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PubMed2002

Technical note: the comparison of hypointense lesions from 'pseudo-T1' and T1-weighted images in secondary progressive multiple sclerosis.

There is a large historical database of dual-echo conventional spin-echo (CSE) magnetic resonance images in multiple sderosis (MS). If new analysis techniques can be developed then this database could provide valuable information. We have investigated a technique in which the late echo of a dual-echo data set is subtracted from the corresponding early echoyielding images, which appear qualitatively similar to T1-weighted images. This study investigated whether the hypointense lesions on the 'pseudo-T1' images (created as described above) were related to hypointense lesions on conventional T1-weighted images. The hypointense lesion areas were measured by a blinded observer using a computer-assisted contouring technique applied to pseudo-T1 and T1-weighted CSE images obtained from 17 patients with secondary progressive MS (SPMS). The mean hypointense lesion area from T1-weighted images was 2218 +/- 2072 mm2, compared to 1426 +/- 1353 mm2 from pseudo-T1 images (p = 0.008). There was, however, a strong correlation between the values obtained from the two sets of images (r = 0.93, p < 0.001). The strong correlation between the values obtained from the two sets of images suggests that pseudo-T1 images may be useful to investigate a subgroup of more destructive lesions in MS from historical databases and in future prospective studies when imaging time is limited.

Brain↗
PubMed2006

During 3 years treatment of primary progressive multiple sclerosis with glatiramer acetate, specific antibodies switch from IgG1 to IgG4.

In this study we analyzed the humoral immune response to glatiramer acetate in 16 GA-treated primary progressive MS patients and 9 placebo patients from the PROMiSe study. We have demonstrated that all multiple sclerosis patients (n=16) continuously treated with GA for 3 years developed anti-GA antibodies that peaked at month 3 and remained elevated during the whole study. We have also demonstrated that initially GA-reactive antibodies of the IgG1 subclass predominate, peaking at month 9 of therapy, but after 9 months IgG1 decreases while anti-GA antibodies of the IgG4 subclass increase and remain high for the 3 years of follow-up. These results support a shift from Th1 to Th2 in the antibody response to glatiramer acetate treatment.

Antibody Specificity↗
PubMed2000

ESIMS--an ongoing clinical trial in secondary progressive multiple sclerosis.

The design of a double-blind, placebo-controlled, European-Canadian Study on IVIG treatment in multiple sclerosis-ESIMS- is described. Three hundred and eighteen multiple sclerosis patients with a secondary progressive course, are treated with monthly infusions of immunoglobulin 10% 1 g/kg bodyweight or with 0.1 g albumin/vial for 27 months. The primary efficacy parameter is the percentage of patients with a confirmed treatment failure in the EDSS scale and/or the Nine Hole Peg Test Secondary outcome measures are MRI T2 lesion load, Magnetization Transfer Imaging, and MRI brainatrophy measures. Documentation of health resource utilisation and ability to work will cover socio-economic aspects. Recruitment of patients was completed in October 1998. The clinical part of the trial will be completed in April 2001.

Adult↗
PubMed2005

Nursing grand rounds: multiple sclerosis.

Multiple sclerosis (MS) is a highly variable, unpredictable disease and one of the most life-altering diagnoses a person can receive. Because it usually strikes in the prime of life, frequently progresses to disability, and has no cure, MS can make a strong emotional impact--not only on those who suffer from it, but also the healthcare team. Because MS is such a complex, multifaceted disorder, nurses who care for people with MS are faced with numerous clinical challenges. Many of the challenges are unique to MS, demanding, and time-consuming. Well-informed nurses are positioned to evaluate and explain the disease process, assist in the alleviation of symptoms, educate partners and families, and help improve quality of life. A case example can help nurses understand the real-life concerns of a person with MS.

Adult↗
PubMed2003

The effect of transcutaneous electrical nerve stimulation on spasticity in multiple sclerosis patients: a pilot study.

The aim of this study was to examine the effects of transcutaneous electrical nerve stimulation on spasticity in patients with multiple sclerosis. The study was carried out in the Hacettepe University School of Physical Therapy and Rehabilitation. The subjects in the study were 10 clinically definite, primary and secondary progressive type multiple sclerosis outpatients with mild to moderate spasticity in the plantar flexor muscles of the ankle. Stimuli of frequency 100 Hz and pulse width 0.3 msec were used 20 minutes per day for 4 weeks. Patients were assessed by electromyography, Modified Ashworth Scale, and Ambulation Index. Electromyography was performed before and after the daily treatment of spastic muscles with transcutaneous electrical nerve stimulation in order to assess the effect on muscle relaxation. The Modified Ashworth Scale and Ambulation Index were used before and after 4 weeks' treatment. After 4 weeks of treatment, there were statistically significant reductions in spasticity of both extremities as assessed by myoelectric activity and the Modified Ashworth Scale (P < 0.05). Ambulation Index level was not improved significantly (P > 0.05).

