EPILEPSY

PRESENTATION BY: DR MAKOJOA K, INTERN DR – IMED

MAFETENG GOVERNMENT HOSPITAL
AUGUST 2022

MODERATOR: DR MADANI, CONSULTANT PHYSICIAN

EPILEPSY: PRESENTATION OUTLINE
1. INTRODUCTION
2. EPIDEMIOLOGY
3. AETIOLOGY
4. CLASSIFICATION
5. MANAGEMENT PROTOCOLS
6. CONCLUSION
EPILEPSY: INTRODUCTION
• Seizures are a result of excessive electrical discharges in a group of brain cells.
They can vary from the briefest lapses of attention or muscle jerks to severe and
prolonged convulsions, and they can vary in frequency from less than one per year
to several per day.
• Epilepsy, on the other hand is a common chronic condition characterized by
recurrent (at least two) unprovoked seizures which are not induced by a clear
cause such as fever, stress or lack of sleep.
• Diagnosis may be clinical and involves results of neuroimaging, laboratory testing
and EEG for new onset seizures or levels of anti-seizure drugs for previously
diagnosed seizure disorders.
• Treatment includes elimination of the cause if possible, anti-seizure drugs and
surgery (if the drugs are ineffective) (Adamolekun B, 2020).
EPILEPSY: EPIDEMIOLOGY
• In 2020, Boon P. et al, reported that epilepsy affected approximately
50,000,000 people worldwide.
• In Mafeteng GH, currently following up……… of patients in the Clinic
EPILEPSY: AETIOLOGY (WHO-EM/MNH/220/E).

AETIOLOGY

IDIOPATHIC GENETICS BIRTH TRAUMA BRAIN LESIONS SEVERE HEAD INJURIES

EPILEPSY: AETIOLOGY CONT..
- Before Age 2: fever, hereditary or congenital neurologic disorders,
birth injuries, inherited or acquired metabolic disorders
- Age 2 – 14: Idiopathic seizure disorders
- Adults: cerebral trauma, alcohol withdrawal, tumours, strokes and
idiopathic
- Older people: tumours and strokes
EPILEPSY: ILAE CLASSIFICATION -
2017
Focal Onset Generalised Onset Unknown Onset
Aware Impaired Awareness Motor Motor
Tonic – clonic Tonic – clonic
Motor Onset Clonic
Epileptic spams
Automatisms Tonic
Atonic Myoclonic
Clonic Myocloni-tonic-clonic Non-Motor
Epileptic spasms Myoclonic-atonic Behaviour arrest
Hyperkinetic Atonic
Myoclonic Epileptic spasms
Tonic Non – Motor (absence)
Non – Motor Onset Typical
Autonomic Atypical
Behaviour arrest Myoclonic
Cognitive dysfunctiion Eyelid myoclonia
Emotional dysfunction
Sensory dysfunction
Focal to Bilateral Tonic – Clonic Unclassified
EPILEPSY: OTHER TYPES OF
SEIZURES
• Epilepsia partialis continua: rare disorder, continuous focal aware motor seizure, usually
involves arm, hand,or one side of face. Cause usually - structural lesion (stroke) in adults,
focal cerebral cortical inflammatory process (eg Rasmussen encephalitis – chronic viral
infection or autoimmune processes) in children,
• Lennox – Gastaut Syndrome: severe from of epilepsy that causes several types of seizures,
usually begins before age of 4 and can continue to adulthood due usually to brain,
malformations, tuberous sclerosis, perinatal asphyxia, severe head injury, cns infection,
genetics or metabolic disorders
• Febrile Seizures: fever in the absence of intracranial infection, proked seizures
• Dravet Syndrome: severe mayoclonic epilepsy of infancy, develops in early childhood, has
focal and generalized components
• Status Epilepticus: continuous seizure activity , focal or generalized, has 2 forms: convulsive
(prominent motor symptoms), non-convulsive ( without prominent symptoms)
EPILEPSY: DIAGNOSIS
1. Clinical Evaluation
2. Laboratory Tests
3. NeuroImaging (EEG): for new onset seizures
4. Antiseizure Drug Levels: for known seizure disorder
5. Other Testing as clinically indicated: for new-onset or known seizure
disorder
EPILEPSY: DIAGNOSIS - CLINICAL
EVALUATION
History (Socrates)
- Onset: When?
- Character: type of seizure (focal/generalized) and subtype?, post-ictal
phase, precipitating factors, frequency and interval between
episodes
- Associated Factors:
- aura (flashing light, sounds, video, etc)?
- meningism
- Timing: Duration of the seizure
CLINICAL EVALUATION
History Cont….
- Past Medical/Surgical Hx
- Prior neurologic disorders
- Head trauma
- Personal/Social Hx
- Drug use or withdrawal particularly recreational drugs
- Family hx of seizures or neurologic hx
- Sleep deprivation
EPILESPSY: DIAGNOSIS – CLINICAL
EVALUATION
Physical Examination Pseudoseizure Clinical Features
- last longer (mins or more)
General condition:
- no post-ictal confusion
- prolonged confusion (after loss of - no typical tonic phase followed by clonic phase
consciousness) > seizure - intensity max wax and wane
- bitten tongue - vital signs usually remain normal
- patients often actively resist passive eye opening
- incontinence (soiled clothing)
- progression of muscular activity does not
- GCS: verbal response, correspond to true seizure patterns (eg
differentiates generalized tonic- pseudo-seizure movements may include jerks
clonic moving from one side to the other and back and
seizures from pseudoseizures exaggerated pelvic thrusting
EPILEPSY: DIAGNOSIS – CLINICAL
EVALUATION
Differential Diagnoses:
Finding Possible Cause
Fever & Neck Stiffness Meningitis, meningoencephalitis, SAH
Papilloedema Increases ICP
Loss of spontaneous venous pulsations Increased ICP (specificity is 80 – 90%)
Focal neurologic defects (eg asymmetry of Structural brain abnormality (eg tumour,
reflexes or muscle strength stroke), post-ictal paralysis

