What is HIV-1–Associated Progressive Polyradiculopathy?
The human immunodeficiency virus (HIV) is a type of virus that has two categories: HIV-1 and HIV-2. HIV-1 is the stronger and more common type. One of the most frequent health problems linked with HIV-1 is peripheral neuropathy. Peripheral neuropathy is when nerve damage causes sensory changes or pain (sensory polyneuropathy), affects a single nerve (mononeuritis), impacts multiple nerves (mononeuropathy multiplex), or leads to inflammation and damage to myelin – the protective coating around nerve fibers (inflammatory demyelinating polyneuropathy). Additionally, there can also be progressive nerve root damage (polyradiculopathy) and autonomic neuropathy, which affects the nerves that control your heart rate, blood pressure, and other automatic body functions.
Progressive polyradiculopathy in HIV infection progresses gradually, affecting sensory, motor, reflexive, and processes in control of organs like the bladder and rectum. Most of the time, it arises in advanced stages of HIV, but it can also appear suddenly and progress rapidly to irreversible deficits or a fatal result unless treated promptly.
This severe progression of polyradiculopathy generally happens in HIV patients with advanced disease and severe weakening of the immune system. However, with the use of antiretroviral therapy (ART) – a treatment for HIV – these events have become less frequent. It is now primarily seen in patients who are not under treatment. For those who are receiving HIV treatment, uncontrollable infections leading to this syndrome might appear with unexpected characteristics.
What Causes HIV-1–Associated Progressive Polyradiculopathy?
The HIV virus can affect both the central and peripheral nervous systems. However, the reasons for nerve disorders in HIV patients are usually linked to their immune status. Nerve inflammation occurs more often in HIV patients with a higher CD4 count, which is a type of white blood cell that the immune system uses to fight infections. If a patient has a lower CD4 count, nerve disorders can be a result of opportunistic infections, which are infections that occur more frequently in people with weakened immune systems.
A common nerve condition in HIV patients is progressive polyradiculopathy, which is usually associated with a cytomegalovirus (CMV) infection, a type of virus that doesn’t cause problems in most people but can become serious in people with weakened immune systems. However, other infectious agents like varicella-zoster virus (the virus that causes chickenpox and shingles), tuberculosis, treponema pallidum (the bacterium that causes syphilis), Epstein-Barr virus, toxoplasma, cryptococcus, and herpes simplex virus can also cause this nerve condition.
There are also non-infectious causes of nerve conditions in HIV patients, such as primary spinal lymphoma (a type of cancer that begins in the cells of the immune system), metastasis from systemic lymphoma (cancer spread from one part of the body to another), paraneoplastic polyradiculopathy (a nerve disorder related to cancer), and lymphomatous meningitis (a rare type of cancer that affects the tissues covering the brain and spinal cord).
HIV patients can also experience lumbosacral radiculitis, a condition that occurs when the nerves in the lower back and hips become inflamed, often after the reactivation of herpes simplex virus type 2.
Generally, nerve conditions caused by infections and lymphoma-related causes develop gradually and continue to worsen over time. Chronic inflammatory demyelinating polyradiculopathy, a neurological disorder that results in gradual weakness and numbness, and diffuse infiltrative lymphocytosis, a condition that causes swelling in certain areas of the body, are less common. There are also rare cases of HIV patients developing certain nerve syndromes during the process of becoming positively tested for HIV.
One such condition is idanivir-induced epidural lipomatosis, a condition caused by certain HIV medication, which can lead to lumbar polyradiculopathy, a condition that causes pain, numbness, or weakness due to irritation of the nerves in the lower spine. This condition improves once the medication is stopped.
While investigating nerve disorders in known HIV-positive patients, it’s important to rule out causes that are common in the general population, especially in patients who have well-controlled disease thanks to highly active antiretroviral therapy, also known as HAART, which is a combination of several antiretroviral medicines used to slow the rate at which HIV multiplies in the body.
Risk Factors and Frequency for HIV-1–Associated Progressive Polyradiculopathy
Thanks to antiretroviral therapy (ART), HIV has changed from an always-fatal disease to a manageable chronic condition. This perspective shift has brought an increase in complications related to HIV. For instance, while exact numbers are hard to find, between 10 to 15% of people with HIV have visible neurological symptoms, and almost everyone with advanced AIDS shows signs of neuropathy.
This type of neuropathy associated with HIV is commonly seen in adults, with only a few cases noted in children. It’s also worth noting that older people have less chance of recovery. Other risk factors for developing this condition in people with HIV include aging, obesity, diabetes, and severe depression.
Research shows that quick treatment with antiviral medications can bring down the death rate from 100% to 22%.
