Seizure Disorders

3. Susan Aldworth: The Portrait Anatomised, NPG, 2013

4. Learning Objectives
• Taking a seizure history
• What to do with a first seizure in ED
• Assessment and management of acute seizure
• Causes of provoked seizures
• Assessment and management of status epilepticus
• Epileptic seizures vs PNES
• Epilepsy: epidemiology and causes
• Differences between focal and generalised seizures
• Management including drugs and surgery
• Prognosis and SUDEP

5. Case Study
• Julia Roberts, 23F, BIBA to ED at 0300
• On a night out with her friends then suddenly collapsed
and became unresponsive
• Previously well but had been feeling a bit ‘queasy’
• Her friends reported that her head turned to the right
before collapsing, she became stiff and contorted,
screamed and then started jerking which lasted 30
seconds
• She was conscious but drowsy when LAS arrived

6. ED Assessment
• A – patent, self-
maintaining
• B –
o RR16
o SpO2 98%
• C – HS I + II + O
o CRT 2s
o JVP <->
o Euvolaemic
o ECG: SR
• D – GCS E3V5M6
o AMTS 6/10, PEARL
o BM 5.1
o T 36.9
• E – Abdomen SNT, no
injuries
RUL LUL RLL LLL
Power 5 5 5 5
Tone N N N N
Reflexes ++ ++ ++ ++
Coordination N N N N
Sensation N N N N

7. Collapse History
• Before
o When: morning, evening
o Where: at home, work
o Activity: exercise, TV, change in posture, sleep, light, intoxication
o Prodrome: CP, presyncope, SOB, headache, fever, neck stiffness, aura (‘déjà
vu’), dysarthria, limb weakness
• During
o Loss of consciousness vs loss of awareness
o Length of time
o Movements: stiffness, jerking (NB syncope), eye-rolling, tongue-biting,
incontinence, focal (lip-smacking, posturing, automatisms)
o Injuries
• After
o Speed of recovery and level of consciousness on recovery

8. Collapse Background
• PMH:
o Cardiovascular risk factors, neurological risk factors, childhood epilepsy (?
BNFC), head injury
• DH:
o Insulin, corticosteroids, anti-depressants, neuroleptics
• SH:
o Alcohol
o Recreational drugs
• LMP

9. Collateral History
• Julia’s mother:
o Julia had ‘blank spells’ as a child and had difficulty at school because she
was always daydreaming
o Never took medication because mom read online about controlling it
with diet
o Things seemed to get better when she started secondary school
o Uncle has been diagnosed with generalized epilepsy

10. DD
Syncope
Arrythmia
Vasovagal
Dysautonomia
Seizure
• Epilepsy
• Metabolic
• Traumatic
Vascular
Stroke
TIA
Metabolic
• Hypoglycaemia
• Hypontraemia
Psychiatric
• Panic aVack
• PNES
• Breath-holding

11. ED Management
• Ensure airway patency and adequate RR/SpO2.
Give high flow oxygen if appropriate.
• Ensure seizure has terminated
• Look for causes:
o Temperature
o Blood glucose
o Bloods: FBC, U&E, CRP, Bone, HCG, toxicology screen
o ?Neuroimaging
o ?LP

12. Imaging and Referral
• Up to 40% of first seizure patients have abnormal CT
• RCEM guidelines:
o CT scan in ED if intracranial lesion suspected
o Persistent altered mental state, persistent headache, focal or partial onset
before generlisation, heady injury, malignancy, immunocompromise, HIV,
alcoholism, anticoagulation, bleeding diathesis
o If not, defer to outpatient (preferably MRI) unless no reliable follow-up
• No need to admit if no neurological deficit and
investigations normal
• Specialist referral to ‘first fit’ clinic within 2/52
Royal College of Emergency Medicine (2009). Guidelines for management
of first seizure in the emergency department.

13. Medical On Call
• 0300 crash call for Will Smith, 65M, who has just started
fitting on AMU.
• Was found unresponsive near the bathroom door. Then
started seizing 15 seconds ago.
• Admitted for vomiting and diarrhoea ?gastroenteritis
• BG: DM, HTN, CVA, hypercholesterolemia, epilepsy (well-
controlled on Keppra)

14. Assessment
• ABCDE
o Call for help, start high flow O2, ensure IV access, start monitoring
• Look for causes
o CBG
o Temperature
o Bloods
o ECG
• Unwitnessed collapse? History of trauma?
o Neuroimaging for suspected CVA/intracranial bleed
• Medication-related?
o Drug chart for new Rx and omissions, interactions

