Objective: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. Methods: The authors included first-ever strokes occurring between 1994 and 1998. They assessed inc...Objective: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. Methods: The authors included first-ever strokes occurring between 1994 and 1998. They assessed incidence, risk factors, mortality, and recurrence in patients with lacunar stroke. Results: The authors identified 491 patients (15.3%) with lacunar stroke (252 men and 239 women) and 2,153 patients (67.3%) with nonlacunar stroke (998 men and 1,155 women). Crude annual incidence rate for a first-ever lacunar stroke was 33.0/100,000 (95%CI 30.2 to 36.0). At the univariate logistic regression analysis among patients with lacunar stroke there was a higher proportion of cigarette smoking and hypercholesterolemia and a lower proportion of chronic atrial fibrillation than in patients with nonlacunar stroke. For lacunar stroke, the 30-day case-fatality rate was 4.3%(95%CI 2.5 to 6.1) and the 1-year case-fatality rate was 13.0%(95%CI 10.0 to 16.0). During the first year of follow-up the average annual stroke recurrence rate was lower in patients with lacunar (2.83%; 95%CI 1.36 to 4.30) than in those with nonlacunar stroke (5.10%; 95%CI 4.17 to 6.03) while from the second year onward, rates were similar in both groups. Conclusion: In the short term, patients with nonlacunar stroke had more vascular events, but in the long term, the risk of death and of stroke recurrence was similar.展开更多
Background: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly pre...Background: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly predicts the risk of stroke. It is unclear if this is due to arteriolar narrowing or venular dilation. Objective: To investigate whether smaller arteriolar or larger venular diameters are related to the risk of stroke and cerebral infarction. Methods: This study was based on the prospective population-based Rotterdam Study and included 5,540 participants of 55 years or over, who had gradable fundus transparencies and were free of stroke at baseline (1990 to 1993). For each participant, retinal arteriolar and venular diameters were measured on digitized images of one eye. Follow-up for first-ever stroke was complete until January 1, 2002. Results: After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259 had cerebral infarction. Larger venular diameters were associated with an increased risk of stroke (hazard ratio [HR] adjusted for age and sex per SD increase: 1.12 [95%CI: 1.02 to 1.24]) and cerebral infarction (HR: 1.15 [95%CI: 1.02 to 1.29]). Smaller arteriolar diameters were neither related to the risk of stroke (HR per SD decrease: 1.02 [95%CI: 0.93 to 1.13]) nor to the risk of cerebral infarction (HR: 1.02 [95%CI: 0.90 to 1.15]). After additional adjustment for other cardiovascular risk factors, the results did not change. Conclusions: Larger retinal venular diameters are associated with an increased risk of stroke and cerebral infarction. The role of venules in cerebrovascular disease warrants further exploration.展开更多
Background: Mutations in the parkin gene （PRKN） cause autosomal recessive early-onset Parkinson disease （EOPD）. Objective: To investigate the presence of mutations in the PRKN gene in a white family with EOPD and ...Background: Mutations in the parkin gene （PRKN） cause autosomal recessive early-onset Parkinson disease （EOPD）. Objective: To investigate the presence of mutations in the PRKN gene in a white family with EOPD and the genotype-phenotype correlations. Design: Twenty me mbers belonging to 3 generations of the EOPD fam ily with 4 affected subjects underwent genetic analysis. Direct genomic DNA sequ encing, semi-quantitative polymerase chain reaction, real-time quantitative po lymerase chain reaction, and reverse-transcriptase polymerase chain reaction an alyses were performed to identify the PRKN mutation. Results: Compound heterozyg ous mutations （T240M and EX 56 del） in the PRKN gene were identified in 4 patie nts with early onset （at ages 30-38 years）.Although heterozygous T240M and homo zygous EX 56 del mutations in the PRKN gene have been previously described,this is, to our knowledge, the first report of these mutations in compound heterozyg otes. The phenotype of patients was that of classic autosomal recessive EOPD cha racterized by beneficial response to levodopa, relatively slow progression,and m otor complications. All heterozygous mutation carriers （T240M or EX 56 del） and a 56-year-old woman who was a compound heterozygou s mutation carrier （T240M and EX 56 del） were free of any neurological symptoms . Conclusions:Compound heterozygous mutations （T240M and EX56 del） in the PRKN gene were found to cause autosomal recessive EOPD in 4 members of a large white family. One additional member with the same mutation, who is more than 10 years older than the mean age at onset of the 4 affected individuals, had no clinical manifestation of the disease. This incomplete penetrance has implications for ge netic counseling, and it suggests that complex gene-environment interactions ma y play a role in the pathogenesis of PRKN EOPD.展开更多
