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The neuroradiology of AIDS
The Neuroradiology By Gordon Sze, Michael
N. Brant-Zawadzki,
ARLY REPORTS on the neurologic complications of AIDS followed almost immediately the initial description of the syndrome itself. A multitude of unusual neoplasms and opportunistic pathogens were found to affect the central nervous system (CNS). Some resulted from systemic dissemination; others primarily targeted the neural axis. Since then, the spectrum of neurologic abnormalities in AIDS has widened considerably. The discovery of the class of putative etiologic agents, the retroviruses, known as the human immunodeficiency viruses (HIV),’ AIDS-associated retrovirus (ARV),’ lymphadenopathy virus (LAV),3 and immunodeficiency-associated virus (IDAV)4 was soon followed by isolation of the nucleic acid of the virus in the brain itself.’ This and related evidence, including culture of the virus from brain tissue,6 suggest that the virus may be directly involved in the pathogenesis of several of the neurologic syndromes, both acute and chronic, associated with AIDS. By virtue of the neurotropism, as well as lymphotropism of this virus,‘*’ the CNS may suffer devastating consequences not only from the opportunistic infections that typify the syndrome in the rest of the body, but also from the damage due to the HIV virus itself. If the virus does have this capability, then the neural axis occupies an unfortunately unique niche in the body, with possibly the most extensive range of AIDS related abnormalities of any single organ system. In addition, it may well be that the
David Norman,
and T. Hans Newton
full effects of chronic HIV infection on the brain are not yet apparent. Approximately 10% of all AIDS patients present initially with neurologic symptoms.* During the course of their illness, an additional 25% to 30% of patients develop neurologic abnormalities.‘.” At autopsy, from 55% to 95% have documented pathologic change in the CNS.9,“-‘3 These entities can be divided into infectious and neoplastic categories.
E
INFECTION Nonviral
Infections
Both nonviral and viral infections attack the CNS. Of the nonviral infections, Cryptococcus neoformans and Toxoplasma gondii are the most common, affecting the CNS in 4.3% and 2.2%, respectively, of all AIDS patients, at first presentation,‘4 or 58% and 30%, respectively, of all AIDS patients presenting with CNS disease in the United States. Cryptococcosis
Cryptococcosis generally presents as a subacute meningitis, with headache the most common and occasionally the sole symptom.’ Other findings include fever, meningeal signs, confusion, seizures, and, rarely, focal deficits.15 Pathologically, Cryptococcus causes a granulomatous meningitis, occasionally with small granulomas in the cerebral cortex. Cryptococcoma has been reported but is much less common.16 In AIDS patients, the symptoms and pathologic findings are often muted, perhaps due to the inability of these patients to mount a significant cell-mediated immune response. This failure may also be responsible for the frequent lack of radiographic findings. Most often both CT” and MR are normal. The thick basilar exudate often typical of fungal meningitis is rarely seen in these patients. Associated findings, such as hydrocephalus, either communicating or obstructive, are also unusual, although many patients with AIDS may have ex vacua ventricular dilatation due to atrophy.
From the Neuroradiology Section, Department of Radiology, University of California, San Francisco. Gordon Sze: Clinical Instructor in Radiology, University of California. San Francisco; currently, Assistant Professor of Radiology, Memorial Sloan-Kettering Cancer Center, Cornell University School of Medicine; Michael N. BrantZawadzki: Associate Professor of Radiology, University of California, San Francisco: David Norman: Professor of Radiology, University of California, San Francisco: T. Hans Newton:Professor of Radiology, Neurology, and Neurosurgery, University of California, San Francisco. Address reprint requests to Gordon Sze, MD, Department of Radiology, Memorial Sloan-Kettering Cancer Center, I275 York Ave. New York, NY 10021. 0 I987 by Grune & Stratton, Inc. 0037-198X/87/2201-0007$05.00/0
42
of AIDS
Toxoplasmosis
Toxoplasmosis is proportionately more common in patients from tropical Third World counSeminars
in Roenrgenology,
Vol XXII,
No 1 (January).
1987:
pp 42-53
NEURORADIOLOGY
OF AIDS
tries, probably reffecting the increased incidence of the disease in the general population of these countries.‘4 It presents as a mass lesion, commonly with focal neurologic abnormalities, seizures, and decreased mental status.‘**” Pathologically, the parasites may be observed within the inflamed brain tissue, with surrounding vasculitis, perivascular infiltrate, and peripheral astrocytosis.” Radiographically, focal intraparenchymal lesions such as toxoplasmosis generally exhibit low density areas on noncontrast CT.74 Following administration of contrast, these areas usually enhance in either an irregular nodular or ring pattern, although occasionally they may not enhance at a11.2’~22In these cases, double dose delayed scans may show enhancement.” The lesions are generally multiple and bilateral. Involvement of the deep gray matter, especially the basal ganglia, occurs in about 75% of cases.g,‘o~23 They do not evolve as typical abscesses with a clearly defined capsule and liquefied center, again probably due to the muted immunologic response of the host.23 Hemorrhagic lesions are uncommon. In the last few years, MR has begun to supplant CT in the work-up of AIDS patients with suspected mass lesions. Because of its extreme sensitivity to altered water content and the absence of bony artifact, MR has proven able to depict lesions, especially when early, when CT is negative (Fig 1). On TI-weighted images, ill-defined regions of low signal intensity are present. On T2-weighted images, these regions become isointense to highly intense and are surrounded by the high intensity signal of edema (Fig 2). Initial studies with gadolinium indicate that this paramagnetic contrast agent behaves similarly to iodinated contrast with CT. Again, irregularly enhancing lesions, often ringlike, are seen on TI-weighted images after the application of gadolinium. The increased sensitivity of MR is important in establishing the diagnosis and instituting proper therapy as early as possible. Furthermore, MF often demonstrates additional lesions, one of which may be more accessible to biopsy. The presence of multiple lesions favors an infectious rather than a neoplastic etiology. Verification of another lesion may obviate the need for biopsy, since most reports now advocate a
43
trial of antitoxoplasmosis therapy in these cases.‘o.24 Response is often dramatic, with decrease in the size of the lesion and the surrounding edema in as short a time as a few days. However, total resolution of the lesions may take as long as 6 months.g Other Nonviral
Infections
Although many other nonviral infections may attack the CNS in patients with AIDS, differentiation on the basis of imaging studies alone is impossible. The pathogens include Candida albicans and other fungi, Mycobacteria, and rarely other bacteria. Although much less common than Cryptococcus, Candida may be the most frequent of the other fungi. Most often they cause abscesses that cannot be differentiated radiographically from the much more common toxoplasmosis. A 5-month-old infant with AIDS has been reported with probable candida meningoencephalitis*‘; another patient had multiple microabscesses secondary to disseminated candidiasisg Such microabscesses may not show on CT.” Whether MR will prove more sensitive has not yet been determined. Other unusual fungal pathogens include Coccidioides, Aspergillus, and Mucor. Multiple microabscesses of the brain have been seen in a patient with disseminated coccidioidomycosis’; aspergillosis and mucormycosis have also been reported with abscess formation.26*27 Mycobacterial species are represented by Mycobacterium tuberculosis and Mycobacterium avium-intracellulare (MAI). M tuberculosis has occurred most often in patients from underdeveloped tropical countries, especially Haiti, presumably because of a higher rate of previous infection. Several patients, mostly Haitian, have been reported with tuberculoma or tuberculous abscess in the brain.‘7.24.28.29Again, differentiation from other causes is not possible by imaging studies alone. These lesions closely resemble the focal masses of toxoplasmosis. Tuberculous meningitis may also be present, although the thick, basilar purulent exudate typical of this infection in immunocompetent patients has not been reported, presumably due to the weakened host defense systems. Prior to the advent of AIDS, disseminated infection with MA1 was rare, even in immunosuppressed patients. However, it has become a
SZE ET AL
Fig 1. Toxoplasmosis in a 35-year-old man with known AIDS and recent development of headache and cerebellar signs. (A) Contrast enhanced CT scan suggests heterogeneity in the posterior fossa. (6) MR scan discloses multiple ring-like lesions of high intensity on TZ-weighted images (TR 2,000 ms, TE 80 ms). Brain stem involvement is also much more clearly depicted. Proved by biopsy.
