Abstract:
:Fingolimod is the first oral disease-modifying therapy approved for relapsing forms of multiple sclerosis (MS). Following phosphorylation in vivo, the active agent, fingolimod phosphate (fingolimod-P), acts as a sphingosine 1-phosphate (S1P) receptor modulator, binding with high affinity to four of the five known S1P receptors (S1P1, S1P3, S1P4 and S1P5). The mechanism of action of fingolimod in MS has primarily been considered as immunomodulatory, whereby fingolimod-P modulates S1P1 on lymphocytes, selectively retaining autoreactive lymphocytes in lymph nodes to reduce damaging infiltration into the central nervous system (CNS). However, emerging evidence indicates that fingolimod has direct effects in the CNS in MS. For example, in the MS animal model of experimental autoimmune encephalomyelitis (EAE), fingolimod is highly efficacious in both a prophylactic and therapeutic setting, yet becomes ineffective in animals selectively deficient for S1P1 on astrocytes, despite maintained normal immunologic receptor expression and functions, and S1P-mediated immune activities. Here we review S1P signaling effects relevant to MS in neural cell types expressing S1P receptors, including astrocytes, oligodendrocytes, neurons, microglia and dendritic cells. The direct effects of fingolimod on these CNS cells observed in preclinical studies are discussed in view of the functional consequences of reducing neurodegenerative processes and promoting myelin preservation and repair. The therapeutic implications of S1P modulation in the CNS are considered in terms of the clinical outcomes of MS, such as reducing MS-related brain atrophy, and other CNS disorders. Additionally, we briefly outline other existing and investigational MS therapies that may also have effects in the CNS.
journal_name
J Neurol Scijournal_title
Journal of the neurological sciencesauthors
Groves A,Kihara Y,Chun Jdoi
10.1016/j.jns.2013.02.011subject
Has Abstractpub_date
2013-05-15 00:00:00pages
9-18issue
1-2eissn
0022-510Xissn
1878-5883pii
S0022-510X(13)00088-9journal_volume
328pub_type
杂志文章,评审abstract::The predictive validity of evoked potentials (EPs) and event-related potentials (ERPs) in multiple sclerosis (MS) has not yet been fully investigated, as only the sensitivity of these tests has sofar been reported. EPs (short, middle and long latency auditory evoked potentials and visual evoked potentials) and ERPs (v...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(92)90087-2
更新日期:1992-05-01 00:00:00
abstract::Fast 60 degree head rotations of nine patients with cerebellar deficits were analysed and compared with those of nine normal subjects. The surface EMG activity from both Splenii capitis muscles were recorded. The triphasic pattern of reciprocal innervated neck muscles with regard to the duration, amplitude and onset o...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/s0022-510x(97)00276-1
更新日期:1998-02-18 00:00:00
abstract::Nutritional deficiency may be the cause of a genuine optic neuropathy, sometimes associated with involvement of the peripheral nervous system. Nutritional optic neuropathies are usually bilateral, painless, chronic, insidious and slowly progressive. Most often, they present as a non-specific retrobulbar optic neuropat...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2007.06.038
更新日期:2007-11-15 00:00:00
abstract::Dementia of the Alzheimer type (DAT) and vascular dementia (VaD) are the two major subtypes of dementia. In our epidemiological study of DAT in an Arab community in Wadi Ara, Israel, we found a high prevalence of late onset DAT. Illiteracy, smoking, diabetes mellitus (DM) and hypertension are very frequent in Wadi Ara...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/s0022-510x(02)00269-1
更新日期:2002-11-15 00:00:00
abstract:PURPOSE:To determine conditions which influence transfer of iopamidol from lumbosacral cerebrospinal fluid (CSF) to blood. METHODS:Iopamidol transfer was measured in 32 patients over 180 min after radiculography and compared with patient variables. RESULTS:Iopamidol transfer began early in 12 patients, more slowly in...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/s0022-510x(02)00340-4
更新日期:2003-01-15 00:00:00
abstract::Somatoform Disorders (SFMD) were recently described in Parkinson Disease (PD) and Dementia with Lewy Bodies (DLB). The present paper updates the observations in our cohort of patients and further details clinical phenomenology. Of 3178 patients consecutively referred to our Institutions from 1999, 1572 subjects had ne...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2011.07.010
更新日期:2011-11-15 00:00:00
