The following neurological diseases can be treated by
Gamma KnifeŽ Radiosurgery:
Pituitary Tumors
Pituitary tumors arise from the pituitary gland within the base of the skull.
These tumors are almost always benign. Symptoms arise when these tumors secrete
hormones or become large enough to compress adjacent structures. Rarely, these
tumors may spontaneously hemorrhage.
As tumors enlarge, normal pituitary function is destroyed. This produces
various hormonal deficiencies, since the pituitary controls the action of other
endocrine glands. Pressure on near-by structures produces double vision, facial
numbness. The optic nerves are directly above the pituitary gland and upward
growth of pituitary tumors frequently causes progressive visual loss. This
visual loss typically begins from each side of the field of vision leading to
tunnel vision.
(return to Top)
Acoustic Neuromas
Benign tumors of the vestibular nerve (vestibular schwannomas or acoustic
neuromas) begin within the base of the skull and slowly expand into the skull
cavity. Slow and progressive destruction of hearing in the affected ear, a sense
of imbalance, weakness of facial movement, and facial numbness occurs
progressively in most patients. Interestingly, there is minimal or no growth in
some individuals. Thousands of patients with acoustic neuromas have been treated
over the past 25 years by means of the Gamma Knife and the results compare
favorably with the published results of microsurgery. Reports of re-operation on
individuals treated by Gamma Knife being more difficult or dangerous are
unsubstantiated. Re-operation is quite rare and failure of control may be
retreated by radiosurgery. There are no reports of cancer being caused by
radiosurgery.
(return to Top)
Meningiomas
Radiosurgery is quite useful in the control of meningiomas. This can be the
primary treatment for difficult to operate skull-based tumors or in the
treatment of tumors recurring after open surgery. Skull- based meningiomas
frequently recur after operation and conventional surgery may occasionally lead
to increased cranial nerve dysfunction. Tumors arising from the cavernous sinus,
and petroclival tumors of the posterior fossa are especially good candidates for
GK radiosurgery, as complications of complex, skull base surgery are avoided.
There is an expectation that more than 90% of tumors treated by Gamma Knife will
be controlled.
(return to Top)
Metastatic Brain Tumors
Summary
Metastatic disease can be viewed as two simultaneously occurring diseases. Brain
cancer and systemic cancer (elsewhere in the body). Each disease has quite
different mortality rates. Untreated brain metastases are rapidly fatal, while
systemic cancer may not be.
Metastatic brain disease is a focal disease and focal control of the tumor is
paramount to patient survival. The approach in the past has been to treat
metastatic brain disease as a whole brain disease, with whole brain radiation
(WBR). Because of poor local control of tumor growth when treated solely by WBR,
brain metastases in the past were rapidly lethal. Therefore patients with brain
metastases did not benefit from many advances in cancer therapy (immunotherapy,
chemotherapy, conformal radiotherapy etc.) because these therapies don't
effectively reach brain metastases and individuals died quickly from
neurological progression.
Now neurological progression can be effectively controlled in most patients
harboring a few intracranial metastases with aggressive focal treatment (surgery
or radiosurgery) in combination with WBR. WBR can be given immediately following
focal treatment or at the time of recurrence. Control can be extended by
frequent MR surveillance of the brain and radiosurgical treatment of new
metastases months or years later. With control of intracranial disease, advances
in cancer therapy will prolong survival, since most patients now succumb later
to systemic, rather than intracranial disease. Aggressive, focal treatment is
only beneficial in patients with controlled or no systemic disease and
independent health (Karnofsky Performance Score (KPS)> 70). Age is also a
determinant of outcome, with better outcomes in individuals who are less than 60
years old.
Radiosurgery is an appealing substitute for open surgery in the treatment of
brain metastases. It is non invasive, cost effective, safe and in many cases an
outpatient procedure. The very nature of metastases lends them readily to
radiosurgical technique: they are well delineated on MR or CT images, usually do
not invade the surrounding brain and are spherical, and most patients harbor 4
or less metastatic deposits. But is radiosurgery as effective as open surgery?
 |
 |
Metastatic brain tumor before
treatment |
Metastatic brain tumor 2 months
after treatment |
|
(Results will vary from patient to patient) |
There are many retrospective studies to suggest radiosurgery is as effective
as open surgery. Perhaps the most compelling is a multi-institutional study
where patients with single brain metastases treated by WBR and radiosurgery (RS)
were identified as having the same prognostic criteria as the patients entered
into the 1990 Patchell study comparing WBR and WBR + surgery groups. In this
retrospective study Auchter and others showed survivals in patients treated with
radiosurgery+WBR comparable to the surgery+WBR group reported by Patchell
(medial survival 56 weeks for RS v. 40 weeks for surgery). RS also controlled
local disease (14 % local recurrence) while distant recurrence was seen in 22%.
