Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at UCSF and review of the literature

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✓ In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984. Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed.

Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one). Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one). Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three). Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction. Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection.

Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one).

In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.

Abstract

✓ In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984. Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed.

Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one). Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one). Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three). Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction. Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection.

Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one).

In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.

Although cases were retrospectively recognized as early as 1978, the first reports of the unusual occurrence of Kaposi's sarcoma, Pneumocystis carinii pneumonia, or other opportunistic infections in previously healthy homosexual males and intravenous drug abusers appeared in 1981.44,53,62,63,97,130 In 1982, Mildvan and coworkers99 reported four previously healthy homosexual males with Pneumocystis carinii, Cryptococcus neoformans, Candida albicans, herpes simplex virus, and cytomegalovirus (CMV) opportunistic infections. These patients developed fever, leukopenia, and diminished delayed hypersensitivity, as well as proctitis, perianal ulcerations, and lymphadenopathy. They all demonstrated a persistent and profound selective decrease in both the function and the number of T lymphocytes of the helper/inducer subset and a possible activation of the suppressor/cytotoxic subset. Several other groups confirmed the occurrence of opportunistic infections and/or Kaposi's sarcoma in previously healthy patients.50,66,137,138 Common to all of these patients was a defect in cellular immunity which was considered to be important in the pathogenesis of the disease; as a consequence, the syndrome was named the “acquired immunodeficiency syndrome” (AIDS).

The Acquired Immunodeficiency Syndrome
Definition

The Centers for Disease Control (CDC) have, for the purpose of epidemiological surveillance, defined AIDS as a “reliably diagnosed disease that is at least moderately indicative of an underlying cellular immunodeficiency in a person who has no known underlying cause of cellular immunodeficiency nor any other cause of reduced resistance reported to be associated with that disease.”29 Patients with this syndrome characteristically present with malignant tumors, the most common of which are Kaposi's sarcoma and non-Hodgkin's lymphoma,33,53,138 and/or infections that are infrequently seen in immunocompetent persons. These opportunistic infections most frequently include Pneumocystis carinii pneumonia, cryptococcal meningitis, and atypical mycobacterial infections. Those patients fulfilling the full diagnostic criteria, as established by the CDC, are placed into AIDS Category A1. In addition, there is a larger number of patients not fulfilling these strict criteria but who present with syndromes that suggest milder or prodromal forms of AIDS. The most common of these is termed the “gay lymphadenopathy syndrome.”6,27

Risk Groups

The vast majority of patients with AIDS have been identified as homosexual or bisexual males.24 In an attempt to identify risk factors in homosexual patients with AIDS, Jaffe, et al.,78 have evaluated 50 homosexual and bisexual males with AIDS and compared them with 120 matched healthy homosexual controls. Major risk factors in these patients with AIDS included a history of multiple and repeated infections with classic and enteric sexually transmitted diseases, including syphilis, non-B hepatitis, and acute amebiasis, and a history of multiple and diverse sexual practices. Intravenous drug abuse was identified as a factor in only 12% and 0% of homosexuals in New York and San Francisco, respectively; by contrast, 60% of heterosexual men and women with AIDS were admitted intravenous drug abusers.

Although initial reports suggested that only homosexual males and drug addicts were at risk of contracting AIDS, several other groups at risk have subsequently been identified. Reports of AIDS in recent Haitian immigrants to the United States without other known risk factors have appeared.103,118 Additional cases of AIDS in Haitians still residing in Haiti have recently been confirmed.109 Of 61 Haitian AIDS patients, 15 had Kaposi's sarcoma and 45 had opportunistic infections. Other risk factors were identified in only approximately 20% of patients.

Pneumocystis carinii pneumonia was initially documented in three patients with hemophilia A in 1982.28 Since then, several additional reports of hemophiliac patients contracting AIDS have appeared.32,49 Weintraub, et al.,149 demonstrated altered T cell immunity in hemophiliacs frequently receiving Factor VIII concentrate, while Lederman, et al.,86 disclosed impairment of cell-mediated immunity in patients with classic hemophilia, regardless of treatment. More recently, Essex and coworkers47 identified antibodies to membrane antigens from human T cell leukemia virus, a suggested etiological agent of AIDS, in the plasma of 5% to 19% of hemophiliacs tested.

Blood transfusion alone appears to place patients at risk for acquiring AIDS.18,37 Of 2157 patients with AIDS reported up to August, 1983, 65 (3%) had no known risk factors. Of these, 18 (28%) had received blood components within 5 years of the onset of illness. The median latency between transfusion and the onset of illness was 27½ months; blood products were obtained from between two and 48 donors for each patient. Seven of these 18 cases had at least one high-risk donor identified by either interview or T cell analysis. At the present time, the CDC has recorded 108 transfusion-associated cases of AIDS; 94 of these cases were in adults and 14 were in children under 5 years of age (Jaffe HW, personal communication, January, 1985).

As the scope of patients at risk for contracting AIDS has broadened, it has become apparent that women with a history of intravenous drug abuse or with a history of sexual partnership with either an intravenous drug abuser or an AIDS patient are also at risk.26,98 Several case reports of children with AIDS have also appeared.30,108,123 The CDC first reported four infants with unexplained immunodeficiency and opportunistic infections. The mother of one child was an AIDS patient and the mother of a second was a prostitute; both had a history of intravenous drug abuse. The remaining two children were Haitian. Also mentioned were six cases of children with isolated unexplained opportunistic infections and 12 with unexplained immunodeficiency alone. Oleske, et al.,108 reported eight cases of AIDS in young children up to 9 months of age, and Rubinstein, et al.,123 reported seven children with AIDS born to promiscuous and drug-addicted mothers. These investigators postulated a perinatal or in utero transmission of viral-induced infectious immunodeficiency. Ninety-four children with AIDS have been reported to the CDC as of January, 1985. Children with AIDS most commonly present with an unusual prodrome consisting of a failure to thrive, hepatosplenomegaly, and a culture-negative interstitial pneumonia. Kaposi's sarcoma is very rare in this patient group (Jaffe HW, personal communication, June, 1984).

Epidemiology

The initial report of five cases of homosexual men with Pneumocystis pneumonia in Southern California was published in 1981.62 By December 1983, 3000 AIDS cases had been reported to the CDC. The clinical presentation of these cases included 51% with Pneumocystis carinii pneumonia, 26% with Kaposi's sarcoma, 7% with both of these, and 16% with opportunistic infections caused by organisms other than Pneumocystis carinii. More recent CDC figures reveal a total of 7857 reported patients, of whom 3737 (47.6%) have died to date (Jaffe HW, personal communication, January, 1985).

Geographic analysis of these cases revealed that 42% of AIDS cases were reported in New York City, while San Francisco and Los Angeles accounted for 12% and 8%, respectively. Patients with AIDS have been noted in 42 states as well as Washington, D.C., and Puerto Rico, and in several areas throughout the world, including Japan,102 Europe,124 and Africa.34,107 The number of AIDS cases reported to the CDC had been doubling approximately every 6 months, although a report in June, 1983, from Dr. David Sencer of the New York City Health Department suggested that the rate of increase in the number of new reported cases in New York was decreasing.4 Since other areas of the country have been noted on epidemiological studies to lag behind New York by about 1 year, it was hoped that the number of cases reported elsewhere would parallel the trend observed in New York. Recent data (Jaffe HW, personal communication, June, 1984), however, reveal that the New York City Health Department registered 70 new cases of AIDS each month during 1983. Unfortunately, from January to April, 1984, the incidence increased to 90 new cases per month, and 170 new cases were reported in May, 1984. Furthermore, over the 5-week period from May 1 to June 4, 1984, 100 new cases were reported weekly from all parts of the United States. Thus, the number of reported cases is still increasing rapidly.

Evaluation of the overall distribution of AIDS among the populations at risk reveals that 71% of patients are homosexual or bisexual males, 17% are heterosexual intravenous drug abusers of either sex, 5% are Haitian immigrants, and 1% each are hemophiliacs and female drug abusers or sexual partners of AIDS patients. Although 6% of AIDS patients have no known risk factors, case histories were not available in half of these patients.24 The differential incidence of Kaposi's sarcoma among various groups of AIDS patients suggests that subtypes of this disorder may exist. DeJarlais, et al.,40 reported that 46% of homosexual and bisexual male AIDS patients developed Kaposi's sarcoma, whereas only 3.8% of heterosexual intravenous drug abusers who developed AIDS had this disorder. Kaposi's sarcoma presented before opportunistic infections in 43 of their 52 cases. Patients with an initial diagnosis of Kaposi's sarcoma had a 50% greater survival rate at 12 months as compared to the group presenting with opportunistic infections. Jaffe, et al.,77 evaluated the first 1000 AIDS cases in the United States and reported that, while 44% of homosexual males with AIDS have Kaposi's sarcoma, only 16% of intravenous drug abusers with AIDS have this illness, and none of the hemophiliac patients with AIDS contracted Kaposi's sarcoma during their illness.

