• Seizures are considered acute symptomatic if they occur within the first 7 days of cerebrovascular disease; TBI, including intracranial surgery; CNS infections, multiple sclerosis relapse. Longer timeframes may be appropriate depending on the ‘activity’ of the underlying condition (e.g. a flare of an infectious lesion or a further bleed from an AVM).

• For alcohol withdrawal the seizure must occur within 7–48 h of the last drink.

• Seizures in the setting of a brain tumour may more appropriately classified as epilepsy

Drug resistant epilepsy (ILAE 2009) – replaces term refractory epilepsy

• Failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom

Epidemiology

• 5-10% of the population will have a seizure in their lifetime

• 25-30% due to acute brain disturbance

• 30% of people who ever have a seizure will eventually be diagnosed with epilepsy

Recurrence rate in acute brain disturbance (see below for more details)

• If no structural damage – less than 3%

• If structural damage 12.5% (1/8)

Recurrence rate if unprovoked:

• After one seizure 30-50%

• After 2 unprovoked seizures 70-80% -diagnosis of epilepsy

If a second seizure is to occur 60-70% occur within 6 months

Epilepsy

• Incidence 0.3-0.5%

• Prevalence 0.5-1%

• Lifetime risk 1.4%-3.3%

Seizure types and Classification

Seizure Classification

Focal

• Predominant symptoms at onset

o Use the earliest prominent symptom

o Brief behavioural arrest is common but not used as a descriptor unless it remains the prominent symptom

o The descriptor may not be the most prominent feature of the entire seizure, but the earliest (e.g. starts with prominent but brief automatisms and then has prolonged tonic phase – automatisms would be the descriptor used)

• Focal to bilateral tonic-clonic

o The term secondary generalised was avoided so ensure it was clear that the seizure has a focal onset and the bilateral spread does not have importance in aetiology

• Awareness

o Retained knowledge of self and environment

o Different to responsiveness (which may also be useful to record separately)

o It is noted that there are multiple types of altered consciousness

• Definition

o Originate in networks limited to one hemisphere

o They may be discretely localised or more widely distributed

o They may originate in subcortical structures

Generalised

• Definition

o Originating at some point within and rapidly engaging, bilaterally distributed networks

o The seizure has a consistent focus of onset.

Unknown Onset

• It is suggested that defining the onset as focal or generalised should only be done when there is a >80% chance of certainty

• In many seizures the details surrounding the onset is unknown

• Unknown onset should be used in these circumstances

• Epilepsy syndromes will be grouped according to aetiology (see Epilepsy Syndromes)

New Term	Description	Old Term
Hyperkinetic	Agitated thrashing or leg pedalling movements	Hypermotor
Behaviour arrest	Arrest (pause) of activities, freezing immobilization.
Cognitive	Pertaining to thinking and higher cortical functions. Specific cognitive impairments Can be negative: E.g. aphasia, apraxia, neglect, Can be positive: de ja vu, jamais vu, illusions, halucinations	Psychic
Epileptic spasms	A sudden flexion, extension or mixed flexion-extensionof predominantly proximal and truncal muscles that is more sustained than a myoclonic movement but less sustained than a tonic seizure. Limited forms may occur: grimacing, head nodding or subtle eye movements. Frequently occur in clusters.	Epileptic spasms
Emotional	E.g. Fear, Joy, laughing (gelastic), crying (dacrystic)
Clonic	Jerking, either symmetric or asymmetric, that is regularly repetitive and involves the same muscle groups
Absence	Sudden onset Interruption of ongoing activities Blank stare Possible brief up-ward deviation of the eyes Unresponsive when spoken to A few seconds to 30sec Very rapid recovery (with no post-ictal confusion)	Absence
Tonic	A sustained increase in muscle contraction lasting a few seconds to minutes
Myoclonic	Sudden, brief (<100ms) involuntary single or multiple contractions of muscles or muscle groups.
Absence, atypical	An absence seizure with changes in tone that are more pronounced than in typical absence OR the onset or cessation is not abrupt Often associated with slow, irregular, generalised spike wave activity	Absence, atypical

