Table 1: World Health Organization proposed new classification of CNS tumors I. Tumors of neuroepithelial tissue A. Astrocytic tumors Astrocytoma Variants: fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants: giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma B. Oligodendroglial tumors Oligodendroglioma Anaplastic (malignant) oligodendroglioma C. Ependymal tumors Ependymoma Variants: cellular papillary, epithelial, clear cell, mixed Anaplastic (malignant) ependymoma Myxopapillary ependymoma Subependymoma D. Mixed gliomas Mixed oligo-astrocytoma Anaplastic (malignant) oligo-astrocytoma Others E. Choroid plexus papilloma Choroid plexus papilloma Choroid plexus carcinoma F. Neuroepithelial tumors of uncertain origin Astroblastoma Polar spongioblastoma Gliomatosis cerebri G. Neuronal and mixed neuronal-glial tumors Gangliocytoma Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos) Desmoplastic infantile ganglioglioma Dysembryoplastic neuroepithelial tumor Ganglioglioma Anaplastic (malignant) ganglioglioma H. Pineal tumors Pineocytoma Pineoblastoma Mixed pineocytoma/pineoblastoma I. Embryonal tumors Medulloepithelioma Neuroblastoma Variant: ganglioneuroblastoma Ependymoblastoma Retinoblastoma Primitive neuroectodermal tumors (PNET) with multipotential differentiation - neuronal, astrocytic, ependymal, muscle, melanocytic, etc. a. Medulloblastoma Variants: desmoplastic, medullomyoblastoma, melanocytic medulloblastoma b. Cerebral (supratentorial) and spinal PNETs II. Tumors of cranial and spinal nerves Schwannoma (syn: neurilemmoma, neurinoma) Variants: cellular, plexiform, melanotic Neurofibroma Variants: circumscribed (solitary), plexiform, mixed neurofibroma/schwannoma Malignant peripheral nerve sheath tumor (MPNST)(syn: neurogenic sarcoma, anaplastic neurofibroma, malignant schwannoma ) Variants: epithelioid, MPNST with divergent mesenchymal and/or epithelial differentiation, melanotic III. Tumors of the meninges A. Tumors of meningothelial cells 1. Meningioma Histologic types: Meningothelial (syncytial) Transitional/mixed Fibrous (fibroblastic) Psammomatous Angiomatous Microcystic Secretory Clear cell Chordoid Lymphoplasmacyte-rich Metaplastic variants (xanthomatous, myxoid, osseous, chondroid) 2. Atypical meningioma 3. Anaplastic (malignant) meningioma Variants: of a-k above, papillary B. Mesenchymal, non-meningothelial tumors Benign: Osteocartilagenous tumors Lipoma Fibrous histiocytoma Others Malignant Mesenchymal chondrosarcoma Malignant fibrous histiocytoma Rhabdomyosarcoma Meningeal sarcomatosis Others C. Primary melanocytic lesions Diffuse melanosis Melanocytoma Malignant melanoma Variant: meningeal melanomatosis D. Tumors of uncertain origin Hemangiopericytoma Capillary hemangioblastoma IV. Hemopoietic neoplasms Malignant lymphomas Plasmacytoma Granulocytic sarcoma Others V. Germ cell tumors Germinoma Embryonal carcinoma Yolk sac tumor (endodermal sinus tumor) Choriocarcinoma Teratoma Variants: immature, teratoma with malignant transformation Mixed germ cell tumors VI. Cysts and tumor-like lesions Rathke's cleft cyst Epidermoid cyst Dermoid cyst Colloid cyst of the third ventricle Enterogenous cyst (syn: neuroenteric cyst) Neuroglial cyst Other cysts Lipoma Granular cell tumor (syn: choristoma, pituicytoma) Hypothalamic neuronal hamartoma Nasal glial heterotopias VII. Tumors of the anterior pituitary Pituitary adenoma Pituitary carcinoma VIII. Local extensions from regional tumors Craniopharyngioma Variants: adamantinomatous, squamous, papillary Paraganglioma (syn: chemodectoma) Chordoma Variant: chondroid chordoma Chondroma Chondrosarcoma Adenoid cystic carcinoma (syn: cylindroma) Others IX. Metastatic tumors
II. Tumors of nerves A. Schwannoma A. Neurofibroma III. Tumors of the coverings of the brain (meninges) A. Meningioma IV. Germ cell tumors (embryologically derived cell types) A. Germinoma B. Others: embryonal carcinoma, choriocarcinoma, teratoma V. Other malformative tumors and tumor-like lesions A. Craniopharyngioma B. Rathke's cleft cyst C. Epidermoid and Dermoid cyst D. Colloid cyst of the third ventricle E. Lipoma F. Hamartoma VI. Tumors of the pituitary gland VII. Metastatic tumors to brain from elsewhere in the body
Background: Prior to the advent of MRI, imaging of the cranial nerves (CNs) was difficult, and mass lesions arising from these nerves often could be detected only indirectly by looking at bony changes in the skull base foramen or by using invasive techniques such as cisternography and angiography. Current imaging techniques provide noninvasive highly detailed imaging of most of the CNs and the lesions (eg, schwannomas) that affect them. Patients with CN schwannomas can present with loss of function of the affected nerve, but also can be asymptomatic with the lesion incidentally discovered on CT or MRI scans performed for another reason. CN schwannomas are usually isolated lesions, except when associated with neurofibromatosis type 2 (NF2), a rare autosomal dominant disorder occurring in approximately 1 in 50,000 live births. NF2 is also called the MISME Syndrome (Multiple Inherited Schwannomas, Meningiomas, and Ependymomas). Pathophysiology: Schwannomas arise from the nerve sheath and consist of Schwann cells in a collagenous matrix. Histologically, the terms Antoni type A neurilemoma and type B neurilemoma are used to describe varying growth patterns in schwannomas. Type A tissue has elongated spindle cells arranged in irregular streams and is compact in nature. Type B tissue has a looser organization, often with cystic spaces intermixed within the tissue. The cystic spaces can result in high T2 MRI signal. Tumors originating in Schwann cells can be detected immunohistochemically by positive test results to the S100 antigen. Frequency: In the US: Schwannomas comprise 6-8% of intracranial neoplasms. Autopsy studies have shown incidence rates of occult vestibular schwannomas as high as 2.7%. A study of patients undergoing MRI for other indications revealed an estimated prevalence of 0.07%. Vestibular schwannomas are the most common CN schwannomas followed by trigeminal and facial, and then glossopharyngeal, vagus, and spinal accessory nerve schwannomas. Schwannomas involving the oculomotor, trochlear, abducens, and hypoglossal nerves are quite rare. NF2 is characterized by bilateral vestibular schwannomas. Schwannomas of the other CNs occur more frequently in NF2, and the presence of one of the rare CN schwannomas should raise the question of NF2. Meningiomas and intramedullary ependymomas of the spinal cord also occur in NF2. Mortality/Morbidity: Morbidity resulting from schwannomas includes nerve dysfunction and brainstem compression. Mortality may result from mass effect with brainstem compression. Race: No racial predilection has been described in schwannomas. Sex: No sex predilection has been described in schwannomas. Anatomy: CNs III-XII are peripheral nerves that arise from the brainstem and exit the skull base through their respective foramina. Motor neurons of the oculomotor nerve (CN III) leave the midbrain at the level of the tegmentum and emerge in the interpeduncular cistern. Here, it passes between the posterior cerebral artery (PCA; above) and the superior cerebellar artery (SCA; below) and turns anteriorly to enter the cavernous sinus. Within the cavernous sinus, the oculomotor nerve runs along the lateral wall and is the most superior of all the nerves in the sinus. The nerve enters the orbit via the superior orbital fissure and then splits into superior and inferior divisions. From the trochlear nucleus in the midbrain, fibers of the trochlear nerve (CN IV) cross the midline dorsal to the cerebral aqueduct and exit the midbrain dorsally. From here, the fibers run around the midbrain to the ventral surface. Like the oculomotor nerve, the trochlear nerve also courses between the PCA and SCA, along the lateral wall of the cavernous sinus, and enters the orbit at the superior orbital fissure. The trigeminal nerve (CN V) exits the brainstem at the level of the mid pons, and its 3 divisions, the ophthalmic (CN V1), maxillary (CN V2), and mandibular (CN V3) branches run together anteriorly towards the trigeminal ganglion located in the Meckel cave. From here, the mandibular division exits inferiorly via the foramen ovale. The maxillary and ophthalmic divisions continue anteriorly along the lateral aspect of the cavernous sinus. Eventually, the ophthalmic division enters the orbit via the superior orbital fissure, while the maxillary division exits the cranial vault through the foramen rotundum. The abducens nerve (CN VI) exits the brainstem ventrally at the level of the junction of the pons and medullary pyramid and runs anterolaterally towards the dorsum sellae, passing over the petrous apex where it makes a sharp turn to enter the cavernous sinus. Within the sinus, the abducens nerve is medial to CN IV, CN V1, and CN V2. Along with the oculomotor and trochlear nerves, the abducens nerve also enters the orbit via the superior orbital fissure, then enters the deep surface of the lateral rectus muscle. The courses of the facial (CN VII) and vestibular (CN VIII) nerves are associated intimately. They exit the brainstem at the pontomedullary junction, with the facial nerve slightly medial to the vestibular nerve. From there, they enter the internal auditory canal (IAC). Once in the IAC, the facial nerve courses in the superior-anterior quadrant of the canal, while the vestibular division of the vestibular nerve courses within the posterior superior and inferior quadrants, and the cochlear division courses in the inferior-posterior quadrant. CN VIII then enters the labyrinth. (The mnemonic for this is &quot;Seven-Up and Coke (Cochlear) down.&quot;) The facial nerve enters the labyrinth (labyrinthine segment), courses anteriorly in the temporal bone to the geniculate ganglion, turns posteriorly to pass beneath the lateral semicircular canal (tympanic segment), then turns inferiorly to course through the mastoid (vertical segment) and exits the temporal bone via the stylomastoid foramen. Finally, the facial nerve runs within the parotid gland (parotid segment) before branching. The glossopharyngeal (CN IX), vagus (CN X), and accessory (CN XI) nerves emerge cranial to caudal, in that order, from the ventral medulla, lateral to the medullary olive. From there, they course towards the jugular foramen and exit the skull base at the jugular foramen. The glossopharyngeal nerve is located within the pars nervosa of the jugular foramen, and the vagus and accessory nerves are located within the more posterior pars vascularis. The hypoglossal nerve (CN XII) is formed by the fusion of multiple rootlets that emerge from the ventrolateral sulcus between the medullary olive and pyramid. The nerve exits the cranial vault via the hypoglossal canal, then lies medial to CN IX, CN X, and CN XI. Clinical Details: Presenting symptoms of schwannomas typically are based on the affected nerve. Vestibular nerve: Patients with vestibular schwannomas present with sensorineural hearing loss, tinnitus, and disequilibrium. Very rarely, patients can present with acute sensorineural hearing loss secondary to hemorrhage into a vestibular schwannoma. The lesions arise from either the inferior or superior division of the vestibular nerve, but typically cause symptoms due to mass effect on the adjacent cochlear nerve. Some authors report that these lesions arise more frequently from the inferior division of the nerve, but others cite equal frequency for superior and inferior divisions. Trigeminal nerve: Trigeminal schwannomas can present with facial pain and/or atrophy of the muscles of mastication. Facial nerve: The presentation of facial schwannomas is quite variable and depends on the segment of the facial nerve from which the tumor arises. Symptoms can range from facial palsy to compressive hearing loss resulting from ossicular interference. Tumors in the IAC can present with vestibular symptoms resulting from compression of the intimately associated vestibular nerve. Facial schwannomas in the middle cranial fossa or distal to the stylomastoid foramen can be several centimeters in size at the time of presentation because no immediately adjacent sensitive structures exist. Glossopharyngeal, vagus, or accessory nerves: Schwannomas in the jugular foramen, arising from the glossopharyngeal, vagus, or accessory nerves, can present with variable amounts of cerebellar and acoustic symptoms, depending on the extent of intracranial growth of the mass. They also can present with glossopharyngeal dysfunction (eg, hoarseness, difficulty swallowing) and/or spinal accessory symptoms (trapezius atrophy). Oculomotor, trochlear, or abducens nerves: Schwannomas involving the oculomotor, trochlear, and abducens nerves are very rare. Presenting symptoms can include palsy of the affected muscle and ipsilateral cavernous sinus symptoms if the mass is located within the cavernous sinus. Hypoglossal nerve: Hypoglossal schwannomas are rare lesions that can present with ipsilateral deviation of the tongue, possibly with associated ipsilateral hemiatrophy. Preferred Examination: MRI with gadolinium-contrast medium is the technique of choice for imaging the CNs. MRI provides the highest degree of soft tissue resolution, can image in multiple planes, and is not encumbered by bone artifact from the skull base. CT is ideal for evaluating the secondary effects on the neural foramen. Limitations of Techniques: CT evaluation is limited primarily to bony changes in the skull base. Artifact from the skull base limits soft tissue resolution of CT, particularly for small lesions. Plain films play no role in the evaluation of the lesions. Aside from patient incompatibility resulting from claustrophobia or incompatible hardware, the only significant imaging drawback of MRI is that CT can be more sensitive in detecting adjacent bone destruction than MRI. Brain, Lymphoma Brain, Metastases Glomus Tumor (Head and Neck) Meningioma , Brain Neurofibromatosis Type I Neurofibromatosis Type II Other Problems to be Considered: The differential diagnosis varies based upon location, but meningiomas can occur in similar regions and have similar imaging appearances. The differing growth patterns, as well as the dural tail and associated hyperostosis that can be seen with meningiomas, often are helpful differentiating factors (see Image 5 ). Cerebrospinal fluid (CSF) spread of metastatic disease or lymphoma can present as a focal CN mass (see Image 16 , Image 18 ). Neuritis (inflammation of a nerve) potentially can be confused with a mass (see Images 10-11 ). NF2 is one of the phacomatoses characterized by multiple intracranial schwannomas, meningiomas, and ependymomas. Bilateral vestibular schwannomas are diagnostic of this entity, but patients can have schwannomas involving any CN (CN III-XIII; see Image 6 ).