Functional independence was 44 weeks, similar to the Patchell study of 38 weeks.
Also compelling are the outcome of large numbers of patients treated by
radiosurgery with control rates varying from 80 to 95%, largely dependent on
tumor type and size.
Since brain metastases are a focal disease, non-invasive, outpatient focal
treatment is appealing. In certain circumstances radiosurgery alone may be the
best treatment. Pirzkall and co-workers reviewed their experience with 311
metastases treated in 236 patients. Only 78 patients had WBR, the rest were
treated with radiosurgery alone. Interestingly local recurrence was only 11%
with radiosurgery alone vs. 8% when WBR was added. Distant recurrences of 23 %
were reduced to 15 % when WBR was added.
(return to Top)
Astrocytomas
There are basically two types of brain tumors. Primary brain tumors arise
from the cell tissues, which make up the brain, its blood vessels and the
tissues which surround the brain within the skull. On the other hand, secondary
brain tumors arise outside the skull and travel through the blood stream to
lodge and grow within the brain. Unfortunately these metastatic brain tumors are
usually malignant. They grow and kill rapidly unless treated. Common sites of
origin for metastatic tumors are cancers of the breast, lung, and skin
(melanoma).
The most common primary brain tumors arise from brain tissue itself. Glial cells
are the supporting cells of the brain, which provide a structural framework to
contain and nourish brain neurons. For unknown reasons these cells undergo a
change, which results in slow or rapid growth by cell replication.
Diagnosis
Gliomas develop many symptoms. The more benign gliomas occur in younger people
and may first present as a seizure. Depending on the area of the brain involved,
a progressive neurological problem, such as weakness, numbness, or speech
problems can develop. Since the more malignant tumors enlarge rapidly, symptoms
of increased pressure in the head are common: headache, visual loss, and
personality change. Headache is characteristically worse in the morning when
awakening. On rare occasions a glial tumor can bleed spontaneously, presenting
with an acute neurological deficit: a stroke.
The classification of gliomas is based upon the appearance of these tumors under
the microscope. This requires a biopsy of tumor tissue and in general is
predictive of the behavior of the tumor and the outlook for the patient. Glial
tumors are divided into two basic cell types: astrocytomas and
oligodendrogliomas. The most common grading system for astrocytomas is the
following World Health Organization (WHO) system:
Grade I: pilocytic astrocytoma
Grade II: fibrillary astrocytoma,pleomorphic xanthroastrocytomasubependymal
giant-cell astrocytoma
Grade III: anaplastic astrocytoma
Grade IV: glioblastoma
 |
 |
 |
| grade II: fibrillary astrocytoma |
grade III: anaplastic astrocytoma |
grade IV: glioblastoma multiforme |
The grade II astrocytomas behave in a benign fashion with a period of years
before tumor progression. These tumors may become malignant over time. The
initial presentation is usually in a young individual who has had a seizure.
Some surgeons prefer an attempt at complete excision of low-grade gliomas in the
belief that removal will delay or prevent recurrence. There is no scientific
evidence this tactic is useful. Gliomas deep within the brain or in sensitive
brain regions are not candidates for excision. This leaves the option of
radiation therapy. Current data indicates that fractionated radiotherapy early
in the course of the disease or later with clinical progression (growth) of the
tumor has no influence on survival, although early radiotherapy may delay the
time of progression.
Gamma Knife radiosurgery is an additional option. This is used instead of open
surgery to "remove" a small volume of gliomas. It is especially useful in small,
deep tumors.
(return to Top)
Glioblastomas
There exists no published randomized trial comparing standard treatment of
glioblastomas and anaplastic astrocytomas with standard treatment and
radiosurgery. A recent study of patients treated with a Gamma Knife boost
following surgery or biopsy, and patients treated at recurrence of disease,
roughly 6 months after initial treatment showed improved survival benefit from
GK radiosurgery. Survival after treatment with first recurrence of GBM was
somewhat better (30 months) than initial boost treatment (20 months). About 1 in
5 patients with GBM required reoperation after GK radiosurgery, mostly for tumor
recurrence rather than tumor necrosis. The 2-year survival rate for GBM was 51%.
