THE CLASSIFICATION OF SEIZURES AND EPILEPSY SYNDROMES Leslie A. Rudzinski, Jerry J. Shih ABSTRACT This chapter focuses on the classification of seizures and epilepsy syndromes based on the International League Against Epilepsy’s classification systems from 1981 and 1989, respectively, which are still used today in clinical practice and have formed the basis for a worldwide standardized approach to diagnosing, treating, and studying seizure disorders. This classification system is based on clinical seizure semiology and EEG correlation and makes a distinction between focal and gener- alized seizures. The clinical semiology and localization of simple partial, complex partial, and generalized seizures are discussed. Some common partial and gener- alized epilepsy syndromes are also highlighted. Continuum Lifelong Learning Neurol 2010;16(3):15–35. INTRODUCTION Understanding the classification of epi- leptic seizures is the first step toward the correct diagnosis, treatment, and prog- nostication of the condition. The initial management of a patient with seizures begins with an understanding of the pa- tient’s seizure type and, if pertinent, epi- lepsy syndrome. Specific seizure types or syndromes often respond better to spe- cific medications or surgical approaches. Some seizure types or syndromes carry a benign prognosis or high likelihood of seizure remission by a certain age. Other seizure syndromes may carry a far poorer prognosis, and early knowledge of this allows focused treatment and lifestyle modifications for patients and families. In epilepsy, taking a good seizure history is of paramount importance. A detailed chronologic account of the patient’s seizures beginning with the age at which the earliest signs and symptoms of the seizures began is helpful in classifying the patient’s type of epilepsy. The classification of epileptic sei- zures is still largely based on clinical observation and expert opinions. The International League Against Epilepsy (ILAE) first published a classification system in 1960. The last official update for seizures was published in 1981, and the last official update for the epi- lepsies was published in 1989. By de- finition, epilepsy is diagnosed after a patient has had two or more unpro- voked seizures. The 1981 and 1989 updates form the officially accepted classification system, although efforts to develop a clinically meaningful revision 15 Relationship Disclosure: Dr Rudzinski has nothing to disclose. Dr Shih has received personal compensation for consulting activities from URL Pharma, Inc. Dr Shih has received research support from Eisai, Inc., GlaxoSmithKline, and the National Science Foundation. Dr Shih’s research work has been funded, entirely or in part, by a grant to his university from a pharmaceutical or device company. Unlabeled Use of Products/Investigational Use Disclosure: Drs Rudzinski and Shih have nothing to disclose. KEY POINT A The initial management of a patient with seizures begins with an understanding of the patient’s seizure type and, if pertinent, epilepsy syndrome. Copyright # 2010, American Academy of Neurology. All rights reserved. Note: Text referenced in the Quintessentials Preferred Responses, which appear later in this issue, is indicated in yellow shading throughout this chapter.
Transcript
THE CLASSIFICATIONOF SEIZURES ANDEPILEPSY SYNDROMESLeslie A. Rudzinski, Jerry J. Shih
ABSTRACT
This chapter focuses on the classification of seizures and epilepsy syndromes basedon the International League Against Epilepsy’s classification systems from 1981and 1989, respectively, which are still used today in clinical practice and haveformed the basis for a worldwide standardized approach to diagnosing, treating,and studying seizure disorders. This classification system is based on clinical seizuresemiology and EEG correlation and makes a distinction between focal and gener-alized seizures. The clinical semiology and localization of simple partial, complexpartial, and generalized seizures are discussed. Some common partial and gener-alized epilepsy syndromes are also highlighted.
INTRODUCTIONUnderstanding the classification of epi-leptic seizures is the first step toward thecorrect diagnosis, treatment, and prog-nostication of the condition. The initialmanagement of a patient with seizuresbegins with an understanding of the pa-tient’s seizure type and, if pertinent, epi-lepsy syndrome. Specific seizure typesor syndromes often respond better to spe-cific medications or surgical approaches.Some seizure types or syndromes carry abenign prognosis or high likelihood ofseizure remission by a certain age. Otherseizure syndromes may carry a far poorerprognosis, and early knowledge of thisallows focused treatment and lifestylemodifications for patients and families.In epilepsy, taking a good seizure historyis of paramount importance. A detailed
chronologic account of the patient’sseizures beginning with the age at whichthe earliest signs and symptoms of theseizures began is helpful in classifying thepatient’s type of epilepsy.
The classification of epileptic sei-zures is still largely based on clinicalobservation and expert opinions. TheInternational League Against Epilepsy(ILAE) first published a classificationsystem in 1960. The last official updatefor seizures was published in 1981,and the last official update for the epi-lepsies was published in 1989. By de-finition, epilepsy is diagnosed after apatient has had two or more unpro-voked seizures. The 1981 and 1989updates form the officially acceptedclassification system, although efforts todevelop a clinically meaningful revision
15
Relationship Disclosure: Dr Rudzinski has nothing to disclose. Dr Shih has received personal compensationfor consulting activities from URL Pharma, Inc. Dr Shih has received research support from Eisai, Inc.,GlaxoSmithKline, and the National Science Foundation. Dr Shih’s research work has been funded, entirely orin part, by a grant to his university from a pharmaceutical or device company.Unlabeled Use of Products/Investigational Use Disclosure: Drs Rudzinski and Shih have nothing to disclose.
KEY POINT
A The initial
management
of a patient
with seizures
begins with an
understanding
of the patient’s
seizure type and,
if pertinent,
epilepsy
syndrome.
Copyright # 2010, American Academy of Neurology. All rights reserved.
Note: Text referenced in the Quintessentials Preferred Responses, which appearlater in this issue, is indicated in yellow shading throughout this chapter.
to the current system are continuing.This chapter will focus primarily on thecurrently accepted standard based onthe 1981 and 1989 reports and brieflynote some of the proposed changesunder consideration by the ILAE.
CLASSIFICATION OF EPILEPTICSEIZURES
Partial Seizures
Partial or focal seizures comprise oneof the two main classes of epileptic sei-zures, with generalized seizures beingthe other. Partial seizures are subdi-vided between simple and complex par-tial seizures, which are distinguished bythe presence or absence of impairmentof consciousness. Simple partial sei-zures are defined as seizures withoutimpairment of consciousness, while com-plex partial seizures are defined as sei-zures with impairment of consciousness.Consciousness is defined as the ‘‘degreeof awareness and/or responsiveness ofthe patient to externally applied stimuli.’’1
Responsiveness refers to the abilityof the patient to respond to externalstimuli, and awareness refers to therecall of events occurring during theictal period. These two features of con-sciousness are usually tested duringand after a seizure in an epilepsy moni-toring unit. A patient may be able tofollow commands during a seizure butmay not be able to recall portions ofthe event afterward, which indicatesintact responsiveness but impairedawareness.
Partial seizures manifest themselvesin many different forms, depending onwhich area of the cortex is involved inthe onset and spread of the ictal dis-charge. Partial seizures originate froma focal area of cerebral cortex and mayspread to other cortical regions eitherunilaterally or bilaterally. A partial sei-zure may manifest with motor signs,autonomic symptoms, somatosensoryor special sensory symptoms, or psy-
chic symptoms. The term aura comesfrom the Latin word breeze and issynonymous with a simple partial sen-sory or psychic seizure. An aura oftenreflects the location of the seizure-onset zone, although exceptions exist.
