Abstract:
OBJECTIVE:Our goal was to define the genetic cause of the profound hypomyelination in the taiep rat model and determine its relevance to human white matter disease. METHODS:Based on previous localization of the taiep mutation to rat chromosome 9, we tested whether the mutation resided within the Tubb4a (β-tubulin 4A) gene, because mutations in the TUBB4A gene have been described in patients with central nervous system hypomyelination. To determine whether accumulation of microtubules led to progressive demyelination, we analyzed the spinal cord and optic nerves of 2-year-old rats by light and electron microscopy. Cerebral white matter from a patient with TUBB4A Asn414Lys mutation and magnetic resonance imaging evidence of severe hypomyelination were studied similarly. RESULTS:As the taiep rat ages, there is progressive loss of myelin in the brain and dorsal column of the spinal cord associated with increased oligodendrocyte numbers with accumulation of microtubules. This accumulation involved the entire cell body and distal processes of oligodendrocytes, but there was no accumulation of microtubules in axons. A single point mutation in Tubb4a (p.Ala302Thr) was found in homozygous taiep samples. A similar hypomyelination associated with increased oligodendrocyte numbers and arrays of microtubules in oligodendrocytes was demonstrated in the human patient sample. INTERPRETATION:The taiep rat is the first animal model of TUBB4 mutations in humans and a novel system in which to test the mechanism of microtubule accumulation. The finding of microtubule accumulation in a patient with a TUBB4A mutation and leukodystrophy confirms the usefulness of taiep as a model of the human disease. Ann Neurol 2017;81:690-702.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Duncan ID,Bugiani M,Radcliff AB,Moran JJ,Lopez-Anido C,Duong P,August BK,Wolf NI,van der Knaap MS,Svaren Jdoi
10.1002/ana.24930subject
Has Abstractpub_date
2017-05-01 00:00:00pages
690-702issue
5eissn
0364-5134issn
1531-8249journal_volume
81pub_type
杂志文章abstract::We have recently reported homozygous mutations in the PINK1 gene in three consanguineous families with early-onset parkinsonism (EOP) linked to the PARK6 locus. To further evaluate the pathogenic role of PINK1 in EOP and to draw genotype-phenotype correlates, we performed PINK1 mutation analysis in a cohort of Italian...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20256
更新日期:2004-09-01 00:00:00
abstract:OBJECTIVE:Normal aging is often associated with a decline in learning and memory functions. This decline is manifested to a much greater extent in Alzheimer's disease. Recent studies have indicated statins, a class of cholesterol-lowering drugs, as a potential therapy for Alzheimer's disease. Our objective was to deter...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21053
更新日期:2006-12-01 00:00:00
abstract::Detrusor hyperreflexia is a relevant clinical symptom for patients suffering from Parkinson's disease. In a series of 16 patients, we demonstrated that subthalamic deep brain stimulation has a significant and urodynamically recordable effect leading to a normalization of pathologically increased bladder sensibility. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10806
更新日期:2004-01-01 00:00:00
abstract::A 9-year-old, blind boy with severe mental retardation with a chronic sleep/wake disturbance had a circadian rhythm of 24.75 hours and an internal desynchronization of the endogenous rhythms. Treatment with oral melatonin given at 6 PM induced a regular sleep/wake pattern. Melatonin, in this patient, convincingly entr...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290318
更新日期:1991-03-01 00:00:00
abstract:OBJECTIVE:Mutations of the selenoprotein N gene (SEPN1) cause SEPN1-related myopathy (SEPN1-RM), a novel early-onset muscle disorder formerly divided into four different nosological categories. Selenoprotein N (SelN) is the only selenoprotein involved in a genetic disease; its function being unknown, no treatment is av...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21644
更新日期:2009-06-01 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::Recently, the mutation causing early-onset generalized torsion dystonia has been identified as a GAG deletion in the gene for an adenosine triphosphate-binding protein named torsinA. We describe a German family with 5 clinically affected individuals carrying this mutation. In at least 4 of the 5 patients, the disease ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440119
更新日期:1998-07-01 00:00:00
abstract:OBJECTIVE:Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome, but it has been difficult to dissociate the effects of epilepsy from the role of antiepileptic drugs. To distinguish the effects of chronic seizures from medication, we used the laboratory rat, be...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21518
更新日期:2008-12-01 00:00:00
abstract::The nucleus basalis of Meynert, which supplies diffuse cholinergic fibers to the cerebral neocortex, was investigated in two cases of parkinsonism-dementia complex of Guam (PDG). The nucleus basalis of the two PDG patients showed extensive neuron loss when compared with age-matched non-Guamanian controls, suggesting t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410130118
更新日期:1983-01-01 00:00:00
abstract::A 37-year-old woman with primary Sjögren syndrome developed mixed cryoglobulinemia and systemic vasculitis. Subarachnoid hemorrhage occurred as a result of necrotizing anterior spinal arteritis. Although rarely seen in mixed cryoglobulinemia, central nervous system complications have recently been documented in Sjögre...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110614
更新日期:1982-06-01 00:00:00
