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WS6-3 Lambert-Eaton myasthenic syndrome
S80 WS6-3 Lambert-Eaton myasthenic syndrome S.J. Oh1 1 Neurology Department, University of Alabama at Birmingham, Birmingham, Alabama, USA Recent reviews on LEMS: (1) LEMS was associated with small-cell-lung cancer in 75% of cases in 1970. There has been a gradual decrease in the rate of SCLC association in LEMS over the years to 33 to 61% in the recent reports. This may be due to the wider usage of VGCC-ab test. (2) P/Q VGCC-ab test is positive in 67 to 95% of LEMS cases. It is relatively specific for the diagnosis of LEMS. However, false positive has been reported rarely in MG, ALS, and other paraneoplastic syndromes. (3) Thus, electrophysiological diagnostic test is still the gold-standard for the definite diagnostic of LEMS. Diagnostic triad is a low CMAP amplitude, a decrement at low rate stimulation, and an increment after the brief exercise (post-exercise facilitation) or at the high-rate stimulation (HRS). Our 2005 study showed that a 60% increment in either the PEF or HRS test is a desirable alternative to the 100% increment previously considered to be the gold standard for this diagnosis. Our 2008 study showed that ten-second exercise is superior to 30-second exercise for PEF in diagnosis of LEMS. (4) Our 2007 study showed that a clear-cut electrophysiological difference exists in seropositive and seronegative LEMS. No obvious difference was observed in the various clinical features or findings on SFEMG. However, the classic triad of the RNS test is rare, adding to difficulty in diagnosing LEMS in the seronegative group, and making a 60% increment criterion more critical for the diagnosis of this disorder. (5) Our 2009 study showed that 3,4-diaminopyrine (DAP) is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS. This is the third study documenting the effectiveness of 3,4 DAP in randomized-placebo studies. Recently amifampridine (3,4 DAP) phosphate is approved for general use in LEMS in the European Union countries. WS6-4 Clinical electrodiagnostic studies of congenital myasthenic syndromes R.A. Maselli1 Neurology Department University of California Davis, USA
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Congenital Myasthenic Syndromes (CMS) are a heterogeneous group of genetic disorders characterized by failure of neuromuscular transmission. There are many types of CMS and mutations in no fewer than twelve genes have been found to account for several forms of CMS. The identification of the CMS type is essential because a beneficial treatment for one CMS form may be deleterious or even fatal for a different form. The molecular diagnosis of CMS involves arduous genetic studies; however electrodiagnostic studies can greatly facilitate the search for the causative molecular defect. For instance, repetitive compound muscle action potential (CMAP) in response to a single nerve stimulus is characteristically seen in the Slow Channel Syndrome and Deficiency of Endplate Acetylcholinesterase. In contrast, fast receptor ion channel kinetics estimated by the spectral analysis of endplate noise suggests the Fast Channel Syndrome. As another example, worsening of CMAP decrement and single fiber EMG jitter with increasing frequencies of nerve stimulation suggests conditions characterized by small nerve terminals such as Deficiency of Endplate Acetylcholinesterase and Deficiency of Laminin beta 2. Contrary, improvement of CMAP decrement and single fiber EMG jitter with increasing frequencies of nerve stimulation suggests conditions resembling the Lambert Eaton Syndrome. Thus, a careful analysis of electrodiagnostic studies can provide invaluable help for the molecular diagnosis and treatment of CMS. WS7. Ocular movement WS7-1 Saccade-related cortical activity I. Bodis-Wollner1 1 Dept. Neurology, Suny Downstate Medical Center, Brooklyn NY, USA Rapid, conjugate eye movements, called saccades, are executed many times during the waking hours. Many of these saccades occur without an external triggering event. Such saccades, executed under voluntary control, link attentional and exploratory ehavior with motor output. It is of special interest therefore to investigate brain mechanism involved in supranuclear control of voluntary saccades.
