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A Japanese nationwide survey on congenital myotonic dystrophy
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Abstracts 2016 / Neuromuscular Disorders 26 (2016) S88–S212
mainly diagnosed because of a positive family history (72.7%), followed by developmental delay (63.7%). Children with cDM1 showed delayed motor development, but all patients acquired independent walking at a median age of 20 months (IQR 12.25–25.5). They also showed more severe neurocognitive problems with a median total IQ of 59 (IQR 55–66), while the median total IQ in the jDM1 group was 76.5 (IQR 64–91.25). Percussion and relaxation myotonia were more frequently found in jDM1, 69.7% and 81.8% respectively. Cardiac conductance disorders were more frequent in cDM1. In conclusion, DM1 is a multisystem disorder with a variable phenotype. Our study illustrates the impact of the physical and cognitive disabilities and the importance of cardiac, orthopedic and ophthalmological follow-up. These long term natural history data will facilitate the development of relevant outcome measures for future clinical trials. http://dx.doi.org/10.1016/j.nmd.2016.06.396
P.368 A Japanese nationwide survey on congenital myotonic dystrophy M. Shichiji 1, K. Ishigaki 1, K. Ishiguro 1, T. Sato 1, T. Murakami 1, T. Matsumura 2, M. Osawa 1, S. Nagata 1 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 National Hospital Organization Toneyama National Hospital, Osaka, Japan In Japan, 99% of patients with myotonic dystrophy (DM) are classified as having type 1 (DM1), and congenital myotonic dystrophy (CDM) has been reported only in DM1. Although 95% of mothers are affected by DM1 and many show characteristic signs during pregnancy, approximately 60% are given the DM1 diagnosis after delivery. It is important to ascertain the actual incidence and perinatal complications in both DM1 mothers and CDM babies. We herein present the results of a large survey of obstetricians, neonatologists and pediatric neurologists. As primary research, we conducted a national survey in written questionnaire form. To achieve an exhaustive survey, we sent the questionnaire to 2480 birthing facilities registered by the “Japan Society of Obstetrics and Gynecology”, 1126 pediatric neurologists registered by the “The Japanese Society of Child Neurology”, and 274 NICU delegates registered by the “Japanese Neonatologist Association”. In the questionnaire for obstetricians, we asked when the mothers affected by DM1 received their own diagnosis. For the neonatologists and pediatricians, we asked the number of patients with CDM, and whether or not the delivery had served as the mother’s opportunity to be diagnosed with DM1. We obtained valid answers from 1405 birthing facilities (the collection rate was 26.6%), 612 pediatric [KI1] neurologists (54.4%), and 73 neonatologists (56.7%). According to the answers from obstetricians, half of the mothers with DM1 had been diagnosed before pregnancy. Among those undiagnosed prior to pregnancy, 60% had been diagnosed during pregnancy. By contrast, according to the answers from pediatricians and neonatologists, the mothers tended to be diagnosed with DM1 after delivery. It was confirmed that the perinatal stage provides an opportunity to diagnose DM1 in affected mothers, as indicated by past reports. This study will provide more detailed information on the perinatal problems of both DM1 mothers and CDM babies in Japan. http://dx.doi.org/10.1016/j.nmd.2016.06.397
P.369 NMR voxel-based morphometry and functional analysis as neural correlates of neuropsychological dysfunction in DM1 G. Siciliano 1, S. Baldanzi 1, P. Cecchi 2, C. Simoncini 1, G. Ricci 1, S. Fabbri 2, R. Lorio 3, F. Bevilacqua 3, M. Cosottini 1, C. Angelini 3 1 University of Pisa, Pisa, Italy; 2 Azienda Ospedaliero Universitaria Pisana, Pisa, Italy; 3 IRCCS San Camillo, Lido Venice, Italy The variable phenotypic spectrum of myotonic dystrophy type 1 (DM1) includes central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations,
as well as brain functional activation, by nuclear magnetic resonance (NMR) in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and brain 3T-MRI protocol. GM and WM changes were evaluated calculating brain parenchymal fraction (BPF), voxel-based morphometry (VBM), white matter lesion load (LL% and Fazekas scale) and tract based spatial statistical (TBSS). Patients showed main impairment in executive and mnesic domains with visuospatial involvement, significantly related to BPF. VBM revealed clusters of widespread GM reduction and TBSS revealed areas of decreased fractional anisotropy (FA) and increased radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD) in patients compared to a group of matched healthy controls. Multiple regression analysis showed areas of significant negative relationship between atrophy in the left temporal lobe and verbal memory, and between RD and mnesic and visuo-spatial cognitive domains. Our data show extensive atrophy in DM1 over both cerebral hemispheres. Global atrophy, expressed with BPF, correlated with impaired executive and visuo-spatial abilities. TBSS results indicate that the involvement of normal appearance WM beyond the signal changes detected with conventional MR imaging (Fazekas scale and LL%), was associated to neuropsychological deficit. Finally, brain functional NMR activation showed fronto-temporal correlates of anosognosia. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1. http://dx.doi.org/10.1016/j.nmd.2016.06.398