15. Acute Seizures: Aetiology
• Vascular
o CVA, bleeds
• Infective
o Meningo-encephalitis
o HIV
• Metabolic/Endocrine
o Glucose
o Electrolytes (Na, Ca, Mg)
o Hepatic encephalopathy
o Vitamins
o Temperature
• Drugs
o Too much: cocaine, neuroleptics,
TCAs, aspirin, lithium
o Too little: insulin, corticosteroids, AEDs,
anxiolytics, alcohol
• Neoplastic
o Tumours
o Hydrocephalus
• Trauma
• Autoimmune
o Encephalitis, vasculitis
• Degenerative
o MS, dementia

16. Acute Seizures:
Immediate Management
SPECIALIST REFERRAL IF PRIMARY NEUROLOGICAL DISORDER
LOOK FOR AND EXCLUDE CAUSES
TERMINATION
Diazepam 10mg IV or 20mg PR Lorazepam 4mg IV q 10-20 mins Buccal midazolam 5-10mg
AIRWAY
Left lateral position to prevent aspiration
ET tube if apnoeic or persistent airway threat

17. Acute Seizures:
Management
• In this case Mr Smith was a known epileptic who
had not taken his medication for 3/7 due to poor
oral intake and vomiting
• Intracranial and metabolic causes were excluded
by CT and serology
• He was discussed with neurology who advised
restarting on maintenance AED and follow-up in
outpatient clinic

18. Status Epilepticus
• Neurological emergency: 30 min of continous seizure
activity or 2+ seizures without full recovery of
consciousness between seizures
• Convulsive:
o Repetitive tonic-clonic movements
• Non-convulsive:
o Lethargy, confusion, involuntary movements
• Immediate management:
o ABCDE + oxygen + call for help
o Attach cardiac and O2 monitors, get IV access
o Investigations: ABG, bloods, portable CXR (?aspiration)
o Monitoring: HR, BP, SpO2, ECG. EEG if refractory.

19. Status Epilepticus
Lorazepam 4mg IV every 10-20 mins.
Repeat 1-2 times.
Phenytoin or fosphenytoin 20mg/kg
over 20mins. Alternatively
phenobarbitol bolus 10-15mg/kg.
Intubation and ITU. General
anaesthesia with propofol,
midazolam or sodium thiopental.

20. PNES
• Psychogenic non-epileptic seizures (‘pseudoseizures’),
involuntary
• Usually 15-35y, 80% female, associated with mood disorders,
chronic pain, epilepsy (10%), past neurological and FH of
epilepsy
• Features: duration > 2min, recall for period of
unresponsiveness, fluctuating course
• Simple tests: hand drop, roll onto side, mirror test
• Other evidence: normal pupillary responses, flexor plantars

21. PNES vs organic seizures
Feature Dissociative Organic
Gradual onset, eyes closed,
thrashing violent movements,
side-to-side head movements
Common Rare
Opisthotonus, plevic thrusting Common Very Rare
Automatisms Rare Common
Incontinence Occasional Common
Tongue biting Very Rare Common
Weeping Common Very Rare
Stereotyped AVacks Common Very Rare
Investigations: prolactin, creatine kinase, VT/ EEG (but abnormal in 15%)
Rugg-Gunn, F. Smalls, J (2015) Epilepsy: a practical guide. ILAE

22. Epilepsy
Tlazlteotl

23. Epilepsy

24. Seizures and Epilepsy
• Seizure: Transient occurrence of signs and or symptoms due to
abnormal or excessive synchronous neuronal activity
• Provoked seizure: seizure caused by acute injury or disorder of
the CNS
• Unprovoked seizure: seizure where no acute cause found
• Epilepsy: Seizure disorder characterised by recurrent,
unprovoked seizures
• Diagnosis: at least 2 unprovoked seizures occurring >24h
apart, or a specific epilepsy syndrome
Fisher et al. (2014). A practical clinical definition of epilepsy (2014).

25. Epidemiology
• Incidence 50 / 100 000, prevalence 1% at 20y, 3% at
75y, slightly male predominant
• 75% occurs in developing countries
Associated Conditions Risk Factors
Stroke and vascular disease LBW
Infections Family History
Brain tumours Age
Head Injury Drug Use
Dementia Childhood Seizures
CP and ASD ?BFNC
Learning Disability
Aidan, N. Sander, JW. The incidence and prevalence of epilepsy (2015). ILAE

26. Aetiology
• Genetics
o Complex heritability, often
neuronal or synaptic proteins
o Monogenetic disorders e.g.
Angleman syndrome (UB3A),
Rett syndrome (MECP2), Benign
neonatal familial convulsions
(KCQN2), Dravet syndrome
(SCN1A)
• Congenital brain
malformations
o Focal cortical dysplasia
o Tuberous sclerosis (TSC1/2)
o Lissencephaly/schizencephaly
• Stroke and CVD (11-21%)
o 5% have seizure in first month
• Tumours (4-7%)
o 30% of BTs will have seizures
o Benign vs malignant
• Trauma (2-6%)
o Up to 30% TBI patient will develop
epilepsy. Age, severity and
seizures are predictive.
• Infection (0-3%)
o Meningo-encephalitis
o Neurocystericosis, HIV
Aidan, N. Sander, JW. The incidence and prevalence of epilepsy (2015). ILAE

