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EPILEPSY
PRESENTED BY DR KD DELE IJAGBULU
DEPARTMENT OF FAMILY MEDICINE | DORA NGINZA HOSPITAL
INTRODUCTION
& EPIDEMIOLOGY
INTRODUCTION
• Epilepsy is a neurological disorder that is characterized by an enduring
predisposition to generate epileptic seizures and is associated cognitive,
psychological and social consequences (Fischer et al, 2017)
• An epileptic seizure is a transient behavioural change caused by abnormal
excessive or synchronous neuronal activity in the brain, and is associated
with objective signs or subjective symptoms such as loss of awareness,
stiffening, jerking, a sensation that rises from the abdomen to the chest, a
smell of burnt rubber or déjà vu
IMPACT OF EPILEPSY ON QUALITY OF LIFE
• Epilepsy affects all age
• No sex difference, however it is often underreported among females.
• It is a common and one of the most disabling neurological disorders.
• Epilepsy can substantially impair quality of life owing to seizures, comorbid
mood and psychiatric disorders, cognitive deficits and adverse effects of
medications.
IMPACT OF EPILEPSY ON QUALITY OF LIFE
• Seizures can be fatal owing to direct effects on autonomic and arousal
functions or owing to indirect effects such as drowning and other
accidents.
• The accurate diagnosis of seizures is essential as misdiagnosis and
inaccurate medication often have severe consequences.
• Although many patients have seizure control using a single medication,
others require multiple medications, resective surgery, neuromodulation
devices or dietary therapies.Also or clinical trials of new ASDs
IMPACT OF EPILEPSY ON QUALITY OF LIFE
• Epilepsy can be a significant burden for patients and caregivers.
• Adverse effects (by the condition and the medications) contribute to
decreased quality of life.
• One-third of patients will continue to have uncontrolled seizures.
• Children and adolescents who are trying to be socially accepted have
increased difficulty e.g. when their AED cause sedation
IMPACT OF EPILEPSY ON QUALITY OF LIFE
• There have been different moves to reduce stigma associated with
epilepsy
• For example, changing the nomenclature: It is strongly encouraged to
discontinue the use of the term epileptic to reduce stigma;
• however, antiepileptic drug (AED) remains the terminology used in the
literature; however, newer literatures are beginning to use the term “Anti-
seizure drugs” (ASD)
IMPACT OF EPILEPSY ON QUALITY OF LIFE
• For many patients, seizures can remit; however some might relapse after
remission.
• Epilepsy is considered resolved when
• an individual is seizure free and older than the applicable age for an
age-dependent epilepsy syndrome, or,
• when the person has remained seizure free for ≥10 years with no anti-
seizure medication for the past 5 years
IMPACT OF EPILEPSY ON QUALITY OF LIFE
• The loss of driving privileges
• Social stigma
• Employment difficulties
• Loss of marriage, and other relationships
• Wrong diagnosis of epilepsy (common) leads to the improper use of anti-
seizure medications leading to anti-seizure-drug-associated adverse effects,
including inducing further seizures
EPIDEMIOLOGY
• Almost 10% of people will experience a seizure during their lives.
• Epilepsy is the third leading contributor to the global burden of disease
for neurological disorders and affects 65 million people worldwide.
• the prevalence of epilepsy is 6.4 cases per 1,000 persons and the annual
incidence is 67.8 cases per 100,000 person-years
• Both prevalence and incidence are higher in low-income and middle-
income countries (LMICs) than in high-income countries, however
underreported due to stigma associated, mostly among women.
EPIDEMIOLOGY
• The incidence of epilepsy is bimodal: highest in younger age groups (for
example, in infancy and early childhood) and in older age groups (for
example, more than 50–60 years of age).
• Whereas the prevalence tends to be lowest in infants and children,
increases in early adulthood – midlife and decreases later in life.
• The higher prevalence of Epilepsy in LMICs is believed to be partly due to
a higher frequency of traffic accidents, birth injuries and neuroinfectious
disorders (such as neurocysticercosis) that can cause epilepsy in LMICs
Incidence of epilepsy by age—composite of 12 studies in developed countries, 1988–2005.. SOURCE:
Thurman, 2011. https://www.nap.edu/read/13379/chapter/3#26
estimated number of patients in Scotland consulting a GP or practice nurse at least once in the financial year 2012/13.
https://www.isdscotland.org/Health-topics/General-practice/Gp-consultations/Health-Conditions/Epilepsy/index.asp
AETIOLOGY
PRECIPITANTS
• Alcohol withdrawal
• Fever
• Head injury and surgery
• Infections
• Metabolic abnormalities
• Photosensitivity and auditory
stimuli
• Sleep deprivation
• Stress
• Drugs
CAUSES OF EPILEPSY
• Structural: stroke and brain tumours
• Genetic: SCN1A-related epilepsies),
• Infectious: bacterial or viral brain infections
• Metabolic: facilitated glucose transporter member 1 (GLUT1) deficiency
• Immune: multiple sclerosis and autoimmune encephalitis
• Unknown aetiologies
CAUSES OF EPILEPSY…
STRUCTURAL
• Neurotrauma – Multiple
• De novo status epilepticus – TLE
• Stroke – Multiple
• Blood–brain barrier damage – Multiple
• Cortical dysplasia – Multiple
• Glioblastoma - Multiple
• Developmental epileptic encephalopathies –
infantile spasm,multiple
GENETIC OR PRESUMED GENETIC
• Tuberous sclerosis complex – Tuberous
sclerosis complex
• Spontaneous mutations – Absence epilepsy
• Induced monogenic mutations – Multiple
• Developmental epileptic encephalopathies –
Infantile spasms, Dravet syndrome
CAUSES OF EPILEPSY…
• Other causes include primary CNS dysfunction or underlying metabolic
derangement or systemic diseases
• Common causes:
• In children, congenital and genetic causes
• In young adult, tumours, alcohol and drugs
• In elderly, cerebrovascular diseases
CAUSES ACCORDINGTO AGE
• Neonates
• Perinatal hypoxia and ischaemia
• Intracranial haemorrhage/trauma
• Acute CNS infection
• Metabolic disturbance (hypo – glycaemia, calcaemia and magnesaemia;
pyridoxine deficiency)
• Drug withdrawal
• Developmental disorders
• Genetic disorders
CAUSES ACCORDINGTO AGE
• >1 month to <12yrs
• Febrile seizures
• Genetic disorders
• CNS infection
• Developmental disorders
• Trauma
• Idiopathic
CAUSES ACCORDINGTO AGE
• Adolescents (12-18yrs)
• Trauma
• Genetic disorders
• Infection
• Brain tumours
• Illicit drugs
• Idiopathic
CAUSES ACCORDINGTO AGE
• 18-35yrs
• Trauma
• Alcohol withdrawal
• Illicit drug use
• Brain tumour
• Idiopathic
MORTALITY
EPILEPSY CAN BE LETHAL DUETO THE DIRECT & INDIRECT EFFECTS
OF SEIZURES
• THE DIRECT EFFECTS: e.g.
