Characterizing Acute-Onset Small Fiber Neuropathy

Neurology® Neuroimmunology & Neuroinflammation · 7 authors, 1 centre

AI SUMMARY

FIDELITY 100%

POPULATION20 patients with probable or definite acute-onset small fiber neuropathy (60% women; median age 44.2 years)

INTERVENTIONDiagnostic workup including clinical exam, neurophysiologic tests (LEPs, WDT, ESC), skin biopsy, and serum antibody studies; treatment with corticosteroids (n=3) or IVIg (n=2)

COMPARISONHealthy subjects (n=10) and diseased controls (n=12) for serum reactivity studies

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TL;DR

This case series of 20 patients describes acute-onset small fiber neuropathy (AOSFN) as a predominantly non–length-dependent, symmetric painful neuropathy often triggered by infection or vaccination. Diagnosis is supported by laser-evoked potentials (60% abnormal) and skin biopsy (55% abnormal), and in vitro studies suggest an immune-mediated origin with IgG reactivity against nerve tissue in 70% of patients. Clinically, 65% of patients showed partial or complete recovery, while corticosteroids appeared beneficial in a small subset.

Full summary

2,943 CHARS

**Background:** Small fiber neuropathy (SFN) preferentially involves thinly myelinated Aδ-fibers and unmyelinated C-fibers. Immune-mediated SFN is increasingly recognized, but acute-onset SFN (AOSFN) remains poorly described. This study characterizes a series of AOSFN cases with clinical, neurophysiologic, pathologic, and experimental assessments.

**Methods:** Between April 2017 and April 2022, consecutive patients with probable or definite AOSFN (maximal symptom progression within 28 days) were included from a tertiary neuromuscular center. Diagnosis followed NEURODIAB criteria. All patients underwent clinical examination, nerve conduction studies (to exclude large fiber involvement), and small fiber assessments: laser-evoked potentials (LEPs), warm detection thresholds (WDT), electrochemical skin conductance (ESC), and epidermal nerve fiber density (ENF) from skin biopsies. Serum was tested for various antibodies (e.g., anti-FGFR3, anti-CASPR2) and for IgG/IgM reactivity against mouse sciatic nerve teased fibers, dorsal root ganglion (DRG) sections, and cultured DRG. Sera from 10 healthy subjects and 12 diseased controls were also analyzed.

**Key Results:** Twenty patients were included (60% women; median age 44.2 years [IQR 35.7–56.2]). A precipitating event was present in 16 patients (80%): infection (8), new medication (5), or vaccination (3). Median progression phase duration was 14 days [5–28]. Pain was reported by 17 patients (85%), paresthesia by 14 (70%), and autonomic involvement by 12 (60%). The clinical pattern was non–length-dependent in 17 patients (85%). Diagnosis was definite in 18 patients (90%) and probable in 2. LEPs were abnormal in 60% (12/20), ENF in 55% (6/11), WDT in 39% (7/18), and ESC in 31% (5/16). CSF analysis was normal in all 5 tested patients. Anti-FGFR3 antibodies were positive in 4/18 (22%), anti-CASPR2 in 1/20. In vitro, IgG immunoreactivity against nerve tissue was found in 14/20 patients (70%) but not in controls. Binding patterns included unmyelinated fibers, Schwann cells, paranodes, juxtaparanodes, and DRG. Three patients treated with oral corticosteroids (1 mg/kg for 1 month) improved; two patients treated with IVIg showed no benefit. At last follow-up (median 4.8 years), 13 patients (65%) had partial or complete recovery, 5 had chronic course, and 4 had relapses.

**Clinical Implications:** AOSFN should be considered in patients with acute, symmetric, non–length-dependent neuropathic pain, especially after infection or vaccination. LEPs appear more sensitive than WDT or ESC for diagnosis. The high rate of IgG reactivity against nerve tissue supports an immune-mediated pathogenesis, though specific pathogenic antibodies remain elusive. Corticosteroids may be beneficial in the acute phase, while IVIg showed no efficacy in this small sample. The variable disease course (monophasic, relapsing, or chronic) mirrors other acute-onset immune neuropathies.

