EPILEPSY The Sacred Disease

Fajar Herbowo Niantiarno

5th Grade Medical School Of Diponegoro University Central Java-Indonesia

10 December 2013

History of Epilepsy

Sakikku Tablet Written in Assyrian- Babylonia 1067-1046 B.C (3000 years ago)

Famous People with Seizure and Epilepsy

Fisher R. Overview of Epilepsy.2010

Questions
--What do you think of when you hear epilepsy ?---Is it important for you to know what is epilepsy ?--

Opinions
To be honest, very difficult disease, afraid, weird, strange. Those were the impression of epilepsy before I learnt about that in university Of course yes. I think ignorant makes prejudice, as I used to be. Correct knowledge leads me good comprehension
4th , Jumpei Ushikai Grade Medical Student of Kagoshima University

Epidemiology
Indonesia 100 / 100,000 (Developing Country) 0.5 % 220 million Incidence Prevalence Total Population Japan 50 / 100,000 (Developed Country) 0.8 % 126 million

1.1 million
440,000

Total estimation of people with Epilepsy

Intractable*

1 million
300,000

*Approximately 440,000 in Indonesia and 300,000 in Japan are becoming drug resistant or intractable, making them appropriate candidates for epilepsy surgery

EEG Invention

Epileptic Seizure

Epileptogenic Zone Propagation / Spreading line

Symptomatogenic Zone

Epileptic Seizure
Partial Generalized

Seizures beginning locally

Bilaterally symmetric, without localized onset

Classification Of Epileptic Seizure

Epileptic Seizure Partial Generalized Unclassified

Simple
Consciousness Motor Somatosensory Automatism Psychic

Complex
Altered Consciousness

...Seizure are symptoms of a syndrome and should be classified solely according to its ictal semiology and not according to suspected epileptic syndrome

Absence

Tonic-Clonic

Atypical

Tonic

Clonic

Myoclonic

Terminology
Epilepsy is disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiological, cognitive, psychological, and consequence of this condition
International League Against Epilepsy (Fisher et al., 2005)
Epilepsy Seizure

Epileptic Seizure is transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous activity cortex or subcortical grey structure without any provocation

Alcohol withdrawal

Epilepsy ?
Febrile Seizure

Classification of Epilepsies and Epileptic Syndromes

Location-related (focal, local, partial) Generalized

Epileptic Syndrome Is defined by the location of the epileptogenic zone All available information and findings are used to determine the epilepsy syndrome

Idiopathic (primary)

Idiopathic (primary)

Symptomatic (secondary)

Symptomatic (secondary)

Cryptogenic

Cryptogenic

Adopted from Commission on Classification, ILAE

Diagnostic Evaluation
History 1. Patient 2. Reliable observer

Physical Exam

EEG 1. Interictal 2. Ictal 3. Long term

Brain structure and function 1. MRI 2. PET,SPECT 3. MEG

Epileptic Seizure

Epileptic Syndromes

Temporal Lobe Epilepsy (TLE)

One of the types of epilepsy syndrome

The most epileptogenic region, and the most intractable (refractory) to anti-epileptic drugs (AED)
Engel J Jr, 1998, Schmidt D et al, 2003

- Mesial temporal epilepsy

- Neo-cortex temporal epilepsy

Characteristic of TLE Symptoms

Eloquent cortex

Amygdala and hippocampus

Hippocampus

Clinical Symptoms of TLE

Speech arrest, psychic symptoms, epigastric aura (simple partial seizure) Memory impairment Automatism with loss of consciousness (complex partial seizure)

Secondarily Generalize

Refractory Epilepsy
Refractory cases

24% 76%

Generalized Partial

..The failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether mono-therapies or in combination) to achieve sustained seizure freedom..

From 76% of partial cases : 66% had temporal lobe epilepsy, and 35% had hippocampal sclerosis on MRI
Semah et al, Neurology 1998;51:1256-62/ data from Paris 1990-1997

Etiology
Based on pathologic substrate of resected brain tissue in TLE patients treated surgically
Hippocampal Sclerosis

Non Hippocampal Sclerosis*

*Non Hippocampal Sclerosis includes infection, trauma, hamartomas, malignancies, vascular malformations, cryptogenic and idiopathic

Lesional pathologies were detected in 79/100 cases, consist of : 59 Hippocampal sclerosis/ Mesial Temporal Sclerosis (MTS) 6 cases of Angioma (2 AVM, 3 cavernous Angioma, 1 venous angioma)

Visually normal MRI were seen in 21/100 cases

(surgery was performed in some of these cases based on either Long-term Ictal EEG, invasive subdural grid EEG, or FDG-PET studies )

5 tumor cases (2 DNT, 2 astrocytoma gr II, 1 PXA)