• sudden unexpected death in epilepsy
• status epilepticus
• Accidents such as : drowning motor
vehicle accidents, falls and burns
• THE INDIRECT EFFECTS: e.g.
• aspiration pneumonia,
• suicide 5-25x more in epileptics
• adverse effects of ASDs or psychiatric
drugs, such as obesity and
cardiovascular side effects
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
• The spread of electrical activity between cortical neurones is normally
restricted.
• Synchronous discharge of neurones in normal brain takes place in small groups
only.
• During a seizure, large groups of neurones are activated repetitively and hyper-
synchronously,There is failure of inhibitory synaptic contact between neurones.
• This causes high voltage spike-and-wave activity on EEG.
Epilepsy and inflammation in the brain. https://www.semanticscholar.org/paper/Epilepsy-and-inflammation-in-
the-brain%3A-overview-Vezzani/86351e1c5e25a373c2b3b13977efd2ec679cfa7a
CLASSIFICATION
HISTORICAL PERSPECTIVES
• For over 35 years, the terms partial and generalized seizures were used to
describe types of seizures:
• Partial (seizures starting in one area or side of the brain) and
• Generalized (seizures starting in both sides of the brain at the same time).
• Partial seizures were further classifies into
• Simple partial seizures (Person is aware of what happens during the event.)
• Complex partial seizures: (Person has some impaired awareness during the
seizure.)
CLASSIFICATION
1. Seizures may present with a variety of symptoms, and awareness may be
either intact or impaired.
2. Seizures are further described by the presence of motor movements,
including automatisms or other motor activity, and by nonmotor onset
symptoms, including sensory or autonomic symptoms.
CLASSIFICATION
• Seizure onset can be :
• Focal: when abnormal neuronal activity arises in one or more localized
brain regions or hemisphere;
• Generalized: when abnormal neuronal activity begins in a widespread
distribution over both hemispheres; or
• Of unknown onset: if the available clinical and laboratory data cannot
identify whether the onset is focal or generalized.
CLASSIFICATION
• The International League against Epilepsy (ILAE) published in the April
2017 edition of Epilepsia three companion articles on the classification of
seizures and the epilepsies,
• (These represent a long-awaited update on the original 1981 and 1989
classifications).
• The new classification provide a modern descriptive template for epilepsy;
by using more accessible, transparent language suitable for clinicians,
scientists, and patients
CLASSIFICATION
• The new classification presents three levels of terminology, involving
1. Where seizures begin in the brain
2. Level of awareness during a seizure
3. Other features of seizures – e.g. motor vs non-motor.
The management of epilepsy in children and adults by Perucca P, et al. MJA 208 (5) j 19 March 2018
CLASSIFICATION
The management of epilepsy in children and adults by Perucca P, et al. MJA 208 (5) j 19 March 2018
ONSET: DEFINING WHERE SEIZURES BEGIN
• The first step is to separate seizures by how they begin in the brain.
• The type of seizure onset is important because it affects choice of seizure
medication, possibilities for epilepsy surgery, outlook, and possible causes.
ONSET: DEFINING WHERE SEIZURES BEGIN
• Focal seizures: Previously called partial seizures, these start in an area or network of
cells on one side of the brain.
• Generalized seizures: Previously called primary generalized, these engage or involve
networks on both sides of the brain at the onset.
• Unknown onset: If the onset of a seizure is not known, the seizure falls into the
unknown onset category. Later on, the seizure type can be changed if the beginning of a
person’s seizures becomes clear.
• Focal to bilateral seizure: A seizure that starts in one side or part of the brain and
spreads to both sides has been called a secondary generalized seizures.The new term for
secondary generalized seizure would be a focal to bilateral seizure. (Now the term
generalized refers only to the start of a seizure. )
DESCRIBING AWARENESS
• Whether a person is aware during a seizure is of practical importance
• This is because it is one of the main factors affecting a person’s safety
during a seizure.
• Awareness is used instead of consciousness, because it is simpler to
evaluate.
DESCRIBING AWARENESS
• Focal aware: If awareness remains intact, even if the person is unable to talk or respond
during a seizure, the seizure would be called a focal aware seizure.This replaces the term
simple partial.
• Focal impaired awareness: If awareness is impaired or affected at any time during a seizure,
even if a person has a vague idea of what happened, the seizure would be called focal impaired
awareness.This replaces the term complex partial seizure.
• Awareness unknown: Sometimes it’s not possible to know if a person is aware or not, for
example if a person lives alone or has seizures only at night
• Generalized seizures: These are all presumed to affect a person’s awareness or
consciousness in some way.Thus no special terms are needed to describe awareness in
generalized seizures.
OTHER FEATURES OF SEIZURES
• Many other symptoms may occur during a seizure.
• In this basic system, seizure behaviours are separated into groups that
involve movement.
1. DESCRIBING MOTOR AND OTHER SYMPTOMS IN
FOCAL SEIZURES
• Focal motor seizure: This means that some type of movement occurs during the event.
For example twitching, jerking, or stiffening movements of a body part or automatisms
(automatic movements such as licking lips, rubbing hands, walking, or running).
• Focal non-motor seizure: This type of seizure has other symptoms that occur first, such
as changes in sensation, emotions, thinking, or experiences. It is also possible for a focal
aware or impaired awareness seizure to be sub-classified as motor or non-motor onset.
