Seizures
Short Notes
A seizure is defined as:
‘An abnormal, unregulated electrical discharge that occurs within the brain’s grey matter and transiently interrupts normal brain function’.
Epilepsy is defined as:
A brain disorder characterised by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition’.
A seizure may occur in a normal brain when provoked by reversible stressors e.g. hypoglycaemia.
Epilepsy is diagnosed when 2 or more seizures have occurred independent of reversible factors.
‘An abnormal, unregulated electrical discharge that occurs within the brain’s grey matter and transiently interrupts normal brain function’.
Epilepsy is defined as:
A brain disorder characterised by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition’.
A seizure may occur in a normal brain when provoked by reversible stressors e.g. hypoglycaemia.
Epilepsy is diagnosed when 2 or more seizures have occurred independent of reversible factors.
Seizures result from a sudden imbalance of the excitatory and inhibitory forces within cerebral neurons. The result is sudden onset net excitation.
The number of potential causes is massive:
The number of potential causes is massive:
- Hypoxia
- Metabolic derangement: hypoglycaemia, uraemia, hepatic encephalopathy
- Electrolytes disturbance: Hypo/hypernatraemia, hypo/hypercalcaemia, hypomagnesaemia
- Drugs: Cocaine, cyclosporine. Aminophylline, antidepressants, antipsychotics (some), isoniazid
- Drug withdrawal: Alcohol, benzodiazepines, barbituates (i.e. sedatives)
- CNS infection: Meningitis, encephalitis, rabies, malaria
- CNS trauma
- Ischaemia: stroke, vasculitis, cerebral venous thrombosis
- Cerebral oedema: eclampsia, hypertensive encephalopathy
- Expanding lesions: CNS neoplasm, intracranial haemorrhage
- Hyperpyrexia; febrile convulsions (child), heatstroke
The wide range of neurological functions means that seizures can present in a wide variety of ways. The main clinical differentiation is between generalised seizures (involving both hemispheres, usually with loss of consciousness) or focal seizures (starting in a specific cerebral location with a wide range of consequences)
The subtypes of generalised seizures include:
The subtypes of generalised seizures include:
- Tonic-clonic
- Absence
- Typical
- Atypical
- With special features
- Myoclonic
- Clonic
- Tonic
- Atonic
- Simple focal – There is preservation of consciousness. Previously referred to as simple partial
- Complex focal – consciousness is impaired. Previously complex partial.
- Secondary generalised – there is progression to a generalised seizure state.
- Aura – involving subjective psychic or sensory phenomenon only
Management will focus on initial identification and correction of any cause for the seizure.
For those patients who will have an ongoing predisposition to seizures e.g. an epilepsy diagnosis, the antiepileptic drugs are usually started, depending on the seizure type.
For those patients who will have an ongoing predisposition to seizures e.g. an epilepsy diagnosis, the antiepileptic drugs are usually started, depending on the seizure type.
Long Notes
A seizure is defined as:
‘An abnormal, unregulated electrical discharge that occurs within the brain’s grey matter and transiently interrupts normal brain function’.
Epilepsy is defined as:
'A brain disorder characterised by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition’.
A seizure may occur in a normal brain when provoked by reversible stressors e.g. hypoglycaemia.
Epilepsy is diagnosed when 2 or more seizures have occurred independent of reversible factors.
‘An abnormal, unregulated electrical discharge that occurs within the brain’s grey matter and transiently interrupts normal brain function’.
Epilepsy is defined as:
'A brain disorder characterised by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition’.
A seizure may occur in a normal brain when provoked by reversible stressors e.g. hypoglycaemia.
Epilepsy is diagnosed when 2 or more seizures have occurred independent of reversible factors.
Pathophysiology
Seizures result from a sudden imbalance of the excitatory and inhibitory forces within cerebral neurons. The result is sudden onset net excitation.
Given the vast array of activities that the brain is involved in, the result of this excitation is massively varied. At a simple level it can be considered as representing the function region of the brain that is involved e.g. motor cortex, auditory cortex.