Generalised neuromuscular irritability eg - Drug toxicity ( eg sympathomimetics)

tremulousness, hyperreflexia - Withdrawal symptoms (eg alcohol,
sedatives)
- Certain metabolic disorders eg
hypocalcaemia, hypomagnesia

Skin lesions (eg axillary freckling or café-au-lait - Neurocutaneous disorders eg

spots, hypomelanotic skin macules, shagreen neurofibromatosis, tuberous sclerosis)
patches)
EPILEPSY: DIAGNOSIS -
INVESTIGATIONS
Laboratory
1. New Onset Seizure Disorder
- Urea & Electrolytes, Creatinine
- Serum glucose
- LFTs
2. Known Seizure Disorder
- Rule out treatable disorder
EPILEPSY: DIAGNOSIS -
INVESTIGATIONS
• NeuroImaging
- Head CT, sometimes MRI to exclude mass or haemorrhage
NB; no to be done in febrile seizures where neurologic status rapidly returns to
normal
- ElectroEncephalopathy (EEG):
- epileptiform abnormalities (spikes,sharp waves, spike and
slow-wave complexes, poly spike and slow wave complexes)
- epileptiform abnormalities may be bilateral, symmetric and
synchronous in patients with generalized –onset seizures and may be
localized in patients with focal-onset seizures
EGG CONNECTION
EEG TRACE
EPILEPSY: DIAGNOSIS -
INVESTIGATIONS
Some EEG Findings:
- Epileptiform abnormalities in temporal lobe foci between seizures
(intraictal) in focal impaired awareness seizures originating in the temporal
lobe
- Intraictal bilateral symmetry bursts of 4 to 7 Hz epileptiform activity in
primarily generalized tonic-clonic seizures
- Focal epileptiform discharges in focal-to-bilateral tonic-clonic seizures
- Spikes and slow-wave discharges occurring bilaterally at a rate of 3/sec
and usually normal background EEG activity in typical absence seizures
NB: EEG is less likely to detect abnormalities if seizures are infrequent.
EEG
Other types of EEG
- Inpatient Combined Video-EEG Monitoring:
Usually for 2 to 7 days. It records EEG activity and clinical behavior
simultaneously.
It is the most sensitive EEG testing available and is thus useful in
differentiating epileptic from non-epileptic seizures
- Ambulatory EEG
Can be done while patients are at home.
It may be useful if seizures recur in patients who cannot be admitted to
hospital for a long time
EPILEPSY: DIAGNOSIS -
INVESTIGATIONS
• Neuropsychologic Testing
It may be helpful in identifying functional deficits before and after
surgery and help predict social and psychologic prognosis
EPILEPSY: PROGNOSIS
• With treatment seizures are eliminated in 1/3 of patients with
epileptic seizures, frequency is reduced by > 50% in another
• About 60% of patients whose seizures are well-controlled by drugs
can eventually stop the drugs
• Epileptic seizures are considered resolved when patients have been
seizure-free for 10 years and have not taken anti-seizure drugs for the
last 5 years of that time period
EPILEPSY: TREATMENT – GENERAL