The prion protein (PrP) is central to the prion diseases, although a role in other neurodegenerative diseases has been postulated. A common polymorphism (Met or Val) at codon 129 of the PrP gene (PRNP) features promin...The prion protein (PrP) is central to the prion diseases, although a role in other neurodegenerative diseases has been postulated. A common polymorphism (Met or Val) at codon 129 of the PrP gene (PRNP) features prominently in the risk and phenotype, of prion disease, and an abnormality in its distribution frequency may signal a role for PrP in other diseases. We conducted a case-control study to compare the PRNP codon 129 genotype distribution in Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and primary progressive aphasia (PPA), including 281 AD, 256 ALS,39 PPA, and 415 healthy control subjects. Statistical analysis was applied to determine the presence or absence of disease-specific genotype associations. The distribution of codon 129 genotypes was similar among healthy control, AD, and ALS subjects, although the heterozygous state was significantly overrepresented (age-adjusted odds ratio, 8.47) in PPA, a rare condition of unknown cause.Although these findings do not entirely exclude a role for PrP in AD or ALS, they do not support the codon 129 genotype as a risk factor for either disease. However, the strong association between heterozygosity and PPA raises new questions about its cause and the role of PrP in other neurodegenerative diseases.展开更多
The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyper...The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network.展开更多
Background: Although more than 160 cases of iatrogenic Creutzfeldt-Jakob disease (iCJD) from human growth hormone (hGH) treatment have been documented, to our knowledge abnormal cerebellar findings on magnetic resonan...Background: Although more than 160 cases of iatrogenic Creutzfeldt-Jakob disease (iCJD) from human growth hormone (hGH) treatment have been documented, to our knowledge abnormal cerebellar findings on magnetic resonance imaging (MRI) have not been reported. Objective: To report a case of hGH-related iCJD with abnormal cerebellar MRI findings on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRI (DWI). Design: Case report. Setting: Outpatient neurology clinic at a university medical center. Patient: A 33-year old man who had sub acute gait ataxia and blurred vision. Results: Beginning 19 years prior, this pa tient had received cadaveric pituitary-derived hGH treatment for at least 5 yea rs. Magnetic resonance imaging revealed FLAIR and DWI abnormalities, particularl y in the cerebellum. He died 7 months after disease onset of autopsyconfirmed iC JD. Pathological changes corresponded largely to MRI findings. Conclusions: To o ur knowledge, this is the first case of hGH-related iCJD with FLAIR and DWI abn ormalities within the cerebellum. As symptoms referable to the cerebellum occur early in iCJD, it suggests that these MRI sequences may allow earlier diagnosis of this form of prion disease.展开更多
Background: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia that is manifested by dream enactment behavior. The electrophysiologic substrate for RBD on polysomnography is rapid eye movement sleep with...Background: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia that is manifested by dream enactment behavior. The electrophysiologic substrate for RBD on polysomnography is rapid eye movement sleep without atonia. Rapid eye movement sleep behavior disorder likely stems from neuronal network dysfunction in the brainstem, although it is not yet clear which specific networks are involved. Rapid eye movement sleep behavior disorder is often associated with the sporadic synucleinopathies but rarely associated with the sporadic tauopathies. There are no reports on the possible association of rapid eye movement sleep without atonia and RBD with any familial tauopathy. Objective: To characterize the clinical sleep and polysomnography features in a kindred with a familial tauopathy. Methods: We performed standard polysomnography in 11 members of the pallidopontonigral degeneration kindred irrespective of any sleep-related complaints. Neuropathologic findings were analyzed in those who subsequently underwent autopsy. Results: Six affected and 5 genealogically at-risk family members were studied. None of the 11 had a history of dream enactment behavior. Nine of the 11 members attained sufficient rapid eye movement sleep on polysomnography, and the electrophysiologic features of rapid eye movement sleep without atonia and behavioral manifestations of RBD were absent in all subjects. Neuropathologic examination of 4 affected individuals revealed marked nigral degeneration in 3 along with mild degenerative changes in the locus coeruleus, pontine nuclei and tegmentum, and medullary tegmentum. Conclusions: These findings argue against nigral degeneration being the primary cause of RBD. The absence of the historical, electrophysiologic, and behavioral manifestations of RBD in this kindred provides further evidence that RBD is rare in the sporadic and familial tauopathies. The difference in frequencies of RBD associated with the synucleinopathies compared with the tauopathies suggests differences in the selective vu展开更多
