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Neurofibromatosis,
NF1 and NF2, causes tumors to grow along the nerves,
often leading to significant pain and disability. A
compre-hensive center with the expertise of neurologists,
neurosurgeons and geneticists, along with advanced diagnostic
capabilities, can provide significant relief to adults
and children with this disorder.
Kathy Ramo has a new
appreciation for something most people take for granted—washing
her face. She has neurofibromatosis, type 1 (NF1), a
chronic genetic disease that causes tumors to develop
along the body’s nerves. A tumor had emerged on
her jaw, causing Ms. Ramo a great deal of pain.
“Every time I washed
my face or bumped against the tumor, the pain was unbelievable,”
says Ms. Ramo, who was diagnosed with NF1 when she was
11. She was examined by Dr.
Allen Maniker, associate professor of neurosurgery
at New Jersey Medical School, a specialist in peripheral
nerve and spine surgery, and a “team member”
of the Neurofibromatosis Center of New Jersey at University
Hospital. He recommended removing the troublesome tumor—which
in addition to causing pain, was growing quickly—as
well as three others on Ms. Ramo’s forehead, chin,
and chest.
“I had same-day
surgery on July 23 this year, which was a Friday, and
I was back at work on Monday,” says Ms. Ramo,
a 44-year-old secretary for an accounting department.
Although the tumors and the pain are gone and she’s
feeling great, Ms. Ramo knows that someday she, her
daughter, or her niece, all of whom have NF1, may need
to call on Dr. Maniker again.
Same
Name, Different Conditions
NF1 and neurofibromatosis,
type 2 (NF2), share a name, but are actually quite different.
NF1 tumors, which are usually benign but can become
malignant, grow on or below the skin and peripheral
nerves of the body. With NF2, the tumors are also benign
but grow in dangerous areas—on the cranial and
spinal nerves. Of the two, NF1 is far more common, affecting
about 1 in 3,000 people; NF2 occurs in about 1 in 40,000
people.
For both conditions,
patients who are proactive in seeking medical care typically
fare better than those who procrastinate. “When
a medical problem occurs in patients with NF, the sooner
they seek treatment, the better able we are to keep
them healthy,” says Dr.
Beth Pletcher, associate professor of pediatrics
at New Jersey Medical School, a geneticist, and medical
director of the Neurofibromatosis Center of New Jersey.
NF1 tumors often appear
as small lumps; these dermal neurofibromas, found in
or under the skin, are usually both benign and painless.
A less common type of tumor, the plexiform tumor, grows
along the body’s peripheral nerves (the nerves
that carry messages between the body and the brain);
about 5 percent to 10 percent of the time, a plexiform
tumor will degenerate into a neurofibrosarcoma, a rare
type of malignant soft tissue sarcoma. When a previously
painless tumor becomes painful or grows rapidly, it
may indicate the degeneration of a benign tumor into
neurofibrosarcoma.
For a variety of reasons,
many NF1 patients will have surgery to remove tumors.
Tumors can press against the spinal cord, causing significant
pain or making it difficult for a person to walk. Surgical
removal of a neurofibrosarcoma, in some cases followed
by radiation therapy, can optimize a patient’s
chances for survival. For other patients, the tumors
have grown so large that surgery is desired for cosmetic
reasons.
“Neurofibromatosis
is not a surgically curable disorder, but surgery often
has an important role in restoring function, improving
appearance, and in some cases, can be life saving,”
says Dr. Maniker.
Removal of NF1 tumors
can be very complex, especially with plexiform tumors,
which intertwine with nerve fibers. Along with removing
the tumor, the neurosurgeon is concerned about preserving
nerve function. University Hospital is one of the few
area hospitals to use intraoperative electromyography
(EMG). An EMG records a muscle’s electrical activity,
which can indicate the status of nerve function. “We
conduct continuous EMG monitoring during an operation
to ensure that, in the process of removing the tumor,
the nerves are not harmed,” says Dr. Maniker.
It was intraoperative
EMG that brought Cynthia Mudd to University Hospital.
She had other neurofibromas removed by her surgeon in
Bergen County, but the size and location of one particular
tumor—believed to be growing on her sciatic nerve—led
that surgeon to recommend Dr. Maniker and the use of
intraoperative EMG.
“The tumor was
on my right thigh and the size of a grapefruit,”
says Ms. Mudd, a speech language pathologist and the
mother of five. “I’d be walking, and the
leg would buckle, causing shooting pain.” In February
2003, Ms. Mudd’s tumor was successfully removed
without detriment to the nerves, preserving her leg
function.
