Language in a BrainstormLanguage in a Brainstorm

Language and EpilepsyLanguage and EpilepsyRichard Webster

Paediatric NeurologistChildren’s Hospital Education Research Institute

(CHERI)

Language and epilepsyLanguage and epilepsy

Case: A boy who lost languageCase: A boy who lost languageAcquired Epileptic AphasiaAcquired Epileptic AphasiaHow are language impairment and How are language impairment and epilepsy related?epilepsy related?Language in other epilepsy syndromesLanguage in other epilepsy syndromes

A boy who stopped talkingA boy who stopped talking

9 year old boy 9 year old boy Three week history of Three week history of –– Complete loss of language (aphasia) Complete loss of language (aphasia)

Severe problems with comprehension (receptive Severe problems with comprehension (receptive aphasia) and speech (expressive aphasia) aphasia) and speech (expressive aphasia)

–– Major behavioural disturbance Major behavioural disturbance

Epileptic seizures Epileptic seizures

This had happened before …This had happened before …

Occurred during a 3 month holiday in ChileOccurred during a 3 month holiday in ChileLost almost all expressive language Lost almost all expressive language –– Only phrases “I hate you” and “I’ll kill you”Only phrases “I hate you” and “I’ll kill you”

Aggressive and hyperactiveAggressive and hyperactiveThree epileptic (tonicThree epileptic (tonic--clonic) seizures whilst clonic) seizures whilst in Chilein ChileSpeech and behaviour improved two weeks Speech and behaviour improved two weeks before return to Australiabefore return to Australia

Second episode of aphasia Second episode of aphasia

Three months later …Three months later …Over a week he lost all spoken languageOver a week he lost all spoken language–– Initially unclear speechInitially unclear speech–– Lost all comprehension of speechLost all comprehension of speech–– Completely mute Completely mute –– Distressed by normal soundsDistressed by normal sounds

Aggressive and hyperactiveAggressive and hyperactiveNeurological examination normalNeurological examination normalBrain MRI normalBrain MRI normal

Drawing during aphasiaDrawing during aphasia

AAble to match written words to ble to match written words to pictures pictures –– sometimes inaccuratelysometimes inaccurately

Reading during aphasiaReading during aphasia

Able to read with profound receptive Able to read with profound receptive aphasiaaphasia–– Although some impairments of higher level Although some impairments of higher level

languagelanguage

Implies Implies –– Dysfunction of verbal decoding (superior Dysfunction of verbal decoding (superior

temporal gyrus)temporal gyrus)–– Relative preservation of occipital (visual cortex) Relative preservation of occipital (visual cortex)

connections with Wernicke’s area (posterior periconnections with Wernicke’s area (posterior peri--sylvian)sylvian)

EEGs and epilepsyEEGs and epilepsyAn EEG measures the brains An EEG measures the brains electrical activityelectrical activity–– Records scalp electrical activity Records scalp electrical activity

coming from the brain beneath coming from the brain beneath the electrode the electrode

The summated electrical fields The summated electrical fields produced by millions of nerve produced by millions of nerve cellscellsSpikeSpike–– The simultaneous discharge of The simultaneous discharge of

millions of millions of neuronesneurones–– Often followed by a slow waveOften followed by a slow wave–– Focal (one region of the brain)Focal (one region of the brain)–– GeneralisedGeneralised (many brain regions)(many brain regions)

AWAKE

ASLEEP

DiagnosisDiagnosis

Acquired Epileptic Aphasia Acquired Epileptic Aphasia (Landau(Landau--KleffnerKleffner Syndrome)Syndrome)

LandauLandau--KleffnerKleffnerSyndromeSyndrome

–– ““Syndrome of Acquired Aphasia with Convulsive Syndrome of Acquired Aphasia with Convulsive Disorder in Children” Disorder in Children” NeurologyNeurology 19571957

–– Five children referred to the Central Institute for Five children referred to the Central Institute for the Deaf, St Louis Missouri (now > 200 children)the Deaf, St Louis Missouri (now > 200 children)

