Neuropsychology of Epilepsy

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Birmingham 2006

• Neuropsychology of Epilepsy
• Pam Thompson
• Department of Clinical Experimental Epilepsy,
• Institute of Neurology
• National Society for Epilepsy

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Cognitive functions

• Attention
• Perception
• Memory
• Language
• Constructional skills
• Executive skills

working episodic semantic remote prospective proce
dural
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Two cerebral hemispheresleft verbal
right
visual/spatial
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?
Visual impairments
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?
spatial deficits dyslexia dyscalculia
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?
comprehension semantic event memory
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Frontal lobes

• one third of brain
• rich connections to other regions
• still maturing into adolescence
• incomplete development in learning disability ?
• size competencies distinguish
• man from other mammals
• females from males ?

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Frontal lobes

• attentional deficits
• sustaining
• focusing
• mental slowness
• impaired monitoring feedback
• mental inflexibility
• impaired judgement
• impaired insight

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Neuropsychological Assessment

• systematic assessment of cognitive functions
• standardised tests
• comparisons between people
• same person over time
• range of functions
• attention
• memory
• language
• perception
• executive skills

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Neuropsychological Assessment

• intellectual level
• Wechsler Intelligence Scales
• WAIS, WAIS-R,WAIS-III
• tap a range of functions
• long history
• large normative sample
• VIQ PIQ FSIQ

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Neuropsychological Assessment
IQ population Classification
gt130 2 Very Superior
120-129 7 Superior
110-119 16 High Average
90-109 50 Average
80-89 16 Low Average
70-79 7 Borderline
lt69 2 Mentally Impaired
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Neuropsychological Assessment

• assessing for deterioration
• educational occupational history
• NART
• 50 words of increasing difficulty
• all irregularly spelt
• chaos
• dough
• yacht
• sanguine
• fiduciary

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Memory assessmentepisodic

• conversations/instructions
• names
• studying for exams
• recognising new people
• routes
• spatial layouts
• personal events

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Memory assessmentepisodic

• Verbal Non-verbal (visual) tests
• Story Recall
• Mr Jack Stevens was killed yesterday when
  his car exploded outside the police station in
  Ballymena , County Antrim. He had been a sports
  reporter for the Belfast Herald. Police are
  treating his death as suspicious.
• Verbal learning
• List 15 words presented 5 times

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Memory assessmentepisodic
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Everyday memory failures

• How frequently do you
• Forget where youve put things?
• Have to go back to check?
• Forget you were told something?
• Find a word on the tip of your tongue?
• Forget peoples names?
• Forget to take your tablets?
• Memory rating 0-3

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Measuring executive skills

• Cognitive estimates
• How fast do race horses gallop?
• Phonemic fluency
• Words beginning with letter s
• Digit Span
• Forwards backwards
• (Working memory)

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Measuring executive skillsTrail Making Test
1
? ? ? ? ?
? ? ?
? ?
? D
C
B
? ? A
? ? E

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Measuring executive skillsStroop Test
red blue green green blue red red red blue green

red blue green green blue red red red blue green



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Epilepsy cognitive impairments

• disordered brain function
• increased risk of cognitive problems
• seizure related
• direct/indirect
• drug related
• underlying brain damage
• important to identify as hidden
• school, work social functioning

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conversationscognitive demands

• perception recognise the person
• memoryplace the person, when you met them
  last,personal details,what said last time
• languageexpress self coherently,fluently
  derive meaning from
  what said
• attentionlisten to content,non-verbal
  cues,monitoring what said, turn taking
• planninganticipate impact of what saying
• even more demanding with gt one person

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Intelligence

• myth of low intelligence intellectual
  deterioration
  
• statistics show that in two thirds of
  epileptics the intellect and nervous system
  suffer considerably . Failure of memory, partial
  insanity and hopeless imbecility are frequently
  part of the epileptic condition
  
• Textbook 1914

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Intelligence

• demonstrated PWE span the entire spectrum of
  intellectual ability
• syndromes where arrest decline
• Lennox Gastaut
• Rasmussens Encephalitus
• Baltic Myoclonus
• Co-morbidity
• Downs Syndrome 10
• Autism 30

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Transient cognitive disturbance
1.ictal deficits

• subclinical seizures
  
• transient cognitive impairment (TCI)
• simple partial seizures
  déjà vu, jamais vu
• overt seizures
  expressive dysphasia, memory
  disturbance
  