Simple Partial Seizures
Focal motor seizures can originate inthe precentral gyrus or spread to theprecentral gyrus from neighboring cor-tical regions. They can remain focal,causing right hand clonic activity, forexample, or can spread or ‘‘march’’along the motor strip involving dif-ferent areas of the motor homuncu-lus. This type of seizure is known as aJacksonian seizure and often clinicallymanifests as clonic activity originatingin the hand and then marching upthe ipsilateral arm, shoulder, face, anddown the leg. After a focal motor sei-zure, postictal weakness (Todd paral-ysis) can last for minutes to hours. Themechanism of Todd paralysis is thoughtto be either from ‘‘neuronal exhaustiondue to the increased metabolic activityof the discharging focus’’ or from ‘‘in-creased inhibition in the region of thefocus.’’1 Epilepsia partialis continua isdefined as a continuous focal motorseizure that remains confined to aspecific body part and usually consistsof clonic movements that can persistfor up to months with preserved con-sciousness.1 Epilepsia partialis continuacan be seen in Rasmussen syndrome,focal lesions (cortical dysplasia, vascularlesions, or tumors), nonketotic hyper-glycemia, and some inborn errors ofmetabolism (myoclonic epilepsy withragged red fibers [MERRF]).2
Case 1-1 illustrates a patient withmedically refractory focal motor sei-zures. In a series of 14 patients withfocal motor seizures who underwent epi-lepsy surgery at Mayo Clinic, 11 patientswere seizure free postoperatively.3
Other types of focal motor seizuresoriginating from the language area
Continuum Lifelong Learning Neurol 2010;16(3)
16
KEY POINTS
A The 1981 and
1989 updates
form the
officially
accepted
classification
system,
although efforts
to develop a
clinically
meaningful
revision to the
current system
are continuing.
A Partial seizures
manifest
themselves
in many
different forms,
depending on
whichareaof the
cortex is involved
in the onset and
spread of the
ictal discharge.
A An aura often
reflects the
location of the
seizure-onset
zone, although
exceptions
exist.
A Epilepsia partialis
continua is
defined as a
continuous focal
motor seizure
that remains
confined to a
specific body
part and usually
consists of clonic
movements that
can persist for
up to months
with preserved
consciousness.
"CLASSIFICATION
Continuum Lifelong Learning Neurol 2010;16(3)
17
Case 1-1A 40-year-old woman had begun having multipledaily seizures at the age of 31, characterized byright facial tingling, right hand pain, clonicmovements of right hand or face, or dystoniawith occasional right leg involvement. No impairmentof consciousness was present. She often had apostictal Todd paralysis of the right hand. She failedtreatment with six antiepileptic drugs (AEDs) andwas on lamotrigine and phenytoin. Her brain MRI(Figure 1-1) showed abnormal T2 signal in the leftanterolateral parietal region consistent with an area ofcortical dysplasia. Her interictal EEG demonstrated leftcentrotemporoparietal spike-and-wave discharges.During prolonged video EEG monitoring, she had20 simple partial seizures, eight were without EEGcorrelate, and 12 were of left centroparietal onset(Figure 1-2). After intracranial EEG monitoring andcortical stimulation mapping, she underwent a focalleft parietal cortical resection. The pathologicdiagnosis was cortical dysplasia with balloon cells(Taylor type IIB) with marked gliosis. She was stillseizure free 4 months after surgery. She had reducedright hand dexterity, cortical sensory loss in the hand,and numbness in her fingers, which were improving.
FIGURE 1-1 This 3-tesla MRI brain (fluid-attenuated inversionrecovery, coronal view) performed using theseizure protocol shows abnormal T2 signal in the
left anterolateral parietal region with extension into the deep whitematter consistent with an area of cortical dysplasia.
FIGURE 1-2 This ictal EEG (Laplacianmontage) shows the leftparasagittal, midline, and right
parasagittal regions from top to bottom. Alow-amplitude beta frequency discharge beginsin the left central region (C3) (A), which evolvesinto a theta frequency spike-and-wave dischargeover the left centroparietal region (C3, P3) (B),which slows and then ends (C ).
continued on page 18
include those with a motor speecharrest or vocalization. Versive seizuresoriginating from the dorsolateral fron-tal cortex (frontal eye fields) involvecontralateral head, eye, or trunk devi-ation. Tonic seizures originating fromthe supplementary motor area (SMA)involve abrupt bilateral or asymmetricposturing usually of the contralateralarm; sometimes the contralateral armis abducted, externally rotated, and ele-vated, and the head is also deviatedcontralaterally. This has been termedthe fencing posture or M2e sign. Con-sciousness is usually preserved.
Simple partial seizures can also haveautonomic symptoms, such as vomit-ing, sweating, piloerection, pupil dila-tion, pallor, flushing, borborygmi, andincontinence. Simple partial seizureswith somatosensory symptoms origi-nating from the postcentral gyrus mayinclude feelings of focal paresthesias(pins and needles), numbness, warmth,or electrical shocklike sensations thatcan also spread like Jacksonian sei-zures (a sensory Jacksonian march).Simple partial seizures with somato-sensory symptoms can also originatefrom the secondary sensory area thatlies above the sylvian fissure anteriorto the precentral gyrus. Secondarysensory seizures are characterized bymore widespread involvement of thesensation (contralateral, ipsilateral, andbilateral involvement) and may includesymptoms of feeling cold, pain, or thedesire to move.4 Sensory seizures canalso originate from the supplementarysensory area, which is just posterior to
the SMA, and involve tingling, the de-sire for movement, feeling stiff, pulling,pulsing, and heaviness.5 Finally, sen-sory seizures can also originate fromthe insular cortex. The symptoms of-ten involve the naso-oropharyngeal-laryngeal regions and consist of throatparesthesias, warmth, tightening, or asense of strangulation or suffocation.6
Simple partial seizures with specialsensory symptoms include visual, au-ditory, gustatory, olfactory, and vertig-inous symptoms. Visual seizures canoriginate from primary visual cortexand consist of primary visual halluci-nations, such as flashing lights, spots,stars, or circles of colored light thatcan appear in the contralateral visualfield or directly ahead. More complexvisual hallucinations originate from vi-sual association cortex and can includeseeing persons or scenes. One patientdescribed seeing Fred Flintstone andthe gingerbread man at the onset ofseizures. Postictal darkness or blind-ness can follow simple visual seizures.Auditory seizures, which arise from thelateral temporal region, specifically thesuperior temporal gyrus and Heschl gy-rus, can include the clinical symptomsof buzzing, ringing, hearing a rushingsound, hyperacusis, hypoacusis, sounddistortion, or hearing words or music.Olfactory seizures originating from theuncinate gyrus or mesial temporal re-gion typically involve smelling unpleas-ant odors, such as burning rubber,smoke, or sulfur. Gustatory sensationsoriginating from the temporal lobe,insula, or parietal operculum can be
Continuum Lifelong Learning Neurol 2010;16(3)
18
Comment. This case illustrates partial seizures from the left perirolandic region presenting asfocal motor seizures and postictal Todd paralysis. The early sensory symptoms reported by thepatient indicate onset from the left parietal region with spread anteriorly to the precentral gyrus.Patients with partial-onset seizures who are medically refractory should be referred tocomprehensive epilepsy centers for further evaluation.
Continued from page 17
"CLASSIFICATION
pleasant or unpleasant and usually aredescribed as a metallic taste but canalso be bitter or sweet. On rare occa-sions, vertiginous symptoms may alsobe a type of simple partial seizure thatoriginates from the lateral temporalregion.
