Epilepsy
Epilepsy is a discontinuous process.
Depending on the patient, seizures of any type have varying periodicity that
may relate to the sleep cycle, the menstrual or other hormonal cycle or to
unpredictable bodily rhythms. Certain seizures may occur one or more times a
day in some individuals, but at much longer intervals in others. Even the
clinical inter-seizure state may be characterised by more or less continuously
abnormal cerebral electrical activity, as demonstrated on surface
electroencephalography or on deep brain recordings. Therefore, two clinical
states of the brain characterise the individual with epilepsy : the actual
ictal or seizure disturbance and the inter-ictal state.
Many
investigations of epileptogenesis during the past century have centered on the
anatomic, physiologic and metabolic states involved in neuronal hyper
excitability.
The
metabolic environment of the cerebral neurons is most important. Acetylcholine and
related transmitter substances, aminoacids including glutamic and gamma amino
butyric acids (GABA) and other components are involved as well as those in
oxidative cycles. A critical factor is the maintenance of resting neuronal
potential by intraneuronal and extraneuronal distribution of electrolytes.
Shifts in this cationic balance have been
associated with seizures and on enhanced permeability of the neural
membrane. Increased intraneuronal sodium and extraneuronal potassium, for
example, and changes in the control of their transport by calcium, may precede
seizure activity. These metabolic distortions, along with an excess in
excitatory transmitters, may produce the partial depolorisations necessary to
support repetitive discharges and the eventual propagation of seizures.
Nevertheless,
the occurrence of repetition and propagation of neuronal discharges as the
hallmark of epileptogenesis remains difficult to understand.
One
of the most difficult questions in epileptogenesis is how a seizure state has
its inception. This becomes important especially when there is an early brain
insult or injury because of either a genetic factor responsible for a neural
abnormality or because of a neuronal susceptibility to excitatory activity,
trauma, or a disease affecting the neurons. The myoclonic epilepsies are an
example of specific cellular neuronal abnormalities of various aetiologies.
An
important factor to be considered is time. The interval between the insult and
the development of recurrent seizure activity may appear silent, a period
during which cerebral function apparently progresses normally. This silent
interval can last from weeks to years.
The
silent interval was described by Gowers thus : “The third mode of onset is with
a single severe fit, and no other fit or sign of epilepsy for months or even
years, when another attack occurs, after which they usually become frequent.”
A
link between early major convulsions and later development of temporal lobe
epilepsy was suggested by Lennox and emphasis was given on possible vascular
pathogenesis. The silent interval was associated with the development of scar
formation in the meninges and brain parenchyma by Penfield. Local vascular
abnormality in association with atrophic microvascular areas was emphasised by
him. The conclusion given by him was that any acute brain injury can be
followed by progressive scarring or “epileptogenic ripening”. “The whole
question of what the ripening process may be after brain injury is synonymous
with the real secret of epilepsy”.
Epilepsy
is a sort of hurricane in the brain; its onset is marked by a transition from
the customary uncoordinated (perhaps
even chaotic) firings of neighbouring neurons into (ironically enough) a
periodic common firing. The organising principle behind epileptic seizures, by
contrast, is not yet known (Raima Larter et al).
The
mystery parameter behind the triggering of an epileptic seizure might be the
speed of communication among the synchronized neurons. And this speed, in turn,
might be related to how glial cells process calcium ions. The glial cells are
now known to be sensitive to neurotransmitters which initiate waves of calcium
concentration among the glia like water waves rolling around the pool. Thus,
the coming and going of epilepsy might be related to a chemical wave in the
brain.