P.370 Toward an appropriate neuropsychological assessment protocol for children with myotonic dystrophy type 1 S. Geuens 1, N. Goemans 1, E. Thiery 2, J. Van Herck 1, J. Lemiere 1, L. De Waele 1 1 University Hospitals Leuven, Leuven, Belgium; 2 University Hospital Ghent, Ghent, Belgium Myotonic dystrophy type 1 (DM1) is a common neuromuscular disorder characterized by physical, cognitive, behavioral and psychiatric symptoms. Despite the important impact of the non-physical aspects on daily functioning, limited research is available about the neuropsychological features in children with DM1. This explorative study evaluates an evidence-based battery of neuropsychological investigations to assess children with DM1. The selected tests cover multiple neuropsychological functioning aspects and are sensitive enough to detect subtle impairment. We evaluated the Wechsler Intelligence Scale for Children (WISC-III-NL), the Attention Network Task (ANT), the Children Memory Scale (CMS), the Developmental Test of Visual Motor Integration (VMI) and behavior questionnaires (Child Behavior Checklist (CBCL), Teacher’s Report Form (TRF), Youth Self Report (YSR) and the Behavior Rating Inventory of Executive Function (BRIEF) parents, teachers and adolescents). Eight DM1 patients (11–19 years old) with mean length of CTG repeats of 514 (140–930, n = 7) were assessed. All tests were proven adequate and feasible for this population. The results showed lower scores for intelligence, abstract reasoning, visual and verbal working memory, cognitive flexibility and visual motor integration. There was a negative correlation between length of CTG-repeats and total IQ, visual memory and visual perception. Surprisingly, verbal memory correlated positively with CTGrepeats. In conclusion, we evaluated the feasibility and sensitivity of a neuropsychological test battery for children with DM1. These patients show impaired scores on several neuropsychological functions, but a DM1-specific profile could not be demonstrated in this small sample. Defining an appropriate neuropsychological assessment protocol for DM1 patients will provide important insights in support of adequate neuropsychological counseling and development of outcome measures to assess interventions. http://dx.doi.org/10.1016/j.nmd.2016.06.399
Abstracts 2016 / Neuromuscular Disorders 26 (2016) S88–S212
mainly diagnosed because of a positive family history (72.7%), followed by developmental delay (63.7%). Children with cDM1 showed delayed motor development, but all patients acquired independent walking at a median age of 20 months (IQR 12.25–25.5). They also showed more severe neurocognitive problems with a median total IQ of 59 (IQR 55–66), while the median total IQ in the jDM1 group was 76.5 (IQR 64–91.25). Percussion and relaxation myotonia were more frequently found in jDM1, 69.7% and 81.8% respectively. Cardiac conductance disorders were more frequent in cDM1. In conclusion, DM1 is a multisystem disorder with a variable phenotype. Our study illustrates the impact of the physical and cognitive disabilities and the importance of cardiac, orthopedic and ophthalmological follow-up. These long term natural history data will facilitate the development of relevant outcome measures for future clinical trials. http://dx.doi.org/10.1016/j.nmd.2016.06.396
P.368 A Japanese nationwide survey on congenital myotonic dystrophy M. Shichiji 1, K. Ishigaki 1, K. Ishiguro 1, T. Sato 1, T. Murakami 1, T. Matsumura 2, M. Osawa 1, S. Nagata 1 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 National Hospital Organization Toneyama National Hospital, Osaka, Japan In Japan, 99% of patients with myotonic dystrophy (DM) are classified as having type 1 (DM1), and congenital myotonic dystrophy (CDM) has been reported only in DM1. Although 95% of mothers are affected by DM1 and many show characteristic signs during pregnancy, approximately 60% are given the DM1 diagnosis after delivery. It is important to ascertain the actual incidence and perinatal complications in both DM1 mothers and CDM babies. We herein present the results of a large survey of obstetricians, neonatologists and pediatric neurologists. As primary research, we conducted a national survey in written questionnaire form. To achieve an exhaustive survey, we sent the questionnaire to 2480 birthing facilities registered by the “Japan Society of Obstetrics and Gynecology”, 1126 pediatric neurologists registered by the “The Japanese Society of Child Neurology”, and 274 NICU delegates registered by the “Japanese Neonatologist Association”. In the questionnaire for obstetricians, we asked when the mothers affected by DM1 received their own diagnosis. For the neonatologists and pediatricians, we asked the number of patients with CDM, and whether or not the delivery had served