Now we’re moving to case number 2

Slide 1
K, 11 years old, male child, presented with chief complaints of episodic “rage attacks” from
last 1 year. The patient was apparently asymptomatic 1 year back and was well adjusted to
his personal and social life when he showed a “rage attack” lasting for not more than 5 min.
The episode was sudden in onset without any precipitating or aggravating factor. During the
episodes, he suddenly became very violent and started hitting others and breaking things,
which were within his reach. He would shout and use abusive languages.

Slide 2
The violent behavior was unprovoked and nondirectional. During such episodes, the patient
would not respond to any verbal command and would keep on moving around in an abnormal
way. It would be difficult to control him and lot of force was needed to control him. He
would calm down by himself after around 5 min. He also did not have any memory for any of
the episodes. Following the episodes, he would feel exhausted and would complain about
numbness in his limbs. He would prefer to lie down and take rest for 15–20 min following the
episodes. In the beginning, the episodes used to occur at a frequency of twice–3 a month. As
the illness progressed, the number of episodes increased to twice–3 times a week in last 3
months. During the interepisodic period, the patient was totally asymptomatic.

Slide 3
Past history, family history, premorbid temperament, and personal history was
noncontributory, and there were no other symptoms suggestive of generalized tonic-clonic
seizure. Patient’s old treatment records showed that patient was earlier diagnosed as
psychosis NOS (not otherwise specified), bipolar disorder, and dissociative disorder by three
different clinicians. The patient was also prescribed olanzapine 10 mg for 2 months, but there
was no response. Detailed child psychiatry assessment and neurological examinations did not
reveal any abnormality.

Slide 4
Detailed routine blood and urine investigations including thyroid and other endocrine
functions were within normal limits. On the basis of history, mental status examination,
neurological examination, psychological evaluation, and appropriate laboratory tests, a
differential diagnosis of intermittent explosive disorder, dissociative disorder, and partial
seizures was kept. MRI brain was within normal limits and EEG (electroencephalogram)
showed spike and slow wave discharges in bilateral frontotemporal leads.

Slide 5
On the basis of EEG changes, our diagnosis was revised to complex partial seizure. The
patient was started on sodium valproate, and dose was gradually increased to 600 mg/day
over a period of next 4 weeks as per his body weight. There was a significant reduction in his
“rage attacks.” He is currently well adjusted in his personal and social life.
We’re going to start the literature review of epilepsy.

Slide 1
International League Against Epilepsy (ILAE) definition. Epilepsy is a disorder of the brain
characterized by an enduring predisposition to generate epileptic seizures, and by the
neurobiologic, cognitive, psychological, and social consequences of this condition. The
definition of epilepsy requires the occurrence of at least one epileptic seizure. The difference
between seizure and epilepsy is: a seizure is an event and epilepsy is the disease involving
recurrent unprovoked seizures.

Slide 2
A person is considered to have epilepsy if they meet any of the following conditions:
1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart.
2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the
general recurrence risk (at least 60%) after two unprovoked seizures, occurring over
the next 10 years.
3. Diagnosis of an epilepsy syndrome
o Epilepsy is considered to be resolved for individuals who had an age-
dependent epilepsy syndrome but are now past the applicable age or those who
have remained seizure-free for the last 10 years, with no seizure medicines for
the last 5 years.

Slide 3
A range of etiologic groups has been recognized, with emphasis on those that have
implications for treatment. Often the first investigation carried out involves neuroimaging,
ideally MRI where available. This enables the clinician to decide if there is a structural
etiology for the patient’s epilepsy (such as stroke, trauma, infection, or genetic like many
malformations of cortical development). The five additional etiologic groups are genetic,
infectious, metabolic, and immune, as well as an unknown group. A patient’s epilepsy may
be classified into more than one etiologic category; the etiologies are not hierarchical
(hayrarkikeul)