Fig 2. Candida abscess in a 28-year-old reveals an ill-defined low intensity signal fairly well-circumscribed lesion of slightly consistent with edema. Proved by biopsy.
man with AIDS and right-sided weakness. (A) Partial saturation scan (TR 800 msl near the vertex of the brain. (B) On T2-weighted images (TR 2,000 ms. TE 80 ms), a increased intensity, representing the abscess, is surrounded by high intensity signal
NEURORADIOLOGY
OF AIDS
frequent pathogen in AIDS patients3’ although CNS involvement is unusual. In the brain, granuloma formation has been noted.3’ MA1 has been demonstrated at autopsy in the brain of a patient with subacute encephalitis,” although this may have been the result of accidental contamination.32 Other atypical mycobacterial species have been reported elsewhere in the body, but not as yet in the CNS. Pyogenic bacterial infection of the CNS is unusual in AIDS, probably due to the fact that the primary deficit is cell-mediated immunity rather than humoral. A case of Escherichia coli meningoencephalitis has been reported*‘j; another patient was found to have an abscess containing Nocardia and Salmonella.33 Other bacterial infections have been caused by actinomycetales33 and by spirochetes. Meningovascular syphilis has been reported in two cases,8’26 with a normal CT scan in one. Details of the other patient are not available. Viral Infections
Viral diseasesmay be divided into two categories, those in which the etiology is still in doubt, and those that are clearly opportunistic, such as progressive multifocal leukoencephalopathy (PML). The manifestations of the first category are best described in terms of syndromes rather than specific diseaseentities, and include subacute encephalitis, recurrent or chronic aseptic meningitis, and subacute viral meningitis. In all of these viral syndromes, most reports initially favored cytomegalovirus (CMV) as the prime In somecases,the typical “owl’s suspect.9,‘o,32,34135 eye” inclusion bodies of CMV have been documented. In others, positive immunohistochemical staining has been demonstrated.32,36 However, the hypothesis that CMV is the cause of much of the CNS disease is being disputed, and some believe it is a secondary opportunistic infection. Recently, HIV has been proposedas the most likely primary pathogen in these syndromes.6537,38 The first suggestion that the AIDS virus might have neurotropic, as well as lymphotropic action arose because these agents are morphologically, genomically, and taxonomically related to visna, a retrovirus responsible for a slowly degenerative neurologic diseaseof sheep.39Since then, HIV nucleic acids have been isolated in the brain of five of 15
45
patients with AIDS suffering from encephalopathy.’ In another recent series, cultures for HIV proved positive in ten of 16 patients with AIDSrelated dementia,6 even in casesin which blood cultures were negative, making accidental contamination unlikely. Antibodies to HIV were found within the blood-brain barrier of the CSF in 22 of 23 patients4’ providing evidence that the virus was replicating in the CNS. Recently, HIV has been implicated in viral meningitis, as well as in subacute dementia, with the isolation of the virus in six of seven patients with AIDS or AIDS-related conditions who presented with unexplained chronic meningitis.h The etiology of subacute viral myelitis may also be HIV. Postmortem cultures of the lumbar spinal cord in a patient with distal myelopathy and vacuolar degeneration grew HIV.(’ Additional causesof these syndromes have been suggested: parainfectious conditions,4”42 other viruses (eg, adenovirus),43 and metabolic or toxic effects.44s45 At this point, the evidence for a role for HIV in the causation of at least some of the CNS pathology seemshighly persuasive,although ultimately, disparate organisms may be found to be responsible for these syndromes. Possibly the more fulminant and necrotizing events are secondary to superimposed infections, especially CMV or herpes simplex virus (HSV), while the more subacute and gradually evolving syndromes may be the result of the neurotropic action of the AIDS virus itself.
Syndromes Possibly Caused bv HI k Subacute encephalitis. The most common neurological entity in AIDS is subacute encephalitis, which constitutes from 22 to 36% of all patients with neurologic symptoms.‘.‘“,” The syndrome presents with mild confusion or loss of memory. The neurologic dysfunction usually progressesto marked psychomotor retardation and dementia. Occasionally, the symptoms are accompanied by focal findings or seizures. Eventually, coma and death, usually from intercurrent infection, may ensue. Pathologically, atrophy is prominent.3’ Microglial nodules are present in the gray matter. White matter changesare typified by occasional microglial cells, perivascular infiltrate, focal
SZE ET AL
46
vacuolation, and frequent small poorly defined foci of demyelination interspersed in a general pattern of myelin pallor.13 Reactive astrocytosis may be seen in both white and gray matter. In some patients, the white matter changes predominate, while in others, the gray matter is more extensively involved.32 Radiographically, CT scans are normal or show only atrophy, usually mild, but sometimes striking. Occasionally, diffuse low density is present in the white matter.” MR findings are similarly normal or show only atrophy. Occasionally, MR discloses high intensity in the white matter on T2-weighted images. These pathologic areas may be focal or may coalesce and involve much of the white matter. They may represent the pathologically demonstrated areas of demyelination. Subacute viral myelitis. Increasingly, subacute viral myelitis is being identified in AIDS.13 Symptoms include leg weakness, incontinence, ataxia, and spasticity. Pathologically, a vacuolar myelopathy primarily restricted to the lateral and posterior columns of the spinal cord, especially in the midthoracic level is usually present, often associated with demyelination4’ This finding has been described in about one third of all patients with AIDS.1394S Since the spinal cord is grossly normal, myelography and CT have been normal. To date, no reports have been published regarding pathologic correlation with MR in this syndrome. Viral meningitis. Also associated with AIDS is viral meningitis.6*9X’0 Symptoms are typified by headaches, fever, and meningeal signs. Clinically, viral meningitis in AIDS usually remits spontaneously, although it may recur. Radiographitally, these patients have normal CT and MR scans. Opportunistic
Viral Infections
Progressive multifocal leukoencephalopathy. Many reports have appeared of PML in
patients with AIDS.9*‘0,46 Symptoms include headache, dementia, and focal deficits. The causative agent is a Papova virus, almost always the JC virus, which presumably becomes reactivated in immunosuppressed patients following asymptomatic childhood infection.4’ Histologically, bizarre hypertrophic astrocytes with inclusion bodies in the oligodendrocytes can be demon-
