2
$364 Wednesday, November 9, 2005 Poster Abstracts ON 2,7; Schwab England OFF 50,5, ON 76,4. UPDRS I: 3,0± 3,0; II: 20,5±4,9; III OFF: 50,0±11,6, ON: 27,8±8,8; IV: 8,9±3,2. Six months later: Hoehn Yahr: OFF/OFF: 3,7; ON/ON 2,3; Schwab England OFF/OFF 61,3; ON/ON 84,7. UPDRS I: 2,1 ± 1,7; II: 16,0±5,5; III: OFF/OFF 44,5±16,3; OFF/ON: 34,5±10,2; ON/ OFF: 32,9 ± 11,7; ON/ON: 23,8 ± 7,3; IV: 4,7 ± 1,4. Antiparkinsonian medications were reduced in a mean of 38%. No important surgical complications occurred, only two surgical infections. Conclusion: In our series DBS of STN is a safety alternative for Parkinson's disease patients with poor clinical control in pharmaco- logical therapy. At the time of exposition, figures of one year of evolution will be available. 1039 Adult Stein Cells froin Persons wilh Parldnson's Disease are Therapeutic in a Rat Modal WaTtle Murrell 1, Michael Domlellan 1, Andrew Wetzig 1, Tom Bume 1, Peter Silburn ~, Alan Mackay-Sim 1. 1Eskitis Institute For Cell And iVloleeular Therapies, Griffith University, Brisbane, Australia; 2Princess Alexandra Hospital, Brisbane, Australia Background: Parkinson's disease is a complex disorder resulting primarily from degeneration of dopanffnergic neurons in the sub stantia nigra that project to the caudate-putamen. We recently demonstrated a multipotent adult stem cell in olfactory mucosa (Murrell et al., 2005). The aim of this study was to test whether these adult stem cells would be therapeutic in a rat model of Parkinson's disease. Methods: Olfactory adult stem cells were grown from biopsies of olfactory nlucosa of persons with Parkinson's disease, and from controls. Rats were unilaterally injected into the caudate-putamen with 6-hydroxydoparnine to destroy the dopaminergic input from the substantia nigra. Amphetamine-induced rotational behaviour was measured after the lesion and after transplantation of stem cells into the caudate putanlen on the lesioned side. All animals were immune- suppressed with daily injections of cyclosporine. Results: Transplantation of human adult olfactory stem cells reduced the amphetamine-induced rotational behaviour in six animals, three transplanted with cells from persons with Parkinson's disease and three with cells from controls. Tiffs therapeutic effect was evident at 3 weeks post-transplantation and persisted for 3 months. There was no change in rotational behaviour in three saline-injected control rats. The caudate putanlen of transplanted animals contained hunlan-derived cells that expressed both tyrosine hydroxylase and dopamine trans- porter. Conclusion: These results indicate that adult stem cells from human olfactory nlucosa are a potential source for autologous transplantation for the treatment of Parkinson's disease and other neurodegenerative disorders. Murrell W, et al. (2005) Multipotent stem cell in adult olfactory mucosa Developmental Dynamics (in press). 1040 ~rUllt Oxidative and Anti-oxidative Agenls Assodaled with Parldnson's Disease: Electron Spine Resonance (ESR) Study Makita, y1, Aizawa, H ~, Enomoto, S a, Kimura, T ~, Yahara, 02 1Asahikawa Medical College, Asahikawa, Japan; 2National Organiza- tion Doh&u Hospital, Asahikawa, Japan Background: Oxidative stress is strongly associated with Parkinson's disease (PD). Anti-Parkinson's disease agents may make another effect of systemic changes in vivo. Method: We measured 30 PD samples and 15 normal controls serum level of hydoxyradical scavenge potential with Hydroxy Radical Scavenge Assay (HRSA) using ESR system. Common anti-Parkinson's disease drug was measured as same method. Drug samples consisted of levodopa, amantadine, dopanffne-agonists, selegiline, zonisanffde. We received letters with all patient's consents. Results: In PD group, hydroxy radical scavenge level was declined (iJ < 0.005). Selegiline had best potential ofhydroxy radical scavenge. Contusion: We suggested PD in systemic had declined radical scavenge level. We may chose selegiline as a first selection of PD therapy. 