Abstract:
OBJECTIVE:What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. METHODS:Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. RESULTS:Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. INTERPRETATION:These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Lutkenhoff ES,Chiang J,Tshibanda L,Kamau E,Kirsch M,Pickard JD,Laureys S,Owen AM,Monti MMdoi
10.1002/ana.24423subject
Has Abstractpub_date
2015-07-01 00:00:00pages
68-76issue
1eissn
0364-5134issn
1531-8249journal_volume
78pub_type
杂志文章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::The etiopathogenesis of Parkinson's disease (PD) has been elusive. Recently, several lines of evidence have converged to suggest that defects in the ubiquitin-proteasome system and proteolytic stress underlie nigral pathology in both familial and sporadic forms of the illness. In support of this concept, mutations in ...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.10512
更新日期:2003-01-01 00:00:00
abstract::During passive extension of the elbow, the triceps muscle normally shows a burst of electromyographic activity. This shortening reaction (SR) is known to be exaggerated in extrapyramidal disease states, but the effects of cerebellar disease are unknown. The SR was measured in both arms of a patient with hemiataxia, th...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110307
更新日期:1982-03-01 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::Ten patients developed a subacute lower motor neuron syndrome as a remote effect of Hodgkin's disease or other lymphoma. The illness usually followed a benign course independent of the activity of the underlying neoplasm. Seven of the patients improved spontaneously, and 3 became neurologically normal. Two patients di...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050310
更新日期:1979-03-01 00:00:00
abstract:OBJECTIVE:To investigate the frequency and subtypes of mild cognitive impairment (MCI) in idiopathic rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease (PD) in association with RBD. METHODS:One hundred and twelve subjects without dementia or major depression including 32 idiopathic RBD patients, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21680
更新日期:2009-07-01 00:00:00
abstract:OBJECTIVE:Fast oscillations (FOs) were first explored from scalp electroencephalographic (EEG) data from hypsarrhythmia in West syndrome (infantile spasms) to investigate the meaning of FOs in this epileptic encephalopathy. METHODS:In 17 infants with West syndrome, we conservatively detected fast frequency peaks that ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24299
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Narcolepsy is caused by the loss of hypocretin/orexin neurons in the hypothalamus, which is likely the result of an autoimmune process. Recently, concern has been raised over reports of narcolepsy in northern Europe following H1N1 vaccination. METHODS:The study is a retrospective analysis of narcolepsy onset...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22587
更新日期:2011-09-01 00:00:00
abstract::The regional metabolic rate for glucose (rMRglu) was studied in macaque monkeys after spinal cord transection at T10, both during spinal shock and after reflexes had returned. The rMRglu was measured in all Rexed layers in cord segments both caudal and rostral to the level of the transection utilizing the quantitative...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140106
更新日期:1983-07-01 00:00:00
abstract::A total of 36 patients with Batten disease (juvenile-onset neuronal ceroid lipofuscinosis), homozygous or heterozygous for the major mutation, a 1.02-kb deletion, in the CLN3 gene, were studied to relate their genotype to their clinical phenotype. The onset of visual failure and epilepsy was highly concordant in both ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410420517
更新日期:1997-11-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22692
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVE:Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Attributable to the complex alterations involved in epileptogenesis, it is likely that multitargeted approaches ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24804
更新日期:2016-12-01 00:00:00
abstract:OBJECTIVES:African Americans are at greater risk for developing Alzheimer's disease (AD) dementia than non-Hispanic whites. In addition to biological considerations (eg, genetic influences and comorbid disorders), social and environmental factors may increase the risk of AD dementia. This paper (1) assesses neuroimagin...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25948
更新日期:2021-02-01 00:00:00
abstract:OBJECTIVE:Cognitive impairment is common in epilepsy, particularly in memory function. Interictal spikes (IISs) are thought to disrupt cognition, but it is difficult to delineate their contribution from general impairments in memory produced by etiology and seizures. We investigated the transient impact of focal IISs o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21896
更新日期:2010-02-01 00:00:00
abstract::Previous studies using two seizure paradigms, electroconvulsive shock and kindling, suggested potential sites of endogenous thyrotropin-releasing hormone (TRH) action in specific epileptogenic areas. We studied TRH gene expression and TRH receptors in rat limbic areas using the kindling model of epilepsy. Immunoassaya...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410330112
更新日期:1993-01-01 00:00:00
abstract::We have observed many focal dilatations or very small aneurysms in terminal arterioles and capillaries of 4 of 5 patients and 6 dogs who had recently undergone cardiopulmonary bypass. A smaller number of sausagelike dilatations distended medium-sized arterioles. Two other patients had a small number of the same microv...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410280403
更新日期:1990-10-01 00:00:00
abstract:OBJECTIVE:Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (ie, loba...