Simple partial seizures with psychicsymptoms indicate a disturbance ofhigher cortical function. For example,dysphasic symptoms include expres-sive or receptive language disturbancesand may involve repetition of a wordor phrase (epileptic palilalia). Dysmne-sic symptoms involve a distortion ofmemory and include deja vu, jamais vu,deja entendu, jamais entendu, autoscopy,or panoramic vision (Table 1-1). Othercognitive disturbances, such as dreamystates, distorted time sense, derealiza-tion, or a sense of unreality, may bepresent. Emotional symptoms includepleasure, fear, or anger that occurs inparoxysms lasting seconds to minutes.Patients may have illusions that resultin distorted perceptions of themselvesor nearby objects. Structured hallucina-tions can take the form of music orscenes and may affect multiple sensorymodalities (eg, somatosensory, visual,
olfactory, gustatory). Primitive halluci-nations originate from the correspond-ing primary sensory area, whereas morecomplex and elaborate hallucinationsoriginate from the corresponding as-sociation cortices. Psychic auras oftenoriginate from the temporal lobe.
Complex Partial Seizures
Complex partial seizures are partial sei-zures with impairment of conscious-ness. They may start as simple partialseizures (auras) and progress to com-plex partial seizures or may begin ascomplex partial seizures with impair-ment of consciousness at the onset ofthe seizure. They may or may not in-volve automatisms. The clinical fea-tures of the complex partial seizuredepend on the region affected by ab-normal electrical activity. Complex par-tial seizures usually originate in thefrontal or temporal lobes but can oc-cur in parietal or occipital lobe.
Generalized Seizures
Absence seizures are characterized by asudden-onset behavioral arrest, a blankstare, unresponsiveness, and some-times a brief upward rotation of the
Continuum Lifelong Learning Neurol 2010;16(3)
19
TABLE 1-1 Psychic Auras
Psychic Aura Definition
Deja vu An illusion of a familiar memory
Jamais vu A familiar visual experience becomes unfamiliar
Deja entendu An auditory illusion of something familiar
Jamais entendu A familiar auditory experience becomes unfamiliar
Autoscopy Seeing oneself in external space, as if the mind hasleft the body
Depersonalization A feeling of unreality in one’s sense of self; feelingas if in a dream or watching oneself act
Macropsia/micropsia Objects appear larger or smaller than usual
Macracusia/micracusia Sounds are louder or softer than usual
KEY POINTS
A Simple partial
seizures with
somatosensory
symptoms
originating
from the
postcentral
gyrus may
include feelings
of focal
paresthesias
(pins and
needles),
numbness,
warmth, or
electrical
shocklike
sensations that
can also spread
like Jacksonian
seizures
(a sensory
Jacksonian
march).
A Visual seizures
can originate
from primary
visual cortex
and consist of
primary visual
hallucinations,
such as flashing
lights, spots,
stars, or circles
of colored light
that can appear
in the
contralateral
visual field or
directly ahead.
A Psychic auras
often originate
from the
temporal lobe.
A The clinical
features of the
complex partial
seizure depend
on the region
affected by
abnormal
electrical activity.
eyes. The duration is typically a fewseconds to half a minute. Little to nopostictal confusion is present, and pa-tients typically resume the activity theywere doing prior to the seizures. Thisseizure type is also referred to as sim-ple absence. The ILAE’s 1981 classi-fication recognizes five subtypes ofabsence seizures: (1) with impairmentof consciousness only, (2) with mildclonic components, (3) with atonic com-ponents, (4) with tonic components,and (5) with automatisms. In absencewith mild clonic components, subtleclonic movements of the eyelids, cor-ner of the mouth, or upper extremitiesoccur, sometimes at a frequency of3 Hz. In absence with atonic compo-nents, a loss of postural tone causesthe head to drop, the trunk to slumpforward, the arms to drop, or the gripto relax. Falls are rare. In absence withtonic components, tonic muscle con-traction of the trunk and neck exten-sors may cause the head to extend andthe trunk to arch, thus causing retro-pulsion. Tonic contraction of the neckmuscles may cause the head or trunkto deviate to one side. In absence withautomatisms, the patient engages inpurposeful or semipurposeful repeti-tive movements while consciousnessis impaired. Examples of automatismsmay include lip licking, chewing, lipsmacking, swallowing, grimacing, smil-ing, yawning, fumbling with the hands,picking, scratching, rubbing, or aim-less walking. Absence with autonomicphenomena is another subtype withsigns of tachycardia, pallor, flushing,piloerection, salivation, or urinary in-continence. A mixture of clonic, atonic,tonic, automatic, and autonomic fea-tures may occur and is also referredto as complex absence. The ictal EEGpattern in absence seizures is a 3-Hzgeneralized monomorphic spike-and-wave discharge with abrupt onset andtermination.7 Absence seizures in theEEG laboratory can be precipitated by
hyperventilation and, less commonly,photic stimulation.
Atypical absence seizures are usu-ally seen in patients with symptomaticgeneralized epilepsy. They are similarto absence seizures in that they haveboth simple and complex presenta-tions. One distinguishing feature is thatthey are less abrupt in onset clinically.The seizures are usually less than 10 sec-onds but may be prolonged and resultin absence status. They also are notusually induced by hyperventilationor photic stimulation. The ictal EEGpattern consists of a less monomorphicslow spike-and-wave discharge charac-terized by a blunt sharp wave and oc-curs at a frequency of less than 2.5 Hz.
Tonic-clonic seizures, also knownas grand mal seizures, are character-ized by abrupt loss of consciousnessfollowed by tonic contraction of themuscles. This leads to the ictal cry,where air is forcefully expired against aclosed glottis. The mouth is forcefullyclosed, which can result in a tonguebite. The pupils become dilated andthe eyes deviate upward. The upperextremities often symmetrically abductand flex at the elbows, while the lowerextremities may briefly flex and thenextend and adduct with the toespointed. Clonic activity ensues, whichis initially rapid and then slows, en-sues. Gasping respirations occur as therespiratory muscles are involved in theclonic activity. The patient may be-come cyanotic. Urinary incontinence mayoccur. At the end of the seizure, thepatient is unconscious for a brief periodof time and then gradually recovers.Patients typically report generalizedmuscle soreness and sometimes a head-ache postictally.
Tonic-clonic seizures may occur in-dependently, arise from other general-ized seizures, or occur during second-ary generalization of a partial-onsetseizure. The semiologic features of tonic-clonic seizures in primary generalized
Continuum Lifelong Learning Neurol 2010;16(3)
20
KEY POINTS
A Examples of
automatisms
may include lip
licking, chewing,
lip smacking,
swallowing,
grimacing,
smiling,
yawning,
fumbling with
the hands,
picking,
scratching,
rubbing, or
aimless walking.
A One feature that
distinguishes
atypical absence
seizures from
absence seizures
is that they are
less abrupt in
onset clinically.
A Tonic-clonic
seizures may
occur
independently,
arise from other
generalized
seizures, or
occur during
secondary
generalization of
a partial-onset
seizure.
"CLASSIFICATION
epilepsy may be bilaterally symmetric orinvolve a forced head deviation to eitherside.8 During secondarily generalizedpartial-onset seizures, patients oftenassume a figure-4 posture in which thecontralateral arm extends and theipsilateral arm flexes at the elbow. Thisposture can occur with the legs as well.Tonic-clonic seizures may lead to in-juries such as burns, head injuries,vertebral compression fractures, shoul-der dislocations, and tongue and cheeklacerations.