Findings: On noncontrast CT, most schwannomas are isodense with brain parenchyma. Calcification or areas of hemorrhage are rare. On contrast-enhanced CT, the enhancement pattern typically is homogeneous. Bone window images can demonstrate remodeling of the adjacent skull base, such as expansion of the IAC by vestibular schwannomas and the facial canal by facial schwannomas (see Image 7 ). Expansion of the jugular foramen by CN IX, CN X, or CN XI schwannomas also can be seen. Thin-collimation CT imaging of the skull base can be helpful for evaluating bone destruction, which is useful for differentiating jugular foramen schwannomas from paragangliomas (see Image 23 ). For further details regarding specific CN schwannomas, see MRI Findings. Degree of Confidence: For large lesions, a mass can be diagnosed using CT scans with a high degree of confidence. Distinguishing a schwannoma from a meningioma may not be possible using CT. For small lesions, a mass affecting a CN cannot be excluded confidently. False Positives/Negatives: CT findings can be falsely negative for small lesions. Occasionally, a false-positive diagnosis occurs because of streak artifact in the cerebellar pontine angle cistern mimicking a lesion. CAT SCAN Section 5 of 10 Findings: Vestibular schwannomas are visualized on CT as strongly, but heterogeneously, enhancing cerebellopontine angle masses extending from the IAC. On precontrast imaging, they are isodense to hypodense with respect to brain tissue and may have associated cysts or hemorrhage. The pressure of the tumor often results in widening of the IAC, best visualized using bone windows. Gas CT cisternography, with 0.5- to 1-mm slices, can demonstrate small tumors within the IAC, which typically are missed on routine CT. Small schwannomas of the other CNs easily are overlooked or not visualized because of their proximity to osseous structures and the relatively poor contrast resolution of CT. Intracranial meningiomas present as enhancing extra-axial masses often with internal calcifications and adjacent hyperostosis, best visualized with bone windows. Adjacent white matter decreased attenuation commonly is seen when tumors are large. This likely represents edema. The persistence of this abnormality for years after the tumor has been resected suggests the likely existence of a demyelinating factor as well. When large enough, meningiomas may exhibit mass effect on the brain parenchyma and can be aggressive at times, invading adjacent bone. Without contrast, meningiomas may have the same attenuation as the brain but typically have higher attenuation values resulting from the presence of calcium and a high nuclear-to-cytoplasmic ratio. Small tumors can be missed, particularly over the calvarium and in the posterior fossa, where beam-hardening artifact is the worst. Spinal schwannomas appear either as dumbbell-shaped enhancing masses extending out the neural foramina or as intradural extramedullary masses in the spinal canal. CT shows widening of the foramina or pressure erosion on the adjacent vertebral body, and sagittal reformatted images are useful. Spinal meningiomas are found as intradural extramedullary masses usually in the thoracic spine. They are best imaged on CT myelography although they usually show enhancement on contrast CT. Occasionally, meningiomas extend into the neural foramen and appear as dumbbell-shaped masses with widening of the neural foramen. In these cases, distinguishing them from schwannomas or neurofibromas is difficult. Spinal ependymomas are intra-axial enhancing masses seen most frequently in the cervical cord and conus. When involving the conus or filum, an ependymoma may be pedunculated and appear as an extra-axial mass. Cervical cord ependymomas are well-marginated enhancing tumors that may exhibit associated cyst formation. Degree of Confidence: Perform CT only in patients with NF-2 in whom MRI is contraindicated, since MRI provides superior tumor imaging and characterization. When CT must be used, perform high-resolution techniques in the axial and coronal planes and consider CT cisternography for detecting small tumors. Even when visualized, the type of tumor often is difficult to identify on CT, since a large amount of overlap is seen in tumor appearance. While CT myelography is adequate in depicting the extra-axial lesions of NF-2, it is relatively poor at detecting ependymomas. CT with 3-dimensional volumetric rendering can be useful for preoperative planning in patients with NF-2 with associated scoliosis or spinal dystrophy.
Findings: Similar to CT imaging, MRI findings of schwannomas tend to be homogeneous masses, which typically are isointense or slightly hypointense to gray matter on T1-weighted images and slightly hypointense to CSF on T2-weighted images. Enhancement following gadolinium administration typically is homogeneous, although larger schwannomas can show areas of cystic degeneration and signal heterogeneity, often on the bases of increased areas of Antoni type B histology. Recently, high-resolution thin-section heavily T2-weighted 3-dimensional sequences have been used to look for acoustic neuromas. On these sequences, individual nerves within the cistern and IAC can be visualized as linear filling defects within the bright CSF. Small masses can be identified without the use of an intravenous contrast agent (see Image 3 ). MRI Section 6 of 10 Findings: Vestibular schwannomas are well-defined masses arising from the IAC and frequently extending out into the cerebellopontine angle, demonstrating an ice cream cone or mushroom shape (see Image 1). Vestibular schwannomas often have heterogeneous signal, but typically are isointense to hypointense on T1-weighted images and hyperintense on T2-weighted images. High-resolution heavily T2-weighted sequences have been used to detect small vestibular schwannomas and appear to be approximately as sensitive as contrast MRI. Using this technique, the bright cerebrospinal fluid (CSF) around CN VII and CN VIII is used as a contrast agent, and schwannomas appear as small rounded masses that efface the CSF in the canal. This technique also is useful in detecting cochlear involvement by the tumor as the cochlear turns can normally be easily identified as curvilinear areas of increased signal. Following contrast administration, they enhance avidly but often heterogeneously, particularly in larger tumors. Nonenhancing areas of necrosis often are present as the tumors enlarge, and associated cysts or blood products from internal hemorrhage may be present. Other CN schwannomas have a similar MRI appearance and differ only in location, occurring along the paths of the other CNs. The multiplanar capability of MRI is particularly useful in distinguishing a CN schwannoma from a meningioma adjacent to a nerve. Meningiomas in NF-2 have the same distribution and signal characteristics as spontaneous meningiomas, occurring most frequently along the falx and over the convexities (see Image 4). Meningiomas are extra-axial tumors, thus demonstrate cortical buckling and a CSF cleft. A confluent area of white matter increased T1 and decreased T2 signal may be seen in the adjacent brain parenchyma and likely results from a combination of vasogenic edema and demyelination. Tumors typically are isointense with gray matter on all sequences and, when small, can be difficult to detect without contrast. Signal intensity can vary and almost any combination of T1 and T2 signals can be seen. Cyst formation is uncommon but calcification occurs frequently and can cause the tumor to appear heterogeneous. Following gadolinium administration, intense and generally homogeneous enhancement is seen, and a dural tail of enhancing dural tissue often is found extending from the tumor’s dural attachment although this is not specific for meningioma. Meningiomas in patients with NF-2 may be more aggressive than spontaneously occurring ones, and the tumor may invade the adjacent calvarium and extend into the paranasal sinuses (see Image 2). Spinal meningiomas also are associated with NF-2 and often are multiple in number. Unlike intracranial meningiomas, the spinal type calcifies in fewer than 10% of patients (see Image 3). Tumors typically are intradural and extra-axial but can present as dumbbell-shaped masses extending through the neural foramen. In this situation, distinction from a neurofibroma or schwannoma is difficult although the schwannoma should be brighter on T2-weighted images. Meningiomas usually are isointense to cord on all image sequences and enhance strongly following gadolinium administration. While most meningiomas have a broad dural attachment similar to their intracranial counterparts, dural tail signs are found less frequently. Spinal ependymomas found in NF-2 are divided into two groups, those that occur in the upper cord and those that occur in the conus. Cord tumors are well-marginated, intensely enhancing lesions, frequently associated with cyst formation and hemorrhage. Ependymomas may be isointense or hypointense to cord on T1-weighted images and are always bright on T2-weighted images although a peripheral rim of decreased T2 signal has been proposed as suggestive of ependymoma. Conus ependymomas more often are large tumors that can fill the entire spinal canal with heterogeneous signal and enhancement. When small, the tumors may be well-marginated intra-axial lesions but when larger, they may appear to be arising from the extra-axial space. Multiple extradural masses extending through the neural foramina are found in both NF-1 and NF-2, although unlike NF-1, in NF-2, these tumors usually are schwannomas. Tumors often have both an intraspinal and extraspinal component, demonstrate a classic dumbbell shape, and typically are multilevel and bilateral. Signal intensities are the same as in intracranial schwannomas, and strong contrast enhancement is seen. Because of the multifocality of the tumors and an association with scoliosis, coronal MRI often is helpful. Degree of Confidence: MRI is the imaging modality of choice in NF-2 and is accurate in detecting even small tumors. Separation of intracranial schwannomas from meningiomas may be difficult at times but usually is of little clinical value. The evaluation of the extent, size, and number of intracranial tumors in NF-2 is accomplished best by MRI because of its multiplanar capability, contrast resolution, and the spectrum of pulse sequences, each of which adds different information. Spinal meningiomas, schwannomas, and ependymomas also are visualized best on MRI. No other imaging modality usually is necessary either at the time of diagnosis or as part of a follow-up regimen. While MR can image osseous vertebral abnormalities associated with the disease, CT visualizes them better.
MRI findings of specific schwannomas are the following: Vestibular nerve: Vestibular schwannomas are the most common CN schwannomas. Typically, the masses are located in the cerebellopontine angle (CPA) and are centered at the porus, with extension into the IAC. Their appearance has been termed comet tail or ice cream cone. The long axis of the tumors lies parallel to the petrous surface. Occasionally, tumors can be entirely intracanicular, in which case, the primary differential diagnosis is a meningioma of the CPA. Unlike vestibular schwannomas, meningiomas tend to form obtuse angles with the adjacent petrous bone, typically are hemispherical in appearance, and often extend into the middle fossa via herniation (see Images 1-5). Degree of Confidence: A diagnosis of a CN mass can be made with a high degree of confidence using MRI. False Positives/Negatives: False-positive findings occur primarily in the jugular fossa where slow flow in the jugular bulb can mimic a mass. A false-negative diagnosis can occur if inadequate imaging is performed, ie, image slices are too thick or imaging lacked fat suppression when evaluating the skull base.
Clinical History: 68 year old male with left sided hearing loss. Findings: T1 weighted axial pre and post contrast images as well as T1 weighted post contrast coronal images demonstrate a left cerebellopontine angle mass. This demonstrates low signal on the T1 weighted images and enhances peripherally and heterogeneously centrally following the intravenous administration of contrast. In addition, there is widening of the internal auditory canal. Diagnosis: Acoustic schwannoma. Discussion: Acoustic schwannomas account for approximately 75% of all cerebellopontine angle masses. They most commonly arise from the vestibular branch of the 8th nerve. However, they can arise from other cranial nerves such as the facial or trigeminal nerve. Involvement of the intracanalicular portion of the 8th nerve produces enlargement and erosion of the internal auditory canal. The lesions are commonly hypo to isointense with brain on T1 weighted images. There is marked enhancement following the intravenous administration of contrast. On T2 weighted images, lesions are typically iso to slightly hyperintense. The differential diagnosis for cerebellopontine angle masses include acoustic schwannomas, meningiomas, epidermoids, arachnoid cysts and aneurysms. Specifically, the superior cerebellar as well as the anterior inferior cerebellar artery course through the cerebellopontine angle. The presentation of bilateral schwannomas involving the 8th cranial nerve can be seen with neurofibromatosis 2. Other lesions such as multiple meningiomas and epidermoid tumors can be seen in these patients as well. References: James P. Earls, MC, et al. Radiographics. General Case of the Day. November 1994;1424-1427. Osborn AG. Diagnostic Neuroradiology . Mosby, St. Louis, 1994;437-448. Taveras JM. Neuroradiology , 3rd Edition, Williams & Wilkins, 1996:684-693. Return to Neuro Imaging Page Submitted by: Simeon Abramson, M.D. C. F. Lanzieri, M.D.
