Epilepsy (include pharmacology) Flashcards
What is epilepsy?
Epilepsy is the most common neurological disorder, characterised by recurrent seizures
How many different types of seizures are there?
Over 40
How can you diagnose epilepsy?
EEG/MRI/CAT(CT) (hard to see anything in an MRI or CAT scan
According to the international league against epilepsy (ILAE), what are the main categories of epilepsy?
Focal and generalised
What are the characteristics/auras of a temporal onset of seizure?
Auras: smell/taste, ‘déjà vu’, ‘jamais vu’, emotional changes
Oral automatisms: gestures eg dystonic or fidgetting
What are the characteristics/auras of a frontal onset of seizure?
Motor seizures: Brief, frequent, cluster,
Often bilateral eg kicking, cycling, violent, bizarre. Head version
Commonly on waking from sleep
What are the characteristics/auras of a parietal onset of seizure?
Sensory seizures: somatosensory (tingling/warmth)
Auras: Nausea, choking, sinking sensations, Illusions of body distortion
Look at these symptoms: Visual hallucinations – simple or complex (shapes to scenes)
Vision may black out
Visuo-spatial distortions
Head turning, headache, nausea
An epilepsy induced from which location would get these symptoms?
Occipital
What is the main characteristic of focal aware seizures?
No loss of consciousness or post-ictal confusion
Which lobe of the brain are focal aware seizure mostly found?
Temporal lobe
What are the main characteristic of focal with impaired awareness seizures?
Altered consciousness, but may seem fully aware. There may be some post-ictal confusion
May experience auras
If the patient presented with automatisms (chewing, swallowing, repeated displacement behaviour), what type of focal seizure is this?
Focial with impaired awareness
Which lobe of the brain are focal with impaired awareness seizures mostly found?
Temporal lobe
What are the two types of jacksonian seizures?
Focal aware motor and focal aware sensory
What are the characteristics of a focal aware motor (jacksonian) seizure?
Short-lasting, ripple of muscle activity, may be localised to one group of muscles or progress, usually distal to proximal, through the limbs and trunk (following HAL)
What are the characteristics of a focal aware sensory (jacksonian) seizure?
Short lasting sensory changes, may be localised to one area or progress, usually distal to proximal, through the limbs and trunk (following HAL)
What are the characteristics of a focal to bilateral tonic clonic seizure?
Focal seizure progressing to generalised (tonic-clonic)
If a patient presented with unilateral motor effects during the seizure and experienced an aura prior to the onset, what type of seizure do they have?
Focal to bilateral tonic clonic
What are the symptoms of a generalised tonic clonic seizure?
Tonic phase - whole body stiffness, breathing may stop (cyanosis), loss of bladder control
Clonic phase – muscle jerks
Followed by unconsciousness, muscle relaxation, slow regain of consciousness, confusion, sleepy, headaches and aching limbs, no recall of episode
What is a generalised obsence seizure?
Rare in adults, generally starts between 6-12 yrs
Girls > Boys
Symptoms: seem to ‘switch-off’ but cannot be alerted or woken up
Whole brain involved, low level activity
Responds well to anti-epileptics
Why is a status epilepticus generalised tonic clonic seizure treated as a medical emergency?
Whole brain involved
Ictal period of > 5 mins
Repeated seizures with no recovery between (>30 mins)
Other forms: long-lasting, absence or focal-type seizures
What is the type of seizure which Sav, Risheka and Arpita have?
Generalised myoclonic - sudden jerks (like when falling asleep), possibly familial
What are the symptoms of each form of seizure?
Generalised clonic
Generalised tonic
Generalised Atonic
Generalised clonic – repeated twitches and jerks no stiffness
Generalised tonic – all muscle contract, whole body stiffness
Generalised Atonic – ‘drop attacks,’ muscle tone lost
How can you diagnose an NEAD?
Diagnosis can be made through a video EEG. There may be differences in: Duration Eye opening Location of tongue biting - tips Recollection
What are the advantages of using an Electroencephalogram (EEG)?
Useful for investigating gross cortical activity
Non-invasive and painless
Can be used over long periods
Cost effective
How many plate electrodes does the EEG have?
24-158
Where is the ground electrode for the EEG?
ear
What do EEG’s record?
Activity patterns of populations of neurons by recording changes in gross current flow
Levels of synchrony between neurons causes changes in patterns, if fire together give larger amplitude oscillations
Patterns of synchrony cause rhythms
What are the different types of rhythms seen in EEG?
