When the ambulance braked at the doors of the MGH in the early-morning
hours of March 13, the medical team on board sighed in relief. Throughout
the night, as they raced back to Boston from northern Vermont, they
knew that one of the biggest snowstorms in recent years was marching
up the coast toward New England.
But while one storm had been beaten,
another waited to challenge a team of MGH specialists. The patient
who arrived in that ambulance was a five-month-old child whose brain
was wracked by the electrical storms of severe, uncontrolled epilepsy.
Little Ian Pelkey appeared perfectly
fine when he was born in October 1992. Although he seemed rather
fussy at times and rarely slept through the night, generally he
was an alert, happy baby.
Now freed from almost constant seizures, Ian Pelkey is learning
how to walk. The helmet protects his healing brain fron the usual
bumps and bruises oftoddler hood.
But when he was about four months
old, Ian began to 'space out,' recalled his mother, Lynn Pelkey.
'At first we thought he was just starting to notice things, to focus
on them. But then we realized it was more like he was going into
The episodes became more frequent
and severe. The child's eyes rolled back in his head, his muscles
became rigid -- characteristic symptoms of epileptic seizures. By
now Ian's parents knew that something was seriously wrong. On the
advice of their pediatrician, they took the child to the Medical
Center Hospital of Vermont in Burlington, 40 miles from their home
in St. Albans.
The MCHV neurologists gave Ian a complete
examination and prescribed standard anti-seizure drugs, which initially
appeared effective. But the day after the child came home, the seizures
Back in the hospital, Ian's condition
became increasingly uncontrollable. Despite large doses of medication,
he was soon having literally hundreds of seizures a day -- sometimes
without a stop.
'We knew we had to find a hospital
better equipped to handle Ian's problem,' Ms. Pelkey said. The Vermont
doctors agreed and arranged Ian's transfer to the MGH.
Once Ian had safely arrived, the MGH
specialists began a lengthy search for a cause of his seizures.
Infantile epilepsy sometimes results from a brain injury occurring
either before or during birth. In other instances, seizures are
traced to abnormally developed brain tissue. Often no specific cause
can be found.
Some seizures appear to involve the
entire brain simultaneously, while others -- called focal seizures
-- emanate from a specific area. The difference is important, as
the generalized seizures respond better to medication.
The MGH team first conducted a 24-hour
electroencephalogram (EEG). This measurement of the brain's electrical
activity usually takes place over a couple of hours. But in cases
like Ian's, specialists make readings over a full day with simultaneous
video recording of physical activity. This allows neurologists to
correlate overt symptoms with what actually happens in the brain.
Ian's readings showed the numerous,
almost constant seizures, but the source of the problem was unclear.
'At first it appeared that the seizures were very broad, rather
diffuse throughout his brain,' said MGH neurologist Daniel B. Hoch,
'But there also was evidence suggesting
a focus of epileptic activity in the left frontal lobe [the part
of the brain right above the eyes]. EEG readings taken in between
seizures indicated a possible structural abnormality in the same
Following up this observation, the
MGH team ordered a PET (positron emission tomography) scan, an advanced
imaging technique -- pioneered at the MGH and other institutions--
that reveals activity within the brain.
'We were fortunate enough to get what's
called an ictal PET -- a PET image taken while he was in seizure
-- which clearly showed an area of overactivity in the left frontal
lobe,' MGH neurosurgeon G. Rees Cosgrove, MD , explained. 'This
led us to take another look at the MRI [magnetic resonance imaging]
studies, which initially had appeared normal.'
Dr. Rees Cosgrove
Close examination of the MRI, which
gives a detailed look at the brain's structure, revealed a subtle
area of abnormal tissue, also in the left frontal lobe. Additional
MRI studies, specially processed to enhance the images, clearly
identified the structural flaw.
The largest part of the brain, called
the cerebrum, consists of a thin, outer layer of grey matter surrounding
internal white matter. The grey matter contains the brain cells
involved in thought, movement, and sensation; the white matter contains
fibers that carry signals from one part of the brain to another.
Within the suspect portion of Ian's
brain was an area of grey matter that was up to five times thicker
than it should have been. This kind of abnormality -- called cortical
dysplasia -- is known to be associated with epileptic seizures.
Identifying this structural flaw held
out the possiblility that surgery to remove the tissue could relieve
Ian's symptoms. But because the child was so young and because of
the risks associated with any brain surgery, the MGH team first
tried different medication-based strategies to control the seizures.
'You always exhaust the medical options
before you go to surgery,' said Elizabeth C. Dooling, MD, the MGH
pediatric neurologist who oversaw Ian's care.
Initially the drugs reduced Ian's
seizures to one or two per day -- enough that he was able to return
home for several months. But it was not long before the seizures
again became more frequent.
'He just kept getting worse,' Mrs.
