Managing Epilepsies in Children and Adolescents

1
Managing Epilepsies in Children and Adolescents

• Kurupath Radhakrishnan
• R. Madhavan Nayar Center for Comprehensive
  Epilepsy Care,
• Sree Chitra Tirunal Institute for Medical
  Sciences Technology,
• Trivandrum, Kerala

40 minutes
2
Epidemiologic survey
Out reach epilepsy clinics
300km
Radhakrishnan et al. Epilepsia 2000411027-35
3
Age-specific prevalence rates of epilepsy in
Kerala
43
4.6 per 1000 people
10-19
Radhakrishnan et al Epilepsia 2000411027-35
4
Risk factors for epilepsy in KeralaCase-control
study
362 cases and controls Significant on
multivariate analysis
Sudheeran et al. Epilepsy Behav 2009
5
10th graders KAP on epilepsy

• 1200 students 10th class
• Heard about epilepsy 98
• Yes
• Is epilepsy a mental disease? 59
• Is epilepsy a contagious disease? 14
• Do you think epilepsy is a hindrance to happy
  life? 62
• Do you think epilepsy affects education? 41
• Can they have married life? 58
• Do you think epilepsy can be cured? 47
• Do you think people with epilepsy are
  discriminated? 45

Pandian et al., Epilepsy Behav 20069492-7
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Growing up with the seizures

• Seizures/AEDs during formative years affect
• Cognitive development
• Personality
• Behavior
• Learning, schooling,
• Social and emotional development

Even well controlled epilepsy is associated with
adverse psycho-social outcome
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Social and Education Outcomes in Childhood-Onset
Epilepsy99 patients with uncomplicated epilepsy
(66 in remission)vs.Controls
Sillanpaa et al. NEJM 1998
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Epilepsy and marriage

• 82 women epilepsy onset prior to marriage, 5 yrs
• after marriage
• 55 concealed, 45 disclosed
• Marriage outcome sig. better in disclosed.
• Disclosed were sig. more employed
• Disclosure is risky, but concealing would have
  long-term disastrous consequences on married
  life. Being employed is important for a woman
  with epilepsy as it makes her less dependent on
  the spouse and his family on money matters, and
  more confident in making independent decisions

Santosh et al., Epilepsia 2007481007-10
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Epilepsy and co-morbidities
38
30
30
Epilepsy
9
5
Kudrjavcev T, 1985 Hauser 1987 Olson 1988
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Neurologist
Teachers
Minimal seizures
Child psychologist
Minimal seizures
Child with Epilepsy
Better QOL
Happy family
Minimal side-effects
Family
Psychiatrist
Speech Therapist
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Managing epilepsy in children

• Syndromic diagnosis is the key
• Holistic multi-axial approach needed
• Comprehensive evaluation
• Parental education and support
• Assess etiology co-morbidities
• Better QOL rather than absolute seizure freedom
  is the goal

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Epilepsy syndromes in children
Undetermined (12)
Generalized (29)
LRE (59)
Shinnar, Berg at al. 1999 2002
13


Generalized
LRE
10 yr
BRE
Reading Epilepsy
JME
1 yr
JAE
CAE
BOE
GTCS on awacken
BMEI
1 month
Idiopathic
BNFC BNC
West
EIEE EME
LGS
Symptomatic LRE (Temporal, frontal)
Neonatal Sz
Doose
Myoclonic absences
SMEI
Rasmussens
Nonidiopathic
ESES
LKS
14
Genetically determined syndromes
1,2,3 Well defined with known gene product
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Epilepsy syndromes and prognosis

Universally good BFNC/BFC BMEI CAE BRE BOE
Uncertain Symptomatic LREs JAE JME GTCS
(unclassified) Myoclonic absences LKS Reading
epilepsy
Universally poor Epileptic encephal. (EIEE, West,
LGS) SMEI ESES Rasmussens enceph.
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Starting AED treatment

• Usually after two unprovoked seizures
• Exceptions
• Benign seizure susceptibility syndromes
• May not require treatment
• Benign localization-related epilepsy syndromes
• Even with one seizure
• Epileptic encephalopathies, FCD

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AED therapy
Epileptic encephalopathies
LRE
IGE
VPA, LTG, TPM, CLB (ACTH, VGB)
VPA, LTG, TPM
CBZ, LTG, TPM, VPA
1st line
LVT, CLB, CLP
LVT
LVT, CLB, CLP
2nd line
CBZ,OXCBZ, TGB
CBZ,OXCBZ, TGB (LTG in SMEI)
Avoid
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Outcome of newly diagnosed epilepsy
144 persons with epilepsy lt16 years followed
for 37 years
67 Terminal Remission
33 Non-remission
19 after relapse 48 no relapse
19 Drug resistant from the start 14 Remission
to Relapse
20-30
Results remarkable similar across the
studies (Kwan Brodie, NEJM, 2000 Berg
Shinnar, Ann Neurol 2006)
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Epilepsy surgery procedures

• Palliative surgeries
• Corpus callosotomy
• Multiple subpial transactions
• Vagus nerve stimulation
• Curative surgeries
• Removal of an epileptogenic focus or discrete
  lesions
• Focal corticectomy
• Gyrectomy
• Lesionectomy
• Antero-mesial temporal lobectomy
• Selective amygdalohippocamectomy
• Gross removal of malfunctioning brain tissue
• Multilobar resections
• Hemisherectomy/hemispherotomy

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Epilepsy surgeries
March 1995 August 27, 2009 Type No Tempo
ral resections 839 Extratemporal
resections 144 Callosotomy
21 Hemispherect/rotomy 47 Hypothamic
hamartoma resection 10 VNS
14 Total 1075
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Pediatric (18 yr) epilepsy surgeries
244/947 25.8
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How epilepsy surgeries in children are different
from adults?