strated. Because the JC virus attacks the myelinproducing oligodendrocytes, PML is manifested by demyelination and edema. CT scans demonstrate low density in the white matter of the affected regions, typically in a parietooccipital distribution, However, approximately 10% of cases are solely infratentorial, affecting the brain stem and/or cerebellum. Rarely, extension into the grey matter is observed. MR has proved superior in detecting these lesions due to its greater sensitivity to changes in water content (Fig 3). Loss of the hydrophobic myelin results in increased local water content. This sensitivity may be of clinical, as well as diagnostic benefit, since transient improvement with therapy has been reported.47 However, although sensitive, MR is not specific. As previously noted, we have seen a similar appearance in cases in which biopsy or autopsy did not show PML, but revealed subacute encephalopathy. Viral Encephalitis. CMV plays a role in at least some cases of CNS pathology.34,36*48Frank necrotic foci of acute encephalitis often demonstrate the typical inclusion bodies of CMV. Both the CT and MR appearances are identical to those of other mass lesions in AIDS. Prominent ependymitis has been noted in several patients, often as a near terminal event. The distribution strikingly resembles that seen in congenital CMV disease.36 Cytomegalic cells are found in the periventricular areas3’ and CMV has been grown out of CSF cultures.48 Enhancing areas in the subependymal regions appear on CT scans with contrast, whereas MR discloses areas of high signal intensity in a periventricular distribution (Fig 4). Irregular extension of the high intensity signal into the adjacent white matter aids in differentiating this entity from pure transependymal fluid flow typical of hydrocephalus, which generally appears as a smooth thin band surrounding the ventricles. Further work will most likely show a role for many other viruses in encephalitis. By itself, herpes simplex encephalitis is not diagnostic of AIDS. However, while nearly all adult cases of herpes simplex encephalitis are caused by HSV-I, in AIDS patients it may also occur from HSV-II.49 Prior to the advent of AIDS, HSV-II encephalitis was usually restricted to infants and only seven cases had been reported in adults, some of whom were clearly
Fig 3. (A and B) Progressive multifocal leukoencephalopathy mental status changes. TP-weighted MR scans (TR 2,000 parietooccipital lobes bilaterally. Proved at autopsy.
Fig 4. Viral ependymitis and encephalitis. A 40-year-old opportunistic infections. He now shows decreased mental enhancement of the ependyma of the lateral ventricles. (Bj intensity surrounding the ventricles on T2-weighted images. extension into adjacent white matter, helping to differentiate
ms,
in a 32-year-old TE 35/70
ms)
man with disclose
known AIDS high signal
presenting intensity
in
with the
with a history of Pneumocystis carinii pneumonia and other status and lethargy. (A) Contrast-enhanced CT scan shows MR scan (TR 2,000 ms, TE 40 msj demonstrates high signal The contour of the high signal is irregular and shows uneven this entity from hydrocephalus. Proved at autopsy.
SZE ET AL
48
immunodeficient. The CT and MR scans of patients with AIDS and HSV-I or HSV-II infection disclose low density in the temporal lobes, either unilaterally or bilaterally. MR is more sensitive. Bilateral temporal lobe changes are almost pathognomonic of herpes simplex encephalitis. Levy et al9 report a probable case of varicella zoster encephalitis in which CSF cultures were positive, but autopsy was not performed. This finding is not surprising in light of the suspected association between herpes zoster radiculitis and the later development of AIDS. Viral myelitis. In addition to fulminant encephalitis, necrotizing myelitis, of rapid onset and progression, has occasionally been seen in AIDS. Two cases, one resulting in quadriplegia in 17 days, have been attributed to HSV-II.SG52 Myelography and CT scans were negative in both cases. An additional case of ascending myelitis was attributed to CMV at autopsy.53 To our knowledge, MR has so far not been performed in such a case. In another AIDS case, a patient presented with a rapidly evolving BrownSequard syndrome. On MR, we found a localized high intensity focus at the cervical medullary junction consistent with necrosis, which was verified at autopsy. Histology was consistent with CMV. NEOPLASMS Primary
Lymphoma
Prior to the advent of AIDS, primary CNS lymphoma was an unusual neoplasm, constituting ~2% of all lymphomas. A significant percentage appeared in patients with immunodeficient states, either congenital, as in the Wiskott-Aldrich syndrome, acquired, as in Sjogren syndrome, or iatrogenic, as in organ transplant recipients.54,55 Lymphoma has appeared in approximately 6.4% of all AIDS patients presenting with CNS disease.14 Over 20 AIDS patients with primary CNS lymphoma have been treated in our institution. Symptoms are indistinguishable from those of other focal intracerebral masses.54*56 Pathologically, these tumors resemble the primary CNS lymphoma seen with other causes of immunodysfunction.” Virtually all of them are high-grade lymphomas, either of immunoblastic
sarcoma type or the small noncleaved cell lymphoma. 54,58s9 These are roughly equivalent to the diffuse histiocytic lymphoma or the diffuse undifferentiated lymphoma of the Rappaport classification,60 and are aggressive lesions. The average life expectancy following diagnosis is usually only a few months. Radiographically, primary CNS lymphoma classically shows well-circumscribed slightly hyperdense lesions that enhance uniformly, These occur in the periventricular zone, and are associated with little edema.61x62In AIDS, these tumors appear totally different.22*54 Noncontrast CT scans generally show hypodense regions. These enhance irregularly, often in a nodular or ringlike pattern, and surrounding edema may be prominent (Fig 5A). About one third are multifocal.62A6 All of our cases were multicentric at careful autopsy.” Therefore, in a patient with multiple mass lesions, lymphoma cannot be excluded, although toxoplasmosis and other infectious etiologies may be more likely. We have seen several cases with a negative CT scan.9,57In one, autopsy showed diffuse lymphomatous infiltration of the brain with micronodular areas of involvement. However, the CT scan preceded the terminal event by several weeks and presumably the deposits were too small for visualization at the time of the scan. As expected, MR reveals only ill-defined regions of diminished intensity on Tl-weighted images which, along with surrounding edema, become high intensity on T2-weighted images (Fig 5B and C). The appearance with both CT and MR is nonspecific, resembling that of other focal mass lesions in AIDS. Several diffuse diseases may affect the same patient simultaneously. We have seen six patients who presented with contrast-enhancing lesions typical of toxoplasmosis. However, only some of the lesions responded to antitoxoplasmosis therapy; other lesions continued to grow. An additional biopsy demonstrated simultaneous lymphoma and toxoplasmosis (Fig 6). Systemic
Lymphoma
While primary CNS lymphoma more frequently involves the brain parenchyma, systemic lymphoma usually invades the meninges.67*68 Because of this, symptoms often include radicu-
NEURORADIOLOGY
OF AIDS
49
Fig 5. lmmunoblastic lymphoma in a 42-year-old man with AIDS, somnolence, and left hemiplegia. (A) Contrastenhanced CT scan shows a discrete area of irregular ring enhancement in the right basal ganglia. A similar lesion was present in the left occipitoparietal region. (6) Partial saturation MR scans (TR SO0 ms) reveals a low intensity signal with mass effect in the corresponding basal ganglia region. (C) TZ-weighted image (TR 2,000 ms, TE 30 ms) discloses the lesion as an ill-defined high intensity signal surrounded by considerable edema. A similar appearance was noted in the left occipitoperietal region. Proved by biopsy and autopsy.
