Epilepsy Flashcards
How are seizures classified?
The International Classification of Epileptic Seizures ICES
Partial seizures (beginning focally) -
1) SIMPLE (consciousness not impaired)
- with motor symptoms
- with somatosensory or special sensory symptoms e.g. taste, smell
- with autonomic symptoms
- with psychological e.g. jamais, vu, deja vu
2) COMPLEX (with impairment of consciousness)
- beginning as a simple partial seizure and progressing to a complex partial seizure
- impairment of consciousness at the onset
Partial seizures becoming secondarily generalised
Generalised seizures
1) Absence seizure
- typical (petit mal)
- atypical
2) Others
- Myoclonic seizure
- clonic seizure
- tonic seizure
- tonic-clonic seizure (grand mal)
- atonic seizure
Unclassified seizure
What % of the population experience seizures during their lifetime? What % have recurrent seizures?
3-5%
0.5% of population, 90% of which are well controlled by medication.
When does epilepsy most commonly present?
Childhood or adolescence
NB. Grand mal seizures have two peaks of incidence, one in childhood and is normally of unknown cause, the second is in adults in their 50-60sand is probably secondary to subcortical ischaemic changes in hypertension
In how many patients presenting with epilepsy is a cause found?
Less than 50%
What are the common causes of epilepsy?
Vascular disease Alcohol abuse Cerebral tumours Head injury Partial epilepsies - hippocampal sclerosis, neuronal migrational defects
What factors might predispose a person to epilepsy? (12)
1) Family history - especially true of absence seizures, up to 40% have family history. No single genetic trait can account for all different types of epilepsy, possibly to do with factors that alter membrane structure or function, leading to lower threshold for seizures
2) Antenatal and perinatal factors - infections during pregnancy e.g. rubella and toxoplasmosis. maternal drug use, irradiation, perinatal trauma and anoxia.
3) Trauma and surgery - Severe closed or open head trauma is often follow by seizures. Can be early (1 week) or late (months-years). Surgery to cerebral hemisphere is followed by seizures in about 10% of patients.
4) Metabolic causes - Hypernatraemia, hyponatraemia, hypocalcaemia, hypomagnasaemia, hypoglycaemia.
Uraemia, hepatic failure, acute hypoxia, porphyria.
N.B. Chronic metabolic encephalopathies can produce permanent grey matter damage.
5) Toxic causes -
drugs e.g. phenothiazines, monoamine oxidase inhibitors, tricyclics, amphetamines, lignocaine, nalidixic acid (a synthetic compound which inhibits the multiplication of bacteria, used chiefly to treat urinary infections)
Withdrawal of benzodiazepines or anti epileptic medication can result in seizures if done too quickly.
Chronic alcohol excess
Carbon monoxide, lead, mercury
6) Infectious and inflammatory causes - seizures may be part of the presenting features of encephalitis, meningitis, cerebral access or neurosyphilis, High fevers, especially in children can cause seizures ‘febrile convulsions’
7) Vascular causes - up to 15% of patients with cerebra vascular disease experience seizure, especially with large areas of infarction or haemorrhage
8) Intracranial tumours - sudden onset in adult life, partial, always raises suspicion
9) Hypoxia - seizures after repiratory or cardiac arrest secondary to anoxic encephalopathy
10) Degenerative diseases
11) Photosensitivity - precipitated by flashing lights
12) Sleep deprivation
13) Communication - failure to comply with medications is a common cause of seizures, including status epilepticus. Failure may be due to side-effects or denial about the condition.
What is a partial seizure?
Arises from a localised area of the cerebral cortex.
Clinical manifestation depends of the area of the cortex from where it arises, and how far and fast it spreads.
60% originate in the temporal lobes, and most of the rest in the frontal lobes.
How can partial seizures be divided and what are the characteristics of each?
Simple partial - consciousness not impaired, discharge remains localised. Brief with focal symptoms. Structural brain lesion must be excluded.
Complex partial - Similar to simple but involve loss of consciousness.
Usually originate in the frontal and temporal lobes and while consciousness is lost postural control remains.
Can be a progression of simple partial seizures, last a couple of minutes or up to a couple of hours in ‘non-convulsive status epilepticus’.
Amnesia is common.
Partial with secondary generalisation - partial seizure where the discharge spreads to both hemispheres, resulting in a generalised (usually tonic-clonic) seizure. This may be rapid enough that no focal symptoms are seen initially.
What is the characteristic of generalised seizures?
Bilateral involvement of the cortex at the onset of the seizure. Patient loses conscious from the onset of the seizure so no warning.
How can generalised seizures be categorised?