Clinical History: 44-year-old male with progressive right-sided sensorineural hearing loss. Radiologic Findings: T1-weighted images (Figs. 1 and 2) show a 4 cm x 3 cm right cerebellopontine angle (CPA) mass with decreased signal intensity. It extends into the porous acousticus and maintains acute angles with the petrous bone. A moderate amount of mass effect involves the pons and cerebellum. A T2-weighted image (Fig. 3) demonstrates heterogeneously increased signal intensity in the mass. Following Gadolinium administration, T1-weighted images (Figs. 4 and 5) show intense homogeneous enhancement of the mass. Diagnosis: Vestibular Schwannoma. Discussion: Vestibular schwannomas are the most common tumors of the CPA, accounting for 80-90% of all tumors in this location. They most commonly arise from superior vestibular branch of the 8th nerve, slightly more commonly than inferior vestibular nerves. The 5th and 7th nerves are the next most common nerves of origin of schwannomas. Schwannomas arise from perineural Schwann cells, which are responsible for myelination of peripheral nerves. Although &quot;neuroma&quot; tends to be used interchangeably with &quot;schwannoma&quot;, by strict pathologic definition, neuromas refer to a post-traumatic proliferation of nerve cells rather than a true neoplasm. Arachnoid cysts co-exist in 7-10% of cases of vestibular schwannoma. Bilateral vestibular schwannomas are the primary diagnostic criterion for type 2 neurofibromatosis. The differential diagnosis includes a meningioma, which maintains obtuse angles with the petrous bone and exhibits the dural tail sign. An epidermoid, an aneurysm, and a metastasis is also noted in the differential. References: 1. Willing, Atlas of Neuroradiology, W. B. Saunders, Philadelphia, PA, 1995, pgs. 153-155. 2. Grossman and Yousem, Neuroradiology: The Requisites, Mosby Year Book, St. Louis, MO, 1994, pgs. 73-74. Return to Neuro Imaging Page Submitted by: Rakesh Shah, M.D. Charles F. Lanzieri, M.D. Vestibular Schwannoma and the NF2 Gene Rebecca L. Bamford Development of the majority of human cancers can be traced to alterations in the standard pool of genetic information. Such chance mutations at the cellular level of an individual exhibit a dominant pattern of genetic transmission in families when passed from parent to child. Specifically, this is true of a rare cancer of the eighth cranial nerves known as vestibular schwannoma. Vestibular schwannoma is characterized by the formation of encapsulated tumors resembling bunches of grapes in the Schwann cells of the ears. Symptoms produced by such tumor formation include dizziness, imbalance, nausea, impaired speech and hearing, ringing in the ears, facial paralysis, and the possibility of coma or death at extreme levels of progression of the disease. Vestibular schwannoma has an annual incidence of about 1 in 100,000 people (Moffat 383). They can occur as both sporadic (95%) and familial (5%) disorders (Moffat 383). Sporadic forms of the disease arise from acquired mutations in the nucleus of a single cell that multiply to result in tumor formation. Such spontaneous mutation cannot be passed on to the next generation because both copies of the gene are normal at birth as they are inherited from parents unaffected by the disease. The genetic information of the affected cell is changed in a process separate from gametogenesis. Familial forms of vestibular schwannoma arise from a germline mutation that can be passed on to later generations. Both sex cells and somatic cells contain the mutation, giving familial forms of vestibular schwannoma an autosomally dominant mode of inheritance. Because the trait is autosomally dominant, children have a 50% chance of inheriting the mutant allele from a parent affected by vestilbular schwannoma. For example, a woman that knows that her mother and brother have vestibular schwannoma can expect a 50% chance of developing nerve sheath tumors herself. The onset of vestibular schwannoma also exhibits a phenomenon called genomic imprinting. Here, the genes for vestibular schwannoma are &quot;labeled&quot; (via methylation, for example) for greater expression of the genetic information contributed by one parent. This over expression of genes is not discriminatory and can include those that cause disease. Vestibular schwannoma has been shown to be much more severe if it is inherited from the maternal gene pool. Increased severity includes earlier onset of the disease, as well as more abundant and more rapidly-growing tumors. Based on a family history of the disease then, an individual should seek determination of their own health status as early as possible in order to avoid the pending effects of vestibular schwannoma later in life. Development of familial vestibular schwannoma has been traced to abnormalities involving the NF2 gene on chromosome 22. NF2 is a tumor suppressor gene that, when its genetic code is disturbed, predisposes patients to the development of schwannomas of the vestibular nerves. The exact function of the NF2 gene is yet unknown, but it encodes a structural protein of 595-amino acids called schwannomin. Schwannomin is involved in regulating the stability of the plasma membrane as it connects to the cytoskeleton in Schwann cells. When NF2 is changed, the interactive membrane/cytoskeleton physical properties also change, and the cell is more easily deformed. This deformability leads to accelerated tumorigenesis, as NF2 encoded schwannomin protein does not function adequately and Schwann cells experience differentiation into tumorous growths (Lutchman 2270). In a 1995 study by Lutchman and Rouleau, mouse fibroblast cells transfected with mutated NF2 were shown to experience altered shape because of consequent production of a mutant protein. This protein was inactive, resulting in increased rate of growth and transformed morphology of the cell, especially in the cytoskeleton and its connection to the plasma membrane (Lutchman 2273). Mutations in the NF2 gene on chromosome 22, then, can result in the tumor formation of vestibular schwannoma. Mutations can be divided into 3 categories: point mutations, deletions, and insertions. A 1994 Princeton study found that most insertions and deletions at the NF2 site caused a frameshift mutation that led to early termination of the reading frame in the 14-200bp area of the mutation. Here, the tumors studied had a stop codon created in the site of the mutation. In general, the mutations observed created large scale alteration of the structure of the schwannomin protein encoded, and resulted in inactivation of the NF2 tumor suppressor gene (Lekanne Deprez 1027). The nature of the chromosome 22/NF2 gene mutation is therefore suspected to be the major determinant of Schwann cell proliferation in tumorigenesis vestibular schwannoma. In a clinical setting, tumors symptomatic of vestibular schwannoma can be identified by magnetic resonance imaging (MRI). On a chromosomal level though, conclusive detection of mutations in the NF2 region of chromosome 22 can be accomplished through PCR testing. In this process, RNA samples are isolated from vestibular schwannomas and the enzyme reverse-transcriptase is used to amplify the coding region of the NF2. The PCR-amplified products are then run across an agarose gel to identify varying lengths of RNA occurring because of deletions and insertions in the gene fragment transcripts. Technicians perform this test in order to find evidence in the genetic information gathered congruent with the hypothesis that altered NF2 gene size is causal in vestibular schwannoma (Lekanne Deprez 1024). The functions of a cell are controlled by proteins, which are encoded by our genes. Cancer evolution is a process resulting in uncontrolled cellular growth and tumorigenesis, as a result of the inactivation of tumor suppressor genes. NF2 gene inactivation is similarly linked to the tumor formation characteristic of vestibular schwannoma. Whether sporadic or familial, DNA from vestibular schwannomas demonstrate chromosome 22 abnormalities, the latter only possessing the capability of transmission to generations to come. Vestibular schwannomas grow slowly over a period of years in the eighth cranial nerve. This cancer can become life threatening as these tumors continue to grow and press on the brainstem. Detection of the NF2 mutation at an early stage of development is highly important, if not for the sake of those inflicted by vestibular schwannoma, then for the consideration of the children that will also suffer from the disease in generations to come. References Lekanne, D., Bianchi, A. , Groen, N. (1994) Frequent NF2 Gene Transcript Mutations in Sporadic and Vestibular Schwannomas. American Journal of Human Genetics 54(6): 1022-9. Lutchman, M., Rouleau, G. (1995) The Neurofibromatosis Type 2 Gene Product, Schwannomin, Suppresses Growth of NIH 3T3 Cells. Cancer Research 55(11): 2270-4. Moffat, D., Irving, R. (1995) The Molecular Genetics of Vestibular Schwannoma. Journal of Laryngology and Otology 109(5): 381-4. Rao, U., Surti, U., Hoffner, L., Yaw, K. (1996) Cytogenetic and Histologic Correlation of Peripheral Nerve Sheath Tumors of Soft Tissue. Cancer Genetics and Cytogenetics 88(1): 17-25. References - Vestibular Schwannoma Erickson LS, Sorenson GD, McGavran MH. A review of 140 acoustic neurinomas (neurilemmoma). Laryngoscope 1965; 75:601-627. Leonard J, Talbot M. Asymptomatic acoustic neurilemmoma. Arch Otolaryngol Head Neck Surg 1970;91:117 Sidek D, Michaels L, Wright A. Changes in the inner ear in vestibular schwannoma. In: Iurato S and J.E. Veldman JE eds. Progress in Human Auditory and Vestibular Histopathology. Amsterdam:Kugler Publications, 1996:95-101. Young DF, Eldridge R, Gardner WJ. Bilateral acoustic neuroma in a large kindred. JAMA 1970;214:347-353. Wertelecki W, Rouleau GA, Superneau MD, et al. Neurofibromatosis 2: Clinical linkage studies of a large kindred. N Engl J Med 1988;5:278-283..(6). Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exper Neurol 1993;52:106-113. Igarashi M, Jerger J, Alford BR, Stasney CR. Functional and histological findings in acoustic tumor. Arch Otolaryngol Head Neck Surg 1974;99:379-384. Singh SP, Cottingham SL, Slone W, Boesel CP, Welling DB, Yates AJ. Lipomas of the internal auditory canal. Archiv Pathol Lab Med 1996;120:681-683.
(1) Enhancing small tumor at the right cerebellopontine angle (2) Tumoral component inside the right internal acoustic meatus (3) Membranous labyrinth (4) Pons (5) Cerebellar hemisphere (6) Normal left internal acoustic meatus
Facial nerve: Schwannomas of the facial nerve can occur along any segment but frequently involve the geniculate ganglion and extend proximally or distally from there. MRI and CT imaging characteristics are similar to those for vestibular schwannomas. The location of the mass results in variable growth patterns. In the IAC, facial schwannomas are indistinguishable from vestibular lesions. When crossing the petrous bone to involve both the middle and posterior fossa, facial schwannomas cross in the mid portion of the petrous bone as opposed to trigeminal schwannomas, which cross near the petrous apex. Lesions in the geniculate ganglion can be mistaken for temporal lobe lesions, and imaging in the coronal plane is useful in evaluating the lesions (see Images 8-9).
Trigeminal nerve: Trigeminal schwannomas can arise in the Meckel cave or in the cistern along the course of the nerve. Extension and expansion of the foramen rotundum or ovale is common, and the masses can have a bilobed appearance. Tumors also can grow posteriorly to involve the posterior fossa or anteriorly into the cavernous sinus. Trigeminal schwannomas tend to have a more cystic component than do other schwannomas (see Images 12-15).
Glossopharyngeal, vagus, or accessory nerves: Glossopharyngeal, vagus, or accessory nerve schwannomas are rare and are difficult to distinguish from each other. The tumors are classified based on their growth patterns, with type A lesions growing predominantly intracranially, type B lesions growing predominantly at the jugular foramen, and type C lesions growing predominantly extracranially. CT and MRI characteristics are similar to those seen in other schwannomas. In contrast to the more common paraganglioma in this region, schwannomas expand but do not infiltrate the adjacent bone (see Images 19-20).
Hypoglossal nerve: Hypoglossal schwannomas are similar in growth patterns and imaging characteristics to jugular foramen schwannomas. When large enough, the tumors can erode the hypoglossal canal to such an extent that differentiation from jugular foramen schwannomas can be difficult.
Abducens and trochlear nerves: Schwannomas of CN VI are rare. They have been reported to occur in the prepontine cistern, with a heterogeneous appearance on CT and MRI imaging and extension into the adjacent cavernous sinus. Similar to other schwannomas, meningioma is the primary differential diagnosis, and the presence of areas of cystic change (manifesting as high T2 signal) can sway the likelihood of a diagnosis to schwannoma over meningioma. CN IV schwannomas similarly are rare (see Image 17).
Oculomotor nerve: Schwannomas of the oculomotor nerve have been reported in the literature but are exceedingly rare. The tumors can present as masses in the suprasellar cistern and can be difficult to distinguish from meningiomas in this region.
Discussion: Neurofibromatosis, one of the phakomatoses, is a neurocutaneous disorder inherited in an autosomal dominant pattern. The two most common forms NF-1 and NF-2 have been localized to defects within chromosome 17 and 22, respectively. NF-1 has an incidence of roughly 1:3000 live births. Clinically, NF-1 is diagnosed by the presence of at least two of the following: 1) six or more café-au-lait spots, 2) two or more hemartomas of the iris (Lisch nodules), 3) two or more neurofibromas, 4) one or more plexiform neurofibromas, 5) axillary freckling, 6) one or more bone dysplasias, 7) psuedoarthrosis of a long bone, 8) optic glioma, or 9) a first-degree relative with the diagnosis of NF-1. Radiologically, cerebellar, brain stem, and cerebral astrocytomas are seen with NF-1. On MR T2 weighted images, patients may have high signal intensity foci in the peduncles or deep gray matter of the cerebellum, brain stem or basal ganglia, as is the case for this patient. These features are believed to represent hamartomas, focal areas of gliosis, wallerian degeneration, neuronal migrational disorders, or possibly neoplasms.
Clinical History: 9-year-old male with a history of headaches x two months and hyperreflexia. Findings: Multiple rounded foci of abnormally bright signal are seen in the lentiform nuclei bilaterally, the thalami bilaterally, mesencephalon, and dentate nuclei bilaterally (left greater than right), on FLAIR and T2 weighted images. No abnormal enhancement is seen. Diagnosis: Neurofibromatosis, Type I. Discussion: Neurofibromatosis, one of the phakomatoses, is a neurocutaneous disorder inherited in an autosomal dominant pattern. The two most common forms NF-1 and NF-2 have been localized to defects within chromosome 17 and 22, respectively. NF-1 has an incidence of roughly 1:3000 live births. Clinically, NF-1 is diagnosed by the presence of at least two of the following: 1) six or more café-au-lait spots, 2) two or more hemartomas of the iris (Lisch nodules), 3) two or more neurofibromas, 4) one or more plexiform neurofibromas, 5) axillary freckling, 6) one or more bone dysplasias, 7) psuedoarthrosis of a long bone, 8) optic glioma, or 9) a first-degree relative with the diagnosis of NF-1. Radiologically, cerebellar, brain stem, and cerebral astrocytomas are seen with NF-1. On MR T2 weighted images, patients may have high signal intensity foci in the peduncles or deep gray matter of the cerebellum, brain stem or basal ganglia, as is the case for this patient. These features are believed to represent hamartomas, focal areas of gliosis, wallerian degeneration, neuronal migrational disorders, or possibly neoplasms. References: Rodriguez-Carbajal J, Palacios E, Naidich T. Craniospinal Magnetic Resonance Imaging in Neurofibromatosis. In: Neuroradiology and Radiology of the Head and Neck . Ed. Juan M. Tavares, J.B. Lippincott and Co., Philadelphia; 1988(3):1-13. Grossman RI, Yousem DM. Neuroradiology, The Requisites . Mosby, St. Louis; 1994(9):267. Griffiths PD, Blaser S, Mukonoweshuro W, Armstrong D, Milo-Mason G, Cheung S. Neurofibromatosis Bright Objects in Children with Neurofibromatosis Type I: A Proliferative Potential? Pediatrics. 1999;104(4):e49. Return to Neuro Imaging Page Submitted by: Dauphine Giles-Sweatt C. F. Lanzieri, M.D.
