NeuroTrophic Factors In Relapsing/Remitting And Secondary/Progressive Multiple Sclerosis Patients During Interferon-beta Therapy
Caggiula M, Batocchi AP, Frisullo G, Angelucci F, Patanella AK, Sancricca C, Nociti V, Tonali PA, Mirabella M
Clin Immunol 2006 Jan;118(1):77-82
Institute of Neurology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy; Fondazione Pro Iuventute Don Carlo Gnocchi, Rome, Italy
Although Interferon-beta (IFN-ß) is a widely used disease-modifying therapy in Multiple Sclerosis (MS), the mechanisms responsible for its effects are not fully understood.
Some studies demonstrated that IFN-ß induces Nerve Growth Factor (NGF) secretion by Astrocytes and by Brain Endothelial Cells.
In this study, we determined the production of various NeuroTrophins:
- Brain-Derived NeuroTrophic Factor, (BDNF)
- Glial Cell line-derived NeuroTrophic Factor
- NeuroTrophin 3
- Neurotrophin 4
By Peripheral Blood Mononuclear Cells (PBMCs) in Relapsing/Remitting (RR) and Secondary/Progressive (SP) MS patients during IFN-ß treatment.
There were no main variations in NeuroTrophin production either among all MS patients globally considered or in the group of SPMS subjects.
Instead, in the group of RRMS patients who did not present clinical exacerbation of disease up to the end of the study, we found a significant increase in BDNF production as from 6 months after starting therapy.
Ocular Manifestations Of Multiple Sclerosis
Chen L, Gordon LK
Curr Opin Ophthalmol 2005 Oct;16(5):315-20
University of California, Jules Stein Eye Institute, Ocular Inflammatory Disease Center, Los Angeles, USA, and Greater Los Angeles VA Healthcare System, Los Angeles, California, USA, and Shenzhen Eye Hospital, Shenzhen, Guangdong, PR China
Purpose Of Review
Multiple Sclerosis is an Autoimmune DeMyelinating Disorder of the Nervous System that is commonly manifested by Visual System involvement and that may initially present with Ophthalmologic symptoms.
This paper reviews recent findings regarding the Ocular manifestations in Multiple Sclerosis.
Manifestations of Multiple Sclerosis in the eye include both the Afferent and Efferent Visual Pathways.
Optic Neuritis, the most common Ocular manifestation of Multiple Sclerosis, may be the initial clinical disease manifestation.
Recent long-term follow-up data show that most patients with DeMyelinating Optic Neuritis have an excellent prognosis for recovery of central Visual Acuity.
Evidence is emerging, however, for significant and broad reduction in both contrast sensitivity and color perception in Multiple Sclerosis patients despite near-normal Visual Acuities.
Ocular motor deficits in Multiple Sclerosis include InterNuclear Ophthalmoplegia and Nystagmus, resulting in Diplopia, Oscillopsia, Blurred Visual, Loss of Stereopsis, and reading fatigue.
Multiple Sclerosis also may be associated with Ocular Inflammatory Diseases, in particular Pars Planitis and Retinal Periphlebitis.
Ocular findings may be initial manifestations of Multiple Sclerosis and may predict additional DeMyelinating events.
Recognizing these syndromes and signs will help clinicians to properly evaluate the patient, formulate an appropriate differential diagnosis, be able to discuss the prognosis with the patient, and help develop an effective therapeutic plan.
Glucosamine Abrogates The Acute Phase Of Experimental Autoimmune Encephalomyelitis By Induction Of th2 Response
Zhang GX, Yu S, Gran B, Rostami A
J Immunol 2005 Dec 1;175(11):7202-8
Thomas Jefferson University, Department of Neurology, Philadelphia, PA 19107
Glucosamine, a natural Glucose derivative and an essential component of glycoproteins and proteoglycans, has been safely used to relieve OsteoArthritis in humans.
Recent studies have shown that Glucosamine also possesses ImmunoSuppressive properties and is effective in prolonging graft survival in mice.
Whether this reagent is effective in human Multiple Sclerosis (MS), an inflammatory DeMyelination in the CNS, is not known. We thus investigated the therapeutic effect of Glucosamine on Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS.
We demonstrated that oral, i.p., or i.v. administration of Glucosamine significantly suppressed acute EAE, with reduced CNS inflammation and DeMyelination.
A significant, albeit not strong, blockade of Th1 response and an up-regulation of Th2 Cytokines (IL-5 and IL-10) are observed in the Splenocytes of Glucosamine-treated mice.
Glucosamine also regulates IL-5 and IL-10 in vitro. As Glucosamine is able to effectively suppress acute EAE, has low or absent toxicity, and has been safely used in humans orally.
Our study suggests a potential use for this drug alone or in combination with other disease-modifying immunotherapies to enhance their efficacy and reduce their doses in MS and possibly other Autoimmune Disorders.
