Epilepsy

 

• Background

  Definition

  • Repeated seizures due to abnormal electrical activity in brain.
  • Can be focal (aka partial) – which often suggests an underlying structural disease – or generalized, in which there is simultaneous discharge in both hemispheres.
  • 'Post-ictal' refers to the period immediately after the seizures.

  Epidemiology

  2 age peaks: youth (congenital) and elderly (secondary).

• Risk factors and causes

  Risk factors for idiopathic epilepsy:

  • Family history of epilepsy.
  • Febrile convulsions in childhood.
  • Motor/developmental delay.

  Specific causes:

  • Developmental: cerebral palsy, Down's syndrome.
  • Traumatic brain injury. However, seizures within 30 days of a TBI aren't classified as epilepsy, and conversely, seizures occurring many years later are often not related to the injury.
  • Other structural causes: space-occupying lesion, stroke, hippocampal sclerosis (aka mesial temporal sclerosis, seen in Alzheimer's), tuberous sclerosis.
  • Infectious and autoimmune diseases which cause chronic brain injury can lead to epilepsy. Includes meningitis, syphilis, neurocysticercosis, SLE, PAN, and sarcoidosis.

• Seizure types and features

  Focal seizures

  Classification:

  • Aware (aka simple partial): seizure with retained consciousness.
  • Impaired awareness (aka dyscognitive, complex partial): seizure with impaired consciousness, which may be manifest as a blank stare and/or behavioural arrest. Often features post-ictal confusion if temporal, or a quick recovery if frontal.
  • Focal to bilateral tonic-clonic (aka partial seizure with secondary generalization): starts focal then becomes general. Note this is the only time a generalized seizure can have an aura.
  • Newer classification also divides them into motor onset (e.g. automatisms, clonic, tonic) and nonmotor onset (e.g. autonomic, sensory).

  Aura:

  • Symptoms before main seizure, a 'warning sign'.
  • Commonest in temporal seizures.
  • Symptoms: flashing lights, strange gut feeling, déjà vu, sensing smells.

  Temporal lobe seizures

  • Autonomic symptoms: rising sensation or pain in abdomen, vomiting, flushing, pallor, altered HR.
  • Altered 'higher' functions: déjà or jamais vu, amnesia, altered emotions, delusions, hallucinations (including of smell or taste), dysphasia (also post-ictal).
  • Motor symptoms: complex movements – e.g. singing, driving, undressing – and automatisms e.g. lip smacking, fumbling.

  Frontal lobe seizures

  • Often affects motor cortex, causing abnormal movements – e.g. eye and head movements, peddling movements – or motor arrest.
  • Onset and timing: usually short, quick onset, with rapid recovery. Can be at night and come in clusters.
  • Jacksonian march: tingling spreading from one area to another e.g. from hand up to face.
  • Speech symptoms: vocalisations, dysphasia, speech arrest.
  • Behavioural changes.
  • Recovery usually rapid, but post-ictal phase can feature weakness (Todd's palsy).

  Benign rolandic epilepsy

  • Commonest epilepsy syndrome in children, especially age 5-10 years.
  • Start around the central sulcus (aka Rolandic fissure), which divides the frontal and parietal lobes.
  • Nocturnal seizures: facial twitches including eye flickering and lip smacking, aphasia, salivation.
  • No true post-ictal phase, but may feel a little weak or have altered sensation.
  • Occasionally, can progress to GTCS.

  Parietal lobe seizures

  • Often affects somatosensory cortex, causing abnormal sensations such as tingling or numbness.
  • Motor symptoms if it spreads to pre-central gyrus.

  Occipital lobe seizures

  • Affects visual cortex, causing visual symptoms such as shapes and/or flashes.
  • Shapes are often more colourful and circular than migraine.

  Primary generalized seizures

  Absence seizures (aka petit mal, nonmotor)

  • A behavioural pause, usually <10 seconds, reflecting altered consciousness without change in muscle tone.
  • Starts in childhood.
  • Often characterized by 3 Hz spike and slow-wave complexes on EEG.

  Generalized tonic-clonic seizures (GTCS, aka grand mal, motor)

  • Loss of consciousness
  • Limbs stiffen (tonic) then rhythmically jerk (clonic).
  • Often starts with cry and/or biting the side of the tongue.
  • May be cyanosed due to chest spasm.
  • Urine and/or faecal incontinence.
  • Post-ictal confusion and drowsiness.

  Atonic seizures (aka akinetic)

  • Sudden, brief loss of tone and consciousness.
  • Will fall or regain consciousness and catch themselves.

  Myoclonic seizures

  General features:

  • Sudden jerk of bilateral limbs (usually arms), face, or trunk. May lead to fall.
  • Can be single or multiple.
  • May occur on waking.

