Braced by her partner, Suzanne Tobin shuffled back to her car parked in the cavernous garage at Johns Hopkins Hospital late on the evening of Oct. 22, 2013, distraught about what might happen next.
Tobin, then 60, had been driven by her partner, James Rapp, from their Germantown home to the Hopkins ER in hopes that doctors there could determine what was causing her relentless deterioration. Three months earlier, Tobin had held a full-time job as a copy editor at AARP in the District. She spent an hour before work striding around the Mall for exercise. Now she could no longer walk unassisted, her speech was nearly unintelligible and her left hand was so weak she could no longer hold a book.
Doctors in suburban Maryland had diagnosed a stroke — or possibly a series of strokes — but were unable to explain why Tobin kept getting worse by the week. Her neurologist counseled patience and offered to prescribe antidepressants, drugs that Tobin had told him she had taken for years.
An occupational therapist she’d been seeing had expressed alarm; stroke patients tended to plateau or even improve over time, not to experience a steady downward spiral. “You need to get a new neurologist,” she advised Tobin.
Tobin and Rapp decided their best bet was to head to Hopkins in Baltimore. But after 12 hours and a battery of tests, including a CT, MRI and other scans, emergency physicians sent Tobin home. They found no new stroke — an earlier MRI that Rapp had brought along appeared to show an old one — nor any other problem that would require immediate hospitalization. They advised her to follow up with her regular doctors.
At that point, Tobin recalled, “I was getting so bad I wasn’t sure what was going to happen.”
Less than two months later, Tobin was back at Hopkins, this time for an intensive four-day inpatient workup that produced a far different outcome. Within a day of her admission, neurologists on her medical team, headed by Nicholas Maragakis, suspected a diagnosis both shocking and completely unexpected — and, as it turned out, accurate.
“It was a huge relief,” Rapp said. Since July, doctors had seemed to discount Tobin’s accelerating symptoms, focusing instead on test results that proved to be misleading.
The first sign of a problem occurred in July 2013, when Tobin noticed a droop on the left side of her face, accompanied by slightly slurred speech. Her internist diagnosed Bell’s palsy, a temporary paralysis of the facial nerve that can be caused by a viral infection or Lyme disease. Some cases are mild and require no treatment; the problem simply resolves on its own after several weeks. More severe cases are often treated with prednisone, a corticosteroid that reduces inflammation.
After Tobin’s problem did not improve, her internist prescribed prednisone as well as a short course of physical therapy in the form of mouth exercises to improve her speech.
But Rapp and several of Tobin’s co-workers grew concerned that her symptoms signified something more serious. Despite PT, she began having problems moving her left hand and her speech did not improve.
On her daily walk, Tobin, who formerly worked at The Washington Post, said she noticed that her left foot seemed to be “sticking”; several times she nearly fell. The problem, known as foot drop, can be a sign of a pinched nerve, a stroke or a serious neurological illness, including amyotrophic lateral sclerosis, or ALS, commonly known as Lou Gehrig’s disease.
Her internist sent her to a neurologist. In September, an MRI showed evidence of lesions in the brain’s white matter, which controls overall function, suggestive of a prior stroke. Most strokes are caused by a blood clot, but doctors couldn’t find one. Tobin saw a cardiologist, who ordered tests to determine whether she had atrial fibrillation, an irregular heartbeat that can cause a stroke. Although her heart rate was normal, Tobin began taking a drug to lower her cholesterol, which was elevated, and another to control her elevated blood pressure, which had always been normal but was now rising ominously.
The neurologist had prescribed physical and occupational therapy to help her recover from her stroke. But each time she arrived for a session, therapists discovered that she had deteriorated or that new problems had emerged. Sometimes her blood pressure was deemed too high for PT.
Most worrisome to Tobin was her inability to function. Although she could move her fingers, she was unable to grasp objects with her left hand. Friends grew increasingly unable to understand her on the phone. She had mood swings and cried often. “My emotions felt completely out of control,” she recalled.
By November Tobin, who had stopped working, was so disabled that Rapp hired a part-time aide to care for her while he went to his job as a computer programmer. The trip to Baltimore galvanized his search for a new neurologist. Rapp made appointments with two Montgomery County specialists, one of whom sees stroke patients at Bethesda’s Suburban Hospital, which is affiliated with Hopkins.
