Ganglioglioma and Gangliocytoma

Gangliogliomas (WHO grade I or II) are mixed tumors containing both neural and glial elements. Gangliocytomas (WHO grade I) are less common and contain well-differentiated neuronal cells without a glial component. Less commonly, gangliogliomas may exhibit anaplasia within the glial component and are classified as anaplastic ganglioglioma (WHO grade III). A rare type of gangliocytoma, dysplastic gangliocytoma of the cerebellum (also known as Lhermitte-Duclos disease) exhibits a characteristic “tiger-striped” appearance and is often present in association with Cowden disease, a phacomatosis.

The peak age of onset for gangliogliomas is the second decade. This tumor is usually supratentorial and is most commonly located in the temporal lobe. It is well demarcated, and a cystic component and mural nodule are often observed. Calcification is common.

On MRI (Provenzale et al., 2000) the solid component is usually isointense on T1 and hypo- to hyperintense on T2-weighted images. The cystic component, if present, exhibits CSF signal characteristics. The associated mass effect is variable. With contrast, various enhancement patterns are seen—homogenous or rim pattern—but no enhancement is also possible.

Pilocytic Astrocytomas

Pilocytic astrocytomas have two major groups: juvenile and adult. These tumors are classified as WHO grade I. Juvenile pilocytic astrocytomas are the most common posterior fossa tumors in children. The most common locations are the cerebellum, at the fourth ventricle, third ventricle, temporal lobe, optic chiasm, and hypothalamus (Koeller and Rushing, 2004). The appearance is often lobulated, and the lesion appears well demarcated on MRI. Hemorrhage and necrosis are uncommon. Areas of calcification may be present. The tumor usually exhibits solid as well as cystic components, with or without a mural nodule. The adult form is usually well circumscribed, often calcified, and typically exhibits a large cyst with a mural nodule. On MRI, the solid portions of the tumor are iso- to hypointense on T1 and iso- to hyperintense on T2-weighted images (Arai et al., 2006). The cystic component usually exhibits CSF signal characteristics. The associated edema and mass effect is usually mild, sometimes moderate. With gadolinium, the solid components (including the mural nodule) enhance intensely, but not the cyst, which rarely may show rim enhancement.

Pleomorphic Xanthoastrocytoma

Pleomorphic xanthoastrocytoma is a rare variant of astrocytic tumors. It is thought to arise from the subpial astrocytes and typically affects the cerebral cortex and adjacent meninges and may cause erosion of the skull. The most common location is the temporal lobe. It is classified as WHO grade II. It usually occurs in the second and third decades of life, and patients often present with seizures. On MRI (Tien et al., 1992) usually a well-circumscribed cystic mass appears in a superficial cortical location. A solid portion or mural nodule is often seen, and the differential diagnosis includes pilocytic astrocytoma and ganglioglioma. The signal characteristics are hypointense or mixed on T1, and hyperintense or mixed on T2-weighted images. With contrast, the solid portions and sometimes the adjacent meninges enhance. Calcification may be present. There is mild or no mass effect associated with this tumor.

Low-Grade Astrocytomas

Fibrillary astrocytomas, also termed diffuse astrocytomas, represent approximately 10% of all gliomas. Low-grade (WHO grade I and II) astrocytomas belong to this group (Figs. 33A.17 and 33A.18). These are well-differentiated tumors, usually arising from the fibrillary astrocytes of the white matter. Even though imaging may show a fairly well-defined boundary, these tumors are infiltrative and usually spread beyond their macroscopic border. Two-thirds of cases are supratentorial. A subgroup of these astrocytomas involves specific regions such as the optic nerves/tracts or the brainstem.

Fig. 33A.17 Low-grade glioma. A, On FLAIR image, a faint hyperintense lesion is seen (arrowheads) with somewhat blurred margins in the right corona radiata at the border of the lateral ventricle, extending minimally toward the corpus callosum (arrow). B, On T1-weighted postcontrast image, this lesion does not enhance.

Fig. 33A.18 Tectal glioma. A-B, On axial and sagittal T2-weighted images, a faintly hyperintense mass lesion is seen involving the tectum of the midbrain (arrows). There appears to be at least partial obstruction of the aqueduct, resulting in enlargement of the third and lateral ventricles. C, Following gadolinium administration, the tumor does not enhance (arrows).

Low-grade astrocytomas are iso- or hypointense on T1-weighted images and hyperintense on T2-weighted images. Tissue expansion may be seen, and mass effect (if present) is generally modest. There is little to no associated edema. Fibrillary grade I astrocytomas do not enhance; grade II tumors may exhibit enhancement. The appearance of enhancement in a previously nonenhancing tumor is a worrisome sign of malignant transformation, often due to anaplastic astrocytoma.

Anaplastic Astrocytoma

Anaplastic astrocytoma is classified as grade III by the WHO grading system. It represents 25% to 30% of gliomas, usually appears between 40 and 60 years of age, and is more common in men. Anaplastic astrocytoma is a diffuse infiltrating tumor that often evolves from a well-differentiated astrocytoma as a result of chromosomal and gene alterations. It is most frequently found in the frontal lobes. On MRI, anaplastic astrocytomas appear as poorly circumscribed heterogenous tumors which are iso- to hypointense on T1-weighted and hyperintense on T2-weighted images, with associated hyperintensity in the surrounding white matter representing vasogenic edema. Foci of hemorrhage may be present but not too commonly. There is moderate mass effect associated with the lesions, and with contrast, a variable degree and pattern of enhancement is noted (diffuse or ringlike). This tumor is highly infiltrative, usually cannot be fully removed by surgery, and the median survival is 3 to 4 years.

Oligodendroglioma

Oligodendroglioma accounts for 5% to 10% of all gliomas. It arises from the oligodendroglia that form the myelin sheath of the central nervous system (CNS) pathways. Oligodendroglioma occurs most commonly in young and middle-aged adults, with a median age of onset within the fourth to fifth decades and a male predominance of up to 2 : 1. Seizure is often the presenting symptom. The most common location is the supratentorial hemispheric white matter, and it also involves the cortical mantle. The tumor often has cystic components and at least microscopically, in 90% of cases also shows calcification. Hemorrhage and necrosis are rare, and the mass effect is not impressive. On MRI (Koeller and Rushing, 2005) the appearance is heterogenous, and the tumor is hypo- and isointense on T1 and hyperintense on T2. With gadolinium, the enhancement is variable, usually patchy, and the periphery of the lesion tends to enhance more intensely. Oligodendrogliomas are hypercellular and have been noted to appear hyperintense on diffusion-weighted images (Fig. 33A.19).

Fig. 33A.19 Oligodendroglioma. A mass lesion is seen in the left medial frontal lobe, involving the cortical mantle and underlying white matter. A-B, On T2 and FLAIR images, the tumor is hyperintense. C, On diffusion-weighted image, faint hyperintensity due to the hypercellular nature of this tumor is noted (arrowheads). D, With contrast, a few areas of enhancement are seen that tend to involve periphery of lesion (arrows).

Oligoastrocytoma

Oligoastrocytomas are tumors consisting of a mixture of neoplastic oligodendroglioma and astrocytoma cell populations that may be separate (in which case the tumor is described as biphasic) or intermingled. Oligoastrocytomas cannot be definitively distinguished from oligodendrogliomas on imaging studies, with similar locations, size, and attenuation/signal characteristics. However, calcification is less common (14%) and enhancement more common (50%) in oligoastrocytomas.

Gliomatosis Cerebri

Gliomatosis cerebri, a rare glial neoplasm, usually presents in the third decade of life. The glial tumor cells are disseminated throughout the parenchyma and infiltrate large portions of the neuraxis. Macroscopically it appears homogenous and is seen as enlargement/expansion of the parenchyma; the gray/white matter interface may become blurred, but the architecture is otherwise not altered. The hemispheric white matter is involved first, then the pathology spreads to the corpus callosum, followed by both hemispheres. Later, the deep gray matter (basal ganglia, thalamus, massa intermedia) may be affected as well. Diffuse tumor infiltration often extends into the brainstem, cerebellum, and even the spinal cord. Histologically, most cases of gliomatosis cerebri are WHO grade III.

The MRI appearance is iso- to hypointense on T1 and hyperintense on T2. Hemorrhage is uncommon, and enhancement is also rare, at least in the early stages (Fig. 33A.20). Later, multiple foci of enhancement may appear, signaling more malignant transformation. The imaging appearance is similar to that of encephalitis, lymphoma, or subacute sclerosing panencephalitis, but in these disorders, clinical findings are more pronounced.

Fig. 33A.20 Gliomatosis cerebri. (A) Axial T2-weighted magnetic resonance (MR) image of brain shows bilateral patchy areas of increased signal intensity in periventricular white matter. (B) Axial T2-weighted MR image of brain obtained at the level of the upper pons shows diffuse thickening and hyperintensity of left optic nerve (white arrow) and increased signal intensity in posterior aspect of pons and in cerebellum (black arrows). A focus of very high signal intensity is present in posterior left cerebellar hemisphere (*).

(From Yip, M., Fisch, C., Lamarche, J.B., 2003. AFIP archives: gliomatosis cerebri affecting the entire neuraxis. Radiographics 23, 247-253.)

Glioblastoma Multiforme

Glioblastoma multiforme is a highly malignant tumor classified as grade IV by the WHO. It is most common in older adults, usually appearing in the fifth and sixth decades. GBM is the most common primary brain neoplasm, representing 40% to 50% of all primary neoplasms and up to 20% of all intracranial tumors. It forms a heterogenous mass exhibiting cystic and necrotic areas and often a hemorrhagic component as well. The most common locations are the frontal and temporal lobes. The tumor is highly infiltrative and has a tendency to spread along larger pathways such as the corpus callosum and invade the other hemisphere, resulting in a characteristic “butterfly” appearance. GBM has also been described to spread along the ventricular surface in the subarachnoid space and may also invade the meninges. There are reported cases of extracranial glioblastoma metastases.

Structural neuroimaging distinguishes between multifocal and multicentric glioblastomas. The term multifocal glioblastoma refers to multiple tumor islands in the brain that arose from a common source via continuous parenchymal spread or meningeal/CSF seeding; therefore, they are all connected, at least microscopically. Multicentric glioblastoma refers to multiple tumors that are present independently, and physical connection between them cannot be proven, implying they are separate de novo occurrences. This is less common, having been noted in 6% of cases.

On MRI (Fig. 33A.21) glioblastomas usually exhibit mixed signal intensities on T1- and T2-weighted images. Cystic and necrotic areas are present, appearing as markedly decreased signal on T1-weighted and hyperintensity on T2-weighted images. Mixed hypo- and hyperintense signal changes due to hemorrhage are also seen. The hemorrhagic component can also be well demonstrated by gradient echo sequences or by SWI. The core of the lesion is surrounded by prominent edema, which appears hypointense on T1-weighted and hyperintense on T2-weighted images. Besides edema, the signal changes around the core of the tumor reflect the presence of infiltrating tumor cells and, in treated cases, postsurgical reactive gliosis and/or post-irradiation changes. Following administration of gadolinium, intense enhancement is noted, which is inhomogenous and often ringlike, also including multiple nodular areas of enhancement. The surrounding edema and ringlike enhancement at times makes it difficult to distinguish glioblastoma from cerebral abscess. DWI is helpful in these cases; glioblastomas are hypointense with this technique, whereas abscesses exhibit remarkable hyperintensity on diffusion-weighted images.

Fig. 33A.21 Glioblastoma multiforme. A, Axial FLAIR image demonstrates a mass lesion spreading across the corpus callosum to involve both frontal lobes in a symmetrical fashion (“butterfly” appearance). Tumor is isointense, exerts mass effect on the sulci and the lateral ventricles, and is surrounded by vasogenic edema. B, On axial T1 postcontrast imaging, tumor exhibits heterogenous irregular enhancement, most marked at its periphery.

Owing to its aggressive growth (the tumor size may double every 10 days) and infiltrative nature, the prognosis for patients with glioblastoma is very poor. Despite surgery, irradiation, and chemotherapy the median survival is 1 year.

Ependymoma

Although ependymomas are primarily extraaxial tumors (within the fourth ventricle), intraparenchymal ependymomas arising from ependymal cell remnants of the hemispheric parenchyma are also well known, so this tumor type is discussed here. Ependymomas comprise 5% to 6% of all primary brain tumors; 70% of cases occur in childhood and the first and second decades, and ependymoma is the third most common posterior fossa tumor in children. Ependymomas arise from differentiated ependymal cells, and the most common location (70%) is the fourth ventricle. The tumor is usually well demarcated and is separated from the vermis by a CSF interface. The tumor may be cystic and may contain calcification and hemorrhage, but these features are more common in supratentorial ependymomas. It may extrude from the cavity of the fourth ventricle through the foramina of Luschka and Magendie. Spreading via CSF to the spinal canal (drop-metastases) may occur, but on spine imaging ependymoma is more commonly noted to arise from the ependymal lining of the central canal, presenting as an intramedullary spinal cord tumor. A subtype, myxopapillary ependymoma, is almost always restricted to the filum terminale.

