Abstract:
:The etiology of neurodegenerative diseases remains enigmatic; however, evidence for defects in energy metabolism, excitotoxicity, and for oxidative damage is increasingly compelling. It is likely that there is a complex interplay between these mechanisms. A defect in energy metabolism may lead to neuronal depolarization, activation of N-methyl-D-aspartate excitatory amino acid receptors, and increases in intracellular calcium, which are buffered by mitochondria. Mitochondria are the major intracellular source of free radicals, and increased mitochondrial calcium concentrations enhance free radical generation. Mitochondrial DNA is particularly susceptible to oxidative stress, and there is evidence of age-dependent damage and deterioration of respiratory enzyme activities with normal aging. This may contribute to the delayed onset and age dependence of neurodegenerative diseases. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Potential therapeutic approaches include glutamate release inhibitors, excitatory amino acid antagonists, strategies to improve mitochondrial function, free radical scavengers, and trophic factors. All of these approaches appear promising in experimental studies and are now being applied to human studies.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Beal MFdoi
10.1002/ana.410380304subject
Has Abstractpub_date
1995-09-01 00:00:00pages
357-66issue
3eissn
0364-5134issn
1531-8249journal_volume
38pub_type
杂志文章,评审abstract:OBJECTIVE:The Epi4K Consortium recently identified 4 de novo mutations in the γ-aminobutyric acid type A (GABAA ) receptor β3 subunit gene GABRB3 and 1 in the β1 subunit gene GABRB1 in children with one of the epileptic encephalopathies (EEs) Lennox-Gastaut syndrome (LGS) and infantile spasms (IS). Because the etiology...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24631
更新日期:2016-05-01 00:00:00
abstract::Dopamine transporter messenger RNA (mRNA) expression was assessed by in situ hybridization over individual pigmented neurons from the substantia nigra pars compacta in midbrain sections from 7 parkinsonian and 7 age-matched, neurologically normal patients. In the normal control brains, high levels of expression of dop...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350421
更新日期:1994-04-01 00:00:00
abstract::The monoclonal antibodies anti-Leu-19 and anti-NKH-1 recognize the CD56 differentiation antigen expressed on natural killer (NK) cells and on a T-cell subset. Because CD56 is an isoform of neural cell adhesion molecule (N-CAM), we examined its expression on human muscle using antibodies to Leu-19, NKH-1, and purified ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410310109
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:To design a new class of selective neuronal nitric oxide synthase (NOS) inhibitors, and demonstrate that administration in a rabbit model for cerebral palsy (CP) prevents hypoxia-ischemia-induced deaths and reduces the number of newborn kits exhibiting signs of CP. METHODS:We used a novel computer-based drug...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21555
更新日期:2009-02-01 00:00:00
abstract::We studied sleep patterns for three nights in 10 subjects with moderate to severe progressive supranuclear palsy and correlated the findings with disease severity using quantitative measures of motor, cognitive, and eye movement impairment. All subjects had severe insomnia, spending 2 to 6 hours awake per night; the m...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250609
更新日期:1989-06-01 00:00:00
abstract::In a double-blind crossover study in which patients received placebo or active drug for varying periods, we evaluated the ability of guanidine hydrochloride (20 to 35 mg/kg per day perorally) to improve the rate of recovery in patients with moderate or severe botulism, type A, intoxication. Among 14 patients who recei...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410060117
更新日期:1979-07-01 00:00:00
abstract::Life table methods were used to determine the relative risk of Alzheimer's disease (AD) in relatives of index cases with AD. Risk of AD was assessed in 967 first-degree relatives of 128 probands with clinically diagnosed AD and 572 first-degree relatives of a control group consisting of 84 subjects with Parkinson's di...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250511
更新日期:1989-05-01 00:00:00
abstract:OBJECTIVE:Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12. METHODS:This prospective monocenter study aimed at testing the hypothesis that AED treatment is ass...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22229
更新日期:2011-02-01 00:00:00
abstract::The cervical nerves may play a significant role in primary headache disorders. We reviewed the patterns of pain evoked by stimulation of the first 3 cervical nerves (C1-C3) in 10 patients with chronic occipital pain, 6 of whom also had migraine. Stimulation at the C1 level evoked periorbital and frontal pain in 6 of 6...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23869
更新日期:2013-07-01 00:00:00
abstract::A sensitive enzyme-linked immunosorbent assay method was employed to measure interleukin-2 (IL-2) levels in cerebrospinal fluid (CSF) and sera from 30 patients with multiple sclerosis (MS) and 8 patients with other neurological diseases. Detectable levels of IL-2 were found in 6 sera and 9 CSF samples of 21 patients w...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410240618
更新日期:1988-12-01 00:00:00
abstract::We report the clinical and neuropathological findings in an immunocompetent 19-year-old patient with a fatal acute Epstein-Barr virus (EBV) meningoencephalitis and a lymphoma-like B-lymphocyte response. Our results suggest that an immunotoxic rather than direct viral neuronal invasion mediates brain damage in EBV ence...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199905)45:5<659::aid-ana16>3.0.c
更新日期:1999-05-01 00:00:00
abstract::Recently, variant mRNA transcripts for the astroglial glutamate transporter EAAT2 have been detected in brain tissues of 60% of patients with sporadic amyotrophic lateral sclerosis (SALS). We have tested the hypothesis that the gene for EAAT2 may be defective in some ALS cases. In 16 familial ALS (FALS) pedigrees with...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410430514
更新日期:1998-05-01 00:00:00