27. Focal Cortical
Dysplasia
Hippocampal
Sclerosis
DNET

28. Pathophysiology
• Focus: region of seizure generation, from which a
wave of discharge spreads out across cortex.
Usually neocortex and limbic structures.
• ‘Inter-ictal spikes’: ictogenic discharges that have
low potential for synchronisation and spread.
o If certain criteria are met (‘minimum aggregate’ of neurons, synaptic
connectivity and ion channel priming) the discharge spreads
• Epileptogenesis: chronic changes within focus and
in network connectivity that make seizure
generation and propagation more likely

29. Classification of Seizures
Seizures
Generalised
GTCS
Myoclonic
Absence
Tonic
Atonic
Clonic
Focal
SPS
CPS
Secondary
Generalized
ILAE Classification of Epilepsies (1989). ILAE

30. Classification of Seizures
ILAE (2016). Seizure Type Classification. ILAE

31. Generalised seizures
• GTCS (Grand mal):
o Originates and spreads in both hemispheres. Last seconds to minutes.
o Tonic phase – bilateral myoclonic jerks, then tonic contraction of
extremities and axial muscles, causing extension of neck & limbs.
o Contraction of diaphragm & glottis causes tonic cry.
o Clonic phase – rapid muscle contraction and relaxation causing twitching
and jerking, with eye-rolling, tongue-biting, incontinence.
o Afterward patient is unconscious for up to 1h, may feel exhausted

32. Generalised seizures
• Absence seizures (Petit mal):
o Vacant spells with impairment of consciousness, interruption of activity,
blank state, brief upward rotation of eyes.
o May be mild tonic, atonic, clonic components or automatisms (atypical)
o Classically 3hz spike and wave pattern on EEG
o No post-ictal residual deficit
• Atonic seizures:
o Sudden generalised loss of tone (drop attacks). May fall forward and
cause head and facial injuries.
• Myoclonic seizures
o Brief, shock-like jerks of muscles or groups of muscles. Patient retains
awareness. Often following waking

33. Focal Seizures
• Simple Partial Seizure:
o Not loss of awareness
o Jerky, rhythmic movements in one body segment or ‘Jacksonian march’
o May also be isolated sensory or autonomic features
o Epilepsia partialis continua
• Complex Partial Seizures:
o Last 30 seconds to two minutes, cause loss of awareness or consciousness
o Aura: sensory and psychic, especially TLE, abdominal (rising epigastric
sensation) or psychic (‘déjà vu, jamias vu, fear)
o Automatisms: vocalisations, oral (lip smacking, chewing), manual (picking
fumbling), elaborate, bizarre
• Secondary Generalised:
o CPS that may then extend to the whole cortex and become GTCS

34. Seizure Videos
• https://www.youtube.com/
watch?v=DidGU97hiVQ
• https://www.youtube.com/
watch?v=jrYVudPCY0g

35. Epilepsy Syndromes
• Idiopathic Generalised Epilepsy
o Epilepsy with GTCS on waking
o Childhood Absence Epilepsy
o Juvenile Absence Epilepsy
o Juvenile Myoclonic Epilepsy
• Focal Epilepsy
o Idiopathic partial epilepsy
o Temporal lobe epilepsy
o Frontal lobe epilepsy
• Specific Syndromes
o Rolandic epilepsy
o West syndrome
o Lennox-Gastaut syndrome
o Angelman syndrome
o Rett Syndrome
o Dravet Syndrome
Lennox-Gastaut Angelman
ReV West

36. Diagnosis
• Neuroimaging
o All patients should have structural neuroimaging to exclude an underlying
cause (AAN, NICE)
• EEG and Video Telemetry
o Up to 40% routine EEGs are normal in epilepsy
o Much more diagnosed if during typical seizure
o Higher sensitivity with sleep deprivation, photic
stimulation, alcohol etc
o If non-diagnostic patient may be admitted to VT
unit for observation on the ward
NICE (2016) Epilepsy:
diagnosis and management.

