Term
| What are the 3 main phases of any seizure? |
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Definition
**interictal period occurs between seizures**
1) Aura (pre-ictal phase)- "feels different without cognition being affected"
2) An ictus
3) Post-ictal phase |
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Term
| What is the cardinal feature of epilepsy? |
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Definition
| Sustained spontaneous tendency to generate unpredictable seizures in the absence of consistent provoking factors. |
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Term
| What are 3 types of epilepsy that are caused by mutations in ion channels? |
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Definition
Ion channels cannot regulate membrane potential.
1) Benign Familial Neonatal Convulsions (BFNC)
- KCNQ potassium channel
2) Genetic Epilepsy with Febrile Seizures Plus
- GEFS+
- SCNA sodium channel
3) Idiopathic Generalized Epilepsy (IGE)
- CLCN chloride channel |
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Term
| What are the major glutamate receptor subtypes? |
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Definition
1) AMPA (sodium)
2) Kainate (sodium)
3) NMDA (sodium and calcium)
- sensitive to Extra-cellular magnesium, zinc, glycine, polyamines and other ions |
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Term
True or False:
Both pre- and post-synaptic GABA and glutamate receptors can contribute to Epileptogenic activity? |
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Definition
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Term
| What is the genetic basis for Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE)? |
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Definition
Point missense mutation in nAChR
- proof that either voltage-gated or ligand-gated ion channels can lead to epilepsy in humans. |
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Term
| How are "Interictal Epileptiform Discharges" (IIEDs) generated? |
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Definition
Summated EPSPs and IPSPs of large neuronal aggregation occurring between seizures and registered on scalp EEG.
- Arise from "paroxysmal depolarization shifts" (PDS) of neuronal membranes (different phases involve different ion channels)
- Assume "spikes," "sharps" and "spike or sharp and slow waves"
**APs have higher voltage changes than EPSP/IPSP, but they have insufficient temporal summation to reach scalp (Volume conduction)** |
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Term
| What are "Paroxysmal depolarization shifts" (PDS) and what is their relevance in diagnosing epilepsy? |
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Definition
-Large, prolonged depolarization that leads to bursts of spike activity in the form of a "train of APs" that correspond to interictal discharges recorded at scalp (sum of EPSP and IPSP in space and time).
- Can occur because of intrinsic membrane abnormalities or because of excessive excitatory or reduced inhibitory input. |
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Term
| What is an "epileptic focus"? |
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Definition
Numerous abnormal neurons capable of discharging in an abnormal synchronous manner.
Ex) loss of hyper-polarization following PDS may occur in epileptic focus, leading to generalized tonic-clonic (GTC) seizure followed by fluctuations of membrane potential associated with bursts of APs interrupted by quiet periods (clonic phase) |
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Term
| What factors may contribute to the transition between interictal states and ictal states? |
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Definition
Changes may take place in epileptic focus as well as distant sites, which create environment for "generalized seizures"
1) Neuronal membranes
2) Excitatory or inhibitory factors such as NT and receptors. |
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Term
| How is seizure activity terminated? |
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Definition
Active inhibition and epolarization block
- may involve activation of inhibitory circuits (locus ceruleus-cortical NA system) through changes in extracellular/intracellular ionic environment. |
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Term
| What might the locus ceruleus have to do with seizure-termination? |
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Definition
| Release of NA leads to increased extracellular adenosine, which decreases excitation. |
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Term
| What is the basic "Kindling Model" of Partial Seizures such as Temporal lobe Epilepsy? |
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Definition
Temporal lobe epilepsy is localized to abnormal processing of hippocampal circuitry in medial temporal lobe
3 plausible mechanisms
1) enhanced NMDAR-mediated transmission in dentate granule cells
2) loss of hilar neurons that normally activate inhibitory basket cells
3) synaptic reorganization of granule cell-excitatory cell output and feedback to dentate |
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Term
| What is a "partial seizure"? |
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Definition
Partial Seizures are most frequent seizures in humans, starting in the brain and spreading to various degrees.
Example is Temporal Lobe Epilepsy affecting hippocampal formation circuitry |
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Term
| What is the functional anatomy of the hippicampal formation? |
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Definition
Tri-synaptic Excitatory pathway and Inhibitory pathways
1) Entorhinal cortex is (+) to granule cells in dentate
2) Granule cells (+) hilar interneurons (CA4) and CA3 cells
3) CA3 cells (+) CA1 pyramidal cells via Schaffer collaterals
4) Hilar (mossy fibers) interneurons (+) Basket cells, which (-) Granule Cell layer (negative feedback) |
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Term
| Why might a lesion to Hilar internurons in the hippocampus cause Partial Seizures? |
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Definition
These mossy fibers excite basket cells, which are responsible for providing negative feedback to Hippocampal granule cells in the dentate gyrus.
