Demyelinating disorders

Biologic response modifiers (BRMs) are indicated in patients who have failed an adequate trial of DMARD therapy.1 BRMs may be added to DMARD monotherapy (i.e., methotrexate) or replace ineffective DMARD therapy.22 The decision to select a particular agent generally is based on the prescriber s comfort level with monitoring the safety and efficacy of the medications, the frequency and route of administration, the patient s comfort level or manual dexterity to self-administer subcutaneous injections, the cost, and the availability of insurance coverage.23 In general, BRMs should be avoided in patients with serious infections, demyelinating disorders (e.g., multiple sclerosis or optic neuritis) or heart failure.21... 

Neurologic events Infliximab and other agents that inhibit TNF have been associated in rare cases with optic neuritis, seizure, and new onset or exacerbation of clinical symptoms or radiographic evidence of CNS demyelinating disorders, including multiple sclerosis and CNS manifestations of systemic vasculitis. Exercise caution in considering the use of infliximab in patients with pre-existing or... 

Better definition of lesions in demyelinating disorders (e.g., multiple sclerosis) and, therefore, early identification... 

Rare but serious adverse effects of all anti-TNF agents also include severe hepatic reactions leading to acute hepatic failure, demyelinating disorders, hematologic reactions, and new or worsened congestive heart failure in patients with underlying heart disease. 

Other potential adverse responses include malignancy (e.g., lymphoma), liver disease, heart failure, lupuslike disease, irritation around the injection site, and demyelinating disorders that mimic multiple sclerosis.34,70 88 The incidence of these adverse effects, however, seems to be fairly low. For the most part, these drugs provide an acceptable risk-to-benefit ratio for most people with rheumatoid arthritis. Patients should, however, be screened carefully for any risk factors before beginning drug therapy, and should likewise be monitored periodically for any potential adverse reactions to these drugs. 

Caution in CNS demyelinating disorder, seizure disorder, vasculitis, or imunosuppressed... 

MS), which is a demyelinating disorder. When optic neuritis occurs without disc swelling, the condition is called retrobulbar neuritis. When disc swelling is associated with optic neuritis, the condition is called papillitis. Papilledema is bilateral disc edema associated with increased intracranial pressure OCP). Optic atrophy, the end stage of many optic neuropathies, is characterized by a pale disc and associated with a relative afferent pupillary defect (RAPD) and possible loss of visual acuity, color vision, and visual field. One example of disc atrophy occurs in cases of Leber s hereditary optic neuropathy... 

UccelH A, Zappia E, Benvenuto F, Frassoni F, Mancardi G (2006) Stem cells in inflammatory demyelinating disorders A dual role for immunosuppression and neuroprotection. Expert Opin Biol Tlrer 6 17-22. 

Multiple sclerosis (MS) is the most co imnon human demyelinating disorder of the CNS. The expression of some genes may increase in the CNS of patients with MS. Identify those genes. 

Fowler, R. C., Durbetaki, A. J. (1952). Cyanide and thiocyanate determination in multiple sclerosis and allied demyelinizing disorders. American Journal of Physiology, 171, 724. 

In the CNS, the major demyelinating disorder is multiple sclerosis (MS). MS should be differentiated from other disorders in which the histologic appearance of the lesions and the relapsing and remitting clinical course are similar. Acute MS lesions, in addition to plentiful foamy macrophages with increased proteases, have perivascular FCA-positive lymphocytes, EMA-positive and... 

As with alefacept and efalizumab, significant reductions in psoriatic lesions have been shown for significant numbers of patients. Except for injection-site reactions, the drug is well tolerated. Monthly complete blood counts with a differential should be monitored for the first 3 months of treatment. Potential side effects include aplastic anemia, increased risk of infection, and exacerbation of congestive heart failure and demyelinating disorders. The risk of malignancy is unknown but may be increased with the use of etanercept. 

Nervous system Demyelinating disorders provoked by mAbs are said to affect 0.02-0.2% of treated patients. Three patients with chronic lymphocytic anaemia developed acute inflammatory demyelinating neuropathy while being treated with alemtuzumab [90 ]. All three showed a good clinical response to treatment with intravenous immunoglobulin. 

Quarles, R. H. Myelin-associated glycoprotein in demyelinating disorders. Crit. Rev. NeurobioL 1989, 5 1-28. 

Adrenalectomy in rats is followed by a disturbance of intestinal fat absorption [98], and one could assume that in a child with myelin being still in the developmental stage this may lead to improper myelination. There is, however, no experimental evidence available to support this. Adrenalectomy, being frequently employed for palliative treatment of cancer, has not resulted in a demyelinating disorder as far as can be ascertained from the literature. 

---