Background: Sjgren-Larsson syndrome (SLS) is an early childhood-onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty a...Background: Sjgren-Larsson syndrome (SLS) is an early childhood-onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene (the gene that encodes microsomal fatty aldehyde dehydrogenase). Cerebral proton magnetic resonance spectroscopy in those with SLS demonstrates an abnormal white matter peak at 1.3 ppm, consistent wit h long-chain fatty alcohol accumulation. Objective: To define the clinical cour se and proton magnetic resonance spectroscopic findings of SLS in adults. Design and Setting: Case series in a tertiary care center. Patients: Six siblings of a consanguineous Arab family with early childhood-onset SLS who carry the 682C→T mutation in the ALDH3A2 gene were reinvestigated in adulthood. Results: The 6 affected siblings ranged in age from 16 to 36 years. All exhibited the typical c linical and imaging manifestations of SLS, but their severity markedly varied. N eurological involvement was apparently nonprogressive, and its severity showed n o correlation with age. Cerebral proton magnetic resonance spectroscopy showed a lipid peak at 1.3 ppm, with decreasing intensity in the older siblings. Conclus ion: These observations document significant clinical variability and the nonpro gressive neurological course of SLS in adult siblings with the same ALDH3A2 geno type, and demonstrate possible correlation of proton magnetic resonance spectros copic changes with age, suggesting unknown pathogenic mechanisms to compensate f or the responsible biochemical defect in this disease.展开更多
Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been establ...Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. Methods: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. Results: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95%CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95%CI 2.64 to 10.96), deep brain location (HR 3.25, 95%CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95%CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9%for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4%for those harboring all three risk factors. Conclusions: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.展开更多
We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson’s disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonuser...We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson’s disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonusers. Compared with nonusers, the relative risks were 0.73 for users of fewer than 2 tablets/week, 0.72 for 2 to 6.9 tablets/week, and 0.62 for 1 or more tablets/day (ptrend = 0.03). No association was found between the use of aspirin, other nonsteroidal antiinflammatory drugs, or acetaminophen and PD risk. The results suggest that ibuprofen use may delay or prevent the onset of PD.展开更多
文摘Objective: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. Methods: The authors included first-ever strokes occurring between 1994 and 1998. They assessed incidence, risk factors, mortality, and recurrence in patients with lacunar stroke. Results: The authors identified 491 patients (15.3%) with lacunar stroke (252 men and 239 women) and 2,153 patients (67.3%) with nonlacunar stroke (998 men and 1,155 women). Crude annual incidence rate for a first-ever lacunar stroke was 33.0/100,000 (95%CI 30.2 to 36.0). At the univariate logistic regression analysis among patients with lacunar stroke there was a higher proportion of cigarette smoking and hypercholesterolemia and a lower proportion of chronic atrial fibrillation than in patients with nonlacunar stroke. For lacunar stroke, the 30-day case-fatality rate was 4.3%(95%CI 2.5 to 6.1) and the 1-year case-fatality rate was 13.0%(95%CI 10.0 to 16.0). During the first year of follow-up the average annual stroke recurrence rate was lower in patients with lacunar (2.83%; 95%CI 1.36 to 4.30) than in those with nonlacunar stroke (5.10%; 95%CI 4.17 to 6.03) while from the second year onward, rates were similar in both groups. Conclusion: In the short term, patients with nonlacunar stroke had more vascular events, but in the long term, the risk of death and of stroke recurrence was similar.