Studies of T cell abnormalities among patients with AIDS also suggest that different subtypes of this disorder may exist. Ammann, et al.,4 observed that, in the most severely ill AIDS patients (namely, those presenting with opportunistic infections), there was an extremely marked diminution of T cell function as defined by: a decrease in both the number and function of T cells, a decreased T cell response to mitogens (phytohemagglutinin and pokeweed), and a decreased response to allogenic cells (to less than 10% of normal). The mean ratio of helper T cells to suppressor T cells in this group was 0.4:1. By contrast, in those patients presenting with Kaposi's sarcoma, this mean helper:suppressor ratio was 0.8:1. Furthermore, in patients with generalized lymphadenopathy the mean helper:suppressor ratio was 1.1:1, and T cell response to allogenic cells was normal. Only the T cell response to mitogens was depressed in these patients. It is interesting to note that the serum of AIDS patients contained a subnormal amount of interleukin II, an agent produced by helper T cells that promotes the T cell response to mitogens.

Transmission of AIDS appears to occur by two primary routes: sexual contact and transfusion of blood components. Epidemiological studies have suggested that multiple sexual contacts that traumatize the anal or rectal mucosa may provide the actual avenue of infection.4 The latency period between sexual transmission and the diagnosis of AIDS has been estimated to be from 7 to 24 months.25 Transfusion-associated AIDS has been well documented, particularly in patients receiving multiple transfusions of blood products for the treatment of hemophilia.37 Ammann and coworkers3 reported the case of a child with multiple transfusions at birth and no other known AIDS risk factors. The child developed AIDS 5 months after birth and the donor developed AIDS 7 months after the donation; both died shortly after the onset of the illness. The CDC has reported 18 patients with AIDS and no known risk factors except for prior transfusions within 5 years of the illness. The latency period may therefore range from 5 months to several years.

As of January 14, 1985, 3737 (47.6%) of 7857 patients reported to the CDC with AIDS had died (Jaffe HW, personal communication, January, 1985). This mortality figure is deceptively low, however, because the incidence of life-threatening opportunistic infection increases with time after diagnosis of AIDS, and many of these patients had not been followed for more than a few months. The CDC reports indicate that 80% of AIDS patients are dead by 2 years after diagnosis, and by 3 years the mortality rate is nearly 100%.24 Moss reviewed 170 case histories of patients with AIDS in the San Francisco Bay Area (Ammann, et al.4), and noted that 21 months after diagnosis there was a 50% survival rate in AIDS patients with Kaposi's sarcoma as compared to no survivors among patients with opportunistic infections. In patients with both Kaposi's sarcoma and opportunistic infections, no survivors were identified longer than 15 months after diagnosis.

Etiology

While initial speculation suggested that the drugs abused may be a causative factor in the development of AIDS,61,81 this hypothesis has not been supported by epidemiological data.71 Although several other etiological theories have been proposed, including immunological overload with exhaustion of the immune system by frequent prior infections90 and genetic variation in the HLA-DR5 locus,51 current epidemiological data suggest that AIDS is induced by a transmissible agent which is capable of causing immunosuppression.

Viral agents appear to be the most likely candidates for the etiology of AIDS. Gravell and coworkers65 successfully transmitted the simian form of AIDS from diseased rhesus monkeys to normal monkeys by inoculation with either whole blood or plasma that had been passed through 0.45-µ filters. As the only known infectious agents capable of passing through such filters are viruses, these studies were believed to confirm the viral etiology of AIDS. Several investigators later reported the isolation of Type D retroviruses from the blood of diseased monkeys.38,96,139

The two viruses suggested as the most likely candi-dates responsible for the transmission of AIDS are mutated variants of either CMV or human T cell leukemia virus (HTLV). Drew, et al.,43 have reported the prevalence of CMV infection in homosexual men; CMV has also been associated with the classic form of Kaposi's sarcoma in Africa and Europe,59 and has been isolated from the tissues and secretions of many AIDS victims.4,101,146

Studies linking HTLV, a retrovirus containing ribonucleic acid (RNA), to the transmission of AIDS are somewhat more suggestive. The HTLV was initially described in 1980, when it was isolated from an American patient with mycosis fungoides, a form of T cell lymphoma.115 Essex, et al.,46 found that AIDS patients and homosexual males with chronic generalized lymphadenopathy had a higher prevalence of antibodies directed against membrane antigens of HTLV-infected cells than in a control population. In their study, 19 of 75 reported AIDS patients had antibodies directed to surface antigens of a reference T lymphoid cell infected with HTLV as compared to two of 336 control individuals. An additional eight AIDS patients had lesser titers of these antibodies. Less than 1% of healthy adults in the United States and Europe have antibodies directed against HTLV. Proviral deoxyribonucleic acid (DNA) sequences from HTLV have been isolated from peripheral lymphocytes of AIDS patients.58 The virus itself has been isolated from 30% of all AIDS patients tested in the United States,56 and has been isolated from lymphocytes of AIDS patients in Japan.102 A novel T lymphotropic retrovirus has also been isolated from patients with generalized lymphadenopathy, a pre-AIDS syndrome.14

Jaffe and coworkers79 have used an assay for antibodies to membrane antigens of cells infected by HTLV in order to examine serum from individuals who donated blood to 12 patients with AIDS associated with blood transfusions. Their results demonstrated a significantly greater occurrence of positive results among donors to the AIDS patients as compared to random donors. Of the 12 sets of donors examined, nine sets included a donor whose serum gave positive results for the presence of antibodies to membrane antigen, and in six of these nine the seropositive donor was an individual who was also identified as a possible source of AIDS transmission on epidemiological and immunological grounds.

Most recently, investigators have reported the isolation of a group of cytopathic retroviruses, HTLV Type III (HTLV III), and antibodies against these viruses from patients with AIDS and chronic generalized lymphadenopathy, whereas attempted isolation of these viruses from healthy volunteers was unsuccessful.55,116,125,127 Schüpbach, et al.,128 have recently demonstrated that the cross-reactive antigens found on the surface of infected human cells, which are recognized by antibodies from many AIDS patients, in fact do appear to be of viral origin. Thus, this group of cytopathic retroviruses, HTLV III, appears to be the most likely cause of AIDS.

Treatment

As the mortality figures would suggest, treatment of patients with AIDS has been disappointing. The treatment of the neurological manifestations of AIDS includes radiation therapy for cerebral lymphomas and metastatic Kaposi's sarcoma and specific chemotherapy for central nervous system (CNS) involvement with opportunistic infections (see Tables 3 and 4). Although the initial response to these therapies has been promising, the occurrence of relapse following therapy has been significant.91,153 This has led to the general recommendation that therapy for opportunistic infections of the CNS in patients with AIDS be continued far longer than in immunocompetent patients. Despite rigorous methods, virtually all of these patients have died, either from their CNS disease or from other manifestations of AIDS.

TABLE 3
TABLE 3

Recommended medical treatment for central neurological complications of AIDS*

Therapeutic trials for Kaposi's sarcoma in AIDS patients have been somewhat more promising. Initial trials with the podophyllotoxin VP-16-313 (etoposide) reveal a response rate of about 80%, with almost half of these responses being complete tumor remissions. The incidence of opportunistic infection in these patients during treatment was only 12%.85 Trials with vinblastine have also been encouraging. Lewis, et al.,93 have administered vinblastine to 22 AIDS patients; objective partial or complete remission was achieved in 37%. This remission lasted longer than 8 months.4 The incidence of opportunistic infection was higher (22%) in this overall less healthy group of patients.

Combination chemotherapy for Kaposi's sarcoma in the AIDS patient has also been investigated. Chemotherapy with doxorubicin, bleomycin, and vinblastine has produced objective response rates between 50% and 80%.93 The incidence of opportunistic infections in these patients, however, is extremely high (greater than 50%), suggesting that the additional immunosuppression from these therapies is unacceptable.

Attempts to treat the primary disease process in AIDS patients have been less successful, particularly in light of the unclear etiology of the syndrome. Krown, et al.,84 have reported the effects of recombinant leukocyte A interferon on tumor growth and immune function in 13 AIDS patients with Kaposi's sarcoma. Their use of this agent was based upon reports of its antiviral, immunomodulating, and antineoplastic capabilities. Results of their Phase I trial revealed an objective response rate of 38%. The authors suggested that this treatment is also capable of restoring at least some aspects of cell-mediated immune function.

Groopman, et al.,68 have reported a second trial of interferon therapy for Kaposi's sarcoma in AIDS patients. Eight of 20 patients demonstrated an objective partial response to recombinant alpha interferon administration. The responses were reported to have persisted during a mean follow-up period of 8 months, and all responding patients were still alive.4 The rate of opportunistic infections in this treated group was comparable to that in patients treated with single-agent chemotherapy. Further studies performed with gamma interferon have been less promising (Masur H, personal communication, June, 1984).

Murray and coworkers105 have demonstrated that production of both lymphokines and gamma interferon is impaired in AIDS patients. Interleukin II, one such lymphokine, has been demonstrated to stimulate the function of T cells of AIDS patients in vitro.4 Current clinical trials with interleukin II, however, have also been disappointing (Masur H, personal communication, June, 1984).

Bone marrow transplantation has been suggested as a potentially curative approach to the therapy of AIDS patients.4 However, bone marrow transplants have been performed at the University of California in two unconditioned identical twins; neither patient has demonstrated evidence of benefit. Further studies of bone marrow transplantation therapy for patients with AIDS are currently underway.