Signs and Symptoms of HIV-1–Associated Progressive Polyradiculopathy
HIV-associated progressive polyradiculopathy, a condition that affects the nerves, can be caused by different things; however, the symptoms are typically the same. The timing of the onset can vary depending on the cause. Symptoms relating to infection are usually seen in later stages of HIV, while inflammation-related symptoms can appear in mid to late stages. There is a particular variant of the condition that appears when the body starts producing antibodies against the virus.
Main symptoms include weakness in both sides the lower body, lack of reflexes, and trouble controlling bladder or bowel movements. These can show up in different areas of the peripheral nervous system, not necessarily in the lower back area only. In HIV patients, this condition often looks like cauda equina syndrome (CES), a rare disorder affecting nerves at the end of the spinal cord. Notably, it generally doesn’t affect the neck area. The usual pattern includes gradually worsening weakness and numbness in the legs, and it can often be an indication of an underlying cytomegalovirus disease.
Sensory changes, usually starting in the legs, feet, or saddle region (area around the inner thighs, buttocks, and genitals), can sometimes look uneven. It can either progress rapidly to a state of flaccid paralysis (loss of muscle tone) or a slow, latent progression of symptoms can occur.
Presents first as lower back pain and acute or subacute motor weakness. This is often accompanied by lower-than-normal or unnoticeable reflexes, a specific type of foot response to stimulation, and loss of sphincter control. Occasionally, sensory symptoms might manifest as extreme, shock-like pain spread out in dermatomal pattern—that is, along the nerve’s distribution path, which can occur either spontaneously or be triggered by movement. In some cases, there might be abnormalities in feeling or perception in the sacral area. Involvement of the upper limbs or cranial nerves is rare in this condition.
In cases of inflammation-related polyradiculopathy, patients can still control their sphincter actions, but chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) might show a pattern of recurring symptoms alternating with periods of recovery. In cases associated with a cytomegalovirus (CMV) infection, non-neurological CMV infection is common and may not show symptoms. In syphilis, polyradiculopathy has been seen only during early infection, before the signs of secondary syphilis appear, during which time the patient might test negative for the disease.
A recent report from South Africa described a unique way this syndrome shows up. It presented as acute or subacute severe weakness in the muscles controlled by the lower motor neurons (nerves in the spinal cord that control muscles) in the lower limbs in patients later found to have HIV infection. These patients had normal sensation test results and could control their sphincters. Unlike the typical HIV polyradiculopathy, these patients neither had any identifiable opportunistic infection nor advanced immunosuppression (weakening of the immune system). This group of patients was identified as part of another variant of the condition associated with HIV, or they might be showing a separate clinical presentation of the syndrome.
Testing for HIV-1–Associated Progressive Polyradiculopathy
When a patient is suspected of having polyradiculopathy, which is a condition where several nerve roots become damaged, doctors often need to conduct further tests. This is to make sure there aren’t other neurological conditions present. In addition, these tests help identify the cause of the nerve damage.
One type of test conducted is a Lumbar Puncture, otherwise known as a spinal tap. This procedure is especially common for patients with HIV who are showing neurological symptoms because Cytomegalovirus, a common virus seen in people with weakened immune systems, is often the leading cause of polyradiculopathy. Cerebrospinal fluid (CSF), which is collected during a lumbar puncture, is analyzed for various findings indicative of this condition.
These findings often include higher than normal counts of white blood cells, low levels of glucose (a type of sugar our bodies use for energy), higher than normal protein levels, and the absence of cancerous cells. For viral detection, CSF testing for CMV can be done by polymerase chain reaction (PCR) assay and branched DNA signal amplification assay.
There are many other ways to help diagnose and monitor CMV infection, especially in HIV-positive patients. In some cases, the virus might not be detectable, especially in patients with weakened immune systems.
Another common method of testing in patients with suspected polyradiculopathy is Electrodiagnostic Testing, including tests like electromyography (EMG) and nerve conduction studies. These tests are valuable because they can pinpoint physical abnormalities consistent with nerve root damage.
In addition to these tests, imaging tests like Magnetic Resonance Imaging (MRI) and CT Myelography are also helpful. MRI is typically the first choice; it can easily spot any structural damage that may be causing the polyradiculopathy. If MRI tests do not provide clear results, or the patient has other conditions that prevent them from getting an MRI, CT Myelography, which is a special type of CT scan, is used.
