My first BLOG, July 16, 2009

I am using the Introduction to my book, More Than a Wheelchair, More Than HIV: Overcoming PML, to give everyone more insight to this disease as my first entry to this BLOG. I think it is important for people to know what PML actually is and it is truly a horrific malady brought into fruition by a host of other primary health issues, not only HIV.

The next entry will be a bit more personal and hopefully the BLOG will continue to be so.

“I never thought I would have survived my bout with AIDS and the PML (Progressive Multi-focal Leucoencephalopathy). I could have died a few months after my diagnosis, but here I am!

First, you need to look up Progressive Multi-focal Leucoencephalopathy on the Internet. There are a lot of different sites with a lot of varying information that would keep you busy for hours going to different sites. A trip to the library would have you busy for hours too going through pages of information. Being a 21st Century person, I like the ease and convenience of the Internet and highly recommend using it. I chose to combine the blurbs from NIH (National Institute of Health), AIDSmap.com and AIDSinfonet.org for the best, easiest and most concise outlines of details regarding a brief overview of the PML to give you quick knowledge of this terrible disease by each of these organizations.

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What Is PML?

As of February 2009

From – NIH (National Institute of Health)

What is Progressive Multifocal Leukoencephalopathy?

Progressive multifocal leukoencephalopathy (PML) is caused by the reactivation of a common virus in the central nervous system of immune-compromised individuals. Polyomavirus JC (often called JC virus) is carried by a majority of people and is harmless except among those with lowered immune defenses. The disease occurs, rarely, in organ transplant patients; people undergoing chronic corticosteroid or immunosuppressive therapy; and individuals with cancer, such as Hodgkin’s disease, lymphoma, and sarcoidosis. PML is most common among individuals with acquired immune deficiency syndrome (AIDS). Studies estimate that prior to effective antiretroviral therapy, as many as 5 percent of people with AIDS eventually developed PML. For them, the disease was most often rapidly fatal.

With current HIV therapy, which effectively restores immune system function, as many as half of all HIV-PML patients survive, although they sometimes have an inflammatory reaction in the regions affected by PML. The symptoms of PML are the result of an infection that causes the loss of white matter (which is made up of myelin, a substance the surrounds and protects nerve fibers) in multiple areas of the brain. Without the protection of myelin, nerve signals can’t travel successfully from the brain to the rest of the body. Typical symptoms associated with PML are diverse, since they are related to the location and amount of damage in the brain, and evolve over the course of several days to several weeks. The most prominent symptoms are clumsiness; progressive weakness; and visual, speech, and sometimes, personality changes. The progression of deficits leads to life-threatening disability and death over weeks to months. A positive diagnosis of PML can be made on brain biopsy, or by combining observation of a progressive course of the disease, consistent white matter lesions visible on a magnetic resonance image (MRI) scan, and the detection of the JC virus in spinal fluid.

Is there any treatment?

Currently, the best available therapy is reversal of the immune-deficient state. This can sometimes be accomplished by alteration of chemotherapy or immunosuppression (even if it means losing non-vital transplanted organs). In the case of HIV-associated PML, immediately beginning anti-retroviral therapy will benefit most individuals.

What is the prognosis?

The mortality rates for those with HIV-PML have fallen dramatically from approximately 90 percent to around 50 percent according to most reports. For non-AIDS individuals with PML, the prognosis remains grim; the disease usually lasts for months and 80 percent die within the first 6 months, although spontaneous improvement has been reported. Those who survive PML can be left with severe neurological disabilities.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct research related to PML in laboratories at the NIH, and support additional research through grants to major medical institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure disorders such as PML

From – AIDSMAP.COM

Progressive multifocal leukoencephalopathy (PML) is a rare disease of the central nervous system which results in the destruction of the sheath that covers the nerves. It affects about 4% of people with AIDS.

PML is caused either by primary infection or reactivation of a virus called the JC virus which is a type of papovavirus. The JC virus is named after the initials of the first person with PML in whom the virus was identified. The majority of the population is believed to have been exposed to this virus and to carry it without symptoms in their kidneys, lymphoid tissue, bone marrow and lymphocytes. In an adult or child with a weakened immune system, the virus can be reactivated and spread to the brain by lymphocytes.

Once in the brain, the JC virus infects oligodendrocytes, the brain cells responsible for producing the protective sheath (myelin) around the nerves. Without this protection on the nerves, the nerve cells die and cause lesions in the brain. Neurologic dysfunction may follow quickly, and the condition can rapidly cause serious, life-threatening disease.

