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P922: Comparative detection of fasciculations with ultrasonography and surface electromyography in amyotrophic lateral sclerosis patients
Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
Conclusions: Electrically evoked MD are highly specific for ALS and PMA, more so than fasciculations. The presence of electrically evoked MDs is an early sign of lower motor neuron dysfunction.
P919 Proteomic analysis of muscle tissue from patients with motorneuron disease and controls K. Elf 1 , G. Shevchenko 2 , L. Larsson 1 , I. Nygren 1 , J. Bergquist 2 , H. Askmark 1 , K. Artemenko 2 1 Uppsala University, Neuroscience, Uppsala, Sweden; 2 Uppsala University, Chemistry, Uppsala, Sweden Question: Is there a difference in muscle proteome in patients with ALS compared to controls when analysed with mass spectroscopy (MS) and can that difference be used as a biomarker? Methods: A muscle biopsy was taken from the anterior tibial muscle in 10 ALS-patients and 10 controls without neurological disease. Three controls with other neurological diseases with denervation were also analysed in order get a picture of proteomic change due to denervation. Muscle biopsies were homogenized and the proteins were extracted with detergent lysis buffer. Extracted proteins were on-filter digested with trypsin. Dimethyl isotope labels were used to globally label the tryptic peptides for relative quantification. Individually labelled peptides from patients and controls were combined and analysed by reversed phase nanoliquid chromatography and mass spectroscopy. The same procedure was repeated but with different labels for patients, controls and denervation controls. Results: The abundance of eleven proteins was significantly different between patients and healthy controls. Of these proteins the most interesting were Cytochcrome C oxidase and Valocin containing protein (VCP). Analyses including controls with denervation due to other neurological diseases, did not show the same changes for the eleven proteins, suggesting that the differences found between ALS-patients and healthy controls were not only due to denervation. Conclusions: Muscle proteome analysed with MS is different in patients with ALS as compared to controls. This difference does not seem to be due to denervation solely. Proteomic analysis of muscle tissue might be used as a biomarker for the disease.
P920 Sonographic assessment of nerve and root atrophy in ALS N. Takamatsu 1 , H. Nodera 1 , Y. Shimatani 1 , A. Mori 1 , M. Oda 2 , Y. Terasawa 1 , Y. Izumi 1 , R. Kaji 1 1 Tokushima University, Neurology, Tokushima, Japan; 2 Vihara Hananosato Hospital, Miyoshi, Japan Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease mainly affecting the upper and lower motor neurons. Because reinnervation may preserve muscle strength and a motor action potential until its late stage, a sensitive measure to reflect the axon loss is needed for early diagnosis and follow-up. Therefore, the aim of the study was to assess the degeneration of the nerve roots in ALS by ultrasonography. Material and methods: Thirty-five patients (20 men, 58.0±11 years) who met the diagnostic criteria of ALS (Revised El Escorial with Awaji electrodi-
S291
agnostic criteria) and 37 normal control individuals (13 men, 55.3±8 years) received sonographic evaluation of the right C5, C6, and C7 roots and right median and ulnar nerves at the wrist. The fascicle diameters (FDs) and some of the cross-sectional areas (CSAs) were evaluated and compared. Results: The data from the control individuals showed that the age or gender had no significant effects on the sonographic parameters. There was significant reduction of the FDs and CSAs in the ALS patients than the control individuals in all the parameters (P<0.01). The receiver operating curve analysis showed the areas under the curves (AUCs) were greater in the cervical roots (0.74-0.87) than the peripheral nerves (0.66-0.76). The C6 FD had the greatest AUC. Discussion: The present data revealed the sonographic evidence of atrophy of the cervical nerve roots and peripheral nerves in ALS that likely represents axonal degeneration. Although the present data were similar to the previous presentation assessing the peripheral nerve (Cartwright, et al) in ALS, the evaluation of the nerve root can further utilize the ultrasonographic assessment of the motor nerves that innervate the proximal musculature. The sonographic evaluation of the peripheral nervous system can become a useful measure for diagnosis and progression of ALS.
