Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.32
K. Lindenberg, Eva Buck, G. Landwehrmeyer, E. Calzia
Background Previous work has shown that mitochondrial respiration is not severely affected in the skeletal muscle of pre-symptomatic mHTT-mutation carriers.1 In contrast, patients with manifest HD exhibit a low anaerobic threshold and an increased skeletal muscle lactate production.2 This could result not only from a decreased capacity of the mitochondrial respiratory chain but also from a compromised ATP production process, which depends from the activity of the ATP-synthase and of the adenine nucleotide translocator. Aim The scope of the present study was therefore to compare ex-vivo the maximum respiratory activity in the coupled (OxPhos)-state and in the uncoupled (ETS)-state in skeletal muscle tissue samples from 12 weeks old R6/2 HD model male mice. Methods The mitochondrial respiratory activity in the homogenized tissue samples from 12 R6/2 mice and 11 wildtype controls were quantified according to previously published protocols.1 Results In the skeletal muscle from R6/2 mice we found a lower OxPhos-activity (118±47 [pmol O2/(s x mg tissue)]) compared to control (183±54 [pmol O2/(s x mg tissue)], p=0.006). The activity in the ETS-state did not show a statistically significant difference (148±59 [pmol O2/(s x mg tissue)] vs. 189±80 [pmol O2/(s x mg tissue)], p=0.21). The ratio of both capacities (OxPhos/ETS) was close to unity in the controls, but statistically significantly lower in the R6/2 mice (103±17 [%] vs. 82±6 [%], p=0.005) Conclusions We conclude that in HD, in addition to a possible reduction of the capacity of the mitochondrial respiratory chain, the ATP-production process may also assume a strong limiting role with regard to aerobic metabolism of the skeletal muscle. References . Buck, et al. PLoS One2017. https://doi.org/10.1371/journal.pone.0175248 . Ciammola, et al. Movement Disorders2011;26:130–7.
{"title":"A34 Mitochondrial respiration is limited by atp-production in the skeletal muscle of the R6/2 hd mouse model","authors":"K. Lindenberg, Eva Buck, G. Landwehrmeyer, E. Calzia","doi":"10.1136/jnnp-2018-EHDN.32","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.32","url":null,"abstract":"Background Previous work has shown that mitochondrial respiration is not severely affected in the skeletal muscle of pre-symptomatic mHTT-mutation carriers.1 In contrast, patients with manifest HD exhibit a low anaerobic threshold and an increased skeletal muscle lactate production.2 This could result not only from a decreased capacity of the mitochondrial respiratory chain but also from a compromised ATP production process, which depends from the activity of the ATP-synthase and of the adenine nucleotide translocator. Aim The scope of the present study was therefore to compare ex-vivo the maximum respiratory activity in the coupled (OxPhos)-state and in the uncoupled (ETS)-state in skeletal muscle tissue samples from 12 weeks old R6/2 HD model male mice. Methods The mitochondrial respiratory activity in the homogenized tissue samples from 12 R6/2 mice and 11 wildtype controls were quantified according to previously published protocols.1 Results In the skeletal muscle from R6/2 mice we found a lower OxPhos-activity (118±47 [pmol O2/(s x mg tissue)]) compared to control (183±54 [pmol O2/(s x mg tissue)], p=0.006). The activity in the ETS-state did not show a statistically significant difference (148±59 [pmol O2/(s x mg tissue)] vs. 189±80 [pmol O2/(s x mg tissue)], p=0.21). The ratio of both capacities (OxPhos/ETS) was close to unity in the controls, but statistically significantly lower in the R6/2 mice (103±17 [%] vs. 82±6 [%], p=0.005) Conclusions We conclude that in HD, in addition to a possible reduction of the capacity of the mitochondrial respiratory chain, the ATP-production process may also assume a strong limiting role with regard to aerobic metabolism of the skeletal muscle. References . Buck, et al. PLoS One2017. https://doi.org/10.1371/journal.pone.0175248 . Ciammola, et al. Movement Disorders2011;26:130–7.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"1 1","pages":"A12 - A12"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88656147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.210
Beate Schumann, K. Reetz, I. Dogan, S. Mirzazade, Philipp Honrath, Rena Overbeck, F. Schradt, P. Weydt, C. Werner
Background Dysphagia is a common problem in HD, frequently leading to aspiration pneumonia and consecutive mortality. Objective estimates of prevalence using instrumental diagnostics and data on neuronal correlates of dysphagia in HD are scarce. Similarly, its correlation with other clinical markers is unknown. Thus, we aimed at defining clinical risk factors and neural correlated for HD-associated dysphagia more precisely. Methods/techniques 21 subjects (12 w, 9 m, Shoulson-Fahn stadium I-IV) underwent a full clinical-neurological exam including the UHDRS motor score and cognitive data from neuropsychological tests. A clinical swallowing examination was performed by a trained SLT, as well as videoendoscopic swallow examination (FEES). Patients additionally underwent an MRI scan (T1, 3 Tesla MRI Siemens Prisma). We then correlated validated scores of dysphagia with motor and cognitive scores as well as measures of atrophy from MRI. Results/outcome Mean UHDRS motor score was 33.6 (SD 15.3), mean UHDRS cognition score 158.6 (SD 64.3). In 20 patients, FEES showed penetration or aspiration in 80%. No significant correlations were found between dysphagia severity and any of the clinical markers (motor score, cognition, functional assessment, age, CAG). Voxel based morphometry confirmed atrophy patterns in known swallowing-network areas rather than motor function, e.g. striatum, when comparing patients with no/mild vs. moderate/severe dysphagia. Conclusions Our results so far suggest that dysphagia is not predicted sufficiently well by clinical markers, as aspiration can occur even in early stage of HD, thus necessitating early instrumental assessments in the course of the disease. Arguably, dysphagia should not be referred to as a ‘prevalent motor symptom’, but rather as a distinct entity.
