- Email: [email protected]
Neuroradiologic abnormalities in Aids
63. Epstein DM, Gefter WB, Conard K, et al: Lung disease in homosexual men. Radiology 1982; 143:7. 64. McCauley KI, Naidich DP, Leitman BS, et al: Radiographic patterns of opportunistic lung infections and Kaposi sarcoma in homosexual men. AJR 1982; 139:653. 65. Friedman-Kien AE, Laubenstein LJ, Rubinstein P, et al: Disseminated Kaposi’s sarcoma in homosexual men. Ann Intern Med 1982; 96:693. 66. Hill CA, Harle TS, Manse11 PWA: The prodrome, Kaposi sarcoma, and infections associated with acquired immunodeficiency syndrome: Radiologic findings in 39 patients. Radiology 1983; 149:393. 67. Kornfeld H, Axelrod JL: Pulmonary presentation of Kaposi’s sarcoma in a homosexual patient. Am Rev Resp Dis 1983; 127:248. 68. Misra DP, Sunderrajan EB, Hurst DJ, et al: Kaposi’s sarcoma of the lung. Radiography and patholoa. Thora,x 1982; 37:155. 69. Nash G, Fligiel S: Kaposi’s sarcoma presenting as pulmonary disease in the acquired immunodeficiency syndrome. Diagnosis by lung biopsy. Hum Pathol 1984; 15:sss. 70. Sivit CJ, Schwartz AM, Rockoff SD: Kaposi’s sarcoma of the lung in AIDS: Radiologic-pathologic analysis. AJR 1987;148:25. 71. Garay SM, Belenko M, Fazzini E, et al: Pulmonary manifestations of Kaposi’s sarcoma. Chest 1987; 91:39. 72. Davis SD, Henschke CI, Chamides BK, et al: Intrathoracic Kaposi sarcoma in AIDS patients: Radiographicpathologic correlation. Radiology 1987; 163:495. 73. Ioachim HL, Cooper MC, Hellmen GC: Hodgkin’s disease and the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101:876. 74. Robert MJ, Schneiderman H: Hodgkin’s disease and the acquired immunodeficiency syndrome. Ann Intern Med 1984;101:142. 75. Scheib RG, Siegel RS: Atypical Hodgkin’s disease and the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102:554. 76. Schoeppel SL, Hoppe RT, Dorfman RF, et al: Hodgkin’s disease in homosexual men with generalized lymphadenopathy. Ann Intern Med 1985; 102:68. 77. Stern RG, Gamsu G, Golden JA, et al: Intrathoracic adenopathy: Differential feature of AIDS and diffuse lymphadenopathy syndrome. AJR 1984; 142:689. 78. Prior E, Goldberg AF, Conjalka MS, et al: Hodgkin’s disease in homosexual men an AIDS-related phenomenon? Am J Med 1986; 81:1085. 79. Di Carlo EF, Amberson JB, Metroka CE, et al: Malignant lymphomas and the acquired immunodeficiency syndrome. Arch Path01 Lab Med 1986; 110:1012. 80. Ziegler JL, Beckstead JA, Volberding PA, et al: NonHodgkin’s lymphoma in SO homosexual men. N Engl J Med 1984; 311:565. 81. Irwin LE, Begandy MK, Moore TM: Adenosquamous carcinoma of the lung in the acquired immunodeficiency syndrome. Ann Intern Med 1984; 100:158. 82. Nusbaum MJ: Metastatic small cell carcinoma of the lung in a patient with AIDS. N Engl J Med 1985; 312:1706. 83. Alhashimi MM, Krasnow SH, Johnston-Early A, et al: Squamous cell carcinoma of the epiglottis in a homosexual man at risk for AIDS. JAMA 1985; 2532366. 84. Lozada I?, Silverman S Jr, Conant M: New outbreak of oral tumors, malignancies and infectious diseases strikes young male homosexuals. Can Dent Assoc J 1982; 10:30. Curr
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85. Overly WL, Jakubek DJ: Multiple squamous cell carcinomas and human immunodeficiency virus infection. [letter to editor]. Ann Intern Med 1987; 106:334. 86. Grieco MH, Chinoy-Acharya P: Lymphocytic interstitial pneumonia associated with the acquired immune deficiency syndrome Am Rev Respir Dis 1985; 131:952. 87. Goldman HS, Ziprkowski MN, Charytan M, et al: Lymphocytic interstitial pneumonitis in children with AIDS: A perfect radiographic-pathologic correlation [abstract]. AJR 1985; 145:868. 88. Rubinstein A: Pediatric aids. Curr Probl Pediatr 1986; 16:364.
Neuroradiologic ln Aids
Walter
L. Olsen,
Abnormalities
M.D.
Neurologic signs and symptoms are common in patients infected with the human immunodeficiency virus (HIV). Approximately 39% of all acquired immunodeficiency syndrome (AIDS) victims have neurologic symptoms, and 10% of these patients present with neurologic symptoms before other manifestations of AIDS.l Neuropathologic evidence of central nervous system (CNS) disease in HIV-infected patients is even higher. Several autopsy series have shown CNS pathology in up to 80% of all AIDS patients.24 A variety of infectious and neoplastic diseases are found in these patients. Probably the most important form of infection is the HIV virus itself, which has recently been shown to be neurotropic, attacking brain and spinal cord tissue.5-8 Human immunodeficiency virus has been isolated and cultured from the cerebrospinal fluid, brain, and spinal cord of AIDS and AIDS-related complex patients with neurologic symptoms. The HIV infection causes a subacute encephalitis syndrome characterized by mental deterioration and leads to dementia (the AIDS dementia complex). In addition to the direct effects of the HIV virus on the CNS, AIDS patients are also prone to develop opportunistic infections and neoplasms. The most important infections are viral (cytomegalovirus herpesvirus, varicella virus, and progressive multifocal leukoencephalopathy), protozoan (toxoplasmosis), mycobacterial (tuberculosis and atypi89
FIG 13. Diffuse atrophy. The noncontrast ment of the sulci and ventricles, with AIDS.
head CT images show including the temporal
diffuse horns.
