Axon-Myelin Unit Blistering as Early Event in MS Normal Appearing White Matter.

Abstract:

OBJECTIVE:Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of unknown etiology. Although the prevalent view regards a CD4+ -lymphocyte autoimmune reaction against myelin at the root of the disease, recent studies propose autoimmunity as a secondary reaction to idiopathic brain damage. To gain knowledge about this possibility we investigated the presence of axonal and myelinic morphological alterations, which could implicate imbalance of axon-myelin units as primary event in MS pathogenesis. METHODS:Using high resolution imaging histological brain specimens from patients with MS and non-neurological/non-MS controls, we explored molecular changes underpinning imbalanced interaction between axon and myelin in normal appearing white matter (NAWM), a region characterized by normal myelination and absent inflammatory activity. RESULTS:In MS brains, we detected blister-like swellings formed by myelin detachment from axons, which were substantially less frequently retrieved in non-neurological/non-MS controls. Swellings in MS NAWM presented altered glutamate receptor expression, myelin associated glycoprotein (MAG) distribution, and lipid biochemical composition of myelin sheaths. Changes in tethering protein expression, widening of nodes of Ranvier and altered distribution of sodium channels in nodal regions of otherwise normally myelinated axons were also present in MS NAWM. Finally, we demonstrate a significant increase, compared with controls, in citrullinated proteins in myelin of MS cases, pointing toward biochemical modifications that may amplify the immunogenicity of MS myelin. INTERPRETATION:Collectively, the impaired interaction of myelin and axons potentially leads to myelin disintegration. Conceptually, the ensuing release of (post-translationally modified) myelin antigens may elicit a subsequent immune attack in MS. ANN NEUROL 2021.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Luchicchi A,Hart B,Frigerio I,van Dam AM,Perna L,Offerhaus HL,Stys PK,Schenk GJ,Geurts JJG

doi

10.1002/ana.26014

subject

Has Abstract

pub_date

2021-01-06 00:00:00

eissn

0364-5134

issn

1531-8249

pub_type

杂志文章
  • Botulinum toxin type A for neuropathic pain in patients with spinal cord injury.

    abstract:OBJECTIVE:To evaluate the analgesic effect of botulinum toxin type A (BTX-A) on patients with spinal cord injury-associated neuropathic pain. METHODS:The effect of BTX-A on 40 patients with spinal cord injury-associated neuropathic pain was investigated using a randomized, double-blind, placebo-controlled design. A 1-...

    journal_title:Annals of neurology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/ana.24605

    authors: Han ZA,Song DH,Oh HM,Chung ME

    更新日期:2016-04-01 00:00:00

  • Chronic idiopathic anhidrosis.

    abstract::We describe the cases of eight patients with chronic idiopathic anhidrosis. These patients were heat intolerant and became hot, flushed, dizzy, dyspneic, and weak but did not sweat when the ambient temperature was high or when they exercised. Four patients had preganglionic sudomotor lesions and in the remaining 4 the...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410180312

    authors: Low PA,Fealey RD,Sheps SG,Su WP,Trautmann JC,Kuntz NL

    更新日期:1985-09-01 00:00:00

  • Relationships between extrapyramidal signs and cognitive function in a community-dwelling cohort of patients with Parkinson's disease and normal elderly individuals.

    abstract::The relationship between extrapyramidal sign (EPS) severity and cognitive function was investigated in 184 patients with idiopathic Parkinson's disease (PD) and 301 normal elderly individuals from a community-dwelling cohort in northern Manhattan, New York City. Fifty-six of the patients with PD met criteria for demen...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410330307

    authors: Richards M,Stern Y,Marder K,Cote L,Mayeux R

    更新日期:1993-03-01 00:00:00

  • Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients.

    abstract:OBJECTIVE:Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Although the clinical impact of gray matter pathology in MS brains is unknown, 30 to 40% of MS patients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investiga...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.22337

    authors: Dutta R,Chang A,Doud MK,Kidd GJ,Ribaudo MV,Young EA,Fox RJ,Staugaitis SM,Trapp BD

    更新日期:2011-03-01 00:00:00

  • Residual tumor cells are unique cellular targets in glioblastoma.

