Articles on Medical Diseases and Conditions

Tag: MS

  • Multiple Sclerosis (MS)

    Multiple sclerosis is a chronic demyelinating disease that has a reputation for recurrent illness of unpredictable length and severity. A multifocal demyelinating process in cerebral hemisphere white matter results in various combinations of weakness, ataxia, vision difficulties, and parasthesias, frequently ending in paralysis. Thus, the clinical symptoms, especially early in the disease, can be mimicked by a considerable number of other conditions.

    Cerebrospinal fluid laboratory findings. Routine CSF test findings are nonspecific, and when abnormality is present, the standard CNS test results are similar to those of aseptic meningitis. The CSF total protein is increased in about 25% of cases (literature range, 13%-63%). The cell count is increased in about 30% of cases (literature range, 25%-45%), with the increase usually being mononuclear in type and relatively small in degree.

    The CSF gamma-globulin (IgG) level is increased in 60%-80% of cases (literature range, 20%-88%). Technical methods such as radial immunodiffusion produce more accurate results than electrophoresis. Problems have been recognized in interpretation of CSF gamma-globulin values because elevated serum gamma-globulin levels can diffuse into the CSF and affect values there. Many investigators analyze a specimen of serum as well as of CSF to see if the serum gamma-globulin level is increased. Several ratios have been devised to correct for or point toward peripheral blood protein contamination. The most widely used is the CSF IgG/albumin ratio. Albumin is synthesized in the liver but not in the CNS and therefore can be used to some degree as a marker for serum protein diffusion into the CSF or introduction into the CSF through traumatic lumbar puncture or intracerebral hemorrhage. The IgG/albumin ratio is based on the theory that if serum leaks or is deposited into spinal fluid, albumin and IgG will be present in roughly the same proportion that they have in serum; whereas a disproportionate elevation of IgG relative to albumin suggests actual production of the IgG within the CNS. The normal CSF IgG/albumin ratio is less than 25% (literature range, 22%-28%). About 70% of MS patients have elevated IgG/albumin ratios (literature range, 59%-90%). The IgG/albumin ratio is a little more specific for MS than increase of IgG by itself. However, many conditions produce increased IgG within the CNS, such as chronic CNS infections, brain tissue destruction, CNS vasculitis, systemic lupus erythematosus and primary Sjцgren’s syndrome involving the CNS, and various demyelinating diseases.

    Another way to estimate CNS production of IgG is the IgG index, which is (CSF IgG level/CSF albumin level) ч (serum IgG level/serum albumin level). This index is reported to be abnormal in about 85% (range, 60%-94%) of definite MS patients. A third method for estimating CNS IgG production is the IgG synthesis rate formula of Tourtellote. Sensitivity of this method is about 85% (range, 70%-96%). Consensus seems to be that the IgG index is slightly more sensitive and reproducible than the IgG synthesis rate. Both can be influenced by altered blood-brain barrier permeability or presence of blood in the CSF as well as the various conditions other than MS that induce CNS production of IgG antibody.

    Another useful test is based on the observation that patients with MS demonstrate several narrow bands (“oligoclonal bands”) in the gamma area when their spinal fluid is subjected to certain types of electrophoresis (polyacrylamide gel, high-resolution agarose, or immunofixation; ordinary cellulose acetate electrophoresis will not demonstrate the oligoclonal bands). Oligoclonal banding is present in 85%-90% of MS patients (literature range, 65%-100%. Some of this variation is due to different methods used). Similar narrow bands may be found in subacute sclerosing panencephalitis, destructive CNS lesions, CNS vasculitis, lupus or primary Sjцgren’s syndrome involving the CNS, diabetes mellitus, and the Guillain-Barrй syndrome. A similar but not identical phenomenon has been reported in some patients with aseptic meningitis.