Not deafNot deafPreviously normal languagePreviously normal languageNew fluctuating aphasia New fluctuating aphasia EpilepsyEpilepsyOtherwise neurologically normalOtherwise neurologically normal

Acquired Epileptic Aphasia Acquired Epileptic Aphasia (AEA): Clinical features(AEA): Clinical features

AphasiaAphasia–– Often a receptive aphasia at onset Often a receptive aphasia at onset –– Later children may appear mute Later children may appear mute –– Verbal auditory agnosia Verbal auditory agnosia a problem a problem

with decoding spoken language with decoding spoken language Occasionally children have problems Occasionally children have problems recognising common sounds (auditory recognising common sounds (auditory agnosia)agnosia)May learn to read, write and use sign May learn to read, write and use sign language whilst aphasic language whilst aphasic

Acquired Epileptic Acquired Epileptic Aphasia: Clinical featuresAphasia: Clinical features

SeizuresSeizures–– Range of different seizure types (Range of different seizure types (orooro--facial, absence, GTC)facial, absence, GTC)–– 20% do not have seizures20% do not have seizures

Behaviour disturbanceBehaviour disturbance–– Aggression, irritability, attention deficitAggression, irritability, attention deficit–– Lack of socialisation, autistic features Lack of socialisation, autistic features

Prognosis: Prognosis: seizures and aphasia usually improve seizures and aphasia usually improve in early adolescencein early adolescenceLong term follow up: most have difficulties Long term follow up: most have difficulties with receptive languagewith receptive language–– Varying severity (mild to profound)Varying severity (mild to profound)–– Poor phonological ShortPoor phonological Short--Term MemoryTerm Memory

Acquired Epileptic Acquired Epileptic Aphasia: EEG findingsAphasia: EEG findings

EEG may be normal when awakeEEG may be normal when awake–– Focal temporal or parietal spike or spike and Focal temporal or parietal spike or spike and

wave dischargeswave discharges

EEG in sleepEEG in sleep–– Almost continuous epileptic activity (Electrical Almost continuous epileptic activity (Electrical

Status Epilepticus of Sleep) Status Epilepticus of Sleep) –– Often with a temporal predominanceOften with a temporal predominance–– Most children show resolution of ESES prior to Most children show resolution of ESES prior to

language recoverylanguage recovery

What causes Acquired What causes Acquired Epileptic Aphasia?Epileptic Aphasia?

Brain structure is usually normalBrain structure is usually normal–– Rarely focal temporal lobe lesionsRarely focal temporal lobe lesions

Brain histologyBrain histology–– Normal (biopsies uncommon)Normal (biopsies uncommon)–– No evidence of brain No evidence of brain

inflammation/encephalitisinflammation/encephalitis

Acquired Epileptic Aphasia: Acquired Epileptic Aphasia: Theoretical ConsiderationsTheoretical Considerations

AEA is likely to result from bilateral AEA is likely to result from bilateral damage or dysfunction of the temporal damage or dysfunction of the temporal lobes lobes ((RapinRapin 1987)1987)–– Children with unilateral damage to Children with unilateral damage to

language cortex can relanguage cortex can re--locate language locate language to the other hemisphereto the other hemisphere

–– This does not happen in AEAThis does not happen in AEA

SpecialisedSpecialised ElectrophysiologyElectrophysiology

MEG Spikes generated within the MEG Spikes generated within the SylvianSylvian fissurefissure–– Spikes may be set off by sound Spikes may be set off by sound ((PaetauPaetau R 1994, R 1994,

J. J. ClinClin NeuroNeuro))

MorrelMorrel et alet al (Brain) 1995: single cortical epileptic (Brain) 1995: single cortical epileptic focusfocus–– Methohexital test/ IntraMethohexital test/ Intra--carotid amylobarbitonecarotid amylobarbitone–– Electrocorticography: left sylvian discharges Electrocorticography: left sylvian discharges

(10/14) and bilateral 4/14(10/14) and bilateral 4/14

Cerebral Glucose Metabolism Cerebral Glucose Metabolism (Positron Emission Tomography)(Positron Emission Tomography)