    abstract::Residual tumor cells remain beyond the margins of every glioblastoma (GBM) resection. Their resistance to postsurgical therapy is considered a major driving force of mortality, but their biology remains largely uncharacterized. In this study, residual tumor cells were derived via experimental biopsy of the resection m...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.22036

    authors: Glas M,Rath BH,Simon M,Reinartz R,Schramme A,Trageser D,Eisenreich R,Leinhaas A,Keller M,Schildhaus HU,Garbe S,Steinfarz B,Pietsch T,Steindler DA,Schramm J,Herrlinger U,Brüstle O,Scheffler B

    更新日期:2010-08-01 00:00:00

  • No evidence for genetic association or linkage of the cathepsin D (CTSD) exon 2 polymorphism and Alzheimer disease.

    abstract::Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations an...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/1531-8249(200101)49:1<114::aid-ana18>3.0.c

    authors: Bertram L,Guénette S,Jones J,Keeney D,Mullin K,Crystal A,Basu S,Yhu S,Deng A,Rebeck GW,Hyman BT,Go R,McInnis M,Blacker D,Tanzi R

    更新日期:2001-01-01 00:00:00

  • Stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy.

    abstract:OBJECTIVE:To evaluate the outcomes 1 year and longer following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a large series of patients treated over a 5-year period since introduction of this novel technique. METHODS:Surgical outcomes of a consecutive series of 58 patients with mesial ...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.25180

    authors: Gross RE,Stern MA,Willie JT,Fasano RE,Saindane AM,Soares BP,Pedersen NP,Drane DL

    更新日期:2018-03-01 00:00:00

  • Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke.

    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

    authors: Barreto AD,Fanale CV,Alexandrov AV,Gaffney KC,Vahidy FS,Nguyen CB,Sarraj A,Rahbar M,Grotta JC,Savitz SI,Wake-Up Stroke Investigators.

    更新日期:2016-08-01 00:00:00

  • Hypoperfusion of Wernicke's area predicts severity of semantic deficit in acute stroke.

    abstract::Based on earlier findings that the presence of word comprehension impairment (a deficit in the meaning of words, or lexical semantics) in acute stroke was strongly associated with the presence of hypoperfusion or infarct in Wernicke's area, we tested the hypothesis that the severity of word comprehension impairment wa...

    journal_title:Annals of neurology

    pub_type: 临床试验,杂志文章

    doi:10.1002/ana.1265

    authors: Hillis AE,Wityk RJ,Tuffiash E,Beauchamp NJ,Jacobs MA,Barker PB,Selnes OA

    更新日期:2001-11-01 00:00:00

  • T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy.

    abstract:OBJECTIVE:To determine the clinical consequences of the PMP22 point mutation, T118M, which has been previously considered to either cause an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism. METHODS:We analyzed patients from five separate kindreds and characterized their periph...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.20777

    authors: Shy ME,Scavina MT,Clark A,Krajewski KM,Li J,Kamholz J,Kolodny E,Szigeti K,Fischer RA,Saifi GM,Scherer SS,Lupski JR

    更新日期:2006-02-01 00:00:00

  • Ultrastructural, neurological, and glycosaminoglycan abnormalities in lowe's syndrome.

    abstract::The oculocerebrorenal syndrome (OCRS), Lowe's syndrome, is an X-linked, recessive disease characterized by mental retardation, congenital corneal abnormalities and cataracts, growth failure, rickets, osseous abnormalities, renal dysfunction with periodic acidosis, hypotonia, and areflexia. Ultrastructural studies of s...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410160109

    authors: Wisniewski KE,Kieras FJ,French JH,Houck GE Jr,Ramos PL

    更新日期:1984-07-01 00:00:00

  • Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I.

    abstract::The duration of the antiparkinsonian action of levodopa was studied in 48 patients with various response patterns to the oral administration of the dopamine precursor. Deterioration in motor scores after abrupt cessation of a steady-state intravenous levodopa infusion occurred at two successive rates: an initial rapid...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410240303

    authors: Fabbrini G,Mouradian MM,Juncos JL,Schlegel J,Mohr E,Chase TN

    更新日期:1988-09-01 00:00:00

  • Human immunodeficiency virus infection of dorsal root ganglion neurons detected by polymerase chain reaction in situ hybridization.