Myoclonic seizures are generalizedseizures characterized by brief, irregular,shocklike jerks of the head, trunk, orlimbs. They can be symmetric or asym-metric and involve the whole body,regions of the body, or focal areas. Theytend to occur close to sleep onset andon awakening from sleep. Myoclonicseizures can be a feature of some idio-pathic generalized epilepsies (juvenilemyoclonic epilepsy), symptomatic gen-eralized epilepsies (myoclonic-astaticepilepsy), the progressive myoclonicepilepsies (Lafora disease), and infan-tile spasms. Myoclonus can be positiveor negative. Negative myoclonus refersto the brief loss of postural tone whenthe body part is held against gravity.Consciousness is not impaired, and nopostictal confusion occurs after singlemyoclonic jerks. Myoclonic seizurescan occur in clusters and evolve intoclonic-tonic-clonic seizures, with resul-tant loss of consciousness and postic-tal confusion. The ictal EEG pattern ischaracterized by brief generalized poly-spike or polyspike-and-wave dischargesthat correspond to the myoclonic jerk.
Tonic seizures involve tonic con-traction of the face, neck, axial, or ap-pendicular musculature lasting from10 seconds to 1 minute. They can in-volve extension or flexion of the mus-cles and often lead to falls and headinjuries. They may be more subtle andinvolve only upward eye deviation. Theyoften occur out of non-REM sleep. They
are usually seen in patients with symp-tomatic generalized epilepsy and areone of the common seizure types in pa-tients with Lennox-Gastaut syndrome.They can also occur in epilepsy withmyoclonic-astatic seizures. The ictal EEGusually shows a brief generalized atten-uation of cerebral activity followed bygeneralized paroxysmal fast activity inthe beta frequency range.
Clonic seizures are generalized sei-zures characterized by repetitive rhyth-mic clonic jerks (1 Hz to 2 Hz) withimpairment of consciousness and ashort postictal phase. They can leadinto a clonic-tonic-clonic seizure. It isthought that the repetitive dischargesare due to rhythmic excitatory dis-charges from the cortex.1,2 The ictalEEG demonstrates generalized poly-spike-and-wave discharges or general-ized fast activity.
Atonic seizures are characterized bya sudden loss of muscle tone, which canlead to a head drop, a limb drop, or adrop of the whole body (also known asa drop attack). Brief loss of conscious-ness and injuries occur, particularly tothe face.1 Atonic seizures last less than5 seconds and are followed by minimalpostictal confusion. Atonic seizures maybe preceded by a brief myoclonic jerk ortonic component. Atypical absence sei-zures may have an atonic component.The criteria distinguishing between neg-ative myoclonus, atonic seizures, andsome atypical absences still need to bedeveloped.2 Atonic seizures are usuallyseen in the symptomatic generalizedepilepsies, such as Lennox-Gastaut syn-drome. The ictal EEG typically shows ageneralized high-voltage spike and waveor slow wave followed by a generalizedattenuation of cerebral activity or low-voltage paroxysmal fast activity.
Unclassified Epileptic Seizures
This category listed in the ILAE’s Clas-sification of Epileptic Seizures includes
Continuum Lifelong Learning Neurol 2010;16(3)
21
KEY POINTS
A During secondarily
generalized
partial-onset
seizures,
patients often
assume a
figure-4
posture in which
the contralateral
arm extends and
the ipsilateral
arm flexes at
the elbow.
A Negative
myoclonus
refers to the
brief loss of
postural tone
when the body
part is held
against gravity.
A The criteria for
distinguishing
among negative
myoclonus,
atonic seizures,
and some
atypical
absences still
need to be
developed.
Continuum Lifelong Learning Neurol 2010;16(3)
22
TABLE 1-2 International League Against Epilepsy 1989 InternationalClassification of Epilepsies and Epileptic Syndromes
1. Localization-related epilepsies and syndromes
1.1 Idiopathic
Benign childhood epilepsy with centrotemporal spikes
Childhood epilepsy with occipital paroxysms
Primary reading epilepsy
1.2 Symptomatic
Chronic progressive epilepsia partialis continua of childhood(Kojewnikow syndrome)
Syndromes characterized by seizures with specific modes of precipitation
Temporal lobe epilepsies
Frontal lobe epilepsies
Parietal lobe epilepsies
Occipital lobe epilepsies
1.3 Cryptogenic
2. Generalized epilepsies and syndromes
2.1 Idiopathic
Benign neonatal familial convulsions
Benign neonatal convulsions
Benign myoclonic epilepsy in infancy
Childhood absence epilepsy
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Epilepsy with GTCS on awakening
Other generalized idiopathic epilepsies not defined above
Epilepsies with seizures precipitated by specific modes of activation
2.2 Cryptogenic or symptomatic
West syndrome
Lennox-Gastaut syndrome
Epilepsy with myoclonic-astatic seizures
Epilepsy with myoclonic absences
2.3 Symptomatic
2.3.1 Nonspecific etiology
Early myoclonic encephalopathy
Early infantile epileptic encephalopathy with suppression burst
Other symptomatic generalized epilepsies not defined above
continued on next page
"CLASSIFICATION
all seizures that defy classification be-cause of incomplete data.1 An exampleis a seizure in infancy, which may in-volve chewing, swimming movements,eye movements, jittering, and apnea,and has not yet been subtyped.
CLASSIFICATION OF EPILEPSIESAND EPILEPTIC SYNDROMES
An epileptic disorder can be symp-tomatic, idiopathic, or cryptogenic.Symptomatic is a term that means theetiology is known—usually a structurallesion within the brain. Idiopathic is aterm that refers to an epilepsy of pre-sumed genetic etiology without a struc-tural brain lesion or other neurologicsigns or symptoms. Cryptogenic is a term
that refers to an epilepsy that is pre-sumed to be symptomatic, but the etiol-ogy is unknown.9 The term cryptogenichas been replaced with probably symp-tomatic.10 The currently used 1989 clas-sification system is divided into fourmain categories: (1) localization related(focal, local, or partial), (2) generalized,(3) epilepsies and syndromes undeter-mined whether focal or generalized,and (4) special syndromes (Table 1-2).
An epilepsy syndrome is defined as‘‘a complex of signs and symptomsthat define a unique epilepsy condi-tion.’’10 The groups of syndromes are:idiopathic focal epilepsies of infancy andchildhood, familial (autosomal domi-nant) focal epilepsies, symptomatic (or
Continuum Lifelong Learning Neurol 2010;16(3)
23
KEY POINT
A An epileptic
disorder can be
symptomatic,
idiopathic, or
cryptogenic.
The term
cryptogenic has
been replaced
with probably
symptomatic.
TABLE 1-2 Continued
2.3.2 Specific syndromes
Diseases in which seizures are a presenting or predominant feature
3. Epilepsies and syndromes undetermined whether focal or generalized
3.1 With both generalized and focal seizures
Neonatal seizures
Severe myoclonic epilepsy in infancy
Epilepsy with continuous spike-waves during slow-wave sleep
3.2 Without unequivocal generalized or focal features (ie, sleep relatedGTCS; when the EEG shows both focal and generalized ictal orinterictal discharges, and when focal or generalized onset cannot bedetermined clinically)
4. Special syndromes
4.1 Situation-related seizures
Febrile convulsions
Isolated seizures or isolated status epilepticus
Seizures occurring only when there is an acute metabolic or toxic event(alcohol, drugs, eclampsia, nonketotic hyperglycemia)
Modified with permission from Commission on Classification and Terminology of the International League Against
Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30(4):389–399.
probably symptomatic) focal epilepsies,idiopathic generalized epilepsies, reflexepilepsies, epileptic encephalopathies,progressive myoclonus epilepsies, andseizures not necessarily requiring a di-agnosis of epilepsy (Table 1-3). Morethan 25 specific syndromes are includedin the 1989 ILAE report. A discussionregarding a few of the more commonsyndromes affecting adolescents andadults follows.