Bold text = new ILAE terminology

Seizures	Description	EEG
Focal	Localized to discrete area’s of the cerebral cortex
Simple	Consciousness maintained “With observable motor or autonomic symptoms” Motor Autonomic “With subjective sensory or psychic symptoms only” = aura Sensory - Usually numbness or paraesthsia, visual relatively rare, auditory and vertiginous can also occur - Olfactory - Gustatory - Visceral - Psychic
Complex “With impairment of consciousness or awareness” = Focal dyscognitive	Decreased awareness/ consciousness Automatisms Post-ictal confusion/amnesia Psychic symptoms can occur - Illusions, hallucinations, déjà vu, jamis vu, affective symptoms
Partial with secondary generalization “Evolving to bilateral convulsive seizure”	Usually tonic-clonic seizure
Primarily generalized	Diffuse area’s of the brain simultaneously


Tonic-clonic	May be vague prodrome Tonic phase 10-20sec - Pupils dilated and NR Clonic phase - 8Hz slowing to 4Hz - ~30s - Ends with deep inspiration Gradually increasing relaxation Usually no more than 1min Post-ictal – unresponsive, flaccid, salivation, bowel/bladder incontinence	Tonic phase – progressive increase in generalized low-voltage fast activity followed by generalized high amplitude, polyspike discharges. Clonic phase – spike and wave Post-ictal – generalized slowing.
Absence	Brief, sudden lapses of consciousness (2-10s) without lapses of postural control No post-ictal confusion Subtle movements may accompany Usually begin in childhood (4-8yrs) 15-20% of childhood seizures 60-70% resolve during adolescence 50% will also experience TC seizure 33% will have myoclonic jerks	Generalized, symmetric 3Hz spike and wave discharge that begins and ends suddenly Hyperventilation provokes seizures and EEG changes
Typical
Atypical
With special features	Myoclonmic absence Eyelid myoclonia
Myoclonic	Most common with metabolic syndromes, degenerative CNS disease, anoxic brain injury	Bilateral synchronus spike and wave pattern – at time of myclonus
Myoclonic atonic
Myoclonic tonic
Tonic
Clonic
Atonic	Brief loss of tone 1-2 sec with loss of consciousness No post-ictal confusion Associated with specific syndromes
Unknown
Epileptic spasms

Clinical features (semiology)

• Focal dyscognitive seizures

o 60% temporal vs 40% extratemporal

By Region:

Temporal lobe - Mesial (limbic)

• FDS evolve relatively gradually (1-2min) and last longer (2-10min) than most extra-temporal seizures

Aura

• Visceral – most common – rising epigastic sensation

• Autonomic – pallor or flushing, BP, HR, pupil size, piloerection

• Cephalic

• Gustatory – taste – usually unpleasant

• Dysmnestic – De ja vu

• Affective - fear

Absence

• Often a prominent feature

Automatisms

• Often ipsilateral to side of seizure

• Dystonic posturing usually contralateral

• Oroalimentary – lip smaking, chewing, swallowing

• Gestural – fumbling, fidgeting, undressing, sexually directed actions

Post-ictal

• Dysphasia – useful lateralizing sign indicating dominant lobe focus

Temporal lobe – lateral

Aura

• Simple auditory phenomena - humming, buzzing, hissing, roaring – superior temporal gyrus

• Olfactory – unpleasant and hard to define – sylvian fissure

• Illusions of size – macropsia, micropsia

• Illusions of weight, distance

• Affective auras rare

Motor activity /Automatisms

• More pronounced, less motor arrest

Frontal lobe

• Frequent, brief attacks with tendency to cluster

• Lack the gradual evolution of temporal lobe seizures

• Some forms only occur from sleep

•

• Motor arrest rare

• Prominent motor signs

o Lower limbs

o Cycling, stepping, kicking

o Can be bizarre, highly excited.

• Head and eye version common

o Head version during full consciousness is useful lateralizing sign of contralateral frontal dorsolateral anterior convexity lesion

• 2014 paper suggests 4 groups:

o Elementary motor signs – posterior frontal lobe

o Elementary motor signs, non-integrated gestural motor behaviour – mid frontal, opercular region

o Integrated gestural motor behaviours, distal stereotypies – frontal pole, mesial anterior cingulate

o Fearful behaviour – anterior mesial, cingulate

Diagram

Description automatically generated

Central (peri-rolandic)

• Frequently simple focal seizure (without loss of awareness)

• Contralateral clonic jerking – often with Jacksonian march)

• Bilateral posturing

• Fencing posture – contralateral arm abduction, elevation and flexion with head version to same side – supplementary motor area.