Prior to the introduction of highly active antiretroviral therapy (HAART) people with PML survived an average of two to four months after diagnosis. Survival for longer than one year appears to be more likely among people for whom PML is the first AIDS-defining event, or who have relatively high CD4 cell counts.

HAART has extended the average survival time of people with PML. A recent study found that approximately one-third of patients died within two years of their PML diagnosis, despite treatment with HAART. On average, deaths occurred within twelve weeks of PML diagnosis. Experts have calculated that people with PML will survive an average of three to four years, depending on their baseline CD4 cell count (Berenguer 2003).

Symptoms and diagnosis

PML can cause a variety of symptoms related to mental functioning, including confusion, disorientation, lack of energy, loss of balance, weakness in the arms or legs (usually on only one side of the body), blurred or double vision, speech difficulties and loss of vision in one eye.
Brain scans such as computerised tomography or magnetic resonance imaging can reveal the presence of lesions in the brain. To determine whether these lesions are caused by PML or by other opportunistic infections or cancers (e.g. toxoplasmosis, lymphoma), a polymerase chain reaction (PCR) test can be performed. A PCR test looks for the presence or absence of the DNA of the JC virus in a sample of spinal fluid. However, the PCR test does not produce a definitive diagnosis because some people are JC-negative when diagnosed with PML.

A brain biopsy remains the definitive way to confirm a diagnosis of PML.

Plasma and urine PCR tests for the JC virus have been developed, although their uses in the clinical setting are yet to be determined. In one study, only 41% of people with detectable JC virus in a brain biopsy also had detectable JC virus DNA in their blood (Hou 2000; Whiley 2001).

PCR tests which quantify how much JC virus is in the cerebrospinal fluid (CSF) have also been developed. There is some evidence that high JC viral load is associated with a poor clinical outcome (Garcia de Viedma 2002; Giri 2001). However, as with the plasma and urine tests, they are not currently used outside the research setting.
Progressive multifocal leukoencephalopathy in the age of highly active antiretroviral therapy
PML in the age of HAART remains a life-threatening condition with a relatively poor prognosis. Nevertheless, several studies have shown improved survival of individuals with PML since the introduction of HAART:

A CDC review of 415 cases of PML in the United States found that protease inhibitor use was the most likely factor to improve survival after diagnosis (Dworkin 1999).
Spanish researchers have reported that 30% of people die within two years of their PML diagnosis and that a CD4 cell count above 100 cells/mm3 at diagnosis is associated with increased survival (Berenguer 2003).

A review of the Italian Register Investigative Neuro AIDS (IRINA) Study found that people with PML survived an average of 245 days when prescribed HAART and 66 days when HAART was not available (Antinori 2001).

Retrospective analysis of PML cases at the Johns Hopkins University HIV clinic found survival associated with HAART, but not with use of up to two anti-HIV drugs (Geschwind 2001).
A review of 29 cases found that the average survival of a group of people with PML who received a HAART regimen was greater than 500 days, compared with 127 days for people treated with nucleoside analogues alone, and 123 days for people receiving no anti-HIV therapy (Albrecht 1998).

An American study found that HAART improves the survival of people with PML, although 15 of the 25 people in this study developed PML while taking antiretroviral therapy, including eight people with viral loads below 500 copies/ml (Clifford 1999).

A Spanish review of 27 PML patients found HAART extended survival significantly. People on no antiretroviral treatment or one or two drugs survived for an average of two months, compared with a median survival time of 21.9 months among those on HAART (Asensi 1999).

Researchers from the French Hospital Database compared 109 people who were diagnosed with PML before the introduction of protease inhibitors, with 137 people diagnosed after that time. The risk of death six months after diagnosis was reduced by 63% among people on HAART (Tassie 1999).

However, despite the documented benefits, PML has occurred in individuals being successfully treated with HAART, and there is evidence that PML may worsen in some individuals who experience immune recovery associated with HAART (Chocarro 2000).

This exacerbation of PML is thought to be associated with immune reconstitution, particularly in people with very low CD4 counts who have recently started HAART. For instance, Spanish researchers have argued that inflammatory changes in the brains of four of nine people on HAART and one of 19 on single or dual therapy, suggests a possible link between the potency of the antiviral drugs and the inflammatory reaction (Miralles 2001). A review of hospital admissions conducted at the Chelsea and Westminster Hospital, London, between January 1997 and October 1998 found HAART had uneven effects on PML. Three new cases of PML were reported, although immune recovery illness was unlikely to be the cause in one person who had been on HAART for over two years (Shaw 1999). American doctors have also reported cases of PML in people on HAART with low or undetectable viral loads (Clifford 1999;Tantisiriwat 1999).
Experts believe that antiretroviral therapy improves clinical outcomes by reducing the amount of JC virus in the fluid around the brain (Giudici 2000). In the age of HAART, both high JC viral load and low CD4 cell count at PML diagnosis have been identified as predictors of poor outcome and survival (de Luca 2001; Miralles 2001).