With the increasingly strong evidence that AIDS may be caused by a variant of HTLV, the possibility of producing a vaccine to this virus has been proposed. Unfortunately, there is no precedent for a vaccine against retroviruses, and the type of immunological response that would be promoted by an injection of an inactivated retrovirus is unknown. Investigators have also suggested the use of antiviral drugs against HTLV. Retroviruses contain an enzyme, reverse transcriptase, which allows for conversion of the RNA into DNA, which is then incorporated into the cell's genome. It has been suggested that specific blockade of reverse transcriptase might inhibit transmission of HTLV; unfortunately, no such agents are currently available. Research in these areas is of critical importance to the eventual control and possible eradication of AIDS.

Although the increasing evidence associating HTLV with the induction of AIDS does not allow for the immediate treatment of this disorder, it could permit the identification of infected patients and the possible limitation of the spread of AIDS. Screening of transfusion products and blood donors for HTLV III may eliminate the spread of AIDS through transfusions. Identification of infected patients in a population at risk may also serve to alter behavioral patterns to further limit the spread of the disease. Unfortunately, it has been estimated that the interval from the development of a reliable assay for HTLV in blood products to the elimination of HTLV transmission through transfusion will be at least 2 years (Jaffe HW, personal communication, June, 1984). The Red Cross is currently planning feasibility testing of a microplate enzyme-linked immunosorbent assay for HTLV.95

Neurological Complications of AIDS
Introduction

Of the approximately 550 patients with AIDS or generalized lymphadenopathy treated at the University of California, San Francisco (UCSF) over the 5-year period from 1979 to 1984 (Volberding P, personal communication, June, 1984), we have evaluated 352 patients. Approximately 39% of all patients with AIDS are neurologically symptomatic (124 of the initial 318 patients). This figure is in agreement with the recent report derived from the clinical experience at the New York Hospital-Memorial Sloan Kettering Cancer Institute (NYH-MSK), in which 50 of 162 reported AIDS patients had neurological manifestations of their disease.133 These figures probably significantly underestimate the occurrence of neurological abnormalities in AIDS patients, as our unselected complete autopsy series of 41 patients revealed 30 patients (73%) with pathological abnormalities of the CNS. Also, the subtle neurological signs or symptoms, such as those related to a mild peripheral neuropathy or minor alterations in personality, tend to be overlooked in the patient with an overwhelming systemic illness.

Of the 39% of AIDS patients with neurological abnormalities, approximately one-third have presented because of their neurological complaints.20 Thus, 10% of all AIDS patients present with problems relating to the nervous system. The most frequent presenting neurological syndromes in our series were either aseptic meningitis or herpes zoster radiculitis.20 Many of these patients already had evidence of deficient cell-mediated immunity at the time of neurological presentation, and in time developed either Kaposi's sarcoma, opportunistic infections, or both.

A summary of central neurological complications in patients with AIDS or lymphadenopathy who were seen at UCSF is given in Table 1, and is compared with the total cases recorded to date.

TABLE 1

Central neurological complications in patients with AIDS or lymphadenopathy*

ComplicationsUCSF SeriesTotal Reported
viral syndromes
 subacute encephalitis3554
 atypical aseptic meningitis1721
 herpes simplex encephalitis89
 progressive multifocal leukoencephalopathy26
 viral myelitis33
 varicella-zoster encephalitis11
non-viral infections
Toxoplasma gondii18> 103
Cryptococcus neoformans1641
Candida albicans26
 coccidioidomycosis11
Treponema pallidum12
 atypical Mycobacteria16
Mycobacterium tuberculosis01
Aspergillus fumigatus01
 bacteria (Escherichia coli)01
neoplasms
 primary CNS lymphoma915
 systemic lymphoma with CNS involvement212
 Kaposi's sarcoma23
cerebrovascular accident
 infarction15
 hemorrhage14
miscellaneous/unknown825
total cases128320

UCSF = University of California, San Francisco. The total reported cases include the UCSF series. CNS = central nervous system.

Five patients had two neurological complications each.

Viral Syndromes
Subacute Encephalitis

The most common neurological syndrome affecting patients with AIDS has been termed “subacute encephalitis.”133 Of the 50 patients with neurological dysfunction reviewed in the NYH-MSK series, 18 had subacute encephalitis. In our series, 35 of 156 AIDS patients with neurological disease presented with this syndrome. The precise etiology of this syndrome is unclear, and subacute encephalitis as seen in AIDS patients is not defined elsewhere. The syndrome consists most commonly of a progressive dementia, first appearing as a confusional state accompanying fever or mild metabolic derangement. This is occasionally accompanied by focal motor deficits, signs of frontal lobe damage (frontal release signs), or headache. Cases including hemianopsia, myoclonus, or seizures have been reported.133

Radiological study of these patients is, on the whole, unrevealing. Computerized tomography (CT) frequently shows mild generalized cortical atrophy. In one reported case,91 a ring-enhancing cerebellar lesion demonstrated on CT proved on autopsy to be a focus of CMV inclusion bodies. Recently, magnetic resonance imaging (MRI) has been employed to study these patients. In one such patient treated at UCSF, who presented with a 2-month history of dementia, left hemiparesis, abulia, and frontal release signs bilaterally, MRI revealed bifrontal increases in T2 relaxation times, consistent with edema and inflammation.

Other diagnostic studies performed in these patients have been generally unrevealing. Lumbar puncture is abnormal in three-quarters of the cases, with mild protein elevation (50 to 100 mg/dl) being the most common finding, and mild hypoglycorrhachia and mononuclear pleocytosis being less common. Electroencephalography has demonstrated diffuse nonspecific slowing in some cases.

The clinical course of AIDS patients with subacute encephalitis is slowly progressive over the course of several months, with only rare symptomatic remission. No effective treatment has been found. Our autopsy findings demonstrate mild to moderate cortical atrophy and diffuse changes suggestive of viral invasion of gray and white matter throughout the CNS. The hypothalamus and brain stem are frequently the most severely involved structures. Gray matter lesions consist of microglial nodules which may contain cells characteristic of CMV infection. White matter findings consist of slight myelin pallor, reactive astrocytosis, poorly defined foci of demyelination, and occasional microglial clusters. Inflammatory cells are absent, save for rare perivascular macrophages.133

Brain cultures from patients with subacute encephalitis have revealed diverse pathologies. Snider and coworkers133 have reported cultures from one such brain growing Mycobacterium avium intracellulare. Immunohistochemical stains for CMV were inconclusive, while those for herpes simplex were negative. Electron microscopy of two specimens showed no evidence of viral replication. In our series, two patients suffering from subacute encephalitis had positive cultures for CMV: one sample obtained from the cerebrospinal fluid (CSF) and the other from a postmortem brain section. Three patients had cultures positive for herpes simplex Type I: one sample from the CSF and two from postmortem brain sections. Interestingly enough, one brain culture grew both CMV and herpes simplex, raising the possibility of multiple simultaneous infections.

The suggestion has been made that subacute encephalitis is secondary to CMV infection of the CNS.133 This suggestion is strengthened by the pathological similarity of subacute encephalitis to cases of CMV encephalitis reported in renal transplant patients.10,42,126 The fact that herpes simplex is not the etiological agent is suggested by the observation that the reported pathology for herpes simplex encephalitis in an immunoincompetent patient119 is distinct from that which we have observed in subacute encephalitis.

Although no specific therapy has been proven effective in arresting the course of subacute encephalitis, reports in the literature suggest that vidarabine may be efficacious in the treatment of CMV encephalitis. Phillips, et al.,112 reported two cases of culture-proven CMV encephalitis that responded to vidarabine. In light of the frequency with which subacute encephalitis is seen in AIDS patients and the almost uniformly fatal outcome in untreated cases, clinical trials of vidarabine in AIDS patients with subacute encephalitis may be indicated.

Atypical Aseptic Meningitis

In 1983, we first reported 15 homosexual patients with aseptic meningitis, 13 of whom were admitted between June, 1980, and December, 1982.19 We have seen two additional patients with this syndrome since the appearance of this report. Not only did this represent a significant increase in the number of cases of aseptic meningitis seen at our institution, but these recent cases had frequent atypical features such as recurrence, chronicity, cranial nerve involvement, and long-tract signs. The fifth, seventh, and eighth cranial nerves were most frequently involved. In several of these patients CSF pressure was increased; pleocytosis was present by definition. Protein and glucose patterns were similar to those encountered in subacute encephalitis. In one of these 17 patients, CSF cultures were positive for CMV; this patient de veloped Kaposi's sarcoma 6 months after the first of two bouts with meningoencephalitis, and later became the only patient in this group to undergo a postmortem examination. This revealed findings typical of subacute encephalitis.

