Excitatory Neurotoxicity

Discussion in 'Fibromyalgia Main Forum' started by IngaDinga, Apr 15, 2003.

  1. IngaDinga

    IngaDinga New Member

    Many CFIDS specialists prescribe the drug Klonopin. In the October
    1999 issue of The Fibromyalgia Network, nine CFS/FM specialists
    summarized their most effective treatments, and six included
    Klonopin. Interestingly, the three who did not are primarily FM
    specialists.

    Dr. Cheney prescribes Klonopin to address a condition associated with
    CFIDS called "excitatory neurotoxicity". To explain this condition to
    patients, he draws a line with "seizure" on the far left and "coma"
    on the far right. A big dot in the middle represents where healthy
    people are when awake. A dot somewhat to the right of the middle
    indicates where healthy people are when asleep Ò slightly shifted
    toward coma. He highlights in red the left portion of the line, from
    seizure to the middle, and labels it "Neurotoxic State" (damaging to
    the brain). He highlights in blue the right portion of the line, from
    coma to the middle, and labels it "Healing State".

    In CFIDS, an ongoing injury to the brain shifts patients toward
    seizure. A dot to the left of the middle, marked "injury", represents
    the position of CFIDS patients. This puts us in the red "Neurotoxic"
    zone. When we shift toward seizure, we often experience "sensory
    overload". ItÌs as if our brainÌs "radar" is too sensitive. Our
    neurons (nerve cells) are sensing stimuli and firing when they should
    not. This causes amplification of sensory input. Light, noise, motion
    and pain are all magnified. At the beginning of their illness many
    patients report feeling exhausted, yet also strangely "wired".
    The "wired" feeling is the slight shift towards seizure that occurs
    as a result of the excitatory neurotoxicity.

    Cheney frequently uses the term "threshold potential" when discussing
    excitatory neurotoxicity. (Think of the threshold - bottom - of a
    doorway. The lower it is, the more accessible it is. When it is at
    floor level, everything can enter. When it is raised, access is
    restricted to taller people. If it is too high, no one can enter.)
    Threshold potential refers to how much stimulus it takes to make
    neurons fire. If the threshold potential is too low, even slight
    stimulation is "allowed to enter" and is detected by the neurons.
    This causes the neurons to fire, resulting in sensory overload. If
    the threshold is dropped to nothing, all stimuli get through and the
    neurons fire continuously, resulting in a seizure. If the threshold
    is raised, only stronger stimuli can make neurons fire. A healthy
    personÌs threshold potential naturally raises at bedtime,
    promoting
    sleep. If the threshold potential is too high, you feel drugged or
    drowsy. If the threshold potential is raised extremely high, coma
    results.

    Two receptors in the brain, NMDA and GABA, determine the threshold
    potential. During the waking hours of a healthy person, NMDA and GABA
    should be equally active. This balances the person in the middle of
    the seizure/coma continuum. NMDA stimulates and GABA inhibits. If
    NMDA increases, one moves toward seizure. If GABA increases, one
    moves toward coma.

    In CFIDS, NMDA is more activated than GABA, lowering the threshold
    potential. This causes neurons to fire with very little stimulation,
    resulting in sensory overload. This condition of excitatory
    neurotoxicity is dangerous. Dr. Cheney emphasizes that in an attempt
    to protect itself, the body will eventually kill neurons that fire
    excessively. He states that brain cell loss can result if this
    condition isnÌt addressed.

    How can the brain be protected against excitatory neurotoxicity?
    Klonopin. This long acting benzodiazepine has been Cheney's most
    effective drug for CFIDS over the years. He believes that Klonopin
    and the supplement magnesium may be two of the most important
    treatments for CFIDS patients because of their neuroprotective
    qualities. He recommends 2 or more 0.5 mg tablets of Klonopin at
    night. Paradoxically, very small doses (usually a quarter to a half a
    tablet) in the morning and mid-afternoon improve cognitive function
    and energy. If the daytime dose is low enough, you'll experience
    greater clarity and think better. If the daytime dose is too high,
    you'll become drowsy. Adjust your dose for maximum benefit, taking as
    much as possible without drowsiness. Adjust the morning dose first,
    then take the same amount midafternoon if needed, then take three to
    four times the morning dose at bedtime. Cheney recommends doubling
    the dose during severe relapses.

