Page 348 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Epilepsy
An epileptic seizure (epileptic attack, epileptic Neuronal excitation or the spread of excita-
fit) is triggered by a spontaneous, synchro- tion to neighboring neurons is promoted by a
nized, massive excitation of a large number of number of cellular mechanisms:
neurons, resulting in localized or generalized The dendrites of the pyramidal cells contain
activation of motor (fits or seizures), sensory voltage-gated Ca 2+ channels that open on de-
Systems (sensory impressions), autonomic (e.g., saliva- polarization and thus increase depolarization.
2+
tion), or complex (cognitive, emotional) func-
In lesions of neurons more of these Ca
chan-
nels are expressed. They are inhibited by Mg ,
2+
tions (→ A).
The epileptic seizures can occur locally, for
while hypomagnesemia promotes the activity
Neuromuscular and Sensory area of those neurons that control the right cellular concentration of K reduces K efflux
example, in the left precentral gyrus in the
of these channels (→ A2). An increased extra-
+
+
+
through the K channels, i.e., it has a depolariz-
foot (partial seizure). They can spread from
ing effect and thus at the same time promotes
there to the entire precentral gyrus (Jackson-
2+
the activation of Ca
ian epilepsy). Clonic cramps may spread, as in
channels.
this example, from the right foot to the entire
The dendrites of pyramidal cells are also de-
polarized by glutamate from excitatory synap-
right half of the body (“Jacksonian motor
march”), the patient not necessarily losing
ses (→ A3). Glutamate acts on a cation channel
2+
(NMDA
and one that is permeable to Ca
spread to the other side of the body, the pa-
channel). The NMDA channel is normally
tient will lose consciousness (partial seizure
2+
10 consciousness. However, should the seizures that is impermeable to Ca 2+ (AMPA channel)
blocked by Mg . However, the depolarization
with secondary generalization). Primary gen-
eralized seizures are always associated with that is triggered by activation of the AMPA
loss of consciousness. Certain seizures (“ab- channel abolishes the Mg 2+ block (co-opera-
sences”) can also lead to isolated loss of con- tion of the two channels). Mg 2+ deficiency and
sciousness. depolarization thus favor activation of the
The triggering phenomenon is paroxysmal NMDA channel.
depolarization of individual neurons (paroxys- The membrane potential of the neurons is
mal depolarization shift [PDS]). This is caused normally maintained by the K + channels. A
+
by activation of Ca 2+ channels (→ A1). The en- precondition for this is an adequate K gradi-
tering Ca 2+ first of all opens nonspecific cation ent across the cell membrane. This gradient is
channels and thus causes massive depolariza- created by Na + /K + -ATPase (→ A4). A lack of
tion, which is terminated by opening of the available energy (e.g., due to O 2 deficiency or
+
+
–
+
2+
Ca -activated K and Cl channels. An epilep- hypoglycemia) impairs Na /K -ATPase and
tic seizure occurs when a sufficient number of thus promotes depolarization of the cell.
neurons has been excited. Causes or factors Normally depolarizations are reduced by
+
which favor epilepsy are, for example, genetic inhibitory neurons that activate K and/or Cl –
+
defects (of K channels and others), malforma- channels via GABA, among others (→ A5).
tion of the brain, trauma to the brain (glial GABA is formed by glutamate decarboxylase
scars), tumor, bleeding, or abscesses. Seizures (GD), an enzyme that needs pyridoxine (vita-
may also be provoked or promoted by poison- min B 6 ) as co-factor. Vitamin B 6 deficiency or a
ing (e.g., alcohol), inflammation, fever, cell reduced affinity of the enzyme for vitamin B 6
swelling or (less likely) shrinkage, hypoglyce- (genetic defect) favors the occurrence of epi-
mia, hypomagnesemia, hypocalcemia, lack of lepsy. Hyperpolarization of thalamic neurons
sleep, ischemia or hypoxia, and repetitive sti- can increase the readiness of T-type Ca 2+ chan-
muli (e.g., a flickering light). Hyperventilation nels to be activated, thereby promoting the on-
can lead to cerebral hypoxia, via hypocapnia set of absences.
and cerebral vasoconstriction, and may thus
promote the onset of a seizure. Epileptic sei-
338 zures have a higher incidence among pregnant
women.
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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