Aseptic meningitis presents clinically in an entirely different fashion from subacute encephalitis; common features include headache, fever, and meningeal signs. The clinical course is also different, being self-limited or recurrent rather than progressive. Autopsy findings, however, indicate a marked similarity between these clinical entities. Our observations suggest that the difference in presentation may be a function of immune competence, as virtually all of the patients with subacute encephalitis had AIDS by CDC criteria, whereas none of the 17 patients with atypical aseptic meningitis had AIDS at the time of their initial neurological presentation. Six of these patients have subsequently developed AIDS or significant immunoincompetence on laboratory testing. These findings are also consistent with those of Snider and coworkers,133 who reported four cases of aseptic meningitis; two of these patients were noted to have generalized lymphadenopathy, thought to be a pre-AIDS syndrome. Interestingly, the difference in clinical presentation as a function of immune competence seems to be a recurrent theme in this population of patients. Chronic inflammatory polyradiculoneuropathy, for example, has been seen in 12 of our patients, all of whom have generalized lymphadenopathy, while the pathologically dissimilar distal symmetrical sensorimotor neuropathy has been seen in 13 patients, all of whom have AIDS.

Herpes Simplex Virus Encephalitis

Herpes simplex virus is the most frequent agent causing sporadic (non-epidemic) viral encephalitis. Nearly all adult cases are due to herpes simplex virus Type I (HSV I), which has been cultured from the trigeminal ganglion,12 as opposed to HSV II, which can remain dormant in the sacral ganglia.11 Typically, HSV I produces a hemorrhagic necrotizing encephalitis in the medial temporal and inferior frontal lobes. Clinical manifestations of this illness include headache, fever, seizures, aphasia, and other focal findings. Diagnosis is made reliably only by temporal lobe biopsy; treatment with adenine arabinoside (Ara-A) or acyclovir has been shown to decrease the morbidity and mortality rates associated with this infection.151

In patients with cell-mediated immunodeficiency, it has been suggested that HSV I might produce a mild diffuse encephalitis rather than the typical regional hemorrhagic necrotizing encephalitis.75,119 One case of herpes simplex virus encephalitis in a patient with AIDS has been reported briefly.114

We have recently evaluated eight homosexual patients with immunodeficiency and herpes simplex virus encephalitis. (Dix RD and Bredesen D, in preparation). Five of these patients had AIDS, two had persistent generalized lymphadenopathy, and one had Hodgkin's disease with severe lymphocytopenia. The eight patients fell into four groups, with the rapidity of disease progression and the severity of inflammation being roughly proportional to the degree of immunocompetence. Thus, the two patients with lymphadenopathy suffered an acute illness typical of herpes simplex virus encephalitis in immunologically normal patients in every way except that HSV II was cultured from the temporal lobe biopsy material. Treatment resulted in survival with severe residua.

The second group consisted of two patients with newly diagnosed AIDS who had subacute progressive encephalomyelitis and who had both herpes simplex virus and CMV cultured from multiple sites in the brain and spinal cord at autopsy. One patient presented with ascending myelitis while the other presented with diffuse encephalitis.

The third group consisted of two very debilitated patients, of whom one had AIDS and the other had Hodgkin's disease; each had chronic neurological dysfunction. The patient with AIDS had severe abulia and a mild hemiparesis, both of which showed moderate improvement with acyclovir therapy. Although CT scans revealed no abnormalities, MRI scans demonstrated bifrontal abnormalities which proved at autopsy to be due to a leukoencephalopathy. The patient with Hodgkin's disease had only a flat affect, without other neurological abnormalities; HSV I was cultured from his CSF, but no therapy was given in light of a negative repeat culture.

The last group consisted of two AIDS patients without apparent neurological illness who died of inanition due to parasitic bowel disease. Despite the lack of any pathologically demonstrable encephalitic process, cultures from multiple brain sites were positive for HSV I.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), first described in 1958, is an unusual demyelinating disease in which affected patients present with mental aberrations, blindness, aphasias, hemiparesis, ataxia, and other focal deficits which slowly progress until death.9 The characteristic CT finding has been low-density lesions without contrast enhancement, mass effect, or evidence of edema. Autopsy findings reveal focal myelin loss with sparing of axis cylinders. Of note is the absence of inflammation and the presence of bizarre astrocytes and enlarged oligodendrocytes containing eosinophilic intranuclear inclusions surrounding these areas of demyelination.159 The illness appears to be caused by infection with a papovavirus.106 The results of limited trials of treatment, particularly with vidarabine, have been disappointing.120

Several cases of PML have been reported in patients with AIDS15,133 and in one homosexual man with T cell immune deficiency.100 Our series includes two pathologically verified cases and a third probable case.

Clinically, PML in the AIDS patient appears to behave in a fashion similar to PML in other immunoincompetent patients. Experience with the treatment of PML in AIDS patients has been extremely limited, but Snider, et al.,133 have reported transient modest improvement in one of two patients who were treated with cytarabine.

Viral Myelitis

We have reported one case of necrotizing ascending myelitis in a patient with newly diagnosed Kaposi's sarcoma.145 Following acute onset, ascent from the lumbar spinal cord to the brain stem took 17 days, resulting in complete quadriplegia and cranial polyneuropathy. Myelography was normal, but CSF examination revealed evidence of hemorrhage and inflammation. Cultures of CSF yielded CMV, and postmortem cultures from multiple sites in the brain and spinal cord were positive for both CMV and HSV II. The HSV II was analyzed by restriction endonuclease mapping and was found to be identical to the HSV II cultured from a perirectal lesion which appeared a few days prior to death. One other postmortem evaluation revealed inclusions typical of CMV in the spinal cord. The clinical examination of this patient prior to death revealed only diffuse weakness and hypotonia. A third patient has presented with clinical signs of a transverse myelitis; he is alive at the present time.

Varicella-Zoster Virus Encephalitis

Varicella-zoster virus encephalitis is a very rare illness that has been reported in both immunocompetent and immunoincompetent individuals.80 While being treated for cryptococcal meningitis, one patient with AIDS in our study developed seizures which proved to be difficult to control. Analysis of the CSF revealed no evidence of active cryptococcal infection, but varicella-zoster virus was cultured. Unfortunately, the patient died and permission for autopsy was not obtained.

Non-Viral Infections
Toxoplasma Gondii

Toxoplasmosis, the infection caused by the obligate intracellular protozoan Toxoplasma gondii, is one of the most common infections of animals and man.7 In man, there is an increasing prevalence of positive serological reactions with increasing age. The incidence of toxoplasmosis in adults in the United States ranges from 20% to 70%. The two major routes of transmission of toxoplasmosis to man are oral and congenital,140 with meat ingestion playing a primary role. Although there exists no evidence for direct human-to-human transmission other than from mother to child, the infection of laboratory and autopsy workers has led to the suggestion that trophozoites in human secretions may transmit the infection during its acute stages. Infection with Toxoplasma gondii has been reported to be transmitted by transfusions of whole blood or white blood cells.7

In the immunocompetent patient, infection with Toxoplasma gondii trophozoites results in the invasion and death of cells, producing necrotic regions surrounded by an intense mononuclear cell reaction. Cellular immunity and, to a lesser extent, humoral immunity combine to resolve the acute infection, although tissue cysts allow for the prolonged viability of organisms. In the CNS, acute focal or diffuse meningoencephalitis with cellular necrosis, microglial nodules, and perivascular mononuclear inflammation associated with both intra- and extracellular trophozoites is seen.121 Thrombosis of blood vessels causing large areas of coagulation necrosis may produce mass lesions in the CNS. In immunodeficient hosts, the lack of cell-mediated immunity may result in a persistent acute infection with severe diffuse necrotizing lesions. Pathological analysis of biopsy specimens from AIDS patients reveals necrotizing granulomas, usually with thin capsules and little inflammation.129 Encysted Toxoplasma gondii and tachyzoites are usually present.

At least 103 cases of CNS toxoplasmosis have been reported in patients with AIDS or with evidence of cellmediated immunodeficiency in the setting of homosexuality.2,5,39,41,64,69,70,94,134,148,154 It appears to be more common in Haitian patients with AIDS than in other groups of AIDS patients,113,118 consistent with the higher prevalence of toxoplasmosis in the general populations of tropical regions. Toxoplasmosis is, in fact, the most common reported cause of nervous system dysfunction in Haitian AIDS patients.

At UCSF, we have seen 18 cases of CNS toxoplasmosis in AIDS patients, three of which have been reported previously.91,92 Their presentation usually includes focal deficits, often with an altered level of consciousness; approximately 15% present with seizures. Interestingly, the onset of focal deficits is often preceded by lethargy or confusion for several days to a few weeks.

Analysis of CSF frequently reveals an elevated level of protein, but the frequency of hypoglycorrhachia and mononuclear pleocytosis has varied markedly from study to study.74,133,152,153 Contrast-enhanced CT scans have been abnormal in virtually every reported case, revealing single or multiple ring-enhancing lesions. Homogeneous enhancement133 and lack of enhancement118 have also been reported, and we have seen two patients with diffuse CNS toxoplasmosis who had normal CT scans. Subcortical involvement, usually in the basal ganglia, has been demonstrated in approximately 50% of cases.

In those cases where CT scans have been negative or where lesions were thought to lie in critical brain regions, we have explored the use of MRI in evaluating CNS disease in the AIDS patient. In all cases, MRI confirmed the presence of those lesions seen on CT; in two cases, MRI revealed additional lesions at distant sites, which were amenable to biopsy. In an additional biopsy-proven case, CT was negative but MRI revealed a focal abnormality in the region of the basal ganglia.