The physiology of the inhibitory and excitatory receptors and neurotransmitters is discussed elsewhere but worth considering, as is the functional anatomy of the brain.
It is this combination of the increased excitatory potential and functional anatomy that produces the different presentations of the seizure disorders.
Given the vast array of activities that the brain is involved in, the result of this excitation is massively varied. At a simple level it can be considered as representing the function region of the brain that is involved e.g. motor cortex, auditory cortex.
The physiology of the inhibitory and excitatory receptors and neurotransmitters is discussed elsewhere but worth considering, as is the functional anatomy of the brain.
It is this combination of the increased excitatory potential and functional anatomy that produces the different presentations of the seizure disorders.
Aetiology
The number of causes of seizures is massive.
In a number of cases (of epilepsy) the cause will be unknown., though will probably have some genetic basis.
Important causes:
In a number of cases (of epilepsy) the cause will be unknown., though will probably have some genetic basis.
Important causes:
- Hypoxia
- Metabolic derangement: hypoglycaemia, uraemia, hepatic encephalopathy
- Electrolytes disturbance: Hypo/hypernatraemia, hypo/hypercalcaemia, hypomagnesaemia
- Drugs: Cocaine, cyclosporine. Aminophylline, antidepressants, antipsychotics (some), isoniazid
- Drug withdrawal: Alcohol, benzodiazepines, barbituates (i.e. sedatives)
- CNS infection: Meningitis, encephalitis, rabies, malaria
- CNS trauma
- Ischaemia: stroke, vasculitis, cerebral venous thrombosis
- Cerebral oedema: eclampsia, hypertensive encephalopathy
- Expanding lesions: CNS neoplasm, intracranial haemorrhage
- Hyperpyrexia; febrile convulsions (child), heatstroke
- Angelman syndrome
- Tuberous sclerosis
- Prader-Willi syndrome
- Tay-Sachs
The recommendations of the International League Against Epilepsy (ILAE) are to classify seizure cause as either:
- Genetic
- Structural/metabolic – these may be of genetic origin e.g. tuberous sclerosis, but there is a clear lesion as the cause
- Unknown
Classification
As noted, the massive range of functions of the brain means that there is huge variation in the way that seizures may present.
The main differentiation is between general or focal seizures.
Generalised seizures are seen as originating in (or rapidly expanding to include) both cerebral hemispheres.
This may be cortical or subcortical structures and not necessarily include to entire cortex.
The main differentiation is between general or focal seizures.
Generalised seizures are seen as originating in (or rapidly expanding to include) both cerebral hemispheres.
This may be cortical or subcortical structures and not necessarily include to entire cortex.
Focal seizures can be conceptualised as originating within the networks or one cerebral hemisphere.
This can be a very specific location or more diffuse. It may progress to be generalised.
This can be a very specific location or more diffuse. It may progress to be generalised.
The subtypes of generalised seizures include:
- Tonic-clonic
- Absence
- Typical
- Atypical
- With special features
- Myoclonic
- Clonic
- Tonic
- Atonic
Though there has been a recent change in the nomenclature, the concepts of the focal seizure types remain the same:
- Simple focal – There is preservation of consciousness. Previously referred to as simple partial
- Complex focal – consciousness is impaired. Previously complex partial.
- Secondary generalised – there is progression to a generalised seizure state.
- Aura – involving subjective psychic or sensory phenomenon only
There are a variety of focal seizure phenotypes, which can be conceptualised as being related to the brain region of the abnormal electrical activity:
- Simple contralateral movements – Frontal lobe
- Complex automatic behaviourisms – temporal lobe
- Localised sensory disturbance – sensory cortex (parietal lobe)
- Abnormal taste – Insula
- Olfactory hallucinations – Anteromedial temporal lobe
Presentation
The broad spectrum of seizures types means that there is a wide variety of presentations, especially for the focal types of seizure, making diagnosis a challenge.
Focal Seizures
Focal seizures are of a range of motor, sensory, autonomic and psychic types.
They are characterised by repetitive, stereotypical experiences, which would correlate with focal seizure activity on an EEG.