Ependymomas are hypo- to isointense on T1-weighted, and iso- to hyperintense on T2-weighted images. With gadolinium, intense enhancement is seen, mostly involving the solid components of the tumor, whereas the cystic components tend to exhibit rim enhancement. The differential diagnosis for infratentorial ependymoma includes medulloblastoma, pilocytic astrocytoma, and choroid plexus papilloma.

Lymphoma

Primary CNS lymphoma (PCNSL) is a non-Hodgkin lymphoma, which in 98% of cases is a B-cell lymphoma. It once accounted for only 1% to 2% of all primary brain tumors, but this percentage has been increasing, mostly because of the growing acquired immunodeficiency syndrome (AIDS) population. The peak age of onset is 60 in the immunocompetent population and age 30 in immunocompromised patients. Lesions may occur anywhere within the neuraxis, including the cerebral hemispheres, brainstem, cerebellum, and spinal cord, although the most common location (90% of cases) is supratentorial. PCNSL lesions are highly infiltrative and exhibit a predilection for sites that contact subarachnoid and ependymal surfaces as well as the deep gray nuclei.

The imaging appearance of PCNSL depends on the patient’s immune status. The tumor is hypo- to isointense on T1-weighted and hypo- to slightly hyperintense on T2-weighted images. Contrast enhancement is usually intense. In immunocompetent patients (Zhang et al., 2010) the lesion is often single, tends to abut the ventricular border (Costa et al., 2006), and ring enhancement is uncommon (Fig. 33A.22). In immunocompromised patients, usually multiple, often ring-enhancing lesions are seen, which are most commonly located in the periventricular white matter and the gray/white junction of the lobes of the hemispheres, but the deep central gray matter structures and the posterior fossa may be involved as well. Overall, the imaging appearance appears more malignant in the immunocompromised cases and may be difficult to differentiate from toxoplasmosis. Other components of the differential diagnosis in patients with multiple PCNSL lesions include demyelination, abscesses, neurosarcoidosis, and metastatic disease.

Fig. 33A.22 CNS lymphoma in an immunocompetent individual. A, FLAIR sequence depicts a single hyperintense lesion with spread along the ventricular border. B, After contrast administration, multiple areas of enhancement are seen within the lesion, without a ringlike enhancement pattern.

Hemangioblastoma

Hemangioblastomas represent only 1% to 2% of all primary brain tumors, but in adults they are the most common type of primary intraaxial tumor of the posterior fossa (cerebellum and medulla). These tumors are WHO grade I, well circumscribed, and exhibit a vascular nodule with a usually larger cystic cavity. On MRI the solid portion is hypo- to isointense on T1 and hyperintense on T2-weighted images. Sometimes hyperintense foci are noted on T1; this is due to occasional lipid deposition or hemorrhage within the tumor. The cystic component is usually hypointense on T1 (but may be hyperintense relative to CSF due to high protein content) and markedly hyperintense on T2. On FLAIR images, the cyst fluid is not completely nulled, resulting in bright signal, and the nodule is also hyperintense. There is usually mild surrounding edema. With gadolinium, the solid component exhibits intense enhancement. Hemangioblastomas are seen in 50% of patients with von Hippel-Lindau disease, and approximately one-fourth of all hemangioblastomas occur in these patients (Neumann et al., 1989).

Meningiomas

Meningiomas are the most common primary brain tumors of non-glial origin and make up 15% of all intracranial tumors. The peak age of onset is the fifth decade, and there is a striking female predominance that may be related to the fact that some meningiomas contain estrogen and progesterone receptors. These tumors arise from meningothelial cells. In 1% to 9% of cases, multiple tumors are seen. The most common locations are the falx (25%), convexity (20%), sphenoid wing, petrous ridge (15% to 20%), olfactory groove (5% to 10%), parasellar region (5% to 10%), and the posterior fossa (10%). Rarely an intraventricular location has been reported. Meningiomas often appear as smooth hemispherical or lobular dural-based masses (Fig. 33A.23). Calcification is common, seen in at least 20% of these tumors. Meningiomas also often exhibit vascularity. The extraaxial location of the tumor is usually well appreciated owing to a visible CSF interface between tumor and adjacent brain parenchyma. Meningiomas may become malignant, invading the brain and eroding the skull. In such cases, prominent edema may be present in the brain parenchyma, to the extent that the extraaxial nature of the tumor is no longer obvious.

Fig. 33A.23 Two cases of meningioma. In the first (A-B) two extraaxial mass lesions are seen, one arising from the tentorium and the other from the sphenoid wing in the left middle cranial fossa (arrows). These compress the right cerebellar hemisphere and the left temporal lobe, respectively. A, On T2-weighted image, the masses are mostly isointense with foci of hypointensity. B, After gadolinium administration, the masses enhance homogenously. Note the small dural tail along the tentorium. In the second case (C-D) a large olfactory groove meningioma is presented that exerts significant mass effect on the frontal lobes, corpus callosum, and lateral ventricles. C, On FLAIR image, hyperintense vasogenic edema is seen in the compressed brain parenchyma. D, Tumor enhances homogeneously with gadolinium.

On T1-weighted images, meningiomas are usually iso- to slightly hypointense. The appearance on T2 can be iso-, hypo-, or hyperintense to the gray matter. Although MRI does not reveal the histological subtypes of meningiomas with absolute certainty, there have been observations according to which fibroblastic and transitional meningiomas tend to be iso- to hypointense on T2-weighted images, whereas the meningothelial or angioblastic type is iso- or more hyperintense. Not uncommonly, the skull adjacent to a meningioma will exhibit subtle thickening, a useful diagnostic clue in some cases.

After gadolinium administration, meningiomas typically exhibit intense homogenous enhancement. A quite typical imaging finding on postcontrast images is the dural tail sign, which refers to the linear extension of enhancement along the dura, beyond the segment on which the tumor is based. Earlier this had been attributed to en plaque extension of the meningioma along these dural segments and was thought to be specific for this type of tumor. However, recently it has been recognized that this imaging appearance is not specific to this situation and may be seen in other tumors, secondary to increased vascularity/hyperperfusion or congestion of the dural vessels after irradiation and as a postsurgical change.

Schwannoma

Schwannomas arise from the Schwann cells of the nerve sheath, and the most commonly affected nerve is the vestibular portion of the vestibulocochlear nerve. They are typically bilateral in neurofibromatosis (NF) type 2 (see Fig. 33A.69). The unilateral form sporadically occurs in non-NF patients, with slight female predominance. Schwannomas typically arise in the intracanalicular segment of the eighth cranial nerve where myelin transitions from central (oligodendroglia) to peripheral (Schwann cell) type. If untreated, the tumor grows toward the internal auditory meatus and eventually bulges into the cerebellopontine angle, where it may deform and displace the brainstem. The intra- and extracanalicular parts of the tumor together result in a mushroom or ice cream cone–like appearance. The tumor is iso- to hypointense on T1-weighted images and iso- to hyperintense on T2-weighted images. This pattern may be modified by the presence of cystic changes or calcification. Gadolinium administration causes homogenous enhancement that, together with the performance of axial and coronal thin-slice T2-weighted images, allows for the visualization of even very small intracanalicular schwannomas.

Primitive Neuroectodermal Tumor

Primitive neuroectodermal tumor (PNET) is a collective term that includes several tumors arising from cells that are derived from the neuroectoderm and are in an undifferentiated state. The main tumors that belong to the PNET group are medulloblastomas, esthesioneuroblastomas, and pinealoblastomas. The tumors belonging to the PNET group are fast growing and highly malignant. The most common mode of metastatic spread for PNETs is via CSF pathways, an indication for imaging surveillance of the entire neuraxis when these tumors are suspected.

Medulloblastoma

Medulloblastomas arise from the undifferentiated neuroectodermal cells of the roof of the fourth ventricle (superior or inferior medullary velum, vermis). They represent 25% of all cerebral tumors in children, usually presenting in the first and second decade. The tumor fills the fourth ventricle, extending rostrally toward the aqueduct and caudally to the cisterna magna, frequently resulting in obstructive hydrocephalus. Leptomeningeal and CSF spread may also occur, resulting in spinal drop metastases. Cystic components and necrosis may be present. Calcification is possible. On CT, medulloblastoma typically appears as a heterogeneous, generally hyperdense midline tumor occupying the fourth ventricle, with mass effect and variable contrast enhancement. The MRI signal (Koeller and Rushing, 2003) is heterogenous; the tumor is iso- or hypointense on T1 and hypo-, iso-, or hyperintense on T2. Contrast administration induces heterogenous enhancement (Fig. 33A.24). Restricted diffusion may be seen on DWI/ADC (Gauvain et al., 2001). Consistent with its site of origin, indistinct borders between the tumor and the roof of the fourth ventricle may be observed, aiding in the differential diagnosis, which in children includes atypical rhabdoid-teratoid tumor, brainstem glioma, pilocytic astrocytoma, choroid plexus papilloma, and ependymoma. The adult differential diagnosis includes the latter two entities in addition to metastasis and hemangioblastoma. Medulloblastoma does not tend to extrude via the foramina outside of the fourth ventricle, facilitating differentiation from ependymoma. In children, choroid plexus papilloma is more likely to occur within the lateral ventricle.

Fig. 33A.24 Medulloblastoma. A large mass lesion is seen (*) filling and expanding the fourth ventricle. A, On T1-weighted image, tumor is partially iso- but mostly hypointense. B, On T2-weighted image, tumor shows iso- and hyperintense signal change; it compresses/displaces the brainstem and cerebellum. On sagittal images, note the secondary Chiari malformation (caudal displacement of cerebellar tonsils) due to mass effect (arrow). C, On T1 postcontrast image, there is a heterogeneous enhancement pattern.

Esthesioneuroblastoma

The cells of an esthesioneuroblastoma are derived from olfactory neuroepithelium neurosensory cells, hence its other name: olfactory neuroblastoma. This tumor characteristically extends through the cribriform plate to the anterior cranial fossa, orbit, and paranasal sinuses. Invasion of the brain is possible, and spreading via CSF has been described. The signal intensity of the tumor is variable. On MRI, T1-weighted signal is usually isointense relative to gray matter, while the T2-weighted signal varies from iso- to hyperintense (Schuster et al., 1994). With gadolinium administration, inhomogenous enhancement is seen.

Pineoblastoma

Pineoblastomas are highly cellular tumors that are similar in MRI appearance to pineocytomas. However, they tend to be larger (>3 cm), more heterogenous, frequently cause hydrocephalus, and also may spread via the CSF. This tumor is isointense to gray matter on T1, with moderate heterogeneous enhancement following administration of gadolinium. Like other PNETs, the hypercellularity of pineoblastoma results in T2-weighted signal that tends to be iso- or hypointense relative to gray matter, and restricted diffusion may also be seen. Cysts within the tumor may appear markedly hyperintense on T2, peripheral edema less so. In cases accompanied by hydrocephalus, FLAIR imaging may reveal uniform hyperintensity in a planar distribution along the margins of the lateral ventricles due to transependymal flow of CSF. Peripheral calcifications or intratumoral hemorrhage will exhibit markedly hypointense signal with blooming artifact on T2* (pronounced T2-star) images. Differential diagnostic considerations include germ cell tumor, pineocytoma, and (uncommonly) metastases.

Other Pineal Region Tumors

Besides pineoblastomas, which histologically belong to the group of primitive neuroectodermal tumors, the pineal gland may also develop tumors of pinealocyte origin (pineocytoma) and germ cell tumors.

Pituitary Adenomas

The distinction between micro- and macroadenomas is based on their size: tumors less than 10 mm are microadenomas, the larger tumors are macroadenomas. These tumors may arise from hormone-producing cells, such as prolactinomas or growth hormone–producing adenomas, resulting in characteristic clinical syndromes. Pituitary adenomas are typically hypointense on T1-weighted and hyperintense on T2-weighted images, relative to the surrounding parenchyma. This signal change, however, is not always conspicuous, especially in the case of small microadenomas. Gadolinium administration helps in these cases, when the microadenoma is visualized as relative hypointensity against the background of the normally enhancing gland (Fig. 33A.25). Following a delay, this difference in enhancement is often no longer apparent, and if the postcontrast images are obtained in a later phase, a reversal of contrast may be noted. The adenoma takes up contrast in a delayed fashion and is seen as hyperintense against the more hypointense gland from where the contrast has washed out. Sometimes when the signal characteristics are not conspicuous, only alteration of the size and shape of the pituitary gland or shifting of the infundibulum may indicate the presence of a microadenoma. Because of this, it is important to be familiar with the normal range of pituitary gland sizes, which depend on age and gender. In adults, a gland height of more than 9 mm is worrisome. In the younger population, however, different normal values have been established. Before puberty, the normal height is 3 to 5 mm. At puberty in girls, the gland height may be 10 to 11 mm and may exhibit an upward convex morphology. In boys at puberty, the height is 6 to 8 mm, and the upward convex morphology can be normal. The size and shape of the gland may also change during pregnancy: convex morphology may appear, and a gland height of 10 mm is considered normal.

