Follow up to my question on PML
Nov 2, 2009
The Infectious Disease Specialist (my daughter's doctor) reviewd the MRI and CT Scan and said it was normal.....then proceeded to assure us her condition was not HIV related and sent us searching for a Neurologist.My main concern is..that he didn't even know what PML was or ever heard of it.
Response from Dr. Frascino
I'd suggest your daughter find a more competent HIV disease specialist. I'll repost below some information about locating HIV specialist physicians.
PML mis-diagnosed by Infectious Disease Specialist Nov 1, 2009
How in God's name can someone who calls themself an Infectious Disease Specialist not recognize or atleast consider that his own immunosupressed patient could have PML????
Advertisement Response from Dr. Frascino
Although PML is an opportunistic infection all HIV specialists should be familiar with, making a firm diagnosis of PML can be challenging, as it requires not only a compatible clinical history and MRI findings, but also a brain biopsy positive by DFA stain for JC virus and typical inclusions in specialized cells called oligodendrocytes.
I'll repost below some information about progressive multifocal leukoencephalopathy (PML).
I have PML May 2, 2009
Robert J. Frascino, M.D. Thank you so much for your support and understanding on PML.
I found out that I had HIV in June 2008. On the 2nd of January I was admitted to hospital, and after tests over a two-week period, I was diagnosed with PML. I had lost the ability to hold a conversation and I had poor hearing. Thank goodness, that at the beginning of March 2009, my conversation had improved really good & so had my hearing. My headaches have got much better since March.
I was started on Anti-Depressants at the beginning of March, but in consultation with my Doctor, have been taken off them. The Doctor feels that I have made much progress.
I have many friends that have given me help and support, but the greatest support has come from my partner.
I admit that I have been very upset with what has happened to me. Also, I will miss my job, which was on-stage. I loved being in the wonderful performances.
I wait for your advice and, hopefully, encouragement.
At this time, I feel I am only ready to hear the positives and not the bad points as I feel I wouldnt be able to cope with this information.
Response from Dr. Frascino
I'm not exactly sure what type of advice you want, as you did not ask a question. As for encouragement, sure thing. I'm the most optimistic guy on the planet. No doubt you've had some very significant health challenges this year but look how far you've progressed! I see no reason why you shouldn't expect further improvement as time goes by. Whether you'll be able to resume your work on stage I have no way of predicting based on the limited information presented. But I see no reason why you can't resume some type of activity, perhaps initially on a volunteer basis in the performing arts. Maybe you won't have the center stage spotlight but that doesn't mean you can't be involved in the show.
I'll reprint some information below from the archives that discusses PML. It presents an honest assessment of our current understanding of PML, including prognosis and treatment. Remember to focus on being as well as you can. It's what we all must do each and every day. Good luck. I'm here if you need me.
pml Apr 23, 2009
what, does pml stand for in hiv pos poeple?
Response from Dr. Frascino
Progressive multifocal leukoencephalopathy (PML)! Now there's a name that doesn't just roll of the tongue, eh?
PML is an opportunistic infection caused by Polyomavirus JC. Luckily we are seeing less of this devastating infection than during the early years of the epidemic. I'll reprint some information below that discusses PML.
Progressive Multifocal Leukoencephalopathy (PML) Fact Sheet
PML is a rare AIDS-related condition of the brain, caused by the JC virus. World wide, more than 4 in 5 adults are exposed to this virus, but it only causes disease in people with weakened immune systems. Before AIDS, PML was rarely seen except in people with advanced cancer or bone marrow transplants.
Today, most PML cases occur in people living with HIV, mainly in those with advanced disease and very low CD4+ cell counts. However, it occasionally appears in people with CD4+ cell counts up to 500. Overall, about 1 in 20 people with AIDS will develop PML. It is unclear why, if most people with HIV also have the JC virus, the rate of PML remains so low.
Because it is so rare and because it affects the brain (an organ that is difficult to study), its diagnosis and treatment are poorly understood. In 2005 and 2006, several people with inflammatory diseases were treated with immune therapy (such as natalizumab) to block inflammatory cells and developed PML. This led to renewed interest in researching this rare disease. As PML becomes better understood, some debate may begin on changing the name of the condition to JC Virus Encephalopathy.