Affecting
the Whole Body
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Tumors, like the ones
pictured above, can grow on or below the skin and
peripheral nerves of the body. |
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A multisystem condition
found in children and adults, NF1 affects the body in
other ways than tumors. Several café au lait
spots—flat, light tan to dark brown marks—typically
appear on the skin during infancy and childhood, often
providing the doctor’s first clue that a patient
has NF. Children with NF1 (especially girls) can develop
a rapidly progressive form of scoliosis—curvature
of the spine—that requires surgery. The shin bone
or the forearm can be bowed, and the sphenoid bone at
the base of the skull sometimes is misshapen.
A range of learning disabilities,
usually identified during childhood, affect about 40
percent of people with NF1. The reason why learning
disabilities are so common is not clearly understood;
however, MRIs of NF1 children’s brains have provided
some clues.
“In these images,
small bright spots—probably excess tissue—can
be seen. It’s thought that these bright spots
correlate to some degree with learning disabilities,”
says Dr. Pletcher. “Interestingly, over time,
these bright spots appear to fade.” With appropriate
intervention, she adds, many NF1 children can be successful
in school.
Other complications of
NF1 involve the eyes. Lisch nodules are tiny lumps that
form in the iris; they do not affect vision. Optic nerve
gliomas are another matter. These tumors—usually
found in children—develop on the optic nerve in
one or both eyes, causing decreased vision and in some
cases, blindness. Chemotherapy can be effective for
some cases; other times, surgery to remove the tumor
or reduce its size may be necessary.
Many manifestations of
NF1 occur during childhood, but the condition affects
adults, too. The tumors continue to develop throughout
a person’s life, sometimes never causing problems,
but in other cases, they press against nerves and cause
weakness, numbness, or pain.
High blood pressure is
also a concern for adults with NF1. “The underlying
cause of high blood pressure in NF patients can be different
than the general population,” says Dr. Pletcher.
“Rarely, for NF patients, it can be caused by
narrowing of the blood vessels entering the kidney;
decreased blood flow causes the blood pressure to rise.
For these people, treating the symptoms of blood pressure
rather than the narrowed vessels doesn’t solve
the problem. In a small percentage of NF patients, a
growth on the adrenal gland causes very significant
increase in blood pressure, and the growth needs to
be removed.”
The
Second Type of NF
As mentioned earlier,
NF2 is very different from NF1. The tumors develop within
the central nervous system rather than throughout the
body, and unlike NF1, usually do not present symptoms
until late adolescence or adulthood.
Some of the first symptoms
NF2 patients typically experience are hearing loss;
tinnitus, or ringing in the ears; and balance problems.
That’s because of tumor growth along the eighth
nerve, which leads from the brain to the inner ear.
These tumors, commonly referred to as acoustic neuromas,
grow slowly and are benign.
“The major complication
of acoustic neuromas is hearing loss,” says Dr.
Pletcher. “When these tumors are identified early,
the neurosurgeon can often remove most or all of the
tumor and preserve hearing. But when the tumor is large
and difficult for the surgeon to remove, the patient
can lose hearing in an ear.”
In
the Genes
Why does the body keep
producing tumors in NF patients? The underlying cause
is genetic. In NF1, a person does not produce enough
of a tumor-suppressing protein called neurofibromin.
Researchers have located the NF1 gene on chromosome
17 and identified more than 250 possible mutations.
NF2 patients do not produce enough of the protein merlin,
also a tumor suppressor. The NF2 gene is on chromosome
22.
Both NF1 and NF2 are
autosomal dominant disorders, meaning that someone with
either condition has a 50 percent chance of passing
the defective gene on to his or her children. In certain
cases, prenatal genetic testing can provide some information.
“In a family where
many people have NF1 or NF2, a linkage analysis can
be used to track the specific gene and determine which
chromosome 17 region the fetus received,” says
Dr. Pletcher. “But if the parent is the first
in the family to have neurofibromatosis and his or her
specific mutation can’t be found, then prenatal
testing isn’t feasible.” Genetic tests are
available for children and adults, but have a detection
rate between 65 percent and 70 percent. Additionally,
about half of all NF2 patients have the condition because
of a new mutation.
The decision to have
genetic testing is highly individual. Bart Brelje was
18 when he was diagnosed with NF1 and tuberous sclerosis,
another rare disorder; no one in his family had either
condition. Mr. Brelje has had several surgeries to remove
tumors, and today, a tumor on the left side of his head,
intertwined with nerves in his scalp tissue, is so complex
that surgeons won’t operate on it.