• Auras: The term aura, which describes symptoms a person may feel in the beginning of a
seizure, is not in the new classification.Yet people may continue to use this term. It’s
important to know that in most cases, these early symptoms may be the start of a seizure
1. DESCRIBING MOTOR AND OTHER SYMPTOMS IN
FOCAL SEIZURES
MOTOR ONSET
• automatisms
• atonic
• clonic
• epileptic spasms
• hyperkinetic
• myoclonic
• tonic
NON-MOTOR ONSET
• autonomic
• behaviour arrest
• cognitive
• emotional
• sensory
2. DESCRIBING GENERALIZED ONSET SEIZURES
• Generalized onset seizures can be motor or non-motor.
• Generalized motor seizure:
• The generalized tonic-clonic seizure term is still used to describe seizures with stiffening (tonic)
and jerking (clonic).This loosely corresponds to “grand mal.” Other forms of generalized motor
seizures may happen. Many of these terms have not changed, and a few new terms have been
added. (see image below)
• Generalized non-motor seizure:
• These are primarily absence seizures, and the term corresponds to the old term "petit mal."
These seizures involve brief changes in awareness, staring, and some may have automatic or
repeated movements like lip-smacking.
2. DESCRIBING GENERALIZED ONSET SEIZURES
MOTOR
• tonic-clonic
• clonic
• tonic
• myoclonic
• myoclonic-tonic-clonic
• myoclonic-atonic
• atonic
• epileptic spasms
NON-MOTOR (ABSENCE)
• typical
• atypical
• myoclonic
• eyelid myoclonia
Symptoms MedicalTerm
automatic behaviors automatisms
emotions or appearance of emotions emotions
extension or flexion postures tonic
flushing/sweating/piloerection autonomic
jerking arrhythmically myoclonus
jerking rhythmically clonus
language or thinking problems, deja vu cognitive
lid jerks eyelid myoclonia
limp atonic
numb/tingling, sounds, smells, tastes visions, vertigo sensations
pausing, freezing, activity arrest behavior arrest
thrashing/pedaling hyperkinetic
trunk flexion spasm
DIAGNOSIS
& DIFFERENTIAL DIAGNOSES
DIAGNOSIS
• Often over-diagnosed
• Diagnosis is essentially clinical
• Description of the seizure provided by an eye witness (MOST seizures)
• Sometimes patient self especially in partial onset
• Good history and examination
• Generally no place for a therapeutic trial
DIAGNOSIS/CASE DEFINITION
• The case definition of epilepsy, based on combined clinical and epidemiological
evidence, includes the following:
• Patients with two or more unprovoked or reflex seizures that are >24 hours
apart;
• Patients with one unprovoked or reflex seizure and who have a ≥60% chance of
further seizures over the following 10 years, e.g. patients with a known structural
lesion such as stroke, severe traumatic brain injury or brain infection
• Patients with one or more seizures in the context of a well-defined epilepsy
syndrome (for example, childhood epilepsy with centrotemporal spikes)
NEUROLOGICAL DIFFERENTIAL DIAGNOSIS
EPILEPTIC SEIZURES ARE OFTEN CONFUSED WITH OTHER PHYSIOLOGICAL
DISORDERS AND PSYCHIATRIC DISORDERS
• Benign paroxysmal positional vertigo
• Breath-holding attacks
• Daydreaming
• Migraine
• Parasomnias (such as REM sleep
behaviour disorder)
• Narcolepsy and/or cataplexy
• Syncope; tics
• Periodic leg movements during sleep
• Panic attacks
• Paroxysmal dyskinesia
• Psychogenic non-epileptic seizures
• Sleep apnoea
• Transient global amnesia. and
• Transient ischaemic attacks
MANAGEMENT
MANAGEMENT
• Lifestyle modification
• Education
• Drug treatment
• Surgery
LIFESTYLE MODIFICATION
AVOID FACTORS THAT COULD LOWER SEIZURE THRESHOLD
• Stress
• Alcohol use or withdrawal
• Dehydration
• Drugs & drug interactions
• Photosensitive stimuli (flashing TV
program or computer games)
• Hyperventilation
• Diet & missing meals
• Sleep deprivation
• Extreme fatigue
• Systemic infections
LIFESTYLE MODIFICATION
• Never stop anti-epileptic drug suddenly or omit dose
• Avoid potential harmful situations
• Avoid heights & open fires
• Prefer showering to bathing
• Prefer microwave cooking to gas or electric hobs
• Avoid swimming alone
• Avoid cycling on a busy road
• Avoid solo canoeing
EDUCATION
• Understand epilepsy
• Keep a seizure chart
• Keep a pill box to facilitate daily medication
• Obtain a Medic Alert kit
• Know the name and the dose of the drugs prescribed, and the frequency
of dosing and the necessity of regular ongoing use
• Refrain from driving
CLINICAL APPROACH: EMERGENCY MEASURES
• ABCDE & Manage
• Airway
• FMO2,
• Left lateral position
• HGT,
• Valium 10mg/Ativan 4mg IVI stat
HISTORY
• Main complaint
• Description of seizure
• Duration
• Frequency
• Prev. seizures
• History of trauma
• Associated symptoms
• Past Medical History
• HPT/IHD/AF – Cerebrovascular disease
• DM – Hypoglycaemia
• Social history
• Alcohol – trigger
• Smoking – CVA risk
• Illicit drugs
• Family history of epilepsy (increasedrisk of
recurrence)
EXAMINATION
• Vitals, Saturations
• JACCOLD
• Systemic examination focusing on Neurological exam
• Exclude focal signs
• Check orientation and level of consciousness
• Check for signs of injury
SIDE ROOM/SPECIAL INVESTIGATIONS
• HGT
• FBC
• UEC
• CMP
• LFTs
• Toxic screen/Anti-epileptic levels
• ECG
• CT Brain / MRI
• EEG
• Individualise your patient, based on
history and examination findings
PHARMACOTHERAPY
Epilepsy. By Jeannine M. Conway, PSAP 2018 BOOK 3 • Neurology /Psychiatry
ANTIEPILEPTIC DRUGS
• Principles
• Start low, go slow
• Monitor levels
• Inform of side-effects
• Refractory Epilepsy: Add second drug with different mechanism of
action
FIRST GENERATION AEDS: EFFICACY
AED EFFICACY SPECTRUM
