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P1.060 Pathological observations in seven cases with neurodegeneration with brain iron accumulation (NBIA) with mutations in PANK2 and PLA2G6
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Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
of extrapyramidal disorders, especially in developing countries including India. P1.059 Psychiatric manifestations in dystonia S. Khan1 , C. Kubu2 . 1 Neurology, 2 Psychiatry/Psychology, Cleveland Clinic, Cleveland, OH, USA Objectives: To investigate the prevalence of psychiatric symptoms in patients with dystonia presenting for surgical evaluation and to assess the relationship between psychiatric symptoms and various dystonia features. Introduction: Patients with dystonia often present with comorbid psychiatric symptoms, a clinical observation which is intuitively reasonable given the prominent role of the basal ganglia in the pathophysiology of dystonia and neuropsychiatric symptoms. Recently published data have demonstrated rates of 30% to 37.3% depression in dystonic patients. Methods: 63 consecutive patients presenting for surgical evaluation for dystonia were identified. Patients were classified as primary and secondary dystonia. Primary dystonia was further classified according to distribution and age of onset. Secondary dystonia was divided into psychogenic, tardive, and dystonia due to all other causes. Those with prior neurosurgery were excluded. Demographic information, BDI, BAI and MMPI scores were collected retrospectively. Results: Of the 25 patients with primary dystonia, 23.8% had moderate to severe depression. There was a trend for women and patients with younger age of onset to endorse a higher severity of depression. 21.3% had moderate to severe anxiety. Patients with pschogenic dystonia had a higher mean BDI and BAI. Conclusions: A high proportion of patients with dystonia endorsed significant depression and anxiety highlighting the need to carefully screen for psychiatric symptoms and treat accordingly. No significant differences were identified when looking at demographic and disease specific variables. Our data suggest that patients with psychogenic dystonia had a tendency to endorse greater psychological distress compared to other groups. P1.060 Pathological observations in seven cases with neurodegeneration with brain iron accumulation (NBIA) with mutations in PANK2 and PLA2G6 A. Li1 , C. Paisan-Ruiz1 , K. Bhatia2 , S. Schneider2 , J. Hardy1 , D. Kidd3 , J. Chataway4 , J. Holton1 , H. Houlden1 , T. Revesz1 . 1 Molecular Neuroscience, Institute of Neurology, UCL, 2 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, 3 Department of Clinical Neurosciences, Royal Free Hospital, 4 National Hospital for Neurology and Neurosurgery, London, UK Introduction: Mutations in the PANK2 and PLA2G6 gene have been shown to cause a recessive autosomal disorder known as NBIA. These disorders are clinically characterised by motor symptoms such as dystonia and parkinsonism and pathologically characterised by the occurrence of axonal swellings throughout the CNS. Objective: We present clinical and neuropathological findings of four cases with PLA2G6 mutations and three cases with PANK2 mutations, all cases were late-infantile onset. We also plan to investigate the distribution of the PANK2 and PLA2G6 proteins. Material & methods: Brain tissue was available from Queen Square Brain Bank, (UCL, London) and NICHD Brain and Tissue Bank (Baltimore) including one biopsy case and six postmortem cases. Sections were stained with routine histology and immunohistochemistry with antibodies to alpha-synuclein, tau (AT8), ubiquitin, p62, neurofilament (RT97 and SM131), GFAP, and CD68. Results: Ages of death for PANK2 cases ranged from 10–20 years and two of the three cases showed mild neurofibrillary tau pathology. Ages of death for PLA2G6 cases were between 5–32
years. Two of the four PLA2G6 cases showed accumulation of phosphorylated tau in cortical structures and additionally, three of the four cases showed accumulation of alpha-synuclein in typical Lewy bodies (LB) and neurites. Conclusions: Mild tau pathology was observed some PANK2 and PLA2G6 cases; however LBs and alpha-synuclein accumulation were the main pathological event in cases with PLA2G6 mutations. Investigations of tau and LB pathology involved with PANK2 and PLA2G6 mutations may further elucidate mechanisms involved in the tauopathy and synuclein disorders. P1.061 Interoceptive mirroring to guide assessment of writer’s cramp E. Lim, A. Quek, R. Seet. Neurology, National University of Singapore, Singapore, Singapore Introduction: Mirror/overflow movements may aid in assessment/ management of writer’s cramp. Patients use sensory tricks to relieve dystonic posturing. Brissaud postulated that imagination plays a part in these sensory tricks. Greene reported that imagined tasks helped to relieve dystonia. Aims: We assessed whether imagining the act of writing aided in the assessment of writer’s cramp. Method: 12 patients (4 female, 8 male) with writer’s cramp were assessed clinically at rest, during the act of writing (dominant/ non-dominant hands), when they were assessed for mirror/ overflow movements) and when asked to imagine themselves writing with either hand. They were assessed for dystonic posturing at rest, on writing and whilst imagining themselves writing. Results: 12 patients of mean age 47.8 years (range 17–81), with writer’s cramp averaging 8.4 years’ duration (range 1–30), were assessed. 