Epilepsia Flashcards
Define seizure, epileptogenesis, and epilepsy.
(1) A seizure is a paroxysmal derangement of cerebral function due to uncontrolled, excessive discharges from an aggregate of neurons.
(2) Epilepsy refers to a tendency toward recurrent seizures. Recognizing the distinction between seizures and epilepsy is essential: epilepsy requires chronic treatment (with antiseizure medication and, in some cases, surgery), whereas therapy for an isolated seizure is directed toward the underlying cause and may not require anticonvulsants. Furthermore, epilepsy often has profound psychosocial ramifications for the patient and is thus a diagnosis to be assigned with care.
(3) Epileptogenesis is the sequence of events that turns a normal neuronal network into a hyperexcitable network.
Visualize the network properties of the cerebral cortex that give rise to the EEG.
(1) The EEG shows 8 tracings, with each tracing representing the voltage differences detected between pairs of scalp electrodes.
(2) The arrangement of the electrodes is depicted and the numbers of the tracing correlate with the numbered pairs of electrodes (i.e. the first four tracings are from the front to the back of the head on the left, and the next four tracings are from the front to the back of the head on the right).
Draw a diagram that depicts the basic mechanisms underlying an EEG “spike”.
(1) First, extracellular recordings (in which the tip of the recording electrode is floating in the extracellular space and picking up the summated activity of many nearby cells) showed that, during a seizure, populations of neurons are bursting synchronously
(2) Next, intracellular recordings, which measure activity of individual neurons, showed that a neuron in a seizure focus fires off a rapid series of action potentials. This activity, termed a “Paroxysmal Depolarization Shift (PDS)”, is a result of a series of opening and closing of ligand-gated and voltage-gated ion channels that create a broad wave of depolarization due to the influx of calcium into the cell, with a superimposed train of action potentials due to this sustained depolarization.
(3) These observations should now allow you to understand why a seizure is defined as “a paroxysmal derangement of cerebral function due to uncontrolled, excessive discharges from an aggregate of neurons”. That is, during a seizure, a large number of neurons are all undergoing bursts of activity characterized by PDSs in a relatively synchronous manner, which would explain why spiking activity can be detected by extracellular recordings and the EEG (which measure the behavior of populations of neurons, not individual neurons).
Understand the classification system for seizures, and recognize the clinical features that would discriminate between a focal seizure with or without dyscognitive features, an absence seizure, a tonic-clonic seizure, a myoclonic seizure, and a focal seizure that secondarily generalizes.
(1) Focal seizures arise from a focus.
(2) Focal seizures without dyscognitive features involve a small amount of cortex that does not affect the ability to interact with the outside world (the rest of the cortex continues to function normally), so the person remains fully conscious. Focal seizures with dyscognitive features involve cortex in a region that results in an impairment of the person to interact normally with the outside world (ranging from language or memory disturbance to a decreased level of consciousness).
(3) The term secondarily generalized is reserved for a focal seizure that spreads diffusely to both hemispheres and results in a convulsion. These seizures deserve special comment because they are common and are frequently misdiagnosed as being purely generalized (i.e., without a clear focal onset). This distinction is important, however, since the focal onset may signify a focal CNS lesion that needs to be identified. The clinical manifestations of focal seizures depend on what part and how much of the cortex is involved.
(4) For example, if the seizure discharges are in the motor cortex, the clinical symptom may be repetitive twitching of a hand or extremity. Likewise, discharges in sensory cortex may cause unusual sensory disturbances of the contralateral body. The most common focus for focal seizures is within the temporal lobe, and patients may describe auditory or visual hallucinations, a sense of familiarity (deja vu) or strangeness (jamais vu), or excessive emotionality. If the seizure progresses from a focal seizure without dyscognitive features (aura) to one with dyscognitive features, observers may see repetitive movements (automatisms) such as lip-smacking, chewing or scratching, as well as more complicated behaviors such as walking or running.
(5) Generalized seizures may arise from discrete regions of the brain, but they rapidly engage neural networks in both hemispheres and cause bilateral, generalized seizure activity. Since both hemispheres are involved, a major symptom of generalized seizures is a loss of consciousness. Two important types of generalized seizures include tonic/clonic and absence seizures.
(6) The typical tonic/clonic seizure has an abrupt onset, with a tonic phase of excessive sustained muscle contraction, followed by a clonic phase of rhythmic contraction of the extremities. The entire seizure typically lasts no more than 1-2 minutes; if much longer than this, it may be status epilepticus, a condition you need to recognize because it requires aggressive therapy (see later in the chapter).
