- Email: [email protected]
2.3.1 NEW VIEWS ON HUNTINGTON'S DISEASE PHENOTYPE
S82
Tuesday, 13 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S81–S159
Parallel Session Cortical Dysfunction in PD Chairperson: Ivan Bodis Wollner, Brooklyn, USA
08:30–10:00
2.2.1 PET STUDIES IN PARKINSON’S DISEASE MOTOR AND COGNITIVE DYSFUNCTION N. Pavese. Imperial College London & MRC, London, UK Positron emission tomography (PET) has led to significant advances in the knowledge of the neurobiology and pathophysiology of Parkinson’s disease (PD) and has also greatly contributed to the understanding of potential mechanisms involved in the development of treatment-induced complications. Initially, PET was mostly used to assess in vivo the severity of the nigrostriatal dopaminergic dysfunction and the resulting motor symptomatology in PD. It has been demonstrated that PET measurements of putaminal dopaminergic function, as measured by [18 F]-Fluorodopa uptake, correlate well with stages of disease and symptom severity in PD patients, particularly with bradykinesia and rigidity. Analysis of metabolic changes across the brain has identified specific brain networks associated with the main motor features of the disease, including bradykinesia and tremor. The growing availability of new imaging radiotracers for monoaminergic and cholinergic neurons has enabled the evaluation of non-dopaminergic brain pathways that are likely to be involved in the pathophysiology of non motor symptoms of PD, including depression and cognitive impairment. Finally, b-amyloid imaging agents have been used to assess the influence of coexistent cortical Alzheimer pathology in PD. This review summarizes the findings from PET studies that have investigated pathophysiology and treatment of motor dysfunction and cognitive impairment in PD. 2.2.2 FRONTO-PARIETAL COHERENCE AND IMPAIRED VOLUNTARY SACCADES IN PARKINSON DISEASE (PD) I. Bodis-Wollner, M.A. Javaid, S. Glazman. Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA Spatially distinct frontal eye field (FEF) and posterior parietal (PP) cortices are associated with volitional movements. Forgacs et-al (2008) described posterior perisaccadic gamma (35–45 Hz) modulation with voluntary saccades. It was impaired in PD (Javaid et-al 2010). We quantified perisaccadic EEG amplitude/power changes over frontal and PP scalp recording sites as healthy subjects self-initiated voluntary saccades. Electro-cap and electro-oculogram with ISCAN camera were used to record EEG and saccades. Subjects (43; ages 19–67 yrs, 8-females) repetitively executed horizontal volitional saccades to a mark, 15degree right or left and back to central fixation. 2-minute EEG was recorded from each subject. Each perisaccadic EEG segment underwent continuous wavelet transformation (WT) across 5–70 Hz band-range. The WT power spectra were trial-averaged and registered to the initiation of the saccade, independently for rightward and leftward saccades. Intrasaccadic beta and gamma power increased posteriorly, not frontally. Gamma increase was confined to saccade initiation. Gamma and beta powers attenuated in post-saccadic EEG epochs. Alpha-band power increased in controls prior to saccadic commencement followed by post-saccadic suppression, posteriorly and frontally. PD patients elicit hypometric saccades with steps. Rieger et-al (2008) found FEF dysfunction on fMRI in PD. Beta/alpha and gamma phase-amplitude coupling and potentially impaired fronto-parietal communication in PD merits investigation.