Pelkey recalled. 'The doctors were trying different drugs, and he
was in and out of the hospital up here. We really felt like we were
grasping at straws.'
One day before Ian was scheduled to
return for a follow-up visit, he was again brought to the MGH by
ambulance. 'I knew he wouldn't leave without the surgery,' his mother
'Of course my husband and I were scared
to death,' she added. 'We knew that removing a portion of his brain
had real risks -- paralysis, loss of function -- but we also knew
that he wouldn't stand a chance if the surgery was not done.'
In preparing to operate on Ian, Dr.
Cosgrove and his colleagues turned to one of the most recent developments
in imaging -- computer technology that allows information from different
kinds of images to be fused into a single picture.
A sophisticated MRI study provided
a detailed three-dimensional image of Ian's brain that could be
reproduced from any angle or cross-section. Then that information
was combined with data on brain activity from the PET scan. (see
'Fusing these two data sets gives
you a representation of both the anatomy and function of the individual
patient's brain. And we found that the area of overactivity from
the PET scan correlated precisely with the anatomic abnormality
from the MRI,' Dr. Cosgrove said.
The picture created from the fused
images also showed the pattern of folds and furrows on Ian's brain
-- a pattern that is slightly different for each individual. This
information helped Dr. Cosgrove map the location of key areas controlling
movement, areas to avoid in the operation.
'During the operation, we were able
to recognize the features we'd seen in the images,' he added. 'What
the computers were showing us was what we actually found during
Before removing the abnormal tissue,
Dr. Cosgrove placed EEG electrodes directly on the surface of Ian's
brain. Even though the child was under anesthesia with no evidence
of seizures, the electrodes showed that cells in the abnormal area
were firing in an epileptic pattern. The area was then carefully
removed using standard neurosurgical techniques.
Since the operation in July, Ian has
not had a single seizure and appears to be developing normally.
Dr. Dooling noted that the child now wears a special helmet to protect
his head as he is learning navigate the world as any toddler does.
He also continues to take antiseizure medications. 'After getting
those seizures under control, we don't want to take any chances,'
Although the operation removed a significant
portion of Ian's brain, his future prospects are quite good. 'This
was not normal brain tissue. It really did not have any function
except to give rise to seizures,' explained Dr. Cosgrove, who is
also an assistant professor of neurosurgery at Harvard Medical School.
He added that in young children the
brain is very adaptable. If an area controlling a particular function
must be removed, that activity can be taken over by the corresponding
area on the opposite side of the brain. 'The younger the child is,
the less likely there will be any deficit.'
Lynn Pelkey helps her son Ian celebrate his first birthday.
Andrew J. Cole, MD, chief of the MGH
Epilepsy Service, pointed out that Ian's story shows how important
it is to search for a potential structural cause of seizures.
'Right now we don't know how many
cases of severe childhood epilepsy are associated with a structural
abnormality, because doctors haven't always looked for one. In Ian's
case, the standard MRI exam didn't allow us to diagnose him. We
needed information from the more sophisticated techniques.'
A few weeks after Ian's first birthdayr,
his mother reported, 'He's pulling himself up to his feet, trying
to walk, and getting into everything. Sometimes I look at him and
think, 'What a little miracle!'
Images Create a Road Map for Surgery
While none of the imaging techniques
used to plan Ian Pelkey's surgery were unique to the MGH, his treatment
represented one of the first combined uses of these methods in treating
The two types of imaging used -- MRI
and PET -- both have advantages and disadvantages. MRI produces
highly detailed images of the structure of bodily organs, but standard
MRIs do not reflect how an organ is functioning. PET images show
function but cannot pinpoint the activity's exact location.
Combining the great wealth of information
produced by both methods required an intricate and powerful computer
program, developed in the MGH Radiology Department.
Bradley R. Buchbinder, MD, an MGH
neuroradiologist, explained that most previous work integrating
structural and functional brain imaging (some of which has been
done at the MGH) focused on locating the sites of various activities
-- vision, hearing, thought -- in the normal brain. Ian Pelkey's
treatment may have been the first in which these techniques were
used to create a map to guide an operation.
Neurosurgeon G. Rees Cosgrove, MD,
said, 'Most decisions about how you're going to do a procedure should
be made before you enter the operating room. This kind of imaging
helps the surgeon perform very detailed and individualized preoperative
planning. When this gets integrated with other techniques we're
using, we hope to be able to do smaller, more precise, and safer
Dr. Buchbinder adds that the MGH researchers
-- including Drs. Cosgrove-- are also investigating the use of such
integrated imaging in planning treatment of tumors, abnormal blood
vessels, and other problems within the brain.
They also will be comparing the merits
of PET to new MRI techniques that can show brain function. 'If we
could do all of this with MR, these techniques could have broader
application, because only a few institutions are able to conduct
PET scans,' said Dr. Buchbinder. 'But we have to investigate that