As noted above, these can range from repetitive motor actions through to more complex automated behaviours e.g. lip smacking, and pure sensory experiences.
The common automatisms include chewing, lip-smacking, mumbling and playing with the hands.
They are defined as complex if consciousness is impaired as part of the seizure. This can be hard to determine retrospectively but is best done by asking patients if they fully remember the events.
Witnessed complex focal seizures usually starts with ‘behavioural arrest’ followed by the focal seizure activity, such as automatisms. They usually last for 1-2 mins and there can often be a 1-2 minute period of post-ictal features afterwards.
It is common for patients with complex focal seizures to have an aura beforehand warning them of an impending seizure (indeed this aura can be seen as being a focal seizure).
They are characterised by repetitive, stereotypical experiences, which would correlate with focal seizure activity on an EEG.
As noted above, these can range from repetitive motor actions through to more complex automated behaviours e.g. lip smacking, and pure sensory experiences.
The common automatisms include chewing, lip-smacking, mumbling and playing with the hands.
They are defined as complex if consciousness is impaired as part of the seizure. This can be hard to determine retrospectively but is best done by asking patients if they fully remember the events.
Witnessed complex focal seizures usually starts with ‘behavioural arrest’ followed by the focal seizure activity, such as automatisms. They usually last for 1-2 mins and there can often be a 1-2 minute period of post-ictal features afterwards.
It is common for patients with complex focal seizures to have an aura beforehand warning them of an impending seizure (indeed this aura can be seen as being a focal seizure).
Generalised Seizures
The 6 main types of generalised seizures are characterised by their clinical and EEG features. As noted above, consciousness is usually lost in all of these.
Tonic-clonic
These are sometimes referred to as grand mal seizures.
There is sudden loss of consciousness, followed by a fall and several motor behaviours.
There is initially a tonic extension of the extremities followed by clonic rhythmical movements of the limbs, trunk and head.
This usually lasts 1-2 minutes and there is often a prolonged post ictal period with confusion, drowsiness, and amnesia.
Unlike secondarily generalised seizures there is often little warning in the form of aura or focal seizure activity.
These are sometimes referred to as grand mal seizures.
There is sudden loss of consciousness, followed by a fall and several motor behaviours.
There is initially a tonic extension of the extremities followed by clonic rhythmical movements of the limbs, trunk and head.
This usually lasts 1-2 minutes and there is often a prolonged post ictal period with confusion, drowsiness, and amnesia.
Unlike secondarily generalised seizures there is often little warning in the form of aura or focal seizure activity.
Absence
These are a brief impairment of consciousness, often with no aura or postictal state and few automatisms.
They usually last only 10-30 seconds with no falling and resumption of the preceding activity immediately afterwards.
Any automatisms that do occur are usually facial e.g. repeated blinking.
These usually start during childhood and can persist into adulthood.
They can be precipitated by hyperventilation and can sometimes be hard to detect, simply appearing to be staring episodes.
Atypical absence seizures often include more noted movements and a less complete loss of awareness. They are often associated with neurological injury or developmental abnormalities.
These are a brief impairment of consciousness, often with no aura or postictal state and few automatisms.
They usually last only 10-30 seconds with no falling and resumption of the preceding activity immediately afterwards.
Any automatisms that do occur are usually facial e.g. repeated blinking.
These usually start during childhood and can persist into adulthood.
They can be precipitated by hyperventilation and can sometimes be hard to detect, simply appearing to be staring episodes.
Atypical absence seizures often include more noted movements and a less complete loss of awareness. They are often associated with neurological injury or developmental abnormalities.
Myoclonic seizures are brief jerks of a limb or the trunk. Consciousness is usually not impaired and indeed myoclonic jerks may not be epileptic in origin e.g. falling asleep.
If they progress to more rhythmic jerks, then they may termed clonic seizures. Again, consciousness may not be impaired.
If they progress to more rhythmic jerks, then they may termed clonic seizures. Again, consciousness may not be impaired.
History
The focus of an assessment is initially to determine whether a seizure or a mimic disorder has occurred. Other causes of transient loss of consciousness must be considered e.g. simple syncope, cardiac dysrhythmia.