• Sensory symptoms can occur – often followed by jerking movement as seizure spreads anteriorly

• Post-ictal Todd’s paresis common

Parietal

• Aura is common (85%)

• Somatosensory (75%)

o Parietal operculum

• Often multiple aura’s in one patient

• Illusions of body distortion

• Illusion of body parts in space

• Panic attacks/ictal fear

• Ictal pain

• Ictal vertigo

• Mesial parietal

o Recurrent, brief, asymmetrical tonic seizures, rapid recovery

• Intraparietal Sulcus

o Spinning seizures – sense of spinning, turning around while standing, rolling over in bed

• Inferior parietal lobule

o Often temporal like

Occipital

• Visual symptoms

• Elementary visual hallucinations most common – colours, shapes, flashes, patterns

• Complex illusions can occur

• Vision blackouts also common – but often associated with illusions.

Insula

• Anterior

o Abdominal pain

o Gustatory

• Inferior

o Limbic symptoms

• Posterior

o Warmth or pain

o Auditory

• Ref: Lecture at ESA 2018

Cingulate

• Anterior

o Anxiety, Fear

o Hypermotor

• Middle

o Complex movments

• Posterior

o Abdominal aura

o De ja vu

o Hypermotor

o Can be similar to mesial temporal semiology

• Ref: Lecture at ESA 2018

By Symptom:

Symptom	Localisation	Lateralisation	Correlation
Sensory
Well-defined somatosensory symptoms	Parietal (primary sensory cortex)	Contralateral	High
Poorly defined somatosensory symptoms (e.g. bilateral)	Parietal (S2 or SMA)	None	Low

Gustatory Aura	Insular

Olfactory sensations	Anterior mesio- temporal lobe	None		?Associated with amygdala lesions
Vertigo	Insular – parietal – temporal junction	None	?
Vertigo – yaw sensation (spinning around vertical axis)	Posterior temporal
Vertigo – spinning around horizontal axis	Parietal opercular
Ascending visceral feelings	mesio – temporal, insular, supplementary motor area	None press tab moderate
Unilateral elementary visual phenomena	Occipital	Contralateral	High	Visual phenomena are often bilateral – which is non lateralising.
Complex visual hallucinations and illusions	Parieto-temporal (association cortex)	None	?
Elementary auditory manifestations (if unilateral)	Primary auditory cortex (Heschell’s gyrus)	Contralateral	Low (Lat)	It is difficult for patients to lateralise sounds.

Déjà vu	Mesio temporal	None
Ictal fear	Amygdala	None
Orgasmic aura	Non-dominant mesio temporal or para-sagittal parietal region	None

Lateralised ictal headache	Temporal or occipital	Ipsilateral	Moderate
Postictal headache	Non-localising
Pre-ictal headache	?

Motor
Forced head version (Versive seizures)	Frontal, temporal	Contralateral	High	Versive = eye, head, body movement, forced, sustained unnatural posture. Probably due to activation of frontal eye field. Occurs earlier in frontal lobe seizures.
Non-versive head turning	Temporal	Ipsilateral	Moderate	Often will then turn to the contralateral side as the seizure becomes bilateral TC.
Eye deviation (without head deviation)	Non-localising
Unilateral clonic	Frontal > temporal	Contralateral	High (~92% for Lat)	Frontal clonic – early with preserved consciousness. Temporal clonic – may occur later, after automatisms.
Unilateral tonic	Extratemporal >>temporal	Contralateral	High (Lat)	Generated in cortical motor areas. Only lateralising if truly unilateral.
Unilateral dystonia	Temporal > frontal	Contralateral	High	Dystonic posturing – unnatural tonic posturing with a rotatory component.
Asymmetric termination of clonic phase	Temporal and frontal	Ipsilateral to the last cloni	High (80% for Lat)
Figure 4 sign (just prior to BTCS)	SMA	Contralateral (to extended arm)	High (Lat)	Importantly its significance is limited to the situation where it occurs just prior to BTCS.
Unilateral eye blinking	Unknown	Ipsilateral (to blinking eye)	High (Lat)	Rare
Ictal Nystagmus	?Occipital	Contralateral to fast phase	?
Hand position				See Siegel and Tatum. Neurology Vol 87 2016
- Fan	Onset of GGE TCS
- Fist	Tonic and clonic phase of GGE, Clonic phase of FBTCS
- Index finger pointing	Onset of focal epilepsy FBTCS
- Claw	Psychogenic events
- Flaccid	Psychogenic events
Negative motor phenomena
Negative myoclonus	Central region	Contralateral	?
Ictal akinesia		Contralateral	High (Lat)	Different to dystonia which must be excluded Negative motor area’s – anterior to face motor area in frontal lobe