Without this inhibition, there is too much stimulation to CA1 pyramidal cells via CA3 pyramidal cells. |
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Term
| What is the "dormant basket cell hypothesis" of partial seizures? |
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Definition
| Inhibitory basket cells that usually project to the hippocampal granule cell layer in the dentate gyrus have lost their excitatory input from Hilar internurons, and are therefore "dormant." |
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Term
| What is a common feature of patients affected by medication-resistant temporal lobe epilepsy? |
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Definition
They have a history of prolonged febrile convulsion during early childhood resulting from early brain insults.
These insults create pathological substrates that are susceptible to neuronal hyper-excitability (often through a "second insult") |
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Term
| What pathological features are associated with Temporal lobe epilepsy (TLE)? |
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Definition
Appear as "Mesial Temporal Sclerosis" (MTS) on MRI
1) Gliosis in hippocampus
2) Selective neuron loss
3) Axonal and Dendritic reorganization (mossy fiber sprouting)
4) Dispersion of dentate granule cell layer with appearance of ectopic granule cells
5) Altered NT and receptor expression |
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Term
| What are "absence seizures"? |
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Definition
- Generalized, non-convulsive epileptic seizures that consist of suddenly occurring brief episode of staring with impairment of awareness
- 3hz- spike-and-wave discharge on EEG appearing in all electrodes
- May involve "deep structure" generation (Thalamo-cortical Circuitry) |
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Term
| What is the functional anatomy of the "thalamo-cortical" circuitry involved in the generation of absence seizures? |
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Definition
1) L4/L5 cortical pyramidal cells (glutamatergic) and thalamic relay neurons (TRN) (glutamatergic) are reciprocally connected.
2) Cortical neurons and TRN cells excite GABA-ergic Reticular Thalamic Nucleus (RTN) cells
3) RTN cells inhibit TRN cells (GABAb) and other RTN cells (GABAa) |
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Term
| How are Thalamic Relay (TRN) and Reticular Thalamic (RTN) neurons able to influence the flow of information between the thalamus and cortex? |
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Definition
Remember, this circuitry is important for "absence" seizures.
1) Possess low-threshold T-type calcium channels that enable a "burst-firing mode" followed by an "inactive mode."
- Activation of T channels can lead to depolarization and AP generation followed by intense hyper-polarization
2) Large Hyperpolarization (called "de-inactivation") is necessary to remove "inactive mode" (enabled by through GABAb receptors on TRNs)
3) GABAb agonists produce seizures by facilitating de-inactivation of T channels, and antagonists have opposite effect.
4) Mutual inhibition of RTNs by GABAa receptors decreases inhibition of GABAergic output to TRNs and reduces degree of hyperpolarization (delaying de-inactivation of T channels) |
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Term
| Why might a lesion to Reticular Thalamus Neuronal networks generate absence seizures? |
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Definition
1) Lesioning these cells decreases their GABA-ergic output to GABAb receptors on TRN neurons
2) Lack of GABA-ergic stimulation of TRN neurons prevents "de-inactivation" of T-type Calcium channels and prevents excitatory output to cortical pyramidal cells in layer 4/5 |
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Term
| What might the effect of injecting a GABAa agonist bilaterally into the reticular nucleus of an animal model? |
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Definition
Reduce Absence Seizure activity
1) GABAa receptors are located on RTN neurons, which reciprocally inhibit each-other, and inhibit TRN neurons through GABAb receptors.
2) Inhibiting these cells with a GABAa agonist would prevent their GABA-ergic output to TRNs, and prevent de-inactivation of T-type calcium channels in TRNs.
3) Without de-inactivation of these calcium channels, TRNs cannot excite cortical pyramidal cells, thus reducing absence-seizure frequency |
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Term
| What is the basic model of "Factors Preventing and Promoting Seizures"? |
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Definition
1) Fluid and electrolyte balance, nutrition, hormonal balance and adequate sleep favor "Cortical stability"
2) Trauma, infection, fever, fluid/electrolyte misbalance, high anxiety, ect. favor "Cortical excitability) |
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Term
| What is the difference between Epileptic and Non-Epileptic Seizures? |
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Definition
1) Epileptic seizures
- Focal (with or without syncope and can evolve to Convulsive)
- Generalized (Convulsive-Tonic-clonic, Tonic, Clonic vs. NonConvulsive- Absence, Myoclonic, Atonic)
2) Non-Epileptic seizures include paroxysmal events unassociated with EEG changes reflecting "paroxysmal, abnormal cerebral discharges"
- Psychogenic
- Syncope
- Migraine
- Movements
- Sleep-related
- Cerebrovascular
- Metabolic |
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Term
| What does clinical diagnosis of Epilepsy depend upon? |
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Definition
| 2 or more episodes of unprovoked seizures, implying continuing tendency to spontaneous recurrent seizures. |
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Term
| What is "Status epilepticus" (SE)? |
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Definition
May be caused by both partial and generalized seizures and classified as "electrographic SE" if deemed SE only by EEG
1) Seizure lasting longer than 5 minutes in an adult or 10 minutes in a child (classically 30 minutes)
OR
2) A series of seizures where consciousness or other behavioral functions do not recover between attacks. |
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Term
| What do you do if you encounter a patient in convulsive status epilipticus? |
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Definition
Immediately administer Benzo with a long-acting AED such as fosphenytoin (30-50% morbidity without treatment).
