This section will not cover all of epilepsy as it is a major subspeciality within neurology. But here is an introduction to get you started.
Epilepsy is a clinical diagnosis supported by electoencephalography (EEG) evidence of seizure or certain inter-ictal findings. Epilepsy is a disorder of recurrent unprovoked seizures. Classically, it requires at least 2 seizure to make the diagnosis and the seizures must be unprovoked. This distinguishes epilepsy from provoked seizures due to another medical condition such as hyponatremia for example. Furthermore, there are many different types of epilpesy syndromes; well beyond the scope of this article. There are other important topics that are not discussed here such as the approach to new onset seizure, the management of status epilepticus and childhood febrile seizures.
Epilepsy has many different types and can be classified in many ways. Idiopathic epilepsies, such as idiopathic generalized epilepsy and juvenile myoclonic epilepsy, are disorders on to themselves. Epilepsy may also be a consequence of previous injury to the brain such as in post stroke epilepsy, and in epilpesy post traumatic brain injury; two common types of epilepsy in adults. Another way to look at epilepsy is by presence of a seizure focus or a lesion. Some types of lesional epilepsy include epilepsy due to mesial temporal sclerosis, epilepsy due to cortical dysplasia and epilepsy due to arteriovous malformations (AVMs). Lastly, brain tumors may present with seizures or with epilepsy.
Type of epilepsy and seizure type are different things. Seizure may be simple partial, complex partial, secondarily generalized or primary generalized. There are other types of seizures too. A patient with a given type of epilepsy may have one seizure type e.g. absence epilepsy. Or in other cases multiple seizure types for example in Lennox-Gestuat syndrome. The names can be confusing initially but this will make sense as you read through and you practice classifying your patients.
Brief note on some seizure types:
Partial seizures are seizure that begin in one part of the brain. The patient often will experience symptoms related to activation of that part of the brain e.g. hand jerking. If the seizure does not spread this is called a simple partial seizure. If the seizure occurs or spreads to limbic structures or temporal lobe structures it can impair consciousness or memory. Seizures with interruption of memory or consciousness are called complex partial seizures. If the seizure spreads to involve both hemispheres this will lead to generalized tonic-clonic seizures. This is called secondarily generalized seizure. Some patients with secondarily generalized seizures will have asymmetry of movement with one side of the body being stiff and the head turned to that side (head version). Some patients will have a Jacksonian march; where the partial seizure activity spreads along the body from the lips to the hand to the arm to the shoulder then the leg and generalizes. This mirrors the electrical seizure activity spreading along the motor homunculus. In partial seizures there may be warning that the patient experiences before a seizure; called an aura. Auras may include an experience of de ja vu; the patient feels that they have already experienced what is going on. They feel as if they are reliving the events that are currently occurring. Other auras including a rising epigastric sensation. These clues in partial seizures can tell us where the seizures start.
In some patients there is no partial seizure but the seizures appear to involve both hemispheres from the outset. This is called primary generalized seizure. With generalized seizure, the patient often has tongue or cheek biting and bladder or bowel incontinence. During the tonic phase the limbs stiffen up, and in the clonic phase they jerk. The patients eyes are typically open but the patient is unaware of what is going on. Post ictal symptoms include feeling fatigue, lethargy, confusion, and a mild to moderate headache.
Epilepsy is a clinical diagnosis supported by electoencephalography (EEG) evidence of seizure or certain inter-ictal findings.
Epilepsy is a disorder of recurrent unprovoked seizures. Classically, it requires at least 2 seizure to make the diagnosis and the seizure must be unprovoked.
Clinical features of epilepsy, in general:
The clinical features of epilepsy are usually described in 3 phases depending on whether they occur before, during or after a seizure. Pre-ictal (auras or prodromal) features, ictal features and post-ictal features. Not all patients will have pre-ictal or post-ictal features. Auras may suggest partial epilepsy and some of the other features may suggest the epilepsy syndrome. We refer to the clinical description of the seizures as the seizure semiology. It is valuable to interview both the patient and the person witnessing the seizures to obtain the information.
Try to describe the seizure types the patient experience (see the discussion above). Is it one seizure type or multiple seizure types? Is it partial or generalized? Was there an aura or prodrome? The aura may give a clue to where in the brain the seizure originates.