atrophy Atrophy
cal mycobacteria), and fungal (cryptococcosis, candidiasis, histoplasmosis). Meningovascular syphilis has also been reported.’ The most common neoplasm is primary CNS lymphoma. Peripheral non-Hodgkin’s lymphoma may also metastasize to the brain or spine. Other cancers, including Kaposi’s sarcoma, only rarely metastasize to the CNS. The radiologic manifestations of the various diseases that affect the brains of AIDS patients fall into four categories. The most common finding is diffuse cortical atrophy. This is associated with the AIDS dementia complex. The second most common is white matter disease, which is generally caused by viral infection. One or more mass lesions constitute the third most common finding. These are almost always caused by either toxoplasmosis or primary CNS lymphoma. The least commonly observed pattern is leptomeningeal or ependymal disease, caused by either infection or metastatic tumor. These patterns and the disease entities that produce them are discussed in the subsequent section. Afterward there is a discussion of AIDS in the spine and in the head and neck area. so
in a 24-year-old is the commonest
INTRACRANIAL
homosexual man with AIDS. There finding on neuroimaging studies
MANIFESTATIONS
is enlargeof patients
OF AIDS
ATROPHY
Diffuse cerebral atrophy is very common in patients with AIDS, occurring in more than 30% of patients with neurologic symptoms” The cause of the atrophy in these patients is probably direct infection from the HIV virus. As mentioned previously, HIV is a neurotropic virus that attacks Tlymphocytes and may also infect the brain and spinal cord. When HIV attacks brain tissue, it may produce a syndrome characterized by impaired memory and concentration, with psychomotor slowing that progresses to dementia. The syndrome has been termed the subacute encephalitis syndrome* and the AIDS dementia complex.“’ *’ Dementia is a very common clinical finding in AIDS patients, occurring in more than one half of all cases.‘l At autopsy most of these patients have evidence of gross cerebral atr0phy.l’ Although other disease processes such as cytomegalovirus infection, cachexia, and dehydration may also result in diffuse cerebral atrophy, it is likely that the AIDS dementia complex caused by HIV infection is the most common cause for atrophy. Both comCurr
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puted tomography (CT) and magnetic resonance (MR) are useful for demonstrating diffuse cerebral atrophy characterized by enlargement of the sulci and ventricles (Fig 13). Both supratentorial and infratentorial atrophy may be present. Associated white matter abnormalities, also probably secondary to HIV infection, are best demonstrated with T,-weighted MR images, as discussed in the following section. The extent of atrophy present usually correlates with the degree of intellectual impairment. However, some patients with severe dementia may show little or no atrophy on imaging studies. Patients with atrophy appear to be at greater risk for subsequent development of intracranial mass lesions.” WHITE MATTER
DISEASE
White matter disease is common in patients infected with HIV. This is usually the result of viral infections, including HIV, cytomegalovirus, papovavirus, varicella-zoster virus, and herpes simplex virus. Another less common cause is ischemic encephalopathy, which has been seen at autopsy in patients with severe hypoxia from opportunistic
FIG 14. HIV encephalitis. This T,-weighted (SE2,OOOBO) MR image shows extensive areas of abnormal high signal in the centrum semiovale bilaterally (arrows). There is no mass effect. The abnormal white matter signal represents demyelination, which in this case was secondary to HIV infection. Progressive multifocal leukoencephalopathy could have a similar appearance. Curr
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pneumonia.3 T,-weighted MR is the most sensitive modality for detecting white matter changes in patients with AIDS. Most diseases of white matter produce demyelination, which manifests itself as high signal intensity on T,-weighted images and contrasts markedly with normal, low signal white matter (Fig 14). Although less sensitive than T2weighted MR, CT may also show white matter abnormalities as areas of low attenuation without significant mass effect or contrast enhancement. Pathologically, HIV infection is the most common cause of white matter disease in patients with AIDS. The pathologic hallmark of Hn! infection is the presence of multinucleated giant cells that are most prominent in the cerebral white matter.l’ These multinucleated giant cells are associated with focal areas of demyelination and white matter vacuolation.4 The centrum semiovale is the most severely affected area, but any white matter tract may be involved, including the brainstem and cerebellum. The subcortical gray matter may also be affected, but the cerebral cortex is usually spared.” At autopsy, these changes are found in approximately 28% of all AIDS patients.4 Although there has been no radiologicopathologic correlation in patients with HIV encephalitis, it is likely that this accounts for much of the white matter disease seen on neuroimaging studies. Navia et al. described 70 patients with the AIDS dementia complex,l’ two of whom underwent MR examination. T,-weighted images showed focal areas of high signal intensity in the white matter. We have also imaged several patients with HIV infection of the brain and no other neuropathologic process. In these patients, MR showed patchy areas of increased signal intensity in the white matter on T,-weighted images. As previously described, atrophy is also a very common finding with HIV encephalitis. Unfortunately, there are no distinguishing features yet described to distinguish the white matter changes of HIV encephalitis from other white matter diseases in patients with AIDS. Another viral infection that may cause white matter disease in AIDS patients is progressive multifocal leukoencephalopathy. Its incidence in AIDS patients ranges from 2% to 7%,1’3’4’*3 which is much lower than the incidence of HIV brain infection. The disease is caused by a papovavirus (the J-C virus). Demyelination and necrosis of the white matter is seen most prominently in the subcortical areas of the cerebrum and in the centrum semiovale. Diffuse and focal neurologic findings may be seen, depending on the site of white matter involvement. The disease is invariably fatal, with a mean time to death of approximately 18 weeks.13 Computed tomography and MR show lesions in 91
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-,,_
_
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.
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_
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i
FIG 15. Progressive multifocal leukoencephalopathy. A, there is a focal area of decreased attenuation in the left centrum semiovale (arrow) on this contrast-enhanced CT scan. There is no mass effect or contrast enhancement. The low density extends out to the gray-white junction. B, the T,-weighted (SE2,000/70) MR scan is more striking. There is high signal intensity extending from the centrum semiovale to the gray-white junction (arrows) without mass effect. Brain biopsy revealed progressive multifocal leukoencephalopathy.
the white matter without significant mass effect. The lesions may be single or multiple. T,-weighted MR images show areas of high signal intensity in the subcortical white matter and centrum semiovale. With CT, lesions are of low attenuation without contrast enhancement. The findings are usually more striking with MR than with CT, and MR may show areas of involvement not seen with CT (Fig 15). Other viral infections may also occasionally cause white matter disease in patients with AIDS. Cytomegalovirus is a common infection of the brain in AIDS patients and may produce glial nodules in the gray and white matter on pathologic examination. However, frank tissue necrosis is rate4 For this reason, it is believed that symptomatic cytomegalovirus infection is probably uncommon.14 Similarly, patients with documented cytomegalovirus brain infection usually have a normal CT or MR study.l’ However, gross demyelination secondary to cytomegalovirus infection has 92
been reported in the pathologic literature,16 and CT has shown demyelination in a severe case of cytomegalovirus encephalitis.l’ Herpes simplex virus (I and II) and varicella-zoster virus are unusual infections in patients with AIDS, occurring in only 2% or fewer of AIDS patients at autopsy.3’4 Both of these viruses may produce white matter abnormalities?4 The acute encephalitis that is seen in otherwise normal patients with herpes simplex infection is seen only in more immunocompetent patients with AIDS-related complex. The more immunosuppressed patients with AIDS usually have a less acute, diffuse encephalitis that may be associated with white matter lesions on MR scanning.* In addition to causing a multifocal encephalitis affecting primarily white matter, varicella-zoster infections may also produce a vasculitis in patients with ophthalmic zoster skin lesions.17 This vasculitis may lead to cerebral infarcts. Again, these diseases are unusual in patients with AIDS. Curr
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MASS LESIONS Mass lesions from infections or neoplasms occur commonly in patients with AIDS. In a recent autopsy series, 23% of 153 AIDS patients had focal macroscopic CNS disease.4 With neuroimaging studies, more than 20% of AIDS patients with neurologic symptoms are found to have mass lesi0ns.l’ Toxoplasmosis and primary CNS lymphoma are the most common mass lesions in AIDS.++’ 1619 Other less common mass lesions include Candida abscesses, tuberculomas, cryptococcomas, and metastatic lesions. The most common intracranial mass lesion in patients with AIDS is toxoplasmosis. This occurs in approximately 10% of all AIDS patients.‘j4 The organism, Toxoplasma gondii, is an obligate intracellular protozoan that causes a subclinical, mild infection in a large percentage of the world’s population. In the United States, 20% to 70% of adults are seropositive for toxoplasmosis, indicating prior subclinical infection.’ In AIDS and other immunosuppressed patients, life-threatening illness results from reactivation of the previously acquired infection.” In the brain, this causes a necrotizing encephalitis. Clinically, focal neurologic findings correspond to the site of brain involvement, especially late in the disease. Early in the disease, however, diffuse symptoms may be present in addition to
FIG 16. Toxoplasmosis.’ Bilateral basal ganglia ring-enhancing mass sions (arrows} are demonstrated by this contrast-enhanced study. There is marked surrounding edema. This appearance typical of toxoplasmosis. Cur-r
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leCT is