PET studies (acutely) PET studies (acutely) –– Abnormal metabolism predominantly Abnormal metabolism predominantly

affecting the temporal lobeaffecting the temporal lobe–– Superior and middle temporal Superior and middle temporal gyrigyri (both (both

right and left) right and left) –– PeriPeri--sylviansylvian cortex (decreased)cortex (decreased)–– MacquetMacquet et al Brain 1995et al Brain 1995

Theories regarding the Theories regarding the cause of Epileptic Aphasiacause of Epileptic Aphasia

PathogenesisPathogenesis–– 1. Language regression is due to ESES 1. Language regression is due to ESES

“ Persistent convulsive disturbance in brain “ Persistent convulsive disturbance in brain tissue largely concerned with linguistic tissue largely concerned with linguistic communication results in functional ablation communication results in functional ablation of these areas. ” of these areas. ” Landau & Landau & KleffnerKleffner 19571957Transient damage/ InhibitionTransient damage/ Inhibition

–– 2. The EEG abnormalities and seizures an 2. The EEG abnormalities and seizures an epiphenomena secondary to an as yet epiphenomena secondary to an as yet unidentified cerebral pathologyunidentified cerebral pathology

Something inhibits transfer of languageSomething inhibits transfer of language

TreatmentTreatment

Standard antiStandard anti--epileptic medication epileptic medication rarely effectiverarely effectiveHigh dose steroids frequently effectiveHigh dose steroids frequently effective–– Powerful antiPowerful anti--epileptic medicationepileptic medication–– Does this treat unrecognised brain Does this treat unrecognised brain

inflammation?inflammation?–– Relapse after withdrawalRelapse after withdrawal

Outcome after MSTOutcome after MST

Language improvement in 50%Language improvement in 50%–– First words 12 weeks after surgeryFirst words 12 weeks after surgery–– All children with language recovery All children with language recovery

showed normalisation of EEGshowed normalisation of EEG–– MorrelMorrel et al Brain 1995et al Brain 1995

CaveatsCaveats–– These children were at an age when LKS These children were at an age when LKS

may spontaneously improvemay spontaneously improve

The association between The association between epilepsy and languageepilepsy and language

1. Language impairment and epilepsy may 1. Language impairment and epilepsy may result from focal brain damageresult from focal brain damage

Language and epilepsy:Language and epilepsy:Epileptic encephalopathyEpileptic encephalopathy

2. Functional language impairment during 2. Functional language impairment during an epileptic dischargean epileptic discharge3. Functional impairment after a prolonged 3. Functional impairment after a prolonged epileptic dischargeepileptic discharge–– Focal weakness after a motor fit Focal weakness after a motor fit

Todd’s paresisTodd’s paresis

–– Language difficulties after temporal lobe seizuresLanguage difficulties after temporal lobe seizures–– Impairment can result fromImpairment can result from

Transient metabolic dysfunction/ damageTransient metabolic dysfunction/ damageActive cerebral inhibitionActive cerebral inhibition

Language impairment and epilepsy: Language impairment and epilepsy: A common cause?A common cause?

4. Language impairment may not be due to 4. Language impairment may not be due to focal disease focal disease Language requiresLanguage requires–– Rapid processing Rapid processing –– Good working memoryGood working memory–– AttentionAttention

Biological factors that lead to epilepsy may Biological factors that lead to epilepsy may impair these processesimpair these processes–– Eg Ion channel disordersEg Ion channel disorders

Language and epilepsy:Language and epilepsy:TopiramateTopiramate

5. Treatment with 5. Treatment with topiramatetopiramate can be can be associated with language regressionassociated with language regressionWord finding difficultiesWord finding difficulties–– Normal controls show significant Normal controls show significant

language deficits when given language deficits when given topiramatetopiramate–– Meador et al Neurology 2005;64:2108Meador et al Neurology 2005;64:2108--21142114

–– Case reports of reversible language Case reports of reversible language regression associated with regression associated with topiramatetopiramate

