- Email: [email protected]
S4.2 Sensori-motor integration in dystonia
Symposia / Clinical Neurophysiology 117 (2006) S41–S48
S3.7 Repetitive transcranial magnetic stimulation (RTMS) in stroke recovery U. Ziemann JW Goethe-University Hospital, Department of Neurology, Germany Sensorimotor recovery after a cerebral stroke is typically associated with representational plasticity in the lesioned and non-lesioned sensorimotor cortex. Very likely, longterm potentiation (LTP), i.e., strengthening of synaptic contacts, is one important candidate mechanism of this plasticity. Studies in animal and intact human motor cortex demonstrated that certain experimental manipulations such as increase of excitability of the training motor cortex or decrease of excitability of the opposite motor cortex enhance LTP and motor learning. One important means to change motor cortical excitability is RTMS. High-fre´ 5 Hz) increases excitability of the stimquency RTMS (!Y ulated motor cortex whereas low-frequency RTMS (1 Hz) decreases it. RTMS studies in healthy subjects showed that unimanual motor learning can be enhanced by high-frequency RTMS of the training motor cortex or low-frequency RTMS of the opposite motor cortex. Very recent studies have now started to address the question whether similarly beneficial effects can be obtained in stroke patients in order to enhance motor recovery and motor relearning. The available evidence that high-frequency RTMS of the lesioned motor cortex or low-frequency RTMS of the non-lesioned motor cortex improves outcome and enhances motor learning will the reviewed in this presentation. In summary, stroke rehabilitation research is now in the exciting situation of emerging scientifically based treatment concepts and encouraging first clinical trial data, but what is needed is to affirm the true usefulness of these operational strategies in alleviating disability after stroke by largescale controlled clinical studies, and to further explore possibilities how to individualise and optimise treatment concepts in a given patient in accord with his residual functional brain circuitry. doi:10.1016/j.clinph.2006.07.126
S4.1 Studies of cortical connectivity in movement disorders J. Rothwell Institute of Neurology, UK A large number of studies have examined the pathophysiology of intracortical connections within the motor cortex using the paired pulse TMS method of Kujirai et al. (1993). Here, we present new data about connectivity between the dorsal premotor cortex (PMd) and primary motor cortex in healthy subjects and patients with Parkinson’s disease, dystonia, or after hemispheric stroke. Three methods of investigating function in PMd have been
S47
explored in healthy subjects. (1) Single conditioning pulses to the PMd evoke inhibition or facilitation of the ipsilateral and contralateral motor cortex at interstimulus intervals of 6–10 ms, with the polarity of the effect depending on the intensity of the conditioning stimulus. (2) Paired pulse stimulation of PMd (cf. Kujirai et al., 1993) leads to interactions between a small S1 and a larger S2 at intervals of 5 and 15 ms that can be demonstrated by their effects on excitability of primary motor cortex. (3) Repetitive stimulation of PMd can cause lasting changes in excitability of ipsilateral motor cortex as probed by single pulse TMS in relaxed subjects. I will describe the abnormalities in single pulse conditioning in patients after stroke; changes in paired pulse effects on PMd in patients with writers cramp; and differences in the lasting effects of repetitive PMd TMS in patients with Parkinson’s disease both on and off their normal medication. doi:10.1016/j.clinph.2006.07.127
S4.2 Sensori-motor integration in dystonia G. Abbruzzese University of Genoa, Department of Neurosciences, Italy Background: Dystonia is a syndrome characterized by sustained muscle contractions causing repetitive twisting movements and abnormal postures. Dystonia is regarded as a motor disorder, but neurophysiologic and behavioural studies indicate that sensory functions may be defective. It has been proposed that an abnormal processing of somatosensory inputs may lead to inadequate sensorimotor integration (Abbruzzese & Berardelli, 2003). Methods: Using an optoelectronic motion analysis system and a dynamometric platform we investigated the effect of continuous lateral neck muscles vibration during stepping-in-place and stance in 16 patients with cervical dystonia (CD). In addition, we studied the effect of botulinum toxin type A (BT-A) injections in 10 patients with writer’s cramp by measuring the ratio between pre- and postinjection values of maximal M-wave (M-max), maximal voluntary contraction (MVC), tonic vibration reflex (TVR) of the injected muscles. Results: (1) The effect of lateral neck vibration on body rotation during stepping was inconsistent (smaller sensitivity) or opposite to normal in CD patients. During stance a larger than normal body sway was observed in patients. At variance with normal subjects, no relationship existed between vibration-induced body displacement during stance and body rotation during stepping. (2) The TVR was significantly more depressed (and for a longer period) than the MVC and M-max after BT-A injections. Conclusion: Our observations support the idea that integration of neck proprioceptive input is impaired in CD. The special sensitivity of TVR to suppression by BoNTA is probably mediated by the chemodenervation of intra-
S48
Symposia / Clinical Neurophysiology 117 (2006) S41–S48
fusal muscle fibers. Although it is not clear whether sensorimotor integration abnormalities would depend on the pathogenesis of the disease or on an adaptive process, dystonia cannot be regarded as a purely motor disorder but depends also on the transformation of abnormal afferent inputs into abnormal motor outputs. doi:10.1016/j.clinph.2006.07.128
S4.3 Cortical plasticity in Parkinson’s disease A. Berardelli
of the train. Conversely in patients, rTMS left the MEP size almost unchanged. References Bagnato S, Agostino R, Modugno N, Quartarone A, Berardelli A. Plasticity of the motor cortex in Parkinson’s disease patients On and Off therapy. Mov Disord 2006;21(5):639–45. Kargerer FA, Summers JJ, Byblow WD, Taylor B. Altered corticomotor representation in patients with Parkinson’s disease. Mov Disord 2003;18:919–27. Ueki Y, Mima T, Ali Kotb M, et al. Altered plasticity of the human motor cortex in Parkinson’s disease. Ann Neurol 2006;59:60–71.