the changes in mental state of the AIDS dementia % complex. Both CT’ and MR are useful for imaging patients with suspected toxoplasmosis (Figs 16-18). Magnetic resonance may be slightly more sensitive but is not more specific than CT.‘l In general, T,weighted MR is the optimal screening technique. With CT, the delayed double-dose contrast technique (using up to 80 gm of iodine intravenously) is more sensitive than the single-dose technique (using 40 gm of iodine intravenously).‘8’21 With both CT and MR, multiple mass lesions with significant surrounding edema are usually seen. Solitary lesions are less common. The cerebral cortex and subcortical gray matter (basal ganglia) are the most common locations. However, any portion of the brain, including the cerebellum and brainstem may be involved. With MR, toxoplasmosis lesions are usually of low signal intensity on T,-weighted images and medium to high signal intensity on TZweighted images. The surrounding vasogenic edema is of high signal intensity on T,-weighted images and may obscure the margins of the abscess. With CT, the lesions almost always enhance following intravenous contrast administration.18 Ring or nodular enhancement is the most common patternl” lg Biopsies are not routinely performed on patients with suspected toxoplasmosis. Toxoplasmosis is effectively treated with antibiotic therapy (usually sulfadiazine and pyrimethamine). Response to therapy is usually dramatic, both clinically and radiographically, usually occurring within 2 weeks.” Therefore, patients with mass lesions are almost always treated empirically with antitoxoplasmosis antibiotics and are then rescanned 2 weeks later. Biopsy is reserved only for those patients who fail to respond to the therapeutic trial.20~ZZBiopsy may also be performed earlier if the patient’s clinical status deteriorates. Primary lymphoma is the next most common mass lesion found in patients with AIDS. Prior to the AIDS epidemic, primary CNS lymphoma was a rare disease, but it is now found in approximately 6% of all AIDS patients at autopsy? Clinically, diffuse and focal neurologic findings may be found, depending on the site of involvement. The prognosis is extremely poor, with most patients surviving less than 2 months.23 Radiation therapy may sometimes produce tumor regression, but it has not significantly changed the poor prognosis. In non-AIDS patients with primary CNS lymphoma, the typical CT appearance before contrast, is a solitary, iso-dense or hyperdense lesion that enhances homogeneously following contrast administration (Fig 19) .24,25 Ring enhancement and multiple lesions are less common (Fig 20).24 Most AIDS patients also have this pattern. However, al93
CT scan shows slight low density in the midbrain but is otherwise unremarkable. No ring-enhancing mass lesions are seen. B, the T,-weighted (SE2,000/70) MR study was performed 2 days later. A large rounded mass lesion is identified in the midbrain (large arrows). Several smaller rounded mass lesions are seen in the temporal lobes bilaterally (small arrows). T,-weighted MR is frequently more sensitive than CT in detecting focal CNS disease in patients with AIDS. C, 3 weeks following antibiotic treatment for toxoplasmosis this Tz-weighted (SE2,000/70) A,, ^L.L^ I^^:^^^ have significantly decreased in size. :orrelated with the radiological imorovement
most 50% of patients with AIDS and primary CNS lymphoma have lesions that show ring enhancement with central necrosisF5 About one half of the AIDS patients with CNS lymphoma have multiple lesions.23 Most lesions are located in the supratentorial gray or white matter. Basal ganglia involvement is less common, especially in AIDS patients.25 In a minority of patients, lymphoma may spread diffusely along subependymal or white matter routes, As with most lesions imaged with MR, primary CNS lymphoma is of high signal intensity on T,-weighted images and low signal intensity on T1weighted images. The borders of the lesions may be obscured by high signal intensity of surrounding vasogenic edema, which is usually of moderate severity. Although unusual, fungal infections, mycobacterial infection, and metastatic tumors may occasionally present as mass lesions in patients with AIDS. Fungal infections are common, occurring in as many as 15% of all AIDS patients3j4 However, 94
these infections usually appear as meningitis rather than as mass lesions. There are rare reports of fungal abscesses found at autopsy.2-5 Most of these lesions are small and are not diagnosed before death, hence the paucity of radiology literature on the imaging characteristics of fungal abscesses in AIDS. Tuberculomas and tuberculous abscesses are also rare in patients with AIDS. Several large autopsy series demonstrated no intracranial mycobacterial infections in AIDS patients .*, 3,4 However, intracranial tuberculosis has been reported in patients with AIDS, primarily in intravenous drug abusersz6 Ring-enhancing lesions with vasogenic edema are seen with CT. The MR appearance of a tuberculoma has not been described. Intracranial metastatic lesions in patients with AIDS are also quite unusual. The most common neoplasm to metastasize to the brain is nonHodgkin’s lymphoma, which occurs in approximately 2% of cases.4 Kaposi’s sarcoma only rarely metastasizes to the brain.’ Metastatic non-HodgCurr
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FIG 18. Toxoplasmosis before and after therapy. A and B, the contrast-enhanced CT study shows multiple ring and nodular enhancing mass lesions bilaterally. The lesions are identified in both basal ganglia (large arrows) and in the cortical areas (curved arrows) bilaterally. Most of the lesions are surrounded by significant vasogenic edema. The multiplicity, location, and enhancement pattern of these lesions are typical of toxoplasmosis. C and D, this study was performed 2 weeks following antibiotic therapy. Most of the lesions have disappeared. Mild residual mass effect is seen in the right basal ganglia (arrow). There was clinical improvement as well.
kin’s lymphoma usually manifests itself as leptomeningeal or ependymal disease rather than as parenchymal masses.
LEPTOMENINGEAL DISEASE
AND EPENDYMAL
Leptomeningeal and ependymal disease is the least commonly observed neuroimaging pattern in patients with AIDS. However, pathologic evidence of leptomeningeal or ependymal disease is common. Meningitis may be caused by HIV, cytomegalovirus, fungi (especially Cryptococcus), mycobacteria, toxoplasmosis, and syphilis. Cryptococcal meningitis occurs in approximately 15% of all AIDS patients,3’4 and aseptic meningitis, probably Curr
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caused by HIV infection in most cases, occurs in as many as 13%. In general, contrast-enhanced CT is more sensitive than MR in detecting leptomeningeal disease (Fig 21).27 However, patients with leptomeningeal or ependymal disease usually have normal CT and MR studies. If positive, contrastenhanced CT shows exaggerated enhancement of the meninges or ependyma. Meningitis may involve the arteries at the base of the brain and lead to infarcts that can be seen with either CT or MR. Meningitis may also lead to communicating hydrocephalus. Lymphoma may also cause leptomeningeal or ependymal enhancement. Peripheral non-Hodgkin’s lymphoma may metastasize to the brain, and primary CNS lymphoma may also spread along leptomeningeal or ependymal pathways. Contrast95
FIG 19. Primary CNS lymphoma. A, the noncontrast head CT scan shows two masses that are hyperdense compared with brain (arrows). is significant vasogenic edema. 6, following intravenous contrast administration, there is marked homogeneous enhancement lesions. This appearance of high-density masses precontrast with homogenous enhancement after contrast is typical of primary lymphoma and is unusual in toxoplasmosis
enhanced CT scans show enhancement of the leptomeninges or ependyma that is often nodular or irregular in pattern, However, irregular thickening of these membranes may also be seen with infections.
MYEiLOPATHY Myelopathy is another common neurologic syndrome in patients with AIDS. It may be caused by intrinsic cord pathology or by extrinsic compression by extradural lesions. The most common cause is that of intrinsic cord pathology, found in more than 20% of all AIDS patients at autopsy.” Pathologically, there is demyelination and vacuolation involving the lateral and posterior columns of the spinal cord in a pattern similar to subacute combined degeneration. However, serum vitamin Blz and folate levels are usually normal in these patients. The thoracic cord is usually most severely involved. The cause of the myelopathy is unclear, but there is accumulating evidence that it probably results from direct infection by HIV. Human immunodeficiency virus has been cultured 96
There of the CNS
from the spinal cord in some patients.6 Cytomegalovirus, varicella, and other viruses may also cause myelopathy in AIDS patients.16, l7 Myelography in these patients is usually normal. The MR characteristics of the AIDS myelopathy have not been reported. A less common cause of myelopathy is extrinsic compression from epidural tumors or abscesses. In our experience, non-Hodgkin’s lymphoma is the most common cause for extrinsic compression of the cord. Lymphoma may metastasize to the vertebrae or may extend into the spinal canal via the neural foramina. Other tumors may also metastasize to the vertebrae and cause extradural compression of the dural sac. These lesions may be evaluated by myelography, intrathecal contrast CT studies, or MRI imaging (Fig 221. Unlike myelography or intrathecal CT studies, MR may not show the presence of a complete myelographic block. However, the relationship of the tumor to the cord in multiple planes is well shown with this technique. The presence or absence of a block is less important than the degree of cord compression, which MR demonstrates better than other techniques. Cur-r
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gree of cellulitis. This manifests as thickening and infiltration of the adjacent subcutaneous fat, which is the hallmark of a bacterial infection. Computed tomography shows thickening and increased density of the subcutaneous fat (Fig 231. T,-weighted MR reveals thickening and increased signal intensity within the fat. Although there may be a small amount of infiltration of the subcutaneous fat by tumors and mycobacterial infections, there is usually no significant thickening unless radiation treatment has been administered. Mycobacterial lymph node infections, including M. avium-intracellulare infections, typically have very low density centers on CT studies. Generally, the density of nodes infected by‘bacteria is lower than that of the nodes involved by tumor. Adjacent cellulitis is not a prominent feature. Kaposi’s sarcoma and non-Hodgkin’s lymphoma are the most common head and neck tumors encountered in HIV-infected patients.“’ Kaposi’s sarcoma of the head and neck is extremely common in patients with AIDS, occurring in 15% of all pa-
FIG 20. Primary CNS lymphoma. There is a ring-enhancing mass with a low-density center in the deep left frontal lobe. There nificant surrounding edema. This was the only lesion present. biopsy revealed primary CNS lymphoma. In patients with approximately 50% of primary CNS lymphoma lesions will ring enhancement.