What Are the Symptoms? Symptoms do not occur when a person is first infected with JC virus. However, when it infects the brain and begins to cause disease, the infection rapidly forms lesions. This begins to affect various body functions controlled by the brain and nervous system.
A frightening aspect of PML is that there's no "usual" course of disease. Whatever brain areas that are affected by the JC virus will determine how PML appears in an individual. For example, if the virus strikes the part of the brain that controls sight, vision could be lost. If it strikes the part that controls speech or motor skills, one could lose the ability to talk or walk. There is no predicting where or how the virus will attack, and thus what functions will be impaired.
Early symptoms of PML may include weakness in one side of the body or limbs (sometimes very severe), blurred or loss of vision (possibly on one side), fatigue and/or impairments in learned skills that may range from language impairments (aphasia) to memory loss, confusion, disorientation or a loss of balance. Nearly 1 in 5 people with PML disease report having seizures.
Symptoms are similar to those of other HIV-related conditions that affect the brain, including toxoplasmosis (toxo), lymphoma of the central nervous system (CNS lymphoma), AIDS dementia complex (ADC), cryptococcal meningitis, HIV encephalopathy and cytomegalovirus (CMV) and herpes infections of the central nervous system. Therefore, it's important to consult with a specialist, called a neurologist, when these symptoms occur to assure a correct diagnosis.
PML is most often mistaken for toxo. Typically, a doctor may suspect PML if treatments fail for other conditions, like toxo. PML can also occur at the same time as swelling of the brain (HIV encephalopathy) and toxo.
How Do You Diagnose PML? Diagnosing PML is tricky. PML, toxoplasmosis, AIDS dementia complex, cryptococcal meningitis and lymphoma, CMV and even herpes virus infections in the brain can appear like one another on an MRI scan, a type of x-ray of the brain. All of these conditions have been associated with HIV. Because the lesions can look similar on an MRI, it's important to continue the diagnosis by doing a brain biopsy. This way the exact cause can be determined and treated properly. A small hole is drilled into the skull and a piece of tissue is removed and examined. If the JC virus is found in the tissue, PML is diagnosed. A brain biopsy is considered the gold standard for diagnosing PML.
Some people who are presumed to have PML will elect not to have a brain biopsy. Doctors, as well as some surgeons, may not recommend it because it is invasive and causes discomfort. Even if a definite diagnosis of PML comes back, no therapies are very effective at treating the condition with the exception of changes in anti-HIV therapy. A doctor and patient may opt to make these changes regardless of a definitive PML diagnosis.
The main benefit of doing a biopsy is to rule out other possible brain diseases that may be more readily treated. If a person decides not to have the biopsy to confirm PML, doctors sometimes still recommend treating these other common brain diseases on the off chance that the condition is treatable.
When the brain biopsy is not done, PML will be diagnosed using three pieces of information. This includes: 1) if the state of health is consistent with PML symptoms; 2) if JC virus DNA is present in the cerebral spinal fluid; and 3) if MRI tests show lesions mainly in the brain's white matter. However, using anti-HIV therapy complicates the choice to do a brain biopsy in diagnosing PML. The lesions may look different, including more inflammation than what's normally seen, when potent anti-HIV therapy is used.
Another form of x-ray called a computed tomographic (CT) scan may show problems in the brain, but it is not as sensitive as an MRI. Testing for antibodies to the JC virus in blood or urine is also not a good way to detect active JC virus. This is because up to 4 in 5 adults already have these antibodies, with or without HIV infection.
How Do You Treat PML? Until recently, a diagnosis of PML was quite grim. The one therapy used for treating it, a toxic drug called cytosine arabinoside (ara-C, cytarabine, Cytosar-Ur), is given through a shunt directly into the brain. It has shown marginal, if any, benefit. It is no longer routinely used, though some feel that new drug delivery systems warrant renewed research.
Before the arrival of potent anti-HIV therapy, the average time from diagnosis of PML to death was 1-3 months. Recent studies show that using aggressive anti-HIV therapy may result in an indefinite remission of PML for some people.
Nearly 1 in 10 people with PML have recovered with or without treatment. Spontaneous recovery or stabilization is more likely to occur in people with CD4+ cell counts above 200. The unpredictable nature of this issue presents a perplexing challenge to doctors treating PML.