abstract:OBJECTIVE:To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI). METHODS:Biochemical, Western blot, histological, immunohistochemical, electron microscopic, electrophysiological, and behavior assessments were performed to investigate (1) SCI-induced PLA2 activity, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20798
更新日期:2006-04-01 00:00:00
abstract::A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, c...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410370515
更新日期:1995-05-01 00:00:00
abstract::Although nerve conduction slowing is a well-accepted abnormality in rats with acute experimental diabetes, reports of neuropathological changes in diabetic rat nerves have been inconsistent. To examine this further, we studied electrophysiological and morphological features of posterior tibial nerves and their distal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080207
更新日期:1980-08-01 00:00:00
abstract::A patient is described with the dermatological features of blue rubber bleb nevus syndrome (BRBNS), focal seizures, and lateralized neurological signs. CAT scan demonstrated a nonenhanced density in the region of the vein of Galen. Neuropathological examination showed that this density was a clot within a vein of Gale...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030522
更新日期:1978-05-01 00:00:00
abstract::Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progressi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10094
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVE:To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis. METHODS:A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intentio...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1002/ana.21079
更新日期:2007-01-01 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: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::The phenotype of severe congenital hydrocephalus secondary to neural cell adhesion molecule L1 (L1CAM) gene mutations includes the distinct finding of brainstem corticospinal tract hypoplasia. Using diffusion-weighted imaging (DWI), we failed to demonstrate anisotropy in the corticospinal tracts of the basis pontis in...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Ferric ion-ferrocyanide (Fe-FeCN) staining was used to stain nodes of Ranvier in remyelinating central nervous system (CNS) axons following viral-induced demyelination. As at normal nodes, Fe-FeCN staining was observed on the cytoplasmic surface of the nodal axolemma of remyelinated fibers. These fibers were identifie...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080606
更新日期:1980-12-01 00:00:00
abstract::Acute Epstein-Barr virus (EBV) infection of the central nervous system (CNS) is associated with meningoencephalitis and other neurological syndromes and with CNS lymphomas (CNSLs). Diagnosis is based on serological studies and more recently on detection of EBV DNA in cerebrospinal fluid (CSF) by polymerase chain react...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10321
更新日期:2002-11-01 00:00:00
abstract::We have conducted a trial to randomly assess the efficacy and tolerance of intravenous immunoglobulin (i.v.Ig) or plasma exchange (PE) in myasthenia gravis (MG) exacerbation and to compare two doses of i.v.Ig. Eighty-seven patients with MG exacerbation were randomized to receive either three PE (n = 41), or i.v.Ig (n ...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/ana.410410615
更新日期:1997-06-01 00:00:00
abstract::Autosomal dominant spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. Recently, mild CAG repeat expansion in the alpha1A voltage-dependent calcium channel gene has been found to be associated with a type of autosomal dominant SCA (SCA6). We analyzed 98 J...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410420609
更新日期:1997-12-01 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::Patients with the acquired immunodeficiency syndrome (AIDS) commonly display evidence of gross cerebral atrophy, but its true incidence and pathophysiology in the general AIDS population are unknown. In this study, we measured cerebrospinal fluid (CSF) spaces in 64 consecutively autopsied patients with AIDS, compared ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410320107
更新日期:1992-07-01 00:00:00
abstract::An in vitro preparation has been developed in which epileptogenesis in mammalian central nervous system tissue may be studied. Addition of sodium penicillin to the medium bathing slices of guinea pig hippocampus induced epileptiform activity similar to that seen in hippocampal penicillin foci in vivo. Epileptiform eve...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410010510
更新日期:1977-05-01 00:00:00
abstract::The prevalence of migraine is much greater in female than male individuals. Cortical spreading depression (CSD) is thought to be a fundamental mechanism of migraine, and CSD in rodents is used as a model for migraine. We used optical intrinsic signal imaging and electrophysiological techniques to investigate CSD in C5...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21138
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:The effect of prestroke aspirin use on initial severity, hemorrhagic transformation, and functional outcome of ischemic stroke is uncertain. METHODS:Using a multicenter stroke registry database, patients with acute ischemic stroke of three subtypes (large artery atherosclerosis [LAA], small vessel occlusion ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24602
更新日期:2016-04-01 00:00:00
abstract::Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050112
更新日期:1979-01-01 00:00:00
abstract::Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe struct...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00