Also determine the frequency of seizures and the duration of the event. The duration of the ictal phase and the post ictal phase.
Epilepsy syndromes, by affected lobes:
Temporal lobe epilepsy:
- Prodrome & aura.
- Ictal: automatisms (oral, motor, ipsilateral arm), contralateral dystonic posturing, versive head movements contralaterally
- Postictal phase.
Frontal lobe epilepsy:
- Rare prodrome, unusual to have aura
- Ictal: brief, tonic gaze contralateral, contralateral head version, hypermotor
- Genital manipulation may occur, facial expression of fear may occur
- Rarely postictal
Occipital lobe epilepsy:
- Unusual to have aura
- Icta: visual hallucination (elemental or formed), twinkling, pulsing lights,
Parietal lobe seizures:
- Contralateral paraesthesia, contralateral pain
Epilepsy with seizures occurring more frequently around the menstrual cycle
EEG in epilepsy:
- Specificity is better than sensitivity
- A normal EEG doesn’t exclude partial epilepsy
- Abnormal interictal epileptiform discharges IEDs can occur in people who never develop epilepsy e.g. normal people or people with other pathology.
- Standard EEG should include hyperventilation & photic stimulation.
- Standard EEG (routine EEG)
- Sleep EEG
- Prolonged EEG
- Repeated standard EEG do 4 serial but not more
- Long term video EEG monitoring
- Ambulatory EEG
EEG findings related to seizure type:
Generalised 3 Hz spike and wave discharges, exacerbated by hyperventilation
Background: usually normal
Atypical absence seizures:
Generalised spike & wave discharge 1.5-2.5 Hz (<3Hz).
Background: usually abnormal
Generalised 10 Hz activity in tonic phase
- Rhythmic spike and wave
- Slow wave
- or sharp slow wave.
Low voltage fast activity, polyspike and wave, or electrodecrement
Investigations in Epilepsy, in general:
The purpose of investigations in epilepsy is to exclude other causes of seizure, classify the type of epilepsy and to determine if there is an underlying lesion. All patients should get basic blood tests, EEG and MRI. The exception is children with febrile seizures or neonates, MRI may be done at a later stage if indicated. Consider other testing as necessary.
- See section above
Indications for MRI in epilepsy or seizures:
- If focal features are present
- Or If onset after 25 y.o. or before 1 y.o.
- Or if considering surgery
- Or if seizures continue in spite of medications
- May be entirely normal or reveal other abnormalities
- DWI: may be abnormal after a seizure in the hippocampus, cerebral cortex, or thalamus
- May reveal Hippocampal sclerosis
- Malformations of cortical development:
- Focal cortical dysplasia: focal cortical thickening, simplified gyration, blurred White-grey junction, prolonged T2, especially frontal lobe
- Heterotopia: subepindymal, subcortical or band/diffuse
- Vascular malformations, small tumours
- Neurocysticercosis: see under neurocysticercosis
- FBC, ESR, blood chemistry panel, Syphilis serology, Liver enzymes
Treatment of epilepsy, in general:
Epilepsy requires expertise and referral to neurologist is the standard of care.
- Address driving advise according to medical and local legal criteria. There are some work implications for certain professions: pilots, commercial drivers
- Sudden unexplained death in epilepsy SUDEP may occur in patients with poor control
- Address advice regarding medication use in pregnancy, teratogenicity and pregnancy planning
- Most patients achieve seizure control. Consider investigation for medication refractory epilepsy if 2 adequate trials of medications fail. However, this should not prevent further medication trials. This should occur in parallel.
Antiepileptics drugs (AEDs):
- Please see the neuropharmacology notes and clinical trials notes
- AEDs are selected based on epilepsy syndrome, seizure type, patient co-morbidities, fertility status, side effect profile and socio-economic factors
- Certain medications work better for generalized epilepsy e.g. valproic acid or topiramate. Others work well for partial epilepsy such as lamotrigine or carbamazepine. There are medications to avoid in women of child-bearing potential e.g. valproic acid and others. Other types of epilepsy syndrome have specific medications such as ethosuximide and lamotrigine in absence epilepsy and ACTH in infantile spasms. There are some medications with good side effect profiles and broad spectrum of efficiacy with very few drug interactions such as levetiacetam.