11 had mirror movements of the involved hand and 3 had mirror movements in the contralateral hand. Only 1 patient had overflow movements in the uninvolved hand with imagined writing tasks (interoceptive overflow movements), but 9 had interoceptive overflow movements in the involved hand. Interoceptive movements were consistent with overflow/mirror movements when writing, but were of smaller amplitude and less obvious. Discussion: Interoceptive overflow movements can assist in the management and assessment of patients with writer’s cramp. Interoceptive overflow movements occur only in patients demonstrating overflow/mirroring whilst writing. P1.062 Genetic contribution to young onset dystonia in a Taiwanese cohort C.-S. Lu1 , Y.-H. Wu-Chou2 , H.-C. Chang1 , T.-H. Yeh1 , S.-C. Lai1 , R.-S. Chen1 , Y.-H. Weng1 , C.-L. Huang3 . 1 Department of Neurology, 2 Human Molecular Genetics Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, 3 Department of Neurology, Saint Paul’s Hospital, Taoyuan, Taiwan R.O.C. Background: Idiopathic dystonia is relatively common in Taiwan but the genetic etiology has been rarely reported. In our previous genetic analysis for a few subsets of dystonia patients, we have successfully identified mutations of Torsin A, GCH1and SGCE in limited familial and sporadic patients. Here, we re-analyzed the contribution of these genes to a subset of young onset dystonia whose symptom began before the age of 26. The parkin mutation was analyzed too. Subjects and Methods: Patients with young onset dystonia were selected for the study. A total of 73 patients (females 38 and males 35) consisted with 30 familial (16 families) and 43 sporadic. The mean age at onset was 15.19±6.96 years (range, 2–26). Their presentations were focal dystonia in 37, general dystonia 18, multifocal dystonia 9, segmental dystonia 6, hemidystonia 3. The mutation was analyzed by PCR, SSCP, DHPLC, direct sequence, and MLPA on the GCH1, SGCE, Torsin A and Parkin genes.
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
of extrapyramidal disorders, especially in developing countries including India. P1.059 Psychiatric manifestations in dystonia S. Khan1 , C. Kubu2 . 1 Neurology, 2 Psychiatry/Psychology, Cleveland Clinic, Cleveland, OH, USA Objectives: To investigate the prevalence of psychiatric symptoms in patients with dystonia presenting for surgical evaluation and to assess the relationship between psychiatric symptoms and various dystonia features. Introduction: Patients with dystonia often present with comorbid psychiatric symptoms, a clinical observation which is intuitively reasonable given the prominent role of the basal ganglia in the pathophysiology of dystonia and neuropsychiatric symptoms. Recently published data have demonstrated rates of 30% to 37.3% depression in dystonic patients. Methods: 63 consecutive patients presenting for surgical evaluation for dystonia were identified. Patients were classified as primary and secondary dystonia. Primary dystonia was further classified according to distribution and age of onset. Secondary dystonia was divided into psychogenic, tardive, and dystonia due to all other causes. Those with prior neurosurgery were excluded. Demographic information, BDI, BAI and MMPI scores were collected retrospectively. Results: Of the 25 patients with primary dystonia, 23.8% had moderate to severe depression. There was a trend for women and patients with younger age of onset to endorse a higher severity of depression. 21.3% had moderate to severe anxiety. Patients with pschogenic dystonia had a higher mean BDI and BAI. Conclusions: A high proportion of patients with dystonia endorsed significant depression and anxiety highlighting the need to carefully screen for psychiatric symptoms and treat accordingly. No significant differences were identified when looking at demographic and disease specific variables. Our data suggest that patients with psychogenic dystonia had a tendency to endorse greater psychological distress compared to other groups. P1.060 Pathological observations in seven cases with neurodegeneration with brain iron accumulation (NBIA) with mutations in PANK2 and PLA2G6 A. Li1 , C. Paisan-Ruiz1 , K. Bhatia2 , S. Schneider2 , J. Hardy1 , D. Kidd3 , J. Chataway4 , J. Holton1 , H. Houlden1 , T. Revesz1 . 