lopathy and multiple cranial nerve neuropathy, as well as headache and mental status changes.69 The pathologic findings are consistent with leptomeningeal spread, and frank parenchymal metastasis is much less common. Histologic subtypes most often associated with CNS spread consist of the same high-grade lymphomas69 that
typify AIDS patients. Extension into the CNS has been reported in about 20% of AIDSassociated systemic lymphoma.58~70 Radiographically, both CT and MR are usually negative in leptomeningeal spread. This reflects the reports in the literature that meningeal enhancement is a rare finding.“‘,68 We have
50
SZE ET AL
Fig 6. lmmunoblastic lymphoma in a 44-year-old man with AID6 and biopsy-diagnosed cerebral toxoplasmosis. On antitoxoplasmosis therapy (pyrimethamine and sulfadiaxine). most of the lesions resolved. However, a contrastenhanced CT scan (A) reveals a persistent and growing ring lesion in the right centrum semiovale, with a low density center surrounded by considerable edema. The Tl-weighted MR image showed an ill-defined low signal intensity in this region. (B) The TZ-weighted image (TR 2.000 ms, TE 60 ms) discloses a slightly intense core in the center of a large area of highly intense edema. An additional focus was noted on the left on other scans. (Cl After administration of gadolinium-DTPA, the Tl-weighted imege showed enhancement of the lesion in similar fashion to the contrast-enhanced CT scan. Biopsy confirmed.
seen two cases of lymphoma with hydrocephaIus associated with leptomeningeal spread. Parenchymal CNS metastases in secondary lymphoma resemble those of the primary form in radiographic appearance. Several cases of epidu-
ral spinal cord compression from lymphomatous masses in AIDS patients have been reported.‘0*7037’As in other CNS involvement, highgrade lymphoma was found. Of incidental note, epidural spinal cord compression was also
NEURORADIOLOGY
reported ma.” Kaposi
OF AIDS
in an AIDS
51
patient with
plasmacyto-
Sarcoma
Although common elsewhere in the body, Kaposi sarcoma is extremely rare in the CNS. Several pathologically proven cases.have been reported.2’,72173 CT shows contrast-enhancing parenchymal masses,typical of brain metastasis. In addition, these lesionsare often hemorrhagic. To date, we are not aware of any MR description of the findings in Kaposi sarcoma metastatic to the brain. VASCULAR
COMPLICATIONS
Several reports have detailed cerebrovascular complications in patients with AIDS.9V’0,‘2 In
some cases,intracerebral hemorrhage has been secondary to a CNS neoplasm, either lymphoma or Kaposi sarcoma, as mentioned previously. In others, vascular complications occurred as a result of diseaseelsewhere. Snider et al” report two patients with infarction, one angiographitally proven of embolic origin, felt secondary to nonbacterial thrombotic endocarditis. The other had bilateral basal ganglia infarcts associated with Ramsay-Hunt syndrome, a cranial nerve neuropathy secondary to varicella zoster infection. This casestrongly suggestsherpetic vasculitis as the precipitating event. In one patient, an aneurysm of the tip of a basilar artery leaked, probably exacerbated by idiopathic thrombocytopenic purpura, a syndrome that has been associated with AIDS.74
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1985;68:333-339
38. Levy JA, Kaminsky LS, Morrow WJ, et al: Infection by the retrovirus associated with the acquired immunodeficiency syndrome. Clinical, pathological, and molecular features. Ann Intern Med 1985;103:694-699 39. Gonda MA, Wong-Staal F, Gallo RC, et al: Sequence homology and morphological similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science 1985;227:173177 40. Resnick L, deMarzo-Veronese F, Schupbach J, et al: Intra blood-brain-barrier synthesis of HTLV-III-Specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex. N Engl J Med 1985;313:1498-1504 41. Britton CB, Miller JR: Neurologic complications in
acquired immunodeficiency syndrome (AIDS). Neural Clin 1984;2:315-339 42. Goldstick L, Mandybur TI, Bode R: Spinal cord degeneration in AIDS. Neurology 1985;35:103-106 43. Horoupian DS, Pick P, Spigland I, et al: Acquired immune deficiency syndrome and multiple tract degeneration in a homosexual man. Ann Neural 1984;15:502-505 44. Kimbrough RD: Vacuolar myelopathy in patients with the acquired immunodeficiency syndrome. N Engl J Med 1985;313:827 (letter) 45. Petit0 CK, Navia BA, Cho E, et al: Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med 1985;312:87&879 46. Krupp LB, Lipton RB, Swerdlow ML, et al: Progressive multifocal leukoencephalopathy: Clinical and radiographic features. Ann Neural 1985;17:344-349 47. Marriott PJ, O’Brien MD, Mackenzie ICK, et al: Progressive multifocal leucoencephalopathy: Remission with cytarabine. J Neural Neurosurg Psychiatry 1975;38:205209 48. Edwards RH, Messing R, McKendall RR: Cytomegalovirus meningoencephalitis in a homosexual man with Kaposi’s sarcoma: Isolation of CMV from CSF cells. Neurology 1985;35:560-562 49. Dix RD, Waitzman DM, Follansbee S, et al: Herpes simplex virus type 2 encephalitis in two homosexual men with persistent lymphadenopathy. Ann Neural 1985;17:203-206 50. Britton CB, Mesa-Tejada R, Fenoglio CM, et al: A new complication of AIDS: Thoracic myelitis caused by herpes simplex virus. Neurology 1985;35:1071-1074 51. Dix RD, Bredesen DE, Erlich KS, et al: Recovery of herpesviruses from cerebrospinal fluid of immunodeficient homosexual men. Ann Neural 1985;18:611-614 52. Tucker T, Dix RD, Katzen C, et al: Cytomegalovirus and herpes simplex virus ascending myelitis in a patient with acquired immune deficiency syndrome. Ann Neural 1985;18:74-79 53. Bagley PH. Scott DA, Smith LS, et al: Cytomegalovirus infection, ascending myelitis, and pulmonary embolus. Ann Intern Med 1986;104:587 (letter) 54. Gill PS, Levine AM, Meyer PR, et al: Primary central nervous system lymphoma in homosexual men: Clinical, immunologic and pathologic features. Am J Med 1985;78:742-748 55. Letendre L, Banks PM, Reese DF, et al: Primary lymphoma of the central nervous system. Cancer 1982;49:939-943 56. Helle TL, Britt RH, Colby TV: Primary lymphoma of the central nervous system. Clinicopathological study of experience at Stanford. J Neurosurg 1984;60:94-103 57. So YT, Beckstead JH, Davis RL: Primary central nervous system lymphoma in acquired immune deficiency syndrome: Clinical and pathologic study. Ann Neural 1986;20 (in press) 58. Ioachim HL, Cooper MC, Hellman GC: Lymphomas in men at high risk for acquired immune deficiency syndrome (AIDS). A study of 21 cases.Cancer 1985;56:2831-2842 59. Levine AM, Gill PS, Meyer PR, et al: Retrovirus and malignant lymphoma in homosexual men. JAMA 1985;254:1921-1925