Other
Automatisms	Temporal >frontal	Ipsilateral	High	Often associated with contralateral dystonic posturing – which has the greater lateralising significance. Preserved responsiveness during automatisms infers right sided onset.

Ictal speech	Temporal	Non-dominant	High	Clearly understandable words or phrases
Autonomic
Ictal urinary urge	Temporal	Non-dominant	?
Ictal bradycardia	Temporal	None
Ictal tachycardia	Insula	Non-dominant
Ictal piloerection (unilateral)	Temporal	Ipsilateral	?	Rare (0.14%)
“Cold shivers”/goosebumbs	Temporal	Dominant		(Stefan et al 2002)

Ictal spitting	Temporal lobe	Non-dominant		Rare
Ictal vomiting	Temporal (+?insula)	Non-dominant		Often associated with an epigastric aura
Ictal laughing	Hypothalamic hamartoma or temporal or frontal	-	-
Ictal weeping (dacrystic seizures)	Mesio temporal	None	-
Peri-ictal water drinking	Temporal	Non-dominant		?Incidence up to 15%
Peri-oral myoclonia	Generalised
Rhythmic Ictal non-clonic Hand movements (RINCH) – simple movement, not like automatism	Temporal	Contralateral

Post-ictal signs
Postictal dysphasia	Dominant hemisphere	-	High	Must be distinguished from impaired consciousness
Postictal paresis (Todd’s)	Temporal or frontal	Contralateral	High (Lat)	Incidence 6-40%
Postictal nose wiping	Temporal, frontal	Ipsilateral	High (Lat 50-97%)
Postictal coughing	?temporal	Nil	Mod (Loc)	Some studies say left, others right – therefore no clear lateralising value

* From Rossetti and Kaplan (2010) Seizure semiology; European neurology.

Aetiology

Acute symptomatic seizures

	Risk of acute seizures	Risk of chronic seizures
Stroke
Ischaemic stroke	2.5-5.0	11
ICH	16
SAH	10	7
Infection
Bacterial meningitis	17-24	2.7
Encephalitis		>20
Cerebral abscess	17
Neurocysticercosis
Cerebral malaria	40
HIV		~15% pre- and 6% post HAART
Inflammatory
MS		~3x risk, 3.1% at 15years
ADEM	10-20
SLE	10-20
Wegener’s	<5
Bechcet’s	<5
NMDA encephalitis	75
Metabolic
Hyponatraemia	5-15
Hypernatraemia	Rare
Liver failure	Rare
Drugs
Alcohol withdrawal	33
Marijuana	?Nil	?Nil
Cocaine	1-8
Heroin use	OR 27	OR 4.7
Ketamine	?Nil	?Nil
Head injury
Closed	2-6
Mild		Nil
Mod		1-4
Severe		10-15
Open		30-50
Neurodegenerative diseases
Alzheimer		6-fold risk
Huntington disease		5
CJD		10

*Acute symptomatic seizures, Practical Neurology 2012 12:154

Drugs

• Alcohol

• Acute intoxication probably does not cause seizures

• Acute withdrawal – 6-48hours can lower seizure threshold

Medications

Drug	Risk
Anti-psychotics	All probably have increased risk, listed below have higher risk

Clozapine	1-4%
Chlorpromazine	1-9%
Trifluoperazine
Anti-depressants	Risk ranges from <1-4%
SSRI’s, MAOI’s	Lowest risk
Antibiotics
B-Lactams (Especially - Benzylpenicillin,cephazolin, imipenem)
Isoniazid
Quinolones (ciprofloxacin, norlfoxacin)
Other
Theophylline	High

Tumours

Risk of seizures:

