Refresher course - epilepsy

H Leung, Division of Neurology,

Department of Medicine and
Therapeutics, CUHK
 Introduction
•  Epilepsy – neurological disease with abnormal
discharges of brain
•  In HK, > 70,000 chronic patients
•  Epilepsy can lead to loss of consciousness and
injury to the body
•  Hospital service provides the majority of care to
epilepsy patients – medications / surgery
 Seizures are common!

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 ILAE OFFICIAL
REPORT

if 1 seizure only => rely on condition 2 for dx

Epilepsy is a disease of the brain defined by any of the following conditions
exclude other causes of acute symptomatic seizure
1. A least two unprovoked (or reflex) seizures occurring >24 h apart

2. 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

3. Diagnosis of an epilepsy syndrome based on EEG

Epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but
are now past the applicable age or those who have remained seizure-free for the last 10 years, with no
seizure medicines for the last 5 years.
The approach to patients with suspected
seizures

•  Good history from both patient and witnesses.

Events prior to, during and afterwards.
•  Past history, medications, allergy
•  Social and family history
•  Neurological and cardiovascular examinations

Risk factors
History of presenting
syncope: can have twitching or myoclonic jerk, but shorter duration
complaints
vasovagal: after prolonged
standing => venous pooling
=> hypotension, bradycardia
Investigations
Key summary
abnormal discharge (pathological)
Syncope Seizure
Cardiac diseases, cardiac Febrile convulsion, family
medications, hx of NPC with RT. history of seizures, head
Family history of cardiac disease injury, encephalitis, FH
aura: deja vu, jamais vu,
e.g. blood taking, stress epigastric sensation
Situational elements, shorter
Aura, longer duration, more
duration, less convulsive elements convulsive elements, stereotypy
but not to complete exclusion, of events, prolonged clouding
pallor, cold clammy hands
signs of 2nd sympathetic activation, of consciousness, more
quick recovery injuries TLE: automatism
Blood tests, CXR, ECG Blood tests
Lying/standing BP CT brain or MRI brain
Special investigations: echo, holter,
transcranial doppler
EEG
carotid doppler, TCD, tilt-table test,
loop recorder, autonomic function
tests
 Electroencephalogram

performed in ICU
ICU admisison: if status epilepticus give electrical stimulation => test
whether specific lobes are functional

electrodes 1-2cm distance: can pick up more signals

Periodic lateralized epileptiform discharges over left parieto-temporal area
 by contrast, this is generalised epilepsy
spike and wing pattern, paroxysmal (comes once a while)
only comes when hyperventilate
can diagnose this as epilepsy syndrome based on EEG!!
Management of 1st seizure
always need to exclude acute severe cause: bleeding, stroke, encephalitis drug, metabolic & systemic insult

50% of hospital attendances with 1st seizures are

acute symptomatic seizures

20% of 1st seizures were misdiagnosed as other

non-epileptic presentations

Ask the following questions: “Is it a seizure?” “Is it

the first?” “Is there acute medical cause?”
 Drug treatment of status
epilepticus
loprazepam (ativan) or diazepam
Intravenous ativan at doses
of 1-4 mg (bolus)
Assess ABC
OR *ativan 4mg over 2min
max 8mg
in real life => if complete 1 vial => should consider
maintenance therapy of anticonvulsant therapy

Loading dose of phenytoin

Consult ICU for intubation
15mg/kg (usually
(protection of airway) and syringe pump/driver: 300mg in 30min
IV anesthetic agent => must need resp support 500mg-750mg)
can develop hypotension,over 30m-1h
intravenous sedation (e.g arrhythmia, arrest!

Cardiac monitoring
because phenytoin is Na channel blocker!

propofol/ midazolam) phenytoin: not soluble in D5 or NS => precipitation

undiluted
*Handbook of Internal Medicine 2015 N12 purple glove syndrome: extravasation of phenytoin during infusion
 What are acute
symptomatic seizures?
Seizures in the setting of an acute medical condition:

Structural
Malignant brain tumour, intracerebral haemorrhage, acute
ischaemic stroke, head injury, other specific structural encephalitis, meningitis

lesions e.g. RPLS

renal patient: lesion in posterior & occipital lesion

Systemic severe hypoNa, severe hypoglycemia, hypoCa, uremia

Electrolyte disturbance (Na, Glu, Ca, urea)

Intoxication drug withdrawal more seizure than intoxication

Withdrawal
 Drug treatment of epilepsy
Annual recurrence after the 1st seizure (if unprovoked)
hence newly diagnosed epilepsy: usually put on 2 years