Potent Anti-HIV Therapy Several groups have reported symptom-free survival after a PML diagnosis of over ten years and counting for some people using potent anti-HIV therapy. Factors associated with improved survival include using an anti-HIV regimen with a protease inhibitor and changing to a new regimen after a PML diagnosis.
A more recent study shows extremely encouraging results, perhaps the best to date, with "enhanced" anti-HIV therapy. This is when Fuzeon (enfuvirtide, T-20) is added to a traditional regimen with protease inhibitors. At six months, the survival rate was 3 out of 4 people and the trend suggested this survival rate may hold to one year and beyond.
While there are no guidelines for anti-HIV therapy and PML, it would be fair to make a few assumptions based on gathered information. After a presumptive diagnosis of PML is made and whether or not a person elects to have a brain biopsy, it seems advisable to start or change to a new potent anti-HIV regimen including a protease inhibitor. Experienced neurologists who choose to treat PML with anti-HIV drugs once recommended using anti-HIV drugs that penetrate the blood-brain barrier. This included using high doses of AZT daily (1,000-1,200mg) because lower doses are not as effective at crossing this barrier. More recently, however, experts have changed their thinking about the importance of using drugs that cross the blood-brain barrier in a potent anti-HIV regimen when treating PML.
Increasingly they believe that the benefits of anti-HIV therapy are due to better immune responses throughout the body. This supports the notion of creating the most potent possible regimen based on resistance testing, history of anti-HIV drug use, and cross resistance issues. This is supported by the very encouraging results of the "enhanced" therapy study -- where adding Fuzeon appears to have a profoundly beneficial effect, but is not believed to cross the blood-brain barrier whatsoever.
Cytosine Arabinoside (Ara-C) Cytosine arabinoside (ara-C, cytarabine, Cytosar-Ur) is currently used as chemotherapy for leukemia and cancer. For treating PML it was commonly given through a shunt into the brain and/or directly into a vein (intravenously). Experienced neurologists may dose ara-C through a shunt (called intrathecally) into the brain at doses of 10mg/m2 for three days, followed by 10mg/m2 twice a week for two weeks, then 20-30mg/m2 each week thereafter. The common dose of ara-C when given into a vein is 2mg/kg in 5-day cycles, every 15 or 30 days.
Side effects include nausea, consistent fevers and bone marrow toxicity. These effects are dependent on its dose and schedule and vary in severity. Ara-C can harm an unborn child in pregnant women. Checking blood work is necessary, including daily platelet, leukocyte counts and bone marrow exams during treatment. Some doctors give a dose of G-CSF (granulocyte colony stimulating factor, Neupogen) for one week before starting ara-C to relieve bone marrow toxicity. Prednisone may help reduce side affects.
While ara-C was once considered standard-of-care for people with PML who chose treatment, it has fallen out of favor due to its side effects, low success rate and the superior responses seen from using potent anti-HIV therapy.
Experimental Treatments Cidofovir: Several studies of the anti-CMV drug, cidofovir, first looked encouraging for treating PML. However, over time these studies failed to show any benefit and so it is no longer recommended for treating PML.
Corticosteroids: There is some debate about adding corticosteroids to potent anti-HIV therapy for treating PML. Those opposed to using them say they may further weaken the immune system, which is critical in successfully treating PML. There are also a few cases where the development of PML has been associated with their use. Those in favor of using corticosteroids note that increased inflammation associated with using anti-HIV therapy may be quieted by using these steroids and thus aid PML recovery. Currently, experts are interested in studying corticosteroids as an added therapy to potent anti-HIV therapy for PML.
Interferon Therapy: Researchers have been interested in using both Interferon-alpha and Interferon-beta to treat PML. In test tube studies, both are active against the JC virus. However, studies in people with PML have been terribly underwhelming. Researchers feel that if there were better ways to target the therapy to the brain lesions and the virus, it may be worth revisiting the research on these therapies.
5HT2a Antagonists: This includes drugs like Remeron (mirtazapine) -- a drug usually used to treat depression -- and other similar drugs. Some speculate that this class of drugs might be useful in treating PML. Experts have gathered anecdotal information as they ponder further research. Their first reaction to the anecdotes is that they are not terribly impressive. Even still, when added to anti-HIV therapy, this class may provide a new therapy.