Treatment

HAART is currently used to treat people with AIDS who develop PML. There are no proven treatments specifically for PML although several drugs have been tested.

Cidofovir (Vistide) is one agent which has been investigated as a potential PML therapy although evidence to date is inconclusive. An Italian team has reported longer survival among 27 people treated with HAART plus cidofovir compared with 16 treated with HAART alone (De Luca 2001). In this study, cidofovir was independently associated with reduced risk of death. A Spanish team initially reported that cidofovir therapy was associated with survival in 118 people with PML who were treated with HAART but full analysis of these data showed that cidofovir had no impact on prognosis (Berenguer 2003).

Other studies have also found that cidofovir is ineffective against PML. An American study, ACTG 363, found that cidofovir had no impact on PML lesions or survival in 24 people (Marra 2002). Furthermore, a French study found that cidofovir provided no benefit additional to antiretroviral therapy as a treatment for PML (Gasnault 2001). Several case studies in wihch cidofovir was used to treat PML have also produced inconclusive results. Finally, one study has found that the addition of cidofovir to HAART in patients with PML reduced survival time (Wyen 2004).

There have been some anecdotal reports of reduction in symptoms among people treated with cytarabine (also known as ara-C) injected either into a vein (intravenously) or into the spinal column (intrathecally), but a controlled trial found no difference in the death rate between people treated with antiretroviral drugs alone and those who also received cytarabine (Hall 1998).

Similarly, case reports suggested that interferon alpha may have benefit, but a retrospective review found that interferon alfa had no benefit in addition to HAART (Geschwind 2001).
The anti-cancer drug topotecan (Hycamtin) is being tested as a possible treatment for PML in the United States. However, early data on this drug suggests it has little or no impact on PML (Dupont 2001).

*****More information is available on this site.

From Aidsinfonet.org: fact sheet # 516

What is PML?

Progressive Multifocal Leucoencephalopathy is a serious viral infection of the brain.
“Encephalo” means brain. “Pathy” means disease. Encephalopathy is a disease of the brain. “Leuco-” means white. Leucoencephalopathy is a disease of the white matter of the brain.
“Progressive” means that this disease gets worse in a short time. “Multifocal” means that it shows up in several places at the same time.

Researchers estimate that about 6% of people with AIDS develop PML. Most cases of PML show up in people with CD4 counts below 100. The exact rate is hard to know because PML is difficult to diagnose.

Most cases of PML used to be fatal. People diagnosed with PML lived an average of 6 months, and most died within 2 years. However, if people with PML start taking strong antiretroviral medications (ARVs) to control their HIV, they can survive much longer. Now only about half of people with HIV and PML die from PML.

The “JC” virus causes PML. Between 80–85% of all adults are exposed to this virus worldwide. In people with weakened immune systems, JC virus can become active.

How can PML be detected?

The first symptoms of PML are weakness or coordination problems in an arm or leg. There may be difficulty thinking or speaking. Vision and memory problems, seizures, and headaches can occur.

These symptoms can also occur with other opportunistic infections, including toxoplasmosis, lymphoma, inner ear infections, or cryptococcal meningitis. It is important to rule out these other diseases.

PML can be diagnosed using a scan of the brain by magnetic resonance imaging (MRI). Another way to test for PML is by checking spinal fluid. The sample is taken by inserting a needle into the spinal canal. This procedure is called a spinal tap.

How is PML treated?

A major problem with treating any brain infection is the “blood-brain barrier.” The blood vessels around the brain are different from the rest of the body. They are “tightly woven” to protect the brain from toxic substances. Chemicals that dissolve in fat can get through. Those that dissolve in water can’t. Unfortunately, this includes most antibiotics and many other medications.
There is currently no proven treatment for PML. Research studies have had conflicting results. Some possible treatments have not been carefully studied. However, PML has slowed down or stopped in some patients taking strong ARVs to fight HIV.

Ara-C (Cytosine arabinoside or cytarabine) has been tried against PML. It was given intravenously, or pumped directly into the brain. It seemed to work in one small study, but not in later ones. Ara-C is very toxic, and damages bone marrow.

