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At least 793 records · Page 44Linked to original sources
PubMed2007

Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation.

Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids.

Animals↗
PubMed2006

Update on multiple sclerosis.

In this article the basic features of the focal MR imaging lesions and the underlying pathology are reviewed. Next, the diffuse pathology in the normal-appearing white and gray matter as revealed by conventional and quantitative MR imaging techniques is discussed, including reference to how the focal and diffuse pathology may be in part linked through axonal-neuronal degeneration. The MR imaging criteria incorporated for the first time into formal clinical diagnostic criteria for multiple sclerosis are next discussed. Finally, a discussion is provided as to how MR imaging is used in monitoring subclinical disease either before or subsequent to initiation of treatment, in identifying aggressive subclinical disease, and treatment of nonresponders.

Atrophy↗
PubMed2003

Effect of inspiratory muscle training in patients with multiple sclerosis.

OBJECTIVE: To evaluate whether inspiratory muscle training (IMT) improves inspiratory muscle strength, respiratory capacity, fatigue, and subjective perception of physical endurance in patients with advanced multiple sclerosis (MS). DESIGN: Randomized controlled trial. SETTING: Outpatient clinic in Sweden. PARTICIPANTS: Fifteen severely disabled patients with MS, randomized to a training or control group. INTERVENTION: Seven patients trained with a Threshold inspiratory muscle trainer, twice every other day, with 3 sets of 10 loaded inspirations (40%-60% of patients' maximal inspiratory pressure [Pimax]) over a 10-week period. MAIN OUTCOME MEASURES: Spirometry, Pimax, maximal expiratory pressure (Pemax), clinical assessments, and questionnaires on the patients' fatigue severity and physical endurance were evaluated. RESULTS: After training, the Pimax (P<.008) and Pemax (P<.02) increased in the training group. The improvement in Pimax after 10 weeks of training was higher than the improvement in the control group (P<.01) and was maintained 1 month after the training period ended. The training affected neither respiratory function nor the patients' symptoms. CONCLUSIONS: IMT had a beneficial effect on inspiratory muscle strength in patients with MS and is recommended as a complement to ordinary physical training.

Adult↗
PubMed1999

Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.

BACKGROUND: Multiple sclerosis results from T-cell-dependent inflammatory demyelination of the central nervous system. Our objective was long-term suppression of inflammation with short-term monoclonal antibody treatment. METHODS: We depleted 95% of circulating lymphocytes in 27 patients with multiple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclonal antibody, Campath-1H. Clinical and haematological consequences of T-cell depletion, and in-vitro responses of patients' peripheral-blood mononuclear cells were analysed serially for 18 months after treatment. FINDINGS: Radiological and clinical markers of disease activity were significantly decreased for at least 18 months after treatment. However, a third of patients developed antibodies against the thyrotropin receptor and carbimazole-responsive autoimmune hyperthyroidism. The depleted peripheral lymphocyte pool was reconstituted with cells that had decreased mitogen-induced proliferation and interferon gamma secretion in vitro. INTERPRETATION: Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.

Adult↗
PubMed2003

Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions.

Matrix metalloproteinases (MMPs) are proteases involved in extracellular matrix (ECM) remodeling, leukocyte infiltration into lesions and myelin degradation in the central nervous system (CNS) disease multiple sclerosis (MS). We have investigated whether MMP-12 (macrophage metalloelastase) is expressed in MS lesions at various stages. In control patient tissue and (p)reactive MS lesions, only occasional microglial and astrocyte staining was detected. In contrast, in active demyelinating lesions, phagocytic macrophages were MMP-12 positive. A lower proportion of phagocytes was positive for MMP-12 in chronic active demyelinating lesions and inactive lesions. This suggests a role for MMP-12 during demyelination in MS.

Adult↗
PubMed2006

Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study.

BACKGROUND: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis. METHODS: 1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis. FINDINGS: The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0.92 (95% CI 0.77-1.08, p=0.30) and for the 5 mg glatiramer acetate treated group was 0.98 (0.83-1.15, p=0.76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated. INTERPRETATION: 5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.

Administration, Oral↗
PubMed2002

Tuberculous involvement of the oesophagus with oesophagobroncheal fistula.

Tuberculous involvement of the oesophagus is a rare disease. Even if it is suspected, diagnosis is often difficult though dysphagia and chest pain are the most common symptoms without any other specific signs of tuberculosis. The diagnosis is based on oesophagography, oesophagoscopy, bronchoscopy, and computed tomographic scan. Suspected tuberculosis can be confirmed with histology, smear, and culture. The two most common differential diagnoses are Crohn's disease and carcinoma. The case is reported of a female patient with tuberculous involvement of the oesophagus, who developed an oesophagobroncheal fistula during steroid treatment started for suspicion of Crohn's disease. The patient was immunocompromised due to treatment with azathioprine that she was receiving for multiple sclerosis. The fistula was successfully treated by antituberculous chemotherapy alone.