Adult↗
PubMedDate not supplied

Magnetic resonance imaging in primary progressive multiple sclerosis.

Ten to fifteen percent of patients with multiple sclerosis (MS) have a condition that is progressive from onset without a preceding relapsing-remitting phase: this is known as primary progressive multiple sclerosis (PPMS). Patients with PPMS tend to be older, often present with motor symptoms and, in contrast to relapsing MS, are as likely to be male as female. The conventional magnetic resonance imaging (MRI) characteristics of PPMS include a tendency to lower lesion loads and lower rate of new lesion formation. In common with relapsing MS, the relation between conventional MRI abnormalities and clinical condition is poor. Studies using newer MRI techniques, such as magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI), have also been carried out. These techniques are sensitive to a wider range of abnormalities within tissue, and their increased pathological specificity may be helpful in clarifying the underlying pathology of the condition.

Contrast Media↗
PubMed2004

Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis.

Multicentre baseline proton magnetic resonance spectroscopic data on primary progressive multiple sclerosis (PPMS) patients are acquired and analysed, using automatic analysis software. The metabolite ratios did not differ from centre to centre. The average N-acetylaspartate/creatine (NAA/Cr) ratio in PPMS was significantly lower compared to normal controls. No significant differences were observed in this ratio between lesion-containing regions (LCR) and normal-appearing tissues (NAT). Strong lipid resonances, even in the absence of lesions, are observed in the both grey and white matter in these patients. These observations suggest extensive diffuse and/or microscopic pathology in PPMS. No significant correlation between any of the metabolite ratios and the Extended Disability Scale Score (EDSS) or with other MR measures such as lesion burden and enhancement volumes is observed.

Brain↗
PubMed2004

The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients.

OBJECTIVE: The purpose of this study was to examine the relationships between cognitive functioning, whole brain magnetic transfer ratio (MTR) imaging, supratentorial 1H-magnetic resonance spectroscopy imaging (1HMRSI), and conventional T1 and T2 imaging in a homogenous sample of SPMS patients. METHODS: Nineteen patients underwent a single 90-min imaging session that obtained T1-and T2-weighted images and MTR. 1HMRSI was obtained on 14 of these patients. Patients underwent a neuropsychological battery, which was used to create an integrated measure of cognitive impairment. Cognitive impairment was the dependent variable in two hierarchical multiple regression analyses in which T2 lesion load, T1 lesion load, and MTR or NAA/Cr were entered sequentially. RESULTS: MTR was significantly related to cognitive functioning (deltaR2 = 0.22, P = 0.02) after accounting for T2 lesion load (deltaR2 = 0.33, P = 0.01) and T1 lesion load (deltaR2 = 0.00, P = 0.98). NAA/Cr was not significantly related to cognitive functioning. CONCLUSIONS: Cognitive dysfunction may act as a clinical marker of normal appearing brain tissue pathology in multiple sclerosis.

Adult↗
PubMed2005

Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis.

BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody that depletes CD20(+) B cells, has demonstrated efficacy in peripheral neurological diseases. Whether this efficacy can be translated to neurological diseases of the central nervous system with possible autoimmune B-cell involvement remains unknown. OBJECTIVE: To determine the effect of rituximab on cerebrospinal fluid B cells in patients with multiple sclerosis. DESIGN: Four patients with primary progressive multiple sclerosis were treated with rituximab. Cerebrospinal fluid and peripheral blood B-cell subsets were identified by flow cytometry from each patient before and after rituximab treatment. RESULTS: The B cells in cerebrospinal fluid were not as effectively depleted as their peripheral blood counterparts. Rituximab treatment temporarily suppressed the activation state of B cells in cerebrospinal fluid. The residual B cells underwent expansion after rituximab treatment. CONCLUSION: The effect(s) of rituximab on the cerebrospinal fluid B-cell compartment is limited in comparison with the effect(s) on the B cells in the periphery, but this finding will need to be confirmed in a larger group of MS patients.

Adult↗
PubMed2004

Dysregulation of IL-10 and IL-12p40 in secondary progressive multiple sclerosis.

