‘Laverne and Shirley’ Star’s Death

News

Actor David Lander, known for his role as Andrew “Squiggy” Squiggman on the sitcom “Laverne & Shirley,” died at the age of 73 at Cedars-Sinai Medical Center in Los Angeles, from complications of multiple sclerosis. In a statement to CNN, “David’s family hopes his fans will remember him for all the laughter he brought into the world.”

Lander was originally diagnosed with multiple sclerosis in 1984, a year after “Laverne & Shirley” ended its 8-year run. He began to experience dizziness and numbness in his hands and feet. A spinal tap revealed his diagnosis, but he kept it a secret to all but his family, as he thought it would end his career in Hollywood. In 1999, he publicly revealed his diagnosis in a memoir entitled, “Fall Down Laughing: How Squiggy Caught Multiple Sclerosis and Didn’t Tell Nobody.” In 2000, the National MS Society named Lander one of their National Ambassadors. He toured the country and became an advocate for patients with MS, speaking at conventions and fundraisers.

He particularly wanted to educate patients about early intervention for those newly diagnosed. In a 2007 interview with Brain & Life, Lander explained how much the outlook on MS changed since he was diagnosed: “When I was first diagnosed with multiple sclerosis, there was nothing you could do about it. Doctors would say, ‘diagnose and adios.’ Now, there are many treatments available to control this progressive disease.” His doctor originally painted a bleak picture, saying he wasn’t sure that Lander would ever walk again. After trials of corticosteroid and interferon-beta-1a, Lander was able to live a very full life. In addition to his MS advocacy work, he was a scout for baseball’s Seattle Mariners, did voice-over work for a number of television shows and video games, and wrote reviews of handicap-accessible areas in ballparks.

We first wrote about multiple sclerosis for MedPage Today in December 2010. The story, which included Lander, also pointed out a number of public figures (including Michelle Obama’s father) who were diagnosed with the disease. Quite a bit has changed in the treatment of MS since that time.

What is Multiple Sclerosis?

MS is a neuroinflammatory disease that affects myelin, nerve cell bodies, and the axons in the brain, spinal cord, and optic nerve. The term multiple sclerosis refers to the distinctive areas of scar tissue (sclerosis or plaques) that are visible in the white matter of people who have MS.

MS is the most common disabling neurological disease of young adults with symptom onset generally occurring between the ages of 20 to 40 years. In MS, the immune system cells that normally protect us from viruses, bacteria, and unhealthy cells mistakenly attack the protective myelin sheath of nerves in the central nervous system.

According to the National Multiple Sclerosis Society, MS is thought to affect more than 1 million people in the U.S. As with most autoimmune disorders, twice as many women as men are affected by MS. In addition, MS is more common in colder climates: the further from the equator, the higher the risk.

What are the signs and symptoms of MS?

The symptoms of MS usually begin over one to several days, but in some forms, they may develop more slowly. They may be mild or severe and may go away quickly or last for months. Sometimes the initial symptoms of MS are overlooked because they disappear in a day or so and normal function returns. Most people with MS have a relapsing-remitting form of the disease, in contrast to a more slowly developing form called primary progressive MS. Progressive MS can also be a second stage of the illness that follows years of relapsing-remitting symptoms (called secondary progressive MS).

Relapsing-remitting MS accounts for approximately 85%-90% of cases at onset. Secondary progressive MS usually occurs 10-20 years after the onset of the disease. Primary progressive MS is characterized by progressive disability from the onset of the disease with occasional plateaus or temporary minor improvements. The mean age of onset is 40.

A diagnosis of MS is often delayed because MS shares symptoms with other neurological conditions and diseases.

Early MS symptoms often include:

  • Vision problems such as blurred or double vision, or optic neuritis, which causes pain with eye movement and a rapid loss of vision
  • Muscle weakness, often in the hands and legs, and muscle stiffness accompanied by painful muscle spasms. It may be severe enough to affect walking or standing
  • Tingling, numbness, or pain in the arms, legs, trunk, or face
  • Clumsiness, particularly difficulty staying balanced when walking
  • Bladder control problems
  • Intermittent or more constant dizziness

MS may also cause later symptoms such as:

  • Mental or physical fatigue which accompanies the early symptoms during an attack
  • Mood changes such as depression or difficulty with emotional expression or control
  • Cognitive dysfunction — problems concentrating, multitasking, thinking, learning, or difficulties with memory or judgment

How is MS treated?

There is no cure for MS, but there are treatments that can reduce the number and severity of relapses and delay the long-term disability progression of the disease.