Valproic acid All seizure types
Benzodiazepines All seizure types
Phenobarbital Most seizure types
Carbamazepine Focal seizures and generalised tonic-clonic seizures
Phenytoin Focal seizures and generalised tonic-clonic seizures
Ethosuximide Absence seizures
Primidone Most seizure types
SECOND GENERATION AEDS: EFFICACY
AED EFFICACY SPECTRUM
Lamotrigine Most seizure types
Gabapentin Focal seizures
Oxcarbazepine Focal seizures and generalised tonic-clonic seizures
Topiramate Most seizure types
Vigabatrin Focal seizures and infantile spasm
Pregabalin Focal seizures
Brivaracetam Focal seizures
AED ADVERSE EFFECTS
Drug Common Serious
Carbamazepine Nausea/vomiting, ataxia, dizziness,somnolence,
blurred vision, pruritus
SJS,TEN, hypersensitivity reaction, aplastic
anemia/agranulocytosis,AV heart block,
hepatic failure, hyponatremia
Gabapentin Somnolence, sedation, dizziness, ataxia, tremor,
peripheral oedema, increased weight
DRESS, anaphylaxis, angioedemaa
Lamotrigine Dizziness,ataxia, somnolence, headache,
double vision, blurred vision, nausea/vomiting
SJS,TEN, DRESS, hemophagocytic
lymphohistiocytosis, aseptic meningitis
Phenobarbital Somnolence, sedation, impaired cognition,
depressed affect
Hypersensitivity reactions
Epilepsy. By Jeannine M. Conway, PSAP 2018 BOOK 3 • Neurology /Psychiatry
Drug Common Serious
Phenytoin Nystagmus, ataxia, slurred speech, decreased
coordination, somnolence, confusion, dizziness,
gingival hyperplasia
SJS,TEN, anaphylaxis, DRESS, hematologic
abnormalities, hepatic failure
Valproate Abdominal pain, nausea, vomiting, somnolence,
insomnia, tremor, asthenia, alopecia, weight
changes, blurred vision
Hyperammonaemia, thrombocytopenia,
hepatic failure, pancreatitis
Ethosuximide Nausea/vomiting, loss of appetite, abdominal
discomfort, ataxia, dizziness,headache,
somnolence
Agranulocytosis, aplastic anemia, SJS,TEN,
DRESS, depression
Topiramate Paraesthesia, anorexia, weight loss, fatigue,
dizziness, somnolence, word finding difficulty,
memory impairment
Metabolic acidosis, vision changes and
glaucoma, kidney stones, oligohidrosis and
hyperthermia, Hyperammonemia
AED ADVERSE EFFECTS
Epilepsy. By Jeannine M. Conway, PSAP 2018 BOOK 3 • Neurology /Psychiatry
SPECIAL CONSIDERATIONS
WOMEN’S HEALTH
• The highest risk of major congenital malformations is with exposure to
valproate, which has an odds ratio of 6.7–9.3,
• Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin resulted in
a risk of major congenital malformations with odds ratios of 2–3 with a 95% CI
of 1.2–5.
• There is a greater risk with exposure to phenobarbital and topiramate (OR 4.2–
5.5; 95% CI, 2.4–9.7).
• Beyond teratogenicity risk, in utero exposure to valproate results in reduced
neurocognitive abilities and low IQ.
Meador KJ, Loring DW. (2016). Developmental effects of antiepileptic drugs and the need for
improved regulations. Neurology 2016;86:297-306.
WOMEN’S HEALTH
• Pre-pregnancy planning and education are important.
• Ideally, the woman has to be seizure free for at least 9 months before
pregnancy.
• Folic acid should be taken while trying to become pregnant or while at
risk of pregnancy, ideally for at least 1–3 months before conception.
STUDY ON AED IN PREGNANCY
• The same principles apply for withdrawal of AEDs in seizure-free women as in any
person with epilepsy
• This needs to be carefully planned months before conception
• In those women who continue to need treatment the aim should be to achieve seizure
control with the lowest possible dose of monotherapy. Polytherapy is best avoided where
possible
• Treatment should be optimised and where necessary the continuation of AEDs reviewed
Review Management of women with epilepsy during pregnancy.Authors Naghme Adab / DavidW
Chadwick. 2016. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1576/toag.8.1.020.27204
STUDY ON AED IN PREGNANCY…
• The choice of AED is determined primarily by the type of epilepsy
• There is accumulating evidence of a greater risk with valproate exposure in utero for
both major malformations and later development
• Safer alternatives include carbamazepine, lamotrigine
• There is clinical consensus and observational data indicating the superiority of valproate
over other AEDs for seizure control, and no justification for switching every woman of
childbearing age on valproate to an alternative drug
Review Management of women with epilepsy during pregnancy. Authors Naghme Adab / DavidW
Chadwick. 2016. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1576/toag.8.1.020.27204
CHILDREN
• A large, randomized, double-blind trial addressed the relative difference in efficacy and
tolerability between ethosuximide, valproate, and lamotrigine.
• The study included 451 children, and the primary outcome was freedom from treatment
failure, with failure defined as continued seizures or excessive drug toxicity, evaluated at
weeks 16 and 20.
• There was no difference between ethosuximide and valproate (53% and 58% respectively,
p=0.35), whereas patients taking lamotrigine were less likely to meet the study outcome,
probably because of a lack of seizure control (29%, p<0.0001).
• Adverse effects were not significantly different between the drugs.
Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy:
initial monotherapy outcomes at 12 months. Epilepsia 2013;54:141-55.
REFERENCES
1. Fisher, R. S. et al. (2017). Operational classification of seizure types by the
International League Against Epilepsy: Position Paper of the ILAE
Commission for Classification and Terminology. Epilepsia 58, 522–530.
