Neurological science

1. Epilepsy
DR ANGWAFOR S.A (MD, MSC, PHD)
NEUROLOGIST
ASSISTANT LECTURER, UNIVERSITY OF BAMENDA

2. Objectives
 Define epilepsy
 Be familiar with the 2017 revised ILAE classification of epilepsy
 Understand the global burden of epilepsy
 Enumerate main causes and risk factors for epilepsy especially in Cameroon
 Understand guiding principles in the management of epilepsy
 Be familiar with medications used to treat epilepsy and their mode of action
 Enumerate common complications and comorbidities of epilepsy

3. Outline
 Definition of epilepsy
 Epidemiology of epilepsy
 Classification of epilepsy
 Main causes and risk factors for epilepsy
 Management of epilepsy: guiding principles
 Key learning points

4. Criteria for definition of epilepsy
 At least two unprovoked (or reflex) seizures occurring
> 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

5. Definition of epilepsy (ILAE)
 Epilepsy is a brain disease characterized by an enduring
predisposition to generate epileptic seizures
 It carries neurological, cognitive, psychological and social
consequences.
 People with epilepsy have recurring seizures that often occur
spontaneously and without warning

6. Epidemiology; key concepts
 Active epilepsy: Regular treatment with antiseizure medicines or when the
most recent seizure has occurred within the last 5 years
 Incidence of epilepsy: The number of new cases of epilepsy over a
specified period of time divided by the number of the population at risk
 Lifetime prevalence: The risk of having epilepsy at some point during the
lifetime
 Treatment gap; Proportion of people with epilepsy with no treatment or with
inadequate treatment

7. Prevalence of epilepsy
 Affects 50 million people worldwide
 80% live in LMICs
 The overall lifetime prevalence of epilepsy is 7.6 per
1000 population (95% CI: 6.17–9.38)
 The point prevalence of active epilepsy is 6.4 per 1000
persons (95% CI: 5.57–7.30)

8. Prevalence of epilepsy in Cameroon

9. Incidence of epilepsy
 The pooled incidence rate of epilepsy is 61.4 per 100 000
person-years
 Low- and middle-income countries (LMICs): 139.0 (95% CI:
69.4–278.2)
 High-income countries (HIC): 48.9 (95% CI: 39.0–61.1)
 Batibo Health District: 171.1 (95% CI 114-254.60)
 Centre Region: 350/100,000 person-years

10. Causes of epilepsy
 Structural: Traumatic brain injury, stroke, cerebral malformations,
tumour, birth injuries, brain infectious
 Genetic; strong family history, specific epilepsy gene(s), not
synonymous with inherited
 Infectious; meningitis, encephalitis, parasitic infections (NCC,
Malaria, trypanosoma, toxoplasmosis
 Others; Metabolic, Immune, Unknown

11. Infectious causes: Neurocysticercosis
 Parasite; Taenia solium
 Occurs when humans become aberrant intermediate hosts
 Up to 60% of epilepsy in some LMICs attributable to epilepsy
 Transmission favoured by poor hygiene
 Pathophysiological stages: vesicular, vesicular, colloidal, granulo-
nodular and granulomatous/calcified stages
 Treatment: AEDs, steroids, antiparasitic drugs

12. Infectious causes; Onchocerciasis
 Parasite: Onchocerca volvulus
 Transmission: through the simulium fly bred in fast flowing rivers
 Neurological features: Nakalanga syndrome, nodding syndrome,
Onchocerciasis associated epilepsy???
 Seizure mechanisms: unknown
 Epidemiological association with epilepsy: ecological studies,
case control, cohort,

13. Infectious causes; Malaria
 Caused by Plasmodium falciparum
 Malaria one of common causes of seizures in children in
endemic areas
 Distinguish between febrile seizures and malaria-
associated seizures
 Epilepsy in up to 10% after recovery from malaria

14. Other parasites associated with epilepsy
 Toxoplasmosis
 Toxocariasis
 Human African Trypanosomiasis
 Sparganosis
 Schistosomiasis
 Paragonimiasis