Individuals with anaplastic astrocytoma faired better with a median survival of
32 months and 2 year survival of 67%. The tumors treated with radiosurgery were
small, 6 cm 3. (Kondziolka D, et al .J Neurosurg. 1997;41:776-785).
In general, we treat glioblastoma and anaplastic astrocytoma with an attempt
to remove a maximum volume of abnormal tissue aimed by frameless stereotactic
surgery (Sofamor-Danek Stealth system). A MR scan is performed within 48 hours
of surgery and residual, enhancing tissue is boosted with radiosurgery followed
by conventional radiation therapy. Alternately, recurrence is treated with GK
radiosurgery as long as the tumor nidus is small. Our reoperation rate is low.
Controlled studies need to be completed to conclusively demonstrate the role of
radiosurgery in the treatment of malignant gliomas.
(return to Top)
Trigeminal Neuralgia
Trigeminal neuralgia is a facial pain syndrome consisting of sharp,
lancinating pain in the face. The pain is often described as shock-like stabs of
pain. The pain is only on one side of the face and may be elicited by touching
trigger points in the skin or gums. There is no associated numbness (unless
there is co-existing multiple sclerosis). Often there may be spontaneous
remissions from pain lasting weeks to years. Interestingly, this pain usually
responds to carbamazepine (Tegretol), an oral anticonvulsant medication.
Trigeminal neuralgia is usually caused by compression of the sensory
(trigeminal) nerve within the skull by a small artery or vein at the point where
the nerve joins the brain stem. Sometimes a small, benign tumor compressed the
nerve, causing jolts of electrical shock-like pain to radiate into the face. A
few percent of tic patients suffer from multiple sclerosis. In this case the
inflammatory response affecting the brain also involves the trigeminal nerve,
causing paroxysmal pain.
Tic douloureaux is unique among pain disorders because nearly all treatments
work for a period of time. Over the years peripheral nerve avulsion, heating,
cooling, compressing, decompressing, chemical ablation, and irradiation have all
enjoyed varying degrees of success. Because of the effectiveness of
carbamazepine (Tegretol), its use is usually the first level of treatment. Other
anticonvulsants may be tried, but these are not usually as effective. When oral
medication fails to control this dreadful pain, other surgical measures are
quite effective:
Gamma Knife radiosurgery can successfully treat tic pain. A single,
non-invasive morning treatment has resulted in excellent pain relief in 58%;
good pain relief in 36% and failed pain relief in 6%. Transient facial numbness
is rare. Long term recurrence rates are unknown. This treatment is a suitable
alternative to anticonvulsant therapy and compares favorably to other
treatments.
(return to Top)
Arteriovenous Malformations
Arteriovenous malformations (AVM's) are an unusual collections of arteries
and veins which are congenital in origin and occur throughout the body. When
they occur within the brain they cause symptoms in various ways. Most
importantly. they can spontaneously bleed resulting in a stroke with lasting
neurological problems or even death. Additional symptoms include a seizure,
progressing neurological deficits, and headaches.
AVM's have several forms, such as a direct connection between an artery and
vein, an AV fistula. Unusual collections of veins which bleed and cause seizures
are cavernous angiomas. Abnormalities of very small vessels are capillary
angiomas. The most important (and dangerous) are AVM's which have both arterial
and venous components. These AVM's have a 3 to 4% chance of spontaneous
hemorrhage each year. Roughly 10% of the hemorrhages will be fatal and about 15%
of victims will suffer a continuing neurological deficit, such as weakness,
sensory or visual loss, speech abnormality, etc.
Diagnosis
The gold standard for diagnosis is a cerebral angiogram. The radiologist
advances a catheter into the arteries which supply the brain and images the AVM
nidus by injecting radio-opaque dye with serial x-rays of the skull. MR
techniques can also identify AVM's.
