- Email: [email protected]
P7.6 Follow-up in Stiff Person Syndrome with immunoglobulin treatment
S90
Poster presentations: Poster session 7. Movement disorders
photographs selected from the International affective picture system. Each photograph was presented for 2s and was interposed by a black screen. Extracellular neuronal activity and electrooculography were recorded during the task. Neuronal recordings were manually assigned to particular subcortical structures according to their specific firing pattern. Action potentials of individual neurons were identified using WaveClus, an unsupervised spike detection and sorting tool. The relationship between the activity of individual neurons and the EM was assessed by correlation analysis. Results: Out of the 119 detected neurons, 81 were located in the STN, 19 in the SNr and 19 in the GPi. EM-related neurons were found in all three nuclei: 14 (17%) in the STN, 2 (11%) in the SNr and 5 (26%) in the GPi (P < 0.05). Two different categories of EM-related neurons were identified, as their firing rate correlated with EM amplitude either positively or negatively. Conclusions: Our results suggested that each of the explored structures STN, SNr and GPi contain relatively high ratios of neurons involved in the execution and/or control of eye movements. ˇ R 309/09/1145, C ˇ VUT SGS.SGS10/279/OHK3/ Supported by grants GAC 3T/13 and project Mˇ SM 0021620849. P7.3 Mechanisms underlying abnormalities in the membrane properties of simulated demyelinating neuropathies and neuronopathies 1
1
D.I. Stephanova , M. Daskalova Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria 1
Introduction: Recently, the multiple nerve excitability properties have been measured in healthy subjects and patients with Charcot-MarieTooth disease type 1A (CMT1A), chronic inflammatory demyelinating e syndrome (GBS), multifocal motor polyneuropathy (CIDP), Guillain Barr´ neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) using a noninvasive threshold tracking technique. Objective: To reveal the mechanisms underling abnormalities in the membrane properties obtained in simulated by us demyelinating neuropathies (CMT1A, CIDP, GBS, MMN) and neuronophathies (ALS), the present study compares these abnormalities. The current kinetics defining the abnormalities in the propagating and accommodative processes are also compared for the simulated neuropathies. Methods: The membrane properties are calculated in simulated cases (1) of internodal, paranodal and simultaneously of paranodal internodal demyelinations, each of them systematic or focal and (2) of three progressively greater degrees of ion channel dysfunction of human motor nerve fibres. Our double cable model is used to calculate the membrane properties such as potentials (action, electrotonic, extracellular), strength-duration time constants, rheobases and recovery cycles. The model and its software are given. Results: The comparison between the calculated and experimentally recorded membrane properties shows that the mild systematic demyelinations are specific indicators for hereditary and chronic demyelinating neuropathies (CMT1A, CIDP) and the severe focal demyelinations are specific indicators for acquired demyelinating neuropathies (GBS, MMN). The axonal channel dysfunctions simulated are specific indicators for motor neuron diseases such as ALS. Conclusions: The membrane properties in the demyelinating neuropathies are quite different from those in the neuronopathies, because of the different fibre electrogenesis. The abnormalities obtained can be used as specific indicators for the discussed diseases.
