From the trenches: A clinician’s
perspective
Gogi Kumar,MD
Assistant Professor
WSUBSOM
Medical Director
Department of Child Neurology
Dayton Children’s Hospital
My Trench
General Cope’s Trench
Case
• 13 year old with first unprovoked seizure
• Mom hears a thud in the morning , finds her
in the shower having a generalized tonicclonic seizure
• Seizure lasts for 2 minutes
• Sleep deprived
• CT scan, urine pregnancy and drug screen is
negative
• EEG:
• I diagnose her with new onset primary
generalized epilepsy
• Suggest starting on Lamictal
First Question
What is Epilepsy?
Definition of Epilepsy
• 2005 ILAE definition: 2 unprovoked seizures
>24 hours apart
• Epilepsy is a disorder of the brain
characterized by an enduring predisposition to
generate epileptic seizures
A practical clinical definition of epilepsy
Fisher et al Epilepsia,55(4):475-482,2014
ILAE Task force
Epilepsy is a disease of the brain defined by any one
of the following:
1.Atleast 2 unprovoked (reflex seizures)
occurring >24 hour apart
2.One unprovoked seizure(or reflex)seizure and a
probability of further seizures similar to the general
recurrence rate (at least 60%) after two unprovoked
seizures occurring over the next 10 years
3.Diagnosis of an epilepsy syndrome
2nd Question
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Can you do any other test to be sure?
Blood test? MRI?
Does epilepsy get better?
How will I know when epilepsy has resolved?
Epilepsy Biomarkers
Engel et al Epilepsia 2013 August;54(04)61-69
Biomarker is an objectively measured characteristic
of a normal or pathological process.
Uses in epilepsy include
 Predict the development of epilepsy
 Confirm the presence of epilepsy
 Measure progression
 Predict pharmaco-resistance
 Confirm that the condition is resolved
 Used to create animal models
 Reduce the cost of the clinical trial
Epilepsy Biomarkers
Electrophysiology
Imaging
Ictal patterns and interictal spikes
Frequencies, duration, source
localization, morphology, field size
Routine MRI Measures Enhancement
(BBB)
Functional (FMRI) Spectroscopy (MRS)
Diffusion Tensor (DTI) Susceptibility (SWI)
High frequency oscillations
Activation procedures
Photic Stimulation Hyperventilation
Sleep Deprivation Drug Induction
PET (Positron Emission Tomography)
FDG (Deoxyglucose) FMZ (Flumazanil)
AMT (alphamethyltryptophane) PK
(Inflammation)
Excitability TMS
(Transcranial Magnetic Stimulation)
Direct Electrical Stimulation
(Part of Surgical Workup)
SPECT (Single Photon Emission Computed
Tomography)
Engel et al Epilepsia 2013
August;54(04)61-69
3rd Question
• What kind of epilepsy does my child have?
• I was reading about seizures while waiting for
you to come and see us and read about focal
and generalized seizures. Can you tell me
more about this?
The Organization of the Epilepsies: Report of the ILAE Commission on Classification
and Terminology
Ingrid E Scheffer et al
• For each patient, we should aim to diagnose
seizure type(s), electroclinical syndrome and
etiology where possible.
Organization of epilepsies
Electro clinical syndrome: age of onset, seizure
types, EEG patterns, imaging features and comorbidities such as intellectual impairment
Benign is replaced by ‘Self limited’
She has ‘Genetic generalized epilepsy’
Organization of epilepsies
Etiological
(1) Genetic
(2) Structural
(3)Metabolic
(4) Immune
(5) Infectious
(6) Unknown
Organization of epilepsies
Descriptors of focal seizures according to degree of impairment during seizure*
Without impairment of consciousness or awareness
• With observable motor or autonomic components – “Focal motor” and “autonomic”
can be used
• Involving subjective sensory or psychic phenomena only – “aura” can also be used
• Replaces term “simple partial seizure”
With impairment of consciousness or awareness
• “Dyscognitive” can also be used. It is understood that dyscognitive may not always
mean altered awareness but it is used here to denote altered consciousness or
awareness which may be response tested
• Replaces term “complex partial seizure”
Evolving to a bilateral convulsive seizure
• May include tonic, clonic or tonic and clonic components in any order
• Replaces term “secondarily generalized seizure”
Question no 4
• Are you sure it is generalized and not focal?
Focal abnormalities in idiopathic generalized
epilepsy
Seneviratne et al Epilepsia,55(8);1157-1169,2014
• Aura:25% to 54%, visual/epigastric/preictal
prodromal symptoms
• Focal semiology:35%to 46% include head
version/eye version/focal myoclonic jerks
• Absence seizures: Automatisms are common
during hyperventilation
• EEG: Focal interictal abnormalities found in
1/3rd
Focal abnormalities in idiopathic generalized
epilepsy
Seneviratne et al Epilepsia,55(8);1157-1169,2014
Cortical focus theory :
Cortical focus within the perioral regions of
somatosensory cortex led the thalamus by a
mean of 8.1 m sec during the first 500ms of an
absence seizure.
