Abstract:
:Although the cause of multiple sclerosis (MS) has remained obscure, many findings support an autoimmune pathogenesis on the background of a complex interaction between multiple genes and environmental factors. Accordingly, targeting the immune system has been a rational approach for the treatment of MS. The development of disease-modifying immunomodulatory drugs with partial efficacy, coupled with advances in understanding the pathophysiology and pathology of MS, has provided momentum to explore more specific and hopefully more effective immune-based therapeutic strategies. With increased knowledge and appreciation of the contribution of neurodegenerative processes to disease pathology, the therapeutic challenges, however, have become even more formidable. Future treatments will likely need both to target inflammation and to focus on promotion of neuroprotection and repair. In this review, we discuss the most promising therapeutic approaches for MS currently in the pipeline.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Hemmer B,Hartung HPdoi
10.1002/ana.21289subject
Has Abstractpub_date
2007-10-01 00:00:00pages
314-26issue
4eissn
0364-5134issn
1531-8249journal_volume
62pub_type
杂志文章,评审abstract::Human prion diseases can occur as an idiopathic disorder (sporadic Creutzfeldt-Jakob disease) or can be acquired, as is the case for variant Creutzfeldt-Jakob disease. These disorders are characterized by the accumulation of a protease-resistant form of the host-encoded prion protein termed PrP(Sc) in the brains of af...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20127
更新日期:2004-06-01 00:00:00
abstract::Plasma valproate concentrations were monitored prospectively in 54 previously untreated adult patients with epilepsy. Dose and plasma concentration were highly correlated. Adverse effects were common in association with plasma levels above 100 micrograms/ml. In patients suffering tonic-clonic seizures without focal sy...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410140107
更新日期:1983-07-01 00:00:00
abstract::Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy, in which leukocytes and humoral components of the immune system proposedly initiate localized inflammation. An important pathogenic role for anti-GM1 ganglioside antibodies has been suggested. Therefore, we evaluated anti-GM1 IgG antibody-induced leukocyt...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10503
更新日期:2003-05-01 00:00:00
abstract::Solitary neoplastic proliferation of plasma cells (plasmacytoma) rarely occurs in the central nervous system. The longest follow-Up in nine previously reported patients was 5 years. We have followed two patients with solitary intracranial plasmacytoma for 8 and 13 years, respectively. At the time of biopsy diagnosis, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110514
更新日期:1982-05-01 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::Three patients with inferior branch palsies of the oculomotor nerve are described. Two were under 10 years of age and the third was 30 years old at the onset. All 3 presented with painless diplopia. The onset was sudden in 2 patients and progressive in the third. The palsy cleared within a short time in the 2 patients...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410020414
更新日期:1977-10-01 00:00:00
abstract::We studied sleep patterns for three nights in 10 subjects with moderate to severe progressive supranuclear palsy and correlated the findings with disease severity using quantitative measures of motor, cognitive, and eye movement impairment. All subjects had severe insomnia, spending 2 to 6 hours awake per night; the m...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250609
更新日期:1989-06-01 00:00:00
abstract::Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease. However, the mechanisms by which activation of glutamate receptors produce parkinsonism are unknown. Therefore, we examined whether the glutamate agonists N-methyl-D-aspartate (NMDA), alpha-amino-3-hy...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340413
更新日期:1993-10-01 00:00:00
abstract::The anatomy of the recently discovered diencephalospinal dopaminergic system is summarized and its possible role in physiological and pathological processes suggested. The cell bodies of origin of this system are localized periventricularly in the dorsal hypothalamus and caudal thalamus, and the terminal innervations ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140302
更新日期:1983-09-01 00:00:00
abstract:OBJECTIVE:Intracranial electroencephalography (ICEEG) with chronically implanted electrodes is a costly invasive diagnostic procedure that remains necessary for a large proportion of patients who undergo evaluation for epilepsy surgery. This study was designed to evaluate whether magnetic source imaging (MSI), a noninv...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21660
更新日期:2009-06-01 00:00:00
abstract::Patients with senile dementia of the Alzheimer type frequently have difficulty performing visual tasks. These difficulties may be due, at least partially, to degenerative changes in both the primary visual pathway and the visual association areas. To determine whether retinal ganglion cell dysfunction contributes to v...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260208
更新日期:1989-08-01 00:00:00
abstract::Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third o...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410370710
更新日期:1995-05-01 00:00:00
abstract::Hippocampal depth electrodes are often used to localize seizure onset in patients who may have temporal lobe epilepsy (TLE). A number of features of the spontaneous seizures and of their ictal onset patterns can be analyzed from these recordings. We compared a number of the typical electroencephalographic (EEG) change...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410380513
更新日期:1995-11-01 00:00:00
abstract::For unknown reasons, placebos reduce seizures in clinical trials in many patients. It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using Seizuretracker.com, a patient-centered database of 684,825 seizures, we simulated "placebo" and "drug" trials....