Background: Neurofibromatosis 2 (NF-2) is an inherited autosomal dominant syndrome characterized by multiple schwannomas, meningiomas, and ependymomas. The most common tumor associated with the syndrome is the vestibulocochlear schwannoma, and as many as 10% of patients with this tumor have NF-2. While it shares a name with neurofibromatosis type 1 (NF-1; von Recklinghausen disease), the two diseases are separate entities. Neurofibromas rarely are found in NF-2, which has led some to propose that the disease be termed schwannomatosis or MISME syndrome, the acronym for the following terms: Multiple Inherited Schwannomas Meningiomas Ependymomas The term MISME is becoming used widely as a mnemonic to remember the disease. While a presumed case of NF-2 first was described in 1882 by Wishart, the disease was not separated from von Recklinghausen disease until 1987, when it was demonstrated that the two disorders arose from different chromosomes. The genetic defect responsible for NF-2 is a deletion of a portion of chromosome 22, the same chromosomal abnormality found in spontaneous spinal schwannomas, indicating that a single location causes Schwann cell tumor growth. In 1988, the National Institutes of Health released a conference statement regarding neurofibromatosis that addressed the diagnosis of NF-2. The criteria decided upon for the diagnosis of NF-2 included either one of the following: Bilateral cranial nerve (CN) VIII masses seen with appropriate imaging techniques (eg, CT or MRI) A first-degree relative with NF-2 and either a unilateral CN VIII mass or two of the following: Neurofibroma Meningioma Glioma Schwannoma Juvenile posterior subcapsular lenticular opacity A revision to these diagnostic criteria of NF-2 recently has been proposed, with the addition of a segment of presumptive or probable NF-2. These modified criteria are listed as follows (adapted from Gutmann et al): Definite diagnosis of NF-2 Bilateral CN VIII schwannomas on MRI or CT (no biopsy necessary) First-degree relative with NF-2 and either unilateral early onset vestibular schwannoma (age <30 y) or any two of the following: Meningioma Glioma Schwannoma Juvenile posterior subcapsular lenticular opacity (juvenile cortical cataract) Presumptive diagnosis of NF-2 Early onset unilateral CN VIII schwannomas on MRI or CT detected at younger than age 30 years and one of the following: Meningioma Glioma Schwannoma Juvenile posterior subcapsular lenticular opacity Multiple meningiomas (>2) and unilateral vestibular schwannoma or one of the following: Glioma Schwannoma Juvenile posterior subcapsular lenticular opacity Although CN schwannomas occur spontaneously as well, except for CN VIII schwannomas, they are relatively rare. Thus, the presentation of any patient with multiple CN schwannomas, an unusual intracranial schwannoma, or a single schwannoma of CN III, CN IV, or CN VI should prompt screening for NF-2. In addition, consider the diagnosis in the workup of patients with multiple extra-axial brain or spine tumors, whether they are meningiomas or schwannomas. Pathophysiology: Lesions of the brain and spine eventually occur in almost all patients with NF-2. CN VIII (vestibulocochlear) schwannomas are the hallmark of the disease, but schwannomas can be found involving any CN from III-XII, with CN V (trigeminal) as the next most frequently involved. Spontaneously occurring vestibular schwannomas have a similar appearance but typically occur later in life. Dural-based meningiomas commonly are seen in NF-2 and often are multiple in number, occasionally seeding the meninges with tiny tumor foci. Meningiomas found in NF-2 resemble spontaneously occurring meningiomas in location and appearance, although similar to vestibular schwannomas, they occur at an earlier age. Consider the diagnosis of NF-2 in any patient younger than 30 years with meningioma or CN schwannoma. Ependymomas are the most common intraparenchymal tumor in NF-2, although schwannomas rarely present as a solely intraparenchymal lesion, and gliomas rarely are associated with the syndrome. Multiple studies have described benign intracranial calcifications, particularly of the choroid plexus, cerebellar hemispheres, and cerebral cortex, in association with the disease. Spinal tumors seen in NF-2 include meningiomas, ependymomas, and schwannomas. Schwannomas may present as intradural extramedullary masses or may involve the exiting nerve roots. Nerve root tumors in NF-2 may present as dumbbell-shaped lesions extending through the neural foramina similar to the neurofibromas of NF-1, but histology reveals that most of these are schwannomas. Meningiomas present as intradural extramedullary masses similar to spontaneous meningiomas, typically involving the thoracic spine and often multiple in number. Most intramedullary spine tumors in NF-2 are ependymomas, arising in either the upper cervical cord or the conus. Recently, different genotypes in NF-2 have been correlated with differing incidences of various spinal neoplasms, since patients with frameshift and nonsense mutations have higher incidences of all spinal tumors but especially intramedullary tumors. A few ocular abnormalities occur in NF-2, including a form of early-onset cataract termed juvenile posterior subcapsular lenticular (or lens) opacity. Hamartomas of the retina and choroids are common in NF-2, and a patient's vision may be affected by optic nerve sheath meningiomas. While patients with NF-2 may have cutaneous schwannomas that resemble skin tags, they rarely have café-au-lait spots and do not demonstrate the cutaneous neurofibromas that typically result in the early diagnosis of NF-1. Since symptoms from vestibular schwannomas usually begin in the third decade, patients with NF-2 typically are diagnosed later in life compared to those with NF-1. Frequency: In the US: Incidence of NF-2 is 1 per 30,000-40,000 persons. Internationally: Incidence of NF-2 is 1 per 30,000-40,000 persons. Mortality/Morbidity: Hearing loss resulting from vestibular schwannomas comprises the most common morbidity associated with the disorder. When small, vestibular tumors can be resected completely with preservation of hearing; however, if the tumors are large, debulking often is all that is possible without damaging the facial and vestibulocochlear nerves. Other tumors, such as meningiomas and ependymomas, cause symptoms based on mass effect on adjacent structures and occasionally are debulked or removed, although typically they are followed only with serial MRI scans. Despite the large number of tumor types found in NF-2, malignant transformation is rare and may be iatrogenic in many patients. In one international study by Baser et al, 5% of patients who received external beam radiation developed malignant tumors at previously radiated sites, while fewer than 1% of patients not radiated developed malignancies. This suggests that the number of malignancies in the first group were radiation associated, similar to data regarding hereditary retinoblastoma. Fortunately, radiation therapy has a limited role in NF-2 and is reserved for aggressive tumors and for patients who refuse surgical intervention. Race: No racial predilection exists, although since the disease is autosomal dominant with a high penetrance, many patients have a strong family history. Sex: Male-to-female ratio approaches 1:1 since the disease is autosomal dominant. Age: Typically, the diagnosis of NF-2 is made in the second or third decade of life, with a peak in the 20s. The diagnosis usually is made as a result of symptoms associated with CN VIII schwannomas. NF-2 may be diagnosed earlier in children with a family history of the disease, as a result of early screening, or in those who initially present with diplopia or vision loss. As a result of its high penetrance, NF-2 patients almost always present prior to age 60 years. Most are diagnosed before age 40 years. Anatomy: The vestibulocochlear nerve (CN VIII) leaves the brainstem at the level of the mid pons and runs through the ambient cistern towards the internal auditory canal (IAC), adjacent to the facial nerve. Within the canal, CN VIII runs in the inferior portion, underneath the crista falciformis. Bill's bar, a thin layer of arachnoid tissue that can have a small osseous component, divides the upper portion of the canal into anterior and posterior segments, separating the upper portion of the vestibular nerve (posterior) from the facial nerve (anterior). While in sporadic cases a CN VIII schwannoma involves only the vestibular nerve, in NF-2, the facial nerve and entire vestibulocochlear nerve often are encased by the tumor, making resection much more problematic. Clinical Details: Clinical presentation varies, but approximately 45% of patients first are diagnosed because of symptoms resulting from vestibular schwannomas, such as hearing loss, tinnitus, balance impairment, and weakness in the facial nerve distribution. This is because CN VIII schwannomas are symptomatic at a relatively small size. Meningiomas and other schwannomas are the next most common tumors to cause initial symptoms resulting from mass effect on adjacent structures. Less frequently, skin tumors and visual loss are the initial findings. An exception exists when NF-2 is diagnosed in the pediatric population. In these patients, ocular abnormalities are the most common reason to consider the diagnosis, although some children are diagnosed through screening when a family history is present. MacCollin et al found that in 18 patients younger than 16 years, ocular abnormalities were the presenting symptom in 8, and only 1 patient presented with hearing loss. Symptoms related to spinal tumors (eg, paraplegia, pain) and skin tumors each occurred in 4 patients. While CN VIII schwannomas may begin to be symptomatic in the teens, most patients are not diagnosed until the third decade, with a mean age at diagnosis of 20 years. A proposed mild form of NF-2, the Gardner form, has been described as occurring later in life as a result of a smaller tumor burden. The disease may be exacerbated during pregnancy. Preferred Examination: Screen for NF-2 using contrast-enhanced MRI of the brain and entire spine. Contrast is important for detecting small schwannomas, particularly of the spinal nerve roots, as well as small intraparenchymal ependymomas. Newer sequences, such as high-resolution fast spin-echo (FSE) T2 cisternography and true inversion recovery, can aid evaluation of CNs. Contrast-enhanced CT or gas CT cisternography, as well as myelography, have had limited roles since the emergence of MRI, but occasionally must be used in patients in whom MRI is contraindicated. Limitations of Techniques: As a result of its excellent contrast and multiplanar capabilities, MRI optimally depicts the number, size, location, and extent of the CNS neoplasms found in NF-2. However, MRI does not detect most of the ocular abnormalities associated with the disease; these are evaluated best using funduscopy. In addition, cortical and choroid plexus calcifications may be missed on MRI, particularly when using FSE techniques. These are visualized better on CT. Gas CT cisternography, in which injected intrathecal gas is maneuvered to outline the CN VIII, is more sensitive than routine CT but is invasive and less sensitive than MRI. Myelography and CT myelography can depict the spinal schwannomas well, but since they cannot visualize intra-axial tumors, they are used only when patients cannot undergo MRI. Differential Diagnosis Meningioma , Brain Meningioma , Spine Neurofibromatosis Type I Schwannoma , Cranial Nerve Tuberous Sclerosis Other Problems to be Considered: Other phakomatoses Cowden disease (associated with multiple meningiomas, neurofibromas, and hamartomas, including Lhermitte-Duclos disease [cerebellar gangliocytoma] but not associated with vestibular schwannomas) Multiple meningiomatosis and meningioangiomatosis (considered by some to be formes frustes of NF-2; others consider them separate diseases) Basal cell nevus syndrome (Gorlin syndrome; also associated with meningiomas, astrocytomas, medulloblastomas, but not associated with schwannomas)
Neurofibromatosis type 2 issues Bilateral Acoustic neuromas: size determines the approach to management. If there is a large lesion causing displacement of the pons or obstructive hydrocephalus, it should be addressed first and as soon as possible. Permanent shunting should be given consideration. If there are bilateral large tumors, the larger tumor should be addressed first. If there is a small and a large tumor, the small tumor should be observed. Hearing preservation: hearing preservation with surgery in small tumors is at best difficult in NF2 due to the nature of the tumor which interdigitates with the nerve fibers. Radiation therapy in the form of stereotaxic radiosurgery offers some potential in this respect only for small tumors and only on short follow up. The benefits should be carefully balanced against the potential for maligancy in patients who are young. Hearing preservation goes hand in hand with the management of tumors. A conservative approach may be taken with observation of the small tumors and plan for cochlear implantation after surgery if the nerve has been anatomically preserved. In cases of bilateral nerve loss, which is the majority, consideration should be given to brainstem implantation. Meningiomas: serial MRI examinations are required to give sequential assessment of tumor growth in these situations. Intervention is required in instances of continued growth, rapid growth or evidence of intratumoral bleeding or compromise of CNS structures. NF2 patients should have serial MRI's of the entire central neuraxis on a biannual basis or annual basis. Their families should also be screened and genetic counseling should be arranged for these individuals early on in the diagnosis and treatment of their disease.
Meningiomas are the most common non-glial primary tumor of the CNS. Meningiomas are also the most common extraaxial primary tumor of the CNS. They represent 15-25% of all intracranial primary tumors. Most patients are in the 5th and 6th decades (40's - 50's). The 2x-4x female predilection is most likely due to hormone receptors for progesterone and estrogen. The tumor arises from the arachnoid cap cells and is usually a slowly growing intradural intracranial mass, with a broad base of attachment to the overlying dura. Hyperostosis of the overlying skull occurs in 15-25% of cases and may be a &quot;sympathetic reaction&quot; - or - can indicate invasion of the skull.
Clinical History: This patient is a 27-year-old female who presented from a referring hospital secondary to a mass seen on CT exam. She had been complaining of double vision and intermittent headache for five months. Findings: On MRI a large approximately 7.8 x 5.8 cm in the anterior-posterior and transverse dimension extraaxial mass is seen arising from the dura in the region of the left frontal lobe. The mass appears isointense to gray matter on T1 weighted images and isointense to slightly bright on T2 weighted images and contains multiple flow voids. There is a significant associated mass effect and buckling of the underlying cortex. There is significant mass effect on the left lateral ventricle, inferiorly on the corpus callosum, and medially there is midline shift of approximately 1.2 cm to the right. There is no significant associated edema. On cerebral angiogram, the left anterior cerebral artery is exhibiting round shift from left to right (round shift usually represents presence of an anterior/frontal mass adjacent to the anterior cerebral artery). The main blood supply to this tumor is from the anterior falcine artery arising from the left ophthalmic artery and the anterior division of the right middle meningeal artery off the external and carotid artery. On the delayed images of the cerebral angiogram in the venous phase, it is noted that the superior sagittal sinus is attenuated by the mass. This is felt to represent either effacement from the mass or direct invasion by the mass. Surgically, effacement of the superior sagittal sinus (SSS) carries a poor prognosis because the SSS cannot be sacrificed (as it can be when there is complete occlusion) without the additional risk of vascular infarctions. Diagnosis: Left falcine meningioma. Discussion: Most meningiomas arise from specialized meningothelial cells in arachnoid granulations. Multiple meningiomas occur in 1 to 9% cases and approximately 50% of these patients have neurofibromatosis 2 and therefore an abnormality on chromosome 22. Meningioma is the most common nonglial primary CNS tumor accounting for 15-20% of primary neoplasms. The World Health Organization divides meningiomas into three basic categories: meningioma (common, typical, or benign) - 95%, atypical meningioma - 5%, and anaplastic or malignant meningioma 1-2%. The peak age is between 40 and 60, with a preponderance of females in about a three to one ratio. Since meningiomas arise from arachnoid cap cells, they are typically found along dural sinuses and sutures. Most commonly, they are seen parasagittally (25%). Other locations include the convexity (20%), sphenoid ridge (15-20%), and olfactory groove (5-10%). References: Osborn A. Diagnostic Neuroradiology , Mosby; 1994:584-601. Brant WE. Fundamentals of Diagnostic Radiology, 2nd Edition . Williams & Wilkins; 1999:134-136. Schwartz RB. Neuroradiology of Brain Tumors. Neurologic Clinics 1995; 13:739-740. Return to Neuro Imaging Page Submitted by: Brian J. Sabb, D.O. C. F. Lanzieri, M.D.
On cerebral angiogram, the left anterior cerebral artery is exhibiting round shift from left to right (round shift usually represents presence of an anterior/frontal mass adjacent to the anterior cerebral artery). The main blood supply to this tumor is from the anterior falcine artery arising from the left ophthalmic artery and the anterior division of the right middle meningeal artery off the external and carotid artery. On the delayed images of the cerebral angiogram in the venous phase, it is noted that the superior sagittal sinus is attenuated by the mass. This is felt to represent either effacement from the mass or direct invasion by the mass. Surgically, effacement of the superior sagittal sinus (SSS) carries a poor prognosis because the SSS cannot be sacrificed (as it can be when there is complete occlusion) without the additional risk of vascular infarctions.
Diagnosis : Intra ventricular craniopharyngioma MRI shows a well defined, hyperintense lesion entirely within the third ventricle on both the T1 and T2 weighted images. Nodular hypointensities seen peripherally within this lesion on both T1WI and T2WI were thought to represent hemosiderin. Contrast enhancement was not well appreciated. Imaging features are characteristic for craniopharyngioma though the intra ventricular location is unusual. Diagnosis was confirmed on histopathology following near-complete excision of the lesion performed through a frontal craniotomy. Discussion : Craniopharyngiomas are relatively common childhood intra cranial tumors which account for about 6-9% of all childhood tumors with a peak incidence in the second decade of life and a second peak in the fifth to sixth decade of life.They are known to arise from squamous epithelial rests which are thought to be remnants of Ratke's pouch, located in the pars tuberalis along the pituitary stalk. Therefore, these tumors grow in the supra sellar or less frequently in the intra sellar region, but are also found in locations like the sphenoid, tuberculum sella, nasopharynx, and the third ventricle. Further reading : Jeffrey Rush, John Kusske, Don De Feo, Henry Fribam. Inraventricular craniopharyngioma. Neurology 1975; 25 : 1094-6. M Banna. Review article. Craniopharyngioma - based on 160 cases. BJR 1976; 49:206-223. Contribution : Dr. Prashant Shetty, Dr Manu Shroff, Dr Harsh Merchant
Clinical History: Evaluate for tumor patient with signs and symptoms of intracranial tumor. Findings: There is a 3.8 x 2.8 x 3.5 cm. lesion identified in the craniocaudal, transverse, and AP dimension respectfully within the suprasellar region in an extraaxial location. This causes splaying of the cerebral peduncles. This lesion demonstrates increased signal on the T1 weighted images, Turbo SPIN T2 images, and STIR images. This is compatible with proteinaceous fluid. There is enlargement of the lateral ventricles compatible with hydrocephalus. The third ventricle is seen to be compressed. The fourth ventricle is of normal contour. Given the patient's age and location and signal intensity, this finding is most compatible with a suprasellar craniopharyngioma, this correlated with pathology from a biopsy specimen. Diagnosis: Craniopharyngioma. Discussion: Craniopharyngiomas arise from squamous epithelial rest along Rathke's cleft. This are typically well delineated cystic masses. The contents of the cyst can vary from fluid material to a proteinaceous material. This explains the variable signal that is seen on MRI. Craniopharyngiomas account for 2 to 5% of all intracranial masses. These lesions occur most frequently in patients under the age of 20 with 40% of these tumors occurring in children between the ages of eight and 12 years of age. Craniopharyngiomas account for half of all suprasellar masses in this age group. There is no gender bias. Craniopharyngioma are mainly confined to the sellar region. More than 75% of these tumors are completely suprasellar or have a large suprasellar mass with smaller intrasellar component. 20% of these lesions are found as a primary intrasellar process. Headache is the most common symptom, although endocrine deficiency, visual disturbance, and interruption of CSF flow are often seen. As mentioned previously, the MR findings are variable due to the variable nature of the contents of these cysts. Plain films may demonstrate eggshell calcification or heterogenous calcification in the suprasellar region. CT scan may demonstrate an isodense to cystic lesion in the suprasellar region with rim calcifications. Rim calcification is seen quite commonly (80 to 90%) when these lesions appear in childhood, as seen on the postoperative head CT. These lesions may show rim enhancement, or if the lesion is partially cystic, the sellar portion will demonstrate enhancement.