abstract:BACKGROUND:The treatment of amyotrophic lateral sclerosis (ALS) is still disappointing. Repetitive transcranial magnetic stimulation (rTMS) has been suggested to modify the rate of disease progression in ALS. OBJECTIVE:In a pilot controlled study, we tested the effect of 5-Hz rTMS on motor performance, fatigue and qua...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2008.01.011
更新日期:2008-07-15 00:00:00
abstract:OBJECTIVES:To address practical issues in measuring autoantibodies to neuronal cell-surface antigens (NSAs) in various autoimmune neurological disorders (ANDs). METHODS:We retrospectively reviewed the clinical information of 221 patients with clinically suspected ANDs who underwent antibody testing for NSAs between Ja...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2018.04.009
更新日期:2018-07-15 00:00:00
abstract::The etiology of Parkinson's disease is mainly unknown. Immune abnormalities have been reported, including the occurrence of autoantibodies against neuronal structures and abnormal T cell functions. gamma delta+ T cells represent a recently recognized T cell subpopulation which is considered to play a role in immune re...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(94)90154-6
更新日期:1994-01-01 00:00:00
abstract::We describe a patient presenting with vertical one-and-a-half syndrome and concomitant contralesional horizontal gaze paresis as the result of a solitary neurocysticercosis (NCC) lesion in the right midbrain extending into the thalamomesencephalic junction. The patient received an albendazole-dexamethasone course whic...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2012.08.022
更新日期:2012-12-15 00:00:00
abstract:BACKGROUND:To evaluate the presence of ischemic and hemorrhagic lesions in brain MRI of patients with Fabry disease (FD). METHODS:Brain MRI studies in 46 consecutive patients were evaluated using classic sequences as well as GRE-weighted images, for ischemic lesions and chronic microbleed detection. Of the 36 adult pa...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2011.03.020
更新日期:2011-06-15 00:00:00
abstract::The rat double-SAH model is one of the standard models to simulate delayed cerebral vasospasm (CVS) in humans. However, the proof of delayed ischemic brain damage is missing so far. Our objective was, therefore, to determine histological changes in correlation with the development of symptomatic and perfusion weighted...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2010.03.023
更新日期:2010-06-15 00:00:00
abstract:OBJECTIVE:Neurodegenerative diseases are often characterized by the presence of intracellular or extracellular protein aggregates in the central nervous system. Mutations of TARDBP gene have been shown to cause Amyotrophic Lateral Sclerosis and have been reported to present with clinical heterogeneity including parkins...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2018.04.043
更新日期:2018-07-15 00:00:00
abstract::Eclampsia accounts for a third of maternal mortality in developing countries. The neurological manifestations of eclampsia consist of seizures and alteration of sensorium or coma on a background of pre-eclampsia. Occasionally there can be focal neurological deficits too. Recent studies with CT scan and MRI have demons...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0022-510x(97)00274-8
更新日期:1998-02-18 00:00:00
abstract::We review post-infectious and post-vaccination neurological syndromes involving peripheral and central nervous system (CNS) and report an illustrative case of simultaneous occurrence of Guillain-Barré syndrome (GBS), confirmed by nerve conduction velocities, plus MRI-demonstrated transverse myelitis (TM) and acute enc...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2018.09.028
更新日期:2018-12-15 00:00:00
abstract::Encephalitogenic activity of myelin basic protein (MBP) isolated in a form retaining binding to all myelin lipids was tested in Lewis rats. Immunization with this new stable lipid-bound and native-like preparation (LB-MBP), induced experimental autoimmune encephalomyelitis (EAE) as intensively as the classical lipid f...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(93)90196-6
更新日期:1993-10-01 00:00:00
abstract::Ninety-four asymptomatic patients with internal carotid artery occlusion were followed for a mean of 44 months, 16% suffered strokes and 11.7% reported transient ischemic attacks (TIA). The annual stroke and TIA rates were 4.4% and 3.2%, respectively, the annual mortality was 11.3%. In 27 asymptomatic patients progres...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(90)90262-l
更新日期:1990-09-01 00:00:00
abstract::Psychiatric disorders seem to be more frequent in patients with epilepsy (PWE) than the general population. Although researchers have documented a strong association between epilepsy and psychiatric comorbidities, the nature of this relationship is poorly understood. According to this, psychiatric diseases are often u...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2014.05.043