Treatments for attacks

Corticosteroids, such as intravenous methylprednisolone, are prescribed for courses of 3 to 5 days. Intravenous steroids quickly and potently suppress the immune system and reduce inflammation. They may be followed by tapered doses of oral corticosteroids. Clinical trials have shown that these drugs hasten recovery from MS attacks, but do not alter the long-term outcome of the disease.

Plasma exchange (plasmapheresis) can treat severe flare-ups in people with relapsing forms of MS who do not have a good response to methylprednisolone. This treatment has not been shown to be effective for secondary progressive or chronic progressive MS.

Disease-modifying treatments

Current therapies approved by the FDA are designed to modulate or suppress the inflammatory reactions of the disease. They are most effective for relapsing-remitting MS at early stages of the disease.

Injectable medications include:

Beta interferon drugs (Rebif, Betaseron, others) are among the most common medications to treat MS. Interferons are signaling molecules that regulate immune cells. Potential side effects of these drugs include flu-like symptoms (which usually fade with continued therapy), depression, or elevation of liver enzymes. Some individuals will notice a decrease in the effectiveness of the drugs after 18 to 24 months of treatment. If flare-ups occur or symptoms worsen, doctors may switch treatment to alternative drugs.

Glatiramer acetate (Copaxone) changes the balance of immune cells in the body, but how it works is not entirely clear. Side effects are usually mild and consist of local injection site reactions or swelling.

Infusion treatments include:

Natalizumab (Tysabri) is administered intravenously once a month. It works by preventing cells of the immune system from entering the brain and spinal cord. It is very effective but is associated with increased risk of a serious and potentially fatal condition called progressive multifocal leukoencephalopathy (PML). Natalizumab is generally recommended only for individuals who have not responded well to or who are unable to tolerate other first-line therapies.

Ocrelizumab (Ocrevus) is administered intravenously every six months and treats adults with relapsing or primary progressive forms of MS. It is the only FDA-approved disease-modifying therapy for primary progressive MS. The drug targets the circulating immune cells that produce antibodies, which also play a role in the formation of MS lesions. Side effects include infusion-related reactions and increased risk of infections. Ocrelizumab may increase the risk of cancer as well.

Alemtuzumab (Lemtrada) is administered for 5 consecutive days followed by 3 days of infusions one year later. It targets proteins on the surface of immune cells. Because this drug increases the risk of autoimmune disorders, it is recommended for those who have had inadequate responses to two or more MS therapies.

Mitoxantrone (Novantrone), which is administered intravenously four times a year, has been approved for especially severe forms of relapsing-remitting and secondary progressive MS. Side effects include the development of certain types of blood cancers in up to 1% of those with MS, as well as with heart damage. This drug should be considered as a last resort to treat people with a form of MS that leads to rapid loss of function and for whom other treatments did not work.

Oral treatments include:

Fingolimod (Gilenya) is a once-daily medication that reduces the MS relapse rate in adults and children. It is the first FDA-approved drug to treat MS in adolescents and children as young as 10. The drug prevents lymphocytes from leaving the lymph nodes and entering the blood, brain, and spinal cord. Fingolimod may result in a slow heart rate and eye problems when first taken. Fingolimod can also increase the risk of infections, such as herpes virus infections, or in rare cases be associated with PML.

Dimethyl fumarate (Tecfidera) is a twice-daily medication used to treat relapsing forms of MS. Its exact mechanism of action is not currently known. Side effects of dimethyl fumarate are flushing, diarrhea, nausea, and lowered white blood cell count.

Teriflunomide (Aubagio) is a once-daily medication that reduces the rate of proliferation of activated immune cells. Teriflunomide’s side effects can include nausea, diarrhea, liver damage, and hair loss.

Cladribine (Mavenclad) is administered as two courses of tablets about one year apart. Cladribine targets certain types of white blood cells that drive immune attacks in MS. The drug may increase the risk of developing cancer and should be considered for individuals who have not responded well to other MS treatments.

Diroximel fumarate (Vumerity) is a twice-daily drug similar to dimethyl fumarate but with fewer gastrointestinal side effects. Scientists suspect these drugs, which have been approved to treat secondary progressive MS, reduce damage to the brain and spinal cord by making the immune response less inflammatory, although their exact mechanism of action is poorly understood.

Siponimod (Mayzent) is taken orally and has a similar mechanism of action to fingolimod. Siponimod has been approved by the FDA to treat secondary progressive MS.

Clinical trials have shown that cladribine, diroximel fumarate, and dimethyl fumarate decrease the number of relapses, delay the progress of physical disability, and slow the development of brain lesions.

Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.

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