302 Pathophysiology of seizures

Question 1

How do seizures spread?

Answer 1

Simple partial seizures
-local cortical spread

Complex partial seizures
-usually bilateral via white matter commissures

Secondary generalized seizures
-via thalamus

Question 2

What are primary generalised seizures?

Answer 2

-Tonic-clonic
-Myoclonic, brief muscle jerks, typically UL
-Absence, loss awareness usually < 30 secs
immediate recovery

Question 3

What does tonic-clonic mean?

Answer 3

Involves both tonic (stiffening) and clonic (twitching or jerking) phases of muscle activity

Question 4

What does semiology mean?

Answer 4

The study of signs
Eg. symptoms that act as signs to show where in the brain the seizure is happening

Question 5

What is the semiology of a frontal lobe partial seizure?

Answer 5

-Often nocturnal
-Asymmetric fencing posture (SMA)
-Hyper-motor seizures (ventral)
-Cycling movements of legs, alternating limb movements, right-to-left head rolling, or agitated behaviour

Question 6

What is the semiology of a primary visual cortex partial seizure?

Answer 6

-Simple visual hallucinations
Eg. flashing blobs or shapes

-One visual hemifield
-Post-ictal amaurosis

Question 7

What is amaurosis?

Answer 7

A temporary loss of vision in one or both eyes due to a lack of blood flow to the retina

Question 8

What is the semiology of a medial temporal partial seizure?

Answer 8

-Olfactory hallucinations
-Deja vu
-Epigastric rising “butterflies”
-Chewing, lip smacking, swallowing

Question 9

What is the semiology of a lateral temporal partial seizure?

Answer 9

-Auditory hallucinations
-Language disturbances - dominant hemisphere
-Vestibular hallucinations
-Complex visual hallucination - imagery, scenes

Question 10

What is the semiology of a insular cortex partial seizure?

Answer 10

-Gustatory halluination - often unpleasant
Choking feeling
-Peri-oral parasthesia
-Pain
-Hyperventilation
-Tachycardia
-Vomiting
-Hyper-motor
-Automatisms

Question 11

What is the semiology of a primary somatosensory cortex partial seizure?

Answer 11

Tingling

Question 12

What are automatisms?

Answer 12

Involuntary, non-purposeful, stereotyped, and repetitive behaviours

Usually occur in association with impaired awareness:
-Concussion
-Syncope
-Complex partial seizures

Pathophysiology:
-Release phenomena (disinhibition)
-Central pattern generator (excitation)

Question 13

What is juvenile myoclonic epilepsy?

Answer 13

Most common primary generalized epilepsy

Onset 8-30 years (mean 14 years)

-Myoclonic, absence and generalized tonic clonic seizures

Excellent response to valproate ± clonazepam

Question 14

What is temporal lobe epilepsy?

Answer 14

Epilepsy that starts in the temporal lobe area of your brain

-Slow waves in fronto-parietal networks & DMN
-Thalamic involvement
-Bilateral temporal lobe involvement
-Left hemisphere involvement

?Spread of seizure activity to “pools” of inhibitory subcortical GABA neurones
?Inhibition of subcortical arousal systems in the upper brainstem, thalamus, hypothalamus and basal forebrain

Question 15

What is the pathophysiology of seizures?

Answer 15

Initiation
-Abnormal balance of excitatory vs inhibitory neuronal processes (esp glutamate vs GABA), leading to hyper-synchronization of pyramidal neurone firing

Propagation
-Feed forward and backward excitation
-Inactivation of inhibitory chloride channels

Termination
-Active process involving synchronous slow wave activity, on-off synchrony breaks the circuit
-Adenosine (purine) accumulation - also involved in sleep pressure
-Inhibitory neurotransmitters
-Endogenous opiates peptides

Question 16

What are the different causes of seizures?

Answer 16

Idiopathic
Alcohol
Tumour
Post traumatic
Cardiovascular disease

Question 17

What are Monogenic Epilepsies?