~30%, maybe increased to 50% if additional risk factors

Approx. 60-70% of patients are rendered seizure-free

with 1st or 2nd anti-epileptic drugs (Kwan, 2000)

When the 1st drug fails, the options are substitution vs

add-on therapy.
which one? not black and white, depends on how patient responds to first drug
if control partially well => give add-on
if first drug doesn’t control seizure at all => logical to switch to another drug by taking off first drug completely
 SANAD study
important data to decide when patient can start driving again
HK: 1st tx failure / 2nd tx failure cannot drive => can only drive when take off the dx of epilepsy (10 years no recurrence & 5 years not on drug)

44% of patients newly diagnosed with epilepsy had a first

treatment failure

50% of patients who failed their first treatment also failed

their second treatment.

75% of patients who failed their first treatment will

subsequently gain at least 12-month remission in the
following 6 years

Bonnett et al Neurology 2014; 83(6): 552-560

 AED Regulatory Status in Hong Kong
phenobarbital, phenytoin, valproate, levetiracetam: IV preparation
other drugs: oral (must IV for status epilepticus)

Add-on + Add-on only

Monotherapy
Phenobarbital (Pb)
Phenytoin (PHT) Clobazam
“Established”
Carbamazepine (CBZ) Clonazepam
Valproate (VPA)
Lamotrigine (LTG) Zonisamide(ZNS)* not registered, off label use
Gabapentin (GBP) Pregabalin(PGB)
Lacosamide (LCS)
Oxcarbazepine (OXC) Perampanel(PER)
“New”
only indicated for
add-on therapies
Topiramate (TPM)
Levetiracetam (LEV)

* Only labelled-patient basis in Hong Kong; Bold +Italic iv preparation available in HK

 Risk of serious allergic
reactions

FDA requirement to check

HLA*B1502 in Chinese
population

•  Skin rash 5 – 10% Carbamazepine, phenytoin, lamotrigine, (oxcarbazepine)

•  Steven-Johnson Syndrome 0.1-6% overall
 Side effect profiles
Add-on + Add-on only
Monotherapy
Phenobarbital (Pb) – cognitive SE
Phenytoin (PHT) – gum hypertrophy Clobazam (dependence)
Carbamazepine (CBZ) – rash, hyponatraemia Clonazepam (dependence)
Valproate (VPA) – weight gain, PCOS?
Lamotrigine (LTG) – rash, mild cytopenia Vigabatrin (visual field defect)
Gabapentin (GBP)- cognitive SE Lacosamide (LCS) (QT
prolongation)
Oxcarbazepine (OXC) - hyponatraemia Retigabine (RTG) (bladder
Topiramate (TPM) – renal stone, glaucoma, dysfunction, pigmentation)
numbness
Pregabalin (PGB) – slight oedema
Levetiracetam (LEV) – behavioural problem
 Pharmacokinetic Interactions
Hepatic Cytochrome P450 enzymes (CYP)
CYP inducers
Phenobarbitone ↑ metabolism Other AEDs
Non-AEDs e.g. OC pills,
Primidone
↓ blood level warfarin, etc.
Phenytoin
Carbamazepine

CYP inhibitor ↓ metabolism

Valproate Other AEDs
↑ blood level
 Case Illustration
Therapeutic
range

2
1.8
INR 1.6
1.4
1.2
1

Phenytoin started
 Interaction with NOACs (new oral
anticoagulants)
Dabigatran Rivaroxaban Apixaban
CBZ -66%(ESC guideline) (red) -50% (ESC guideline) Reduction in rivaroxaban
(yellow) level
Administered with cauation -54% (ESC guideline) (red)
(MIMS) Adm with caution (MIMS)

Pb -66% (ESC guideline) (red) -50% (ESC guideline) Reduction in rivaroxaban

(yellow) level
Administered with caution -54% (ESC guideline) (red)
(MIMS) Adm with caution(MIMS)

PHT -66% (ESC)(red) -50% (ESC) (yellow) -54% (ESC) (red)

Reduction ? In dabigatran Administered with caution Administered with caution
level. Not mentioned in (MIMS) (MIMS)
MIMS
VPA Not mentioned in MIMS Not mentioned (MIMS) Not mentioned (MIMS)?
Caution as VPA may cause
thrombocytopenia
 Pregnancy and epilepsy

Most recent updates on guidelines

AAN guidelines x3 in 2009

Hong Kong Epilepsy Guideline 2009 (will be

revised as consensus statement 2015)
 Pregnancy and epilepsy

Relationship between MCM(major congenital malformations) and

AED(antiepileptic drugs) – highest for VPA (6.2% for monotherapy).
Counselling needed for choice, dose, poly-therapy, obstetric risks.