Multiple sclerosis (MS) is a putative T helper 1 (Th-1) mediated inflammatory disorder of the central nervous system, and levels of pro-inflammatory and anti-inflammatory cytokines have been found to correlate with changes in MS relapses. However, it is unclear if cytokine profiles differ between relapsing-remitting (RRMS) versus secondary progressive (SPMS) disease stages. Cytokine production (IL-2, IL-4, IL-5, IL-10, IL-12p40, TNF-alpha, and IFN-gamma) was assessed by cytometric bead array (CBA) and intracellular cytokine staining from alphaCD3 antibody and mitogen stimulated peripheral blood mononuclear cells (PBMCs) from female RRMS and SPMS patients, and healthy controls. Significantly increased production of IL-12p40 and decreased production of IL-10 were observed in SPMS patients. Differences in immune responsiveness in RRMS and SPMS are important in the understanding of the evolution of the immunopathogenesis of the disease and for the development of disease type specific treatments.

Adult↗
PubMed2004

Mitoxantrone therapy in multiple sclerosis and acute leukaemia: a case report out of 644 treated patients.

As a rare complication of mitoxantrone (MITOX) therapy in multiple sclerosis (MS), a therapy-related acute leukaemia (TRAL) may develop. The incidence is difficult to estimate, as frequently single cases are reported, up to now a total of eight MS patients. Here we report a new case out of 644 patients. This is a 45-year-old female patient with secondary progressive MS who developed TRAL after a total dose of 48 mg/m2 MITOX. The TRAL was classified as acute myeloblastic leukaemia (AML) M4eo and showed an inversion of chromosome 16 and a partial trisomy 11. Her TRAL was treated with chemotherapy followed by allogeneic bone marrow transplantation. It responded well to the transplantation, whereas the MS symptoms initially worsened but have nearly returned to the pretransplantation level. This report brings the currently published frequency of MITOX-associated TRAL in MS therapy to five in a total of 2336 treated MS patients, representing an incidence of 0.21%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Peripheral blood leukocyte NO production in MS patients with a benign vs progressive course.

BACKGROUND: Nitric oxide (NO) may play a role in tissue destruction and axonal degeneration in multiple sclerosis (MS). OBJECTIVE: To investigate NO production by peripheral blood leukocytes (PBL) in patients with a benign and progressive course of MS. METHODS: PBL were isolated from 25 patients with a benign course of MS (BMS), 33 with secondary progressive MS (SPMS), 21 with primary progressive MS (PPMS), and 29 healthy individuals. Leukocyte supernatants were assayed for nitrite concentration, which is an index of NO generation, using the Griess reaction. Serum levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-12 were measured using ELISA. RESULTS: Compared to healthy controls, nitrite concentrations were higher in patients with BMS (p < 0.001), SPMS (p < 0.001), and PPMS (p < 0.05). There were no significant differences among the three clinical subgroups of MS. There was a correlation between nitrite concentrations and serum levels of IL-12 (p = 0.04), but not of TNFalpha. CONCLUSION: Increased NO production by PBL in patients with MS is independent of the disease course.

Adult↗
PubMed2001

[A preliminary result of treatment of progressive multiple sclerosis with autologous peripheral blood stem cell transplantation in China].

OBJECTIVE: To explore the clinical effect for treatment of progressive multiple sclerosis (PMS) by autologous peripheral blood stem cell transplantation (Auto-PBSCT). METHODS: One PMS patient was chosen. Peripheral blood stem cells (PBSCs) were mobilized with cyclophosphamide and G-CSF. The CD34+ cells harvesting was performed by continuous flow leukapheresis using a CS3000 plus blood separator. About 12.2 x 10(6) CD34+ cells/kg was collected and preserved at -196 degrees C in liquid nitrogen. PBSCs were reinfused after conditioned by CTX (120 mg/kg) and TBI(10 GY). G-CSF was used to help hematopoietic and immunologic reconstitution. RESULTS: After transplantation the patient received clinical remission, and the abnormal signals of MRI in T1-T4 disappeared, the examination results of the neuro-electrophysiology and T cell subgroup were improved obviously. There was no relapse after 6 months follow up. CONCLUSIONS: Auto-PBSCT is effective and safety for PMS. Duration of remission remains to be decided in long-term follow up.

Adult↗
PubMed2001

Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine.

Previous studies suggest that aminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. Although the mechanism underlying the beneficial effect on fatigue remains unclear, it has been proposed that aminopyridines may help to improve conduction in demyelinated central pathways, implicating both axonal and synaptic mechanisms. The objective of the present study is to determine whether 4-AP decreases daily-living fatigue in progressive multiple sclerosis. The effect of 4-AP on other neurophysiological and neuropsychological parameters was also considered. A 'double-blind', randomized, 'placebo-controlled', crossover trial was conducted on 54 patients with progressive multiple sclerosis. All patients received treatment with placebo and 32 mg per day of 4-AP, each for 6 months. The main outcome measure was the Fatigue Severity Scale. Secondary measures were EDSS, cognitive functions and neurophysiological parameters. Forty-nine patients (91%) completed the study. Changes in fatigue scores, EDSS and cognitive functions were not significantly different between 4-AP and placebo. However, when patients treated with 4-AP were divided into two groups according to the serum level of 4-AP, a significant effect on fatigue compared with placebo was observed in the 'high level' (>30 ng/ml) group (P=0.05). Synchronization of motor evoked potentials improved during 4-AP with respect to placebo (P=0.019) and this correlated positively with fatigue reduction (P=0.010). No relevant side effects were observed.