1 Molecular Neuroscience, Institute of Neurology, UCL, 2 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, 3 Department of Clinical Neurosciences, Royal Free Hospital, 4 National Hospital for Neurology and Neurosurgery, London, UK Introduction: Mutations in the PANK2 and PLA2G6 gene have been shown to cause a recessive autosomal disorder known as NBIA. These disorders are clinically characterised by motor symptoms such as dystonia and parkinsonism and pathologically characterised by the occurrence of axonal swellings throughout the CNS. Objective: We present clinical and neuropathological findings of four cases with PLA2G6 mutations and three cases with PANK2 mutations, all cases were late-infantile onset. We also plan to investigate the distribution of the PANK2 and PLA2G6 proteins. Material & methods: Brain tissue was available from Queen Square Brain Bank, (UCL, London) and NICHD Brain and Tissue Bank (Baltimore) including one biopsy case and six postmortem cases. Sections were stained with routine histology and immunohistochemistry with antibodies to alpha-synuclein, tau (AT8), ubiquitin, p62, neurofilament (RT97 and SM131), GFAP, and CD68. Results: Ages of death for PANK2 cases ranged from 10–20 years and two of the three cases showed mild neurofibrillary tau pathology. Ages of death for PLA2G6 cases were between 5–32
years. Two of the four PLA2G6 cases showed accumulation of phosphorylated tau in cortical structures and additionally, three of the four cases showed accumulation of alpha-synuclein in typical Lewy bodies (LB) and neurites. Conclusions: Mild tau pathology was observed some PANK2 and PLA2G6 cases; however LBs and alpha-synuclein accumulation were the main pathological event in cases with PLA2G6 mutations. Investigations of tau and LB pathology involved with PANK2 and PLA2G6 mutations may further elucidate mechanisms involved in the tauopathy and synuclein disorders. P1.061 Interoceptive mirroring to guide assessment of writer’s cramp E. Lim, A. Quek, R. Seet. Neurology, National University of Singapore, Singapore, Singapore Introduction: Mirror/overflow movements may aid in assessment/ management of writer’s cramp. Patients use sensory tricks to relieve dystonic posturing. Brissaud postulated that imagination plays a part in these sensory tricks. Greene reported that imagined tasks helped to relieve dystonia. Aims: We assessed whether imagining the act of writing aided in the assessment of writer’s cramp. Method: 12 patients (4 female, 8 male) with writer’s cramp were assessed clinically at rest, during the act of writing (dominant/ non-dominant hands), when they were assessed for mirror/ overflow movements) and when asked to imagine themselves writing with either hand. They were assessed for dystonic posturing at rest, on writing and whilst imagining themselves writing. Results: 12 patients of mean age 47.8 years (range 17–81), with writer’s cramp averaging 8.4 years’ duration (range 1–30), were assessed. 11 had mirror movements of the involved hand and 3 had mirror movements in the contralateral hand. Only 1 patient had overflow movements in the uninvolved hand with imagined writing tasks (interoceptive overflow movements), but 9 had interoceptive overflow movements in the involved hand. Interoceptive movements were consistent with overflow/mirror movements when writing, but were of smaller amplitude and less obvious. Discussion: Interoceptive overflow movements can assist in the management and assessment of patients with writer’s cramp. Interoceptive overflow movements occur only in patients demonstrating overflow/mirroring whilst writing. P1.062 Genetic contribution to young onset dystonia in a Taiwanese cohort C.-S. Lu1 , Y.-H. Wu-Chou2 , H.-C. Chang1 , T.-H. Yeh1 , S.-C. Lai1 , R.-S. Chen1 , Y.-H. Weng1 , C.-L. Huang3 . 1 Department of Neurology, 2 Human Molecular Genetics Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, 3 Department of Neurology, Saint Paul’s Hospital, Taoyuan, Taiwan R.O.C. Background: Idiopathic dystonia is relatively common in Taiwan but the genetic etiology has been rarely reported. In our previous genetic analysis for a few subsets of dystonia patients, we have successfully identified mutations of Torsin A, GCH1and SGCE in limited familial and sporadic patients. Here, we re-analyzed the contribution of these genes to a subset of young onset dystonia whose symptom began before the age of 26. The parkin mutation was analyzed too. Subjects and Methods: Patients with young onset dystonia were selected for the study. A total of 73 patients (females 38 and males 35) consisted with 30 familial (16 families) and 43 sporadic. The mean age at onset was 15.19±6.96 years (range, 2–26). Their presentations were focal dystonia in 37, general dystonia 18, multifocal dystonia 9, segmental dystonia 6, hemidystonia 3. The mutation was analyzed by PCR, SSCP, DHPLC, direct sequence, and MLPA on the GCH1, SGCE, Torsin A and Parkin genes.