Diagnosis: Craniopharyngioma. Discussion: Craniopharyngiomas arise from squamous epithelial rest along Rathke's cleft. This are typically well delineated cystic masses. The contents of the cyst can vary from fluid material to a proteinaceous material. This explains the variable signal that is seen on MRI. Craniopharyngiomas account for 2 to 5% of all intracranial masses. These lesions occur most frequently in patients under the age of 20 with 40% of these tumors occurring in children between the ages of eight and 12 years of age. Craniopharyngiomas account for half of all suprasellar masses in this age group. There is no gender bias. Craniopharyngioma are mainly confined to the sellar region. More than 75% of these tumors are completely suprasellar or have a large suprasellar mass with smaller intrasellar component. 20% of these lesions are found as a primary intrasellar process. Headache is the most common symptom, although endocrine deficiency, visual disturbance, and interruption of CSF flow are often seen. As mentioned previously, the MR findings are variable due to the variable nature of the contents of these cysts. Plain films may demonstrate eggshell calcification or heterogenous calcification in the suprasellar region. CT scan may demonstrate an isodense to cystic lesion in the suprasellar region with rim calcifications. Rim calcification is seen quite commonly (80 to 90%) when these lesions appear in childhood, as seen on the postoperative head CT. These lesions may show rim enhancement, or if the lesion is partially cystic, the sellar portion will demonstrate enhancement. References: Woodruff WW. Fundamentals of Neuroimaging . W.B. Saunders, Co., Philadelphia; 1993:352-356. Osborn AG. Diagnostic Neuroradiology . Mosby, St. Louis; 1994(15)654-657.
Clinical History: 51-year-old male with unspecified neurological symptoms four months status post head trauma. Findings: Image #1 is an axial T2 WI of the head demonstrating a lesion with homogeneously increased signal intensity within the sella turcica. Image # 2 is a coronal T1 WI of the sella region. In this image, the lesion is decreased in signal intensity at the anterior aspect of the sella. Image #3 is a coronal T1 WI post gadolinium of the same region as image #2, in which the lesion does not enhance. The lesion does not appear to be a part of the adeno or neurohypophysis. Diagnosis: Rathke's cleft cyst. Discussion: Rathke's cleft cysts (RCC) are non-neoplastic and are derived from the embryonic remnants of Rathke's pouch. The majority of RCC are asymptomatic and are incidental findings in 10-23% of autopsies. The most common clinical symptoms are those due to mass effect and include visual deficits, pituitary dysfunction, as well as headaches. The MRI appearance of symptomatic RCC is variable, although most can be divided into two groups. Both are high signal on T2 and WI. However, the first group is low on T1 WI and typically has a more insidious onset, presents at a later age, usually with compressive symptoms of the optic tract. The second group is iso-high signal intensity on T1 and WI and presents at an earlier age, usually with headache. The difference in T1 WI is thought to be due to high protein content of the cystic contents or hemorrhage. Less likely etiologies would include arachnoid, epidermoid, or dermoid cysts, pituitary adenoma, or craniopharyngioma. References: Mukherjee N, et al. Clinical, Radiological and Pathological Features of patients with Rathke's Cleft Cyst: Tumors That May Recur. The Journal of Clinical Endocrinology and Metabolism. 1997;82(7):2357-2362. Saeki N, et al. MRI Findings and Clinical Manifestations in Rathke's Cleft Cyst. Acta Neurochirurgica. 1999;141:1055-1061. Shin JL. Cystic Lesions of the Pituitary: Clincopathological Features Distinguishing Craniopharyngioma, Rathke's Cleft Cyst, and Arachnoid Cyst. 1999; 84(21):3972-3982. Return to Neuro Imaging Page Submitted by: Robert Lee, M.D. Alel Schoenberger C. F. Lanzieri, M.D.
MRI pituitary adenoma CC: Orthostatic lightheadedness HX: This 76 y/o male complained of several months of generalized weakness and malaise, and a two week history of progressively worsening orthostatic dizziness. The dizziness worsened when moving into upright positions. In addition, he complained of intermittent throbbing holocranial headaches, which did not worsen with positional change, for the past several weeks. He had lost 40 pounds over the past year and denied any recent fever, SOB, cough, vomiting, diarrhea, hemoptysis, melena, hematochezia, bright red blood per rectum, polyuria, night sweats, visual changes, or syncopal episodes. He had a 100+ pack-year history of tobacco use and continued to smoke 1 to 2 packs per day. He has a history of sinusitis. EXAM: BP 98/80 mmHg and pulse 64 BPM (supine); BP 70/palpable mmHG and pulse 84BPM(standing). RR 12, Afebrile. Appeared fatigued. CN: unremarkable. Motor and Sensory exam: unremarkable. Coord: Slowed but otherwise unremarkable movements. Reflexes: 2/2 and symmetric throughout all 4 extremities. Plantar responses were flexor, bilaterally. The rest of the neurologic and general physical exam was unremarkable. LAB: Na 121 meq/L, K 4.2 meq/L, Cl 90 meq/L, CO2 20meq/L, BUN 12mg/DL, CR 1.0mg/DL, Glucose 99mg/DL, ESR 30mm/hr, CBC WNL with nl WBC differential, Urinalysis: SG 1.016 and otherwise WNL, TSH 2.8 IU/ML, FT4 0.9ng/DL, Urine Osmolality 246 MOSM/Kg (low), Urine Na 35 meq/L, COURSE: The patient was initially hydrated with IV normal saline and his orthostatic hypotension resolved, but returned within 24-48hrs. Further laboratory studies revealed: Aldosterone (serum)<2ng/DL (low), 30 minute Cortrosyn Stimulation test: pre 6.9ug/DL(borderline low), post 18.5ug/DL (normal stimulation rise), Prolactin 15.5ng/ML(no baseline given), FSH and LH were within normal limits for males. Testosterone 33ng/DL(wnl). Sinus XR series (done for history of headache) showed an abnormal sellar region with enlarged sella tursica and destruction of the posterior clinoids. There was also an abnormal calcification seen in the middle of the sellar region. A left maxillary sinus opacity with air-fluid level was seen. Goldman visual field testing was unremarkable. Brain CT and MRI revealed suprasellar mass most consistent with pituitary adenoma. He was treated with Fludrocortisone 0.05 mg BID and within 24hrs, despite discontinuation of IV fluids, remained hemodynamically stable and free of symptoms of orthostatic hypotension. His presumed pituitary adenoma continues to be managed with Fludrocortisone as of this writing(1/1997), though he has developed dementia felt secondary to cerebrovascular disease (stroke/TIA).
Case #20: Sellar HCT: Pituitary mass CC: HA and vision loss HX: 71 y/o RHM developed a cataclysmic headache on 11/5/92 associated with a violent sneeze. The headache lasted 3-4 days. On 11/7/92, he had acute pain and loss of vision in the left eye. Over the following day his left pupil enlarged and his left upper eyelid began to droop. He was seen locally and a brain CT showed no sign of bleeding, but a tortuous left middle cerebral artery was visualized. The patient was transferred to UIHC 11/12/92. FHX: HTN, Stroke, Coronary artery disease, melanoma. SHX: Quit smoking 15 years ago. MEDS: Lanoxin, Capoten, Lasix, KCL, ASA, Voltaren, Alupent MDI PMH: CHF, Atrial Fibrillation, Obesity, Anemia, Duodenal Ulcer, Spinal AVM resection 1986 with residual T9 sensory level, hyperreflexia and bilateral babinski signs, COPD. EXAM: 35.5C, BP 140/91, P86, RR20. Alert and oriented to person, place, and time. CN: No light perception OS, Pupils: 3/7 decreasing to 2/7 on exposure to light (i.e., fixed/dilated pupil OS). Upon neutral gaze the left eye deviated laterally and inferiorly. There was complete ptosis OS. On downward gaze their was intorsion OS. The left eye could not move superiorly, medially or effectively downward, but could move laterally. EOM were full OD. The rest of the CN exam was unremarkable. Motor, Coordination, Station and Gait testing were unremarkable. Sensory exam revealed decreased pinprick and light touch below T9(old). Muscle stretch reflexes were increased (3+/3+) in both lower extremities and there were bilateral babinski signs (old). The upper extremity reflexes were symmetrical (2/2). Cardiovascular exam revealed an irregularly irregular rhythm and lung sounds were coarse bilaterally. The rest of the general exam was unremarkable. LAB: CBC, PT/PTT, General Screen were unremarkable except for a BUN 21mg/DL. CSF: protein 88mg/DL, glucose 58mg/DL, RBC 2800/mm3, WBC 1/mm3. ANA, RF, TSH, FT4 were WNL. Impression: CN3 palsy and loss of vision. Differential diagnosis: temporal arteritis, aneurysm, intracranial mass. COURSE: The outside Brain CT revealed a tortuous left MCA. A four-vessel cerebral angiogram revealed a dolichoectatic basilar artery and tortuous LICA. There was no evidence of aneursym. Transesophageal Echocardiogram revealed atrial enlargement only. Neuroopthalmologic evaluation revealed: Loss of color vision and visual acuity OS, RAPD OS, bilateral optic disk pallor (OS > OD), CN3 palsy and bilateral temporal field loss, OS >> OD . ESR, CRP, MRI were recommended to rule out temporal arteritis and intracranial mass. ESR 29mm/Hr, CRP 4.3mg/DL(high) , The patient was placed on prednisone. Temporal artery biopsy showed no evidence of vasculitis. MRI scan could not be obtained due to patient weight. Sellar CT was done instead: coronal sections revealed sellar enlargement and upward bowing of the diaphragm sella suggesting a pituitary mass. In retrospect sellar enlargement could be seen on the angiogram X-rays. Differential consideration was given to cystic pituitary adenoma, noncalcified craniopharyngioma, or Rathke's cleft cyst with solid component. The patient refused surgery. He was seen in Neuroopthalmology Clinic 2/18/93 and was found to have mild recovery of vision OS and improved visual fields. Aberrant reinnervation of the 3rd nerve was noted as there was constriction of the pupil (OS) on adduction, downgaze and upgaze. The upper eyelid, OS, elevated on adduction and down gaze, OS. EOM movements were otherwise full and there was no evidence of ptosis. In retrospect he was felt to have suffered pituitary apoplexy in 11/92.
Case #18: MRI brain and brainstem, 10/30/92: Pituitary adenoma impinging on optic chiasm. CC: Superior bitemporal incongruous hemianopia discovered by local optometrist on routine exam. HX: This 47 y/o RHM presented to his local optometrist in 9/92 for routine evaluation. He had no complaint of visual loss, HA, nausea/vomiting, lymphadenopathy, weight change, galactorrhea, impotence, temperature intolerance, hot or cold flashes, or personality change. Visual field testing revealed a superior bitemporal incongruous hemianopia and he was referred to NeuroOpthalmology at UIHC. EXAM: Vital signs: unremarkable. Visual acuity with correction: 20/40-1 OD and 20/40 OS. No RAPD, Confrontational visual fields were full to finger counting and there was no red desaturation. EOM were full OU. No nystagmus. Goldmann visual fields revealed a superior bitemporal defect. Slit lamp exam was unremarkable. Intraocular pressures were normal (OD 11, and OS 11). Optic discs were sharp and pink bilaterally with cup:disc ratio: 0.5OD and 0.4OS. The rest of the neurological and general physical exam was unremarkable. LABS: General Screen, CBC, TSH, FT4, PRL were unremarkable. MRI Brain and Brainstem with & without contrast, 10/30/92 revealed a 2cm x 2cm x 3cm mass in the pituitary fossa. The mass has low signal intensity on T1 weighted images. There is enhancement of the periphery of the mass on the post-gadolinium images. The mass causes marked superior displacement of the optic chiasm; this most likely accounts for the bitemporal visual field defect. The findings were felt to be most consistent with a pituitary adenoma. COURSE: The patient underwent uncomplicated transphenoidal resection of the pituitary lesion on 11/18/92. Pathological analysis was consistent with pituitary adenoma. NeuroOpthalmological follow-up exam on 4/2/93 showed resolution of the visual field defect. Visual acuity improved to 20/20 OD and 20/16 OS.
Brain metastasis is suspected when a patient with a lung cancer has headaches or disturbances of brain function such as changes in thinking, speech, vision, balance and muscular activity, among others. When a brain metastasis is suspected, a computerized tomogram CT scan or MRI scan is indicated. If metastases are found, neurologic or neurosurgical consultation is in order and corticosteroids may be required to avoid complications caused by swelling of the brain. Brain metastasis is usually treated with radiation therapy. Recent advances in this area include the ability of radiation therapists to more accurately target brain metastases using a new technique called stereotactic radio-surgery. In some carefully selected cases, the tumor can be surgically removed by a neurosurgeon and the patient cured.
