Seizures

Introduction

• Status epilepticus = Seizure activity >= 5 minutes or two or more seizures without regaining consciousness between seizures
• Refractory status epilepticus = Persistent seziure activity despite IV administration of adequate doses or two anticonvulsant drugs
• Classified as generalised, partial or unclassified (inadequent information)
• 10% of population will have at least one seizure in their lifetime
• 1-3% of population will develop epilepsy in their lifetime
  • Requires 2 or more unprovoked seizures more than 24 hours apart
  • Does not include simple febrile or neonatal seizures
  • Status epilepticus = 1 seizure event

Acute symptomatic seizure vs. unprovoked seizure

• Acute symptomatic seizure (ASS)
  • 20% risk of recurrence in subsequent 10 years
  • 1/4 of all seizure presentations to ED
  • Necessitate identifying underlying cause and treating it
  • Most commonly in a German study were alcohol withdrawal (74%), ICH (11%), ischaemic stroke (4%), intoxication (3%), structural lesions (3%), hyponatraemia (2%), hypoglycaemia (2%)
  • Predictors include male sex, no prior diagnosis of epilepsy and generalised tonic-clonic semiology
• Unprovoked seizures (US)
  • >60% risk of recurrence in subsequent 10 years
  • 3/4 of all seizure presentations to ED

First seizures

• Acute symptomatic – Known CNS insult
• Remote symptomatic – No acute provocation but recent CNS insult >1 week ago
• Progressive encephalopathy – In associated with progressive neurological diseases e.g. neurodegenerative, neurocutaneous or malignancies
• Febrile (children)
• Cryptogenic – No precipitating CNS insult

First seizures

• Acute symptomatic causes
  • Hypoxia
  • Hypoglycaemia
  • Head trauma
  • Meningitis/encephalitis including HIV
  • Metabolic – HypoNa, HypoCa, Hyperthyroid, uraemia and eclampsia
  • Drug overdose – Alcohol, TCA, theophylline, cocaine, amphetamine, isoniazid
  • Drug withdrawal – Alcohol, benzo, narcotics, cocaine, anticonvulsants
  • Cerebral tumor
  • Stroke

Generalised seizures

• Nearly simultaneous activation of entire cerebral cortex
• Begins with abrupt LOC 
• Generalised tonic-clonic seizures
  • Rigid tonic phase, trunk and extremities extended, patient falls to ground
  • Tonic phase subsides followed by coarse trembling evolving into symmetric rhythmic clonic jerking phase of trunk and extremities
  • Often apnoeic and may be cyanotic
  • Often urinate and may vomit
  • Patient left flaccid, unconscious with deep, rapid breathing
  • 60-90 seconds usually
  • Post-ictal confusion, myalgias and fatigue can last hours or more

Generalised seizures

• Absence seizures
  • Brief, lasting seconds with sudden altered consiousness but no change in postural tone
  • Appear confused, detached or withdrawn and any current activity ceases
  • May stare or have twitching/automatisms
  • Typically resume preceding activity without post-ictal phase
  • Classically in school-age children (i.e. daydreaming)
    • Can occur >100 times per day and generally resolve with maturation
  • In adults more likely minor complex partial seizures and should not be termed absence seizures

Partial (focal) seizures

• Electrical discharges in one area of the brain initially
• More likely to be structural lesion
• Simple partial focal seizures
  • Seizure remains localised with no loss of consciousness
  • Unilateral limb symptoms = motor cortex
  • Visual disturbance = Occipital
  • Bizarre olfactory or gustatory = medial temporal lobe
    • Often termed auras if followed by secondary generalisation
• Can become secondarily generalised and focal portion may be so short as diagnosis can only be made by focal spike on EEG

Partial (focal) seizures

• Complex partial seizures
  • Focal seizures with loss of consciousness
  • AKA temporal lobe epilepsy
  • Commonly very bizarre and misdiagnosed as psychiatric disorders
  • Symptoms include automatisms, visceral symptoms (butterflies), hallucinations (olfactory, gustatory, visual or auditory), memory disturbances, distorted perception and affective disorders (fear, paranoia, depression, ecstacy)
  • Lip smacking, fiddling with clothing, repeating short phrases