NEURORADIOLOGY
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OF AIDS
60. Rosenberg SA, Berard CW, Brown BW Jr, et al: National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas. Summary and description of a working formulation for clinical usage. Cancer 1982;49:2112-2135 6 1. Palacios E, Gorelick PB, Gonzalez CF, et al: Malignant lymphoma of the nervous system. J Comput Ass& Tomogr 1982;6:689-701 62. Spillane JA, Kendall BE, Moseley IF: Cerebral lymphoma: Clinical radiological correlation. J Neural Neurosurg Psychiatry 1982;45: 199-208 63. Cellerier P, Chiras J, Gray F, et al: Computed tomography in primary lymphoma of the brain. Neuroradiology 1984;26:485-492 64. Enzmann DR. Krikorian J, Norman D, et al: Computed tomography in primary reticulum cell sarcoma of the brain. Rndiology 1979;130:165-170 65. Kazner E, Wilske J, Steinhoff H, et al: Computer assisted tomography in primary malignant lymphoma of the brain. J Comput Assist Tomogr 1978;2: 125-l 34 66. Tadmor R, Davis KR, Roberson GH, et al: Computed tomography in primary malignant lymphoma of the brain. J Comput Assist Tomogr 1978;2: 135-I 40 67. Levitt LJ, Dawson, DM, Rosenthal DS, et al: CNS involvement in the non-Hodgkin’s lymphomas. Cancer 1980;45:545-552
68. Pagani JJ, Libshitz HI, Wallace S, et al: Central nervous system leukemia and lymphoma: Computed tomographic manifestations. AJR 1981;137:1 195- 1201 69. Mackintosh FR, Colby TV, Podolsky WJ, et al: Central nervous system involvement in non-Hodgkin’s lymphoma: An analysis of 105 cases. Cancer 1982;49:586595 70. Ziegler JL, Beckstead JA, Volberding PA, et al: Non-Hodgkin’s lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 1984;3 11:565- 570 7 1. Cheesman SH, Gang DL: Case records of the Massachusetts General Hospital: Weekly clinicopathological exercises. Case 9-1986. A 40-month-old girl with the acquired immunodeficiency syndrome and spinal-cord compression. N Engl J Med 1986;3 14:629-640 72. Gorin FA, Bale JF, Halks-Miller sarcoma metastatic to the CNS. Arch 165
M, et al: Kaposi’s Neural I985;42:162-
73. Levy RM, Pons VG, Rosenblum ML: Central system mass lesions in the acquired immunodeticiency drome (AIDS). J Neurosurg 1984;61:9-16 74. Abrams update. AIDS 1986;162:3
D: Idiopathic thrombocytopenic File, San Francisco General
nervous synpurpura Hospital
N. Brant-Zawadzki,
ARLY REPORTS on the neurologic complications of AIDS followed almost immediately the initial description of the syndrome itself. A multitude of unusual neoplasms and opportunistic pathogens were found to affect the central nervous system (CNS). Some resulted from systemic dissemination; others primarily targeted the neural axis. Since then, the spectrum of neurologic abnormalities in AIDS has widened considerably. The discovery of the class of putative etiologic agents, the retroviruses, known as the human immunodeficiency viruses (HIV),’ AIDS-associated retrovirus (ARV),’ lymphadenopathy virus (LAV),3 and immunodeficiency-associated virus (IDAV)4 was soon followed by isolation of the nucleic acid of the virus in the brain itself.’ This and related evidence, including culture of the virus from brain tissue,6 suggest that the virus may be directly involved in the pathogenesis of several of the neurologic syndromes, both acute and chronic, associated with AIDS. By virtue of the neurotropism, as well as lymphotropism of this virus,‘*’ the CNS may suffer devastating consequences not only from the opportunistic infections that typify the syndrome in the rest of the body, but also from the damage due to the HIV virus itself. If the virus does have this capability, then the neural axis occupies an unfortunately unique niche in the body, with possibly the most extensive range of AIDS related abnormalities of any single organ system. In addition, it may well be that the
David Norman,
and T. Hans Newton
full effects of chronic HIV infection on the brain are not yet apparent. Approximately 10% of all AIDS patients present initially with neurologic symptoms.* During the course of their illness, an additional 25% to 30% of patients develop neurologic abnormalities.‘.” At autopsy, from 55% to 95% have documented pathologic change in the CNS.9,“-‘3 These entities can be divided into infectious and neoplastic categories.
E
INFECTION Nonviral
Infections
Both nonviral and viral infections attack the CNS. Of the nonviral infections, Cryptococcus neoformans and Toxoplasma gondii are the most common, affecting the CNS in 4.3% and 2.2%, respectively, of all AIDS patients, at first presentation,‘4 or 58% and 30%, respectively, of all AIDS patients presenting with CNS disease in the United States. Cryptococcosis
Cryptococcosis generally presents as a subacute meningitis, with headache the most common and occasionally the sole symptom.’ Other findings include fever, meningeal signs, confusion, seizures, and, rarely, focal deficits.15 Pathologically, Cryptococcus causes a granulomatous meningitis, occasionally with small granulomas in the cerebral cortex. Cryptococcoma has been reported but is much less common.16 In AIDS patients, the symptoms and pathologic findings are often muted, perhaps due to the inability of these patients to mount a significant cell-mediated immune response. This failure may also be responsible for the frequent lack of radiographic findings. Most often both CT” and MR are normal. The thick basilar exudate often typical of fungal meningitis is rarely seen in these patients. Associated findings, such as hydrocephalus, either communicating or obstructive, are also unusual, although many patients with AIDS may have ex vacua ventricular dilatation due to atrophy.
From the Neuroradiology Section, Department of Radiology, University of California, San Francisco. Gordon Sze: Clinical Instructor in Radiology, University of California. San Francisco; currently, Assistant Professor of Radiology, Memorial Sloan-Kettering Cancer Center, Cornell University School of Medicine; Michael N. BrantZawadzki: Associate Professor of Radiology, University of California, San Francisco: David Norman: Professor of Radiology, University of California, San Francisco: T. Hans Newton:Professor of Radiology, Neurology, and Neurosurgery, University of California, San Francisco. Address reprint requests to Gordon Sze, MD, Department of Radiology, Memorial Sloan-Kettering Cancer Center, I275 York Ave. New York, NY 10021. 0 I987 by Grune & Stratton, Inc. 0037-198X/87/2201-0007$05.00/0
42
of AIDS
Toxoplasmosis
Toxoplasmosis is proportionately more common in patients from tropical Third World counSeminars
in Roenrgenology,
Vol XXII,
No 1 (January).
