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Neurofibromatosis – Neurosurgical Treatment and Follow-up
therapy targeted at blocking the precise dysfunctional pathway; this is NFII. Children with NFII often present with non-vestibular tumours.
being applied for the treatment of multiple tumour types. An example Clinical management of NFII patients cannot be based on the
of this is the inactivation of Ras using farnesyl transferase inhibitors, expectation of similar natural evolution.
11
Although some studies of
which inhibit the post-translational modification and activation of Ras.
2,8
the growth rate of VS in NFII indicate that it is generally higher in
younger patients, there are great variations, both between patients
The introduction of more precise predictive tests, the further and over time in the same patient. No predictors for the rate of
development of biologically based therapies and the team approach to increase of the tumours have been identified.
their management will definitely lead to significant advances in the
supervision of patients with NFI. All of these characteristics, as well as the association with other
central nervous system tumours, determine the scope of the problems
facing the neurosurgeon. Treatment options include observation,
radiosurgery or surgical treatment.
9
Several surgical approaches have
The tailored therapeutic approach
been put forward, such as partial or total tumour removal via the
may provide a breakthrough in the
retrosigmoid or the middle fossa approach, aiming at hearing
preservation, total removal of the tumour with placement of an
management of neurofibromatosis
auditory brainstem implant and decompression of the cochlear nerve
type I patients.
at the internal auditory canal (IAC).
Personal Series
Over a period of more than 35 years, the senior author (MS) has
Neurofibromatosis Type II operated on more than 165 patients with NFII. The total number of VS
NFII is an autosomal-dominant inherited disease with an incidence of surgeries in these patients is 210. Twenty-four per cent of all patients
approximately 1:33,000 to 1:50,000.
5,9
The lifelong tendency to form were deaf pre-operatively, with preserved unilateral hearing in 34%
new central nervous system tumours such as schwannomas, and with preserved bilateral hearing 42%. Total tumour removal was
meningiomas, gliomas and neuromas pre-determines the impossibility achieved in 85% of the operated tumours. In 15%, deliberate subtotal
of a definitive cure for these patients. Treatment is focused on life removal was performed for brainstem decompression and hearing
prolongation, preservation of cranial nerve function or auditory preservation in the hearing ear only. The subtotal removal and IAC
rehabilitation and, thus, the maintenance of quality of life.
10
decompression led to long-term hearing preservation in 10.4% of the
Management of bilateral vestibular schwannomas (VS) differs in a patients. The overall rate of hearing preservation in the series was
number of ways from sporadic unilateral tumours, and the 35%. If patients with preserved useful pre-operative hearing only are
major management concern is the disabling consequences of included, the rate is 65%. Twenty-three per cent of patients retained
acquired deafness. bilateral hearing after surgery. The anatomical integrity of the facial
nerve was preserved in 89%.
The criteria for NFII are bilateral VS or a parent, sibling or child with NFII,
and either unilateral vestibulocochlear nerve tumour or any one of the
following: neurofibroma, meningioma, glioma, schwannoma, posterior
capsular cataract or opacity at a young age.
11,12
NFII is caused by a
single germline mutation of the chromosome band 22q12.
13
The
Our treatment goal has always been
normal allele is lost due to a somatic mutation in the cells giving rise to
the tumour. It has been estimated that NFII has the highest
total tumour removal.
spontaneous mutation rate of any human genetic disorder
(approximately 50%). If a person inherits the abnormal gene, there is a
95% chance that she or he will develop a bilateral VS. However, no
evidence of other affected family members can be found in
approximately 50% of patients. It is supposed that the disease is a Facial Nerve Preservation
sequence of two germline mutations (the ‘double hit’ hypothesis). No Some surgeons advocate subtotal tumour removal considering the
differences have been reported between mutations detected in patients absence of clear arachnoidal plane to the facial nerve and,
with NFII and those in patients with sporadic tumours. correspondingly, the increased risk of its injury. However, regrowth of
the residual tumour is highly probable because of the typical young
Molecular analysis of NFII revealed that the mutation affects a gene age of the patients and the fact that in NFII VS characteristically grow
that encodes a protein with 595 amino acids, otherwise known as the rapidly. Surgeries in cases of recurrences are more difficult and more
Schwannomin/Merlin protein. This gene product is thought to signal dangerous. Our treatment goal has always been total tumour removal.
cellular growth inhibition and is related to a family of proteins – the The only exceptions have been made in order to preserve hearing
ezrin-radixin-moesin family – that links the actin cytoskeleton to function or facial nerve integrity. Deliberate subtotal resections have
the cell membrane molecules.
13–15
been performed for brainstem decompression and for hearing
preservation in the remaining hearing ear. Facial nerve preservation
Bilateral VS that become manifest in the second or third decade of life was possible in all cases except if the schwannoma (or multiple
are the hallmark of NFII and occur in about 95% of adult patients with schwannomas) arise from the facial nerve, or no cleavage plane
EUROPEAN NEUROLOGICAL DISEASE 2007 15
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