    abstract::A predominantly sensory peripheral neuropathy is common with human immunodeficiency virus (HIV) infection, but the cause is unknown. Formalin-fixed dorsal root ganglia (DRG), obtained at postmortem from patients with neuropathy and HIV infection and from control subjects, were examined for the presence of HIV DNA by u...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410420315

    authors: Brannagan TH 3rd,Nuovo GJ,Hays AP,Latov N

    更新日期:1997-09-01 00:00:00

  • The pressure difference between eye and brain changes with posture.

    abstract:OBJECTIVE:The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in as...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.24713

    authors: Eklund A,Jóhannesson G,Johansson E,Holmlund P,Qvarlander S,Ambarki K,Wåhlin A,Koskinen LO,Malm J

    更新日期:2016-08-01 00:00:00

  • Electroconvulsive therapy treatment of depression in a patient with adult GM2 gangliosidosis.

    abstract::Adult GM2 gangliosidosis is a rare disorder that often presents with both neurological and psychiatric syndromes. Effective treatment of the psychotic and affective symptoms associated with this disorder has been complicated by poor treatment response and the concern that many psychotropic agents may worsen the underl...

    journal_title:Annals of neurology

    pub_type: 杂志文章,评审

    doi:10.1002/ana.410310320

    authors: Renshaw PF,Stern TA,Welch C,Schouten R,Kolodny EH

    更新日期:1992-03-01 00:00:00

  • Alzheimer's disease and Parkinson's disease: distinct entities or extremes of a spectrum of neurodegeneration?

    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

    authors: Perl DP,Olanow CW,Calne D

    更新日期:1998-09-01 00:00:00

  • Vigabatrin increases human brain homocarnosine and improves seizure control.

    abstract::Homocarnosine, a dipeptide of gamma-aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amounts (0.4-1.0 micromol/g) than in other animals. The antiepileptic drug vigabatrin increases hu...

    journal_title:Annals of neurology

    pub_type: 临床试验,杂志文章

    doi:10.1002/ana.410440614

    authors: Petroff OA,Mattson RH,Behar KL,Hyder F,Rothman DL

    更新日期:1998-12-01 00:00:00

  • Levodopa induces dyskinesias in normal squirrel monkeys.

    abstract::This study assessed whether or not levodopa induces dyskinesias in normal (ie, unlesioned) squirrel monkeys. All six animals treated twice daily with levodopa (15 mg/kg with carbidopa by oral gavage) for two weeks developed choreoathetoid dyskinesias, whereas none of the vehicle-treated animals displayed any abnormal ...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.1099

    authors: Togasaki DM,Tan L,Protell P,Di Monte DA,Quik M,Langston JW

    更新日期:2001-08-01 00:00:00

  • Childhood socioeconomic status and adult brain size: childhood socioeconomic status influences adult hippocampal size.

    abstract:OBJECTIVE:To investigate in older adults without dementia the relationships between socioeconomic status (SES) in childhood and magnetic resonance imaging (MRI)-derived brain volume measures typical of brain aging and Alzheimer's disease (AD). METHODS:Using a cross-sectional and longitudinal observation approach, we i...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.22631

    authors: Staff RT,Murray AD,Ahearn TS,Mustafa N,Fox HC,Whalley LJ

    更新日期:2012-05-01 00:00:00

  • Necrotizing arteritis and spinal subarachnoid hemorrhage in Sjögren syndrome.

    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

    authors: Alexander EL,Craft C,Dorsch C,Moser RL,Provost TT,Alexander GE

    更新日期:1982-06-01 00:00:00

  • Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells.

