Introduction : Diencephalic epilepsy
displays itself as an automatic and autonomic
seizure accompanied or not by headaches. Among
the causes for this disorder one has to exclude
tumors or vascular malformation. It is not
always possible to differenciate this disorder
from basilar migraine that can also be
accompanied by seizures automatism and
EEG-abnormalities. However in basilar migraine
sometimes a specific vertebro-basilar spasticity
demonstrated in angiogram can serve as an
indication for proper diagnosis.
Often no pathological structure can be found
in the so called diencephalic epilepsy. This
kind of epilepsy and the basilar migraine
benefit of common antiepileptic drugs. A new
light was shed on the subcortical origin of
epileptic activity by the finding thar
5-endorphin neurons and receptors localized in
the thalamo-hypothalamic regions may be involved
in the generation of epileptic-activiry. Based
on these data we tried to treat a patient who
suffered from diencephalic epilepsy with
carbamezapine, and Naloxon HCL.
Case report : S.S. a 35 years old
fernale, was admitted for a neurological
check-up, because of attacks of yawning
that were accompaniedby severe occipital
headaches, and because those attacks became very
frequent. This disease started 8 years ago, and
it was characterized by attacks of
yawning that had not fit her state, or
without external cause, the attack was
characterized by a series of yawnings with a
frequency of 4-7 yawnings per minute,
each attack lasted from 10 to 30 minutes. The
attacks appeared suddendly («Out of the
blue sky»), without any external or
internal stimulation and without any aura. The
attacks were accompanied very often by severe
occipital headaches with extension of the head;
the pains were characterized by a feeling of
pressure in the sub-occipital region thar lasted
as long as tlic yawning (10-12 seconds). Another
characteristic of these attacks was their
irregular appearance. The patient suffered very
often of several attacks a day, sometirnes of
one attack a day, and some times the intervals
between the attacks lasted weeks or even
months.
The attack was not accompanied by alteration
or loss of conscious, or any other movement, but
at the end of it the patient remained very tired
physically and mentally, and she complained of
difficulties in concentration and reduces
capacity of comprehension; on the other hand she
did not complain of distortion in the perception
and in the interpretation of the reality, or any
change in her self perception.During these 8
years no other signs appeared, and no change was
observed in the attacks. Her ananmestic inquiry
negated a head injury, or a cranio-cerebral
disease congenital or acquired. The neurological
and physical examnation were normal; the
laboratory examination were normal and included:
blood gas during the attack and in the intervals
between the attacks; electrolites; T3/T,4,
serological tests, coagulation factors and
functions, including thrombocytes aggregation,
and urine levels of serotonine, skull and
cervical x-rays, computarized tomography (CT) of
the brain, 4 vessels angiography of the
brain.
The standard EEG examination was normal
between the attacks and during the attack it
registered a slight posterior irregularity
without irritative tendency and without a focus.
Registration with sphenoidal electrodes brings
about general outburst in the intervals between
the attacks and a disrhytmic state with general
paroxysmal patterns during an attack. A
psychodiagnostic examination demonstrated an
organic pattern that was characterized by
disturbed perception and space organization
.
A therapeutic trial with carbamezapine
(Tegretol) 20 x 4 ameliorated her clinical
state. The frequency of the yawnings per attack
was reduced to 1-2 per minute and the total
number of attacks per day were reduced in
comparison to that before the trial. Another
observation was that the patient complained on
less intense occipital headaches in spite of the
improvement that was achieved with treatment
with Tegretol, the patient continued to suffer
from sporadic attacks. Therefore we decided on
another therapeutic trial by injecting
intravenously Naloxon HCI a pure opiate
antagonist. (This trial was done after two weeks
of washout from Tegretol). 0.8 mg of Naloxon was
injected intravenously by a one a time shot, 1-2
minutes after the beginning of the attack; two
minutes after the injection the yawning and the
headaches stopped; paresthesia (burning) that
the patient complained of in the frontal right
orbital region disappeared as well. The
drowsiness and weakness that normally appeared
after an attack disappeared this time.
Administration of a physiological solution as a
placebo in the sanie conditions did not change
the natural history of the attacks.