更新日期:2014-08-15 00:00:00
abstract::DNA amplification of three Mycobacterium tuberculosis-specific DNA sequences by the polymerase chain reaction (PCR) were evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM). The DNA sequences amplified were a 123 bp region of the IS6110 insertion elements which occur in multiple copies in the myco...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(94)90220-8
更新日期:1994-05-01 00:00:00
abstract::Further observations on a family with facioscapulohumeral (FSH) muscular dystrophy due to mitochondrial myopathy, and on a case with lipid storage myopathy are reported. One member of the family with FSH muscular dystrophy died due to a viral pneumonia, during which she developed gross hyperlacticacidaemia and acidosi...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(78)90003-5
更新日期:1978-02-01 00:00:00
abstract::Over the last 30 years glucose intolerance has been reported in a significant percentage of patients with amyotrophic lateral sclerosis (ALS). Currently, a controversy exists in determining whether the carbohydrate abnormality is disease-specific or secondary to decreased glucose utilization due to muscle atrophy. A r...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(84)90154-0
更新日期:1984-03-01 00:00:00
abstract:OBJECTIVES:To characterize the clinical, demographic and epidemiological features of MS patients from the only specialised MS centre in Iraq. METHODS:Data for consecutive Iraqi MS patients attending the Baghdad Multidiscipline MS Clinic between 2000 and 2002 who fulfilled Poser et al. criteria for clinically definite ...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2005.03.033
更新日期:2005-07-15 00:00:00
abstract::On December 31, 1988 there were 201 registered multiple sclerosis patients in Kuwait, an overall prevalence rate (PR) of 10.2 per 100,000; among them were 186 Arabs, of whom 72 were Palestinians and 51 Kuwaitis. Comparison of these two subgroups, who had a similar age distribution revealed that the disease was 2 1/2 t...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(90)90024-h
更新日期:1990-12-01 00:00:00
abstract::We present 2 patients in whom the predominant neurological complication following lightning strike was spinal cord injury. One patient, who was followed for 5 years, showed clinical, electrophysiologic and MRI evidence of cervical spinal cord injury. This patient had significant recovery, which in part, may be related...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2008.09.020
更新日期:2009-01-15 00:00:00
abstract::Using special soft tissue X-ray investigations the authors have found that the increase in volume of the calf musculature in progressive muscular dystrophy does not seem to be in complete accordance with the criteria of pseudohypertrophy. It has been demonstrated that this structural alteration of the musculature does...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(79)90074-1
更新日期:1979-09-01 00:00:00
abstract::Opsoclonus-myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. Human herpes virus-6 (HHV-6) can rarely cause encephalitis in immunocompetent children and adults. Here we report on a case of OMS associated with HHV-6 rhomboencep...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2014.04.013
更新日期:2014-06-15 00:00:00
abstract::The volume of the lumbar sac measured in 4 subjects was found to be 15.5 ml. Exactly 15 ml of lumbar cerebrospinal fluid (L-CSF) was permitted to flow freely out during a lumbar puncture in 20 neurological patients and small samples of the L-CSF were collected in the beginning (sample 1), at the middle (sample 2), and...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(77)90103-4
更新日期:1977-03-01 00:00:00
abstract::Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus place...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jns.2016.08.052
更新日期:2016-11-15 00:00:00
abstract:OBJECTIVE:GM1 ganglioside has been suggested as a treatment for Parkinson's disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitud...
journal_title:Journal of the neurological sciences
pub_type: 临床试验,杂志文章
doi:10.1016/j.jns.2015.06.028
更新日期:2015-09-15 00:00:00
abstract::Demonstration of the direct involvement of cranial blood vessels by varicella zoster virus (VZV) is facilitated by immunohistochemistry (IHC), in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques. The extent to which an inflammatory vasculitis serves as the pathogenic mechanism for VZV encephalom...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/s0022-510x(98)00171-3
更新日期:1998-08-14 00:00:00