2
Methods: Three types of progressively greater systematic demyelinations [such as internodal systematic demyelinations (ISDs), paranodal systematic demyelinations (PSDs) and paranodal internodal systematic demyelinations (PISDs)] without/with aqueous layers are simulated using our previous multi-layered model of human motor nerve fibre. The calculated membrane properties are as follows: potentials (action, electrotonic), strength-duration time constants, rheobases and recovery cycles. The model and its software are given. Results: The effect of the aqueous layers is different and depends on the demyelinated type. All membrane properties are worsened / improved when the aqueous layers are taken into account in the ISDs/PSDs, respectively. The effect of the aqueous layers is significantly higher/lower on the accommodative and adaptive processes than on the propagating processes in the ISDs/PSDs, respectively. The aqueous layers do not modulate the membrane properties in the PISDs. Conclusions: The multi-layered model used approximates to a higher degree the calculated membrane properties to those in patients with Charcot-Marie-Tooth disease type 1A and chronic inflammatory demyelinating polyneuropathy also illustrated in this presentation. The study provides new and important information on the mechanisms underlying abnormalities in the nerve excitability properties in patients with demyelinating neuropathies. P7.5 Plasticity in primary motor cortex and clinical symptoms have different susceptibility to L-DOPA in drug-naive Parkinsonian patients S. Meunier1 , T. Joseph2 , B. Vellayudhan2 , A. Kishore2 CR ICM INSERM U975, Paris, France, 2 SCTIMST, Trivandrum, India
1
Introduction: A single dose of L-dopa restores the defective LTP-like plasticity in patients with advanced Parkinson’s disease (PD) on chronic L-dopa treatment (Ueki et al 2006, Morgante et al 2006). The effect on L-DOPA on LTP and LTD-like plasticity in drug-naive PD is not reported so far. Objectives: To test the effect of a single dose L-DOPA on LTP and LTD-like plasticity of motor cortex (M1) in denovo cases of early PD. Methods: Intermittent and continuous theta burst stimulation (iTBS/ cTBS) were used to induce LTP and LTD-like plasticity respectively, in M1 in 10 healthy volunteers and on 10 patients with early asymmetric denovo PD. The tests were done after clinical scoring (UPRD part III) on both sides in untreated state and 1 hour after a single dose of L-dopa (100mg) on 2 separate days. Mean values of MEP were measured immediately after TBS and every 10 minutes till 30minutes after both TBS protocols. Results: In the untreated state both LTD and LTP-like plasticity were defective in PD patients. Even though patients showed good clinical improvement following a single dose (100mg) of L-dopa on their less and the more affected sides, LTP- and LTD-like plasticity did not exhibit any changes compared to the untreated state. There were no significant differences in the baseline MEPs or thresholds of excitability of M1 cortex of the groups. Conclusions: LTP/LTD-like plasticity is significantly and similarly impaired in both M1 cortices of early untreated PD irrespective of the asymmetry of the clinical status. Plasticity did not improve after a single dose of L-DOPA. A chronic exposure to exogenous L-DOPA might be needed to influence plasticity. P7.6 Follow-up in Stiff Person Syndrome with immunoglobulin treatment M.J. Pablo1 , M. Bestue2 , P. Tamargo1 , F. Romero1 , I. Benavente1 Department of Neurophysiology, San Jorge Hospital, Huesca, Spain, 2 Department of Neurology, San Jorge Hospital, Huesca, Spain
1
P7.4 Effect of the myelin sheath aqueous layers on the membrane properties of simulated demyelinating neuropathies 1
2
2
1
D.I. Stephanova , S.M. Krustev , N. Negrev , M. Daskalova 1 Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria, 2 Medical University, Varna, Bulgaria Introduction: Studies of native myelin by X-ray and neutron diffraction have demonstrated that the myelin lamellae are not tightly compacted, but separated by cytoplasmic and extracellular spaces, so that up to half the volume fraction of myelin is taken up by water. Objective: To expand our studies on the mechanisms underlying clinical decline of the nerve excitability properties in patients with demyelinating neuropathies, the effect of the myelin sheath aqueous layers on multiple membrane properties of simulated fibre demyelinations is investigated.
Introduction: Stiff Person Syndrome is a rare and disabling central nervous system disorder, probably under-diagnosed, characterized by muscle stiffness and episodic spasms that involve axial and limb musculature. It is associated with high titers of antibodies against glutamic acid decarboxylase (GAD65) and frequently with autoimmune disorders. Rigidity and spasms are symptomatically treated with benzodiazepines, baclofen, tiagabine and levetiracetam. Treatment with intravenous immunoglobulin is well-tolerated and effective. Other therapies such as plasmapheresis and rituximab have been tried, with good responses. Objectives: To present the 4-year follow-up of a 62-year-old patient clinically and electrophysiologically diagnosed with stiff person syndrome with a good response to IV immunoglobulin treatment.