    Antibodies have been produced against myelin components, and a radioassay for myelin basic protein (MBP) is available in some reference laboratories. The MBP level is reported to be increased in 70%-80% of patients with active MS (literature range, 62%-93%), depending to some extent on the status of active demyelination. Incidence is less if the disease is not active or if steroid therapy is being given. The various demyelinating conditions other than MS also produce abnormal MBP assay results. The MBP level may also be increased in destructive CNS lesions such as a CVA, in some patients with the Guillain-Barrй syndrome, and in some patients with CNS lupus erythematosus.

    Summary. Of the various laboratory tests for MS, the two most widely used are the spinal fluid IgG index and presence of oligoclonal bands. Of these, the best single test is probably oligoclonal banding. CT and MRI can often demonstrate focal demyelinized areas in the CNS, with CT reported to show abnormality in 40%-60% of patients with definite MS and MRI positive findings in about 90% (range, 80%-100%). Neither CT nor MRI is currently able to differentiate MS with certainty from other CNS demyelinizing diseases.

  • Safety of complementary therapies

    Few complementary therapies have been fully scientifically evaluated, especially in relation to MS. Almost any therapy, scientifically evaluated or not, that has the power to produce very good and positive results, has the potential to do harm. Although complementary therapies are considered as ‘natural’ and, almost by association, to be intrinsically safe, this is not always the case. For example, some herbal medicines have to be very carefully targeted to symptoms and very sensitively administered, otherwise they may be harmful. So it is important both to ask about side effects, i.e. those other than the wanted effects, of
    complementary therapies, and to be alert in case they occur. Note that practitioners may expect initial ‘reactions’ or ‘aggravations’ or symptoms as part of the effective working of the therapy. A competent therapist should both warn you about these and what to do, if and when they occur.

  • The future of DMTs (disease-modifying therapies) in MS

    It is undoubtedly true that we are in a very exciting phase of development of DMTs. Although we cannot yet talk about a cure, we can now consider seriously the possibility of slowing down the course of the disease and not just ameliorating the symptoms of relapses. However, the results of research so far seem to suggest that the earlier the current DMTs (the interferons and glatiramer acetate) are given in the course of the disease, the more effect they are likely to have. One current controversy is how early these drugs should be given. Some believe that
    they should be given at the very earliest sign of MS, others that these drugs should wait upon a full and clear diagnosis on more comprehensive criteria. Their cost is a major issue, particularly in relation to medium- and long-term benefits that have not yet been fully proven, and is a significant factor that has had to be considered by every healthcare system.
    For people whose MS is more advanced, and particularly is progressive in nature, the effects of these DMTs seem to be very substantially less. As such people form the majority of those with MS at any one time, then many people will still feel disappointed that few possibilities exist for them in controlling their disease. However, there is very active research being undertaken at the moment to evaluate whether different combinations of any of the current DMTs could affect the course of Multiple Sclerosis for such people.

  • Approaches to treatment

    There are now two basic approaches to treating MS medically.
    First there are drugs that aim to suppress, minimize or halt the destructive immune response, that is the inflammation and the accompanying symptoms that occur when MS is in an active phase. In this context the overall aim is to move from controlling one or more relapses, to minimizing and ideally halting further disease progression. Steroid drugs have been used for many years to try and control the inflamma- tion attending relapses and lessen symptoms, but they have little effect on the underlying disease. More recently, drugs based on beta-interferon and others based on glatiramer acetate are showing more promise in not only assisting in the control of relapses, but also appearing to modify the disease course in some people, as their effects seem to continue for several years. There are also as many as 50 promising individual therapies undergoing clinical trials at any one time, although few will end up
    being used in clinical practice, and the drugs are often targeted to only very specific types of the disease.
    The second approach is to assess and treat the individual symptoms (e.g. spasticity, continence difficulties, pain or fatigue) that result from the damage to the CNS. In this respect there is no single drug treatment
    – an ‘MS drug’ – for all the symptoms of MS because of the immense variation and different rates of progression in each individual. Fortunately, MS is a condition where many symptoms can, in most cases, be relatively well managed for long periods of time.