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CT assessment of CNS complications of AIDS. (Directed Reading).

Although acquired immunodeficiency syndrome (AIDS) is not directly fatal, individuals with the disease are susceptible to a host of life-threatening opportunistic infections and complications. This article focuses on the central nervous system (CNS) complications of HIV/AIDS and computed tomography's role in diagnosing these conditions. After completing the article, readers will know the signs and symptoms, causes or proposed causes and computed tomographic (CT) appearance of 4 important CNS complications of HIV/AIDS:

* Progressive multifocal leukoencephalopathy (PML).

* Toxoplasmosis.

* CNS lymphoma.

* AIDS dementia complex (ADC).

In late spring of 1981, Morbidity and Mortality Weekly Report published a report on 5 cases of pneumocystis carinii pneumonia (PCP).

According to the report, all of the individuals diagnosed with PCP were previously healthy young men, described as homosexuals, residing in Los Angeles, Calif. Two of the 5 reported cases resulted in death. (1)

This report prompted an examination of the PCP cases by the Centers for Disease Control and Prevention (CDC). The CDC investigation resulted in identification of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). (2) Once thought to be a disease occurring only in homosexual men, it now is known that the virus can infect anyone, including heterosexual men and women, the unborn and children.

Consider the following statistics reported by the CDC in December 2000: (3)

* More than 700 000 Americans have been reported to have AIDS.

* More than 400 000 Americans have died from complications associated with AIDS.

* More than 300 000 Americans are presently living with AIDS (the highest number reported in the 20-year history of the disease).

* Since the identification of AIDS, more than 1 000 000 Americans have been infected.

HIV/AIDS is considered a worldwide pandemic. The virus is the number one cause of death on the African continent and the fourth leading cause of death worldwide. To date, 21.8 million individuals have died from complications associated with the disease, including 4.3 million children. In 2000, 5.3 million people were diagnosed with HIV infection and 3 million died from AIDS-associated complications; 500 000 of these deaths were children. (4)

Physiological Mechanisms Of AIDS/HIV

HIV is one of more than 400 known viruses. A virus is a pathogen made of nucleic acid embedded in a protein shell, which grows and reproduces after infecting host cells. All viruses are capable of attaching to the membrane of certain cells, invading the cytoplasm of the cell, taking over cellular function, reproducing and assembling themselves into forms that can infect other cells. (5)

Viruses are classified by genome core, host, method of reproduction, mode of transmission and disease produced. Classified by method of reproduction, HIV is a retrovirus. Retroviruses, a group that also includes leukoviruses and lentiviruses, carry what is known as reverse transcriptase. (6) In reverse transcriptase, ribonucleic acid (RNA) serves as the template for deoxyribonucleic acid (DNA) copies that are incorporated into the host cells.

HIV infects lymphocytes, the white blood cells (WBCs) responsible for most of the body's immune protection. Lymphocytes represent less than 1% of the cells in circulating blood. HIV infection damages or destroys these cells, resulting in the immune system's inability to defend the body against harmful bacteria, fungi and other viruses that cause disease. (3) There are 2 types of lymphocytes: B and T. T cells originate in the thymus gland and comprise approximately 75% of all lymphocytes. (5)

CD[4.sup.+] T lymphocytes serve as host cells for HIV infection. CD4 is an antigen, a cell surface molecule that determines a cell's immunological ancestry, functional development or stage of maturity. CD[4.sup.+] T lymphocytes are responsible for many immunological functions that, if lost, cause a progressive decline in immune system response. (7) HIV has the ability to "hide" in T cells for years, causing no symptoms in the infected individual. (8)

HIV attaches itself to the CD[4.sup.+] T lymphocytes and penetrates the cells. Once inside the cell, HIV infuses its own genetic material into the host cells and uses them to replicate itself. The new copies of the virus then leave the host cells, enter the bloodstream and search for new CD[4.sup.+] T lymphocytes to invade. The old host cells die. This is a repetitious cycle, with HIV producing more than 10 billion new particles per day and the immune system responding by producing up to 2 billion new CD[4.sup.+] T lymphocytes daily. (9) Statistically, especially without medical intervention, HIV ultimately wins as the number of CD[4.sup.+] T lymphocytes decreases, causing severe immune deficiency. This severe deficiency in people with HIV infection is known as AIDS.

Transmission of HIV

Unlike the viruses that cause the common cold, HIV cannot be transmitted through casual contact like shaking hands, hugging, or platonically kissing an infected individual. HIV infection most commonly occurs through sexual contact with someone who is infected, although contact with infected blood and other body fluids also may transmit the virus. (10) The CDC reports the following body fluids as known transmitters of HIV: (11)

* Blood.

* Semen.

* Vaginal secretions.

* Breast milk.

* Other body fluids with blood components.

In addition, the CDC has reported the following body fluids as suspected in transmitting the virus:

* Cerebrospinal fluid (CSF).

* Synovial fluid.

* Amnionic fluid.

Men who have sex with men are at greatest risk for acquiring the virus, although unprotected sex with anyone infected with the virus puts an individual at increased risk for becoming infected. The virus can enter the body through the rectum, vagina, vulva, penis or mouth during sex. (10) Having another sexually transmitted disease (STD) increases the risk of contracting HIV infection. (12) These diseases primarily include chlamydia, gonorrhea, herpes, syphilis and bacterial vaginosis. (10)

Sharing drug needles or syringes also is associated with acquiring HIV. (9) Needles and syringes that have been used by an infected person may be contaminated with infected blood. If a needle or syringe then is used by another person, the virus may enter that person's body, leading to infection. Men who have sex with men and inject drugs have a substantial risk of becoming infected, with more than 43 000 such infections reported as of December 1998. (13) Accidental exposure of health care workers to HIV-infected blood through needlesticks has been reported as very low. The average risk is said to be approximately 3 in 1000. (6)

Transmission of the virus also can occur through transfusion of blood and blood products, including whole blood, fresh-frozen plasma, packed red cells and platelets, especially before 1985 when the American Red Cross began screening the blood supply for HIV antibodies. More than 3 million Americans receive blood transfusions every year. The U.S. Food and Drug Administration (FDA) inspects 3000 donor centers and updates requirements, policies and standards aimed at preventing disease transmission through blood transfusions. (14) At present, the risk of acquiring HIV infection from blood transfusion is 1 in every 450 000 to 600 000 transfusions. (9)

Between one fourth and one third of HIV-infected pregnant women who are not being treated for the virus will pass HIV on to their babies. If the woman is being treated, however, the risk decreases by as much as 66%. (9)

Rarely, HIV transmission has been reported to have occurred through an organ or tissue transplant from an infected donor. (15)

Diagnosing HIV Infection

Many people who are infected with HIV have no symptoms for many years. When symptoms do occur, they may be attributed to other diseases, illnesses or infections. Some of the symptoms associated with HIV infection include: (11)

* Diarrhea of more than a week in duration.

