Myelopathy is a term used to describe any disease that affects the spinal cord, which can result in loss of mobility or sensation. HIV-associated myelopathy is the leading cause of spinal cord disease in HIV (human immunodeficiency virus) patients.
The most common type of myelopathy that affects HIV patients is called vacuolar myelopathy. This form occurs when the fatty tissue called the myelin sheath, which normally covers and protects the nerves, separates from the spinal cord and forms cavities or vacuoles.
Since the myelin sheath is responsible for ensuring that electrical signals from nerves are properly directed to the brain, individuals who have vacuolar myelopathy experience problems with bodily movements and functions.
Although the exact cause of vacuolar myelopathy remains unknown, it has been suggested that HIV itself is responsible for nervous system damage. The disease occurs during the late stages of HIV infection, when the CD4 counts are low. HIV primarily targets the CD4 cells, which are helper T-cells that help fight against disease and infection.
Vacuolar myelopathy has been associated with AIDS dementia complex (ADC), peripheral neuropathies (peripheral nervous system disorder that affects sensations in the hands and feet), and opportunistic nervous system infections and cancers, such as cytomegalovirus (type of herpes virus), progressive multifocal leukoencephalopathy (disease that affects the white matter of the brain), and lymphoma (cancer of the lymph nodes).
Researchers believe that up to 30% of adults with AIDS (acquired immune deficiency syndrome) experience some level of damage to the myelin. The incidence of vacuolar myelopathy may be much higher among HIV-infected children.
Highly active antiretroviral therapy (HAART), which is the standard treatment for HIV and AIDS, has led to a decline in vacuolar myelopathy. Before HAART was introduced, 5-20% of adult HIV patients in clinical studies and 25-55% of adult HIV patients in histological studies were diagnosed with vacuolar myelopathy. Since then, it is estimated that fewer than 10% of AIDS patients develop myelopathy.
The prognosis is poor for individuals who develop vacuolar myelopathy because there is currently no treatment available for the condition. Most patients die within six months of developing symptoms of myelopathy.
The cause of HIV-associated vacuolar myelopathy remains unknown. Researchers have suggested that when HIV infects cells in the nervous system, it causes an over-production of cytokine tumor necrosis factors (protein produced by white blood cells that causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication) and an under production of interleukin-4 and interleukin-10 (proteins that stimulate the immune system). The myelin sheath may become damaged when the cytokines are not regulated properly.
It has also been suggested that the condition is caused by an HIV infection of cells in the central nervous system called oligodendrocytes. These cells produce and maintain myelin.
The condition has also been associated with vitamin B12 deficiency, although it does not appear to cause vacuolar myelopathy. Vitamin B12 plays a vital role in the metabolism of fatty acids that are essential for maintaining healthy myelin. Prolonged B12 deficiency can lead to nerve degeneration and irreversible neurological damage. Vitamin B12 deficiency is relatively common among HIV patients. It is unclear whether low vitamin B12 levels influence HIV disease progression, or whether they are merely a consequence of disease progression. Most HIV patients who have gastrointestinal problems are unable to adequately absorb the vitamin. Gastrointestinal problems in HIV patients are often caused by opportunistic infections or are a side of effect of antiretrovirals.
Common symptoms include numbness in the limbs, quick tendon reflexes, muscle weakness, sensory abnormalities in the legs, difficulty coordinating movement, impotence (erectile dysfunction), frequent urination, and incontinence (inability to control urination). As the condition progresses, the patient may experience paralysis of the lower limbs.
General: A diagnosis is based on the clinical observation of signs and symptoms and the exclusion of other causes of myelopathy via blood tests, imaging studies, and cerebrospinal fluid tests.
Blood test: A blood test may be performed to rule out other causes of myelopathy. A sample of blood is taken from the patient and analyzed in a laboratory for disease-causing agents.
Imaging studies: A magnetic resonance imaging (MRI) or computerized tomography (CT) scan is often used to rule out other possible causes of myelopathy. Other possible causes may include infections, degenerative disk disease, neoplasms (tumor growth), or degenerative spinal disease.