Natural history
It is important to understand the natural history of AVM's since this impacts
the advise given to patients who harbor unruptured and asymptomatic
malformations. Surgery can cure AVM's, but not all AVM's are amenable to open
operation because of the risk. This risk is generally predictable from the size
and position of the AVM. The age and general health of the patient also factor
into the pre-operative equation. An important contribution to the estimation of
pre-operative risk was the Spetzler-Martin grading system. This paradigm assigns
points according to AVM size, position in eloquent (important functioning) brain
and the presence of deep, draining veins. The higher the score, the greater the
risk of post-operative problems.
Treatment
Surgical excision of the AVM brings an immediate cure, but not all AVM's can
safely be removed. Gamma Knife radiosurgery can play a role in the obliteration
of smaller AVM's. This technique has the advantage that is non-invasive and
accomplished in a single session. The disadvantage is that the effects of
focused radiation occur over months and years, during which time the patient is
still at risk for spontaneous hemorrhage. In general, AVM's under 1 cm in
diameter have a 90% chance of obliteration, while those under 2 cm have an 80%
change of cure. Only about 50% of malformations 3 cm in size are obliterated.
Interventional radiology can reduce the blood supply to AVM's and rarely cure
them. This technique is performed by selectively filling the feeding arteries,
or veins with clotting agents by a catheter during angiography. Endovascular
therapy usually plays a supporting role, reducing the blood supply to aid open
surgery or to reduce the size of the AVM before Gamma Knife radiosurgery.
Once an AVM has ruptured, surgery is indicated to prevent repeat hemorrhage.
Most experts advise emergency operation for patients in danger of death from
very large clots. Smaller, minimally symptomatic or asymptomatic bleeds can be
managed medically, as the hematoma is gradually reabsorbed from the brain
tissue. Early re-bleeding is rare in AVM's (6% in the first 6 months after
initial hemorrhage and there is no proof early surgery can reduce the eventual
outcome in individuals with a deficit, since the brain damage has already
occurred.
 |
 |
Case treated by Ladislau Steiner MD PhD & Dheerendra Prasad MD, Lars Leksell
Center for Gamma Knife Radiosurgery, Charlottesville VA. |
|
AVM before treatment |
After treatment |
|
(return to Top)
Obsessive Compulsive Disorder
The birth date of a surgical procedure is often problematical. There is no
doubt, however, as to the birth of functional neurosurgery for psychiatric
disorders. In July 1935. John Fulton of Yale University brought two chimpanzees
to an international meeting in London who had had their frontal lobes removed.
This procedure produced a dramatic change in their behavior, rendering them much
less aggressive. Other physicians attending the meeting included Egas Moniz, a
Portuguese neurosurgeon and Walter Freeman, an American psychiatrist. Moniz
prophetically questioned if "it would not be possible to alter anxiety states in
man by surgical means?" By the Fall of 1935 Moniz had answered this question by
performing the first human lobotomy. The following year, Freeman and James
Watts, a neurosurgeon, had taken up the procedure in the US. During the next ten
years various methods of frontal leukotomy were developed by Moniz, Freeman and
Watts. A large world-wide population of institutionalized, psychotic individuals
facilitated this development as there was no truly effective medical treatment
available.
In 1949 Egas Moniz won the Nobel Prize for Medicine, lending frontal lobotomy
a cachet of respectability. By this time the reckless enthusiasm of Walter
Freeman had produced the transorbital (ice pick) leukotomy. This freed him from
the necessity (and constraint) of involving Dr. Watts in the performance of this
procedure and brought even further abuse.
The introduction of chlorpromazine in 1952 for the treatment of psychiatric
illness caused a precipitous decline in surgical procedures to alter human
behavior. Functional neurosurgery on the human limbic system no longer seemed
necessary or desirable.
Recent advances in neurosurgery for movement disorders have caused a renewed
interest in the effects of surgery in the limbic system. Since 1952 advances in
neuropharmacology and other psychiatric treatments have remained the basis for
management of patients suffering from Obsessive Compulsive Disorder (OCD), major
affective disorder (depression) and anxiety states. A minority of individuals
remain refractory to conventional treatment. These individual remain disabled
and may be considered for neurosurgical procedures.
Four surgical procedures have evolved over the past 50 years to alter limbic
lobe expression of emotional disorders. These new operations arose from a need
to limit the untoward effects of classical frontal leukotomy: postoperative
seizures, disinhibition and other personality disturbances. These techniques are
anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, limbic
leukotomy (combined subcaudate tractotomy, and cingulotomy. Each procedure has
its advocates; each seems to produce similar results with low morbidity.
