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2.011 Familial genes in sporadic Parkinson's disease
S88
Tuesday, 11 December 2007
occur during pregnancy and are coincident with uraemia, iron depletion, polyneuropathy, spinal disorders, and rheumatoid arthritis. For the hereditary forms, at least seven gene loci, located on chromosomes 2, 4, 9, 12, 14, 17 and 20, have been traced so far. Prevalence in the general population is between 3% and 9%, increases with age, and is higher in women than in men. Periodic limb movements in sleep (PLMS), recorded with either polysomnography or actigraphy are the characteristic motor feature of RLS and may lead to severe sleep disruption with frequent awakenings. Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people. Pathophysiology and treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic treatment with levodopa and dopamine agonists is the first choice in idiopathic restless legs syndrome. Since 2006, ropinirole and pramipexole are licensed for RLS treatment in the US and Europe. Augmentation is the most important side effect of dopaminergic treatment and defined by a paradoxical worsening of RLS symptoms during therapy mostly with higher dosages of levodopa. Various other drugs, such as opioids, gabapentin, and benzodiazepines, provide alternative treatment possibilities. Educational goals: 1. To better recognize and assess RLS and PMLS 2. To understand the pathophysiology of these disorders 3. To adequately treat RLS and PMLS
Room B 2.005 Transcranial magnetic stimulation Y. van der Werf1° , V. Della Maggiore2° 1 Amsterdam, Netherlands; 2 Buenos Aires, Argentina The session will discuss recent developments in clinical, preclinical and fundamental use of Transcranial Magnetic Stimulation (TMS). The focus will be on movement and movement disorders, including possible effects on cognition and emotion that are relevant for the movement disorders. The different modes of TMS consist of single-pulse TMS, double-pulse TMS and repetitive TMS. These techniques can be used alone or in combination for therapeutic and research purposes. Depending on the research goal or clinical problem, TMS can be used to manipulate and study both excitatory and inhibitory processes in the brain. The combination of TMS with brain imaging techniques has shown that stimulation applied at the level of the cortex affects activity of interconnected networks in the brain, allowing manipulation of functional circuits rather than separate foci. The several techniques will be demonstrated live in the session and illustrated with recent and current projects including therapeutic use of repetitive TMS for Parkinson’s disease, TMS as a tool to study movement adaptation, and TMS as a probe for abnormalities of cortical and subcortical processing in various movement disorders. Educational goals: 1. To understand recent developments in transcranial magnetic stimulation 2. To understand the various techniques and applications of TMS 3. To understand the use of TMS in both, assessing and treating movement disorders
13.00−15.00
Room D
Young Scientists Oral Presentations Chair: Donald B. Calne, Vancouver, BC, Canada Co-Chair: Ivan Bodis-Wollner, New York, NY, USA 2.011 Familial genes in sporadic Parkinson’s disease O. Ross1° , J. Aasly, L. White, J.M. Gibson, T. Lynch, R. Uitti, Z. Wszolek, C.-H. Lin, R.-M. Wu, M. Farrer 1 Jacksonville, FL, USA Objective: To examine the role variants of genes associated with familial parkinsonism have to play in the common sporadic Parkinson’s disease. Method: We performed association studies with different age-, gender-, and ethnically-matched Parkinson’s disease patient-control series from Norway, USA, Ireland and Taiwan to investigate the frequency of common variants in three familial genes; SNCA, PRKN and LRRK2. Results: Although no significant association was observed for the PRKN −258 promoter SNP, significant ‘risk’ effects were observed for SNCA in the Irish and Lrrk2 G2385R in the Taiwanese. Conclusion: These results show that common the genetic variants can play an important role in sporadic disorders and that the full potential of this disease component is still to be realised. Moreover, our findings for Lrrk2 G2385R demonstrate that common genetic coding variants contribute to Parkinson’s disease in a population specific manner which may have important implications for future genome-wide association studies.