History

• Confirm actual seizure
• Preceding aura, abrupt or gradual onset, progression of motor activity, bladder/bowel incontinence, oral injury and whether localised/generalised and symmetrical or unilateral
• If known epilepsy, clarify baseline seizure pattern and type of seizures
• Precipitating factors
  • Alcohol, missed doses, poor sleep, dose changes, increased strenuous activity, infection, eletrolyte disturbances, substance abuse or withdrawal or drug interactions
• If first seizure
  • Ask about nocturnal tongue biting, previous unexplained injuries or enuresis (likely previously unrecognised seizures), any previous head injuries, headaches, pregnancy, systemic illness, toxin exposure, drug ingestion/withdrawal and alcohol use

Examination

• Vital signs, BSL
• Initially treat as trauma
• Posterior shoulder dislocations often missed
• Pulmonary aspiration, tongue laceration and dental fracture are common
• Full neuro and follow GCS closely to not miss NCSE
• Transient focal deficit following simple or complex focal seizure = Todd’s paresis and should resolve within 48 hours

DDx

• Seizure
• Syncope
• Dissociative attack
• Hyperventilation syndrome
• Migraine headache – May have aura similar to partial seizures and may have focal neurological symptoms during the migraine, however, not active movement disorders
• Movement disorders – Dystonia, chorea, myoclonic jerks, tremors or tics

Labs

• If known seizure disorder, may only require BSL and pertinent anticonvulsant levels
• First seizure
  • Serum glucose, VBG, Chem20, pregnancy test and toxicological studies as indicated
  • Lactic acidosis should clear within 30 minutes
  • Prolactin level remains elevated for 15-60 minutes and helpful if diagnosis in doubt
  • Consider anticonvulsant levels if not sure if known seizure disorder
    • Presence makes this more likely
• Therapeutic level of anticonvulsant is that at which seizures are controlled without unacceptable side effects NOT the lab-defined level
• A marked change in previously stable level suggests non-compliance, change in medication, malabsorption or interaction
• Very low level suggests non-compliance and is the most common cause of a breakthrough seizure
• Lactate >3 is suggestive of true seizure vs. dissociative attack

Imaging

• First seizure or change in seizure pattern – Non-contrast CT brain
  • If no focal signs and complete recovery after first seizure abnormalities on CT in <1% of patients
  • Urgent MRI probably preferred (especially in children) as more sensitive and no radiation but availability dictates preference
• Suspicion of intracranial process or injury – Non-contrast CT brain
• Follow-up contrast-enhanced CT or MRI often required if first episode to rule out tumors or vascular anomalies
• ¼ of adults with new-onset seizure will have visualised pathology on MRI with rates increasing to 53% with focal seizures

Lumbar puncture

• Indicated if febrile or immunocompromised or SAH considered

EEG

• Emergent EEF considered if persistent, unexplained altered LOC to evaluate for NCSE or subtle status epilepticus

Treatment

• Uncomplicated seizure ongoing
  • Recovery position, ensure open airway, suction and airway adjuncts if required
  • If fails to abate at 5 minutes, IV midazolam 5mg
  • Midaz x 2 q5min
  • Then IV levetiracetam
  • Then IV sodium valproate
  • Then midazolam infusion +- I&V +- phenobarbitone coma
  • Lacosamide may play a role also
• If 2 or more seizures – Clobazam 10mg BD PO/NG for 72 hours

Treatment

• Known history of seizures
  • Identify and correct any precipitants
  • Supplemental dosing + loading dose of usual agent if known
  • Take level prior to loading dose to identify non-compliance
  • IV or oral depending on pharmacology and clinical situation
  • If cannot get level e.g. levetiracetam just give usual dose +- load before discharge
  • If levels within therapeutic range and single seizure, specific treatment may not be required if seizure pattern and frequency falls within the expected range for the patient
  • If outside usual pattern, consult with regular neurologist re: dosing/medication change if no clear precipitant identified

Treatment

• First unprovoked seizure
  • Decision to begin outpatient anticonvulsant therapy depends on risk of recurrent seizures vs. risk-benefit ratio of anticonvulsant therapy
  • If first unprovoked seizure with normal mental status, normal neurological examination, no acute or chronic comorbidities, normal labs and normal non-contrast CT head – Can safely discharge home with f/u after discussion with neurology service 
  • If not meeting above criteria – admit
  • If provoked secondary seizure – admit, treat underying cause and generally anticonvulsant therapy initiated (unless precipitant easily removed)
  • Instructions on discharge to avoid swimming, working with hazardous tools or machines, driving or working at heights