2. Devinsky O, et al, (2018). Epilepsy. Disease PrimersVolume 3, Article
Number 18024, doi:10.1038/Nrdp.2018.24
3. Brodie, M.J. et al. (2018).The 2017 ILAE classification of seizure types and
the epilepsies: what do people with epilepsy and their caregivers need to
know? Epileptic Disord,Vol. 20, No. 2,April 2018
4. Conway JM & Tallian KB (2018). Epilepsy. PSAP 2018 BOOK 3 •
Neurology /Psychiatry
5. Perucca P, et al. (2018). The management of epilepsy in children and
adult. MJA 208 (5) j 19 March 2018

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Epilepsy. Presented by Dr KD DELE. 17102019

  • 1. EPILEPSY PRESENTED BY DR KD DELE IJAGBULU DEPARTMENT OF FAMILY MEDICINE | DORA NGINZA HOSPITAL
  • 2.
  • 4. INTRODUCTION • Epilepsy is a neurological disorder that is characterized by an enduring predisposition to generate epileptic seizures and is associated cognitive, psychological and social consequences (Fischer et al, 2017) • An epileptic seizure is a transient behavioural change caused by abnormal excessive or synchronous neuronal activity in the brain, and is associated with objective signs or subjective symptoms such as loss of awareness, stiffening, jerking, a sensation that rises from the abdomen to the chest, a smell of burnt rubber or dĂ©jĂ  vu
  • 5. IMPACT OF EPILEPSY ON QUALITY OF LIFE • Epilepsy affects all age • No sex difference, however it is often underreported among females. • It is a common and one of the most disabling neurological disorders. • Epilepsy can substantially impair quality of life owing to seizures, comorbid mood and psychiatric disorders, cognitive deficits and adverse effects of medications.
  • 6. IMPACT OF EPILEPSY ON QUALITY OF LIFE • Seizures can be fatal owing to direct effects on autonomic and arousal functions or owing to indirect effects such as drowning and other accidents. • The accurate diagnosis of seizures is essential as misdiagnosis and inaccurate medication often have severe consequences. • Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies.Also or clinical trials of new ASDs
  • 7. IMPACT OF EPILEPSY ON QUALITY OF LIFE • Epilepsy can be a significant burden for patients and caregivers. • Adverse effects (by the condition and the medications) contribute to decreased quality of life. • One-third of patients will continue to have uncontrolled seizures. • Children and adolescents who are trying to be socially accepted have increased difficulty e.g. when their AED cause sedation
  • 8. IMPACT OF EPILEPSY ON QUALITY OF LIFE • There have been different moves to reduce stigma associated with epilepsy • For example, changing the nomenclature: It is strongly encouraged to discontinue the use of the term epileptic to reduce stigma; • however, antiepileptic drug (AED) remains the terminology used in the literature; however, newer literatures are beginning to use the term “Anti- seizure drugs” (ASD)
  • 9. IMPACT OF EPILEPSY ON QUALITY OF LIFE • For many patients, seizures can remit; however some might relapse after remission. • Epilepsy is considered resolved when • an individual is seizure free and older than the applicable age for an age-dependent epilepsy syndrome, or, • when the person has remained seizure free for ≥10 years with no anti- seizure medication for the past 5 years
  • 10. IMPACT OF EPILEPSY ON QUALITY OF LIFE • The loss of driving privileges • Social stigma • Employment difficulties • Loss of marriage, and other relationships • Wrong diagnosis of epilepsy (common) leads to the improper use of anti- seizure medications leading to anti-seizure-drug-associated adverse effects, including inducing further seizures
  • 11. EPIDEMIOLOGY • Almost 10% of people will experience a seizure during their lives. • Epilepsy is the third leading contributor to the global burden of disease for neurological disorders and affects 65 million people worldwide. • the prevalence of epilepsy is 6.4 cases per 1,000 persons and the annual incidence is 67.8 cases per 100,000 person-years • Both prevalence and incidence are higher in low-income and middle- income countries (LMICs) than in high-income countries, however underreported due to stigma associated, mostly among women.
  • 12.
  • 13. EPIDEMIOLOGY • The incidence of epilepsy is bimodal: highest in younger age groups (for example, in infancy and early childhood) and in older age groups (for example, more than 50–60 years of age). • Whereas the prevalence tends to be lowest in infants and children, increases in early adulthood – midlife and decreases later in life. • The higher prevalence of Epilepsy in LMICs is believed to be partly due to a higher frequency of traffic accidents, birth injuries and neuroinfectious disorders (such as neurocysticercosis) that can cause epilepsy in LMICs
  • 14. Incidence of epilepsy by age—composite of 12 studies in developed countries, 1988–2005.. SOURCE: Thurman, 2011. https://www.nap.edu/read/13379/chapter/3#26
  • 15. estimated number of patients in Scotland consulting a GP or practice nurse at least once in the financial year 2012/13. https://www.isdscotland.org/Health-topics/General-practice/Gp-consultations/Health-Conditions/Epilepsy/index.asp
  • 17. PRECIPITANTS • Alcohol withdrawal • Fever • Head injury and surgery • Infections • Metabolic abnormalities • Photosensitivity and auditory stimuli • Sleep deprivation • Stress • Drugs
  • 18. CAUSES OF EPILEPSY • Structural: stroke and brain tumours • Genetic: SCN1A-related epilepsies), • Infectious: bacterial or viral brain infections • Metabolic: facilitated glucose transporter member 1 (GLUT1) deficiency • Immune: multiple sclerosis and autoimmune encephalitis • Unknown aetiologies
  • 19. CAUSES OF EPILEPSY… STRUCTURAL • Neurotrauma – Multiple • De novo status epilepticus – TLE • Stroke – Multiple • Blood–brain barrier damage – Multiple • Cortical dysplasia – Multiple • Glioblastoma - Multiple • Developmental epileptic encephalopathies – infantile spasm,multiple GENETIC OR PRESUMED GENETIC • Tuberous sclerosis complex – Tuberous sclerosis complex • Spontaneous mutations – Absence epilepsy • Induced monogenic mutations – Multiple • Developmental epileptic encephalopathies – Infantile spasms, Dravet syndrome
  • 20. CAUSES OF EPILEPSY… • Other causes include primary CNS dysfunction or underlying metabolic derangement or systemic diseases • Common causes: • In children, congenital and genetic causes • In young adult, tumours, alcohol and drugs • In elderly, cerebrovascular diseases
  • 21. CAUSES ACCORDINGTO AGE • Neonates • Perinatal hypoxia and ischaemia • Intracranial haemorrhage/trauma • Acute CNS infection • Metabolic disturbance (hypo – glycaemia, calcaemia and magnesaemia; pyridoxine deficiency) • Drug withdrawal • Developmental disorders • Genetic disorders
  • 22. CAUSES ACCORDINGTO AGE • >1 month to <12yrs • Febrile seizures • Genetic disorders • CNS infection • Developmental disorders • Trauma • Idiopathic
  • 23. CAUSES ACCORDINGTO AGE • Adolescents (12-18yrs) • Trauma • Genetic disorders • Infection • Brain tumours • Illicit drugs • Idiopathic
  • 24. CAUSES ACCORDINGTO AGE • 18-35yrs • Trauma • Alcohol withdrawal • Illicit drug use • Brain tumour • Idiopathic
  • 25. MORTALITY EPILEPSY CAN BE LETHAL DUETO THE DIRECT & INDIRECT EFFECTS OF SEIZURES • THE DIRECT EFFECTS: e.g. • sudden unexpected death in epilepsy • status epilepticus • Accidents such as : drowning motor vehicle accidents, falls and burns • THE INDIRECT EFFECTS: e.g. • aspiration pneumonia, • suicide 5-25x more in epileptics • adverse effects of ASDs or psychiatric drugs, such as obesity and cardiovascular side effects
  • 27. PATHOPHYSIOLOGY • The spread of electrical activity between cortical neurones is normally restricted. • Synchronous discharge of neurones in normal brain takes place in small groups only. • During a seizure, large groups of neurones are activated repetitively and hyper- synchronously,There is failure of inhibitory synaptic contact between neurones. • This causes high voltage spike-and-wave activity on EEG.