Temporal Lobe Epilepsies
Temporal lobe seizures are the mostcommon type of partial epilepsy. Tem-poral lobe seizures often begin withan aura.11 Auras may include viscero-sensory symptoms (epigastric, thoracic,and warm ascending sensations) orsensory illusions or hallucinations. Theictal event is usually characterized by ablank stare, loss of contact with theenvironment, oroalimentary or vocalautomatisms, hand automatisms, up-per limb tonic or dystonic posturing,early head or eye deviation, and dys-phasia. Oroalimentary automatisms aredefined as stereotyped, repetitive move-ments of the mouth, tongue, lips, orjaw that have the appearance of chew-ing or lip smacking. They may also in-volve gulping, swallowing, or spitting.Hand automatisms are repetitive, pur-poseless movements of the hands, in-cluding grasping, fumbling, and search-ing movements. Both oroalimentary andhand automatisms often localize to themesial temporal lobe (Table 1-4). Interms of lateralization (determiningright versus left hemispheric involve-ment), unilateral automatisms and post-ictal dysphasia were determined tohave the highest predicative value. Uni-lateral automatisms are typically ipsi-lateral to the region of seizure onset,and postictal dysphasia is lateralized tothe dominant hemisphere.12 Nondom-inant temporal lobe seizures can havepreservation of language and respon-siveness with minimal postictal confu-
sion. Patients with right temporal lobeepilepsy due to mesial temporal scle-rosis may be able to speak normallyduring the seizure. Patients with lefttemporal lobe seizures due to mesialtemporal sclerosis often make promi-nent paraphasic errors during andafter seizures. Specific semiologic fea-tures are also helpful in distinguishingbetween mesial, mesial-lateral, and lat-eral temporal lobe epilepsy. Mesialtemporal lobe seizures are often char-acterized by an initial epigastric sensa-tion or viscerosensory sensation, fear,a dreamy state, longer seizure dura-tion, delayed loss of contact, and de-layed oroalimentary and upper limbautomatisms. Lateral temporal lobe sei-zures are characterized by an initial sen-sory illusion or hallucination (mainlyauditory), an initial loss of contact, ashorter duration (less than 1 minute),and frequent secondary generaliza-tions. The mesial-lateral temporal lobeseizures described were similar to themesial temporal seizures but had anearlier loss of contact and earlier oro-alimentary, verbal, and vocal automa-tisms.13 It is important to distinguishbetween mesial (limbic) and lateral(neocortical) temporal lobe epilepsy ifone is considering a surgical optionsuch as a temporal lobectomy, as post-surgical seizure freedom and compli-cation rates differ.
Frontal Lobe Epilepsies
Frontal lobe seizures are the secondmost common type of focal epilepsyand occur in approximately 30% of pa-tients with partial epilepsy.14 Frontallobe seizures are often confused withpseudoseizures because of the bizarreclinical semiology. Frontal lobe seizuresare usually brief (less than 30 seconds),tend to occur in clusters, can occurmultiple times per day, and often haveminimal or no postictal confusion. Theclinical semiology includes an abrupt on-set of stereotyped hypermotor behavior
Continuum Lifelong Learning Neurol 2010;16(3)
24
KEY POINTS
A Both
oroalimentary
and hand
automatisms
often localize to
the mesial
temporal lobe.
In terms of
lateralization
(determining
right versus left
hemispheric
involvement),
unilateral
automatisms
and postictal
dysphasia were
determined to
have the highest
predicative
value.
A It is important
to distinguish
between mesial
(limbic) and
lateral
(neocortical)
temporal lobe
epilepsy if one
is considering a
surgical option
such as a
temporal
lobectomy, as
postsurgical
seizure
freedom and
complication
rates differ.
A Frontal lobe
seizures are
usually brief
(less than 30
seconds), tend
to occur in
clusters, can
occur multiple
times per day,
and often have
minimal or no
postictal
confusion.
"CLASSIFICATION
Continuum Lifelong Learning Neurol 2010;16(3)
25
TABLE 1-3 Example of a Classification of Epilepsy Syndromes
Groups of Syndromes Specific Syndromes
Idiopathic focal epilepsies ofinfancy and childhood
Epilepsy with generalized tonic-clonicseizure only
Generalized epilepsies with febrileseizures plusa
continued on next page
and may include vocalizations, gesturalor sexual automatisms, and bilateral legautomatisms consisting of pedaling orbicycling movements. The seizure se-
miology of frontal lobe seizures variesdepending on what region of the fron-tal lobe is involved. The patient mayhave asymmetric tonic extension of the
Seizures not necessarilyrequiring a diagnosisof epilepsy
Benign neonatal seizures
Febrile seizures
Reflex seizures
Alcohol-withdrawal seizures
Drug or other chemically induced seizures
Immediate and early posttraumatic seizures
Single seizures or isolated clusters of seizures
Rarely repeated seizures (oligoepilepsy)
a Syndromes in development.
Modified with permission from Engel J Jr, International League Against Epilepsy (ILAE). A proposed diagnostic schemefor people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology.Epilepsia 2001;42(6):796–803.
"CLASSIFICATION
proximal extremities, as in SMA seizures,or clonic activity of the contralaterallimb, as in seizures from the lateralconvexity. Seizures originating from the
mesial frontal region or SMA are char-acterized by vocalizations and abrupttonic extension of the proximal extrem-ities that may be bilateral and is often
Continuum Lifelong Learning Neurol 2010;16(3)
27
TABLE 1-4 Localization and Lateralization of Ictal SeizureSemiology
Clinical Event Localization/Lateralization
Head turn
Early nonforced Ipsilateral temporal
Forced
Early forced Frontal
Late forced Contralateral temporal (in process of generalizing)
Ocular version Contralateral occipital
Focal clonic Contralateral perirolandic or temporal
Postictal nose rubbing Ipsilateral temporal > frontal (to hand used)
Postictal cough Temporal
Bipedal automatisms Frontal > temporal
Hypermotor Supplementary motor area
Ictal spitting Right temporal
Automatisms with reservedresponsiveness
Right temporal
Gelastic Hypothalamic, mesial temporal
Ictal vomiting/retching Right temporal
Ictal urinary urge Nondominant temporal
Loud vocalization Frontal > temporal
Ictal speech arrest Temporal
Ictal speech preservation Nondominant hemisphere
Postictal aphasia Language-dominant hemisphere
asymmetric. Minimal impairment ofconsciousness or postictal confusion ispresent. Lateral dorsal frontal lobe sei-zures are characterized by speech arrest,forced thinking, contraversive head andeye deviation, and automatisms such aslaughing, crying, sniffing, chewing, orkicking. Orbitofrontal seizures are char-acterized by prominent autonomic symp-toms (eg, flushing, mydriasis, tachycardia),automatisms, and loud vocalizations.They can also appear similar to mesialtemporal lobe seizures because of rapidspread to this region. Cingulate gyrusseizures are similar to SMA seizures butalso involve behavioral arrest, oroali-mentary automatisms, gestural or sex-ual automatisms, mood changes, andsometimes urinary incontinence. Be-cause of the extensive interregional con-nectivity within the frontal lobe andrapid seizure propagation, frontal lobeseizures are difficult to localize on thebasis of clinical semiology.
Parietal Lobe Epilepsies
Parietal lobe seizures account for lessthan 10% of focal seizures. Often theyarise from clinically silent areas andonly manifest symptoms when the sei-zure spreads to other functional cor-tical regions. They can spread to theoccipital, temporal, or frontal regions.Clinically, patients may report somato-sensory symptoms, most commonly inthe face and hand, contralateral to theseizure focus. In nondominant parietallobe seizures, patients can have spatialneglect of the contralateral body or en-vironment. In dominant parietal lobeseizures, patients may have languagedysfunction. Case 1-1 is an example ofa patient with focal parietal-onset sei-zures that manifest with contralateralsensory and motor symptoms.