1. Structural : a structural etiology refers to abnormalities visible on structural

neuroimaging where the electro clinical assessment with imaging findings lead to
reasonable inference that the imaging abnormality is the likely cause of the seizures.
Structural etiologies maybe acquired such as stroke, trauma, infection, or genetic like
many malformations of cortical development
2. Genetic etiology : The concept of a genetic epilepsy is that it results directly from a
known or presumed genetic mutation in which seizures are a core symptom of the
disorder. The epilepsies in which a genetic etiology has been implicated are quite
diverse and, in most cases, the underlying genes are not yet known. Such as Benign
Familial Neonatal Epilepsy, most families have mutations of one of the potassium
channel genes.
3. Infection : The most common etiology worldwide is where epilepsy occurs as a result
of an infection such as meningitis or encephalitis (ensefalaitis). These infections
sometimes have a structural correlation.
 4. Metabolic Epilepsy : Metabolic causes refer to a well-delineated (delinieted)
metabolic defect with manifestations of biochemical changes throughout the body.
such as porphyria, uremia aminoacidopathies, or pyridoxine dependent seizures.
5. Immune : The concept of immune epilepsy is that it results directly from an immune
disorder in which seizures are a core symptom of the disorder. An immune etiology
can be conceptualized as where there is evidence of autoimmune-mediated central
nervous system inflammation.
6. Unknown : the last is unknown etiology. In this category it is not possible to make a
specific diagnosis apart from the basic electroclinical semiology such as frontal lobe
epilepsy

Slide 4
Pathophysiology
During a seizure, clusters of neurons in the brain become temporarily impaired and start
sending out a lot of excitatory (iksaitetory) signals, over and over again, and these said to be
“paroxysmal”. These paroxysmal electrical discharges are thought to happen due to either too
much excitation (iksaitation) or too little inhibition. The main excitatory neurotransmitter in
the brain is glutamate, and NMDA is the primary receptor that responds to glutamate by
opening ion channels that let calsium in. Some patients with epilepsy seem to have fast or
long-lasting activation of these receptors. On the other side, the main inhibitory
neurotransmitter in the brain is GABA, which binds to GABA receptors that tell the cell to
inhibit the signal by opening channels that let in chloride. Some patients with epilepsy seem
to have genetic mutations in which their GABA receptors are dysfunctional. In addition to
potentially having a primary genetic cause, these receptors and ion channels might be
affected by other causes like what I’ve said before in etiology, such as brain trauma, stroke,
brain mass, CNS infection. Whether it’s a decrease in inhibition or an increase in activation,
when group of neurons start firing simultaneously, over and over, it’s often noticed by others
as obvious outward signs like jerking, moving, and losing consciousness, but can also be
subjective experience that are only noticed by the person experiencing it, like fears,
hallucination. It all depends on which neurons in the brain are affected.

Slide 5
Classification
The classification of seizures from ILAE 2017 is based on 3 key features.
1. Where seizures begin in the brain
2. Level of awareness during a seizure
3. Other features of seizures

The first step is to separate seizures by how they begin in the brain. The type of seizure onset
is important because it affects choice of seizure medication, possibilities for epilepsy surgery,
outlook, and possible causes.
 Focal seizures: Previously called partial seizures, start in an area or network of cells
on one side of the brain.
 Generalized seizures: Previously called primary generalized engage or involve
networks on both sides of the brain at the onset.
  Unknown onset: If the onset of a seizure is not known, the seizure falls into the
unknown onset category. Later on, the seizure type can be changed if the beginning of
a person’s seizures becomes clear.
 Focal to bilateral seizure: A seizure that starts in one side or part of the brain and
spreads to both sides has been called a secondary generalized seizures. Now the term
generalized refers only to the start of a seizure. The new term for secondary
generalized seizure would be a focal to bilateral seizure.

Whether a person is aware during a seizure is of practical importance because it is one of the
main factors affecting a person’s safety during a seizure.
 Focal aware: If awareness remains intact, even if the person is unable to talk or
respond during a seizure, the seizure would be called a focal aware seizure. This
replaces the term simple partial.
 Focal impaired awareness: If awareness is impaired or affected at any time during a
seizure, even if a person has a vague (veig) idea of what happened, the seizure would
be called focal impaired awareness. This replaces the term complex partial seizure.
 Awareness unknown: Sometimes it’s not possible to know if a person is aware or not,
for example if a person lives alone or has seizures only at night. In this situation, the
awareness term may not be used or it would be described as awareness unknown.
 Generalized seizures:  are all presumed to affect a person’s awareness or
consciousness in some way. Thus no special terms are needed to describe awareness
in generalized seizures.