Special populations

• HIV
  • Increased risk of mass lesions, encephalopathy, herpes zoster, toxoplasmosis, Cryptococcus, neurosyphilis and meningitis
  • Perform extensive investigations including LP if no evidence of raised ICP or mass lesion
  • If no explanation found, contrast CT or MRI required
• Neurocysticercosis
  • CNS infection with larval phase of Taenia solium (pork tapeworm)
  • Most common cause of secondary seizures in the developing world
  • Mostly parasitic invasion of brain parenchyma and cyst formation
  • Over 1-2 years, cyst degenerates and becomes fibrotic leaving focal scar
  • In 80-90% of cases, lesions resolve within 3-6 months and seizures cease
  • In most cases, neuroimaging is non-diagnostic. CT or MRI may show a 1-2cm cystic lesion and 1-3mm mural nodule (the parasite) with ring-enhacement of oedema, calcified lesion or hydrocephalus
  • Definitive diagnosis requires clinical picture, serologic testing and neuroimaging
  • Seizures are usually controlled with anticonvulsant monotherapy

Special populations

• Pregnancy
  • Most are not first-time seizures and evaluation is usually as per normal with the addition of obstetric evaluation for gestation and fetal well-being
  • If >20 weeks in the setting of HTN, proteinuria, and oedema = eclampsia
  • MgSO4 is the treatment of choice (4g)
  • >50% reduction compared to IV diazepam in seizure recurrence, pneumonia, ICU admission and assisted ventilation
• Alcohol abuse
  • Associated through missed doses of anticonvulsants, sleep deprivation, head injury risk, toxic co-ingestants, electrolyte abnormalities, hypoglycaemia and withdrawal seizures
  • Treat any alcohol-abusing patient with first seizure as for anyone else but always consider escalating doses of diazepam for withdrawal control

Status epilepticus

• Most common causes
  • Subtherapeutic anticonvulsant levels
  • Preexisting neurological conditions e.g. CNS infection, trauma, haemorrhage, stroke
  • Acute stroke
  • Anoxia/hypoxia
  • Metabolic abnormalities e.g. hypoNa, hypoCa, hypo/hyperglycaemia, uraemia, hepatic encephalopathy
  • Alcohol or drug intoxication or withdrawal
• U-shaped incidence curve: Mostly <1yo and >60yo
• Accounts for 1-8% of all hospital admissions for epilepsy
• More common in children and the elderly, disabled and those with structural cerebral pathology (specifically frontal lobe)
• Still occurs most commonly in those without a previous history of epilepsy (60%)
• Defined as single seizure >=5 min or two or more seizures without recovery of consciousness between seizures
  • Based on less likely to resolve spontaneously, less likely to be controlled by anticonvulsants and more likely to cause neuronal damage

Status epilepticus

• Mortality 2.7% if seizure <1 hour
• Mortality 32% if seizure >1 hour
• The longer it goes for, the greater the neuronal damage/death and the more refractory to treatment
  • Direct excitotoxic neuronal damage via excessive intracellular calcium flux through opening of NMDA channels and indirect hypoxic, hypotensive and hypothermic injury
  • Initial sympathetic drive is lost with subsequent ongoing high cerebral metabolic rate but inadequate cerebral blood flow and risk of cerebral ischaemia
• Most common causes for failed control of seizures
  • Inadequate anticonvulsant drug therapy
  • Failure to initiate maintenance anticonvulsant drug therapy
  • Hypoxia, hypotension, metabolic disturbance untreated
  • Failure to identify underlying cause
  • Failure to recognise medical complications e.g. hyperpyrexia, hypoglycaemia
  • Misdiagnosis of dissociative attack

Status epilepticus

• Failure to regain consciousness following treatment
  • Hypoxia, hypoglycaemia, cerebral oedema, hypotension, hyperpyrexia as a consequence of seizure activity
  • Sedation from anticonvulsants
  • Progression of underlying disease process
  • Non-convulsive status epilepticus (25% of cases)
  • Subtle generalised status epilepticus