吞咽困难是HD患者的常见问题，经常导致吸入性肺炎和连续死亡。使用仪器诊断客观估计HD患者吞咽困难的患病率和神经元相关数据是稀缺的。同样，其与其他临床指标的相关性尚不清楚。因此，我们旨在更精确地定义hd相关吞咽困难的临床危险因素和神经相关性。方法/技术21名受试者(12 w, 9 m, Shoulson-Fahn体育场I-IV)接受了全面的临床神经学检查，包括UHDRS运动评分和神经心理测试的认知数据。临床吞咽检查由训练有素的SLT进行，以及视频内窥镜吞咽检查(费用)。患者还接受了MRI扫描(T1, 3 Tesla MRI Siemens Prisma)。然后，我们将吞咽困难的有效评分与运动和认知评分以及MRI的萎缩测量相关联。平均UHDRS运动评分为33.6分(SD 15.3)，平均UHDRS认知评分为158.6分(SD 64.3)。在20例患者中，80%的患者出现穿透或吸入。吞咽困难严重程度与任何临床指标(运动评分、认知、功能评估、年龄、CAG)均无显著相关性。当比较无/轻度吞咽困难与中度/重度吞咽困难患者时，基于体素的形态测量证实了已知吞咽网络区域的萎缩模式，而不是运动功能，例如纹状体。到目前为止，我们的研究结果表明，临床标志物不能充分预测吞咽困难，因为即使在HD早期也可能发生误吸，因此有必要在疾病过程中进行早期仪器评估。可以说，吞咽困难不应该被称为“普遍的运动症状”，而是作为一个独特的实体。
{"title":"H32 Neuronal correlates and clinical predictors for dysphagia in huntington’s disease","authors":"Beate Schumann, K. Reetz, I. Dogan, S. Mirzazade, Philipp Honrath, Rena Overbeck, F. Schradt, P. Weydt, C. Werner","doi":"10.1136/jnnp-2018-EHDN.210","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.210","url":null,"abstract":"Background Dysphagia is a common problem in HD, frequently leading to aspiration pneumonia and consecutive mortality. Objective estimates of prevalence using instrumental diagnostics and data on neuronal correlates of dysphagia in HD are scarce. Similarly, its correlation with other clinical markers is unknown. Thus, we aimed at defining clinical risk factors and neural correlated for HD-associated dysphagia more precisely. Methods/techniques 21 subjects (12 w, 9 m, Shoulson-Fahn stadium I-IV) underwent a full clinical-neurological exam including the UHDRS motor score and cognitive data from neuropsychological tests. A clinical swallowing examination was performed by a trained SLT, as well as videoendoscopic swallow examination (FEES). Patients additionally underwent an MRI scan (T1, 3 Tesla MRI Siemens Prisma). We then correlated validated scores of dysphagia with motor and cognitive scores as well as measures of atrophy from MRI. Results/outcome Mean UHDRS motor score was 33.6 (SD 15.3), mean UHDRS cognition score 158.6 (SD 64.3). In 20 patients, FEES showed penetration or aspiration in 80%. No significant correlations were found between dysphagia severity and any of the clinical markers (motor score, cognition, functional assessment, age, CAG). Voxel based morphometry confirmed atrophy patterns in known swallowing-network areas rather than motor function, e.g. striatum, when comparing patients with no/mild vs. moderate/severe dysphagia. Conclusions Our results so far suggest that dysphagia is not predicted sufficiently well by clinical markers, as aspiration can occur even in early stage of HD, thus necessitating early instrumental assessments in the course of the disease. Arguably, dysphagia should not be referred to as a ‘prevalent motor symptom’, but rather as a distinct entity.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"5 1","pages":"A78 - A78"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85284217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.71
Aikaterini S. Papadopoulou, K. Sathasivam, Laila Blomer, Sandra Fieńko, Edward J. Smith, C. Landles, G. Bates
Background Huntington’s Disease (HD) is an inherited neurodegenerative disorder caused by the expansion of a CAG repeat in the HTT gene. We have recently shown that incomplete splicing of HTT mRNA, in both HD patients and mouse models, produces a HTTexon1 and Httexon1 transcript respectively, that is translated into the highly pathogenic exon 1 HTT protein. Aims The aim of this study was to investigate the role of this Httexon1 transcript in the pathogenesis of the disease, and to characterize primary cells from HD mouse models that could be used to screen for agents designed to lower the levels of the HTT transcripts. Methods/techniques We have established mouse embryonic fibroblasts (MEFs) from the zQ175 mouse model as well as deriving mouse cortical neuronal cultures. We have used our novel multiplex Quantigene assay, to measure the levels of all mouse Httexon1 and full-length Htt transcripts in these cells, and RNAscope to localize these transcripts. We have developed a TR-FRET assay that is specific for the exon 1 HTT protein. We have used immunoprecipitation western blot and TR-FRET to detect full-length and exon 1 HTT. Results/outcome We show that our Quantigene assay generates comparable data to the much more time-consuming quantitative PCRs for the zQ175 MEFs. We show that most of the mutant transcript in the zQ175 MEFs is incompletely spliced, and that these cells can be used for compound screening by multiplex Quantigene assays. The exon 1 HTT protein can be measured in these cells. Primary neurons from zQ175 mice show a higher level of incompletely spliced Htt than has been detected in brain tissue. The localization of the Htt transcripts in primary neurons will be discussed. Conclusions We conclude that we have good in vitro models and a variety of techniques to investigate the role of the Httexon1 transcripts in the pathogenesis of HD and screen for therapeutic agents. This work is supported by the CHDI foundation.