* Dry cough.

* Fatigue (severe and unexplained).

* Fever (greater than 37.8 [degrees] C or 100 [degrees] F and recurrent).

* Memory loss, depression or other neurological disorders.

* Night sweats (profuse).

* Pneumonia.

* Red, brown, pink or purplish blotches on or under the skin, or inside of the eyelids, nose or mouth.

* Swollen lymph nodes in the axilla, groin or neck.

* Weight loss.

* White spots or unusual blemishes in the mouth, on the tongue or in the throat.

The only definitive means of diagnosing the presence of HIV infection is through medical tests specifically designed to detect HIV antigens or antibodies. (See Table 1.) Currently, the most frequently used screening tests for HIV are the Enzyme Linked Immunosorbent Assay (ELISA) for HIV, the Western Blot for AIDS and the Coulter HIV-1 p24 Antigen Assay, all requiring blood samples, and the OraSure Western Blot, which uses an oral specimen for diagnosis. In addition, there is also an FDA-approved HIV home test kit, the Home Access Express HIV-1 Test System. (14,16)

ELISA

As a virus infects the body, the immune system responds by producing proteins called antibodies that circulate in the blood and try to destroy the virus. The ELISA reagent changes color if the HIV antibody is present in a venous blood sample. ELISA is relatively inexpensive to perform compared with other HIV diagnostic tests and is generally the initial test used to screen individuals suspected of infection. ELISA is said to be more than 99% effective in detecting the virus, although it cannot detect HIV infection until antibodies have developed, and it produces false-positive results in about 2 of every 1000 individuals. If ELISA is positive, repeat ELISA is recommended, followed by Western Blot.

Western Blot for AIDS

The Western Blot also requires a venous blood sample. The sample is exposed to a special paper embedded with selected fragments of the virus. If HIV antibodies are present in the sample, they will bind to the virus, producing a specific pattern or blot.

This test is more expensive than ELISA but definitively rules out HIV infection and has a very low false-positive result rate. It is used to confirm a positive ELISA test result.

Coulter HIV-1 p24 Antigen Assay

Used in addition to ELISA, this test screens blood for HIV antigens instead of antibodies. Both it and ELISA are used to screen the blood supply for the presence of HIV infection. HIV antigens can be detected in the blood sooner than HIV antibodies.

OraSure Western Blot

OraSure Western Blot is a procedure whereby a treated cotton pad is used to collect a specimen from between the gum and check. Using Western Blot technology, the specimen is tested to determine if the characteristic HIV pattern or blot appears.

From HIV+ to AIDS

HIV infection normally leads to the development of AIDS, especially if left untreated. Physicians use the Amplicor HIV-1 Monitor Test to predict the risk of HIV progression in infected individuals. The test measures levels of HIV in the blood (ie, viral load). (14) Higher viral loads are associated with increased risk of progression to AIDS. (7) As the viral load increases, infected individuals become increasingly prone to a host of life-threatening opportunistic infections (OIs). The list of OIs is lengthy and includes: (10)

* Bacterial infections: Mycobacterium avium complex (MAC). Tuberculosis (TB)--the most common OI associated with HIV infection worldwide. Salmonellosis. Bacillary angiomatosis.

* Viral infections: Cytomegalovirus (CMV). Viral hepatitis. Herpes simplex virus (HSV). Progressive multifocal leukoencephalopathy (PML).

* Fungal infections: Candidiasis. Cryptococcal meningitis--the most common central nervous system (CNS) infection associated with HIV.

* Parasitic infections: Pneumocystis carinii pneumonia (PCP)--the most common OI associated with AIDS in the United States. Toxoplasmosis. Cryptosporidiosis.

* Malignancies: Kaposi sarcoma--the most common cancer identified in HIV-infected individuals. Non-Hodgkin lymphoma.

* Other: Wasting syndrome.

Many people remain asymptomatic for a decade or longer as the virus continues to multiply and destroy the immune system. However, asymptomatic individuals can infect others during this period.

Progression of HIV to AIDS is evidenced partially by tests that measure the amount of HIV in the bloodstream. The concentration of the virus in the blood is a good indicator of how likely an infected person is to develop complications associated with OIs. (17) Tests that measure CD[4.sup.+] T lymphocytes are essential tools in guiding the medical management of individuals infected with HIV. (7)

In early 1993, the CDC revised its 1987 classification system for HIV infection and expanded the definition of AIDS to include all HIV+ individuals, age 13 years or older, who have fewer than 200 CD[4.sup.+] T lymphocytes per milliliter of blood (healthy individuals have at least 1000 CD[4.sup.+] T lymphocytes per milliliter) and those with one or more clinical conditions associated with advanced HIV infection (AIDS). (10) These conditions are listed in Table 2.

Medical imaging and radiation therapy hold a significant place in the diagnosis and treatment of opportunistic infections and other conditions associated with HIV/AIDS. Specifically, computed tomography (CT), magnetic resonance (MR) and positron emission tomography (PET) are quite useful in evaluating these disorders.

HIV/AIDS Neurological Manifestations/Complications

HIV enters the brain of an individual soon after infection occurs and remains throughout the duration of the disease. (18) Most researches agree that HIV does not infect CNS cells (neurons) directly, but causes cell death indirectly. Researchers have surmised that HIV targets macrophages, white blood cells abundantly present in the brain, and it is these virus-laden microphages that cause CNS cell destruction. (19) As the HIV infection progresses, it often is observed throughout the CNS as the individual experiences one or more HIV/AIDS neurological complications. (20) This is especially true if an HIV-infected individual's CD[4.sup.+] T-lymphocyte count drops below 100/[micro]L of blood. (21) HIV/AIDS neurological complications include: (20)

* AIDS dementia complex (ADC).

