Epilepsy

Question 0

Seizure

Answer 0

Localized or disturbed populations of brain neurons discharge synchronously and extensively
A seizure is a symptom of brain dysfunction rather than a disease entity

Question 1

Epidemiology

Answer 1

1% of the population
2nd most prevelent neuro disease
1/3 of all patients its not curable
morbidity for health care

Question 2

Epilsepy

Answer 2

Chronic disorder characterized by recurrent, unprovoked seizures
Epileptic brain contains enduring alterations in structure and function that predispose to seizures

Question 3

Cause of Seizure

Answer 3

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

Question 4

Acute Cerebral Insults

Answer 4

Situations where any normal brain under the right circumstances could have a seizure. such as:

1. Metabollic disturbances (hyponatremia, hypocalcemia)
2. Toxins-etOH, illicit drugs, antibiotics, antidepressants
3. Infections-encephaltis or fever
4. Acute head trauma or acute stroke

Question 5

Enduring Epileptic Alterations

Answer 5

1. Remote causes-malformations in embrogenesis, scars or tumours later in life
2. Idiopathetic/cryptogenic causes-occurs when neuroimaging is normal, increasingly recognized to have genetic etiologies

Question 6

Classification by location

Answer 6

1. Partial-localized or focal, frontal is motor manifestations, parietal/occipital is sensory and visual, temporal is sensory, psychological or emotional
2. 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
3. Tonic Clonic
4. Complex Partial seizure-starts at temporal with an aura and is a type of secondary seizure but can stay partial

Question 7

Descriptive Classification of Seizures

Answer 7

1. Simple-no alteration in consciousness
   2.Complex-impaired consciousness
2. Convulsive-involuntary muscle contractions
3. Non-convulsive-no discernible muscle contractions
   Consciousness always impaired when both cerebral hemispheres are seizing

Question 8

Pathogenesis of Epilepsy

Answer 8

1. 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

Question 9

Channelopathies Causing Epilepsy

Answer 9

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.

Question 10

Malformation of Cortical Devlopment

Answer 10

1. Disorders of neuronal proliferation-lissencephaly or megalencephaly. localized increase of focal cortical dysplasia
2. Disorder of Neuronal Migration-periventricular nodular heterotopia. Subcortical band heterotopia (double cortex sydrome)
3. Disorder of Organization-Polymicrogyria, schizencephaly

Question 11

Causes of epilepsy

Answer 11

1. Genetic Abnormalities-Lis 1, doublecortin, ARFGEF2, Filimin A. Encode for proteins involved in microtubule stabalization, cell migration
2. Prenatal Infections-TORCH infections, toxoplasmosis, Rubella, cytomeglovirus, Herpes Simplex
3. Prenatal hypoxic (ischemic injury)
4. Often unknown cause in individual cases
5. Local Distortions of circuitry-loss of normal feedback inhibition. Anormal excitatory projections
6. REsults in electrically unstable (and epileptogenic) regions of the cortex

Question 12

Focal Cortical Dysplasia

Answer 12

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

Question 13

Acquired Epilepsy

Answer 13

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.

Question 14

Hippocampal Formation

Answer 14

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

Question 15

Abscence Epilepsy

Answer 15

Dysregulation of a physiological neuronal network.
normal birth, development and no other past medical history
Seizures starting in childhood or adolescence
Abscence-starring and eyelid fluttering for 5-10s
Often in children thought to be day dreamers-start preforming poorly in school
MRI is normal
EEG-characteristic generlized, rythmic patterns.
Medication-no surgery required

Question 16

Pathogenesis of Absence Epilepsy:

Physiological Thalamo-Cortical Networks

Answer 16

Underlie normal neuronal firing pattern in sleep and wakefullness
Thalamic relay (TR) neurons have widespread connections throughout the cortex.Thalamic relay neurons have 2 main firing patterns:
1. Tonic mode-awake
2. Burst mode-nREM sleep
control of mode occurs via interactions with nucleus reticularis thalami (NRT)

Question 17

Pathogenesis in Absence Epilepsy

Answer 17

Dysregulated transition from tonic mode to bursting mode in firing.
TR neurons