{"title":"B19 Development of in vitro models to investigate the pathogenesis of huntington’s disease and screen for therapeutic agents","authors":"Aikaterini S. Papadopoulou, K. Sathasivam, Laila Blomer, Sandra Fieńko, Edward J. Smith, C. Landles, G. Bates","doi":"10.1136/jnnp-2018-EHDN.71","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.71","url":null,"abstract":"Background Huntington’s Disease (HD) is an inherited neurodegenerative disorder caused by the expansion of a CAG repeat in the HTT gene. We have recently shown that incomplete splicing of HTT mRNA, in both HD patients and mouse models, produces a HTTexon1 and Httexon1 transcript respectively, that is translated into the highly pathogenic exon 1 HTT protein. Aims The aim of this study was to investigate the role of this Httexon1 transcript in the pathogenesis of the disease, and to characterize primary cells from HD mouse models that could be used to screen for agents designed to lower the levels of the HTT transcripts. Methods/techniques We have established mouse embryonic fibroblasts (MEFs) from the zQ175 mouse model as well as deriving mouse cortical neuronal cultures. We have used our novel multiplex Quantigene assay, to measure the levels of all mouse Httexon1 and full-length Htt transcripts in these cells, and RNAscope to localize these transcripts. We have developed a TR-FRET assay that is specific for the exon 1 HTT protein. We have used immunoprecipitation western blot and TR-FRET to detect full-length and exon 1 HTT. Results/outcome We show that our Quantigene assay generates comparable data to the much more time-consuming quantitative PCRs for the zQ175 MEFs. We show that most of the mutant transcript in the zQ175 MEFs is incompletely spliced, and that these cells can be used for compound screening by multiplex Quantigene assays. The exon 1 HTT protein can be measured in these cells. Primary neurons from zQ175 mice show a higher level of incompletely spliced Htt than has been detected in brain tissue. The localization of the Htt transcripts in primary neurons will be discussed. Conclusions We conclude that we have good in vitro models and a variety of techniques to investigate the role of the Httexon1 transcripts in the pathogenesis of HD and screen for therapeutic agents. This work is supported by the CHDI foundation.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"28 1","pages":"A26 - A26"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86993738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.64
M. Rodinová, J. Křížová, Hana Štufková, B. Bohuslavova, Georgina Askeland, Z. Dosoudilova, Š. Juhás, Z. Ellederová, J. Zeman, L. Eide, J. Motlík, H. Hansíková
Background Skeletal muscle wasting and atrophy is one of the severe clinical impairment connected with progression of Huntington’s disease (HD). Mitochondrial dysfunction may play significant role in aetiology of the HD but exact condition of mitochondria as the major energy-producing organelles during development of the HD in muscle has not yet been carefully investigated. The aim of the study was the longitudinal monitoring of mitochondrial function in skeletal muscle of transgenic minipigs expressing the N-terminal part of human mutated huntingtin (TgHD). We investigated muscle (q. femoris) from 24, 36, 48 and 66 month old TgHD and age-matched wild-type (WT) siblings (6 TgHD + 6 WT in each age). Methods Respiratory chain complexes (RCC), citrate synthase (CS), pyruvate dehydrogenase (PDH) activity and levels were analyzed by spectrophotometric, radioisotope and immunoelectrophoretic methods. Respiration was measured by polarography. Ultrastructure was analyzed by transmission electron microscopy. Genome integrity was assessed by q-PCR. The effect of HD, gender and aging were statistically analyzed. Results Ultrastructural analyses in 48 month-old TgHD revealed local disorganization of myotubules, dilatation of sarcoplasmic reticulum, increased content of glycogen, higher density of mitochondria and incipient cristae disarrangement in comparison with WT. Activity of CS and RCC complex IV were significantly decreased in TgHD. Oxygen consumption showed significantly decreased ratio CII/CIV in TgHD contrary to WT. Protein analyses proved lower content of OPA1 protein which is necessary for correct mitochondrial fusion and quality control from 48 month-old TgHD animals. Genotype specific effect on mitochondrial DNA (mtDNA) damage but not on mtDNA copy number or nuclear DNA damage in TgHD was observed in the age of 66 month. Conclusions Our results showed that mitochondrial function in muscle decreases slowly during premanifest stage of HD and biochemical phenotype appears at the age of 48 months. Mitochondrial disturbances may contribute to energetic depression of skeletal muscle in HD and are in concordance with mobility problems observed in this large animal model after 48 month of life. Supported by: Czech-Norwegian Research Programme 7F14308, NPUI LO1609 (MSMT), RVOVFN64165
{"title":"B12 Longitudinal view of mitochondrial bioenergetics in skeletal muscle of premanifest transgenic minipig model for huntington’s disease","authors":"M. Rodinová, J. Křížová, Hana Štufková, B. Bohuslavova, Georgina Askeland, Z. Dosoudilova, Š. Juhás, Z. Ellederová, J. Zeman, L. Eide, J. Motlík, H. Hansíková","doi":"10.1136/jnnp-2018-EHDN.64","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.64","url":null,"abstract":"Background Skeletal muscle wasting and atrophy is one of the severe clinical impairment connected with progression of Huntington’s disease (HD). Mitochondrial dysfunction may play significant role in aetiology of the HD but exact condition of mitochondria as the major energy-producing organelles during development of the HD in muscle has not yet been carefully investigated. The aim of the study was the longitudinal monitoring of mitochondrial function in skeletal muscle of transgenic minipigs expressing the N-terminal part of human mutated huntingtin (TgHD). We investigated muscle (q. femoris) from 24, 36, 48 and 66 month old TgHD and