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

Üçeyler N, Kahn AK, Kramer D, Zeller D, Casanova-Molla J, Wanner C, Weidemann F, Katsarava Z, Sommer C - BMC Neurol (2013)

Bottom Line: Data were compared with healthy controls using non-parametric statistical tests.Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function.PREP amplitudes further decreased with advance in disease severity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, University of Wurzburg, Josef-Schneider-Str, 11, 97080 Wurzburg, Germany. ueceyler_n@klinik.uni-wuerzburg.de

ABSTRACT

Background: Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).

Methods: In this case-control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.

Results: All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.

Conclusion: Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.

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Related in: MedlinePlus

Pain-related evoked potential amplitudes from face, hands, and feet stratified for gender and disease severity. Boxplots show the comparison of PREP PPA stratified for renal function. Male Fabry patients with impaired renal function have reduced PREP PPA after eliciting PREP from face (p = 0.012, a), hands (p = 0.007, b), and feet (p = 0.007, c). *p < 0.05, **p < 0.01.
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Figure 3: Pain-related evoked potential amplitudes from face, hands, and feet stratified for gender and disease severity. Boxplots show the comparison of PREP PPA stratified for renal function. Male Fabry patients with impaired renal function have reduced PREP PPA after eliciting PREP from face (p = 0.012, a), hands (p = 0.007, b), and feet (p = 0.007, c). *p < 0.05, **p < 0.01.

Mentions: PREP data from both sides were pooled, since there was no difference between the right and left side for any subject group, investigated area, or PREP parameter. Stimulus intensities did not differ between groups for all three areas. PREP N1 and P1 latencies did not differ between FD patients and controls (Figure 2a-c). Peak-to-peak amplitudes (PPA), however, were lower in male Fabry patients compared to male controls upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01, Figure 2d-f). Male Fabry patients also had lower PPA compared to female patients (hand: p < 0.05, foot: p < 0.01, Figure 2d-f). When comparing data of male Fabry patients with GFR < 60 and GFR > 60 with data of healthy male controls, only patients with impaired renal function showed reduced PPA after eliciting PREP from face (p = 0.012), hands (p = 0.007), and feet (p = 0.007, Figure 3a-c). Stimulus intensities did not differ between patients and controls at any site. Women with reduced α-GAL activity did not differ from women with normal enzyme activity as for PREP parameters. Additional file 3: Figure S3 shows an example of a PREP recording after stimulation at the face.


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

Üçeyler N, Kahn AK, Kramer D, Zeller D, Casanova-Molla J, Wanner C, Weidemann F, Katsarava Z, Sommer C - BMC Neurol (2013)

Pain-related evoked potential amplitudes from face, hands, and feet stratified for gender and disease severity. Boxplots show the comparison of PREP PPA stratified for renal function. Male Fabry patients with impaired renal function have reduced PREP PPA after eliciting PREP from face (p = 0.012, a), hands (p = 0.007, b), and feet (p = 0.007, c). *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672069&req=5

Figure 3: Pain-related evoked potential amplitudes from face, hands, and feet stratified for gender and disease severity. Boxplots show the comparison of PREP PPA stratified for renal function. Male Fabry patients with impaired renal function have reduced PREP PPA after eliciting PREP from face (p = 0.012, a), hands (p = 0.007, b), and feet (p = 0.007, c). *p < 0.05, **p < 0.01.
Mentions: PREP data from both sides were pooled, since there was no difference between the right and left side for any subject group, investigated area, or PREP parameter. Stimulus intensities did not differ between groups for all three areas. PREP N1 and P1 latencies did not differ between FD patients and controls (Figure 2a-c). Peak-to-peak amplitudes (PPA), however, were lower in male Fabry patients compared to male controls upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01, Figure 2d-f). Male Fabry patients also had lower PPA compared to female patients (hand: p < 0.05, foot: p < 0.01, Figure 2d-f). When comparing data of male Fabry patients with GFR < 60 and GFR > 60 with data of healthy male controls, only patients with impaired renal function showed reduced PPA after eliciting PREP from face (p = 0.012), hands (p = 0.007), and feet (p = 0.007, Figure 3a-c). Stimulus intensities did not differ between patients and controls at any site. Women with reduced α-GAL activity did not differ from women with normal enzyme activity as for PREP parameters. Additional file 3: Figure S3 shows an example of a PREP recording after stimulation at the face.

Bottom Line: Data were compared with healthy controls using non-parametric statistical tests.Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function.PREP amplitudes further decreased with advance in disease severity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, University of Wurzburg, Josef-Schneider-Str, 11, 97080 Wurzburg, Germany. ueceyler_n@klinik.uni-wuerzburg.de

ABSTRACT

Background: Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).

Methods: In this case-control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.

Results: All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.

Conclusion: Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.

Show MeSH
Related in: MedlinePlus