14th ECCN / 4th ICTMS/DCS Methods: IV immunoglobulin was administered once a month during the first two years, and every three-four months in the next two years. He became asymptomatic six months after the beginning of the treatment. The patient was recorded on video before and after the treatment, showing the clinical improvement. Blink reflex and EMG studies were carried out in agonist and antagonist muscles, in supine and bipedestation positions. Results: The first two EMG studies showed continuous muscular activity and spasms in abdominal and back muscles. The next study showed an improvement, with no involuntary muscular activity. An EMG per year has been performed for the last two years and the results were within normal limits. Conclusion: Our patient had a very good response to IV immunoglobulin treatment. Four years after the diagnosis he remains asymptomatic, with normal EMG studies. P7.7 Prefrontal stimulation in Tourette syndrome e1 , S. Lalli1 , S. Piacentini1 , O. Gambini2 , A. Franzini1 , G. Messina1 , F. Ferr` D. Perani3 , A. Albanese4 1 Fondazione IRCCS-Istituto Neurologico “Carlo Besta”, Milan, Italy, 2 DMCO, Universit` a degli Studi di Milano, Milan, Italy, 3 Universit` a Vita e a Cattolica del Sacro Cuore, Salute San Raffaele, Milan, Italy, 4 Universit` Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milan, Italy Introduction: Pharmacological treatment of Tourette’s syndrome is based mainly on neuroleptics and other agents interacting with the dopaminergic system, with major side effects. Recently it has been shown that a slow repetitive magnetic stimulation (rTMS) to supplementary motor area (SMA) resulted in a significant clinical improvement. Objectives: Aim of this study was to evaluate safety and efficacy of an innovative therapeutic approach, i.e. prefrontal cortical stimulation, in patients affected with Tourette Syndrome. Methods: Six patients were selected for epidural cortical stimulation (5 men, 1 woman, mean age 36.3±8.6). Among them, four patients underwent a bilateral implant of electrodes for epidural cortical stimulation in the pre-frontal area. Psychiatric, behavioural and cognitive evaluations were performed before surgery and after 1, 3, 6 and 12 months from surgery. Each subject underwent three resting 18Ffluorodeoxyglucose PET scans before and 6 and 12 months after surgery. Results: No adverse events have been reported by our group of patients. Analysis of the clinical data up to 6 month shows that all patients improved the scores for assessment, in different percentage, after surgery. Hamilton scale for depression (HAM-D 21 items) and Hamilton for anxiety (HAM-A) show an improvement both for anxiety and depression symptoms after surgery. Conclusions: This is the first study on the effects of chronic epidural prefrontal cortical stimulation (CS) in Gilles de la Tourette. All four patients responded well to prefrontal cortical stimulation, although to differing degrees. The procedure is safe ad effective on motor and phonemic tics. Tics did not disappear entirely. After CS, one patient required no medication. Among the three left patients, drug requirements remained stable or slightly reduced. More data on long term follow up will be required before for proposing prefrontal stimulation for treatment of pharmacological resistant cases P7.8 Premotor cortical stimulation in primary dystonia e1 , D. Perani2 , S. Lalli1 , S. Piacentini1 , A. Franzini1 , G. Messina1 , F. Ferr` A. Albanese3 1 Fondazione IRCCS-Istituto Neurologico “Carlo Besta”, Milan, Italy, 2 Universit` a Vita e Salute, Ospedale San Raffaele, Milan, Italy, 3 Universit` a Cattolica del Sacro Cuore, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milan, Italy Introduction: Pharmacologic treatments of dystonia have limited efficacy and are often unsatisfactory. The current mainstay of treatment is the botulinum toxin which has a number of limitations. There is preliminary evidence that motor cortex stimulation, can be efficacious in controlling upper limb dystonia. We have recently observed that epidural motor cortex stimulation can improve primary fixed dystonia. Objectives: Aim of this study is to evaluate the efficacy and safety of the premotor and motor cortical stimulation in patients with primary dystonia syndromes.
