A 67-year-old man with a history of myocardial infarction and splenectomy for polycythemia rubra vera presented with the complaint of recurrent frontal headaches which had increased in frequency over the past 6 months. The pain was predominantly retro-orbital and was not relieved with analgesics. He had no focal neurologic signs and no other significant past medical history. A non-contrast CT of the head and gadolinium-enhanced MR of the brain were performed (figures 1-4).
Prepared by Brian J. Fortman, MD; Brian S. Kuszyk, MD; and
Norman Beauchamp, MD, Department of Radiology, The Johns Hopkins
Hospital, Baltimore, MD.
A 67-year-old man with a history of myocardial infarction and
splenectomy for polycythemia rubra vera presented with the
complaint of recurrent frontal headaches which had increased in
frequency over the past 6 months. The pain was predominantly
retro-orbital and was not relieved with analgesics. He had no focal
neurologic signs and no other significant past medical history. A
non-contrast CT of the head and gadolinium-enhanced MR of the brain
were performed (figures 1-4).
Non-contrast CT of the head showed multiple areas of high
attenuation corresponding to densely calcified subependymal
nodules, as well as a calcified nodule in the left cerebellar
hemisphere (figure 1). There was a prominent heterogeneous nodule
on the right, adjacent to the interventricular foramen of Monro. A
cavum septum pellucidum and cavum vergae also were present.
Gadolinium-enhanced MRI of the brain showed multiple areas of
decreased signal intensity within the subependyma on T2-weighted
images, compatible with calcification (figure 2). There was marked
cortical irregularity and pachygyria in the left posterior temporal
and parietal regions in addition to the lesion near the foramen of
Monro (figure 3). This heterogeneous lesion showed significant
enhancement with gadolinium. There also were subtle areas of gray
matter heterotopia noted in the subcortical white matter (figure
3). The patient had previously undergone CT scanning and renal
ultrasound during his hospitalization for splenectomy due to
polycythemia vera (figures 4A,4B). Review of his renal ultrasound
showed several focal areas of increased echogenicity within the
kidneys. His abdominal CT revealed multiple focal areas of
decreased attenuation in both kidneys measuring 30 to 50 HU,
compatible with angiomyolipomas. A review of all previous chest
radiographs found no evidence of pulmonary parenchymal disease.
Tuberous sclerosis (Bourneville's disease)
Tuberous sclerosis (TS), or Bourneville's disease, is an
autosomal-dominant (AD) neurocutaneous syndrome with an approximate
incidence of 1:10,000 to 50,000. The classic triad of mental
retardation, seizures, and a papular facial nevus known as adenoma
sebaceum is observed in less than 50% of patients.
More commonly, TS presents as a forme fruste, a partial or arrested
form of the disease. There is considerable genetic heterogeneity in
TS, and several transmitted gene loci, as well as spontaneous
mutations, have been postulated to occur.
The variable phenotypic expressivity of TS, as well as the
variety of organ systems affected, leads to a substantial number of
cases first presenting in adolescence and early adulthood. It is
atypical for a patient to present at 67 years of age with such
classic findings of TS, though reports do exist. Our patient showed
no cutaneous manifestations of the disease and had no history of
As the classic clinical triad of TS is seen in the minority of
patients, it is now universally accepted that the radiologic
hallmarks of this disorder are sufficient for diagnosis. Pathologic
diagnoses are rarely obtained due to the hamartomatous nature of
most lesions. This patient demonstrated the classic central nervous
system (CNS) manifestations of TS as seen on CT and MRI. Multiple
calcified subependymal nodules along with cortical tubers, subtle
white matter abnormalities, and an enhancing heterogeneous lesion
adjacent to the foramen of Monro are diagnostic. Other lesions that
may occur near the foramen of Monro include central neurocytoma,
colloid cyst, and subependymoma.
The characteristic location and enhancement of this lesion,
along with the other CNS findings, make a giant cell astrocytoma
highly likely. Most, if not all, patients with subependymal giant
cell astrocytomas (SGCAs) are believed to have TS.
SGCAs are histologically benign but may enlarge with time and cause
The patient's renal findings also are typical of TS.
Angiomyolipomas occur in 40 to 80% of cases. These
characteristically appear as hyperechoic foci on ultrasound and
multiple foci of fat attenuation on CT. Such lesions have no
malignant potential and are often clinically silent, although some
surgeons recommend resection of lesions greater than 5 cm due to
the risk of hemorrhage. When multiple and bilateral, these lesions
often are the initial finding, which suggests a subclinical case of
TS when renal US or abdominal CT is performed for other
indications. The presence of renal involvement with the TS complex
increases the patient's risk of developing renal cell carcinoma,
and prudent screening with computed tomography is recommended.
Other systemic manifestations of TS include cutaneous macules,
cardiac rhabdomyomas, pulmonary lymphangiomyomatosis, pancreatic
and splenic hamartomas, sclerotic bone lesions, and vascular
aneurysms or stenosis.
The differential diagnosis for multiple calcified subependymal
nodules is essentially limited to tuberous sclerosis or congenital
"TORCH" infections such as cytomegalovirus or, less commonly,
toxoplasmosis. In our case, MRI of the brain revealed lesions which
are typical of cortical tubers. The prominent enhancing nodule
adjacent to the foramen of Monro is the classic appearance of a
subependymal giant cell astrocytoma. These findings, along with the
patient's subtle gray matter heterotopias are typical cerebral
manifestations of TS. Both CMV and toxoplasmosis could lead to
migrational abnormalities and heterotopias; however, in our
patient, the enhancing nodule near the foramen of Monro and the
absence of findings such as microcephaly and chorioretinitis make
this much less likely. The presence of bilateral renal
angio-myolipomas confirms the of TS in this patient. The patient
declined a neurosurgical consult at that time and elected close
follow up to monitor for the development of hydrocephalus.
The diagnosis of TS in this patient is not only important for
his future medical treatment, but is also relevant to the patient's
family. Even if this patient represents the proband within the
family, it is likely that at least one of his children will have
subclinical disease or carry the TS gene. For this reason, medical
screening and genetic counseling is advised for families of newly
diagnosed TS patients. Ongoing research continues to better define
the genetic heterogeneity of TS and may lead to gene-guided therapy
for patients with TS and other phakomatoses in the future. Several
organizations and societies now exist in the United States and
abroad to offer support and information to patients and families
affected by TS.