University of Rome ‘‘La Sapienza’’, Department of Neurological Sciences and Neuromed, Italy
doi:10.1016/j.clinph.2006.07.167
In patients with Parkinson’s disease the technique of magnetic stimulation has provided important information on the excitability and plasticity of cortical motor areas. Studies investigating cortical topography have shown that in PD the corticomotor area is larger and extends more towards the anterior regions in Parkinsonian patients than in normal subjects (Kargerer et al., 2003). Specific topographic changes can also be studied with paired associative stimulation (PAS). This technique entails delivering lowfrequency electrical stimulation to the right median nerve paired with single-pulse TMS of the motor cortex. Previous studies suggested that in normal subjects PAS induces a stimulation of the motor cortex similar to that induced in protocols of experimental models inducing long-term potentiation. In normal subjects PAS facilitated MEP amplitude only in the APB muscle and not in the ADM muscles whereas in patients off therapy it strongly facilitated MEP amplitudes in the APB muscle and increased MEP size also in the ADM muscle. In normal subjects after PAS the duration of the cortical silent period increased but in patients off therapy remained unchanged. The abnormal responsiveness of sensorimotor cortex to PAS in patients with PD could reflect disordered plasticity within the motor cortex and an abnormal LTP-like mechanism (Bagnato et al., 2006). Changes in cortical plasticity have been also demonstrated by Ueki et al. (2006) in patients with PD with a protocol of associative plasticity similar to that proposed by Stefan et al. (2000). In this study, however, the PAS effect was less in patients when off compared with normal subjects. The explanation for the difference is not yet clear. The studies of Ueki et al. (2006) and of Bagnato et al. (2006) both demonstrate that dopamine deficiency can modify plasticity of motor cortex and suggest that the abnormal plasticity in the motor cortex of PD patients might be associated with higher motor dysfunction, including motor learning. In patients with Parkinson’s disease and dyskynesias abnormalities of plasticity of cortical motor areas have been demonstrated with the technique of repetitive transcranial magnetic stimulation. In healthy subjects at rest, rTMS produced motor-evoked potentials that progressively increased in amplitude over the course
S4.4 Psychogenic movement disorders and weakness R. Chen Toronto Western Research Institute, University of Toronto, Division of Neurology, Canada Psychogenic movement disorders and weakness is often seen in subspecialty practice and neurophysiological studies are often useful in establishing the diagnosis. Patients with psychogenic tremor may have variable frequencies, co-activation sign and increase in tremor with weight loading. With voluntary movement of another limb, they may demonstrate distractibility, entrainment and EMG coherence between voluntary movement and tremor. Patients with psychogenic muscle jerks or myoclonus usually have long duration (>70 ms) EMG burst and may have a premovement potential or desynchronization of EEG preceding the muscle jerks. In patients with psychogenic weakness, transcranial magnetic studies demonstrated normal motor thresholds and central motor conduction times, confirming that the corticospinal tract is intact. Neurophysiological studies are also useful in demonstrating the pathophysiology of psychogenic disorders. Functional imaging studies have found altered regional cerebral blood flow in patients with hysterical anesthesia and weakness. Patients with psychogenic dystonia were found to have reduced cortical inhibition measured with transcranial magnetic stimulation, and alteration of spinal reflexes such as forearm reciprocal inhibition and cutaneous silent period, similar to the findings in patients with organic dystonia. The finding that psychogenic and organic dystonia share similar physiological abnormalities in the cortex and spinal cord suggest that they may be due to plastic changes in the central nervous system in response to dystonic posturing. They may also be related to underlying psychiatric disturbances or an endophenotypic trait that predispose to both types of dystonia. The finding also raises the possibility that treatment such as sensory training may benefit both types of patients. doi:10.1016/j.clinph.2006.07.129
S3.7 Repetitive transcranial magnetic stimulation (RTMS) in stroke recovery U. Ziemann JW Goethe-University Hospital, Department of Neurology, Germany Sensorimotor recovery after a cerebral stroke is typically associated with representational plasticity in the lesioned and non-lesioned sensorimotor cortex. Very likely, longterm potentiation (LTP), i.e., strengthening of synaptic contacts, is one important candidate mechanism of this plasticity. Studies in animal and intact human motor cortex demonstrated that certain experimental manipulations such as increase of excitability of the training motor cortex or decrease of excitability of the opposite motor cortex enhance LTP and motor learning. One important means to change motor cortical excitability is RTMS. High-fre´ 5 Hz) increases excitability of the stimquency RTMS (!Y ulated motor cortex whereas low-frequency RTMS (1 Hz) decreases it. RTMS studies in healthy subjects showed that unimanual