The path that brought Mary Beth Bidwell to the bed of a magnetic resonance imaging machine at Pennsylvania Hospital – her head shaved and topped with a plastic, water-filled cap and a huge helmet – began 12 years ago.
Bidwell, now a 52-year-old bookkeeper for PGA Magazine, was diagnosed with essential tremor, a condition that makes seven million Americans shake only when they try to do things. Bidwell had it worst in her dominant left hand, which made it hard for her to type and write, key components of her work. She felt conspicuous when she couldn't hold a spoon during a company chili cook-off. Essential tremor is not fatal, but it worsens over time and can be disabling.
Bidwell had not been doing well on propranolol, a medication often used for tremors. Her dose kept going up, but her hand still shook mightily when she tried to aim the TV remote or raise a glass of water. Plus, the drug causes fatigue, weight gain, and low blood pressure.
She had no interest in deep brain stimulation, the primary surgical intervention. It involves opening the skull, inserting wires into the brain, and stimulating a malfunctioning part of the thalamus with electricity to control the tremors. She was very interested, though, when she heard about a new noninvasive procedure that uses 1,024 converging beams of ultrasound to destroy the same part of the thalamus, the ventralis intermedius.
It can help only one arm, but, at best, she could emerge from the MRI with a newly steady dominant hand. Bidwell signed up for a clinical trial of MR-guided focused ultrasound treatment (MRgFUS) at Penn Medicine.
Bidwell's hairdresser cut off 16 inches of her hair in anticipation of the shaved head. The night before her procedure, Bidwell and her husband, Lon, waited nervously in their Glenside home. She got a massage to relax before spending hours in the cramped MRI.
Bidwell knew that the procedure wasn't perfect, and that she was only Penn's second patient. Her big question: "Is it going to work for me?"
The team that would treat Bidwell on June 8 was led by Gordon Baltuch, a tall neurosurgeon with wavy, graying hair who has done more than 1,100 deep brain stimulation procedures and is director of Penn's Center for Functional and Restorative Neurosurgery.
Focused ultrasound is just a new way of doing a thalamotomy, or removal of part of the thalamus, he said. That procedure has fallen out of favor because of its risks. It can still be done with radiation, but MRI-guided ultrasound is more precise, and surgeons get immediate feedback on the results. Deep brain stimulation has the huge advantage of being modifiable, but bleeding and infections can occur. Like Bidwell, some patients simply won't try it.
Baltuch was drawn to the ultrasound approach because it uses cutting-edge technology – just the pre-procedure brain mapping requires MRI, CT, and diffusion tensor imaging – and because he appreciates its "elegance" and potential to help older patients who might not fare well in surgery. The patient scheduled after Bidwell was 86.
Some surgeons question whether focused ultrasound is better than current options, but he thinks research institutions such as Penn must keep trying new things. "If you're not going to be the one who goes ahead and does this stuff, why be here?" he asked. "That's sort of our mission and vision."
A few blocks away, Jefferson Health neurosurgeon Chengyuan Wu, who specializes in brain stimulation for epilepsy, essential tremor, and Parkinson's disease, was skeptical. "I think it's interesting, but I don't think it's actually ready for prime time," he said of the ultrasound technique. He's worried about complications, including limb numbness and walking problems. It may seem safer not to open the skull, he said, but "ultimately, you're getting something burned in your brain, and that is irreversible."
Penn is the only place in the region doing this focused ultrasound treatment. The procedure was approved by the Food and Drug Administration for one type of MRI machine last July. The type Penn is using was added in May.
Approval was based on a study involving 76 patients that was reported in the New England Journal of Medicine in August. Scores on a measure of hand tremor severity and function improved by 47 percent at three months and 40 percent at 12 months after the procedure. (The difference in those two scores could have been due to chance.) Complications were common, though. Thirty-six percent of the patients had gait disturbance initially, and 9 percent still had impairment at 12 months. Thirty-eight percent had tingling or numbness immediately after the surgery. Problems persisted in 14 percent after a year.
Richard Schallhorn, vice president of neurosurgery at InSightec, the Israeli company that makes equipment needed for the procedures, said that all of the complications were considered mild and that results should improve as centers gain experience.
InSightec is also testing whether the approach can be used for Parkinson's and epilepsy symptoms as well as to temporarily open the blood-brain barrier to enhance treatment of Alzheimer's disease.
