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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

Sensory profile of Fabry patients. The bar graphs show the z-score sensory profiles of quantitative sensory testing (QST) at the left dorsal foot in Fabry patients compared to healthy controls. Healthy controls are represented by the black zero line. Z-scores < 0 display loss of function, z-scores >0 show gain of function. a) Male Fabry patients have elevated detection thresholds for cold and warm (CDT, WDT), while the thermal sensory limen (TSL) for changing temperatures and the vibration detection threshold (VDT) was not different from controls. b) Female Fabry patients do not differ from female controls except for slightly elevated WDT. *p < 0.05, **p < 0.01.
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Figure 1: Sensory profile of Fabry patients. The bar graphs show the z-score sensory profiles of quantitative sensory testing (QST) at the left dorsal foot in Fabry patients compared to healthy controls. Healthy controls are represented by the black zero line. Z-scores < 0 display loss of function, z-scores >0 show gain of function. a) Male Fabry patients have elevated detection thresholds for cold and warm (CDT, WDT), while the thermal sensory limen (TSL) for changing temperatures and the vibration detection threshold (VDT) was not different from controls. b) Female Fabry patients do not differ from female controls except for slightly elevated WDT. *p < 0.05, **p < 0.01.

Mentions: In line with previous reports [4,5,23] we found elevated CDT (p < 0.01) and WDT (p < 0.05) in male Fabry patients compared with male controls (Figure 1a). Female patients did not differ from female controls (Figure 1b). Male patients had higher thermal perception thresholds and impaired vibration sense compared to female FD patients (CDT: p < 0.05, WDT: p < 0.001, TSL: p < 0.01, VDT: p < 0.01). PHS was present in none of the male patients and in 9/45 (20%) female FD patients. As shown earlier male patients with impaired renal function (GFR < 60 ml/min/1.73 m2) had most severe impairment in thermal perception (Additional file 2: Figure S2). Women with reduced α-GAL activity did not differ in QST parameters from women with normal enzyme activity.


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)

Sensory profile of Fabry patients. The bar graphs show the z-score sensory profiles of quantitative sensory testing (QST) at the left dorsal foot in Fabry patients compared to healthy controls. Healthy controls are represented by the black zero line. Z-scores < 0 display loss of function, z-scores >0 show gain of function. a) Male Fabry patients have elevated detection thresholds for cold and warm (CDT, WDT), while the thermal sensory limen (TSL) for changing temperatures and the vibration detection threshold (VDT) was not different from controls. b) Female Fabry patients do not differ from female controls except for slightly elevated WDT. *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 1: Sensory profile of Fabry patients. The bar graphs show the z-score sensory profiles of quantitative sensory testing (QST) at the left dorsal foot in Fabry patients compared to healthy controls. Healthy controls are represented by the black zero line. Z-scores < 0 display loss of function, z-scores >0 show gain of function. a) Male Fabry patients have elevated detection thresholds for cold and warm (CDT, WDT), while the thermal sensory limen (TSL) for changing temperatures and the vibration detection threshold (VDT) was not different from controls. b) Female Fabry patients do not differ from female controls except for slightly elevated WDT. *p < 0.05, **p < 0.01.
Mentions: In line with previous reports [4,5,23] we found elevated CDT (p < 0.01) and WDT (p < 0.05) in male Fabry patients compared with male controls (Figure 1a). Female patients did not differ from female controls (Figure 1b). Male patients had higher thermal perception thresholds and impaired vibration sense compared to female FD patients (CDT: p < 0.05, WDT: p < 0.001, TSL: p < 0.01, VDT: p < 0.01). PHS was present in none of the male patients and in 9/45 (20%) female FD patients. As shown earlier male patients with impaired renal function (GFR < 60 ml/min/1.73 m2) had most severe impairment in thermal perception (Additional file 2: Figure S2). Women with reduced α-GAL activity did not differ in QST parameters from women with normal enzyme activity.

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