Brain inflammation/autism/CFS...spinal taps?

[Guest guest]

Copied this from the group, and am posting it because

I 've seen people here talk recently about CFS/FM being similar to

autism.

Have spinal fluid analyses been used in CFS research, and have they

indicated anything? Do they routinely test for microglia activation

mentioned below, or is that innovative and done only in a research

setting like s Hopkins?

If brain inflammation is the problem, at least in some cases of CFS,

how do you treat that? Anything other than the things discussed here

(mercury chelation, abx if neurolyme is the problem)...?

Focus Narrows in Search for Autism's Cause By SANDRA BLAKESLEE

Published: February 8, 2005

There comes a point in every great mystery when a confusing set of

clues

begins to narrow. For scientists who study autism, that moment may be

near,

thanks to a combination of new tools for examining brain anatomy and

of

old-fashioned keen observation.

Within the last year, several laboratories have reported finding

important new

clues about the mysterious syndrome that derails normal childhood

brain

development.

For the first time, they say, a coherent picture is emerging.

In autism, subtle brain abnormalities are present from birth. Infants

and

toddlers move their bodies differently. From 6 months to 2 years,

their heads

grow much too fast. Parts of their brain have too many connections,

while other

parts are underconnected.

Moreover, their brains show signs of chronic inflammation in the same

areas

that show excessive growth. The inflammation appears to last a

lifetime.

" Autism is still a confusing disorder, but one thing is now clear, "

said Dr.

Pat R. Levitt, a neuroscientist who is the director of the Kennedy

Center for

Research on Human Development at Vanderbilt University in

Nashville. " There is a

specific disruption of circuitry in brain development. We can really

dig in and

begin to explain the splintered brains of autistic children. "

To that end, Dr. Levitt and two dozen leading brain researchers held a

three-day " autism summit " in Malibu, Calif., sponsored by the Cure

Autism Now

Foundation, to discuss this emerging view and to plan collaborative

studies. The

meeting ended Sunday.

" Up to now, there was no theory to link one anatomical study to the

next, "

said Dr. T. Greenough of the University of Illinois, an

expert on brain

development. " We now have a theoretical framework that can generate

predictions

to test. "

People with autism have great difficulty with social interaction.

Some cannot

speak. Many are clumsy. A common trait is obsessive attention to

certain

details. Symptoms can be severe to mild.

Diagnoses of the disorder have increased in recent years, although no

one

knows why. One child in 166 born today may fall on the autism

spectrum.

Researchers agree that an unknown number of genes interact with

unidentified

environmental factors to produce the disorder. The new clues focus on

brain

development and circuitry, and especially on the brain's white

matter. White

matter contains fibers that connect neurons in separate areas of the

brain,

whereas gray matter contains the neurons themselves. " You can think

of this

distinction as analogous to that between cables, or white matter, and

circuit

boards, or gray matter, inside a computer, " said Dr.

Belmonte, an autism

researcher at the University of Cambridge in England. " Even though

each

individual circuit board may be intact, if the cables are disrupted

then the

computer can't function. "

Using a new technique called morphometric analysis, in which post-

mortem brain

tissue is divided into tiny parcels and examined, Dr. Martha Herbert,

a

pediatric neurologist at Harvard Medical School, found an anomaly in

the white

matter of autistic brains - it is asymmetrical.

In autism, white matter grows normally until 9 months, Dr. Herbert

said. Then

it goes haywire. By 2 years, excessive white matter is found in the

frontal

lobes, the cerebellum and association areas, where higher-order

processing

occurs.

The right side of the brain, the nonverbal hemisphere, is especially

encased

in white matter. The two sides of the brain are poorly connected.

Moreover,

small functional regions in each hemisphere tend to be prematurely

insulated by

excess white matter.

Another clue was reported last year by Dr. Courchesne, a

neuroscientist

at the University of California, San Diego. Using a simple tape

measure, he

found that newborns who later developed autism had smaller head

circumferences

than average. From 1 to 2 months of age, their brains suddenly begin

to grow

rapidly. Another spurt occurs between 6 months and 2 years, giving

rise to

exceptionally large heads.

At age 3, one child could wear his father's baseball cap, Dr.

Courchesne said.