motor learning can be enhanced by high-frequency RTMS of the training motor cortex or low-frequency RTMS of the opposite motor cortex. Very recent studies have now started to address the question whether similarly beneficial effects can be obtained in stroke patients in order to enhance motor recovery and motor relearning. The available evidence that high-frequency RTMS of the lesioned motor cortex or low-frequency RTMS of the non-lesioned motor cortex improves outcome and enhances motor learning will the reviewed in this presentation. In summary, stroke rehabilitation research is now in the exciting situation of emerging scientifically based treatment concepts and encouraging first clinical trial data, but what is needed is to affirm the true usefulness of these operational strategies in alleviating disability after stroke by largescale controlled clinical studies, and to further explore possibilities how to individualise and optimise treatment concepts in a given patient in accord with his residual functional brain circuitry. doi:10.1016/j.clinph.2006.07.126
S4.1 Studies of cortical connectivity in movement disorders J. Rothwell Institute of Neurology, UK A large number of studies have examined the pathophysiology of intracortical connections within the motor cortex using the paired pulse TMS method of Kujirai et al. (1993). Here, we present new data about connectivity between the dorsal premotor cortex (PMd) and primary motor cortex in healthy subjects and patients with Parkinson’s disease, dystonia, or after hemispheric stroke. Three methods of investigating function in PMd have been
S47
explored in healthy subjects. (1) Single conditioning pulses to the PMd evoke inhibition or facilitation of the ipsilateral and contralateral motor cortex at interstimulus intervals of 6–10 ms, with the polarity of the effect depending on the intensity of the conditioning stimulus. (2) Paired pulse stimulation of PMd (cf. Kujirai et al., 1993) leads to interactions between a small S1 and a larger S2 at intervals of 5 and 15 ms that can be demonstrated by their effects on excitability of primary motor cortex. (3) Repetitive stimulation of PMd can cause lasting changes in excitability of ipsilateral motor cortex as probed by single pulse TMS in relaxed subjects. I will describe the abnormalities in single pulse conditioning in patients after stroke; changes in paired pulse effects on PMd in patients with writers cramp; and differences in the lasting effects of repetitive PMd TMS in patients with Parkinson’s disease both on and off their normal medication. doi:10.1016/j.clinph.2006.07.127
S4.2 Sensori-motor integration in dystonia G. Abbruzzese University of Genoa, Department of Neurosciences, Italy Background: Dystonia is a syndrome characterized by sustained muscle contractions causing repetitive twisting movements and abnormal postures. Dystonia is regarded as a motor disorder, but neurophysiologic and behavioural studies indicate that sensory functions may be defective. It has been proposed that an abnormal processing of somatosensory inputs may lead to inadequate sensorimotor integration (Abbruzzese & Berardelli, 2003). Methods: Using an optoelectronic motion analysis system and a dynamometric platform we investigated the effect of continuous lateral neck muscles vibration during stepping-in-place and stance in 16 patients with cervical dystonia (CD). In addition, we studied the effect of botulinum toxin type A (BT-A) injections in 10 patients with writer’s cramp by measuring the ratio between pre- and postinjection values of maximal M-wave (M-max), maximal voluntary contraction (MVC), tonic vibration reflex (TVR) of the injected muscles. Results: (1) The effect of lateral neck vibration on body rotation during stepping was inconsistent (smaller sensitivity) or opposite to normal in CD patients. During stance a larger than normal body sway was observed in patients. At variance with normal subjects, no relationship existed between vibration-induced body displacement during stance and body rotation during stepping. (2) The TVR was significantly more depressed (and for a longer period) than the MVC and M-max after BT-A injections. Conclusion: Our observations support the idea that integration of neck proprioceptive input is impaired in CD. The special sensitivity of TVR to suppression by BoNTA is probably mediated by the chemodenervation of intra-
S48
Symposia / Clinical Neurophysiology 117 (2006) S41–S48
fusal muscle fibers. Although it is not clear whether sensorimotor integration abnormalities would depend on the pathogenesis of the disease or on an adaptive process, dystonia cannot be regarded as a purely motor disorder but depends also on the transformation of abnormal afferent inputs into abnormal motor outputs. doi:10.1016/j.clinph.2006.07.128
S4.3 Cortical plasticity in Parkinson’s disease A. Berardelli
of the train. Conversely in patients, rTMS left the MEP size almost unchanged. References Bagnato S, Agostino R, Modugno N, Quartarone A, Berardelli A. Plasticity of the motor cortex in Parkinson’s disease patients On and Off therapy. Mov Disord 2006;21(5):639–45. Kargerer FA, Summers JJ, Byblow WD, Taylor B. Altered corticomotor representation in patients with Parkinson’s disease. Mov Disord 2003;18:919–27. Ueki Y, Mima T, Ali Kotb M, et al. Altered plasticity of the human motor cortex in Parkinson’s disease. Ann Neurol 2006;59:60–71.