Serological data have not been reliable,91,92,113,133 usually failing to reflect acute infection with Toxoplasma gondii. Elevated immunoglobulin (Ig) M Toxoplasma titers, usually a good indicator of active toxoplasmosis, have been uniformly negative in AIDS patients with cerebral toxoplasmosis.113 In fact, in the three cases we have reported,92 none of the single titers (Sabin-Feldman dye test, IgG-indirect fluorescence, IgM-indirect fluorescence, or IgM-enzyme linked immunosorbent assay) were diagnostic of active infection. Nevertheless, Toxoplasma titers may be helpful in certain clinical situations. First, the rare occurrence of nondetectable IgG titers effectively rules out active toxoplasmosis, even in the AIDS population. Second, it has been suggested that baseline IgG titers be obtained for all patients at the time a diagnosis of AIDS is reached,113 so that a rise in IgG titer may be assessed early in the course of any ensuing nervous system illness. Although this may prove to increase the speed and sensitivity of diagnosis of cerebral toxoplasmosis in the AIDS patient, some cases would still be missed by this method, including 20% of those reported by Snider, et al.133

Consideration of whether to perform a biopsy must take into account the location of the lesion(s), the serological data, if available, and the observation that some AIDS patients have polymicrobial infections with different organisms isolated from separate cerebral lesions.91,92 Two patients were reported, one had Toxoplasma brain abscesses and CMV microabscesses and the second had a cryptococcoma with CMV microabscesses. In these cases of polymicrobial infection, different organisms were cultured from distinct lesions. We have recently evaluated an additional three patients who, upon biopsy, had multiple intracranial pathologies. Two patients demonstrated both Toxoplasma gondii infection and primary CNS lymphoma in the same needle biopsy specimen, while a third patient had infection secondary to both Toxoplasma gondii and atypical mycobacteria. Thus, our series includes five patients with multiple intracranial pathology.

These observations, along with the lack of sensitivity of serological tests, has led us to suggest brain biopsy of all AIDS patients with CNS mass lesions. Pitchenik, et al.,113 on the other hand, have suggested that empirical treatment with pyrimethamine and sulfadiazine may be appropriate in cases where the location of the lesion makes biopsy hazardous, especially if a fourfold rise in IgG titer or a single IgG titer of greater than 1:1000 has been demonstrated. This approach will probably be less successful in non-Haitian AIDS patients,92 in whom diagnoses other than toxoplasmosis, including lymphoma or fungal abscesses, are not as rare relative to the incidence of toxoplasmosis. In addition, the significant decrease in the morbidity and mortality rates associated with biopsy procedures, especially with stereotaxic techniques or ultrasound guidance,8,32 makes medical treatment of these patients without a definitive diagnosis seem unwise.

Treatment with pyrimethamine and sulfadiazine has resulted in dramatic improvement in several reported cases,91,92,118,133,152,153 but the mortality rate still approaches 70%. Half of these patients, however, died of systemic rather than neurological complications and of illnesses other than toxoplasmosis. Early treatment response has been followed by relapse in approximately 30% of cases.91,92,118,152,153

Cryptococcus Neoformans

Cryptococcosis, the most common fungal infection of the CNS, usually appears in association with other systemic illnesses,144 although it may occur in otherwise normal individuals. A common soil fungus, Cryptococcus usually infects via the respiratory tract. Clinically, most cases are subacute in onset and present with symptoms of meningitis, although occasionally patients present with signs or symptoms of intracranial pressure elevation secondary to hydrocephalus or with focal neurological deficits.

Specific diagnosis relies upon the demonstration of the Cryptococcus neoformans organism in the CSF. India ink preparations can be diagnostic, but often a positive latex agglutination test for cryptococcal antigen in the CSF is the only evidence of infection.1,135 Despite appropriate treatment with amphotericin B, the mortality rate in immunocompetent hosts is 40%. The discovery of flucytosine (5-fluorocytosine) may result in more successful chemotherapy of this infection.16 The pathological findings of this CNS infection are those of a granulomatous meningitis with the addition of small granulomas and cysts, which form within the cerebral cortex, and occasionally large granulomas and cystic nodules, which form deep in the brain.1

A total of 41 cases of cryptococcal meningitis have been reported by various authors in patients with AIDS,50,60,87,91,92,103,109,118,133,147,150,151 and three cases of intracerebral cryptococcoma have been reported in AIDS patients.87,91,92,113,118 The series at UCSF includes 16 patients with cryptococcal meningitis, one of whom developed an intracerebral cryptococcoma.

Presentation of cryptococcal meningitis in patients with AIDS usually parallels that of immunocompetent hosts with headache, confusion, or seizures, but is often atypical, presumably due to the minimal inflammatory response to the infection. In one patient, disseminated cryptococcosis was diagnosed by supraclavicular lymph node biopsy. There were no neurological symptoms or signs, and CSF evaluation was normal save for a positive india ink preparation, cryptococcal antigen, and culture. Two additional patients in our series also had CSF analysis with normal opening pressure, a normal cell count, and normal glucose and protein levels, but with positive CSF cryptococcal antigen. In both cases, headache was the sole neurological complaint and the neurological examination was normal. On the basis of this limited experience, we suggest that CSF evaluations in patients with AIDS always include cryptococcal antigen assays, and that the CSF be evaluated in AIDS patients with recent onset of headaches, even in the absence of other neurological signs or symptoms.

The CT scans of AIDS patients with cryptococcal infection may demonstrate cerebral atrophy or hydrocephalus, or may be entirely normal.82,150 The appearance of cryptococcoma on CT has not been reported; our patient with cryptococcoma had no evidence of a mass lesion on the last CT scan 4 months prior to his death.

Treatment in most cases has included amphotericin B and 5-fluorocytosine. The placement of Ommaya reservoirs for direct intraventricular drug administration has been performed in several cases. Despite therapy, prognosis has been extremely grave, with the course complicated by recurrence and by other opportunistic infections. In the largest reported series,150 four of nine patients survived, although the length of the follow-up period was not specified. The two patients reported by Snider, et al.,133 responded to amphotericin B but died of other opportunistic infections several months later; neither had evidence of cryptococcal meningitis at autopsy.

Candida Albicans

Usually associated with diabetes, leukemia, lymphoma, and intravenous drug abuse, candidiasis is a relatively unusual infection of the CNS.144 Presentation is the same as that of other fungal infections, and diagnosis depends upon microscopic examination and culture of the CSF. Treatment has included potassium iodide, sulfonamides, streptomycin, penicillin, nystatin, and amphotericin B.

Four cases of Candida albicans infection of the CNS have been reported in association with AIDS, including three patients with brain abscesses.82,91,92,114,133 One of these patients had a polymicrobial infection including Toxoplasma gondii and Staphylococcus epidermidis in addition to Candida species. One 5-month-old child with AIDS was reported with probable Candida meningoencephalitis.108 These infections accompanied disseminated candidiasis in two cases and oral Candida infection in one case. The patients with Candida abscesses presented with focal neurological signs, while the pediatric case was brought for treatment of failure to thrive. One patient survived,114 one died, one was lost to follow-up review, and in one case the outcome is unknown. We have seen an additional patient with disseminated candidiasis, who lapsed into coma and died. At autopsy, the patient was found to have multiple Candida microabscesses throughout the cortex and pons.

Coccidioidomycosis

Despite the early recognition of disseminated coccidioidal infection,117 coccidioidomycosis continues to be a major health problem throughout the entire southwestern United States.45 Meningeal infection by coccidioidomycosis was first recognized in 1909,48 and is involved in one-half to one-third of the cases of disseminated coccidioidomycosis. Immunosuppressive therapy has been demonstrated to cause dissemination of previous localized infection.104 Although the majority of cases have a subclinical or chronic, relapsing, long-lasting meningitis, coccidioidal meningitis can present as a rapid, fulminant illness in the immunodeficient patient.45 Treatment of coccidioidal meningitis involves the long-term intracisternal administration of amphotericin B, often accomplished through an Ommaya reservoir.156

We have evaluated one patient with AIDS and disseminated coccidioidomycosis who died recently. At autopsy, the patient was found to have multiple coccidioidal microabscesses throughout the cerebellum.

Aspergillus Fumigatus

One case of Aspergillus brain abscess in an AIDS patient has been reported recently.17 Details concerning presentation, clinical course, and outcome are not available.

Mycobacteria

The pathology and presentation of Mycobacterium tuberculosis meningitis have been well described.1 Two stages occur in the pathogenesis of this meningitis. The first is a bacterial seeding of the meninges and underlying brain with the formation of tubercles, and the second is comprised of rupture of one or more of these tubercles with discharge of bacteria into the subarachnoid space. Infection with other mycobacterial species is less well investigated.

