Kindling is a neurological mechanism through which repeated exposures to a stimulus can sensitize an individual so that even a small stimulus produces a reaction. In neurological circles, kindling has been linked to seizures. Among allergists, kindling is known as "sensitization." It accounts for why even a hint of peanut can cause anaphylactic shock in an allergic individual. Kindling also is involved in FM and other pain syndromes.
"Viral exposure early in life could trigger an immunologic cascade with significant effects on kindling. The release of TNF-alpha and other mediators could contribute to immunologic sensitization through inflammation and corticosteroid mediation. This then might leave an individual primed to respond in an adverse fashion to a future stressor event through amygdala and hippocampal kindling. The response to a stressor event then might reintroduce an inflammatory response that could contribute to the development of lesions and symptomatology. This could help explain why viral exposure does not necessarily trigger immediate symptomatology."This model is in keeping with the theory of occult infection - an infection which remains latent, or asymptomatic, until a second stressor is introduced. However, Jason et al. took the model one step further by proposing that the repetition of the exposure over time leads not only to an increasingly sensitive nervous system (which is why relapses often manifest differently from the initial illness), but to a prolonged inflammatory cycle.
Below is Dr. Seastrunk's excellent explanation of kindling. The treatment he recommended for kindling was Neurontin (gabapentin), a neuro-inhibitory drug also favored by Dr. Jay Goldstein. Some ME/CFS patients have reported benefits from gabapentin, however, as with all treatments, responses to gabapentin are mixed.
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KINDLING , FOCAL BRAIN INJURY AND
CHEMICAL and ELECTRICAL SENSITIVITY in the production of
"Environmental Disease"
by Jay Seastrunk
Kindling
In the 1960's while doing research at
Tulane Medical School, I became interested in the correlation between
the electrical manifestation of brain activity and behavior. I was
fortunate enough to be able to participate in deep electrode long
term implant studies in non-psychotic and psychotic individuals. This
experience strongly imprinted in me the connection between brain
activity and behavior. In reviewing the literature for Dr. R. G.
Heath, my department chairman, I came across the "mirror focus"
literature.
In 1949, Pope et.al., described the
"mirror focus" phenomenon, while working with Penfield on
man and monkeys. In "mirror focus" development, an
epileptic focus (a mirror focus) is found to develop in the
hemisphere opposite to an original epileptic focus, even though there
has never been an injury in that hemisphere. This developed focus
takes ten to fifteen years to emerge in humans. In 1969, Goddard and
two other researchers in the field of epilepsy published an article
entitled, "A Permanent Change in Brain Function Resulting from
Daily Electrical Stimulation". They were curious as to why an
incubation period often elapsed between a traumatic brain injury, and
the occurrence of a first seizure, months to years after the injury.
What they discovered was that repeated
applications of either chemical or electrical irritants to the brains
of animals eventually produce intense seizure discharges, even if
each one of the irritating stimulation themselves is incapable of
producing a seizure. They discovered that a stimulus to the brain,
that ordinarily would produce no change in either the animal's
behavior or in the electrical activity of its brain, did produce
significant changes in both behavior and electrical activity, if it
were repeated and repeated. They called the repeated stimulus "a
chronic irritant", and the resulting effect "kindling."
In Vietnam veterans, psychosis took fifteen years to emerge following
brain injury illustrating that the limbic and/or more subtle
behavioral manifestations of brain injury take a long time to emerge
perhaps related to the "kindling" phenomena.
In 1992, Bell and her co-workers
applied this reasoning to chemical sensitivity. They pointed out that
the olfactory system of animals and humans permits access (via the
nose) of environmental chemicals directly into the brain. These
molecules pass into the entry point of the smell system, called the
olfactory bulb. Numerous projections from this part of the brain are
present in the upper regions of the nose and permit aromas, perfumes,
aromatic hydrocarbons, and solvents to pass into the brain. Even more
remarkable than the fact that these molecules pass directly into the
brain, is the fact that they can progress neuron by neuron to the
furthest reaches of the emotional portion of the brain, called the
limbic system.
The limbic system, located primarily in
the temporal lobe, serves not only as the location of our
emotions, but even more
interestingly, it is the location where we organize our information
into understandable categories. This is because in animals, smeil has
great significance. An odor can mean the difference between food or
poison, and friend or foe, so it is reasonable that odors and their
significance would be closely linked in the animal brain.
The limbic system, located partially in
the temporal lobe, serves, not only as the location of our emotional
system, but even more interestingly, as an information organizer,
where we process information into understandable perceptions,
wheather they are olfactory, visual, tactile, or auditory. Memory
with its emotional conections is stored here However, it is tuned
into many more inputs than just a single sensory perception. In fact,
it seems to be tuned into all possible inputs, whether sensory,
imaginative, verbal, or motor. This is why odors, movements, sights,
sounds, ideas, or a combination of these can rapidly trigger
memories, emotions, and behaviors.
When the limbic temporal lobe is
injured, the individual cannot always recall memories at will, even
though the memory is still in the brain. Individuals affected with
chemical injuries frequently report that they are having memory
problems, yet are surprised when psychological tests show no memory
damage. This is because the system where the memories are stored,
which is analogous to the bookshelves in a library is intact; it is
the memory organization and retrieval system or the card catalogue of
the library that has been injured.
How does the kindling and the mirror
focus phenomenon fit into this? Researchers into epilepsy have long
known that the olfactory and limbic systems are particularly
susceptible to kindling. In fact, two limbic structures, the amygdala
and the hippocampus are frequently used in animals to study epilepsy,
because of the ease with which they can be kindled.
