Clinical and Laboratory Profiles of Idiopathic Small Fiber Neuropathy in Children: Case Series

Kafaie, Jafar; Balushi, Ali Al; Kim, Min‐Soo; Pestronk, Alan

doi:10.1097/cnd.0000000000000178

Cited by 13 publications

(20 citation statements)

References 12 publications

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“…Non–length‐dependent IENFD pathological findings were associated with presence of autoantibodies. This is consistent with previous studies of TS‐HDS antibodies showing an increased frequency of pain in the upper extremities and of FGFR‐3 antibodies in patients who often had evidence of a neuronopathy rather than a neuropathy. The clinical distribution of symptoms did not segregate with antibody status.…”

Section: Discussionmentioning

confidence: 99%

“…Our results regarding FGFR‐3 antibodies in SFN from the present study are similar to those in the original report on FGFR‐3 antibodies in sensory neuropathies . In both series, FGFR‐3 antibodies occurred in 15% of patients and were significantly associated with non–length‐dependent syndromes.…”

Section: Discussionmentioning

confidence: 99%

“…Length‐dependent SFN had IENFD that was more reduced at distal sites (ankle or calf) than at proximal sites (lower or upper thigh). For non–length‐dependent SFN, IENFD was prominently reduced at proximal sites . Clinical characterizations of patients were as follows: length‐dependent, if the symptoms were present initially only in the feet, although the symptoms may have spread over time; and non–length dependent, if symptoms began in the arms, trunk, or face.…”

Section: Methodsmentioning

confidence: 99%

“…Trisulfated heparin disaccharide (TS‐HDS) and fibroblast growth factor‐3 (FGFR‐3) autoantibodies are associated with sensory‐predominant neuropathies or neuronopathies, and occur in up to 40% of SFN cases . TS‐HDS is a disaccharide component of the glycosylation moieties of heparin and heparan sulfate.…”

Section: Introductionmentioning

confidence: 99%

“…Genetic defects of FGFR‐3 cause achondroplasia and other bony abnormalities. Patients with IgG antibodies to FGFR‐3 often have neuropathies and immune‐related disorders …”

Section: Introductionmentioning

confidence: 99%

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Cryptogenic small‐fiber neuropathies: Serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor‐3

et al. 2019

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Introduction Causes of small‐fiber peripheral neuropathies (SFN) are often undefined. In this study we investigated associations of serum autoantibodies, immunoglobulin G (IgG) vs fibroblast growth factor receptor‐3 (FGFR‐3), and immunoglobulin M (IgM) vs trisulfated heparan disaccharide (TS‐HDS) in cryptogenic SFN. Methods One hundred fifty‐five patients with biopsy‐proven SFN and no identified cause for their neuropathy were blindly tested for serum IgM vs TS‐HDS and IgG vs FGFR‐3. Results Forty‐eight percent of SFN patients had serum antibodies, 37% with IgM vs TS‐HDS and 15% with IgG vs FGFR‐3. TS‐HDS antibodies were more frequent in SFN patients than in controls (P = .0012). Both antibodies were more common in females, and with non–length‐dependent nerve pathology. Nintey‐two percent of patients with acute‐onset SFN had serum IgM vs TS‐HDS. Discussion Autoantibodies directed against TS‐HDS and FGFR‐3 suggest an immune disorder in otherwise idiopathic SFN. Serum IgM vs TS‐HDS may be a marker for SFN with an acute onset.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Genetic defects of FGFR‐3 cause achondroplasia and other bony abnormalities. Patients with IgG antibodies to FGFR‐3 often have neuropathies and immune‐related disorders …”

Section: Introductionmentioning

confidence: 99%

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Cryptogenic small‐fiber neuropathies: Serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor‐3

et al. 2019

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Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy

2019

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IMPORTANCE Small-fiber polyneuropathy involves preferential damage to the thinly myelinated A-delta fibers, unmyelinated C sensory fibers, or autonomic or trophic fibers. Although this condition is common, most patients still remain undiagnosed and untreated because of lagging medical and public awareness of research advances. Chronic bilateral neuropathic pain, fatigue, and nausea are cardinal symptoms that can cause disability and dependence, including pain medication dependence.OBSERVATIONS Biomarker confirmation is recommended, given the nonspecificity of symptoms. The standard test involves measuring epidermal neurite density within a 3-mm protein gene product 9.5 (PGP9.5)-immunolabeled lower-leg skin biopsy. Biopsies and autonomic function testing confirm that small-fiber neuropathy not uncommonly affects otherwise healthy children and young adults, in whom it is often associated with inflammation or dysimmunity. A recent meta-analysis concluded that small-fiber neuropathy underlies 49% of illnesses labeled as fibromyalgia. Initially, patients with idiopathic small-fiber disorders should be screened by medical history and blood tests for potentially treatable causes, which are identifiable in one-third to one-half of patients. Then, secondary genetic testing is particularly important for familial and childhood cases. Treatable genetic causes include Fabry disease, transthyretin and primary systemic amyloidosis, hereditary sensory autonomic neuropathy-1, and ion-channel mutations. Immunohistopathologic evidence suggests that small-fiber dysfunction and denervation, especially of blood vessels, contributes to diverse symptoms, including postexertional malaise, postural orthostatic tachycardia, and functional gastrointestinal distress. Preliminary evidence implicates acute or chronic autoreactivity in some cases, particularly in female patients and otherwise healthy children and young adults. Different temporal patterns akin to Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy have been described; here, corticosteroids and immunoglobulins, which are often efficacious for inflammatory neuropathic conditions, are increasingly considered.CONCLUSIONS AND RELEVANCE Because small fibers normally grow throughout life, improving contributory conditions may permit regrowth, slow progression, and prevent permanent damage. The prognosis is often hopeful for improving quality of life and sometimes for abatement or resolution, particularly in the young and otherwise healthy individuals. Examples include diabetic, infectious, toxic, genetic, and inflammatory causes. The current standard of care requires prompt diagnosis and treatment, particularly in children and young adults, to restore life trajectory. Consensus diagnostic and tracking metrics should be established to facilitate treatment trials.

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Therapeutic plasma exchange for peripheral neuropathy associated with trisulfated heparan disaccharide IgM antibodies: A case series of 17 patients

Olsen

Tormey

Tseng

et al. 2021

J of Clinical Apheresis

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Background Small fiber neuropathy (SFN) can be associated with autoantibodies, including those of IgM class with specificity for the trisulfated heparan disaccharide (TS‐HDS) antigen. We hypothesized that, as an IgM autoantibody‐mediated disorder, TS‐HDS‐associated SFN symptoms may be reduced with therapeutic plasma exchange (TPE). Study methods This was an observational analysis of all patients referred for TPE from 2018 to 2020 following laboratory confirmation of SFN with TS‐HDS autoantibodies; a loading course of 3 to 5 procedures over 2 weeks was completed, with some patients returning for monthly procedures. The following data were collected: demographics, symptoms and duration, TS‐HDS levels, skin biopsy results, reported responses to TPE, and TPE‐associated adverse events. Results Of the 17 subjects, 12 (71%) were female and the mean age was 57.5 years (range 27‐94). The most common reported symptom was lower extremity paresthesia (88% of subjects). The mean number of TPE procedures completed per subject was 9 (range 3‐18), with 71% (12/17) reporting symptomatic improvement or slowed disease progression. About 15% of procedures were associated with an adverse event, with vasovagal reactions being the most common; 53% of patients had at least one adverse event. Conclusions Given a reported symptomatic response rate of more than 70%, TPE may be a treatment option for individuals with autoimmune‐mediated SFN associated with increased titers of TS‐HDS IgM autoantibodies. Since TPE‐associated adverse events appear common in this population, close monitoring during procedures is warranted.

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Clinical and Laboratory Profiles of Idiopathic Small Fiber Neuropathy in Children: Case Series

Cited by 13 publications

References 12 publications

Cryptogenic small‐fiber neuropathies: Serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor‐3

Cryptogenic small‐fiber neuropathies: Serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor‐3

Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy

Therapeutic plasma exchange for peripheral neuropathy associated with trisulfated heparan disaccharide IgM antibodies: A case series of 17 patients

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