  • 28. Epilepsy and inflammation in the brain. https://www.semanticscholar.org/paper/Epilepsy-and-inflammation-in- the-brain%3A-overview-Vezzani/86351e1c5e25a373c2b3b13977efd2ec679cfa7a
  • 30. HISTORICAL PERSPECTIVES • For over 35 years, the terms partial and generalized seizures were used to describe types of seizures: • Partial (seizures starting in one area or side of the brain) and • Generalized (seizures starting in both sides of the brain at the same time). • Partial seizures were further classifies into • Simple partial seizures (Person is aware of what happens during the event.) • Complex partial seizures: (Person has some impaired awareness during the seizure.)
  • 31. CLASSIFICATION 1. Seizures may present with a variety of symptoms, and awareness may be either intact or impaired. 2. Seizures are further described by the presence of motor movements, including automatisms or other motor activity, and by nonmotor onset symptoms, including sensory or autonomic symptoms.
  • 32. CLASSIFICATION • Seizure onset can be : • Focal: when abnormal neuronal activity arises in one or more localized brain regions or hemisphere; • Generalized: when abnormal neuronal activity begins in a widespread distribution over both hemispheres; or • Of unknown onset: if the available clinical and laboratory data cannot identify whether the onset is focal or generalized.
  • 33. CLASSIFICATION • The International League against Epilepsy (ILAE) published in the April 2017 edition of Epilepsia three companion articles on the classification of seizures and the epilepsies, • (These represent a long-awaited update on the original 1981 and 1989 classifications). • The new classification provide a modern descriptive template for epilepsy; by using more accessible, transparent language suitable for clinicians, scientists, and patients
  • 34. CLASSIFICATION • The new classification presents three levels of terminology, involving 1. Where seizures begin in the brain 2. Level of awareness during a seizure 3. Other features of seizures – e.g. motor vs non-motor.
  • 35. The management of epilepsy in children and adults by Perucca P, et al. MJA 208 (5) j 19 March 2018
  • 37. The management of epilepsy in children and adults by Perucca P, et al. MJA 208 (5) j 19 March 2018
  • 38. ONSET: DEFINING WHERE SEIZURES BEGIN • The first step is to separate seizures by how they begin in the brain. • The type of seizure onset is important because it affects choice of seizure medication, possibilities for epilepsy surgery, outlook, and possible causes.
  • 39. ONSET: DEFINING WHERE SEIZURES BEGIN • Focal seizures: Previously called partial seizures, these start in an area or network of cells on one side of the brain. • Generalized seizures: Previously called primary generalized, these engage or involve networks on both sides of the brain at the onset. • Unknown onset: If the onset of a seizure is not known, the seizure falls into the unknown onset category. Later on, the seizure type can be changed if the beginning of a person’s seizures becomes clear. • Focal to bilateral seizure: A seizure that starts in one side or part of the brain and spreads to both sides has been called a secondary generalized seizures.The new term for secondary generalized seizure would be a focal to bilateral seizure. (Now the term generalized refers only to the start of a seizure. )
  • 40. DESCRIBING AWARENESS • Whether a person is aware during a seizure is of practical importance • This is because it is one of the main factors affecting a person’s safety during a seizure. • Awareness is used instead of consciousness, because it is simpler to evaluate.
  • 41. DESCRIBING AWARENESS • Focal aware: If awareness remains intact, even if the person is unable to talk or respond during a seizure, the seizure would be called a focal aware seizure.This replaces the term simple partial. • Focal impaired awareness: If awareness is impaired or affected at any time during a seizure, even if a person has a vague idea of what happened, the seizure would be called focal impaired awareness.This replaces the term complex partial seizure. • Awareness unknown: Sometimes it’s not possible to know if a person is aware or not, for example if a person lives alone or has seizures only at night • Generalized seizures: These are all presumed to affect a person’s awareness or consciousness in some way.Thus no special terms are needed to describe awareness in generalized seizures.
  • 42. OTHER FEATURES OF SEIZURES • Many other symptoms may occur during a seizure. • In this basic system, seizure behaviours are separated into groups that involve movement.
