The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes

Terkelsen, Astrid Juhl; Karlsson, Páll; Lauria, Giuseppe; Freeman, Roy; Finnerup, Nanna Brix; Jensen, Troels Staehelin

doi:10.1016/s1474-4422(17)30329-0

Cited by 246 publications

(235 citation statements)

References 97 publications

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“…In small fiber neuropathies (SFNs) the thinly myelinated (Aδ) and unmyelinated (C) fibers responsible for the transmission of thermal and noxious sensory input are affected 12. Clinically, this nerve damage translates to symptoms of sharp, painful, or burning paresthesia; sensory loss or numbness; and the inability to discriminate between hot and cold sensations.…”

Section: Clinical Presentationmentioning

confidence: 99%

“…Symptoms may be vague, described as a tight feeling or abnormal sensation in the soles of the feet, intolerance of tactile stimuli (inability to wear socks or touch bedsheets), or a sensation of restless legs. The distribution of symptoms may have a length dependent or non-length dependent pattern that affects the limbs, trunk, face, or it may have a combination of patterns 12404142. Depending on the underlying cause, the onset of symptoms may be gradual, with slowly progressive worsening, or subacute with more rapid progression.…”

Section: Clinical Presentationmentioning

confidence: 99%

“…Motor strength, proprioception, and muscle stretch reflexes should be preserved in patients with pure SFN. Skin may have a dry, atrophic, or discolored appearance 1240…”

Section: Clinical Presentationmentioning

confidence: 99%

“…201 It is a reproducible and reliable technique with a specificity greater than 90%, sensitivity approaching 80%, and favorable positive and negative predictive values 12202203204. Multiple large cohort studies have been conducted to establish normative values for IENFD at the distal leg because age, ethnicity, and sex are known to produce variations 202203205.…”

Section: Diagnostic Approachmentioning

confidence: 99%

“…Peripheral sensory nerves vary in size and function, ranging from the smallest unmyelinated C fibers and thinly myelinated Aδ fibers that conduct noxious and thermal information12 to the larger Aβ fibers that transmit proprioceptive and vibratory information 3. As a result, disorders of sensory nerve function are diverse and depend on the type of nerve fiber that is affected; patients present with a wide range of symptoms, from pain predominant (small fiber) to ataxia predominant (large fiber) problems.…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.

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Section: Clinical Presentationmentioning

confidence: 99%

Section: Clinical Presentationmentioning

confidence: 99%

“…Motor strength, proprioception, and muscle stretch reflexes should be preserved in patients with pure SFN. Skin may have a dry, atrophic, or discolored appearance 1240…”

Section: Clinical Presentationmentioning

confidence: 99%

Section: Diagnostic Approachmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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Corneal confocal microscopy to detect early immune‐mediated small nerve fibre loss in AL amyloidosis

Thimm¹,

Carpinteiro

Oubari

et al. 2022

Ann Clin Transl Neurol

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Objective: Light chain (AL) amyloidosis is a life-threatening disorder characterised by extracellular deposition of amyloid leading to dysfunction of multiple organs. Peripheral nerve involvement, particularly small fibre neuropathy, may be associated with poorer survival. Corneal confocal microscopy (CCM) is a rapid and non-invasive imaging technique to quantify corneal small nerve fibres and immune cells in vivo. We aimed to evaluate CCM as a tool for early diagnosis of peripheral nerve involvement in AL amyloidosis. Methods: CCM and nerve conduction studies (NCS) were undertaken in 21 newly diagnosed, treatment-na€ ıve AL amyloidosis patients and 21 age-and sex-matched healthy controls. Corneal nerve fibre density (CNFD), corneal nerve branch density and fibre length, and cell infiltrates were quantified in the sub-basal layer of the cornea. Results: There was a significant reduction in CNFD and nerve fibre length, even without large fibre affection and an increase in cell density, particularly around corneal nerve fibres in patients with AL amyloidosis compared to controls. Additionally, cell infiltration correlated with reduced nerve fibre density in patients with AL amyloidosis, but reduced CNFD did not correlate with laboratory parameters of organ dysfunction. Interpretation: Our study is the first to show that CCM allows rapid non-invasive identification of early small nerve fibre damage associated with immune cell infiltration in patients with AL amyloidosis. CCM detects peripheral nerve involvement more sensitively than NCS.

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Tuning in C‐nociceptors to reveal mechanisms in chronic neuropathic pain

Jonas

Namer

Stockinger

et al. 2018

Annals of Neurology

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Sinusoidal electrical stimulation at 4Hz enables preferential activation of C-nociceptors in pig and human skin that accommodates during ongoing (1-minute) stimulation. Absence of such accommodation in neuropathic pain patients suggest axonal hyperexcitability that could be predictive of alterations in peripheral nociceptor encoding and offer a potential therapeutic entry point for topical analgesic treatment. Ann Neurol 2018;83:945-957.

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The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes

Cited by 246 publications

References 97 publications

Diagnosis and management of sensory polyneuropathy

Diagnosis and management of sensory polyneuropathy

Corneal confocal microscopy to detect early immune‐mediated small nerve fibre loss in AL amyloidosis

Tuning in C‐nociceptors to reveal mechanisms in chronic neuropathic pain

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