  Syndromes:

  • Juvenile myoclonic epilepsy (JME): morning myoclonus, GTCS on awakening, and sometimes absences and photosensitivity. Often leads to lifelong myoclonic epilepsy.
  • Infantile spasms (aka West syndrome): limb and trunk myoclonus ('salaam sign') starting <1 year old, severe developmental delay, 1/3 die by adulthood.
  • Generalized epilepsy with febrile seizures plus (GEFS+): autosomal dominant syndrome of febrile and/or afebrile seizures of any type, starting in infancy and hard to treat. Can be accompanied by developmental delay and death. Includes severe myoclonic epilepsy of infancy (SMEI), aka Dravet's syndrome.

  Non-specific features

  Triggers, especially for generalized seizures:

  • ↓Sleep
  • Alcohol
  • Fever
  • Flickering light.
  • Drugs, or drug withdrawal.

  Other features:

  • In any given patient, it is usually the same kind of seizure every time.
  • Rarely, there will be a prodrome of hours to days, characterized by altered mood, behaviour, or cognition.
  • Many seizures have a crescendo pattern, especially GTCS.

• DDx: Seizures

  Epilepsy.

  Non-epileptic seizures:

  • Non-epileptic attack disorder (NEAD).
  • Acute trauma may cause a concussive seizure, featuring a tonic phase within 2 seconds of injury, then a clonic phase for minutes.
  • Cardiovascular: stroke, haemorrhage, pre-eclampsia, arrhythmia. Note that true epilepsy – i.e. recurrent seizures – can develop later as a result of stroke.
  • Metabolic: ↓O2, altered Na+, ↓Ca2+, altered glucose, uraemia.
  • Infection: meningitis, encephalitis, fever. Fever can also be a trigger of true epilepsy in those with known disease.
  • Drugs: alcohol or benzodiazepine withdrawal, tricyclic antidepressants, cocaine, tramadol, theophylline.
  • Other: ↑ICP, liver disease.

• History

  Presenting complaint:

  • What happened before, during, and after.
  • Get a collateral too.
  • Establish what seizure type it is.
  • Triggers
  • Look for distinguishing features of true epilepsy vs. non-epileptic attack disorder (NEAD).

  Past medical history:

  • Previous seizures.
  • Other symptoms not previously attributed to epilepsy e.g. funny sensations (focal), spaced out (absence), clumsy in morning (myoclonic), seizing in sleep (wake up in wet bed with bitten tongue).

  Risk factors.

  Wider issues:

  • Driving, work dangers, contraceptive pill.

• Investigations

  Key points:

  • It is usually a clinical diagnosis, so the history is vital.
  • EEG is often not that useful: 40% sensitive, 80% specific. To improve sensitivity, seizures can be induced – with hyperventilation, photic stimulation, or sleep deprivation – especially if localization is important for treatment decisions. Also useful for helping to diagnose specific seizure syndromes.
  • MRI or CT head can help localise the cause of a focal seizure and rule out other causes such as tumour or stroke.

  In an acute setting, rule out non-epileptic seizures:

  • Glucose
  • U+E
  • Serum drug levels, if appropriate.
  • Everyone who presents with a suspected seizure, collapse, or loss of consciousness should have an ECG to rule out a cardiac cause that may predispose to sudden death e.g. long QT.

• Management

  Acute seizure management

  • Remove obstacles, call ambulance and give benzodiazepine (BZD) if >5 minutes. Most seizures are shorter than this.
  • Buccal midazolam (IM from paramedics) or PR diazepam at home, and IV lorazepam in hospital.
  • Never give >2 doses BZD outside of hospital, and you must have resus facilities available if giving IV BZD.
  • ABC and O2.
  • Recovery position after seizure.
  • Prescribe midazolam/diazepam for future use.

  Long-term antiepileptic drugs (AEDs)

  Starting and switching:

  • Only 50% having a 1st seizure go on to have a 2nd seizure, so treatment should be delayed until then.
  • Ideally use 1 AED at a time, building up dose until seizure-free or side effects are intolerable.
  • Taper and overlap if switching.
  • 50% are seizure-free on 1 drug, and a further 15% on 2 or 3.
  • If poorly controlled on 2 or 3, review diagnosis, and if disabling consider surgery – if there is an identified lesion – or vagus nerve stimulation.