Morbidity thought to arise from underlying disease process, but may be contributed to by prolonged electrical discharge. |
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Term
| What epidemiological features define Epilepsy? |
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Definition
1) 0.5-1% of population in US (highest among <15 years and > 65 years)
2) 2.5-3 million americans affected and 10% of americans will have seizure at some point.
3) 180-200,000 new cases each year
4) Many environmental factors increase likelihood of seizures. |
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Term
| What are the 5 major etiologies of seizures and epilepsy? |
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Definition
TAFGI
- Generally either "Structural" or "Genetic"
1) Toxic-metabolic
- Systemic illness
- Drugs/toxins
2) Acquired structural lesions
- Infections, Vascular, Trauma, Neoplastic, MTS
3) Familial
- Primary generalized epilepsy
- Benign focal epilepsy
- Febrile convulsions
- ADNFLE
4) Genetic syndromes (other)
- Tuberous sclerosis
- Neurofibromatosis
5) Idiopathic causes (genetic)
- 100 susceptibility genes |
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Term
| What are the predominant etiologies of symptomatic epilepsies by age? |
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Definition
1) <14 (developmental)
2) 15-24 (brain injury)
3) 25-44 (brain tumor)
4) >45 (Vascular) |
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Term
| What are the most common causes of epilepsy? |
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Definition
1) Head injury (15-24)
2) CVD (>45)
3) Infections
4) medication withdrawal |
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Term
| What are the different types of "focal" and "generalized" seizures? |
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Definition
1) Focal (1 hemisphere)
- Without impairment of consciousness or awareness (subjective sensory, subjective psychic, observable autonomic or observable motor)
- With impairment of consciousness
- Evolving to bilateral, Convulsive seizure
2) Generalized (both hemispheres)
- Tonic-clonic (any combo)
- Absence (typical, atypical, with special features)
- Myoclonic (myoclonic, atonic or tonic)
- Clonlic
- Tonic
- Atonic
3) Unknown
- epileptic spasms |
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Term
| What is "Todd's paralysis"? |
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Definition
Focal seizure with observable motor components without impairment of consciousness or awareness.
- Post-ictal weakness in affected region. |
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Term
| What is the "Jacksonian march"? |
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Definition
| The phenomenon when abnormal muscle movements resulting from an ipsilateral focal seizure spread to other muscles on the same side. |
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Term
A patient is staring at the wall, but with impaired consciousness and recall.
He is smacking his lips and tapping on the table.
All of a sudden he appears normal, but is lethargic and exhausted.
What happened? |
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Definition
Focal seizure of temporal lobe involving subjective psychic phenomenon (with impairment of awareness).
Lip-smacking and tapping are "automatisms" and he is later experiencing "postictal lethargy". |
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Term
A patient appears to have fainted right after letting out a shrill cry. His body is stiff.
He is breathing laboriously, his back spontaneously arching, his heart is racing and his mouth is foaming.
He intermittently exhibits convulsions.
The whole event lasts several minutes.
What is going on and what should you be concerned about after the patient comes to? |
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Definition
Generalized tonic-clonic seizure (GTCS) (can be primary or secondary to focal seizure- important for treatment)
Agitation or depression are common following the seizure! |
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Term
A 5 year old suddenly falls to the ground, with noted decreased muscle tone.
What might have happened? |
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Definition
| Atonic generalized seizure (more common in young people) |
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Term
| What is the link between Absence and GTCS seizures? |
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Definition
| 50% of those with Absence seizures between 4-12 years old develop GTCS later in life |
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Term
| What is the most important aspect of diagnosing Seizure disorders? |
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Definition
HISTORY
- context
- provocative features
- warnings
- evolution of experience |
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Term
| What are the 5 major diagnostic methods utilized for seizure disorders? |
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Definition
1) EEG- sum of EPSP and IPSP from apical dendrites of pyramidal cells in upper cortex (modified by thalamus)
- video-EEG or long-term monitoring is GOLD STANDARD
- look for spikes and sharp-waves
2) MRI- cerebral structural status
3) PET- focally decreased metabolism
4) SPECT- IV-injected radioisotopes to look at CBF.
5) MEG- non-invasive for small brain centers (LOCALIZATION) |
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Term
| What is the difference between the types of Convulsive and Non-convulsive seizures? |
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Definition
Both are generalized
1) Convulsive
- Tonic-clonic
- Tonic
- Clonic
2) Non-convulsive
- Absence
- Myoclonic
- Atonic |
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