HEAD
AND
NECK
lesion is sigBrain AIDS, show
DISEASE
Approximately 40% of patients with AIDS have head and neck lesions.” Clinically, Kaposi’s sarcoma, fungal and viral infections, sinusitis, chronic cough, and neck masses are the most commonly encountered abnormalities. Most of these patients are adequately evaluated by clinical or laryngoscopic examination. However, complete evaluation by conventional means is difficult, and in some cases imaging studies are necessary. In our experience with more than 40 patients, three categories of disease are imaged in patients with AIDS or AIDS-related complex: infections, tumors, and benign lymphoid hyperplasia.30 The most common infections are caused by bacteria or mycobacteria. We have also seen unusual infections caused by Pneumocystis and Rhinosporidium. The mycobacterial infections may be caused by either tuberculosis or atypical organisms such as Mycobacterium avium-intracellulare. Because Hn/-infected patients often respond poorly to antibiotic therapy, early imaging with CT or MR is helpful in planning for surgical drainage. Bacterial infections frequently present as deep neck abscesses with a marked deCurr
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FIG 21. Cytomegalovirus ependymitis. The contrast-enhanced CT study shows abnormal enhancement around the frontal horn of the left lateral ventricle (arrows). There is also mild ventricular and sulcal enlargement for age (40 years). At autopsy, infection of the ependyma with CMV was found in the left frontal horn. Evidence of diffuse cytomegalovirus infection throughout the brain was also found. 97
FIG 22. Non-Hodgkin’s lymphoma metastatic to the spine. This CT study was performed shortly after an mass that extends out the right neuroforamen is seen. The dural sac and spinal cord (curved anteriorly. The mass has caused a complete myelographic block with nonvisualization of the evidence of bone destruction. The extension of the tumor through the neuroforamen suggests which was proved in this case.
iopamidol myelogram. A large epidural arrow) are compressed and displaced sac on the lower sections. There is no a round cell tumor such as lymphoma,
FIG 23. Submandibular space abscess. The contrast-enhanced and peripheral enhancement (arrow). There is marked arrows). This degree of cellulitis is typical of a bacterial 98
CT scan shows a mass in the left submandibular space with low density centrally thickening and increased density of the adjacent subcutaneous fat (curved abscess and is uncommon with mycobacterial infections and tumors. Curr
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FIG 24. Non-Hodgkin’s lymphoma of the neck. The contrast-enhanced CT study shows two large nodal masses in the right neck (arrows). Each has a smooth, thin enhancing rim with homogeneous tissue centrally. There is no adjacent cellulitis in the subcutaneous tissue. The homogeneity of the tissue and the lack of adjacent inflammatory reaction are typical of non-Hodgkin’s lymphoma.
tients. There is also a slightly increased incidence of squamous cell carcinoma in the oral and nasopharyngeal areas.31 Kaposi’s sarcoma can usually be adequately evaluated clinically, but suspected deep involvement may lead to radiologic evaluation. Barium pharyngography shows nodular lesions without ulcerations.3z Computed tomography and MR show nodular or polypoid masses of the oral cavity or pharyngeal mucosa. When involved, lymph nodes will frequently contain low density centers on CT examination3’ There is usually no adjacent cellulitis. Non-Hodgkin’s lymphoma usually presents as a nasopharyngeal mass or as nodal neck masses. Lymphoma is usually of homogeneous density without low density centers on CT. There may be thin peripheral enhancement (Fig 24). With MR, there is usually homogeneous signal intensity on both T,- and T,-weighted images. Again, there is usually no overlying cellulitis. Squamous cell carcinoma in AIDS patients is similar to that of patients not infected with HIV. Benign lymphoid hyperplasia is common in patients with AIDS and manifests itself as enlargeCurr
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FI$28. Benign adenoidal enlargement. A, the T,-weighted (PS600/20) sagittal MR study shows smooth enlargement of the adenoids with a slightly lobulated contour (arrows). The signal intensity is intermediate. 6, T2-weighted (SE2,000/60) axial MR shows increased signal intensity within the adenoids and a relatively flat anterior border (arrows). Multiple, small retropharyngeal parotid and subcutaneous lymph nodes are also seen (curved arrows). These findings are typical of benign lymphoid hyperplasia in patients with AIDS or AIDS-related complex.
ment of the lymph nodes, tonsils, and adenoids. Occasionally, the degree of enlargement is so prominent that a neoplasm is suspected. Computed tomography or MR may then be requested. With both CT and MR, benign adenoidal enlargement shows a smooth, flat anterior margin (Fig 25). The adenoidal tissue is of medium signal intensity on T1 weighting and of high signal intensity on T, weighting. Enlarged tonsils and lymph nodes also are of high signal intensity on T,-weighted images (see Fig 25). Magnetic resonance is more sensitive 99
than CT for detecting lymph nodes in the neck. The nodes are usually less than 2 cm in diameter with benign lymphoid hyperplasia. With CT, benign lymph nodes do not have necrotic centers. REFERENCES
1. Levy RM, Bredesen DE, Rosenblum ML: Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at LJCSF and review of the literature. J Neurosurg 1985; 62:475-495. 2. Moskowitz LB, Hensley GT, Chan JC, et al: The neurupathology of acquired immune deficiency syndrome. Arch Path01 Lab Med 1984; 108:867-872. 3. Anders KH, Guerra WF, Tomiyasu U, et al: The neuropathology of AIDS. UCLA experience and review. Am J Path01 1986;124:537-558. 4. Petit0 CL, Cho E-S, Lemann W, et al: Neuropathology of acquired immunodeficiency syndrome (AIDS): An autopsy review. J Neurolpathol Exp New-01 1986; 45:635646. 5. Levy JA, Shimabukuru .I, Hollander H, et al: Isolation of AIDS-associated retrovirus from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet 1985;2386-588. 6. Ho DD, Rota TR, Schooley RT, et al: Isolation of HTLVIII from cerebrospinal fluid and neural tissues of patients with neumlogic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 1985;313:1493-1497. 7. Black PH: HTLV-III, AIDS, and the brain. N Engl J Med 1985;313:1538-1540. 8. Shaw GM, Harper ME, Hahn BH, et al: HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227:177-182. 9. Johns OR, Tierney M, Felsenstein D: Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;316:1569-1572. 10. Levy RM, Rosenbloom S, Perrett LV: Neuroradiologic findings in AIDS: A review of 200 cases. AJR 1986; 147:977-983. 11. Navia BA, Jordan BD, Price RW: The AIDS dementia complex: I. Clinical features. Ann Neurol 1986; 19:517524. 12. Navia BA, Cho E-S, Petit0 CK, et al: The AIDS dementia complex: II. Neuropathology. Ann Neurol 1986; 19:525535. 13. Krupp LB, Lipton RB, Swerdlow ML, et al: Progressive multifocal leukoencephalopathy: Clinical and radiographic features. Ann Neurol 1985; 87:344-349. 14. Navia BA, Price RW: Central and peripheral nervous system complications of AIDS. Clin Immunol Allergy 1986; 6:543-557. 15. Post MJD, Hensley GT, Moskowitz LB, et al: Cytomegalic inclusion virus encephalitis in patients with AIDS: CT, clinical, and pathological correlation. AJR 1986; 146:1229-1234. 16. Moskowitz LB, Gregorios JB, Hensley GT, et al: Cytomegalovirus. Induced demyelination associated with
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31.