S91 Methods: Seven patients affected by focal or segmental dystonia were selected for epidural cortical stimulation. Two patients had primary fixed cervical dystonia (FD, fixed dystonia); four had primary mobile cervical dystonia (MD, mobile dystonia). One patient had a right upper limb focal dystonia. Patients with cervical dystonia received a bilateral implant, while patient with hand dystonia a monolateral implant. A videotaped structured neurological examination and the following outcome measures were collected: Burke-Fahn-Marsden rating scale, Toronto western spasmodic torticollis rating scale. Behavioural and cognitive evaluations were performed before surgery, 6 and 12 months after surgery. Each subject underwent three resting 18F-fluorodeoxyglucose PET scans before and 6 and 12 months after surgery. Results: No adverse events have been reported by our group of patients. In patients with mobile cervical dystonia there was an improvement of the BFMS and TWSTRS, from the pre-surgery evaluation up to the 12 months follow up visit. In patients with fixed cervical dystonia a substantial inefficacy of premotor cortical stimulation emerged through the 12-month observation period. Conclusions: The procedure appears to be safe within the parameter used with these patients. The benefit of the premotor stimulation seems to be consistent and persistent after 12 months of stimulation among patients with mobile dystonia, cervical and hand dystonia. Our, findings strength the neurophysiological data on the therapeutic effects of premotor rTMS given the normalization of SICI and RI and provide insight into therapeutic effects of premotor stimulation in dystonia in patients affected by mobile dystonia. P7.9 Subthalamic activity during a motor inhibition task M. Alegre1 , I. Obeso2 , J. Lopez-Azcarate3 , M. Cruz Rodriguez-Oroz1 , L. Wilkinson2 , J. Guridi1 , M. Valencia3 , J. Artieda1 , M. Jahanshahi2 , J.A. Obeso1 1 CIMA and Clinica Universidad de Navarra, Pamplona, Spain, 2 Institute of Neurology, UCL, London, United Kingdom, 3 CIMA, Pamplona, Spain Introduction: Several fMRI studies have suggested that the subthalamic nucleus (STN) may play a role in response inhibition. Deep brain stimulation of the STN, a common treatment in advanced stages of Parkinson’s disease, gives the opportunity to record directly local field potential (LFP) activity from this nucleus in the immediate postoperative period. Objectives: Our aim was to study the changes in activity of the STN related to the inhibition of a motor response. Methods: We studied the LFP of the STN during a stop/go task recording through the stimulators implanted in 8 PD patients, in both “off” and “on” motor states. The task consisted of a warning signal, followed after 0.5 s by a right or left arrow (50% each) that indicated the patient to press one specific key. A red X appeared in a 50% of the trials shortly after the go signal, indicating the subject to inhibit his response. The interval between the go signal (arrow) and the stop signal (red X) was adjusted after each trial in order to make the subject succeed a 50% of the times. The signal (recorded continuously) was segmented usign the different types of stimuli (go signal, stop signal) and the response (key press), and analyzed by means of time-frequency transforms. Results: A beta power decrease was observed after the go signal in all cases. The decrease, however, was smaller and shorter when the patient successfully inhibited the response than when there was no stop signal, or when the patient was unable to inhibit the response. The sucesful inhibition of the response was also accompanied by a gamma decrease in STN activity, while there was an increase in this band when a response (adequate or inadequate) was given. There was an increase in theta power in all cases, but the increase was highest when the subject was unable to supress the response (when there was a response despite the presence of a stop signal). Conclusions: The inhibition of a motor response is accompanied by a decrease in gamma activity in the STN. On the other hand, the inability to supress the response is associated to an increase in theta power.