Alpha – 8-13Hz
Mainly occipital, quiet, eyes shut, meditation
Beta >14Hz
Parietal and frontal, activity and tension, sleep spindles
Gamma – 40Hz
‘binding,’ learning and memory
Theta – 4-7Hz
Parietal and temporal, alertness, L&M
Delta <3.5 Hz
Cortical, deep sleep, coma
During a seizure, what happens to GABA, Ach transmission, Na+ channel activity and K+ channel activity?
Reduction in GABA
Increase in ACh transmission
Increase in Na+ channel activity
Decrease in K+ channel activity
What are the three types of treatment for epilepsy?
Pharmacological First line approach for seizures Anticonvulsants/Antiepileptic drugs (AEDs)* Surgical removal of aberrant areas (found by MRI/CAT/electrical stim) Implants VNS – vagal nerve stimulation DBS – deep brain stimulation
What is the treatment for Focal and Focal to generalised seizures?
First Line:
Carbamazepine
Lamotrigine
Sodium valproate
Second Line (adjuncts): Clobazam, gabapentin, topiramate
What is the treatment for generalised tonic clonic?
First Line: Sodium valproate Lamotrigine Also: Carbamazepine Oxcarbazepine
Second Line (adjuncts): Clobazam, levetiracetam, topiramate
What is the treatment for generalised absence atypical?
First Line:
Ethosuximide
Sodium Valproate*†
Second line:
Lamotrigine*
What is the treatment for status epilepticus?
Status epilepticus generalised tonic clonic :
Commence i.v. Lorazepam (repeated after 10 mins) (can use buccal Midazolam/i.v. diazepam)
Buccal Midazolam/Rectal diazepam (if resusc facilities not available)
After 25 mins: phenytoin sodium or phenobarbital sodium*
After 45 mins: Anaesthetize with thiopental, midazolam or non-barbiturate anaesthetic (propofol)
What is the treatment for a generalised myoclonic seizure?
First Line: Sodium valproate.
Name some Na+ channel blocker epilepsy drugs.
Phenytoin Carbamazepine Lamotrigine Sodium Valproate Zonisamide
How do Na+ channels blockers block?
Only block channels in inactivated state
What are some side effects of Na+ channel blockers?
Teratogenicity! - especially Sodium Valporate
CNS effects, cognitive impairment, visual impairment
Peripheral neuropathy
Skin problems
Gum hyperplasia
Anaemia and other blood disorders
Osteomalacia
Name some Ca2+ channel blockers.
Ethosuximide (T-type Ca2+ blocker)
Gabapentin
Lamotrigine
What is Antiepileptic Hypersensitivity Syndrome?
Major side-effect
Starts 1-8 weeks from treatment initiation
Initial signs: Fever, rash, swollen lymph nodes
Severe signs: Blood, liver kidney and respiratory abnormailites, vasculitis and organ failure
What would you do if your patient had Antiepileptic Hypersensitivity Syndrome?
Withdraw drug immediately
Topical steroids and antihistamines for rash
Systemic corticosteroids?
Beware of rebound seizure activity
What drug inhibits GABA transporters?
Tiagabine
What drug inhibits GABA transaminase?
Vigabatrin
What is the mechanism of action of Gabapentin?
Enhance activation of GABAA mediated channels, indirectly alter the activity at the GABA channel. Increases GABA synthesis and also acts as a muscle relaxant
What is the difference between Benzodiazepines and Barbiturates?
Benzodiazepines act as a co-agonist to the GABAA receptors (of the gamma unit), whereas Barbiturates act on the beta unit. Thus both increase GABA activity.
How do Benzodiazepines and Barbiturates work?
Reduce neuronal transmission by enhancing inhibition
Which drug acts as a GABA antagonist and therefore can cause seizures?
Flumazenil
What type of modulators for Barbiturates?
Positive allosteric modulators (co-agonists) of GABAA receptors.
Name some examples of Benzodiazepines?
Diazepam and Lorazepam
What are the Side Effects of BDZs and Barbs?
Short-term use only (< 12 weeks) Tolerance and dependency can develop Withdrawal on termination Impaired motor coordination (↓muscle tone) Impaired cognitive performance Sedation Disturbed sleep patterns (↓SWS) Retrograde amnesia
What are some future targets of epilepsy drugs?
Glutamate Antagonists AMPA Metabotropic Gap Junction inhibitors Enzymes Cannabinoids Steroids CO2
