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Glatiramer acetate is a synthetic, random copolymer widely used as a first-line agent for the treatment of relapsing-remitting multiple sclerosis (MS). While earlier studies primarily attributed its clinical effect to a shift in the cytokine secretion of CD4+ T helper (T(h)) cells, growing evidence in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), suggests that glatiramer acetate treatment is associated with a broader immunomodulatory effect on cells of both the innate and adaptive immune system. To date, glatiramer acetate-mediated modulation of antigen-presenting cells (APC) such as monocytes and dendritic cells, CD4+ T(h) cells, CD8+ T cells, Foxp3+ regulatory T cells and antibody production by plasma cells have been reported; in addition, most recent investigations indicate that glatiramer acetate treatment may also promote regulatory B-cell properties. Experimental evidence suggests that, among these diverse effects, a fostering interplay between anti-inflammatory T-cell populations and regulatory type II APC may be the central axis in glatiramer acetate-mediated immune modulation of CNS autoimmune disease. Besides altering inflammatory processes, glatiramer acetate could exert direct neuroprotective and/or neuroregenerative properties, which could be of relevance for the treatment of MS, but even more so for primarily neurodegenerative disorders, such as Alzheimer's or Parkinson's disease. In this review, we provide a comprehensive and critical overview of established and recent findings aiming to elucidate the complex mechanism of action of glatiramer acetate. [ABSTRACT FROM AUTHOR]

Glatiramer acetate, formerly known as copolymer 1, is a mixture of synthetic polypeptides composed of four amino acids. Glatiramer acetate has been shown to be effective in preventing and suppressing experimental autoimmune encephalitis (EAE), the animal model of multiple sclerosis (MS). Therefore it was tested in several clinical studies, where it was found to slow the progression of disability and to reduce the relapse rate and the magnetic resonance imaging (MRI)-defined disease activity and burden in relapsing-remitting MS. As a daily standard dose, 20mg of glatiramer acetate is injected subcutaneously. After injection, glatiramer acetate undergoes rapid degradation to amino acids and shorter peptides; so it is not possible to measure any systemic plasma concentrations or excretion rates. Two major mechanisms have been proposed to explain the effects of glatiramer acetate in EAE and MS: the induction of glatiramer acetate-reactive T helper 2 (Th2)-like regulatory suppressive cells and the interference with T cell activation as an altered peptide ligand. The most common adverse effects were mild injection site reactions (erythema, inflammation and induration). The most remarkable adverse event is the acute and transient immediate postinjection reaction manifested by flushing, chest tightness, palpitations and dyspnoea. Other reported adverse effects are transient chest pain and lymphadenopathy. Antibodies to glatiramer acetate induced during treatment do not interfere with its clinical effects. In several controlled clinical studies, glatiramer acetate has been shown to provide consistent, reproducible clinical benefits in the target population of patients with relapsing-remitting MS. The safety profile and risk-benefit ratio are excellent. Overall, glatiramer acetate is very well tolerated and has an excellent risk-benefit profile in patients with relapsing-remitting MS. [ABSTRACT FROM AUTHOR]

Focuses on the possible therapeutic use of statins in multiple sclerosis. Amelioration or prevention of disease expression in several experimental autoimmunie encephalomyelitis animal models; Demonstration of an adoptive T-cell transfer model; Mechanism of action of statins.

Presents a discussion on the presented research data on cytokine production in the different clinical forms of multiple sclerosis. Analysis of the cytokine profiles of in vitro nonspecificaly activated peripheral blood lymphocytes; Use of intracellular flow cytometric methods.

Abstract Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

A 32-year-old man presents an intermittent weakness in his legs and arms. His symptoms have progressively deteriorated over the past 6 months. He has trouble swallowing, which deteriorates when he continues to eat. He reports that his head is heavy and hard to hold up. On examination he has dysarthria and weakness of facial muscles, tongue and neck. He displays progressive fatigability in upward gaze during the Simpson test. Bilateral fatigable ptosis, diplopia, weakness of his neck flexion, and shoulder abduction are noted. Edrophonium testing demonstrated a dramatic transient improvement in his dysarthria, and a diagnosis of myasthenia gravis (Ossermanns and Genkins III) with high titre acetylcholine receptor antibodies (137 nmol/l) and Titin antibodies (20 nmol/l) were confirmed. The decremental response to repetitive stimulation studies of the accessory nerve was at 50%. In the ct-thorax we saw a 9 × 5 cm hypodense tumor ( Fig. 1 ) and additionally ventral and paravertebral also tumors suspicious as possible metastases. Our patient was then commenced on treatment with pyridostigmine and incrementally increasing prednisolone. Initially the patient had a benefit from the therapy, but later he developed a myasthenic crisis. His spirometry deteriorated from 3 to 0.8 l. An intravenous immunoglobulin therapy was commenced. His respiratory function was almost normally again. A thymectomy was performed in the Clinic for Thorax, Heart and Vascular Surgery two months later. Also a pneumectomy right, pericardectomy were necessary because of miliary infestation of the right lung. Additionally a resection of diaphragm was necessary because of 2 metastases. The patient became an intrathoracal chemotherapy with cisplatin. The histology showed a high differentiated carcinoma of thymus (Masaoka IVa, WHO Type B3) with infiltration of the diaphragma, pericard, pleura visceralis et parietalis and the lung parenchyma. The postoperative course was accompanied by pain of the upper thoracic aperture. A symptomatic therapy with opiates could only alleviate the pain. We made an ultrasound scan of the thorax. A pleural effusion was suspected and 1.5 l of old blood was punctured. After this puncture the patient showed signs of a cardiogenic shock. There was a heart luxation to the right side in ct thorax ( Fig. 2 ) without pneumothorax. The patient had a heart rate of 115. Under the therapy with beta blocker became his resting heart rate lower. The echocardiography showed a normal ejection fraction. The surgeons saw no need for another operation. After this episode two rehabilitations had to be prematurely terminated because of myasthenic exacerbation and a bad fitness of the patient. The patient needed a therapy with immunoglobulines 3 times altogether because of bulbar symptoms like dysphagia and dysarthria under the basic therapy with azathioprine 150 mg, prednisolone 30 mg and pyridostigmine 120 mg daily. The patient is still complaining about pain in the upper thoracic aperture and his physical fitness is reduced. Up to 10–15% of patients with myasthenia gravis have a thymoma. Only 7% of the patients have a malignant thymoma (Masaoka IVa) like our patient. The overall survival rates five years are 71%. The recurrence of this malignant thymoma is 34%. We intend to give our Patient adjuvant chemotherapy in the next weeks. [ABSTRACT FROM AUTHOR]