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T44. Abnormalities of motor axonal properties in amyotrophic lateral sclerosis
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Abstracts / Clinical Neurophysiology 129 (2018) e1–e65
were studied by EMG which represents an average of 16.5 muscles studied per patient. Of the 1,844 muscles studied, 649 were reported to show fasciculation potentials (34%) and 1067 showed fibrillation potentials (58%). None of the patients diagnosed with ALS had 0 muscles showing fibrillation potentials. However, 15 patients (12%) were reported to have 0 muscles showing fasciculation potentials. The number of ALS patients with 5 or fewer muscles showing fasciculation potentials was high at 54 (48%) compared to the number of ALS patients with 5 or fewer muscles showing fibrillation potentials, which was only 16 (14%). Conclusion: This retrospective review of EMG findings in ALS patients suggests that fasciculation potentials are not identified as often as fibrillation potentials. All patients with a final diagnosis of ALS had fibrillation potentials on their EMG study whereas 12% of patients with a final diagnosis of ALS did not have fasciculation potentials identified on their EMG study. Thus, absence of fasciculation potentials should not be considered an unusual circumstance in ALS patients or an argument against the diagnosis of ALS. In contrast, fibrillation potentials are an expected finding in patients with ALS and the absence of fibrillation potentials does provide a strong argument against the diagnosis of ALS. doi:10.1016/j.clinph.2018.04.044
T44. Abnormalities of motor axonal properties in amyotrophic lateral sclerosis—Tomoko Nakazato *, Kazuaki Kanai, Genko Oyama, Yasushi Shimo, Nobutaka Hattori (Japan) ⇑
Presenting author.
Introduction: To date, changes of axonal sodium and potassium currents have been reported in amyotrophic lateral sclerosis (ALS) (Bostock et al., 1995; Kanai et al., 2006), and the association to prognosis and characteristic symptoms such as fasciculations has been discussed. To confirm the previously reported changes, multiple axonal excitability properties were measured in patients with ALS, and compared with age-matched controls. Methods: A total of 55 patients with sporadic ALS, who visited to Juntendo University Hospital from 2013 to 2017, were included in the study. Multiple excitability measurements were performed in the median nerve at the wrist using a computerized program (QTRAC with multiple excitability protocol, Institute of Neurology, London, UK). Results: The age range of the patients was from 30 to 82 years old (median 62.7 years old), and there were 31 male and 24 female. As clinical phenotypes, 13 patients were bulber onset type, 31 were upper limbs onset type, 9 were lower limbs onset type, and 2 were multiple onset type. In ALS, there were extremely greater changes in depolarizing threshold electrotonus (P < 0.001) and greater supernormality in the recovery cycles (P < 0.001). Strength-duration time constant was prolonged in ALS (P < 0.001). Conclusion: This study suggested increased persistent sodium currents and reduced potassium currents in motor axons, as well as previous studies. Both of these changes lead to axonal hyperexcitability, and may contribute to the generation of fasciculations. Because neuronal hyperexcitibility is one of hypotheses of cause of neuronal death in ALS, these changes may also contribute motor neuronal death in ALS. doi:10.1016/j.clinph.2018.04.045
T45. Effects of fampridine administration on central motor conduction failure in multiple sclerosis patients—Alessia Di Sapio *, Stefano Giorgi, Antonio Bertolotto, Francesca Sperli, Federica Melillo, Walter Troni (Italy) ⇑
Presenting author.