Even though the procedure is now FDA-approved, Penn decided to continue its trial with a few patients who had already signed up. That was lucky for Bidwell, because insurance coverage is still iffy. FDA approval does not guarantee insurance payment. Some centers are charging $35,000 to $40,000, said Ramya Singh, an InSightec vice president. Penn has not yet set a price.
A Stanford study published in April found that focused ultrasound was cost effective for essential tremor when compared with a type of radiation treatment and deep-brain stimulation. It estimated that the ultrasound treatment would cost about the same as stereotactic radiosurgery: $20,600.
Mary Beth Bidwell arrived at the hospital at 6:30 a.m. It takes time to shave a head so closely that nary a follicle might deflect an ultrasonic beam. Then a circular frame was screwed tightly onto her skull in four places. The plastic cap filled with circulating cold water would fit over it to keep Bidwell's skull cool during the treatment and provide a medium for the waves, which travel better in water than air.
It was 9:45 when she arrived outside the chilly MRI room on a gurney, escorted by six Penn and InSightec employees, including Baltuch. Nine people helped transfer her to the MRI table and fit her into the helmet, attached to the table. Her head had to stay perfectly still during the procedure.
Next came the painstaking work of making sure the ultrasound beams were targeted properly, partly by repositioning the helmet. Baltuch would do the procedure itself from a computer keyboard in the control room as an InSightec employee helped him navigate the software.
Baltuch asked questions such as: "Where did you get the laterality of the corticospinal tract?" His target within the thalamus is not obvious on an MRI scan. It must be located using other brain landmarks. Baltuch's goal was to bring the temperature to 55 to 60 degrees Celsius (131 to 140 degrees F) to create a box-shaped 4x5x6-millimeter lesion (smaller than a dry black bean) near the intersection of the motor thalamus and the sensory thalamus. Too small and Bidwell's tremor would remain. Too big and there would be complications. His first patient, John Lukens, a construction project manager from Plymouth Meeting, had no side effects and thought his tremors were gone. Baltuch still detected slight shaking. Every brain is different.
With feedback from the MRI about position and temperature in the target area, Baltuch's team fired test "sonications," waves strong enough to warm the target, but too weak to damage cells. Periodically, the staff would slide out Bidwell's table and ask her to draw a spiral. Gradually, the lines became smoother. Repeatedly, they asked whether she felt any numbness. She never did.
In the control room, Baltuch said this felt like high-stakes surgery, even though he wasn't touching the patient.
"There's no eraser on the pencil here," he said. " … The art of this is knowing when to stop."
The fourth time Bidwell drew a spiral, the result looked normal. The staff smiled. Baltuch did one final sonication, the 15th, to bring the brain tissue to the target temperature. MRI images said the lesion was the right size. "We're done," Baltuch declared.
By about noon, it was time for Bidwell to come out of the machine. She said she would miss the water cap, which felt like a massage. It was weird to have surgeons using screwdrivers to take the frame off her skull. Then she discovered that she could hold a bottle without shaking. She smiled. She started thinking about clasping necklaces and buttoning blouses, little things that most women can take for granted.
"I'll be happy when I can pluck my eyebrows," she said.
Bidwell's enthusiasm dimmed a little by early evening. There were no tremors, but her left hand felt weak. It was still weak the next morning, and her upper lip drooped slightly on the left. There was still no numbness and all of her sensations felt normal, but there was a big problem when she stood up for Baltuch's nurse practitioner, Hanane Chaibainou. Bidwell's left knee buckled, and it took two occupational therapists to help her walk into the hall and back. Baltuch suspected she had some swelling, a normal response to any brain damage. "It looks like the lesion we made is a good lesion and it's where we want it to be," he told her. "I think it's going to get better with time."
Bidwell was realizing that, even though no one had cut open her skull, she had had brain surgery. It would take a while to recover.
Over the next week, her condition improved rapidly. She graduated from a walker to a cane and could walk, carefully, with neither in her house. Her hand still felt weak, but it didn't shake. "It's kind of cool," she said. She was able to to eat soup without spilling for the first time in 10 years and type accurately, though her hand tired easily.
She realized she should have considered side effects more carefully. "I feel naive because I feel like I didn't even give a thought to not having mobility in my hand to function," she said. She now knew it might take months to fully recover. She was optimistic that she would.
Two weeks out, walking felt normal to her and she had graduated from occupational therapy. She was still concerned about fine motor skills such as writing, but she was improving every day. She was looking forward to returning to work soon.