PICO

PPOPULATION

20 patients with probable or definite acute-onset small fiber neuropathy (60% women; median age 44.2 years)

IINTERVENTION

Diagnostic workup including clinical exam, neurophysiologic tests (LEPs, WDT, ESC), skin biopsy, and serum antibody studies; treatment with corticosteroids (n=3) or IVIg (n=2)

OOUTCOME

Clinical features, diagnostic test sensitivity, disease course, and serum IgG immunoreactivity against nerve tissue

STUDY TYPE

case_report

SPECIALTY

neurology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10766082

Characterizing Acute-Onset Small Fiber Neuropathy

Neurology® Neuroimmunology & Neuroinflammation

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ABSTRACT

Background and Objectives Immune-mediated small fiber neuropathy (SFN) is increasingly recognized. Acute-onset SFN (AOSFN) remains poorly described. Herein, we report a series of AOSFN cases in which immune origins are debatable. Methods We included consecutive patients with probable or definite AOSFN. Diagnosis of SFN was based on the NEURODIAB criteria. Acute onset was considered when the maximum intensity and extension of both symptoms and signs were reached within 28 days. We performed the following investigations: clinical examination, neurophysiologic assessment encompassing a nerve conduction study to rule out large fiber neuropathy, laser-evoked potentials (LEPs), warm detection thresholds (WDTs), electrochemical skin conductance (ESC), epidermal nerve fiber density (ENF), and patient serum reactivity against mouse sciatic nerve teased fibers, mouse dorsal root ganglion (DRG) sections, and cultured DRG. The serum reactivity of healthy subjects (n = 10) and diseased controls (n = 12) was also analyzed. Data on baseline characteristics, biological investigations, and disease course were collected. Results Twenty patients presenting AOSFN were identified (60% women; median age: 44.2 years [interquartile range: 35.7–56.2]). SFN was definite in 18 patients (90%) and probable in 2 patients. A precipitating event was present in 16 patients (80%). The median duration of the progression phase was 14 days [5–28]. Pain was present in 17 patients (85%). Twelve patients (60%) reported autonomic involvement. The clinical pattern was predominantly non–length-dependent (85%). Diagnosis was confirmed by abnormal LEPs (60%), ENF (55%), WDT (39%), or ESC (31%). CSF analysis was normal in 5 of 5 patients. Antifibroblast growth factor 3 antibodies were positive in 4 of 18 patients (22%) and anticontactin-associated protein-2 antibodies in one patient. In vitro studies showed IgG immunoreactivity against nerve tissue in 14 patients (70%), but not in healthy subjects or diseased controls. Patient serum antibodies bound to unmyelinated fibers, Schwann cells, juxtaparanodes, paranodes, or DRG. Patients' condition improved after a short course of oral corticosteroids (3/3). Thirteen patients (65%) showed partial or complete recovery. Others displayed relapses or a chronic course. Discussion AOSFN primarily presents as an acute, non–length-dependent, symmetric painful neuropathy with a variable disease course. An immune-mediated origin has been suggested based on in vitro immunohistochemical studies.

CITATION EXPORT

Thierry Gendre, Jean-Pascal Lefaucheur, Tarik Nordine et al.. Characterizing Acute-Onset Small Fiber Neuropathy. Neurology® Neuroimmunology & Neuroinflammation. (2024). https://doi.org/10.1212/NXI.0000000000200195

AUTHORS

7 · 1 CENTRES

Thierry Gendre, Jean-Pascal Lefaucheur, Tarik Nordine, Yasmine Baba-Amer, François-Jérôme Authier, Jérôme Devaux, Alain Créange

From the Service de Neurologie (T.G., A.C.), CHU Henri Mondor APHP; Centre de Référence des Maladies Neuromusculaires Nord/Est/Ile-de-France (T.G., J.-P.L., T.N., F.-J.A., A.C.); Unité de Neurophysiologie Clinique (J.-P.L., T.N.), CHU Henri Mondor APHP; Unité de Recherche EA 4391 (J.-P.L., T.N., A.C.), Faculté de Santé, UniversitéParis Est Créteil; IMRB INSERM U955-Equipe 10 (Y.B.-A., F.-J.A.), UniversitéParis Est Créteil; Service d’Anatomo-Pathologie (F.-J.A.), CHU Henri Mondor APHP, Créteil; and Institut de Génomique Fonctionnelle (J.D.), Universitéde Montpellier, CNRS, INSERM, France.