Clinical diagnosis and management of small fiber neuropathy: an update on best practice

Devigili, Grazia; Cazzato, Daniele; Lauria, Giuseppe

doi:10.1080/14737175.2020.1794825

Cited by 40 publications

(52 citation statements)

References 140 publications

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“…Major limits of our study include the small size of each genetic CMT subtype (in any case comparable with previous investigations which were mainly focused on CMT1A), unavailability of information regarding warm/ cold sensation, and lack of a skin biopsy, the gold standard for the diagnosis and characterization of smallfiber neuropathies (Devigili et al, 2020). In a research context, systematic investigations by skin biopsy will help to better understand why NP was variably encountered in different genetic CMT subtypes.…”

Section: Discussionmentioning

confidence: 75%

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Peretti

Squintani

Taioli

et al. 2022

European Journal of Pain

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Background: Pain, either nociceptive or neuropathic (NP), is a common symptom in Charcot-Marie-Tooth (CMT) disease. Methods:We investigated small fibers involvement and its correlation with pain in different CMT subtypes through a systematic clinical and neurophysiological study. We enrolled 50 patients: 19 with duplication of PMP22 (CMT1A), 11 with mutation of MPZ (CMT1B, CMT2I/J, or CMTDID), 12 with mutation of GJB1 (CMTX1), and 8 with mutation of MFN2 (CMT2A and CMT2A2B). Pain was rated with the 11-point Numerical Rating Scale and characterized through Neuropathic Pain Symptoms Inventory. Laser-evoked potentials (LEPs) were recorded after right foot and hand stimulation and N2-P2 complex amplitude and latency were compared with those of 41 controls.Results: Overall pain prevalence was 36%. NP was present in 14.6% of patients, with a length-dependent distribution in 85.7% of cases, and it was significantly more frequent in CMT1A (p < 0.001). Aδ fibers involvement greatly varies between CMT subtypes, reflecting differences in molecular pathology and pathophysiologic mechanisms. Prolonged N2 latency from foot stimulation was noted in 11 CMT1A patients, 5 of which report NP. MPZ-CMTs displayed different neurophysiological phenotypes and a very low prevalence of NP. LEPs were normal in all but one CMTX1 patients, although lower limbs N2-P2 amplitude was significantly reduced in males (p = 0.043). MFN2-CMTs were NP free and LEPs recordings were all normal. NP strictly correlated with LEPs alterations (p = 0.017).Conclusions: NP prevalence varies among CMTs subtypes and is mainly related to Aδ fibers impairment.Significance: Neuropathic pain is a frequent finding in Charcot-Marie Tooth disease and is related to Aδ fibers impairment. Patients at higher risk are those belonging to certain genetic subtypes (i.e. CMT1A and CMT2J) or with laserevoked potentials abnormalities. While managing this disease, clinicians should be aware of this symptom in order to offer best treatment options to their patients.

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Section: Discussionmentioning

confidence: 75%

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Peretti

Squintani

Taioli

et al. 2022

European Journal of Pain

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“…Also due to the retrospective design, and to the collaborative nature of the clinically-driven investigations, some testing is incomplete. For example, the missing ENMG data leads to a limitation in the diagnosis of SFN based on recent recommendations [14], which however are not yet consensual [82]. Nevertheless, small nerve fiber impairment was assessed using two complementary tests in 89% of patients and both were pathological in 58% of them.…”

Section: Limitationsmentioning

confidence: 99%

Characterization of small fiber neuropathy in hypermobile Ehlers Danlos Syndrome

Fernandez

Rozier

Vautey

et al. 2022

Preprint

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Ehlers Danlos syndromes (EDS) are heritable connective tissue disorders. The hypermobile form (hEDS) is the most frequent, yet the only one without an identified genetic mutation. Patients suffering from symptomatic joint hypermobility, yet not fulfilling the hEDS criteria, enter the Hypermobility Spectrum Disorder (HSD) category. In addition to musculoskeletal pain affecting joints, hEDS/HSD patients often describe painful sensations, hypoesthesia, and autonomic symptoms suggesting a neuropathic component. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A-δ and C-fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series N≤20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing. In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data and standardized questionnaires. All the patients reported moderate to severe pain interfering with daily life. A decreased thermal detection (QST) was shown in 55/79 patients (70%) and a decreased IENFD in 54/69 patients (78%). Hence a small fiber neuropathy (both abnormal IENFD and QST) was definite in 40/69 patients (58%), possible in 23/69 patients (33%) and excluded in only 6/69 patients (9%). These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research.

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“…The underlying pathophysiology of SFPN is complex, with a multitude of known causes including familial/genetic syndromes, metabolic disorders including diabetes mellitus, autoimmunity (Sjogren's syndrome being the most common), and more ( 34 ). However, up to 50% of cases are idiopathic, without a known cause ( 35 ). The fibers implicated in SFPN, αδ fibers as well as unmyelinated c fibers, provide sensory innervation not only to the skin, but also provide autonomic innervation to the viscera.…”

Section: Introductionmentioning

confidence: 99%

“…Cardiac testing in these same patients can also reliably predict other forms of more peripheral autonopathy ( 44 ). SFPN, on the other hand, may be inconsistent in distribution and non-length dependent ( 35 ). A skin biopsy-based finding of SFPN+ is not correlated with autonomic changes reflected in a sensitive and specific test for autonomic failure—the composite autonomic severity score (CASS) ( 45 )- used in other models.…”

Section: Introductionmentioning

confidence: 99%

Small Fiber Polyneuropathy May Be a Nexus Between Autonomic Nervous System Dysregulation and Pain in Interstitial Cystitis/Bladder Pain Syndrome

Wolff

Walker

2022

Front. Pain Res.

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a highly heterogeneous chronic and debilitating condition which effects millions of women and men in the United States. While primarily defined by urinary symptoms and pain perceived to be emanating from the bladder, IC/BPS patients frequently have co-occurring conditions and symptoms, many of which affect diverse body systems related to autonomic nervous system function. The impact on the autonomic system appears to stem from increased sympathetic innervation of the urinary tract, along with increased systemic sympathetic tone and decreased parasympathetic tone. Concurrent with these findings is evidence for destruction of peripheral sympathetic innervation to the sweat glands which may relate to small fiber polyneuropathy. It is unknown to what degree the wider alterations in autonomic function are also related to destruction/alterations in the small fibers carrying autonomic innervation. This potential nexus is an important point of investigation to better understand the unclarified pathophysiology of interstitial cystitis/bladder pain syndrome, the numerous co-occurring symptoms and syndromes, and for the identification of novel targeted therapeutic strategies.

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Clinical diagnosis and management of small fiber neuropathy: an update on best practice

Cited by 40 publications

References 140 publications

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Characterization of small fiber neuropathy in hypermobile Ehlers Danlos Syndrome

Small Fiber Polyneuropathy May Be a Nexus Between Autonomic Nervous System Dysregulation and Pain in Interstitial Cystitis/Bladder Pain Syndrome

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