Fig. 33A.25 Pituitary microadenoma. A, Axial T2-weighted image demonstrates a round area of hyperintensity on right side of pituitary gland (arrow). B, On coronal noncontrast T1-weighted image, the gland has an upward convex morphology, and there is a vague hypointensity in its right side (arrow). C, On coronal T1-weighted postcontrast image, the microadenoma is well seen as an area of hypointensity (arrow) against the background of the normally enhancing gland parenchyma.

While microadenomas are localized to the sellar region, macroadenomas may become invasive and extend to the suprasellar region and displace/compress the optic chiasm or even the hypothalamus. Extension to the cavernous sinus is also possible.

Craniopharyngioma

Craniopharyngiomas are believed to originate from the epithelial remnants of the Rathke pouch. This WHO grade I tumor may be encountered in children, and a second peak incidence is in the fifth decade (Eldevik et al., 1996). The most common location is the suprasellar cistern (Fig. 33A.26), but intrasellar tumors are also possible. The tumor may cause expansion of the sella or erosion of the dorsum sellae. In the suprasellar region, displacement of the chiasm, the anterior cerebral arteries, or even the hypothalamus is possible. Craniopharyngiomas have both solid and cystic components. Histologically, the more common adamantinomatous and the less common papillary forms are distinguished. The adamantinomatous type frequently exhibits calcification. The MRI signal is heterogeneous. Solid portions are iso- or hypointense on T1, whereas cystic components exhibit variable signal characteristics depending on the amount of protein or the presence of blood products. On T2, the solid and cystic components are sometimes hard to distinguish, as they are both usually hyperintense. Areas of calcification may appear hypointense on T2. With contrast, the solid portions of the tumor exhibit intense enhancement.

Fig. 33A.26 Craniopharyngioma. A, On sagittal T1-weighted image, a suprasellar mass lesion has a prominent T1 hypointense cystic component (arrows). B, On sagittal T2-weighted image, the cyst is hyperintense. C, With gadolinium, both the rim of the cyst and the solid portion of the mass exhibit enhancement (arrows).

Acute Ischemic Stroke

With the introduction of thrombolytic therapy in the treatment of acute ischemic stroke, timely diagnosis of an ischemic lesion, determining its location and extent, and demonstrating the amount of tissue at risk has become essential (see Chapter 51A). CT imaging remains of great value in the evaluation of acute stroke; it is readily available, and newer CT modalities including CT angiography and CT perfusion imaging are coming into greater use. The applicability of CT to acute stroke continues to be enhanced by the ever-increasing rapidity with which scans can be acquired, allowing for greater coverage of tissues with thinner slices. The technological advances allowing for rapid acquisition of data have led to 4D imaging, where complete 3D data sets of the brain are serially obtained over very short time intervals, allowing for higher temporal and spatial resolutions in brain perfusion studies of acute ischemic stroke patients.

CT is very useful in detecting hyperdense hemorrhagic lesions as the cause of stroke. Early ischemic stroke, however, may not cause any change on unenhanced CT, making it difficult to determine the extent of the ischemic lesion and the amount of tissue at risk. CT is especially limited in evaluating ischemia in the posterior fossa, owing to streak artifacts at the skull base. Despite these limitations, early signs of acute ischemia on unenhanced CT may be helpful in the first few hours after stroke. CT signs of acute ischemia include blurring of the gray/white junction and effacement of the sulci due to ischemic swelling of the tissues. Blurring of the contours of the deep gray matter structures is of similar significance. In cases of internal carotid artery occlusion, middle cerebral artery main segment (M1) occlusion, or more distal occlusions, intraluminal clot may be seen as a focal hyperdensity, sometimes referred to as a hyperdense MCA, or hyperdense dot sign (Fig. 33A.29).

Fig. 33A.29 Evolving ischemic stroke in the territory of the left middle cerebral artery. On this noncontrast CT scan, a hyperdense signal is seen in the distal left internal carotid artery and in the M1 segment of the left middle cerebral artery, indicating presence of a blood clot (arrowheads). There is hypodensity in the corresponding area of the left hemisphere, demonstrating the evolving ischemic infarct.

Several MRI modalities as well as CT perfusion studies are capable of providing data regarding cerebral ischemia and perfusion to assist in the evaluation for possible thrombolytic therapy very early after symptom onset. DWI with ADC mapping is considered to be the most sensitive method for imaging acute ischemia (Figs. 33A.30 to 33A.33 [Figs. 33A.31, B; 33A.32, B; and 33A.33 available online only]). In humans, the hyperintense signal indicating restriction of diffusion is detected within minutes after onset (Hossmann and Hoehn-Berlage, 1995).

Fig. 33A.30 Acute ischemic stroke in the territory of the middle cerebral artery. A, On diffusion-weighted imaging, a hyperintense area of restricted diffusion is seen in the territory of the left middle cerebral artery. Note evolving mass effect on the sulci and left lateral ventricle and the mild midline shift. B, On apparent diffusion coefficient map, corresponding hypointensity is seen in the same area.

Fig. 33A.31 Acute ischemic stroke in the territory of the anterior cerebral artery. A, On diffusion-weighted imaging, a hyperintense area of restricted diffusion is seen in the right medial frontal lobe, involving the territory of the anterior cerebral artery. B, On apparent diffusion coefficient map, corresponding hypointensity is seen in the same area (for the image, see online version of this chapter).

Fig. 33A.32 Acute ischemic stroke in the territory of the posterior cerebral artery. A, On diffusion-weighted imaging, a hyperintense area of restricted diffusion is seen in the left medial occipital lobe, involving the territory of the posterior cerebral artery. B, On apparent diffusion coefficient map, corresponding hypointensity is seen in the same area (for the image, see online version of this chapter).

Fig. 33A.31 B, On apparent diffusion coefficient map, corresponding hypointensity is seen in the same area.

Fig. 33A.32 B, On apparent diffusion coefficient map, corresponding hypointensity is seen in the same area.

Fig. 33A.33 Acute ischemic stroke in the left anterior watershed area. On diffusion-weighted imaging, a hyperintense area of restricted diffusion is seen in the left frontal lobe, involving the watershed zone between the anterior and middle cerebral artery.

Temporal Evolution of Ischemic Stroke on Magnetic Resonance Imaging

Acute Stroke

Initially, the hyperintense signal on DWI is caused by decreased water diffusivity due to swelling of the ischemic nerve cells (for the first 5 to 7 days), then it increasingly results from the abnormal T2 properties of the infarcted tissue (T2 shine-through). For this reason, a reliable estimation of the age of the ischemic lesion is not possible by looking at DWI images alone. Imaging protocols for acute ischemic stroke usually include T1- and T2-weighted fast spin echo images, FLAIR sequences, and DWI with ADC maps. These sequences together confirm the diagnosis of ischemia, determine its extent, and allow for an approximate estimation of the time of onset (Srinivasan et al., 2006). On ADC maps, the values decrease initially after the onset of ischemia (i.e., the signal from the affected area becomes progressively more hypointense). This reaches a nadir at 3 to 5 days but remains significantly low until the seventh day after onset. After this time, the values increase (the signal gets more and more hyperintense) and return to the baseline values in 1 to 4 weeks (usually in 7 to 10 days). Therefore, ADC maps are quite useful for the estimation of the age of the lesion: if the signal of the area is hypointense on an ADC map, the lesion is likely less than 7 to 10 days old. If the area is isointense or hyperintense on the ADC map, the onset was likely more than 7 to 10 days ago. As already noted, although these signal changes take place on ADC maps, the DWI images remain hyperintense, without noticeable changes of intensity by visual inspection.

On T2-weighted (including FLAIR) images, the signal intensity of the ischemic area is normal in the initial hyperacute stage, increases markedly over the first 4 days, then becomes stable. In a research setting, computing the numerical values of hyperintensity in infarcted tissue on serial T2-weighted scans can demonstrate a consistent sharp signal increase after 36 hours, distinguishing lesions younger or older than 36 hours. This is certainly not possible by visual inspection used in clinical practice.

One purpose of MRI in the evaluation of acute stroke is to determine the extent of irreversible tissue damage and to identify tissue that is at risk but potentially salvageable. The combination of DWI and PWI is frequently used for this purpose (Fig. 33A.34). Evaluation is based on the premise that diffusion-weighted images delineate the tissue that suffered permanent damage (although in some cases, restricted diffusion is reversible, corresponding to ischemia without infarction), whereas areas without signal change on DWI but abnormal signal on perfusion-weighted images represent tissue at risk, the so-called ischemic penumbra. If there is a mismatch between the extent of DWI changes and perfusion deficits, the latter being larger, reperfusion treatment with intravenous or intraarterial thrombolysis or other intravascular techniques is justified to salvage the brain tissue at risk. If the extent of diffusion and perfusion abnormalities is similar or the same, the tissue is thought to be irreversibly injured, with no penumbra, and therefore the potential benefit from reperfusion treatment may not be high enough to justify the risk of hemorrhage associated with thrombolytic treatment.

Fig. 33A.34 Ischemic penumbra in acute right middle cerebral artery stroke. A, Diffusion-weighted image reveals a small, circumscribed area of restricted diffusion in the paraventricular region of the right centrum semiovale (arrow). B, Magnetic resonance perfusion-weighted image demonstrates a much larger perfusion deficit, as revealed by increased mean transit time, indicated in red. The perfusion deficit outside the small area of restricted diffusion represents the ischemic penumbra.

Chronic Ischemic Stroke (3 Weeks and Older)

Areas of complete tissue destruction with death not only of neurons but of glia and necrosis of other supporting tissues as well, will eventually appear as cavitary lesions filled with fluid that have signal characteristics identical to CSF: hyperintensity on T2-weighted images and marked hypointensity on T1 images and FLAIR sequences. The region of encephalomalacia is bordered by a glial scar (reactive gliosis) that is hyperintense on T2 and FLAIR images (Fig. 33A.35; Fig. 33A.35, B available online only). Although the initial signal changes on DWI frequently predict the final extent of tissue destruction, changes on DWI can also disappear, and the final size of tissue cavitation can be best determined on T1-weighted images, which should be part of every stroke follow-up imaging protocol. Tissue in the margins of the cavitary lesion, and often in other areas of the brain as well, may have undergone extensive neuronal loss resulting only in atrophy but not in signal intensity changes, even on T2-weighted images (partial infarction).

Fig. 33A.35 Chronic ischemic stroke. A, On FLAIR image, a large area of encephalomalacia is seen in the territory of the left middle cerebral artery. Hypointense CSF-like cavity is surrounded by hyperintense signal change in adjacent parenchyma, indicating gliosis. Note ex-vacuo enlargement of adjacent segment of left lateral ventricle. B, On noncontrast T1-weighted image, the cavity of encephalomalacia appears as CSF-like hypointensity. Areas of gliosis appear as faint zones of hypointensity (for the image, see online version of this chapter).

Fig. 33A.35 B, On noncontrast T1-weighted image, the cavity of encephalomalacia appears as CSF-like hypointensity. Areas of gliosis appear as faint zones of hypointensity.

Besides signal changes, chronic ischemic infarcts lead to secondary changes in the brain. Owing to the loss of tissue, ex vacuo enlargement of the adjacent CSF spaces (sulci and adjacent ventricular segments) occurs. Pathways that originate from or pass through the infarcted area undergo wallerian degeneration, which is seen as T2-hyperintense signal change along the course of these pathways (Fig. 33A.36). Later, the hyperintensity may resolve, but the loss of pathways may result in volume loss of the structures they pass through (e.g., cerebral peduncle, pons, medullary pyramid), noted as decreased cross-sectional area.

Fig. 33A.36 Wallerian degeneration. A, Coronal T2-weighted image demonstrates a chronic lacunar ischemic lesion in the right internal capsule (arrow). From here, a linear hyperintense signal change is seen extending caudally along the course of the degenerating corticospinal tract fibers, through the right cerebral peduncle into the pons (arrowheads). B-D, Serial T2-weighted axial images of the brainstem demonstrate the hyperintense signal of the degenerating fibers (arrows) in the right cerebral peduncle (B), right pontine tegmentum (C), and in the right medullary pyramid (D).

Watershed Ischemic Stroke

These ischemic lesions involve the border zones between the vascular territories of the major cerebral arteries. Superficial border zone infarcts are between different major branches of the circle of Willis (such as anterior watershed infarcts between the anterior and middle cerebral arteries (see Fig. 33A.33) and posterior watershed infarcts between the middle and posterior cerebral arteries). Deep border zone infarcts develop between the superficial and deep branches of a cerebral artery.