Generalised tonic-clonic -
Typically no warning, sudden loss of consciousness and fall to the ground.
Followed by the ‘tonic’ phase, normally last about 10 seconds where the body is stiff, elbows are flexed and legs extended. Breathing stops and the patient may become cyanotic.
Followed by the clonic phase. Usually lasts for 1-2 mins, characterised by violent generalised rhythmical shaking. Eyes are open and roll back, tongue may be bitten and patient is tachycardic. Bladder and bowel control may be lost. Frequency of shaking generally decreases until seizure stops.
Following seizure the patient of can not be roused of several minutes and awakes with confusion (postictal confusion), myalgia, headache and retrograde amnesia. Often patients will fall asleep after a convulsion which can be mistaken for unconsciousness.
Clonic seizures - are the same as before but without the tonic phase.
Absence seizures - Typical age at onset between 4-12. Attacks occur several times a day, duration 5-15 seconds.
Vacant staring, may be eye-blinking and myoclonic jerks.
Associated with a characteristic EEG pattern of 3-per-second generalised spike-and-wave discharges.
Atypical absence seizures associated with more sever epilepsy syndromes e.g. Lennox-Gastut syndrome, EEG usually shows less specific changes.
Myoclonic seizures - abrupt, brief involuntary movements that can involve the whole body or parts.
NB not all myoclonus is the result of epilepsy, epileptic if it occurs in the context of a seizure disorder and is cortical rather than brainstem or spinal cord.
Atonic and tonic seizures - rare generalised seizures, often called ‘drop attacks’. Typically occur in severe epilepsy syndromes. Atonic seizures involve a sudden loss of tone in postural muscles, causing the fall. Tonic seizures involve a sudden increase in muscle tone, causing rigidity which leads to a fall.
What is the most important element of diagnosis in epilepsy?
Clinical history - features supporting diagnosis of seizure include pupil dilatation, raised BP and HR, extensor plantar responses, central and peripheral cyanosis.
In generalised seizures pO2 and pH are lowered, creatine kinase is raised, marked elevation of serum prolactin
What other investigations can be used to aid diagnosis?
Brain imaging (more important for later presentation)
EEG - extremely useful if recorded during an attack, though intricate EEG may show focal spike or slow waves suggesting subclinical seizure activity, though normal 50% of the time.
Blood tests
What are the possible differential diagnoses for epilepsy?
1) Syncope - vasovagal attacks, arrythmias, carotid sinus hypersensitivity, postural hypotension.
There is usually prodromal pallor, nausea, sweating, tends not to occur when recumbent. Patient is floppy during a syncope event, rigid in seizure. Incontinence can occur, and limb jerking though not coordinated like in seizure.
2) Non-epileptic or functional seizures.
Surprisingly common. How do you tell a pseudoseizure? More common in young men with a past psychiatric history, seizures tend to be refractory to all drugs, vital jobs tend to remain unchanged, plantar responses are flexor, normal serum prolactin levels, EEG shows no seizure activity.
3) TIA - can even involve loss of consciousness if the brainstem is deprived of O2 from a problem in the posterior circulation, though very uncommon.
4) Migraine - syncope can occur during migraine, also aura of migraine can be confused with pre-seizure symptoms. However, progression of symptoms is much slower in migraine.
5) Hypoglycaemia - this can cause behavioural disturbances and seizures.
When should drug therapy be considered for epilepsy?
Important ascertain and cure the potential provoking factor, e.g. alcohol. Only 30-60% of patient have recurrent seizures within 2 years after the first episode. These rates rise after 2 or more seizures.
Drug therapy is therefore considered after 2 or more unprovoked seizures have occurred within a short period.
Treatment may be started after 1 episode alone in patients with known neurological deficits since birth, abnormal EEG or progressive neurological disorder.
What is the ideal drug regime used to treat epilepsy?
A monotherapy is preferred to minimise drug interaction and side effects.
80% of patients are seizure free with monotherapy.
Which are the most common anticonvulsants used in the treatment of epilepsy and how do they work?
Na channel blockers - Carbemazapine, sodium valproate, phenytoin, lamotrigine - act by producing use-dependent block of neuronal sodium channels. Their anticovulsant action is due to their ability to prevent high-frequency repetitive activity. The drugs bind preferentially to inactivated channels, stabilising them in the inactive state.
Enhancement of GABA -
Vigabatrin - irreversible inhibitor of GABA-transaminase, which increases brain GABA levels, and central GABA release.
Tiagabine - inhibits the reputake of GABA
Benzodiazepines (clobazam +clonazepam) and phenobarbitol - also increase central inhibition by enhancing GABA action.