1041 Parkin gene therapy for Alpha Synucleinopathy: A rat model of Parkinson's disease Mochizuld, H, Yamada, M, Mizuno, Y. Department of Neurology, ,,~untendo University School of Medicine Background: Parkin is known to mitigate ~-sylmclein-induced neuronal cell death, suggesting that parkin gene therapy could be suitable for Parkinson's disease (PD). However, there are no studies on the inhibitory effects of parkin on ~-synudeinopathy in rat or mice brains. Method: In the present study, a recombinant adeno-associated viral (rAAV) vector system was used for human ~ sytruclein gene transfer to rat substantia nigra (SN). This transfection induced ~-synudeinopathy and the model appeared to more closely resemble the human disease. The effect of parkin was examined by co-infection of rAAV-parkin with rAAV-c~ sytruclein into dopanfinergic neurons in SN. Result anti Conclusions: At 13 weeks post-rAAV infection, c~ sytmclein overexpression induced dopaminergic neuron loss. However, co- expression of parkin mitigated ~-synuclein toxidty with neither decrease in the amount of cz-synudein protein nor formation of inclusions remJrfiscent of Lewy bodies (LB). Moreover, c~-sytruclein- induced dopaminergic neuron loss consequently resulted in motor dysfunction, which was also mitigated by parkin. Our results indicate that parkin gene therapy is effective against ~-synudein, suggesting its potential suitability for patients with PD. 1042 Spike Characterization in The Human Subthalainus and Substantia Nigra Mrakic-Sposta, S 1, Marceglia, S 1 , Egidi, M ~ , Tamma, F ~, Caputo, E ~, Carrabba, G ~, Bmrbieri, S ~, Bertolasi, L ~, Priori, A ~. 1Fondazione IRCCS Ospedale Polielinieo, Milano; 2Cliniea Neurologiea, Azienda Ospedaliera San Paolo, ~filano, Italy; 3Dipartimento di Scienze Neurologicke e della l/Tsione, Universitfi di Verona, Verona, Italy Background: Intraoperative microrecordings are determinant for a precise localization of the subthalamic nucleus (STN) during stereo- tactic, neurosurgery for the deep brain stimulation (DBS). However, the spike descriptors in the STN have been poorly characterized. Tiffs study aimed to evaluate the spike descriptors in the STN and in the substantia nigra pars reticulata (SNr) in 11 patients (21 sides of the brain) undergoing DBS surgery. Methods: Signals were captured through bipolar microelectrodes (Inomed mod. 230760, tip impedance 1.5-2.5 Mr2 at 1KHz), band- passed 300Hz-5KHz and differentially amplified. The STN and the SNr were identified through a the TC-MRI fusion-based neuroimaging technique and data matching with a digitized stereotactic atlas. Results: In the core of the STN the spikes were mainly biphasic with an initial upward (negative) deflection with a total frequency of 70 ± 4,04 Hz [mean± SEM], duration of 1,4 ± 0,05ms, rise time of 0,7 ± 0,07ms, amplitude of 35,5± 2,22~aV and area 25,8 ± 1,91~aVms; the 75% of the spikes analyzed were assamnetric. In the core of the SNr the spikes were mostly monophasic with upward deflection or biphasic with an initial upward (negative) deflection. The total frequency was 79 ± 6,81Hz, the duration 2,1 ± 0,13ms, the rise time 1 ± 0,07ms, the amplitude 46,7±3,88 pV and the area 37,9±2,67pVms; the 60% of the spikes analyzed were symmetric.. Contusions: In conclusion, besides the firing pattern, only spike morphology can help in differentiating between the STN and the SNr during stereotactic neurosurgery.

