Archive for the ‘blood-brain barrier’ Category

West Nile: background and 2013 updates

Monday, July 22nd, 2013

We were a ways up in the mountains for a dinner yesterday and I cautioned the people who were hosting that mosquitoes could easily be found at their 7,600 foot level. I said the West Nile season was usually in August and September, but one of my gourmet group told me there had already been a first case in Colorado and West Nile positive mosquitoes in our county. What I discovered online was 94% of West Nile symptomatic cases occur between July and September.

Heed the warning!Today I found the West Nile advisory page for Larimer County where we live and the CDC's West Nile statistics that mention 23 cases nationwide through July 16th with three deaths. Forty-three percent of the patients had West Nile Neuroinvasive Disease (WNND); the others had West Nile Fever (WNF). Twenty-nine states and the District of Columbia have reported human disease thus far.

And it's still early in the Summer of 2013.

Then I went back to the last of the four articles in the July 17th edition of JAMA; this one covers information intended for physicians and goes into more depth than the others. Its title is West Nile Virus: Review of the Literature. I thought there would be a few nuggets of information that might be useful for an extended audience

To start with, West Nile is endemic in every state in our country except Alaska and Hawaii. That means it is found in each of those regions on an ongoing basis without the need to be imported each year. An example I found said chickenpox is endemic in the UK, but malaria is not. Canada has had no cases of either WNF or WNND thus far in 2013, but had 428 cases last year with five provinces reporting patents with the virus.

Here it is a much more frequent disease problem that has led to the three worst outbreaks of arbovirus neuroinvasive disease in US history, each leading to ~3,000 cases of encephalitis, meningitis or sudden onset of severe muscle weakness (AKA acute flaccid paralysis). Arboviruses are those carried by ticks, mosquitoes and similar species. Older adults don't have a greater chance of developing WNF, but a markedly increased chance of WNND. One of fifty who catch West Nile and are over 65 get this dire form; that's sixteen times the rate for those age 16 to 24. The death rate in patients with WNND is ~10%, lower in relatively young patents, higher in the 65+ age bracket: one series reported 0.8% mortality for those under 40 and 17% for patients over 70. It's unknown how the virus crosses the blood-brain barrier, the super-tightly-packed cells that line the brain's blood vessels, preventing passage of most substances.

2012 was a really bad year for human disease in this country. The CD's final summary for that year included 5,674 cases, with 2,873 of those being WNND, and 286 deaths. The state of Texas had 37% of all reported cases and California, Louisiana, Mississippi, Michigan, Oklahoma and South Dakota were also hot spots for West Nile.

The virus has been found in over 325 bird species in the US and 65 different mosquito species, but only a few members of the Culex mosquito family have been shown to transmit West Nile to humans. Culex mosquitoes bite us from dusk to dawn, so, as I mentioned in my last post, I've changed what I wear when outside during those hours.

Passerine (perching) birds can infect mosquitoes; the robin isn't as plentiful as some species, but has a high serum viremia (lots of the virus in its blood), so is an important reservoir. If we are bitten by an infected mosquito and go on to develop WNF we'd have a low serum viremia, so a second mosquito biting us won't get the virus from us. Mosquito bites are responsible for almost all human cases; rarely one can occur after an organ transplant or a transfusion.

Higher-temperature areas both shorten the time a mosquito infected with the virus becomes infectious when it bites again and also improve the efficiency of it transmitting the virus to a bird. Of the 5 lineages of the virus only two have caused significant human outbreaks, but the 1999 New York City lineage has genetically altered subsequently to improve viral transmission. I don't know if this is true worldwide, but there have been significant outbreaks in Russia, Israel, Greece and Romania since the early 1990s.

Most who get a West Nile infection, as I've mentioned before, remain subclinical (e.g., without enough symptoms to need medical attention). In a study of blood donors who had West Nile viremia, but no significant symptoms initially, 38% eventually saw a physician and 2% were hospitalized. Only 5% of those seeking a diagnosis got the correct one!