Inhibition of Calcium channels - Drugs like ethosuximide, valproate, lamotrigine reduce the oscillatory calcum current between the thalamus and the cerebral cortex which is present in absence seizures. The reduce the current through T type calcium channels.
Which type is grand mal?
Generalised tonic clonic seizures
Which type is petit mal?
Absence seizures
What are the nice guidelines regarding drug treatment of seizures?
First line drug treatment for primary generalised epilepsy in adults are sodium valproate and lamotrigine.
For absence epilepsy in children, use ethosuximide and sodium valproate.
For partial seizures, use carbemazepine and lamotrigine.
What is the problem with phenytoin, phenobarbital and vigabatrin?
Many patients still take phenobarbital and phenytoin for generalised seizures, but these are being phased out because of the SE profile.
Vigabatrin is rarely used now because of its propensity to cause visual field defects.
Phenobarbital is still used in refractory epilepsy and status epilepticus.
What if a drug doesn’t work?
If a first line drug does not resolve the epilepsy then it is swapped for another first line drug. Then first line drugs are combined, and finally second line drugs are added.
How is the drug started.
Start low and go slow.
Which drugs are liver enzyme inducers?
Phenytoin, phenobarbital, topiramate and carbemazepine. This is particularly important when the patient is on the oral contraceptive pill which can be rendered ineffective unless the dose is increased.
Anticonvulsants also block pathways in the liver for the metabolism of other products, e.g. carbamazepine blocks the metabolism of lamatrogine increasing its half life.
What are the main SEs of anticonvulsants?
Acute toxicity - drowsiness, slowed cognition, some cause non-specific encephalopathy associated with nystagmus, ataxia, dysarthria, confusion (normally if blood serum levels of the drug are high)
Idiosyncratic toxicity - skin rashes with carbemazapine, phenytoin, lamatrogine. These are often avoided by building up the drug slowly.
Chronic toxicity - particularly associated with phenytoin, causing coarsened faces, acne, hirsutism, gum hypertrophy, peripheral neuropathy
Teratogenicity and pregnancy - increased risk, especially in those on polytherpary, sodium valproate carries the highest individual risk. Main risk is neural tube defects. Folic acid is given before conception and during first trimester. Vitamin K is also used for both the mother on the medication and the newborn.
What is the issue around withdrawal?
Any patient who has been seizure free for 2 years should be considered for withdrawal of treatment. This may induce seizures so should be attempted with caution. Has implications with driving, employment and self-esteem so should be a decision closely involving the patient.
What is status epilepticus?
A seizure or a series of seizures that lasts more than 30 mins without the patient regaining consciousness.
Convulsive status epilepticus is of particular concern as it carries a mortality rate of around 20%.
For this reason emergency treatment of seizures should begin if any seizure lasts more than 5 minutes, or if repeated convulsions have occurred within the hour.
What does the emergency treatment for status epilepticus involve?
Normal emergency DR ABCDE treatment.
Airway, venous access, administering O2.
Infusion with normal saline.
Blood tests - ABG, glucose, U+Es, renal and liver function, anticonvulsant levels.
What is the stage by stage treatment plan?
1) Premonitory stage - (0-10 mins) rapid treatment may prevent status. Lorazepam, diazepam, midazolam, paraldehyde
2) Early status - (10-30 mins) another dose of fast acting benzodiazepine e.g. lorazepam I.V.
3) Established status - (30-60 mins) I.V. phenytoin or phenobarbital
4) Refractory status - (after 60 mins) by this stage anaesthesia is required with ventilation and intensive care treatment. I.V thiopental or propofol are commonly used. EEG monitoring. Neuromuscular blockade must be avoided as if seizures return then they may go unnoticed.
Is there a surgical treatment for epilepsy?
Yes, if there is an identifiable localised site of onset for the seizures. Epilepsy should also have been shown to be intractable to medical therapy.
Most commonly temporal, but also some extra temporal cortical excisions, hemispherectomies, corpus colosotomies.
Temporal lobe and extra temporal have an 80 and 40% success rate respectively.
What is the cause of mortality in epilepsy?
Status epilepticus, accidents during seizures, SUDEP sudden unexpected death in epilepsy. This last could be a factor of respiratory or cardiovascular arrest, or unknown.
What is the implication of epilepsy to driving?
Any seizures must be reported to the DVLA and they will assess the patient’s safety to drive.
- No driving within 1 year of a seizure (6 months if there is no history of seizures or diagnosis of epilepsy)
- Nocturnal seizure sufferers can drive during the day as long as no day seizures in last 3 years
- In seizures cause by one off symptoms, DVLA will assess patients on individual basis
- If patient is coming off medication they are recommended to stop driving for 6 months while they come off medication.
