Epilepsy.. by hosam Maarouf Alhussin

1. Epilepsy

2. Definitions
Seizure: the clinical manifestation of an abnormal and
excessive excitation and synchronization of a population of
cortical neurons
Epilepsy: two or more recurrent seizures unprovoked by
systemic or acute neurologic insults
Fisher RS, Boas WV, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League against Epilepsy (ILAE) and the International
Bureau for Epilepsy (IBE). Epilepsia 2005;46:470–472.

3. Mechanism
• Normally brain electrical activity is non-synchronous, as neurons do not
normally fire in sync with each other, but rather fire in order as signals
travel throughout the brain.
• Its activity is regulated by various factors both within the neuron and the
cellular environment. Factors within the neuron include the type,
number and distribution of ion channels, changes to receptors and
changes of gene expression. Factors around the neuron include ion
concentrations, synaptic plasticity and regulation of transmitter
breakdown by glial cells. Chronic inflammation also appears to play a
role.
• Another mechanism of epilepsy may be the up-regulation of excitatory
circuits or down-regulation of inhibitory circuits following an injury to
the brain

4. Generalized seizures
• Originate at some point
within and rapidly engage
bilaterally distributed
networks
• Can include cortical and
subcortical structures
but not necessarily the
entire cortex

6. • Originate within
networks limited
to one hemisphere
• May be discretely
localized
or more widely
distributed.…
Focal seizures

7. Statistics
• As of 2015, about 39 million people have epilepsy.
• Nearly 80% of cases occur in the developing world.
• In 2015, it resulted in 125,000 deaths, an increase from 112,000 in
1990.
• About 5–10% of people will have an unprovoked seizure by the age of
80, and the chance of experiencing a second seizure is between 40%
and 50%.

8. Epilepsy is a disorder of the brain defined by any of
the following conditions:
• At least two unprovoked (or reflex) seizures occurring more than 24
hours apart
• One unprovoked (or reflex) seizure and a probability of further seizures
similar to the general recurrence risk (at least 60%) after two
unprovoked seizures, occurring over the next 10 years
• Diagnosis of an epilepsy syndrome
Furthermore, epilepsy is considered to be resolved for individuals who had
an age-dependent epilepsy syndrome but are now past that age or those
who have remained seizure-free for the last 10 years, with no seizure
medicines for the last 5 years.

10. What has changed in ILAE 20171
• Partial seizures (depending on the body part affectyed) are now called focal
seizures (focus in the brain)
• The same is true for the epilepsy itself: those we called patiral epilepsies now
should be called focal
• The terms ‘simple’ (without consciousness loss) and ‘complex’ (with
consciousness loss) partial seizures have changed to ‘focal aware’ and ‘focal
with impaired awareness’
• There is no ‘aura’ before seizures anymore
• Secondary generalized seizures are called now ‘focal to bilateral clonic-tonic’
1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang
YH, Zuberi SM. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi:
10.1111/epi.13709.

11. Notes
• Atonic seizures and epileptic spasms would not have level of awareness
specified
• Pedalling grouped in hyperkinetic rather than automatisms
• Cognitive seizures
• impaired language
• other cognitive domains (agnosia, dissociation, left-right confusion,
memory impairment, dyslexia, ‘forced’ thoughts)
• positive features eg déjà vu, hallucinations, perceptual distortions
• Emotional seizures: anxiety, fear, joy, etc, gelastic (laughing),
dacryocystic (crying)
• Automatisms: orofacial, sexual actions, vocalizations, tapping,
undressing, walking/running
• Autonomic: tachy-/bradycardia, sweating, abdominal symptoms,
hyper-/hypoventilation, nausea/vomiting, mydriasis, paleness/redness
of skin, erection

12. Focal motor seizure with impaired awareness
with automatisms

14. Focal tonic seizure with automatisms with impaired awareness

15. Focal atonic-tonic-clonic seizure

19. Myoclonic seizures / Infantile spasms

20. Focal to bilateral clonic-tonic seizure

21. Focal cognitive seizure with impaired
awareness

22. Focal emotional (gelastic) seizures with
impaired awareness

24. Generalized clonic-tonic seizure

28. Typical absence (generalized non-motor)

30. EEG patterns in absence
Typical absence Atypical absence

31. Absence with eyelid myoclonia

32. Unknown
Immune
Infectious
Structural
Etiology
Metabolic
Genetic
Co-morbidities
Epilepsy types
Focal Generalized
Combined
Generalized
& Focal
Unknown
Focal
Epilepsy Syndromes
Seizure types
Generalized
onset
Unknown
onset
Focal
onset

33. Etiology
Tuberous Sclerosis
GLUT1 deficiency
Unknown
Immune
Infectious
Structural
Metabolic
Genetic
Seizure types
Generalized
onset
Unknown
onset
Focal
onset

34. Epilepsy types
Focal Generalized
Combined
Generalized
& Focal
Unknown
Focal
• Where unable to make an Epilepsy Syndrome diagnosis or
a diagnosis of Etiology
• Many examples
• Temporal lobe epilepsy
• Generalized tonic-clonic seizures in a 5 year old with generalized
spike-wave
• Both focal impaired awareness seizures and absence seizures in
a patient
• Cannot tell if tonic-clonic seizure is focal or generalized

35. “unknown onset” seizures
• It can occur with or without motor manifestations.
• As an example, the first tonic-clonic seizure in an adult patient is used
(sometimes it happens without witnesses).
• If its focal origin is clarified in the future, it will be reclassified into
“focal into bilateral tonic-clonic seizure”,
• If its generalized nature is proved, it will be called “generalized tonic-
clonic”.
Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, Lagae L, Moshé SL, Peltola J, Roulet Perez E, Scheffer IE, Zuberi SM Operational classification of
seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):522-
530. doi: 10.1111/epi.13670.

36. Epileptic encephalopathy
• a condition in which epileptiform activity on the EEG contributes to cognitive and
behavioral impairment. At the same time, global or selective defects can grow over time.
• According to the severity of manifestations, epileptic encephalopathy represents as a
spectrum of conditions and can be observed in any epilepsy and at any age.
• Syndromes related to epileptic encephalopathy can be both genetic (monogenic cases of
West syndrome, Dravet syndrome, etc.), and acquired (for example, the same West
syndrome, but as a result of hypoxic-ischemic encephalopathy of newborns).
• Many epileptic encephalopathies are accompanied by "massive" epileptiform activity on
the EEG, and a decrease in this activity can lead to improved development of the child
• Developmental delay may precede seizure onset
• Co-morbidities - eg. cerebral palsy, autism spectrum disorder, intellectual disability
Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi: 10.1111/epi.13709.

37. Epileptic activity itself
contributes to severe cognitive and
behavioral impairment above and
beyond that expected from the
underlying pathology and that these
can worsen over time
Developmental and/or Epileptic encephalopathies
Berg et al 2010

38. Principles of treatment (interictal)
• Generalized – valproic
acid
• Focal – carbamazepine,
oxcarbazepine
• Second-line drugs for all types – lamotrigine, levitiracetam,
etosuximide, phenitione, etc.
• Third-line drugs for all types – topiramate, ACTH, corticosteroids
• Surgical treatment (usually for focal epilepsies)

39. Management of acute seizure
• Status epilepticus develops: for generalized – 30 min
• For focal – 60min
• 1. Midazolam / diazepam / phenytoin – IM / IV – every 5 minutes up to
3 times
• 2. If 1 is not effective - Valproic acid / levitiracetam - IV / IV drip
• 3. If 2 is not effective – drugs for general anesthesia (sodium thiopental,
etc.) + corticosteroids IM/IV