Abstract:
:The mucopolysaccharidoses are caused by inherited deficiencies of lysosomal enzymes involved in the degradative pathway of glycosaminoglycans. Lysosomal storage leads to cellular and organ dysfunction, including mental retardation. Storage lesions are found throughout the diseased brain, but little is known about the cellular and molecular mechanisms that underlie brain dysfunction. In the mouse model of mucopolysaccharidosis VII, we found that specific regions of the brain are vulnerable to neurodegeneration, characterized by the presence of ubiquitin inclusions, neurofilament inclusions, and reactive astrogliosis. The pathological lesions were found predominantly in the hippocampus and cerebral cortex, and they increased progressively with age. Treatment with a recombinant viral vector to correct the enzymatic defect quantitatively reversed the neurodegenerative lesions in targeted regions to normal levels.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Heuer GG,Passini MA,Jiang K,Parente MK,Lee VM,Trojanowski JQ,Wolfe JHdoi
10.1002/ana.10373keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
762-70issue
6eissn
0364-5134issn
1531-8249journal_volume
52pub_type
杂志文章abstract::Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [18F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glu...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140605
更新日期:1983-12-01 00:00:00
abstract::Basis pontis lacunes cause contralateral but rarely ipsilateral ataxia. We explored this phenomenon with isotope tract tracing in the rhesus monkey. Labeled pontocerebellar fibers cross midline and disperse widely in the opposite hemipons before coalescing in the brachium pontis. This anatomical arrangement suggests t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20060
更新日期:2004-04-01 00:00:00
abstract:OBJECTIVE:Low vitamin D status at birth may be associated with risk of adult onset multiple sclerosis, but this link has not been studied directly. We assessed the relation between neonatal vitamin D concentrations, measured in stored blood samples, and risk of multiple sclerosis. METHODS:This was a population-based c...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24210
更新日期:2014-09-01 00:00:00
abstract::Nineteen patients aged 4 to 44 years with generalized epilepsy and generalized 3 Hz spike-and-wave activity, were monitored for 24 or 36 hours on one to nine occasions to determine the time distribution of ictal and interictal electroencephalographic discharges and the consistency of the time patterns observed. Two pa...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080506
更新日期:1980-11-01 00:00:00
abstract::A 51-year-old diabetic woman developed bilateral rhinoorbitocerebral phycomycosis. Successful treatment was accomplished by correction of the ketoacidosis, surgical debridement, and amphotericin B therapy. Rhinoorbitocerebral phycomycosis is a fulminant and frequently fatal disease most often seen in debilitated hosts...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410060210
更新日期:1979-08-01 00:00:00
abstract::Two families with a point mutation in mtDNA associated with myoclonic epilepsy and ragged-red fiber disease showed pronounced clinical heterogeneity. The mothers of the two families had adult-onset myopathy with ragged-red fibers, partial deficiency of cytochrome c oxidase, and sensory neuropathy. Members of the first...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410330613
更新日期:1993-06-01 00:00:00
abstract::Two distinct deficits of ocular smooth pursuit could be demonstrated using two types of visual stimulus motion in a patient who had suffered bilateral occipitoparietal lobe infarction. First, in response to constant-velocity (zero acceleration) target motion, smooth pursuit gain (eye velocity/target velocity) was mild...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410170213
更新日期:1985-02-01 00:00:00
abstract::An inception cohort of 40 children and adolescents with traumatic brain injury and suspected diffuse axonal injury were studied using a new high-resolution magnetic resonance imaging susceptibility-weighted technique that is very sensitive for hemorrhage. A blinded comparison was performed between the extent of parenc...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20123
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:Neuronal loss, a key substrate of irreversible disability in multiple sclerosis (MS), is a recognized feature of MS cortical pathology of which the cause remains unknown. Fibrin(ogen) deposition is neurotoxic in animal models of MS, but has not been evaluated in human progressive MS cortex. The aim of this st...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24997
更新日期:2017-08-01 00:00:00
abstract::Neurofilaments, assembled from NF-L (68 kd), NF-M (95 kd), and NF-H (115 kd), are the most abundant structural components in large myelinated axons, particularly those of motor neurons. Aberrant neurofilament accumulation in cell bodies and axons of motor neurons is a prominent pathological feature of several motor ne...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400410
更新日期:1996-10-01 00:00:00
abstract:OBJECTIVE:Nonketotic hyperglycinemia is a neurometabolic disorder characterized by intellectual disability, seizures, and spasticity. Patients with attenuated nonketotic hyperglycinemia make variable developmental progress. Predictive factors have not been systematically assessed. METHODS:We reviewed 124 patients stra...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24485
更新日期:2015-10-01 00:00:00
abstract::The published information on glutamate levels in cerebrospinal fluid (CSF) and modifications in neurological disorders is controversial. In the present study, we demonstrated a metabolic instability of glutamate in untreated CSF and a spurious elevation of its levels by the current methods of CSF acidification. These ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410330316
更新日期:1993-03-01 00:00:00
