Lecture 8: Epilepsy Flashcards
What is epilepsy?
A chronic disease characterized by recurrent seizures
What is a seizure?
A sudden, brief disruption of the normal functioning of neurons in the brain
Causes of epilepsy
Stroke
Brain tumor
Brain infection
Past head injury
Metabolic problems
Other neurological conditions
Genetic factors
Causes of seizures
High fever, especially in infants
Drug use, alcohol withdrawal
Near-drowning or lack of oxygen from another cause
Metabolic disturbances
Head trauma
Brain tumor, infection, stroke
Complication of diabetes or pregnancy
Classification of seizures
Partial (focal): initiated in neurons in a localized area of one cerebral hemisphere (include simple, complex and secondary generalization)
Generalized: simultaneous activation of both cerebral hemispheres (include tonic-clonic and absence)
Unclassified seizures
Partial seizure subclassifications
Simple - no loss of consciousness
Complex - impaired consciousness often with automatisms
Secondary generalization - seizures spread to activate both hemispheres
Generalized seizures subclassifications
Tonic-clonic - loss of consciousness, extension then jerking of body
Absence - impaired consciousness sometimes with automatisms
Motor homunculus in seizures
Seizures are sometimes associated with motor activity or sensations, which can give insight as to the brain location of the seizure focus
Simple partial seizure characteristics
Pressure in stomach, rises to chest
Smells odor
Nervous
Aura
What is the EEG?
Electroencephalogram (EEG)
record of electrical activity of
brain by placing the electrodes on the scalp.
EEG partial seizure
Abnormal activity in specific brain regions
See figure
Complex partial seizure characteristics
Funny face
Surprised and distressed
picking things off shirt
Partial Seizure with Secondary Generalization Characteristics
Tingling in an extremity that turns into jerking and spreads
Generalized tonic clonic seizure characteristics
Shrieks
Muscles activated
Teeth clench
EEG in tonic clonic seizures
abnormal electrical activity in all brain regions
Generalized absence seizure characteristics
Typically in children
Absence of aura
Loss of consciousness
EEG of generalized absence seizures
Slow wave electrical activity in all brain regions
What is an anti-epileptic drug?
adrugwhichdecreases the frequency and/or severity of seizures in people with epilepsy
Treats the symptom of seizures, not the underlying epileptic condition
Does not prevent the development of epilepsy in individuals who have acquired a risk for seizures (e.g., after head trauma, stroke, tumor)
What is the goal of AEDs?
to maximize quality of life by eliminating seizures (or diminish seizure frequency) while minimizing adverse drug effects
Mechanisms of drug action
- Use dependent blockade of voltage-dependent sodium channels - Reduce the rate of sodium channel opening
- Inhibit excitiatory (Glutamate) neurotransmission - Decrease glutamate exposure and reduce neuronal firing
- Increase inhibitory (GABA) neurotransmission - Enhance chloride influx, hyperpolarize neurons and reduce neuronal firing
- Block voltage - activated calcium channels - Neurons in thalamus are dependent on calcium channel pacemaker currents for depolarization, Depolarization of thalamic neurons activates cortical neurons
Use dependent block of sodium channels
See figure
Balancing GABA and glutamate
In a normal neuron, excitation and inhibition are balanced
Neurons susceptible to seizure activity show enhanced excitation or decreased inhibition
Increasing GABA activity can decrease seizure activity in both situations
Decreasing Glutamate activity can also decrease seizure activity
See figure
How does blocking the voltage-activated calcium channels work?
Neurons in thalamus are dependent on calcium channel pacemaker currents for depolarization
Blocking these channels slows the pacemaker
Depolarization of thalamic neurons activates
cortical neurons
Other uses for AEDs
Bipolar disorder
Carbamazepine and valproate are approved
Other AEDs have shown beneficial effect (topirimate, lamotrigine, gabapentin)
Anxiety disorders
Alcohol abuse
Spasticity
Migraine, cluster headache
Neuropathic pain (especially gabapentin)
Status epilepticus
medical emergency; IV diazepam (Valium) or IV lorazepam (Ativan) are used to stop the seizures.
Phenytoin may then be initiated for longer term control
How to dose AEDs
Antiepileptics are gradually increased to therapeutic concentrations to minimize adverse effects and are withdrawn gradually to reduce the risk of inducing seizures
Additional considerations when giving AEDs
Blood level monitoring (maintain therapeutic levels)
Pregnancy (AEDs can harm fetus, but so can uncontrolled seizures, lowest effect dose should be used, only one drug at a time, monitor blood levels)
Oral contraceptives (enhanced metabolism)
Vitamin D metabolism (can cause osteomalacia - softening of bones)
Enhanced vitamin K metabolism (can cause bleeding disorders)
Enhanced metabolism of other anti-epileptics