Occipital Lobe Epilepsies
Occipital lobe seizures also account forless than 10% of focal seizures. They
are characterized by elementary visualhallucinations of fixed or moving flash-ing white or colored lights that start inthe contralateral visual field and canspread to the entire visual field. Pa-tients may also report a whiting out orblacking out of their vision. The eyesmay deviate contralaterally, and theeyelids may rapidly blink. The subse-quent clinical features of the seizureare determined by where the seizuredischarge spreads. If the seizure spreadsto the posterior temporal region (areaof visual association cortex), complexvisual hallucinations may occur. Oc-cipital seizures may also spread to themesial temporal, parietal, and periro-landic regions and mimic seizures fromthose regions.
Autosomal DominantNocturnal Frontal LobeEpilepsy
Autosomal dominant nocturnal frontallobe epilepsy (ADNFLE) is a familial au-tosomal dominant focal epilepsy char-acterized by clusters of brief seizures(5 to 30 seconds) during non-REMsleep (stages N2 and N3). They are of-ten initially misdiagnosed as night-mares or parasomnias. The mean ageof onset is around 12 years of age (range1 to 30). The seizures themselves arecharacterized by brief motor attacks,usually with a dystonic or dyskineticcomponent. During a seizure patientsmay have complex and bizarre behav-iors, shouting, bimanual and bipedalautomatisms, mumbling, urinary incon-tinence, and rarely violent behavior.The ictal EEG may demonstrate a fron-tally predominant ictal discharge in ap-proximately 30% of patients and focalbackground attenuation or focal rhyth-mic slowing over the anterior headregions in about 55% of patients.15
The CHRNA4 gene on chromosome20, which encodes the neuronal nico-tinic acetylcholine receptor (nAChR)�4 subunit, is mutated in patients with
Continuum Lifelong Learning Neurol 2010;16(3)
28
KEY POINT
A Because of the
extensive
interregional
connectivity
within the
frontal lobe and
rapid seizure
propagation,
frontal lobe
seizures are
difficult to
localize on the
basis of clinical
semiology.
"CLASSIFICATION
ADNFLE type 1. The CHRNB2 on chro-mosome 1 is mutated in patients withADNFLE type 3. The molecular patho-genesis of how these mutations causeADNFLE is unknown.16
Autosomal Dominant PartialEpilepsy With AuditoryFeatures
Autosomal dominant partial epilepsywith auditory features (ADPEAF) orautosomal dominant lateral temporalepilepsy (ADLTE) is also a familial au-tosomal dominant focal epilepsy charac-terized by lateral temporal lobe epilepsyand auditory aura. It is caused by amutation in the LGI1 gene (leucine-rich glioma-inactivated 1 gene), whichis expressed in neurons in the neo-cortex and limbic regions.16 Mutationsin the LGI1 gene have been found in50% of families with this type of epi-lepsy.17 The age of onset is between 1and 60 years with a mean of 18 years.The seizures are characterized by au-ditory auras (64%), complex visual hallu-cinations (17%), psychic auras (16%),autonomic features (12%), vertiginoussensations (9%), other sensory symptoms(13%), and aphasia (17%). Most auditoryauras are simple in nature (eg, hum-ming, buzzing, ringing). A minority ofpatients report complex hallucinations,such as music or voices. The MRI of thebrain is normal, and patients typicallyhave a good response to treatmentwith AEDs.18,19
Mesial temporal lobe epilepsy withhippocampal sclerosis is a symptom-atic focal epilepsy and subcategorizedas a limbic epilepsy (versus neocorticalepilepsy). Mesial temporal lobe epilepsyis one of the most common types of epi-lepsy referred for epilepsy surgery andis often refractory to AEDs. The age ofonset is between late childhood andmidadolescence. Patients often had fe-
brile convulsions in infancy or earlychildhood. Most patients report an aura.Common auras include an epigastricsensation (a rising sensation, butterflies,nausea), fear, olfactory hallucinations,lightheadedness, and deja vu.20 Com-plex partial seizure semiology may alsoconsist of ipsilateral upper extremityautomatisms and ipsilateral early non-forced head turn. Contralateral dys-tonic posturing, Todd paralysis, andlate forced head turn prior to second-ary generalization can also be seen.
Hippocampal sclerosis is the mostcommon pathologic substrate foundin patients with mesial temporal lobeepilepsy who undergo surgical resec-tion. Hippocampal sclerosis is stronglyassociated with prolonged febrile sei-zures in childhood, but the cause is stillunknown. Most patients who undergosurgical resection for mesial temporallobe epilepsy with hippocampal sclero-sis become seizure free (Case 1-2).21
Juvenile Absence Epilepsy
Juvenile absence epilepsy ( JAE) is clas-sified as an idiopathic generalized epi-lepsy. The age of onset is typically at orafter puberty between the ages of 10and 17. Unlike in childhood absenceepilepsy in which absence seizures canoccur hundreds of times per day, ab-sence seizures in JAE may only occursporadically. Consciousness is less im-paired with absence seizures in JAE com-pared to absences in childhood absenceepilepsy. Patients with JAE can have gen-eralized tonic-clonic seizures (usually onawakening), myoclonic seizures, andeven absence status epilepticus. Theictal EEG pattern resembles that ofchildhood absence epilepsy (3-Hz spikeand wave), but the discharges tend tovary slightly in frequency (usually greaterthan 3 Hz), are more irregular, and in-clude more polyspike discharges. Astrong genetic component links to chro-mosomes 5, 8, 18, and 21. The responseto AEDs is usually excellent.22
Continuum Lifelong Learning Neurol 2010;16(3)
29
KEY POINTS
A Mesial temporal
lobe epilepsy is
one of the most
common types
of epilepsy
referred for
epilepsy surgery
and is often
refractory to
antiepileptic
drugs.
A Patients with
juvenile absence
epilepsy can
have generalized
tonic-clonic
seizures (usually
on awakening),
myoclonic
seizures, and
even absence
status
epilepticus.
Continuum Lifelong Learning Neurol 2010;16(3)
30
Case 1-2A 33-year-old man presented for evaluation of medically refractory partial epilepsy. His risk factorfor epilepsy included a complex febrile seizure at the age of 6 months. He had recurrence of hisseizures at the ages of 6 and 24 with anintervening seizure-free period of up to 12years. He described his current seizures asan aura of ‘‘a funny feeling in his stomach’’followed by nausea. Sometimes hisaura would be followed by decreasedresponsiveness, staring, and lip smacking.These seizures were typically 1 to 2 minutesin duration. He failed treatment with threeAEDs. His MRI brain scan (Figure 1-3)showed modest atrophy of the body ofthe hippocampus on the right associatedwith minimal increased signal consistentwith mesial temporal sclerosis. His interictalEEG showed right anterior and midtemporalsharp waves and right temporalintermittent rhythmic delta activity.
During a recorded seizure, he hadright hand automatisms consisting ofrepetitively rubbing his leg, followedby mouth-chewing movements. Hisleft arm remained immobile and stiffthroughout the seizure. He was initiallyunresponsive to the technician, but toward
modest atrophy of the body of the righthippocampus with mildly increased signalconsistent with mesial temporal sclerosis.