MEASURES
In general, especially for generalized tonic-clonic seizures
- Prevent further injuries: loosen clothing, pillow under head, recovery position, nothing in the
mouth
Risky Activities
- no to activities that demands 100% consciousness eg driving, swimming, climbing, operating
power tools, bathing in a bath-tab
These activities can resume once seizures are controlled for >6months, but with appropriate
safeguards
Substance Use
- Patients to avoid illicit drugs like phencyclidine, amphetamines which can trigger seizures
- Alcohol to be avoided at all costs
- Avoid other drugs like haloperidol and phenothiazines, they lower seizure threshold
EPILEPSY:TREATMENT (DRUGS AND MOA). COURTESY OF NEAL
M.J. 2012
EPILEPSY: TREATMENT
Generalised Convulsive Status Epilepticus
- Immediate aborting of fits is mandatory. Endotracheal intubation may be done if airway is compromised
- IV Access
- IV lorazepam 0.05 to 0.1mg/kg (typically 4mg IV dose for adults),
Then followed by long-acting agent
Preferred long-acting agents are:
- IV phenytoin 15mg to 20 mg/kg, given at a rate of 50mg/min
- IV valproate 20 – 40mg/kg loading over 30 mins, then 4 – 8mg/kg po tds
- IV levetiracetam 1500 – 3000mg over 25mins, then 1500mg po tds
- IV Fosphenytoin 15 – 20mg/kg PE given at a rate of 100-150PE/min
NB: PE = Phenytoin Equivalents, 1mg phenytoin = 1.5mg fosphenytoin
If IV access is not obtained, other options include: IM fosphenytoin + SL/PR benzodiazepines
EPILEPSY EMERGENCY
If seizures persist after using 2 agents = Refractory Status Epilepticus.
Third Agent Options
- phenobarbital, propofol, midazolam,levetiracetam and valproate.
- IV phenobarbital 15 -20mg/kg @ 100mg/min (in children: 3mg/kg/min)
Fourth Options
- If still refractory, further IV phenobarbital 5-10mg/kg or
IV valproate 20 – 40mg/kg
Firth Option
- Intubation + general anesthesia
- GA Options: - propofol 1-2mg/kg @ 100mg/min
- pentobarbital 5-8mg/kg loading dose, then infusion of 2-4mg/kg/hr until EEG manifestations of seizure
acivity have been suppressed.
Infusions should be continued for ≥ 24 hours then stopped so that EEG can be repeated and reassessed
POSTTRAUMATIC SEIZURES
Post-Traumatic Seizures:
Drugs are given to prevent seizures if head injury causes significant structural injury
eg large contusions or haematomas, brain laceration, depressed skull fracture or if
GCS < 10.

The drugs reduce risk of seizures during 1st week after injury but do not prevent
permanent posttraumatic epilepsy months or years later
They have to be stopped after 1 week unless seizures occur.

If seizures begin > 1 week after head injury, long term treatment with drugs is
required.
EPILEPSY: TREAMENT – LONG TERM
DRUG THERAPY
Antiseizure may be required indefinitely.
No single drug controls all types of seizures and different patients
require different drugs.