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24470
更新日期:2015-09-01 00:00:00
abstract:OBJECTIVE:Cerebral aneurysms can cause substantial morbidity and mortality, specifically if they rupture, leading to nontraumatic subarachnoid hemorrhage (SAH). This meta-analysis summarizes evidence about the accuracy of noninvasive computed tomographic (CT) angiography for diagnosing intracranial aneurysms in symptom...
journal_title:Annals of neurology
pub_type: 杂志文章,meta分析
doi:10.1002/ana.22270
更新日期:2011-04-01 00:00:00
abstract::Two women suffered from a similar, slowly progressive illness characterized by upper and lower motor neuron involvement, sensory disturbances, and neurogenic bladder. Radiographic examinations showed cerebral atrophy and, in one, changes on computerized tomography suggesting leukodystrophy. Sural nerve biopsies reveal...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410130411
更新日期:1983-04-01 00:00:00
abstract::Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10061
更新日期:2002-01-01 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::Unilateral lesions of the occipital visual areas performed on postnatal day 5 (P5) in the ferret are not compensated by the appearance, in the lesioned hemisphere, of visual responses at ectopic locations. Instead, when parts of the visual areas are spared, they show abnormal retinotopic organizations; furthermore, ca...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10591
更新日期:2003-07-01 00:00:00
abstract::Patients with atrial fibrillation are at risk for cerebral embolism; however, the roles of chronic anticoagulation or antiplatelet therapy for stroke prevention in patients with nonvalvular atrial fibrillation have been controversial. Recently, the results of three large prospective randomized trials that examined the...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410300402
更新日期:1991-10-01 00:00:00
abstract::We report on 3 anti-Hu-positive patients who presented with clinical and electroencephalographic (EEG) features of epilepsia partialis continua (EPC). Two of the patients had an associated small cell carcinoma. Magnetic resonance imaging (MRI) disclosed a hyperintense nonenhancing focal lesion in T2-weighted images in...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199902)45:2<255::aid-ana18>3.0.c
更新日期:1999-02-01 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: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
更新日期:2016-08-01 00:00:00
abstract::A 45-year-old woman was diagnosed as having the unclassified form of botulism. Her intestines may have been predisposed to colonization with Clostridium botulinum because of a jejunoileal bypass procedure that had been done several years earlier. One other similar case has been reported. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200516
更新日期:1986-11-01 00:00:00
abstract::The mechanism underlying mirrored activity/movements in normal individuals is unknown. To investigate this, we studied 11 adults and 39 children who performed sequential finger-thumb opposition or repetitive index finger abduction. Surface electromyographic (EMG) activity recorded from the left and right first dorsal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199905)45:5<583::aid-ana6>3.0.co
更新日期:1999-05-01 00:00:00
abstract::Ross River virus (strain T48) infection in mice causes an encephalomyelitis characterized by focal, primary demyelination in the cerebellum, brain stem, and spinal cord. Maximal serum and brain content of virus occurs on days 2 and 4, respectively. Virus is not detectable in serum after day 3 or in brain after day 9. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410120411
更新日期:1982-10-01 00:00:00
abstract::Friedreich's ataxia (FA) is the most frequently inherited ataxia. To test the hypothesis that iron is increased in the cerebellum of patients with FA, we developed a multigradient echo magnetic resonance sequence for the three-dimensional imaging of brain iron-induced contrast. Relaxation rate (R2*) values in the unaf...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199907)46:1<123::aid-ana19>3.0.c
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVE:Patients with temporal lobe epilepsy often display cognitive comorbidity with recurrent seizures. However, the cellular mechanisms underlying the impairment of neuronal information processing remain poorly understood in temporal lobe epilepsy. Within the hippocampal formation neuronal networks undergo major r...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24348
更新日期:2015-04-01 00:00:00
abstract::Polymorphonuclear neutral protease activity (PMN-NPA) was examined in 87 patients with definite multiple sclerosis (MS) (48 active, 39 inactive), 49 patients with other neurological diseases (OND), 24 patients with immune-mediated non-neurological diseases (INND), and 32 normal subjects. PMN-NPA was found to be signif...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410180519
更新日期:1985-11-01 00:00:00
abstract::Magnetic resonance imaging is a highly sensitive method for the detection of the lesions of multiple sclerosis and renders possible the study and the evolution of early lesions. Previous reports on magnetic resonance imaging following gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) injection demonstrated that...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340507
更新日期:1993-11-01 00:00:00