Poster presentations: Poster session 7. Movement disorders
photographs selected from the International affective picture system. Each photograph was presented for 2s and was interposed by a black screen. Extracellular neuronal activity and electrooculography were recorded during the task. Neuronal recordings were manually assigned to particular subcortical structures according to their specific firing pattern. Action potentials of individual neurons were identified using WaveClus, an unsupervised spike detection and sorting tool. The relationship between the activity of individual neurons and the EM was assessed by correlation analysis. Results: Out of the 119 detected neurons, 81 were located in the STN, 19 in the SNr and 19 in the GPi. EM-related neurons were found in all three nuclei: 14 (17%) in the STN, 2 (11%) in the SNr and 5 (26%) in the GPi (P < 0.05). Two different categories of EM-related neurons were identified, as their firing rate correlated with EM amplitude either positively or negatively. Conclusions: Our results suggested that each of the explored structures STN, SNr and GPi contain relatively high ratios of neurons involved in the execution and/or control of eye movements. ˇ R 309/09/1145, C ˇ VUT SGS.SGS10/279/OHK3/ Supported by grants GAC 3T/13 and project Mˇ SM 0021620849. P7.3 Mechanisms underlying abnormalities in the membrane properties of simulated demyelinating neuropathies and neuronopathies 1
1
D.I. Stephanova , M. Daskalova Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria 1
Introduction: Recently, the multiple nerve excitability properties have been measured in healthy subjects and patients with Charcot-MarieTooth disease type 1A (CMT1A), chronic inflammatory demyelinating e syndrome (GBS), multifocal motor polyneuropathy (CIDP), Guillain Barr´ neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) using a noninvasive threshold tracking technique. Objective: To reveal the mechanisms underling abnormalities in the membrane properties obtained in simulated by us demyelinating neuropathies (CMT1A, CIDP, GBS, MMN) and neuronophathies (ALS), the present study compares these abnormalities. The current kinetics defining the abnormalities in the propagating and accommodative processes are also compared for the simulated neuropathies. Methods: The membrane properties are calculated in simulated cases (1) of internodal, paranodal and simultaneously of paranodal internodal demyelinations, each of them systematic or focal and (2) of three progressively greater degrees of ion channel dysfunction of human motor nerve fibres. Our double cable model is used to calculate the membrane properties such as potentials (action, electrotonic, extracellular), strength-duration time constants, rheobases and recovery cycles. The model and its software are given. Results: The comparison between the calculated and experimentally recorded membrane properties shows that the mild systematic demyelinations are specific indicators for hereditary and chronic demyelinating neuropathies (CMT1A, CIDP) and the severe focal demyelinations are specific indicators for acquired demyelinating neuropathies (GBS, MMN). The axonal channel dysfunctions simulated are specific indicators for motor neuron diseases such as ALS. Conclusions: The membrane properties in the demyelinating neuropathies are quite different from those in the neuronopathies, because of the different fibre electrogenesis. The abnormalities obtained can be used as specific indicators for the discussed diseases.