Other Possible Interventions: for study include interleukin-2 (IL-2), topoisomerase inhibitors (topotecan, camptothecan, etc.), adoptive cell therapy (enhancing JC virus specific cellular immunity) and RNAsi.
Commentary Currently, some doctors assert that PML is not treatable. However, many people have responded to various treatments. Although anti-HIV therapy does not directly affect the JC virus, the wise use of it appears to greatly impact survival after a PML diagnosis, most likely because the immune system recovers and starts to control the JC virus once HIV replication is arrested.
It is important to realize that successful PML treatment at best usually means only stabilizing or partly resolving symptoms, even when brain lesions shrink. This is different from a complete resolution of symptoms. Despite an arrest or decrease of lesions in the brain, someone with PML may face lifelong symptoms. These may include weakness on one side of the body or limbs, loss of vision and/or permanent impairment of certain functions (slurred speech, memory loss, disorientation, loss of balance, etc.), even if survival is extended and PML lesions stabilize or improve.
In one reported case of complete resolution of PML lesions in the brain after starting HAART -- despite their loss -- partial vision loss caused by the JC virus in the part of the brain that controls sight remained permanent. This suggests that treating PML early and aggressively is wise as the damage that is allowed to continue, unchecked, may be permanent. It is not uncommon, however, after a brain injury or disease for the brain to repair somewhat, or for other parts of the brain to compensate and for symptoms from the condition to improve.
PML is difficult to study. Factors that add to this difficulty include the rapid onset of symptoms, similarities to other conditions like toxo, and the fact that some people spontaneously recover or stabilize for unknown reasons. Most information on PML treatments now comes from small studies and anecdotal reports.
PML diagnosis remains a problem. A brain biopsy is quite invasive and therefore less invasive techniques need to be developed. A spinal tap (lumbar puncture) is hardly non-invasive, but compared to a brain biopsy it's a far better choice to many people.
Among people with HIV, about 30% without and 70% with PML have detectable JC virus floating in their blood. Given the large percentage of people with measurable levels of JC virus without PML, using blood as a way to diagnose PML is not practical. Far too many people without PML could be misdiagnosed as having PML. Using cerebral spinal fluid (CSF) to diagnose PML may provide a medium ground, but it's not perfect.
The Bottom Line PML is a rare condition affecting the brain, caused by the JC virus. PML is difficult to diagnose, definitive diagnosis requires a brain biopsy. JC virus DNA levels in cerebral spinal fluid are prognostic. Higher levels relate to more aggressive disease. Using potent anti-HIV therapy, including a protease inhibitor, has had a profound positive effect on treating PML. Using a protease inhibitor after a PML diagnosis, as well as changing to a new anti-HIV regimen with a protease inhibitor, has resulted in quadrupling the survival rates of some people living ten years or more after a PML diagnosis. A new study shows that "enhanced" anti-HIV therapy, or adding the drug enfuvirtide to a regimen, may be very promising. Whether or not adding newer classes of drugs, like integrase inhibitors, are equally promising has yet to be seen.
Need a Private doctor Aug 14, 2008
I am HIV Positive living in Seattle area. I currently don't have one and i am looking urgently in a private clinic? Do you know a good one? I asked this question earlier & was told about Peter Shalit who is fully booked until end of year. Please let me know if you have a good one in mind. Thank You.
Response from Dr. Frascino
I would suggest you consult the American Academy of HIV Medicine Web site (www.aahivm.org). There you will find a list of certified HIV specialists arranged by locale. There are a number of well-qualified HIV specialists in the Seattle area. Be sure you hook up with one that you trust and with whom you can easily communicate. Your health insurance plan may have some restrictions, so remember to check this out as well. I'll repost some information below from the archives pertaining to locating an HIV specialist.
Choosing an HIV Care Provider
July 18, 2007
Why Is Choosing an HIV Care Provider Important?
Treating HIV disease is very complicated. There are choices to consider at every stage of the disease. It's best if you and your health care provider work together as a team. That makes it easier to choose and stick to your treatment plan. "Care provider" means a doctor, a physician's assistant, or a nurse practitioner.
