Biernacki K, Antel JP, Blain M, Narayanan S, Arnold DL, Prat A
Arch Neurol 2005 Apr;62(4):563-8
Montreal Neurological Institute, McGill University, NeuroImmunology Unit and McConnell Brain Imaging Center
Interferon-ß therapy has been shown to reduce the rate of clinical relapse and the frequency of Magnetic Resonance Imaging-defined T2- weighted lesions in patients with Multiple Sclerosis (MS).
When given early, Interferon-ß also reduces the rate of development of Brain Atrophy and improves Axonal integrity. Nerve Growth Factor (NGF) can retard the severity and course of Experimental Allergic Encephalomyelitis.
To determine whether Interferon-ß effects on patients with MS could be related to modulation of NeuroTrophin-3 production within the Central Nervous System.
We studied NeuroTrophin production by human glial and Brain Endothelial Cells in response to coculture with MS patient-derived Lymphocytes, and correlated levels of NGF secretion with clinical and Magnetic Resonance Imaging-defined markers of disease.
We demonstrate that production of NGF by human Brain Microvascular Endothelial Cells is triggered by interaction with T-Lymphocytes derived from MS patients.
No such response was observed using human adult Microglia or human fetal Astrocytes.
Nerve Growth Factor production by Endothelial Cells was potentiated by pretreating Lymphocytes with Interferon-ß in vitro, and by using Lymphocytes derived from MS patients treated with Interferon-ß in vivo.
By using this assay, we show that levels of NGF induced by Lymphocytes from MS patients inversely correlate with Magnetic Resonance Imaging measures of Brain Atrophy and Axonal Injury.
These findings suggest that Interferon-ß-mediated production of NGF at the level of the Blood-Brain Barrier, whether acting as an ImmunoModulator or directly on Neural Cells, is another potential mechanism contributing to the Magnetic Resonance Imaging-defined effect of Interferon-ß on Brain Atrophy when given early in the course of MS.
Effective Combination Of Minocycline And Interferon-ß In A Model Of Multiple Sclerosis
Giuliani F, Fu SA, Metz LM, Yong VW
J NeuroImmunol 2005 Aug;165(1-2):83-91
University of Calgary, Department of Clinical Neurosciences, Calgary, Alberta, Canada
The objective of the current study was to investigate whether minocycline improves the effect of an existing Multiple Sclerosis (MS) medication, Interferon-ß, on Experimental Autoimmune Encephalomyelitis (EAE) in mice.
When used at sub-optimal doses, neither medication affected EAE but their combination at these doses led to the significant alleviation of EAE disease severity scores and histological outcomes.
In culture, the toxicity of T-Cells to Neurons was alleviated by their prior exposure to Minocycline or Interferon-ß and their combination further attenuated Neuronal death.
Collectively, these results suggest the utility of the combination of Minocycline and Interferon-ß in MS.
Impact Of The Medicare Modernization Act On Low-Income Persons
Havrda DE, Omundsen BA, Bender W, Kirkpatrick MA
Ann Intern Med 2005 Oct 18;143(8):600-8
Shenandoah University School of Pharmacy and Amherst Family Practice, Winchester, Virginia 22601, USA
Low-income Medicare beneficiaries without prescription benefits have high out-of-pocket medication expenses that can discourage adherence to treatment regimens.
The Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 created a temporary drug discount card program and a prescription benefit with low-income provisions to assist with medication expenditures for eligible seniors.
To determine the impact of the new drug discount card and prescription benefit on medication expenditures by low-income Medicare recipients who require pharmaceutical company assistance for obtaining medications.
Design & Setting
Retrospective, nonrandomized evaluation. Family practice physicians' office in northern Virginia.
137 Medicare recipients without prescription coverage who received assistance from pharmaceutical companies for medications.
Patients were stratified into 3 categories according to income, household size, and the Federal Poverty Line (FPL), as defined by the new Medicare act.
Participants' long-term oral and inhaled medications, dosages, and instructions for use were obtained. The MMA criteria for low-income provisions were applied for the drug discount program and for the prescription benefit.
Medication costs under the new Medicare benefits were compared with those incurred without assistance and with the use of pharmaceutical company programs for the cohort and FPL categories.
In all income categories, medication costs were lower after enrollment in all programs than those of patients without assistance. Compared with pharmaceutical company assistance, Medicare drug discount cards resulted in less savings for all income groups.