Many other symptoms may occur during a seizure. In this classification system, seizure
behaviors are separated into groups that involve movement.
 Focal motor seizure: means that some type of movement occurs during the event. For
example twitching, jerking, or stiffening movements of a body part or automatisms
(automatic movements such as licking lips, rubbing hands, walking, or running).
 Focal non-motor seizure: This type of seizure has other symptoms that occur first,
such as changes in sensation, emotions, thinking, or experiences.
 It is also possible for a focal aware or impaired awareness seizure to be sub-classified
as motor or non-motor onset.
 Auras: The term aura, which describes symptoms a person may feel in the beginning
of a seizure, is not in the new classification. Yet people may continue to use this term.
It’s important to know that in most cases, these early symptoms may be the start of a
seizure.

Seizures that start in both sides of the brain, called generalized onset, can be motor or non-
motor.
 Generalized motor seizure: The generalized tonic-clonic seizure term is still used to
describe seizures with stiffening (tonic) and jerking (clonic). This loosely corresponds
to “grand mal.” Other forms of generalized motor seizures may happen. Many of
these terms have not changed, and a few new terms have been added. (see image
below)
 Generalized non-motor seizure: are primarily absence seizures, and the term
corresponds to the old term "petit mal." These seizures involve brief changes in
 awareness, staring, and some may have automatic or repeated movements like
lipsmacking.

The last classification is unknown onset seizures. When the beginning of a seizure is not
known, this classification still gives a way to describe whether the features are motor or non-
motor.

Slide 6
Next we are going to talk about status epilepticus. Status epilepticus had previously been
defined as continuous seizure activity lasting greater than 30 min. Since the majority of
seizures are brief, and once a seizure lasts more than 5 minutes it is likely to be prolonged,
status treatment protocols have used a 5-minute definition to minimize both the risk of
seizures reaching 30 minutes and the adverse outcomes associated with needlessly
intervening on brief, self-limited seizures. International League Against Epilepsy (ILAE)
redefined status epilepticus as ongoing seizure activity due to failure of mechanisms
responsible for seizure termination or initiation of mechanisms provoking ongoing seizures
causing prolonged seizures after time point t1, and which can have long-term consequences
after time point t2, with t1 and t2 being 5 min and 30 min, respectively for convulsive status
epilepticus, 10 min and 60 min for focal status epilepticus with impaired consciousness, and
10–15 min and unknown for absence status epilepticus. SE is differentiated into convulsive
SE and non-convulsive SE.

 Convulsive SE : Seizure activities that lasts >5 minutes  or 2 seizures without return
of consciousness within the seizures
 Non-Convulsive SE : An epileptic seizure with changes in consciousness or behavior
without clear signs of motoric manifestations but there are evidence of seizure in EEG

Slide 7
By the duration, SE is divided into early, established, and refractory SE
Early is defined by an SE that last for 5 to 30 minutes
Established SE is a continuous seizure activity lasting greater than 30 min
And refractory SE refers to seizures that persist despite treatment with adequate doses of two
or three initial anticonvulsants

1. Bila saat pengentian OAE terjadi kekambuhan, bagaimana terapinya? Lalu apa yang dapat
menyebabkan terjadinya kekambuhan saat penghentian OAE?
Jika terjadi kekambuhan maka segera dilakukan terapi menggunakan obat antiepilepsi dengan
dosis efektif terakhir atau dosis sebelum dilakukan pengurangan. Kemudian dilakukan
evaluasi kembali. Kekambuhan ini umumnya besar kemungkinan terjadi pada keadaan :
-usia tua, dimana semakin tua usia, kemungkinan timbul kekambuhan semakin tinggi
- ditemukan EEG abnormal
- epilepsi simtomatis
- bangkitan yang sulit terkontrol dengan OAE
- penggunaan lebih dari satu OAE atau politerapi
- telah mendapat terapi 10 th atau lebih