Vol 13, No 7 (July 1999) Management of Brain Metastases Patrick Y. Wen, MD Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts Jay S. Loeffler, MD Northeast Proton Therapy Center, Massachusetts General Hospital and Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts Abstract Introduction Method of Spread and Distribution Clinical Manifestations Diagnosis Management Goals Symptomatic Therapy Definitive Treatment Prognosis Summary References Reviewers' Comments: Rifaat M. Bashir , MD , University of Nebraska Medical Center, Omaha, Nebraska William R. Shapiro, MD , Barrow Neurological Institute, Phoenix, Arizona Brain metastases are the most common type of brain tumor in adults and are an increasingly important cause of morbidity and mortality in cancer patients. In recent years, important advances have been made in the diagnosis and management of brain metastases. These advances include the widespread use of magnetic resonance imaging (MRI), enabling small metastases to be detected; the introduction of stereotactic radiosurgery; and the performance of studies that have clarified the role of surgery and postoperative radiation therapy for single brain metastases. As a result, most patients receive effective palliation, and the majority do not die from their brain metastases. However, further studies are needed to define the optimal role of conventional treatments and to develop more effective novel therapies. [ONCOLOGY 13(7):941-961, 1999] Introduction Brain metastases are a common complication in cancer patients and an important cause of morbidity and mortality. They develop in approximately 10% to 30% of adults and 6% to 10% of children with cancer.[1-6] Each year in the United States, an estimated 97,800 to 170,000 new cases of brain metastasis are diagnosed.[1,2,6] This number may be increasing as a result of the increased ability of magnetic resonance imaging (MRI) to detect small metastases and improvements in systemic therapy, leading to longer patient survival.[1,6-9] In adults, the primary tumors most often responsible for brain metastases are lung cancer (50%), breast cancer (15% to 20%), unknown primary tumor (10% to 15%), melanoma (10%), and colon cancer (5%).[1-3,10] In children, the most common sources of brain metastases are sarcomas, neuroblastoma, and germ cell tumors.[1,4,11] Studies using MRI suggest that the proportion of single metastases is lower than was previously believed, accounting for only one-third to one-fourth of patients with cerebral metastases.[7,12] Metastases from breast, colon, and renal cell carcinomas are often single, while melanoma and lung cancer have a greater tendency to produce multiple metastases.[1,13] Method of Spread and Distribution The most common mechanism of metastasis to the brain is by hematogenous spread. These metastases are usually located directly beneath the junction of the gray and white matter. Brain metastases tend to occur at this site because the blood vessels decrease in size at this point and act as a trap for clumps of tumor cells. Brain metastases also tend to be more common at the terminal “watershed areas” of arterial circulation.[1,13] The distribution of brain metastases roughly follows the relative weight of (and blood flow to) each area. Approximately 80% of brain metastases are located in the cerebral hemispheres, 15% in the cerebellum, and 5% in the brainstem. For unclear reasons, pelvic (prostate and uterus) and gastrointestinal tumors have a predilection to metastasize to the posterior fossa. Clinical Manifestations It is estimated that more than two-thirds of patients with cerebral metastases experience neurologic symptoms during the course of their illness. The clinical features of brain metastases are extremely variable, and the presence of brain metastases should be suspected in any cancer patient who develops new neurologic symptoms. The majority of patients with brain metastases present with progressive neurologic dysfunction resulting from a gradually expanding tumor mass and the associated edema, or, rarely, from the development of obstructive hydrocephalus. Approximately 10% to 20% of patients present acutely with seizures, while another 5% to 10% present acutely as a result of strokes caused by embolization of tumor cells, invasion or compression of an artery by tumor, or hemorrhage into a metastasis.[8,14,15] Melanoma, choriocarcinoma, and thyroid and renal carcinomas have a particular propensity to bleed. The clinical presentation of brain metastases is similar to that of other brain tumors and includes headaches, focal neurologic dysfunction, cognitive dysfunction, and seizures. Headaches occur in approximately 40% to 50% of patients with brain metastases. These are usually dull, nonthrobbing, and often indistinguishable from tension headaches. The headaches are usually on the same side as the tumor, although they can be diffuse. Headaches characteristic of increased intracranial pressure, such as early morning headaches, or headaches exacerbated by coughing, bending, and straining, are present in less than half of patients with brain metastases. The headaches may be associated with nausea, vomiting, and transient visual obscurations. Patients with multiple metastases and posterior fossa metastases have a higher frequency of headaches. (Papilledema is observed in fewer than 10% of patients at the time of presentation.) Focal neurologic dysfunction is the presenting symptom in 20% to 40% of patients. Hemiparesis is the most common complaint, but the precise symptom varies depending on the location of the metastases. Cognitive dysfunction, including memory problems and mood or personality changes, are the presenting symptoms in one-third of patients, while seizures are the presenting symptom in another 10% to 20%.[17-20] Diagnosis Brain metastases must be distinguished from primary brain tumors, abscesses, demyelination, cerebral infarctions or hemorrhages, progressive multifocal leukoencephalopathy, and the effects of treatment, including radiation necrosis. In a study by Patchell et al, 11% of patients who were initially felt to have a single brain metastasis eventually were found to have a different diagnosis after the lesion was biopsied. Half of the nonmetastatic lesions were primary brain tumors, while the other half were infections. The false-positive rate for diagnosis of multiple metastases undoubtedly is significantly lower than the 11% rate for single metastases. Nonetheless, in any patient in whom the diagnosis of brain metastases is in doubt, a biopsy should be performed since this is the only reliable method of establishing the diagnosis. Breast cancer patients with a single dural-based lesion pose a particular diagnostic dilemma. Since the incidence of meningiomas is increased in patients with breast cancer, it is important to differentiate a dural-based metastasis from a meningioma.[22,23] Frequently, imaging studies are inconclusive, and a biopsy or surgical resection of the lesion is needed. In addition to diagnosing brain metastases, it is also important to differentiate patients with a single or solitary metastasis from those with multiple brain metastases since their subsequent treatment differs. The term “single brain metastasis” refers to a single cerebral lesion, with no implication made regarding the extent of extracranial disease. “Solitary brain metastasis” describes the relatively rare occurrence of a single brain metastasis that is the only known site of metastatic cancer in the body. Although computed tomographic (CT) scans detect the majority of brain metastases, the best diagnostic test for brain metastases is contrast-enhanced MRI. [12,24,25] This test is more sensitive than enhanced CT scanning or nonenhanced MRI in detecting lesions in patients suspected of having cerebral metastases, and in differentiating these metastases from other central nervous system (CNS) lesions.[ 24,25] Radiographic features that help differentiate brain metastases from other CNS lesions include the presence of multiple lesions (which helps distinguish metastases from gliomas or other primary tumors), localization of the lesion at the gray-white matter junction, more circumscribed margins, and relatively large amounts of vasogenic edema compared to the size of the lesion. In the majority (80%) of patients, brain metastases develop after the diagnosis of systemic cancer (metachronous presentation).[1,2] However, in some patients, brain metastases may be diagnosed before the primary tumor is found (precocious presentation) or at the same time as the primary is detected (synchronous presentation). For patients who present with brain metastases without a known primary tumor, the lung should be the focus of the evaluation. Over 60% of these patients will have a lung primary or pulmonary metastases from a primary tumor located elsewhere.[1,26,27] If the chest radiograph is nondiagnostic, a chest CT scan should be performed, as this significantly increases the likelihood of detecting a lung tumor. These patients also should have a CT scan of the abdomen and pelvis and a bone scan to determine the extent of metastatic disease. Breast cancer is an uncommon cause of brain metastases without a known primary tumor, possibly due to its earlier detection on physical examination, and its tendency to produce brain metastases in the setting of widely disseminated disease.  Management Goals The management of patients with brain metastases can be divided into symptomatic and definitive therapy. Symptomatic therapy includes the use of corticosteroids for the treatment of peritumoral edema, anticonvulsants for control of seizures, and anticoagulants or inferior vena cava filters for the management of venous thromboembolic disease. Definitive therapy includes treatments directed at eradicating the tumor itself, such as surgery, radiotherapy, and chemotherapy. Symptomatic Therapy Corticosteroids Corticosteroids were first used for treating peritumoral edema by Kofman et al in 1957 in patients with breast cancer. Galicich et al introduced the use of dexamethasone in 1961, and this has remained the standard treatment for peritumoral edema ever since. Corticosteroids produce their antiedema effect by reducing the permeability of tumor capillaries,  and are indicated in any patient with symptomatic edema. Most patients are started on dexamethasone, which, compared with other corticosteroids, has relatively little mineralocorticoid activity, thus reducing the potential for fluid retention. In addition, dexamethasone may be associated with a lower risk of infection and cognitive impairment. Dexamethasone therapy is usually started as a 10-mg loading dose, followed by 4 mg four times a day; however, there is some evidence that lower doses may be as effective. Although most patients improve symptomatically within 24 to 72 hours, neuroimaging studies may not show a decrease in the amount of edema for up to 1 week. In general, headaches tend to respond better than do focal deficits. If 16 mg of dexamethasone is insufficient, the dose may be increased up to 100 mg/d. Steroid dose is usually tapered following irradiation, although the tapering process may begin earlier in patients with minimal peritumoral edema. Adverse Effects—Despite their usefulness, corticosteroids are associated with a large number of well-known side effects, including myopathy, weight gain, fluid retention, hyperglycemia, insomnia, gastritis, acne, and immunosuppression. The frequency of these complications can be reduced by using the lowest possible dose. There is increasing evidence that brain tumor patients who receive corticosteroids are at increased risk of developing Pneumocystis carinii pneumonia. This complication can be prevented by treating patients who are on prolonged courses of a corticosteroid, especially those over the age of 50 years, with trimethoprim/sulfamethoxazole prophylaxis. Anticonvulsants As mentioned previously, seizures are the presenting symptom in approximately 10% to 20% of patients with brain metastases, and occur at some stage of the illness in another 10% to 20% of patients.[17-20] Patients with brain metastases who present with seizures should be treated with standard anticonvulsants. In order to minimize toxicity, the lowest effective anticonvulsant dose should be used and polytherapy should be avoided whenever possible. Electroencephalography may be useful if the diagnosis of seizures is in doubt but is not routinely needed for patients who give a clear history of seizures or, conversely, do not have symptoms suggestive of seizures. Adverse Effects and Drug Interactions—In addition to the usual complications of anticonvulsants, brain tumor patients experience an increased incidence of particular side effects, especially drug rashes. Approximately 20% of brain tumor patients treated with phenytoin and undergoing cranial irradiation develop a morbilliform rash and a small percentage develop Stevens-Johnson syndrome.[35,36] Stevens-Johnson syndrome also has been described in brain tumor patients receiving carbamazepine, while patients receiving phenobarbital have an increased incidence of shoulder-hand syndrome. In addition to producing adverse effects, anticonvulsants also have clinically significant interactions with other drugs commonly used in patients with brain metastases. Phenytoin induces the hepatic metabolism of dexamethasone and significantly reduces its half-life and bioavailability. Conversely, dexamethasone may also reduce phenytoin levels. A number of chemotherapeutic agents commonly used in cancer patients interact with phenytoin, causing serum drug levels to fall and potentially leading to breakthrough seizures. Also, hepatic enzyme–inducing anticonvulsants, such as phenobarbital and phenytoin, may interfere with chemotherapeutic agents, such as paclitaxel (Taxol). Role in Patients With Supratentorial Metastases—Because the risk of seizures in patients with infratentorial metastases is very low, anticonvulsant therapy usually is not indicated. The role of anticonconvulsant therapy in patients with supratentorial brain metastases who have not had a seizure is controversial. Cohen et al retrospectively reviewed 160 patients with brain metastases who had not suffered a seizure. They found that patients receiving prophylactic phenytoin had the same frequency of late seizures (10%) as did patients receiving no antiseizure prophylaxis. Glantz et al conducted a prospective, placebo-controlled, randomized study evaluating the efficacy of valproic acid in protecting 74 patients with newly diagnosed brain metastases from seizures. There was no significant difference in the incidence of seizures between patients receiving valproic acid (35%) or placebo (24%), suggesting that prophylactic anticonvulsants were not effective in these patients. Weaver et al conducted a prospective, randomized study of prophylactic anticonvulsants in 100 brain tumor patients who had not had seizures, including 60 with metastases. Overall, 26% of patients had seizures during the study. There was no difference in the seizure rate between patients who did and did not receive anticonvulsants. Recently, Glantz et al performed a meta-analysis of the randomized clinical trials addressing this issue. They concluded that there is no statistical evidence showing a significant benefit of prophylactic anticonvulsants. Recommendations—Because of the increased incidence of allergic reactions in patients with brain metastases receiving anticonvulsant therapy, and the lack of clear evidence that anticonvulsant therapy reduces the incidence of seizures, routine anticonvulsant therapy is probably unnecessary in patients with brain metastases who have not experienced a seizure. Possible exceptions to this are patients with brain metastases in areas of high epileptogenicity (eg, the motor cortex), patients with multiple metastases from melanoma,  and patients with both brain metastases and leptomeningeal metastases. These patients have a higher incidence of seizures and may benefit from prophylactic anticonvulsant therapy. Treatment of Venous Thromboembolic Disease Venous thromboembolic disease is common in patients with brain metastases, occurring in approximately 20% of patients. The optimal therapy is unknown. These patients are often perceived to be at increased risk of intracranial hemorrhage when treated with anticoagulants because of the vascularity of the tumors and anecdotal case reports of hemorrhage. As a result, the majority of brain metastases patients with venous thromboembolic disease are managed with inferior vena cava filtration devices rather than anticoagulation. However, Levin et al found that complications occur in up to 60% of brain tumor patients with venous thromboembolic disease who are treated with inferior vena cava filters. Moreover, several retrospective studies have suggested that the risk of intracranial hemorrhage may not be significantly increased in patients with primary brain tumors who are anticoagulated after the immediate postoperative period. More recently, Schiff and DeAngelis reviewed the Memorial Sloan-Kettering experience with anticoagulation in patients with brain metastases who developed venous thromboembolic disease. Of the 42 patients who received anticoagulation at some stage of their treatment, only 3 (7%) experienced cerebral hemorrhage, 2 in the setting of overanticoagulation. These studies suggest that anticoagulation may be more effective than inferior vena cava filter placement, and is acceptably safe when the prothrombin time is maintained within the normal range, especially in patients with brain metastases that generally do not hemorrhage, such as breast cancer. Definitive Treatment The definitive management of brain metastases is directed at relieving neurologic symptoms and achieving long-term tumor control. The therapeutic modalities available include surgery, radiotherapy, radiosurgery, chemotherapy, and hormonal therapy. The optimal combination of therapies for each patient depends on a careful evaluation of numerous factors, including the location, size, and number of brain metastases; the patient’s age, general condition, and neurologic status; and the extent of the systemic cancer, as well as its response to past therapy and its potential response to future treatments. Surgery The goals of surgery in patients with brain metastases are: to provide immediate relief of symptoms resulting from the mass effect of the tumor; to establish a histologic diagnosis; and to improve local control of the tumor. Recent advances in neuroanesthesia and neurosurgery, including the use of computer-assisted stereotaxy, intraoperative functional mapping, intraoperative ultrasound, and functional and intraoperative MRI, have significantly improved the safety of surgical resection of brain metastases.