Lecture 16: Epilepsy Flashcards
What is epilepsy?
- Epilepsy is a broad term that includes a group of neurological disorders characterized by epileptic seizures.
- Epilepsy is more a symptom of several diseases, than a disease itself;
- Defined by the occurrence of at least one epileptic seizure, but characterized by recurrent seizures.
What are epileptic seizures?
- Epileptic seizures are defined as a brief episode of abnormally excessive cortical neuronal activity.
- Sudden, excessive and out of control action potentials within the brain’s gray matter;
- Range from brief, undetectable seizures to prolonged, vigorous shaking;
- Associated with variety of physical injuries (e.g. broken bones);
- In both generalized and partial cases, neurons within affected area fire with a synchrony that never occurs during normal behavior.
Why was epilepsy stigmatized?
- People thought epilepsy was contagious, via “evil breathe” and would avoid epileptic patients (would spit at them, refuse to eat around them, etc.)
- Until 1956, people with epilepsy could not marry in 17 states of the United States
- In ancient religious tradition, seizures were considered a punishment by God, or the work of demons.
- Hippocrates noted that head injuries to soldiers and gladiators lead to seizures;
- Concluded there must be a physical cause.
What are generalized seizures and what are the different types?
- Widespread; Involves activation of entire cerebral cortex of both hemispheres;
- In many cases they grow from a focus but point of origin is not always known.
1. Tonic-clonic (grand mal) > most severe; shaking, convulsing
2. Absence (petit mal) > unresponsive, blinking repeatedly;
3. Atonic (loss of muscle tone; temporary paralysis);
- In many cases they grow from a focus but point of origin is not always known.
What is tonic-clonic (grand mal) seizures?
Tonic phase (ongoing)
- Beginning of a grand mal seizure;
- Muscles contract forcefully;
- Patient is fully unconscious;
- Rigid posture is sustained for ~15 seconds.
Clonic phase (rhythmic)
- Muscles begin trembling, then start jerking convulsively;
- Muscles move quickly at first, then more and more slowly;
- Eyes roll into back of head;
- Face is contorted, tongue may be bitten (off);
- Intense activation of autonomic nervous system (sweating, salivating);
- After ~30 seconds, muscles relax and patient resumes breathing.
What are partial seizures and what are the types?
– Definite focus or source of irritation;
– Involves only a small, circumscribed area of the cortex;
– Typically begin in specific area of the motor or sensory cortex > clonic movement of part of a limb vs. abnormal sensations (aura), respectively.
1. Simple (no major change in consciousness)
> Localized motor seizure
> Motor seizure with progression of movements as seizure spreads along the primary motor cortex;
> Sensory (somatosensory, visual, auditory, olfactory, vestibular)
> Psychic (forced thinking, fear, anger, etc.)
> Autonomic (e.g. sweating, salivating, lip smacking/chewing, etc.)
2. Complex (with altered consciousness)
> Includes subtypes 1 – 5 above.
Partial Seizures —> Generalized Cortical Seizures (Simple or complex partial seizures that evolve to generalized cortical seizures (grand mal))
What are the clinical symptoms of epilepsy?
- The clinical symptoms/behavioral features of a seizure are entirely dependent on the population of neurons involved.
- Most generalized seizures include activity from virtually all cortical neurons.
- Consciousness is lost;
- All muscle groups may be activated.
- Convulsions occur if the abnormal activity involves the motor cortex (Wild, uncontrollable activity of muscles)
Tonic (ongoing) activity vs. Clonic (rhythmic) patterns
What is the Jacksonian March?
- Jacksonian Epilepsy (i.e. partial/focal seizures) begin in one specific part of the brain (foci) and spread through adjacent parts of the brain.
- Electrical activity is slowly marching across the motor (or sensory) cortex;
- Orderly, sequential progression of clonic movements in a seizure;
- Typically begins with foot, hand or face; occupy the most cortical real estate
What are Auras?
– Often grand mal seizures are preceded by changes in mood, abnormal motor movements, or other sensory anomalies > referred to as auras.
– Auras are a preview or transient sensory event that typically occurs before the onset of a seizure.
– Nature of aura varies according to the location of the focus.
– K-9’s have the ability to sense auras and alert the necessary help to avoid damage to an epileptic patient.
