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Mechanism of Seizures, Treatment of Seizures and Epilepsy - Coggle Diagram
Mechanism of Seizures
UNDERLYING ETIOLOGY
Pathologic process that disrupt neuronal function & connectivity
First Mechanisms of Seizures
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Etiology
Genetic epilepsies
A disorder in ion channel function and/or structure → aberrant signal transduction
Dravet syndrome
Loss of function pathogenic variant in SCN1A (encodes a voltage sodium channel) → decreased excitability in inhibitory GABAergic interneuron → excitability and epilepsies
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Human cortical dysplasia
Expression of the NR2B subunit of the NMDA receptor is increased → excessive depolarizing currents
Fragile X syndrome
Hypotized that variants in FMR → enhanced glutamatergic signaling (via mGluR5 receptor)
Rett syndrome
Variants in MECP2 → increased NMDA receptor expression → epilepsy and other symptoms associated w/ the disorder
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Autoimmune
Autoantibodies sometimes generated because of cross-reactivity from a recent infection/ secondary to malignancy → bind to extracellular receptors/ other proteins expressed in neurons → inflammatory response, some cases seizures
Other epilepsy syndrome
Associated with autoantibodies targeting:
- Voltage gated potassium channel complex (anti LGI2, anti CASPR2)
- GABA receptor (GABA-A, GABA-B)
- Glycine receptors
- Glutamic acid decarboxylase (GAD)
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SEIZURE-RELATED NEURONAL INJURY
As often is demonstrated by MRI in patients after prolonged status epilepticus or those with long term drug resistant epilepsy
Fourth Mechanism of Seizure
Imaging/ MRI Finding:
acute swelling of the hippocampus/ other regions after status epilepticus and long term hippocampal artrophy with sclerosis on MRI
Evidence based:
Surgically resected epileptic tissue that apoptotic pathways are activated in foci of drug resistant epilepsyThere's evidence that the patophysiology of epileptic seizures (focal/ generalized) + co-excisting comorbidites → involves disruption of neural networks of the brain
- Resulting not only in increased excitability + but often associated abnormal neurologic dysfunction
EPILEPTOGENESIS
Mechanism through which the brain/ part of it → turns epileptic
Second Mechanisms of Seizures
Molecular cell signaling pathways:
- the mammalian target of rapamycin (mTOR)
- the Ras/ERK
- repressor element 1 (RE1) - silencing transcription factor (REST) pathways
mTOR pathway is seen in tuberous sclerosis, hemimegalencephaly, cortical dysplasia
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RESULTANT EPILEPTIC STATE OF INCREASED EXCITABILITY
Present in all patients irrespective of the underlying etiology or mechanism of epileptogenesis
Third Mechanism of Seizures
Explanation:
A dysregulation of glutamatergic excitation vs GABAergic inhibition occurs in epileptogenic neurons → creates a seizure focus or network
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