Anterior capsulotomy (AC) was introduced by Talairach in 1949 and further
developed by Lars Leksell. The procedure involves the production of small,
bilateral lesions in the anterior limb of the internal capsule to interrupt
frontothalamic pathways as they pass beneath the head of the caudate nucleus and
putamen just posterior the tip of the frontal horn of the lateral ventricle in
the anterior limb of the internal capsule. Destructive lesions may be made with
radiofrequency thermocoagulation or radiosurgical technique (Gamma Knife).
As in all functional surgery treatment results are difficult to quantify.
Mindus and co-workers reviewed 362 cases reported in the literature and found
64% of 213 patients undergoing anterior capsulotomy had achieved a satisfactory
result (1). Another study from the Karolinska Institute by Mindus and others cited
22 patients treated by thermal lesions for OCD. When measured by the obsessive
compulsive sub scale of the Comprehensive Psychopathological Rating Scale, 23%
were worse; 9% improved from 1 to 25%; 23% improved 26% to 50%; 13% improved 51%
to 75% and 32% improved by 75% to 100% (2).
A very recent paper from the Karolinska group with anatomical analysis of
results in patients treated 10 to 20 years ago found a common anatomic volume
(in the right anterior limb of the internal capsule) in all successfully treated
individuals. All patients with poor results had no lesion in this region.
Overall, 7/9 Gamma Knife and 9/14 thermal lesion patients had good outcomes (3).
Currently a double-blind, placebo controlled study of Gamma knife capsulotomy
is underway at the Karolinska Hospital, Brown and Harvard Universities.
Post-operative complications included weight gain in a majority of patients,
transient episodes of confusion in most, lasting weeks; rare complaints of
fatigue, and slovenliness. Intracranial hemorrhage, infection and seizures are
quite rare and not expected from the non invasive Gamma Knife radiosurgical
technique (4).
Criteria to be considered for radiosurgery include:
- Individuals who fulfill the criteria for obsessive- compulsive disorder and
major affective disorder as defined by the Statistical Manual of Mental
Disorders, Third Edition, Revised
- Chronicity: patients under at least 5 years of treatment
- Severity as may be measured by the Yale-Brown Obsessive Compulsive Scale score
of > 20 for OCD or a Beck Depression Inventory score of > 30
- Disability as measured by a Global Assessment of Function score of < 50
- Disorder has been shown to be unresponsive to conventional psychiatric and
pharmacological treatment
- Patient can give informed consent
- Patient and family agree to participate in pre-operative and post-operative
programs of psychological evaluation, treatment and follow-up (1,2)
The radiosurgical technique consists of bilateral lesions in the anterior
limb of the internal capsule using standard Gamma Knife procedures. These
include the placement of a stereotactic coordinate frame under local anesthesia
followed by MR imaging of the internal capsule and treatment planning with Gamma
Plan software. Actual treatment with the Gamma Knife will require approximately
60 minutes. Patients should experience no immediate side effects (other than
local discomfort from the frame placement) and may require an overnight stay in
the hospital. Radiosurgical technique avoids surgical sequellae, such as
infection, wound healing problems, seizures and hemorrhage, and is less
expensive. Retreatment may be undertaken if necessary.
It is anticipated that these patients will be followed at intervals with
appropriate psychological measures in an effort to document the results of
surgery on a psychological, functional and anatomical basis.
(return to Top)
References
(1) Cosgrove GR, Rauch SL: Psychosurgery. Neurosurg Clin N Amer 6:167-176, 1995
(2) Mindus P, Rasmussen SA, Lindquist C: Neurosurgical treatment of refractory
obsessive-compulsive disorder: implications for understanding frontal lobe
function J Neuropsych 6:467-477, 1994
(3) Lippitz B, Mindus P, Meyerson BA, Kihlstorm L, Lindquist C. Lesion topography
and outcome after thermocapsulotomy or Gamma Knife capsulotomy for
obsessive-compulsive disorder:relevance of the right hemisphere. Neurosurg
44:452-460, 1999
(4) Mindus P, Nyman H: Normalization of personality characteristics in patients with
incapacitating anxiety disorders after capsulotomy. Acta Psychiatr Scand
83:283-291, 1991
|
En Espaņol
