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OPL008 ∞-Synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson's disease
Oral Platform Abstracts hypo-metabolism in 2; bilateral striatal hypometabolism in 2 and 1 had middle cerebral artery ischemia. Following the PET scans, the diagnosis of PD remained unchanged in 19/34;diagnosed as CBGD in 2; PSP in 9; AD in 3 and infarct in 1. Conclusion: Multi-tracer PET imaging contributes in differentiating PD fi'om Parkinsonian syndromes.
OPL008 -Synuclein redistributes to neuromdanin lipid in the s~bstantia nigra early in Parkinson's disease Halliday, G.M 1, Ophof, A 1, Broe, M 1, Jensen, P.H 2, Kettle, E 1, Fedorow, H 1, Cartwright, M 1, Griffiths, F 1, Shepherd, C 1 and Double, K.L ~. 1Prince of Wales Medical Research Institute, Sydney,
Australia; 2Institute of Medical Biocherniswy, Universityof Aarhus, Aarhus, Denmark The distribution and tempo of neuronal loss in Parkinson's disease (PD) correlates poorly with the occurrence of the characteristic pathological inclusions. A comparison between thirteen P D patients and agematched controls demonstrated only the substantia nigra had consistent significant cell loss early in the disease course, with greater cell loss correlating with increasing disease duration. Pigmented neurons in later stages o f degeneration with obvious Lewy body formation had a significant reduction in intracelhilar pigment. In contrast, nigral neurons of normal morphological appearance and no characteristic. pathology in PD exhibited significantly increased pigment density associated with a concentration o f c~-synuclein to the lipid component of the pigment and a loss of associated cholesterol. These changes in vulnerable but apparently healthy nigral neurons occurred without any change in cell size or amount o f pigment. The increase in pigment density is consistent with previously reported increases associated with oxidation and iron loading, reactions known to precipitate c~-synuclein. The selectivity of the changes observed in nigral neurons suggests that these early intracellular changes predispose these neurons to more rapid cell loss in PD. The increased concentration of neuronal ~-synuclein and pigment in normal nigral neurons may predispose these neurons to precipitate c~-synuclein around pigment-associated lipid under oxidative conditions. Overall these changes may trigger a cascade of events, leading to larger intracelhilar aggregates of c~-synuclein and the dispersement of protective pigment precipitating cell death in PD.
OPL009 Visual perceptual impairments with sleep deprivation parallel Bafint's Syndrome visual neglect Russo ~¢1~, Sing H 2, Kendall A ~, Johnson D ~, Santiago S, Escolas S4, Holland D 5, Thorne D ~, Hall D ~, Redmond D 3. 1US Army
Aeromedical Research Laboratory, USA; 2Walter Reed Army Institute of Research, USA; 3Henry M. Yackson Foundation for the Advancement of Military Medicine, USA; 4 US Army Medical Research and Materiel Command, USA; S United States Air Force 3 I l th Human Systems tVing, USA Backgrouml: Visual neglect phenomena have been demonstrated in acute sleep deprivation and correlated with flight performance in pilots (1). This presentation will discuss visual perception and motor performance in pilots in over 26.5 hours of continuous wake. Methods: Eight military pilots (m, 31-52 y/o, mean 37yrs) on flight status were recruited to perform the primary task of flying a simulated 12.5-hours ovemdght mission after a day of continuous wakefulness, and perform the secondary task of responding to repeated 20-minute presentations of light stimuli displayed in random sequence while the pilot maintained airspeed of 275 knots immediately behind and below a simulated tanker aircraft. Complex performance was measured through deviations from a pre-established azimuth heading during the visual perception task. Results: Significant visual perceptual impairment, significant complex motor performance impairment each began during the 19th hour of
Monday, November 7, 2005
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continuous wake in patterns consistent with biparietal and prefrontal impairment. Visual perception impairments significantly correlated with flight heading impairments at r - 0.97. Condasions: Impairments on a choice visual perception task and on a complex motor flight performance task began at 19 hours of continuous wake. The implications are that acute sleep deprivation can impair both visual perception and motor performance at an earlier time than many individuals may be aware. OPL010 Increased dopamine D2-receptor availability in patients with Restless Legs Syndxome as uleasuxed with Positron Fzi;ission Toulography Cervenka, S l, PMhagen, SE 2, Comley, RA 3, Panagiotidis, 04, Matthews, JC 3'5, Lai, RY s, Halldin, C 1 and Farde, L ~. 1Dept of