Watershed infarcts result from cerebral hypoperfusion that tends to damage the border zone regions. Bilateral, roughly symmetrical watershed infarcts are often due to hypotension, cardiac failure, or hypoxemia. In unilateral cases, one of these factors is usually coupled with arterial stenosis or occlusion. For this reason, MRA or CTA evaluation of the carotid and vertebral arteries for hemodynamically significant stenosis is also warranted.

Ischemic Stroke of Thromboembolic Origin

This stroke type results from occlusion of one or more major cerebral arteries or their branches. The occlusion may be due to in situ thrombus formation or embolization from a distant source. Emboli can be of cardiac origin, but they may also be the result of artery-to-artery embolization, commonly due to carotid or aortic arch atherosclerotic disease. Structural imaging studies are essential for the evaluation of potential embolic sources. Since embolic strokes usually involve major intracranial arteries and their branches, typical branch patterns can be identified with imaging. Interpretation of the branch pattern seen on imaging helps distinguish between strokes in the anterior (supplied by the internal carotid arteries) and posterior circulation (supplied by the vertebral and basilar arteries); imaging may also provide information regarding an embolic source. Unilateral anterior strokes often are due to embolization from the proximal internal carotid artery, a preferential site for atherosclerotic plaque formation. Likewise, unilateral embolic stroke in the posterior circulation necessitates evaluation of the vertebrobasilar system. It should be kept in mind that in case of the quite common anatomical variant of fetal origin of the posterior cerebral arteries (termed fetal PCA when they are predominantly fed by large posterior communicating arteries, which are variably present and arise from the internal carotids), posterior circulation stroke may result from embolization from the anterior circulation. Multiple, especially bilateral, cortical ischemic strokes almost always suggest an embolic origin. If the strokes are bilateral and/or involve both the anterior and posterior circulation, a more proximal embolic source such as the aortic arch or heart can be suspected. Reperfusion injury is a common phenomenon in embolism, and in this stroke type, hemorrhagic transformation of varying degree is often seen.

Lacunar Ischemic Stroke

Lacunar ischemic strokes constitute 20% to 25% of all strokes and are typically seen in patients with hypertension and diabetes. This stroke type is thought to be due to narrowing and in situ thrombosis of the small, deep-penetrating arteries such as the lenticulostriate arteries. The most common locations include basal ganglia, internal capsule, and thalamus. According to structural imaging criteria, their size is usually less than 15 mm in diameter. Acutely, lacunar infarctions may exhibit restricted diffusion if the resolution of the ADC map is high enough to differentiate such from background signal variation. Chronic lacunes have a smoothly rounded, well-defined appearance. The encephalomalacic core of chronic lacunar infarctions follows CSF signal on all pulse sequences, appearing markedly hyperintense on T2 and hypointense on both T1 and FLAIR. There is often a thin rim of hyperintense signal on FLAIR due to gliosis, which helps differentiate lacunes from large Virchow-Robin spaces (Fig. 33A.37).

Fig. 33A.37 Chronic lacunar ischemic stroke and microvascular ischemic changes in the hemispheric white matter. A, On axial FLAIR image, a small lacunar area of encephalomalacia is seen in the left corona radiata (arrow). It has hypointense CSF-like signal in its center and is surrounded by a rim of hyperintensity, indicating gliosis. In addition, there are extensive hyperintense signal changes in the hemispheric white matter. Some of these are confluent, close to the ventricular borders, others involve the external capsules or are scattered in other regions of the white matter. These lesions have the imaging appearance of microvascular ischemic changes. B, On noncontrast T1-weighted image, the lacunar stroke appears as a hypointense CSF-like cavity. Faint hypointense signal change appears in the zones of microvascular ischemia.

Venous Stroke

Venous stroke may follow the thrombosis of cerebral veins (cortical draining veins and the cerebral deep venous system) or of one or more intracranial venous sinuses. The pathogenesis of venous ischemia/stroke is fundamentally different from arterial strokes. Thrombosis of the efferent channels (veins or sinuses) causes elevation of venous pressure, leading to congestion/dilatation of upstream capillaries and venules. This results in interstitial edema, which makes the area of venous infarction/ischemia hyperintense on T2-weighted and FLAIR pulse sequences. Rupture of the vessels may occur, leading to the frequently observed hemorrhagic component of these lesions, best visualized on GRE images. Further changes depend on the severity and duration of venous occlusion. Often the congestion is brief or transient, and the ischemic tissue recovers. In these cases, the sometimes very prominent signal changes can resolve, and no residual deficits will remain. In more severe cases that progress to infarction, restriction of diffusion (hyperintense signal on DWI and hypointense signal on ADC maps) is a common finding due to cytotoxic edema. Cytotoxic and vasogenic edema also results in hypointense signal on T1-weighted images. The venous etiology of the stroke is suggested by the morphological appearance of the lesion. Its distribution does not follow an arterial branch pattern. The appearance of the hyperintense signal changes on T2-weighted images and FLAIR sequences is also different; oftentimes heterogeneous signal changes are noted within the venous infarction, consisting of a “curly cue” or “fudge-swirl” pattern. Tumor-like appearances are also possible.

In cases of ischemia/stroke that are suspected to be of venous origin, it is important to carefully evaluate the draining veins in the area, and the sinuses as well, to look for thrombosis. The normal flow voids on MRI may be absent, replaced in some cases by hyperintense signal changes on FLAIR or hyperdensities on CT that exhibit a tubular or curvilinear string-like morphology. However, the pattern and distribution of cortical draining veins is very variable, which makes it difficult to pinpoint abnormalities of individual veins. Sometimes there is a striking absence of visualizable draining veins. Conversely, in cases of sinus thrombosis, massive engorgement of the veins may be seen. Venous thrombosis frequently starts at the level of a draining vein. In these cases, MR venography (MRV) may be initially unremarkable. MRV will become abnormal only later when the thrombosis progresses to the venous sinuses. Suspected cases of venous stroke are often best evaluated with two modalities: conventional MRI or CT in conjunction with MRV or a CT venogram.

Microvascular Ischemic White Matter Lesions, “White Matter Disease,” Binswanger Disease

Diffuse or patchy T2-hyperintense signal changes in the deep hemispheric and subcortical white matter are probably the most common abnormal findings on MRI in the adult and elderly patient population. The terms microvascular ischemic changes or chronic small vessel disease are frequently used to describe these lesions on imaging studies. Their etiology and clinical significance have been debated extensively.

Certain hyperintense signal changes are considered normal incidental findings, with no clinical relevance. A uniformly thin, linear, T2 hyperintensity that has a smooth outer border along the border of the body of the lateral ventricles is often seen in the elderly population and likely represents fluid or gliotic changes in the subependymal zone. It tends to be more pronounced at the tips of the frontal horns (ependymitis granularis). This finding is thought potentially to be due to focal loss of the ependymal lining with gliosis and/or influx of interstitial fluid into these regions.

Patchy signal changes within the white matter of the cerebral hemispheres beyond a relatively low threshold (generally, one white matter hyperintensity per decade of life is felt to fall within the normal range) are pathological and are most commonly of ischemic origin. According to the most accepted hypothesis, these hyperintensities are the result of gradual narrowing or occlusion of the small vessels of the white matter, the diameters of which are less than 200 micrometers (hence the terms microvascular lesions or small vessel disease). Pathologically, these lesions are composed of focal demyelination and gliosis. The lumen of the involved vessels is narrow or occluded; their walls may exhibit arteriosclerotic changes and commonly amyloid deposits. On imaging studies, they have a chronic appearance, with diffuse borders and no surrounding edema or evidence of mass effect. They are generally associated with some degree of central atrophy, which tends to worsen with higher lesion loads. The distribution of these lesions changes only very gradually on serial scans, often showing minimal to no significant difference on studies spaced several years apart.

While age by itself can cause such changes, and the incidence of these lesions increases with age in people 40 years or older, there are several other risk factors that can make them more numerous. These include hypertension, diabetes, hypercholesterolemia, and smoking. Indeed, patients with these medical problems are more likely to have an elevated number of ischemic white matter lesions.

Chronic ischemic white matter lesions are hypodense on CT, but MRI is much more sensitive and reveals more extensive lesions (Fig. 33A.38; Fig. 33A.38, B-C available online only). On MRI, the lesions are hyperintense on T2 and FLAIR sequences. They may or not be visible as T1 hypointensities. It is possible that only lesions visible on T1-weighted images may be clinically significant. Common locations are the periventricular (PV) and more commonly, the deep white matter, but subcortical lesions are also common, with sparing of the U-fibers. The lesions can be isolated, scattered, or more confluent, especially in the PV zone. Morphologically, individual lesions generally exhibit indistinct borders with a diffuse “cotton-wool” appearance and range in size from punctate to small. Regions of confluent lesions may appear large and more commonly affect the deep white matter anterior and posterior to the bodies of the lateral ventricles, symmetrically within the parietal and frontal lobes. Deep white matter lesions also often occur in a distribution parallel to the bodies of the lateral ventricles on axial views, with an irregular band-like or “beads-on-string” appearance often separated from the PV lesions by an intervening band of relatively unaffected white matter. Involvement of the external capsules is also characteristic. These patterns of lesion distribution and morphology are often best seen on FLAIR. Contrary to the lesions of multiple sclerosis (MS), microvascular ischemia tends not to involve the temporal lobes or the corpus callosum. Besides the hemispheric white matter, microvascular ischemic lesions often also involve the basis pontis.

Fig. 33A.38 Microvascular ischemic white matter changes. A, Axial FLAIR image reveals extensive hyperintense areas in the hemispheric white matter bilaterally. Some are confluent at the borders of the ventricles, others are scattered in other regions. Note the “band” of hyperintensity in the left hemisphere parallel to the border of the lateral ventricle. B-C, On axial FLAIR and T2-weighted images, faint hyperintense signal changes are seen in the pontine tegmentum bilaterally, exhibiting the typical imaging appearance of microvascular ischemia (arrows) (for images, see online version of this chapter).

Fig. 33A.38B-C Microvascular ischemic white matter changes. B-C, on axial FLAIR and T2-weighted images, faint hyperintense signal changes are seen in the pontine tegmentum bilaterally, exhibiting the typical imaging appearance of microvascular ischemia (arrows).

The clinical significance of ischemic white matter lesions depends on their extent and location. The presence of a few small, scattered, ischemic white matter lesions on T2-weighted images is clinically meaningless, and these are usually considered a normal imaging manifestation of aging. Patients may feel more comfortable with descriptions such as “age spots of the brain” to convey their benign nature when verbally discussing results. More extensive lesions also visible on T1-weighted sequences, however, are more likely to be associated with neurological abnormalities such as abnormal gait, dementia, and incontinence. In ischemic arteriolar encephalopathy or Binswanger disease, there is pronounced, widely distributed, and confluent PV and deep white matter signal change. In more severe cases, the confluent hyperintensity also involves the internal and external capsules or subcortical white matter. Besides confluent lesions, coexisting multiple scattered T2 hyperintensities are also very common. Ischemic white matter lesions are often intermixed with lacunar ischemic strokes and generalized cerebral volume loss is also frequently noted.

Scattered small, nonspecific-appearing, seemingly microvascular white matter hyperintensities have a broader differential diagnosis in the younger patient population. Multiple small T2 hyperintense lesions in the hemispheric white matter can be caused by migraine, trauma, inborn errors of metabolism, vasculitis (including Sjögren syndrome, lupus, Behçet disease, and primary CNS vasculitis), Lyme disease, and MS. Since the MRI appearance of these is nonspecific, clinical correlation is always warranted. In many instances, these white matter lesions are idiopathic, and future serial imaging studies are needed for follow-up.

Cadasil

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant inherited vascular disease. Pathologically there is destruction of the smooth muscle cells in the small and medium-sized penetrating arteries, with deposition of osmiophilic material and fibrosis leading to progressive thickening of the arterial wall and narrowing of the lumen. As a result, leukoencephalopathy and multiple ischemic strokes occur. Over 90% of patients have detectable mutations of the NOTCH3 gene, which encodes a transmembrane receptor primarily expressed in arterial smooth muscle cells. On MRI, multiple focal infarcts and T2-hyperintense white matter lesions are seen. The white matter lesions may involve the external capsules and, very characteristically, the anterior temporal lobe white matter in a confluent fashion that includes the subcortical arcuate fibers (Fig. 33A.39). This latter finding is helpful for the structural imaging diagnosis and helps distinguish CADASIL from “sporadic” ischemic arteriosclerotic vascular disease.

Fig. 33A.39 CADASIL. A-C, Axial FLAIR images demonstrate diffuse, confluent hyperintense signal changes in the deep and subcortical white matter. Multiple chronic lacunar infarcts are also seen bilaterally (arrowheads). Note characteristic confluent hyperintensity (arrows) in the anterior temporal lobe white matter (C), involving the subcortical fibers as well.