32.
acquired immune deficiency syndrome. Arch Path01 lab Med 1984; 108:873-877. Ryder JW, Croen K, Kleinschmidt-DeMasters, BK, et al: Progressive dementia encephalitis three months after resolution of cutaneous zoster in a pat&Q$h AIDS. Ann Neural 1986; 19:182-188. Post MJD, Kursunoglu SJ, Hensley GT, et al: Cranial CT in acquired immunodeficiency syndrome: Spectrum of diseases and optimal contrast enhancement technique. AIR 1985; 145:929-940. Whelan MA, Kricheff II, Handler M, et al: Acquired immunodeficiency syndrome: Cerebral computed tomographic manifestations. Radiology 1983; 149:477484. Navia BA, Petit0 CK, Gold JWM, et al: Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome: Clinical and neumpathological findings in 27 patients. Ann Neural 1986; 19224-238. Post MJD, Sheldon JJ, Hensley GT, et al: Central nervous system disease in acquired immunodeficiency syndrome: Prospective correlation using CT, MR imaging and pathologic studies. Radiology 1986; 158:141-148. Cohn J, McMeeking A, Cohen W, et al: Response and survival in patients treated for presumed versus proven CNS to toxoplasmosis. Paper presented at the Third International Conference on Acquired Immunodeficiency Syndrome (AIDS), Washington, DC, June l-5, 1987. So YT, Beckstead JH, Davis RL: Primary central nervous system lymphoma in acquired immune deficiency syndrome: A clinical and pathological study. Ann Neurol 1986;20:566-572. Jack CR Jr, Reese DF, Scheithauer BW: Radiographic findings in 32 cases of primary CNS lymphoma. AJR 1986;146:271-276. Lee YY, Bnmer JM, Van Tassel P, et al: Primary central nervous system lymphoma: CT and pathologic correlation. A.JR 1986; 147:747-752. Bishburg E, Sunderam G, Reichman LB, et al: Central nervous system tuberculosis with the acquired immunodeficiency syndrome and its related complex. Ann Intern Med 1986; 105:210-213. Davis PC, Friedman NC, Fry SM, et al: Leptomeningeal metastases: MR imaging. Radiology 1987; 163:449454. Petit0 CL, Navia BA, Cho E-S, et al: Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med 1985; 312:874-879. Marcusen DC, Sooy CD: Otolaryngologic and head and neck manifestations of acquired immunodeficiency syndrome (AIDS). Larynsoscope 1985; 95:401-405. Olsen WL, Dillon WP, Lynch MA, et al: CT and MR of head and neck pathology in patients with AIDS or ARC. Paper presented at the 25th American Society of Neuroradiology Meeting, New York, May 10-15, 1987. Silverman S, Migliorati CA, Lozada-Nur F, et al: Oral findings in people with or at high risk for AIDS: A study of 375 homosexual males. J Am Dent Assoc 1986; 112:187-192. Emery CD, Wall SD, Federle MP, et al: Pharyngeal Kaposi’s sarcoma in patients with AIDS. AJR 1986; 147:919-922.
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85. Overly WL, Jakubek DJ: Multiple squamous cell carcinomas and human immunodeficiency virus infection. [letter to editor]. Ann Intern Med 1987; 106:334. 86. Grieco MH, Chinoy-Acharya P: Lymphocytic interstitial pneumonia associated with the acquired immune deficiency syndrome Am Rev Respir Dis 1985; 131:952. 87. Goldman HS, Ziprkowski MN, Charytan M, et al: Lymphocytic interstitial pneumonitis in children with AIDS: A perfect radiographic-pathologic correlation [abstract]. AJR 1985; 145:868. 88. Rubinstein A: Pediatric aids. Curr Probl Pediatr 1986; 16:364.
Neuroradiologic ln Aids
Walter
L. Olsen,
Abnormalities
M.D.
Neurologic signs and symptoms are common in patients infected with the human immunodeficiency virus (HIV). Approximately 39% of all acquired immunodeficiency syndrome (AIDS) victims have neurologic symptoms, and 10% of these patients present with neurologic symptoms before other manifestations of AIDS.l Neuropathologic evidence of central nervous system (CNS) disease in HIV-infected patients is even higher. Several autopsy series have shown CNS pathology in up to 80% of all AIDS patients.24 A variety of infectious and neoplastic diseases are found in these patients. Probably the most important form of infection is the HIV virus itself, which has recently been shown to be neurotropic, attacking brain and spinal cord tissue.5-8 Human immunodeficiency virus has been isolated and cultured from the cerebrospinal fluid, brain, and spinal cord of AIDS and AIDS-related complex patients with neurologic symptoms. The HIV infection causes a subacute encephalitis syndrome characterized by mental deterioration and leads to dementia (the AIDS dementia complex). In addition to the direct effects of the HIV virus on the CNS, AIDS patients are also prone to develop opportunistic infections and neoplasms. The most important infections are viral (cytomegalovirus herpesvirus, varicella virus, and progressive multifocal leukoencephalopathy), protozoan (toxoplasmosis), mycobacterial (tuberculosis and atypi89
FIG 13. Diffuse atrophy. The noncontrast ment of the sulci and ventricles, with AIDS.
head CT images show including the temporal
diffuse horns.
atrophy Atrophy
cal mycobacteria), and fungal (cryptococcosis, candidiasis, histoplasmosis). Meningovascular syphilis has also been reported.’ The most common neoplasm is primary CNS lymphoma. Peripheral non-Hodgkin’s lymphoma may also metastasize to the brain or spine. Other cancers, including Kaposi’s sarcoma, only rarely metastasize to the CNS. The radiologic manifestations of the various diseases that affect the brains of AIDS patients fall into four categories. The most common finding is diffuse cortical atrophy. This is associated with the AIDS dementia complex. The second most common is white matter disease, which is generally caused by viral infection. One or more mass lesions constitute the third most common finding. These are almost always caused by either toxoplasmosis or primary CNS lymphoma. The least commonly observed pattern is leptomeningeal or ependymal disease, caused by either infection or metastatic tumor. These patterns and the disease entities that produce them are discussed in the subsequent section. Afterward there is a discussion of AIDS in the spine and in the head and neck area. so
in a 24-year-old is the commonest
INTRACRANIAL
homosexual man with AIDS. There finding on neuroimaging studies
MANIFESTATIONS
is enlargeof patients
OF AIDS
ATROPHY
Diffuse cerebral atrophy is very common in patients with AIDS, occurring in more than 30% of patients with neurologic symptoms” The cause of the atrophy in these patients is probably direct infection from the HIV virus. As mentioned previously, HIV is a neurotropic virus that attacks Tlymphocytes and may also infect the brain and spinal cord. When HIV attacks brain tissue, it may produce a syndrome characterized by impaired memory and concentration, with psychomotor slowing that progresses to dementia. The syndrome has been termed the subacute encephalitis syndrome* and the AIDS dementia complex.“’ *’ Dementia is a very common clinical finding in AIDS patients, occurring in more than one half of all cases.‘l At autopsy most of these patients have evidence of gross cerebral atr0phy.l’ Although other disease processes such as cytomegalovirus infection, cachexia, and dehydration may also result in diffuse cerebral atrophy, it is likely that the AIDS dementia complex caused by HIV infection is the most common cause for atrophy. Both comCurr
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puted tomography (CT) and magnetic resonance (MR) are useful for demonstrating diffuse cerebral atrophy characterized by enlargement of the sulci and ventricles (Fig 13). Both supratentorial and infratentorial atrophy may be present. Associated white matter abnormalities, also probably secondary to HIV infection, are best demonstrated with T,-weighted MR images, as discussed in the following section. The extent of atrophy present usually correlates with the degree of intellectual impairment. However, some patients with severe dementia may show little or no atrophy on imaging studies. Patients with atrophy appear to be at greater risk for subsequent development of intracranial mass lesions.” WHITE MATTER
DISEASE
White matter disease is common in patients infected with HIV. This is usually the result of viral infections, including HIV, cytomegalovirus, papovavirus, varicella-zoster virus, and herpes simplex virus. Another less common cause is ischemic encephalopathy, which has been seen at autopsy in patients with severe hypoxia from opportunistic
FIG 14. HIV encephalitis. This T,-weighted (SE2,OOOBO) MR image shows extensive areas of abnormal high signal in the centrum semiovale bilaterally (arrows). There is no mass effect. The abnormal white matter signal represents demyelination, which in this case was secondary to HIV infection. Progressive multifocal leukoencephalopathy could have a similar appearance. Curr