P921 ALS dysphagia: different BoNT/A response for different pathophysiology D. Restivo, A. Casabona, E. Alfonsi, A. Nicotra, M. Elia, M.C. Romano, M. Zappia, R. Marchese-Ragona Neurological Unit, Nuovo “Garibaldi” Hospital, Department of Internal Medicine, Catania, Italy Background: Dysphagia is a very common and troublesome complication in Amyotrophic Lateral Sclerosis (ALS) that may be due to upper and/or lower motor neuron (UMN/LMN) involvement. So far, no pharmacological treatment has provided to be successful in ALS-associated dysphagia. Aims: This study looked at the effect of botulinum neurotoxin type A (BoNT/A) in ALS patients with dysphagia due to isolated UMN involvement or combined UMN/LMN impairment associated with oral phase and/or oro-pharyngeal muscles involvement. Establishing whether different pathophysiological mechanisms underlie different responses to BoNT/A treatment may have important patient management implications. Patients and methods: Thirty-five sporadic ALS patients with dysphagia were screened. Twenty-out-of-35 with upper esophageal sphincter (UES) hyperactivity were included in the study. Based on the presence or absence of LMN impairment, the 20 patients were divided into 2 groups. Irrespective of the groups, all 20 patients were treated with BoNT/A into the UES. The study outcome was dysphagia severity scored using the Penetration Aspiration Scale (PAS), measured before and 2, 4 and 20 weeks after injection. Results: Significant mean PAS reduction at week 2 and 4. The botulinumdependent PAS reduction was entirely associated to the variability showed by the group of patients with no sign of LMN impairment (group 2) and was not observed in group 1. Conclusions: The significant improvement observed in patients with isolated UES dysfunction suggests that different pathophysiology of ALS dysphagia predisposes patients to different response to treatment with BoNT/A. This treatment may represent an alternative treatment to PEG or prolong PEG-free time.
P922 Comparative detection of fasciculations with ultrasonography and surface electromyography in amyotrophic lateral sclerosis patients C. Vial, L. Quesnel-Mazurier, J. Svahn, C. Roche, S. Sanchez, J. Bourbon, F. Bouhour Neurological hospital Pierre Wertheimer, ENMG Neuromuscular Department, Lyon-Bron, France
Figure 1
Since Awaji criteria in 2008 [1], fasciculations are of particular importance in the diagnosis of amyotrophic lateral sclerosis (ALS) to assess lower motor neuron involvment. Both surface EMG and ultrasonography (US) are non invasive and painful methods that have demonstrated accuracy for detection of fasciculations in comparison to clinical and electrophysiological examination [2]. The objective of this study was to compare detection of fasciculations with surface EMG and US in ALS patients and its contribution to the diagnosis. This study prospectively enrolled 18 patients who were referred to our
S292
Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
EMG clinic for early diagnosis of ALS. All patients were classified according clinical and electrophysiological examinations using Awaji algorithm. We performed US and EMG examinations in 15 muscles for only one (tongue, paraspinalis T10, abdominal) or both sides (deltoid, flexor carpi ulnaris, first dorsal interosseus, vastus medialis, tibialis anterior, gastrocnemius). Using 13-6 mHz linear array transducer and surface electrodes, each muscle was screened during 30 seconds to determine presence or absence of fasciculations. 11 males and 6 females were included. Fasciculations were detected in 64.6% of 270 muscles with surface EMG whereas 62.4% (p=0.64) with US, and only 35.1% according to clinical examination and 50% to electromyography. Frequencies of fasciculations were higher in limbs muscle using surface EMG and for axial muscle using ultrasonography. Proportion of the patients with the definite category of the awaji criteria increased from 22% using only EMG to 56% with US and 38.8% with EMG (p=0.5). These results confirm help for diagnostic of both non invasive methods. US was more sensitive for detection of fasciculations in axial and deep muscles and it was easier to use and less liable to artefacts. Both techniques weren’t much more sensitive for tongue like in Misawa study [2]. Surface EMG and US improve detection rate of fasciculations. US can be a useful tool to increase Awaji algorithm sensitivity in ALS. References: [1] De Cavarlho M, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 2008 [2] Misawa S, et al.Ultrasonographic detection of fasciculations markedly increases diagnostic sensitivity of ALS. Neurology. 2011