West Nile in pregnancy, in one study of 71 women who delivered 72 babies, did not result in any malformations or infected infants.

Fatigue may last a long time.

Fatigue may last a long time.

Full recovery is the norm for those who have either uncomplicated WNF or meningitis, but they may be fatigued for a considerable length of time. In a 2004 study of 98 patents, almost all had this symptom and its median duration was 38 days. The patient's age didn't predict the duration of symptoms.

There are four licensed equine vaccines, but none for us. Several candidate human vaccines have gone through early trials, but no large-scale clinical trials have been attempted. Given that, if amazes me that even during outbreaks few of us use insect repellents that have proven efficacy.

If this West Nile season is like last year's, please heed the warnings, empty the water containers at intervals, avoid gardening at dusk or later and use an insect spray.

The brain and even the life you save may be your own.




Thanks for the Memory: part 2: Dementias

Tuesday, June 19th, 2012

It's on the tip of my tongue

In 1990 I needed neurosurgery. The mass which was removed turned out to be benign, but I had a major post-op bleed and was left with a considerable scar on my right frontal cortex. Up to that point I'd had, as I often said, "the fourth best memory in the family."

Afterwards my brain worked well enough. But I had considerable problems moving information from short-term to long-term memory. So when I bought the Harvard Medical School booklet mentioned in my last post, I was intrigued by the research that has been done on the subject and how it applied to me and to others, especially as we age.

Most of us worry about dementia; the Aging, Demographics and Memory Study figures, published in 2007 looking at people 71 or older, estimated there were 3.9 million people with dementia in the US in 2002. Of that group, 2.4 million had Alzheimer's disease. The crucial factor, I thought, was the prevalence, the total number living with a disease, went up with age from 5% of people in the 71 to 79 year old group to 37.4% in those 90 and above. And there are lots more of us living to that age than before.

It's become clear that having a stroke, what used to be termed a "cerebrovascular accident" (CVA), is another major route for developing dementia. A 2010 study in the journal Stroke describes dementia associated with "first-ever stroke" in a French city of 150,000 inhabitants over a 24-year period. Out of nearly 4,000 patents suffering a CVA, 20.4% had dementia. Risk factors for the outcome included age, diabetes, prior heart attack, and atrial fibrillation (an irregular heart rhythm associated with a risk of emboli, blood clots that can be dislodged, travel to the brain and clog an artery).

These figures clearly included those with new-onset dementia, but, because of the study's design, didn't exclude those who may have had the problem prior to their stroke. Nonetheless a history of stroke nearly doubles the prevalence of dementia in people over 65.

Another group with an increased incidence of neurocognitive (thinking/memory) issues includes the roughly 40 million infected with HIV. At least 30% of that group have associated brain function impairment ranging from minor or mild symptoms to full-fledged dementia. With the newer anti-retroviral drug treatments, the incidence (new cases) of HIV-associated dementia (HAD) has markedly decreased, although with people living longer with the virus, overall there are more HAD patients.

There is a roadblock between the circulation and the brain itself, the blood-brain barrier (BBB), which serves, in usual circumstances, to prevent microbes from invading the central nervous system. The human immunodeficiency virus can penetrate the BBB in several ways: one of which is by hitching a ride inside one kind of immune cells called monocytes. This is termed a "Trojan Horse" method.

Another disease, affecting 1.3 million Americans, is termed Lewy Body Dementia (LBD). It's closely associated with the dementia seen in Parkinson's disease. Both have deposits of an abnormal protein that causes difficulties in brain function. In LBD these proteins are found in several areas of the brain; with Parkinson's they are more localized.

Let's get the right pill to help, not hinder

So why is it important to know what kind of dementia a person has?

Some types respond poorly to medications that may help other forms, at least to a limited extent. And LBD patients may be helped by meds that offer less benefit to Alzheimer patients.

It's not always easy, but an experienced neurologist can often sort out which person has which disease.