For Tobin, weekday afternoons between 2 and 4, after the aide left and before Rapp came home from work, were especially tough. “I remember sitting on the couch waiting for Jim to come one day and I started thinking, ‘I can’t live like this indefinitely and I don’t want to burden Jim or my family,’ ” she wrote in an e-mail. The thought of suicide flitted through her mind. “That had to be the nadir for me.”
By early December, a new round of brain MRIs showed additional white matter lesions, a sign of further neurological injury. A spinal tap failed to find an infection. Multiple sclerosis, ALS, Lyme disease and lymphoma had been ruled out. The neurologist at Suburban, who strongly suspected that her problem was not a stroke, referred her to Hopkins for an inpatient workup.
After a round of specialized blood tests, the Hopkins team quickly zeroed in on two diagnoses they considered most likely. The first was a malignant brain tumor. Tobin’s CD4 count, which measures a type of white blood cell that fights infection, was an alarmingly low 31; normal counts range from 500 to 1,500. Her level was equivalent to that of people with AIDS before a new class of drugs called antiretrovirals controlled the virus, preventing its progression. But tests showed that Tobin did not have HIV or AIDS; something else had decimated her immune system.
A second spinal tap revealed the answer. Tobin’s spinal fluid had high levels of the JC virus. This common virus, which affects most people in childhood, usually lies dormant and rarely causes problems — except in people with weakened immune systems.
In immunocompromised people, the CD4 cells that normally keep the virus in check are vanquished and the JC virus replicates and invades the brain, attacking the central nervous system by destroying the myelin coating that protects nerve cells. The result is a rare disorder called progressive multifocal leukoencephalopathy. What appeared to be Bell’s palsy and then a stroke were actually the first signs of PML.
The disease is life-threatening; if left untreated, it kills 30 to 50 percent of those affected in the first three months after diagnosis. In patients who survive, the result is typically significant permanent neurological damage. Tobin was immediately given drugs to prevent infection and bolster her immune system.
But one mystery endures: the underlying cause of Tobin’s PML. In addition to HIV, the condition can be triggered by leukemia and lymphoma as well as medications, including chronic use of corticosteroids, such as those taken for years after an organ transplant to battle rejection. In some cases, patients who have taken certain drugs for multiple sclerosis or rheumatoid arthritis have developed it; in 2009, a psoriasis drug was withdrawn from the market after it was linked to several fatal cases of PML.
Doctors have combed through Tobin’s records and her medical history but have been unable to discover what wiped out her immune system. Her low CD4 count has been classified as idiopathic CD4+ lymphocytopenia, or ICL.(Idiopathic diseases are those whose causes are unknown.)
“They are both such rare conditions that maybe 10 or 20 people have both” ICL and PML, said Bryan Smith, a neurologist at the National Institute of Neurological Disorders and Stroke. Smith treated Tobin at Hopkins last year before moving to NIH. Now he sees her in conjunction with a PML study in which she is enrolled. (Tobin is also part of an ICL study at NIH.)
The cause, Smith said, “may just be random bad luck.” Unknown genetic factors also may play a role. Smith said there is no way to know how long Tobin’s immune system had been deteriorating, a process that might have taken months or even years. And the five-month delay in diagnosis, he said, probably did not have a negative impact, “except emotionally.” The stroke misdiagnosis, he said, is not surprising because both stroke and PML can appear to be similar on brain scans. But stroke patients, he noted, do not deteriorate as Tobin did.
So far there is little effective treatment for PML. Tobin takes a cocktail of drugs, including an antibiotic and an antifungal to ward off infections as well as mefloquine, an anti-malaria drug that has shown mixed effectiveness in treating PML. Although her CD4 count remains low, the level of JC virus in her spinal fluid has steadily diminished.
After her diagnosis in December 2013, Tobin spent several weeks as an inpatient at the National Rehabilitation Hospital in Washington learning how to walk and talk again. She then entered an outpatient brain injury program, returning to Hopkins periodically to see neurologists and rehabilitation specialists.
“She is doing remarkably well and is so upbeat,” Smith said.
Tobin can now walk and has regained some use of her left hand. Her speech has markedly improved in the past six months, and her e-mails are thoughtful and detailed. She has resumed driving with special adaptive equipment. But she is conscious of her limitations. “I’m like a 2-year-old in terms of the amount of help I still need,” she said. “I can’t cook, and my short-term memory is totally gone.”
Among the hardest things about coping with her condition and her impaired immune system, Tobin said, are her inability to work and the necessity of avoiding illnesses transmitted by her young grandchildren or their parents.
Of her life now she says, “It’s hope for the best, plan for the worst.”