• DNET 80-100%

• Low-grade astrocytoma 75%

• Meningioma 30-60%

• High-grade astrocytoma 30-50%

• Brain metastases 20-35%

• Primary CNS lymphoma 10%

Overall Causes of Seizure

Adults

• Unknown 62%

• Stroke 9%

• Trauma 9%

• Alcohol 6%

• Neurodegenerative disease 4%

• Encephalopathy 3.5%

• Tumours 3%

• Infection 2%

Causes of seizure (by age)

Neonates

(less than 1 month)

Hypoxia/ischaemia

ICH

Acute infection

Metabolic

Drug withdrawal

Developmental disorders

Genetic disorders

Infants and children

(1month to 12 years)

Febrile seizures

Genetic disorders

CNS infection

Developmental disorders

Trauma

Idiopathic

Adolescents

(12-18yrs)

Trauma

Genetic

Infection

Tumour

Drug use

Idiopathic

Young adults

18-35yrs

Trauma

Alcohol withdrawal

Drug use

Tumour

Idiopathic

Older adults

Over 35yrs

Cerebrovascular disease

Tumour

Alcohol withdrawal

Metabolic

Alzheimer’s/degenerative disease

Idiopathic

Acute symptomatic seizures

Specific Epilepsy Syndromes

Patient Evaluation

History

Previous seizures including history of febrile seizures
CNS lesions

Trauma, CVA, tumour, vascular malformations

Prenatal/perinatal history – i.e. any complications of pregnancy, hypoxia, need for intensive care.
Developmental milestones
Family history
Drug or alcohol abuse
Precipitating factors:

Sleep deprivation, systemic disease, electrolyte/metabolic disturbance, acute infection, drugs – legal/illegal, alcohol.
Note: OSA can worsen seizure – think of this if well controlled epileptic worsens with age

Symptoms:

Aura’s or other associated phenomena not previously diagnosed as seizure
Behaviour
Vocal
Motor
Eyes

Motionless stare – MTLE
Flickering – absence
Deviated – focal
Rolled back – syncope
Closed – non-epileptic

Respiration pattern
Autonomic – drooling, pallor, N+V
LOC

Post ictal

Amnesia
Lethargy
Confusion
Sleepiness

· Headache

Muscle ache
Tongue biting
Incontinence
Transient focal weakness
N+V

Physical examination

Neurological examination
Signs of infection
Cutaneous markers of CNS disease
Signs of trauma
Signs of metabolic disease
CVS examination for risk of cerebrovascular disease

Investigations

Bloods:

Glucose, calcium, magnesium, U+E, LFT
Toxin/drug screen
Serum prolactin

Lumbar puncture – if meningitis suspected or HIV pos

Specific Serum Markers of Seizure

• CK

• Prolactin

Ammonia

• Study (2016 Epilepsia 57(8)1228) - 78 patients admitted for VEM for diagnostic purposes

o Ammonia sample taken 15-60min post ictal

o Baseline ammonia was slightly higher in generalised convulsive seizure group

o Significant increase in Ammonia in generalised convulsive seizure group only (not in focal sz or PNES)

o A cut point of >80umol/L gave Sn 53.9% and Sp 100%

EEG

Abnormal in 29% (range 8 to 50%) of adult patients presenting with first seizure
Increased incidence of abnormalities in sleep deprivation
During event
Interictal

60% are normal in patients with known epilepsy

Imaging

CT in emergency cases, otherwise MRI (although no good evidence)
A significant abnormality is present in ~10% of adult patient with first seizure (CT or MRI)
(Dr Archer) “80% of significant abnormalities will be detected on CT-B’

Differential diagnoses

Migraines
Psychotic disorders
TIA/CVA
Syncope
Differentiating from syncope:

	Seizure	Syncope
Precipitating	Usu none	Stress, valsalva, cardiac event
Premonitory symptoms	None or aura	Tiredness, nausea, sweating, tunnelling of vision
Posture	Variable	Usually erect
Transition to unconciouness	Usu. Immediate	Gradual
Duration of unconsciousness	Minutes	Seconds
Duration of tonic or clonic movt.	30-60 seconds	Never more than 15sec
Facial appearance during event	Cyanosis, frothing at mouth	Pallor
Aching muscles after event	Often	Sometimes
Biting of tongue	Sometimes	Rarely
Incontinence	Sometimes	Sometimes
Headache	Sometimes	Rarely