15. Comorbidities of epilepsy
 Greater risk of psychiatric, neurodegenerative and medical
conditions than the general population
 a dual pathology due to a shared aetiology or because of a
causal relationship
 Comorbidities often have a negative impact on the quality of
life of people with epilepsy, sometimes more than the
seizures themselves

16. Treatment gap
 About 10% in HIC but up to 95% in LMIC
 Higher in rural than urban areas
 Causes:
 Stigma
 Lack of skilled manpower
 Unaffordable cost of AEDs
 Unavailable AEDs

17. Premature mortality
 Up to 10X increased risk of death
 Risk of death: seizures, underlying aetiology, unrelated to
epilepsy
 Causes of Death:
 Status epilepticus
 Sudden unexpected death in epilepsy (SUDEP)
 Unintentional injuries

19. Epilepsy syndromes
 An epileptic disorder characterised by a cluster of signs and
symptoms customarily occurring together
 Includes such items as; the type of seizure, aetiology, anatomy,
precipitating factors, age of onset, severity, chronicity, diurnal and
circadian cycling, and sometimes prognosis.
 Unlike epilepsy disease, a syndrome does not necessarily have a
common aetiology and prognosis

20. Types of epilepsy syndromes
 Idiopathic epilepsy:only epilepsy, with no underlying
structural brain lesion or other neurological signs or
symptoms, presumed to be genetic and usually age
dependent
 Symptomatic epilepsy; epileptic seizures are the result of
one or more identifiable structural lesions of the brain

21. Types of epilepsy syndromes (Cont’d)
 Cryptogenic; unknown cause but presumed symptomatic
 Genetic epilepsy; the direct result of a known or
presumed genetic defect(s) in which seizures are the core
symptom of the disorder
 Benign epilepsy; epileptic seizures are easily treated or
require no treatment and remit without sequelae

22. Common idiopathic epilepsy syndromes
 Childhood absence epilepsy
 Juvenile myoclonic epilepsy
 Idiopathic epilepsy with GTCSs

23. Childhood absence epilepsy
 Age at onset in between 4 and 10 years; 2/3 are girls
 Normal development and neurological exam
 Typical absence seizures; 4-20 seconds, frequent (tens per day),
abrupt onset and severe LOC
 EEG: bilateral, synchronous and symmetrical 3 Hz GSWD, on a
normal background activity

24. Childhood absence epilepsy (Cont’d)
 No other seizures absent but GTCSs may occur in adolescence
after remission of absence seizures
 Prognosis; excellent
 Treatment; monotherapy with Valproate or ethosuximide

25. Juvenile myoclonic epilepsy
 Myoclonic jerks on awakening; 1-9 years after onset of absence
 GTCSs on awakening; usually few months after onset of
myoclonus
 Typical absence in > 2/3 of patients; begin between 5 and 16
years
 Seizures occur within 30 min to 1 hour of awakening

26. Juvenile myoclonic epilepsy (Cont’d)
 Seizure precipitating factors: sleep deprivation, fatigue and
excessive alcohol intake
 Aetiology ; genetically determined, probably polygenic
 EEG usually abnormal, with 3–6 Hz GPSWD, and with intra-
discharge fragmentations and unstable intra-discharge frequency
 Treatment; Valproate, Levetiracetam

27. Epilepsy with GTCSs only
 Age at onset ; from 6 to 47 years with a peak at 16 or 17 years
 GTCSs can occur on awakening, randomly, during sleep, while awake
 Main type; Epilepsy with GTCS on awakening (EGTCSA)
 Precipitating factors: sleep deprivation, fatigue, excess alcohol
 Aetiology ; genetic
 EEG; GPSWD in half of patients with pure EGTCSA
 Treatment; Valproate, Levetiracetam, Lamotrigine, Phenobarbital

28. Pharmacological treatment
Aim; total freedom from seizures with no clinically significant
adverse effects
 This has now been broadened to include optimal outcomes of
health-related quality of life with regard to physical, mental,
educational, social and psychological functioning of the patient
 Anti-epileptic drugs (AEDs) are effective in 80% of cases
 20% may need epilepsy surgery