> Minutes, sometimes hours before onset of seizure;
> Changes in human behavior, scent, etc.;
> No scientific evidence to explain this mechanism.
What causes epilepsy?
– Typically abnormal activity in the cortex, however can originate or spread to sub-cortical regions.
– There are many factors that have been associated with development of epilepsy:
> Stroke; Brain tumors; Neuro-trauma; Neuro-infections; Birth defects/genetic abnormalities.
– Certain environmental factors have been shown to be epileptogenic (ex. flashing lights)
» Infections causing high fevers can produce seizure -changes in temperatures, especially with mutated channels, can cause action potentials
– One of the most common causes of seizures is scarring, which may be produced by injury. Scarring irritates the brain tissue surrounding it, causing an increase in neural activity; Typically patients who experience brain trauma don’t show seizures for considerable amounts of time
Why do people with seizures lose the ability to do certain skills?
- Between seizures, surrounding inhibitory neurons increase activity as a compensatory mechanism.
- This is because the brain is compensating for the increase in electrical activity by making more GABA (inhibitory) neurons and shutting off all these neurons around the scar. These neurons could be involved in that particular ability or skill. This excess of inhibitory neurons will inhibit the neurons responsible for that particular function
What is kindling?
– atypical neuronal activity seen in epilepsy generates plastic changes in cortical circuitry.
– plasticity is when neuronal synapses strengthen, it makes it easier for one neuron to excite the other post-synaptic neuron. This is thought to be one of the causes of epilepsy.
– Kindling is a commonly usedmodelfor the development ofseizuresandepilepsy,in which the duration and behavioral involvement of induced seizures increases after seizures are induced repeatedly.
» Stimulating electrode is placed in the brain (e.g. amygdala);
» Weak electrical stimulation is applied - no discernable effect on behavior is observed;
» As weak stimulation is repeated once a day for several weeks, it begins to produce behavioral and electrical indications of a seizures;
» Over time, the weak stimulation causes full-blown grand-mal seizures. This is because when one neuron fires and stimulates the other neuron, over time, it increases the strength of the synapse between the neurons and as the synapse becomes stronger, stimulation of that neuron could cause a seizure because all those synapses have become much stronger so even a slight stimulation will cause widespread electrical activity
– The effects of kindling are more-or-less permanent;
Years later, the same weak stimulus leads to full blown seizure;
– Weak stimulation produces long-lasting changes in the excitability of the brain that time cannot reverse.
What is the genetic cause of epilepsy?
– mutant sodium-channel
»A single amino-acid mutation in the extracellular region of sodium channels can cause inherited generalized epilepsy;
»Mutation leads to dysfunctional inactivation of sodium channels in presence of elevated temperature; (stay open too long or don’t close)
»Typically occurs in early childhood (3 months – 5 years);
»Fevers are enough to elicit dysfunctional Na+ channel, prolonging action potentials and leading to epileptic seizures
– Other known mutations that can lead to familial epilepsy involve synaptic inhibition:
» Mutations that affect the synthesis or release of GABA, enzymatic degradation, or its activity on receptors; mutation that affects anything involving GABA can cause seizures because GABA is inhibitory and if you don’t have that inhibitory function (brakes) then it can cause excess electrical activity
» Drugs that block GABA are called convulsant -they’re preventing the “brakes” so it can cause seizures. Drugs that increase GABA are called anti-convulsant
How can epilepsy be treated?
– Since there is no one, single cause of epilepsy, there is also no single treatment
– Anticonvulsant drugs are typically used to manage epilepsy in patients.
» Enhance GABA neurotransmission;
» Reduce/counter excitability;
» Benzodiazepines, barbiturates, alcohol, etc.
– Surgery can also be used in cases where epilepsy is unresponsive to other forms of treatment.
» Removal of brain region where seizures originate (foci);
» Disconnecting hemispheres (transecting the corpus collosum) to avoid spreading of hyperactivity
Are seizures harmful?
– Seizures can cause brain damage.
» ~50% of patients with epilepsy show evidence of damage to the hippocampus; excitotoxic lesions (too much excitation) can lead to neurons dying
» Amount of damage correlates to # and severity of seizures the patient has experienced.
– Status epilepticus is a condition in which a patient undergoes a series of seizures, without regaining consciousness.
» Excessive glutamate release during seizure;
» Causes significant hippocampal damage