Treatment:

• Treatment of underlying condition

• Avoidance of precipitating factors

• Anti-epileptic drug therapy

• Avoidance of dangerous activities

• Driving

o Operating machinery or at heights

o Swimming alone

• Treat/screen for concomitant problems

o Depression

• Overall effective in 60-70% of patients

Ketogenic Diet

• Effective, especially in paediatric populations

•

Surgery

• Temporal lobe resections

o 60-70% chance of being seizure free

• Vagal nerve stimulation

o 50% reduction in 30-40% of patients

• Deep brain stimulation

o Under investigation

Refer for surgery when (rule of 2’s):

· 2 years of seizures

· >2seizures/month

· >2monotherapies trialed

· One trial of two drugs combined

Prognosis with treatment

Patterns of treatment response in newly diagnosed epilepsy,

• Kwan Neurology 2012

• 1098 patients

• Median F/U 7yrs

• Seizure freedom defined as one year

Drug Regimens	% of total cohort Seizure free	% Seizure free on particular regimen	% polytherapy
Monotherapy	49.5	49.5
Second	13.3	36.7	30.8
Third	3.7	24.4	36.5
Fourth	1.0	16.2	45.5
Fifth	0.4	12.5	75
Sixth	0.2	12.5	50
Seventh	0.2	22.2	50
Eighth	0	0
Ninth	0	0

Monotherapy vs polytherapy

• Only 6% of all patients achieved seizure freedom on polytherapy

• Of the occasional successes achieved on latter drug regimens – most were on polytherapy (see table above)

Classified patients into 4 categories/patterns:

Pattern

Description

Becoming and remaining seizure free within 6 months of treatment

Becoming and remaining seizure free after 6 months of treatment

Fluctuating between periods of seizure freedom and relapse

Never seizure free for any complete year

37%

(25% immediately)

22%

16%

25%

Treatment withdrawal

• Trial in late 1980’s (MRC AED Withdrawal Study Group. Lancet 1991;337:1175-80)

o Patients seizure free for 2 years were randomised to continue treatment or wean and cease

o At 2 years after randomisation seizure freedom was maintained in :

- 78% of patients continuing on medication

- 59% of patients who ceased

o i.e. absolute increased risk of recurrence of 19%, NNT to result in one recurrence = 5.

• Study from China regarding focal epilepsy (Wang et al. CNS drugs 2019, 33; 1121)

o Patients made their own decision regarding cessation – followed for several years

o Chance of remaining seizure free after 5 years depended on how many years the patient had been seizure free prior to medication cessation. Ranging from 39% if seizure free for 2-3years up to 64% if seizure free 5+ years.

• Systematic review and meta-analysis (Lamberink et al. Lancet Neurology 2017, 16:523)

o Devised a decision tool to predict risk of seizure recurrence:

http://epilepsypredictiontools.info/aedwithdrawal

• If a seizure is going to recur 2/3^rd will happen within first year

• If seizures occur with medication cessation 95% regained seizure control at 1 year (MRC study)

o Other studies found figures of 76% to 85%

Changing Treatment

• If a patient is seizure free and wishes to change treatment what is the risk of seizure?

o 12 patients changing vs matched controls (Finamore et al. Epilepsia 57(8) 1294 2016)

- 14% excess risk of seizure in next 6 months compared to controls

o Another study suggested 18% (Wang Epilepsia 2012)

Refractory/Drug resistant Epilepsy

· ILAE 2010

o Epilepsy in which seizures persist and seizure freedom is very unlikely to be attained with further AED therapy

o Failure of adequate trial of two tolerated and appropriately chosen and used AED schedules (either as monotherapy or combination) to achieve sustained seizure freedom.