–– Vader et al Neurology 2004;62:299Vader et al Neurology 2004;62:299--300300

Language in Temporal Lobe Language in Temporal Lobe and Generalised Epilepsy and Generalised Epilepsy

Language impairment in Complex Partial Language impairment in Complex Partial Seizures (CPS) Seizures (CPS) –– Caplan et al Epilepsia 2004Caplan et al Epilepsia 2004

–– Spoken Language QuotientSpoken Language QuotientCPS 90 CPS 90 ± 18.5, controls 104± 18.5, controls 104 ± 14.5 p = 0.0001± 14.5 p = 0.0001

Evidence about language impairment in Evidence about language impairment in generalisedgeneralised epilepsy is contradictoryepilepsy is contradictory

Language and Language and generalised epilepsygeneralised epilepsy

Contradictory informationContradictory information–– Evidence of abnormal Evidence of abnormal

Auditory Event Related Auditory Event Related Potentials to phonetic and Potentials to phonetic and semantic stimulisemantic stimuli

–– HenkinHenkin et al Epilepsia 2003et al Epilepsia 2003Relative preservation of Relative preservation of language despite cognitive language despite cognitive impairment in children impairment in children with childhood absence with childhood absence epilepsyepilepsy–– PatariaPataria et al Neurology 2004et al Neurology 2004

Developmental Language Developmental Language Impairment and epilepsyImpairment and epilepsy

Is there an increase in Is there an increase in epileptiformepileptiformactivity in children with DLI?activity in children with DLI?–– 50% of children with language 50% of children with language

impairment found to have epileptic impairment found to have epileptic activity on overnight EEGactivity on overnight EEG((PicardPicard et al Dev Med Child et al Dev Med Child NeuroNeuro 1998)1998)

No history of seizuresNo history of seizures

–– Ascertainment uncertainAscertainment uncertainShould we treat this activity?Should we treat this activity?

ConclusionsConclusions

1. Epileptic discharges can produce an acquired 1. Epileptic discharges can produce an acquired language impairment (Acquired Epileptic Aphasia)language impairment (Acquired Epileptic Aphasia)–– Verbal auditory Verbal auditory agnosiaagnosia (word deafness)(word deafness)–– Not always associated with seizuresNot always associated with seizures

2. Language impairments are common in Temporal 2. Language impairments are common in Temporal Lobe EpilepsyLobe Epilepsy3. There is little information about the frequency of 3. There is little information about the frequency of language disorders in language disorders in generalisedgeneralised epilepsyepilepsy4. There is probably an increased incidence of 4. There is probably an increased incidence of epileptic activity in children with Developmental epileptic activity in children with Developmental Language ImpairmentLanguage Impairment–– But the significance is unclearBut the significance is unclear

AcknowledgementsAcknowledgements

A/Prof Annie Bye, SCHA/Prof Annie Bye, SCHDr Heather Johnston, SCH/ Dr Michael Dr Heather Johnston, SCH/ Dr Michael Rosier, Canberra HospitalRosier, Canberra HospitalJenny McIntyre, SCHJenny McIntyre, SCHSamantha Samantha SoeSoe, CHW, CHW

When to suspect AEAWhen to suspect AEA

1. Language regression and seizures 1. Language regression and seizures +/+/-- behavioural disturbancebehavioural disturbance2. Verbal auditory agnosia2. Verbal auditory agnosia–– Severe receptive difficultiesSevere receptive difficulties–– Otherwise good nonOtherwise good non--verbal language verbal language

skillsskills

3. Fluctuating aphasia3. Fluctuating aphasia

Who should undergo Who should undergo language assessmentlanguage assessment

1. Children with clear language delays 1. Children with clear language delays and epilepsyand epilepsy2. Children with temporal lobe epilepsy2. Children with temporal lobe epilepsy3. Children with epilepsy and poor 3. Children with epilepsy and poor school performance (esp. reading) and school performance (esp. reading) and difficulty with socialisationdifficulty with socialisation