P923 Complex fasciculation potentials and survival in amyotrophic lateral sclerosis T. Shimizu 1 , Y. Fujimaki 1 , S. Nakatani-Enomoto 2 , K. Watabe 3 , I. Nakano 1 , P. Rossini 4 , Y. Ugawa 2 1 Tokyo Metropolitan Neurological Hospital, Neurology, Tokyo, Japan; 2 Fukushima Medical University School of Medicine, Neurology, Fukushima, Japan; 3 Tokyo Metropolitan Institute of Medical Science, ALS/Neuropathy Project, Tokyo, Japan; 4 Catholic University of The Sacred Heart, Neurology, Rome, Italy Question: Our aim was to investigate the relationship between distribution of fasciculation potentials (FPs) and clinical features, and the correlation between FPs and survival in patients with amyotrophic lateral sclerosis (ALS). Methods: In 85 patients with sporadic ALS, we prospectively performed needle EMG in five to seven muscles of each patient. The shape of the detected FPs was analyzed by inspection, and FPs with >4 phases were judged as complex FPs. We followed the patients until the endpoint (death, tracheostomy, or ventilator use), and analyzed the correlation between complex FPs and survival period using the Cox proportional hazard model. Results: Complex FPs were observed in 47 patients (55.3%) in at least one muscle, more frequently in the muscles with normal strength or mild weakness. The presence of complex FPs was associated with shorter survival (hazard ratio 3.055; 95% CI 1.417-7.406; p=0.004). The median survival times after the disease onset were 3.1 and 1.5 years for patients without and with complex FPs, respectively (p=0.0017). The greater the number of muscles with complex FPs, the shorter the survival and the faster the progression speed. Conclusions: Wide distribution of complex FPs is associated with shorter survival in ALS. Axonal membrane instability and resultant spontaneous firing of distal motor axons might be directly associated with the extension of motor neuron degeneration.
P924 Phrenic nerve motor responses and survival in amyotrophic lateral sclerosis K. Bokuda, T. Shimizu, K. Hayashi, T. Yamazaki, I. Nakano Tokyo Metropolitan Neurological Hospital, Department of Neurology, Tokyo, Japan Question: The aim of the study was to investigate the relationship between phrenic nerve motor responses and respiratory function, and survival prognosis in patients with amyotrophic lateral sclerosis (ALS). Methods: In 84 patients with sporadic ALS, we performed peripheral
electrical stimulation of the phrenic nerves at the posterior edge of the sternocleidomastoid muscle. Diaphragm motor responses were recorded from the disk electrodes placed on the xiphoid process (active) and on the costal margin of the mid-clavicle sagittal line (inactive). Peak-to-trough amplitudes of diaphragm M waves (Damp) were measured. We evaluated forced vital capacity (%FVC) as respiratory function. Endpoints were set at the time of death, tracheostomy, or ventilator use, and the survival periods were calculated from the time of examination to the endpoints. We analyzed the correlation between the phrenic response size and respiratory function test, and survival periods. Results: %FVC was 65.1% (mean) (SD 29.3), and Damp was 0.44 mV (0.28). There was a weak significant correlation between the values of %FVC and Damp (R2 =0.097; p=0.008). The significant difference in survival rate was noted between the patients with Damp ≥ and <0.4 mV (Cox model, hazard ratio 3.009; p=0.003). Multivariate analysis showed that Damp was one of the independent predictive factors for survival after the examination. Conclusions: Phrenic nerve motor responses reflect respiratory function and predict survival prognosis after the examination. The amplitude size <0.4 mV may lead us to consider further respiratory support including non-invasive ventilation for ALS patients.
