Overview
Definitions
- Seizure: an acute change in neurological function produced by abnormal synchronous activity in the cerebral cortex
- Epilepsy: a predisposition to having seizures
Seizures can be classified in several ways:
- In terms of underlying cause:
- In terms of semiology (clinical picture)
- In terms of which parts of the cortex are involved
Types of seizure by cortical origin:
- Focal seizure with retained consciousness: a seizure originating from a single region which does not spread and does not cause any impairment of consciousness.
- Focal seizure with impairment of consciousness: a seizure which originated from a localised region of cortex but spreads and leads to impairment of consciousness.
- Generalised seizure: a seizure originating from bilateral cerebral hemispheres which usually produces loss of consciousness at its onset
Pathogenesis
Causes of seizures
Acute symptomatic seizures are seizures which occur in the context of an acute CNS illness. Common causes include:
Infection
- Meningitis
- Encephalitis
- Cerebral abscess
Vascular
- Stroke
- Arterial
- SAH
- Ischaemic
- Haemorrhagic
- Venous thrombosis
- Arterial
- Subdural haematoma
Trauma
- TBI
Endocrine/metabolic
- Hypoglycaemia
- Hypocalcaemia
- Hypomagnasaemia
- Uraemia
- Hyper/hypothyroidism
Toxic
- Alcohol
- Intoxication
- Withdrawal
- BDZ withdrawal
- Most recreational drugs
Causes of epilepsy
Some people diagnosed with epilepsy have a clear underlying factor promoting epileptogenesis. In others, epilepsy is presumed to multifactorial. In the majority there is no obvious inciting factor causing the epilepsy. The list of likely causes depends mainly on the patient’s age: genetic and metabolic conditions mainly present in childhood, whereas space-occupying lesions, neurodegenerative disorders, and other causes are more likely causes in people who present with adult-onset epilepsy. Causes can be classified as follows:
- Structural
- Neurodevelopmental abnormalities
- Space-occupying lesions
- Neurodegenerative disease
- Post-infarction
- Hippocampal sclerosis
- Genetic
- ‘Idiopathic’ generalised epilepsies of childhood
- Channelopathies
- Metabolic
- Mitochondrial disorders
- Enzyme deficiencies
- Immune
- NMDA encephalitis
- Paraneoplastic encephalitis
- Infectious
- Neurocysticercosis
- TB
- HIV
Clinical presentation
Focal seizures without impaired consciousness
- Manifestations depend on
- Initial Location
- Spread
- Locations
- Most common site: temporal lobes
- Also frontal lobes
- More rarely, parietal or occipital lobes
- Characteristics
- Brief
- Intense
- Specific manifestations
- Focal motor signs
- Autonomic signs (flushing, sweating, vomiting)
- Sensory signs (flashing lights, unpleasant odours, tastes, vertigo, paraesthesiae, pain)
- Psychic symptoms (déjà vu, depersonalisation, fear, illusions, hallucinations)
Focal seizures with impaired consciousness
- Definition : impairment of consciousness
- Can either start with impaired consciousness or progress from a simple partial seizure
- Characteristics
- Automatic behaviours
- plucking at clothes, fiddling, lip smacking, chewing, grimacing, undressing, purposeless activities
- Last for minutes
- Post-ictal
- confusion
- amnesia
- Automatic behaviours
Focal and generalised seizures
- Definition: generalised seizures which originate as partial seizures
- Can be difficult to diagnose as the initial, localised onset can progress rapidly
- Usually >> generalised tonic-clonic but can also lead to
- Unilateral tonic-clonic
- Tonic
- Atonic
Generalised seizures
- Definition: a seizure arising bilaterally in the cortex which involves loss of consciousness at the onset à there is usually no warning
- Classification:
- Generalised tonic-clonic
- Absence
- Myoclonic
- Atonic
- Tonic
- clonic
Type | Aura | During | Post-ictal |
GTCS | No warning | Tonic phase: ‘all-over’ rigidity, +/- apnoea, unilateral tongue-biting
Clonic phase: rhythmic jerking of all 4 limbs Relaxation phase |
Drowsiness
Confusion Headache Myalgia Incontinence
|
Absence | No warning | Blank appearance
Eyelid fluttering Head flopping |
Mild confusion |
Myoclonic | No warning
Occur in morning |
Brief, involuntary jerky movement | None |
Atonic | No warning | ‘Drop attack’: sudden loss of tone | None |
Tonic | No warning | Sudden rigidity >> fall | Rapid recovery |
DIAGNOSIS
General points
- Epilepsy is primarily a clinical diagnosis
- It is a diagnosis with implications e.g. driving, so be careful
- Investigations and symptoms may be entirely normal/absent between attacks
- Main differential diagnosis in an adult
- Syncope
- Migraine
- Panic attack
- TIA
- NEAD
- Main differential diagnoses in a child
- Breath-holding attacks
- Pavor nocturnis – night terrors
Key differentials and how to rule them out
- Syncope
- Prodrome: can be a bit like an aura. Prodrome in vasovagal syncope is usually very clear.
- Hot/flush
- Dizzy
- Vision becomes grey
- Situation: rarely when sitting (unless cardiogenic)
- Precipitant: usually there is a precipitant
- The attack: some limb jerking may occur especially if they are propped up as this compromises cerebral blood flow. Very rare to have proper tonic-clonic jerking.
