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Multiple Sclerosis – Diagnosis, Management

Diagnostic Evaluation

Establishing a definitive diagnosis is often difficult, with much uncertainty concerning prognosis once the diagnosis is made.

Multiple sclerosis can be difficult to diagnose since its signs and symptoms may be similar to other medical problems. Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process especially in the first stages of the disease. Historically, the Schumacher and Poser criteria were both popular.

Currently, the Mc Donald criteria focus on a demonstration with clinical, laboratory and radiologic data of the dissemination of MS lesions in time and space for non-invasive MS diagnosis, though some have stated that the only proved diagnosis of MS is autopsy, or occasionally biopsy, where lesions typical of MS can be detected through histopathological techniques.

Clinical data alone may be sufficient for a diagnosis of MS if an individual has suffered separate episodes of neurologic symptoms characteristic of MS. Since some people seek medical attention after only one attack, other testing may hasten and ease the diagnosis.

The most commonly used diagnostic tools are neuroimaging, analysis of CSF and evoked potentials.

  • MRI of the brain and spine shows areas of demyelination (lesions or plaques). Contrast can be administered to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.
  • Testing of CSF obtained from a LP ( Lumber Puncture) can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS.
  • The nervous system of a person with MS responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials.
  • MRI scan of the spine are important to help diagnose and follow MS.

Management

MS treatment is dynamic and rapidly evolving, covering two main areas: direct treatment of MS, and treatment of the effects or symptoms resulting from MS. Treatment is aimed at relieving symptoms and helping the patient function. However, a therapeutic relationship between the patient and nurse creates a critical and strong bond that is essential across the long trajectory of the illness. Although there is no known cure for multiple sclerosis, several therapies have proven helpful. As with any medical treatment, medications used in the management of MS have several adverse effects. Alternative treatments are pursued by some patients, despite the shortage of supporting, comparable, replicated scientific study.

Treating Exacerbations

  • A true exacerbation of MS is caused by an area of inflammation in the CNS.
  • The treatment most commonly used to control exacerbations is I.V., high-dose corticosteroids. Solu-Medrol (ethylprednisolone) is one of the most commonly used corticosteroids in MS.
  • Plasmapheresis (plasma exchange) is only considered for the 10% who do not respond well to standard corticosteroid treatment.

Disease-modifying treatments

Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions at 1–3 month intervals. Current Disease-Modifying Drugs

  • Corticosteroids or adrenocorticotropic hormone are used to decrease inflammation, shorten duration of relapse or exacerbation.
  • Immunosuppressive agents may stabilize the course.
  • Interferon beta-1a and interferon beta-1b are being used for treatment of rapidly progressing symptoms in some patients.
  • Copolymer-1, a mixture of synthetic polypeptides composed of four amino acids, has been effective in reducing relapse rates and disability in patients with relapsing-remitting MS.
  •  Immunomodulator are used in relapsing-remitting disease.
  • Mitoxantrone (Novantrone), a chemotherapeutic agent used for the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting Multiple sclerosis to reduce neurologic disability and frequency of clinical relapses.

Fingolimod was approved for MS by the FDA in 2010, and in Europe in 2011. After this approval, there are six disease-modifying treatments for MS approved by regulatory agencies of various countries, being the other five:

  1. Interferon beta-1a.
  2. Interferon beta-1b.
  3. A third medication is glatiramer acetate, a non-interferon, non-steroidal immunomodulator.
  4. The fourth medication, mitoxantrone, is an immunosuppressant also used in cancer chemotherapy.
  5. The fifth is a humanized monoclonal antibody immunomodulator, natalizumab.

The interferons and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex, Natalizumab and mitoxantrone are given by IV infusion at monthly intervals.

All six kinds of medications are modestly effective at decreasing the number of attacks in relapsing-remitting MS (RRMS) while the capacity of interferons and glatiramer acetate is more controversial. Studies of their long-term effects are still lacking. Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab, both in terms of relapse rate reduction and halting disability progression. Mitoxantrone may be the most effective of them all; however, it is generally not considered as a long-term therapy, as its use is limited by severe secondary effects. The earliest clinical presentation of RRMS is the clinically isolated syndrome (CIS). Treatment with interferons during an initial attack can decrease the chance that a patient will develop clinical MS.

Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in patients with secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in patients in short-term follow-up. No treatment has been proven to modify the course of primary progressive MS.

As with many medical treatments, these treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferon treatments. Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons produce symptoms similar to influenza; some patients taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes. More dangerous but much less common are liver damage from interferons, severe cardiotoxicity, infertility and acute myeloid leukemia of mitoxantrone, and the putative link between natalizumab and some cases of progressive multifocal  leukoencephalopathy.

Management of the effects of MS

As for any patient with neurologic deficits, a multidisciplinary approach is key to improving quality of life; however, there are particular difficulties in specifying a ‘core team’ because people with MS may need help from almost any health profession or service at some point.

Under the direction of a physiotherapist, participation in physical activity can be safe and has been proven beneficial for patients with MS. Research has supported the rehabilitative role of physical activity in improving muscle power, mobility, mood, bowel health, general conditioning and quality of life. However, it is important to be cautious about not overworking or overheating the patient during the course of exercise. Physiotherapists have the expertise needed to adequately prescribe exercise programs that are suitable for the individual. The FITT equation (frequency of exercise, intensity of exercise, type of exercise and time/duration of exercise) is typically used to prescribe exercises. Depending on the patient, activities may include resistance training, walking, swimming, yoga,  and others. Determining an appropriate and safe exercise program is challenging and must be carefully individualized to each patient being sure to account for all contraindications and precautions.

CHRONIC SYMPTOM MANAGEMENT

  • Treatment of spasticity with agents, such as baclofen (Lioresal), dantrolene (Dantrium), diazepam (Valium); physical therapy; nerve blocks and surgical intervention
  • Control of fatigue with amantadine (Symmetrel) and lifestyle changes
  • Treatment of depression with antidepressant drugs and counseling
  • Bladder management with anticholinergics, intermittent catheterization for drainage, prophylactic antibiotics
  • Bowel management with stool softeners, bulk laxative, suppositories
  • Multidisciplinary rehabilitation management with physical therapy, occupational therapy, speech therapy, cognitive therapy, vocational rehabilitation, and complementary and alternative medicine as indicated to restore or maintain functions essential to daily living in individuals who have lost these capacities through the disease process
  • Control dystonia with carbamazepine (Tegretol)
  • Management of pain syndromes with carbamazepine (Tegretol), phenytoin (Dilantin), perphenazine/amitriptyline (Triavil), and nonpharmacologic modalities

Medications to control symptoms may include:

  • Medicines to reduce muscle spasms such as Lioresal (Baclofen), tizanidine (Zanaflex), or a benzodiazepine
  • Cholinergic medications to reduce urinary problems
  • Antidepressants for mood or behavior symptoms
  • Amantadine for fatigue

The following may also be helpful for people with MS

  • Physical therapy, speech therapy, occupational therapy, and support groups
  • Assistive devices, such as wheelchairs, bed lifts, shower chairs, walkers, and wall bars
  • A planned exercise program early in the course of the disorder
  • A healthy lifestyle, with good nutrition and enough rest and relaxation
  • Avoiding fatigue, stress, temperature extremes, and illness
  • Changes in what patient eat or drink if there are swallowing problems
  • Making changes around the home to prevent falls and ease in moving around
  • Social workers or other counseling services to help you cope with the disorder and get assistance (such as Meals-on-Wheels)

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