• non-convulsive status
  
• days weeks
• mental slowness,peudo-dementia
• pre post-ictal changes
  

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subclinical seizures

• Sarah
• infant school teacher
• forgetting events days/week before
• problems following conversations
• routine ok childrens names lesson plans
• working memory impairment
• episodic memory with rehearsal intact
• ambulatory EEG
• 2 hr assessment 80 seizure activity

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unrecognised seizures

• LD presenting with challenging behaviour
• CPS 18 - 40/m
• 22 hours EEG recordings
• A number of frontal seizures with frontal
  lobe semiology are recorded. There were further
  sub-clinical features to indicate ictal
  involvement of the R frontal lobe
• The interictal EEG shows marked abnormalities
  for much of the time,with frequent runs of
  paroxysmal epileptiform discharges

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ictal language disturbance

Brief to counsel 6. Fee to counsel for Mr X 7.
Attending hearing, respondents undertakings,
order made inter alia interim residence
granted 15 Dec 2002 court welfare officer
prepared 8.Since your last bedsprings Fain
look in the sight of Emu the Eel and slide on
the glide trying to water ski
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ictal language disturbance

From the Outstanding from the Client aherleg
number From the Spotet owt of luggage the sped
or louggae spent a touring office spent
understand from a Swpent hair from Birthspring a
Hind Mister a Long haired long hearied before
lodging triumph walk belong hair outstanding,
walk ing long telephoned outstanding
outstretching out streched early walk from there
questing earlyoutstanding long outstanding
standing foooo. 9. Conference 40 mins
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ictal memory disturbance

• Dr Z attending a patient when I felt the
  onset of a petit mal. The next thing I recollect
  I was at a desk talking to someone else
• made a full physical examination
• arrived at the correct diagnosis
• recommended to the patient a course of treatment
• written up in the patient notes

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ictal disturbance

• subclinical seizures
  
• transient cognitive impairment (TCI)
  
• overt seizures
  expressive dysphasia,memory
  disturbance
  
• non-convulsive status
  prolonged attentional deficits
  (absence status) mental slowness
  pseudodementia (CPStatus)
• pre post-ictal changes

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GRNon-convulsive status

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Transient cognitive disturbance
2.medication

• research studies conflicting findings
  controversial
• marketing tool for drugs efficacy
• consensus cognitive impairment ? polytherapy
• all AEDs can cause cognitive impairment
• where cognitive change co-incides with medication
  changes
• adverse cognitive effects potentially reversible

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AEDS Healthy Volunteers

DRUG PLACEBO PHTVPACBZCL
B PLACEBO DRUG
PHTVPACBZCLB
Days
1 14
28


Asst.1 Asst. 2
Asst. 3
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Newer compounds

• Martin et al 1999 healthy volunteers
• 4 wks TPM,LTG,GBP
• TPM impaired attentionreduced verbal
  fluency (50)
• Salinsky et al 2004
• 12 wks OXC, PHT
• motor speed and RT slowed
• OXCPHT
• Mecarelli et al 2004
• 8 days CBZ, OXC, LEV
• neg effects CBZ gtOXCgtLEV
• Meador et al 2005
• neg effects TPM

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PWE

• older compoundsadults
• adverse cognitive effects
• PBgtBZDsgtPHTgtCBZVPAgtLTG
• newer compounds
• TPMgtLEVGPTOXC
• children
• at risk group
• lack of conclusive findings
• Loring Meador 2004 review

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Test scores before,during following withdrawal
of TPM
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NTImpact of TPM on IQ

TPM TPM -
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Number of different AEDs Assessment Unit N30
MA (mg) CLZ 2 CBZ 1200 LEV 3000 LTG
600 ATZ 250 PHT 300
Number of AEDS
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Inter-ictal deficits

• memory most frequently reported deficit
• confirmed by research
• temporal lobes
• most epileptogenic region
• very vulnerable- head injury
  statusmeningitis
• brain structures most involved with memory
• bilateral damage amnesia
• unilateral material specific deficits

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Impact of deficits

• ? frequency warring for person family
• ? academic occupation performance
• social functioning
• erode confidence and reduce self-esteem

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Memory

• Patricia 47years LHS
• bimonthly partial seizures
• I can cope with the seizures but my memory
  problems do get me down and tend to aggravate
  people as I tend to repeat myself a lot
• How frequently do you?
• -forget you were told something yesterday or
  a few
• days ago and have to be reminded?
• -repeat to someone what you have already
  told them?