Furthermore, because Glucosamine functions not simply as an ImmunoSuppressant, but as a mild ImmunoModulator, administration of Glucosamine provides a novel ImmunoRegulatory approach for Autoimmune Disorders.
Panitch H, Goodin D, Francis G, Chang P, Coyle P, O'connor P, Li D, Weinshenker B; for the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group
J Neurol Sci 2005 Dec 15;239(1):67-74
University of Vermont College of Medicine, Neurology Health Care Service, 1 South Prospect Street, Burlington, VT 05401, USA
The EVIDENCE trial demonstrated that Interferon-ß-1a (IFN-ß-1a) , 44 mcg subcutaneously (sc) three times weekly (tiw) (Rebif(R)), was significantly more effective than IFN-ß-1a, 30 mcg intramuscularly (im) once weekly (qw) (Avonex(R)).
In reducing relapses and Magnetic Resonance Imaging (MRI) activity in patients with Relapsing/Remitting Multiple Sclerosis at both 24 and 48 weeks of therapy.
We now present final comparative data on these patients, showing that the superior efficacy of IFN-ß-1a, 44mcg sc tiw, for relapse measures and MRI activity, compared with IFN-ß-1a, 30mcg im qw, was sustained for at least 16 months.
The development of AntiBodies to IFN was associated with reduced efficacy on MRI measures and fewer IFN-related adverse events, but did not have an impact on relapse outcomes.
Metabolite Changes In Early Relapsing/Remitting Multiple Sclerosis A Two Year Follow-Up Study
Tiberio M, Chard DT, Altmann DR, Davies G, Griffin CM, McLean MA, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH
J Neurol 2005 Nov 24
Institute of Neurology, NMR Research Group, Queen Square, London WC1N 3BG, UK
Previous in vivo Proton Magnetic Resonance Spectroscopic Imaging (1H-MRS) studies have found reduced levels of N-Acetyl-Aspartate (NAA) in Multiple Sclerosis (MS) lesions, the surrounding Normal-Appearing White Matter (NAWM) and Cortical Gray Matter (CGM), suggesting Neuronal and Axonal Dysfunction and loss.
Other metabolites, such as myoInositol (Ins), Creatine (Cr), Choline (Cho), and Glutamate plus Glutamine (Glx), can also be quantified by 1H-MRS, and studies have indicated that concentrations of these metabolites may also be altered in MS.
Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-Acetyl-Aspartyl-Glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early Relapsing/Remitting MS (RRMS).
Twenty RRMS subjects and 10 healthy control subjects underwent 1H-MRS examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM.
At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7%, p = 0.003), as well as in the CGM (-8.7%, p = 0.009).
NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects.
While Neuronal and Axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible.
Compared with other MR imaging measures, serial 1H-MRS may be relatively less sensitive to progressive pathological tissue changes in early RRMS.
Age-Related Gadolinium-Enhancement Of MRI Brain Lesions In Multiple Sclerosis
Tortorella C, Bellacosa A, Paolicelli D, Fuiani A, Di Monte E, Simone IL, Giaquinto P, Livrea P, Trojano M
J Neurol Sci 2005 Dec 15;239(1):95-9
San Paolo Hospital, NeuroPhysioPathology Unit, Bari, Italy
There is evidence that inflammatory processes in Multiple Sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of Brain Magnetic Resonance Imaging (MRI) lesions in MS patients.
Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients.
Seventy-three patients (36.5%) showed at least one enhancing lesion.
Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans.
Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004).
The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age.
Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p < 0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions.
This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.
NeuroPsychiatric Symptoms In Patients With Multiple Sclerosis
Figved N, Klevan G, Myhr KM, Glad S, Nyland H, Larsen JP, Harboe E, Omdal R, Aarsland D
Acta Psychiatr Scand 2005 Dec;112(6):463-8
Stavanger University Hospital, Section of Geriatric Psychiatry, Stavanger, Norway
To explore the range of psychiatric symptoms in patients with Multiple Sclerosis (MS) and their association with Neurological disability.
Patients diagnosed with MS during 1998-2000 in Rogaland and Hordaland counties, western Norway, were included.
Psychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI). Patients with Systemic Lupus Erythematosus (SLE) served as controls.
Eighty-six of 93 eligible MS patients were included, and 80% showed at least one psychiatric symptom. The most frequent symptoms were depression (59%), sleep disturbance (48%), irritability/emotional lability (42%), and apathy (31%).
Depression was associated with higher disability score. MS patients showed significantly higher NPI irritability score (P = 0.002), appetite disturbance score (P < 0.001), and apathy score (P = 0.01) than SLE patients.
Neuropsychiatric symptoms occur frequently in patients with MS. Irritability and apathy are independent of disability and chronic disease and represent unique disease manifestations.