Epilepsy

Front 1

Seizures

Back 1

Clinical manifestation of an abnormal & excessive excitation of a population of cortical neurons

Front 2

Epilepsy Definition

Back 2

- “a disorder of the brain characterised by an enduring predisposition to generate epileptic seizures”
- “occurrence of at least one unprovoked seizure” which is in contrast to an older definition which required at least two unprovoked seizures
- unprovoked tendency towards recurrent seizures

Front 3

Focal Seizures

Back 3

› Focal (partial) - Activation of neurons in a relatively small, discrete region
- Clinical manifestation reflects region of brain in which they occur
- Sensory or motor
- Complex partial seizures – impairment of consciousness (once diencephalon is involved loss of conciousness)
- Familiarity (déjà vu) or strangeness (jamais vu), automatisms,
hallucinations (auditory and visual), temporal lobe epilepsy

can be a developmental focal umour tht can spread and cause generalised tonic clonic

Front 4

Generalised Seizures

Back 4

› Generalised - Characterised by involvement of both hemispheres and
widespread neuronal activation
- Tonic – extension of the extremities, rigid stretching
- Atonic – sudden loss of muscle tone
- Clonic (Myoclonic) – repetitive muscle twitching
- Tonic-clonic (grand mal) – distinct tonic phase followed by a clonic phase (full
body spasms with intermittent relaxation)
- Generalised absence seizures (petit mal) –brief lapse of consciousness

Front 5

Not all antiepileptic drugs are anticonvulsants

Back 5

-

Front 6

Mechanisms of Anticonvulsants

Back 6

1. Enhance Na+ channel inactivation
- reduce firing frequency of neurons
2. Inhibit excitatory amino acid release
- block Ca2+ or K+ channels
3. Enhance GABA action
4. Inhibit GABA breakdown
5. Inhibit GABA uptake

Front 7

Na Channel Inactivation

Back 7

- use dependent
- red. of sustained high-fq firing APs, specifically act on rapid firing neurons

phenytoin, carbamazepine & lamotrigine

Front 8

Inhibit Excitatory amino acid release

Back 8

- used for generalised absence seizures
- T-type Ca2+ channel blokcer

Ethosuximide

Front 9

Valproate

Back 9

Mech 1, 2 & 4
its Mech 4 action lead to newer generation anticonvulsants research

Front 10

Enhance GABA actions

Back 10

Act at GABAa
- increase affinity for GABA
- inc. Cl- conductance
- prolongs open time of the channel

UNWANTED sedative side effects

Phenobarbitone, BZDs (BZDs bind at the interface between alpha and gamma subunits)

Front 11

Inhibit GABA breakdown

Back 11

- vigabatrin
- synthetic structural analogue of GABA
- specific inhibtor of GABA-Transaminase

Front 12

Inhibit GABA Uptake

Back 12

Tiagabine- derivative of nipecotic acid (transportable inhibitor)
- GAT1 inhibitor

Front 13

Mechanism unknown

Back 13

Gabapentin and pregabalin

Front 14

Genetics of Epilepsy

Back 14

› Since the first “gene” to cause epilepsy was discovered in 1995, more than 25 different genes have been found
› Virtually all known mutations that cause epilepsy are found in ion channel subunits

Front 15

EEG

Back 15

Display of fluctuations in voltage which occur over the scalp generated by postsynaptic potentials in cortical neurones.
- normal EEG doesnt exclude epilepsy
- if normal repeat after sleep dep.

Front 16

Aetiology

Back 16

Infancy & childhood
–Birth injury
–Inborn error metabolism
–Congenital malformn.
Childhood & adolescence
–Idiopathic/genetic syndrome (idopathic not caused by anything and so by inference genetic)
–CNS infection
Adolescence & young adult
–Head trauma
Older adult
–Stroke
–Brain tumor

1. cortical dysplasia (classical trauma @ frontal eye fields)

Front 17

Childhood absence epilepsy

Back 17

peak onset 6-7 years, girls > boys
–family history of epilepsy
–Absences very frequent
EEG, 3Hz spike and wave complexes,
»clinical seizures produced by hyperventilation
remission in approx. 80% by adolescence
–generalised tonic clonic seizures, 20-40%
–ethosuximide, valproate, lamotrogine

