Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with ...Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.展开更多
Background: Chronic progressive external ophthalmoplegia (CPEO) is a mitochond rial cytopathy presenting with ptosis and external ophthalmoparesis. Mitochondri al disorders are characterized by a broad clinical spectr...Background: Chronic progressive external ophthalmoplegia (CPEO) is a mitochond rial cytopathy presenting with ptosis and external ophthalmoparesis. Mitochondri al disorders are characterized by a broad clinical spectrum and genetic backgrou nd with marked genotype/phenotype variability. The routine diagnostic work-up u sually includes clinical and laboratory examinations as well as histological and histochemical analysis of skeletal muscle biopsy. In our case only an additiona l molecular biological examination allowed the diagnosis of CPEO. Patient and Me thods: We report a 35-year-old woman with a 7-years history of slowly progres sive diplopia due to impaired ocular motility and bilateral ptosis. We performed ophthalmological and neurological examinations, laboratory testing, lower limb skeletal muscle biopsy including histo logical and histochemical investigations, biochemical analysis of respiratory ch ain enzymes in skeletal muscle homogenate and molecular genetic testing of skele tal muscle DNA. Results: Although clinical, laboratory, histological and biochem ical analyses did not give any hints suggesting a mitochondrial cytopathy, molec ular genetic testing of total DNA from skeletal muscle tissue by Southern blot a nalysis finally revealed a 3.8 kb mitochondrial DNA deletion with a degree of he teroplasmy of 45%. Conclusions: In patients with unexplained binocular diplopia , oculomotor deficits and/or acquired ptosis, an underlying mitochondrial cytopa thy should be considered. Even in the case of inconspicuous skeletal muscle hist ology and biochemistry, molecular genetic testing of skeletal muscle DNA is advi sable in order to establish the diagnosis.展开更多
Background and Purpose -Ultrasound examination of the carotid arteries yiel ds several quantitative measures that may serve as intermediate phenotypes in ge netic studies. This study was undertaken to compare the heri...Background and Purpose -Ultrasound examination of the carotid arteries yiel ds several quantitative measures that may serve as intermediate phenotypes in ge netic studies. This study was undertaken to compare the heritabilities of 3 ultr asound measures: intima-media thickness (IMT), plaque score, and maximal steno sis. Methods -We studied 565 individuals from 154 families ascertained by an a ffected parent with carotid artery atherosclerosis. IMT, plaque score, and maxim al stenosis of the carotid arteries were examined by B-mode ultrasound and ana lyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage ana lysis routines). Covariates were age, sex, weight, height, body mass index (BMI) , arterial hypertension, diabetes mellitus, amount of nicotine consumed, and pla sma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HD L) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VII I, factor XIII, fibrinogen, and von Willebrand factor (vWF). Results -After ac counting for the covariables age, sex, hypertension, diabetes mellitus, and Lp(a ), heritability of IMT was estimated as h2=0.61± 0.17 (P=0.001). Variation of p laque score was influenced by age, sex, hypertension, diabetes mellitus, hyperch olesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these wer e considered, no significant heritability could be detected. Heritability of ste nosis was estimated as h2=0.47± 0.07 (P=0.006), with age, sex, BMI, hypertensio n, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariat es. Conclusions -Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than tho se influencing known risk factors. This makes MT a promising candidate for use a s an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.展开更多
Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in...Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in 31 PCNSL patients and 142 controls. We found significantly less carriers of the methionine synthase c. 2756A> G (D919G) missense polymorphism among the patients (0.16 vs 0.42; odds ratio 0.26, CI(95%): 0.09-0.74; P=0.005), suggesting a protective function of the G allele. These data stimulate further epidemiological and functional studies focusing on the role of homoeysteine and folate metabolism in lymphoma tumorigenesis.展开更多
Purpose: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA) mu tation analysis in acquired juvenile unilateral upper eyelid ptosis. Methods: A1 3-year-old boy presented with acquired, slowly progressiv...Purpose: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA) mu tation analysis in acquired juvenile unilateral upper eyelid ptosis. Methods: A1 3-year-old boy presented with acquired, slowly progressive unilateral ptosis. We performed ophthalmological and neurological examinations, laboratory testing, skeletal muscle biopsy including histological and histochemical investigations, biochemical analysis of respiratory chain enzymes in skeletal muscle homogenate and molecular genetic testing of skeletal muscle DNA. Results: Though clinical, laboratory, histological and biochemical analyses did not reveal any hints sugg esting a mitochondrial cytopathy, molecular genetic testing by Southern blot ana lysis of total DNA from skeletal muscle tissue showed a 5.8 kb mtDNA deletion th us proving the diagnosis of mitochondrial chronic progressive external ophthalmo plegia(CPEO). Conclusions: In patients with unexplained acquired juvenile unilat eral ptosis, an underlying mitochondrial cytopathy should be considered even in cases of inconspicuous ancillary examinations comprising skeletal muscle histolo gy and biochemistry. To establish the diagnosis, molecular genetic testing of DN A derived from skeletal muscle tissue is essential in those patients.展开更多
基金Intramural funding of the Dept.of Neurology,Kiel University.
