Multiple Sclerosis

Background

Early Stage squareMultiple sclerosis (MS) is a disease characterized by an autoimmune, inflammatory insult on the myelin sheath that insulates the nerve fibers of the central nervous system. The subsequent inflammation, demyelination, and axon degeneration disrupts the ability of parts of the nervous system to communicate, resulting in the various clinical manifestations. While the exact cause of MS is unknown, the most widely accepted theory involves the interplay between an initial autoimmune attack with possible genetic and environmental triggers.

Common symptoms include fatigue, motor weakness, gait/balance problems, numbness/tingling in the limbs or face, visual problems, bowel/bladder problems, and pain. These symptoms tend to occur in two major patterns -- as isolated attacks followed by improvement (relapsing-remitting course) or as a gradual progression over time; however, permanent neurological dysfunction often occurs as the disease advances.

MS is the most common autoimmune disease of the central nervous system and is second only to trauma as a cause of neurological disability beginning in early to middle adulthood. MS affects women about 2x more often than men, with an average age at disease onset of 30. MS affects approximately 2.5 million people globally, with 18,000 deaths each year.

Current Treatment

For the most common relapsing-remitting form, therapy can be divided into three categories: (1) treatment of acute attacks, (2) treatment with medications that reduce the biologic activity of MS, (3) symptomatic treatment. Currently, there is no cure for MS, but several therapies are beneficial in preventing new attacks, returning function after attacks, and preventing disability.

Acute Attacks/Demyelinating Episodes
Administration of high dose intravenous or oral glucocorticoids provides short term symptomatic relief, but does not seem to have a significant effect on long-term recovery.

Disease Modifying Therapy
Any patient with a definitive diagnosis of relapsing-remitting MS should begin disease modifying therapy as most of the immune response occurs early in the disease course. 

  • Immunomodulatory agents have been shown to benefit patients with MS through reducing the rate of relapses and slowing the accumulation of brain lesions on MRI.
  • Healthy lifestyle with regular exercise and a healthy diet is suggested for most patients. Dietary supplementation with omega-3 unsaturated fatty acids and/or vitamin D may also be recommended.

Symptomatic Therapy

  • Specific medications aimed at symptoms (i.e. spasticity, bladder dysfunction, pain, depression) have also been shown to be beneficial in MS.

Focused Ultrasound Research

Focused ultrasound has been used to non-invasively and accurately heat and destroy a predefined volume of tissue in the patient’s brain for numerous central nervous system diseases such as tumors and tremors. Preclinical studies have already demonstrated remyelination of axons with laser light in an optogenic model.  Another method of applying focused ultrasound is to pulse the ultrasound beam, which could nondestructively activate neurons by decreasing demyelination and increasing remyelination. Initial reports of success with this approach will lead to further research with this technique.

Notable Papers

Yoo SH, Croce P, Margolin RW, Lee SD, Lee W. Pulsed focused ultrasound changes nerve conduction of earthworm giant axonal fibers. Neuroreport. 2017 Mar 1;28(4):229-233. doi: 10.1097/WNR.0000000000000745.

Darvas F1, Mehić E1, Caler CJ2, Ojemann JG1, Mourad PD3. Toward Deep Brain Monitoring with Superficial EEG Sensors Plus Neuromodulatory Focused Ultrasound. Ultrasound Med Biol. 2016 Aug;42(8):1834-47. doi: 10.1016/j.ultrasmedbio.2016.02.020. Epub 2016 May 13.

Feinstein A, Freeman J, Lo AC. Treatment of progressive multiple sclerosis: what works, what does not, and what is needed. Lancet Neurol. 2015;14(2):194-207.

Campbell E, Coulter EH, Mattison PG, Miller L, McFadyen A, Paul L. Physiotherapy rehabilitation for people with progressive Multiple Sclerosis: a systematic review. Arch Phys Med Rehabil. 2015. pii:S0003-9993(15)01063-1.

     

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