FIGURE 1-4 This ictal EEG (longitudinal bipolarmontage) shows both temporal regions(left on top, right on bottom). The right
temporal seizure begins as a rhythmic sharply contouredtheta frequency discharge over the right mid-temporalregion (A), slows to a delta frequency (B), and then ends.
continued on page 31
"CLASSIFICATION
Juvenile Myoclonic Epilepsy
Juvenile myoclonic epilepsy (JME) is alsoclassified as an idiopathic generalizedepilepsy. The age of onset is in the mid-teens between the ages of 12 and 18.Patients may present with myoclonicjerks on awakening in the morning. Pa-tients may first ignore the myoclonicjerks, often attributing them to clumsi-ness. Sometimes the diagnosis is notmade until the patient has a generalizedtonic-clonic seizure. The myoclonus usu-ally involves the neck, shoulders, arms,or legs with the upper extremities beingmore frequently affected. Conscious-ness is usually not impaired during themyoclonic seizures. Generalized tonic-clonic and absence seizures are alsoseen. Generalized tonic-clonic seizuresmay also occur in the morning onawakening and can be triggered bysleep deprivation, alcohol, and stress.Often, several myoclonic jerks may pre-cede a generalized tonic-clonic seizure,which is known as a clonic-tonic-clonicseizure. Approximately 50% of patientscan be photosensitive. The ictal EEGconsists of generalized polyspike-and-wave discharges greater than 3 Hz. Astrong genetic component links to chro-mosomes 2, 3, 5, 6, and 15. The responseto AED treatment is excellent but needsto be continued lifelong in most patientsbecause of a high rate of relapse.22
Epilepsy With GeneralizedTonic-Clonic Seizures onAwakening
This syndrome is also known as epi-lepsy with generalized tonic-clonic sei-zures only and is classified as one ofthe idiopathic generalized epilepsies.The age of onset is the second decadeof life. Generalized tonic-clonic sei-zures occur more than 90% of the time,with absence and myoclonic seizuresoccurring less frequently. Seizures oc-cur 1 to 2 hours after awakening fromsleep or during periods of relaxationin the evening. Sleep deprivation, al-cohol, and photic stimulation can beprecipitating factors. The ictal EEG dem-onstrates frontally predominant fastrhythmic spiking. The prognosis is goodif the patient is adequately treated withAEDs and avoids provoking factors.9,22
Reflex Epilepsies and ReflexSeizures
The reflex epilepsies are syndromesin which all or most seizures are preci-pitated by sensory stimuli. The purereflex epilepsies are characterized byseizures that are always or most alwaysprecipitated by a specific stimulus. Out-side the context of pure reflex epi-lepsy, patients with generalized or focalepilepsy syndromes may have both re-flex seizures and spontaneous seizures.
Continuum Lifelong Learning Neurol 2010;16(3)
the end of the seizure he was able to follow commands, speak normally, and spell his namecorrectly. He did not remember the memory words but was able to read normally after theseizure. Electrographically, seizures began with a right temporal rhythmic theta frequencydischarge maximal in the midtemporal region (Figure 1-4). He underwent a right temporallobectomy with amygdalohippocampectomy and was still seizure free on medication 10 monthsafter his surgery.
Comment. This patient’s seizure semiology illustrates a typical nondominant mesial temporallobe seizure with an epigastric aura, ipsilateral hand automatisms, contralateral dystonicposturing, ictal preservation of speech and responsiveness, and absence of postictal dysphasia.Various studies have reported that 60% to 85% of patients with mesial temporal sclerosis whounderwent temporal lobectomy had a good outcome in terms of seizure control.
31
Continued from page 30
Triggers of generalized reflex seizuresmay include photic stimulation, think-ing, and decision making. Focal reflexseizures may be triggered by somato-sensory stimulation, proprioception,walking, eating, bathing in hot water,reading, writing, auditory stimuli, mu-sic, startle, or vestibular stimulation.23
Lennox-Gastaut Syndrome
Lennox-Gastaut syndrome is classified asan epileptic encephalopathy. The ageof onset is usually before age 8 with apeak age of onset between 3 and 5years. Rarely, the disorder can presentin early adulthood. The syndrome ischaracterized by a triad of multiple sei-zure types (tonic and atypical absenceare the most common), slow spike andwave on EEG (1.0 Hz to 2.5 Hz), andsome degree of mental retardation.The etiology can be symptomatic orcryptogenic. It may evolve from Westsyndrome. Tonic seizures are consid-ered a prerequisite for the diagnosis.Atonic seizures are also common. My-oclonic, generalized tonic-clonic, uni-lateral clonic, and partial seizures canoccur less frequently. Nonconvulsivestatus epilepticus can occur in morethan 50% of patients and involvesnear-continuous atypical absence sei-zures interrupted by brief tonic sei-zures. The interictal EEG is char-acterized by slow spike-and-wavecomplexes (less than 2.5 Hz) and ac-tivation of generalized paroxysmal fastactivity during sleep. The diagnosismay be difficult to make at first be-cause not all features of the syndromemay be present. The seizures in Lennox-Gastaut syndrome are typically refrac-tory to medical treatment.24
Progressive MyoclonicEpilepsies
These diseases are characterized bymyoclonic jerks, seizures (generalizedtonic-clonic, absence, clonic, partial)and dementia caused by cerebral and
cerebellar atrophy. The myoclonus istermed massive myoclonus, which cancause falls and lead into generalizedtonic-clonic seizures. Patients may ex-hibit cerebellar dysfunction, action myo-clonus, or extrapyramidal dysfunction.Childhood development is normal un-til the age of onset. The autosomal re-cessive forms include Lafora disease,Unverricht-Lundborg disease, the neu-ronal ceroid lipofuscinoses, sialidosis,action myoclonus–renal failure syn-drome, and Gaucher disease. The au-tosomal dominant form is dentatoru-bropallidoluysian atrophy. Progressivemyoclonic epilepsy is also seen insome mitochondrial cytopathies, suchas MERRF (Case 1-3).
TRENDS
The ILAE classifications are based onconcepts formulated prior to modernneuroimaging and genomic research.The 1989 classification was not a truescientific classification but rather an or-ganized list built on concepts that nolonger correspond to or accuratelydescribe our increasing knowledge ofseizures and the epilepsies. Numerousattempts have been made by the ILAECommittee2,10 and individual investi-gators25 to revise the current classifica-tion. These attempts have generatedcontroversy, and the lack of consensushas blocked any formal revision. Themost recent ILAE Commission on Clas-sification and Terminology report ( July2009)26 recommended a revised andsimplified classification for seizures andnew terminology and concepts, but nota new classification for the epilepsies. Atthe time of this writing, the Commissionreport had not been officially approved.
CONCLUSION
The current ILAE Classification System forseizures and the epilepsies has formedthe basis for a worldwide standardizedapproach to diagnosing, treating, and
Continuum Lifelong Learning Neurol 2010;16(3)
32
KEY POINTS
A Lennox-Gastaut
syndrome is
characterized by
a triad of
multiple seizure
types (tonic and
atypical absence
are the most
common), slow
spike and wave
on EEG (1.0 Hz
to 2.5 Hz), and
some degree
of mental
retardation.
A The most
recent ILAE
Commission on
Classification
and Terminology
report (July
2009)
recommended a
revised and
simplified
classification for
seizures andnew
terminology and
concepts, but
not a new
classification for
the epilepsies.
