Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study

Üçeyler, Nurcan; Káhn, Ann-Kathrin; Krämer, Daniela; Zeller, Daniel; Casanova‐Mollá, Jordi; Wanner, Christoph; Weidemann, Frank; Katsarava, Zaza; Sommer, Claudia

doi:10.1186/1471-2377-13-47

Cited by 80 publications

(63 citation statements)

References 36 publications

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“…However, with the finding that abnormalities were also found in the patients without FD (specificity 80%), it is safe to draw the conclusion that small nerve fibre assessment is most likely an unsuitable tool for establishing the diagnosis of FD in patients who present with an uncertain diagnosis. In previous studies, it has been shown that all male and most female patients with (mostly classical) FD have small nerve fibre pathology, as assessed with QST alone or in combination with an IENFD assessment (Dutsch et al 2002;Laaksonen et al 2008;Biegstraaten et al 2011Biegstraaten et al , 2012€ Uçeyler et al 2011€ Uçeyler et al , 2013. With this study, we confirmed our hypothesis that in patients with the nonclassical phenotype QST and/or IENFD may be abnormal, even in the absence of pain.…”

Section: Discussionsupporting

confidence: 80%

“…Previous studies have shown that all male and most female patients with (classical) FD have an abnormal quantitative sensory testing (QST) profile and a decreased intraepidermal nerve fibre density (IENFD) in a skin biopsy at the distal leg (Dutsch et al 2002;Laaksonen et al 2008;Biegstraaten et al 2011Biegstraaten et al , 2012€ Uçeyler et al 2011€ Uçeyler et al , 2013. We hypothesized that QST and IENFD could aid in the diagnosis of FD in patients who initially present with an uncertain diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

et al. 2015

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Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an a-galactosidase A enzyme deficiency due to pathogenic variants in the agalactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite diagnosis of FD has important consequences for treatment and counselling.Objectives: We assessed the diagnostic value of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) for patients with an uncertain FD diagnosis.Methods: All patients with a GLA variant who initially presented at the Academic Medical Center with an uncertain FD diagnosis were included. A biopsy of an affected organ in a patient or family member showing FD characteristic storage is used as a reference standard for a diagnosis of FD. All patients underwent a comprehensive QST protocol and IENFD assessment which was compared to age and gender-matched healthy controls. Sensitivity and specificity were calculated for a combination of !1 abnormal QST modality and an abnormal IENFD.Results: Twenty-six patients participated (nonclassical FD n ¼ 18, 9 males; no FD n ¼ 5, 3 males; uncertain n ¼ 3, 1 male). Of the patients classified as nonclassical FD, 28% had !1 abnormal QST modalities, and 83% had an abnormal IENFD. From the patients without FD, 20% had !1 abnormal QST modality, and IENFD was abnormal in 25% (1 not available). Sensitivity was 28% and specificity 80%.Conclusions: In our study cohort, QST and IENFD could not reliably distinguish patients with FD from those without FD.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

et al. 2015

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“…The assessment of cold perception is thought to be an important somatosensory entity, which may be altered in the early stage of small‐fibre neuropathy (such as in Fabry's disease; (Maag et al, ; Uceyler et al, )). Previous studies reported cold sensation loss in 40% of polyneuropathy, 63% of postherpetic neuralgia, 50% of peripheral nerve injury and 49% of central pain patients (Maier et al, ).…”

Section: Discussionmentioning

confidence: 99%

Cold‐evoked potentials versus contact heat‐evoked potentials—Methodological considerations and clinical application

Hüllemann

Nerdal

Sendel

et al. 2019

European Journal of Pain

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Background Previous studies investigated cold‐evoked potentials (CEPs) for the assessment of the integrity of cold‐mediating A‐delta fibres and the spinothalamic tract. Nevertheless, several methodological questions remained unanswered to proceed to clinical application. How do latencies and amplitudes vary between CEPs and contact heat‐evoked potentials (CHEPs)? Are there differences between variable and fixed thermode positions or between glabrous and hairy skin? Are CEPs recordable in patients with abnormal cold processing? Methods A total of 16 healthy subjects were tested with CEPs and CHEPs at the face, hand and foot. Variable and fixed thermode positions, hairy and glabrous skin were compared. Three patients with abnormal cold processing were tested with CEPs and quantitative sensory testing. Results Compared to CEPs, CHEPs latencies were significantly longer at all locations, amplitudes were significantly larger at the face and the hand whilst comparable at the foot. CEPs and CHEPs did not differ significantly between variable and fixed thermode positions using inter stimulus intervals of 8–12 s. CEP latencies were increased by around 20% at the glabrous skin. Patients with known abnormal cold processing (central pain, polyneuropathy, Fabry's disease) showed increased N2 latencies as compared to normal controls. Conclusions Inter stimulus intervals of 8‐12 s allow the use of a fixed thermode position for reliable CEPs/CHEPs recording. Hairy skin stimulation results in faster latencies as compared to glabrous skin, without influencing EP amplitudes. In patients with abnormal cold processing, CEPs are recordable and increased latencies may be expected as compared to healthy controls and the healthy contralateral side. Significance Cold‐evoked potentials are an innovative, non‐invasive technique to assess cold detection and processing objectively. This study shows that CEP can be recorded from the hairy and glabrous skin, regardless of using fixed or variable thermode positions. Loss of A‐delta fibre function leads to an increased CEP latency, consistent with loss of cold detection in the QST.

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“…The pathophysiology of pain in Fabry disease is not fully understood; however, SFN as a result of glycolipid accumulation in the dorsal root ganglia has been proposed [39] and confirmed [40] as a mechanism. Indeed, small fibre conduction is impaired in men with Fabry disease and worsens with advanced disease severity [41]. Indeed, 100% of male patients and 57% of female patients have a decrease of IENF density [40].…”

Section: Fabry Diseasementioning

confidence: 99%

Small-fibre neuropathies and skin: news and perspectives for dermatologists

Miséry

Bodéré

Genestet

et al. 2014

European Journal of Dermatology

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Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study

Cited by 80 publications

References 36 publications

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

Cold‐evoked potentials versus contact heat‐evoked potentials—Methodological considerations and clinical application

Small-fibre neuropathies and skin: news and perspectives for dermatologists

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