1042 Spike characterization in the human subthalamus and substantia nigra

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Page 1: 1042 Spike characterization in the human subthalamus and substantia nigra

$364 Wednesday, November 9, 2005 Poster Abstracts

ON 2,7; Schwab England OFF 50,5, ON 76,4. UPDRS I: 3 ,0± 3,0; II: 20,5±4,9; III OFF: 50,0±11,6, ON: 27,8±8,8; IV: 8,9±3,2. Six months later: Hoehn Yahr: OFF/OFF: 3,7; ON/ON 2,3; Schwab England OFF/OFF 61,3; ON/ON 84,7. UPDRS I: 2,1 ± 1,7; II: 16,0±5,5; III: OFF/OFF 44,5±16,3; OFF/ON: 34,5±10,2; ON/ OFF: 32,9 ± 11,7; ON/ON: 23,8 ± 7,3; IV: 4,7 ± 1,4. Antiparkinsonian medications were reduced in a mean of 38%. No important surgical complications occurred, only two surgical infections. Conclusion: In our series DBS of STN is a safety alternative for Parkinson's disease patients with poor clinical control in pharmaco- logical therapy. At the time of exposition, figures of one year of evolution will be available.

1039 Adult Stein Cells froin Persons wilh Parldnson's Disease are Therapeutic in a Rat Modal

WaTtle Murrell 1, Michael Domlellan 1, Andrew Wetzig 1, Tom Bume 1, Peter Silburn ~, Alan Mackay-Sim 1. 1Eskitis Institute For Cell And iVloleeular Therapies, Griffith University, Brisbane, Australia; 2Princess Alexandra Hospital, Brisbane, Australia

Background: Parkinson's disease is a complex disorder resulting primarily from degeneration of dopanffnergic neurons in the sub stantia nigra that project to the caudate-putamen. We recently demonstrated a multipotent adult stem cell in olfactory mucosa (Murrell et al., 2005). The aim of this study was to test whether these adult stem cells would be therapeutic in a rat model of Parkinson's disease. Methods: Olfactory adult stem cells were grown from biopsies of olfactory nlucosa of persons with Parkinson's disease, and from controls. Rats were unilaterally injected into the caudate-putamen with 6-hydroxydoparnine to destroy the dopaminergic input from the substantia nigra. Amphetamine-induced rotational behaviour was measured after the lesion and after transplantation of stem cells into the caudate putanlen on the lesioned side. All animals were immune- suppressed with daily injections of cyclosporine. Results: Transplantation of human adult olfactory stem cells reduced the amphetamine-induced rotational behaviour in six animals, three transplanted with cells from persons with Parkinson's disease and three with cells from controls. Tiffs therapeutic effect was evident at 3 weeks post-transplantation and persisted for 3 months. There was no change in rotational behaviour in three saline-injected control rats. The caudate putanlen of transplanted animals contained hunlan-derived cells that expressed both tyrosine hydroxylase and dopamine trans- porter. Conclusion: These results indicate that adult stem cells from human olfactory nlucosa are a potential source for autologous transplantation for the treatment of Parkinson's disease and other neurodegenerative disorders. Murrell W, et al. (2005) Multipotent stem cell in adult olfactory mucosa Developmental Dynamics (in press).

1040 ~rUllt Oxidative and Anti-oxidative Agenls Assodaled with Parldnson's Disease: Electron Spine Resonance (ESR) Study

Makita, y1, Aizawa, H ~, Enomoto, S a, Kimura, T ~, Yahara, 02 1Asahikawa Medical College, Asahikawa, Japan; 2National Organiza- tion Doh&u Hospital, Asahikawa, Japan

Background: Oxidative stress is strongly associated with Parkinson's disease (PD). Anti-Parkinson's disease agents may make another effect of systemic changes in vivo. Method: We measured 30 PD samples and 15 normal controls serum level of hydoxyradical scavenge potential with Hydroxy Radical Scavenge Assay (HRSA) using ESR system. Common anti-Parkinson's disease drug was measured as same method. Drug samples consisted of levodopa, amantadine, dopanffne-agonists, selegiline, zonisanffde. We received letters with all patient's consents.

Results: In PD group, hydroxy radical scavenge level was declined (iJ < 0.005). Selegiline had best potential ofhydroxy radical scavenge. Contusion: We suggested PD in systemic had declined radical scavenge level. We may chose selegiline as a first selection of PD therapy.

1041 Parkin gene therapy for Alpha Synucleinopathy: A rat model of Parkinson's disease

Mochizuld, H, Yamada, M, Mizuno, Y. Department of Neurology, ,,~untendo University School of Medicine

Background: Parkin is known to mitigate ~-sylmclein-induced neuronal cell death, suggesting that parkin gene therapy could be suitable for Parkinson's disease (PD). However, there are no studies on the inhibitory effects of parkin on ~-synudeinopathy in rat or mice brains. Method: In the present study, a recombinant adeno-associated viral (rAAV) vector system was used for human ~ sytruclein gene transfer to rat substantia nigra (SN). This transfection induced ~-synudeinopathy and the model appeared to more closely resemble the human disease. The effect of parkin was examined by co-infection of rAAV-parkin with rAAV-c~ sytruclein into dopanfinergic neurons in SN. Result anti Conclusions: At 13 weeks post-rAAV infection, c~ sytmclein overexpression induced dopaminergic neuron loss. However, co- expression of parkin mitigated ~-synuclein toxidty with neither decrease in the amount of cz-synudein protein nor formation of inclusions remJrfiscent of Lewy bodies (LB). Moreover, c~-sytruclein- induced dopaminergic neuron loss consequently resulted in motor dysfunction, which was also mitigated by parkin. Our results indicate that parkin gene therapy is effective against ~-synudein, suggesting its potential suitability for patients with PD.