4-Aminopyridine↗
PubMed2000

Interferon beta-1b and secondary progressive multiple sclerosis: licence extension. Useful, but further assessment required.

(1) Interferon beta-1b is now licensed to treat patients with secondary progressive multiple sclerosis. (2) The clinical file that we compiled on this indication, includes a double-blind placebo-controlled trial in which 718 patients were treated for 2-3 years. The trial is methodologically sound. (3) In this trial, interferon beta-1b, at the only dose tested (8 MIU every two days by the subcutaneous route), significantly reduced the progression of the disability linked to the disease. After 2-3 years of treatment the percentage of patients confined to a wheelchair was, in absolute values, 16.7% in the interferon beta-1b group and 24.6% in the placebo group. (4) In this trial the adverse effects linked to interferon beta-1b were already known, i.e. mainly a 'flu-like syndrome at the outset of treatment, and reactions at the injection site. (5) More than a quarter of patients on interferon beta-1b had neutralising antibodies against interferon beta-1b. More follow-up is needed to determine the possible impact of these antibodies on treatment efficacy and on the possible risk of autoimmune diseases. (6) Treatment with interferon beta-1b is still costly.

Adjuvants, Immunologic↗
PubMed2005

[Blood serum of patients with secondary progressive multiple sclerosis changes neuron electric activity].

An effect of 20% blood serum estimated by the changes of background and excited spike activity of Retzius' neuron by Hirudo medicinalis, which does not contain myelin, has been studied in 2 groups of patients. The first group comprised patients with serum, containing antibodies to gangliosides, and the second one--patients without such antibodies. Incubation of Reitzius neurons in the serum with GM1-antibodies within 40 min resulted in the change of spike form, increase of cell stimulation threshold by average 20%, reduction of the frequency of spontaneous impulse activity by average 28%, decrease of the spikes number in response to the lower frequency (0.5 Hz) synaptic stimulation and inhibition of adaptation to the high frequency (10 Hz) stimulation. The use of the serum without GM1-antibodies caused a different change of the spike form and increased the stimulation threshold by 8% and sparser background impulse activity of the neuron by 40%. During low frequency synaptic activation of the neuron (0.5%), there was sensitivity disturbance and inhibition of the electric response to the high frequency stimulation. The results suggest that neuron injuries in multiple sclerosis may develop before morphological appearances of myelin lesions.

Adult↗
PubMed2004

Imaging primary progressive multiple sclerosis: the contribution of structural, metabolic, and functional MRI techniques.

Patients with primary progressive multiple sclerosis (PPMS) typically experience a progressive disease course from onset, leading to the accumulation of severe neurological disability. This is in contrast with the observation that the burden and activity of lesions on conventional magnetic resonance imaging (MRI) scans of the brain are much lower in patients with PPMS than in those with other less disabling forms of the disease. Studies with structural and functional MRI techniques are providing relevant contributions to the understanding of the mechanisms underlying the accumulation of irreversible neurological deficits in patients with PPMS. The results of these studies underpin that the main factors possibly explaining the clinical/MRI discrepancy observed in patients with PPMS include the presence of a diffuse tissue damage that is beyond the resolution of conventional imaging, the extent of cervical cord damage, and the impairment of the adaptive capacity of the cortex to limit the functional consequences of subcortical pathology.

Central Nervous System↗
PubMed2001

The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis.

OBJECTIVE: To assess the prevalence of Sjögren syndrome (SS) in patients with primary progressive MS (PPMS). BACKGROUND: SS may be considered in the differential diagnosis of MS. Age at onset and clinical presentation are similar in SS and PPMS. However, occurrence of SS in definite cases of PPMS has been recently reported. METHODS: Proposed clinical and laboratory diagnostic criteria for SS were systematically assessed in 60 consecutive patients with PPMS. The authors questioned all patients about xerophthalmia and xerostomia, biopsied minor salivary glands, and performed a Schirmer test, a salivary gland scintigraphy, and anti-Ro (SSa) and anti-La (SSb) serologies. RESULTS: Ten patients (16.6%) met four or more criteria for SS. This prevalence is higher than in the general population (1 to 5%) and implies that SS can mimic PPMS. CONCLUSIONS: The authors propose that SS should be screened for systematically in patients with PPMS.

Adult↗