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pneumonia.3 T,-weighted MR is the most sensitive modality for detecting white matter changes in patients with AIDS. Most diseases of white matter produce demyelination, which manifests itself as high signal intensity on T,-weighted images and contrasts markedly with normal, low signal white matter (Fig 14). Although less sensitive than T2weighted MR, CT may also show white matter abnormalities as areas of low attenuation without significant mass effect or contrast enhancement. Pathologically, HIV infection is the most common cause of white matter disease in patients with AIDS. The pathologic hallmark of Hn! infection is the presence of multinucleated giant cells that are most prominent in the cerebral white matter.l’ These multinucleated giant cells are associated with focal areas of demyelination and white matter vacuolation.4 The centrum semiovale is the most severely affected area, but any white matter tract may be involved, including the brainstem and cerebellum. The subcortical gray matter may also be affected, but the cerebral cortex is usually spared.” At autopsy, these changes are found in approximately 28% of all AIDS patients.4 Although there has been no radiologicopathologic correlation in patients with HIV encephalitis, it is likely that this accounts for much of the white matter disease seen on neuroimaging studies. Navia et al. described 70 patients with the AIDS dementia complex,l’ two of whom underwent MR examination. T,-weighted images showed focal areas of high signal intensity in the white matter. We have also imaged several patients with HIV infection of the brain and no other neuropathologic process. In these patients, MR showed patchy areas of increased signal intensity in the white matter on T,-weighted images. As previously described, atrophy is also a very common finding with HIV encephalitis. Unfortunately, there are no distinguishing features yet described to distinguish the white matter changes of HIV encephalitis from other white matter diseases in patients with AIDS. Another viral infection that may cause white matter disease in AIDS patients is progressive multifocal leukoencephalopathy. Its incidence in AIDS patients ranges from 2% to 7%,1’3’4’*3 which is much lower than the incidence of HIV brain infection. The disease is caused by a papovavirus (the J-C virus). Demyelination and necrosis of the white matter is seen most prominently in the subcortical areas of the cerebrum and in the centrum semiovale. Diffuse and focal neurologic findings may be seen, depending on the site of white matter involvement. The disease is invariably fatal, with a mean time to death of approximately 18 weeks.13 Computed tomography and MR show lesions in 91
l..
-,,_
_
‘..
.
_
..”
_
-,-
i
FIG 15. Progressive multifocal leukoencephalopathy. A, there is a focal area of decreased attenuation in the left centrum semiovale (arrow) on this contrast-enhanced CT scan. There is no mass effect or contrast enhancement. The low density extends out to the gray-white junction. B, the T,-weighted (SE2,000/70) MR scan is more striking. There is high signal intensity extending from the centrum semiovale to the gray-white junction (arrows) without mass effect. Brain biopsy revealed progressive multifocal leukoencephalopathy.
the white matter without significant mass effect. The lesions may be single or multiple. T,-weighted MR images show areas of high signal intensity in the subcortical white matter and centrum semiovale. With CT, lesions are of low attenuation without contrast enhancement. The findings are usually more striking with MR than with CT, and MR may show areas of involvement not seen with CT (Fig 15). Other viral infections may also occasionally cause white matter disease in patients with AIDS. Cytomegalovirus is a common infection of the brain in AIDS patients and may produce glial nodules in the gray and white matter on pathologic examination. However, frank tissue necrosis is rate4 For this reason, it is believed that symptomatic cytomegalovirus infection is probably uncommon.14 Similarly, patients with documented cytomegalovirus brain infection usually have a normal CT or MR study.l’ However, gross demyelination secondary to cytomegalovirus infection has 92
been reported in the pathologic literature,16 and CT has shown demyelination in a severe case of cytomegalovirus encephalitis.l’ Herpes simplex virus (I and II) and varicella-zoster virus are unusual infections in patients with AIDS, occurring in only 2% or fewer of AIDS patients at autopsy.3’4 Both of these viruses may produce white matter abnormalities?4 The acute encephalitis that is seen in otherwise normal patients with herpes simplex infection is seen only in more immunocompetent patients with AIDS-related complex. The more immunosuppressed patients with AIDS usually have a less acute, diffuse encephalitis that may be associated with white matter lesions on MR scanning.* In addition to causing a multifocal encephalitis affecting primarily white matter, varicella-zoster infections may also produce a vasculitis in patients with ophthalmic zoster skin lesions.17 This vasculitis may lead to cerebral infarcts. Again, these diseases are unusual in patients with AIDS. Curr
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MASS LESIONS Mass lesions from infections or neoplasms occur commonly in patients with AIDS. In a recent autopsy series, 23% of 153 AIDS patients had focal macroscopic CNS disease.4 With neuroimaging studies, more than 20% of AIDS patients with neurologic symptoms are found to have mass lesi0ns.l’ Toxoplasmosis and primary CNS lymphoma are the most common mass lesions in AIDS.++’ 1619 Other less common mass lesions include Candida abscesses, tuberculomas, cryptococcomas, and metastatic lesions. The most common intracranial mass lesion in patients with AIDS is toxoplasmosis. This occurs in approximately 10% of all AIDS patients.‘j4 The organism, Toxoplasma gondii, is an obligate intracellular protozoan that causes a subclinical, mild infection in a large percentage of the world’s population. In the United States, 20% to 70% of adults are seropositive for toxoplasmosis, indicating prior subclinical infection.’ In AIDS and other immunosuppressed patients, life-threatening illness results from reactivation of the previously acquired infection.” In the brain, this causes a necrotizing encephalitis. Clinically, focal neurologic findings correspond to the site of brain involvement, especially late in the disease. Early in the disease, however, diffuse symptoms may be present in addition to
FIG 16. Toxoplasmosis.’ Bilateral basal ganglia ring-enhancing mass sions (arrows} are demonstrated by this contrast-enhanced study. There is marked surrounding edema. This appearance typical of toxoplasmosis. Cur-r
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leCT is
the changes in mental state of the AIDS dementia % complex. Both CT’ and MR are useful for imaging patients with suspected toxoplasmosis (Figs 16-18). Magnetic resonance may be slightly more sensitive but is not more specific than CT.‘l In general, T,weighted MR is the optimal screening technique. With CT, the delayed double-dose contrast technique (using up to 80 gm of iodine intravenously) is more sensitive than the single-dose technique (using 40 gm of iodine intravenously).‘8’21 With both CT and MR, multiple mass lesions with significant surrounding edema are usually seen. Solitary lesions are less common. The cerebral cortex and subcortical gray matter (basal ganglia) are the most common locations. However, any portion of the brain, including the cerebellum and brainstem may be involved. With MR, toxoplasmosis lesions are usually of low signal intensity on T,-weighted images and medium to high signal intensity on TZweighted images. The surrounding vasogenic edema is of high signal intensity on T,-weighted images and may obscure the margins of the abscess. With CT, the lesions almost always enhance following intravenous contrast administration.18 Ring or nodular enhancement is the most common patternl” lg Biopsies are not routinely performed on patients with suspected toxoplasmosis. Toxoplasmosis is effectively treated with antibiotic therapy (usually sulfadiazine and pyrimethamine). Response to therapy is usually dramatic, both clinically and radiographically, usually occurring within 2 weeks.” Therefore, patients with mass lesions are almost always treated empirically with antitoxoplasmosis antibiotics and are then rescanned 2 weeks later. Biopsy is reserved only for those patients who fail to respond to the therapeutic trial.20~ZZBiopsy may also be performed earlier if the patient’s clinical status deteriorates. Primary lymphoma is the next most common mass lesion found in patients with AIDS. Prior to the AIDS epidemic, primary CNS lymphoma was a rare disease, but it is now found in approximately 6% of all AIDS patients at autopsy? Clinically, diffuse and focal neurologic findings may be found, depending on the site of involvement. The prognosis is extremely poor, with most patients surviving less than 2 months.23 Radiation therapy may sometimes produce tumor regression, but it has not significantly changed the poor prognosis. In non-AIDS patients with primary CNS lymphoma, the typical CT appearance before contrast, is a solitary, iso-dense or hyperdense lesion that enhances homogeneously following contrast administration (Fig 19) .24,25 Ring enhancement and multiple lesions are less common (Fig 20).24 Most AIDS patients also have this pattern. However, al93
