Disease multifocal

Ocular toxoplasmosis is an important cause of posterior segment infection in older patients, with reports of disease presentation describing many atypical findings, including diffuse disease, multifocal lesions, and areas of involvement greater than three disc diameters in size. These individuals were not immunocompromised, but the disease severity was attributed to the decline in immune function that naturally occurs with aging. 

Peripheral neuropathies maybe widely disseminated or focal. Patients with disseminated polyneuropathy, whether demyelinative or axonal, usually demonstrate distal sensory and/or motor impairment. Multifocal neuropathy, also referred to as mononeuropathy multiplex, is often a consequence of lesions affecting the vasa nervorum, the blood vessels that supply peripheral nerves. The most common diseases to compromise the vasa nervorum and cause infarction of nerve fascicles are diabetes mellitus and periarteritis nodosa. Other frequent causes of mononeuropathy multiplex include infection (e.g. Lyme disease and leprosy) and multiple compression injury (e.g. bilateral carpal tunnel syndrome). When mononeuropathy... 

Progressive multifocal leukoencephalopathy (PML) is historically a rare demyelinating disease that is usually associated with disorders of the reticuloendothelial system, neoplasias and immunosuppressive therapy [1, 2]. However, it has become more important in clinical medicine because it is frequently seen as an opportunistic secondary infection in immunocompromised persons with AIDS. PML is characterized by focal lesions that are noninflammatory and caused by infection of oligodendrocytes with the JC papovavirus. 

Automatic atrial tachycardias such as multifocal atrial tachycardia appear to arise from supraventricular foci with enhanced automatic properties. Severe pulmonary disease is the underlying precipitating disorder in 60% to 80% of patients. 

Natalizumab was approved by the U.S. FDA for the treatment of MS in November 2004, and is being evaluated in Phase 3 clinical trials for IBD and CD.105 Based on Phase 3 clinical trials in MS patients, natalizumab appeared to be safe, since an increased rate of infection was not observed after 1 year of treatment.106 The safety of combined treatment with immunosuppressants, other than short courses of corticosteroids, was not evaluated and was not recommended because of the potential for an increased risk of infections. Flowever, barely three months after its approval, natalizumab was voluntarily withdrawn from the MS market by its manufacturer and all ongoing clinical trials were suspended due to the occurrence of a rare neurological disease, progressive multifocal leukoencephalopathy (PML), in 3 out of approximately 3,000 patients enrolled in clinical trials (2 in MS and 1 in CD).107 108 109... 

Van Assche, G. et al., Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn s disease, N. Engl. J. Med., 353, 2005. 

Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, et al Targeted disruption of the mouse transforming growth factor-pj gene results in multifocal inflammatory disease. Nature 1992 359 693-699. 

Thiotepa has antitumor activity against ovarian and breast cancers and lymphomas. However, it has been largely supplanted by cyclophosphamide and other nitrogen mustards for treatment of these diseases. It is used by direct instillation into the bladder for multifocal local bladder carcinoma. 

Natalizumab has shown significant efficacy for a subset of patients with moderate to severe Crohn s disease. Unfortunately, in initial clinical trials of patients with Crohn s disease and multiple sclerosis, 3 of 3100 patients treated with natalizumab developed progressive multifocal leukoencephalopathy due to reactivation of a human... 

W11. Wotherspoon, A. C., Doglioni, C., and Isaacson, P. G., Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) A multifocal disease. Histopathology 20, 29-34 (1992). 

Natalizumab (Tysabri), an anti-a4 integrin monoclonal antibody approved for the treatment of multiple sclerosis, was recently withdrawn from the market temporarily due to cases of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system associated with immunosuppression [32], These cases highlight our incomplete understanding of the immune system and the translation of preclinical results to humans. 

Neurological involvement in Behcet s disease may be subclassified into two major forms a vascular-inflammatory process with focal or multifocal parenchymal involvement and a cerebral venous sinus thrombosis with intracranial hypertension. The vasculitis and meningitis may affect cerebral arteries, particularly in the posterior circulation, to cause ischemic stroke and possibly intracranial hemorrhage (Farah et al. 1998 Krespi et al 2001 Siva et al. 2004 Borhani Haghighi et al. 2005). 

De Vries JJ, den Dunnen WF, Timmerman EA et al. (2006). Acute posterior multifocal placoid pigment epitheliopathy with cerebral vasculitis a multisystem granulomatous disease. Archives of Ophthalmology 124 910-913... 

M. M. Shull, I. Ormsby, A. B. Kier, S. Pawlowski, R J Diebold, M. Yin, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature, 359, (6397), 693-699, 1992. 

Multifocal inflammatory disease Transforming growth factor- Pi 24... 

This approach has been explored in attempts to treat progressive multifocal leukoencephalopathy/ a rapidly fatal disease caused by the JC virus and characterized by regions of central nervous system demyelination and markedly altered neuroglia. The virus is known to be sensitive in vitro to the action of cytosine arabi-noside (ARA-C) concentrations of 40 M (10 pg/mL) or more (12). Because the agent crosses the blood-brain barrier slowly Hall et al. (13) designed a study to test whether intraventricular/intrathecal administration of ARA-C could successfully treat JC virus in humans. ARA-C was administered as a bolus into the cerebrospinal fluid (CSF) space at the initial rate of 50 mg every 7 days. This ARA-C regimen was found to be... 

While inflammation is associated negatively with vasculitis and autoimmune disease, it is also necessary to protect normal cells from viral and bacterial infection. Many of the therapies that act positively as immunosuppressants have an initial inflammatory response. While lENp is an effective therapy in the inflammatory phases of MS, the initial response to each injection is an increase in inflammatory cytokines, IL-2 and lENy (Elliott et al., 2001). Conversely, natalizumab a therapy that show ed great potential in phase EE trials for aggressive MS by blocking activated lymphocyte trafficking into the CNS was withdrawn because of deaths due to progressive multifocal leukoencephalopathy. 

Giorgio, A., Francica, G., Aloisio, T., Tarantino, L., Pierri, R, Pellicano, M., Buscarini, L., Livraghi, T. Multifocal fatty infiltration of the liver mimicking metastatic disease. Gastroenterol. Internal. 1991 4 169 — 172... 

Three patients with chloroquine retinopathy have been studied with multifocal electroretinography (15). All three had been taking chloroquine for rheumatological diseases and all had electroretinographic changes that were more sensitive than full field electroretinography. It may be that multifocal electroretinography will be a useful technique in the assessment of suspected cases of subtle chloroquine retinopathy. 

Vidarsson B, Mosher DF, Salamat MS, Isaksson HJ, Onundarson PT. Progressive multifocal leukoencephalopathy after fludarabine therapy for low-grade lymphoproliferative disease. Am J Hematol 2002 70(1) 51. ... 

---