For the prescription benefit, persons with incomes less than 135% of FPL had the greatest benefit because of low-income subsidies.
Persons ineligible for low-income subsidies receiving the standard benefit had a smaller reduction in out-of-pocket costs and variable monthly expenditures; they realized a superior savings with pharmaceutical company assistance programs.
The generalizability of these findings is limited because the authors used a discount pharmacy to determine drug costs for persons receiving no assistance, could not determine asset criteria for the MMA drug benefit low-income subsidy, and used a selected Medicare population.
In a low-income Medicare population without prescription coverage, pharmaceutical company programs offered considerable savings and were superior to the Medicare drug discount cards.
For the Medicare prescription plan, the greatest savings was among those eligible for low-income subsidies.
Month-to-month medication costs may vary substantially for persons ineligible for such subsidies, and pharmaceutical company assistance may be a better alternative.
Plasma Cerebrosterol And Magnetic Resonance Imaging Measures In Multiple Sclerosis
Karrenbauer VD, Leoni V, Lim ET, Giovannoni G, Ingle GT, Sastre-Garriga J, Thompson AJ, Rashid W, Davies G, Miller DH, Bjorkhem I, Masterman T
Clin Neurol NeuroSurg 2006 Jul;108(5):456-60
Karolinska University Hospital, Huddinge, Division of Neurology, Department of Clinical Neuroscience, Neurology Clinic, R54, 141 86 Stockholm, Sweden
The concentration in plasma of the Brain-specific Cholesterol metabolite cerebrosterol has been proposed as a biomarker of NeuroDegeneration in Multiple Sclerosis (MS) and other Neurological Diseases.
It is unknown, however, which pathophysiological process in MS best accounts for variations in plasma cerebrosterol.
Patients And Methods
In this study, we related plasma cerebrosterol concentrations in 46 MS patients - 27 with a Relapsing/Remitting (RR) disease course and 19 with a Primary/Progressive (PP) course - to three conventional Magnetic Resonance Imaging measures:
On T1-weighted Brain scans, volume of Gadolinium-enhanced lesions (a marker of active inflammation) and hypointense lesions (a marker of edema or axonal loss) and on T2-weighted scans, volume of hyperintense lesions (a marker of disease extent).
By multiple-regression analysis, we uncovered negative correlations between the Cerebrosterol-Cholesterol ratio in plasma and both age at sampling (beta=-0.35 and p=0.079 in RRMS; beta=-0.76 and p=0.006 in PPMS) and volume of T2-weighted lesions (beta=-0.52 and p=0.078 in RRMS; beta=-0.50 and p=0.247 in PPMS).
We hypothesize that decreases in plasma Cerebrosterol may reflect the total spatiotemporal burden of MS-the cumulative effects of its dissemination in space and its duration in time.
Imaging Of Inflammatory Lesions At 3.0 Tesla In Patients With Clinically Isolated Syndromes Suggestive Of Multiple Sclerosis: A Comparison Of Fluid-Attenuated Inversion Recovery With T2 Turbo Spin-Echo
Wattjes MP, Lutterbey GG, Harzheim M, Gieseke J, Traber F, Klotz L, Klockgether T, Schild HH
Eur Radiol 2006 Jul;16(7):1494-500
University of Bonn, Department of Radiology, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany
The aims of this study were to determine and compare the sensitivity of T2 turbo spin-echo (T2 TSE) and Fluid-Attenuated Inversion Recovery (FLAIR) sequences at 3.0 T.
In the detection of inflammatory lesions in patients with Clinically Isolated Syndromes suggestive of Multiple Sclerosis.
Forty-nine patients were examined with a 3.0 T MRI system using 5 mm axial sections of T2 TSE (2:19 min), FLAIR (4:00 min) and pre- and postcontrast T1 spin-echo sequences (3:37 min).
Brain lesions were counted and categorized according to their anatomic location. Patients were classified according to Barkhof MRI criteria for FLAIR and T2 TSE sequences.
The FLAIR sequence detected more lesions in every anatomic region except for the InfraTentorial region.
The higher sensitivity was significant for the total number of lesions (p < 0.01), the JuxtaCortical (p < 0.01), and the PeriVentricular (p=0.01) region.