Specific Anticonvulsants

Specific Issues

Driving (See Driving and Neurological Disease)

Epilepsy and Suicide

RR = 2 when all patients with psychiatric disease excluded
Highest risk during first half year after diagnosis
? common pathogenic mechanism in terms of receptor abnormalities

SUDEP (Sudden unexpected death in epilepsy)

Epidemiology

Australia ~280 deaths/year

Mean age of death from epilepsy 52

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Rates

	Per 1000/year
New onset epilepsy	~ 0.35
General population of epilepsy	~ 0.9-2.3
Refractory seizures	~4.0 (1.1-5.9)
Surgery candidates/failed surgery	6.3-9.3
Associated mental retardation	~3.0

• Incidence seems to be fairly even across age groups (children vs adults)

Pathogenesis

· Respiratory causes probably important (apnoea seems to be important common factor)

· ?Cerebral shutdown

· Small proportion cardiac cause (0.1-0.4% of seizures observed to cause asystole)

Risk factors

· Seizures:

o GTCS

o Recent or frequent seizures (>3 seizures in last year ~8x risk)

· Medications:

o Non-compliance

o Recent and frequent changes in medication

o Patients on polytherapy (polytherapy and >3seizures ~25x risk)

· Environment

o ?Lack of nocturnal supervision/sleeping alone

· ?Alcohol

· ?Depression

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Table

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References

SUDEP NEJM 2011, SUDEP Lancet 2011
Ryvlin Lancet Neurol 2013
Thurman Epilepsia 2014

Epilepsy and Pregnancy

• Fertility

o Equal in young women

o Reduced in older women with epilepsy compared to controls - ?due to decreased desire to have children or ability to have children

• Risk of offspring developing epilepsy

o GGE – offspring have 1/12 chance of inheriting epilepsy (~8%)

o Focal epilepsy – offspring have 1/50 chance (2%)

o Background rate ~1%

• Increased maternal mortality during pregnancy

o 4-7% of all maternal deaths in UK associated with epilepsy

o 10x risk of controls

o Largely SUDEP - ?due to coming off medication due to fear of malformations

• Increased pregnancy complications/morbidity

o 2-4X risk of complications (Haemorrhage, transfusion, preterm delivery)

o Caesarean section increased – Australian pregnancy registry – 39.2% vs 29.9%

• Seizure risk

o Overall 15% of women with epilepsy will have GTCS during pregnancy ?unknown if this is any different from baseline

o 2/3 patients have no change in seizures during pregnancy

- ?1/3 improve, 1/3 stay the same, 1/3 get worse

o However clearly increased risk of seizure during delivery – 2-2.5%

o Reasons for worse seizures during pregnancy:

- Change in metabolism of medication

- Vomiting

- Sleep deprivation

- Withdrawal of medication (due to side effect concerns)

- ?Effect of pregnancy on seizure threshold

• Seizure effect on foetus

o May be a slightly higher rate of spontaneous abortions

o One study shows association with preterm delivery and lower birth weight

o One study demonstrated lower verbal IQ in children with 5 or more TCS during pregnancy

o Vast majority of studies suggest increased seizures DO NOT increase rate of congenital malformation

o Isolated focal seizures unlikely to have any significant impact

• Discussion list:

o Risk of medications on pregnancy

o Risk of seizures on pregnancy

o Folate

o Medication adjustment during and after pregnancy

o Morning sickness (redose if vomiting after dose – recommendations vary from 15-60min after dose)

o Risk of seizures peri-partum

- Avoid prolonged labour, lower threshold for pain relief

o Sleep deprivation

o New-born safety

- Bathing baby

- Red

o Anxiety and depression

• Effect of AEDs – See Anticonvulsants

Epilepsy and female hormones – menstruation and menopause

Catamenial epilepsy

3 patterns

• C1 during menstruation

• C2 during ovulation

• C3 during anovulatory cycles

• Majority C1

• Trial of progesterone

o Overall no benefit

o Subgroup with C1 may have some benefit

• Old trial (1982) suggested clobazam effective:

o 20-30mg for 10 days starting 2 days prior to usual onset of seizures.

Menopause

• May get better or worse

• More often gets worse in the perimenopause

Seizures from sleep

Studied in WA database (presented ESA 2015)

• 239 patients with first seizure from sleep (23% of all first seizures)

• 89 patients (40%) eventually developed an awake seizure

• Median onset awake seizure 1.6 years (range 1-12 years)

• 13% risk of seizure in first year drops off substantially thereafter

• After 2 consecutive sleep seizures one year risk of awake seizure is 5%

• After 3 risk is 1.5%

References

“Evaluation of first seizure” Neurology 2007 69:pg1996-2007

“Initial Management of Epilepsy” NEJM 2008 359;2 pg166