文摘Background: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly predicts the risk of stroke. It is unclear if this is due to arteriolar narrowing or venular dilation. Objective: To investigate whether smaller arteriolar or larger venular diameters are related to the risk of stroke and cerebral infarction. Methods: This study was based on the prospective population-based Rotterdam Study and included 5,540 participants of 55 years or over, who had gradable fundus transparencies and were free of stroke at baseline (1990 to 1993). For each participant, retinal arteriolar and venular diameters were measured on digitized images of one eye. Follow-up for first-ever stroke was complete until January 1, 2002. Results: After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259 had cerebral infarction. Larger venular diameters were associated with an increased risk of stroke (hazard ratio [HR] adjusted for age and sex per SD increase: 1.12 [95%CI: 1.02 to 1.24]) and cerebral infarction (HR: 1.15 [95%CI: 1.02 to 1.29]). Smaller arteriolar diameters were neither related to the risk of stroke (HR per SD decrease: 1.02 [95%CI: 0.93 to 1.13]) nor to the risk of cerebral infarction (HR: 1.02 [95%CI: 0.90 to 1.15]). After additional adjustment for other cardiovascular risk factors, the results did not change. Conclusions: Larger retinal venular diameters are associated with an increased risk of stroke and cerebral infarction. The role of venules in cerebrovascular disease warrants further exploration.
文摘Background: Mutations in the parkin gene （PRKN） cause autosomal recessive early-onset Parkinson disease （EOPD）. Objective: To investigate the presence of mutations in the PRKN gene in a white family with EOPD and the genotype-phenotype correlations. Design: Twenty me mbers belonging to 3 generations of the EOPD fam ily with 4 affected subjects underwent genetic analysis. Direct genomic DNA sequ encing, semi-quantitative polymerase chain reaction, real-time quantitative po lymerase chain reaction, and reverse-transcriptase polymerase chain reaction an alyses were performed to identify the PRKN mutation. Results: Compound heterozyg ous mutations （T240M and EX 56 del） in the PRKN gene were identified in 4 patie nts with early onset （at ages 30-38 years）.Although heterozygous T240M and homo zygous EX 56 del mutations in the PRKN gene have been previously described,this is, to our knowledge, the first report of these mutations in compound heterozyg otes. The phenotype of patients was that of classic autosomal recessive EOPD cha racterized by beneficial response to levodopa, relatively slow progression,and m otor complications. All heterozygous mutation carriers （T240M or EX 56 del） and a 56-year-old woman who was a compound heterozygou s mutation carrier （T240M and EX 56 del） were free of any neurological symptoms . Conclusions:Compound heterozygous mutations （T240M and EX56 del） in the PRKN gene were found to cause autosomal recessive EOPD in 4 members of a large white family. One additional member with the same mutation, who is more than 10 years older than the mean age at onset of the 4 affected individuals, had no clinical manifestation of the disease. This incomplete penetrance has implications for ge netic counseling, and it suggests that complex gene-environment interactions ma y play a role in the pathogenesis of PRKN EOPD.
文摘The prion protein (PrP) is central to the prion diseases, although a role in other neurodegenerative diseases has been postulated. A common polymorphism (Met or Val) at codon 129 of the PrP gene (PRNP) features prominently in the risk and phenotype, of prion disease, and an abnormality in its distribution frequency may signal a role for PrP in other diseases. We conducted a case-control study to compare the PRNP codon 129 genotype distribution in Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and primary progressive aphasia (PPA), including 281 AD, 256 ALS,39 PPA, and 415 healthy control subjects. Statistical analysis was applied to determine the presence or absence of disease-specific genotype associations. The distribution of codon 129 genotypes was similar among healthy control, AD, and ALS subjects, although the heterozygous state was significantly overrepresented (age-adjusted odds ratio, 8.47) in PPA, a rare condition of unknown cause.Although these findings do not entirely exclude a role for PrP in AD or ALS, they do not support the codon 129 genotype as a risk factor for either disease. However, the strong association between heterozygosity and PPA raises new questions about its cause and the role of PrP in other neurodegenerative diseases.
文摘The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network.
