Contrary to ciclosporin and tacrolimus, drugs that affect the first phase of T lymphocyte activation, sirolimus affects the second phase, namely signal transduction and lymphocyte clonal proliferation. It binds to FKBP1A like tacrolimus, however the complex does not inhibit calcineurin but another protein, mTOR . Therefore, sirolimus acts synergistically with ciclosporin and, in combination with other immunosuppressants, has few side effects. Also, it indirectly inhibits several T lymphocyte-specific kinases and phosphatases, hence preventing their transition from G 1 to S phase of the cell cycle. In a similar manner, Sirolimus prevents B cell differentiation into plasma cells, reducing production of IgM, IgG, and IgA antibodies.
Effects of steroid withdrawal are known to emulate and kick start many other medical complications as well. Weakness, loss of appetite, fatigue, nausea, weight loss, vomiting, diarrhea (further resulting in liquid and electrolyte complications), as well as abdominal pain are some of the most common effects that steroid withdrawal is often associated with. Constant decrease in blood pressure which simultaneously causes a person to faint or causes fits and dizziness are other complications the steroid use can cause.
Blood sugar levels are known to have dropped in many people who consume steroids. In women, menstrual changes have been reported widely. Muscle and joint pains, fever, changes in mentality, as well as elevation in calcium levels have been reported in some cases. Gastrointestinal contractions decrease dramatically which may ultimately lead to the swelling of the intestine .
To evaluate for the potential for other conditions, it would be appropriate to consider several blood tests in the initial evaluation of the patient with suspected MS. These tests include complete blood count (CBC), antinuclear antibodies (ANA), serum test for syphilis (RPR, VDRL, etc.), fluorescent treponemal antibody test (FTA), Lyme titer, ESR and, possibly, angiotensin converting enzyme level (a test for sarcoidosis). Imaging (MRI if at all possible) should be performed to rule out alternative diagnoses and because MRI can provide information about dissemination of disease. Over 90% of patients with MS have abnormalities on the MRI scan. Multifocal white matter disease of MS is easily observed but not easily differentiated from vascular lesions, gliotic scars or other forms of inflammation (see Chap. 11 ). As yet, there are no entirely pathognomonic criteria for MS on an MRI scan, but McDonald criteria are used in research studies. Spinal fluid examination may show evidence of immunologic activity in the CNS: slight elevation of mononuclear white blood cells (pleocytosis) is often found, and CSF oligoclonal IgG bands and increased globulin to albumin ratio can be found in 90% of cases. There may also be an increase in CSF myelin basic protein levels, which is evidence of actual damage to myelin. Evidence of subclinical demyelinated lesions can be provided by MRI, visual, somatosensory, or brain stem auditory evoked responses. The "hot bath test" is an historically interesting test. A hot bath often amplifies symptoms and worsens deficits by raising body temperature (which slows conduction in demyelinated plaques).