2
Methods: Three types of progressively greater systematic demyelinations [such as internodal systematic demyelinations (ISDs), paranodal systematic demyelinations (PSDs) and paranodal internodal systematic demyelinations (PISDs)] without/with aqueous layers are simulated using our previous multi-layered model of human motor nerve fibre. The calculated membrane properties are as follows: potentials (action, electrotonic), strength-duration time constants, rheobases and recovery cycles. The model and its software are given. Results: The effect of the aqueous layers is different and depends on the demyelinated type. All membrane properties are worsened / improved when the aqueous layers are taken into account in the ISDs/PSDs, respectively. The effect of the aqueous layers is significantly higher/lower on the accommodative and adaptive processes than on the propagating processes in the ISDs/PSDs, respectively. The aqueous layers do not modulate the membrane properties in the PISDs. Conclusions: The multi-layered model used approximates to a higher degree the calculated membrane properties to those in patients with Charcot-Marie-Tooth disease type 1A and chronic inflammatory demyelinating polyneuropathy also illustrated in this presentation. The study provides new and important information on the mechanisms underlying abnormalities in the nerve excitability properties in patients with demyelinating neuropathies. P7.5 Plasticity in primary motor cortex and clinical symptoms have different susceptibility to L-DOPA in drug-naive Parkinsonian patients S. Meunier1 , T. Joseph2 , B. Vellayudhan2 , A. Kishore2 CR ICM INSERM U975, Paris, France, 2 SCTIMST, Trivandrum, India
1
Introduction: A single dose of L-dopa restores the defective LTP-like plasticity in patients with advanced Parkinson’s disease (PD) on chronic L-dopa treatment (Ueki et al 2006, Morgante et al 2006). The effect on L-DOPA on LTP and LTD-like plasticity in drug-naive PD is not reported so far. Objectives: To test the effect of a single dose L-DOPA on LTP and LTD-like plasticity of motor cortex (M1) in denovo cases of early PD. Methods: Intermittent and continuous theta burst stimulation (iTBS/ cTBS) were used to induce LTP and LTD-like plasticity respectively, in M1 in 10 healthy volunteers and on 10 patients with early asymmetric denovo PD. The tests were done after clinical scoring (UPRD part III) on both sides in untreated state and 1 hour after a single dose of L-dopa (100mg) on 2 separate days. Mean values of MEP were measured immediately after TBS and every 10 minutes till 30minutes after both TBS protocols. Results: In the untreated state both LTD and LTP-like plasticity were defective in PD patients. Even though patients showed good clinical improvement following a single dose (100mg) of L-dopa on their less and the more affected sides, LTP- and LTD-like plasticity did not exhibit any changes compared to the untreated state. There were no significant differences in the baseline MEPs or thresholds of excitability of M1 cortex of the groups. Conclusions: LTP/LTD-like plasticity is significantly and similarly impaired in both M1 cortices of early untreated PD irrespective of the asymmetry of the clinical status. Plasticity did not improve after a single dose of L-DOPA. A chronic exposure to exogenous L-DOPA might be needed to influence plasticity. P7.6 Follow-up in Stiff Person Syndrome with immunoglobulin treatment M.J. Pablo1 , M. Bestue2 , P. Tamargo1 , F. Romero1 , I. Benavente1 Department of Neurophysiology, San Jorge Hospital, Huesca, Spain, 2 Department of Neurology, San Jorge Hospital, Huesca, Spain
1
P7.4 Effect of the myelin sheath aqueous layers on the membrane properties of simulated demyelinating neuropathies 1
2
2
1
D.I. Stephanova , S.M. Krustev , N. Negrev , M. Daskalova 1 Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria, 2 Medical University, Varna, Bulgaria Introduction: Studies of native myelin by X-ray and neutron diffraction have demonstrated that the myelin lamellae are not tightly compacted, but separated by cytoplasmic and extracellular spaces, so that up to half the volume fraction of myelin is taken up by water. Objective: To expand our studies on the mechanisms underlying clinical decline of the nerve excitability properties in patients with demyelinating neuropathies, the effect of the myelin sheath aqueous layers on multiple membrane properties of simulated fibre demyelinations is investigated.
Introduction: Stiff Person Syndrome is a rare and disabling central nervous system disorder, probably under-diagnosed, characterized by muscle stiffness and episodic spasms that involve axial and limb musculature. It is associated with high titers of antibodies against glutamic acid decarboxylase (GAD65) and frequently with autoimmune disorders. Rigidity and spasms are symptomatically treated with benzodiazepines, baclofen, tiagabine and levetiracetam. Treatment with intravenous immunoglobulin is well-tolerated and effective. Other therapies such as plasmapheresis and rituximab have been tried, with good responses. Objectives: To present the 4-year follow-up of a 62-year-old patient clinically and electrophysiologically diagnosed with stiff person syndrome with a good response to IV immunoglobulin treatment.