Oral Presentations: Workshops Current techniques involve functional MRI. PET scanning, EEG (in particular oscillatory EEG components, revealed by wavelet transformation wEEG) and single pulse Transcranial Magnetic Stimulation (sTMS). Multiple cortical areas have been shown to be active in voluntary saccade paradigms: these include the frontal eye fields, the supplementary eye field, the parietal area known as ‘LIP’ and the occipital, striate cortex. Depending on task, the dorsolateral prefrontal cortex, the insular cortex, and the precuneus are activated. Some of these areas are strongly activated in covert attention paradigms, ie when no eye movement is executed suggesting anatomical-functional links between the saccadic and cognitive system. Among supranuclear anatomy in particular the superior colliculus and the pulvinar are relevant to the non-motor preparatory phase (‘Pre-emptive Perception’) of saccades. He basal ganglia are heavily involved in saccade programming and calculating expected reward fro a goal directed but non-reflex saccade. The skeletomotor loop of the basal ganglia is distinct from its the oculomotor loop. Studies in Parkinson Disease patients reveal an important role of the neurotransmitter dopamine: it slows prosaccades and improves antisaccades. WS7-2 Saccades in neurological disorders Y. Terao1 , Y. Ugawa2,3 1 Department of Neurology, University of Tokyo, Japan, 2 Department of Hazard Assessment, National Institute of Industrial Health, Japan, 3 Department of Neurology, Fukushima Medical University, Japan In actions of daily life, there is a close spatial and temporal coupling between the eye and hand movements; when manipulating an object, we first turn our gaze to it, and the hand subsequently reaches the object to grasp it. Therefore, there must be an important contribution of gaze in the performance of daily actions. Oculomotor tasks in experimental settings have revealed saccade abnormalities in various neurological disorders, such as an initial hypometric saccade followed by multiple corrective saccades, and impaired initiation of voluntary saccade tasks as well as impaired suppression of reflexive saccades in patients with Parkinson disease (PD). But how such abnormalities translate into actual behavior remains to be clarified. We predicted that gaze abnormalities contribute to motor slowness in neurological disorders such as PD. On the other hand, inadvertent eye movements made just before a voluntary action (saccadic intrusion) may also interfere with the initiation of subsequent voluntary motor and oculomotor actions. We show in this communication that slowed movements in PD patients may result from the delay in directing the gaze toward the object of interest, or the delay in visuomotor processing after the gaze has acquired the object. Therefore, apart from the delay to initiate a movement or the prolongation of movement time, PD patients are slow in performing motor actions because they are slow to acquire the target with multistep saccades or in preparing actions based on visuospatial information collected by saccades. Meanwhile, saccade intrusion before a voluntary movement delays the onset of subsequent motor but not oculomotor action in PD. Inhibition of oculomotor system after saccade intrusions may also affect initiation of motor actions. Finally, we show that PD patients are slowed in scanning a visual scene, which contributes to impaired deployment of attention and collection of visual information from the outer world. WS7-3 DBS and saccade performance A. Yugeta1 1 Toronto Western Research institute, University of Toronto, Canada The basal ganglia (BG) have two output pathways concerning eye movements: the thalamocortical pathways and the BG-brainstem projections. The former projects back to the frontal and supplementary eye field, although little is known physiologically and pharmacologically. However, the role of the latter on saccade has been demonstrated anatomically, pharmacologically, and physiologically. Through the BGsuperior colliculus (SC) pathway and the cortico-tectal pathways, the SC is the common terminal for controlling saccades. Therefore, saccades reflect the output of the BG, and can be a good indicator of BG function. Parkinson’s disease (PD) impairs not only somatomotor but also oculomotor functions. PD patients have difficulty in initiating voluntary saccades, whereas reflexive saccades to visual targets are
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Congenital Myasthenic Syndromes (CMS) are a heterogeneous group of genetic disorders characterized by failure of neuromuscular transmission. There are many types of CMS and mutations in no fewer than twelve genes have been found to account for several forms of CMS. The identification of the CMS type is essential because a beneficial treatment for one CMS form may be deleterious or even fatal for a different form. The molecular diagnosis of CMS involves arduous genetic studies; however electrodiagnostic studies can greatly facilitate the search for the causative molecular defect. For instance, repetitive compound muscle action potential (CMAP) in response to a single nerve stimulus is characteristically seen in the Slow Channel Syndrome and Deficiency of Endplate Acetylcholinesterase. In contrast, fast receptor ion channel kinetics estimated by the spectral analysis of endplate noise suggests the Fast Channel Syndrome. As another example, worsening of CMAP decrement and single fiber EMG jitter with increasing frequencies of nerve stimulation suggests conditions characterized by small nerve terminals such as Deficiency of Endplate Acetylcholinesterase and Deficiency of Laminin beta 2. Contrary, improvement of CMAP decrement and single fiber EMG jitter with increasing frequencies of nerve stimulation suggests conditions resembling the Lambert Eaton Syndrome. Thus, a careful analysis of electrodiagnostic studies can provide invaluable help for the molecular diagnosis and treatment of CMS. WS7. Ocular movement WS7-1 Saccade-related cortical activity I. Bodis-Wollner1 1 Dept. Neurology, Suny Downstate Medical Center, Brooklyn NY, USA Rapid, conjugate eye movements, called saccades, are executed many times during the waking hours. Many of these saccades occur without an external triggering event. Such saccades, executed under voluntary control, link attentional and exploratory ehavior with motor output. It is of special interest therefore to investigate brain mechanism involved in supranuclear control of voluntary saccades.