    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

    authors: Grzeschik SM,Ganta M,Prior TW,Heavlin WD,Wang CH

    更新日期:2005-08-01 00:00:00

  • Imaging correlates of axonal swelling in chronic multiple sclerosis brains.

    abstract:OBJECTIVE:T2-weighted magnetic resonance imaging is a sensitive tool for monitoring progression of multiple sclerosis, but it does not provide information on the severity of the underlying tissue damage. Measurement of T1 hypointensities and magnetization transfer ratio (MTR) can potentially distinguish lesions with mo...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.21113

    authors: Fisher E,Chang A,Fox RJ,Tkach JA,Svarovsky T,Nakamura K,Rudick RA,Trapp BD

    更新日期:2007-09-01 00:00:00

  • Development of a functional magnetic resonance imaging protocol for intraoperative localization of critical temporoparietal language areas.

    abstract::The aim of this study was to evaluate the use of functional magnetic resonance imaging as an alternative to intraoperative electrocortical stimulation mapping for the localization of critical language areas in the temporoparietal region. We investigated several requirements that functional magnetic resonance imaging m...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.10117

    authors: Rutten GJ,Ramsey NF,van Rijen PC,Noordmans HJ,van Veelen CW

    更新日期:2002-03-01 00:00:00

  • Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group.

    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

    authors: Gajdos P,Chevret S,Clair B,Tranchant C,Chastang C

    更新日期:1997-06-01 00:00:00

  • Measurement of the scrapie agent using an incubation time interval assay.

    abstract::The titer of the scrapie agent was determined by measurements of time intervals from inoculation to onset of illness and from inoculation to death. Both intervals were found to be inversely proportional to the size of the dose injected intracerebrally into random-bred weanling Syrian hamsters. The logarithms of the ti...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410110406

    authors: Prusiner SB,Cochran SP,Groth DF,Downey DE,Bowman KA,Martinez HM

    更新日期:1982-04-01 00:00:00

  • Site of autonomic deficit in harlequin syndrome: local autonomic failure affecting the arm and the face.

    abstract::The site of autonomic deficit was investigated in 4 patients with loss of thermoregulatory flushing and sweating on one side of the face but no associated miosis (harlequin syndrome). In 2 patients the sudomotor deficit included the hand. Signs of postganglionic sympathetic deficit included pathological lacrimal sweat...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410340610

    authors: Drummond PD,Lance JW

    更新日期:1993-12-01 00:00:00

  • Approach to the diagnosis of neurotransmitter diseases exemplified by the differential diagnosis of childhood-onset dystonia.

    abstract::We present our approach to the diagnosis of pediatric neurotransmitter diseases exemplified by the differential diagnosis of children presenting with dystonia. This approach is based upon the primary aim of early diagnosis of treatable conditions and the need for a logical series of investigations. We have tried to be...

    journal_title:Annals of neurology

    pub_type: 杂志文章,评审

    doi:10.1002/ana.10628

    authors: Assmann B,Surtees R,Hoffmann GF

    更新日期:2003-01-01 00:00:00

  • Abnormal breathing patterns during sleep in diabetes.

    abstract::Nineteen diabetic patients, 12 type I (insulin-dependent) and 7 type II (late-onset, non-insulin-dependent), underwent nocturnal polygraphic monitoring after a daytime medical evaluation that included tests of vagal responses and, in 6 patients, pulmonary function and hypercapnic and hypoxic responses. Five lean type ...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410170415

    authors: Mondini S,Guilleminault C

    更新日期:1985-04-01 00:00:00

  • UCHL-1 is not a Parkinson's disease susceptibility gene.

    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

    authors: Healy DG,Abou-Sleiman PM,Casas JP,Ahmadi KR,Lynch T,Gandhi S,Muqit MM,Foltynie T,Barker R,Bhatia KP,Quinn NP,Lees AJ,Gibson JM,Holton JL,Revesz T,Goldstein DB,Wood NW

    更新日期:2006-04-01 00:00:00

  • Cerebral granulomatous angiitis associated with isolation of human T-lymphotropic virus type III from the central nervous system.

    abstract::A 42-year-old homosexual man without evidence of immune deficiency developed cerebral granulomatous angiitis in association with the isolation of human T-lymphotropic virus type III (HTLV-III) from brain tissue and cerebrospinal fluid. This syndrome may be an additional neurological sequela of HTLV-III infection. ...

    journal_title:Annals of neurology

    pub_type: 杂志文章

    doi:10.1002/ana.410200316

    authors: Yankner BA,Skolnik PR,Shoukimas GM,Gabuzda DH,Sobel RA,Ho DD

    更新日期:1986-09-01 00:00:00