age-matched wild-type (WT) siblings (6 TgHD + 6 WT in each age). Methods Respiratory chain complexes (RCC), citrate synthase (CS), pyruvate dehydrogenase (PDH) activity and levels were analyzed by spectrophotometric, radioisotope and immunoelectrophoretic methods. Respiration was measured by polarography. Ultrastructure was analyzed by transmission electron microscopy. Genome integrity was assessed by q-PCR. The effect of HD, gender and aging were statistically analyzed. Results Ultrastructural analyses in 48 month-old TgHD revealed local disorganization of myotubules, dilatation of sarcoplasmic reticulum, increased content of glycogen, higher density of mitochondria and incipient cristae disarrangement in comparison with WT. Activity of CS and RCC complex IV were significantly decreased in TgHD. Oxygen consumption showed significantly decreased ratio CII/CIV in TgHD contrary to WT. Protein analyses proved lower content of OPA1 protein which is necessary for correct mitochondrial fusion and quality control from 48 month-old TgHD animals. Genotype specific effect on mitochondrial DNA (mtDNA) damage but not on mtDNA copy number or nuclear DNA damage in TgHD was observed in the age of 66 month. Conclusions Our results showed that mitochondrial function in muscle decreases slowly during premanifest stage of HD and biochemical phenotype appears at the age of 48 months. Mitochondrial disturbances may contribute to energetic depression of skeletal muscle in HD and are in concordance with mobility problems observed in this large animal model after 48 month of life. Supported by: Czech-Norwegian Research Programme 7F14308, NPUI LO1609 (MSMT), RVOVFN64165","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"7 1","pages":"A23 - A24"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87435065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.121
A. Ho, O. Quarrell
Introduction Juvenile onset Huntington’s disease (JOHD) is defined as onset ≤20 years. Although most patients are cared for within the family, the experiences of family-carers of JOHD is lacking. This study explores the perspective of JOHD family-carers together with their health status. Methods Twenty six JOHD family-carers (with an average age 45 years) completed the EQ-5D questionnaire. They were also asked about their experience as carers and their responses were analysed qualitatively. Results Family-carers reported positive elements, which were growth in the carer’s character, strength of the JOHD patient’s character, enriched family experiences, and supportive external relationships. Negative points reported were the personal and emotional toll on carers, toll on the family, and issues with external parties regarding JOHD. Carers’ responses on what would be helpful centred on financial support, respite, and an increase in both the quantity and quality of services appropriate for JOHD. Family-carers’ health status was lower than normal for their age group (EQ-5D visual analogue scale rating=73, EQ5-D index score=0.74). Pain/Discomfort was most affected in family-carers, followed by Mobility, with poorer scores for those caring for more severely affected JOHD patients. Conclusions Family-carers face a high physical and emotional toll, especially when JOHD patients become severely affected. Greater understanding and acknowledgement of this is needed to address the health and quality of life of carers. [Research funded by the NHS National Institute for Health Research. Research for Patient Benefit stream. PB-PG-112–29056]
{"title":"F17 Juvenile onset huntington’s disease: the health status and perspective of family carers","authors":"A. Ho, O. Quarrell","doi":"10.1136/jnnp-2018-EHDN.121","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.121","url":null,"abstract":"Introduction Juvenile onset Huntington’s disease (JOHD) is defined as onset ≤20 years. Although most patients are cared for within the family, the experiences of family-carers of JOHD is lacking. This study explores the perspective of JOHD family-carers together with their health status. Methods Twenty six JOHD family-carers (with an average age 45 years) completed the EQ-5D questionnaire. They were also asked about their experience as carers and their responses were analysed qualitatively. Results Family-carers reported positive elements, which were growth in the carer’s character, strength of the JOHD patient’s character, enriched family experiences, and supportive external relationships. Negative points reported were the personal and emotional toll on carers, toll on the family, and issues with external parties regarding JOHD. Carers’ responses on what would be helpful centred on financial support, respite, and an increase in both the quantity and quality of services appropriate for JOHD. Family-carers’ health status was lower than normal for their age group (EQ-5D visual analogue scale rating=73, EQ5-D index score=0.74). Pain/Discomfort was most affected in family-carers, followed by Mobility, with poorer scores for those caring for more severely affected JOHD patients. Conclusions Family-carers face a high physical and emotional toll, especially when JOHD patients become severely affected. Greater understanding and acknowledgement of this is needed to address the health and quality of life of carers. [Research funded by the NHS National Institute for Health Research. Research for Patient Benefit stream. PB-PG-112–29056]","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"1 1","pages":"A45 - A46"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82999817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.144
E. Sitek, W. Sołtan, J. Sławek