1987:
pp 42-53
NEURORADIOLOGY
OF AIDS
tries, probably reffecting the increased incidence of the disease in the general population of these countries.‘4 It presents as a mass lesion, commonly with focal neurologic abnormalities, seizures, and decreased mental status.‘**” Pathologically, the parasites may be observed within the inflamed brain tissue, with surrounding vasculitis, perivascular infiltrate, and peripheral astrocytosis.” Radiographically, focal intraparenchymal lesions such as toxoplasmosis generally exhibit low density areas on noncontrast CT.74 Following administration of contrast, these areas usually enhance in either an irregular nodular or ring pattern, although occasionally they may not enhance at a11.2’~22In these cases, double dose delayed scans may show enhancement.” The lesions are generally multiple and bilateral. Involvement of the deep gray matter, especially the basal ganglia, occurs in about 75% of cases.g,‘o~23 They do not evolve as typical abscesses with a clearly defined capsule and liquefied center, again probably due to the muted immunologic response of the host.23 Hemorrhagic lesions are uncommon. In the last few years, MR has begun to supplant CT in the work-up of AIDS patients with suspected mass lesions. Because of its extreme sensitivity to altered water content and the absence of bony artifact, MR has proven able to depict lesions, especially when early, when CT is negative (Fig 1). On TI-weighted images, ill-defined regions of low signal intensity are present. On T2-weighted images, these regions become isointense to highly intense and are surrounded by the high intensity signal of edema (Fig 2). Initial studies with gadolinium indicate that this paramagnetic contrast agent behaves similarly to iodinated contrast with CT. Again, irregularly enhancing lesions, often ringlike, are seen on TI-weighted images after the application of gadolinium. The increased sensitivity of MR is important in establishing the diagnosis and instituting proper therapy as early as possible. Furthermore, MF often demonstrates additional lesions, one of which may be more accessible to biopsy. The presence of multiple lesions favors an infectious rather than a neoplastic etiology. Verification of another lesion may obviate the need for biopsy, since most reports now advocate a
43
trial of antitoxoplasmosis therapy in these cases.‘o.24 Response is often dramatic, with decrease in the size of the lesion and the surrounding edema in as short a time as a few days. However, total resolution of the lesions may take as long as 6 months.g Other Nonviral
Infections
Although many other nonviral infections may attack the CNS in patients with AIDS, differentiation on the basis of imaging studies alone is impossible. The pathogens include Candida albicans and other fungi, Mycobacteria, and rarely other bacteria. Although much less common than Cryptococcus, Candida may be the most frequent of the other fungi. Most often they cause abscesses that cannot be differentiated radiographically from the much more common toxoplasmosis. A 5-month-old infant with AIDS has been reported with probable candida meningoencephalitis*‘; another patient had multiple microabscesses secondary to disseminated candidiasisg Such microabscesses may not show on CT.” Whether MR will prove more sensitive has not yet been determined. Other unusual fungal pathogens include Coccidioides, Aspergillus, and Mucor. Multiple microabscesses of the brain have been seen in a patient with disseminated coccidioidomycosis’; aspergillosis and mucormycosis have also been reported with abscess formation.26*27 Mycobacterial species are represented by Mycobacterium tuberculosis and Mycobacterium avium-intracellulare (MAI). M tuberculosis has occurred most often in patients from underdeveloped tropical countries, especially Haiti, presumably because of a higher rate of previous infection. Several patients, mostly Haitian, have been reported with tuberculoma or tuberculous abscess in the brain.‘7.24.28.29Again, differentiation from other causes is not possible by imaging studies alone. These lesions closely resemble the focal masses of toxoplasmosis. Tuberculous meningitis may also be present, although the thick, basilar purulent exudate typical of this infection in immunocompetent patients has not been reported, presumably due to the weakened host defense systems. Prior to the advent of AIDS, disseminated infection with MA1 was rare, even in immunosuppressed patients. However, it has become a
SZE ET AL
Fig 1. Toxoplasmosis in a 35-year-old man with known AIDS and recent development of headache and cerebellar signs. (A) Contrast enhanced CT scan suggests heterogeneity in the posterior fossa. (6) MR scan discloses multiple ring-like lesions of high intensity on TZ-weighted images (TR 2,000 ms, TE 80 ms). Brain stem involvement is also much more clearly depicted. Proved by biopsy.
Fig 2. Candida abscess in a 28-year-old reveals an ill-defined low intensity signal fairly well-circumscribed lesion of slightly consistent with edema. Proved by biopsy.
man with AIDS and right-sided weakness. (A) Partial saturation scan (TR 800 msl near the vertex of the brain. (B) On T2-weighted images (TR 2,000 ms. TE 80 ms), a increased intensity, representing the abscess, is surrounded by high intensity signal
NEURORADIOLOGY
OF AIDS
frequent pathogen in AIDS patients3’ although CNS involvement is unusual. In the brain, granuloma formation has been noted.3’ MA1 has been demonstrated at autopsy in the brain of a patient with subacute encephalitis,” although this may have been the result of accidental contamination.32 Other atypical mycobacterial species have been reported elsewhere in the body, but not as yet in the CNS. Pyogenic bacterial infection of the CNS is unusual in AIDS, probably due to the fact that the primary deficit is cell-mediated immunity rather than humoral. A case of Escherichia coli meningoencephalitis has been reported*‘j; another patient was found to have an abscess containing Nocardia and Salmonella.33 Other bacterial infections have been caused by actinomycetales33 and by spirochetes. Meningovascular syphilis has been reported in two cases,8’26 with a normal CT scan in one. Details of the other patient are not available. Viral Infections
Viral diseasesmay be divided into two categories, those in which the etiology is still in doubt, and those that are clearly opportunistic, such as progressive multifocal leukoencephalopathy (PML). The manifestations of the first category are best described in terms of syndromes rather than specific diseaseentities, and include subacute encephalitis, recurrent or chronic aseptic meningitis, and subacute viral meningitis. In all of these viral syndromes, most reports initially favored cytomegalovirus (CMV) as the prime In somecases,the typical “owl’s suspect.9,‘o,32,34135 eye” inclusion bodies of CMV have been documented. In others, positive immunohistochemical staining has been demonstrated.32,36 However, the hypothesis that CMV is the cause of much of the CNS disease is being disputed, and some believe it is a secondary opportunistic infection. Recently, HIV has been proposedas the most likely primary pathogen in these syndromes.6537,38 The first suggestion that the AIDS virus might have neurotropic, as well as lymphotropic action arose because these agents are morphologically, genomically, and taxonomically related to visna, a retrovirus responsible for a slowly degenerative neurologic diseaseof sheep.39Since then, HIV nucleic acids have been isolated in the brain of five of 15
45
patients with AIDS suffering from encephalopathy.’ In another recent series, cultures for HIV proved positive in ten of 16 patients with AIDSrelated dementia,6 even in casesin which blood cultures were negative, making accidental contamination unlikely. Antibodies to HIV were found within the blood-brain barrier of the CSF in 22 of 23 patients4’ providing evidence that the virus was replicating in the CNS. Recently, HIV has been implicated in viral meningitis, as well as in subacute dementia, with the isolation of the virus in six of seven patients with AIDS or AIDS-related conditions who presented with unexplained chronic meningitis.h The etiology of subacute viral myelitis may also be HIV. Postmortem cultures of the lumbar spinal cord in a patient with distal myelopathy and vacuolar degeneration grew HIV.(’ Additional causesof these syndromes have been suggested: parainfectious conditions,4”42 other viruses (eg, adenovirus),43 and metabolic or toxic effects.44s45 At this point, the evidence for a role for HIV in the causation of at least some of the CNS pathology seemshighly persuasive,although ultimately, disparate organisms may be found to be responsible for these syndromes. Possibly the more fulminant and necrotizing events are secondary to superimposed infections, especially CMV or herpes simplex virus (HSV), while the more subacute and gradually evolving syndromes may be the result of the neurotropic action of the AIDS virus itself.