[7,49,50] For patients who are candidates for surgery, the most important factor to consider is the extent of extracranial disease ( Figure 1a , Figure 1b , Figure 1c and Figure 1d ). Patients with extensive systemic disease generally have a very limited prognosis and only rarely benefit from surgery. Other important factors influencing the decision concerning surgery include the presence of single or multiple metastases, the location of the tumor, the neurologic status of the patient, and the interval between diagnosis of the primary neoplasm and the brain metastasis.[7,51-53] Single Brain Metastasis—Until relatively recently, the optimal therapy for patients with a single brain metastasis was controversial. A number of uncontrolled, retrospective studies had suggested that patients with a single brain metastasis who underwent surgical resection in addition to radiotherapy generally had better outcomes than patients who were treated with radiotherapy alone. However, these studies were limited by the inevitable selection bias resulting from the inclusion in surg-ical series of patients in better condition.[10,51-57] Three randomized, prospective studies have now evaluated the role of surgery as an adjunct to whole-brain radiation therapy (WBRT) in patients who have a single brain metastasis.[21,58-60] Patchell et al were the first to address this issue in a prospective, randomized study. They randomly assigned 54 patients with or without active systemic cancer and a single brain metastasis to receive either biopsy of the metastasis followed by whole-brain radiation (36 Gy in 12 fractions) or surgical resection followed by radiotherapy. Of the 54 original patients, 6 (11%) did not have a metastasis and were excluded from the study, leaving 48 patients. The patients treated with surgery and whole-brain radiation had fewer local recurrences than did those who received whole-brain radiation alone (20% vs 52%), as well as improved survival (40 vs 15 weeks) and a better quality of life, as measured by Karnofsky performance status. The median time to recurrence for patients receiving surgery and radiotherapy was > 59 weeks, as compared with 21 weeks for patients receiving whole-brain radiation alone. Multivariate analysis showed that the factors that correlated significantly with increased survival were surgical treatment of the metastasis, the absence of extracranial disease, longer time to the development of the brain metastasis, and younger age. A second, prospective, randomized trial evaluating the role of surgery in patients with a single brain metastasis was conducted by Vecht et al.[58,59] In this study, 63 patients with a single brain metastasis (documented by CT scanning) were randomized to receive either surgery and whole-brain radiation or whole-brain radiation alone. The radiotherapy dose was an unconventional scheme of two fractions per day of 2 Gy each, for a total of 40 Gy given over 2 weeks. Unlike the study of Patchell et al, patients in this study who were randomized to radiotherapy alone did not undergo a stereotactic biopsy to confirm the diagnosis of metastasis, and MRI was not performed to exclude multiple small metastases that may have been missed by CT imaging. The overall survival of patients treated with surgery and radiotherapy was significantly longer than that of patients treated with radiotherapy alone (10 vs 6 months; P = .04). In addition, combined-modality treatment also resulted in significantly increased functionally independent survival (7.5 vs 3.5 months; P = .06). The greatest benefit of surgery plus whole-brain radiation was seen in patients with stable extracranial disease (median survival, 12 vs 7 months; median functionally independent survival, 9 vs 4 months). Patients with active extracranial disease had a median survival of only 5 months and a functionally independent survival of 2.5 months and did not appear to benefit from the addition of surgery. This is consistent with the concept that the extent of systemic disease largely determines patient survival and overcomes any potential advantage that the addition of surgery may provide in controlling the brain metastasis.[6,7] Patients over 60 years old had decreased survival rates compared to younger patients (hazard ratio of dying, 2.74; P = .001). This finding is consistent with the general importance of age as an adverse prognostic factor in patients with brain tumors. In contrast to these two studies, a more recent, multicenter, randomized study conducted by Mintz et al failed to detect a difference in survival or quality of life between patients who underwent surgery plus radiotherapy and those who had radiotherapy alone. In this study, the 43 patients randomized to radiotherapy alone had a median survival of 6.3 months, as compared with a median survival of only 5.6 months in the 41 patients randomized to surgery plus radiotherapy. The failure of this study to demonstrate that the addition of surgery to radiotherapy improved patient outcome may be due to the fact that it included patients with a lower baseline median Karnofsky performance score and a higher proportion of patients with extracranial disease.[60,61] A fourth study, conducted by the Radiation Therapy Oncology Group (RTOG) and the Southwest Oncology Group (SWOG), was initially intended to be a randomized comparison of surgery plus radiotherapy vs radiotherapy alone. However, because of poor patient accrual, the study’s design was changed to a prospective physician preference trial. Ultimately, 80 of the 97 registered patients were evaluable. After correction for other prognostic factors, patients treated with surgery and radiotherapy showed greater neurologic improvement than did patients receiving whole-brain radiation alone (79% vs 59%), as well as decreased recurrence (22% vs 45%) and improved survival. Overall, these studies provide support for the use of surgery in addition to whole-brain radiation in patients with a single brain metastasis and stable extracranial disease. Multiple Brain Metastases—The role of surgery in patients with multiple brain metastases is usually limited to: resection of a large, symptomatic, or life-threatening lesion; obtaining tissue for diagnosis in patients without a known primary tumor; or differentiating a brain metastasis from other cerebral lesions such as a meningioma. However, as surgical techniques have improved, the feasibility of resecting multiple lesions has increased. In one study, Bindal et al evaluated the efficacy of surgery in 56 patients with multiple brain metastases. These patients were divided into those who had one or more lesions remaining after surgery (group A; N = 30) and those who had all lesions removed (group B; N = 26). Also, the patients in group B were matched (by tumor type, presence or absence of extracranial disease, and time from diagnosis of primary tumor to diagnosis of brain metastases) to patients undergoing surgery for a single metastasis (group C; N = 26). The median survival durations for patients in groups A, B, and C were 6, 14, and 14 months, respectively. These results suggest that if all lesions can be removed surgically in patients with multiple brain metastases, the outcome is significantly improved, and is comparable to the outcome of patients who undergo surgery for a single lesion. However, in contrast to this study, Hazuka et al found that surgery was of little benefit in patients with multiple brain metastases. They described a series of 28 patients with a single metastasis and 18 patients with multiple metastases. The patients with multiple metastases who underwent surgery and radiation therapy had a median survival of only 5 months, compared to a 12-month median survival for patients with single brain metastases. In the studies of both Bindal et al and Hazuka et al, surgical morbidity and mortality for patients with multiple brain metastases were low and were comparable to morbidity and mortality reported for patients with a single metastasis undergoing surgery. However, the conflicting results of the two studies make it difficult to draw firm conclusions regarding the value of surgical resection in patients who have multiple brain metastases. Recurrent Metastatic Brain Tumors—Surgery may have a role in patients who develop recurrent disease after standard treatment for brain metastases, especially in those with a single, symptomatic lesion. In an early study, Sundaresan et al reported the results of reoperation in 21 patients with brain metastasis. Two-thirds of the patients experienced neurologic improvement after the second surgery; this improvement lasted a median of 6 months. No patient died, and only one patient experienced a worsening of neurologic deficits after surgery. Bindal et al reviewed 48 patients who underwent reoperation for recurrent brain metastasis at M. D. Anderson Cancer Center. The median interval between the first craniotomy and the diagnosis of recurrence was 6.7 months, and the median survival time after reoperation was 11.5 months. Following surgery, symptoms improved in 75% of patients and deteriorated in 10.4% of patients. There was no operative mortality. Multivariate analysis revealed that survival was negatively affected by the presence of systemic disease (P = .008), Karnofsky performance status < 70 (P = .008), time to recurrence < 4 months (P = .008), age > 40 years (P = .051), and primary tumor type of breast or melanoma (P = .028). Arbit et al reported on 109 patients with recurrent brain metastases from non-small-cell lung cancer who were treated at Memorial Sloan-Kettering Cancer Center. Of these patients, 32 (30%) underwent a reoperation. The median interval between the first and second operation was 5 months. The median survival duration following the second operation was 10 months. Patients who underwent reoperation survived significantly longer than the 77 patients who did not undergo a second procedure (median survival from the time of the first operation, 15 vs 10 months; P < .001). These results provide support for surgical resection of recurrent brain metatases in selected patients with symptomatic lesions. Factors that should be considered when deciding whether surgery is advisable include: the length of time since the initial operation, the location of the recurrent tumor, the age and performance status of the patient, the extent of extracranial disease, and the radiosensitivity of the tumor.[6,68] In general, the sooner the metastasis recurs after the initial resection, the less likely it is that a second operation will provide a significant period of palliation.[7,68] Radiation Therapy Radiation therapy has been the mainstay of treatment for patients with brain metastases for nearly 40 years. Overall, conventional whole-brain radiation therapy increases median survival to 3 to 6 months.[1,10] Radiation is effective in the palliation of neurologic symptoms and also significantly decreases the likelihood of death due to neurologic causes. Unfortunately, for most patients, overall survival is more likely to be determined by the activity and extent of extracranial disease than by success or failure of radiation therapy or surgery in controlling brain metastases. The main goal of radiation therapy is to improve neurologic deficits caused by the tumor deposit. The published overall response rate is symptom-dependent, but ranges from 64% to 85%.[17,69,70] In one study, 74% of patients had improvement of neurologic symptoms, such as headaches, with radiation therapy, and 65% maintained this improvement for the duration of their lives or for at least 9 months. Cranial nerve deficits improve in approximately 40% of patients. However, the potential for improvement is directly related to the time from diagnosis to radiation therapy. Early treatment is generally associated with a better outcome. The majority of patients with significant neurologic dysfunction improve with the use of steroids and radiotherapy, while less than 50% of patients with moderate neurologic dysfunction will improve following therapy.  Optimal Dose-Fractionation Schedule—The optimal dose-fractionation schedules for patients with brain metastases have been evaluated in randomized trials conducted by the RTOG.[72,73] Two RTOG trials of several dose-fraction schedules were subsequently reported together. In the first trial, patients were randomized to 40 Gy in 4 weeks, 40 Gy in 3 weeks, 30 Gy in 3 weeks, or 30 Gy in 2 weeks. The second trial randomized patients to 40 Gy in 3 weeks, 30 Gy in 2 weeks, or 20 Gy in 1 week. The overall response and median survival rates were equivalent in all arms of these studies. Median survival was 18 weeks in the first trial and 15 weeks in the second. Brain metastasis was the cause of death in 40% of patients in both trials. Patients treated in the shortest time and with larger fractions responded more quickly, but the duration of the clinical response and the time to progression were similar in each treatment arm. Symptoms were palliated in 75% to 80% of the patients in all treatment arms of these protocols. In order to explore the efficacy and toxicity of ultrarapid treatment schedules, the RTOG treated 26 patients with 10 Gy in one fraction and 36 patients with 12 Gy in two fractions. The promptness of response, percentage of patients demonstrating neurologic improvement, and overall survival with this schedule were similar to the results obtained with more protracted schedules described abo
Brain tumor neuroimaging 4 17th may 02
Brain Tumor Neuroimaging - 4 Dr Deb
Others tumors <ul><li>II. Tumors of nerves </li></ul><ul><li>III. Tumors of the coverings of the brain (meninges) </li></ul><ul><li>IV. Germ cell tumors </li></ul><ul><li>V. Other malformative tumors and tumor-like lesions </li></ul><ul><li>VI. Tumors of the pituitary gland </li></ul><ul><li>VII. Metastatic tumors to brain from elsewhere in the body </li></ul>
II. Tumors of nerves <ul><li>Schwannoma </li></ul><ul><li>Neurofibroma </li></ul>
Vestibular schwannoma <ul><li>Vestibular schwannoma arises on the eighth cranial nerve. </li></ul><ul><li>usually unilateral, but in 9% of cases is bilateral </li></ul><ul><li>Commonly asymptomatic </li></ul><ul><li>hearing loss and tinnitus are early symptoms produced by involvement of the cochlear division of the nerve </li></ul><ul><li>In the later stages vertigo with abnormal caloric and electronystagmographic responses develop from damage to the vestibular division itself. </li></ul>
CT Scan in Schwanoma <ul><li>Plain CT, most schwannomas are isodense with brain parenchyma. </li></ul><ul><li>Calcification or areas of hemorrhage are rare. </li></ul><ul><li>On contrast-enhanced CT, the enhancement pattern typically is homogeneous </li></ul>
<ul><li>On contrast-enhanced CT, the enhancement pattern typically is homogeneous. </li></ul><ul><li>Bone window images can demonstrate remodeling of the adjacent skull base, such as expansion of the IAC by vestibular schwannomas and the facial canal by facial schwannomas </li></ul><ul><li>Expansion of the jugular foramen by CN IX, CN X, or CN XI schwannomas also can be seen. </li></ul>
<ul><li>Thin-collimation CT imaging of the skull base can be helpful for evaluating bone destruction, which is useful for differentiating jugular foramen schwannomas from paragangliomas </li></ul>
MRI in Schwannomas <ul><li>isointense or slightly hypointense to gray matter on T1-weighted images and slightly hypointense to CSF </li></ul><ul><li>on T2-weighted images. </li></ul><ul><li>Enhancement following gadolinium administration typically is homogeneous, although larger schwannomas can show areas of cystic degeneration and signal heterogeneity, </li></ul><ul><li>often on the bases of increased areas of Antoni type B histology. </li></ul><ul><li>high-resolution thin-section heavily T2-weighted 3-dimensional sequences, individual nerves within the cistern and IAC can be visualized as linear filling defects within the bright CSF </li></ul><ul><li>Small masses can be identified without the use of an intravenous contrast agent </li></ul>
