Jennifer Batten是在上世纪80年代末在吉他音乐界崛起的,当时各种吉他杂志立即注意到她,《Guitar for the Practicing Musician》杂志的首席编辑提到她时写道:"这是在吉他音乐界最有能力的一位女性,她将威胁到所有男性吉他演奏家...Jennifer Batten是在上世纪80年代末在吉他音乐界崛起的,当时各种吉他杂志立即注意到她,《Guitar for the Practicing Musician》杂志的首席编辑提到她时写道:"这是在吉他音乐界最有能力的一位女性,她将威胁到所有男性吉他演奏家在这个领域的权威地位.而她的多指点弦技巧也将是对点弦技巧的一个完美终结.又一位来自MI音乐学院的天才".展开更多
Background: Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) is an autosomal recessive neurodegenerative disorder characterized by blindness, seizures, and relentless decline in cognitive, motor, and be...Background: Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) is an autosomal recessive neurodegenerative disorder characterized by blindness, seizures, and relentless decline in cognitive, motor, and behavioral function. Onset is in the early school years, with progression to death typically by late adolescence. Development of a clinical instrument to quantify severity of illness is a prerequisite to eventual assessment of experimental therapeutic interventions Objective: To develop a clinical rating instrument to assess motor, behavioral, and functional capability in JNCL. Methods: A clinical rating instrument, the Unified Batten Disease Rating Scale (UBDRS), was developed by the authors to assess motor, behavioral, and functional capability in JNCL. Children with verified JNCL were evaluated independently by three neurologists. Intraclass correlation coefficients (ICCs) were used to estimate the interrater reliability for total scores in each domain. Interrater reliability for scale items was assessed with weighted κstatistics. Results: Thirty-one children with confirmed JNCL (10 boys, 21 girls) were evaluated. The mean age at symptom onset was 6.1 ±1.6 years, and the mean duration of illness was 9.0 ±4.4 years. The ICCs for the domains were as follows: motor=0.83, behavioral=0.68, and functional capability=0.85. Conclusions: The Unified Batten Disease Rating Scale (UBDRS) is a reliable instrument that effectively tests for neurologic function in blind and demented patients. In its current form, the UBDRS is useful for monitoring the diverse clinical findings seen in Batten disease.展开更多
The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1...The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome.Batten patien ts did not possess autoantibodies against other type 1 diabetes-associated auto antigens and human leukocyte antigen genotypes revealed no specific associations with this disease.展开更多
Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life.Here,we summarize emerging links between the most common ...Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life.Here,we summarize emerging links between the most common late life neurodegenerative disease,Alzheimer’s disease,and the most common early life neurodegenerative diseases,neuronal ceroid lipofuscinoses.Genetic studies reported an overlap of clinically diagnosed Alzheimer’s disease and mutations in genes known to cause neuronal ceroid lipofuscinoses.Accumulating data strongly suggest dysfunction of intracellular trafficking mechanisms and the autophagy-endolysosome system in both types of neurodegenerative disorders.This suggests shared cytopathological processes underlying these different types of neurodegenerative diseases.A better understanding of the common mechanisms underlying the different diseases is important as this might lead to the identification of novel targets for therapeutic concepts,the transfer of therapeutic strategies from one disease to the other and therapeutic approaches tailored to patients with specific mutations.Here,we review dysfunctions of the endolysosomal autophagy pathway in Alzheimer’s disease and neuronal ceroid lipofuscinoses and summarize emerging etiologic and genetic overlaps.展开更多
文摘Jennifer Batten是在上世纪80年代末在吉他音乐界崛起的,当时各种吉他杂志立即注意到她,《Guitar for the Practicing Musician》杂志的首席编辑提到她时写道:"这是在吉他音乐界最有能力的一位女性,她将威胁到所有男性吉他演奏家在这个领域的权威地位.而她的多指点弦技巧也将是对点弦技巧的一个完美终结.又一位来自MI音乐学院的天才".
文摘Background: Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) is an autosomal recessive neurodegenerative disorder characterized by blindness, seizures, and relentless decline in cognitive, motor, and behavioral function. Onset is in the early school years, with progression to death typically by late adolescence. Development of a clinical instrument to quantify severity of illness is a prerequisite to eventual assessment of experimental therapeutic interventions Objective: To develop a clinical rating instrument to assess motor, behavioral, and functional capability in JNCL. Methods: A clinical rating instrument, the Unified Batten Disease Rating Scale (UBDRS), was developed by the authors to assess motor, behavioral, and functional capability in JNCL. Children with verified JNCL were evaluated independently by three neurologists. Intraclass correlation coefficients (ICCs) were used to estimate the interrater reliability for total scores in each domain. Interrater reliability for scale items was assessed with weighted κstatistics. Results: Thirty-one children with confirmed JNCL (10 boys, 21 girls) were evaluated. The mean age at symptom onset was 6.1 ±1.6 years, and the mean duration of illness was 9.0 ±4.4 years. The ICCs for the domains were as follows: motor=0.83, behavioral=0.68, and functional capability=0.85. Conclusions: The Unified Batten Disease Rating Scale (UBDRS) is a reliable instrument that effectively tests for neurologic function in blind and demented patients. In its current form, the UBDRS is useful for monitoring the diverse clinical findings seen in Batten disease.
文摘The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome.Batten patien ts did not possess autoantibodies against other type 1 diabetes-associated auto antigens and human leukocyte antigen genotypes revealed no specific associations with this disease.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,425373668,HE 3220/4-1)(to GH).
文摘Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life.Here,we summarize emerging links between the most common late life neurodegenerative disease,Alzheimer’s disease,and the most common early life neurodegenerative diseases,neuronal ceroid lipofuscinoses.Genetic studies reported an overlap of clinically diagnosed Alzheimer’s disease and mutations in genes known to cause neuronal ceroid lipofuscinoses.Accumulating data strongly suggest dysfunction of intracellular trafficking mechanisms and the autophagy-endolysosome system in both types of neurodegenerative disorders.This suggests shared cytopathological processes underlying these different types of neurodegenerative diseases.A better understanding of the common mechanisms underlying the different diseases is important as this might lead to the identification of novel targets for therapeutic concepts,the transfer of therapeutic strategies from one disease to the other and therapeutic approaches tailored to patients with specific mutations.Here,we review dysfunctions of the endolysosomal autophagy pathway in Alzheimer’s disease and neuronal ceroid lipofuscinoses and summarize emerging etiologic and genetic overlaps.