2. Apa indikasi dilakukan neuroimaging pada kasus epilepsi? Apakah harus selalu dilakukan?
Jawab :
Indikasi CT scan dan MRI dilakukan pada kasus kejang bila muncul kejang tidak
terprovokasi (unprovoked) di usia dewasa. Tujuan neuroimaging pada kondisi ini adalah
untuk menentukan lesi struktural (tumor, kalsifikasi, abnormalitas vaskular, dll) penyebab
epilepsi. Untuk CT scan sendiri lebih ditujukan pada kasus kegawatdaruratan karena lebih
cepat dan lebih tersedia serta lebih mudah dilakukan pada pasien yg kondisinya kurang stabil.

Untuk MRI yg cukup sering digunakan dalam kasus elektif terdapat 2 situasi dasar untuk
melakukan MRI :
1. Pasien yang baru terdiagnosa epilepsi yg blm dilakukan pemeriksaan lebih lanjut bisa
dilakukan MRI dulu (sesuai algoritma yg sudah dijelaskan)
2. seizure berulang yang memiliki indikasi untuk tindakan operasi karena terdapat kelainan
struktural

Biasanya MRI tdk dilakukan bila epilepsi sudah tipikal secara klinis seperti
juvenilemyoclonic epilepsy, focal epilepsy of childhood.

PET, SPECT, MRS di indikasi dalam memberikan informasi apabila terdapat perubahan
aliran darah regional di otak berkaitan dengan bangkitan, dan mendeteksi perubahan
metabolik.
Oleh karena itu lebih digunakan pada keadaan interictal.

3. Bagaimana membedakan kasus psikiatri yang terkait dengan epilepsi seperti pada case
report ini dengan yang berupa kasus psikiatri yang bukan karena epilepsi?
Jawab :
Dalam hal ini dapat dilihat pada case report ini kasus psikiatri yang terjadi hanya berdiri
sendiri tanpa gejala atau kriteria psikiatri lain nya, misalnya pada kasus pertama halusinasi
auditorik nya bersifat atipikal dan hanya berlangsung dalam beberapa menit. Dari
pemeriksaan mental juga tidak menuju ke arah gangguan psikiatri. Lalu saat pasien diberikan
terapi pada awalnya tidak responsif karena penyebab nya bukan berasal dari gangguan
psikiatri nya, dan setelah diberi OAE memberikan hasil yang signifikan. Peran anamnesis
juga penting untuk menilai faktor risiko seperti stress, situasi sosial, keadaan ansietas atau
takut terus menerus yang mengarah ke gangguan psikiatri. Selain itu karateristik klinis dari
PF, dan juga EEG dapat sangat membantu dalam mendiagnosa epilepsi.
tambahan jawaban nomor 3
membedakan diagnosis antara epilepsi dan non epilepsi biasanya dapat dilakukan dengan
mendapatkan anamnesis yang detail/rinci mengenai kejadiannya baik dari pasien maupun dari
witnesses. ditekankan kembali juga pada pasien dengan dugaan epilepsi, anamnesis yang
rinci dan eksplorasi gejala individu adalah cara paling baik untuk menegakkan diagnosis yang
akurat bahkan sampai 90%. persyaratan dasar dalam evaluasi epilepsi adalah untuk
menentukan apakah manifestasi pada pasien memiliki gejala inti epilepsi yaitu, tidak
dipicu/diprovokasi, onset mendadak, paroksismal, dan durasi episode singkat. Namun, durasi
yg berkepanjangan juga tidak boleh disingkirkan untuk kemungkinan epilepsi karena bisa
saja hal tersebut merupakan tanda dari status epileptikus. seperti jawaban sebelumnya juga
selain anamnesis, PF umum dan neuro, EEG, MRI (meskipun tidak harus selalu dilakukan)
dapat membantu penegakkan diagnosis
4. Apakah pada pasien epilepsi akan selalu ditemukan abnormalitas pada EEG?
Jawab :
Tidak selalu, misalnya pada focal seizures yang berasal dari daerah cortex yang tidak dapat di
deteksi dengan EEG standar. Namun EEG dapat selalu terlihat abnormal pada pasien dengan
generalized tonic-clonic seizure. Biasanya pada pasien dengan riwayat epilepsi, EEG
interictal bisa normal pada 60% kasus. Oleh karena itu EEG saja tidak dapat selalu
menegakkan diagnosis epilepsi. Apabila ditemukan EEG normal juga tidak dapat langsung
mengeksklusi epilepsi. Hal ini juga disebabkan aktivitas otak pada sebagian besar pasien
akan kembali seperti semula, dan sulit untuk selalu mendapatkan rekaman EEG pada pasien
yang dalam keadaan seizure. Biasanya bisa di provokasi abnormalitas gelombang otak
dengan cahaya terang, napas dalam (hiperventilasi).