"CLASSIFICATION
studying seizure disorders. The seizureclassification system is primarily basedon clinical semiology and EEG correla-tion, with a major distinction madebetween focal and generalized seizures.Focal seizures are further subdividedinto simple and complex partial sei-zures, with the presence or absence ofimpairment of consciousness distin-guishing the two. Generalized seizures
are divided into absence, tonic, tonic-clonic, myoclonic, or atonic seizures.The epilepsy classification system high-lights specific syndromes defined fromanatomic-pathologic bases (mesial tem-poral lobe epilepsy with hippocampalsclerosis) to electroclinical bases (Lennox-Gastaut syndrome). This system hasbeen useful for both clinicians and re-searchers over the past 20 years, but
Continuum Lifelong Learning Neurol 2010;16(3)
33
Case 1-3A 25-year-old Iranian man presented for the evaluation of medically refractory epilepsy, cognitivedecline, dysarthria, and gait ataxia. He was healthy until myoclonic and clonic-tonic-clonic seizuresbegan at the age of 7. His family described episodes of massive myoclonus where he may fall out ofbed or fall to the ground. His cognitionbegan to decline around the age of 16.Over the past several years, he lost theability to care for himself and lived athome with his parents, requiring helpwalking, bathing, and eating. Themyoclonus was frequent, oftenstimulus-induced, and interfered with hisability to speak, stand, and walk. Hisneurologic examination was abnormal anddemonstrated cognitive impairment,dysarthria, limb ataxia, and tremor. HisMRI demonstrated mild generalizedcerebral and cerebellar atrophy. Hisinterictal and ictal EEG showed a normalbackground with trains of repetitivegeneralized sharp waves firing at afrequency of 7 Hz (Figure 1-5). Numerousbrief myoclonic seizures consisting ofbilateral shoulder abduction and a headjerk were recorded. Negative myoclonicseizures were also recorded and consistedof a loss of tone in the face, arms, or trunkif the body part involved in the seizure washeld against gravity. Serologic testing wasunremarkable. Axillary skin biopsy wasnegative for Lafora bodies or any otherocclusions suggestive of a lysosomal storagedisease. Family members refused genetictesting for Unverricht-Lundborg disease.
Comment. It is important to distinguish between JME and the progressive myoclonic epilepsies.As opposed to the progressive myoclonic epilepsies, the myoclonus in JME is not stimulus induced.Patients with JME usually respond well to AEDs, have a normal background on EEG, and have nocognitive, cerebellar, or extrapyramidal dysfunction. Appropriate serologic and genetic testing aswell as axillary skin biopsy should be considered in patients thought to have progressivemyoclonic epilepsy.
FIGURE 1-5 This ictal EEG (referential montage with thebilateral mastoid electrodes as the reference)shows a 1-second burst of generalized sharp
waves firing at a frequency of 7 Hz followed by movementartifact. The patient’s clinical seizure during this discharge wasa brief myoclonic jerk consisting of bilateral shoulderabduction when lying supine.
new data from modern neuroimagingtechniques, molecular biology studies,and genetics research will likely lead toa substantive revision of the currentclassification system in the near future.
Until that time arrives, however, thecurrent classification system for sei-zures and the epilepsies provides thecommon language for clinicians andresearchers worldwide.
REFERENCES
1. Commission on Classification and Terminology of the International League AgainstEpilepsy. Proposal for revised clinical and electroencephalographic classification ofepileptic seizures. From the Commission on Classification and Terminology of theInternational League Against Epilepsy. Epilepsia 1981;22(4):489–501.
2. Engel J Jr. Report of the ILAE classification core group. Epilepsia 2006;47(9):1558–1568.
4. Penfield W, Rasmussen T. The cerebral cortex of man. New York: Macmillan, 1950.
5. Lim SH, Dinner DS, Pillay PK, et al. Functional anatomy of the human supplementarysensorimotor area: results of extraoperative electrical stimulation. ElectroencephalogrClin Neurophysiol 1994;91(3):179–193.
6. Nguyen DK, Nguyen DB, Malak R, et al. Revisiting the role of the insula in refractorypartial epilepsy. Epilepsia 2009;50(3):510–520.
7. Penry JK, Porter RJ, Dreifuss RE. Simultaneous recording of absence seizures withvideo tape and electroencephalography: a study of 374 seizures in 48 patients. Brain1975;98(3):427–440.
8. Ochs R, Gloor P, Quesney F, et al. Does head-turning during a seizure have lateralizingor localizing significance? Neurology 1984;34(7):884–890.
9. Commission on Classification and Terminology of the International League AgainstEpilepsy. Proposal for revised classification of epilepsies and epileptic syndromes.Commission on Classification and Terminology of the International League AgainstEpilepsy. Epilepsia 1989;30(4):389–399.
10. Engel J Jr; International League Against Epilepsy (ILAE). A proposed diagnostic schemefor people with epileptic seizures and with epilepsy: report of the ILAETask Force on Classification and Terminology. Epilepsia 2001;42(6):796–803.
11. Quesney LF. Clinical and EEG features of complex partial seizures of temporal lobeorigin. Epilepsia 1986;27(suppl 2):S27–S45.
12. Chee MW, Kotagal P, Van Ness PC, et al. Lateralizing signs in intractable partialepilepsy: blinded multiple-observer analysis. Neurology 1993;43(12):2519–2525.
13. Maillard L, Vignal JP, Gavaret M, et al. Semiologic and electrophysiologic correlationsin temporal lobe seizure subtypes. Epilepsia 2004;45(12):1590–1599.
14. Bancaud J, Talairach J. Clinical semiology of frontal lobe seizures. Adv Neurol1992;57:3–58.
Continuum Lifelong Learning Neurol 2010;16(3)
34
KEY POINT
A The seizure
classification
system is
primarily based
on clinical
semiology and
EEG correlation,
with a major
distinction made
between focal
and generalized
seizures.
"CLASSIFICATION
15. Oldani A, Zucconi M, Asselta R, et al. Autosomal dominant nocturnal frontal lobeepilepsy: a video-polysomnographic and genetic appraisal of 40 patients anddelineation of the epileptic syndrome. Brain 1998;121(pt 2):205–223.
16. Hirose S, Mitsudome A, Okada M, Kaneko S. Genetics of idiopathic epilepsies.Epilepsia 2005;46(suppl 1):38–43.
17. Ottman R, Winawer MR, Kalachikov S, et al. LGI1 mutation in autosomal dominantpartial epilepsy with auditory features. Neurology 2004;62(7):1120–1126.
18. Michelucci R, Poza JJ, Sofia V, et al. Autosomal dominant lateral temporal epilepsy:clinical spectrum, new epitempin mutations, and genetic heterogeneity in sevenEuropean families. Epilepsia 2003;44(10):1289–1297.
19. Michelucci R, Pasini E, Nobile C. Lateral temporal lobe epilepsies: clinical and geneticfeatures. Epilepsia 2009;50(suppl 5):52–54.
20. French JA, Williamson PD, Thadani VM, et al. Characteristics of medial temporallobe epilepsy: I. results of history and physical examination. Ann Neurol1993;34(6):774–780.
21. Ozkara C, Uzan M, Benbir G, et al. Surgical outcome of patients with mesial temporallobe epilepsy related to hippocampal sclerosis. Epilepsia 2008;49(4):696–699.
22. Beghi M, Beghi E, Cornaggia CM, Gobbi G. Idiopathic generalized epilepsies ofadolescence. Epilepsia 2006:47(suppl 2):107–110.
23. Xue LY, Ritaccio AL. Reflex seizures and reflex epilepsy. Am J ElectroneurodiagnosticTechnol 2006;46(1):39–48.
24. Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensusapproach on diagnosis, assessment, management, and trial methodology. LancetNeurol 2009;8(1):82–93.
26. Commission on Classification and Terminology. Revised terminology andconcepts for organization of the epilepsies: report of the commission onclassification and terminology. www.ilae-epilepsy.org/Visitors/Documents/ClassificationSummaryReportwebAug2009.pdf. Updated 2009. AccessedApril 7, 2010.
