Multiple sclerosis complications end life of legendary Mouseketeer

Multiple sclerosis is an important topic to be aware of as you prepare for the ABIM board exam. This week an important news topic brings light to the topic of multiple sclerosis.   Before Britney Spears, Christina Aguilera and Keri Russell, there was Annette Funicello. On April 8, after a long struggle with multiple sclerosis (MS), Funicello, one of the original Mouseketeers passed away from complications of the autoimmune demyelinating disease. She was 70 at the time of her death and reported to be in a coma prior to her passing.   After enthralling television audiences of the “Mickey Mouse Club” in the 1950s, she transitioned to movies. In 1987, while promoting the film Back to the Beach, she began to experience vertigo spells. At age 45, she fit the MS profile of a young woman between the ages of 20-50 years having neurological complaints. Her imbalance led to unsteady gait to the degree that rumors spread that she was an alcoholic. To quell those rumors, she went public with her struggle with MS in 1992. Unfortunately, the disease continued to run its course. By 2004, she was unable to walk and by 2009, she lost her ability to speak, similar to the way many patients with MS find their condition deteriorate.   Diagnosing MS can be challenging due to the wide array of non-specific CNS symptoms that can arise often interspersed with times of normal sensory and motor function. Think of just about any neurological symptom and it can be a presentation of MS: Fatigue, numbness, diplopia, weakness, bladder incontinence, pain, tremors, memory difficulties and muscle stiffness.   Findings on MRI can help support a clinical diagnosis. Usually on T2-weighted images, multiple demyelinating lesions in the white matter surrounding the brain ventricles (called “Dawson’s finger” lesions), corpus callosum (dividing the left and right cerebral hemispheres), brainstem and spinal cord can be seen. For definitive diagnosis, at least two distinct symptomatic attacks involving two discrete CNS areas are required—a criterion clinicians recall as being “separated in space and time.”   Blood tests do not usually lead to the diagnosis but CSF findings typically show the following: normal opening pressure, normal glucose, slightly elevated protein, and between 5-40 WBCs/µL. About 80% of patients have more than 2 oligoclonal bands and an elevated IgG level in the CSF. However, neither is specific for MS as conditions such as Guillain-Barre syndrome, Lyme disease, lymphoma, lupus cerebritis may feature these findings.   Women with MS often experience a reduction in the frequency of their relapses in the third trimester of pregnancy but then an increase within the first six months post-partum. In Funicello’s case, her pregnancies were over a decade before she began experiencing her presenting vertigo. Her three children, being first-degree relatives, have a 20-50 times greater risk of being diagnosed with MS than the general population.   Funicello was born in Utica, New York to Italian-American parents. Some risk factors of MS include female gender, birthplaces with higher latitude away from the equator, and European descent. She spent most of her life in Southern California, where she worked on television and film projects and eventually settled down. Of note, along with exercise, heat tends to worsen symptoms of MS in an association known as the Uhthoff phenomenon.   The news of her passing comes on the heels of a new treatment for MS. Last month, dimethyl fumarate—a chemical initially used to prevent the growth of mold on furniture and inside shoes—was approved by the FDA after demonstrating a 44% and 53% reduction in relapses in two trials.   While there is no cure for MS, several medications have been developed to manage the symptoms. Since the 1990s, medications self-administered subcutaneously or intramuscularly, such as interferon-beta 1a (Avonex), interferon-beta 1b (Betaseron), and glatiramer (C opaxone), have been the mainstay of therapy. However, recently researchers have made inroads into offering more convenient oral medications.   In addition to dimethyl fumarate, which will be sold by Biogen Idec under the name Tecfidera—other oral medications include fingolimod (FDA approved in 2010) and teriflunomide (FDA approved in September 2012).   While the details of this case won’t be on the ABIM board exam, multiple sclerosis could be – so learn this concept well!