2.2.3 THE FRONTOSTRIATAL CIRCUITRY AND BEHAVIORAL COMPLICATIONS IN PD A.P. Strafella. University of Toronto, Toronto, ON, Canada We often need to plan novel actions or inhibit prepotent ones. These action decisions depend on accurate representations of reward or losses and the inhibition of impulses. In Parkinson’s disease (PD), the decision of which action to take, and the inhibition of harmful actions, can be worsened by dopaminergic therapy leading to impulse control disorders. The combination of PET, fMRI and psychopharmacology is beginning to reveal the mechanisms of poor impulse control in PD. Here, we show the results of neuroimaging studies conducted in PD patients providing evidence of significant abnormalities in those striatal and prefrontal areas associated with reward. Proposed mechanisms include abnormal functioning of mesolimbic structures resulting in dysregulation of dopamine. Video-Supported Session Huntington’s Disease Chairperson: Jean-Marc Burgunder, Switzerland
08:30–10:00
2.3.1 NEW VIEWS ON HUNTINGTON’S DISEASE PHENOTYPE J.-M. Burgunder. Department of Neurology, University of Bern, Bern, Switzerland The major clinical characteristics of Huntington’s disease, chorea starting on the face and generalizing to the body, with mental and behavioural impairment, chronically progressing up to death, have been well known since its first description in 1872. However, a number of questions remained about the phenotype and its variability, the relationship between the different signs and symptoms, and about their onset phase. In the last couple of years major initiatives, mainly sponsored by Cure HD Initative, including two prospective cohort studies (Cohort by the Huntington Study Group in the USA, and Registry by the European Huntington’s Network) and two intensive explorations of the presymptomatic and the early phase of the disease (Predict and Trak HD), have been started. The recently published results have shed a new light about HD phenomenology, including apathy and selective cognitive impairment. Moreover, abnormal results in motor and cognitive function, together with morphological changes can be demonstrated already years before expected over clinical manifestation. Significant changes can be measured in these parameters over a relative short period of time even in presymptomatic patients. These data demonstrate a real progress in the development of biomarkers needed to perform therapeutic trials for disease modifying treatments. 2.3.2 HUNTINGTON’S DISEASE IN CHINA H. Shang. Department of Neurology, West China Hospital/Sichuan University, Chengdu, China Huntington’s disease is thought to be very rare in China, but the reasons are not clear. Furthermore, due to the paucity of publications, the phenotype is not well known. A thorough analysis of the China National Knowledge Infrastructure with reports on HD between 1980 and April of 2011 disclosed a total of 92 studies involving 279 patients, only rarely with genetic confirmation. Most of the features were similar as in the West, but the prevalence was higher in men and cognitive symptoms were very rarely reported at onset. In order to get more reliable data, we have started to build up a cohort of patients assessed with established clinical instruments and with molecular genetic testing. In Chengdu, we now have collected data on about 30 patients of Han origin. Mean age at onset
Tuesday, 13 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S81–S159
Parallel Session Cortical Dysfunction in PD Chairperson: Ivan Bodis Wollner, Brooklyn, USA
08:30–10:00
2.2.1 PET STUDIES IN PARKINSON’S DISEASE MOTOR AND COGNITIVE DYSFUNCTION N. Pavese. Imperial College London & MRC, London, UK Positron emission tomography (PET) has led to significant advances in the knowledge of the neurobiology and pathophysiology of Parkinson’s disease (PD) and has also greatly contributed to the understanding of potential mechanisms involved in the development of treatment-induced complications. Initially, PET was mostly used to assess in vivo the severity of the nigrostriatal dopaminergic dysfunction and the resulting motor symptomatology in PD. It has been demonstrated that PET measurements of putaminal dopaminergic function, as measured by [18 F]-Fluorodopa uptake, correlate well with stages of disease and symptom severity in PD patients, particularly with bradykinesia and rigidity. Analysis of metabolic changes across the brain has identified specific brain networks associated with the main motor features of the disease, including bradykinesia and tremor. The growing availability of new imaging radiotracers for monoaminergic and cholinergic neurons has enabled the evaluation of non-dopaminergic brain pathways that are likely to be involved in the pathophysiology of non motor symptoms of PD, including depression and cognitive impairment. Finally, b-amyloid imaging agents have been used to assess the influence of coexistent cortical Alzheimer pathology in PD. This review summarizes the findings from PET studies that have investigated pathophysiology and treatment of motor dysfunction and cognitive impairment in PD. 2.2.2 FRONTO-PARIETAL COHERENCE AND IMPAIRED VOLUNTARY SACCADES IN PARKINSON DISEASE (PD) I. Bodis-Wollner, M.A. Javaid, S. Glazman. Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA Spatially distinct frontal eye field (FEF) and posterior parietal (PP) cortices are associated with volitional movements. Forgacs et-al (2008) described posterior perisaccadic gamma (35–45 Hz) modulation with voluntary saccades. It was impaired in PD (Javaid et-al 2010). We quantified perisaccadic EEG amplitude/power changes over frontal and PP scalp recording sites as healthy subjects self-initiated voluntary saccades. Electro-cap and electro-oculogram with ISCAN camera were used to record EEG and saccades. Subjects (43; ages 19–67 yrs, 8-females) repetitively executed horizontal volitional saccades to a mark, 15degree right or left and back to central fixation. 2-minute EEG was recorded from each subject. Each perisaccadic EEG segment underwent continuous wavelet transformation (WT) across 5–70 Hz band-range. The WT power spectra were trial-averaged and registered to the initiation of the saccade, independently for rightward and leftward saccades. Intrasaccadic beta and gamma power increased posteriorly, not frontally. Gamma increase was confined to saccade initiation. Gamma and beta powers attenuated in post-saccadic EEG epochs. Alpha-band power increased in controls prior to saccadic commencement followed by post-saccadic suppression, posteriorly and frontally. PD patients elicit hypometric saccades with steps. Rieger et-al (2008) found FEF dysfunction on fMRI in PD. Beta/alpha and gamma phase-amplitude coupling and potentially impaired fronto-parietal communication in PD merits investigation.