* Cryptococcal meningitis.

* Cytomegalovirus (CMV) encephalitis.

* Myelopathy.

* Myopathy.

* Neurosyphilis.

* Peripheral neuropathy.

* Primary CNS lymphoma.

* Progressive multifocal leukoencephalopathy (PML).

* Radiculomyelitis.

* Toxoplasmosis.

Neurological manifestations of AIDS account for only about 10% of initial case presentations, although it is estimated that 40% to 60% of patients with AIDS have neurological complications from the disease. Post-mortem results have shown that the rate of involvement is in fact significantly higher, at between 73% and 87%. (22)

These complications continue to be a source of significant morbidity and mortality associated with HIV/AIDS. Consequently, it is imperative that early and accurate diagnosis is rendered so that treatment alternatives can be considered and provided. And, as with most other diseases, medical imaging and medical laboratory procedures are the main tools used to diagnose the disease and associated complications.

Computed Tomography and HIV/AIDS Neurological Complications

Although relatively young imaging techniques, CT and MR are currently in widespread use. The first CT scanners were installed in the United States in the mid 1970s, with MR units being installed in the 1980s. Both quickly evolved into essential diagnostic tools. The capabilities of these imaging tools have increased along with the increasing prevalence of HIV/AIDS in this country and throughout the world. MR is mentioned because it plays an important role in the diagnosis of HIV/AIDS central nervous system complications, especially those involving white matter lesions and vasogenic edema. (23) However, both CT and MR are excellent diagnostic tools for disorders of the central nervous system.

This Directed Reading focuses on the following CNS complications associated with HIV/AIDS:

* Progressive multifocal leukoencephalopathy (PML).

* Toxoplasmosis.

* CNS lymphoma.

* AIDS dementia complex (ADC).

The images presented in this Directed Reading were collected, along with the official radiographic reports, from several different CT departments. All procedures were performed on patients who had HIV/AIDS and symptoms suggestive of CNS complications or OIs associated with the infection. All followed an established protocol for evaluating the brains of individuals with HIV/AIDS. This protocol involves 5 mm contiguous axial scans from skull base to vertex, in brain windows. The official reports are referenced as findings within this Directed Reading. Institutional Review Board (IRB) approval was sought and granted for the use of this information.

Progressive Multifocal Leukoencephalopathy

PML is a viral infection that causes extensive demyelinating lesions in the brain, brain stem and cerebellum. PML is caused by the JC Papova virus. JC are the initials of the first patient in whom the virus was isolated. PML is a white matter disease carried without symptoms in a large percentage of the general population. (5) Problems occur when the PML virus infects an individual with an immunosuppressive neoplastic disorder such as Hodgkin lymphoma, chronic lymphocytic leukemia, lymphosarcoma or HIV/AIDS.

PML is a very serious viral infection when the immune system has been severely damaged. (9) This may explain why it is rarely identified in early HIV infection, but is increasingly prevalant in later stages. It has been reported that up to 5% of HIV+ patients had PML as their first AIDS-defining infection or developed it after the diagnosis of AIDS. (24)

One theory is that the JC Papova virus infects the kidneys and remains there until the host becomes immunocompromised, then travels via the bloodstream to the brain. Once in the brain, it is thought that the virus infects and destroys specialized neural cells that form myelin in the brain, called oligodendrocytes. Myelin insulates neural fibers and assists with transmitting information into and out of the brain. Demyelination results in lesions within the brain. These lesions usually occur at the junction of the gray and white matter. (25) It is common for PML to cause a solitary brain lesion; however, the disease is progressive and lesions in several areas may be detected (hence, "multifocal"). (26)

Symptoms of PML infection are not unlike those associated with other CNS abnormalities. The brain lesion or lesions associated with PML can affect the motor, sensory or intellectual functions of brain tissue, depending on where they occur. Reported symptoms include: (27,28)

* Disturbances in coordination and movement.

* Unilateral limp or muscular weakness.

* Visual field disturbances.

* Aphasia.

* Apraxia.

* Memory loss.

* Headache.

* Confusion.

* Dementia.

* Seizures.

* Facial weakness.

* Ataxia.

* Dysphasia.

* Hemiparesis.

Because PML is an infection of the white matter of the brain, and MR is superior to CT in imaging white-matter diseases, the American College of Radiology (ACR) has designated MR as the medical imaging technique of choice for diagnosis when PML infection is suspected. But because CT units are more widely available, neurological CT scans are less expensive than MR studies and CT is capable of imaging white-matter disorders (although not as effectively and extensively as MR), the ACR has designated CT as number 2 in appropriateness criteria for the diagnosis of PML. (29) In the majority of subjects studied (more than 100 adults), CT was performed before MR, and MR usually was recommended if CT was inconclusive. The ACR further explains that either CT or MR may be used to evaluate CNS disorders in HIV-infected infants and children. (23)

When PML is suspected, CT neurologic exams may be requested without contrast or with and without contrast. Protocol for these procedures may follow departmental standards or be developed specifically to evaluate suspected CNS pathology in patients with HIV/AIDS. CT images positive for PML generally demonstrate low-density, white-matter lesions that: (28)

* Have little or no mass effect.

* Produce minimal, if any, enhancement following contrast media injection.

* Usually are located in the posterior aspect of the brain along the gray-white matter interface (basal ganglia).

* Do not distort the contour of the brain.

Figures 1 and 2 demonstrate CT findings in patients with HIV/AIDS and PML. Figure 1 demonstrates findings of a nonenhancing lesion located in the left frontoparietal region, with cytotoxic edema and minimal mass effect. This CT scan was performed with and without intravenous contrast media. Differential diagnosis in this HIV+ patient included infection, PML and lymphoma. The radiologist noted the absence of enhancement, making CNS lymphoma unlikely. The report noted findings consistent with PML, although it stated other OIs also should be considered.