CT scan shows slight low density in the midbrain but is otherwise unremarkable. No ring-enhancing mass lesions are seen. B, the T,-weighted (SE2,000/70) MR study was performed 2 days later. A large rounded mass lesion is identified in the midbrain (large arrows). Several smaller rounded mass lesions are seen in the temporal lobes bilaterally (small arrows). T,-weighted MR is frequently more sensitive than CT in detecting focal CNS disease in patients with AIDS. C, 3 weeks following antibiotic treatment for toxoplasmosis this Tz-weighted (SE2,000/70) A,, ^L.L^ I^^:^^^ have significantly decreased in size. :orrelated with the radiological imorovement
most 50% of patients with AIDS and primary CNS lymphoma have lesions that show ring enhancement with central necrosisF5 About one half of the AIDS patients with CNS lymphoma have multiple lesions.23 Most lesions are located in the supratentorial gray or white matter. Basal ganglia involvement is less common, especially in AIDS patients.25 In a minority of patients, lymphoma may spread diffusely along subependymal or white matter routes, As with most lesions imaged with MR, primary CNS lymphoma is of high signal intensity on T,-weighted images and low signal intensity on T1weighted images. The borders of the lesions may be obscured by high signal intensity of surrounding vasogenic edema, which is usually of moderate severity. Although unusual, fungal infections, mycobacterial infection, and metastatic tumors may occasionally present as mass lesions in patients with AIDS. Fungal infections are common, occurring in as many as 15% of all AIDS patients3j4 However, 94
these infections usually appear as meningitis rather than as mass lesions. There are rare reports of fungal abscesses found at autopsy.2-5 Most of these lesions are small and are not diagnosed before death, hence the paucity of radiology literature on the imaging characteristics of fungal abscesses in AIDS. Tuberculomas and tuberculous abscesses are also rare in patients with AIDS. Several large autopsy series demonstrated no intracranial mycobacterial infections in AIDS patients .*, 3,4 However, intracranial tuberculosis has been reported in patients with AIDS, primarily in intravenous drug abusersz6 Ring-enhancing lesions with vasogenic edema are seen with CT. The MR appearance of a tuberculoma has not been described. Intracranial metastatic lesions in patients with AIDS are also quite unusual. The most common neoplasm to metastasize to the brain is nonHodgkin’s lymphoma, which occurs in approximately 2% of cases.4 Kaposi’s sarcoma only rarely metastasizes to the brain.’ Metastatic non-HodgCurr
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FIG 18. Toxoplasmosis before and after therapy. A and B, the contrast-enhanced CT study shows multiple ring and nodular enhancing mass lesions bilaterally. The lesions are identified in both basal ganglia (large arrows) and in the cortical areas (curved arrows) bilaterally. Most of the lesions are surrounded by significant vasogenic edema. The multiplicity, location, and enhancement pattern of these lesions are typical of toxoplasmosis. C and D, this study was performed 2 weeks following antibiotic therapy. Most of the lesions have disappeared. Mild residual mass effect is seen in the right basal ganglia (arrow). There was clinical improvement as well.
kin’s lymphoma usually manifests itself as leptomeningeal or ependymal disease rather than as parenchymal masses.
LEPTOMENINGEAL DISEASE
AND EPENDYMAL
Leptomeningeal and ependymal disease is the least commonly observed neuroimaging pattern in patients with AIDS. However, pathologic evidence of leptomeningeal or ependymal disease is common. Meningitis may be caused by HIV, cytomegalovirus, fungi (especially Cryptococcus), mycobacteria, toxoplasmosis, and syphilis. Cryptococcal meningitis occurs in approximately 15% of all AIDS patients,3’4 and aseptic meningitis, probably Curr
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caused by HIV infection in most cases, occurs in as many as 13%. In general, contrast-enhanced CT is more sensitive than MR in detecting leptomeningeal disease (Fig 21).27 However, patients with leptomeningeal or ependymal disease usually have normal CT and MR studies. If positive, contrastenhanced CT shows exaggerated enhancement of the meninges or ependyma. Meningitis may involve the arteries at the base of the brain and lead to infarcts that can be seen with either CT or MR. Meningitis may also lead to communicating hydrocephalus. Lymphoma may also cause leptomeningeal or ependymal enhancement. Peripheral non-Hodgkin’s lymphoma may metastasize to the brain, and primary CNS lymphoma may also spread along leptomeningeal or ependymal pathways. Contrast95
FIG 19. Primary CNS lymphoma. A, the noncontrast head CT scan shows two masses that are hyperdense compared with brain (arrows). is significant vasogenic edema. 6, following intravenous contrast administration, there is marked homogeneous enhancement lesions. This appearance of high-density masses precontrast with homogenous enhancement after contrast is typical of primary lymphoma and is unusual in toxoplasmosis
enhanced CT scans show enhancement of the leptomeninges or ependyma that is often nodular or irregular in pattern, However, irregular thickening of these membranes may also be seen with infections.
MYEiLOPATHY Myelopathy is another common neurologic syndrome in patients with AIDS. It may be caused by intrinsic cord pathology or by extrinsic compression by extradural lesions. The most common cause is that of intrinsic cord pathology, found in more than 20% of all AIDS patients at autopsy.” Pathologically, there is demyelination and vacuolation involving the lateral and posterior columns of the spinal cord in a pattern similar to subacute combined degeneration. However, serum vitamin Blz and folate levels are usually normal in these patients. The thoracic cord is usually most severely involved. The cause of the myelopathy is unclear, but there is accumulating evidence that it probably results from direct infection by HIV. Human immunodeficiency virus has been cultured 96
There of the CNS
from the spinal cord in some patients.6 Cytomegalovirus, varicella, and other viruses may also cause myelopathy in AIDS patients.16, l7 Myelography in these patients is usually normal. The MR characteristics of the AIDS myelopathy have not been reported. A less common cause of myelopathy is extrinsic compression from epidural tumors or abscesses. In our experience, non-Hodgkin’s lymphoma is the most common cause for extrinsic compression of the cord. Lymphoma may metastasize to the vertebrae or may extend into the spinal canal via the neural foramina. Other tumors may also metastasize to the vertebrae and cause extradural compression of the dural sac. These lesions may be evaluated by myelography, intrathecal contrast CT studies, or MRI imaging (Fig 221. Unlike myelography or intrathecal CT studies, MR may not show the presence of a complete myelographic block. However, the relationship of the tumor to the cord in multiple planes is well shown with this technique. The presence or absence of a block is less important than the degree of cord compression, which MR demonstrates better than other techniques. Cur-r
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gree of cellulitis. This manifests as thickening and infiltration of the adjacent subcutaneous fat, which is the hallmark of a bacterial infection. Computed tomography shows thickening and increased density of the subcutaneous fat (Fig 231. T,-weighted MR reveals thickening and increased signal intensity within the fat. Although there may be a small amount of infiltration of the subcutaneous fat by tumors and mycobacterial infections, there is usually no significant thickening unless radiation treatment has been administered. Mycobacterial lymph node infections, including M. avium-intracellulare infections, typically have very low density centers on CT studies. Generally, the density of nodes infected by‘bacteria is lower than that of the nodes involved by tumor. Adjacent cellulitis is not a prominent feature. Kaposi’s sarcoma and non-Hodgkin’s lymphoma are the most common head and neck tumors encountered in HIV-infected patients.“’ Kaposi’s sarcoma of the head and neck is extremely common in patients with AIDS, occurring in 15% of all pa-
FIG 20. Primary CNS lymphoma. There is a ring-enhancing mass with a low-density center in the deep left frontal lobe. There nificant surrounding edema. This was the only lesion present. biopsy revealed primary CNS lymphoma. In patients with approximately 50% of primary CNS lymphoma lesions will ring enhancement.