Table below highlights the drugs in current use:

EPILEPSY: TREATMENT – LONG
TERM DRUGS
Seizure Type 1st Line 2nd Line
Focal (partial) seizures carbamazepine or lamotrigine Levetiracetam, oxcarbazepine or
valproate
Generalised Tonic-Clonic Seizures valproate or lamotrigine carbamazepine, clobazam,
levetiracetam, topiramate
Absence Seizures valproate or ethosuximide lamotrigine
Myoclonic Seizures valproate Levetiracetam or topiramate,
NB. NO carbamazepine nor
oxcarbazepine, they worsen
seizures
Tonic/Atonic Seizures valproate or lamotrigine
EPILEPSY:TREATMENT – TYPICAL
DOSAGES
Drug Dose
carbamazepine 100mg po bd initially
increase by 200mg/day every 2 weeks up
to max 100mg bd

lamotrigine 25mg/d as monotherapy, increase by 50mg/day every 2 weeks up to 100mg

bd (max. 250mg bd)
-1/2 a dose if patient is on valproate
- double dose if carbamazepine or
phenytoin (max. 350mg bd)
COMMONLY USED THERAPIES
Drug Dose
valproate initially 300mg bd
increase by 100mg bd every 3 days up
to max of 30mg/kg (or 2.5g )od
Levetiracetam initially 250mg od
increase by 250mg bd every 2/52 up to
max 1.5gbd (if eGFR > 80
ml/min/1.73m2)
OTHER TREATMENT MODALITIES
Surgical Intervention
Is an option for seizures that are refractory to medical interventions but lots
of costly investigations have to be done
Vagus Nerve Stimulation
Used in patients with intractable seizures. Left vagus nerve with an implanted
pacemaker-like device (or vagus nerve stimulator)
Adverse effects are: deepening voice during stimulation, cough and
hoarseness
Brain Responsive Neurostimulation
- Complicated procedure of implanting a device intracranially
EPILEPSY: TREATMENT – ADVANCE
IN
Treatment of epilepsy with drugs dates as far back as 1900.
And several agents were developed over these ages eg
1900 – 1950: phenobarbital and phenytoin
1951 – 1985: carbamazepine, diazepam, valproate, ethosuximide etc
1986 – 2000: lamotrigine, lorazepam, oxcarbazepine etc
2001 – 2015: lacosamide, perampanel, stripentol, etc
2015 – 2021: cannabidiol, brivaracetam, cenobamate, everolimus,
fenfluramine
ADVANCES IN EPILEPSY
• The new agents have come in with more advantages over the older
ones with better pharmacological profile.
• It is not only new agents that have been introduced into the ,market
but new formulations as well. Eg intranasal diazepam & midazolam.
EPILEPSY: TREATMENT – FUTURE
PROSPECTS
There is extensive research ongoing in many areas, which will improve
epilepsy outcomes.
- In most recent times, 1 year ago a smartphone app has been developed to
assist non-specialist health practitioners for better prescriptions. The app is
freely available and obtainable on www.epipick.org
- Biomarker – guided therapies are underway
- Precision therapies are being developed eg utilization of ketogenic diet to
control seizures associated with Glucose Transporter Type 1 (GLUT 1)
deficiency syndrome.
- Examples of drugs under clinical trials include: carisbamate, annex 2-73 etc
EPILEPSY: CONCLUSION
There is ongoing multi-disciplinary efforts to improve clinical outcomes
for people with epilepsy due to:
- advances in IT,
- development of novel precision therapies,
- identification of biomarkers to guide drug development and
- ultimately introduction of truly innovative disease modifying
therapies
REFERENCES
Perucca E. The Pharmacological Treatment of Epilepsy:Recent
Advances and Future Perspectives. (2021)3:22.
https://doi.org/10.1186/s42494-021-00055-z
Boon P. et al. Recommendations for the Treatment of Epilepsy in Adult
and Pediatric Patients in Belgium: 2020 Update. (2021)121:241- 257.
https://doi.org/10.1007/s13760-020-0148-y
Adamolekun B. Seizure Disorders. (2022) in MSD Manual
Neal M.J, 2012. Medical Pharmacology at a glance. 7th Edition. Wiley-
Blackwell. London
WHO. Epilepsy and Seizures.2019
THANK YOU