Use of folic acid is a recommended for women of child-bearing age

Use of vitamin K in the last month of 3rd trimester if patient taking

enzyme-inducing AED to avoid haemorrhagic complications

Issue of breast-feeding should be counselled and individualized.

 Driving and epilepsy

Road Traffic (Driving licences) Regulations (Cap. 374B)

May be Neither support
Should be
considered nor refute
considered
Traffic accidents due to transient loss of
consciousness and medical conditions

In the last 3
years, 55 serious
MVA in HK
 Driving and epilepsy

After a 1st seizure

Canada (CCMTA) 3 months

Australia(Austroads) 6 months

UK 6 months unless risk of further seizure>20%/annum

USA Under evaluation, cannot drive. If neurological and cardiac

investigations normal, may drive again
New Zealand May resume driving 1 year seizure free

Sweden 2 years

HK No guideline or consensus. (Hui, 2001), recurrence risk after 1st

seizure is 30% 2 years. After 1st acute symptomatic seizure, if
cause prone to recur, recurrence rate 32% at 2 years, but if
reversible 12% at 2 years (Leung, 2009)
 Driving and epilepsy

After diagnosis of epilepsy

Canada (CCMTA) 6 months and on medications, if >1 per year, 1 year

Australia(Austroads) 6 months and on treatment

UK 1 year and issue of 3-year licence only

USA Differs from states to states

New Zealand May resume driving 1 year seizure free

Sweden 2 years

HK Prohibits all who are diagnosed with epilepsy from driving, whether or
Rx or not. Terminal remission according to ILAE ~5 years seizure- free.
HK epilepsy guideline: inactive epilepsyà may apply for driving licence
under special circumstances but outcome subject to approval by
Transport Department
 For professional drivers?

After 1st seizure

Canada (CCMTA) 3 months

Australia(Austroads) 5 years

UK 5 years after medications taken off

USA Differs from states to states

New Zealand 5 years after medications taken off

Sweden 5 years

HK No guideline or consensus. Rehabaid has guideline which states

that a 10-year period if required
 For professional drivers?

Epilepsy
Canada (CCMTA) 5 years

Australia(Austroads) 10 years

UK 10 years after medications taken off

USA Differs from states to states

New Zealand 5 years after medications taken off

Sweden 5 years

HK Epilepsy diagnosis prohibits all professional drivers from driving

 Legal aspects
Mandatory reporting by physicians?
Involves doctors in the policing process, mistrust by patients to doctors

Countries in which mandatory reporting are in place

Sweden, Luxembourg, Austria, Denmark, Spain, 2 states of Australia, 6
states of USA

HK
No such enforcement, physicians should encourage patients to voluntarily
report their illness to Transport Department. Good practice to document
that you have discussed this with the patient in the medical notes
Licencing in HK: < 60 years, 10 year renewable, 60-70 years, 3 year-
renewable, >70 medical check-up + 1 year or 3 year renewable.
Station approach to epilepsy as
a chronic case

Introduce yourself and

establish rapport.
Go through the severity and
frequency of seizures since
last follow-up

Any hospital admissions?

Station approach to epilepsy as
a chronic case
Go to past history and identify
risk factors, if any (HI, feb
convulsion, FH, encephalitis, Go through the medications.
drug abuse) Check compliance. Any side
effects? Any operation
done?

Allergy
Station approach to epilepsy as
a chronic case
General inspection:
dysmorphic features, facial
haemangiomas, adenoma
Directed cranial nerve
sebaceum
examination: fields, ocular
movement, facial n, V
sensory, hearing

Ataxia?
Station approach to epilepsy as
a chronic case
Establish the plan for
medications this current visit.
Other additional InX.
If time allows, address other
issues: pregnancy, driving,
occupation

Listen to the patient. Allow

yourself 1 min to tidy up.
Present findings.
 Conclusions/take-home
message
Have some general ideas about seizures/epilepsy

Revise on how to take a history to differentiate the major

differential diagnosis of transient loss of consciousness

How to respond to ward-call/complaints of seizures on the

ward

How to manage an outpatient consultation for chronic epilepsy