Based on patient history and the prevalence of certain diseases in their local area, additional tests might be performed. These tests examine for signs of other diseases such as tuberculosis, syphilis, and lymphoma among other conditions. For example, in patients with both HIV and syphilis, syphilis tests should be done since it is possible for these patients to first show signs of polyradiculopathy before any other indication of syphilis. However, these tests can sometimes be falsely negative in patients with severe immune system weakening. If no initial cause for polyradiculopathy is found, doctors may opt to repeat the syphilis testing.
Treatment Options for HIV-1–Associated Progressive Polyradiculopathy
The treatment for patients with HIV and progressive polyradiculopathy, a condition where there’s progressive inflammation of multiple nerves in the body, depends mainly on two things: treating what might cause the condition and controlling HIV itself. So when we deal with potential cases, it’s not uncommon for doctors to use drugs that target a common virus related to HIV, called cytomegalovirus (CMV).
Considering how often CMV-related polyradiculopathy occurs, doctors often start preventative treatment when the patient’s CD4 count, which is a measurement of the strength of the body’s immune system, drops very low. In addition, doctors also start patients on Antiretroviral therapy (ART), a treatment that helps restrain the HIV virus and helps the body grow back its CD4 cells. However, it’s worth noting that if a patient hasn’t started taking any ART, doctors generally wait for 14 days before introducing it. This is to keep the body from overreacting and worsening the condition—a phenomenon known as Immune reconstitution inflammatory syndrome (IRIS).
If a patient with HIV and CMV-related polyradiculopathy has a severe form of the disease, doctors generally use an intravenous (injected into a vein) medication called ganciclovir for 2-3 weeks, while they often prescribe oral valganciclovir for a milder form of the disease. After that, the patient might be asked to continue taking the oral medication for up to 6 months or until their CD4 count increases significantly. If the treatment doesn’t work – which can be indicated by persistent oddity in spinal fluid or if the patient had previously been unsuccessfully treated with similar medication, combination drugs or alternative drugs might be considered. In cases of resistance to ganciclovir, another drug called foscarnet can be used alone or in combination with yet another drug named cidofovir.
With a proper start to the treatment, neurological symptoms, symptoms that affect the nervous system, can be controlled within two weeks, and the test results for the virus become negative in about three weeks. Despite the treatment, though, some neurological complications might persist. The prescribed antiviral drugs usually prevent more damage from the virus but don’t entirely cure its presence in the patient. Therefore, there’s also a chance for the disease to show up again. So some researchers suggest these types of patients continue taking ganciclovir indefinitely.
If other infectious agents are responsible for the condition, doctors may give appropriate antibiotics and in some cases, steroids to manage the inflammation. If the condition is a result of cancer or similar diseases, chemotherapy and/or radiotherapy could be successful in inducing remission, or temporary end to the disease symptoms. Blood plasma removal and replacement (plasmapheresis) and immunotherapy have been used in patients with HIV to manage inflammation-related diseases. In refractory, stubborn cases, or if the cause is non-infectious, doctors might need to perform surgeries that relieve the pressure on nerves and stitch two or more spinal bones together. Doctors generally reserve surgeries for cases where nothing else is working and if the neurological symptoms are rapidly deteriorating because of potential complications related to the procedure itself and anesthesia.
Supportive treatments, intended to relieve pain and improve function, are also recommended for patients with radiculopathy, the condition of inflamed nerves. Treatments might include injections of corticosteroids into the space around the spinal cord, or a procedure to alleviate the pressure on the spinal cord. Pain relievers, anti-inflammatory drugs, opioids, physical therapy, and tractions can also be employed although there is no strong evidence supporting their use.
What else can HIV-1–Associated Progressive Polyradiculopathy be?
If someone shows signs of a condition called progressive sensorimotor polyradiculopathy, which describes a situation where multiple nerve roots that detect sensation and control movement are affected, there are several possible causes that doctors should think about:
- Transverse myelitis: This involves the inflammation of the spinal cord which results in weakness and numbness of the limbs, and can also affect the ability to feel heat, cold, and pain. This condition progresses quickly and can be detected with certain types of tests.
- Miller Fischer syndrome: This is a variant of a condition called Guillain-Barré syndrome that also involves nerve damage, and it’s often associated with eye movement issues and problems with balance and coordination.
- Neurosyphilis: This is a complication of syphilis, a sexually transmitted infection, that affects the nervous system. It is confirmed with blood tests.
- Toxic polyradiculopathy: This condition happens when something toxic, like a certain type of cancer medication or a substance like ethylene glycol (found in antifreeze), harms the nerve roots.
- Inflammatory polyradiculopathy: This can happen in people with certain types of diseases that cause inflammation, like lupus, Sjogren’s syndrome, or conditions that result in abnormal levels of proteins in the blood.