The rate of brain growth gradually slows from 2 to 4 years, reaching

a peak a

year later. A 5-year-old with autism has the same size brain as a

normal

13-year-old.

But by midadolescence, when normally developing children catch up, the

autistic child's brain is again comparatively smaller.

Dr. Ruth Carper, who works with Dr. Courchesne, went on to show that

the

frontal lobes, the slowest and latest brain region to develop, have

the biggest

size increase of all. But the nerve cells in this region, which is

responsible

for social reasoning and decision making, are actually much smaller

than normal

and " underpowered, " Dr. Carper said.

A third clue, from the laboratory of Dr. Marcel A. Just, a

neuroscientist at

Carnegie Mellon University in Pittsburgh, reaffirms the odd circuitry

in autism.

In a study published in November, he found that people with autism

remembered

letters of the alphabet in a part of the brain that ordinarily

processes shapes.

That is, the subjects used a basic sensory region to deal with higher-

level

concepts.

" Autism results from a failure of various parts of the brain to work

together, " Dr. Just said. " Distinct brain areas work independently.

People with

autism are good at details but bad at conceiving the whole. "

Local networks are overconnected, he said. Long-range networks are

underconnected.

Skewed brain wiring could explain a fourth clue: clumsiness. Dr.

Philip

Teitelbaum, an expert on human movement patterns at the University of

Florida,

studies how babies with autism learn to roll over, sit up, crawl and

walk. By

looking at videotapes of their early months, before their disorders

are

diagnosed, he finds that autistic children use unusual strategies for

locomotion. It is as if the parts of their brains that control

movements are not

properly connected.

A fifth clue, also reported in November, may turn out to be a major

piece of

the puzzle. Dr. Pardo-Villamizar, an assistant professor of

neurology and

pathology at s Hopkins, studied the brain tissue of 11 people

with autism

who died at ages 5 to 44. He found a pattern of inflammation in the

same regions

that appear to have excess white matter.

The brain has an innate immune system separate from the body's immune

system,

Dr. Pardo said. A sentinel cell type, called microglia, is always on

the lookout

for trouble. When activated, the cells elicit inflammation and growth

factors.

Another cell type, astroglia, helps pattern the brain in fetal

development and

is later involved in synaptic activity. The astroglia were also

elevated in the

11 brains.

Dr. Pardo then examined spinal fluid in six living children with

autism. He

found evidence of activated microglia, hence inflammation, along with

astroglia.

It is not yet clear whether the inflammation is protective or

destructive, Dr.

Pardo said. In either case, inflammation is most marked in the same

areas

highlighted in all the other studies showing the same abnormal

circuitry.

Other researchers have begun studies to find out whether genes

involved in

innate immunity and prenatal wiring are involved in the disorder.

A crucial question is why does the brain grow rapidly and then stop

growing,

Dr. Courchesne said. What accounts for the timing of the defect?

Dr. Herbert and others wonder whether the white matter is really

larger.

" We don't know what is inside those enlarged areas, " she said. " It

could be

more axons, more white matter, or more glial cells and astrocytes. "

Dr. , a white matter expert at Case Western Reserve

University

School of Medicine in Cleveland, said he planned to examine white

matter from

autistic brains to see what gives them their " odd architecture " and

perhaps

discover the cause of the overgrowth.

Studies are under way to dissect the white matter in greater detail.

While these new clues are exciting, they do not lead to immediate

treatments.

Parents should not, for example, rush to give their autistic children

anti-inflammatory medications at this time, Dr. Pardo said, because

the link

between autism and inflammation is still preliminary, and in any

case, the drugs

do not affect the type of inflammation particular to the brain.

On the other hand, once autism is diagnosed, often around age 2 or 3,

when the

frontal lobes fail to activate properly, therapies might focus on

activating

multiple brain areas at the same time. This would not cure the

disorder, Dr.

Herbert said, but could theoretically lead to improvement.

Meanwhile, other clues remain elusive. " Parents will tell you that

when their

child spikes a high fever, the child becomes lucid and

communicative, " said Dr.

Levitt, of Vanderbilt. " A fever is a neuroinflammatory response. That

suggests

the circuit defects could be reversible. We just don't know. "