2.012 Perry’s syndrome is a unique TDP-43 proteinopathy C. Wider1° , D. Dickson, D. Calne, J. Stoessl, L. Gutmann, S. Calne, L. Brown, Z. Wszolek 1 Jacksonville, FL, USA Objective: The objective is to report clinical and neuropathologic findings of a patient from the Canadian kindred described by Perry and coworkers and another patient from West Virginia with the same syndrome. Both individuals had autosomal dominant Parkinsonism, hypoventilation, depression and weight loss (Perry’s syndrome). Method: Both patients were followed longitudinally by neurologists. Brains were sent to Mayo Clinic for evaluation, which included immunohistochemistry for tau, a-synuclein, ubiquitin and TDP-43. Results: At age 51 the Canadian patient presented with weight loss, breathing difficulties, mild postural and rest tremor, masked face, mild depression and severe central-type hypoventilation. He died at age 54. The West Virginia patient developed sleeping difficulties, fatigue and lethargy at age 40. He had a masked face, axial and upper limb rigidity and decreased arm swing. He died suddenly four years later. At autopsy both patients had marked neuronal loss and gliosis in the substantia nigra associated with swollen dystrophic axons. Some residual neurons had eosinophilic cytoplasmic inclusions, but there were no Lewy bodies or neurofibrillary tangles. Less affected brain regions included the lentiform nucleus, hypothalamus, periaqueductal gray matter, locus coeruleus, raphe nucleus and brainstem reticular formation. Ubiquitin immunoreactive inclusions and dystrophic neurites were noted in the substantia nigra. They were subsequently shown to be immunoreactive for TDP-43, a recently described marker for frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Neuronal cytoplasmic inclusions were present in the basal ganglia, hypothalamus, thalamus, substantia nigra and pontine and medullary tegmentum. TDP-43-immunoreactive inclusions were not detected in cortex, hippocampus or motor neurons. Conclusion: Our study shows for the first time that Perry’s syndrome is a TDP-43 proteinopathy. Unlike FTLD and ALS, TDP-43 inclusions
Tuesday, 11 December 2007
occur during pregnancy and are coincident with uraemia, iron depletion, polyneuropathy, spinal disorders, and rheumatoid arthritis. For the hereditary forms, at least seven gene loci, located on chromosomes 2, 4, 9, 12, 14, 17 and 20, have been traced so far. Prevalence in the general population is between 3% and 9%, increases with age, and is higher in women than in men. Periodic limb movements in sleep (PLMS), recorded with either polysomnography or actigraphy are the characteristic motor feature of RLS and may lead to severe sleep disruption with frequent awakenings. Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people. Pathophysiology and treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic treatment with levodopa and dopamine agonists is the first choice in idiopathic restless legs syndrome. Since 2006, ropinirole and pramipexole are licensed for RLS treatment in the US and Europe. Augmentation is the most important side effect of dopaminergic treatment and defined by a paradoxical worsening of RLS symptoms during therapy mostly with higher dosages of levodopa. Various other drugs, such as opioids, gabapentin, and benzodiazepines, provide alternative treatment possibilities. Educational goals: 1. To better recognize and assess RLS and PMLS 2. To understand the pathophysiology of these disorders 3. To adequately treat RLS and PMLS
Room B 2.005 Transcranial magnetic stimulation Y. van der Werf1° , V. Della Maggiore2° 1 Amsterdam, Netherlands; 2 Buenos Aires, Argentina The session will discuss recent developments in clinical, preclinical and fundamental use of Transcranial Magnetic Stimulation (TMS). The focus will be on movement and movement disorders, including possible effects on cognition and emotion that are relevant for the movement disorders. The different modes of TMS consist of single-pulse TMS, double-pulse TMS and repetitive TMS. These techniques can be used alone or in combination for therapeutic and research purposes. Depending on the research goal or clinical problem, TMS can be used to manipulate and study both excitatory and inhibitory processes in the brain. The combination