Six patients with AIDS and mycobacterial involvement of the CNS have been reported. One Haitian patient had a tuberculoma and subsequently developed Toxoplasma encephalitis.113 The presentation and course of illness in that patient was not discussed. Three other patients had the syndrome of subacute encephalitis: Mycobacterium avium intracellulare was cultured from the brain in one and demonstrated histologically in another; this organism was cultured from multiple organs in the third. A summary of 61 Haitian AIDS patients109 included 11 cases of tuberculosis, none of which was reported to have CNS involvement. One patient at UCSF was demonstrated at biopsy to have a lesion containing both Toxoplasma gondii and atypical mycobacterium.

Bacteria

Reports of bacterial CNS complications have been conspicuously absent from the AIDS literature. Not one of the 50 patients reported by Snider, et al.,133 nor the 124 neurologically symptomatic patients reported here had a bacterial CNS complication. A report of one case of Escherichia coli meningoencephalitis has recently appeared in abstract form; details of the case were not presented.17

Treponema Pallidum

Only one case of syphilitic meningoencephalitis has been reported in a patient with AIDS.17 We have also treated a homosexual patient with meningovascular syphilis, cutaneous anergy, and lymphopenia. After 3 years of follow-up study, the patient has demonstrated no additional abnormalities suggestive of the diagnosis of AIDS.

Neoplasms
Primary CNS Lymphoma

Primary malignant lymphomas are rare tumors of the CNS, representing less than 1.5% of primary brain tumors.72 While systemic lymphoma frequently invades the meninges,67 primary CNS lymphomas more frequently involve the brain parenchyma.21 Prior to the recognition of AIDS, primary CNS lymphomas were frequently seen in both renal and cardiac allograft recipients.13,73,110 Patients with immunosuppression as a result of AIDS also appear to be at risk for developing these neoplasms.

Fifteen cases of primary CNS lymphoma have been reported in patients with AIDS.82,88,91,92,114,132,133,150 We have encountered nine such cases, two of which were reported previously.91,92 Of a group of 12 AIDS patients with primary CNS lymphoma, five presented with encephalopathy and one with cranial polyneuropathy and intrinsic brain-stem pathology. In six cases the lymphomas were discovered at autopsy, and in two cases the presentation was not reported. Duration of symptoms until death was less than 1 month in all cases.

The CT findings were reported in eight cases. In four the scans demonstrated hypodense areas with peripheral enhancement, in one homogeneous enhancement was revealed, and in three the scan was normal. Autopsy in one of the latter cases demonstrated diffuse infiltration of the brain by lymphoma. Cerebrospinal fluid analysis was reported in six patients. In three patients, the CSF contained elevated protein levels (to 145 mg%) and depressed glucose levels (to 35 mg%), while in the other three CSF analysis was normal. Cytological examination of the CSF in one patient revealed atypical cells.

Only two of the 12 patients underwent radiation therapy.150 Despite subsequent improvement on CT, one of these patients deteriorated clinically and died within 3 months. The second patient has shown clinical and radiological improvement after radiation therapy, and continues to do well 3 months after biopsy.

Pathological analysis reveals that these lymphomas appear to be very similar to primary CNS lymphomas seen in patients with other immune dysfunction, such as patients with Wiskott-Aldrich syndrome and those who have undergone renal transplantation.110,132 These tumors are large-cell lymphomas, formerly referred to as “histiocytic lymphomas” or “microgliomas.”

Systemic Lymphoma with CNS Involvement

Homosexual patients appear to be at increased risk for developing squamous carcinoma of the oral cavity, cloacagenic carcinoma of the rectum, and a tumor similar to Burkitt's lymphoma.158 The presence of a systemic lymphoid malignancy, however, somewhat paradoxically mitigates against the official diagnosis of AIDS, since any immune deficiency may not be separable from that due to the malignancy itself.24 Finally, whether or not the incidence of systemic lymphomas other than Burkitt's lymphoma or of multiple myeloma is in fact increased in patients at high risk for AIDS is presently unknown.

These criticisms notwithstanding, nine cases of systemic lymphoma affecting the CNS have been reported in homosexual patients. Six of these patients have had tumors similar to Burkitt's lymphoma, two had largecell lymphoma, and one had immunoblastic sarcoma. One homosexual patient with CNS manifestations of plasmacytoma has also been reported.133,158 We have evaluated an additional two patients with CNS complications of large-cell lymphoma.

In this group of 12 patients, eight patients had neoplastic meningitis, five of whom had multiple cranial neuropathies. Also included were three cases of epidural spinal cord compression, and one case of intracerebral hemorrhage from metastasis. Transient improvement was recorded in nine patients following therapy, but eight of the 12 died within 10 months after the onset of neurological symptoms.

Kaposi's Sarcoma

Until the recent outbreak of AIDS, Kaposi's sarcoma was rarely documented in Europe or North America; there was a reported annual incidence of 0.02 to 0.06 per 100,000 population.53,122 This neoplasm most often affected elderly men,142 and responded well to therapy, with a mean survival period in the range of 8 to 13 years. A more virulent disseminated form of the disease occurs primarily in younger males endemically in equatorial Africa.141,143 A similar aggressive form of Kaposi's sarcoma has been reported in a variety of immunosuppressed patients, including those undergoing renal transplantation,111 those receiving immunosuppressive therapy for systemic lupus erythematosus,83 and those receiving corticosteroid therapy.54,89 Although Kaposi's sarcoma has been a primary feature of AIDS, CNS presentation of this neoplasm has been remarkably rare.

One case of Kaposi's sarcoma possibly metastatic to the brain has been reported,76 but details of presentation and location were not discussed and pathological verification was not available. Our series includes two pathologically proven cases of Kaposi's sarcoma metastatic to the brain.82,91,92 One patient suffered a transient hemiplegia lasting approximately 15 minutes. Upon CT evaluation, the patient was found to have a right frontal lesion. Despite the good local response of the lesion to radiotherapy, the patient died 3 months later of disseminated Kaposi's sarcoma. The second patient had vague complaints of dizziness which were not evaluated. Autopsy revealed widely metastatic Kaposi's sarcoma as well as multiple cerebellar and cerebral metastases. In both cases, the metastatic lesions were hemorrhagic. A third patient demonstrated brachial plexus involvement of metastatic Kaposi's sarcoma resulting in a brachial plexopathy.

Cerebrovascular Complications

Several patients have been reported with cerebrovascular complications presumed to arise as a consequence of AIDS.57,133 These include four patients with either hemorrhagic or bland cerebral infarction and three patients with intracerebral hemorrhage. We have evaluated one patient each with cerebral infarction and intracerebral hemorrhage as well as the two patients reported above with hemorrhagic metastatic Kaposi's sarcoma.

The cerebral infarctions have been reported as secondary to nonbacterial thrombotic endocarditis in four cases and possible herpes zoster arteritis in one patient. Intracerebral hemorrhage was secondary to CNS lymphoma in three cases, of which one was complicated by thrombocytopenia and biopsy, and another was the result of rupture of a basilar tip aneurysm in the setting of thrombocytopenia. Interestingly, one patient with nonbacterial thrombotic endocarditis responded to anticoagulation therapy with a complete resolution of neurological deficits, and these deficits did not recur.

Miscellaneous Complications

Several patients have presented with illnesses that elude etiological classification. The series reported by Snider, et al.,133 included unclassifiable focal brain lesions in three patients and a self-limited aseptic meningitis in four, two of whom had Bell's palsy. Berger, et al.,17 reported three patients with unexplained tremor, five with a metabolic encephalopathy, and two with unexplained seizures.

We have managed three patients with Bell's palsy, presumably as a consequence of aseptic meningitis. Another patient with hypotonia and wasting did not receive further treatment because of severe systemic illness. At autopsy, the patient was found to have mild gliosis and a few microglial nodules involving the anterior horns of the spinal cord, possibly suggestive of viral myelitis. Another patient presented with a left hemiparesis, and CT revealed a low-density nonenhancing basal ganglia lesion. Four biopsy procedures in two patients were nondiagnostic; the patients were treated with pyrimethamine and sulfadiazine with stabilization of the clinical condition in one. The other died. A total of eight patients in our series remain without definitive diagnosis.

Disorders of the Cranial and Peripheral Nerves

A summary of the cranial and peripheral nerve complications in patients with AIDS or lymphadenopathy who were seen at UCSF is given in Table 2, and compared with the total cases recorded to date.

TABLE 2

Cranial and peripheral nerve complications in patients with AIDS or lymphadenopathy*

ComplicationsUCSF SeriesTotal Reported
cranial nerve syndromes
 multiple cranial neuropathies secondary to chronic inflammatory polyneuropathy55
 multiple cranial neuropathies secondary to lymphoma05
 Bell's palsy35
peripheral nerve syndromes
 chronic inflammatory polyneuropathy1212
 distal symmetrical neuropathy513
 herpes zoster radiculitis66
 myalgias22
 myopathy02
 polymyositis01
total cases3351

UCSF = University of California, San Francisco. The total reported cases include the UCSF series.

Distal Symmetrical Neuropathy

Thirteen patients with AIDS have developed a distal symmetrical sensorimotor neuropathy.20,133 Ten of these patients reported painful dysesthesias. Sensory symptoms predominated in 11 patients, with both large and small fiber involvement. Weakness and atrophy distally were predominant in only two patients. Electromyography and nerve conduction studies were performed in five patients,133 and demonstrated mild slowing of nerve conduction velocities and minimal evidence of denervation in four. Sural nerve and muscle biopsies were normal in one patient.

