Epilepsy Flashcards
Seizure
Localized or disturbed populations of brain neurons discharge synchronously and extensively
A seizure is a symptom of brain dysfunction rather than a disease entity
Epidemiology
1% of the population
2nd most prevelent neuro disease
1/3 of all patients its not curable
morbidity for health care
Epilsepy
Chronic disorder characterized by recurrent, unprovoked seizures
Epileptic brain contains enduring alterations in structure and function that predispose to seizures
Cause of Seizure
Any local or global insult resulting in a disturbance in the brains cortex.
Enduring epileptic alteration in the brain
-Remote symptomatic causes and idiopathic/cryptogenic causes
Acute Cerebral Insults
Situations where any normal brain under the right circumstances could have a seizure. such as:
- Metabollic disturbances (hyponatremia, hypocalcemia)
- Toxins-etOH, illicit drugs, antibiotics, antidepressants
- Infections-encephaltis or fever
- Acute head trauma or acute stroke
Enduring Epileptic Alterations
- Remote causes-malformations in embrogenesis, scars or tumours later in life
- Idiopathetic/cryptogenic causes-occurs when neuroimaging is normal, increasingly recognized to have genetic etiologies
Classification by location
- Partial-localized or focal, frontal is motor manifestations, parietal/occipital is sensory and visual, temporal is sensory, psychological or emotional
- Generalized means the seizure is wide spread and diffuse. Primary means it starts in both hemispheres synchronously with onset. Secondary starts with a localized area of the cortex and then spreads throughout both hemispheres
- Tonic Clonic
- Complex Partial seizure-starts at temporal with an aura and is a type of secondary seizure but can stay partial
Descriptive Classification of Seizures
- Simple-no alteration in consciousness
2.Complex-impaired consciousness - Convulsive-involuntary muscle contractions
- Non-convulsive-no discernible muscle contractions
Consciousness always impaired when both cerebral hemispheres are seizing
Pathogenesis of Epilepsy
- Molecular Level-one way of looking at epilepsy is an enduring imbalance between neuronal excitation and inhibition.
Excitation: Glutamate, NMDA and AMPA, Na+ and Ca2+
Inhibition: K+, Cl-, GABA, GABA(A), GABA (B)
Meds: Block Na+ channels, inhibit glutamate release, block NMDA or non NMDA receptor, enhancing GABA(A)-receptor mediated inhibition
Channelopathies Causing Epilepsy
Numerous genetic defects described in the past 20 years.
Very commonly genes encode for ion channels
Severe Myoclonic Epilsepsy in Infants:
Clinical phenotype first described in 1978.
-first year of life in infants-normal previously
-post fever- hemi-clonic convulsions or generalized tonic clonic seizures
-seizures recur within months often provoked by fever
-within one year, children developmentally regress
-children often survive into adulthood with intractable epilepsy and developmental delay.
-Genetics: NaV1.1 (sodium channel encoded by SCN1A gene), 95% are de novo mutations, NAV1.1 are experssed primary in cortical inhibitory interneurons. Therefore, overall causing excess braine xcitation vs. inhibition.
Malformation of Cortical Devlopment
- Disorders of neuronal proliferation-lissencephaly or megalencephaly. localized increase of focal cortical dysplasia
- Disorder of Neuronal Migration-periventricular nodular heterotopia. Subcortical band heterotopia (double cortex sydrome)
- Disorder of Organization-Polymicrogyria, schizencephaly
Causes of epilepsy
- Genetic Abnormalities-Lis 1, doublecortin, ARFGEF2, Filimin A. Encode for proteins involved in microtubule stabalization, cell migration
- Prenatal Infections-TORCH infections, toxoplasmosis, Rubella, cytomeglovirus, Herpes Simplex
- Prenatal hypoxic (ischemic injury)
- Often unknown cause in individual cases
- Local Distortions of circuitry-loss of normal feedback inhibition. Anormal excitatory projections
- REsults in electrically unstable (and epileptogenic) regions of the cortex
Focal Cortical Dysplasia
1st or 2nd decade of life. usually milk or no developmental delay but frequent seizures.
Seizure types are dictated by the location of the dysplasia (frontal, occipital etc)
MRI is subtle Need EEG
Surgery required
Acquired Epilepsy
Any process that permanently damages cortex can cause for later development of focal epilepsy.
Strokes, vascular formations, tumors, traumatic brain injuries, strokes and other caauses of sclerosis
Most common focal epilsepy is mesialtemperal lobe epilepsy. Mesial temporal lobe is the amygdala, hippocampal formation and parahippocampus.
These structures form part of the limbic system and are important in laying down memories.
Hippocampal Formation
Dentate gyrus, hippocampus proper (CA1, 2, 3, 4) subiculum and entorhinal cortex
Prone to synchrony-large feedforward excitation:
1. Preforant pathay (PP): entorhinal cortex (EC) to dentate gyrus (DG)
2. Mossy fibres extend from granule cells in DG to CA3 pyramidal cells in hippocampus proper
3. CA3 pyramidal cells in CA1
4. CA1 pyramidal cells excite neurons in subiculum and in turn the EC
5. Inhibitory interneurons in DG provide some control over the circuit
Neurons in mesial temporal love are particularly vulnerable to damage in early life: hypoxic injury, infections (TORCH), prolonged febrile seizures (neurotoxicity). Selective neuronal loss: CA1 and CA3 (inhibitory interneurons in DG)
Moss fibres sprout to innervate neighbouring DG cells
Patients: often have history of prolonged febrile generalized-tonic clonic seizures during infancy or early childhood or traumatic birth. Develop complex-partial seizures later in childhood, adolescence or adulthood.
MRI-atrophy and scarring in mesial temporal lobe seen
EEG-between seizures-unilateral or bilateral temporal lobe spikes. Rhythmic activity over one temporal lobe.
Treatment: intitially antiepileptic nedications 2/3 occassionally surgery to remove temporal lobe. 1/3