LP53 Electromyographic evidence for repair of motor neurons in patients with ALS W. Schulte-Mattler 1 , I. Kobor 1 , D. Baldaranov 1 , A. Khomenko 1 , S. Johannesen 1 , T.-H. Bruun 1 , C. Bischoff 2 , U. Bogdahn 1 1 University of Regensburg, Neurology, Regensburg, Germany; 2 Neurologische Gemeischaftspraxis am Marienplatz, Muenchen, Germany Question: Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the degeneration of both upper and lower motor neurons. Repair of motor neurons has not been observed in patients with ALS so far; collateral sprouting frequently is found, it causes the polyphasic motor unit action potentials (MUAPs) in concentric needle electromyograms (CNEMG) recorded from patients with ALS. Axonal growth would yield small, instable, polyphasic, so called nascent MUAPs. To detect neural repair, we screened for nascent MUAPs in patients with ALS. Methods: 11 patients with definite ALS according to the El Escorial criteria were studied. Four patients were in a compassionate use treatment program with s.c. rec-hu-G-CSF. CNEMG recordings from hypothenar muscles of at least 50 seconds duration were analyzed independently by two of the authors, WSM and CB, with particular respect to nascent MUAPs. CB was fully blinded throughout his analysis. Results: Nascent MUAPs were consistently found in all patients treated with G-CSF and in one of the other patients. In one other patient nascent MUAPs were found only by CB. The difference between treated and untreated patients was statistically significant (Fisher’s exact test). Conclusions: The presence of nascent MUAPs indicates that repair of motor neurons may occur in ALS patients spontaneously. The higher incidence of signs of repair in patients treated with G-CSF is encouraging. Moreover it is in line with the findings of Pitzer et al. (JNC 2010) and Henriques et al (Mol. Therapy 2011) who described identical phenomena in an SOD1 G93A experimental ALS mouse model. Therefore it may be worthwhile to further elucidate these repair mechanisms ALS.
Poster session 53. Movement disorders 2 P925 Somatosensory evoked potential (SEP) modulation by quadripulse transcranial magnetic stimulation (QPS) in benign myoclonus epilepsy patients S. Nakatani-Enomoto 1 , R. Hanajima 2 , M. Hamada 2 , Y. Terao 2 , H. Matsumoto 2 , Y. Shirota 2 , S. Ohminami 2 , S. Okabe 2 , M. Hirose 1 , K. Nakamura 1 , T. Furubayashi 3 , S. Groiss 1 , S. Kobayashi 1 , H. Mochizuki 1 , H. Enomoto 1 , Y. Ugawa 1 1 Fukushima Medical University, Neurology, Fukushima, Japan; 2 The University of Tokyo, Neurology, Tokyo, Japan; 3 Tohoku Bunka Gakuen University, Health and Social Services, Miyagi, Japan Objective: Quadripulse transcranial magnetic stimulation (QPS) applied
Conclusions: Electrically evoked MD are highly specific for ALS and PMA, more so than fasciculations. The presence of electrically evoked MDs is an early sign of lower motor neuron dysfunction.
P919 Proteomic analysis of muscle tissue from patients with motorneuron disease and controls K. Elf 1 , G. Shevchenko 2 , L. Larsson 1 , I. Nygren 1 , J. Bergquist 2 , H. Askmark 1 , K. Artemenko 2 1 Uppsala University, Neuroscience, Uppsala, Sweden; 2 Uppsala University, Chemistry, Uppsala, Sweden Question: Is there a difference in muscle proteome in patients with ALS compared to controls when analysed with mass spectroscopy (MS) and can that difference be used as a biomarker? Methods: A muscle biopsy was taken from the anterior tibial muscle in 10 ALS-patients and 10 controls without neurological disease. Three controls with other neurological diseases with denervation were also analysed in order get a picture of proteomic change due to denervation. Muscle biopsies were homogenized and the proteins were extracted with detergent lysis buffer. Extracted proteins were on-filter digested with trypsin. Dimethyl isotope labels were used to globally label the tryptic peptides for relative quantification. Individually labelled peptides from patients and controls were combined and analysed by reversed phase nanoliquid chromatography and mass spectroscopy. The same procedure was repeated but with different labels for patients, controls and denervation controls. Results: The abundance of eleven proteins was significantly different between patients and healthy controls. Of these proteins the most interesting were Cytochcrome C oxidase and Valocin containing protein (VCP). Analyses including controls with denervation due to other neurological diseases, did not show the same changes for the eleven proteins, suggesting that the differences found between ALS-patients and healthy controls were not only due to denervation. Conclusions: Muscle proteome analysed with MS is different in patients with ALS as compared to controls. This difference does not seem to be due to denervation solely. Proteomic analysis of muscle tissue might be used as a biomarker for the disease.
