Abstract:
:Monoclonal antibodies that target CD20 expressing B cells represent an important new treatment option for patients with multiple sclerosis (MS). B-cell-depleting therapy is highly effective against relapsing forms of the disease and is also the first treatment approach proven to protect against disability worsening in primary progressive MS. Moreover, evolving clinical experience with B-cell therapy, combined with a more sophisticated understanding of humoral immunity in preclinical models and in patients with MS, has led to major progress in deciphering the immune pathogenesis of MS. Here, we review the nuanced roles of B cells in MS autoimmunity, the clinical data supporting use of ocrelizumab and other anti-CD20 therapies in the treatment of MS, as well as safety and practical considerations for prescribing. Last, we summarize remaining unanswered questions regarding the proper role of anti-CD20 therapy in MS, its limitations, and the future landscape of B-cell-based approaches to treatment. Ann Neurol 2018;83:13-26.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Greenfield AL,Hauser SLdoi
10.1002/ana.25119subject
Has Abstractpub_date
2018-01-01 00:00:00pages
13-26issue
1eissn
0364-5134issn
1531-8249journal_volume
83pub_type
杂志文章,评审abstract:OBJECTIVE:The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages ...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.24656
更新日期:2016-06-01 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::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::Most neurodegenerative disorders are thought to result primarily from the accumulation of misfolded proteins, which interfere with protein homeostasis in neurons. For a subset of diseases, however, noncoding regions of RNAs assume a primary toxic gain-of-function, leading to degeneration in many tissues, including the...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21948
更新日期:2010-03-01 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:A better understanding of the manuscript peer-review process could improve the likelihood that research of the highest quality is funded and published. To this end, we aimed to assess consistency across reviewers' recommendations, agreement between reviewers' recommendations and editors' final decisions, and ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24218
更新日期:2014-08-01 00:00:00
abstract::Mutations of the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause autosomal recessive Charcot-Marie-Tooth disease type 4A. We report four additional families with recessive mutations (487C-->T, Q163X; 359G-->A, R120Q) of GDAP1; Q163X occurred in three unrelated Hispanic families that had the...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10505
更新日期:2003-03-01 00:00:00
abstract::After unilateral cortical lesions in neonatal rats, the spared unablated hemisphere is known to demonstrate remarkable neuroanatomical plasticity in corticofugal connectivity. This same type of structural plasticity is not seen after similar lesions in adult rats. One possibility for the lack of such a plastic respons...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199906)45:6<778::aid-ana12>3.0.c
更新日期:1999-06-01 00:00:00
abstract::This report reviews the fundamental principles and the changing concepts of nerve stimulation techniques, and discusses the proper application of these techniques in the differential diagnosis of peripheral nerve disorders. Nerve conduction studies help delineate the extent and distribution of the neural lesion and di...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160402
更新日期:1984-10-01 00:00:00
abstract:OBJECTIVE:Episodic memory retrieval is reliant upon cognitive control systems, of which 2 have been identified with functional neuroimaging: a cingulo-opercular salience network (SN) and a frontoparietal executive network (EN). In Alzheimer's disease (AD), pathology is distributed throughout higher-order cortices. The ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24199
更新日期:2014-08-01 00:00:00
abstract::Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. We examined whether Alzheimer's disease (AD) is associated with increased oxidative damage to nDNA and mtDNA in postmortem brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isola...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410360510
更新日期:1994-11-01 00:00:00
abstract::Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290104
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:Transient high-frequency oscillations (HFOs; 150-600Hz) in local field potentials generated by human hippocampal and parahippocampal areas have been related to both physiological and pathological processes. The cellular basis and effects of normal and abnormal forms of HFOs have been controversial. This lack ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24324
更新日期:2015-02-01 00:00:00
abstract::This study provides preliminary evidence that computer-derived parameters of interictal spike waveforms can be used to assess seizure hazard in a quantitative manner. Thirteen children with spike foci and simple or complex partial seizures were studied before and during treatment with carbamazepine or phenobarbital; s...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200612