1042 Spike Characterization in The Human Subthalainus and Substantia Nigra

Mrakic-Sposta, S 1, Marceglia, S 1 , Egidi, M ~ , Tamma, F ~, Caputo, E ~, Carrabba, G ~, Bmrbieri, S ~, Bertolasi, L ~, Priori, A ~. 1Fondazione IRCCS Ospedale Polielinieo, Milano; 2Cliniea Neurologiea, Azienda Ospedaliera San Paolo, ~filano, Italy; 3Dipartimento di Scienze Neurologicke e della l/Tsione, Universitfi di Verona, Verona, Italy

Background: Intraoperative microrecordings are determinant for a precise localization of the subthalamic nucleus (STN) during stereo- tactic, neurosurgery for the deep brain stimulation (DBS). However, the spike descriptors in the STN have been poorly characterized. Tiffs study aimed to evaluate the spike descriptors in the STN and in the substantia nigra pars reticulata (SNr) in 11 patients (21 sides of the brain) undergoing DBS surgery. Methods: Signals were captured through bipolar microelectrodes (Inomed mod. 230760, tip impedance 1.5-2.5 Mr2 at 1KHz), band- passed 300Hz-5KHz and differentially amplified. The STN and the SNr were identified through a the TC-MRI fusion-based neuroimaging technique and data matching with a digitized stereotactic atlas. Results: In the core of the STN the spikes were mainly biphasic with an initial upward (negative) deflection with a total frequency of 70 ± 4,04 Hz [mean± SEM], duration of 1,4 ± 0,05ms, rise time of 0,7 ± 0,07ms, amplitude of 35,5± 2,22~aV and area 25,8 ± 1,91~aVms; the 75% of the spikes analyzed were assamnetric. In the core of the SNr the spikes were mostly monophasic with upward deflection or biphasic with an initial upward (negative) deflection. The total frequency was 79 ± 6,81Hz, the duration 2,1 ± 0,13ms, the rise time 1 ± 0,07ms, the amplitude 46,7±3,88 pV and the area 37,9±2,67pVms; the 60% of the spikes analyzed were symmetric.. Contusions: In conclusion, besides the firing pattern, only spike morphology can help in differentiating between the STN and the SNr during stereotactic neurosurgery.

Page 2: 1042 Spike characterization in the human subthalamus and substantia nigra

Poster Abstracts Wednesday, November 9, 2005 $365

Corresponding author: Prot~ Alberto Priori MD, Padiglione Ponti, Dipartimento di Sdenze Neurologiche Universit~ di Milano, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, Milano 20122 Italy.

1043 Cydog~am analysis of 12ozen gait in ParkinS0llitn

Naito, Y, Kuzuhara, S. Mie Universi(v Graduate School of Medicine, Tsu, Japan

Background: Frozen gait is often observed in patients with various parkinsonisms. Postural instability is one of the underlying impair- ments responsible for frozen gait. C~clogram displays dynamic foot pressure and can evaluate the displacement of the centre of pressure (COP) while walking. Objectives: Ten patients with parkinsonism presenting frozen gait including 5 with PD, 2 with PSP and 3 with vascular pseudo- parkinsonism (VP) were studied. Methods: Dynamic foot pressure was recorded by the GANGAS T M

gait analysis system. Dynantic COP changes and serial foot pressure transitions from heel to toe were analyzed while self-paced walking. Results: In healthy subjects, the dynamic COP moved from posterior to anterior and from left to right as steps went on and formed butterfly-shape trace on cyclogram. The foot pressure curve showed two peaks corresponding with heel contact and toe off. In PD, the dynamic COP displaced forward, and the foot pressure curve turned to mono peak, suggesting impaired load transition from heel to toe in freezing of gait. In contrast, the dynamic COP displaced backward in PSP, and the foot pressure curve revealed overload on heel, suggesting impaired balance. In VP, swing movements of COP transfer from right to left were only seen, as the gait vector to forward disappeared on freezing, presenting with so called stomping. Conclusion: The pattern of frozen gait is different among conditions reflecting impairments of balance-function and postural reflex in individual diseases. Cydogram is useful to analyse the patterns of dynamic COP displacements and body balance in frozen gait.

1044 A survey on the prevalence of cognitive disorders among Parldnson's disease

Najafi, NI 1, Reissifar, R 1, Najafi, F 2. Qsfahan Unive,ity of Medical Sciences; 2Tehran University of Medical Sciences

Background: Cognitive disorders include delirium, dementia and anmesia. The prevalence of cognitive disorders in PD is unknown in our society so these disorders enhance PD features. We determine the prevalence of cognitive disturbances during first six months in 2004. Methods: This is cross sectional study of 92 patients having the symptoms for at least one year and Modified Hoehn and Yahr Staging (2-5). We to ok Minimal Mental Status Examination o f patients. Score > 30 : no problenl, score: 25 30 means doubtful, score below 25 means the cognitive disturbance was present in our patients. Results: The average age of patients: 61 years. 44.6% of patients had a score below 20 that was considered as having cognitive disorders that more common in males than females. The most common of cognitive disorders include dementia 23.9%, delirium 12% and anlnesia 9.8% Conclusion: With better education, appropriate treatment and screen- ing for cognitive disturbances in such patients we can postpone the cognitive problems and decrease their duration and severity.