Features to enquire about include tongue biting, incontinence, aura, and post ictal features, which increase the likelihood of the event representing a tonic-clonic features.
A routine full history should assess for relevant risk factors in the past medical history, family history, drug history and social history.
Features to enquire about include tongue biting, incontinence, aura, and post ictal features, which increase the likelihood of the event representing a tonic-clonic features.
A routine full history should assess for relevant risk factors in the past medical history, family history, drug history and social history.
Clinical examination is usually unremarkable but clinical signs may indicate an underlying causative pathology e.g. tumour, meningits.
If a patient is presenting acutely or is unwell, a full A – E assessment approach should be used.
Whether or not patients drive should be asked, as DVLA restrictions apply.
If a patient is presenting acutely or is unwell, a full A – E assessment approach should be used.
Whether or not patients drive should be asked, as DVLA restrictions apply.
The features that are commonly seen in pseudoseizures are important to bear in mind when assessing a possible seizure. These include:
- Preserved consciousness
- Asymmetrical movements/poorly coordinated thrashing
- Back arching and pelvic thrusting
- Eyes held shut
- Purposeful movements
- Pedalling of the legs
Investigation
New seizures need careful evaluation to investigate for causative factors. These investigations will be tailored to the clinical presentation, and patients with known seizure disorders will often require little investigation.
Tests include:
Tests include:
- Bloods: including FBC, U&Es, CRP, glucose, LFTs, bone profle, Magnesium
- CT head: to investigate for acute bleed or large mass
If the cause remains unclear and further seizure activity occurs, further investigation may include:
- Lumbar puncture
- MRI scan: to more accurately assess for a CNS lesion
- EEG
- Prolactin: are typically elevated 3-4 fold in generalised tonic-clonic seizures. Can be useful to help differentiate from no-epileptic seizure disorders.
Measurement of anti-epileptic drug levels can be helpful in cases of seizures in patients established on these drugs, particularly because of the renowned instability of these drugs from a therapeutic levels perspective.
Management
The primary management goal involves stabilising the patient if they are acutely unwell.
Persisting seizure activity is described as status epilepticus and is a medical emergency. Its management is discussed elsewhere as part of the acute management of seizures.
The next focus is on correcting or otherwise managing any triggering factors e.g. hyponatraemia, infections.
Once this is completed, there are a number of patients for whom they will still be at risk of further seizures, and these patients will require initiation of anti-epileptic drugs (AEDs).
Patients and their relatives should be given advice about safety, given the risk of seizures occurring at any time. They should avoid dangerous activities such as climbing, swimming, driving, until control is obtained.
Relatives should be advised on first aid procedures; loosening tight clothing, cushioning head, recovery position.
Drugs which can trigger seizures should be avoided e.g. cocaine, and alcohol intake minimised.
Persisting seizure activity is described as status epilepticus and is a medical emergency. Its management is discussed elsewhere as part of the acute management of seizures.
The next focus is on correcting or otherwise managing any triggering factors e.g. hyponatraemia, infections.
Once this is completed, there are a number of patients for whom they will still be at risk of further seizures, and these patients will require initiation of anti-epileptic drugs (AEDs).
Patients and their relatives should be given advice about safety, given the risk of seizures occurring at any time. They should avoid dangerous activities such as climbing, swimming, driving, until control is obtained.
Relatives should be advised on first aid procedures; loosening tight clothing, cushioning head, recovery position.
Drugs which can trigger seizures should be avoided e.g. cocaine, and alcohol intake minimised.
Treatment with AEDs should be on the recommendation of a specialist, or by a specialist in the case of children and young adults.
It is generally only recommended after the diagnosis of epilepsy has been confirmed. This will therefore require at least 2 seizures to have occurred.
It is generally only recommended after the diagnosis of epilepsy has been confirmed. This will therefore require at least 2 seizures to have occurred.
Pharmacology
The evidence for the choice of AED in many circumstances appears to be relatively poor. The initial choice of drug is based on the classification of seizure disorder.
