ARTICLE
Auteur(s) : Cyril
BN Confavreux1, F Cotton2, J-G
Tebib1
1Service de rhumatologie 2B, Centre hospitalier
Lyon-Sud, Chemin du Grand-Revoyet, 69495 Pierre-Bénite, France
2Service de radiologie, Centre hospitalier Lyon-Sud,
Chemin du Grand-Revoyet, 69495 Pierre-Bénite, France
Case
A 69-year-old man with prostatic adenocarcinoma metastatic to bone
was admitted for rapidly deteriorating mental status, headaches
with vomiting, diplopia related to VIth cranial nerve palsy, left
C7-C8 paresthesia, swallowing and speech difficulties.
His medical history was marked by an infiltrative prostatic
adenocarcinoma discovered in 1995 with a prostatic specific antigen
(PSA) at 53 μg/L treated by endoscopic resection and surgical
castration (T2a Nx M0 and Gleason score = 6). The patient responded
and PSA decreased to 20 μg/L in June 1996. He became hormone
refractory very rapidly since PSA level increased to 58 μg/L in
December 1996 and bone pain lead to diagnosis of diffuse
metastastic bone disease. He was treated with nonsteroidal
anti-androgens (flutamide) and radiotherapy on the right hip with a
good symptomatic effect on pain and stabilization of PSA levels. In
1998, diffuse pain returned and the disease became unresponsive to
second line flutamide treatment. He then received daily anti-tumor
estrogens (diethylstilbestrol) with a good functional result and
decrease of PSA until 2002.
At admission, clinical examination revealed total left facial
and hypoglossal nerve paralysis. The left tricipital reflex was
absent. Standard biological tests were normal while PSAvalues were
high (543 μg/L). Cerebrospinal fluid was not examined because of
high intracranial pressure.
Cervical magnetic resonance imaging (MRI) revealed neoplastic
infiltration of vertebrae, metastatic epiduritis and cranial nerve
trapping at the basis of the skull. Furthermore, cerebral images
demonstrated extensive supratentorial pachymeningitis with at least
four nodules, encroaching on inner layers of the dura mater. The
largest nodule located in the right temporal region measured 4 x
3 cm, and was responsible of a mass effect on the temporal
lobe and the lower part of the frontal lobe as well as of external
compression of the right middle cerebral artery (( figure 1 )). On diffusion
weighted imaging (DWI) and apparent diffusion coefficient (ADC)
maps, no restricted diffusion was observed within the temporal area
of T2 increased signal intensity (( figure 2 )). Perfusion
images demonstrated low vascularity within edema in contrast with
high vascularity inside meningeal nodules (mean rCBV: 3.2 ± 1.3)
and persistent leakage of contrast agent during bolus phase of
dynamic imaging (( figure 3 )). Other
metastases lay adjacent to the dura mater of the superior
longitudinal sinus, one near the lateral left sinus with a mass
effect on the cerebellar hemisphere and another in the right
frontal region (( figure
4 )). The patient dramatically improved with steroid
therapy at 1 mg/kg/day and local radiotherapy was proposed.
However, he was readmitted three weeks later before the beginning
of radiotherapy in a coma with left hemiparesis and died a few days
later. The family refused autopsy.
Discussion
Central nervous system complications of hormone refractory prostate
cancer are well known in practice [1]. They have been more
extensively observed since the introduction of new chemotherapeutic
agents in the treatment of this disease. The most common
neurological complications are epidural spinal cord compression and
toxic metabolic encephalopathies. Indeed the spine is one of the
most common sites of bony metastases in patients with prostate
cancer. Spinal compression is induced by the combination of the
enlarging tumoral mass, edema and sometimes pathologic vertebral
fracture. If suspected and diagnosed early, epidural spinal cord
compression is treatable. Otherwise, once neurological function is
affected, outcome is poor. Diagnosis has been revolutionized by the
introduction of magnetic resonance imaging to determine the extent
of the lesion and the presence of other sites involved. Suppurative
bacterial infections are a classical differential diagnosis in
these fragile patients and must be eliminated.
Intracranial metastases represent less than 5 % of patients
with prostate cancer and occurred usually at a terminal phase of
the disease [2]. MRI is the most sensitive test for diagnosis. The
vast majority of them are located in the dura mater as in the case
of our patient. Prostate cancer is one of the most common causes of
dural metastases, together with lung and breast cancer. These
metastases may act as a mass lesion, compressing the underlying
brain, producing seizures, headaches or focal neurological deficit.
Adjacent bone may or may not be involved. At tha basis of the
skull, cranial nerve trapping may be responsible for various
clinical presentations depending on the localization of the lesion.