5. Apa hubungan antara epilepsi dengan kehamilan sehingga perlu di refer ke spesialis?
Pada kehamilan berkaitan dengan peningkatan kadar estrogen dan progresteron yang
bermakna serta terjadinya perubahan metabolisme hormon dan OAE sehingga dapat
memengaruhi frekuensi bangkitan. Tentunya epilepsi dapat menyebabkan komplikasi bagi
maternal dan fetal. Pada maternal bs tjd bangkitan berulang, status epileptikus, bangkitan saat
persalinan, hipertensi kehamilan, persalinan preterm. Sedangkan bagi fetus bisa terjadi
keguguran, kelainan kongenital, hipoksia, kurang usia kehamilan dan berat badan lahir,
prematus, IQ rendah dan perilaku abnormal. Selain itu tidak ada OAE yang dianggap aman
pada kehamilan. Terdapat peningkatan teratogenitas pada penggunaan politerapi.

6. Bagaimana cara membedakan seizure tipe atonic dengan syncope tanpa melakukan
pemeriksaan penunjang? apakah bisa?
neurocardiogenic/vasovagal syncope umumnya mudah didiagnosis karena gejala prodormal
seperti pusing, lemah, berkeringat, mual, pandangan kabur hampir selalu diingat jelas oleh
pasien. inkontinensia urin tidak jarang terjadi pada syncope namun tongue biting biasanya
lebih mengarah ke convulsion. penting juga untuk mencari apakah ada witnesses yang dapat
menjelaskan bagaimana pasien saat terjatuh, biasanya pasien syncope diceritakan terjatuh
seperti rubuh/tergelincir sementara pasien dengan kejang biasanya posisi jatuhnya kaku.
kesadaran juga pulih kembali setelah syncope sedangkan kebingungan atau mengantuk sering
terjadi setelah kejang. mungkin akan lebih sulit apabila pada pasien syncope terjadi
mioklonik yang dapat dilaporkan sebagai aktivitas kejang. riwayat khas pemicu syncope juga
dapat membantu seperti misalnya dehidrasi, kepanasan, berdiri lama. sehingga anamnesis
sangat penting untuk membantu menegakkan diagnosis.

7. Bagaimana membedakan pseudoseizure dengan epilepsi? Pseudoseizure banyak pelvic

thrust, lidah yg tergigit biasa tip kalo seizure di sisi lidahh, pseudoseizure biasanya ada
kehati2an kalo akan terluka karena pasien sadar, seizure tidak ada kehati2an terhadap akan
terluka.
pseudoseizure atau kejang psikogenik biasanya muncul sebagai serangan kejang yang tidak
berespons terhadap AED. Seperti kejang pada umumnya, gejala yang ditimbulkanpun mirip
dan bervarasi dari episode convulsive atau perubahan kesadaran atau sensasi sementara,
namun biasanya orang dengan pseudoseizure yang gejalanya menyerupai generelized tonic-
clonic seizure dapat memberitahu bahwa ia sadar terhadap lingkungannya bahkan selama
periode kejang berlangsung. meski demikian, dari sumber yang kami baca diagnosis yang
tegas dapat dibuat dengan bantuan EEG. pseudo seizure dan epilepsi dikatakan juga dapat
terjadi pada pasien yang sama sehingga sulit untuk mendiagnosis, namun anamnesis yang
baik dapat membantu penegakkan diagnosis.

Pada pasien epilepsi ambang batas kejangnya rendah, tiap orang beda2, misal stres dikit
kejang