Chronic Inflammatory Polyneuropathy

In contrast to the distal symmetrical neuropathy noted in the 13 AIDS patients mentioned above, 12 homosexual patients with persistent generalized lymphadenopathy developed chronic inflammatory polyneuropathy (Lipkin I and Parry G, unpublished data), manifested by mononeuropathy multiplex in nine, distal asymmetrical neuropathy in two, and distal symmetrical neuropathy in one. All patients had accompanying systemic complaints such as fever, night sweats, and malaise. Cranial nerve involvement was noted in five cases and extensor plantar responses in four.

The CSF was abnormal in all eight patients in whom it was evaluated. The most sensitive indicator, the Ig index, defined as the ratio of CSF to serum Ig's divided by the ratio of CSF to serum albumin, was abnormal (> 0.72) in all five patients so tested. Nerve biopsy was compatible with the diagnosis of chronic inflammatory polyneuropathy in four of five patients, and was normal in one; biopsy did not demonstrate vasculitis in any of the five cases.

Spontaneous resolution occurred in six patients over 2 to 8 weeks. Steroids effected no improvement in four treated patients. Plasmapheresis was beneficial to both patients so treated. Interestingly, three of the 12 patients developed AIDS from 1 to 6 months after their initial diagnosis of chronic inflammatory polyneuropathy.

Herpes Zoster Radiculitis

Typical herpes zoster radiculitis occurred in six patients in our series. In four patients this disorder preceded the development of Kaposi's sarcoma, while in one patient it was followed by the development of opportunistic infection. Neurological presentation preceded the development of these other illnesses by as much as 3 years.

Myalgias and Polymyositis

Prominent myalgias were reported by two of our patients, although no associated weakness was present. Snider and coworkers133 reported one case of polymyositis in a patient with AIDS. Both the patient's symptoms and the elevated serum creatine phosphokinase resolved without treatment. Two additional cases of myopathy have been reported briefly.17 The incidence of disorders of the peripheral nervous system in association with AIDS is clearly underestimated in light of the patients' other severe and life-threatening illnesses.

Clinical Evaluation and Therapy

This section presents recommendations for the clinical evaluation and therapy of the patient with AIDS and neurological dysfunctions.

Central Neurological Dysfunctions

The flow chart presented in Fig. 1 describes our recommended approach to the patient with AIDS and central neurological dysfunction. Faced with an AIDS patient complaining of symptoms referable to the CNS, we first recommend CT scanning. In those patients with space-occupying lesions, an attempt is made to determine whether the CT abnormality represents an ischemic infarction, in which case medical therapy is indicated. All other space-occupying lesions are then ultimately biopsied. If the CT lesion(s) lies in a critical brain region, MRI should be performed if this imaging modality is available; our experience indicates that MRI may reveal lesions which are not apparent on CT scanning and which might be more amenable to biopsy (Figs. 2 and 3). Following biopsy, appropriate therapy is then administered as noted above and in Table 3. Patients with nondiagnostic biopsies are followed clinically and undergo repeat CT scanning (or MRI) at regular frequent intervals, and at any time deterioration of their clinical condition occurs. Repeat biopsy should be considered if lesions have increased in size or if any new lesions have been demonstrated.

Fig. 1.
Fig. 1.

Recommended approach to the patient with AIDS and central neurological symptoms. CT = computerized tomography scan; CSF = cerebrospinal fluid; CVA = cerebrovascular accident; MRI = magnetic resonance imaging.

Fig. 2.
Fig. 2.

Serial computerized tomography (CT) scans and magnetic resonance image (MRI) of an AIDS patient with herpes simplex virus II encephalitis. A: Normal contrast-enhanced CT scan on the 1st hospital day. B: Contrast-enhanced CT scan on hospital Day 3. A lesion is seen in the posterior inferior portion of the left frontal lobe. C: Contrast-enhanced CT scan on hospital Day 5. There is increasing size and degree of enhancement of the lesion first seen 2 days earlier. D: Magnetic resonance image obtained on hospital Day 5. The lesion seen on CT scanning is well visualized. A second lesion is seen in the contralateral insular cortex. The diagnostic biopsy was obtained from the lesion visualized only on MRI.

Fig. 3.
Fig. 3.

Computerized tomography (CT) scan and magnetic resonance image (MRI) of a patient with AIDS and autopsy-proven leukoencephalopathy who presented with subacute encephalitis. Left: The CT scan was interpreted as normal. Right: An MRI obtained the same day revealed marked bifrontal high-signal intensity reflecting an increased T2 relaxation time. An autopsy later demonstrated bifrontal leukoencephalopathy in the abnormal region identified on the MRI.

Patients who do not have space-occupying lesions demonstrated on CT scans are then categorized on the basis of the CT findings. Cerebrospinal fluid is obtained in all of these patients and a number of laboratory studies are performed, including routine culture and sensitivity testing, viral cultures, cell count, protein and glucose measurement, testing for venereal disease or cryptococcal antigens, india ink preparation, and cytological investigations. Hydrocephalus is treated with shunting and, if the presence of Cryptococcus is confirmed, placement of an Ommaya reservoir for the instillation of chemotherapy should be considered.

In the case of a patient with a normal CT scan or with only diffuse atrophy, the demonstration of a focal neurological deficit should lead to further diagnostic MRI, if available. If a region of abnormality is identified on MRI, biopsy of that lesion should be performed. If MRI is negative or if the neurological examination of the patient with a normal CT scan is nonspecific, the patient should be treated on the basis of the CSF examination. If all tests are nondiagnostic, the patient should be observed and repeat evaluation of CT scans and CSF profiles should be performed at regular intervals.

In patients whose CT scans are abnormal due to the presence of meningeal enhancement, a diffuse neoplastic or infectious process is suggested. The patient should be treated according to the results of CSF cytological and infectious evaluation (Table 3). Patients with no demonstrable CSF abnormality warrant close followup monitoring for the development of a potentially treatable neurological illness. This approach is in contrast to the suggestion of Snider, et al.,133 who recommend radiation therapy based on the assumed diagnosis of lymphoma.

Because a single elevated Toxoplasma titer is of little value, and as the presence of possible polymicrobial CNS infection in the patient with AIDS makes the serodiagnosis of toxoplasmosis unwise, we do not recommend the use of Toxoplasma titers as a primary diagnostic tool in lieu of biopsy. Serial Toxoplasma titers should be obtained on all AIDS patients, however, because an acute rise in Toxoplasma titers may signal acute toxoplasmosis and may suggest treatment for those patients in whom other tests, including biopsy, are nondiagnostic.

Cranial or Peripheral Nerve Dysfunction

A flow chart depicting the suggested approach to the patient with AIDS and peripheral or cranial nerve dysfunction is presented in Figs. 4 and 5, and Table 4. These AIDS patients presenting with an isolated unilateral peripheral seventh nerve palsy have been demonstrated almost exclusively to have atypical aseptic meningitis. These patients should be treated according to the results of CSF examination; CT scanning is not necessarily indicated. The patient presenting with cranial nerve dysfunction other than an isolated unilateral seventh nerve palsy should undergo CT scanning. Subsequent evaluation and treatment should follow the same approach as presented for patients with symptoms referable to the CNS (see previous section).

Fig. 4.
Fig. 4.

Recommended approach to the patient with AIDS and cranial neuropathy. VII = seventh nerve; LP = lumbar puncture; CSF = cerebrospinal fluid; TB = tubercular; CT = computerized tomography.

Fig. 5.
Fig. 5.

Recommended approach to the patient with AIDS and peripheral neuropathy. LP = lumbar puncture; EMG/NCV = electromyography and nerve conduction velocity studies; Ig = immunoglobulin.

TABLE 4

Recommended medical treatment for cranial and peripheral nerve complications of AIDS

ComplicationsTherapy
cranial nerve syndromes
 multiple cranial neuropathies secondary to chronic inflammatory polyneuropathyconsider plasmapheresis
 multiple cranial neuropathies secondary to lymphomaradiation therapy & specific chemotherapy
 Bell's palsysymptomatic therapy
peripheral nerve syndromes
 chronic inflammatory polyneuropathyconsider plasmapheresis
 distal symmetrical neuropathysymptomatic therapy; consider amitriptyline
 herpes zoster radiculitisAra-A or acyclovir
 myalgiassymptomatic therapy
 myopathysymptomatic therapy
 polymyositissymptomatic therapy

In patients presenting with purely peripheral nervous system symptoms, it is critical to determine if the symptoms are symmetrical. As most AIDS patients with asymmetrical peripheral nerve dysfunction have been demonstrated to have chronic inflammatory polyneuropathies, further evaluation should be directed toward establishing or eliminating this diagnosis. Lumbar puncture for CSF evaluation including Ig index should be performed. Electromyography (EMG) and nerve conduction velocity (NCV) studies as well as nerve biopsy may be of value in making the diagnosis. If the patient's peripheral nervous symptoms are demonstrated to be secondary to some process other than chronic inflammatory polyneuropathy, they should be treated accordingly. Plasmapheresis might be considered for patients demonstrated to have chronic inflammatory polyneuropathies.