Oral Presentations: Workshops Current techniques involve functional MRI. PET scanning, EEG (in particular oscillatory EEG components, revealed by wavelet transformation wEEG) and single pulse Transcranial Magnetic Stimulation (sTMS). Multiple cortical areas have been shown to be active in voluntary saccade paradigms: these include the frontal eye fields, the supplementary eye field, the parietal area known as ‘LIP’ and the occipital, striate cortex. Depending on task, the dorsolateral prefrontal cortex, the insular cortex, and the precuneus are activated. Some of these areas are strongly activated in covert attention paradigms, ie when no eye movement is executed suggesting anatomical-functional links between the saccadic and cognitive system. Among supranuclear anatomy in particular the superior colliculus and the pulvinar are relevant to the non-motor preparatory phase (‘Pre-emptive Perception’) of saccades. He basal ganglia are heavily involved in saccade programming and calculating expected reward fro a goal directed but non-reflex saccade. The skeletomotor loop of the basal ganglia is distinct from its the oculomotor loop. Studies in Parkinson Disease patients reveal an important role of the neurotransmitter dopamine: it slows prosaccades and improves antisaccades. WS7-2 Saccades in neurological disorders Y. Terao1 , Y. Ugawa2,3 1 Department of Neurology, University of Tokyo, Japan, 2 Department of Hazard Assessment, National Institute of Industrial Health, Japan, 3 Department of Neurology, Fukushima Medical University, Japan In actions of daily life, there is a close spatial and temporal coupling between the eye and hand movements; when manipulating an object, we first turn our gaze to it, and the hand subsequently reaches the object to grasp it. Therefore, there must be an important contribution of gaze in the performance of daily actions. Oculomotor tasks in experimental settings have revealed saccade abnormalities in various neurological disorders, such as an initial hypometric saccade followed by multiple corrective saccades, and impaired initiation of voluntary saccade tasks as well as impaired suppression of reflexive saccades in patients with Parkinson disease (PD). But how such abnormalities translate into actual behavior remains to be clarified. We predicted that gaze abnormalities contribute to motor slowness in neurological disorders such as PD. On the other hand, inadvertent eye movements made just before a voluntary action (saccadic intrusion) may also interfere with the initiation of subsequent voluntary motor and oculomotor actions. We show in this communication that slowed movements in PD patients may result from the delay in directing the gaze toward the object of interest, or the delay in visuomotor processing after the gaze has acquired the object. Therefore, apart from the delay to initiate a movement or the prolongation of movement time, PD patients are slow in performing motor actions because they are slow to acquire the target with multistep saccades or in preparing actions based on visuospatial information collected by saccades. Meanwhile, saccade intrusion before a voluntary movement delays the onset of subsequent motor but not oculomotor action in PD. Inhibition of oculomotor system after saccade intrusions may also affect initiation of motor actions. Finally, we show that PD patients are slowed in scanning a visual scene, which contributes to impaired deployment of attention and collection of visual information from the outer world. WS7-3 DBS and saccade performance A. Yugeta1 1 Toronto Western Research institute, University of Toronto, Canada The basal ganglia (BG) have two output pathways concerning eye movements: the thalamocortical pathways and the BG-brainstem projections. The former projects back to the frontal and supplementary eye field, although little is known physiologically and pharmacologically. However, the role of the latter on saccade has been demonstrated anatomically, pharmacologically, and physiologically. Through the BGsuperior colliculus (SC) pathway and the cortico-tectal pathways, the SC is the common terminal for controlling saccades. Therefore, saccades reflect the output of the BG, and can be a good indicator of BG function. Parkinson’s disease (PD) impairs not only somatomotor but also oculomotor functions. PD patients have difficulty in initiating voluntary saccades, whereas reflexive saccades to visual targets are