Front 18

Juvenile myoclonic epilepsy

Back 18

–age of onset, 12-16 years
»myoclonic seizures, early morning occurrence
»generalized (clonic-)tonic-clonic seizures, 90-95%
»absence seizures occur in 10-33% of cases

VALPORATE drug of choice

Front 19

Genetic Contribution to epilepsy

Back 19

Risks are greater for generalised than focal epilepsies
–Generalised epilepsies: risk to sibs ~ 10%
–Focal epilepsies: risk to sibs < 5%
–Febrile seizures: risk to sibs ~ 8%

Front 20

Twin Studies

Back 20

»“idiopathic” epilepsy syndromes (genetic);
eg. Childhood Absence Epilepsy
»monozygotic 70.2%, dizygotic 7.5%
»Structural focal epilepsy (acquired);
eg. Head injury, encephalitis, tumour
»monozygotic 10.8%, dizygotic 5.6%

Front 21

Channelopathies
- simple inheritance (only account for a small proportion of epilepsy syndromes)

Back 21

VG Channelopathies
Ligand Gated Channelopathies
Non-Channel genes

Front 22

Laceration to lateral margin of tongue specific to what seizure?

Back 22

Tonic clonic

Front 23

Questions for a first seizure?

Back 23

Seizure or not?
Seizure type?
–focal onset, postictal deficits
Evidence of CNS dysfunction?
–school, work, hemiparesis, PMH
Any precipitating factors?
What investigations to order?
Do we start an AED?
What precautions to advise?

Front 24

Seizure Precipitants

Back 24

Low (less often, high) blood glucose
Low sodium, calcium, magnesium
Stimulant/other proconvulsant intoxication
Sedative withdrawal
Severe sleep deprivation

Front 25

Evaluation of a first seizure

Back 25

History, physical
Blood tests: FBC, electrolytes, glucose, Ca, Mg, hepatic and renal function
Lumbar puncture only if meningitis or encephalitis suspected (CT scan)
Urine drug screen
Electroencephalogram
CT or MR brain scan

Front 26

Relapse Rate after 1st seizure

Back 26

wide range from studies, pooled data 51%
most recurrences in 1st year, usually 3-6mo
Predictive factors
–idiopathic (32%) vs remote symptomatic (57%)
»abnormal exam, structural lesion on CT/MRI
–abnormal EEG, epileptiform (58%)
–partial seizures, especially remote symptomatic
Relapse rate is reduced by AED treatment

Front 27

AIMS of AED Tx

Back 27

Choose appropriate medication
–valproate for generalised seizures
Use a single drug, monotherapy
–simplifies treatment, reduces adverse effects
Make the patient seizure free
–without dose related side effects
if seizures recur, increase dose
–maximal tolerated dose
–need to observe for 2-3x usual seizure interval

Front 28

Prognosis

Back 28

70% have a good prognosis for control of seizures and remission
–better for idiopathic than symptomatic
–better for generalised than partial
20% need regular medication and may have breakthrough seizures
5-10% poorly controlled

Front 29

Convulsive Syncopy

Back 29

is common and often miss Dx as epilepsy

Front 30

Syncopy DDx Seizure

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Precipitating factors
Light-headed, tinnitus
limp fall, convulsive movements
brief
rapid recovery
no incontinence or tongue bite
Normal EEG

Front 31

Seizure DDx Syncopy

Back 31

Supine, sleep
Aura, CPS
tonic clonic evolution
duration minutes
postictal confusion (often wake up in hosiptial bed not knowing how they got there)
muscle soreness, injury, lateral margin tongue bite
Abnormal EEG

Front 32

DDx Seizures

Back 32

Seizure
Syncope
Migraine
Cerebral ischaemia
Movement disorder
Sleep disorder
Metabolic disturbance
Psychiatric disturbance

Front 33

Refractory seizure disorder

Back 33

Review the diagnosis
–are the seizures epileptic?
Review the medical therapy
–compliance with medication?
–adequate trials of AEDs?
Consider alternatives to medical therapy
–epilepsy surgery in partial seizure disorders

Front 34

Epilepsy surgery

Back 34

Failure of antiepileptic medication
–Trials of different drugs, >2 often predicts refractory seizures
–Identify epileptic focus;
»Video EEG, MRI, PET, SPECT
–show it could be removed safely
Temporal lobectomy
Focal cortical resection of frontal, parietal or occipital lobes