There are several issues you may want to consider in choosing an HIV care provider. You might decide to have them be your "regular doctor" for all of your health issues. You might use a different care provider for most health issues and use your HIV provider as a specialist. If your regular provider isn't an HIV specialist, be sure they regularly get expert advice on HIV issues.
Training and Experience
Many people with HIV/AIDS get their care from physicians who are specialists in infectious diseases. However, especially now that people are living longer with HIV, it's important to deal with all of your health issues. You might prefer to have a family practitioner or a specialist in internal medicine as your primary physician.
No matter what their specialty, you will get better HIV care from providers who have experience treating people at all stages of HIV disease. Be sure to ask how many patients with HIV they have treated, and how many they currently see. HIV patients do better when their physicians have more experience treating HIV disease.
Do You Have Similar Ideas About Treating HIV?
Some providers are conservative. They prefer "tried and true" methods. Others are more aggressive. They are willing to try new and experimental treatments. Some are optimistic by nature, and focus on the hopeful or positive side when they talk about test results or future prospects. Others are more realistic. Some are pessimistic.
Some providers are comfortable suggesting "complementary and alternative" therapies such as massage, acupuncture, or herbs. Others stick strictly to Western medicine.
If you want a lot of emotional support, you probably won't be comfortable with a health care provider who only talks about test results. The more comfortable you are with their approach to HIV treatments, the easier it will be for you to get the kind of health care you want. Talk to providers and their patients before you make your choice.
The Provider-Patient Relationship
Many patients do better when they take an active role in planning their own health care. These patients do a lot of reading on their own, and bring information to their providers. They work together to make health care decisions.
Other patients are more comfortable with the provider making important decisions. Decide how you want to work with your provider. See if that fits with the way the provider likes to work with patients.
Help Your Provider Help You
Make sure that your provider has all the information needed to give the best advice about your treatment. This starts with your medical records, which may have to be transferred from another office. When you start working with a new provider, they will probably do a lot of tests to collect "baseline" information. This helps you see how well you're doing as time goes by.
Be sure your provider knows how you feel about using medications, and about your illness. Some people don't mind taking a lot of pills. Other people would rather take as few as possible. Are you willing to change your diet, or the amnount of exercise you do? Your provider should also know about other treatments you are using or want to try, including non-medical ones.
Be honest about your lifestyle. Your eating, sleeping, and work patterns can make a difference for your health care. So can your sexual practices and use of recreational drugs. If your provider seems too judgmental, try to change providers. It's better to have a provider who really knows you instead of holding back information.
Let your provider know about the important people in your life: the people who will support you if you get sick, or will help you make important medical decisions.
The best care provider won't do you any good if you can't get in to see them. Ask them (or their receptionist) how long it usually takes to get an appointment. Find out how well they usually stay on schedule during the day.
The type of insurance you have could limit your choice of a provider. Maybe the provider isn't on the list for your health maintenance organization (HMO) or insurance plan. Be sure to find out how you will be able to pay for their services.
Remember, you don't need an HIV specialist to help you with most of your health care needs. If a good HIV provider is hard to find, or if it's hard to get an appointment, use a non-HIV care provider for your general health care. Just be sure that when you are dealing with HIV issues, you see an experienced HIV provider, or one who consults with an expert in HIV.
Some people are very concerned about keeping their HIV status private. You might choose to get your HIV care from a provider in another town to protect your privacy. You will need to find your own balance between confidentiality and convenience.
Your health care needs might change as time goes by. Also, your ideas about treatment could change. Although you will probably get better medical care from a provider who has known you for a long time, you always have the right to stop seeing one provider and change to another.
To Find a Health Care Provider ...
You can get help finding a care provider from your case manager or from your local Department of Health. You can also ask other people living with HIV. The American Academy of HIV Medicine has a web page to help you find a doctor at http://aahivm.org/web/index.php?option= com_comprofiler&task=usersList.
The Bottom Line
HIV medical care is very complicated, and changes quickly. This makes it important to find an HIV care provider who works with HIV/AIDS patients and is committed to staying up to date. Your relationship with an HIV provider will be better if you are comfortable with each other's personal style and approach to dealing with health issues in general, and HIV in particular.
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