Background Huntington’s disease (HD) patients tend to underestimate the severity of chorea. Aims The study aimed at assessing the possible impact of manual dexterity task completion on the awareness of chorea in HD. It was hypothesized that the patients’ tendency to underestimate chorea will decrease after the confrontation with a demanding motor task so that post-task ratings of chorea will be higher and more consistent with the objective measures than the pre-test ratings. Methods/techniques: Ten symptomatic HD patients (aged 58±11 years with the age of motor onset 52±10 years, the median Unified Huntington’s Disease Rating Scale- UHDRS total motor score 39.50 and median Total Functional Capacity-TFC score 8) completed the Nine Hole Peg Test (the 9HPT), pegboard task, used to assess manual dexterity. The participants estimated the degree of chorea interference with task performance on a 10-point scale (from 0 – no interference to 10-major interference) both prior and post task performance with each hand. Results/outcome: The patients’ median ratings of chorea increased from 0.50 (pre) to 1.50 (post) in the dominant hand motor coordination and from 2.50 (pre) to 3.00 (post) in the non-dominant hand. The ratings of involuntary movements were significantly influenced by the motor task performance with the non-dominant hand (p=0.04), but not with the dominant hand (p=0.12). Also the patients’ post-task chorea ratings concerning the non-dominant hand were highly correlated with the objective 9HPT performance (rho=0.93 for involuntary movements and rho=0.90 for both coordination and slowing) and chorea in the upper extremity as assessed in UHDRS motor (rho=0.65). Conclusions The preliminary results show that the awareness of motor impairment in a patient may vary and that the patients are less unlikely to underestimate motor symptoms after being confronted with a demanding motor tasks.
{"title":"F40 Do patients with huntington’s disease become more aware of chorea after being confronted with demanding motor tasks?","authors":"E. Sitek, W. Sołtan, J. Sławek","doi":"10.1136/jnnp-2018-EHDN.144","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.144","url":null,"abstract":"Background Huntington’s disease (HD) patients tend to underestimate the severity of chorea. Aims The study aimed at assessing the possible impact of manual dexterity task completion on the awareness of chorea in HD. It was hypothesized that the patients’ tendency to underestimate chorea will decrease after the confrontation with a demanding motor task so that post-task ratings of chorea will be higher and more consistent with the objective measures than the pre-test ratings. Methods/techniques: Ten symptomatic HD patients (aged 58±11 years with the age of motor onset 52±10 years, the median Unified Huntington’s Disease Rating Scale- UHDRS total motor score 39.50 and median Total Functional Capacity-TFC score 8) completed the Nine Hole Peg Test (the 9HPT), pegboard task, used to assess manual dexterity. The participants estimated the degree of chorea interference with task performance on a 10-point scale (from 0 – no interference to 10-major interference) both prior and post task performance with each hand. Results/outcome: The patients’ median ratings of chorea increased from 0.50 (pre) to 1.50 (post) in the dominant hand motor coordination and from 2.50 (pre) to 3.00 (post) in the non-dominant hand. The ratings of involuntary movements were significantly influenced by the motor task performance with the non-dominant hand (p=0.04), but not with the dominant hand (p=0.12). Also the patients’ post-task chorea ratings concerning the non-dominant hand were highly correlated with the objective 9HPT performance (rho=0.93 for involuntary movements and rho=0.90 for both coordination and slowing) and chorea in the upper extremity as assessed in UHDRS motor (rho=0.65). Conclusions The preliminary results show that the awareness of motor impairment in a patient may vary and that the patients are less unlikely to underestimate motor symptoms after being confronted with a demanding motor tasks.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"56 1","pages":"A54 - A54"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90910934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/JNNP-2018-EHDN.176
Federica Terenzi, C. Ferrari, C. Bartolozzi, F. Rotella, E. Ghelli, Eleonora Mascherini, E. Volpi, S. Latorraca, S. Bagnoli, B. Nacmias, S. Piacentini, S. Sorbi
Objective The protocol for genetic test in at-risk individuals for Huntington Disease provides a neurological examination and a psychiatric evaluation before to begin the psychological counseling, that provides to engage the client in at least two or more psychological session aimed to support the decision-making process. The present study investigated the at-risk subjects’ decision to engage psychological counselling and to carry out genetic test. Materials The collected data were obtained through the recruitment of people with HD and their families within the European Huntington’s Disease Network (EHDN). Using the EHDN Registry, data on clinical signs and symptoms of HD are collected together with the family history of the disease and the data obtained by neurocognitive tests and self-report questionnaires. Methods One hundred and three individuals at risk for Huntington Disease have been included in the study, obtained from clinical data collected from 2007 and 2017 at the HD Center in Careggi Teaching Hospital. Data were manually retrieved from clinical records and included in a database for analyses. Results Forty-four (42.7%) subjects, out of 103 at-risk individuals, decided to start the protocol and engaged on psychological counselling about decision making for genetic test. Thirty-one (70.4%) subjects, out of 44 subjects who undertook the protocol, decided to carry out genetic test,while thirteen (30.6%) subjects decided to temporarily stop the psychological counselling. Within our sample, 18 females (58%) have undergone genetic test, among them 13 (72,2%) were in reproductive period (average age of 29,4 years). Discussion The study examined changes in decision-making for and against the predictive genetic test for Huntington’s disease during psychological counselling. Our data highlight that a high proportion of subjects changed the initial decision of having the genetic test after psychological counselling, preferring uncertainty to the chance of a negative result.