One of these is a called “numb chin syndrome” and corresponds to a
lesion located in foramen ovale which induces a numbness of the
ipsilateral chin by involvement of the mandibular division of the
trigeminal nerve. Differential diagnosis in this case is a
metastasis of the jaw involving the mental branch of the mandibular
nerve [3]. Brain metastases from prostate carcinoma are very rare
[4]. In the M.D Anderson Cancer Center experience, Tremont-Lukats
reports 0.63 % of parenchymal metastases in a retrospective
study of 16,280 patients over more than 50 years. A part of these
metastases were asymptomatic and discovered at autopsy. The most
common clinical presentation was nonfocal neurological symptoms
related to intracranial hypertension. Prognosis was very poor with
a median survival of 1 month in untreated and of 3.5 months in
treated patients [5].
Prostate cancer may induce other neurological clinical disorders
such as encephalopathy related to chronic disseminated
intravascular coagulation, carcinomatous meningitis or venous sinus
thrombosis by mass effect of a dural metastasis. Paraneoplastic
syndromes are very uncommon are are more likely to be observed in
patients with a small cell component [6].
In our observation, anatomic brain involvement correlated fully
with clinical data. On one hand, tumoral epiduritis extended to the
brainstem and trapped left cranial nerves explained peripheral
signs: left radiculalgia and left cranial nerve palsies. On the
other hand intracranial localizations induced intracranial
hypertension and cognitive function disorders. The rarity of the
latter site associated with an epidural localization logically
raise the possibility of a common mechanism where the parenchymal
cortical appearance could simply be due to the voluminous extension
of the meningeal process. Diffuse pachymeningitis is marked in MRI
by a highly intense dura mater signal after contrast administration
(open arrow, ( figure
1 )B) usually not so clearly seen under physiological
conditions.
In some areas, epiduritis develops and forms nodules which have
many meningeal features: they are peripherally located in the brain
and in the nodule compressing the temporal lobe, a cleavage plane
is clearly visible between the invaded dura mater and the cerebral
cortex (( figure 1 )A)
corresponding to cerebrospinal fluid in subarachnoid spaces. In the
literature, some observations are also in favor of a dural origin
of the nodules [7, 8].
Increased signal intensity observed on T2-weighted images ((
figure 1 )B) was
attributed to vasogenic edema. Indeed, low or variable signal
intensity on diffusion weighted images (DWI) associated with an
elevated apparent diffusion coefficient (ADC) is characteristic of
vasogenic edema (( figure 2 )) [9, 10]. In
addition, perfusion images (( figure 1 )B) demonstrated
low vascularity within the edema and in contrast very high
vascularity inside meningeal nodules. ADC maps could not
differentiate between intra-axial and extra-axial lesions. However,
in our case, the high ADC value (1.75 ± 0.05 * 10-3
mm2/s) in the temporal area of the T2 hypersignal
confirmed that there was no restricted diffusion and then excluded
an acute ischemic lesion. The value of rCBV is the parameter of
most interest for tumor lesion [11]. First, the persistent leakage
of contrast agent during the bolus phase of dynamic imaging is
characteristic of extra-axial neoplasms [10]. Secondly, as it was
emphasized in a recent study [12], rCBV values could distinguish
dural metastases from meningiomas (mean rCBV = 8.97 ± 4.34 in the
study of Kremer et al.).
Our MRI study of the lesions suggests that the neoplastic
process develops from the meningeal region without direct
participation of the brain parenchyma apart from localized organic
edema. A pathophysiological hypothesis of such metastases had been
first proposed by Batson. For him, metastatic dissemination to
central nervous system occurred when increased abdominal pressure
reversed venous flow at the pelvic level and forced blood from the
prostatic venous plexus into the the vertebral vein system. Indeed
venous plexus and sinuses at the base of the skull are in close
contact with the epidural plexus venosus vertebralis internus and
could explain dissemination of neoplastic cells present in the
blood flow to the dura mater [13]. A more traditional pathway of
hematogenous dissemination towards bone marrow and lungs is
suspected.
This technique of advanced MRI (perfusion-diffusion) combined to
morphological data, clinical history and other localizations allow
a fast non-invasive diagnosis. Indeed, these patients are in
deteriorated condition and have a poor prognosis. Svare [14]
reported a series of 11 patients for whom the median survival after
diagnosis of cranial nerve dysfunction was only 5 months. Thus a
fast and well tolerated diagnostic technique is essential to
propose an appropriate treatment as early as possible. In our
patient, we observed a dramatic improvement with high dose
corticosteroids but unfortunately we did not manage to begin
radiotherapy. In the literature, Seymore [15] and Svare [14] report
a 90 % response rate to combined treatment: high dose
corticosteroids followed by radiotherapy (30 Gy in
10 fractions). Most of their reported responses lasted until
death.
Thus even if prognosis is not altered by this approach, it seems
worthwhile to propose, as supportive care, in hormone-resistant
prostate cancer patients presenting with cranial nerve dysfunction
and high intracranial pressure due to pachymeningitis, a combined
treatment of high dose corticosteroids followed by radiotherapy as
soon as possible.
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