更新日期:1986-12-01 00:00:00
abstract::The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199911)46:5<732::aid-ana8>3.0.co
更新日期:1999-11-01 00:00:00
abstract::To elucidate the mechanism by which carbamazepine lowers somatostatin concentration in cerebrospinal fluid of humans, the effect of carbamazepine on secretion of this peptide was studied in rat cerebral cell cultures. Concentrations of carbamazepine within the therapeutic range (4 x 10(-5) M) inhibited spontaneous rel...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290412
更新日期:1991-04-01 00:00:00
abstract::A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) g...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410222
更新日期:1997-02-01 00:00:00
abstract::A comprehensive analysis of cerebral hemodynamics and metabolism was carried out in 14 patients with pseudotumor cerebri. Tracer techniques were employed to measure cerebral blood flow (CBF) and vascular reactivity to acute changes in arterial carbon dioxide tension and blood pressure, cerebral blood volume (CBV), and...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040203
更新日期:1978-08-01 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::Four hundred five children from the Helsinki area who were 1 month to 16 years old were treated for acute encephalitis at the Children's Hospital, University of Helsinki, from January 1968 through December 1987. Encephalitis occurred most commonly in children 1 to 1.9 years of age, among whom the incidence was 16.7 pe...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290508
更新日期:1991-05-01 00:00:00
abstract::Growth hormone (GH) is neuroprotective, presumably through its actions on GH receptor-mediated pathways. Here, we examined the effects of GH using in vitro and in vivo assays of human immunodeficiency virus (HIV)-induced neuronal injury. Neuronal cultures were in assays of neurotoxicity induced by supernatants from HI...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10729
更新日期:2003-11-01 00:00:00
abstract::Cylindrical spirals are unique membranous structures that were detected in skeletal muscle of a mother and one of her two children; all three have percussion myotonia but no evidence of weak or wasted skeletal muscles. Muscle cramps, stiffness, posteffort muscle tightness, myotonic lid lag, and the cylinders appear or...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410070608
更新日期:1980-06-01 00:00:00
abstract::A 53-year-old man was diagnosed 8 years earlier with globoid cell leukodystrophy (GLD, Krabbe disease) by his severe deficiency of galactocerebrosidase (GALC) activity. He was found to have eight nucleotide changes on the two copies of his GALC gene, including two in the leader sequence, four considered polymorphisms,...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400119
更新日期:1996-07-01 00:00:00
abstract::The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivit...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220607
更新日期:1987-12-01 00:00:00
abstract::To characterize the protein composition of degenerating neurons in Alzheimer disease, enriched fractions of isolated cortical neurons from postmortem Alzheimer brain were compared by ultrastructural and biochemical techniques to neuronal isolates from aged normal controls and from patients with the nonfibrillary degen...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080504
更新日期:1980-11-01 00:00:00
abstract:OBJECTIVE:Migraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated CaV 2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV 2.1 channels and a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24449
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:To understand the mechanisms of skeletal muscle destruction and resistance to enzyme replacement therapy in Pompe disease, a deficiency of lysosomal acid alpha-glucosidase (GAA), in which glycogen accumulates in lysosomes primarily in cardiac and skeletal muscles. METHODS:We have analyzed compartments of the...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20807
更新日期:2006-04-01 00:00:00
abstract::We report the clinical, imaging, and laboratory features of 8 patients with Devic's neuromyelitis optica. All patients had severe myelopathy and optic neuritis. In no patient was the brain, the brainstem, or the cerebellum affected, even after several years of disease. Various immunosuppressive treatments failed to be...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340211
更新日期:1993-08-01 00:00:00
abstract::Benign familial neonatal convulsions (BFNC) is a rare dominantly inherited epileptic syndrome characterized by frequent brief seizures within the first days of life. The disease is caused by mutations in one of two recently identified voltage-gated potassium channel genes, KCNQ2 or KCNQ3. Here, we describe a four-gene...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199909)46:3<305::aid-ana5>3.0.co
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. METHODS:Subjects were 436 well-character...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22520
更新日期:2011-11-01 00:00:00