P920 Sonographic assessment of nerve and root atrophy in ALS N. Takamatsu 1 , H. Nodera 1 , Y. Shimatani 1 , A. Mori 1 , M. Oda 2 , Y. Terasawa 1 , Y. Izumi 1 , R. Kaji 1 1 Tokushima University, Neurology, Tokushima, Japan; 2 Vihara Hananosato Hospital, Miyoshi, Japan Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease mainly affecting the upper and lower motor neurons. Because reinnervation may preserve muscle strength and a motor action potential until its late stage, a sensitive measure to reflect the axon loss is needed for early diagnosis and follow-up. Therefore, the aim of the study was to assess the degeneration of the nerve roots in ALS by ultrasonography. Material and methods: Thirty-five patients (20 men, 58.0±11 years) who met the diagnostic criteria of ALS (Revised El Escorial with Awaji electrodi-
S291
agnostic criteria) and 37 normal control individuals (13 men, 55.3±8 years) received sonographic evaluation of the right C5, C6, and C7 roots and right median and ulnar nerves at the wrist. The fascicle diameters (FDs) and some of the cross-sectional areas (CSAs) were evaluated and compared. Results: The data from the control individuals showed that the age or gender had no significant effects on the sonographic parameters. There was significant reduction of the FDs and CSAs in the ALS patients than the control individuals in all the parameters (P<0.01). The receiver operating curve analysis showed the areas under the curves (AUCs) were greater in the cervical roots (0.74-0.87) than the peripheral nerves (0.66-0.76). The C6 FD had the greatest AUC. Discussion: The present data revealed the sonographic evidence of atrophy of the cervical nerve roots and peripheral nerves in ALS that likely represents axonal degeneration. Although the present data were similar to the previous presentation assessing the peripheral nerve (Cartwright, et al) in ALS, the evaluation of the nerve root can further utilize the ultrasonographic assessment of the motor nerves that innervate the proximal musculature. The sonographic evaluation of the peripheral nervous system can become a useful measure for diagnosis and progression of ALS.
P921 ALS dysphagia: different BoNT/A response for different pathophysiology D. Restivo, A. Casabona, E. Alfonsi, A. Nicotra, M. Elia, M.C. Romano, M. Zappia, R. Marchese-Ragona Neurological Unit, Nuovo “Garibaldi” Hospital, Department of Internal Medicine, Catania, Italy Background: Dysphagia is a very common and troublesome complication in Amyotrophic Lateral Sclerosis (ALS) that may be due to upper and/or lower motor neuron (UMN/LMN) involvement. So far, no pharmacological treatment has provided to be successful in ALS-associated dysphagia. Aims: This study looked at the effect of botulinum neurotoxin type A (BoNT/A) in ALS patients with dysphagia due to isolated UMN involvement or combined UMN/LMN impairment associated with oral phase and/or oro-pharyngeal muscles involvement. Establishing whether different pathophysiological mechanisms underlie different responses to BoNT/A treatment may have important patient management implications. Patients and methods: Thirty-five sporadic ALS patients with dysphagia were screened. Twenty-out-of-35 with upper esophageal sphincter (UES) hyperactivity were included in the study. Based on the presence or absence of LMN impairment, the 20 patients were divided into 2 groups. Irrespective of the groups, all 20 patients were treated with BoNT/A into the UES. The study outcome was dysphagia severity scored using the Penetration Aspiration Scale (PAS), measured before and 2, 4 and 20 weeks after injection. Results: Significant mean PAS reduction at week 2 and 4. The botulinumdependent PAS reduction was entirely associated to the variability showed by the group of patients with no sign of LMN impairment (group 2) and was not observed in group 1. Conclusions: The significant improvement observed in patients with isolated UES dysfunction suggests that different pathophysiology of ALS dysphagia predisposes patients to different response to treatment with BoNT/A. This treatment may represent an alternative treatment to PEG or prolong PEG-free time.