14th ECCN / 4th ICTMS/DCS Methods: IV immunoglobulin was administered once a month during the first two years, and every three-four months in the next two years. He became asymptomatic six months after the beginning of the treatment. The patient was recorded on video before and after the treatment, showing the clinical improvement. Blink reflex and EMG studies were carried out in agonist and antagonist muscles, in supine and bipedestation positions. Results: The first two EMG studies showed continuous muscular activity and spasms in abdominal and back muscles. The next study showed an improvement, with no involuntary muscular activity. An EMG per year has been performed for the last two years and the results were within normal limits. Conclusion: Our patient had a very good response to IV immunoglobulin treatment. Four years after the diagnosis he remains asymptomatic, with normal EMG studies. P7.7 Prefrontal stimulation in Tourette syndrome e1 , S. Lalli1 , S. Piacentini1 , O. Gambini2 , A. Franzini1 , G. Messina1 , F. Ferr` D. Perani3 , A. Albanese4 1 Fondazione IRCCS-Istituto Neurologico “Carlo Besta”, Milan, Italy, 2 DMCO, Universit` a degli Studi di Milano, Milan, Italy, 3 Universit` a Vita e a Cattolica del Sacro Cuore, Salute San Raffaele, Milan, Italy, 4 Universit` Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milan, Italy Introduction: Pharmacological treatment of Tourette’s syndrome is based mainly on neuroleptics and other agents interacting with the dopaminergic system, with major side effects. Recently it has been shown that a slow repetitive magnetic stimulation (rTMS) to supplementary motor area (SMA) resulted in a significant clinical improvement. Objectives: Aim of this study was to evaluate safety and efficacy of an innovative therapeutic approach, i.e. prefrontal cortical stimulation, in patients affected with Tourette Syndrome. Methods: Six patients were selected for epidural cortical stimulation (5 men, 1 woman, mean age 36.3±8.6). Among them, four patients underwent a bilateral implant of electrodes for epidural cortical stimulation in the pre-frontal area. Psychiatric, behavioural and cognitive evaluations were performed before surgery and after 1, 3, 6 and 12 months from surgery. Each subject underwent three resting 18Ffluorodeoxyglucose PET scans before and 6 and 12 months after surgery. Results: No adverse events have been reported by our group of patients. Analysis of the clinical data up to 6 month shows that all patients improved the scores for assessment, in different percentage, after surgery. Hamilton scale for depression (HAM-D 21 items) and Hamilton for anxiety (HAM-A) show an improvement both for anxiety and depression symptoms after surgery. Conclusions: This is the first study on the effects of chronic epidural prefrontal cortical stimulation (CS) in Gilles de la Tourette. All four patients responded well to prefrontal cortical stimulation, although to differing degrees. The procedure is safe ad effective on motor and phonemic tics. Tics did not disappear entirely. After CS, one patient required no medication. Among the three left patients, drug requirements remained stable or slightly reduced. More data on long term follow up will be required before for proposing prefrontal stimulation for treatment of pharmacological resistant cases P7.8 Premotor cortical stimulation in primary dystonia e1 , D. Perani2 , S. Lalli1 , S. Piacentini1 , A. Franzini1 , G. Messina1 , F. Ferr` A. Albanese3 1 Fondazione IRCCS-Istituto Neurologico “Carlo Besta”, Milan, Italy, 2 Universit` a Vita e Salute, Ospedale San Raffaele, Milan, Italy, 3 Universit` a Cattolica del Sacro Cuore, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milan, Italy Introduction: Pharmacologic treatments of dystonia have limited efficacy and are often unsatisfactory. The current mainstay of treatment is the botulinum toxin which has a number of limitations. There is preliminary evidence that motor cortex stimulation, can be efficacious in controlling upper limb dystonia. We have recently observed that epidural motor cortex stimulation can improve primary fixed dystonia. Objectives: Aim of this study is to evaluate the efficacy and safety of the premotor and motor cortical stimulation in patients with primary dystonia syndromes.
