• surgical treatment

    From ScienceDaily@1:317/3 to All on Wed Mar 8 21:30:44 2023
    surgical treatment
    A noninvasive way to avoid the repeat failures of shunt placement in
    patients with hydrocephalus has been the holy grail of scientists in the field


    Date:
    March 8, 2023
    Source:
    Massachusetts General Hospital
    Summary:
    Researchers have learned that the same molecular pathway is
    involved in both the infectious and hemorrhagic forms of acquired
    hydrocephalus, a life-threatening disease that triggers a massive
    neuroinflammatory response and swelling of the ventricles of
    the brain.


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    FULL STORY ==========================================================================
    Mass General researchers have discovered a novel molecular mechanism responsible for the most common forms of acquired hydrocephalus,
    potentially opening the door to the first-ever nonsurgical treatment for
    a life-threatening disease that affects about a million Americans. As
    reported in the journal Cell, the team uncovered in animal models the
    pathway through which infection or bleeding in the brain triggers a
    massive neuroinflammatory response that results in increased production
    of cerebrospinal fluid (CSF) by tissue known as the choroid plexus,
    leading to swelling of the brain ventricles.


    ========================================================================== "Finding a nonsurgical treatment for hydrocephalus, given the fact
    neurosurgery is fraught with tremendous morbidity and complications,
    has been the holy grail for our field," says Kristopher Kahle, MD, PhD,
    a pediatric neurosurgeon at MGH and senior author of the study. "We've identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain
    bleed or brain infection in acquired hydrocephalus.

    We're hopeful these findings will pave the way for approval of an anti- inflammatory drug to treat hydrocephalus, which could be a game-changer
    for populations in the U.S. and around the world that don't have
    access to surgery." Acquired hydrocephalus occurs in about one of
    every 500 births globally. It is the most common cause of brain surgery
    in children, though it can affect people at any age. In underdeveloped
    parts of the world where bacterial infection is the most prevalent form
    of the disease, hydrocephalus is often deadly for children due to the
    lack of surgical intervention. Indeed, the only known treatment for
    acquired hydrocephalus is brain surgery, which involves implantation
    of a catheter-like shunt to drain fluid from the brain. But about half
    of all shunts in pediatric patients fail within two years of placement, according to the Hydrocephalus Association, requiring repeat neurosurgical operations and a lifetime of brain surgeries.

    By deciphering the unique cellular and molecular biology that occurs
    within the brain after infection or severe hemorrhage, the MGH-led
    research team has taken a major step toward nonsurgical, pharmacologic treatment for humans. Pivotal to the process is the choroid plexus, the
    brain structure that routinely pumps cerebrospinal fluid into the four ventricles of the brain to keep the organ buoyant and injury-free within
    the skull. An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles
    with cerebral spinal fluid and immune cells from the periphery of the
    brain -- a so-called "cytokine storm," or immune system overreaction,
    so often seen in COVID-19 infections -- swelling the brain ventricles.

    "Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from hemorrhage in the
    brain," explains co-author Bob Carter, MD, PhD, chair of the Department
    of Neurosurgery at MGH. "Dr. Kahle's lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators
    like rapamycin, a drug that's been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune
    system to prevent organ rejection." MGH researchers are continuing
    to explore how rapamycin and other repurposed drugs which quell the inflammation seen in acquired hydrocephalus could be turned into an
    effective drug treatment for patients. "What has me most excited is that
    this noninvasive therapy could provide a way to help young patients who
    don't have access to neurosurgeons or shunts," emphasizes Kahle. "No
    longer would a diagnosis of hydrocephalus be fatal for these children."
    Kahle is director of Pediatric Neurosurgery at MGH, and director of the
    Harvard Center for Hydrocephalus and Neurodevelopmental Disorders. Carter
    is chief of Neurosurgery Service at MGH and professor of Surgery at
    Harvard Medical School.

    The study was funded by the National Institutes of Health and the
    Hydrocephalus Association.

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    ========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Stephanie M. Robert, Benjamin C. Reeves, Emre Kiziltug, Phan Q. Duy,
    Jason K. Karimy, M. Shahid Mansuri, Arnaud Marlier, Garrett
    Allington, Ana B.W. Greenberg, Tyrone DeSpenza, Amrita K. Singh,
    Xue Zeng, Kedous Y.

    Mekbib, Adam J. Kundishora, Carol Nelson-Williams, Le Thi Hao,
    Jinwei Zhang, TuKiet T. Lam, Rashaun Wilson, William E. Butler,
    Michael L.

    Diluna, Philip Feinberg, Dorothy P. Schafer, Kiavash Movahedi, Allen
    Tannenbaum, Sunil Koundal, Xinan Chen, Helene Benveniste, David D.

    Limbrick, Steven J. Schiff, Bob S. Carter, Murat Gunel,
    J. Marc Simard, Richard P. Lifton, Seth L. Alper, Eric Delpire,
    Kristopher T. Kahle. The choroid plexus links innate immunity to
    CSF dysregulation in hydrocephalus. Cell, 2023; 186 (4): 764 DOI:
    10.1016/j.cell.2023.01.017 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2023/03/230308112221.htm

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