H G Zouari1,2,3, S Ng Wing Tin4,5, A Wahab1,2, T Damy6,7,8, J-P Lefaucheur1,2,8. 1. EA 4391, Faculté de Médecine, Université Paris Est Créteil, Créteil, France. 2. Service de Physiologie, Explorations Fonctionnelles, Unité de Neurophysiologie Clinique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France. 3. Service d'Explorations Fonctionnelles, CHU Habib Bourguiba, Sfax, Tunisie. 4. Service de Physiologie, Explorations Fonctionnelles et Médecine du Sport, Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris, Bobigny, France. 5. EA 2363, UFR SMBH, Université Paris 13, Bobigny, France. 6. Service de Cardiologie, Unité d'Insuffisance, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France. 7. GRC Institut de Recherche sur l'Amylose, Faculté de Médecine, Université Paris Est Créteil, Créteil, France. 8. Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France.
Abstract
BACKGROUND AND PURPOSE: Distal involvement of autonomic nerve fibers is critical in familial amyloid polyneuropathy (FAP) due to transthyretin (TTR) mutation. This study compares different methods for assessing autonomic foot innervation in TTR-FAP patients. METHODS: Three groups of seven TTR-FAP patients were included, according to disease severity: clinically asymptomatic, moderate or advanced neuropathy. The autonomic investigation included the eutectic mixture of local anesthetics test and laser Doppler flowmetry for vasomotor aspects and the Sudoscan® (measuring electrochemical skin conductance) and Neuropad® test for sudomotor aspects. Somatic innervation was assessed by performing nerve conduction studies, quantitative sensory testing [including vibration, cold and warm detection threshold (WDT) measurements] and laser evoked potentials. RESULTS: The results of all neurophysiological tests varied according to TTR-FAP severity (P ≤ 0.01, Kruskal-Wallis test), except for the eutectic mixture of local anesthetics test and laser Doppler flowmetry variables. In addition, the sudomotor tests (Sudoscan or Neuropad) or WDT measurement provided early markers of neuropathy in two of the seven asymptomatic carriers. Finally, all neurophysiological results correlated with the Neuropathy Impairment Score (r values between -0.88 and -0.66, P < 0.005, Spearman test), except the cold detection threshold. CONCLUSIONS: The Neuropad test could be used to detect TTR-FAP onset, but confirmation requires electrochemical skin conductance and WDT measurement. The Sudoscan technique, but not the Neuropad test (at least assessed at a fixed time point), could be valuable to follow the progression of the neuropathy. Follow-up investigation should also include large-fiber investigation (e.g. nerve conduction studies and vibration detection threshold). Conversely, reliable tests for assessing vasomotor disturbances in limb extremities of TTR-FAP patients are still awaited.
BACKGROUND AND PURPOSE: Distal involvement of autonomic nerve fibers is critical in familial amyloid polyneuropathy (FAP) due to transthyretin (TTR) mutation. This study compares different methods for assessing autonomic foot innervation in TTR-FAPpatients. METHODS: Three groups of seven TTR-FAPpatients were included, according to disease severity: clinically asymptomatic, moderate or advanced neuropathy. The autonomic investigation included the eutectic mixture of local anesthetics test and laser Doppler flowmetry for vasomotor aspects and the Sudoscan® (measuring electrochemical skin conductance) and Neuropad® test for sudomotor aspects. Somatic innervation was assessed by performing nerve conduction studies, quantitative sensory testing [including vibration, cold and warm detection threshold (WDT) measurements] and laser evoked potentials. RESULTS: The results of all neurophysiological tests varied according to TTR-FAP severity (P ≤ 0.01, Kruskal-Wallis test), except for the eutectic mixture of local anesthetics test and laser Doppler flowmetry variables. In addition, the sudomotor tests (Sudoscan or Neuropad) or WDT measurement provided early markers of neuropathy in two of the seven asymptomatic carriers. Finally, all neurophysiological results correlated with the Neuropathy Impairment Score (r values between -0.88 and -0.66, P < 0.005, Spearman test), except the cold detection threshold. CONCLUSIONS: The Neuropad test could be used to detect TTR-FAP onset, but confirmation requires electrochemical skin conductance and WDT measurement. The Sudoscan technique, but not the Neuropad test (at least assessed at a fixed time point), could be valuable to follow the progression of the neuropathy. Follow-up investigation should also include large-fiber investigation (e.g. nerve conduction studies and vibration detection threshold). Conversely, reliable tests for assessing vasomotor disturbances in limb extremities of TTR-FAPpatients are still awaited.
Keywords:
Neuropad; Sudoscan; amyloidosis; early markers; eutectic mixture of local anesthetics; laser Doppler flowmetry; small fiber neuropathy; transthyretin