Syndromes Possibly Caused bv HI k Subacute encephalitis. The most common neurological entity in AIDS is subacute encephalitis, which constitutes from 22 to 36% of all patients with neurologic symptoms.‘.‘“,” The syndrome presents with mild confusion or loss of memory. The neurologic dysfunction usually progressesto marked psychomotor retardation and dementia. Occasionally, the symptoms are accompanied by focal findings or seizures. Eventually, coma and death, usually from intercurrent infection, may ensue. Pathologically, atrophy is prominent.3’ Microglial nodules are present in the gray matter. White matter changesare typified by occasional microglial cells, perivascular infiltrate, focal
SZE ET AL
46
vacuolation, and frequent small poorly defined foci of demyelination interspersed in a general pattern of myelin pallor.13 Reactive astrocytosis may be seen in both white and gray matter. In some patients, the white matter changes predominate, while in others, the gray matter is more extensively involved.32 Radiographically, CT scans are normal or show only atrophy, usually mild, but sometimes striking. Occasionally, diffuse low density is present in the white matter.” MR findings are similarly normal or show only atrophy. Occasionally, MR discloses high intensity in the white matter on T2-weighted images. These pathologic areas may be focal or may coalesce and involve much of the white matter. They may represent the pathologically demonstrated areas of demyelination. Subacute viral myelitis. Increasingly, subacute viral myelitis is being identified in AIDS.13 Symptoms include leg weakness, incontinence, ataxia, and spasticity. Pathologically, a vacuolar myelopathy primarily restricted to the lateral and posterior columns of the spinal cord, especially in the midthoracic level is usually present, often associated with demyelination4’ This finding has been described in about one third of all patients with AIDS.1394S Since the spinal cord is grossly normal, myelography and CT have been normal. To date, no reports have been published regarding pathologic correlation with MR in this syndrome. Viral meningitis. Also associated with AIDS is viral meningitis.6*9X’0 Symptoms are typified by headaches, fever, and meningeal signs. Clinically, viral meningitis in AIDS usually remits spontaneously, although it may recur. Radiographitally, these patients have normal CT and MR scans. Opportunistic
Viral Infections
Progressive multifocal leukoencephalopathy. Many reports have appeared of PML in
patients with AIDS.9*‘0,46 Symptoms include headache, dementia, and focal deficits. The causative agent is a Papova virus, almost always the JC virus, which presumably becomes reactivated in immunosuppressed patients following asymptomatic childhood infection.4’ Histologically, bizarre hypertrophic astrocytes with inclusion bodies in the oligodendrocytes can be demon-
strated. Because the JC virus attacks the myelinproducing oligodendrocytes, PML is manifested by demyelination and edema. CT scans demonstrate low density in the white matter of the affected regions, typically in a parietooccipital distribution, However, approximately 10% of cases are solely infratentorial, affecting the brain stem and/or cerebellum. Rarely, extension into the grey matter is observed. MR has proved superior in detecting these lesions due to its greater sensitivity to changes in water content (Fig 3). Loss of the hydrophobic myelin results in increased local water content. This sensitivity may be of clinical, as well as diagnostic benefit, since transient improvement with therapy has been reported.47 However, although sensitive, MR is not specific. As previously noted, we have seen a similar appearance in cases in which biopsy or autopsy did not show PML, but revealed subacute encephalopathy. Viral Encephalitis. CMV plays a role in at least some cases of CNS pathology.34,36*48Frank necrotic foci of acute encephalitis often demonstrate the typical inclusion bodies of CMV. Both the CT and MR appearances are identical to those of other mass lesions in AIDS. Prominent ependymitis has been noted in several patients, often as a near terminal event. The distribution strikingly resembles that seen in congenital CMV disease.36 Cytomegalic cells are found in the periventricular areas3’ and CMV has been grown out of CSF cultures.48 Enhancing areas in the subependymal regions appear on CT scans with contrast, whereas MR discloses areas of high signal intensity in a periventricular distribution (Fig 4). Irregular extension of the high intensity signal into the adjacent white matter aids in differentiating this entity from pure transependymal fluid flow typical of hydrocephalus, which generally appears as a smooth thin band surrounding the ventricles. Further work will most likely show a role for many other viruses in encephalitis. By itself, herpes simplex encephalitis is not diagnostic of AIDS. However, while nearly all adult cases of herpes simplex encephalitis are caused by HSV-I, in AIDS patients it may also occur from HSV-II.49 Prior to the advent of AIDS, HSV-II encephalitis was usually restricted to infants and only seven cases had been reported in adults, some of whom were clearly
Fig 3. (A and B) Progressive multifocal leukoencephalopathy mental status changes. TP-weighted MR scans (TR 2,000 parietooccipital lobes bilaterally. Proved at autopsy.
Fig 4. Viral ependymitis and encephalitis. A 40-year-old opportunistic infections. He now shows decreased mental enhancement of the ependyma of the lateral ventricles. (Bj intensity surrounding the ventricles on T2-weighted images. extension into adjacent white matter, helping to differentiate
ms,
in a 32-year-old TE 35/70
ms)
man with disclose
known AIDS high signal
presenting intensity
in
with the
with a history of Pneumocystis carinii pneumonia and other status and lethargy. (A) Contrast-enhanced CT scan shows MR scan (TR 2,000 ms, TE 40 msj demonstrates high signal The contour of the high signal is irregular and shows uneven this entity from hydrocephalus. Proved at autopsy.