Discussion : Yawning is an autonomic
and automatic phenomenon, that can express a
metabolic disturbance with a decreased
consumption of oxygen in the brainstem. On the
other hand, the yawning, as an automatic and
autonomic phenomenon, can express a situation of
a diencephalic epileptic stimulation. An
electroencephalographic dysrhytmia was described
also in basilar migraine, which may be
accompanied by neurological deficit. The fact
that only the sphenoidal EEG registration
brought out an EEG with a paroxysmal pattern,
during an attack, demonstrated that we are
dealing with a phenoinenon that has epileptic
features. On the other hand the severe occipital
headaches could suggest as though we were
dealing with an attack of basilar migraine.
Absence of a spastic arteriography picture does
not negate this diagnosis because the
examination was done between the attacks. The
blood gas during the attacks and in the
intervals between the attacks (with normal
levels of P02 and PC02) negate metabolic
disturbance as a reason for the attacks. Since
all the laboratory examinations negate a
structural reason for the attacks (in the
vascular system of the meninges and nerves), it
means that we are dealing with a pure
diencephalic epliepsy. The organicity of the
attack is sustained by the psychodiagnostic test
that brings out an organic pattern and not an
hysterical one.
The analysis of the attack demonstrates that
it consists of a combination of three major
components: automatism, pain, and paroxysimal
EEG. The therapeutic trial with antiepileptic
drugs ameliorates her suite, which suggests that
the attack was eplieptic. The treatment with
Naloxon that shortened the attack and changed
its course (pains and paresthesla disappeared)
may shed new light on the epileptic and algic
mechanism of the diencephalic epilepsy and bind
it to the opiatic systems of the brain. It is
well known that leucinenkephalin and
methionin-enkephalin, and ß-endorphin,
cause epileptic attacks in rats, when the origin
for this epileptic activity is sub-cortical in
the thalamus. It was also demonstrated that
there is an anatomico-topographical difference
in the seat of the opiate receptors that are
bound to the epileptic activity and to analgetic
activity, and that there is a difference in the
dosage of Naloxon that is required in order to
block their activity . In addition, there is a
difference between the opiate receptors that are
involved in epilepsy, and those which are
involved in analgesia . The µ receptors are
probably involved in the analgetic mechanism,
and the K (kappa) receptors involved in the
epileptic activity.
These receptors are localized in the
diencephalon (and in the thalamus as part of
it), and the ß-endorphin,
methioninenkephalin, and leticinenkephalin are
active there in. On the other hand it is
possible that alpha-hydroxybutyrate, which is in
high concentration in the human brain and which
possesses neurophysiological and
neuropharmacological characteristics that are
similar to those of the enkeplialins and
endorphins, can be blocked as well by Naloxon.
It is possible that alpha-hydroxybutyrate acts
on the opiate receptors directly or through the
enkephalinic system. Endogenous endorphins are
released in the brain by a pain-stimuli and they
are involved in the analgesic mechanism. In
patients who suffered from neurogenic pains were
fourid low levels of endorphins, whereas, in
patients who were less sensitive to pains high
levels of endorphins were found.
In our case it is possible that there is a
shifting of endorphins from receptors that are
involved in formation of analgesia to those that
are involved in formation of epileptic states.
This shifting can explain simultaneously the
epileptic state, and the relative decrease in
opiate ligands in the opiate receptors that have
an important role in analgesia process (and pain
control as well); and the opposal shifting after
the treatinent with Naloxon. This explanation
raises the question about the differences in the
affinity of the different opiate receptors
(those which are involved in pain and those
which are involved in epilepsy) toward opiate
agonists and antagonists. Another possibility is
that the gamma-hydroxybutyrate acts upon
different opiate receptors, and that the Naloxon
activity on the opiate receptors is mediated
through the gamma-hydroxybutyrate.
The fact that treatment with carbamazepine
ameliorates the clinical state does not disagree
with the «opiate-proposal» which was
described: because carbamazepine acts on the
membranes, stabilizing the nerves membranes. In
conclusion there is a possibility that
diencephalic epilepsy is related to a disturbed
diencephalic opiate activity or to
gamma-hydroxybutyrate activity in this
region.
