The factors that can trigger convulsions in people or laboratory animals with apparently normal brains include: administration of convulsant drugs or toxins (e.g. cocaine, certain antibiotics — especially when kidney function is compromised); electrical stimulation (e.g. electroconvulsive shock); the abrupt withdrawal of certain drugs (notably alcohol or barbiturates) after prolonged use; overheating in infants (‘febrile’ convulsions); and excessive fluid intake (water intoxication).
The term ‘convulsion’ is also used to describe the muscular spasms (tetany) seen when calcium levels in the blood are low (hypocalcaemia). This condition can be caused in a variety of ways, including low calcium in the diet, vitamin D deficiency, over-breathing, and prolonged vomiting.
The type of convulsion that results from epileptiform activity depends on the regions of the brain invaded by the seizure and on the pattern of the seizure discharge. The details are difficult to unravel because large parts of the brain can be active simultaneously.
EpilepsyThe most common forms of convulsions are those associated with epilepsy (a disorder characterized by recurrent spontaneous seizures). However, just as convulsions do not always indicate epilepsy, neither does epilepsy always cause convulsions. Epilepsy is not normally diagnosed until the patient has experienced more than one seizure without an obvious trigger of the kind listed above. Seizures may result in convulsions (or motor fits), but they also can occur without overt motor activity.
It is more accurate to talk of epilepsies, rather than epilepsy, since there is a diverse group of clinical conditions that share the abrupt interruption of brain function, usually with intense, synchronous activity. The classification of these conditions is revised from time to time by the International League Against Epilepsy Commission on Classification. The classification distinguishes between focal epilepsies (those where a site of onset in the brain can be localized, at least to one hemisphere), and primary generalized epilepsies (where a definite site of onset cannot be localized). Focal epilepsies can spread widely and become secondarily generalized. The location of the focus in the brain determines the clinical symptoms.
The primary generalized epilepsies include tonic clonic seizures, previously known as grand mal, with dramatic convulsions that would be recognized as epilepsy by most lay people. Primary generalized epilepsies also include ‘absence seizures’, which do not lead to obvious convulsions: these were previously known as petit mal and can be mistaken for daydreaming. Other epilepsies in this group are characterized by collapse of posture (‘atonic’ epilepsy). Focal epilepsies originating in the forebrain area called the hippocampus, and associated regions, produce complex, partial convulsions, together with disturbances of consciousness, and often with co-ordinated, if inappropriate, vocalizations.
Mechanisms of epileptiform activityAnimal models of epilepsy have provided detailed theories of how neuronal activity can be organized into epileptic seizure discharges. In the process they have also taught us a great deal about the normal operation of neuronal networks in the hippocampus, cerebral cortex, and thalamus.
Experiments, mainly on brain slices maintained in vitro, combined with realistic computer simulations, have shown that focal epileptic discharges generally depend on the mutual excitation of pyramidal nerve cells, the main excitatory neurons of the brain, through synapses in which glutamate is the neurotransmitter. The necessary conditions are that there are strong, wide-ranging connections between pyramidal cells, and that the total population of neurons is large. This kind of circuitry, capable of generating epileptic discharges, is present in many cortical areas, but is normally held in check by a variety of mechanisms, including the action of neurons that inhibit the pyramidal cells, using gamma-amino butyric acid (GABA) as their neurotransmitter. When the synapses of these inhibitory neurons are blocked by drugs (such as of picrotoxin or penicillin), the excitatory network can sustain a chain reaction leading to an epileptiform discharge.
This kind of experimental approach has greatly improved our understanding of normal brain function. It has also provided a very convincing account of how brief epileptic discharges, lasting a few tenths of a second, can be induced in experimental animals. These discharges seem to correspond to the abnormal brain activity known as interictal spikes that is seen in the EEG between full focal seizures in humans (‘interictal’ means ‘between seizures’).
It is more difficult to understand the transition between these ‘spikes’ and full seizures lasting between tens of seconds and minutes. Indeed, the underlying causes of most clinical epilepsies, both in man and in domestic animals, remain uncertain. In some cases the seizures clearly result from a tumour pressing on the surrounding brain tissue. Head injury can also lead to epilepsy. There can be an inherited disposition to epilepsy, although in many cases, genetics is just one of many risk factors. Focal seizures are often associated with structural abnormalities of the cortex, caused by failures of migration of nerve cells during development or sometimes by adverse conditions around the time of birth.
Anticonvulsant drugsThese work in a variety of ways. Many of them prevent neurons firing rapidly (e.g. carbemazepine, lamotrigine). Others enhance the function of inhibitory synapses (e.g. barbiturates, benzodiazepam, vigabatrin). Some have multiple actions.
John G. R. Jefferys, and Roger D. Traub
Traub, R. D. and and Jefferys, J. G. R. (1996). Epilepsy in vitro: electrophysiology and computer modeling. In Epilepsy: a comprehensive textbook, (ed J. Engel Jr. and T. A. Pedley). Raven Press, New York.
"convulsions." The Oxford Companion to the Body. . Encyclopedia.com. (May 22, 2019). https://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/convulsions
"convulsions." The Oxford Companion to the Body. . Retrieved May 22, 2019 from Encyclopedia.com: https://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/convulsions
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