journal_title:Annals of neurology
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1002/ana.25079
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain lar...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25827
更新日期:2020-09-01 00:00:00
abstract::Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation inclu...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140506
更新日期:1983-11-01 00:00:00
abstract::Intracranial abscesses are uncommon in the newborn. Observation of 2 infants and a review of the literature reveal that the offending organism was a Citrobacter in 12 of the 16 documented cases. In the Neonatal Meningitis Cooperative Study this organism was responsible for meningitis in only 4%. However, an analysis o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080308
更新日期:1980-09-01 00:00:00
abstract::Twenty-six patients with late-stage Parkinson disease were given 0.4 to 15 mg of pergolide mesylate daily in addition to, or as replacement for, levodopa or bromocriptine therapy. Despite treatment with individually determined optimum doses of levodopa, bromocriptine, and anticholinergics, they had shown response fail...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410120305
更新日期:1982-09-01 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::Spinal muscular atrophy (SMA) is a motor neuron disease caused by dysfunction of the survival motor neuron (SMN) gene. Human SMN gene is present in duplicated copies: SMN1 and SMN2. More than 95% of patients with SMA lack a functional SMN1 but retain at least one copy of SMN2. Unlike SMN1, SMN2 is primarily transcribe...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20548
更新日期:2005-08-01 00:00:00
abstract::Nineteen patients with radiologically confirmed stroke, and varying degrees of hemiparesis, were studied using somatosensory evoked potentials and the recently developed technique of transcutaneous motor cortex stimulation. The functional deficit caused by stroke was assessed at the time of evoked potential testing an...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250111
更新日期:1989-01-01 00:00:00
abstract::Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson's disease, whereas if this process also occurs in the cortical neurons, it is considered pathognomonic for dementia with Lewy bodies. However, the link between alpha-synuclein incorporation into ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20321
更新日期:2005-01-01 00:00:00
abstract::Because the symptomatic treatments for multiple sclerosis (MS) are limited, new approaches have been sought. Anatomical studies of MS lesions show a relative preservation of axons, and clinical studies suggest that some of the neurological impairment in patients with MS is physiological. Electrophysiological studies s...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410360728
更新日期:1994-01-01 00:00:00
abstract::Various C-terminally truncated amyloid beta peptides (Abeta) are linked to Alzheimer's disease (AD) pathogenesis. Cerebrospinal fluid (CSF) concentrations of Abeta38, Abeta40, and Abeta42 were measured by enzyme-linked immunosorbent assay in 30 patients with AD and 26 control subjects. CSF Abeta42 levels was decreased...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20508
更新日期:2005-07-01 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:OBJECTIVE:Small-fiber sensory and autonomic symptoms are early presentations of familial amyloid polyneuropathy (FAP) with transthyretin (TTR) mutations. This study aimed to explore the potential of skin nerve pathologies as early and disease-progression biomarkers and their relationship with skin amyloid deposits. ME...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25433
更新日期:2019-04-01 00:00:00
abstract:OBJECTIVE:To identify brain regions, cell types, or both that generate abnormal electrical discharge in tuberous sclerosis complex (TSC). Here we examined excitatory and inhibitory synaptic currents in human tissue samples obtained from a TSC patient with no discernible cortical tubers and acute neocortical brain slice...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21058
更新日期:2007-02-01 00:00:00