Lumbar puncture (spinal tap): A lumbar puncture (spinal tap) is usually performed to rule out other possible causes of myelopathy, such as cytomegalovirus (type of herpes virus), shingles (viral nerve infection), or herpes simplex virus (viral infection that causes blister-like lesions around the mouth and lips, the anus, or the genital area). During the procedure, a needle is inserted between two vertebrae and a small sample of cerebrospinal fluid (CSF) is removed. Individuals who have vacuolar myelopathy typically have normal CSF results. If the condition is caused by a virus, such as cytomegalovirus, shingles, or the herpes simplex virus, the viral particles will be present in the fluid.
General: There is currently no treatment available for vacuolar myelopathy. However, highly active antiretroviral therapy (HAART) may help prevent the condition from developing in HIV patients. Physical therapy may also help improve or maintain muscle coordination. Since vitamin B12 does not appear to cause vacuolar myelopathy, it is unlikely that supplementation with vitamin B12 is an effective treatment.
Highly active antiretroviral therapy (HAART): Individuals who have a low CD4 count have an increased risk of developing vacuolar myelopathy. Therefore, it is recommended that HIV/AIDS patients receive highly active antiretroviral therapy (HAART) to restore the body's immune system, which fights against diseases and infections. While these drugs cannot cure HIV infection or AIDS, they can suppress the virus. HAART combines drugs from at least two different classes of antiretroviral drugs.
Currently, the U.S. Food and Drug Administration (FDA) has approved 28 antiretroviral drugs to treat HIV. These drugs fall into three major classes:
reverse transcriptase (RT) inhibitors, fusion inhibitors, and protease inhibitors. In July 2006, the FDA approved a multi-class combination called Atripla©.
Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA into HIV DNA. There are two main types of RT inhibitors: non-nucleoside RT inhibitors and nucleoside/nucleotide RT inhibitors. Non-nucleoside
RT inhibitors bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Rescriptor©, Sustiva©, and Viramune©.
Nucleoside/nucleotide RT inhibitors
serve as faulty DNA building blocks. Once they are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved drugs include Combivir©, Emtriva©, Epivir©, Epzicom©, Hivid©, Retrovir©, Trizivir©, Truvada©, Videx EC©, Videx©, Viread©, Zerit©, and Ziagen©.
Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. Only one fusion inhibitor, Fuzeon©, is FDA approved.
Protease inhibitors (PIs) interfere with the protease enzyme that HIV uses to produce infectious viral particles. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the virus to cleave nascent proteins for final assembly of new virons.
FDA approved protease inhibitors include Agenerase©, Aptivus©, Crixivan©, Invirase©, Kaletra©, Lexiva©, Norvir©, Prezista©, Reyataz©, and Viracept©.
Physical therapy: Physical and occupational therapy may help the individual maintain muscle strength and coordination. During physical therapy, the patient will participate in therapeutic exercises and modalities that are designed to help the patient restore as much muscle movement and coordination as possible.
Vitamin B12 (cobalamin): If patients are unable to absorb the vitamin in the gastrointestinal tract, the vitamin may need to be administered intramuscularly or intranasally. The recommended dietary allowances (RDAs) of vitamin B12 (cobalamin) are 2.4 micrograms per day for adults and adolescents aged 14 years and older, 2.6 micrograms per day for adult and adolescent pregnant females, and 2.8 micrograms per day for adult and adolescent breastfeeding females. RDAs have not been established for all pediatric age groups; therefore, adequate intake (AI) levels have been used instead. The RDA and AI of vitamin B12 are: infants 0-6 months, 0.4 micrograms (AI); infants 7-12 months, 0.5 micrograms (AI); children 1-3 years, 0.9 micrograms; children 4-8 years, 1.2 micrograms; and children 9-13 years, 1.8 micrograms.
Currently, there is insufficient available evidence on the safety and efficacy of integrative therapies for the treatment or prevention of HIV-associated vacuolar myelopathy
Individuals who have low CD4 cell counts have an increased risk of developing vacuolar myelopathy. Therefore, it is recommended that HIV/AIDS patients receive highly active antiretroviral therapy (HAART) to restore the body's immune system. While these drugs cannot cure HIV infection or AIDS, they can suppress the virus. HAART combines drugs from at least two different classes of antiretroviral drugs.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
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