Status epilepticus

• Investigations
  • FBC, Chem20, VBG, Anticonvulsant levels, urinalysis, CK, toxicology screen
  • CT head
  • LP
    • 20% will have modest WBC pleocytosis and need meningitis cover until excluded by culture
• Indications for continuous EEG
  • Refractory SE to aid anticonvulsant titration
  • Neuromuscular blockade
  • Ongoing ALOC despite apparent cessation of seizure activity
  • Suspected NCSE
  • Suspected pseudoseizures

Non-convulsive seizures

• Important cause of altered behaviour and conscious level
• May precede or follow convulsive episodes
• Can involve any sensory modalities, vertiginous episodes, automatisms, autonomic dysfunction or psychic disturbances e.g. déjà vu
• Easily confused with migraine, CVA or psychiatric conditions
• May be partial or generalised
• Non-convulsive status epilepticus accounts for 25% of all status epilepticus
• Acute treatment is the same once diagnosis considered

Non-convulsive status epilepticus

• Consider in any patient with ALOC, particularly those with CNS injury, metabolic disturbance, hepatic encephalopathy and sepsis
• Diagnosed in 8-18% of critically ill patients with ALOC of unknown cause
• Absence status epilepticus
  • Bilateral diffuse synchronous seizures. Relatively benign. Mostly children.
• Complex partial status epilepticus
  • Lateralised seizure activity on EEG with confusion, agitation, bizarre/aggressive behaviour or coma
  • Lip smacking, automatisms and gaze deviation may occur

Status epilepticus

• At 5 minutes:
  • Dramatic reduction in GABA receptors, increased glutamine/NMDA receptor expression leading to greatly diminished seizure threshold
  • BBB compromised leading to CNS penetration of albumin and potassium – hyperexcitatory chemicals
• 20 minutes
  • Hypotension, hypoxia, metabolic acidosis, hyperthermia, hypoglycaemia
  • Cardiac dysrhythmias, rhabdo and pulmonary oedema
• 2 hours
  • Neurotoxic amino acids and calcium released into cells leading to necrosis and apoptosis
  • All makes anticonvulsants far less effective
• Non-convulsive status epilepticus
  • Prolonged post-ictal period, subtle motor signs, twitching, blinking, eye deviation, fluctuation mental status or unexplained stupor or confusion in the elderly
• Epilepsia partialis continua
  • Focal tonic-clonic seizure with normal alertness mostly in distal leg or arm

Status epilepticus

• Treatment
  • First line
    • Midazolam IV 5mg up to 2 doses
  • Second line
    • Leviteracetam 2g IV in 100mL N/saline over 10-15min and/or
    • Valproate 800mg (<80kg) or 1200mg (>80kg) in 100mL N/saline over 10 minutes and/or
    • Phenobarbitone 400-800mg in 100mL N/saline over 15-20 minutes
  • Administer at least 2 of above before progressing
  • Third line
    • Midazolam infusion 1mg/mL at 0.05mg/kg/hr (max 5mg/hr at commencement)
    • Stat phenytoin 1g over 30 minutes once midazolam infusion started
    • Titrate midazolam infusion every 30 minutes by 0.5mg/hr until seizure aborted (up to 10mg/hr)
    • Lacosamide may also play a role
• Post-ictal phase
  • Clobazam 5-10mg PO once able to tolerate oral medicines

Agents

• IV lorazepam = IV diazepam
  • Lorazepam slightly slower onset (3 min vs. 2 min) but longer duration of action (12-24 hours vs. 15-60min)
  • Lorazepam showed fewer recurrent seizures
  • Lorazepam more effective than phenytoin or phenobarbital as initial drug
• Fosphenytoin
  • Water-soluble prodrug of phenytoin converted to phenytoin in plasma and not diluted with propylene glycol or ethanol (therefore lacks cardiac depressant effects)
  • 20 Phenytoin Equivalents/kg at 150 PE/min over 10-15 minutes
• Phenytoin
  • Diluted with propylene glycol and ethanol – hypotension and cardiac depressant effects
  • 20mg/kg IV at rate no faster than 25mg/min (up to 50mg/kg if status epilepticus but need to monitor closely for hypotension)
    • 1g simply not enough
  • Load everyone even if on oral phenytoin (as likely to be subtherapeutic anyway and no evidence of harm)
  • Cannot be mixed with glucose-containing fluids
  • Contraindicated in second or third degree heart block due to sodium-channel blockade and prolonged QT