[FIGURES 1-2 OMITTED]

Figure 2 shows more classic CT signs of PML infection. This lesion is located along the gray-white matter interface, is nonenhancing postcontrast and produces no distortion of surrounding structures. The radiologist's impression of this image was also probable PML.

As stated earlier, when CT is inconclusive or further evaluation is indicated, MR may be recommended. MR may be better at demonstrating a classic finding in PML called leukoencephalopathy (ie, degeneration of the white matter in the brain).

Infection with the PML virus is a serious diagnosis. Because the infection normally is seen in late HIV infection, its presence indicates that the host's immune system has been severely damaged and that treatment for the HIV infection is either ineffective or no treatment has been received. Positive findings on CT or MR alone may not provide the diagnosis. Other diagnostic tools such as blood tests, cerebrospinal fluid (CSF) analysis and brain biopsy also may be used. Brain biopsy is the current "gold standard" for PML diagnosis. (28)

PML infection progresses rapidly and until the advent of new antiviral treatment drugs, a diagnosis of PML meant death within 4 to 6 months. Since the advent of these new drugs and their aggressive use, patients with PML are surviving longer. (24)

Toxoplasmosis

Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii, a protozoan. Frequently referred to as "toxo," T gondii is one of the major causes of latent CNS infection worldwide. Toxo infection occurs as a result of ingesting contaminated raw or undercooked meat, or through contact with feces from an infected cat. (6) Other modes of infection include transmission from mother to fetus, organ transplantation and granulocyte transfusion. (29) Because the modes of transmission vary, there are 2 forms of toxoplasmosis: congenital and acquired. The acquired form is further divided into 2 types: lymphadenopathic and disseminated.

About half of all Americans are infected with T gondii. In most of them, the infection causes no symptoms or harm. (30) Because HIV/AIDS infection seriously damages the immune system, dormant infections may become active, or the impaired immune system may provide the opportunity for T gondii infection.

Toxoplasmosis usually infects the brain but can infect other areas, especially the eyes. In patients with HIV/AIDS, toxoplasmosis generally occurs when CD[4.sup.+] T-lymphocyte counts drop below 200/[micro]L. (30) It is the most common OI of the brain in patients with AIDS, and in those who have dormant toxoplasmosis infection and CD[4.sup.+] T-lymphocyte counts of 50/[micro]L or less, the risk of activation increases profoundly. (31) Symptoms of CNS toxoplasmosis infection include: (27,30)

* Headache (severe, unresolved with medication).

* Confusion.

* Lethargy.

* Low-grade fever.

* Weakness.

* Mood and personality changes.

* Speech disturbances.

* One-sided weakness or numbness.

* Seizures.

* Vision changes (double vision, light sensitivity, blindness).

Left untreated, symptoms progress, leading to coma and death. (30) Some empirical studies have shown that 50% to 70% of CNS symptoms or deficits in patients with advanced HIV infection are a result of toxoplasmosis. (32,33)

Because toxoplasmosis infection in patients with AIDS usually produces brain abscesses with characteristic central avascular areas surrounded by regions of necrotic and inflammatory cells, (29) CT and MR lend themselves to its diagnosis. However, the ACR ranks CT second to MR for imaging intracranial lesions such as those caused by T gondii infection and in the diagnosis of the causes of progressive neurological deficits in patients with AIDS. (23,34) But, other researchers have suggested that CT with contrast enhancement is quite adequate as the initial screening technique and that MR need only be performed if CT findings are normal, inconclusive or demonstrate a solitary lesion. (35)

Positive neurologic CT images in toxoplasmosis infection may demonstrate hypodense masses with the following characteristics: (29,36)

* Mass effect.

* Located in the frontal lobe, parietal lobes, basal ganglia or corticomedullary junction.

* Mass enhancement (usually ring).

Figure 3 shows findings leading to the diagnosis of toxoplasmosis of the brain. It clearly demonstrates classic CT findings attributed to toxoplasmosis. There are low-attenuating areas in most of the left thalamus, posterior aspect of the left internal capsule and posterior basal ganglia. Enhancement may be present in toxoplasmosis, but does not appear in this image. The radiologist's impression was toxoplasmosis in this HIV+ patient.

[FIGURE 3 OMITTED]

Figure 4 demonstrates an enhancing lesion in the left parietal lobe; there is also moderate mass effect and edema. The report stated that the lesion most likely was due to toxoplasmosis, although PML also was a possibility. Enhancement is unusual, although possible, with PML.

[FIGURE 4 OMITTED]

Neither CT nor MR alone should be used to make a definitive diagnosis of CNS toxoplasmosis infection because other CNS pathology, especially CNS lymphoma, can produce very similar radiographic findings. CSF analysis, serologic tests, brain biopsy or other nonimaging diagnostic tools may be used to substantiate positive CT or MR findings. Brain biopsy can provide definitive diagnosis and guide the treatment of patients with CNS toxoplasmosis infection.

Because CNS toxoplasmosis infection can cause serious morbidity and mortality, the earlier the diagnosis, the better. CNS toxoplasmosis is treatable. Patients with HIV/AIDS who receive antiretroviral therapy rarely develop toxoplasmosis. For the few who do, treatment may involve several medications, such as pyrimethamine, folinic acid, sulfadiazine or trisulfa-pyrimidine.

Primary CNS Lymphoma

Lymphoma is a malignant neoplasm originating in the lymphocytes, the same cells that HIV/AIDS attacks and destroys. There are several different types of lymphomas, including Burkitt, cutaneous, T cell, Hodgkin and non-Hodgkin. (5) HIV-associated lymphomas are of the non-Hodgkin type and include primary effusion lymphomas, systemic lymphomas and primary CNS lymphomas. Each of these lymphomas are associated with different outcomes. (37) Lymphomas are generally of B-or T-cell origin; however, CNS lymphomas occurring in the HIV/AIDS population are almost always of the B-cell type and are very aggressive tumors. (38)

Primary CNS lymphoma is confined to individuals with CD[4.sup.+] T-lymphocyte counts of less than 100/[micro]L. Many of those--approximately 75%--have CD[4.sup.+] T-lymphocyte counts of less than 50/[micro]L. CNS lymphoma is a serious disorder, occurring in the most severely immunocompromised HIV/AIDS-infected individuals. (39) After toxoplasmosis, it is the second most common lesion in the brain of people with HIV/AIDS, and in many, it is the presenting condition that leads to a diagnosis of AIDS. (40) The majority of HIV/AIDS patients with CNS lymphoma also have the Epstein-Barr virus (EBV), a member of the herpes virus family. Some researchers have surmised that EBV infection is pivotal in the development of CNS lymphoma. (41)

The onset of CNS lymphoma symptoms is less insidious than for some other CNS OIs. However, some symptoms are the same. They include: (39,40)

* Confusion.

