BACKGROUND: Krabbe disease (KD) is associated with marked central and peripheral demyelination and nerve conduction studies (NCS) typically show a mixed sensorimotor demyelinating peripheral neuropathy (PN). OBJECTIVES: To further characterize the PN in a large cohort of patients with KD and to assess the diagnostic sensitivity of NCS in this condition. METHODS: The authors report the results of electrodiagnostic studies performed in 27 children with KD, ranging in age from 1 day to 8 years, whose diagnosis was confirmed by leukocyte lysosomal enzyme analysis. RESULTS: Based on age-adjusted normative values, 25 of 27 patients had abnormal NCS (sensitivity > 90%) when at least one motor and one sensory nerve were tested in a lower and an upper extremity. Of the 24 patients with the early infantile form of the disease, 23 had abnormal NCS (sensitivity > 95%). Abnormal sural sensory responses (SNR) (82%), F-wave latencies (FWL) (85%), motor conduction velocities (CV) (82%), and distal motor latencies (DL) (76%) were the most sensitive indices. In the lower extremities the sensitivity of motor CV, FWL, and motor DL was 79%, 79%, and 57%, respectively, while in the upper limbs the corresponding sensitivities were 80%, 87%, and 73%. No conduction block was detected and there was uniform slowing of CV. SNR was unobtainable or abnormal in 82% of patients. The compound muscle action potential amplitudes were within normal limits in >70% of lower limb and >45% of upper limb responses. Marked NCS abnormalities were found in a 1-day-old and two 3-week-old neonates, the youngest patients reported to date. NCS were abnormal in 5/9 children with normal EEG or evoked potentials. The severity of the demyelination on NCS correlated well with the clinical severity of the disease. CONCLUSIONS: Peripheral neuropathy occurs very early in Krabbe disease and affects the nerves uniformly. Nerve conduction studies may provide a highly sensitive tool to screen this patient population.
BACKGROUND:Krabbe disease (KD) is associated with marked central and peripheral demyelination and nerve conduction studies (NCS) typically show a mixed sensorimotor demyelinating peripheral neuropathy (PN). OBJECTIVES: To further characterize the PN in a large cohort of patients with KD and to assess the diagnostic sensitivity of NCS in this condition. METHODS: The authors report the results of electrodiagnostic studies performed in 27 children with KD, ranging in age from 1 day to 8 years, whose diagnosis was confirmed by leukocyte lysosomal enzyme analysis. RESULTS: Based on age-adjusted normative values, 25 of 27 patients had abnormal NCS (sensitivity > 90%) when at least one motor and one sensory nerve were tested in a lower and an upper extremity. Of the 24 patients with the early infantile form of the disease, 23 had abnormal NCS (sensitivity > 95%). Abnormal sural sensory responses (SNR) (82%), F-wave latencies (FWL) (85%), motor conduction velocities (CV) (82%), and distal motor latencies (DL) (76%) were the most sensitive indices. In the lower extremities the sensitivity of motor CV, FWL, and motor DL was 79%, 79%, and 57%, respectively, while in the upper limbs the corresponding sensitivities were 80%, 87%, and 73%. No conduction block was detected and there was uniform slowing of CV. SNR was unobtainable or abnormal in 82% of patients. The compound muscle action potential amplitudes were within normal limits in >70% of lower limb and >45% of upper limb responses. Marked NCS abnormalities were found in a 1-day-old and two 3-week-old neonates, the youngest patients reported to date. NCS were abnormal in 5/9 children with normal EEG or evoked potentials. The severity of the demyelination on NCS correlated well with the clinical severity of the disease. CONCLUSIONS:Peripheral neuropathy occurs very early in Krabbe disease and affects the nerves uniformly. Nerve conduction studies may provide a highly sensitive tool to screen this patient population.
Authors: Allison M Bradbury; Jessica H Bagel; Xuntian Jiang; Gary P Swain; Maria L Prociuk; Caitlin A Fitzgerald; Patricia A O'Donnell; Kyle G Braund; Daniel S Ory; Charles H Vite Journal: J Neurosci Res Date: 2016-11 Impact factor: 4.164
Authors: Gregory B Potter; Marta Santos; Muriel T Davisson; David H Rowitch; Dan L Marks; Ernesto R Bongarzone; Magdalena A Petryniak Journal: Hum Mol Genet Date: 2013-04-24 Impact factor: 6.150
Authors: Barbara W van Paassen; Anneke J van der Kooi; Karin Y van Spaendonck-Zwarts; Camiel Verhamme; Frank Baas; Marianne de Visser Journal: Orphanet J Rare Dis Date: 2014-03-19 Impact factor: 4.123
Authors: Vasco Meneghini; Annalisa Lattanzi; Luigi Tiradani; Gabriele Bravo; Francesco Morena; Francesca Sanvito; Andrea Calabria; John Bringas; Jeanne M Fisher-Perkins; Jason P Dufour; Kate C Baker; Claudio Doglioni; Eugenio Montini; Bruce A Bunnell; Krystof Bankiewicz; Sabata Martino; Luigi Naldini; Angela Gritti Journal: EMBO Mol Med Date: 2016-05-02 Impact factor: 12.137