High-dose AZT has been tried against PML, because it crosses the blood-brain barrier. Other substances that have been tried with different degrees of success include acyclovir, heparin, peptide-T, beta interferon, dexamethasone, n-acetylcysteine, topotecan and cidofovir. Some studies show that IV (intravenous) cidofovir can make the brain work better in people with PML.

Because PML can progress rapidly, it is important to begin treatments quickly.

Where can I get more information?

An excellent source of information is the book Progressive Multifocal Leucoencephalopathy (PML): Case Studies and Potential Treatments. Peter and Lisa Brosnan wrote the book in 1993. They are not medical specialists. Lisa’s brother was diagnosed with PML and the Brosnans began searching for possible treatments. Lisa’s brother died, but they continued and published their work.

You can get a copy of their book by writing to Peter Brosnan, 1709 N. Fuller Avenue #25, Los Angeles, CA 90046. To cover his costs, he asks physicians and institutions to send $30, people with AIDS $20, and in cases of hardship he will send it free.

The bottom line

PML is a viral infection of the brain. It is fatal in about 50% of cases. It can be confused with other medical conditions.

There is no approved treatment for PML, although several treatments may be helpful. Any treatment must be started as early as possible. Combination antiretroviral therapy (ART) may slow the progress of PML.

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If someone had told me when I was a senior in high school thirty years ago that twenty-fours years later, I would be classified as a gay man with a disease, called AIDS for short, dealing with complications from a viral infection of the brain called Progressive Multi-focal Leucoencephalopathy and confined to a wheelchair, I would have thought them crazy. But, that was exactly what happened. I was a stubborn man refusing every warning that confronted me on a subject I should have paid more attention to. So, in a matter of months, I went from my lofty life and fell into the depths of HIV/ AIDS/ PML.

Going on nine years since my diagnosis, I am still here in my motorized wheelchair, filled with hope, drive and determination to beat every hurdle I encounter.

I hate being called “handicapped.” I am very fit, active and as mentally competent as ever. Best of all, I have very definite goals. I would never presume to compare my disabilities to those of someone who has lost an arm or a leg. I am fully aware of the advantages I enjoy such as the ability to exercise to build strength to regain muscle coordination and control. I am also lucky because all my mental abilities and memories are intact. Since I have never suffered any short-term or long-term memory loss, various therapies have helped me to type, handwrite, talk and even draw and paint! Most of all, I do not plan to ever give up.

My story travels a long road from my first experiences of being gay to becoming sick and facing death, ending with my fight to recover. I intend to speak frankly, in my own voice, using whatever words I need to drive home my points.

It pissed me off that so little is known about AIDS-related PML. That is why I intend to write as simply and directly as I speak. And I do not intend to preach, I will tell you about the joy as well as the pain. I was never one to be overly emotional, but hope the feeling of my story is conveyed to the reader even if I may seem to be a trivial human being at times especially in my twenties and thirties. I want everyone to know that I was a valuable and vibrant human being before getting sick and almost dying. I did not realize my own worth until beginning in 2000 I had to fight to re-gain so much of what I had lost. As of June 2006, twenty-five years since the introduction of AIDS to human misery, there still is not a cure. Why?

Did everyone stop caring?

I have had to develop most of my routine because no one, not even doctors or the therapists knew what was best for me. Taking bits and pieces from what they taught me, I added exercises based, not only on the recommendations by friends and family, but those that I created to accomplish my goals.

There are so many things I could add to my lists of accomplishments, but I will save them for the last chapter in order to highlight the many hurdles I overcame as I battled each disadvantage the PML placed in front of me. Many things regarding PML are unknown and the “experts” cannot and will not know everything. I had to take all their observations, opinions and suggestions and create my own personal salvation, pushing myself to the limit every day. It’s something that I have to do because I want my life back the way it used to be.

I have heard such heart-wrenching things from other PML survivors. When they tell me how they thought they were the only ones to have survived, tears well up in my eyes. I know the advances in medicines have been phenomenal in combating PML in its early and deadliest stages, but now, what about rehabilitation?

I have been amazed and truly moved by stories told by innocent women and hemophiliacs that contracted HIV from unknown sources. I honestly believe they should never have had to deal with such a disease. Life is not fair, huh? And, the children! I cannot even put into words the indignation I feel when I see or hear of HIV positive children.

I can only hope that very soon EVERYONE will realize very soon how important that their compassion and help is in this seemingly never-ending battle with HIV and AIDS. It would be a terrible testimony to the history of the human race if, after the original surge of interest and concern, everyone just shrugged their shoulders and turned away.

Think, and use your heart.”