Cerebral Venous Sinus Thrombosis

Acute cerebral venous sinus thrombosis results in diminished or absent flow in the involved sinuses. Cerebral venous sinus thrombosis usually causes typical signal changes on MRI (Fig. 33A.40) and severely attenuated or absent flow signal on magnetic resonance venography (MRV). MRV techniques include flow-sensitive modalities such as 2D time of flight and phase contrast imaging, as well as postcontrast high-resolution 3D-SPGR, which offers excellent visualization of the sinuses with a very high spatial resolution and contrast-to-noise ratio.

Fig. 33A.40 Left transverse and sigmoid sinus thrombosis with a small left temporal lobe area of venous ischemia. This 48-year-old patient presented with a new-onset seizure and right visual field deficit that resolved later. A, Axial FLAIR image reveals abnormal hyperintense signal in the left transverse and sigmoid sinus, indicating thrombosis. Compare to the right transverse sinus, with the normal hypointense flow void. This FLAIR image also shows a small but noticeable area of hyperintensity due to venous ischemia in the left temporal lobe. B, Noncontrast T1-weighted image also reveals abnormal hyperintense signal in the involved venous sinuses. Again, compare with the contralateral sinus. C, Postcontrast T1-weighted image reveals normal filling in the sinus on the right, but there is no filling along the visualized segment of the left transverse sinus (arrowheads).

In the appropriate clinical context, a useful sign of venous sinus thrombosis is the absence of a normal hypointense flow void in the involved sinuses on T1- and T2-weighted images and absent flow in the involved sinus on MRV. Nonflowing blood generally results in increased signal intensity on T1 and T2. In the early acute stage, however, the sinuses may still be hypointense. This is followed by signal that is isointense to the gray matter. The typical hyperintense signal on T1- and T2-weighted images appears when methemoglobin is present in the clot. At all stages, therefore, simultaneous review of the MRV or CT angiogram for lack of flow signal and lack of contrast filling in conjunction with conventional MRI may be particularly useful to increase the sensitivity and specificity of detection of sinus thrombosis while also adding information regarding the age of the clot.

Following administration of gadolinium, there may be enhancement of the dural wall of the sinus and along the periphery of the clot, but not within the clot itself, resulting in an “empty delta” appearance. This is classically a CT finding, but the same concept also applies to MRI in the context of the T1-weighted clot signal that varies with clot age. MR demonstrates lack of flow, appearing as absence of contrast-related signal in the involved sinuses. CT angiogram reveals no contrast filling in the thrombosed sinuses. The cortical veins that drain into the involved sinuses may appear engorged on MRV. However, if the thrombosis also involves these draining veins, they too may exhibit lack of signal on MRV, lack of filling on CT angiogram, and lack of flow voids in conjunction with iso- or hyperintense signal on T1- and T2-weighted images.

Variations in the speed of blood flow and anatomical variants of the venous sinuses may change their usual signal characteristics, leading to a false diagnosis of venous sinus thrombosis. Slow flow in a venous sinus may cause increased signal on T1- and T2-weighted images, potentially leading to a false assumption of thrombosis. Gadolinium-enhanced images help in these cases, demonstrating contrast filling/enhancement in the sinuses and confirming the absence of thrombosis. A normal variant of venous sinus hypoplasia/aplasia may result in decreased/absent flow signal on MRV, falsely interpreted as thrombosis. T1- and T2-weighted images, however, are usually able to demonstrate the absence of thrombus in the sinus. These examples highlight the importance of reviewing all necessary image modalities (MRV, T2-weighted images, T1-weighted images with and without contrast) to make or reject a diagnosis of venous sinus thrombosis.

Hyperacute Hemorrhage (0 to 24 Hours)

In the early (hyperacute) phase of intraparenchymal hemorrhage (<24 hours) the red blood cells are intact, and a mixture of oxy- and deoxyhemoglobin is present (Bakshi et al., 1998). In this stage, the signal on T1-weighted images is isointense to the brain, so even larger hematomas may be missed on this pulse sequence. On T2-weighted images, the oxyhemoglobin portion is hyperintense and deoxyhemoglobin is hypointense, resulting in the gradual appearance of a hypointense rim and gradually increasing hypointense foci within the hematoma as the amount of deoxyhemoglobin increases from the periphery. Such hypointense foci are also seen on FLAIR. Between the clot and the deoxyhemoglobin-containing rim, thin intervening clefts of fluid-like T2 hyperintensity may be seen as an initial manifestation of clot retraction. On gradient echo images, hyperacute hemorrhage will exhibit heterogeneously isointense to markedly hypointense signal, the latter corresponding to deoxyhemoglobin content in more peripheral portions of the clot. The amount of edema is mild in this stage, usually seen as a thin rim that is hyperintense on T2 and FLAIR images and hypointense on T1-weighted images (Atlas and Thulborn, 1998).

Acute Hemorrhage (1 to 3 Days)

During this stage, hemoglobin is transformed to deoxyhemoglobin, but the membranes of the erythrocytes are still intact (Bakshi et al., 1998). The hematoma becomes slightly hypointense on T1 and strikingly hypointense on T2-weighted images (Fig. 33A.41). On GRE, proton spins in the presence of paramagnetic deoxyhemoglobin dephase rapidly during TE, resulting in signal loss and, therefore, hypointensity of the hematoma on this pulse sequence. The surrounding edema, which is more extensive during this stage, is hypointense on T1 and hyperintense on T2.

Fig. 33A.41 Two cases of acute parenchymal hemorrhage. A-B, Large acute left basal ganglia hemorrhage. On noncontrast T1-weighted image (A) only faint hypointensity is noted. On axial T2-weighted image (B) the hematoma appears as a striking hypointensity with developing hyperintense edema in surrounding parenchyma. Note associated mass effect. C-D, In this case, the basal ganglia hematoma is in a more advanced stage. On T1-weighted image (C) the area is still mostly hypointense, but its center is now turning hyperintense because of intracellular methemoglobin (arrowheads). On corresponding T2-weighted image (D) the hematoma is still hypointense (as extracellular methemoglobin is also hypointense on T2), but the surrounding hyperintense edema is more prominent, and the mass effect is increased as well. Note that hemorrhage is also present within the ventricle, making the prognosis worse (arrows).

Early Subacute Hemorrhage (3 Days to 1 Week)

As blood degradation evolves, deoxyhemoglobin is converted to methemoglobin. At this stage, the blood degradation products are still intracellular (Bakshi et al., 1998). Intracellular methemoglobin is hyperintense on T1 and hypointense on T2-weighted images. T1 shortening is primarily the result of dipole-dipole interactions between heme iron and adjacent water protons, facilitated by a conformational change that occurs when deoxyhemoglobin is converted to methemoglobin.

Signal changes on T2 occur via a different mechanism. Sequestration of methemoglobin within the intact red blood cell membrane results in a locally paramagnetic environment adjacent to the diamagnetic, methemoglobin-free extracellular compartment. These differences in the local magnetic fields, present at a microscopic level, cause rapid dephasing of proton spins and signal loss during TE as water molecules diffuse rapidly through this heterogeneous environment. Therefore, on T2-weighted images the presence of intracellular methemoglobin results in hypointensity of the hemorrhage. These signal changes start from the periphery of the hematoma where the deoxyhemoglobin-to-methemoglobin transformation first occurs. During this stage, the amount of edema starts to decrease.

Late Subacute Hemorrhage (1 to 4 Weeks)

In the late subacute phase, the membranes of the red blood cells disintegrate, and methemoglobin becomes extracellular (Bakshi et al., 1998). Extracellular methemoglobin contains Fe³⁺, which has five unpaired electrons. This leads to a dipole-dipole interaction which, contrary to intracellular methemoglobin, causes hyperintense signal change on both T1- and T2-weighted images (Fig. 33A.42).

Fig. 33A.42 Late subacute parenchymal hemorrhage. A, On noncontrast T1-weighted image, there is a hematoma in the right corona radiata. This exhibits homogeneous hyperintense signal. B, On T2-weighted image, the hematoma also appears as homogeneous hyperintensity. Signal characteristics are typical for the presence of extracellular methemoglobin in a late subacute hematoma. Note beginning of hypointense hemosiderin deposition at the rim of the hematoma on T2-weighted image (arrowheads).

During this stage (usually 2 weeks after the hemorrhage) hemosiderin deposition begins, typically at the periphery of the hematoma where macrophages reside. A dark peripheral rim appears on GRE and T2-weighted images, initially thin, then progressively thicker. The amount of edema around the hematoma continues to decrease gradually.

Chronic Hemorrhage (>4 Weeks)

In the chronic stage (Bakshi et al., 1998), the core of larger hematomas turns into a slitlike or linear cavity with CSF signal characteristics, being hypointense on T1 and FLAIR and hyperintense on T2-weighted images. At the periphery of the lesion, macrophages continue to remove iron from the extracellular methemoglobin; hemosiderin and ferritin are deposited in their lysosomes, resulting in a rim of hypointense signal on T2-weighted and GRE images. This hypointense rim becomes progressively more prominent during the transition from the late subacute to chronic stage (Fig. 33A.43).

Fig. 33A.43 Chronic parenchymal hemorrhage. A, Axial T2-weighted image reveals a slitlike cavitary lesion in the left parietal lobe. Its center has CSF-like hyperintense signal, but there is a rim of hypointensity due to hemosiderin deposition along its border (arrowheads). B, Axial gradient echo image reveals markedly hypointense hemosiderin deposition along the border of the chronic hemorrhage.

If the hemorrhage is small, eventually its entire area will be occupied by hemosiderin deposition. Smaller hemorrhages or microbleeds, such as those seen in amyloid angiopathy or after head trauma, are visualized as multiple uniformly hypointense foci on GRE images. Susceptibility-weighted images are even more sensitive to magnetic filed distortion due to blood products and can reveal microbleeds that are missed even by conventional gradient echo images. It is important to keep in mind that because of magnetic field distortion, the area of hypointensity on GRE or susceptibility-weighted images is larger than the actual size of the bleed. GRE or, ideally, SWI should be part of every MRI protocol for brain trauma.

Hemorrhage, like many other lesions to the brain, provokes reactive gliosis. In the chronic stage, surrounding gliosis is seen as mildly hyperintense signal on T2 and FLAIR images.

Superficial siderosis, a chronic sequela of bleeding into the subarachnoid space, and cerebral amyloid angiopathy, a hemorrhage-prone condition, are discussed in the online version of this book. Please visit www.expertconsult.com for more information.

Bacterial Meningitis

In the typical uncomplicated form of bacterial meningitis, no abnormalities are seen in the brain parenchyma, and without contrast administration, the meninges may also appear unremarkable. With gadolinium, however, intense meningeal enhancement is seen, usually over the convexities and along the basal cisterns; this is due to vascular engorgement and increased vascular permeability secondary to the inflammatory process. At times, as a complication, ventriculitis may develop, and then the ependymal lining of the ventricles also exhibits enhancement.

Cerebritis, Abscess

Cerebritis and abscess can arise as complications of bacterial meningitis, but they may also spread to the brain hematogenously from another source such as endocarditis or pulmonary abscess. Cerebritis and abscess refer to different stages of the parenchymal infection. In the cerebritis stage, the lesion has poorly defined hyperintensity on T2 and FLAIR sequences and is iso- to hypointense on T1-weighted images. Foci of necrosis may be present. There is surrounding edema, appearing as hypointensity on T1 and hyperintensity on T2 and FLAIR. With gadolinium, a heterogenous irregular enhancement pattern may or may not be present.

If the process continues to cerebral abscess formation, after an average of 2 weeks, the core appears more demarcated, and fibrotic capsule formation is noted. The center of the abscess contains liquefied, necrotic, and purulent material. This is usually hypointense on T1 (but may appear more hyperintense, depending on the protein content) and hyperintense on T2. The rim is iso- to hypointense on T1 and iso- to hypointense on T2. Often the T2 hypointense rim is well seen, separating the hyperintense core from the usually less hyperintense surrounding edema. With gadolinium, the capsule exhibits ring enhancement, which is typically a smooth, thin, complete ring. Sometimes the deeper segment of the enhancing ring is thinner than the superficial. A characteristic feature that supports the diagnosis of abscess is the so-called daughter abscess, which is seen as a smaller ring-enhancing lesion connected to the parent abscess.

Cerebral abscesses are part of the differential diagnosis when ring-enhancing cerebral lesions are encountered. Besides the described ring morphology and the potential presence of daughter abscesses, cerebral abscesses exhibit restriction of diffusion centrally, appearing as hyperintense signal on diffusion-weighted images and hypointensity on ADC maps, which distinguishes them from metastatic and most primary brain tumors (Fig. 33A.45).