文摘Background: Although more than 160 cases of iatrogenic Creutzfeldt-Jakob disease (iCJD) from human growth hormone (hGH) treatment have been documented, to our knowledge abnormal cerebellar findings on magnetic resonance imaging (MRI) have not been reported. Objective: To report a case of hGH-related iCJD with abnormal cerebellar MRI findings on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRI (DWI). Design: Case report. Setting: Outpatient neurology clinic at a university medical center. Patient: A 33-year old man who had sub acute gait ataxia and blurred vision. Results: Beginning 19 years prior, this pa tient had received cadaveric pituitary-derived hGH treatment for at least 5 yea rs. Magnetic resonance imaging revealed FLAIR and DWI abnormalities, particularl y in the cerebellum. He died 7 months after disease onset of autopsyconfirmed iC JD. Pathological changes corresponded largely to MRI findings. Conclusions: To o ur knowledge, this is the first case of hGH-related iCJD with FLAIR and DWI abn ormalities within the cerebellum. As symptoms referable to the cerebellum occur early in iCJD, it suggests that these MRI sequences may allow earlier diagnosis of this form of prion disease.
文摘Background: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia that is manifested by dream enactment behavior. The electrophysiologic substrate for RBD on polysomnography is rapid eye movement sleep without atonia. Rapid eye movement sleep behavior disorder likely stems from neuronal network dysfunction in the brainstem, although it is not yet clear which specific networks are involved. Rapid eye movement sleep behavior disorder is often associated with the sporadic synucleinopathies but rarely associated with the sporadic tauopathies. There are no reports on the possible association of rapid eye movement sleep without atonia and RBD with any familial tauopathy. Objective: To characterize the clinical sleep and polysomnography features in a kindred with a familial tauopathy. Methods: We performed standard polysomnography in 11 members of the pallidopontonigral degeneration kindred irrespective of any sleep-related complaints. Neuropathologic findings were analyzed in those who subsequently underwent autopsy. Results: Six affected and 5 genealogically at-risk family members were studied. None of the 11 had a history of dream enactment behavior. Nine of the 11 members attained sufficient rapid eye movement sleep on polysomnography, and the electrophysiologic features of rapid eye movement sleep without atonia and behavioral manifestations of RBD were absent in all subjects. Neuropathologic examination of 4 affected individuals revealed marked nigral degeneration in 3 along with mild degenerative changes in the locus coeruleus, pontine nuclei and tegmentum, and medullary tegmentum. Conclusions: These findings argue against nigral degeneration being the primary cause of RBD. The absence of the historical, electrophysiologic, and behavioral manifestations of RBD in this kindred provides further evidence that RBD is rare in the sporadic and familial tauopathies. The difference in frequencies of RBD associated with the synucleinopathies compared with the tauopathies suggests differences in the selective vu
文摘Background: Sjgren-Larsson syndrome (SLS) is an early childhood-onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene (the gene that encodes microsomal fatty aldehyde dehydrogenase). Cerebral proton magnetic resonance spectroscopy in those with SLS demonstrates an abnormal white matter peak at 1.3 ppm, consistent wit h long-chain fatty alcohol accumulation. Objective: To define the clinical cour se and proton magnetic resonance spectroscopic findings of SLS in adults. Design and Setting: Case series in a tertiary care center. Patients: Six siblings of a consanguineous Arab family with early childhood-onset SLS who carry the 682C→T mutation in the ALDH3A2 gene were reinvestigated in adulthood. Results: The 6 affected siblings ranged in age from 16 to 36 years. All exhibited the typical c linical and imaging manifestations of SLS, but their severity markedly varied. N eurological involvement was apparently nonprogressive, and its severity showed n o correlation with age. Cerebral proton magnetic resonance spectroscopy showed a lipid peak at 1.3 ppm, with decreasing intensity in the older siblings. Conclus ion: These observations document significant clinical variability and the nonpro gressive neurological course of SLS in adult siblings with the same ALDH3A2 geno type, and demonstrate possible correlation of proton magnetic resonance spectros copic changes with age, suggesting unknown pathogenic mechanisms to compensate f or the responsible biochemical defect in this disease.
文摘Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. Methods: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. Results: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95%CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95%CI 2.64 to 10.96), deep brain location (HR 3.25, 95%CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95%CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9%for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4%for those harboring all three risk factors. Conclusions: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.
文摘We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson’s disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonusers. Compared with nonusers, the relative risks were 0.73 for users of fewer than 2 tablets/week, 0.72 for 2 to 6.9 tablets/week, and 0.62 for 1 or more tablets/day (ptrend = 0.03). No association was found between the use of aspirin, other nonsteroidal antiinflammatory drugs, or acetaminophen and PD risk. The results suggest that ibuprofen use may delay or prevent the onset of PD.
