and compared to the normative reference IEND. Some parts of this analysis have already been published in a comparative study with patients exhibiting NF2 [13]; that protocol focused on establishing a new diagnostic approach for differential diagnosis and is a follow-up protocol to this study.…”

Section: Skin Biopsies and Intraepidermal Nerve Fiber Densitymentioning

confidence: 99%

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C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis

Farschtschi

Mainka

Glatzel

et al. 2020

IJMS

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Schwannomatosis is the third form of neurofibromatosis and characterized by the occurrence of multiple schwannomas. The most prominent symptom is chronic pain. We aimed to test whether pain in schwannomatosis might be caused by small-fiber neuropathy. Twenty patients with schwannomatosis underwent neurological examination and nerve conduction studies. Levels of pain perception as well as anxiety and depression were assessed by established questionnaires. Quantitative sensory testing (QST) and laser-evoked potentials (LEP) were performed on patients and controls. Whole-body magnetic resonance imaging (wbMRI) and magnetic resonance neurography (MRN) were performed to quantify tumors and fascicular nerve lesions; skin biopsies were performed to determine intra-epidermal nerve fiber density (IENFD). All patients suffered from chronic pain without further neurological deficits. The questionnaires indicated neuropathic symptoms with significant impact on quality of life. Peripheral nerve tumors were detected in all patients by wbMRI. MRN showed additional multiple fascicular nerve lesions in 16/18 patients. LEP showed significant faster latencies compared to normal controls. Finally, IENFD was significantly reduced in 13/14 patients. Our study therefore indicates the presence of small-fiber neuropathy, predominantly of unmyelinated C-fibers. Fascicular nerve lesions are characteristic disease features that are associated with faster LEP latencies and decreased IENFD. Together these methods may facilitate differential diagnosis of schwannomatosis.

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Section: Discussionsupporting

confidence: 54%

Section: Laser Evoked Potentialsmentioning

confidence: 73%

Section: Skin Biopsies and Intraepidermal Nerve Fiber Densitymentioning

confidence: 99%

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C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis

Farschtschi

Mainka

Glatzel

et al. 2020

IJMS

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“…Farschtschi et al [24] measured the intraepidermal nerve ber density (IEND) of skin biopsies and found that the IEND of patients with schwannomatosis (97%) was signi cantly lower than the standard reference, while fewer than half (44%) of NF2 patients had such low IEND. (6) Louvrier et al [25] suggested that the key to differential diagnosis between NF2 and schwannomatosis is the use of an ampli cation-based method to sequence tumor suppressor genes in NF2: SMARCB1, LZTR1, SWI/SNF-related matrix-associated actindependent regulator of chromatin subfamily E member 1 (SMARCE1) and suppressor of fused homolog (SUFU).…”

Section: Differential Diagnosismentioning

confidence: 99%

Analysis of Imaging and Pathological Features in 12 Cases of Schwannomatosis and Literature Review

Kang

et al. 2021

Preprint

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Objective We analyzed US, CT, and MR images plus the pathological characteristics of 12 patients with pathologically confirmed schwannomatosis to explore the relationship between imaging and pathology.Method A retrospective analysis was undertaken over a 10-year period (01/01/2000-31/12/2019) of 12 patients undergoing Imaging and pathological examination for schwannomatosis, and the relevant literature was reviewed.Results The median age at diagnosis was 39.4 years (range, 22–56 years). We included the mean diameter of 36 lesions (5.10 ± 0.84 cm; range, 0.5–9.1 cm) in the focal observation. US showed that the mass boundary was clear, and most of the masses were low echo. CT showed that tumors were low density; the plain-scan CT value was 22–35 HU and enhancement amplitude 10–30 HU. MRI showed that most of the tumors were low or medium signal on T1-weighted image (T1WI) and high signal on T2WI; enhancement could be homogeneous or inhomogeneous. We could see the cellular Antoni A and myxoid Antoni B areas of the microscopic morphology. According to the proportions of the two areas, masses could be divided into four types: I, II, III and IV. Immunohistochemical (IHC) staining showed that the expression of S-100 protein was diffusely positive (36/36).Conclusions Imaging examination in schwannomatosis is helpful for localization and characterization of focus, as well as observation of the relationship between the tumor and the surrounding tissue structure. However, the specific diagnosis should also be based on pathological manifestations, IHC results and genetic analysis. Characteristics of mass imaging correlate with pathological changes in the mass.

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“…To assess intraepidermal nerve fiber densities (IENFD), skin punch biopsies were performed in four patients, using a standardized procedure [20,21]. Eight mm punch biopsies were taken 10 cm above the lateral malleolus of the right foot.…”

Section: Skin Biopsiesmentioning

confidence: 99%

Assessment of Peripheral Nervous System Alterations in Patients with the Fabry Related GLA-Variant p.A143T

et al. 2020

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Background The purpose of this study is to examine alterations of the peripheral nervous system (PNS) in oligo-symptomatic patients carrying the Fabry related GLA-gene variant p.A143T by Magnetic Resonance Neurography (MRN) and skin biopsy. This prospective study assessed dorsal root ganglia (DRG) volume L3 to S2, vascular permeability of the DRG L5, S1, and the spinal nerve L5 in five patients carrying p.A143T in comparison to patients with classical Fabry mutations and healthy controls. Moreover, skin punch biopsies above the lateral malleolus of the right foot were obtained in four patients and intraepidermal nerve fiber density (IENFD) was counted individually. Compared to controls, DRG volumes of p.A143T patients were enlarged by 30% (L3, p < 0.05), 35% (L4, p < 0.05), 29% (L5, p = 0.15), 36% (S1, p < 0.01), and 18% (S2, p < 0.05), but less pronounced compared to patients carrying a classical Fabry mutation. Compared to healthy controls, vascular permeability was decreased by 40% (L5 right), 49% (L5 left), 48% (S1 right), and 49% (S1) (p < 0.01–p < 0.001), but non-significant less than patients carrying a classical Fabry mutation. Compared to sex-matched 5% lower normative reference values per decade, IENFD was decreased in three of four patients. MRN and determination of IENFD is able to detect early alteration of the PNS segment in oligo-symptomatic patients with the disease-modifying GLA-variant p.A143T on an individual basis. This procedure might also help in further GLA-variants of uncertain significance for early identification of patients with single major organ manifestation.

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Distinctive low epidermal nerve fiber density in schwannomatosis patients provides a major parameter for diagnosis and differential diagnosis

Cited by 5 publications

References 15 publications

C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis

C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis

Analysis of Imaging and Pathological Features in 12 Cases of Schwannomatosis and Literature Review

Assessment of Peripheral Nervous System Alterations in Patients with the Fabry Related GLA-Variant p.A143T

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