Fig. 33A.45 Cerebral abscess. A, Axial FLAIR image shows a round lesion in the deep left frontal lobe, surrounded by a hypointense rim (arrowheads). Hyperintense edema in adjacent parenchyma extends to various white matter regions. B, Axial T1-weighted postcontrast image shows complete ring enhancement in the capsule of the abscess (arrowheads). Diffuse parenchymal enhancement is noted in the brain medial to the abscess, likely due to cerebritis (arrow). C, Abscess cavity is characteristically hyperintense on diffusion-weighted images (arrow).

Cns Tuberculosis

Tuberculosis may involve the brain parenchyma in the form of tuberculomas, cerebritis, or cerebral abscess. Tuberculomas are isointense on T1; the T2 appearance is variable. At times a mildly T1 hyperintense and T2 hypointense rim is seen around them. Tuberculomas exhibit solid or ring enhancement and, similar to tuberculosis related abscesses, enhance intensely; in cases of ring enhancement, it is usually thicker and more irregular than seen with pyogenic abscesses. In chronic tuberculomas, areas of calcification are sometimes noted. Tuberculous meningitis is another frequent occurrence in this disease, diffusely abnormal meningeal enhancement being most intense along the basal meninges; distinct nodules may also be noted. Ventriculitis with ependymal enhancement is also possible. Tuberculosis-related vasculitis may complicate the disease, causing infarctions of various sizes.

Lyme Disease

In the brain parenchyma, Lyme encephalitis may cause multiple lesions that are slightly hypointense on T1 and hyperintense on T2-weighted images. The most common locations are the subcortical and periventricular white matter, but the thalamus, corpus callosum, and pons may be involved as well. The lesions appear nonspecific, their size ranging from a few millimeters to a centimeter. Vasculitis, demyelinating disease, and microvascular ischemia are frequent differential diagnostic considerations. If present, abnormal enhancement along the meninges and cranial nerve segments may indicate involvement of these structures by Lyme disease.

Cysticercosis

Among the parasitic infections of the CNS, cysticercosis is the most common. It is caused by the larval form of Taenia solium. The infection may involve the parenchyma, but meningeal, subarachnoid, and intraventricular locations are also common. The lesions are usually cystic, and the cysts often exhibit a T1 hyperintense central scolex. Intraparenchymal cysts are common at the gray/white junction, their size ranging from millimeters to a few centimeters. The cyst itself is of variable signal intensity, hypo- to hyperintense on T1 and iso- to hyperintense on T2. The cyst and its leaking contents provoke an inflammatory reaction in the surrounding parenchyma, resulting in edema and later gliosis, both appearing as T2 hyperintensity. With gadolinium, the amount of enhancement depends on the degree of inflammatory reaction. As the larva dies, the cystic lesion usually retracts, and at the chronic stage there is calcification without contrast enhancement.

Herpes Simplex Encephalitis

In adults, herpes encephalitis is caused by herpes simplex virus type 1. The imaging diagnosis is suggested by the location of the lesions. Herpes encephalitis typically involves the medial temporal and limbic frontal regions, including the basal frontal and cingulate gyri and insula. The cerebral cortex is more affected than the white matter. Herpes simplex encephalitis is usually hyperintense on T2 and FLAIR images and mildly hypointense on T1-weighted images (Fig. 33A.46). The encephalitis is frequently hemorrhagic, causing additional signal changes depending on the age of the hemorrhage. Areas of necrosis may be seen as well. Typically, a few days after onset, variable patterns of enhancement may be seen (gyriform, nodular, leptomeningeal, or intravascular). In the chronic stage, varying degrees of encephalomalacia, atrophy, calcification, and gliosis are seen in the affected lobes. Early successful treatment may minimize such sequelae.

Fig. 33A.46 Two cases of herpes simplex encephalitis. A-B, This 68-year-old woman presented with subacute-onset semantic aphasia. Axial and coronal FLAIR images show hyperintense signal involving the left medial temporal lobe and part of the insula (arrows). Involved structures also demonstrate swelling. C-D, In a different patient, even more prominent temporal lobe involvement is seen. On a noncontrast T1-weighted image (C) the left temporal lobe is swollen, and parts of the cortex show faint hyperintensity, indicating potential hemorrhage (arrows). On the postcontrast T1-weighted image (D) gyriform enhancement is seen (arrows).

Human Immunodeficiency Virus Encephalitis

Human immunodeficiency virus (HIV) can affect the brain directly, causing a progressive encephalitis (formerly called AIDS dementia complex), or indirectly by making the host susceptible to opportunistic infections (cerebral toxoplasmosis, progressive multifocal leukoencephalopathy (PML), cytomegalovirus) and certain malignancies (lymphoma) that involve the CNS. HIV encephalitis microscopically appears as microglial nodules and multinucleated giant cells, with demyelination and vacuole formation. The demyelination is seen as hyperintense signal change on T2 and FLAIR images, usually starting in the PV white matter and centrum semiovale. Later the lesions become progressively more diffuse and confluent. Eventually, basal ganglionic and thalamic involvement is also seen. Along with these changes, prominent cerebral atrophy develops, with progressive enlargement of the central and superficial CSF spaces (Fig. 33A.47).

Fig. 33A.47 Human immunodeficiency virus (HIV) encephalopathy. This is a 39-year-old patient with advanced HIV. Axial FLAIR image demonstrates cerebral volume loss and confluent hyperintense demyelination of the white matter in the centrum semiovale and subcortical regions bilaterally.

Cerebral Toxoplasmosis

Toxoplasmosis lesions are usually multifocal and may involve the basal ganglia, thalamus, gray/white junction, cerebral cortex, and PV white matter. The lesions are iso- to hypointense on T1 and hyperintense on T2-weighted images. A significant amount of edema surrounds the lesions, appearing as T1 hypointensity and T2 hyperintensity. With gadolinium, the smaller lesions enhance homogenously, and the larger ones exhibit ring or nodular enhancement. After antibiotic treatment, chronic lesions frequently show calcification and hemosiderin deposits.

In an HIV patient with cerebral lesions, the most common differential diagnostic consideration is lymphoma. The imaging appearance of HIV-related lymphoma is different from that seen in an immunocompetent host (see the brain tumor section of this chapter for details). Functional imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT) may be used to differentiate between lymphoma and toxoplasmosis or other infectious lesions in HIV-positive patients (Heald et al., 1996).

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy is an infectious demyelinating disease caused by the JC polyomavirus. It has been most common in HIV patients, but it is now also a well-known potential complication of natalizumab infusions for MS. The disease initially involves the white matter, most commonly in the frontal, parietal, and occipital lobes. The lesions are hypointense on T1, hyperintense on T2 and FLAIR, usually multifocal, and are initially round or oval then become confluent. They tend to involve the subcortical white matter, including the U-fibers, with later involvement of the deep gray matter, corpus callosum, and posterior fossa. With gadolinium administration, faint enhancement may be present, but usually no enhancement is seen. DWI often reveals restricted diffusion at the spreading outer margins of PML lesions relative to the typically high ADC values within the gliotic and demyelinated central portions, which assists in the differential diagnosis (da Pozzo et al., 2006).

Cytomegalovirus

Imaging findings in CNS cytomegalovirus infections are common but oftentimes nonspecific. On MRI, patchy, sometimes confluent T2 hyperintense signal changes are seen in the white matter in both PV and subcortical locations. Meningitis and ependymal involvement are also possible, seen as enhancement of these structures after gadolinium administration. Cerebral atrophy is often noted.

Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease is a rapidly progressing, fatal dementing illness caused by prions—self-replicating, infectious protein particles. In advanced cases, MRI usually reveals prominent atrophy and gray-matter hyperintense signal changes on T2 and FLAIR sequences. The hyperintensity typically involves the cerebral cortex, basal ganglia, and cerebellum. There is no mass effect, and enhancement is rare. In the early stage of the disease, conventional T2-weighted images may be entirely normal, but diffusion-weighted images may show ribbonlike hyperintensity along the cerebral cortex (Fig. 33A.48), commonly involving the insula and cingulate cortex. Hyperintensity may be also seen in the caudate nucleus, lentiform nucleus, and in the thalamus as well, in a nonvascular distribution. Involvement of the pulvinar is characteristic of the mad-cow variant. Cerebellar cortical involvement is also common. The abnormalities may be uni- or bilateral. FLAIR sequences have been known to display these abnormalities earlier than conventional T2-weighted images, but not as conspicuously as DWI (Shiga et al., 2004; Young et al., 2005).

Fig. 33A.48 Creutzfeldt-Jakob disease. A-B, This 47-year-old patient presented with rapid cognitive decline, unsteady gait, and myoclonus. Diffusion-weighted images demonstrate hyperintense signal that characteristically involves the cortical ribbon of the frontal and parietal lobes, more so on the left side, and the insula. Hyperintense signal change is also seen in the thalamus bilaterally.

Multiple Sclerosis

Multiple sclerosis is a demyelinating disease with autoimmune inflammatory reaction against the myelin sheath of CNS pathways (see Chapter 54). MRI is essential for the diagnosis of MS by demonstrating the typical inflammatory demyelinating lesions disseminated in time and space (Fig. 33A.49). It is also used for disease monitoring and assessment of response to therapy.

Fig. 33A.49 Multiple sclerosis. A-C, Axial and sagittal FLAIR images demonstrate multiple hyperintense lesions in the white matter. The majority of these abut the lateral ventricles, including the temporal horns bilaterally. Several lesions are linear and oriented perpendicular to ventricular borders. On sagittal FLAIR image (C) some lesions exhibit characteristic Dawson fingerlike appearance. D, On midsagittal FLAIR image, lesions are present in the corpus callosum (arrowheads). E, On T1-weighted noncontrast image, two prominently hypointense lesions exhibit a “black hole” appearance (arrows). F-G, Axial T1 postcontrast images demonstrate two enhancing lesions. One is a small, homogeneously enhancing lesion in the left centrum semiovale (arrow), the other is seen in the left parietal subcortical area (arrow). This latter lesion exhibits an “open-ring” enhancement pattern which is very typical for active demyelinating lesions.

MS white matter lesions may occur supratentorially or infratentorially, as well as within the spinal cord (imaging of spinal cord MS lesions is described later). Best evaluated on T2-weighted images, infratentorial lesions may be seen within the medulla, pons, midbrain, or cerebellum. Characteristic locations include the pontine tegmentum, periaqueductal region, cerebral peduncles, middle and superior cerebellar peduncles, and the white matter of the cerebellar hemispheres. Punctate or small lesions that are present directly adjacent to the fourth ventricle or cisterns are sometimes difficult to detect on T2-weighted images but are not uncommon. Infratentorial lesions are generally smaller than supratentorial lesions and are also less frequently hypointense on conventional T1-weighted images; they commonly appear hypointense on T1-weighted 3D spoiled gradient echo pulse sequences.

Supratentorial white matter lesions are usually best appreciated using the FLAIR pulse sequence, which nulls out CSF signal that may obscure periventricular abnormalities on conventional T2-weighted images. PV and subcortical white matter lesions typically are small in size and morphologically are generally ovoid or round on axial images. On sagittal views, PV lesions often exhibit a thin linear or fingerlike morphology (Dawson fingers), with the long axis of the lesion oriented perpendicularly to the wall of the lateral ventricle in a PV distribution. The PV distribution of many MS lesions is well demonstrated on SWI imaging, which reveals a single tiny, profoundly hypointense dot or thin linearity at the center of a significant proportion of demyelinating lesions. It represents a venule and is visible because of the magnetic susceptibility effects of deoxygenated venous blood, to which SWI is particularly sensitive.

Although the distribution of white matter lesions in MS has a somewhat random appearance, the hemispheres characteristically match each other in terms of lesion load, which typically is highest around the ventricles. On sagittal views, PV lesions are usually most numerous adjacent to the bodies and atria of the lateral ventricles, with less involvement of the white matter adjacent to the occipital and temporal horns. The deep white matter of the frontal and parietal lobes typically also tends to exhibit a greater number of lesions than either the occipital or temporal lobes. However, the presence of lesions adjacent to the temporal horns favors a diagnosis of MS. Juxtacortical demyelination is less commonly seen. Juxtacortical lesions, which involve the U-fibers, often exhibit a crescentic morphology and are usually seen only on FLAIR, proton density, or T2-weighted images. Occasionally they are hypointense on T1 as well. When present, this type of lesion favors the diagnosis of MS. Corpus callosum lesions are also relatively specific for MS. They are best visualized on sagittal FLAIR images, typically as punctate hyperintensities along the septocallosal margin (undersurface of the corpus callosum). Thin hyperintense linearities that are contiguous with and perpendicular to the undersurface may also be present. These findings are often superimposed upon a thin irregular band of T2 hyperintensity running along the undersurface of the corpus callosum rostrocaudally. Isolated lesions within the central fibers of the corpus callosum that are noncontiguous with the septocallosal margin are less typical and should raise the level of suspicion for alternate differential diagnoses, discussed in the following section.