37. GTCS: bilateral synchronous 3-5Hz spike and wave
Absence: 3Hz spike and wave
TLE: sharp waves predominantly in temporal leads JME: myoclonic jerk

38. Management: AEDs

39. Management: AEDs
Absences GTCS Focal Myoclonic
1st Ethosuximide
Valproate
Valproate
Lamotrigine
Carbamazepine
Lamotrigine
Valproate
2nd Lamotrigine Carbamazepine**
Oxcarbazepine
Levetiracetam
Oxcarbazepine
Valproate
Levetiracetam
Topiramate
3rd Clobazam
Clonazepam
Levetiracetam
Topiramate
Zonisamide
Clobazam
Lamotrigine
Valproate
Topiramate
Carbamazepine
Clobazam
Gabapentin
Lamotrigine
Leveitracetam
Clobazam
Clonazepam
Pireacetam
Zonisamide
**Carbamazepine/oxcarbazepine exacerbates absence and myoclonic seizures
Hamandi, K. (2015). Choosing antiepileptic drug treatment. ILAE

40. AED Therapy
• Up to 70% patients eventually become seizure-free
on AED therapy
• 47% become seizure-free on first medication, 32%
on second line and 9% on third line/adjunctive
• 30% will have refractory epilepsy
• 30% have seizure recurrence following AED
withdrawal
Neligan, A. Sander, JW. (2015) Prognosis of epilepsy. ILAE

41. Management: Surgery
• Used in refractory focal epilepsy where there is
insufficient response to AEDs and identifiable focus
• Evaluation: video telemetry, neuroimaging, nuclear
medicine (SPECT/PET), MEG, Wada test
• Procedures: lesionectomy, temporal
lobectomy (TLE), hemispherectomy
(Rasmussen’s)
• Up to 64 % seizure-free at 1y
Neligan, A. Sander, JW. (2015) Prognosis of epilepsy. ILAE

42. Management: Ketogenic
diet
• High fat, low carbohydrate, controlled protein diet
for children with refractory epilepsy
• Treatment of choice of for certain epilepsies
associated with metabolic deficiencies
• Theory: ketotic modulation of the tricarboxylic acid
cycle to increase production of GABA
• May also be beneficial in adults

43. Brain Stimulation
• Vagal nerve stimulator: implantable device attached to
the left vagus nerve
o Continuous pulsed vagal stimulation or triggered with magnet
o Mechanism unknown
o Seizure reduction in 1/3rd of refractory patients
• Trigeminal nerve stimulator: similar concept
o Currently in phase III clinical trials
• Responsive nerve stimulator: implantable extracranial
device
o Rses electrode grid to sense seizure activity and deliver shock
o Reported seizure reduction 63% at 2 years

44. Epilepsy and Pregnancy
• 35% increase in Sz frequency, 55% no significant
change,10% decrease
• 3% have GTCS during labour
• Background major congential malformation rate
1-2% - orofacial cleft, cardiac and urinary
abnormalities
• Clearance of all drugs
increased up to 250%
Drug MCM NTD
VPA 11% 3.8%
CBZ 6.7% 1%
PHT 4.3%
LTG 2.7%

45. Epilepsy and Pregnancy
• GTCS (but not focal or myoclonic) carry a small risk of
premature labour
• Try to plan pregnancies by switching to safer AED if patient on
long term valproate
• If unplanned, may be safer to stay on current AED therapy
rather than increase seizure frequency
• AEDS may need to be uptitrated due to increased clearance
• Give all women 5mg folic acid preconception until birth and
give 1mg vitamin K to women on enzyme inducers

46. Driving and Epilepsy
• Personal: must stop driving and inform DVLA. Must be one year
seizure-free with or without AEDs.
• Vocational: must stop driving and inform DVLA. Must be 10
years seizure-free with or without AEDs.
• Provoked: decided on individual basis. May be eligible to
continue driving.
• Isolated: may be eligible to drive after 6 months if no further
seizures.
• Permitted: seizures that do not affect unawareness,
consciousness or ability to drive

47. Prognosis
• Up to 71% of those with first seizure will go on to
have a second.
• 65% manage to stay in remission at 20y follow-up
• Poor prognostic factors: multiple seizure types,
failure of treatment response, focal seizures with
structural abnormalities (especially TLE)
Neligan, A. Sander, JW. (2015) Prognosis of epilepsy. ILAE

48. SUDEP
• SUDEP: sudden death in epilepsy, up to 9.3/1000 cases
(5-10/100 000 generally). Commonly 20-40y.
• Risk factors: early onset epilepsy, intractable seizures, ?
focal, polytherapy, subtherapy, learning disability
• Mechanisms: cardiac arrythmias, airway compromise,
neurogenic pulmonary oedema, central apnoea
• Management: good seizure control, surgery if refractory,
WADD (wearable apnoea detection device)
Rugg-Gunn, F. (2015) Sudden unexpected death in epilepsy. ILAE

49. Learning Points
• Seizure History: before, during and after. Always get
a collateral.
• Managing fits: A*BCDE, get help , IV lorazepam,
• Causes: vascular, metabolic, neoplastic, traumatic,
infective
• Differentiating between focal and generalised
• Management: drugs, surgery, diet, stimulators

50. Questions?
• Please take 2 min to give feedback and complete
mini-quiz below:
• https://goo.gl/forms/3SiiDQqfEdPXgi5E2