abstract::Successful axon regeneration depends on the expression of regeneration-associated genes by axotomized neurons. Here, we demonstrate, for the first time to our knowledge, the expression of regeneration-associated genes by axotomized human CNS neurons. In situ hybridization and immunohistochemistry showed a transient in...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10724
更新日期:2003-10-01 00:00:00
abstract:OBJECTIVE:It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-labe...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/ana.24700
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVE:Huntington's disease (HD) is a monogenic, fully penetrant neurodegenerative disorder, providing an ideal model for understanding brain changes occurring in the years prior to disease onset. Diffusion tensor imaging (DTI) studies show widespread white matter disorganization in the early premanifest stages (pre...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.25309
更新日期:2018-10-01 00:00:00
abstract::Using three adjustments, we have revised a 1976 prevalence count for multiple sclerosis in the United States. The adjustments were made to data from a US national survey; they used 1990 population projections from the US Bureau of the Census, and results of investigations conducted in Weld and Larimer Countries, Color...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410310317
更新日期:1992-03-01 00:00:00
abstract:OBJECTIVE:Charcot-Marie-Tooth type 4J (CMT4J) is a rare autosomal recessive neuropathy caused by mutations in FIG4 that result in loss of FIG4 protein. This study investigates the natural history and mechanisms of segmental demyelination in CMT4J. METHODS:Over the past 9 years, we have enrolled and studied a cohort of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25198
更新日期:2018-04-01 00:00:00
abstract::We used spin-echo magnetic resonance imaging and proton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventric...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410360110
更新日期:1994-07-01 00:00:00
abstract:OBJECTIVE:The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis. METHODS:In this ret...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.21222
更新日期:2008-01-01 00:00:00
abstract::Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase protein family. The members of this protein family function as multiple domain adaptor proteins originally identified at cell junctions and synapses. Insertional mutations or targeted disruption of the CASK ge...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21755
更新日期:2009-10-01 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::Previous imaging studies using 11C-flumazenil in patients with mesial temporal lobe epilepsy and neocortical partial seizure disorders have found focal decreases in gamma-aminobutyric acid type A/benzodiazepine receptor binding. These studies used subjective visual assessment and a region of interest approach to quant...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400210
更新日期:1996-08-01 00:00:00
abstract:OBJECTIVE:Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24151
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVE:Creatine kinase (CK) levels are increased on dried blood spots in newborns related to the birthing process. As a marker for newborn screening, CK in Duchenne muscular dystrophy (DMD) results in false-positive testing. In this report, we introduce a 2-tier system using the dried blood spot to first assess CK w...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.23528
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to neurological debilitation, including motor dysfunction and frank dementia. Although pharmacological control of HIV infection is now possible, HIV-associated neurocognitive disorders (HAND) remain intractable. Here, we report that chronic trea...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22070
更新日期:2010-09-01 00:00:00
abstract::Five monkeys trained to perform with the extremity contralateral to a stimulus had unilateral neglect induced by frontal and reticular formation lesions. Postoperatively the performance of the animals was abnormal only on ipsilateral stimulation, which suggests that the mechanism underlying neglect in these subjects i...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030609
更新日期:1978-06-01 00:00:00
abstract::Systems for automatic assessment of cutaneous touch-pressure, vibratory, and thermal sensation have been developed. These systems use stimuli which are quantified and reproducible, a two-alternative forced-choice technique, and programmed steps to test, score, and report. If normal responses from series of healthy per...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040605
更新日期:1978-12-01 00:00:00
abstract::The long-term effects of brief but repetitive febrile seizures (FS) on memory have not been as thoroughly investigated as the impact of single and prolonged seizure in the developing brain. Using a heated-air FS paradigm, we subjected male rat pups to one, three, or nine episodes of brief FS on days 10 to 12 postpartu...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10789
更新日期:2003-12-01 00:00:00
abstract::Only 6 patients with intracranial hypertension associated with unruptured cerebral arteriovenous malformations have been reported. We report 6 additional patients seen at the Cleveland Clinic during the past 10 years. The average age was 28 years (range, 19-44 years); 4 were women. Symptoms and signs included papilled...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410270504
更新日期:1990-05-01 00:00:00
abstract::The purpose of this study was to explore the feasibility of obtaining magnetic resonance-measured cerebral metabolic rate of oxygen utilization (MR-CMRO(2)) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 +/- 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom o...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.10433
更新日期:2003-02-01 00:00:00