* Lethargy (reported in 60% of cases).

* Memory loss.

* Personality changes.

* Apathy.

* Headache.

* Cranial nerve palsies (excluding facial).

* Seizures.

* Focal weakness.

* Aphasia.

* Hemiparesis.

Left undiagnosed or untreated, CNS lymphoma is associated with an average survival of only around 3 months. (39,41)

Neurologic CT images have a long and positive reputation for detecting cancerous and metastatic lesions. In CNS lymphoma, CT images may demonstrate the following characteristics:

* Hyper- or hypodense solitary lesions that may enhance in a homogeneous, nodular or ring-like pattern.

* Edema and/or mass effect.

* Multiple focal lesions (however, not as often as with toxoplasmosis).

* Lesions generally located in the periventricular gray and white matter, the cerebellum or both.

Figure 5 clearly demonstrates CT findings significant to the radiographic diagnosis of CNS lymphoma, including "ring" enhancement of the periventricular masses and associated edema with mass effect. Figure 6 shows a hyperdense mass located in the superolateral left cerebellar hemisphere in this HIV+ patient.

[FIGURES 5-6 OMITTED]

As with most other pathologies demonstrated on CT or MR, the diagnosis of CNS lymphoma should not be based solely on medical imaging findings. Many pathologies appear very similar on CT, and other diagnostic tests should be used, along with the patient's symptoms, to secure a definitive diagnosis. For CNS lymphoma diagnosis, it is recommended that CSF cytology also be performed, followed by brain biopsy if CSF cytology is negative. (40) CNS lymphoma is a grave diagnosis and even with radiation therapy treatments, long-term survival is unlikely. (41)

AIDS Dementia Complex (ADC)

Any disorder characterized by cognitive deficits may be termed dementia. Dementia is usually an irreversible, progressive decline in mental function, but can be chronic in nature. It may be the result of numerous pathological conditions including, but not limited to: (5)

* AIDS.

* Alzheimer disease.

* B12 deficiency.

* Carbon monoxide poisoning.

* Cerebral anoxia.

* Chronic alcoholism.

* Hypothyroidism.

* Multiple brain infarcts.

* Subdural hematoma.

Dementia takes away personal autonomy by producing a decline in intellectual functioning and interfering with the individual's ability to perform everyday tasks. Activities such as bathing, dressing, eating, toileting and personal hygiene may require assistance. And in later stages, these activities may become the responsibility of others as dementia takes its toll on the mental capacity of the affected person.

CNS and other mental disorders associated with HIV/AIDS have been reported almost as long as the pandemic itself. Several names have been used to describe such disorders: HIV encephalopathy, HIV encephalitis, subacute encephalopathy and progressive dementia, to name a few. (42) In 1985 Navia and Price coined the all-inclusive term "AIDS dementia complex," or ADC (43)

As stated earlier, HIV enters the brain shortly after infection and remains throughout the course of the illness. As with some of the other CNS HIV/AIDS opportunistic infections, the primary cause of ADC is not fully understood. What is known is that prior to the advent and use of antiretroviral therapeutic drugs, ADC occurred at a rate of 7% per year of survival after AIDS diagnosis. At that time, it also was surmised that around 20% of all HIV+ individuals ultimately developed ADC. (44) In the Unites States, it is estimated that 30% to 60% of untreated HIV/AIDS patients develop ADC, along with 20% of those on antiretroviral therapy. (45)

The most recent studies aimed at discovering how HIV causes ADC suggest that macrophages, white blood cells in the brain that act as HIV reservoirs, are to blame for the condition. These studies offer the following explanations of how HIV/AIDS causes ADC: (43,46,47)

* gp 120, a particle on the outer surface of HIV, is cast off of an infected macrophage in the brain, resulting in nerve cell damage or destruction.

* An infected macrophage releases quinolinic acid, a toxic substance, into the brain. The quinolinic acid then binds to the nerve cells, causing destruction. (Note: Elevated levels of quinolinic acid have been found in the CSF of people with ADC.)

* HIV Tat, a molecule secreted by HIV-infected cells, produces proteins called chemokines in the brain. These chemokines attract harmful immune system cells, leading to nerve cell destruction and ADC.

Whatever the method of CNS cell destruction, ADC is more likely to occur after CD[4.sup.+] T-lymphocyte counts fall below 200/[micro]L. (45)

In adults, ADC may produce some of the following behavioral, cognitive or motor symptoms: (44,48)

* Apathy.

* Change in handwriting ability.

* Confinement to bed.

* Depression.

* Decreased libido.

* Difficulty with problem solving.

* Equilibrium problems.

* Forgetfulness.

* Irritability.

* Language impairment.

* Loss of bladder or bowel control.

* Loss of initiative or interest.

* Muscle weakness.

* Poor coordination.

* Poor concentration.

* Reduced spontaneity.

* Slowness in completing normal tasks.

* Spastic gait.

* Withdrawal.

In addition, children with ADC may experience developmental delays, hypertonia, microcephaly and basal ganglia calcifications. (49)

Imaging studies such as CT can substantiate a diagnosis of ADC and rule out other neurologic OIs or neoplasms. CT images positive for ADC may demonstrate: (50)

* Cortical and subcortical atrophy.

* Ventriculomegaly.

* Diffuse sulcal prominence.

* Attenuation of periventricular white matter.