- Leptomeningeal carcinomatosis: This condition involves cancer cells spreading to the meninges, the layers of tissue that cover the brain and spinal cord.
- Vertebral artery dissection: This is a tear in the inner lining of the vertebral artery, which supplies blood to the brain and can result in symptoms similar to damage in the nerve roots.
- Lyme disease: This infection, caused by a tick bite, can also create a picture similar to Guillain-Barré syndrome.
- Neurosarcoidosis: This condition involves inflammation and the formation of tiny clumps of cells in the nervous system.
- Neurobrucellosis: This is caused by a type of bacteria and can result in muscle and nerve issues.
- Hypertriglyceridemia: High levels of triglycerides (a type of fat) in the blood can rarely lead to polyradiculoneuropathy, a similar condition that affects the nerves.
- Post-bariatric surgery complications: Sometimes, patients can experience nerve problems between 6 months to 2 years after weight loss surgery.
- Diabetic Polyradiculopathy: This condition occurs mostly in people with type 2 diabetes, and patients can experience pain and weight loss, or have simultaneous lumbosacral radiculopathy (a condition that affects the lower back).
It’s important for doctors to consider these conditions when diagnosing someone with progressive sensorimotor polyradiculopathy, so that they can identify the correct cause and provide appropriate treatment.
What to expect with HIV-1–Associated Progressive Polyradiculopathy
It’s often easy to misdiagnose or even miss entirely a condition called HIV-1-associated radiculopathy. When this happens, the disease can become very serious, to a point where it’s always deadly unless it’s quickly identified and treated. HIV-associated progressive polyradiculopathy, a condition that affects the nerve roots, is still dangerous even with the advancement of certain HIV treatments (known as HAART), that have otherwise been successful in reducing other neurological complications of HIV.
This is because these treatments aren’t as effective when the patient’s immune system is considerably weakened. Another form of the disease associated with the cytomegalovirus (CMV), a type of herpesvirus, can be fatal incredibly quickly without treatment. Even with treatment, the mortality rate is still alarmingly high, at around 22%.
If CMV is found in the blood, it’s typically a sign that the patient may not do well and might not survive. Additionally, common infections that often occur alongside this condition, such as CMV and another type of herpesvirus (HSV), can lie dormant in the body and therefore have a tendency to come back or flare up. This means that even after the treatment is complete, some neurological issues may persist, leading to disabilities and potentially impacting the patient’s social and economic life in negative ways.
Possible Complications When Diagnosed with HIV-1–Associated Progressive Polyradiculopathy
People with HIV-related nerve root diseases are at a high risk for other infections. It’s crucial to consider how antiviral drugs interact with HIV medications. Carefully choosing a treatment plan and monitoring it regularly can help to prevent or lessen complications.
Symptoms may get worse when you first start antiviral therapy, but this usually improves as treatment continues. If any critical organs or structures in the body are affected, corticosteroids (a type of medication), gradually reduced over time, are often recommended to reduce illness and the risk of death.
In many cases, infection can affect other parts of the nervous system (such as inflammation of the spinal cord or brain) and non-nervous system areas (like inflammation of the eyes, esophagus, or lungs) either when first diagnosed or as the disease progresses. Other opportunistic infections can also appear.
For diseases caused by tumors, growth of the original tumor, spread of the cancer, or interaction with cancer drugs can cause the disease to worsen.
Common Experiences:
- Increased risk for other infections
- Worsening of symptoms when beginning antiviral therapy
- Utilize corticosteroids to reduce illness and risk of death
- Possible infections in other parts of the body
- Worsening disease due to tumor growth or cancer drugs
Preventing HIV-1–Associated Progressive Polyradiculopathy
To protect both the patient and their main caregiver, it’s essential to take steps to prevent the spread of harmful viruses and bacteria, like HIV, HSV, CMV, TB, etc. The highest risk of spread comes from touching moist surfaces of the body or bodily fluids, so good hygiene practices can make a big difference in prevention. For patients with HIV, consistently taking their antiretroviral therapy (HAART) and regular check-ups to count CD4 cells are crucial. CD4 cells are a type of white blood cell that can fight off infections, so knowing their number can indicate the health of the immune system. If the CD4 count drops below 100 cells per microliter of blood, or if the patient has CMV (a type of virus) in their blood or has had it before, it’s advised to have a fundoscopic screening. This screening involves examining the back of the eye for signs of disease, even if the patient doesn’t feel any symptoms. This is applicable to all complications related to HIV, infectious or not. Early identification and immediate treatment can greatly decrease the long-term negative health impacts and risk of death of HIV. So, it’s important for patients to be aware of any changes in their health and visit a healthcare clinic as soon as symptoms appear.
