Question for Dr. Goldberg and Elyse (microglial activation and antivirals)

[Guest guest]

Dear Elyse and Dr. Goldberg,

I have a question that I believe it is very important regarding brain

inflammation, microglial activation and antiviral treatments.

We all know at least in this list that the herpesvirus 6 shows preference for

the temporal lobes. This can be seen in brain SPECT scans in children with

autism.

We also know that this kind of infections can cause microglial immune cell

activation as described by the study #2 below. We know the differences

between HSV encephalitis and HHV6 encephalopathy as described in the study #3

below. Now, the s Hopkins Medicine's

Brain's Immune System Triggered In Autism study (#7) provides evidence of

microglial activation and inflammation in the brains of individuals with autism.

The question that I have for you and I don't think it has been ever asked in

this list is the following. What medical approach do you follow

to reduce microglial activation in the brains of your patients during or after

antiviral treatment, see item 5 below? There are studies that provides

clear evidence that the microglial cells stay activated inducing inflammation

for years after the viral infection has been treated (See #5 and #6 below).

Regards,

1. Prolonged Microglial Cell Activation and Lymphocyte Infiltration following

Experimental Herpes Encephalitis

http://www.jimmunol.org/cgi/content/abstract/181/9/6417

2. Experimental murine herpes simplex virus (HSV)-1 brain infection stimulates

microglial cell-driven proinflammatory chemokine production which precedes the

presence of brain-infiltrating systemic immune cells.

The Journal of Immunology, 2008, 181, 6417 -6426

3. CT and MRI findings of human herpesvirus 6-associated encephalopathy:

comparison with findings of herpes simplex virus encephalitis.

http://www.ncbi.nlm.nih.gov/pubmed/20173155

CONCLUSION: Serial MRI showed transient abnormal signal intensity in the mesial

temporal lobes in patients with HHV-6 encephalopathy but persistent abnormal

signal intensity in both the mesial temporal lobes and the extratemporal regions

in patients with HSE. CT in the early period showed no abnormality in patients

with HHV-6 encephalopathy but definite abnormal findings in patients with HSE.

These differences may be useful in the differential diagnosis of the two

conditions.

4. http://en.wikipedia.org/wiki/Microglia

Herpes simplex virus (HSV) can cause herpes encephalitis in babies and

immunocompetent adults. Studies have shown that long-term neuroimmune activation

persists after the herpes infection in patients.[23] Microglia produce cytokines

that are toxic to neurons; this may be a mechanism underlying HSV-related CNS

damage. It has been found that " active microglial cells in HSV encephalitis

patients do persist for more than 12 months after antiviral treatment. " [23]

5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614272/

Prolonged Microglial Cell Activation and Lymphocyte Infiltration Following

Experimental Herpes Encephalitis

6. Microglia

http://en.wikipedia.org/wiki/Microglia

It has been found that " active microglial cells in HSV encephalitis patients do

persist for more than 12 months after antiviral treatment. "

7. Brain' Immune System Triggered in Autism by s Hopkins Medicine

http://www.hopkinsmedicine.org/Press_releases/2004/11_15a_04.html