Important to differentiate Idiopathic generalized
epilepsy from focal frontal lobe epilepsy with
secondary bilateral synchrony.
Question no 5
• When will she grow out of this?
• How will I know?
Resolution of epilepsy
Fisher et al Epilepsia,55(4):475-482,2014
ILAE Task force
• Epilepsy is resolved for individuals who have
an age dependent epilepsy syndrome and are
now past the age
• Seizure free for the last 10 years with no
seizure medication for the last 5 years.
Long-Term Outcome in Epilepsy with Grand Mal on Awakening: Forty Years of
Follow-up
Holtkamp et al, Annals of Neurology Volume 75,Issue 2 February
2014
42 patients with Epilepsy with Grandmal on Awakening (EGMA)
Follow up of 40.1 +/- 12.6 years(range=20-62).26 of 42 patients with EGMA
(61.9%) were in 5 year terminal remission.
Out of the 26 patients 21 were still taking AEDs and 5 had been completely off
medications.
Age at the time of investigation was the only independent predictor for seizure
freedom. 35.7% in patients younger than 55 years,66.7% in patients between 56
and 65 years and 81.3% in patients older than 65 years.
AED withdrawal was done in 45.2% patients and 63.2% of them had a relapse
47.6% had an university degree and 88.1% were regularly employed.
Natural course and predictors of spontaneous seizure remission
in idiopathic generalized epilepsy :7-27 years of follow up
Podewelis et al Epilepsy Research (2014)108,1221-1227
• 15 IGE patients who refused treatment
• Mean duration of follow up was 15.3 years
• 5 patients had CAE,5 patients had EGCTS,4 patients had JAE (absence
+GTCS), 1 patient had CAE
• Mean age of onset of epilepsy was 15.3 years, mean duration of epilepsy
was 18.3 years and mean duration of follow up was 15.3 years
• Remission rate was 80% in CAE,60% EGTCS and 20% with IGE with
ABS/GTCS.
• Photoparoxysmal response was found in 20% of the patients and it was a
poor prognostic factor
Juvenile myoclonic epilepsy 25 years after seizure
onset : A population based study
Camfield et al Neurology 2009,73;1041-1045
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23 patients
Age at first seizure 10.4+/-4.3 years
Mean follow up of 25.8 years
Average age at follow up was 36 years
11 (48%) no longer received AEDs, 6 of these were
seizure free,3 had myoclonus only and 2 had rare
seizures
• 12 received AED treatment at the end of follow up
• 1/3 rd grew out of their troublesome seizures.17% free
of all seizures.
Question no 6
• Will she have a normal life?
Psychosocial complications in Adult Life
Epidemiologic aspects: Lost in transition Camfield et al
Epilepsia,55(Suppl.3):3-7,2014
Nova scotia cohort IGE
• Psychiatric diagnosis (27%)
• High school graduation (40%)
• Pregnancy outside stable relationships (38%)
• Living alone (23%)
• Unemployment(33%)
• Criminal conviction (7%)
Behavioral changes in Pediatric
epilepsy syndrome
JME
• Impaired abstract reasoning, cognitive speed
and planning
• Janz noted ‘an engaging but emotionally
unstable, fairly immature personality,
wavering between camaraderie and mistrust,
which may lead to difficulties in social
adaptation’
Death in children with epilepsy
• Children with an underlying neurological
disorder sufficient to interfere with daily
activities have a death rate of 25% (Nova
scotia study)
• Risk of SUDEP in children without neurological
disorders is same as general reference
population (Nova scotia study)
Long-Term Mortality in Childhood-Onset Epilepsy
Matti Sillanpää, M.D., Ph.D., and Shlomo Shinnar, M.D., Ph.D.
N Engl J Med 2010; 363:2522-2529 December23,2010
• 245 Finnish children with epilepsy, after 40 years
of follow-up, 60 subjects had died (24%), a rate
three times as high as the expected age- and sexadjusted mortality in the general population.
• A total of 33 of 60 deaths (55%) were related to
epilepsy
• A remote symptomatic cause of epilepsy associated
with an increased risk of death as compared with an
idiopathic or cryptogenic cause (37% vs. 12%,
P<0.001).
• Risk for SUDEP was 7% at 40 years overall and 12% not
in long-term remission and not receiving medication.
Cumulative Risk of All Epilepsy-Related Deaths and Sudden, Unexplained Deaths in Subjects
with Epilepsy.
Sillanpää M, Shinnar S. N Engl J Med 2010;363:2522-2529
Cumulative Rate of Death According to Cause of Epilepsy.
Sillanpää M, Shinnar S. N Engl J Med 2010;363:2522-2529
Conclusions
• Childhood-onset epilepsy was associated with a substantial risk of
epilepsy-related death, including sudden, unexplained death.
• The risk was especially high among children who were not in remission.