<ul><li>Typically, the masses are located in the cerebellopontine angle (CPA) and are centered at the porus, with extension into the IAC. Their appearance has been termed comet tail or ice cream cone </li></ul><ul><li>The long axis of the tumors lies parallel to the petrous surface. Occasionally, tumors can be entirely intracanicular, in which case, the primary differential diagnosis is a meningioma of the CPA </li></ul><ul><li>Unlike vestibular schwannomas, meningiomas tend to form obtuse angles with the adjacent petrous bone, typically are hemispherical in appearance, and often extend into the middle fossa via herniation </li></ul>
<ul><li>Contrast-enhanced T1-weighted image at the level of the internal auditory canal shows a densely enhancing cisternal vestibular schwannoma (white arrow) compressing the adjacent pons and cerebellum and distorting the fourth ventricle. </li></ul>
<ul><li>Contrast-enhanced T1-weighted axial image through the internal auditory canal shows a heterogeneously enhancing intracanalicular/cisternal vestibular schwannoma (white arrow). Anterior to the schwannoma a tumor-related cyst is noted (black arrow). </li></ul>
<ul><li>Intracanalicular vestibular schwannoma. Axial CISS (constructive interference in the steady state) image shows a 3-mm mass in the internal auditory canal as a filling defect within the bright cerebrospinal fluid. </li></ul>
<ul><li>Vestibular schwannoma. Axial contrast-enhanced T1-weighted image confirms the intracanalicular mass seen in Image 3. . </li></ul>
44-year-old male with progressive right-sided sensorineural hearing loss
Female, 55 years, complaining of a right hearing loss and facial hemispasm Copyright, CID, 26.04.99 (1) Enhancing small tumor at the right cerebellopontine angle (2) Tumoral component inside the right internal acoustic meatus (3) Membranous labyrinth (4) Pons (5) Cerebellar hemisphere (6) Normal left internal acoustic meatus
Facial nerve: Schwannomas <ul><li>can occur along any segment but frequently involve the geniculate ganglion and extend proximally or distally from there. </li></ul><ul><li>MRI and CT imaging characteristics are similar to those for vestibular schwannomas. </li></ul><ul><li>The location of the mass results in variable growth patterns. </li></ul><ul><li>In the IAC, facial schwannomas are indistinguishable from vestibular lesions. </li></ul><ul><li>When crossing the petrous bone to involve both the middle and posterior fossa, facial schwannomas cross in the mid portion of the petrous bone as opposed to trigeminal schwannomas, which cross near the petrous apex. </li></ul><ul><li>Lesions in the geniculate ganglion can be mistaken for temporal lobe lesions, and imaging in the coronal plane is useful in evaluating the lesions </li></ul>
<ul><li>Facial schwannoma. Axial T1-weighted image at the level of the internal auditory canal shows a soft tissue mass along the course of the tympanic segment of the facial nerve. </li></ul>
<ul><li>Facial schwannoma. Coronal contrast-enhanced T1-weighted image shows the schwannoma involving the mastoid segment of cranial nerve VII. </li></ul>
<ul><li>Facial neuritis. Axial contrast-enhanced T1-weighted image shows swelling and enhancement of the labyrinthine, geniculate, and tympanic segments of cranial nerve VII. </li></ul>
<ul><li>Facial neuritis. Coronal contrast-enhanced T1-weighted image shows swelling and marked enhancement of the mastoid segment of cranial nerve VII. </li></ul>
Trigeminal schwannomas <ul><li>Trigeminal schwannomas can arise in the Meckel cave or in the cistern along the course of the nerve. </li></ul><ul><li>Extension and expansion of the foramen rotundum or ovale is common, and the masses can have a bilobed appearance. </li></ul><ul><li>Tumors also can grow posteriorly to involve the posterior fossa or anteriorly into the cavernous sinus. </li></ul><ul><li>Trigeminal schwannomas tend to have a more cystic component than do other schwannomas </li></ul>
<ul><li>Trigeminal schwannoma. Coronal T2-weighted image shows a hyperintense mass in the right cavernous sinus. </li></ul>
<ul><li>Trigeminal schwannoma. Axial contrast-enhanced T1-weighted image at the level of the mid pons shows a densely enhancing mass involving the left cranial nerve V within the cistern (black arrow) and Meckel cave (white arrow). </li></ul>
<ul><li>Trigeminal schwannoma. Axial CISS (constructive interference in the steady state) image shows a mass in the region of the cisternal segment of the right cranial nerve V (white arrow). The left cranial nerve V (without tumor) also is visualized (white arrow). </li></ul>
<ul><li>Trigeminal schwannoma. Coronal contrast-enhanced T1-weighted image (same patient as Picture 12) shows the mass arising from the cisternal segment of the right cranial nerve V. The left cranial nerve V (without tumor) also is visualized (white arrow). </li></ul>
Glossopharyngeal, vagus, or accessory nerve schwannomas <ul><li>Glossopharyngeal, vagus, or accessory nerve schwannomas are rare and are difficult to distinguish from each other. </li></ul><ul><li>The tumors are classified based on their growth patterns, with </li></ul><ul><ul><li>type A lesions growing predominantly intracranially, </li></ul></ul><ul><ul><li>type B lesions growing predominantly at the jugular foramen, and </li></ul></ul><ul><ul><li>type C lesions growing predominantly extracranially. </li></ul></ul><ul><li>CT and MRI characteristics are similar to those seen in other schwannomas. In contrast to the more common paraganglioma in this region, schwannomas expand but do not infiltrate the adjacent bone </li></ul>
<ul><li>Glossopharyngeal schwannoma. Axial contrast-enhanced T1-weighted image shows a large extraaxial mass compressing the brainstem (black arrows) and extending into the skull base (white arrows). </li></ul>
<ul><li>Glossopharyngeal schwannoma. Coronal contrast-enhanced T1-weighted image (same patient as Picture 17) shows a mass extending through the skull base via the jugular foramen. </li></ul>
<ul><li>Glossopharyngeal schwannoma. Digital subtraction angiogram from an ascending pharyngeal artery injection reveals a moderately hypervascular schwannoma, which is atypical for schwannomas (same patient as Pictures 17-19). </li></ul>
Hypoglossal schwannomas <ul><li>Hypoglossal schwannomas are similar in growth patterns and imaging characteristics to jugular foramen schwannomas. </li></ul><ul><li>When large enough, the tumors can erode the hypoglossal canal to such an extent that differentiation from jugular foramen schwannomas can be difficult. </li></ul>
Schwannomas of CN VI <ul><li>Schwannomas of CN VI are rare. </li></ul><ul><li>They have been reported to occur in the prepontine cistern, with a heterogeneous appearance on CT and MRI imaging and extension into the adjacent cavernous sinus. </li></ul><ul><li>Similar to other schwannomas, meningioma is the primary differential diagnosis, and the presence of areas of cystic change (manifesting as high T2 signal) can sway the likelihood of a diagnosis to schwannoma over meningioma. CN IV schwannomas similarly are rare (see Image 17). </li></ul>
<ul><li>Cranial nerve IV schwannoma. Axial and coronal contrast-enhanced T1-weighted images demonstrate a small mass involving the cisternal segment of cranial nerve IV adjacent to the midbrain. </li></ul>
Oculomotor nerve Schwannomas <ul><li>Schwannomas of the oculomotor nerve have been reported in the literature but are exceedingly rare. </li></ul><ul><li>The tumors can present as masses in the suprasellar cistern and can be difficult to distinguish from meningiomas in this region. </li></ul>
<ul><li>Notice the whirly swirly pattern and how the cell nuclei are closely bunched together... almost as if they're forming a fence (Verocay bodies). Schwannomas are benign spindle cell tumors that occur along the edges of peripheral nerves. They can usually be removed without damaging the nerve itself. </li></ul>
<ul><li>A high power view of the Schwannoma, emphasizing the slenderness of the spindle cells and their elongate nuclei. </li></ul><ul><li>Compare them with the much plumper spindle cells of the meningioma. </li></ul>
Neurofibromatosis <ul><li>NF-1 and NF-2 chromosome 17 and 22 </li></ul><ul><li>NF-1 </li></ul><ul><ul><li>1) six or more café-au-lait spots, </li></ul></ul><ul><ul><li>2) two or more hemartomas of the iris (Lisch nodules), </li></ul></ul><ul><ul><li>3) two or more neurofibromas, </li></ul></ul><ul><ul><li>4) one or more plexiform neurofibromas, </li></ul></ul><ul><ul><li>5) axillary freckling, </li></ul></ul><ul><ul><li>6) one or more bone dysplasias, </li></ul></ul><ul><ul><li>7) psuedoarthrosis of a long bone, </li></ul></ul><ul><ul><li>8) optic glioma, or </li></ul></ul><ul><ul><li>9) a first-degree relative with the diagnosis of NF-1 </li></ul></ul>
Neurofibromatosis - Radiology <ul><li>cerebellar, brain stem, and cerebral astrocytomas are seen with NF-1. </li></ul><ul><li>On MR T2 weighted images, patients may have high signal intensity foci in the peduncles or deep gray matter of the cerebellum, brain stem or basal ganglia </li></ul><ul><li>These features are believed to represent hamartomas, focal areas of gliosis, wallerian degeneration, neuronal migrational disorders, or possibly neoplasms. </li></ul>
9-year-old male with a history of headaches x two months and hyperreflexia. Multiple rounded foci of abnormally bright signal are seen in the lentiform nuclei bilaterally, the thalami bilaterally, mesencephalon, and dentate nuclei bilaterally (left greater than right), on FLAIR and T2 weighted images. No abnormal enhancement is seen.
Neurofibromatosis 2 <ul><li>37 year old man with a well established family history of neurofibromatosis type 2. Of 4 older siblings, all four had in the past been treated with surgery for bilateral acoustic neuromas and a variety of other CNS tumors </li></ul>Coronal T1 weighted MRI with contrast demonstrating a falx meningioma
Neurofibromatosis 2 Axial MRI with contrast demonstrating a very large acoustic neuroma and two meningiomas of the posterior cranial fossa.
Neurofibromatosis 2 Coronal MRI demonstrating a falx meningioma, a meningioma of the tentorium and an acoustic neuroma on the right side.
Neurofibromatosis 2 <ul><li>Sagital contrast T1 MRI of the same patient demonstrating the extent of the tentorial meningioma </li></ul>
Neurofibromatosis 2 <ul><li>T1 axial, non contrast MRI demonstrating an optic nerve glioma. </li></ul>
Neurofibromatosis 2 <ul><li>Axial T1-weighted postcontrast image demonstrates bilateral internal auditory canal-enhancing masses diagnostic for neurofibromatosis type 2. No biopsy is necessary for the diagnosis. Notice the en-plaque meningioma anterior to the brainstem. </li></ul>
Neurofibromatosis 2 <ul><li>Axial postcontrast T1-weighted image demonstrates a large enhancing sellar meningioma surrounding both internal carotid arteries in this case of neurofibromatosis type 2 (NF-2) (black arrows). Enhancing tissue in the ethmoid air cells also represents meningioma, extending through the cribriform plate. Meningiomas in patients with NF-2 can be more aggressive and invasive than spontaneous meningiomas. Note the small round enhancing extra-axial mass posterior to the tectum (white arrows). While this could represent another meningioma, the shape and location suggest it is a trochlear schwannoma instead. </li></ul>
Neurofibromatosis 2 <ul><li>Sagittal T1-weighted postcontrast image in a patient with known neurofibromatosis 2 demonstrates two midline meningiomas (arrowheads), one over the convexity and one along the vein of Galen. The enhancing mass in the medulla (arrow) most likely is an ependymoma </li></ul>
III. Tumors of the coverings of the brain - Meningioma <ul><li>Meningiomas are the most common non-glial primary tumor of the CNS. Meningiomas are also the most common extraaxial primary tumor of the CNS. </li></ul><ul><li>They represent 15-25% of all intracranial primary tumors. Most patients are in the 5th and 6th decades (40's - 50's). </li></ul><ul><li>The 2x-4x female predilection is most likely due to hormone receptors for progesterone and estrogen. </li></ul><ul><li>The tumor arises from the arachnoid cap cells and is usually a slowly growing intradural intracranial mass, with a broad base of attachment to the overlying dura. </li></ul><ul><li>Hyperostosis of the overlying skull occurs in 15-25% of cases and may be a "sympathetic reaction" - or - can indicate invasion of the skull. </li></ul>
Meningioma <ul><li>Note that arachnoid villi are composed of an outer layer of thick dura invaginated by arachnoid membrane. </li></ul><ul><li>Meningiomas are composed of arachnoid cap cells (outer layer) but they arise from the dura. </li></ul><ul><li>Throughout the dura there are rests of arachnoid cap cells and this is most common in the dura of the superior sagittal sinus because of the arachnoid villi naturally invaginating the dura in this location (Pacchionian granules). </li></ul><ul><li>Because this phenomena is most common in this location this is the region where meningiomas are most common </li></ul>Meningiomas are the 4H Plus tumor: H - hemispheric H - homogeneous H - homogeneously enhancing H - hyperdense (CT) H - hyperostosis H - hormonally reactive (progesterone/estrogen)
Meningioma - Gross <ul><li>This is a meningioma that arose from an arachnoid villus in the superior sagittal sinus. Note that unlike a glial tumor, it does not infiltrate surrounding brain but rather pushes against it; this usually makes meningiomas easier to remove than gliomas </li></ul>
Meningioma <ul><li>This patient is a 27-year-old female who presented from a referring hospital secondary to a mass seen on CT exam. She had been complaining of double vision and intermittent headache for five months </li></ul>
A: Germinoma <ul><li>These tumors arise from germ cells and are most common in the region of the pineal gland. </li></ul><ul><li>They are thought to arise from cells that should have migrated to the gonads during development. </li></ul><ul><li>They are highly infiltrative and rapidly growing </li></ul>
Germinoma <ul><li>The tumor is composed of primitive germ cells distributed in a lobular array separated by a lymphocytic-rich stroma. </li></ul>
V. Other malformative tumors and tumor-like lesions <ul><li>A. Craniopharyngioma </li></ul><ul><li>B. Rathke's cleft cyst </li></ul><ul><li>C. Epidermoid and Dermoid cyst </li></ul><ul><li>D. Colloid cyst of the third ventricle </li></ul><ul><li>E. Lipoma </li></ul><ul><li>F. Hamartoma </li></ul>
A. Craniopharyngioma <ul><li>A 45 year old male presented with history of severe headaches of 2 years duration. </li></ul><ul><li>CT scan was done and it showed a well defined, mildly hyperdense, non enhancing lesion in the Foramen of Monro, with obstructive hydrocephalus, this was reported as a colloid cyst. </li></ul><ul><li>Bilateral ventriculo-peritoneal shunts were introduced, and subsequent scan showed regression of the hydrocephalus. </li></ul><ul><li>A year later, patient developed a progressive loss of memory; an MRI scan of the brain was performed. </li></ul>
A. Craniopharyngioma <ul><li>This photograph of a lateral X-ray of the skull shows the expansion of the sella turcica and calcification in mass (look between arrows). </li></ul>
A. Craniopharyngioma <ul><li>A sagittal section of the brain shows a large craniopharyngioma below the cerebral ventricle. Note the stippled pattern of the tumor </li></ul>
A. Craniopharyngioma <ul><li>This low power view of a section of craniopharyngioma shows a cystic area on the left, in the zones to the center, and lower right epithelia producing acellular substance, and a loose mesenchyme filling the rest of the field. </li></ul>
Colloid Cyst of Third Ventricle <ul><li>Female, 79 years, complaining of recent disorientation and memory loss. </li></ul><ul><li>On CT and MR images : small, round, non-enhancing, hyperdense, hypointense (T2), hyperintense (T1) tumour located in the anterior part of the third ventricle, near the Monro's foramina. </li></ul><ul><li>This lesion leads to obstruction of the Monro's foramina and therefore to lateral ventricles dilatation. We read this lesion as a typical colloid cyst. </li></ul>
<ul><li>HX: 71 y/o RHM developed a cataclysmic headache on 11/5/92 associated with a violent sneeze. The headache lasted 3-4 days. On 11/7/92, he had acute pain and loss of vision in the left eye. Over the following day his left pupil enlarged and his left upper eyelid began to droop. He was seen locally and a brain CT showed no sign of bleeding, but a tortuous left middle cerebral artery was visualized. The patient was transferred to UIHC 11/12/92. </li></ul>
<ul><li>HX: This 47 y/o RHM presented to his local optometrist in 9/92 for routine evaluation. He had no complaint of visual loss, HA, nausea/vomiting, lymphadenopathy, weight change, galactorrhea, impotence, temperature intolerance, hot or cold flashes, or personality change. Visual field testing revealed a superior bitemporal incongruous hemianopia and he was referred to NeuroOpthalmology at UIHC. </li></ul>
VII. Metastatic tumors to brain from elsewhere in the body <ul><li>Note that there are at least five multiple foci of tumor which usually indicates metastases rather than primary tumor. In this case the metastatic nodules are also hemorrhagic and they arose from the lung </li></ul>
VII. Metastatic tumors to brain from elsewhere in the body