29. Old generation AEDs
 Phenobarbital
 Phenytoin
 Carbamazepine
 Sodium Valproate
 Ethosuximide
 Clonazepam
 Clobazam

30. New generation AEDs
 Lamotrigine
 Levetiracetam
 Topiramate
 Oxcarbazepine
 Pregabalin
 Tiagabine
 Gabapentin
 Zonisamide

31. Criteria for choosing AEDs
 Seizure specificity
 Strength of efficacy
 Spectrum of efficacy
 Safety
 Tolerability
 Adverse drug reactions
 Pharmacokinetics

32. Criteria for choosing AEDs (Cont’d)
 Pharmacodynamics
 Drug-drug interactions
 Mechanism of action
 Speed of titration
 Need for laboratory testing
 Frequency of administration and ease of use
Cost of treatment

33. AEDs; mechanism of action
 Blockage of voltage-gated sodium channels; carbamazepine,
lamotrigine, Oxcarbazepine, phenytoin
 Multiple including blockage of voltage gated sodium channels:
phenobarbital, topiramate, Valproate, Zonisamide
 Increasing GABA inhibition; clobazam, clonazepam,
Tiagabine, Vigabatrin

34. AEDs; mechanism of action (Cont’d)
 Blocking T-Type Calcium channels: ethosuximide
 Modified Calcium and neurotransmitter release: Gabapentin,
pregabalin
 Novel; binding to synaptic vesicles 2A Protein; Levetiracetam

35. Adverse effects of some AEDs
 Carbamazepine; idiosyncratic rash, headache, ataxia, nystagmus, diplopia,
tremor, hyponatremia
 Phenytoin; Idiosyncratic rash, ataxia, drowsiness, lethargy, sedation,
encephalopathy, gingival hyperplasia, hirsutism, dysmorphism, rickets,
osteomalacia
 Valproate; Nausea, vomiting, dyspepsia, weight gain, tremor, hair loss,
hormonal in women
 Phenobarbital; Idiosyncratic (rash), severe drowsiness, sedation, impairment
of cognition and concentration

36. Adverse effects AEDs (Cont’d)
 Lamotrigine; Idiosyncratic (rash), tics, insomnia, dizziness, diplopia,
headache, ataxia, asthenia
 Levetiracetam; Irritability, behavioural and psychotic changes, asthenia,
dizziness, somnolence, headache*
 Oxcarbazepine; Idiosyncratic (rash), headache, dizziness, weakness,
nausea, somnolence, ataxia and diplopia, hyponatraemia
 Pregabalin; weight gain, myoclonus, dizziness, somnolence, ataxia,
confusion

37. Starting treatment in newly diagnosed epilepsy
 Ensure that the diagnosis is accurate
 Determine that antiepileptic treatment is necessary
 Select the most appropriate AED for the patients seizures
 Monotherapy should be prioritised; Start low go slow!!
 Involve patient in the decision-making
 Education of patient is key
 Discontinuation of treatment must be slow and in small doses

38. Recommendations for choosing AEDs
 Focal seizures: carbamazepine, phenytoin, phenobarbital, levetiracetam,
lamotrigine, oxcarbazepine
 Primary GTCSs only: Valproate, phenobarbital, phenytoin, levitiracetam,
lamotrigine, topiramate
 Myoclonic seizure only: Clonazepam, valproate, phenobarbital,
levetiracetam
 Absence seizures only; Valproate, Ethosuximide, Lamotrigine

39. Key learning points
 Epilepsy is an ubiquitous brain disease characterized by an
enduring predisposition to generate epileptic seizures
 The classification of epilepsy is a dynamic process that takes into
account the following; epilepsy type, epilepsy syndrome, causes and
comorbidities
 Parasitic diseases are most important causes of epilepsy in LMICs
 Premature mortality is up to six times higher in people with epilepsy

40. Key learning points
 Most but not all idiopathic or genetic epilepsy syndromes respond well to
selected AEDs and have an overall good prognosis
 Overall, there is no difference in efficacy between old and new generation
AEDs in the prophylactic treatment of epilepsy but the latter has a generally
better side effect profile
 The aim of epilepsy treatment is to achieve seizure freedom with minimal or no
adverse effects
 The most important criteria for choice of AEDs low resource settings is cost
and availability