P922 Comparative detection of fasciculations with ultrasonography and surface electromyography in amyotrophic lateral sclerosis patients C. Vial, L. Quesnel-Mazurier, J. Svahn, C. Roche, S. Sanchez, J. Bourbon, F. Bouhour Neurological hospital Pierre Wertheimer, ENMG Neuromuscular Department, Lyon-Bron, France
Figure 1
Since Awaji criteria in 2008 [1], fasciculations are of particular importance in the diagnosis of amyotrophic lateral sclerosis (ALS) to assess lower motor neuron involvment. Both surface EMG and ultrasonography (US) are non invasive and painful methods that have demonstrated accuracy for detection of fasciculations in comparison to clinical and electrophysiological examination [2]. The objective of this study was to compare detection of fasciculations with surface EMG and US in ALS patients and its contribution to the diagnosis. This study prospectively enrolled 18 patients who were referred to our
S292
Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
EMG clinic for early diagnosis of ALS. All patients were classified according clinical and electrophysiological examinations using Awaji algorithm. We performed US and EMG examinations in 15 muscles for only one (tongue, paraspinalis T10, abdominal) or both sides (deltoid, flexor carpi ulnaris, first dorsal interosseus, vastus medialis, tibialis anterior, gastrocnemius). Using 13-6 mHz linear array transducer and surface electrodes, each muscle was screened during 30 seconds to determine presence or absence of fasciculations. 11 males and 6 females were included. Fasciculations were detected in 64.6% of 270 muscles with surface EMG whereas 62.4% (p=0.64) with US, and only 35.1% according to clinical examination and 50% to electromyography. Frequencies of fasciculations were higher in limbs muscle using surface EMG and for axial muscle using ultrasonography. Proportion of the patients with the definite category of the awaji criteria increased from 22% using only EMG to 56% with US and 38.8% with EMG (p=0.5). These results confirm help for diagnostic of both non invasive methods. US was more sensitive for detection of fasciculations in axial and deep muscles and it was easier to use and less liable to artefacts. Both techniques weren’t much more sensitive for tongue like in Misawa study [2]. Surface EMG and US improve detection rate of fasciculations. US can be a useful tool to increase Awaji algorithm sensitivity in ALS. References: [1] De Cavarlho M, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 2008 [2] Misawa S, et al.Ultrasonographic detection of fasciculations markedly increases diagnostic sensitivity of ALS. Neurology. 2011
P923 Complex fasciculation potentials and survival in amyotrophic lateral sclerosis T. Shimizu 1 , Y. Fujimaki 1 , S. Nakatani-Enomoto 2 , K. Watabe 3 , I. Nakano 1 , P. Rossini 4 , Y. Ugawa 2 1 Tokyo Metropolitan Neurological Hospital, Neurology, Tokyo, Japan; 2 Fukushima Medical University School of Medicine, Neurology, Fukushima, Japan; 3 Tokyo Metropolitan Institute of Medical Science, ALS/Neuropathy Project, Tokyo, Japan; 4 Catholic University of The Sacred Heart, Neurology, Rome, Italy Question: Our aim was to investigate the relationship between distribution of fasciculation potentials (FPs) and clinical features, and the correlation between FPs and survival in patients with amyotrophic lateral sclerosis (ALS). Methods: In 85 patients with sporadic ALS, we prospectively performed needle EMG in five to seven muscles of each patient. The shape of the detected FPs was analyzed by inspection, and FPs with >4 phases were judged as complex FPs. We followed the patients until the endpoint (death, tracheostomy, or ventilator use), and analyzed the correlation between complex FPs and survival period using the Cox proportional hazard model. Results: Complex FPs were observed in 47 patients (55.3%) in at least one muscle, more frequently in the muscles with normal strength or mild weakness. The presence of complex FPs was associated with shorter survival (hazard ratio 3.055; 95% CI 1.417-7.406; p=0.004). The median survival times after the disease onset were 3.1 and 1.5 years for patients without and with complex FPs, respectively (p=0.0017). The greater the number of muscles with complex FPs, the shorter the survival and the faster the progression speed. Conclusions: Wide distribution of complex FPs is associated with shorter survival in ALS. Axonal membrane instability and resultant spontaneous firing of distal motor axons might be directly associated with the extension of motor neuron degeneration.
