“We just collapsed,” said his mother, Barbara. Surgeons removed the tumors, but Knodel became completely deaf.
Members of the new neurogenetics oncology progam include Melissa Maciel, medical assistant; Marguerite Knupfer, office assistant; Steven Chang, director; Vee Vo, practice coordinator; Sarah Cassidy, ASL interpreter; Jocelyn Malott, nurse practitioner; Scott Soltys, neurosurgeon; Syed Aftab Karim, neurosurgery fellow; Michelle Klesczewski, nurse practitioner; Kevin Graber, neurologist; Robert Fisher, neurologist; and Iris Gibbs, radiation oncologist.
It was the beginning of a journey now nearly 20 years long; in that time, more than 250 tumors came to grow in Knodel’s body, some as small as a few millimeters, others as large as 6 centimeters.
Doctors diagnosed Knodel with a rare condition called neurofibromatosis 2, caused by a genetic mutation that allows tumors to form anywhere in the body wherever there is a nerve. There is no cure for NF2, as are there none for a family of similarly disabling neurogenetic disorders that repeatedly assault the brain, spine and central and peripheral nervous system with tumors. In some of these disorders, the growths are internal; in others the uncontrolled growths are external, often large and distorted. The tumors can, in certain of these disorders, be cancerous. Patients often endure pain, weakness, numbness and loss of basic body functions. Some may develop a facial paralysis that prevents them from smiling.
As Daniel Knodel and his family began to understand the lifelong and pervasive nature of his disorder, they also began to understand that finding knowledgeable physicians would be a struggle.
More than once, Barbara Knodel said, they found that most doctors had no familiarity with a disorder as rare as NF2. “We had to try to explain what it was, to educate them,” she said. In one instance, without access to such specialized care, her son came close to death. “We almost lost him,” she said. “He was way too complex. There are few doctors who can deal with the complexity of the disease.”
“Imagine how much turmoil and difficulty these patients go through,” he said. Their disorders attack many organs, causing a long list of issues whose treatment requires drawing expertise from a number of fields.
“Patients have to go here for this issue and there for that problem, trying to get care,” he added.
Nor is the removal of one tumor the end of care, as it is with many of Chang’s patients “where you can fix a ruptured aneurysm and the patient goes home,” he said. “These patients have recurring issues.”
Chang decided to do something about it. This month, he and nearly a dozen Stanford physicians and clinicians opened the doors to a clinical neurogenetics oncology program designed to treat these most difficult of patients. It is among a select group of programs worldwide that offer the expertise and experience the Knodels and others with similar needs have long looked for.
Stanford’s program is a team that includes 12 specialists in several fields — neurosurgery, epilepsy, neuro-ophthalmology, neuro-oncology, neuro-otology, neuro-interventional radiology, urology and general surgery. The goal, Chang said, is to give cutting-edge care for conditions including the two types of neurofibromatosis as well as schwannomatosis tuberous sclerosis, von Hippel-Lindau disease, Sturge Weber syndrome and hemorrhagic telangiectasia.
Care is coordinated to ensure that each patient’s visit includes all the necessary exams and procedures to address the multiple medical issues characteristic of these disorders, Chang said. There are so few programs in the United States that many patients must travel long distances for such care.
These disorders are rare. NF2 appears in just one in 40,000; von Hippel-Lindau one in 36,000. Neurofibromatosis 1 is more common: one in 3,000. Without cure, however, living with these systemic disorders requires the most sophisticated care. Knowing what to watch and how to watch for it is part of the skill needed over years of treatment. Knodel’s condition changes, and with each change comes a new challenge. He has already had more than 30 surgeries.
“This disease is worse than cancer,” his mother said. “They cut and cut.”
Since Knodel’s loss of hearing as a teenager, he has faced other serious threats. He had to have a shunt implanted in his brain to drain out spinal fluid that accumulated when his jugular vein occluded. When a tumor grew in a way that paralyzed his eyelids, he had to have spring-like devices inserted to maintain the blinking essential to eye health. Every six months, he must undergo scans of his tumors, especially those in his brain and spine, which threaten many of his remaining physical capabilities. The timing and the choice of tumor removal is, again, an art.
The question is, Chang said, “what will improve quality of life and what will not? These patients may have many surgeries, so it’s important to be as minimalistic as possible.”
Stanford will offer patients ongoing surveillance and the chance to build good working relationships with nurses, nurse coordinators and physicians. The program has built a system to coordinate all treatments and check-ups. “We’re trying to make it as easy as possible for our patients,” Chang said. “We want to take the burden off them.”
That concern includes making sure that at each visit, an American Sign Language interpreter is present to help patients who are deaf, like Knodel. He has also noticed that his Stanford physicians jump quickly to a computer to talk with him by typing, during an appointment or when he’s at home in Southern California. “Stanford has surpassed my expectation with providing accommodations for communicating,” Knodel said. “I’ve been to many hospitals, and Stanford is one of the few who does this. It’s a willingness to do things different for the well-being of the person they’re caring for.”
The program’s multidisciplinary team incorporates collaboration between specialists, essential for patients with disorders that have multiple effects on body systems.
“Increasingly in neuroscience we realize we should do things in a multi-disciplinary way,” said Robert Fisher, MD, a Stanford epilepsy expert, “so we can address all aspects of care. It is a great idea for the new Neurogenetic Oncology program to form itself as a multidisciplinary structure from inception. That’s the best way to get totality of care.”
Iris Gibbs, MD, co-directs the CyberKnife radiosurgery program with Chang; they have worked together for nearly 15 years. “We have to think strategically and carefully about how to introduce surgery, medical management and radiation in their safest and most effective use,” she said. “Having a team that has expertise across various disciplines means we can identify which treatment is appropriate and at what particular time it’s appropriate.”
Several of the team members are also involved in clinical research investigating this group of disorders. Chang, who also heads Stanford’s neuromolecular innovations program, is interested in identifying biomarkers that will help mark disease activity in these neurogenetic patients and make it easier to track its progress.
When her son was first diagnosed with NF2, Barbara Knodel was told to make every day count, that he might only live to be 20. He’s proven them wrong. He’s about to celebrate his 35th birthday. He has also earned a bachelor’s degree from the University of Southern California and a master’s in clinical psychology from CSU-Northridge. As an intern psychotherapist, he started a program to provide counseling for the deaf.
But NF2 remains a difficult obstacle. “Parents sometimes give up because it’s so overwhelming,” said Barbara Knodel. The new Stanford program has given her hope. “It is a rare find,” she said. “It’s an answer to many prayers.”
Sara Wykes is a writer in the communications office at Stanford Hospital & Clinics.