  • 43. 1. DESCRIBING MOTOR AND OTHER SYMPTOMS IN FOCAL SEIZURES • Focal motor seizure: This means that some type of movement occurs during the event. For example twitching, jerking, or stiffening movements of a body part or automatisms (automatic movements such as licking lips, rubbing hands, walking, or running). • Focal non-motor seizure: This type of seizure has other symptoms that occur first, such as changes in sensation, emotions, thinking, or experiences. It is also possible for a focal aware or impaired awareness seizure to be sub-classified as motor or non-motor onset. • Auras: The term aura, which describes symptoms a person may feel in the beginning of a seizure, is not in the new classification.Yet people may continue to use this term. It’s important to know that in most cases, these early symptoms may be the start of a seizure
  • 44. 1. DESCRIBING MOTOR AND OTHER SYMPTOMS IN FOCAL SEIZURES MOTOR ONSET • automatisms • atonic • clonic • epileptic spasms • hyperkinetic • myoclonic • tonic NON-MOTOR ONSET • autonomic • behaviour arrest • cognitive • emotional • sensory
  • 45. 2. DESCRIBING GENERALIZED ONSET SEIZURES • Generalized onset seizures can be motor or non-motor. • Generalized motor seizure: • The generalized tonic-clonic seizure term is still used to describe seizures with stiffening (tonic) and jerking (clonic).This loosely corresponds to “grand mal.” Other forms of generalized motor seizures may happen. Many of these terms have not changed, and a few new terms have been added. (see image below) • Generalized non-motor seizure: • These are primarily absence seizures, and the term corresponds to the old term "petit mal." These seizures involve brief changes in awareness, staring, and some may have automatic or repeated movements like lip-smacking.
  • 46. 2. DESCRIBING GENERALIZED ONSET SEIZURES MOTOR • tonic-clonic • clonic • tonic • myoclonic • myoclonic-tonic-clonic • myoclonic-atonic • atonic • epileptic spasms NON-MOTOR (ABSENCE) • typical • atypical • myoclonic • eyelid myoclonia
  • 47. Symptoms MedicalTerm automatic behaviors automatisms emotions or appearance of emotions emotions extension or flexion postures tonic flushing/sweating/piloerection autonomic jerking arrhythmically myoclonus jerking rhythmically clonus language or thinking problems, deja vu cognitive lid jerks eyelid myoclonia limp atonic numb/tingling, sounds, smells, tastes visions, vertigo sensations pausing, freezing, activity arrest behavior arrest thrashing/pedaling hyperkinetic trunk flexion spasm
  • 48.
  • 50. DIAGNOSIS • Often over-diagnosed • Diagnosis is essentially clinical • Description of the seizure provided by an eye witness (MOST seizures) • Sometimes patient self especially in partial onset • Good history and examination • Generally no place for a therapeutic trial
  • 51. DIAGNOSIS/CASE DEFINITION • The case definition of epilepsy, based on combined clinical and epidemiological evidence, includes the following: • Patients with two or more unprovoked or reflex seizures that are >24 hours apart; • Patients with one unprovoked or reflex seizure and who have a ≥60% chance of further seizures over the following 10 years, e.g. patients with a known structural lesion such as stroke, severe traumatic brain injury or brain infection • Patients with one or more seizures in the context of a well-defined epilepsy syndrome (for example, childhood epilepsy with centrotemporal spikes)
  • 52. NEUROLOGICAL DIFFERENTIAL DIAGNOSIS EPILEPTIC SEIZURES ARE OFTEN CONFUSED WITH OTHER PHYSIOLOGICAL DISORDERS AND PSYCHIATRIC DISORDERS • Benign paroxysmal positional vertigo • Breath-holding attacks • Daydreaming • Migraine • Parasomnias (such as REM sleep behaviour disorder) • Narcolepsy and/or cataplexy • Syncope; tics • Periodic leg movements during sleep • Panic attacks • Paroxysmal dyskinesia • Psychogenic non-epileptic seizures • Sleep apnoea • Transient global amnesia. and • Transient ischaemic attacks
  • 54. MANAGEMENT • Lifestyle modification • Education • Drug treatment • Surgery
  • 55. LIFESTYLE MODIFICATION AVOID FACTORS THAT COULD LOWER SEIZURE THRESHOLD • Stress • Alcohol use or withdrawal • Dehydration • Drugs & drug interactions • Photosensitive stimuli (flashing TV program or computer games) • Hyperventilation • Diet & missing meals • Sleep deprivation • Extreme fatigue • Systemic infections
  • 56. LIFESTYLE MODIFICATION • Never stop anti-epileptic drug suddenly or omit dose • Avoid potential harmful situations • Avoid heights & open fires • Prefer showering to bathing • Prefer microwave cooking to gas or electric hobs • Avoid swimming alone • Avoid cycling on a busy road • Avoid solo canoeing
  • 57. EDUCATION • Understand epilepsy • Keep a seizure chart • Keep a pill box to facilitate daily medication • Obtain a Medic Alert kit • Know the name and the dose of the drugs prescribed, and the frequency of dosing and the necessity of regular ongoing use • Refrain from driving
  • 58. CLINICAL APPROACH: EMERGENCY MEASURES • ABCDE & Manage • Airway • FMO2, • Left lateral position • HGT, • Valium 10mg/Ativan 4mg IVI stat
  • 59. HISTORY • Main complaint • Description of seizure • Duration • Frequency • Prev. seizures • History of trauma • Associated symptoms • Past Medical History • HPT/IHD/AF – Cerebrovascular disease • DM – Hypoglycaemia • Social history • Alcohol – trigger • Smoking – CVA risk • Illicit drugs • Family history of epilepsy (increasedrisk of recurrence)
  • 60. EXAMINATION • Vitals, Saturations • JACCOLD • Systemic examination focusing on Neurological exam • Exclude focal signs • Check orientation and level of consciousness • Check for signs of injury
  • 61. SIDE ROOM/SPECIAL INVESTIGATIONS • HGT • FBC • UEC • CMP • LFTs • Toxic screen/Anti-epileptic levels • ECG • CT Brain / MRI • EEG • Individualise your patient, based on history and examination findings
  • 63. Epilepsy. By Jeannine M. Conway, PSAP 2018 BOOK 3 • Neurology /Psychiatry
  • 64. ANTIEPILEPTIC DRUGS • Principles • Start low, go slow • Monitor levels • Inform of side-effects • Refractory Epilepsy: Add second drug with different mechanism of action
  • 65.
