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Multiple Sclerosis

bob Shin, MD and Neda Frayha, MD
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Multiple Sclerosis is a common neurological condition with diverse presentations including  focal neurological symptoms. Symptoms lasting 24-48 hours and occurring over 30 days apart could be indicative of MS.  Evaluation includes MRI with gadolinium of the head and C-spine. On MRI, classic findings are white matter lesions in 2 of 4 areas: periventricular, juxtacortical, infratentorial, spinal cord. Referral to neurology is recommended to help with diagnosis and to direct treatment. 80-85% of cases are considered relapsing forms of MS. This is a newer and broader classification system compared to what many of us learned in training. There are three generations of treatment: interferons and glatiramer, "MS pills" as oral therapy, and injectable monoclonal antibodies. From one category to the next, there's increased efficacy of treatment as well as increased risk of side effects and need for monitoring.

Patients typically, but not always, experience a far milder clinical course than patients did a generation ago; to quote Dr. Shin, “the future is bright”  

 

 

Pearls:

  • Multiple sclerosis (MS) is an immune-mediated disease that leads to upper motor neuron demyelination (brain and spinal cord) most commonly occurring in women aged 20-40, though it can occur at any age.

  • MS often presents with nonspecific neurologic symptoms with diagnosis depending on a combination of history and physical and neuroimaging. A normal physical exam does not rule out MS.

  • Treatment for MS has been evolving: overall treatments are getting better leading to improving prognosis for those with MS.

 

  • What is multiple sclerosis (MS)? Immune-mediated disease that leads to nerve demyelination in the brain and spinal cord (upper motor neuron).

    • Can be diagnosed at any age but often between ages of 20-40.

    • Affects women more than men.

    • Characterized by episodes/attacks/exacerbations resulting in neurologic disturbances (ie: blurred vision, eye pain, numbness, tingling, weakness, imbalance, bladder symptoms).

  • What should we look out for in primary care? With such non-specific symptoms, MS can be easily missed. MRI imaging has become increasingly important in diagnosis of MS. People who are diagnosed earlier and started on treatment generally do better. Any unusual neurological symptom like a numb arm or blurry vision, especially of some duration (24-48 hours), demands an explanation. Erring on the side of early referral to neurology to not miss the diagnosis given earlier treatment is better, is reasonable.

  • Diagnosis

    • History and physical exam are the cornerstone.

      • “Symptoms separated by time and space”: Multiple episodes that affect multiple parts of the nervou system. Symptoms are usually separated by 30 days to distinguish between two different episodes or a single evolving episode.

      • Upper motor neuron: brisk reflexes, Babinski sign, increased tone, decreased vision (optic neuritis) that doesn’t correct with glasses.

        • Marcus Gunn pupil (aka: afferent pupillary defect):  when shining light to affected eye it does not cause as much constriction to the unaffected eye because the affected eye is not sensing the light as well.

      • Pearl: a normal neuro exam does not exclude MS.

    • Lumbar puncture (LP): 80-90% of MS patients should have oligoclonal bands but early on they may not. If negative, it does not rule out MS. It can be helpful if you’re wanting to rule out other things like infectious meningitis/encephalopathy or mimics like sarcoid. However, LP is not required to diagnose MS.

    • MRI of brain and cervical/thoracic spine w/wo gadolinium is increasingly important because it can detect MS earlier.

      • Four areas where patients get demyelination:

        • 1. Periventricular - all around the ventricles include corpus callosum

        • 2. Juxtacortical - myelin under the surface of the brain

        • 3. Infratentorial - cerebellum or brainstem

        • 4. Spinal cord

      • MRI should cervical spinal cord but you can also just start with the brain in someone you’re uncertain about.

  • Different types of MS

    • Relapsing: attacks with new deficits that may or may not be permanent.

    • Remitting: periods of months to years with no symptoms.

    • Progressive: gradually getting worse.

  • Treatment

    • Treatment became available in the 1990’s and consisted of interferons (Avonex, Betaseron and Copaxone). These are all injectables.

    • Today we have 14 different FDA treatments and another one on its way! Three of them are available in pill form and are at least as effective if not more than the older generation medications.

    • The big guns that carry more risk are the monoclonal antibodies. These  require certification under a special FDA program called REMS (Risk, evaluation and mitigation strategy programs)  to prescribe and administer the medications.

  • Medication monitoring:

    • First-generation medications (interferons): monitor CBC and LFTs to watch for bone marrow suppression and liver damage, both of which are very rare complications.

    • Second-generation medications (pills)

      • Gilenya (fingolimod): may have an artifactual decrease in lymphocyte count

      • Aubagio (teriflunomide): LFT monthly for the first 6 months and then back to once or twice a year.

      • Tecfidera (dimethyl fumarate): CBC every 6 months to watch for lymphopenia.

    • Monoclonal antibodies:

      • Tysaberi (natalizumab): associated wtih with PML (progressive multifocal luekoencephalopathy) caused by the JC virus, so patients will be checked for their JCV antibody. Most of us have had the virus (60%) but for those on treatment the risk of PML increases with time on the medication.

  • Symptom management:

    • Spasticity: baclofen or tizanidine help with relaxation but are also sedating.

    • Fatigue: amantadine (antiviral) helps combat fatigue. Modafinil or armodafinil (stimulants) may also help.

    • Bladder symptoms: urology or urogynecology can be helpful. Botox injection has been proven to be helpful.

    • Pain: typically neuropathic so meds like amitryiptyline or nortriptyline, gabapentin or pregabalin, or SNRIs like duloxetine or venlafaxine. Physical therapy. Aqua therapy.

    • Mood: depression and anxiety are common. SNRIs that will also treat pain.

  • Prognosis: Used to be a devastating diagnosis as it was untreatable but now much better. However, NEDA is  the new goal for treatment and can be achieved in some patients within the first year of treatment.

    • NEDA - no evidence of disease activity - goal for treatment.

      • No more clinical relapses

      • No more changes in MRI scans

      • No accumulation of disability

    • First generation treatments were able to reduce relapses by one third.

    • MS pills have been able to reduce relapses by 50%.

    • Monoclonal antibodies reduce relapses by up to 70%.

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