S91 Methods: Seven patients affected by focal or segmental dystonia were selected for epidural cortical stimulation. Two patients had primary fixed cervical dystonia (FD, fixed dystonia); four had primary mobile cervical dystonia (MD, mobile dystonia). One patient had a right upper limb focal dystonia. Patients with cervical dystonia received a bilateral implant, while patient with hand dystonia a monolateral implant. A videotaped structured neurological examination and the following outcome measures were collected: Burke-Fahn-Marsden rating scale, Toronto western spasmodic torticollis rating scale. Behavioural and cognitive evaluations were performed before surgery, 6 and 12 months after surgery. Each subject underwent three resting 18F-fluorodeoxyglucose PET scans before and 6 and 12 months after surgery. Results: No adverse events have been reported by our group of patients. In patients with mobile cervical dystonia there was an improvement of the BFMS and TWSTRS, from the pre-surgery evaluation up to the 12 months follow up visit. In patients with fixed cervical dystonia a substantial inefficacy of premotor cortical stimulation emerged through the 12-month observation period. Conclusions: The procedure appears to be safe within the parameter used with these patients. The benefit of the premotor stimulation seems to be consistent and persistent after 12 months of stimulation among patients with mobile dystonia, cervical and hand dystonia. Our, findings strength the neurophysiological data on the therapeutic effects of premotor rTMS given the normalization of SICI and RI and provide insight into therapeutic effects of premotor stimulation in dystonia in patients affected by mobile dystonia. P7.9 Subthalamic activity during a motor inhibition task M. Alegre1 , I. Obeso2 , J. Lopez-Azcarate3 , M. Cruz Rodriguez-Oroz1 , L. Wilkinson2 , J. Guridi1 , M. Valencia3 , J. Artieda1 , M. Jahanshahi2 , J.A. Obeso1 1 CIMA and Clinica Universidad de Navarra, Pamplona, Spain, 2 Institute of Neurology, UCL, London, United Kingdom, 3 CIMA, Pamplona, Spain Introduction: Several fMRI studies have suggested that the subthalamic nucleus (STN) may play a role in response inhibition. Deep brain stimulation of the STN, a common treatment in advanced stages of Parkinson’s disease, gives the opportunity to record directly local field potential (LFP) activity from this nucleus in the immediate postoperative period. Objectives: Our aim was to study the changes in activity of the STN related to the inhibition of a motor response. Methods: We studied the LFP of the STN during a stop/go task recording through the stimulators implanted in 8 PD patients, in both “off” and “on” motor states. The task consisted of a warning signal, followed after 0.5 s by a right or left arrow (50% each) that indicated the patient to press one specific key. A red X appeared in a 50% of the trials shortly after the go signal, indicating the subject to inhibit his response. The interval between the go signal (arrow) and the stop signal (red X) was adjusted after each trial in order to make the subject succeed a 50% of the times. The signal (recorded continuously) was segmented usign the different types of stimuli (go signal, stop signal) and the response (key press), and analyzed by means of time-frequency transforms. Results: A beta power decrease was observed after the go signal in all cases. The decrease, however, was smaller and shorter when the patient successfully inhibited the response than when there was no stop signal, or when the patient was unable to inhibit the response. The sucesful inhibition of the response was also accompanied by a gamma decrease in STN activity, while there was an increase in this band when a response (adequate or inadequate) was given. There was an increase in theta power in all cases, but the increase was highest when the subject was unable to supress the response (when there was a response despite the presence of a stop signal). Conclusions: The inhibition of a motor response is accompanied by a decrease in gamma activity in the STN. On the other hand, the inability to supress the response is associated to an increase in theta power.