NEURO210 Study Guide - Final Guide: Partial Seizure, Generalised Epilepsy, Cerebral Cortex
30 Apr 2018
School
Department
Course
EPILEPTOGENESIS: PATHOPHYSIOLOGY OF EPILEPSIES
• Affects about 1% of the population
• Is the second most prevalent neurological disease after headache
Seizure: event wherein localized or distributed populations of brain neurons discharge
synchronously and excessively
Epilepsy: a chronic disorder characterized by recurrent, unprovoked seizures
• Due to a change in structure that predisposes the brain to seizures
Part 1: Classification of Seizures
What causes a seizure?
• Almost any local or global insult resulting in a disturbance in the brain's cortex
• Acute cerebral insults (provoking factors)
⇒ Metabolic disturbances
⇒ Toxins
⇒ Infections
⇒ Acute head trauma, or acute stroke
• Enduring epileptic alternations (usually biochemical imbalances)
• Remote causes: Examples are malformations occurring during embryogenesis, scares
or tumors occurring later in life
• Idiopathic/cryptogenic causes
⇒ Occurs when neuroimaging is normal
⇒ Increasingly recognized to have genetic etiologies
What happens in a seizure?
• Large groups of neurons over one or both hemispheres fire abnormally and synchronously
• This can be seen in an EEG
Classification of Seizures
Partial: seizures localized to a focal area of the cortex
Generalized: seizure widespread and diffuse
• Primary: both hemispheres involved synchronously at onset
• Secondary: starts in a localized area of cortex, then spreads through both hemispheres
"Simple" vs. "Complex"
• Simple: no alternation in consciousness
• Complex: impaired consciousness
"Convulsive" vs. "Non-convulsive"
• Convulsive: involuntary muscle contraction
• Non-convulsive: no muscle contraction
Generalized Tonic-Clonic
• Tonic: stiffness
• Clonic: jerkiness
⇒ Seizures are not well controlled
⇒ Patient will lose consciousness during seizure
⇒ Patient will feel groggy and tired after
Complex Partial Seizure (temporal lobe)
• Focal seizure that is secondarily generalized (expands to other cortical regions)
• Weird facial sounds and movements
⇒ Can start by staring off into space
⇒ Person describes déjà vu or weird smell
Q: Does a simple generalized seizure exist?
No, because consciousness is always impaired when both hemispheres are seizing
Pathogenesis of Epilepsy
• Irregular balance between inhibition and excitation
⇒ Localized region, multiple areas, throughout the brain
• Enduring alternations in neuronal structures of function in the brain that promote imbalance
⇒ Molecular level or network level
!
4 Important Causes of Epilepsy
Genetic defects causing channelopathies
• Enduring balance between excitation and
inhibition
• Drugs help with inhibition
• Genes encoding for ion channels are
mutated
• Example: Severe Myoclonic Epilepsy of
Infancy (SMEI), which is caused by a
mutation in NaV1.1 (sodium) channel
encoded by SCN1A gene. Progression
includes normal development > fever >
abnormal development.
• NaV1.1 mutations cause excess excitation
b/c they are on inhibitory interneurons
• People thought that vaccine-induced
epileptic encephalopathy (VEE) is a thing
but this is not true! Babies basically got a
fever after vaccine and had SCN1A
mutations, therefore VEE = SMEI
Disorders of cortical formation during
embryogenesis
• Normal embryogenesis: neuronal
proliferation, neuronal migration, and
neuronal organization
• Malformation can cause developmental
delays and epilepsy
Proliferation
• Decreased proliferation = Lissencephaly
• Increased proliferation = Megalencephaly
• Localized proliferation increase = Focal
Cortical Dysplasia
Migration
• Impaired migration = Periventricular
Nodular Heterotopia and Subcortical
Band Heterotopia
Organization
• Deranged organization = Polymicrogyria
and Schizencephaly
Causes
• Genetic abnormalities: Lis1,
DoubleCortin, ARFGEF2, Filimin A
• Prenatal infections: TORCH infections
(Toxoplasmosis, Rubella,
Cytomegalovirus, and Herpes Simplex)
which cause local distortion of circuitry
• Prenatal hypoxic-ischemic injury
Epileptogenic neuronal networks later in life
• can be caused by any process that
damages the cortex: strokes, vascular
formations, tumors, traumatic brain
injuries, other causes of sclerosis (think
“V TOTS”)
Mesial Temporal Lobe Epilepsy
• Common focal epilepsy = mesial temporal
lobe (amygdala + hippo + parahippo)
epilepsy
• Hippocamal formation = dentate gyrus +
hippocampus proper (CA1, 2, 3, 4),
subiculum, and entorhinal cortex
• The hippocampal circuit is prone to
synchrony
• Neurons in the mesial temporal lobe are
vulnerable to damage (hypoxic injury,
infections, prolonged febrile seizures)
• Selective neuronal loss: CA1 and CA3,
inhibitory interneurons denate gyrus (DG)
• MRI shows scarring in mesial temporal
lobe
• EEG: rhythmic activity over one temporal
love during seizure
• Treatment: medication or surgery
Dysregulation of physiological neuronal
networks
Absence Seizure
• Common in school children
• Absence: sudden staring, eyelid fluttering
• MRI: normal
Document Summary
Epileptogenesis: pathophysiology of epilepsies: affects about 1% of the population. Is the second most prevalent neurological disease after headache. Seizure: event wherein localized or distributed populations of brain neurons discharge synchronously and excessively. Epilepsy: a chronic disorder characterized by recurrent, unprovoked seizures: due to a change in structure that predisposes the brain to seizures. What causes a seizure: almost any local or global insult resulting in a disturbance in the brain"s cortex, acute cerebral insults (provoking factors) Acute head trauma, or acute stroke: enduring epileptic alternations (usually biochemical imbalances, remote causes: examples are malformations occurring during embryogenesis, scares or tumors occurring later in life, idiopathic/cryptogenic causes. What happens in a seizure: large groups of neurons over one or both hemispheres fire abnormally and synchronously, this can be seen in an eeg. Partial: seizures localized to a focal area of the cortex.