Introduction: Fampridine is a slow-release potassium channel blocker that ameliorates the impaired conduction in CNS demyelinated axons. In multiple sclerosis (MS) patients, wide fluctuations in fatigue perception make difficult to assess the highly variable clinical response to treatment. Previous study reported that central motor conduction time (CMCT) improvement may predict fampridine response. Nevertheless, more than conduction slowdown, central motor conduction failure (CMCF), i.e. conduction block and axonal damage, reflects walking impairment in MS patients. Decrease of Motor Evoked Potentials (MEP) area, much more than amplitude, may detect CMCF. Serial MEP area recordings and analysis, according to a protocol that reduces MEP area random variability, may detect CMCF variation. We evaluated the effects of fampridine on CMCT and CMCF by serial recordings of MEPs from several proximal and distal muscle districts of lower limbs in a MS patients cohort and we correlated the obtained data with clinical outcome. Methods: In 10 MS patients, MEPs to TMS by double-cone coil and maximal Compound Motor Action Potentials (CMAPs) to High Voltage Electrical Stimulation of lumbosacral roots were recorded from Vastus Medialis and Lateralis, Tibialis Anterior, Peroneus Longus and Flexor Hallucis Brevis of both limbs (T1) according to the published method (Di Sapio et al., 2014). Stimulation and recorded sites were marked. In 3 patients the test was repeated after one week (T1b), as control. After 14 days of fampridine treatment, before stopping therapy (T2), the procedure was repeated, strictly maintaining the same stimulation and recording sites and stimulation intensities. The 25-foot walking test (25FWT), 6-min walking test (6’-WT), the Fatigue Score Scale (FSS) and the Modified Fatigue Inventory Scale (MFIS) were administered at each time point. In each patient CMCT, MEP area and MEP Area/CMAP area ratios (ARs) were compared, and if appropriate their variability normalized according to Troni et al. (2016). Patients were classified as neurophysiological responders when 2 or more area/latency indexes significantly improved, remaining the others stable. Moreover, pooled data from the whole cohort in different time-points were compared using T test (Wilcoxon). Results: CMCT, MEP area and AR did not change significantly in patients not receiving fampridine. After fampridine administration 3 patients were classified as responders; the same patients reported fatigue reduction and showed significant improvement in FSS score and 25FWT, while MFIS and 6’WT improved only in 1 patient. By analysing pooled data obtained from responders only, a significant reduction of CMCT (p = 0.0057) and increase in MEP area (p = 0.0014) and AR (p = 0.048) were noted. Conclusion: The CMCF evaluation, together with CMCT, both made more sensitive by adopting multiple recording sites, correlate with self-reported and clinical outcome of fampridine treatment and may help to clarify doubt cases. doi:10.1016/j.clinph.2018.04.046
Abstracts / Clinical Neurophysiology 129 (2018) e1–e65
were studied by EMG which represents an average of 16.5 muscles studied per patient. Of the 1,844 muscles studied, 649 were reported to show fasciculation potentials (34%) and 1067 showed fibrillation potentials (58%). None of the patients diagnosed with ALS had 0 muscles showing fibrillation potentials. However, 15 patients (12%) were reported to have 0 muscles showing fasciculation potentials. The number of ALS patients with 5 or fewer muscles showing fasciculation potentials was high at 54 (48%) compared to the number of ALS patients with 5 or fewer muscles showing fibrillation potentials, which was only 16 (14%). Conclusion: This retrospective review of EMG findings in ALS patients suggests that fasciculation potentials are not identified as often as fibrillation potentials. All patients with a final diagnosis of ALS had fibrillation potentials on their EMG study whereas 12% of patients with a final diagnosis of ALS did not have fasciculation potentials identified on their EMG study. Thus, absence of fasciculation potentials should not be considered an unusual circumstance in ALS patients or an argument against the diagnosis of ALS. In contrast, fibrillation potentials are an expected finding in patients with ALS and the absence of fibrillation potentials does provide a strong argument against the diagnosis of ALS. doi:10.1016/j.clinph.2018.04.044
T44. Abnormalities of motor axonal properties in amyotrophic lateral sclerosis—Tomoko Nakazato *, Kazuaki Kanai, Genko Oyama, Yasushi Shimo, Nobutaka Hattori (Japan) ⇑
Presenting author.