Knowing firsthand what
NF1 can bring, he and his wife, Beth, debated whether
or not to have children. When Mrs. Brelje became pregnant,
the couple met with a genetic counselor. “We did
not opt for any physical tests because aborting our
child was never an option for us,” says Mrs.Brelje.
“We believed, and still do, that Bart's life is
valuable, and any person born with NF also will enrich
this world in their way.”
Four-year-old Jasmine
Brelje, a preschooler and dog lover, was tested for
NF after she developed café-au-lait spots; she,
like her father, has NF1. So far, say her parents, Jasmine
is doing well, reaching her developmental milestones
and with only the café-au-lait spots as evidence
of her condition. Both father and daughter are patients
of Dr. Pletcher’s at University Hospital’s
NF center.
Calling
on the Team
By
its nature, a complex disorder such as NF requires the
skills of a multidisciplinary team. In 1994, when Dr.
Pletcher came to University Hospital, she began an NF
program similar to ones she’d worked on as a physician
on Long Island and during her fellowship in genetics
at Yale.
“Most geneticists
don’t have a large patient base that they follow
over the long term,” says Dr. Pletcher. “I
find it most rewarding to watch my youngest NF patients
grow up and make their way in the world. People with
NF are more proactive and better informed today than
ever before.”
Today, at University
Hospital, she is joined in the treatment of NF patients
by about 16 other physicians—specialists in neurology,
neurosurgery, orthopaedics, otolaryngology, ophthalmology,
plastic surgery, and dermatology, to name a few. (See
the Winter 2004 HealthLink article, "Team Players
Tackle Skull-Based Tumors)
The Neurofibromatosis
Center of New Jersey treats children and adults, many
of whom are already diagnosed. Not every patient is
seen by other doctors affiliated with the center, but
they will be examined by both Dr. Pletcher and an adult
or pediatric neurologist at least once a year. Children
under age 5 come twice a year for developmental monitoring.
Dr.
Stephen Kamin, associate professor of neurology
and neurosciences at New Jersey Medical School, is the
neurologist who evaluates adults. “Many NF patients
will see me once a year for a thorough neurological
history and exam, and they’ll be fine,”
he says. “But when a patient has problems, such
as numbness, pain, or difficulty walking, Dr. Pletcher
and I work together to identify the source of the symptoms
and whether to recommend surgery.”
Neurofibromatosis can
affect a patient’s nervous system in several ways.
When the nerves are involved, a person can experience
weakness, numbness, or pain; problems when walking;
and difficulties with bowel or bladder functions. Identifying
the source of these symptoms can be quite challenging,
says Dr. Kamin. “A patient has weakness in one
leg, but weakness originating from the spinal cord and
the peripheral nerves are two separate issues. We use
the neurological examination along with MRI, nerve conduction
studies, and other tests to reach a diagnosis.”
A
Positive Outlook
There are times when
having neurofibromatosis takes a physical and emotional
toll; that’s the nature of any chronic condition.
Proactive medical care, however, can go a long way toward
helping NF patients maintain their optimal health.
Arlene Henderson, 36,
considers herself fortunate even though she has had
several plexiform tumors removed; corrective scoliosis
surgery; and her left leg amputated below the knee.
It’s better than the prognosis she was given 30
years ago, when doctors told her she’d ultimately
need a wheelchair. A longtime patient at University
Hospital’s NF program, she keeps her annual appointments
with Dr. Pletcher and Dr. Kamin and has been treated
by many other University Hospital physicians.
Several years ago, she
began to experience numbness in her arms and legs when
lying on her back. Ms. Henderson went to some doctors,
not familiar with NF, who could not find the reason
for her problem. In 1999, she was seen by Dr. Michael
Schulder, an associate professor of neurosurgery at
New Jersey Medical School and a member of the University
Hospital NF team.
“Dr. Schulder was
very honest with me. He said I had a tumor on my cervical
spine—a difficult one, but surgically attemptable,”
says Ms. Henderson. “The surgery was a success,
ending a two-year struggle for me.”
Despite her many medical
setbacks, Ms. Henderson has taken college classes, attends
educational seminars, and volunteers as a consumer provider
for a mental health agency. “I’ve never
let NF hold me back,” she says.
To arrange
for a consultation at the Neurofibromatosis Center of
New Jersey at University Hospital, call 973-972-2550
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