2.2.3 THE FRONTOSTRIATAL CIRCUITRY AND BEHAVIORAL COMPLICATIONS IN PD A.P. Strafella. University of Toronto, Toronto, ON, Canada We often need to plan novel actions or inhibit prepotent ones. These action decisions depend on accurate representations of reward or losses and the inhibition of impulses. In Parkinson’s disease (PD), the decision of which action to take, and the inhibition of harmful actions, can be worsened by dopaminergic therapy leading to impulse control disorders. The combination of PET, fMRI and psychopharmacology is beginning to reveal the mechanisms of poor impulse control in PD. Here, we show the results of neuroimaging studies conducted in PD patients providing evidence of significant abnormalities in those striatal and prefrontal areas associated with reward. Proposed mechanisms include abnormal functioning of mesolimbic structures resulting in dysregulation of dopamine. Video-Supported Session Huntington’s Disease Chairperson: Jean-Marc Burgunder, Switzerland
08:30–10:00
2.3.1 NEW VIEWS ON HUNTINGTON’S DISEASE PHENOTYPE J.-M. Burgunder. Department of Neurology, University of Bern, Bern, Switzerland The major clinical characteristics of Huntington’s disease, chorea starting on the face and generalizing to the body, with mental and behavioural impairment, chronically progressing up to death, have been well known since its first description in 1872. However, a number of questions remained about the phenotype and its variability, the relationship between the different signs and symptoms, and about their onset phase. In the last couple of years major initiatives, mainly sponsored by Cure HD Initative, including two prospective cohort studies (Cohort by the Huntington Study Group in the USA, and Registry by the European Huntington’s Network) and two intensive explorations of the presymptomatic and the early phase of the disease (Predict and Trak HD), have been started. The recently published results have shed a new light about HD phenomenology, including apathy and selective cognitive impairment. Moreover, abnormal results in motor and cognitive function, together with morphological changes can be demonstrated already years before expected over clinical manifestation. Significant changes can be measured in these parameters over a relative short period of time even in presymptomatic patients. These data demonstrate a real progress in the development of biomarkers needed to perform therapeutic trials for disease modifying treatments. 2.3.2 HUNTINGTON’S DISEASE IN CHINA H. Shang. Department of Neurology, West China Hospital/Sichuan University, Chengdu, China Huntington’s disease is thought to be very rare in China, but the reasons are not clear. Furthermore, due to the paucity of publications, the phenotype is not well known. A thorough analysis of the China National Knowledge Infrastructure with reports on HD between 1980 and April of 2011 disclosed a total of 92 studies involving 279 patients, only rarely with genetic confirmation. Most of the features were similar as in the West, but the prevalence was higher in men and cognitive symptoms were very rarely reported at onset. In order to get more reliable data, we have started to build up a cohort of patients assessed with established clinical instruments and with molecular genetic testing. In Chengdu, we now have collected data on about 30 patients of Han origin. Mean age at onset