This means that individuals whose
brains have been injured can be kindled by either repeated low level
stimulation of a chemical or electrical irritant, or by a single peak
exposure. Thus, an individual will continue to experience more and
more effects from exposures too weak to affect a previously
unaffected person and possibly become more and more sensitive to
weaker and weaker exposures.
Time-Dependent Sensitization
A second mechanism, called
time-dependent sensitization, is almost identical to kindling.
According to Bell et al. (1992), time-dependent sensitization is very
similar to kindling in that an external substance, e.g. a chemical,
that has no effect at first on an animal's brain will later produce a
major reaction. This sounds almost like kindling, except for a few
minor differences. By definition, kindling eventually leads to
seizures, whereas time-dependent sensitization does not necessarily
lead to seizures. Instead, it can lead to changes in the animal's
behavior, its sensations, cognitions, autonomic nervous system
responses, vestibuiar (balance) responses, motion responses, and/or
or in hs immune or hormonal function.
Another difference is that
time-dependent sensitization can occur after a single intense
exposure, rather than a few small, repeated ones. After the passage
of time, and without further exposure, a new exposure will suddenly
produce the altered experience and/or behavior, or alter the immune
function.
Finally, time-dependent sensitization
shows cross-sensitization, which means that after a given individual
is sensitized, other substances, different from the one causing the
initial exposure, will now produce the altered experience, and/or
behavior or function in a stereotyped way for each individual.
Kindling and time-dependent
sensitization answer one of the most mysterious aspects of chemical
and electrical sensitivity i.e. who gets affected and why? Another
phenomenon, known as cacosmia, must be introduced to understand this
RISK FACTORS FOR CHEMICAL NEUROTOXICITY
On November 13, 1993, over 400 affected
workers, health care professionals, and interested labor and
management representatives listened to Dr. Bell present her latest
findings to a conference hosted by the Washington Toxics Coalition in
Seattle, WA. What she and her co-workers suggested is that there is
an identifiable group of people more at risk for the development of
chemical brain injury than other more resistant individuals.
To be able to identify these
individuals, it is first necessary to understand a new term. The new
term is cacosmia (ca-COS'-mi-a), which means "an altered sense
of smell, accompanied by a tendency to feel ill i.e. nausea,
headache, and dizziness from the odor of chemicals at low levels
(that have no effect on normals." In other words, cacosmic
individuals are the ones who first notice and are affected by the
chemical odors in an environment. Six per cent of college students
report cacosmia when asked if they develop illness when exposed to
pesticides, car exhaust, paint, perfumes, or new carpet. Among the
individuals that were studied, women represented 79% of those
identified as the most cacosmic.
Among both women and men who were
identified as strongly cacosmic, there was a much higher incidence of
reported food allergies, self-reported memory loss, and somatic
symptoms in general, when compared with noncacosmic subjects.
For electromagnetically sensitive
patients, a similar recruitment, sometimes by subliminal visual, or
auditory inputs, or by electromagnetic waves themselves, activate a
kindled brain focus, causing it to fire, producing the
characteristic, stereotyped, repetitive symptoms of that individual's
"reaction".
A second risk factor appears to be
stress. Ester Stemberg described how the central nervous
system affects the immune system through endocrine, paracrine, and
neuronal mechanisms. Bell, also, points out that one of the stress
hormones in the brain, CRH, cannot only itself produce kindling, but
when present in above normal amounts, makes it more likely that other
external stimuli will induce kindling. Stress and sleep deprivation
have long been known to increase epileptic seizures.
I feel that a third necessary factor is
focal brain injury related to trauma, infection, or toxic insult. The
location of this injury determines the scope of the repetitive,
stereotyped symptoms, which becomes the "reaction" kindled
by the external stimulus whether chemical, electrical, and/or stress
and sleep deprived related.
Conclusions
1 It appears that perhaps some of the
mystery of chemical sensitivity syndrome is beginning to disappear.
Repeated small exposures to inhaled toxins, chemical or visual
kindling, auditory, and/or electrical stimulation, or single
overwhelming exposures, acting on focal injuries can bring about
sensitization of the brain's limbic system injury.
2. Because the brain's limbic system
modulates emotions and memory organization systems, emotional and
memory symptoms will be common features of the disease. This area of
the brain also controls balance, gastrointestinal motility, the
autonomic nervous system, and auditory and visual integration of
stimuli as well as memory
3. Repeated exposures after the
kindling or sensitization of the focus has occurred will produce
effects out of proportion to the intensity of the exposure.
4 Cacosmic people seem more at risk
than non-cacsomic people; but this has not yet been proved by a
prospective study.
5. Stress may play some role in who
becomes affected, but how big a role is still uncertain. Stress
definitely increases the occurrence of "reactions", as does
sleep deprivation due to its effect on focal brain irritability.
6. Because a fundamental brain
mechanism is involved in the production of chemical sensitivity,
continued exposure of individuals without protection or treatment is
sure to increase the number of affected individuals and the severity
of the symptoms in any particular individual.
TREATMENT
To be effective, treatment must
interrupt these processes. Certainly avoidance of the stimuli can
stop the setting off of the focal firing either directly or by
stopping the kindling. Medications that stabilize the irritated cell
decreasing its sensitivity to the kindling stimulus would be helpful.
In this approach the amino acid anticonvulsant gabapentin has been
very promising in our experience. Decreasing stress and improving
sleep will also be beneficial. Removing any toxin that is still
present in the brain should also decrease cell irritability.
Desensitizations of all types, allergic, and behavioral, seem to
provide benefit.
References
Bell, I., Miller, C., & Schwartz,
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cit #4 p. 316.
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