  AED choice:

  • For each type: 1st line → switch to 2nd line → switch to or add 3rd line.
  • Focal (± secondary generalization): carbamazepine or lamotrigine → switch to levetiracetam, sodium valproate, or oxcarbazepine → switch to or add clobazam, topiramate, or GBP.
  • GTCS: sodium valproate → switch to lamotrigine (especially in women), carbamazepine, or oxcarbazepine → add clobazam, topiramate, gabapentin, sodium valproate, or lamotrigine.
  • Absence: ethosuximide, sodium valproate, or lamotrigine, switching between then combining if not successful → switch to or add clobazam, clonazepam, levetiracetam, or topiramate.
  • Myoclonus/JME: sodium valproate → switch to or add clonazepam, lamotrigine, levetiracetam, or topiramate.
  • In absence and myoclonic epilepsy, the following are contraindicated: carbamazepine, oxcarbazepine, phenytoin, gabapentin.

  Stopping AEDs:

  • Must be an informed choice.
  • Criteria for trial stop: normal CNS exam, normal IQ, normal EEG, seizure-free for 2 years, and no JME.
  • Taper over 3 months.
  • 50% remain seizure free after stopping.

  Monitoring and advice

  Review:

  • Review annually: children with a specialist, and most adults with a GP.
  • Routine bloods are not necessary.
  • Blood test monitoring is only indicated for: monitoring PHT dose, suspected non-adherence, suspected toxicity, suspected interactions, and uncontrolled seizures in pregnancy. The commonest cause of ↓AED levels is poor adherence.

  Counselling:

  • Driving: can't drive until 1 year seizure-free.
  • Think about safety issues at work.
  • Try and avoid triggers including alcohol and poor sleep.
  • Discuss drug side effects, particularly relating to contraception and pregnancy.

  Drugs to avoid, as they may increase seizure risk:

  • Excess alcohol: may trigger seizures, possibly directly, through sleep disruption, or by disrupting AED function.
  • Fluoroquinolones
  • Aminophylline and theophylline.
  • Methylphenidate

• Complications and prognosis

  Complications:

  • Status epilepticus.
  • Sudden unexpected death in epilepsy (SUDEP): risk factors are uncontrolled or poor compliance, young age, GTCS, learning disability, seizures in sleep, and unwitnessed seizures.
  • Accidents driving or at work.

  Prognosis:

  • 60% with childhood-onset epilepsy go into complete remission by adulthood. For absence seizures, remission rate it 90%.
  • Poorer prognosis if onset age ≥10 years, developmental problems, or drug-resistant disease.

• Antiepileptic drug mechanisms

  • Most AEDs are Na+ channel blockers, reducing the release of excitatory glutamate.
  • Benzodiazepines – lorazepam, clobazam, clonazepam – positively modulate the GABAA receptor on neuronal Cl- channels, thus decreasing neuronal excitability through membrane hyperpolarization.
  • Sodium valproate both blocks Na+ channels and enhances GABA transmission by ↑synthesis, ↑release, and ↓breakdown.
  • Ethosuximide is a T-type calcium channel blocker.

• Antiepileptic drug side effects

  General:

  • Almost all cause some degree of drowsiness.
  • All are teratogens – especially sodium valproate and topiramate – except for levetiracetam.

  Sodium valproate (SVP)

  VALPROATE:

  • Vomiting and nausea, so take with food.
  • Appetite increase and weight gain.
  • Liver failure.
  • Pancreatitis
  • Reversible hair loss. May grow back curly.
  • Oedema
  • Ataxia
  • Tremor
  • Thrombocytopenia
  • Encephalopathy

  Monitoring:

  • LFT at baseline then throughout first 6 months.
  • FBC at baseline for bleeding risk.

  Carbamazepine (CBZ)

  • Unsteadiness, diplopia.
  • Rash, including SJS.
  • Neutropenia
  • SIADH. Only stop CBZ if there are symptoms, however.

  Lamotrigine (LTG)

  • Unsteadiness, diplopia.
  • Rash, including SJS
  • Hypersensitivity syndrome: fever, rash, and organ failure.
  • Headache
  • ↓WBC

  Phenytoin (PHT)

  • Unsteadiness, diplopia.
  • Cerebellar signs: nystagmus, tremor, dysarthria, ataxia.
  • 'Inflammatory': gingivitis, lymphadenopathy, hypersensitivity syndrome.
  • MSK/derm: osteomalacia, rash, coarse face.
  • ↓Intellect, depression.
  • Megaloblastic anaemia due to folate deficiency; consider folate replacement. Also leukopenia, thrombocytopaenia.
  • Hepatotoxicity
  • Levels artificially low in cirrhosis (due to ↓albumin), so avoid giving more and risking toxicity (saturation kinetics).

  Levetiracetam (LEV)

  • Altered mood or behaviour: irritable, aggressive. Affects 1/10
  • Dizziness.

  Topiramate (TPM)

  • Weight loss
  • Altered behaviour
  • Parasthesia
  • Kidney stones

• Antiepileptic drug interactions

  Overview

  • Many AEDs reduce the effectiveness of other drugs as they are enzyme inducers.
  • Some may increase GGT, but continue drug if the patient is well.