Clinical Neuroscience, Karolinska Instituter, Stockholm, Sweden," :Dept of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden; 3Translational Medicine and Genetics, GlaxoSmithKline, Cambridge, United Kingdom; 4Dept of Laboratory Medicine, Karolinslra University Hospital Huddinge, Stockholm, Sweden; SWolfson Molecular Imaging Centre, The University of Manchester, Manchester, United Kingdom; ~Neurology Discovery Medicine, GlaxoSrnithKline, Harlow, United Kingdom Background: Clinical observations support a central role of the doparnine system in Restless Legs Syndrome (RLS) but previous imaging studies o f striatal dopamine D2-receptors have yielded inconclusive results. F~xtrastriatal dopaminergic function has hitherto not been investigated. Methods: Sixteen RLS patients naive to dopanfinergic drugs and 16 matched controls were examined with Positron Emission Tomography. [11C]Raclopride and [~C.]FLB 457 were used to estimate D2-receptor availability in stricture and extrastriatal regions, respectively. Examinations were repeated in the morning (10-13.30) and evening (18-20). Measures were taken to monitor and control for head movement during data acquisition. Results: The diurnal variability in binding potential (BP) with [11C]FLB 457 and [11C]Raclopride was within the previously reported test-retest variability. Patients had significantly higher [llC]Raclopride BP values (12.7 ± 0.3; n -- 16) than controls (12.5 ± 0.2; n -- 16) in striatum (paired t-test; p - 0.021). In extrastriatal regions, the [11C]FLB 457 BP values were significantly higher in thalamus (2.7 ± 0.6 vs. 2.4 ± 0.5; p - 0.034), left insula (1.4 ± 0.4 vs. 1.1 ± 0.2; p - 0.025) and right rostral anterior cingnlate (0.9 ± 0.3 vs. 0.6 ± 0.2; p -- 0.005). Conclusions: The results support the theory of doparninergic dysregulation in RLS. Increased D2-receptor availability in RLS may correspond to lfigher receptor densities, lower levels of endogenous dopanfine, or a combination of both. Interestingly, the brain regions included are implicated in the regulation o f affective and motivational aspects of sensory processing. OPL011 Homolateral Imitative Synkinesis: A Forgotten Sign Needham, M 1, Loy, C 1, MacAnally, L 1, Fung, V 1, Pariente, j2, Morris j1.1Dept of Neurology, Westmead Hospital, Sydney, Australia;
2Service de Neurologie C, Pavillon Riser, CHU Purport, Toulouse, France Background: While much has been written in recent years about mirror movements, where voluntary movements of the fingers on one side invoke involuntary movements of a similar character in contralateral fingers, the related phenomenon of homolateral imitative synkinesis (HIS) has been largely ignored. Here, voluntary movements of the hand invoke similar movements in the ipsilateral leg or vice versa. Both phenomena are seen in normal children but persistence into adulthood implies a pathological process. Method and Results: We describe four patients with HIS. The first was a 71 year-old man with mild right hemiparesis associated with a small
OPL008 -Synuclein redistributes to neuromdanin lipid in the s~bstantia nigra early in Parkinson's disease Halliday, G.M 1, Ophof, A 1, Broe, M 1, Jensen, P.H 2, Kettle, E 1, Fedorow, H 1, Cartwright, M 1, Griffiths, F 1, Shepherd, C 1 and Double, K.L ~. 1Prince of Wales Medical Research Institute, Sydney,
Australia; 2Institute of Medical Biocherniswy, Universityof Aarhus, Aarhus, Denmark The distribution and tempo of neuronal loss in Parkinson's disease (PD) correlates poorly with the occurrence of the characteristic pathological inclusions. A comparison between thirteen P D patients and agematched controls demonstrated only the substantia nigra had consistent significant cell loss early in the disease course, with greater cell loss correlating with increasing disease duration. Pigmented neurons in later stages o f degeneration with obvious Lewy body formation had a significant reduction in intracelhilar pigment. In contrast, nigral neurons of normal morphological appearance and no characteristic. pathology in PD exhibited significantly increased pigment density associated with a concentration o f c~-synuclein to the lipid component of the pigment and a loss of associated cholesterol. These changes in vulnerable but apparently healthy nigral neurons occurred without any change in cell size or amount o f pigment. The increase in pigment density is consistent with previously reported increases associated with oxidation and iron loading, reactions known to precipitate c~-synuclein. The selectivity of the changes observed in nigral neurons suggests that these early intracellular changes predispose these neurons to more rapid cell loss in PD. The increased concentration of neuronal ~-synuclein and pigment in normal nigral neurons may predispose these neurons to precipitate c~-synuclein around pigment-associated lipid under oxidative conditions. Overall these changes may trigger a cascade of events, leading to larger intracelhilar aggregates of c~-synuclein and the dispersement of protective pigment precipitating cell death in PD.