文摘Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.
文摘Background: Chronic progressive external ophthalmoplegia (CPEO) is a mitochond rial cytopathy presenting with ptosis and external ophthalmoparesis. Mitochondri al disorders are characterized by a broad clinical spectrum and genetic backgrou nd with marked genotype/phenotype variability. The routine diagnostic work-up u sually includes clinical and laboratory examinations as well as histological and histochemical analysis of skeletal muscle biopsy. In our case only an additiona l molecular biological examination allowed the diagnosis of CPEO. Patient and Me thods: We report a 35-year-old woman with a 7-years history of slowly progres sive diplopia due to impaired ocular motility and bilateral ptosis. We performed ophthalmological and neurological examinations, laboratory testing, lower limb skeletal muscle biopsy including histo logical and histochemical investigations, biochemical analysis of respiratory ch ain enzymes in skeletal muscle homogenate and molecular genetic testing of skele tal muscle DNA. Results: Although clinical, laboratory, histological and biochem ical analyses did not give any hints suggesting a mitochondrial cytopathy, molec ular genetic testing of total DNA from skeletal muscle tissue by Southern blot a nalysis finally revealed a 3.8 kb mitochondrial DNA deletion with a degree of he teroplasmy of 45%. Conclusions: In patients with unexplained binocular diplopia , oculomotor deficits and/or acquired ptosis, an underlying mitochondrial cytopa thy should be considered. Even in the case of inconspicuous skeletal muscle hist ology and biochemistry, molecular genetic testing of skeletal muscle DNA is advi sable in order to establish the diagnosis.
文摘Background and Purpose -Ultrasound examination of the carotid arteries yiel ds several quantitative measures that may serve as intermediate phenotypes in ge netic studies. This study was undertaken to compare the heritabilities of 3 ultr asound measures: intima-media thickness (IMT), plaque score, and maximal steno sis. Methods -We studied 565 individuals from 154 families ascertained by an a ffected parent with carotid artery atherosclerosis. IMT, plaque score, and maxim al stenosis of the carotid arteries were examined by B-mode ultrasound and ana lyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage ana lysis routines). Covariates were age, sex, weight, height, body mass index (BMI) , arterial hypertension, diabetes mellitus, amount of nicotine consumed, and pla sma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HD L) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VII I, factor XIII, fibrinogen, and von Willebrand factor (vWF). Results -After ac counting for the covariables age, sex, hypertension, diabetes mellitus, and Lp(a ), heritability of IMT was estimated as h2=0.61± 0.17 (P=0.001). Variation of p laque score was influenced by age, sex, hypertension, diabetes mellitus, hyperch olesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these wer e considered, no significant heritability could be detected. Heritability of ste nosis was estimated as h2=0.47± 0.07 (P=0.006), with age, sex, BMI, hypertensio n, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariat es. Conclusions -Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than tho se influencing known risk factors. This makes MT a promising candidate for use a s an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.
文摘Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in 31 PCNSL patients and 142 controls. We found significantly less carriers of the methionine synthase c. 2756A> G (D919G) missense polymorphism among the patients (0.16 vs 0.42; odds ratio 0.26, CI(95%): 0.09-0.74; P=0.005), suggesting a protective function of the G allele. These data stimulate further epidemiological and functional studies focusing on the role of homoeysteine and folate metabolism in lymphoma tumorigenesis.
文摘Purpose: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA) mu tation analysis in acquired juvenile unilateral upper eyelid ptosis. Methods: A1 3-year-old boy presented with acquired, slowly progressive unilateral ptosis. We performed ophthalmological and neurological examinations, laboratory testing, skeletal muscle biopsy including histological and histochemical investigations, biochemical analysis of respiratory chain enzymes in skeletal muscle homogenate and molecular genetic testing of skeletal muscle DNA. Results: Though clinical, laboratory, histological and biochemical analyses did not reveal any hints sugg esting a mitochondrial cytopathy, molecular genetic testing by Southern blot ana lysis of total DNA from skeletal muscle tissue showed a 5.8 kb mtDNA deletion th us proving the diagnosis of mitochondrial chronic progressive external ophthalmo plegia(CPEO). Conclusions: In patients with unexplained acquired juvenile unilat eral ptosis, an underlying mitochondrial cytopathy should be considered even in cases of inconspicuous ancillary examinations comprising skeletal muscle histolo gy and biochemistry. To establish the diagnosis, molecular genetic testing of DN A derived from skeletal muscle tissue is essential in those patients.