    Dr. Cheney most frequently prescribes the combination of Klonopin and
    Doxepin, along with the supplement "Magnesium Glycinate Forte". (Made
    by Douglas Labs, it includes taurine, and is available from
    needs.com.) Magnesium Glycinate alone is a good choice for the more
    budget minded. (It's available from Needs as "Magnesium
    Complex" made by Klaire. Immunesupport sells it as "Magnesium
    Plus".) A common dosage of magnesium is 200 mgs at bedtime. Too much
    magnesium can cause diarrhea, though glycinate is usually the best
    tolerated form.

    Cheney prescribes Doxepin in the form of a commercial elixir
    (10mg/ml). At low doses this tricyclic anti-depressant acts as a very
    potent antihistamine and immune modulator. Doxepin acts
    synergistically with Klonopin to assist sleep, and may improve pain.
    Patients tend to be very sensitive to Doxepin, which can cause
    morning fog and fatigue if the dose is too high (5 to 10 mg or
    higher). He recommends starting at two drops a night and gradually
    increasing the dose until "morning fog" becomes a problem. Most
    patients canÌt tolerate more than half a cc.

    On a handout entitled "Neuroprotection via Threshold Potentials",
    Cheney lists six substances that can protect the brain. Under the
    category "NMDA Blockers" Cheney lists:

    1. parenteral magnesium and taurine (intramuscular injections of
    magnesium and taurine, usually given with procaine)
    2. histamine blockers (Doxepin Elixir)

    Under the category "GABA Agonists" (increases GABA) Cheney lists:
    3. Klonopin
    4. Neurontin
    5. Kava Kava
    6. Valerian Root

    Klonopin is taken "day and night"; Neurontin "night, or day & night";
    kava kava daytime only; and valerian nighttime only. The first four
    are by prescription, the last two are herbs. In my limited
    experience, only certain patients are put on magnesium/ taurine
    injections, and then only for a limited period before switching to
    oral supplements.

    Many myths abound concerning Klonopin. When I asked Dr. Cheney about
    these myths, he shared the following information.

    MYTH NUMBER ONE: THE GENERIC IS JUST AS GOOD. When the generic
    Clonazepam came on the market, many patients switched to it because
    it was less expensive than Klonopin. Cheney then began hearing that
    most patients had to take more Clonazepam to get the same effect.
    Generics aren't exactly identical to the original products, and with
    most drugs the slight variations don't matter. However, most CFIDS
    patients can tell the difference between Klonopin and its generic
    form, Clonazepam. Most find Klonopin to be more effective.

    MYTH NUMBER TWO: KLONOPIN IS ADDICTIVE. Dr. Cheney was adamant that
    Klonopin is not addictive. In treating thousands of patients, Cheney
    has never seen a patient become addicted to Klonopin. He reviewed the
    definition of addiction, stating that it involves: (1) psychosocial
    disruption, (2) accelerated use, (3) inappropriate use, and (4) drug
    seeking behavior.

    Cheney said a case might be made that Klonopin is habituating. It's
    true that it can not be stopped suddenly. You must taper off of it
    gradually. However, Cheney was cautious about even calling it
    habituating. The process of tapering off a drug is not the same thing
    as withdrawal, a term that implies addiction.

    Cheney said to keep in mind that Klonopin is given for a
    physiological problem, excitatory neurotoxicity. It is prescribed to
    adjust the threshold potential: to keep neurons from firing
    inappropriately and being destroyed. He stressed that Klonopin should
    never be given unless you intend to raise the threshold potential. He
    stated, "Problems arise when you begin to use benzodiazapines for
    reasons other than threshold manipulation." However, CFIDS patients
    have a "threshold potential aberration" and need Klonopin (or
    something similar) to avoid brain injury. Cheney has never seen a
    recovered patient have difficulty coming off Klonopin. He
    stated, "When you no longer need the drug, coming off it is very
    easy."

    On the other hand, trouble arises when someone who still has an
    injured brain tries to come off Klonopin. It is like a thyroid
    patient stopping their thyroid medication. Cheney warned, "All hell
    breaks loose". However, it is not because the drug is addicting, and
    it is not withdrawal. The condition still exists, and the body lets
    you know it has a legitimate physical need for the drug. Cheney
    stated, "When a CFIDS patient who is still experiencing the
    underlying mechanisms of brain injury goes off Klonopin, there is a
    burst of excess neural firing and cell death. ThatÌs the havoc we
    hear about that is mistakenly called withdrawal."