Prognosis of SE

• Most strongly associated with age and aetiology
• Overall 30-day mortality is 15-20%
• Children mortality is 3% vs. >60yo 35%
• If precipitated by low anticonvulsant levels or systemic infection = very low mortality
• If Acute CNS or metabolic derangement – worse prognosis
• If post-anoxic injury – near universally fatal
• Refractory SE has worse prognosis (usually due to underlying cause)

Refractory status epilepticus

• 31% patients in status go on to this (failure of 2 agents)
• Propofol
  • Carries risk of propofol infusion syndrome in high doses (>40mg/kg/hr)
• Midazolam infusion
  • Can accumulate in peripheral tissues, particularly in renal insufficiency, leading to prolonged recovery
• Phenobarbital
  • May have minimal benefit in refractory status
  • Longer half-life and slow clearance compared to above leading to prolonged intubation and inability to clinically assess patients
• Ketamine
  • Third-line agent

Alcohol-related seizures

• Contributes to 50% of seizures presenting to ED
• Acute toxicity and withdrawal both contribute
• Also associated with falls, intercurrent disease, coagulopathy, assaults and other drug intoxication
• Phenytoin is ineffective at treatment or prevention of alcohol-related seizures

Drug-related seizures

• Ominous with greatly worsened morbidity and mortality
• Most commonly seen with TCA, isoniazid, antidepressants, antihistamines, theophylline and sympathomimetics
• Tramadol reduces seizure threshold also at normal therapeutic doses

Post-traumatic seizures

• Post-traumatic epilepsy develops in 10-15% of serious head injury survivors
• Risk factors include central parietal injury, dural penetration, hemiplegia, missile wounds and intracerebral haematomas

Seizures and pregnancy

• If previous epilepsy – increased risk of seizures in pregnancy of 17%
• Anticonvulsant levels impacted by reduced protein binding, increased drug binding and reduced absorption
  • Quite unpredictable effect on free drug levels, worst at time of delivery
  • Non-compliance or contentious abstinence of anticonvulsants also plays a critical role
• Generalised convulsive status epilepticus life-threatening to mother and fetus
• All anticonvulsants cross placenta and increase risk of teratogenicity from 3.4% to 3.7% in epileptic mothers
• Only neural tube defects seen with valproate and carbamazepine are specific. Rest of malformations are random
• Risk from uncontrolled seizures greatly outweighs risk of teratogenicity
• Eclampsia
  • 1/300 women with pre-eclampsia progress to eclampsia
  • Seizures are generally brief, self-terminating and preceded by headache and visual disturbance
  • Treatment is irected at controlling seizures and BP and delivery of baby
  • MgSO4 is effective in seizure control and better outcomes for mother and baby than standard anticonvulsant and antihypertensive agents

Intubation

• Consider paralytic agent carefully
• Suxamethonium contraindicated if history of chronic neurological disorders affecting motor end plate e.g. cerebral palsy
• Rocuronium paralyses patient for an extended period of time precluding monitoring of motor seizures
• Suggamadex may be an option

Dissociative attacks

• 20/20 rule suggests 20% of people with epilepsy also suffer true convulsions and vice versa
• Perhaps the majority of ‘seizure’ presentations to ED are actually dissociative attacks
• Suggestive features
  • Lactate <3
  • Multiple seizures
  • Short post-ictal phase
  • No structural brain pathology
  • Previous anxiety/depression/PTSD
  • Other functional disorders
  • Non-stereotyped movements (i.e. different each time)
  • Previous diagnosis
• Importantly, gender, age and previous diagnosis of epilepsy are not predictive either way of true seizure or dissociative attack
• Management
  • If early in functional disease course, admission may be highly beneficial to have confirmatory positive diagnosis of FND, explanation and management pathway initiated
  • Video EEG is the gold standard in confirming diagnosis
  • Providing a positive diagnosis is very important
  • Can describe as a software problem in the brain with a disconnection between functional parts of the brain and subsequent failure of normal brain functions
  • Positive optimistic demeaner that this is treatable helps to prevent recurrent presentations

Last Updated on November 22, 2021 by Andrew Crofton