{"title":"G02 Decision-making in predictive testing in huntington’s disease","authors":"Federica Terenzi, C. Ferrari, C. Bartolozzi, F. Rotella, E. Ghelli, Eleonora Mascherini, E. Volpi, S. Latorraca, S. Bagnoli, B. Nacmias, S. Piacentini, S. Sorbi","doi":"10.1136/JNNP-2018-EHDN.176","DOIUrl":"https://doi.org/10.1136/JNNP-2018-EHDN.176","url":null,"abstract":"Objective The protocol for genetic test in at-risk individuals for Huntington Disease provides a neurological examination and a psychiatric evaluation before to begin the psychological counseling, that provides to engage the client in at least two or more psychological session aimed to support the decision-making process. The present study investigated the at-risk subjects’ decision to engage psychological counselling and to carry out genetic test. Materials The collected data were obtained through the recruitment of people with HD and their families within the European Huntington’s Disease Network (EHDN). Using the EHDN Registry, data on clinical signs and symptoms of HD are collected together with the family history of the disease and the data obtained by neurocognitive tests and self-report questionnaires. Methods One hundred and three individuals at risk for Huntington Disease have been included in the study, obtained from clinical data collected from 2007 and 2017 at the HD Center in Careggi Teaching Hospital. Data were manually retrieved from clinical records and included in a database for analyses. Results Forty-four (42.7%) subjects, out of 103 at-risk individuals, decided to start the protocol and engaged on psychological counselling about decision making for genetic test. Thirty-one (70.4%) subjects, out of 44 subjects who undertook the protocol, decided to carry out genetic test,while thirteen (30.6%) subjects decided to temporarily stop the psychological counselling. Within our sample, 18 females (58%) have undergone genetic test, among them 13 (72,2%) were in reproductive period (average age of 29,4 years). Discussion The study examined changes in decision-making for and against the predictive genetic test for Huntington’s disease during psychological counselling. Our data highlight that a high proportion of subjects changed the initial decision of having the genetic test after psychological counselling, preferring uncertainty to the chance of a negative result.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"42 1","pages":"A66 - A66"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84285905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-ehdn.141
A. Fisher, Anna Lavis, S. Greenfield, H. Rickards
Background In HD, deducing what another person means through their facial emotions is thought to erode as the illness progresses. Emotional recognition data is now being collected in longitudinal studies (Henley, Novak et al. 2012). Aims Showing that the underlying skills of social cognition are impaired in HD through quantitative means leaves a large gap in our knowledge (Bora, Velakoulis et al. 2016). We do not know how the person with HD and those who live with them are experiencing this change, and how it is played out in the many spaces of mundane life. This project aims to capture this ‘social functioning’. Methods Ethnography which employs both participant observation and interacting with participants in a naturalist setting over an extended period will be used. Additionally, using a non-word based participatory method such as photo elicitation (Lorenz 2011) will optimise the views of people with HD who may have communication and cognitive problems. A social convoy map (Sherman et al (2015)) may also be used to establish changes over time. Results/conclusions A submission for the project to ethics review will be take place shortly following a consultation with the UK HDA Public Involvement group – HD Voice. Approximating the real world should allow for a more nuanced person-centred and in-depth portrait of how these concerns affect overall functioning in HD; allowing clinicians to develop more sensitive assessments to capture these issues in way that are meaningful to the community and developing interventions which are aimed at reducing the concerns raised in the context in which they occur. References . Bora E, Velakoulis D, Walterfang M. Social cognition in Huntington’s disease: A meta-analysis. Behavioural brain research2016;297:131. . Henley SM, Novak MJ, Frost C, King J, Tabrizi SJ, Warren JD. Emotion recognition in Huntington’s disease: a systematic review. Neuroscience & Biobehavioral Reviews2012;36(1):237–253. . Lorenz LS. A way into empathy: a ’case’ of photo- elicitation in illness research. Health2011 (London, England: 1997);15(3):259. . Sherman CW, Wan WH, Antonucci TC. Social convoy model. The Encyclopedia of Adulthood and Aging [SK Whitbourne (Ed.)]. 2015.