In patients who present with symmetrical peripheral neurological symptoms, evaluation must be directed toward determining possible secondary causes. If some toxic or metabolic abnormality is discovered, correction should be attempted. If not, patients should undergo lumbar puncture, and EMG and NCV studies, with nerve biopsy if necessary. If the patient's symmetrical neuropathy is not secondary to a toxic or metabolic illness, the patients should be treated symptomatically to control their pain. Amitriptyline may be an effective agent in this regard.

Recommended Precautions During Care of AIDS Patients

One of the most important issues facing the clinician involved in the care of the patient with AIDS concerns the possible transmission of the disease to health care workers and the possible exposure of the patient to potentially harmful opportunistic pathogens. The possibility of direct AIDS transmission to health care workers is remote; only four cases of AIDS have been reported in health care workers not in high-risk categories for contracting the illness.29 Of these four, there is no evidence of transmission of AIDS in the hospital, and that event appears unlikely. No occurrence of AIDS has been reported in physicians or nurses who are not already members of a high-risk group.35

Despite the apparent unlikelihood of AIDS transmission to hospital workers, and since the etiological agent is unknown and the latent period may be several years, infection control measures must be rigorously imposed for patients with this illness. Precautions should be directed at reducing the exposure to blood and body fluids and at reducing the possibility of the transmission of opportunistic pathogens.23,36

The CDC recommends that precautions be taken for “persons and specimens from persons with: opportunistic infections that are not associated with underlying immunosuppressive disease or therapy; Kaposi's sarcoma (patients under 60 years of age); chronic generalized lymphadenopathy, unexplained weight loss and/or prolonged unexplained fever in persons who belong to groups with apparently increased risks of AIDS (homosexual males, intravenous drug abusers, Haitian entrants, hemophiliacs); and possible AIDS (hospitalized for evaluation).” Suggested precautions for health care workers include: wearing of gowns and gloves while handling blood samples, tissue specimens, secretions, or excretions, as well as items and surfaces soiled by these substances; avoiding accidental wounds with potentially contaminated materials, and avoiding contact of open lesions with materials from AIDS patients; and prompt washing of hands after contact with the AIDS patient or any contaminated materials. Masks are not routinely suggested for patients with AIDS unless they are actively coughing around other patients. Masks should be worn by health care workers having direct and sustained contact with a coughing patient or one who is intubated and who is undergoing endotracheal suctioning. Lensed instruments should be sterilized with ethylene oxide or glutaraldehyde after each use,131 and any instrument that comes into contact with blood, tissue, secretions, or excretions must be sterilized before reuse. The CDC further recommends that needles be disposed of promptly in puncture-resistant containers, and that needles should not be reinserted into their original sheaths.

Wormser, et al.,155 have recently reported the cases of 25 hospital employees who were exposed to the blood of patients with AIDS by accidental needle puncture. Two-thirds of the exposures took place during the process of needle disposal. Recapping the needle accounted for 37% of the total exposures, whereas disposition of the used needle accounted for an additional 30%. None of the exposed individuals had any evidence of illness or defects in cell-mediated immunity when recently evaluated. In light of the relatively short followup period (only 13 patients have been followed for 12 months after their exposure) and the probable long latency between infection and the expression of the illness, the authors suggest follow-up monitoring for several years to permit determination of disease accrual rates. They reiterated the suggestion that needles should not be recapped following use on the patient with AIDS and that receptacles with adequate openings for both the needle and the syringe be readily available.

The CDC23 further recommends that blood and other specimens from the patient with AIDS be clearly labeled. All blood should be cleaned from the outside of containers with disinfectant, and all blood samples should be placed in a second impervious container. Blood spills should be immediately cleaned with a disinfectant solution and soiled articles should either be destroyed according to the hospital infection control guidelines or be reprocessed according to hospital policies for hepatitis B-contaminated items.

While recommendation that AIDS patients be routinely given private rooms has not been made, private rooms have been suggested for those patients unable to maintain their personal hygiene, such as those with intractable diarrhea or decreased mental status. Care must be taken to avoid placing the AIDS patient in a room with another immunosuppressed patient or with a patient who might be harboring a potentially harmful opportunistic pathogen.35

The issue of cardiopulmonary resuscitation (CPR) for the AIDS patient has received considerable attention. Although saliva has not been implicated in the transmission of AIDS, Conte35 suggests that bloody saliva may be encountered which might serve to transmit the agent of AIDS. The Task Force on AIDS at UCSF has recommended that resuscitation bags or disposable mouth-to-mouth CPR devices be available for patients with AIDS.36 Conte35 further suggests that CPR certification courses include training in the use of these devices.

The surgeon and operating room personnel are at particular risk for contact with blood or other body fluids from the patient with AIDS. The CDC29 recommends that precautions appropriate for hepatitis B-infected patients be applied to patients with AIDS or suspected AIDS. In addition to the aforementioned precautions, it has been suggested that protective eye-wear be worn in the operating room if the procedures are likely to generate aerosols.35 The value of double-gloving is unknown, but this procedure should be encouraged. Since scalpel and needle-puncture injuries are not likely to be prevented by this technique, the emphasis should still be placed on the avoidance of these events.

In light of the known risk of AIDS transmission through transfusion, concern over the regulation of blood banking centers has been great. Since there is no specific predictive or diagnostic test for screening of blood donors for AIDS at the present time, reliance must be placed on voluntary self-screening and history and physical examination where indicated.22 The screening of donors for the risk of AIDS through blood bank questionnaires began in early 1983 in California and is now practiced in all blood banks. These include specific questions on previous diagnosis of AIDS, AIDS symptoms, sexual contact with AIDS patients, homosexual or bisexual intercourse with several partners, recent entry to the United States from Haiti, past or present use of intravenous drugs, and intercourse with a member of any of these risk groups.

Current recommendations include continuation of the current screening procedures, withdrawing of blood for self donation prior to elective surgery, limitation of the use of transfusions unless clearly indicated, education of potential donors to discourage donation from groups at risk for AIDS, and recruitment of new donors who are not members of documented risk groups. Implementation of a blood bank policy that would permit donations to be designated to individual patients has not been recommended due to the logistic problems that might ensue. If ongoing research confirms an etiological role for HTLV III in the development of AIDS, serological tests for its presence should permit the screening of donated blood and minimize the transmission of AIDS through transfusions. Plans are currently underway in the Red Cross blood banking system to test such screening procedures.95

Addendum

Since the last revision of this review article, we have evaluated 10 additional patients with neurological complications associated with AIDS including: four cases of subacute encephalitis, one case of toxoplasmosis, three cases of cerebral infarctions with no identifiable etiology, and two cases of herpes zoster radiculitis.

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This contribution is the 16th in a series of review articles selected jointly by the Committee on Graduate Education of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, and the Journal of Neurosurgery. — Editor.

This work was supported in part by National Cancer Institute Grants CA-13525, CA-31882, and CA-28529 from the National Institutes of Health.

Article Information

Dr. Rosenblum was the recipient of Teacher-Investigator Development Award 1 K07 NS00604 from the National Institute of Neurological and Communicative Disorders and Stroke.

Address reprint requests to: Mark L. Rosenblum, M.D., c/o The Editorial Office, Department of Neurosurgery, 1340 Ninth Avenue, Suite 210, San Francisco, California 94122.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Recommended medical treatment for central neurological complications of AIDS*

  • View in gallery

    Recommended approach to the patient with AIDS and central neurological symptoms. CT = computerized tomography scan; CSF = cerebrospinal fluid; CVA = cerebrovascular accident; MRI = magnetic resonance imaging.

  • View in gallery

    Serial computerized tomography (CT) scans and magnetic resonance image (MRI) of an AIDS patient with herpes simplex virus II encephalitis. A: Normal contrast-enhanced CT scan on the 1st hospital day. B: Contrast-enhanced CT scan on hospital Day 3. A lesion is seen in the posterior inferior portion of the left frontal lobe. C: Contrast-enhanced CT scan on hospital Day 5. There is increasing size and degree of enhancement of the lesion first seen 2 days earlier. D: Magnetic resonance image obtained on hospital Day 5. The lesion seen on CT scanning is well visualized. A second lesion is seen in the contralateral insular cortex. The diagnostic biopsy was obtained from the lesion visualized only on MRI.

  • View in gallery

    Computerized tomography (CT) scan and magnetic resonance image (MRI) of a patient with AIDS and autopsy-proven leukoencephalopathy who presented with subacute encephalitis. Left: The CT scan was interpreted as normal. Right: An MRI obtained the same day revealed marked bifrontal high-signal intensity reflecting an increased T2 relaxation time. An autopsy later demonstrated bifrontal leukoencephalopathy in the abnormal region identified on the MRI.

  • View in gallery

    Recommended approach to the patient with AIDS and cranial neuropathy. VII = seventh nerve; LP = lumbar puncture; CSF = cerebrospinal fluid; TB = tubercular; CT = computerized tomography.

  • View in gallery

    Recommended approach to the patient with AIDS and peripheral neuropathy. LP = lumbar puncture; EMG/NCV = electromyography and nerve conduction velocity studies; Ig = immunoglobulin.

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