1045 Central Sleep Apnea in Patients with Multiple System Atrophy Developed Tracheostomy: Evaluation of Polysomnography

Nakamma, Y, Yamada, I, Sakamoto, H, Hatanaka, T, Yagi, Y. Department of Neurology, Sakai Hospital, Kinki University School of Medicine, Japan

Background: Multiple system atrophy (MSA) characterized clinically by any combination of autonomic, extrapyramidal or cerebellar symptoms and signs. MSA patients frequently manifest a variety of bulbar or respiratory disturbances, which are life threatening problems. The aim of the study is to evaluate sleep apnea or the respiratory disturbances with polysomnographic exantination (PSG) in patients with MSA who had developed to tracheostomy or death. Method: Twelve patients (six patients with MSA aged 61.7-k 5.2 year- old, disease duration 8.3 -k 3 years, and six patients with pure cerebellar atrophy (CA) aged 68.2±4.2 year-old, disease duration 9 .2±8.8 years, as disease control) were examined. Among of MSA, five patients developed tracheostomy and one patient happened to be a death due to respiratory disturbance. All o f CA didn't have tracheostomy. In PSG, EEGs, EOG, airflow of nose and mouth, and movement of chest and abdomen were measured using Alice4 during one night. The apnea and hypopnea index (AIH), the pattern of sleep apnea and the saturation of surface oxyhemoglobin (SpO2) were evaluated. Results: The average of AHI in MSA was significantly higher than CA (145-: 18.3, 24.2-k 24.3, respectively). In MSA, central sleep apnea was observed, but less than obstructive apnea and hypoapnea. In CA, central sleep apnea was rarely observed. The average of SpO2 was significantly lower in MSA than CA (93.7±1.2%, 95.5±1.4%, respectively). Contusion: The PSG findings showed significantly severe apnea and desaturation during night in MSA who had underwent tracheostomy than CA. Central sleep apnea observed in MSA should be considered as risk factor of progressing tracheostomy.

1046 Parldnson's Disease: The Range of Neuropsydtiatric Complications of Disease and Therapy

Hassan G Nassar, M D l, Hosam El-sawy, M D a, Mukhtar Mabrouk, Ph.d 2. 1Neuropsychiatry Department, Faculty of Medicine, Tanta university; 2Department of Analytical Chemistry, Facul(v of Pharmacy, Tanta University

Objective: To explore the profile of neuropsychiatric and cognitive morbidity in patients with PD and to know the etiology of these disorders whether due to the disease process itself or as a complication of levodopa. Subjects anti Methods: Sixty patients with PD were divided into: Group A (40 patients) receiving levodopa treatment and Group B (120 patients) not receiving levodopa treatment for at least 3 months before examination. Twenty subjects matched with the patients regarding age and sex were chosen as a control group. All subjects were subjected to detailed history, staging of the severity of PD patients, and psychiatric assessment by DSM-IV structured interview, Hamilton Rating Scale for Anxiety and for Depression, Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS). Cognitive functions were assessed by Wechsler Adult Intelligence Scale (WAIS), Trail Making Test, Bendert Gestault Test, Manual Dexterity Test and Wisconsin Card Sorting Test-64 CWCST - 64) (Card Version). Lastly, plasma levels of L-Dopa using High Power Liquid Chromatography (HPLC) was measured. Results: Postural instability, freezing and dyskinesias showed higher percentages in patients receiving levodopa (70%, 60% and 15% respectively). Patients suffering from dyskinesias had significantly higher plasma levels of levodopa. Eighty five percent o f PD patients showed at least one psychiatric symptom. Depression was the most frequent symptom (158.5"/o). Memory disturbance, attxiety, hallucina- tions and delusions were also reported in 53.4%, 40?,'0, 26.6% and 3.3% respectively. Depressive and amviety symptoms showed positive significant correlations with the duration of PD and with each other. Positive and negative psychotic symptoms correlated with the severity of motor symptoms, depressive and anxiety symptoms. No significant relations were found between the severity of any of the psychiatric symptoms and the side of onset of PD. Cognitive fmlctions showed