Abstract:
Objective:Immunological studies have demonstrated a plethora of beneficial effects of dimethyl fumarate (DMF) on various cell types. However, the cellular and molecular targets are incompletely understood and response markers are scarce. Here, we focus on the relation between nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway induction under DMF therapy and the composition of the blood immune cell compartment and clinical efficacy in relapsing-remitting multiple sclerosis (MS) patients. Methods:We explored effects of DMF on peripheral immune cell subsets by flow cytometric and transcriptional analysis of serial blood samples obtained from 43 MS patients during the first year of therapy. Results:Gene expression analysis proved activation of NRF2 signaling under DMF therapy that was paralleled by a temporal expansion of FoxP3+ regulatory T cells, CD56bright natural killer cells, plasmacytoid dendritic cells, and a decrease in CD8+ T cells, B cells, and type 1 myeloid dendritic cells. In a subgroup of 28 patients with completely available clinical data, individuals with higher levels of the NRF2 target gene NAD(P)H quinone dehydrogenase 1 (NQO1) 4-6 weeks after DMF therapy initiation were more likely to achieve no evidence of disease activity status 1 year later. The degree of NQO1 induction further correlated with patient age. Interpretation:We demonstrate that positive effects of DMF on the clinical outcome are paralleled by induction of the antioxidant NRF2 transcriptional pathway and a shift toward regulatory immune cell subsets in the periphery. Our data identify a role of the NRF2 pathway as potential biomarker for DMF treatment in MS.
journal_name
Ann Clin Transl Neuroljournal_title
Annals of clinical and translational neurologyauthors
Hammer A,Waschbisch A,Kuhbandner K,Bayas A,Lee DH,Duscha A,Haghikia A,Gold R,Linker RAdoi
10.1002/acn3.553subject
Has Abstractpub_date
2018-04-16 00:00:00pages
668-676issue
6issn
2328-9503pii
ACN3553journal_volume
5pub_type
杂志文章abstract:OBJECTIVE:Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pat...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.218
更新日期:2015-09-01 00:00:00
abstract:OBJECTIVE:Electroencephalography (EEG) features in the alpha band have been shown to differ between people with epilepsy and healthy controls. Here, in a group of patients with mesial temporal lobe epilepsy (mTLE), we seek to confirm these EEG features, and using simultaneous functional magnetic resonance imaging, we i...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51032
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:The mechanism of action of anti-B cell therapy in multiple sclerosis (MS) is not fully understood. Here, we compared the effect of anti-CD20 therapy on microglial activation in two distinct focal rat models of MS. METHODS:The effect of anti-CD20 therapy on lesion formation and extralesional microglial activa...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.94
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVES:The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and functi...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.384
更新日期:2017-01-16 00:00:00
abstract::Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.74
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVE:To evaluate the effectiveness of levodopa-carbidopa intestinal gel (LCIG) as an add-on rescue therapy following deep brain stimulation (DBS) for treatment of motor fluctuations. BACKGROUND:Both DBS and LCIG are FDA-approved therapies for treatment of motor fluctuations in advanced PD. Few studies have examin...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50889
更新日期:2019-10-01 00:00:00
abstract::Rho-associated kinase (ROCK) is an emerging target in acute ischemic stroke. Early pre-hospital treatment with ROCK inhibitors may improve their efficacy, but their antithrombotic effects raise safety concerns in hemorrhagic stroke, precluding use prior to neuroimaging. Therefore, we tested whether ROCK inhibition aff...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.569
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:To evaluate the CSF levels of chitinase proteins during the presymptomatic and early symptomatic phases of amyotrophic lateral sclerosis (ALS). METHODS:CSF samples were obtained from 16 controls, 55 individuals at-risk for ALS (including 18 carrying a mutation in C9ORF72, 33 in SOD1), 12 ALS patients, and 7 ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51114
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:The early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558) results from de novo missense mutations of SCN8A encoding the voltage-gated sodium channel Nav1.6. More than 20% of patients have recurrent mutations in residues Arg1617 or Arg1872. Our goal was to determine the functional effects of ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.276
更新日期:2015-12-21 00:00:00
abstract:BACKGROUND:Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating be...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50869
更新日期:2019-09-01 00:00:00
abstract:OBJECTIVES:To systematically review the literature on the neuropsychological, psychosocial, and functional profiles of patients with unruptured intracranial aneurysms. METHODS:This review was limited to peer-reviewed research articles that reported cognitive, psychosocial, and/or functional profiles of patients with u...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.41