of TMS with brain imaging techniques has shown that stimulation applied at the level of the cortex affects activity of interconnected networks in the brain, allowing manipulation of functional circuits rather than separate foci. The several techniques will be demonstrated live in the session and illustrated with recent and current projects including therapeutic use of repetitive TMS for Parkinson’s disease, TMS as a tool to study movement adaptation, and TMS as a probe for abnormalities of cortical and subcortical processing in various movement disorders. Educational goals: 1. To understand recent developments in transcranial magnetic stimulation 2. To understand the various techniques and applications of TMS 3. To understand the use of TMS in both, assessing and treating movement disorders
13.00−15.00
Room D
Young Scientists Oral Presentations Chair: Donald B. Calne, Vancouver, BC, Canada Co-Chair: Ivan Bodis-Wollner, New York, NY, USA 2.011 Familial genes in sporadic Parkinson’s disease O. Ross1° , J. Aasly, L. White, J.M. Gibson, T. Lynch, R. Uitti, Z. Wszolek, C.-H. Lin, R.-M. Wu, M. Farrer 1 Jacksonville, FL, USA Objective: To examine the role variants of genes associated with familial parkinsonism have to play in the common sporadic Parkinson’s disease. Method: We performed association studies with different age-, gender-, and ethnically-matched Parkinson’s disease patient-control series from Norway, USA, Ireland and Taiwan to investigate the frequency of common variants in three familial genes; SNCA, PRKN and LRRK2. Results: Although no significant association was observed for the PRKN −258 promoter SNP, significant ‘risk’ effects were observed for SNCA in the Irish and Lrrk2 G2385R in the Taiwanese. Conclusion: These results show that common the genetic variants can play an important role in sporadic disorders and that the full potential of this disease component is still to be realised. Moreover, our findings for Lrrk2 G2385R demonstrate that common genetic coding variants contribute to Parkinson’s disease in a population specific manner which may have important implications for future genome-wide association studies.
2.012 Perry’s syndrome is a unique TDP-43 proteinopathy C. Wider1° , D. Dickson, D. Calne, J. Stoessl, L. Gutmann, S. Calne, L. Brown, Z. Wszolek 1 Jacksonville, FL, USA Objective: The objective is to report clinical and neuropathologic findings of a patient from the Canadian kindred described by Perry and coworkers and another patient from West Virginia with the same syndrome. Both individuals had autosomal dominant Parkinsonism, hypoventilation, depression and weight loss (Perry’s syndrome). Method: Both patients were followed longitudinally by neurologists. Brains were sent to Mayo Clinic for evaluation, which included immunohistochemistry for tau, a-synuclein, ubiquitin and TDP-43. Results: At age 51 the Canadian patient presented with weight loss, breathing difficulties, mild postural and rest tremor, masked face, mild depression and severe central-type hypoventilation. He died at age 54. The West Virginia patient developed sleeping difficulties, fatigue and lethargy at age 40. He had a masked face, axial and upper limb rigidity and decreased arm swing. He died suddenly four years later. At autopsy both patients had marked neuronal loss and gliosis in the substantia nigra associated with swollen dystrophic axons. Some residual neurons had eosinophilic cytoplasmic inclusions, but there were no Lewy bodies or neurofibrillary tangles. Less affected brain regions included the lentiform nucleus, hypothalamus, periaqueductal gray matter, locus coeruleus, raphe nucleus and brainstem reticular formation. Ubiquitin immunoreactive inclusions and dystrophic neurites were noted in the substantia nigra. They were subsequently shown to be immunoreactive for TDP-43, a recently described marker for frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Neuronal cytoplasmic inclusions were present in the basal ganglia, hypothalamus, thalamus, substantia nigra and pontine and medullary tegmentum. TDP-43-immunoreactive inclusions were not detected in cortex, hippocampus or motor neurons. Conclusion: Our study shows for the first time that Perry’s syndrome is a TDP-43 proteinopathy. Unlike FTLD and ALS, TDP-43 inclusions