- After seizure freedom for 2 years, in some cases of epilepsy at attempt at medication withdrawal may be considered. This is dependant on epilepsy syndrome, imaging variables and EEG findings. This is another reason that epilepsy treatment is specialized.
Factors involve in antiepileptic drug choice:
- Epilepsy syndrome
- Seizure type
- Patient co-morbidities
- Potential drug-drug interactions
- Fertility status
- Side effect profile
- Socio-economic factors and access to medications
Medically refractory epilepsy:
Epilepsy is considered medically refractory once the patient has continued seizures in spite of adequate trial of 2 anti-epileptic medications. This diagnosis is designed as a trigger to initiate investigations to determine if the patient is a candidate for non-pharmacological therapy such as epilepsy surgery or vegal nerve stimulator insertion.
This does not mean that the patient will not achieve seizure freedom with subsequent medication trials. However, in patients meeting the above criteria the benefits vs. risk favor initiating investigations for medically refractory epilepsy in parallel with further medication trials. Another consideration is evaluation for possible non-epileptic attacks (or pseudoseizures) as a reason for medication non-response. This often requires video-EEG monitoring. Also note, that some patients may have both epilepsy and non-epileptic attacks.
Investigations in medically refractory epilepsy:
Video EEG monitoring in an epilepsy monitoring unit:
- Absolute interictal spike frequency = or >60 spikes/hr is associated with poor surgical outcome, if <60 spikes/hr it is associated with good surgical outcome for amygldalohippocampectomy. 
- T1,T2, proton density, FLAIR
- to localise cognitive functions including language, and motor & sensory areas. Not as good as WADA test
Neuropsychological assessment: IQ (verbal & nonverbal), learning disability, memory, speech.
SPECT Single photon emission CT, interictal & Ictal:
- Seizures must be frequent enough
- Increased blood flow to seizure focus ictally
- Decreased blood flow to focus interictaly
- Good for temporal lobe epilepsy & frontal lobe epilepsy
Positron emission tomography PET scans:
- Hypometabolism/decreased glucose intake at seizure focus interictally
- Hypermetabolism/increased glucose uptake during a seizure
- More useful for lateralisation than localisation
Wada test: presurgery to lateralise memory and speech.
- Subdural leads
- Depth electrodes
Consider treatment as appropriate. This is a multidisciplinary effort
Left vagal nerve stimulation VNS:
- Especially for partial seizures
- Selective hippocampalectomy for Mesotemporal sclerosis
- Removal of cortical dysplasia
- Unilateral anterior temporal lobectomy
- Corpus callosum section
- Harden CL, Hopp J, Ting TY, et al. ; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy–focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):126-32. doi: 10.1212/WNL.0b013e3181a6b2f8. Epub 2009 Apr 27.
- Morris GL 3rd, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 Oct 15;81(16):1453-9. doi: 10.1212/WNL.0b013e3182a393d1. Epub 2013 Aug 28.
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- EO3 study. Ramsay RE et al. Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994 May-Jun;35(3):627-36.
- EO3 study. George R et al. Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994 May-Jun;35(3):637-43.
- Handforth A et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology. 1998 Jul;51(1):48-55.
- D’Onofrio G, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999 Mar 25;340(12):915-9.
- Daeppen JB et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002 May 27;162(10):1117-21.
- Hessen E, et al. Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy. Epilepsia. 2006 Dec;47(12):2038-45.
- Marson AG, et al; SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007 Mar 24;369(9566):1016-26.
- Marson AG et al; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007 Mar 24;369(9566):1000-15.
- Lossius MI, et al. Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia. 2008 Mar;49(3):455-63. Epub 2007 Sep 19.
- Neal EG et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008 Jun;7(6):500-6. doi: 10.1016/S1474-4422(08)70092-9. Epub 2008 May 2.
- Silbergleit R, et al; RAMPART NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591-600. doi: 10.1056/NEJMoa1107494.
- Trinka E et al; KOMET Study Group. KOMET: an unblinded, randomised, two parallel-group, stratified trial comparing the effectiveness of levetiracetam with controlled-release carbamazepine and extended-release sodium valproate as monotherapy in patients with newly diagnosed epilepsy. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1138-47. doi: 10.1136/jnnp-2011-300376. Epub 2012 Aug 29.
- Berkovic, S.F., et al., Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology, 2007. 69(18): p. 1751-60.