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Verbal Recall

• Mr Jack Stevens was killed yesterday when his
  car exploded outside the police station in
  Ballymena, County Antrim. He had been a sports
  reporter for the Belfast Herald. Police are
  treating his death as suspicious.
  
  

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Verbal Recall

• Right TLE Mr Jack Stevens died when his car
  exploded by the police station in Ballymena ,
  County Antrim. He had been a journalist for a
  Belfast newspaper. His death was being treated as
  suspicious.
• Left TLE about a man..something about a
  bomb..did he die?.
  

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RTLEFigure Recall
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Bilateral hippocampal sclerosis

• 28 years viral illness
• CPS GTCS
• gross difficulty forming new memories
• loss of past memories
• procedural memories intact
• ride a bicycle, play a guitar, talented
  artist

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Bilateral hippocampal sclerosis

I often forget friends faces completely and
usually their names. I forget conversations and
events we shared last time we met,however recent
they are and however good or important they may
have been. This can cause misunderstanding,
irritation hurt If anyone wants to make
friends they must not be daunted by the hard work
it may appear to need.
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Executive skills deficits

• frontal lobes second most epileptogenic brain
  region
• frequently damaged in head injuries
  boxingdrop attacks
• attentional deficits
• cognitive slowing
• impaired monitoring/feedback
• mental inflexibility
• reduced insight
• low motivation

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Executive skills deficits

• EM 18yrs JME
• A levels Music Art
• IQ 125 Superior Ability
• verbally very articulate (1 to 1)
• difficulties in group settings
• impulsive
• limited insight
• poor planning organisational skills
• move away from home disastrous
• lost routine unable to develop one

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Executive skills deficits EM JME

cognitive domain IQ Classification
word knowledge 125 Superior
verbal reasoning 139 Very Superior
spatial reasoning 135 Very Superior
visual analysis 131 Very Superior
naming 122 Superior
verbal memory 119 High Average
visual memory 134 Very Superior
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Executive skills deficits EM JME

cognitive domain IQ Classification
executive skills
attention span 81 Low Average
mental flexibility
speed 100 Average
errors 75 Borderline Impaired
response suppression 65 Mentally Impaired

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Cognitive Decline

• Electical status epilepticus during sleep ESES
• continuous paroxysmal discharges
• persists years onset 3-14 years
• CSWS frontal predominance
• Landau Kleffner Ltemporal predominance
• cognitive regression
• minority full recovery
• short durationlate onset

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Cognitive Decline

• 19th century inevitable consequence
• frequent and severe seizures
• increased incidence of pre-senile dementia
• to explore predictive factors in at risk group
• to assess role of seizure frequency
• factor least well- studied

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Cognitive decline

• studies in a variety of experimental models
  have irrefutably demonstrated that repeated
  seizures have extensive and profound long-term
  effects in neural circuitry and provide no
  reassurance that these effects can by casually
  regarded as benign
• Sutula
  Pitkanen 2002

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Cognitive decline

• studies in a variety of experimental
  models have irrefutably demonstrated that
  repeated seizures have extensive and profound
  long-term effects in neural circuitry and provide
  no reassurance that these effects can by casually
  regarded as benign Sutula
  Pitkanen 2002
• evidence in humans has been more difficult
  to define or quantify.In the past indeed several
  authorities have doubted that damage is prominent
  or clinically relevant
• Shorvon
  2002

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Cognitive decline

• N136
• AO 8 yrs Duration 35 yrs
• 92 partial epilepsy
• 6 TCS 52 CPS (median per yr)
• assessment I 31 yrs II 44years
• interval range 10 to 25yrs

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Cognitive decline

• Intellectual level
• actual WAIS-R potential NART
• Memory
• verbal learning
• Naming
• Executive skills
• trail making
• fluency

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Change in performance
IQ Verbal Verbal Naming Fluency
Trails Learning Recall
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Cognitive decline

• cognitive decline was severe
• across all cognitive domains
• GTCS most potent predictor
• CPS,status remission for memory executive
  skills
• seizures adverse impact
• episodes remission cognitive beneficial

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Neuropsychology of epilepsy
EEG ABNORMALITIES
AEDs
COGNITIVEIMPAIRMENT
PATHOLOGY
MOOD
SEIZURES