Note: Sodium valproate is the most widely recommended first line drug but has significant risks in pregnancy which need consideration.
Different preparations of AEDs can vary in their bioavailability and pharmacological profiles so the preparation should be kept constant.
The aim should be to manage the disorder with a single drug i.e. monotherapy. If this is unsuccessful (after dose titration), then an alternative monotherapy should be the approach before multiple AEDs.
There should be a crossover period of drug titration when switching monotherapy.
The pharmacology of individual drugs is discussed elsewhere.
Note: Sodium valproate is the most widely recommended first line drug but has significant risks in pregnancy which need consideration.
Different preparations of AEDs can vary in their bioavailability and pharmacological profiles so the preparation should be kept constant.
The aim should be to manage the disorder with a single drug i.e. monotherapy. If this is unsuccessful (after dose titration), then an alternative monotherapy should be the approach before multiple AEDs.
There should be a crossover period of drug titration when switching monotherapy.
The pharmacology of individual drugs is discussed elsewhere.
Focal seizures
First line: Carbamazepine, lamotrigine (also can consider levetiracetam, oxcarbazepine, sodium valproate.
Second line/adjunctive: carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate
First line: Carbamazepine, lamotrigine (also can consider levetiracetam, oxcarbazepine, sodium valproate.
Second line/adjunctive: carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate
Generalised Tonic-Clonic
First line: Sodium valproate, lamotrigine (if valproate not suitable). Can also consider carbamazepine, oxcarbazepine
Adjunctive: Levetiracetam, lamotrigine, clobazam, topiramate
Caution: If also absences, myoclonic or juvenile mysoclonic epilepsy then avoid; carbamazepine, oxcarbazepine, gabapentin, pregabalin, phenytoin
First line: Sodium valproate, lamotrigine (if valproate not suitable). Can also consider carbamazepine, oxcarbazepine
Adjunctive: Levetiracetam, lamotrigine, clobazam, topiramate
Caution: If also absences, myoclonic or juvenile mysoclonic epilepsy then avoid; carbamazepine, oxcarbazepine, gabapentin, pregabalin, phenytoin
Absence Seizures
First line: ethosuximide, sodium valproate (first choice if also tonic clonic). Can also consider lamotrigine
Adjunctive: Consider a combination of above
Avoid: carbamazepine, oxcarbazepine, gabapentin, pregabalin, phenytoin
First line: ethosuximide, sodium valproate (first choice if also tonic clonic). Can also consider lamotrigine
Adjunctive: Consider a combination of above
Avoid: carbamazepine, oxcarbazepine, gabapentin, pregabalin, phenytoin
Myoclonic Seizures
First line: Sodium valproate. Also consider levetiracetam, topiramate
Adjunctive: Combination of above
Avoid: carbamazepine, oxcarbazepine, gabapentin, pregabalin, phenytoin
First line: Sodium valproate. Also consider levetiracetam, topiramate
Adjunctive: Combination of above
Avoid: carbamazepine, oxcarbazepine, gabapentin, pregabalin, phenytoin
Tonic/Atonic seizures
First line: Sodium valproate
Adjunctive: Lamotrigine
Avoid: carbamazepine, oxcarbazepine, gabapentin, pregabalin.
First line: Sodium valproate
Adjunctive: Lamotrigine
Avoid: carbamazepine, oxcarbazepine, gabapentin, pregabalin.
References/Links
- M Beers et al. The Merck manual of diagnosis and therapy (18th ed). 2006. Merck research Laboratories. Whitehouse Station, NJ.
- A Berg et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009. 2010. Epilepsia. 51(4); 676-85
- D Ko. Epilepsy and Seizures. Medscape. 2016. (Accessed 21.11.2016, available at http://emedicine.medscape.com/article/1184846-overview#a1)
- C Nickson. Status epilepticus. Life in the Fast Lane. (Accessed 21.11.2016, available at http://lifeinthefastlane.com/ccc/status-epilepticus/)
- NICE. Epilepsies; diagnosis and management. CG137. 2016. (accessed 24.11.16, available at https://www.nice.org.uk/guidance/cg137/)