HEAD
AND
NECK
lesion is sigBrain AIDS, show
DISEASE
Approximately 40% of patients with AIDS have head and neck lesions.” Clinically, Kaposi’s sarcoma, fungal and viral infections, sinusitis, chronic cough, and neck masses are the most commonly encountered abnormalities. Most of these patients are adequately evaluated by clinical or laryngoscopic examination. However, complete evaluation by conventional means is difficult, and in some cases imaging studies are necessary. In our experience with more than 40 patients, three categories of disease are imaged in patients with AIDS or AIDS-related complex: infections, tumors, and benign lymphoid hyperplasia.30 The most common infections are caused by bacteria or mycobacteria. We have also seen unusual infections caused by Pneumocystis and Rhinosporidium. The mycobacterial infections may be caused by either tuberculosis or atypical organisms such as Mycobacterium avium-intracellulare. Because Hn/-infected patients often respond poorly to antibiotic therapy, early imaging with CT or MR is helpful in planning for surgical drainage. Bacterial infections frequently present as deep neck abscesses with a marked deCurr
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1988
FIG 21. Cytomegalovirus ependymitis. The contrast-enhanced CT study shows abnormal enhancement around the frontal horn of the left lateral ventricle (arrows). There is also mild ventricular and sulcal enlargement for age (40 years). At autopsy, infection of the ependyma with CMV was found in the left frontal horn. Evidence of diffuse cytomegalovirus infection throughout the brain was also found. 97
FIG 22. Non-Hodgkin’s lymphoma metastatic to the spine. This CT study was performed shortly after an mass that extends out the right neuroforamen is seen. The dural sac and spinal cord (curved anteriorly. The mass has caused a complete myelographic block with nonvisualization of the evidence of bone destruction. The extension of the tumor through the neuroforamen suggests which was proved in this case.
iopamidol myelogram. A large epidural arrow) are compressed and displaced sac on the lower sections. There is no a round cell tumor such as lymphoma,
FIG 23. Submandibular space abscess. The contrast-enhanced and peripheral enhancement (arrow). There is marked arrows). This degree of cellulitis is typical of a bacterial 98
CT scan shows a mass in the left submandibular space with low density centrally thickening and increased density of the adjacent subcutaneous fat (curved abscess and is uncommon with mycobacterial infections and tumors. Curr
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FIG 24. Non-Hodgkin’s lymphoma of the neck. The contrast-enhanced CT study shows two large nodal masses in the right neck (arrows). Each has a smooth, thin enhancing rim with homogeneous tissue centrally. There is no adjacent cellulitis in the subcutaneous tissue. The homogeneity of the tissue and the lack of adjacent inflammatory reaction are typical of non-Hodgkin’s lymphoma.
tients. There is also a slightly increased incidence of squamous cell carcinoma in the oral and nasopharyngeal areas.31 Kaposi’s sarcoma can usually be adequately evaluated clinically, but suspected deep involvement may lead to radiologic evaluation. Barium pharyngography shows nodular lesions without ulcerations.3z Computed tomography and MR show nodular or polypoid masses of the oral cavity or pharyngeal mucosa. When involved, lymph nodes will frequently contain low density centers on CT examination3’ There is usually no adjacent cellulitis. Non-Hodgkin’s lymphoma usually presents as a nasopharyngeal mass or as nodal neck masses. Lymphoma is usually of homogeneous density without low density centers on CT. There may be thin peripheral enhancement (Fig 24). With MR, there is usually homogeneous signal intensity on both T,- and T,-weighted images. Again, there is usually no overlying cellulitis. Squamous cell carcinoma in AIDS patients is similar to that of patients not infected with HIV. Benign lymphoid hyperplasia is common in patients with AIDS and manifests itself as enlargeCurr
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1988
FI$28. Benign adenoidal enlargement. A, the T,-weighted (PS600/20) sagittal MR study shows smooth enlargement of the adenoids with a slightly lobulated contour (arrows). The signal intensity is intermediate. 6, T2-weighted (SE2,000/60) axial MR shows increased signal intensity within the adenoids and a relatively flat anterior border (arrows). Multiple, small retropharyngeal parotid and subcutaneous lymph nodes are also seen (curved arrows). These findings are typical of benign lymphoid hyperplasia in patients with AIDS or AIDS-related complex.
ment of the lymph nodes, tonsils, and adenoids. Occasionally, the degree of enlargement is so prominent that a neoplasm is suspected. Computed tomography or MR may then be requested. With both CT and MR, benign adenoidal enlargement shows a smooth, flat anterior margin (Fig 25). The adenoidal tissue is of medium signal intensity on T1 weighting and of high signal intensity on T, weighting. Enlarged tonsils and lymph nodes also are of high signal intensity on T,-weighted images (see Fig 25). Magnetic resonance is more sensitive 99
than CT for detecting lymph nodes in the neck. The nodes are usually less than 2 cm in diameter with benign lymphoid hyperplasia. With CT, benign lymph nodes do not have necrotic centers. REFERENCES
1. Levy RM, Bredesen DE, Rosenblum ML: Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at LJCSF and review of the literature. J Neurosurg 1985; 62:475-495. 2. Moskowitz LB, Hensley GT, Chan JC, et al: The neurupathology of acquired immune deficiency syndrome. Arch Path01 Lab Med 1984; 108:867-872. 3. Anders KH, Guerra WF, Tomiyasu U, et al: The neuropathology of AIDS. UCLA experience and review. Am J Path01 1986;124:537-558. 4. Petit0 CL, Cho E-S, Lemann W, et al: Neuropathology of acquired immunodeficiency syndrome (AIDS): An autopsy review. J Neurolpathol Exp New-01 1986; 45:635646. 5. Levy JA, Shimabukuru .I, Hollander H, et al: Isolation of AIDS-associated retrovirus from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet 1985;2386-588. 6. Ho DD, Rota TR, Schooley RT, et al: Isolation of HTLVIII from cerebrospinal fluid and neural tissues of patients with neumlogic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 1985;313:1493-1497. 7. Black PH: HTLV-III, AIDS, and the brain. N Engl J Med 1985;313:1538-1540. 8. Shaw GM, Harper ME, Hahn BH, et al: HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227:177-182. 9. Johns OR, Tierney M, Felsenstein D: Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;316:1569-1572. 10. Levy RM, Rosenbloom S, Perrett LV: Neuroradiologic findings in AIDS: A review of 200 cases. AJR 1986; 147:977-983. 11. Navia BA, Jordan BD, Price RW: The AIDS dementia complex: I. Clinical features. Ann Neurol 1986; 19:517524. 12. Navia BA, Cho E-S, Petit0 CK, et al: The AIDS dementia complex: II. Neuropathology. Ann Neurol 1986; 19:525535. 13. Krupp LB, Lipton RB, Swerdlow ML, et al: Progressive multifocal leukoencephalopathy: Clinical and radiographic features. Ann Neurol 1985; 87:344-349. 14. Navia BA, Price RW: Central and peripheral nervous system complications of AIDS. Clin Immunol Allergy 1986; 6:543-557. 15. Post MJD, Hensley GT, Moskowitz LB, et al: Cytomegalic inclusion virus encephalitis in patients with AIDS: CT, clinical, and pathological correlation. AJR 1986; 146:1229-1234. 16. Moskowitz LB, Gregorios JB, Hensley GT, et al: Cytomegalovirus. Induced demyelination associated with
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