  • 66. FIRST GENERATION AEDS: EFFICACY AED EFFICACY SPECTRUM Valproic acid All seizure types Benzodiazepines All seizure types Phenobarbital Most seizure types Carbamazepine Focal seizures and generalised tonic-clonic seizures Phenytoin Focal seizures and generalised tonic-clonic seizures Ethosuximide Absence seizures Primidone Most seizure types
  • 67. SECOND GENERATION AEDS: EFFICACY AED EFFICACY SPECTRUM Lamotrigine Most seizure types Gabapentin Focal seizures Oxcarbazepine Focal seizures and generalised tonic-clonic seizures Topiramate Most seizure types Vigabatrin Focal seizures and infantile spasm Pregabalin Focal seizures Brivaracetam Focal seizures
  • 68. AED ADVERSE EFFECTS Drug Common Serious Carbamazepine Nausea/vomiting, ataxia, dizziness,somnolence, blurred vision, pruritus SJS,TEN, hypersensitivity reaction, aplastic anemia/agranulocytosis,AV heart block, hepatic failure, hyponatremia Gabapentin Somnolence, sedation, dizziness, ataxia, tremor, peripheral oedema, increased weight DRESS, anaphylaxis, angioedemaa Lamotrigine Dizziness,ataxia, somnolence, headache, double vision, blurred vision, nausea/vomiting SJS,TEN, DRESS, hemophagocytic lymphohistiocytosis, aseptic meningitis Phenobarbital Somnolence, sedation, impaired cognition, depressed affect Hypersensitivity reactions Epilepsy. By Jeannine M. Conway, PSAP 2018 BOOK 3 • Neurology /Psychiatry
  • 69. Drug Common Serious Phenytoin Nystagmus, ataxia, slurred speech, decreased coordination, somnolence, confusion, dizziness, gingival hyperplasia SJS,TEN, anaphylaxis, DRESS, hematologic abnormalities, hepatic failure Valproate Abdominal pain, nausea, vomiting, somnolence, insomnia, tremor, asthenia, alopecia, weight changes, blurred vision Hyperammonaemia, thrombocytopenia, hepatic failure, pancreatitis Ethosuximide Nausea/vomiting, loss of appetite, abdominal discomfort, ataxia, dizziness,headache, somnolence Agranulocytosis, aplastic anemia, SJS,TEN, DRESS, depression Topiramate Paraesthesia, anorexia, weight loss, fatigue, dizziness, somnolence, word finding difficulty, memory impairment Metabolic acidosis, vision changes and glaucoma, kidney stones, oligohidrosis and hyperthermia, Hyperammonemia AED ADVERSE EFFECTS Epilepsy. By Jeannine M. Conway, PSAP 2018 BOOK 3 • Neurology /Psychiatry
  • 71. WOMEN’S HEALTH • The highest risk of major congenital malformations is with exposure to valproate, which has an odds ratio of 6.7–9.3, • Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin resulted in a risk of major congenital malformations with odds ratios of 2–3 with a 95% CI of 1.2–5. • There is a greater risk with exposure to phenobarbital and topiramate (OR 4.2– 5.5; 95% CI, 2.4–9.7). • Beyond teratogenicity risk, in utero exposure to valproate results in reduced neurocognitive abilities and low IQ. Meador KJ, Loring DW. (2016). Developmental effects of antiepileptic drugs and the need for improved regulations. Neurology 2016;86:297-306.
  • 72. WOMEN’S HEALTH • Pre-pregnancy planning and education are important. • Ideally, the woman has to be seizure free for at least 9 months before pregnancy. • Folic acid should be taken while trying to become pregnant or while at risk of pregnancy, ideally for at least 1–3 months before conception.
  • 73. STUDY ON AED IN PREGNANCY • The same principles apply for withdrawal of AEDs in seizure-free women as in any person with epilepsy • This needs to be carefully planned months before conception • In those women who continue to need treatment the aim should be to achieve seizure control with the lowest possible dose of monotherapy. Polytherapy is best avoided where possible • Treatment should be optimised and where necessary the continuation of AEDs reviewed Review Management of women with epilepsy during pregnancy.Authors Naghme Adab / DavidW Chadwick. 2016. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1576/toag.8.1.020.27204
  • 74. STUDY ON AED IN PREGNANCY… • The choice of AED is determined primarily by the type of epilepsy • There is accumulating evidence of a greater risk with valproate exposure in utero for both major malformations and later development • Safer alternatives include carbamazepine, lamotrigine • There is clinical consensus and observational data indicating the superiority of valproate over other AEDs for seizure control, and no justification for switching every woman of childbearing age on valproate to an alternative drug Review Management of women with epilepsy during pregnancy. Authors Naghme Adab / DavidW Chadwick. 2016. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1576/toag.8.1.020.27204
  • 75. CHILDREN • A large, randomized, double-blind trial addressed the relative difference in efficacy and tolerability between ethosuximide, valproate, and lamotrigine. • The study included 451 children, and the primary outcome was freedom from treatment failure, with failure defined as continued seizures or excessive drug toxicity, evaluated at weeks 16 and 20. • There was no difference between ethosuximide and valproate (53% and 58% respectively, p=0.35), whereas patients taking lamotrigine were less likely to meet the study outcome, probably because of a lack of seizure control (29%, p<0.0001). • Adverse effects were not significantly different between the drugs. Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia 2013;54:141-55.
  • 76. REFERENCES 1. Fisher, R. S. et al. (2017). Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 58, 522–530. 2. Devinsky O, et al, (2018). Epilepsy. Disease PrimersVolume 3, Article Number 18024, doi:10.1038/Nrdp.2018.24 3. Brodie, M.J. et al. (2018).The 2017 ILAE classification of seizure types and the epilepsies: what do people with epilepsy and their caregivers need to know? Epileptic Disord,Vol. 20, No. 2,April 2018
  • 77. 4. Conway JM & Tallian KB (2018). Epilepsy. PSAP 2018 BOOK 3 • Neurology /Psychiatry 5. Perucca P, et al. (2018). The management of epilepsy in children and adult. MJA 208 (5) j 19 March 2018