• First Early definition of medical refractoriness
• Uncontrolled seizures and untoward effects of
  AEDs during the formative years can adversely
  affect the cognitive and psychosocial
  developments in children.
• Failure of 2 AEDs, 1 seizures/month,
• 1 year

Berg AT et al. Neurology 2001 56 1445-52.
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How epilepsy surgeries in children are different
from adults?

• Second Neurodevelopmental plasticity
• Positive influence
• Early surgery - less neurological squeal
• Example
• Interhemispheric language transfer lt 6 yr
• Complete callosotomy
• Negative influence
• Late surgery pervasive development

Rathore C, et al. Brain Dev 2007 29
577-85. Depositario-Cabacar et al., Curr Neurol
Neurosci Rep 2008 8 123-9.
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How epilepsy surgeries in children are different
from adults?

• Third Temporal vs. extratemporal resections
• Proportionately more extratemporal resections

Extratemp resections 84/947 9 18 years
44/84 52
Cossu et al. Epilepsia 2008 49 65-72 Kan et
al. Childs Nerv Syst 2008 24 587-91 Kim et al.
J Neurosurg Pediatr 2008 1 277-83.
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How epilepsy surgeries in children are different
from adults?

• Fourth Surgical substrate
• Adults MTS (mesial temporal sclerosis)
• Children MCD (malformations of cortical
  development)
• Tumors DNET, ganglioglioma

Cossu et al. Epilepsia 2008 49 65-72 Kan et
al. Childs Nerv Syst 2008 24 587-91 Kim et al.
J Neurosurg Pediatr 2008 1 277-83.
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Surgically remediable lesional pediatric epilepsy
syndromes

• Malformations of cortical development
• Focal malformations of cortical development
• Heterotopias
• Polymicrogyria and pachygyria
• Microdysgenesis/ MRI negative dysplasias
• Cortical tubers
• Mesial temporal sclerosis
• Low grade neoplasms
• Dysembryoplastic neuroepithelial tumor
• Ganglioglioma
• Low grade astrocytomas
• Nonspecific gliosis secondary to various pre-
  and postnatal insults
• Large unihemispheric pathologies
• Rasssmussens encephalitis
• Hemiconvulsion-hemiplegia-epilepsy (HHE)
  syndrome
• Sturge Weber syndrome
• Hemimegalencephaly
• Vascular malformations
• Arterio-venous malformation

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MTS in children

• 11/113 (10) children (16 yr) from Italy had MTS
  
• (Cossu et al. 2008).
• All of them had secondary MTS Dual pathology
• Extrahippocampal substrate ?MTS

Cossu et al. Epilepsia 2008 49 65-72
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Data from a 16-year old boy
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Data from a 6-year old girl
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Data from a 14-year old boy
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Refractory CPS with poor vision
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(No Transcript)
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How epilepsy surgeries in children are different
from adults?

• Fifth Presurical evaluation strategy needs
  revision according to age and co-operation
• MRI myelination
• VEEG seizure semiology
• IEDs widespread (Gupta et al. Pediatr Neurol
  2007 37 8-15)

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How epilepsy surgeries in children are different
from adults?

• Sixth Post-operative outcome need to be more
  comprehensive
• Seizure outcome
• Neurodevelopmental outcome
• Educational outcome
• Psychological/psychiatric outcome
• QOL outcome
• Parental/caregiver satisfaction

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Seizure outcome curative procedures

• Overall two-thirds become seizure-free
• Seizure freedom by substrate
• Tumor/MTS - gt80
• FCD - gt60
• Normal MRI 30
• Predictors of outcome
• Unifocal lesion in MRI
• Temporal lobe resection
• Complete lesionectomy
• Tumoral pathology

Cossu et al. Epilepsia 2008 49 65-72 Kan et
al. Childs Nerv Syst 2008 24 587-91 Kim et al.
J Neurosurg Pediatr 2008 1 277-83.
36
Seizure outcome palliative procedures

• Class 1. Free of all seizure types
• Class 2 No consciousness impairing seizures and
  drop attacks
• Class 3 Seizures with impaired consciousness,
  but no drop attacks
• Class 4 90 reduction in drop attacks
• Class 5 50 reduction in drop attacks
• Class 6 lt50 reduction in drop attacks
• Class 7 No appreciable change in seizure
  frequency/severity
• Class 8 Worse seizures

Rathore C, et al. Brain Dev 2007 29 577-85
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Parental/caregiver satisfaction questionnaire

• How would you grade seizure status after surgery?
• A) None B) Mild improvement C) Moderate
  improvement D) Marked improvement
• How would you grade change in behavior after
  surgery?
• A) None B) Mild improvement C) Moderate
  improvement D) Marked improvement
• How would you grade change in alertness and
  attentiveness after surgery?
• A) None B) Mild improvement C) Moderate
  improvement D) Marked improvement
• Are you satisfied with the outcome of epilepsy
  surgery undertaken in your child?
• A) Yes B) No
• Would you recommend another child with similar
  problem for epilepsy surgery?
• A) Yes B) No

Rathore C, et al. Brain Dev 2007 29 577-85
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Early discontinuation of AED following surgery

• 68/97 children AED discontinued 6 months after
  surgery
• 57/68 (84) remained seizure
• Those who recurred were easily controlled by
  restarting the AED

Lachhwani DK, et al. Pediatr Neurol 2008 38
340-4.
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