在HD患者中，通过面部表情来推断他人的意思被认为随着疾病的进展而削弱。情绪识别数据现在被收集到纵向研究中(Henley, Novak et al. 2012)。通过定量手段显示HD患者社会认知的潜在技能受损，这在我们的知识中留下了很大的空白(Bora, Velakoulis et al. 2016)。我们不知道患有HD的人和与他们一起生活的人是如何经历这种变化的，以及它是如何在世俗生活的许多空间中发挥作用的。该项目旨在捕捉这种“社会功能”。方法人种学采用参与者观察和与参与者在自然环境中进行长时间的互动。此外，使用非基于单词的参与式方法，如照片引出(Lorenz 2011)将优化HD患者的观点，他们可能有沟通和认知问题。社交车队地图(Sherman等人(2015))也可以用来确定随时间的变化。结果/结论在与英国HDA公众参与小组- HD Voice协商后，将很快提交项目伦理审查。接近真实世界应该允许更细致入微的以人为本和深入的描述这些问题如何影响HD的整体功能;允许临床医生制定更敏感的评估，以对社区有意义的方式捕捉这些问题，并制定干预措施，旨在减少在这些问题发生的背景下引起的关注。参考文献张丽娟，张丽娟，张丽娟，等。亨廷顿舞蹈病患者社会认知的meta分析。行为脑研究2016;297:131。李建军，李建军，李建军，李建军，李建军。亨廷顿舞蹈病的情绪识别:系统回顾。中国生物医学工程学报，2012;36(1):237-253。洛伦茨LS。一种进入同理心的方式:疾病研究中照片启发的“案例”。《健康2011》(英国伦敦:1997年);15(3):259。谢尔曼CW，万WH，安东努奇TC。社会护卫队模式。成人与衰老百科全书[SK惠特伯恩(主编)]。2015.
{"title":"F37 Is social cognition in huntington’s disease more than just a marker for disease progression? – an exploration of social functioning in the day to day experiences of people with hd, their companions and friends","authors":"A. Fisher, Anna Lavis, S. Greenfield, H. Rickards","doi":"10.1136/jnnp-2018-ehdn.141","DOIUrl":"https://doi.org/10.1136/jnnp-2018-ehdn.141","url":null,"abstract":"Background In HD, deducing what another person means through their facial emotions is thought to erode as the illness progresses. Emotional recognition data is now being collected in longitudinal studies (Henley, Novak et al. 2012). Aims Showing that the underlying skills of social cognition are impaired in HD through quantitative means leaves a large gap in our knowledge (Bora, Velakoulis et al. 2016). We do not know how the person with HD and those who live with them are experiencing this change, and how it is played out in the many spaces of mundane life. This project aims to capture this ‘social functioning’. Methods Ethnography which employs both participant observation and interacting with participants in a naturalist setting over an extended period will be used. Additionally, using a non-word based participatory method such as photo elicitation (Lorenz 2011) will optimise the views of people with HD who may have communication and cognitive problems. A social convoy map (Sherman et al (2015)) may also be used to establish changes over time. Results/conclusions A submission for the project to ethics review will be take place shortly following a consultation with the UK HDA Public Involvement group – HD Voice. Approximating the real world should allow for a more nuanced person-centred and in-depth portrait of how these concerns affect overall functioning in HD; allowing clinicians to develop more sensitive assessments to capture these issues in way that are meaningful to the community and developing interventions which are aimed at reducing the concerns raised in the context in which they occur. References . Bora E, Velakoulis D, Walterfang M. Social cognition in Huntington’s disease: A meta-analysis. Behavioural brain research2016;297:131. . Henley SM, Novak MJ, Frost C, King J, Tabrizi SJ, Warren JD. Emotion recognition in Huntington’s disease: a systematic review. Neuroscience & Biobehavioral Reviews2012;36(1):237–253. . Lorenz LS. A way into empathy: a ’case’ of photo- elicitation in illness research. Health2011 (London, England: 1997);15(3):259. . Sherman CW, Wan WH, Antonucci TC. Social convoy model. The Encyclopedia of Adulthood and Aging [SK Whitbourne (Ed.)]. 2015.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"71 1","pages":"A53 - A53"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86371845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.212
Maryluz Camargo
Background Speech and swallowing are functions that deteriorate in people with Huntington’s Disease (HD) over time. Although there are scales to measure the progression of the disease, there are not enough tools with which people with HD and their families can monitor the evolution of problems in speech and swallowing. Aims Have an application for mobile devices that allows to monitor speech and swallowing difficulties. Methods An information search was conducted in the literature to determine the most relevant aspects that could show the progress of the problems in the two areas of interest. For the development of the application we used the Ionic version 3 program with code based on angular 4 and a hybrid platform. Results The application called Tamizaje Oromotor UN -Oromotor Screening UN- was designed to monitor the speech and swallowing of different neurological conditions, including Huntington’s Disease. Through two modules and 14 questions that yield graphic results, people can self-monitor the progress of the difficulties and report to the treating health personnel. The application, free download, can be installed on mobile devices with Android and IOS operating systems. It has a basic data management interface that allows you to export or import information in JSON format. Conclusions Oromotor Screening is a new tool that will allow, in an agile and fast way, people with HD, their families and health personnel, to follow the difficulties in speech and swallowing.