- Recovery: post-syncope it is rare to be confused. Usual to feel shaky and sick.
- Prodrome: can be a bit like an aura. Prodrome in vasovagal syncope is usually very clear.
- Migraine
- Especially basilar migraine, but this will usually occur in tandem with other brainstem symptoms e.g. vertigo, nausea
- Seizures are often followed by headache, so this can be confusing
- Migraine can also show paroxysmal EEG phenomena
- Hyperventilation
- Paraesthesiae
- Carpopedal spasm
- Vertebrobasilar TIA
- Young women
- Associated with vertigo and bilateral visual symptoms
- Possibly tetraparesis
- Transient Global Amnesia
- Middle-age à older people
- Alert & communicative
- Patient may repeat the same question
- Recovery is complete
- Residual amnesia of episode
- Pseudoseizures
- Prolactin levels are increased
NB in partial seizures there may be an ‘autonomic prodrome’ which mimic presyncope.
Epilepsy | NEAD | |
Stereotypy | Stereotyped | Variable |
Cyanosis | Possible | Rare |
Incontinence | ||
Tongue biting | ||
Burns, other injuries | ||
Plantars | Extensor after tonic-clonic | Flexor |
Eyes | Easily opened | Hard to open |
Duration | Seconds-minutes | Variable. Possibly up to 1h |
Ictal EEG | Abnormal | Normal |
Post-ictal EEG | Abnormal | Normal |
Prolactin level post-ictal | Very high after tonic-clonic | Slightly raised |
Association with psychological event | Often | Very often |
Response to AEDs | Excellent | Short-lived |
INVESTIGATIONS
- Bloods (rule out reversible causes)
- Infection
- Metabolic
- Hyponatraemia
- Hypocalcaemia
- Hypoglycaemia
- Hypothyroidism
- Hepatic failure
- Renal failure
- EEG
- Interictal EEG has about 50% sensitivity and 99% specificity
- Repeat EEG improves these stats
- Sleep EEG is even better (80% sensitivity)
- Routine EEG can be improved using
- Photic stimulation
- Hyperventilation
- If these are unsuccessful, consider
- Video telemetry
- Useful pre-surgery
- ?NEAD
- Unusual events during sleep
- Ambulatory EEG
- Artefacts
- Lack of video
- Certain epileptic foci are invisible to scalp EEG:
- Simple partial seizures (if small)
- Orbitofrontal cortex
- Video telemetry
- MRI
- Indications
- Epilepsy + focal neurological signs
- New epilepsy after the age of 20
- New epilepsy in the neonatal period
- MRI is especially useful in diagnosing hippocampal sclerosis
- Indications
Management
~50% of patients with newly diagnosed epilepsy will become seizure-free with the first anti-epileptic drug (AED) prescribed [ref]
Choice of medications is tailored to individual taking into account complex web of:
- efficacy
- tolerability
- drug/comorbidity interactions
- Remember, many AEDs including phenytoin, carbamazepine & topiramate are inducers of the P450 enzyme system
- Caution when co-prescribing warfarin, or oral contraceptive pill
- pregnancy considerations
Monotherapy is generally preferable and increases the probability of compliance. “Start low and go slow” tactics used in titration to reach dose that is both tolerable to efficacious.
In terms of which is the best initial monotherapy, there have been a bunch of head-to-head shortish RCTs, all of which seem to suggest most of the AEDs have comparable efficacy. The largest randomised trial (the SANAD trial) was unblinded but mean follow up was >3 years. SANAD concluded that lamotrigine is best for focal seizures, and valproate is best for generalised, however as above, the choice is also dependent on other patient-specific factors. Specific medications are discussed below:
Simple | Complex | Tonic-clonic | Absence | Mechanism | Side effects | Teratogenicity | |
---|---|---|---|---|---|---|---|
Carbamazepine | 1 | 1 | 1 | Blocks Na channels | P450 inducer, diplopia, ataxia, blood dyscrasia, SJS | High | |
Phenytoin | 1 | 1 | 1 | Blocks Na channels | Cerebellar syndrome, sedation, peripheral neuropathy, hirsuitism, gum hyperplasia, megaloblastic anaemia | High | |
Lamotrigine | 1 | 1 | 1 | 1 | Blocks voltage-gated Na channels | SJS | Low |
Valproate | 1 | 1 | 1 | 1 | Inactivates Na channels, increases GABA | Hepatotoxicity, pancreatitis, tremor, weight gain | High |
Topiramate | 1 | 1 | 1 | Blocks Na channels, increases GABA | Sedation, weight loss | ||
Levetiracetam | 1 | 1 | 1 | Unknown |
What does NICE (CG137) say?
- Focal
- New diagnosis: Carbamazepine or lamotrigine
- Add in: clobazam, gabapentin, levetiracetam, valproate or topiramate
- Generalised
- New diagnosis: Valproate or lamotrigine
- Add in: clobazam, levetiracetam, valproate or topiramate
- Absence
- New diagnosis: Ethosuximide or valproate
- Add in: Lamtorigine
- Avoid: carbamazepine, gabapentin, phenytoin, pregabalin …
- Myoclonic or juvenile myoclonic seizures
- New diagnosis: Valproate
- Add in: levetiracetam or topiramate
- Avoid: lamotrigine and carbamazepine