SZE ET AL
48
immunodeficient. The CT and MR scans of patients with AIDS and HSV-I or HSV-II infection disclose low density in the temporal lobes, either unilaterally or bilaterally. MR is more sensitive. Bilateral temporal lobe changes are almost pathognomonic of herpes simplex encephalitis. Levy et al9 report a probable case of varicella zoster encephalitis in which CSF cultures were positive, but autopsy was not performed. This finding is not surprising in light of the suspected association between herpes zoster radiculitis and the later development of AIDS. Viral myelitis. In addition to fulminant encephalitis, necrotizing myelitis, of rapid onset and progression, has occasionally been seen in AIDS. Two cases, one resulting in quadriplegia in 17 days, have been attributed to HSV-II.SG52 Myelography and CT scans were negative in both cases. An additional case of ascending myelitis was attributed to CMV at autopsy.53 To our knowledge, MR has so far not been performed in such a case. In another AIDS case, a patient presented with a rapidly evolving BrownSequard syndrome. On MR, we found a localized high intensity focus at the cervical medullary junction consistent with necrosis, which was verified at autopsy. Histology was consistent with CMV. NEOPLASMS Primary
Lymphoma
Prior to the advent of AIDS, primary CNS lymphoma was an unusual neoplasm, constituting ~2% of all lymphomas. A significant percentage appeared in patients with immunodeficient states, either congenital, as in the Wiskott-Aldrich syndrome, acquired, as in Sjogren syndrome, or iatrogenic, as in organ transplant recipients.54,55 Lymphoma has appeared in approximately 6.4% of all AIDS patients presenting with CNS disease.14 Over 20 AIDS patients with primary CNS lymphoma have been treated in our institution. Symptoms are indistinguishable from those of other focal intracerebral masses.54*56 Pathologically, these tumors resemble the primary CNS lymphoma seen with other causes of immunodysfunction.” Virtually all of them are high-grade lymphomas, either of immunoblastic
sarcoma type or the small noncleaved cell lymphoma. 54,58s9 These are roughly equivalent to the diffuse histiocytic lymphoma or the diffuse undifferentiated lymphoma of the Rappaport classification,60 and are aggressive lesions. The average life expectancy following diagnosis is usually only a few months. Radiographically, primary CNS lymphoma classically shows well-circumscribed slightly hyperdense lesions that enhance uniformly, These occur in the periventricular zone, and are associated with little edema.61x62In AIDS, these tumors appear totally different.22*54 Noncontrast CT scans generally show hypodense regions. These enhance irregularly, often in a nodular or ringlike pattern, and surrounding edema may be prominent (Fig 5A). About one third are multifocal.62A6 All of our cases were multicentric at careful autopsy.” Therefore, in a patient with multiple mass lesions, lymphoma cannot be excluded, although toxoplasmosis and other infectious etiologies may be more likely. We have seen several cases with a negative CT scan.9,57In one, autopsy showed diffuse lymphomatous infiltration of the brain with micronodular areas of involvement. However, the CT scan preceded the terminal event by several weeks and presumably the deposits were too small for visualization at the time of the scan. As expected, MR reveals only ill-defined regions of diminished intensity on Tl-weighted images which, along with surrounding edema, become high intensity on T2-weighted images (Fig 5B and C). The appearance with both CT and MR is nonspecific, resembling that of other focal mass lesions in AIDS. Several diffuse diseases may affect the same patient simultaneously. We have seen six patients who presented with contrast-enhancing lesions typical of toxoplasmosis. However, only some of the lesions responded to antitoxoplasmosis therapy; other lesions continued to grow. An additional biopsy demonstrated simultaneous lymphoma and toxoplasmosis (Fig 6). Systemic
Lymphoma
While primary CNS lymphoma more frequently involves the brain parenchyma, systemic lymphoma usually invades the meninges.67*68 Because of this, symptoms often include radicu-
NEURORADIOLOGY
OF AIDS
49
Fig 5. lmmunoblastic lymphoma in a 42-year-old man with AIDS, somnolence, and left hemiplegia. (A) Contrastenhanced CT scan shows a discrete area of irregular ring enhancement in the right basal ganglia. A similar lesion was present in the left occipitoparietal region. (6) Partial saturation MR scans (TR SO0 ms) reveals a low intensity signal with mass effect in the corresponding basal ganglia region. (C) TZ-weighted image (TR 2,000 ms, TE 30 ms) discloses the lesion as an ill-defined high intensity signal surrounded by considerable edema. A similar appearance was noted in the left occipitoperietal region. Proved by biopsy and autopsy.
lopathy and multiple cranial nerve neuropathy, as well as headache and mental status changes.69 The pathologic findings are consistent with leptomeningeal spread, and frank parenchymal metastasis is much less common. Histologic subtypes most often associated with CNS spread consist of the same high-grade lymphomas69 that
typify AIDS patients. Extension into the CNS has been reported in about 20% of AIDSassociated systemic lymphoma.58~70 Radiographically, both CT and MR are usually negative in leptomeningeal spread. This reflects the reports in the literature that meningeal enhancement is a rare finding.“‘,68 We have
50
SZE ET AL
Fig 6. lmmunoblastic lymphoma in a 44-year-old man with AID6 and biopsy-diagnosed cerebral toxoplasmosis. On antitoxoplasmosis therapy (pyrimethamine and sulfadiaxine). most of the lesions resolved. However, a contrastenhanced CT scan (A) reveals a persistent and growing ring lesion in the right centrum semiovale, with a low density center surrounded by considerable edema. The Tl-weighted MR image showed an ill-defined low signal intensity in this region. (B) The TZ-weighted image (TR 2.000 ms, TE 60 ms) discloses a slightly intense core in the center of a large area of highly intense edema. An additional focus was noted on the left on other scans. (Cl After administration of gadolinium-DTPA, the Tl-weighted imege showed enhancement of the lesion in similar fashion to the contrast-enhanced CT scan. Biopsy confirmed.
seen two cases of lymphoma with hydrocephaIus associated with leptomeningeal spread. Parenchymal CNS metastases in secondary lymphoma resemble those of the primary form in radiographic appearance. Several cases of epidu-
ral spinal cord compression from lymphomatous masses in AIDS patients have been reported.‘0*7037’As in other CNS involvement, highgrade lymphoma was found. Of incidental note, epidural spinal cord compression was also
NEURORADIOLOGY
reported ma.” Kaposi
OF AIDS
in an AIDS
51
patient with
plasmacyto-
Sarcoma
Although common elsewhere in the body, Kaposi sarcoma is extremely rare in the CNS. Several pathologically proven cases.have been reported.2’,72173 CT shows contrast-enhancing parenchymal masses,typical of brain metastasis. In addition, these lesionsare often hemorrhagic. To date, we are not aware of any MR description of the findings in Kaposi sarcoma metastatic to the brain. VASCULAR
COMPLICATIONS
Several reports have detailed cerebrovascular complications in patients with AIDS.9V’0,‘2 In
some cases,intracerebral hemorrhage has been secondary to a CNS neoplasm, either lymphoma or Kaposi sarcoma, as mentioned previously. In others, vascular complications occurred as a result of diseaseelsewhere. Snider et al” report two patients with infarction, one angiographitally proven of embolic origin, felt secondary to nonbacterial thrombotic endocarditis. The other had bilateral basal ganglia infarcts associated with Ramsay-Hunt syndrome, a cranial nerve neuropathy secondary to varicella zoster infection. This casestrongly suggestsherpetic vasculitis as the precipitating event. In one patient, an aneurysm of the tip of a basilar artery leaked, probably exacerbated by idiopathic thrombocytopenic purpura, a syndrome that has been associated with AIDS.74
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D: Idiopathic thrombocytopenic File, San Francisco General
nervous synpurpura Hospital