P924 Phrenic nerve motor responses and survival in amyotrophic lateral sclerosis K. Bokuda, T. Shimizu, K. Hayashi, T. Yamazaki, I. Nakano Tokyo Metropolitan Neurological Hospital, Department of Neurology, Tokyo, Japan Question: The aim of the study was to investigate the relationship between phrenic nerve motor responses and respiratory function, and survival prognosis in patients with amyotrophic lateral sclerosis (ALS). Methods: In 84 patients with sporadic ALS, we performed peripheral
electrical stimulation of the phrenic nerves at the posterior edge of the sternocleidomastoid muscle. Diaphragm motor responses were recorded from the disk electrodes placed on the xiphoid process (active) and on the costal margin of the mid-clavicle sagittal line (inactive). Peak-to-trough amplitudes of diaphragm M waves (Damp) were measured. We evaluated forced vital capacity (%FVC) as respiratory function. Endpoints were set at the time of death, tracheostomy, or ventilator use, and the survival periods were calculated from the time of examination to the endpoints. We analyzed the correlation between the phrenic response size and respiratory function test, and survival periods. Results: %FVC was 65.1% (mean) (SD 29.3), and Damp was 0.44 mV (0.28). There was a weak significant correlation between the values of %FVC and Damp (R2 =0.097; p=0.008). The significant difference in survival rate was noted between the patients with Damp ≥ and <0.4 mV (Cox model, hazard ratio 3.009; p=0.003). Multivariate analysis showed that Damp was one of the independent predictive factors for survival after the examination. Conclusions: Phrenic nerve motor responses reflect respiratory function and predict survival prognosis after the examination. The amplitude size <0.4 mV may lead us to consider further respiratory support including non-invasive ventilation for ALS patients.
LP53 Electromyographic evidence for repair of motor neurons in patients with ALS W. Schulte-Mattler 1 , I. Kobor 1 , D. Baldaranov 1 , A. Khomenko 1 , S. Johannesen 1 , T.-H. Bruun 1 , C. Bischoff 2 , U. Bogdahn 1 1 University of Regensburg, Neurology, Regensburg, Germany; 2 Neurologische Gemeischaftspraxis am Marienplatz, Muenchen, Germany Question: Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the degeneration of both upper and lower motor neurons. Repair of motor neurons has not been observed in patients with ALS so far; collateral sprouting frequently is found, it causes the polyphasic motor unit action potentials (MUAPs) in concentric needle electromyograms (CNEMG) recorded from patients with ALS. Axonal growth would yield small, instable, polyphasic, so called nascent MUAPs. To detect neural repair, we screened for nascent MUAPs in patients with ALS. Methods: 11 patients with definite ALS according to the El Escorial criteria were studied. Four patients were in a compassionate use treatment program with s.c. rec-hu-G-CSF. CNEMG recordings from hypothenar muscles of at least 50 seconds duration were analyzed independently by two of the authors, WSM and CB, with particular respect to nascent MUAPs. CB was fully blinded throughout his analysis. Results: Nascent MUAPs were consistently found in all patients treated with G-CSF and in one of the other patients. In one other patient nascent MUAPs were found only by CB. The difference between treated and untreated patients was statistically significant (Fisher’s exact test). Conclusions: The presence of nascent MUAPs indicates that repair of motor neurons may occur in ALS patients spontaneously. The higher incidence of signs of repair in patients treated with G-CSF is encouraging. Moreover it is in line with the findings of Pitzer et al. (JNC 2010) and Henriques et al (Mol. Therapy 2011) who described identical phenomena in an SOD1 G93A experimental ALS mouse model. Therefore it may be worthwhile to further elucidate these repair mechanisms ALS.
Poster session 53. Movement disorders 2 P925 Somatosensory evoked potential (SEP) modulation by quadripulse transcranial magnetic stimulation (QPS) in benign myoclonus epilepsy patients S. Nakatani-Enomoto 1 , R. Hanajima 2 , M. Hamada 2 , Y. Terao 2 , H. Matsumoto 2 , Y. Shirota 2 , S. Ohminami 2 , S. Okabe 2 , M. Hirose 1 , K. Nakamura 1 , T. Furubayashi 3 , S. Groiss 1 , S. Kobayashi 1 , H. Mochizuki 1 , H. Enomoto 1 , Y. Ugawa 1 1 Fukushima Medical University, Neurology, Fukushima, Japan; 2 The University of Tokyo, Neurology, Tokyo, Japan; 3 Tohoku Bunka Gakuen University, Health and Social Services, Miyagi, Japan Objective: Quadripulse transcranial magnetic stimulation (QPS) applied