  Contraception

  • Reduce pill effect: CBZ, OCBZ, PHT, TPM.
  • While on any of these AEDs, need to take combined contraceptive pill containing >50 μg estrogen, with a tricycle regimen of 3 x 3 weeks consecutive pill packs followed by 4 days of.
  • If breakthrough bleeding after 2-3 cycles, then consider the pill to be ineffective and further increase the dose of estrogen.
  • As an alternative to the pill, depot injections or Mirena are not affected by AEDs.
  • A higher dose of emergency contraception is usually needed, or use an IUCD.
  • LTG effect is lowered by the pill.

  Warfarin

  • Interacts with CBZ and PHT, so consider alternative AED.
  • If used, increase warfarin dose and increase INR monitoring frequency.

  Auto-induction

  • CBZ, so dose may need to be raised (once poor adherence is ruled out).

• Epilepsy management during pregnancy

  MDT approach:

  • Find out who their neurologist is and ensure joint care with an obstetrician.

  Discuss risks:

  • Higher risk of neural tube defects and cleft palate, mainly due to AEDs: risk is around 5% on AEDs vs. 2.5% in patients not taking AEDs, or 1.5% in the general population. Valproate also carries risk of neurodevelopmental delay.
  • Need to balance risks to baby of AEDs vs. risks of stopping or lowering dose such as status epilepticus and SUDEP.
  • Pregnancy itself does not usually increase seizure frequency, with women previously seizure-free likely to remain so. Risk of GTCS during pregnancy is around 1%.
  • Warn women who have GTCS that it carries a small risk to the fetus – hypoxia, miscarriage, trauma from fall – but it is low. No risk with other seizure types.
  • Epilepsy is a risk factor for other pregnancy complications: hyperemesis, pre-eclampsia, vaginal bleeding.
  • Consider genetic counselling if she has idiopathic epilepsy.

  Medication:

  • Folate 5 mg.
  • AED: any one of LTG, LEV, or CBZ (or OCBZ). TPM may be OK after the first trimester.
  • Avoid SVP, PHT, and polytherapy (especially ≥3), though the latter may be necessary if already on it.

  Monitoring:

  • Ensure they have 20 week scan.
  • PHT and LTG levels may change in pregnancy. However, only monitor them if there are repeated seizures.
  • Continuous CTG in the event of an intra-partum seizure.

  Postnatal:

  • Encourage breastfeeding, as with all mothers. Check BNF re. AED safety.
  • Discuss safety precautions when taking care of baby e.g. change and feed on the floor, don't bathe alone.

• Status epilepticus

  Definition and causes

  • A generalized seizure lasting >30 minutes (some say >5 minutes), or recurrent seizures without regaining consciousness in between.
  • Usually occurs in known epileptics but can be a presenting complaint.
  • Can also be due to other seizure causes: stroke, tumour, alcohol, withdrawal, encephalitis, altered glucose or electrolytes.

  Signs and symptoms

  • Often tonic-clonic, with fever and sweats.
  • Can also be non-convulsive, characterised by confusion, altered mental status, odd behaviour, and derealization.

  Management of prolonged seizure

  For anyone seizing longer than 5 minutes and not responding to first dose of buccal/rectal/IM BZD:

  1. ABC including airway and O2
  2. Get IV access. Take bloods: glucose, U+E, Ca2+, LFT, FBC, tox screen, and AED levels if required.
  3. Give IV glucose, thiamine, or fluids as required.
  4. Give IV lorazepam in slow bolus (30 seconds). Repeat after 10 minutes if required. Beware respiratory arrest.
  5. Other investigations: ECG, and consider EEG, blood cultures, LP, urinalysis and CT. These may be more appropriate later.
  6. If seizure ongoing (20 minutes), give phenytoin loading dose then infusion. ECG monitoring.
  7. If seizures still ongoing (30 minutes i.e. status), anaesthetise with phenobarbital, propofol, or thiopentone. Intubate and transfer to ITU. EEG monitoring.

  Complications

  Death, due to cerebral hypoxia, depletion of neurotransmitters, and ↑lactate.

• Non-epileptic attack disorder (NEAD)

  Functional disease, often looking like a GTCS.

  Differentiating from epilepsy

  • Often lacks a crescendo pattern, but rather is very dramatic from the start.
  • No true post-ictal phase with confusion, but they may say they are tired or weak afterwards.
  • Many seizures in a day, while in true epilepsy >5 separate GTCS in a day is very rare.
  • Features incompatible with a true GTCS: they stay standing, they remember seizing.
  • In a 'focal' functional seizure, they may have bilateral symptoms. In true epilepsy, focal signs should lateralise, although autonomic symptoms are felt all over.