更新日期:2014-03-01 00:00:00
abstract:OBJECTIVE:Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. METHODS:MS patients with serum samples and health-outcome measurements collected longitudinally between 2011 and 2016 were a...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51305
更新日期:2021-01-25 00:00:00
abstract:OBJECTIVE:Heterozygous SHANK3 mutations or partial deletions of the long arm of chromosome 22, also known as Phelan-McDermid syndrome, result in a syndromic form of the autism spectrum as well as in global developmental delay, intellectual disability, and several neuropsychiatric comorbidities. The exact pathophysiolog...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50959
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable c...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.361
更新日期:2016-11-16 00:00:00
abstract:OBJECTIVE:The objective of this study was to investigate the genetic etiology of the X-linked disorder "Hypomyelination of Early Myelinating Structures" (HEMS). METHODS:We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silic...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.203
更新日期:2015-06-01 00:00:00
abstract:Objective:Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from pr...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.558
更新日期:2018-04-02 00:00:00
abstract:OBJECTIVE:To develop, test, and iterate a comprehensive neuromuscular targeted gene panel in a national referral center. METHODS:We designed two iterations of a comprehensive targeted gene panel for neuromuscular disorders. Version 1 included 336 genes, which was increased to 464 genes in Version 2. Both panels used T...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51002
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-ba...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.121
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVE:To determine the frequency of distinctive EGFr cysteine altering NOTCH3 mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database. METHODS:ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASI...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.344
更新日期:2016-09-28 00:00:00
abstract:OBJECTIVE:Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown. METHODS:This investigation used quantitative Magnetic Resonance methodologies, including high resolution and diffusion tensor (DTI) im...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.136
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Analysis of the T-cell receptor (TCR) repertoire in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) can reveal antigen-specific immune responses potentially implicated in the disease process. We applied a new unbiased deep-sequencing method for TCR repertoire analysis to accurately meas...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.310
更新日期:2016-04-20 00:00:00
abstract::The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole-exome sequencing and next-generation sequencing-based ge...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.267
更新日期:2015-12-08 00:00:00
abstract:Objective:We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Methods:Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.540
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVE:Few studies have captured the neuropsychological profile of sporadic Creutzfeldt-Jakob disease (sCJD) with neuropsychological testing, and little is known about cognitive predictors of survival. We characterized baseline neuropsychological performance in sCJD and investigated associations with survival. METH...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51115
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. METHODS:BIOCARD Study participants were cognitively normal and primarily middle-aged (M = 57 years) at baseli...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51120
更新日期:2020-08-01 00:00:00
abstract::FBXO7 is implicated in the ubiquitin-proteasome system and parkin-mediated mitophagy. FBXO7defects cause a levodopa-responsive parkinsonian-pyramidal syndrome(PPS). METHODS:We investigated the disease molecular bases in a child with PPS and brain iron accumulation. RESULTS:A novel homozygous c.368C>G (p.S123*) FBXO7...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51095
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) βamyloid protein (Aβ) and high CSF Tau levels are associated with Alzheimer's disease. We therefore assessed whether lower preoperative CSF Aβ/Tau ratio was associated with higher incidence and greater severity of p...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.58
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVE:To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship. METHODS:Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atro...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50985
更新日期:2020-02-01 00:00:00
abstract::Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChi...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.42
更新日期:2014-04-01 00:00:00
abstract:OBJECTIVE:Pathogenesis in facioscapulohumeral muscular dystrophy (FSHD) appears to be due to aberrant expression, particularly in skeletal muscle nuclei, of the full-length isoform of DUX4 (DUX4-FL). Expression of DUX4-FL is known to alter gene expression and to be cytotoxic, but cell responses to DUX4-FL are not fully...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.158
更新日期:2015-02-01 00:00:00