Figures 7, 8 and 9 demonstrate findings consistent with ADC. Figure 7 shows diffuse sulcal prominence throughout as well as posterior horn ventricular enlargement. Figure 8 further demonstrates sulcal prominence, atrophy and bilateral lateral ventricular enlargement. The radiologist's report noted probable ADC.

[FIGURES 7-9 OMITTED]

Figure 9 is an image from another patient with ADC. This image also demonstrates diffuse sulcal prominence with cortical and cerebellar atrophy. In addition, the radiologist reported the presence of ex vacuo hydrocephalus and the appearance of ventriculomegaly caused by atrophy of the brain (ADC likely).

For an accurate diagnosis of ADC, one of the standard imaging procedures, such as CT, MR or single photon emission computed tomography (SPECT), must be used along with findings from mental status examinations and CSF analysis. (43) Left untreated, the average survival time after ADC diagnosis is about 6 months. Antiretroviral drug therapies can protect patients with HIV/AIDS against and induce remission of ADC. (45)

Conclusion

HIV/AIDS still has a relentless hold on the health of millions of people throughout the world. Diagnosis and treatment of the opportunistic infections and complications of HIV/AIDS are presently the only defenses against the morbidity and mortality associated with AIDS. CNS complications are among the most devastating, and neurologic CT is one of the leading tools used in their diagnosis. The ability to identify CT findings with PML, toxoplasmosis, CNS lymphoma and ADC, and use the findings in conjunction with nonimaging diagnostic tests, are essential to the early diagnosis and treatment of these devastating disorders.
Table 1
Tests Used To Diagnose HIV Infection
In Individuals and Blood Collected for Transfusion

Test Name               Specimen   Purpose

ELISA for HIV           Blood      Detect HIV antibodies in
                                   individuals; screen blood for
                                   transfusion

Western Blot for AIDS   Blood      Confirm HIV+ results from ELISA

Coulter HIV-1 p24       Blood      Detect HIV antigens in blood used
Antigen Assay                      for transfusions

OraSure Western Blot    Oral       Detect HIV antibodies in
                                   individuals
Table 2
AIDS-defining Clinical Conditions (7)

Candidiasis of the bronchi, lungs or trachea
Candidiasis of the esophagus
Cervical cancer (invasive in nature)
Coccidioidomycosis (disseminated/extrapulmonary)
Cryptococcosis (extrapulmonary)
Cryptosporidiosis (chronic/intestinal)
Cytomegalovirus disease (excluding liver, nodes and
  spleen)
Cytomegalovirus retinitis (with blindness)
Encephalopathy (related to HIV)
Herpes simplex (bronchitis, chronic ulcers of more
  than a month's duration, esophagitis or pneumonia)
Histoplasmosis (disseminated/extrapulmonary)
Isosporiasis (chronic intestinal of more than a month's
  duration)
Kaposi sarcoma
Lymphoma (Burkitt or equivalent, immunoblastic or
  equivalent, primary brain)
Mycobacterium avium complex or M. kansasii
  (disseminated/extrapulmonary)
Mycobacterium, other or unidentified (disseminated/
  extrapulmonary)
Mycobacterium tuberculosis (pulmonary or extrapulmonary)
Pneumocystis carinii pneumonia
Pneumonia (recurrent)
Salmonella septicemia (recurrent)
Toxoplasmosis of the brain
Wasting syndrome (associated with HIV)


References

(1.) Centers for Disease Control and Prevention. Pneumocystis pneumonia--Los Angeles. MMWR Morb Mortal Wkly Rep. 1981;30:250-252.

(2.) Centers for Disease Control and Prevention. First report of AIDS. MMWR Morb Mortal Wkly Rep. 2001;50:429.

(3.) Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 2000:12(No. 1).

(4.) Joint United Nation Program on HIV/AIDS. Report on HIV/AIDS global epidemic--June 2000. Geneva, Switzerland: Joint United Nations Program on HIV/AIDS, 2000; UNAIDS 100.13 E.

(5.) Taber's Cyclopedic Medical Dictionary. 19th ed. Philadelphia, Pa: FA Davis Co; 2001.

(6.) Miller-Keene Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health. 6th ed. Philadelphia, Pa: WB Saunders Co; 1977.

(7.) Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep. 1992;41(No. RR-17).

(8.) McCook A. Locating the latent enemy. Sci Am. 2001;284:32.

(9.) Mayoclinica.Com What is HIV/AIDS? Available at: www.mayoclinic.com/home?id=DS0005. Accessed July 13, 2001.

(10.) MSN Health. HIV infection and AIDS. Available at: http://content.health.msn.com/content /dmk/dmk_article-546568. Accessed July 17, 2001.

(11.) CDC Publication. Frequently asked questions on HIV/AIDS. Available at: www.cdc.gov/nchstp /hiv-aids/pubs/faqs.htm. Accessed July 17, 2001.

(12.) MSN Health. The human immunodeficiency virus and its transmission. Available at: http://content .health.msn.com/content/dmk/dmk_article-5462571. Accessed July 24, 2001.

(13.) Centers for Disease Control and Prevention. HIV/AIDS surveillance report: basic statistics--exposure categories. Available at: www.cdc.gov /nchstp/hiv-aids/stats/exposure.htm. Accessed July 17, 2001.

(14.) U.S. Food and Drug Administration. FDA consumer magazine: new ways to prevent and treat AIDS. January-February 1997. Available at: www.fda.gov/fdac/features/1997/197-aids.htm. Accessed July 24, 2001.

(15.) Centers for Disease Control and Prevention. The human immunodeficiency virus and its transmission. Available at: http://content.health.msn.com /content/dmk/dmk_summary-account-1294. Accessed July 17, 2001.

(16.) Zaret B, ed. The Yale University School of Medicine Patient's Guide to Medical Tests. New Haven, Conn: Yale University School of Medicine and GS Sharpe Communications Inc; 1997.

(17.) MSN Health. Medical tests--viral load test. Available at: http://content.health.msn.com/content /asset/yale_lab_tests_test_name_viral_load_test .html. Accessed July 17, 2001.

(18.) Clifford D. Neurological opportunistic infections. Current Opinions in Neurology. 1995;8:175-178.