A 9% increase of InfraTentorial lesions using the T2 TSE sequence was not significant.
The higher sensitivity using the FLAIR sequence resulted in one additional MRI criterion in nine patients, whereas the better detection of InfraTentorial lesions using the T2 TSE sequence resulted in additional MRI criteria in three patients.
In conclusion, FLAIR provides the highest sensitivity when compared with the T2 TSE, although T2 TSE still has a diagnostic relevance in terms of MRI criteria classification.
Home Versus Outpatient Administration Of IntraVenous Steroids For Multiple Sclerosis Relapses: A Randomized Controlled Trial
Chataway J, Porter B, Riazi A, Heaney D, Watt H, Hobart J, Thompson A
Lancet Neurol 2006 Jul;5(7):565-71
National Hospital for Neurology and NeuroSurgery, London, UK
IntraVenous Steroids are routinely used to treat disabling relapses in Multiple Sclerosis, and can be administered in an outpatient or home setting.
We developed a rating scale that allowed us to compare the two strategies formally in a trial setting.
Patients who had a clinically significant Multiple-Sclerosis relapse within 4 weeks of onset were randomly assigned administration of a 3-day regimen of IntraVenous MethylPrednisolone either in an outpatient clinic (n=69) or at home (n=69).
The MS Relapse Management Scale (MSRMS) was developed to measure patients' experiences of relapse management as the primary outcome.
Efficacy of the two treatment modalities was compared in terms of traditional measures and economic cost. A cost-minimisation analysis was also done. Analysis was by intention to treat.
Of 149 eligible patients, 138 consented to participate in the trial and were randomly assigned to a treatment group.
Coordination of care was significantly better in the home-treatment group (median score 4.5 [IQR 3.0-11.4]) than in the hospital-treatment group (12.1 [3.0-18.6]; p=0.024).
The other dimensions of the MSRMS did not differ between groups (p>0.10).
Administration of Steroids was equally safe and effective in either location, and cost was either the same or cheaper when delivered at home than when delivered in hospital.
Treatment of relapses in Multiple Sclerosis with Intravenous Steroids can be effectively and safely administered at home, from both patient and economic perspectives.
Moreover, the trial indicates the importance of explicit and valid outcome measures of all aspects of service delivery when making decisions about health policy.
This finding has implications for complex service delivery care models for long-term diseases.
Motor Assessment Of Upper Extremity Function And Its Relation With Fatigue, Cognitive Function And Quality Of Life In Multiple Sclerosis Patients
Yozbatiran N, Baskurt F, Baskurt Z, Ozakbas S, Idiman E
J Neurol Sci 2006 Jul 15;246(1-2):117-22
Dokuz Eylul University, School of Physical Therapy and Rehabilitation, Izmir, Turkey
The aim of this study was to assess the motor function of upper extremity and its relation with Fatigue, Cognitive function and quality of life in Multiple Sclerosis (MS) patients.
Design, Setting, & Subjects
Cross-sectional and controlled study. Outpatient clinic in a university hospital.
Thirty-one patients with MS (25 women, 6 men; mean age 39.74 +/- 10.10 years; mean EDSS, 2.56 +/- 1.91) and 30 healthy subjects (20 women, 10 men; mean age 33.56 +/- 8.85 years) were enrolled into the study.
Nine-hole peg test (9-HPT) and Valpar Component Work Sample Test (VCWS-4), Upper Extremity Index (UEI), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS), and the Multiple Sclerosis Quality of Life-54 (MSQOL-54).
MS patients showed significant impairment in upper extremity motor functions, Cognitive function and excessive Fatigue compared to controls (p < 0.05).
9-HPT in MS group correlated with EDSS, UEI and MSQOL-54 physical health and Cognitive function, whereas VCWS-4 scores (assembly right, assembly left and disassembly) correlated only with EDSS and UEI.
No correlation was found between the VCWS-4 and Cognitive function and Fatigue in both of the groups. Compared to control group, a strong correlation existed between the 9-HPT and VCWS-4 in MS patients (p < 0.05).
The results indicate that disability level (EDSS), UEI and Cognitive function in MS patients are related with impairment in upper extremity motor function.
This again contributes to an impairment in physical domain of quality of life.
A strong correlation of the 9-HPT with VCWS-4 supports the use of the 9-HPT as a measure of manual dexterity and gross motor functions.