Although it is well known from histopathological studies that MS affects not only the hemispheric white matter but also the cortex and deep gray nuclei, cortical gray matter lesions are uncommonly seen on conventional MRI studies. They may be seen more often with the use of high-field scanners (3.0 T or higher). Of the conventional pulse sequences, high spatial resolution FLAIR images are the most sensitive for cortical gray matter lesions. Detection is limited because the subtle hyperintensity of cortical lesions on FLAIR is only slightly greater than the already relatively hyperintense background of the cortical gray matter. A cortical gray matter lesion may be verified by correlation of the finding on separate FLAIR image stacks acquired in orthogonal planes or by detection of a hypointense lesion of identical morphology and location on T1-weighted 3D spoiled gradient echo pulse sequences. Cortical gray matter lesions generally have a curvilinear contour that conforms to the topology of the cortex but may also overlap with the adjacent white matter. Like deep gray-matter lesions, cortical gray-matter hyperintensities visible on MRI are usually small, in the millimeter range. Deep gray-matter MS lesions tend to be round or oval and are most frequently seen in the thalami.

T1-weighted images are useful for the detection of “black holes,” markedly hypointense lesions that have been shown histopathologically to exhibit more extensive demyelination and axonal loss than other lesions. They always exhibit a correlating hyperintensity on T2-weighted images but may appear centrally hypointense on FLAIR owing to their relatively high free water content. Conversely, not all T2-weighted lesions exhibit T1 hypointensity, and therefore the T1 lesion load is always less extensive than the T2 lesion load. Some MS cases, usually earlier in disease progression, exhibit no T1 hypointense lesions.

T1-weighted postcontrast images are useful for the detection of enhancing lesions in patients with clinical exacerbations. Enhancement may be solid or ringlike. Open-ring configurations are more typical for MS than other disease entities that also exhibit ring enhancement, such as tumors and infections (Masdeu et al., 2000). Five minutes between gadolinium injection and the acquisition of postcontrast images is the minimum acceptable delay for detecting acute demyelinating lesions, but longer delays of up to 30 minutes can significantly increase sensitivity, as can incorporation of magnetization transfer techniques and double or triple doses of gadolinium.

Chronic MS lesions do not exhibit restricted diffusion, appearing on DWI as either isointense to the surrounding brain parenchyma or, less commonly, hyperintense due to T2 shine-through artifact. On the corresponding ADC maps, chronic lesions exhibit normal or high apparent diffusion coefficients. However, as recently described, acute enhancing demyelinating lesions may on rare occasions exhibit high signal on DWI, with corresponding low pixel values (hypointense) on the ADC map, consistent with restricted diffusion (Balashov et al., 2009). Rapid resolution of restricted diffusion in these acute lesions is the rule, and they often evolve to exhibit increased ADC values on follow-up studies.

Nonconventional MRI pulse sequences are commonly used to assess MS in the research environment. SWI is a newer technique that is exquisitely sensitive to the small venules as well as iron deposition, the latter thought to play a pathophysiological role in MS. Magnetization transfer imaging may be used to generate histograms of pixel values within the normal-appearing white matter; such histograms are typically shifted to the left, with lower peak values than in normal individuals. Diffusion tensor imaging is a more advanced application of DWI that is used to measure the directional diffusion of water molecules within white matter tracts. Like magnetization transfer imaging, DTI is useful for the quantification of pathology within normal-appearing white matter.

Inflammatory and Noninflammatory Lesions of the Corpus Callosum

In general neurological practice, the most commonly seen corpus callosum lesions are secondary to MS. FLAIR pulse sequences in the sagittal and axial planes are generally sufficient to assess corpus callosum pathology, although coronal views are also quite helpful. Isolated T2-hyperintense lesions within the central fibers of the genu, body, or splenium of the corpus callosum that are noncontiguous with the septocallosal margin are an uncommon finding. If such lesions exhibit a punctate or “snowball-like” appearance on sagittal views, Susac syndrome should be considered (see Chapter 15). Other small-vessel vasculitides can also result in small or punctate lesions within the corpus callosum.

An isolated medium-sized, bilaterally symmetrical lesion within the central fibers of the splenium that often also exhibits restricted diffusion is a transient finding in epilepsy (Polster et al., 2001) or metabolic encephalopathy (Takanashi et al., 2006). If patchy white-matter T2-hyperintensities are present in conjunction with a reversible splenial lesion, CNS lupus should be considered. When accompanied by multiple acute-appearing white and gray matter lesions, ADEM is more likely, and the corpus callosum lesion in this case is more likely to evolve to a chronic appearance. A T2-hyperintense lesion involving most of the central fibers of the splenium while sparing the periphery is typical of Marchiafava-Bignami disease; its typical morphology is best demonstrated on sagittal views.

The differential diagnosis (Uchino et al., 2006) for an isolated corpus callosum lesion also includes low-grade neoplasm if there is little to no mass effect and absent enhancement. If enhancement or mass effect is present, high-grade malignancies with a predilection for the corpus callosum (e.g., glioblastoma, primary CNS lymphoma), as well as metastases, are differential diagnostic considerations. Focal atrophy of the corpus callosum with overlapping T2-hyperintensity, contiguous with or near a region of cerebral hemispheric encephalomalacia and gliosis, is suggestive of wallerian degeneration. Diffuse axonal injury may also result in lesions of the corpus callosum and if suspected should be further evaluated with T2* or SWI to detect possible microhemorrhages.

Acute Disseminated Encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an acute demyelinating disease that, unlike MS, is typically monophasic. It may follow vaccination or a viral infection. On MRI, multiple hyperintense lesions are seen in the hemispheric white matter, cerebellum, and brainstem. The hemispheric lesions are often subcortical. Although MS may also involve the gray matter, this is much more common in ADEM, and basal ganglia or thalamic lesions are seen in 30% to 40% of cases. The lesions may exhibit vasogenic edema, and hemorrhage may also be seen. The lesions may show diffuse faint enhancement with gadolinium.

Neurosarcoidosis

The prevalence of nervous system involvement in sarcoidosis is approximately 5%. In the brain parenchyma, multiple periventricular T2 hyperintense lesions are frequently noted, which may be due to a vasculitic process and often cannot be distinguished from MS or ischemic microvascular changes. Sarcoidosis may also involve the pituitary infundibulum and hypothalamus (resulting in endocrine symptoms). The granulomatous inflammation may affect the cranial nerves and/or their meningeal coverings as well, resulting in enlargement, hyperintense signal change, and abnormal enhancement. Although sarcoidosis may involve the dura, following gadolinium administration, leptomeningeal enhancement is more commonly noted. It is typically seen along the penetrating blood vessels and the adjacent leptomeninges, and is due to perivascular spread of the granulomatous process (Fig. 33A.50). Sometimes larger intraparenchymal or meningeal enhancing lesions are noted which may be mistaken for primary or metastatic tumors. When involved, the pituitary infundibulum and hypothalamus may also exhibit enhancement. Neurosarcoidosis may also lead to hydrocephalus, either by interfering with CSF absorption through the arachnoid granulations or by obstructing the ventricular system.

Fig. 33A.50 Neurosarcoidosis. A, Axial FLAIR image reveals multiple hyperintense lesions in the deep and subcortical white matter bilaterally. B-C, Axial and coronal T1 postcontrast images show multiple linear areas of enhancement in a leptomeningeal and perivascular distribution, a pattern characteristic of neurosarcoidosis (arrowheads).

Leukodystrophy

Leukodystrophies are genetic degenerative diseases of the white matter. The various genetic defects result in deficiencies of enzymes necessary for myelin production and maintenance. This leads to degeneration/destruction of the myelin sheath of the neural pathways, seen as extensive white matter lesions and progressive atrophy.

Adrenoleukodystrophy

In adrenoleukodystrophy, there is abnormal metabolism of very long chain fatty acids. White matter changes, which are hypointense on T1 and hyperintense on T2 and FLAIR, typically start posteriorly and are seen in the parietal and occipital white matter around the atria of the lateral ventricles and across the splenium of the corpus callosum (Fig. 33A.51). T2-hyperintense signal change may be seen in the lateral geniculate bodies and along the corticospinal tracts. In the regions where active demyelination occurs, gadolinium enhancement may be seen. As the disease progresses, the white matter lesion distribution gradually involves more anterior regions.

Fig. 33A.51 Adrenoleukodystrophy. Axial FLAIR image reveals hyperintense white matter changes across the splenium of the corpus callosum, spreading to the posterior centrum semiovale bilaterally, around the atria of the lateral ventricles.

Radiation Leukoencephalopathy

Radiation therapy may result in damage to the brain parenchyma, and this may happen at various time intervals after treatment (Bakshi et al., 1998). Acute radiation injury that happens during or a few days after treatment may not be seen on MRI. Sometimes, increased mass effect or more intense gadolinium enhancement may be seen in the irradiated area. In early delayed radiation damage, the changes appear in a few weeks or months after irradiation. Signal changes that are hypointense on T1 and hyperintense on T2 and FLAIR appear in the radiated region or in the PV white matter and basal ganglia in cases of whole brain radiation. These may enhance with gadolinium and tend to resolve in a few months. Late delayed radiation injury (which may be focal or diffuse) happens months or several years after treatment and usually follows longer treatment periods or higher radiation doses. The white matter changes (postirradiation leukoencephalopathy) start to appear in PV locations, and with time they become confluent around the borders of the ventricles. The changes can spread to other deep white-matter areas, seen confluently in the centrum semiovale (Fig. 33A.52). The involved white matter may exhibit areas of calcification. Ventricular and cortical sulcal enlargement is common. These changes are typically permanent.

Fig. 33A.52 Radiation-induced leukoencephalopathy. A, Axial FLAIR image exhibits confluent hyperintense signal change in the hemispheric white matter bilaterally. The lesions involve the periventricular deep white matter but also extend to the subcortical zones. B, On the T1-weighted image, faint hypointensity is seen in the involved white matter areas.

Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) is thought to be due to abnormal cerebral vascular autoregulation resulting in vasogenic edema. A common etiology is severe hypertension (often in the setting of eclampsia or renal failure), but various medications can also cause it as a toxic side effect (tacrolimus, cyclosporin, FK-506, cyclophosphamide, interferons, and various chemotherapeutic agents). There is damage to the capillary endothelial junctions, vasodilatation resulting in fluid extravasation, and vasogenic edema. This condition has a predilection for the white matter of the posterior regions of the hemispheres, hence the former name of reversible posterior leukoencephalopathy syndrome (RPLS). In typical cases, variably extensive T1 hypointense and T2 hyperintense vasogenic edema is seen, usually symmetrically in the white matter of the parietal and occipital lobes (Fig. 33A.53). The name of the disease was changed after structural imaging revealed that gray matter, such as the basal ganglia and cerebral cortex, may also be involved (McKinney et al., 2007). It is also to be noted that at times the signal changes may be seen in the more anterior regions in the frontal and temporal lobes as well. With treatment of the underlying condition, such as hypertensive crisis or after withdrawal of the inciting agent, the clinical and imaging findings typically resolve.

Fig. 33A.53 Posterior reversible encephalopathy syndrome. This patient presented with elevated blood pressure, visual changes, altered mental status, and subsequent seizure. Axial FLAIR image shows hyperintense signal change in the occipital subcortical white matter bilaterally, left more than right.

Central Pontine Myelinolysis

Central pontine myelinolysis has been described in cases of rapid correction of hyponatremia but also in malnutrition, alcoholism, and cases of hepatic insufficiency. MRI is the study of choice, and on T2-weighted images, striking hyperintense signal change is seen in the pontine tegmentum and basis pontis that characteristically spares the periphery and the corticospinal tract (Allen, 1984). At times, gadolinium enhancement may be seen at the periphery of the lesion, but usually no enhancement is seen. Although the typical location is the pons, regions of extrapontine demyelination can also be seen in a minority of patients, including the basal ganglia, thalamus, cerebellum, and within the hemispheres.

Traumatic Subarachnoid Hemorrhage

Traditionally, a noncontrast CT scan has been the first-line imaging study to demonstrate traumatic subarachnoid hemorrhage. Acute blood appears hyperdense in the subarachnoid space. The hemorrhage may be seen in the sylvian fissures, interhemispheric fissure, basal cisterns, or in the cortical sulci at the convexities, depending on the site of trauma. Subarachnoid hyperdensity tends to resolve within 5 to 7 days after the hemorrhage, but depending on the amount of subarachnoid blood, this may be a shorter or longer process.