亨廷顿舞蹈症(HD)患者的语言和吞咽功能会随着时间的推移而恶化。虽然有衡量疾病进展的量表，但没有足够的工具让HD患者及其家人监测语言和吞咽问题的演变。目标为移动设备开发一个应用程序，可以监控语言和吞咽困难。方法在文献中进行信息搜索，以确定最相关的方面，可以显示问题的进展，在两个感兴趣的领域。对于应用程序的开发，我们使用了Ionic版本3程序，其代码基于angular 4和一个混合平台。这款名为Tamizaje Oromotor UN (Oromotor Screening UN)的应用程序旨在监测包括亨廷顿舞蹈症在内的不同神经系统疾病患者的语言和吞咽情况。通过两个模块和14个可产生图形结果的问题，人们可以自我监测困难的进展情况，并向治疗人员报告。这款应用可以免费下载，安装在安卓和IOS操作系统的移动设备上。它有一个基本的数据管理接口，允许您以JSON格式导出或导入信息。结论口腔运动筛查是一种新的工具，可以让HD患者、他们的家人和卫生人员以一种敏捷和快速的方式跟踪言语和吞咽困难。
{"title":"H34 Oromotor screening – tamizaje oromotor: new app to monitor speech and swallowing in huntington’s disease","authors":"Maryluz Camargo","doi":"10.1136/jnnp-2018-EHDN.212","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.212","url":null,"abstract":"Background Speech and swallowing are functions that deteriorate in people with Huntington’s Disease (HD) over time. Although there are scales to measure the progression of the disease, there are not enough tools with which people with HD and their families can monitor the evolution of problems in speech and swallowing. Aims Have an application for mobile devices that allows to monitor speech and swallowing difficulties. Methods An information search was conducted in the literature to determine the most relevant aspects that could show the progress of the problems in the two areas of interest. For the development of the application we used the Ionic version 3 program with code based on angular 4 and a hybrid platform. Results The application called Tamizaje Oromotor UN -Oromotor Screening UN- was designed to monitor the speech and swallowing of different neurological conditions, including Huntington’s Disease. Through two modules and 14 questions that yield graphic results, people can self-monitor the progress of the difficulties and report to the treating health personnel. The application, free download, can be installed on mobile devices with Android and IOS operating systems. It has a basic data management interface that allows you to export or import information in JSON format. Conclusions Oromotor Screening is a new tool that will allow, in an agile and fast way, people with HD, their families and health personnel, to follow the difficulties in speech and swallowing.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"74 1","pages":"A79 - A79"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82198436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1136/jnnp-2018-EHDN.231
R. Konvalinková, P. Dušek, K. Doleckova, T. Uhrová, J. Roth, J. Klempír
Unintended weight loss is a negative prognostic factor in Huntington’s disease (HD). Exact mechanism of weight loss and influence of therapeutic intervention on this symptom is still unclear. In Prague centre Registry database containing 309 examinations of patients (age 50.3±13.4 years, disease duration 9.13±3.51 years, number of CAG repeats from 40 to 70) were analysed. Correlation analysis was performed between body mass index (BMI) and Unified Huntington’s Disease Rating Scale – motor subscores (voluntary, oculomotor, chorea, dystonia, rigidity) and functional scales were used. None of the Pearson’s correlation were significant. Our results may indicate that BMI may be independent parameter in this particular stage of the disease course. Of the database, 154 examinations were on risperidone and 155 were without risperidone therapy. Age, CAG repeats and disease duration did not differ between the two groups (p=0.1, p=0.9, p=0.26 respectively). Patients on risperidone therapy had significantly higher weight (Mann-Whitney U-test, p<0.0001). Additionally, we performed a linear model using ordinary least squares calculation to count for the effect of disease progression and motor subscores. The effect of risperidone was independent on the disease progression (i.e. disease duration, CAG expansion, age) and voluntary and involuntary movements. In subsequent analysis, 49 events on tiapride therapy and 260 events off tiapride therapy were compared, weight in those two groups did not differ. A longitudinal study must be performed to prove the causality of risperidone effect on weight in HD.
{"title":"H53 Does the risperidone influence weight in huntington’s disease?","authors":"R. Konvalinková, P. Dušek, K. Doleckova, T. Uhrová, J. Roth, J. Klempír","doi":"10.1136/jnnp-2018-EHDN.231","DOIUrl":"https://doi.org/10.1136/jnnp-2018-EHDN.231","url":null,"abstract":"Unintended weight loss is a negative prognostic factor in Huntington’s disease (HD). Exact mechanism of weight loss and influence of therapeutic intervention on this symptom is still unclear. In Prague centre Registry database containing 309 examinations of patients (age 50.3±13.4 years, disease duration 9.13±3.51 years, number of CAG repeats from 40 to 70) were analysed. Correlation analysis was performed between body mass index (BMI) and Unified Huntington’s Disease Rating Scale – motor subscores (voluntary, oculomotor, chorea, dystonia, rigidity) and functional scales were used. None of the Pearson’s correlation were significant. Our results may indicate that BMI may be independent parameter in this particular stage of the disease course. Of the database, 154 examinations were on risperidone and 155 were without risperidone therapy. Age, CAG repeats and disease duration did not differ between the two groups (p=0.1, p=0.9, p=0.26 respectively). Patients on risperidone therapy had significantly higher weight (Mann-Whitney U-test, p<0.0001). Additionally, we performed a linear model using ordinary least squares calculation to count for the effect of disease progression and motor subscores. The effect of risperidone was independent on the disease progression (i.e. disease duration, CAG expansion, age) and voluntary and involuntary movements. In subsequent analysis, 49 events on tiapride therapy and 260 events off tiapride therapy were compared, weight in those two groups did not differ. A longitudinal study must be performed to prove the causality of risperidone effect on weight in HD.","PeriodicalId":16509,"journal":{"name":"Journal of Neurology, Neurosurgery & Psychiatry","volume":"2 1","pages":"A86 - A86"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89442521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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