4 Cortical Dysplasia (2 FCD, 1 heterotopia, 1 polymicrogyria) 1 Arachnoid cyst

Approach Consideration
Newly Diagnosed Refractory Epilepsy

AED TRIAL 1 Monotherapy AED TRIAL 2 Monotherapy or Polytherapy Treatment Goal Seizure Freedom

Pre operation evaluation Epilepsy surgery

(anterior temporal resection)

VNS Therapy AEDs (polytheraphy) Ketogenic diet

Treatment Goal Maximize QOL Long-term Seizure control Minimize side effects

Temporal Lobe Epilepsy Surgery

The goal is to remove certain part of the brain that suspected as Generator of Epilepsy Discharge Epileptogenic zone

Epilepsy surgery efficacy

Free Seizure Improvement No improvement

Temporal lobe epilepsy surgery

1. Anterior Temporal Lobectomy (conventional) 2. Anterior Medial temporal resection 3. Selective Amygdalohippocampectomy (SAH) Transsylvian SAH Transcortical Transventricular SAH Subtemporal SAH

Pre Surgical Evaluation

Seizure Semiology

One key to successful epilepsy surgery is accurate localization of the seizure onset zone

Electroencephalography

Magnetic Resonance Imaging

Wada test Positron emission tomography (PET), Magnetoencephalography (MEG), MR Spectroscopy and Cerebral angiography

Number of epilepsy surgery performed in Dr.Kariadi Hospital, Central Java-Indonesia

(until Dec. 2009, total 238 patiens)

Operated epilepsy cases in Dr.Kariadi Hospital Central Java-Indonesia

1999 - 2009 ( n : 238 )

Operated 178 180 160 140 120 100 80 60 40 20 0

34

19

7
TLE (MRI Abnormal) TLE (MRI Normal) Extra Temporal Generalized

Post Surgical Evaluation

Seizure states
Using Engel Classification, divided into 4 group. Class I Class II Class III Class IV : Free of disabling seizures : Rare disabling seizures : Worthwhile improvement : No worthwhile improvement

Psychological Adjustment
Adjusting Quality Of Life

Seizure Outcome of Epilepsy Surgery in Indonesia Dr.Kariadi Hospital (2005-2009)

Total 60 50 40 30 20 10 0
75.4% VS

Class I
66.04%

60 50 40

Total Class I Class VS II Class III 78.72% 64.40%

30
20 10 0 < 10 years > 10 years

< 25 year > 25 year old old

Age at surgery

Length of epilepsy
Muttaqin Zaenal, 2010

Neurological History

44 year-old male
When he was 37-year-old, he had a seizure for the first time. Then, he quit from his job in manufacture company because his seizure and also could not get on the train.

He took two kind of Anti epileptic drugs (phenytoin and clobazam), but his seizure
did not stop Past medical history Family history : fever convulsion at 9 month-old : (-)

Neuropsychological Examinations
Neuropsychological test Hand dominant Wada Test Right handed Speech and memory are right hemisphere dominant Score

Seizure Types
Simple partial seizure (monthly) Epigastric sensation Complex partial seizure (monthly)

Simple partial seizure (SPS) and mostly it evolved to Complex

Partial Seizure (CPS) Occasionally, CPS changed into SPS

Lip smacking, Head movements bilaterally, emerged saliva

from his mouth No any other seizure patterns were identified

Extracranial EEG
Interictal phase No seizure pattern ; SP1, F7, T3 single spike Ictal phase
Seizure type
Simple partial seizure Complex partial seizure SPS CPS SPS Generalized seizure Secondary generalized seizure

Frequency
9 times 2 times 5 times 0 0

Imaging Findings
MRI Magnetoencephalography

Axial section of brain MRI FLAIR Image shows hyper-intensity on the left hippocampus

Imaging Findings
FDG-PET

SPECT

Colored area shows FDG low accumulation

IMZ (late phase) Left temporal lobe : Cold

Pre Surgical & Surgical Plan

Focus of the seizure: left medial temporal lobe

L
Surgical plan: Anterior temporal lobectomy

Memory and language dominant hemisphere: Right hemisphere

A. Supine position and skin incision

B. Temporal lobe, sylvian fissure and frontal lobe

Superior temporal fissure

C. Cortical EEG

D. Measuring the resection site

Post operative MRI

L

Post Operation Examinations

Engels outcome classification Ia ; (Seizure Free)
Consumption of AED PHT 200 mg (2 years after operation)
Neuropsychological test Intelligence Quotient Full Score 81 100 Post Operation Post Op. 2 Y

Performance
Verbal

83
83

107
104

Conclusion
Doctors should be more careful in diagnosing epilepsy because epileptic seizure is produced by the consequences of neurobiological, psychological and cognitive phenomenon
Favorable seizure states and neuropsychological improvement after TLE resection surgery can be achieved in 60-80% patients who undergo this procedure, particularly in patient who had concordant findings of epileptogenic site in their pre surgical evaluation

Terima Kasih