OPL009 Visual perceptual impairments with sleep deprivation parallel Bafint's Syndrome visual neglect Russo ~¢1~, Sing H 2, Kendall A ~, Johnson D ~, Santiago S, Escolas S4, Holland D 5, Thorne D ~, Hall D ~, Redmond D 3. 1US Army
Aeromedical Research Laboratory, USA; 2Walter Reed Army Institute of Research, USA; 3Henry M. Yackson Foundation for the Advancement of Military Medicine, USA; 4 US Army Medical Research and Materiel Command, USA; S United States Air Force 3 I l th Human Systems tVing, USA Backgrouml: Visual neglect phenomena have been demonstrated in acute sleep deprivation and correlated with flight performance in pilots (1). This presentation will discuss visual perception and motor performance in pilots in over 26.5 hours of continuous wake. Methods: Eight military pilots (m, 31-52 y/o, mean 37yrs) on flight status were recruited to perform the primary task of flying a simulated 12.5-hours ovemdght mission after a day of continuous wakefulness, and perform the secondary task of responding to repeated 20-minute presentations of light stimuli displayed in random sequence while the pilot maintained airspeed of 275 knots immediately behind and below a simulated tanker aircraft. Complex performance was measured through deviations from a pre-established azimuth heading during the visual perception task. Results: Significant visual perceptual impairment, significant complex motor performance impairment each began during the 19th hour of
Monday, November 7, 2005
$47
continuous wake in patterns consistent with biparietal and prefrontal impairment. Visual perception impairments significantly correlated with flight heading impairments at r - 0.97. Condasions: Impairments on a choice visual perception task and on a complex motor flight performance task began at 19 hours of continuous wake. The implications are that acute sleep deprivation can impair both visual perception and motor performance at an earlier time than many individuals may be aware. OPL010 Increased dopamine D2-receptor availability in patients with Restless Legs Syndxome as uleasuxed with Positron Fzi;ission Toulography Cervenka, S l, PMhagen, SE 2, Comley, RA 3, Panagiotidis, 04, Matthews, JC 3'5, Lai, RY s, Halldin, C 1 and Farde, L ~. 1Dept of
Clinical Neuroscience, Karolinska Instituter, Stockholm, Sweden," :Dept of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden; 3Translational Medicine and Genetics, GlaxoSmithKline, Cambridge, United Kingdom; 4Dept of Laboratory Medicine, Karolinslra University Hospital Huddinge, Stockholm, Sweden; SWolfson Molecular Imaging Centre, The University of Manchester, Manchester, United Kingdom; ~Neurology Discovery Medicine, GlaxoSrnithKline, Harlow, United Kingdom Background: Clinical observations support a central role of the doparnine system in Restless Legs Syndrome (RLS) but previous imaging studies o f striatal dopamine D2-receptors have yielded inconclusive results. F~xtrastriatal dopaminergic function has hitherto not been investigated. Methods: Sixteen RLS patients naive to dopanfinergic drugs and 16 matched controls were examined with Positron Emission Tomography. [11C]Raclopride and [~C.]FLB 457 were used to estimate D2-receptor availability in stricture and extrastriatal regions, respectively. Examinations were repeated in the morning (10-13.30) and evening (18-20). Measures were taken to monitor and control for head movement during data acquisition. Results: The diurnal variability in binding potential (BP) with [11C]FLB 457 and [11C]Raclopride was within the previously reported test-retest variability. Patients had significantly higher [llC]Raclopride BP values (12.7 ± 0.3; n -- 16) than controls (12.5 ± 0.2; n -- 16) in striatum (paired t-test; p - 0.021). In extrastriatal regions, the [11C]FLB 457 BP values were significantly higher in thalamus (2.7 ± 0.6 vs. 2.4 ± 0.5; p - 0.034), left insula (1.4 ± 0.4 vs. 1.1 ± 0.2; p - 0.025) and right rostral anterior cingnlate (0.9 ± 0.3 vs. 0.6 ± 0.2; p -- 0.005). Conclusions: The results support the theory of doparninergic dysregulation in RLS. Increased D2-receptor availability in RLS may correspond to lfigher receptor densities, lower levels of endogenous dopanfine, or a combination of both. Interestingly, the brain regions included are implicated in the regulation o f affective and motivational aspects of sensory processing. OPL011 Homolateral Imitative Synkinesis: A Forgotten Sign Needham, M 1, Loy, C 1, MacAnally, L 1, Fung, V 1, Pariente, j2, Morris j1.1Dept of Neurology, Westmead Hospital, Sydney, Australia;
2Service de Neurologie C, Pavillon Riser, CHU Purport, Toulouse, France Background: While much has been written in recent years about mirror movements, where voluntary movements of the fingers on one side invoke involuntary movements of a similar character in contralateral fingers, the related phenomenon of homolateral imitative synkinesis (HIS) has been largely ignored. Here, voluntary movements of the hand invoke similar movements in the ipsilateral leg or vice versa. Both phenomena are seen in normal children but persistence into adulthood implies a pathological process. Method and Results: We describe four patients with HIS. The first was a 71 year-old man with mild right hemiparesis associated with a small