    MYTH NUMBER THREE: KLONOPIN DISRUPTS STAGE 4 SLEEP. Dr. Cheney said
    that he honestly does not understand this concern. He believes
    Klonopin might disrupt the sleep of people who take it for conditions
    other than the threshold potential aberration found in CFIDS. He also
    acknowledged that if you are looking just for drugs to facilitate
    sleep, Klonopin is certainly not the first one to come to mind, nor
    should it be used to induce sleep in "ordinary" patients. It's not a
    sleep drug per se. However, a large part of the sleep disorder of
    CFIDS is excitatory neurotoxicity and the resulting shift toward
    seizure. If you treat this condition with Klonopin, then you have
    treated a large part of the sleep disorder in CFIDS. Most
    importantly, he said he simply does not see stage 4 sleep disruption
    in his patients on Klonopin.

    Towards the end of this discussion on Klonopin, Cheney smiled, and
    remarked, "But suppose I am wrong about the brain injury and the
    threshold potential aberration and the shift toward seizure? What if
    I'm wrong about your need for Klonopin? I'm absolutely sure I'm
    right, but what's the worst case scenario? Do you know what long term
    studies on Klonopin have shown? Reduced incidence of Alzheimer's
    Disease. AlzheimerÌs Disease is a complicated and convoluted way
    of
    knocking out your neurons, and Klonopin protects your neurons. Now
    it's believed that Klonopin didn't actually stop AlzheimerÌs. It
    just
    delayed its onset so long that everyone died of something else before
    they ever got it - which is to say you won't get Alzheimer's. You'll
    die of something else first."

    The last question Cheney addressed concerned the dose: what happens
    if the dose is too high? He said the only down side was that if you
    took a little too much (we are not talking overdose here) it would
    shift you toward coma on the continuum. It would shut your brain down
    to some degree, and thus impact your ability to function. This is
    inconvenient, but it's not harmful. In fact, it shifts you into
    the "healing state" on the continuum. You may feel like a zombie, but
    your brain is protected and your neurons are not getting fried.
    However, not being able to function isn't an option for most of us,
    so we need to find the maximum dose that doesn't make us drowsy.

    Dr. Cheney emphasized that Klonopin, Doxepin, and magnesium are very,
    very good at protecting the brain from cell death due to excess
    firing. However, they can't stop the underlying mechanisms of CFIDS
    that are injuring the brain in the first place. (Those mechanisms are
    another story, and can only be explained by Dr. Cheney himself,
    hopefully in the video that will be made when he speaks here in the
    Dallas-Ft. Worth area on October 20, 2001.) Though it can't stop the
    underlying mechanisms causing the injury, Klonopin can protect your
    brain and keep your neurons from being destroyed. Then, as Cheney put
    it, "When you come out on the other side of this, you'll have more of
    your brain left."
  2. layinglow

    layinglow New Member

    I have been taking klonopin for about 6 months now, after reading Dr. Cheney's work, and talking with Mikie the Moderator, on her success with Klonopin. This treatment has alleviated many neural conditions from which I was suffering (hyper-excitement, anxiety, restless leg syndrome, neuralgias, inability to fall asleep due to racing brain, 15-20 wake ups per night, sensory overload).

    I believe this drug is a revelevant in the treatment of those who suffer from FM as well as CFS. It is my belief that these disorders are neurological in nature, due to a triggering whether it be trauma, bacterial, viral, the list goes on. Although MRI, and CT has been unable to show CNS damage, SPECT AND PET scans have shown brain injury and damage in CFS and FM patients.

    The symptoms of CFS and FM are neurological in nature: dysregulation of immune, endocrine, adrenal, gastrointestinal, circadian cycle and sleep, mood disorders, myalgias, neuralgias, respiratory, thermal regulation, and in addition to that the neurotoxicity, and cognitive functions that are impaired.

    Klonopin is a wonderful therapy in treating many of the results of what I believe are an injury to various parts of the CNS, and their resulting neurological symptoms,

    LL

    [This Message was Edited on 04/16/2003]
  3. Mikie

    Mikie Moderator

    I have sounded like a broken record recommending this article, but I believe it is one of the most well-written articles on the neurological aspects of our illness that I have seen.

    There is a sister article on stimulants and SSRI's in our library. It follows up on this article and explains why stimulants and SSRI's may exacerbate our neurological problems.

    LL, I'm so happy for you that the Klonopin is working so well for you.

    BTW, I believe since this was written, Kava Kava has been shown to cause some serious side effects, so I would stay away from it.

    Klonopin has made as much difference in my life as the Guai and the ABX treatment.

    Love, Mikie