Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain

Cavalier, Yefim; Albrecht, Phillip J.; Amory, Colum F.; Bernardini, G.; Argoff, Charles E.

doi:10.1093/pm/pnw001

Cited by 7 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another consideration may be that small fibre pathology occurs systemically in some people with chronic WAD. Reduced IENFD has been observed across a range of chronic pain conditions, including fibromyalgia (Grayston et al, 2019), central post‐stroke pain (Cavalier, Albrecht, Amory, Bernardini, & Argoff, 2016) and Gulf War Illness (Klein, Zirpoli, Downs, & Oaklander, 2018). Further, bilateral reductions in IENFD occur in people with unilateral complex regional pain syndrome (Rasmussen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Farrell

Sterling

Irving-Rodgers

et al. 2020

European Journal of Pain

View full text Add to dashboard Cite

Background Mechanisms underpinning ongoing symptoms in chronic whiplash associated‐disorder (WAD) are not well understood. People with chronic WAD can exhibit sensory dysfunction consistent with small nerve fibre pathology, including thermal hypoaesthesia and hyperalgesia. This study investigated small fibre structure and function in chronic WAD. Methods Twenty‐four people with chronic WAD (median [IQR] age 49 [15] years, 16 females) and 24 pain‐free controls (50 [17] years, 16 females) were recruited. Intraepidermal nerve fibre density (IENFD) and dermal innervation were assessed by skin biopsy. This was performed at (a) the lateral index finger on the primary side of pain and (b) superior to the lateral malleolus on the contralateral side. Quantitative sensory testing was performed over the hand. Results The WAD group exhibited lower IENFD at the finger (WAD: median [IQR] 4.5 [4.9] fibres/mm; control 7.3 [3.9]; p = .010), but not the ankle (WAD: mean [SD] 7.3 [3.7] fibres/mm; control 9.3 [3.8]; p = .09). Dermal innervation was lower in the WAD group at the finger (WAD: median [IQR] 3.7 [2.8] nerve bundles/mm2; controls: 4.9 [2.1]; p = .017) but not the ankle (WAD: median [IQR] 2.1 [1.9] nerve bundles/mm2; controls: 1.8 [1.8]; p = .70). In the WAD group, hand thermal and light touch detection were impaired, and heat pain thresholds were lowered (p ≤ .037). Conclusions Findings suggest small fibre structural and functional deficits in chronic WAD, implicating potential involvement of small fibre pathology. Significance Our study found decreased intraepidermal nerve fibre density, reduced dermal innervation, thermal hypoaesthesia and hypersensitivity in people with chronic WAD, suggestive of small fibre pathology. This observation of peripheral nervous system pathology in chronic whiplash provides novel insights on mechanisms underpinning symptoms and challenges commonly held beliefs regarding this condition.

show abstract

Section: Discussionmentioning

confidence: 99%

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Farrell

Sterling

Irving-Rodgers

et al. 2020

European Journal of Pain

View full text Add to dashboard Cite

show abstract

“…All rights reserved partial recovery after motor rehabilitation (Nolano et al, 2018). One report described decrease in fiber nerve density in patients with stroke, pain and central motor symptoms (Cavalier et al 2016). These studies suggested a possible inverse relation between motor activity and small fiber density.…”

Section: Accepted Articlementioning

confidence: 99%

Peripheral and central nervous system correlates in fibromyalgia

Vecchio

Lombardi

Paolini

et al. 2020

European Journal of Pain

View full text Add to dashboard Cite

Background: Fibromyalgia (FM) is a syndrome characterized by altered pain processing at central and peripheral level, whose pathophysiologic mechanisms remain obscure. We aimed at exploring the structural changes of peripheral nociceptor measured by skin biopsy, the functional changes of central nociceptive pathway assessed by laser evoked potentials (LEP), and their correlation with clinical features and comorbidities.Methods: Eight-one patients diagnosed with FM underwent skin biopsies with quantification of intraepidermal nerve fiber density (IENFD) at the thigh and distal leg, and LEP recording by stimulating hand, thigh and foot. Nerve conduction study (NCS), clinical features, comorbidity with migraine and mood disorders, and previous, non-active immune-mediated disorders were recorded.Results: IENFD was reduced in 85% of patients at the thigh and in 12.3% of patients at the distal leg, whereas it was normal in 14.8% of patients. N2P2 habituation index from laser stimulation at the thigh was altered in 97.5% of patients and correlated with reduced IENFD at the thigh. LEP latencies and amplitudes did not differ among groups. No association was found between IENFD, LEP, clinical features, and comorbidities.Conclusions: FM patients most commonly showed a mild loss of peripheral nociceptors at the thigh rather than distal small fiber neuropathy. This finding was associated with an altered habituation index and strengthened the hypothesis that central sensitization plays a key role in the pathogenesis of the disease.Significance: Central impairment of pain processing likely underlies FM, which in most patients is associated with mild proximal small fiber pathology.

show abstract

“…Recently, we have shown greater corneal nerve loss in patients with recurrent stroke, despite comparable vascular risk factors suggesting that assessment of corneal nerve integrity may be a more robust measure of risk of stroke and recurrent stroke compared to the evaluation of conventional risk factors for stroke 28 . Recent skin biopsy studies have also shown a loss of intraepidermal nerve fibres in patients with stroke, particularly those with central post stroke pain 31 , 32 . Given that we have previously shown comparable reductions in intraepidermal nerves and corneal nerves in diabetic neuropathy 33 , our observations suggest that our finding of corneal nerve loss in TIA and stroke represents more global evidence of nerve loss in stroke and TIA.…”

Section: Discussionmentioning

confidence: 99%

Corneal nerve loss in patients with TIA and acute ischemic stroke in relation to circulating markers of inflammation and vascular integrity

Khan

Parray

Akhtar

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) in 105 patients with TIA (n = 24) or AIS (n = 81) and age matched control subjects (n = 56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 h of presentation with a TIA or AIS. CNFL (P = 0.000, P = 0.000), CNFD (P = 0.122, P = 0.000) and CNBD (P = 0.002, P = 0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P = 0.000), IL-6 (P = 0.011) and E-Selectin (P = 0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P = 0.636), MMP-9 (P = 0.098), P-Selectin (P = 0.395) and VEGF (P = 0.831). CNFL (r = 0.218, P = 0.026) and CNFD (r = 0.230, P = 0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P = 0.041, P = 0.043). Patients with TIA and AIS have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease.

show abstract

Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain

Cited by 7 publications

References 20 publications

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Peripheral and central nervous system correlates in fibromyalgia

Corneal nerve loss in patients with TIA and acute ischemic stroke in relation to circulating markers of inflammation and vascular integrity

Contact Info

Product

Resources

About