Introduction: To date, changes of axonal sodium and potassium currents have been reported in amyotrophic lateral sclerosis (ALS) (Bostock et al., 1995; Kanai et al., 2006), and the association to prognosis and characteristic symptoms such as fasciculations has been discussed. To confirm the previously reported changes, multiple axonal excitability properties were measured in patients with ALS, and compared with age-matched controls. Methods: A total of 55 patients with sporadic ALS, who visited to Juntendo University Hospital from 2013 to 2017, were included in the study. Multiple excitability measurements were performed in the median nerve at the wrist using a computerized program (QTRAC with multiple excitability protocol, Institute of Neurology, London, UK). Results: The age range of the patients was from 30 to 82 years old (median 62.7 years old), and there were 31 male and 24 female. As clinical phenotypes, 13 patients were bulber onset type, 31 were upper limbs onset type, 9 were lower limbs onset type, and 2 were multiple onset type. In ALS, there were extremely greater changes in depolarizing threshold electrotonus (P < 0.001) and greater supernormality in the recovery cycles (P < 0.001). Strength-duration time constant was prolonged in ALS (P < 0.001). Conclusion: This study suggested increased persistent sodium currents and reduced potassium currents in motor axons, as well as previous studies. Both of these changes lead to axonal hyperexcitability, and may contribute to the generation of fasciculations. Because neuronal hyperexcitibility is one of hypotheses of cause of neuronal death in ALS, these changes may also contribute motor neuronal death in ALS. doi:10.1016/j.clinph.2018.04.045
T45. Effects of fampridine administration on central motor conduction failure in multiple sclerosis patients—Alessia Di Sapio *, Stefano Giorgi, Antonio Bertolotto, Francesca Sperli, Federica Melillo, Walter Troni (Italy) ⇑
Presenting author.
Introduction: Fampridine is a slow-release potassium channel blocker that ameliorates the impaired conduction in CNS demyelinated axons. In multiple sclerosis (MS) patients, wide fluctuations in fatigue perception make difficult to assess the highly variable clinical response to treatment. Previous study reported that central motor conduction time (CMCT) improvement may predict fampridine response. Nevertheless, more than conduction slowdown, central motor conduction failure (CMCF), i.e. conduction block and axonal damage, reflects walking impairment in MS patients. Decrease of Motor Evoked Potentials (MEP) area, much more than amplitude, may detect CMCF. Serial MEP area recordings and analysis, according to a protocol that reduces MEP area random variability, may detect CMCF variation. We evaluated the effects of fampridine on CMCT and CMCF by serial recordings of MEPs from several proximal and distal muscle districts of lower limbs in a MS patients cohort and we correlated the obtained data with clinical outcome. Methods: In 10 MS patients, MEPs to TMS by double-cone coil and maximal Compound Motor Action Potentials (CMAPs) to High Voltage Electrical Stimulation of lumbosacral roots were recorded from Vastus Medialis and Lateralis, Tibialis Anterior, Peroneus Longus and Flexor Hallucis Brevis of both limbs (T1) according to the published method (Di Sapio et al., 2014). Stimulation and recorded sites were marked. In 3 patients the test was repeated after one week (T1b), as control. After 14 days of fampridine treatment, before stopping therapy (T2), the procedure was repeated, strictly maintaining the same stimulation and recording sites and stimulation intensities. The 25-foot walking test (25FWT), 6-min walking test (6’-WT), the Fatigue Score Scale (FSS) and the Modified Fatigue Inventory Scale (MFIS) were administered at each time point. In each patient CMCT, MEP area and MEP Area/CMAP area ratios (ARs) were compared, and if appropriate their variability normalized according to Troni et al. (2016). Patients were classified as neurophysiological responders when 2 or more area/latency indexes significantly improved, remaining the others stable. Moreover, pooled data from the whole cohort in different time-points were compared using T test (Wilcoxon). Results: CMCT, MEP area and AR did not change significantly in patients not receiving fampridine. After fampridine administration 3 patients were classified as responders; the same patients reported fatigue reduction and showed significant improvement in FSS score and 25FWT, while MFIS and 6’WT improved only in 1 patient. By analysing pooled data obtained from responders only, a significant reduction of CMCT (p = 0.0057) and increase in MEP area (p = 0.0014) and AR (p = 0.048) were noted. Conclusion: The CMCF evaluation, together with CMCT, both made more sensitive by adopting multiple recording sites, correlate with self-reported and clinical outcome of fampridine treatment and may help to clarify doubt cases. doi:10.1016/j.clinph.2018.04.046