Until FLAIR pulse sequences became available, MRI was inferior to CT in detecting subarachnoid blood, especially in the first few days. Conventional T1- and T2-weighted images may completely miss subarachnoid blood in these early stages. However, subarachnoid blood appears hyperintense on FLAIR images (see Fig. 33A.54), and this pulse sequence is considered equal or superior to CT in detecting subarachnoid blood (Woodcock et al., 2001), especially in the posterior fossa and at the skull base, where CT images are often compromised by beam-hardening artifacts. The hyperintense signal change is due to the presence of blood, which changes the zero point of the inversion time of CSF, and therefore signal attenuation in subarachnoid regions containing hemorrhage will not be complete. An important caveat is that subarachnoid hyperintensity on FLAIR may also result from other causes. A common cause is magnetic susceptibility artifact, seen in patients who have braces or other metal devices that distort the magnetic field, which results in a lack of CSF signal suppression and the artifactually hyperintense appearance of CSF adjacent to the anterior frontal lobes.

Besides detection of blood in the acute phase, structural neuroimaging is also very useful to evaluate the potential later complications of subarachnoid hemorrhage. Subarachnoid blood may occlude the arachnoid granulations, leading to impaired CSF absorption, communicating hydrocephalus, and ventriculomegaly. Another late phenomenon that tends to follow repeated episodes of subarachnoid hemorrhage is superficial siderosis. In this condition, hemosiderin is deposited along the leptomeninges and appears as linear areas of hypointensity on T2-weighted images (see Fig. 33A.44 online at www.expertconsult.com).

Subdural Hemorrhage

Subdural hematomas are common sequelae of head trauma and are thought to result from rupture of the bridging veins (veins that drain from the cerebral surface and pierce the dura to enter the adjacent venous sinus). Morphologically they follow the contour of the cerebral surface and can cross the cranial suture lines but not the midline at the falx cerebri and cerebelli. Depending on the size, there is a varying degree of mass effect on the adjacent brain; in the more severe cases, effacement of the adjacent ventricles, midline shift, and various herniation syndromes may occur.

As subdural hematomas age, their imaging appearance changes both on CT and MRI. On CT, acute subdural hematomas appear hyperdense. If the patient remains in a recumbent position, the cellular elements settle to the lower part of the hematoma, which will appear more hyperdense, whereas the “supernatant” is less so. With time, hemoglobin degradation occurs and the density of the hematoma will decrease, eventually becoming hypodense. During this process there is a transitional stage when the density of the hematoma will be very similar or the same as that of the brain, rendering its detection more difficult. Just as with intraparenchymal hematomas, the density depends on the hematocrit, and in severely anemic patients, even acute subdural hematomas may appear iso- or hypodense, leading to erroneous dating.

On MRI, subdural hematomas exhibit a signal evolution similar to that seen with intraparenchymal hemorrhages, but the pace of evolution is different due to a slower decrease of the oxygen content within the hematoma. Acute subdural hematomas (Fig. 33A.55) are initially isointense on T1 and hyperintense on T2, but as deoxyhemoglobin appears, the signal on T2-weighted images becomes hypointense. In the subacute phase, the signal is hyperintense on T1 and hypointense on T2, but in the late subacute stage, the signal will be hyperintense on both T1- and T2-weighted images because of extracellular methemoglobin (Fig. 33A.56). It is important to remember that these stages are not separated sharply, and mixed patterns are often seen; this is due to the presence of oxy- and deoxyhemoglobin in the acute stage and intra- and extracellular methemoglobin in the chronic stage. Rebleeding into an existing subdural hematoma may also occur, resulting in the presence of clots of various ages.

Fig. 33A.55 Acute subdural hematoma. A, Axial noncontrast T1-weighted image shows a subdural collection over the left temporal lobe, which is isointense to the brain parenchyma and therefore somewhat difficult to notice (arrowheads). B, Axial T2-weighted image helps by revealing a much more obvious hyperintense subdural collection in the same area.

Fig. 33A.56 Subacute subdural hematoma. A, On axial T1-weighted image, the subacute subdural hematoma over the right frontal and parietal lobes is hyperintense and easily noticeable. B, On axial T2-weighted image, the hematoma is also hyperintense.

Chronic subdural hematomas (Fig. 33A.57) are hypointense relative to the brain but, having higher protein content, are mildly hyperintense relative to the CSF on T1-weighted images and hyperintense on T2-weighted images. Hemosiderin deposition is not as prominent as in parenchymal hemorrhages because macrophages tend to be cleared by the meningeal circulation. Chronic subdural hematomas may look similar to hyperacute ones on noncontrast images, but because of their vascular membrane, with gadolinium they exhibit enhancement along their periphery. On CT, chronic subdural hematomas appear as hypodense subdural collections. Mass effect is variable depending on the size of the hematoma and degree of cerebral atrophy. If repeated hemorrhage occurs into the subdural collection, the hyperdense fresh blood is seen within the chronic hypodense collection (Fig. 33A.58).

Fig. 33A.57 Chronic subdural hematoma. A, Axial T1-weighted image reveals a right frontal chronic subdural hematoma with signal similar to CSF (arrows). B, On axial T2-weighted image, the chronic hematoma is hyperintense. C, Axial T2-weighted image of a different case. Within the hyperintense subdural collection, multiple hypointense zones are seen; these are due to hemosiderin deposition (arrows). There is prominent mass effect on the hemisphere.

Fig. 33A.58 Chronic subdural hematoma on computed tomography (CT). Axial noncontrast CT scan shows a hypodense subdural collection over the right frontal and parietal lobes. Right hemisphere is compressed, and midline shift is present. Note hyperdense areas within the subdural collection, suggestive of another more recent bleeding episode (arrows).

Epidural Hemorrhage

Contrary to subdural hematoma, epidural hemorrhage is usually arterial in origin and due to laceration of a meningeal artery, most commonly the middle meningeal artery. Epidural hematomas are often lens shaped, respect cranial suture lines, and sometimes the dura itself is seen as a linear structure pushed toward the brain. The evolution of CT and MRI signal characteristics is similar to that of subdural hematomas.

Cortical Contusion

Cerebral contusions result from the brain hitting against the inner table of the skull or sliding against the bony ridges of the base of the skull. The most common locations include the poles and inferior surfaces of the frontal, temporal, and occipital lobes. The injured brain parenchyma exhibits foci of hemorrhage and varying degrees of edema, which may progress later to more confluent hematoma and more swelling. On CT, acute contusions appear as foci of hyperdense hemorrhage with or without swelling. The hematomas get reabsorbed later, and the swelling decreases. In the chronic stage, no residual findings or varying degrees of encephalomalacia may be seen. On MRI, with the appearance of deoxyhemoglobin, a hypointense signal is seen on T2; the surrounding edema is hyperintense on T2 and FLAIR sequences (Fig. 33A.59). Later, in the subacute stage, extracellular methemoglobin is hyperintense on T1- and T2-weighted images. Gradient echo and susceptibility-weighted images are very useful to show the hemorrhagic component of the lesion. Chronic contusions are associated with encephalomalacic cavities of various sizes, exhibiting CSF signal characteristics and surrounded by a hyperintense rim of reactive gliosis on T2 and FLAIR sequences. Variable degrees of hemosiderin deposition appear hypointense on FLAIR, gradient echo, and SWI.

Fig. 33A.59 Contusion with subdural hematoma. A, Axial T2-weighted image demonstrates an area of mixed signal change in the right frontal lobe (arrows). Its center contains hypointense hemorrhagic changes (arrowhead) and is surrounded by hyperintense edema. Note coexisting bilateral traumatic subdural hematomas. B, Gradient echo image reveals more clearly a hypointense signal in the center of the contusion, owing to the presence of blood degradation products.

Diffuse Axonal Injury

The underlying pathomechanism of this entity is shearing injury of the white matter pathways. This may involve the corpus callosum, other fiber tracts of the corona radiata and centrum semiovale, and may also involve the brainstem. The changes on structural neuroimaging can be very subtle, usually in the few-millimeter size range. Such lesions are usually not detected by CT. MRI is the study of choice. On MRI, the lesions appear as foci of hyperintensity seen on T2 and FLAIR sequences. Foci of hemorrhage (usually microbleeds) are also present. For detection of the microbleeds associated with axonal injury, gradient echo or susceptibility-weighted images (Fig. 33A.60) are the most sensitive (Li and Feng, 2009).

Fig. 33A.60 Diffuse axonal injury. Magnetic resonance image from a 42-year-old assault victim. Susceptibility-weighted images reveal multiple hypointense areas (arrowheads) in the left frontal lobe (A), right external capsule (B), and right occipital lobe (C). These are areas of microbleeds associated with axonal injury.

Cerebral Parenchymal Hematoma

The imaging appearance of cerebral hematomas is discussed in the section on hemorrhagic cerebrovascular disease. As described there, for detection of smaller hemorrhagic lesions or microbleeds, gradient echo or SWI are the most sensitive techniques and should be part of every trauma imaging protocol.

Metabolic and Toxic Disorders

Multiple System Atrophy, Cerebellar Subtype

Multiple system atrophy (MSA) is a neurodegenerative disorder that results in symptoms and signs referable to various CNS structures. Depending on the systems involved, three different MSA subtypes are distinguished: MSA-a (autonomic subtype, Shy-Drager syndrome), MSA-p (parkinsonian subtype), and MSA-c (cerebellar subtype).

In the cerebellar subtype of MSA, predominantly infratentorial structures are affected, hence the other name for this entity, olivo-ponto-cerebellar atrophy (OPCA). There may be atrophy of the olivary eminences of the medulla, which is well appreciated on thin-slice axial images. In the pons, a horizontal T2 hyperintense signal change may be noted, characteristically involving the transverse pontine fibers, and often a vertical linear hyperintensity is also seen, corresponding to the degenerating neurons of the raphe nuclei. The constellation of these linear T2 hyperintense areas that cross each other perpendicularly is referred to as the hot-cross-bun sign. Although this sign has been thought to be specific for MSA-c, it has also been described in the other two MSA subtypes, spinocerebellar ataxia (types 2 and 3), parkinsonism with vasculitis (Muqit et al., 2001), fragile X premutation tremor/ataxia syndrome, and in variant Creutzfeldt-Jakob disease (Soares-Fernandes et al., 2009). Another potential finding in MSA-c is T2 hyperintense signal change, extending into the middle cerebellar peduncles in a symmetrical fashion. This finding is not pathognomonic—for instance, occurring also in fragile X premutation tremor ataxia syndrome.

Imaging features of MSA-a and MSA-p, including findings that help distinguish the three subtypes of MSA, are described in the section covering degenerative diseases that primarily cause parkinsonism.

Spinocerebellar Ataxias

Spinocerebellar ataxias (SCA, types 1-29) are genetically heterogeneous disorders resulting in expansion of glutamine-coding CAG triplets of the involved genes. The resultant abnormal proteins (containing polyglutamine) are felt to have a pathogenetic role. In these diseases, variable degrees of cerebellar, brainstem, and spinal cord atrophy are seen with imaging (Fig. 33A.61). The structural imaging appearance is not specific but supports the diagnosis. SCA type 6 is a pure cerebellar syndrome that stands out from the structural imaging standpoint in that there is little extracerebellar atrophy, and the atrophy predominantly involves the vermis, especially the superior vermis. This imaging appearance is similar to that seen in chronic alcohol abuse or phenytoin-related cerebellar toxicity, which are the main differential diagnostic considerations.

Fig. 33A.61 Cerebellar ataxia. MRI from a 42-year-old male with progressive cerebellar ataxia. Sagittal (A) and axial (B) T2-weighted images demonstrate cerebellar and, to a lesser extent, brainstem atrophy. Note enlarged CSF spaces in the posterior fossa.

Friedreich Ataxia

Friedreich ataxia is an autosomal recessive, trinucleotide repeat disease. It is due to mutations in the frataxin gene, resulting in expansion of GAA trinucleotide repeats. Although cerebellar and brainstem atrophy occur in Friedreich ataxia, the most common imaging finding in this disease is a striking atrophy of the spinal cord, best appreciated on axial T1-weighted or FLAIR images. Occasionally, degenerative nonspecific T2 hyperintensities may be noted in the pontine tegmentum.

Ataxia-Telangiectasia

In this multisystem disease, there is progressive cerebellar ataxia, mucocutaneous telangiectasia, and a predisposition to infections and neoplasms. The underlying pathomechanism is a faulty DNA repair mechanism. In the appropriate clinical context, imaging—although not specific—is helpful in supporting the diagnosis. Potential imaging findings, best appreciated on MRI, include cerebellar vermian or hemispheric atrophy and enlargement of the fourth ventricle and/or cisterna magna. In these patients with poor DNA repair, radiation exposure by CT scanning should be avoided if possible.

Fragile X Premutation Syndrome

Fragile X premutation tremor/ataxia syndrome (FXTAS) is an adult-onset degenerative disorder resulting in various combinations of cerebellar ataxia, parkinsonism, tremor, neuropathy, and cognitive problems. On MRI, bilateral T2 hyperintense signal changes may be seen in the middle cerebellar peduncles and sometimes around the dentate nuclei. The main imaging differential diagnostic possibility is OPCA, where symmetrical middle cerebellar peduncle hyperintensity may also be observed.