Adult↗
PubMed2000

Apolipoprotein E (APOE) phenotype and APOE concentrations in multiple sclerosis and acute herpes zoster.

OBJECTIVES: There are three major isoforms of apolipoprotein E (apoE), namely apoE2, apoE3, and apoE4, that are products of three alleles (epsilon2,epsilon3,epsilon4) at a single gene locus on chromosome 19. It is well known that the presence of apoE4 increases the risk for the development of Alzheimer's disease and atherosclerosis. The aim of the study was to examine if apoE polymorphism or apoE levels contribute to the severity of the disease in patients with multiple sclerosis or the outcome of nerve damage in patients with herpes zoster infection. MATERIAL AND METHODS: We examined apoE phenotype of 105 MS patients and 41 patients with herpes zoster. We also measured serum and cerebrospinal fluid (CSF) levels of apoE from 93 patients with definite MS using enzyme linked immunosorbent assay. RESULTS: There were no differences in apoE allele frequencies in MS or herpes zoster patients compared to the allele frequencies of controls. The levels of serum or CSF apoE did not differ from those of age-matched controls, nor did they correlate with the disease activity. CONCLUSION: We conclude that apoE does not contribute to the activity of MS or the outcome of herpes zoster.

Acute Disease↗
PubMed2006

[Measuring fatigue in patients with multiple sclerosis with standardized methods in German speaking areas].

Fatigue describes the presence of a pronounced and advanced state of weariness. People with fatigue need more energy and it takes more effort to perform different activities than expected when compared to the patients disability. Fatigue can be observed in up to 92 % of patients suffering from multiple sclerosis. In the presented study, the German fatigue severity scale (dFSS) was established following the English "Fatigue Severity Scale". We enrolled 20 patients suffering from a primary relapsing multiple sclerosis and compared them to 20 healthy controls. Fatigue was detected if at least 4 points were reached in the dFSS. The dFSS demonstrated high validity and reliability. The dFSS is able to differentiate patients with fatigue from healthy controls. As consequence, the dFSS can be used to evaluate fatigue in German speaking individuals. The presented data demonstrated a good internal consistence. The scale is able to measure fatigue in an economic and rapid fashion. Therefore, it can be used in clinical situations for measuring fatigue in German speaking individuals.

Adult↗
PubMed2002

Enhanced expression of NGF receptors in multiple sclerosis lesions.

The receptor for nerve growth factor (NGF) comprises a 75-kDa (NGFRp75) and a tyrosine kinase A (TrkA) subunit. In view of conflicting opinions on the identity of glial targets of NGF in human central nervous system (CNS), we examined the cellular distribution of both NGF receptor subunits in normal CNS and in chronic multiple sclerosis (MS) lesions. For this, we compared the pattern of recognition of 2 monoclonal antibodies (mAbs) and a polyclonal antiserum to NGFRp75. Only the 2 mAbs specifically recognized NGFRp75, while the polyclonal antiserum showed widespread reactivity. In normal CNS and silent MS lesions, immunohistochemistry with anti-NGFRp75 mAbs and for TrkA revealed perivascular cell reactivity. At the edge of chronic active MS lesions, selective NGFRp75 staining was prominent on reactive astrocytes, while throughout the lesion, NGFRp75 was expressed on microglia/macrophages. The vast majority of mature or precursor oligodendrocytes did not express NGFRp75. Both NGF receptors were co-expressed on a subset of inflammatory cells. Immunoreactivity for NGFRp75 on glial and immune cells did not correlate with the distribution of apoptotic figures, as detected by TUNEL. Thus, expression of NGF receptors in active MS lesions suggests a role for NGF in regulating the autoimmune response at both immune and glial cell levels.

Antibodies↗
PubMed2004

The therapeutic potential of botulinum toxin.

BACKGROUND: Botulinum toxin type A (BTX-A; commercial preparation BOTOX) is most well known for its effect on muscle contraction because of the BTX binding to the presynaptic nerve terminal, inhibiting the release of acetylcholine (ACH). The therapeutic benefit of BTX-A, however, can also be isolated to pain relief alone, suggesting that BTX-A also works through additional modes of action. OBJECTIVE: This article provides insight by an experienced physician into four different case reports. Each case demonstrates the therapeutic potential of BTX-A and the possibility of a different mechanism of action for BTX other than the inhibition of ACH release. RESULTS: Four patients, each with different symptoms such as relapsing-remitting multiple sclerosis, postherpetic neuralgia, peripheral neuropathy, and severe tingling caused by herniation of cervical vertebrae at the level of C8, were treated with BOTOX, and their symptoms were alleviated. CONCLUSIONS: The BTX-A mechanism providing pain relief is hypothesized to be something other than muscle relaxation by inhibiting the release of ACH at the neuromuscular juncture, such as inhibition of the release of substance P or the blocking of autonomic pathways, etc. This article is intended to continue to keep physicians using this substance for dermatologic indications aware of the potential unsuspected effects.

Adult↗