University of Rome ‘‘La Sapienza’’, Department of Neurological Sciences and Neuromed, Italy
doi:10.1016/j.clinph.2006.07.167
In patients with Parkinson’s disease the technique of magnetic stimulation has provided important information on the excitability and plasticity of cortical motor areas. Studies investigating cortical topography have shown that in PD the corticomotor area is larger and extends more towards the anterior regions in Parkinsonian patients than in normal subjects (Kargerer et al., 2003). Specific topographic changes can also be studied with paired associative stimulation (PAS). This technique entails delivering lowfrequency electrical stimulation to the right median nerve paired with single-pulse TMS of the motor cortex. Previous studies suggested that in normal subjects PAS induces a stimulation of the motor cortex similar to that induced in protocols of experimental models inducing long-term potentiation. In normal subjects PAS facilitated MEP amplitude only in the APB muscle and not in the ADM muscles whereas in patients off therapy it strongly facilitated MEP amplitudes in the APB muscle and increased MEP size also in the ADM muscle. In normal subjects after PAS the duration of the cortical silent period increased but in patients off therapy remained unchanged. The abnormal responsiveness of sensorimotor cortex to PAS in patients with PD could reflect disordered plasticity within the motor cortex and an abnormal LTP-like mechanism (Bagnato et al., 2006). Changes in cortical plasticity have been also demonstrated by Ueki et al. (2006) in patients with PD with a protocol of associative plasticity similar to that proposed by Stefan et al. (2000). In this study, however, the PAS effect was less in patients when off compared with normal subjects. The explanation for the difference is not yet clear. The studies of Ueki et al. (2006) and of Bagnato et al. (2006) both demonstrate that dopamine deficiency can modify plasticity of motor cortex and suggest that the abnormal plasticity in the motor cortex of PD patients might be associated with higher motor dysfunction, including motor learning. In patients with Parkinson’s disease and dyskynesias abnormalities of plasticity of cortical motor areas have been demonstrated with the technique of repetitive transcranial magnetic stimulation. In healthy subjects at rest, rTMS produced motor-evoked potentials that progressively increased in amplitude over the course
S4.4 Psychogenic movement disorders and weakness R. Chen Toronto Western Research Institute, University of Toronto, Division of Neurology, Canada Psychogenic movement disorders and weakness is often seen in subspecialty practice and neurophysiological studies are often useful in establishing the diagnosis. Patients with psychogenic tremor may have variable frequencies, co-activation sign and increase in tremor with weight loading. With voluntary movement of another limb, they may demonstrate distractibility, entrainment and EMG coherence between voluntary movement and tremor. Patients with psychogenic muscle jerks or myoclonus usually have long duration (>70 ms) EMG burst and may have a premovement potential or desynchronization of EEG preceding the muscle jerks. In patients with psychogenic weakness, transcranial magnetic studies demonstrated normal motor thresholds and central motor conduction times, confirming that the corticospinal tract is intact. Neurophysiological studies are also useful in demonstrating the pathophysiology of psychogenic disorders. Functional imaging studies have found altered regional cerebral blood flow in patients with hysterical anesthesia and weakness. Patients with psychogenic dystonia were found to have reduced cortical inhibition measured with transcranial magnetic stimulation, and alteration of spinal reflexes such as forearm reciprocal inhibition and cutaneous silent period, similar to the findings in patients with organic dystonia. The finding that psychogenic and organic dystonia share similar physiological abnormalities in the cortex and spinal cord suggest that they may be due to plastic changes in the central nervous system in response to dystonic posturing. They may also be related to underlying psychiatric disturbances or an endophenotypic trait that predispose to both types of dystonia. The finding also raises the possibility that treatment such as sensory training may benefit both types of patients. doi:10.1016/j.clinph.2006.07.129