(7) Absence seizures usually cause a very brief impairment of consciousness because they last only a few seconds. However, they may occur hundreds of times per day. They are characterized by a very specific EEG pattern (3/sec spike and wave).
(8) Tonic seizures have only the tonic, continuous muscle contraction; clonic seizures have the rhythmic contractions; and atonic seizures are characterized by an abrupt loss of tone (which can be particularly dangerous due to the severity of falling).
(9) Myoclonic seizures are characterized by extremely brief, sudden contractions, similar to the sudden movements seen in many normal individuals while falling asleep.
List at least two main causes of seizures in different age groups.
(1) Neonatos: injuria perinatal e DHE
(2) Crianças: febril e sindromes epilepticas
(3) Adultos: trauma e intoxicação
(4) Idosos: cerebrovascular e tumor
Specify the routine laboratory studies for the patient with a first-time seizure and what results of these studies will tell you.
(1) Before embarking on a work-up to determine the cause of the seizure, remember to ask yourself whether the event was a seizure at all. Also, the history should include asking about symptoms that might go along with any of the likely causes for each patient.
(2) The physical exam should be directed toward looking for signs of trauma, infections, metabolic disturbances, etc. In this setting, your neurological exam should focus on finding evidence for abnormal cortical function, such as disturbances in language or vision, or focal motor signs (of the upper motor neuron variety).
(3) Laboratory studies for the work-up of a first-time seizure in an adult are complete blood count, electrolytes, calcium, glucose, liver function, renal function tests, erythrocyte sedimention rate, consider tox screen and consider pregnancy test.
(4) In most cases, an MRI scan is preferable over a CT, but the CT is often the only option in acute situations. Otherwise, it is acceptable to arrange for an outpatient MRI scan, but this should be done as soon as possible.
(5) The EEG, which provides a measurement of neuronal activity along the cerebral cortex, can also be arranged as an outpatient study. Note that the EEG will not rule-in or rule-out the diagnosis of a seizure or epilepsy. These depend on clinical criteria and not EEG findings, i.e., the EEG may be normal in patients with definite epilepsy, and may be abnormal in patients who have never experienced seizures. The EEG may help support a clinical diagnosis of epilepsy if it demonstrates paroxysmal activity of certain types (epileptiform) and may provide a guide to prognosis. The EEG can also help to classify the seizure disorder and suggest the most appropriate drug for initial therapy.
Describe the main factors in deciding whether or not to treat a first-time seizure.
The risk of recurrence is variable (about 30% for patients with a cryptogenic (i.e., unidentified) etiology and a normal EEG compared to 70% for patients with a remote, symptomatic (i.e., identifiable) etiology and an abnormal EEG).
(1) No reversible preciptanting factor
(2) Abnormal neurologic exam
(3) Abnormal EEG and MRI
(4) Risk of serious consequences if seizure recurs (e.g. job duties)
Describe some of the major molecular mechanisms of action of antiepileptic drugs; include one or two drugs that work by each mechanism.
(1) AEDs that interfere with voltage-dependent sodium channels (e.g. phenytoin, carbamazepine, lamotrigine) inhibit sustained high-frequency firing of neurons. As shown in the figure below, the drugs bind preferentially to voltage-gated sodium channels that are in the open or inactivated state. The importance of this state-selective binding is that they inhibit abnormal high-frequency firing at concentrations that do not appreciably inhibit slower (i.e. normal) rates of firing. At slower rates of firing, there is time between action potentials for channels to shift into the closed state, which has low affinity for antiepileptic drugs.
(2) AEDs that reduce activity of voltage-dependent Ca2+ channels (e.g. valproate, ethosuximide) are particular effective for absence seizures, because these seizures arise in part from bursts of action potential from thalamic neurons that are mediated by “T-type” Ca2+ channels.
(3) AEDs that enhance GABA-mediated inhibition (e.g. diazepam, phenobarbital) have perhaps the most straight-forward mechanism of action – they generally suppress the overall excitability of a network.
Describe two drugs considered as first-line therapy for generalized seizures (eg, generalized tonic-clonic or absence) and two for focal seizures (and familiarize yourself with the main pharmacokinetic features and adverse effects).
(1) Generalized-onset tonic clonic: Lamotrigine OR Valproic acid OR Topiramate
(2) Absence: Carbamazepine OR Phenytoin OR Lamotrigine
(3) Focal: Valproic acid OR Ethosuximide OR Lamotrigine