abstract::Inborn errors of urea synthesis can present in the newborn period as a catastrophic illness or later in childhood or adulthood with an indolent course punctuated by hyperammonemic episodes. Because symptoms mimic other neuropsychiatric disorders, it is common for there to be a delay in diagnosis, often with dire conse...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410350204
更新日期:1994-02-01 00:00:00
abstract::The post-poliomyelitis syndrome (PPS) refers to symptoms of new weakness, fatigue, and pain years after recovery from acute poliomyelitis. Oligoclonal IgG bands have been reported in the cerebrospinal fluid (CSF) from PPS patients, suggesting that the syndrome is immune mediated or caused by persistent viral infection...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260604
更新日期:1989-12-01 00:00:00
abstract:OBJECTIVE:The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both wit...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.25669
更新日期:2020-03-01 00:00:00
abstract::Direct DNA tests for mutations in neurogenetic disorders are establishing a new era in diagnostic neurology. These highly accurate and specific tests will greatly improve diagnosis and genetic counseling, lead to more accurate assessment of prognosis, and reduce the cost of diagnostic evaluations. However, the use and...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410380204
更新日期:1995-08-01 00:00:00
abstract::The causes of amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are unknown. Furthermore, treatment for two of these conditions is almost totally lacking. The thesis is presented that each of these disorders is due to lack of a disorder-specific neurotrophic hormone. The hormone would be elaborat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410100602
更新日期:1981-12-01 00:00:00
abstract::We present the clinicopathological features of two siblings from a consanguineous marriage who presented with respiratory hypoventilation and died 10 days and 4 years later, respectively. This disorder showed extensive tau neuropathology, and both had a novel homozygous S352L tau gene mutation. This is the first descr...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10747
更新日期:2003-11-01 00:00:00
abstract::Alzheimer's disease (AD) and Parkinson's disease (PD) are generally considered to be separate and distinct disease entities. However, a considerable amount of evidence demonstrates that these disorders share common clinical and neuropathologic features and that overlap between the two conditions is extensive. For exam...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410440705
更新日期:1998-09-01 00:00:00
abstract::The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199911)46:5<732::aid-ana8>3.0.co
更新日期:1999-11-01 00:00:00
abstract::Biochemical examinations of brain tissue samples obtained from patients with Alzheimer's disease have revealed a decreased quantity of the neurotransmitter acetylcholine and reduced activity of choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine formation. It has been suggested that the choline ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200214
更新日期:1986-08-01 00:00:00
abstract::Epileptic patients experienced an irreversible loss of their peripheral visual field upon treatment with vigabatrin (gamma-vinyl GABA), an inhibitor of the GABA degrading enzyme, GABA transaminase. Subsequently, central visual function was reported to also be irreversibly altered. This visual loss is associated with a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20081
更新日期:2004-05-01 00:00:00
abstract::We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral h...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440518
更新日期:1998-11-01 00:00:00
abstract::In patients with Parkinson's disease and in normal subjects, the influence of tremor on repetitive voluntary movement was investigated in the index finger by comparing frequency of isometric force tremor with frequency of voluntary alternating isometric contractions. Tremor frequency, measured over the range from 0 to...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410300208
更新日期:1991-08-01 00:00:00
abstract::Sporadic amyotrophic lateral sclerosis is a motor neuron disease of unknown origin. Autoimmunity against voltage-gated calcium channels is one mechanism hypothesized to be the cause of the disease. In support of this hypothesis, it was previously reported that amyotrophic lateral sclerosis IgG specifically blocked the...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400505
更新日期:1996-11-01 00:00:00
abstract:OBJECTIVE:Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.22669
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVE:Determining if traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for Parkinson's disease (PD). This constitutes a research priority for the Veterans Administration (VA) with implications for screening policy and prevention. METHODS:Population-based, matched case-control ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25726
更新日期:2020-07-01 00:00:00
abstract::A 41-year-old right-handed man developed disturbances of language and memory after a discrete thalamic infarction. Detailed neuropsychological assessment revealed deficits in verbal fluency, word finding, confrontation naming, and anterograde memory for verbal material. High-resolution computed tomography with stereot...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200604
更新日期:1986-12-01 00:00:00
abstract::Immunohistochemical examination of 20 Down's syndrome brains, using antibodies to alpha-, beta-, and gamma-synuclein, demonstrated many alpha-synuclein-positive Lewy bodies and dystrophic neurites in 50% of amygdala samples from Down's syndrome brains with Alzheimer's disease. Similar lesions were less common in other...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199903)45:3<353::aid-ana11>3.0.c
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:The UCHL-1 gene is widely cited as a susceptibility factor for sporadic Parkinson's disease (PD). The strongest evidence comes from a meta-analysis of small studies that reported the S18Y polymorphism as protective against PD, after pooling studies of white and Asian subjects. Here, we present data that chall...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.20757
更新日期:2006-04-01 00:00:00