PDF(Pubmed)
Abstract：
UNASSIGNED: To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD).
UNASSIGNED: We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau181 and t-tauAg, amyloid, and 18F-FDG PET of five unrelated LD families.
UNASSIGNED: Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 ± 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF Aβ42, amyloid PET) and neurodegenerative (CSF p-tau181 and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer\'s disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase.
UNASSIGNED: Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer\'s disease type.
UNASSIGNED: We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau181 and t-tauAg, amyloid, and 18F-FDG PET of five unrelated LD families.
UNASSIGNED: Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 ± 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF Aβ42, amyloid PET) and neurodegenerative (CSF p-tau181 and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer\'s disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase.
UNASSIGNED: Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer\'s disease type.
摘要：
■评估与神经变性的实验室和仪器相关的电临床特征，以检测Lafora病（LD）的进展。
■我们研究了电临床纵向数据和CSFAβ42，p-tau181和t-tauAg，淀粉样蛋白,5个无关LD家族的18F-FDGPET。
■确定了三个进行性电临床阶段。早期的特点是罕见的，全身强直阵挛性和局灶性视觉癫痫发作，随后在2至12个月的时间内发生肌阵挛症。中间阶段,通常发生在癫痫发作后2年，其特征在于与进行性痴呆和小脑征象相关的癫痫和肌阵挛症恶化。最后,后期,从疾病发作开始平均7±1.41年后演变，以步态共济失调为特征，严重的痴呆,每日/每日肌阵挛症，耐药癫痫,癫痫发作或癫痫持续状态的集群，和医疗并发症。淀粉样蛋白（CSFAβ42，淀粉样蛋白PET）和神经退行性（CSFp-tau181和t-tauAg，FDG-PET）生物标志物表明非阿尔茨海默病类型的认知障碍模式。与在较低阶段进行的第一次扫描相比，在第二次FDG-PET扫描中，共有80％的LD患者表现出更严重的低代谢；颞叶外侧和丘脑低代谢与中期或晚期的存在有关。
■三个电临床和18F-FDGPET进化阶段是LD进展的有用生物标志物，可以帮助评估新的疾病修饰治疗的疗效。传统CSF生物标志物的结合提高了LD患者认知功能下降的诊断准确性，表明非阿尔茨海默病类型的认知障碍。
■我们研究了电临床纵向数据和CSFAβ42，p-tau181和t-tauAg，淀粉样蛋白,5个无关LD家族的18F-FDGPET。
■确定了三个进行性电临床阶段。早期的特点是罕见的，全身强直阵挛性和局灶性视觉癫痫发作，随后在2至12个月的时间内发生肌阵挛症。中间阶段,通常发生在癫痫发作后2年，其特征在于与进行性痴呆和小脑征象相关的癫痫和肌阵挛症恶化。最后,后期,从疾病发作开始平均7±1.41年后演变，以步态共济失调为特征，严重的痴呆,每日/每日肌阵挛症，耐药癫痫,癫痫发作或癫痫持续状态的集群，和医疗并发症。淀粉样蛋白（CSFAβ42，淀粉样蛋白PET）和神经退行性（CSFp-tau181和t-tauAg，FDG-PET）生物标志物表明非阿尔茨海默病类型的认知障碍模式。与在较低阶段进行的第一次扫描相比，在第二次FDG-PET扫描中，共有80％的LD患者表现出更严重的低代谢；颞叶外侧和丘脑低代谢与中期或晚期的存在有关。
■三个电临床和18F-FDGPET进化阶段是LD进展的有用生物标志物，可以帮助评估新的疾病修饰治疗的疗效。传统CSF生物标志物的结合提高了LD患者认知功能下降的诊断准确性，表明非阿尔茨海默病类型的认知障碍。