Answer 17

Related to genes that encode voltage-gated ion channels, including sodium, potassium, and chloride channels

Question 18

What is hippocampal sclerosis?

Answer 18

The commonest cause of drug-resistant epilepsy in adults

The hippocampus is vulnerable to damage from seizure activity

40% of patients with HS have a history of Febrile Convulsions

Question 19

What are Febrile Convulsions?

Answer 19

A seizure that can happen when a child has a fever

Question 20

What factors can cause seizure development?

Answer 20

-Gliosis
-Inflammation
-Impairment of blood–brain barrier
-Neuronal changes
-Re-organization of the extracellular matrix (ECM)

Question 21

What can cause gliosis?

Answer 21

Head injury
Stroke

Question 22

How does gliosis cause seizures?

Answer 22

It can impair glial control of extracellular potassium ions and lead to excessively excitable neuronal border regions

Question 23

What can cause provoked seizures?

Answer 23

It’s an acute response to brain insults
Eg. Brain trauma, stroke, encephalitis, meningitis, Fever, acute renal failure, hypoglycaemia, acute porphyria, electrolyte derangement

Drugs:
cocaine, OD of antidepressants
alcohol withdrawal, benzodiazepines or barbiturate withdrawal

Question 24

What is important to include in a history of seizures?

Answer 24

-Time of day /night
Location & context
-Frequency
-Prodromal features
-Type of fall / collapse
-Triggers / common factors esp standing vs sitting
-Ictus description
-Witnessed account
-Duration of the episode (LOC, convulsion etc)
-Post-ictal features esp confusion, focal neurological symptoms

Question 25

What are some examples of prodromal features of seizures?

Answer 25

-Visual darkening or tunnelling
-Light-headedness
-Vertigo
-Impending sense of loss of consciousness
-Sleepiness
-Heat, flushing
-Rapid onset
-Déjà vu, epigastric, rising sensations, piloerection, smells, tastes
-Focal neurological symptoms of any kind
Panic

Question 26

What does prodromal mean?

Answer 26

The things that happen before the seizure episode

Question 27

What is the significance of tongue biting during a seizure?

Answer 27

Tongue bit in the diagnosis of generalized tonic-clonic seizures

Sensitivity of 24%
Specificity of 99%
Specificity of lateral tongue biting of 100%

Question 28

What is the significance of urinary incontinence during a seizure?

Answer 28

Urinary incontinence in the diagnosis of epileptic episodes

Systematic review 5 studies (221 epilepsy patients and 252 subjects with other episodes of LOC, including mainly syncope and functional episodes

Sensitivity 38%
Specificity 57%

Therefore, urinary incontinence has no value either in the differential diagnosis

Question 29

What are some differentials for syncope?

Answer 29

-Reflex (vaso-vagal, cough, micturition, defecation)
-Othostatic
-Cardiogenic
-Seizures
-Hypoxia eg PE
-Hypoglycemia (diabetics on insulin and insulinoma)
-Vertebrobasilar TIAs
-Intoxication
-Cataplexy
-Drop attacks
-Psychogenic pseudo-syncope

Question 30

Give example of double triple diagnosis’s of syncope

Answer 30

Panic -> hyperventilation -> syncope (due to cerebral vaso-constriction)

Panic -> hyperventilation -> migraine

Panic -> hyperventilation -> seizure (if susceptible)

Vertigo -> vomiting -> syncope

TLE -> arrythmia -> syncope

Syncope -> head injury > tongue bite, prolonged LOC & amnesia

Syncope in the elderly -> sleep

Syncope in the elderly -> TIA

Question 31

What are functional seizures?

Answer 31

AKA psychogenic nonepileptic seizures (PNES) or dissociative seizures (DS)

Characterized by paroxysmal events that semiologically may look like epileptic seizures, but are not due to an underlying epileptic activity