(19.) Link D. Project Inform's AIDS dementia complex (ADC) (HIV/AIDS treatment information). March 1997. Available at: www.projinf.org/FS/dementia .html. Accessed June 25, 2001.

(20.) JAMA HIV/AIDS Information Center. Primary neurologic complications of HIV infection. Available at: www.ama-assn.org/special/hiv/treatment/ updates/neurocom.html. Accessed July 24, 2001.

(21.) HIV Channel. HIV forum: nervous system disorders. Available at: www.hivchannel.com /ensidisorders/indexs.html. Accessed July 24, 2001.

(22.) Villringer K, Jager H, Dichgans M, et al. Differential diagnosis of CNS lesions in AIDS patients by FDG-PET. J Comput Assist Tomogr. 1995;19:532-536.

(23.) ACR Appropriateness Criteria: Imaging of Intracranial Infections (revised). Reston, Va: American College of Radiology; 1999.

(24.) Bowers M. Progressive multifocal leukoencephalopathy. Bulletin of Experimental Treatments for AIDS. San Francisco AIDS Foundation. September 1997.

(25.) Cultler R. Demyelinating disease. In: Scientific American Medicine. Rubenstein E, Federman DD, eds. New York, NY: Scientific American Inc; 1997.

(26.) Fong I, Toma E. The natural history of progressive multifocal leukoencephalopathy in patients with AIDS. Clin Infect Dis. 1995;20:1305-1310.

(27.) National Institute of Health and NINDS. What are the neurological manifestations of AIDS? NIH Fact Sheet. May 26, 2000.

(28.) von Giesen H, Neuen-Jacob E, Dorries K, et al. Diagnostic criteria and clinical procedures: HIV-1 associated progressive multifocal leukoencephalopathy. J Neurol Sci. 1997;147:63-72.

(29.) Lingappy J, Leoung G. Toxoplasmosis and HIV. HIV knowledge base chapter. Available at: http://hivinsite.uncsf.edu/Insite.jsp?page=kb-05 -04-03. Accessed August 25, 2001.

(30.) Gay Men's Health Crisis (GMHC) Fact Sheet. All about toxoplasmosis. Being Alive Newsletter. February 1996.

(31.) Luft B, et al. Risk factors for development of cerebral toxoplasmosis [abstract]. First National Conference on Human Retroviruses, 1993. Abstract 474.

(32.) Circillo S, Rosenblum M. Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients. J Neurosurg. 1990;73:720-724.

(33.) Simpson D, Taqliati M. Neurologic manifestations of HIV infection. Ann Intern Med. 1994;121:769-785.

(34.) ACR Appropriateness Criteria: Progressive Neurological Deficit (revised). Reston, Va: American College of Radiology; 1999.

(35.) Porter S, Sande M. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med. 1992;327:1643-1648.

(36.) Joint Program in Nuclear Medicine. Imaging CNS complication in AIDS. Available at: http:// brighmrad.harvard.edu/cases/jpnm/hcache/1082/ full.htm. Accessed July 24, 2001.

(37.) Kaplan LD, Straus DJ, Testa MA, et al. Randomized trial of standard dose vs. low-dose m BACOD chemotherapy for HIV-associated non-Hodgkin's lymphoma. N Engl J Med. 1997;336:1641-1648.

(38.) Kaplan L. Natural history, treatment, outcomes and causes of death in AIDS-related primary central nervous system lymphoma (PCNSL) [abstract]. Program and Abstracts of the Meeting of the American Society of Clinical Oncology, May 14-17, 1994, Dallas, Tex. Abstract 18.

(39.) HIV Insite. Clinical presentation and management of HIV-associated lymphoma. University of California San Francisco, 2001.

(40.) eMedicine Journal. Malignancies: primary CNS lymphoma. Available at: www.hivpositive.com /F-oi/OppInfections/4-malignancies/4-malcns:html/. Accessed February 23, 2001.

(41.) Levine AM, Sullivan-Halley J, Pike MC, et al. Human immunodeficiency virus-related lymphoma: prognostic factors predictive of survival. Cancer. 1991;68:2466-2472.

(42.) Pajeau A, Roman G. HIV encephalopathy and dementia. Psychiatr Clin North Am. 1992;15:4555-4566.

(43.) Project Inform. AIDS dementia complex (ADC). Available at: www.projinf.org/fs/dementia.html. Accessed June 25, 2001.

(44.) HIV infoweb. HIV and AIDS opportunistic infections: AIDS dementia complex. Available at: www.aegis.com/hivinfoweb/top/oi.html. Accessed June 25, 2001.

(45.) Florian P. HIV-1 encephalopathy and AIDS dementia complex. Emedicine Journal. Feb 12, 2001. Available at: www.emedicine.com/NEURO /top447.html. Accessed August 25, 2001.

(46.) Heyes MP, Brew BJ, Martin A, et al. Quinoline acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol. 1991;29(2):202-209.

(47.) Study yields new insight into HIV-associated dementia [press release]. University of Alabama at Birmingham Office of Media Relations, December 11, 2000.

(48.) Perry S. Organic mental disorders caused by HIV: update on early diagnosis and treatment. Am J Psychiatry. 1990;147:696-710.

(49.) Stover E. CNS effects of HIV-1 infections and AIDS in infants and children: a collaborative research agenda. Pediatr AIDS HIV Infect. Nov 6, 1990:109-119.

(50.) Said G, Saimont A, Lacroix C. Neurological Complications of HIV and AIDS. Philadelphia, Pa: WB Saunders; 1998.

Directed Reading Continuing Education Quiz

DRI0002007 Expiration Date June 30, 2004 * Approved for 1.5 Cat. A CE credits

CT Assessment of CNS Complications of AIDS

To receive Category A continuing education credit for this Directed Reading, read the preceding article and circle the correct response to each statement. Choose the answer that is most correct based on the text. Transfer your responses to the answer sheet on Page 442 and then follow the directions for submitting the answer sheet to the American Society of Radiologic Technologists. You also may take Directed Reading quizzes online at www.asrt.org. New and reinstated members are ineligible to take Directed Readings from journals published prior to their most recent join date.