as the mother’s opportunity to be diagnosed with DM1. We obtained valid answers from 1405 birthing facilities (the collection rate was 26.6%), 612 pediatric [KI1] neurologists (54.4%), and 73 neonatologists (56.7%). According to the answers from obstetricians, half of the mothers with DM1 had been diagnosed before pregnancy. Among those undiagnosed prior to pregnancy, 60% had been diagnosed during pregnancy. By contrast, according to the answers from pediatricians and neonatologists, the mothers tended to be diagnosed with DM1 after delivery. It was confirmed that the perinatal stage provides an opportunity to diagnose DM1 in affected mothers, as indicated by past reports. This study will provide more detailed information on the perinatal problems of both DM1 mothers and CDM babies in Japan. http://dx.doi.org/10.1016/j.nmd.2016.06.397
P.369 NMR voxel-based morphometry and functional analysis as neural correlates of neuropsychological dysfunction in DM1 G. Siciliano 1, S. Baldanzi 1, P. Cecchi 2, C. Simoncini 1, G. Ricci 1, S. Fabbri 2, R. Lorio 3, F. Bevilacqua 3, M. Cosottini 1, C. Angelini 3 1 University of Pisa, Pisa, Italy; 2 Azienda Ospedaliero Universitaria Pisana, Pisa, Italy; 3 IRCCS San Camillo, Lido Venice, Italy The variable phenotypic spectrum of myotonic dystrophy type 1 (DM1) includes central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations,
as well as brain functional activation, by nuclear magnetic resonance (NMR) in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and brain 3T-MRI protocol. GM and WM changes were evaluated calculating brain parenchymal fraction (BPF), voxel-based morphometry (VBM), white matter lesion load (LL% and Fazekas scale) and tract based spatial statistical (TBSS). Patients showed main impairment in executive and mnesic domains with visuospatial involvement, significantly related to BPF. VBM revealed clusters of widespread GM reduction and TBSS revealed areas of decreased fractional anisotropy (FA) and increased radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD) in patients compared to a group of matched healthy controls. Multiple regression analysis showed areas of significant negative relationship between atrophy in the left temporal lobe and verbal memory, and between RD and mnesic and visuo-spatial cognitive domains. Our data show extensive atrophy in DM1 over both cerebral hemispheres. Global atrophy, expressed with BPF, correlated with impaired executive and visuo-spatial abilities. TBSS results indicate that the involvement of normal appearance WM beyond the signal changes detected with conventional MR imaging (Fazekas scale and LL%), was associated to neuropsychological deficit. Finally, brain functional NMR activation showed fronto-temporal correlates of anosognosia. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1. http://dx.doi.org/10.1016/j.nmd.2016.06.398
P.370 Toward an appropriate neuropsychological assessment protocol for children with myotonic dystrophy type 1 S. Geuens 1, N. Goemans 1, E. Thiery 2, J. Van Herck 1, J. Lemiere 1, L. De Waele 1 1 University Hospitals Leuven, Leuven, Belgium; 2 University Hospital Ghent, Ghent, Belgium Myotonic dystrophy type 1 (DM1) is a common neuromuscular disorder characterized by physical, cognitive, behavioral and psychiatric symptoms. Despite the important impact of the non-physical aspects on daily functioning, limited research is available about the neuropsychological features in children with DM1. This explorative study evaluates an evidence-based battery of neuropsychological investigations to assess children with DM1. The selected tests cover multiple neuropsychological functioning aspects and are sensitive enough to detect subtle impairment. We evaluated the Wechsler Intelligence Scale for Children (WISC-III-NL), the Attention Network Task (ANT), the Children Memory Scale (CMS), the Developmental Test of Visual Motor Integration (VMI) and behavior questionnaires (Child Behavior Checklist (CBCL), Teacher’s Report Form (TRF), Youth Self Report (YSR) and the Behavior Rating Inventory of Executive Function (BRIEF) parents, teachers and adolescents). Eight DM1 patients (11–19 years old) with mean length of CTG repeats of 514 (140–930, n = 7) were assessed. All tests were proven adequate and feasible for this population. The results showed lower scores for intelligence, abstract reasoning, visual and verbal working memory, cognitive flexibility and visual motor integration. There was a negative correlation between length of CTG-repeats and total IQ, visual memory and visual perception. Surprisingly, verbal memory correlated positively with CTGrepeats. In conclusion, we evaluated the feasibility and sensitivity of a neuropsychological test battery for children with DM1. These patients show impaired scores on several neuropsychological functions, but a DM1-specific profile could not be demonstrated in this small sample. Defining an appropriate neuropsychological assessment protocol for DM1 patients will provide important insights in support of adequate neuropsychological counseling and development of outcome measures to assess interventions. http://dx.doi.org/10.1016/j.nmd.2016.06.399