* Your answer sheet for this Directed Reading must be received in the ASRT office on or before this date.
 1. The first reports of AIDS and HIV surfaced in:

    a. 1980.
    b. 1981.
    c. 1982.
    d. 1983.

 2. Since the beginning of the pandemic, how many
    Americans have been infected with HIV?

    a. 200 000.
    b. 300 000.
    c. 500 000.
    d. 1 000 000.

 3. HIV/AIDS remains the number -- cause
    of death worldwide, and the number -- cause
    of death on the African continent, respectively.

    a. 1, 4.
    b. 4, 1.
    c. 3, 1.
    d. 1, 3.

 4. Viruses may be classified according to all of the
    following, except:

    a. genome core.
    b. gamete class.
    c. method of reproduction.
    d. mode of transmission.

 5. HIV infects a type of white blood cells known as:

    a. basophils.
    b. eosinophils.
    c. lymphocytes.
    d. monocytes.

 6. HIV destroys a person's -- system.

    a. immune.
    b. endocrine.
    c. reproductive.
    d. lymphatic.

 7. HIV targets:

    a. CD[3.sup.+] T monocytes.
    b. CD[4.sup.+] T monocytes.
    c. CD[3.sup.+] T lymphocytes.
    d. CD[4.sup.+] T lymphocytes.

 8. HIV infection may be acquired through all of the
    following activities except:

    a. casual contact with an infected person.
    b. sexual contact with an infected partner.
    c. contact with infected blood.
    d. contact with other infected body fluids.

 9. What is the risk of acquiring HIV infection from a
    blood transfusion?

    a. 1 in 45 000 to 60 000.
    b. 1 in 100 000.
    c. 1 in 450 000 to 600 000.
    d. 1 in 1 000 000.

10. Which of the following medical tests used to
    detect HIV antibodies or antigens does not
    require a venous blood sample?

    a. Coulter HIV-1 p 24 Antigen Assay.
    b. ELISA for HIV.
    c. OraSure Western Blot.
    d. Western Blot for AIDS.

11. What is the most common opportunistic infection
    (OI) associated with HIV worldwide?

    a. Kaposi sarcoma.
    b. mycobacterium avium complex.
    c. viral hepatitis.
    d. tuberculosis.

12. Neurological complications of HIV/AIDS are
    much more likely to occur if an infected individual's
    defining white blood cell count drops below:

    a. 1000/[micro]L.
    b. 700/[micro]L.
    c. 300/[micro]L.
    d. 100/[micro]L.

13. Which HIV/AIDS neurological complication is
    caused by the JC Papova virus and results in extensive
    demyelinating lesions in the brain, brain stem
    and cerebellum?

    a. AIDS dementia complex (ADC).
    b. CNS lymphoma.
    c. progressive multifocal leukoencephalopathy
       (PML).
    d. toxoplasmosis.

14. Which imaging technique did the American
    College of Radiology (ACR) designate as the first
    choice for suspected progressive multifocal
    leukoencephalopathy (PML)?

    a. CT.
    b. spiral CT.
    c. MR.
    d. SPECT.

15. On CT, lesions with little if any mass effect and
    minimal or no enhancement postcontrast are
    suggestive of:

    a. ADC.
    b. CNS lymphoma.
    c. CNS toxoplasmosis.
    d. PML.

16. Which technique is considered the "gold standard"
    for diagnosing PML?

    a. cerebrospinal fluid analysis.
    b. blood tests.
    c. brain biopsy.
    d. mental status examination.

17. Before the use of several antiviral treatment drugs,
    a diagnosis of PML meant death within
    -- months.

    a. 1 to 2.
    b. 2 to 4.
    c. 4 to 6.
    d. 6 to 8.

18. The parasitic infection that is one of the major
    causes of latent CNS infection globally and generally
    occurs in HIV/AIDS patients with white blood
    cell counts below 200/[micro]L is:

    a. CNS lymphoma.
    b. toxoplasmosis.
    c. Kaposi sarcoma.
    d. candidiasis.

19. Among patients with HIV/AIDS who are receiving
    antiretroviral therapy, toxoplasmosis is a common
    complication.

    a. true.
    b. false.

20. CNS lesions producing mass effect and located in
    the periventricular gray and white matter are likely
    to be related to:

    a. ADC.
    b. CNS lymphoma.
    c. CNS toxoplasmosis.
    d. PML.

21. Even with treatment, in which of the following
    conditions is long-term survival not likely?

    a. ADC.
    b. PML.
    c. CNS lymphoma.
    d. toxoplasmosis.

22. Any disorder that produces cognitive deficits and
    causes an appreciable decline in an individual's
    intellectual functioning is termed:

    a. Alzheimer disease.
    b. dementia.
    c. mental illness.
    d. neuropsychosis.

23. Which of the following findings is associated with
    AIDS dementia complex (ADC) in children?

    a. calcified pineal gland.
    b. calcified choroids plexus.
    c. calcifications in the basal ganglia.
    d. calcifications in the lateral ventricles.

24. Neurologic CT images demonstrating cortical and
    subcortical atrophy, diffuse sulcal prominence,
    ventriculomegaly and periventricular white matter
    attenuation may assist in the diagnosis of:

    a. ADC.
    b. CNS lymphoma.
    c. CNS toxoplasmosis.
    d. PML.

25. Left untreated, the average survival time after
    ADC diagnosis is approximately -- months.

    a. 12.
    b. 10.
    c. 8.
    d. 6.

26. Lesions with defining "rings" on CT are suggestive
    of:

    a. ADC and toxoplasmosis.
    b. CNS lymphoma and ADC.
    c. toxoplasmosis and CNS lymphoma.
    d. PML and toxoplasmosis.


Bettye Greene Wilson, M.A.Ed., R.T.(R)(CT), RDMS, is an associate professor in the School of Health Related Professions at the University of Alabama at Birmingham and a member of the Radiologic Technology Editorial Review Board.
COPYRIGHT 2002 American Society of Radiologic Technologists
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002 Gale, Cengage Learning. All rights reserved.

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Title Annotation:central nervous system
Author:Wilson, Bettye Greene
Publication:Radiologic Technology
Date:May 1, 2002
Words:7710
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