CHAPTER I LITERATURE STUDY

I.

DEFINITION The word epilepsy comes from the Greek and means to be taken, seized or

attacked. Epilepsy is a condition characterized by repeated seizures due to a disorder of the brain cells. It is a life-long tendency, though the seizures may start at any time during life and occur sporadically or frequently.

II. EPIDEMIOLOGY About 2 in 100 people in the United States will experience an unprovoked seizure once in life; of the 125,000 new cases that develop each year, up to 50% are in children and adolescents. The incidence of idiopathic localization-related epilepsy was 1.7/100,000 (7% of all cases). An additional 13.6/100,000 (56%) had symptomatic localization-related epilepsy.

III. ETIOLOGY Epilepsy may develop after a particular identifiable event (e.g., asphyxia, head injury, meningitis), in which case it is called symptomatic epilepsy, or it may develop without any identifiable cause, and then it is called idiopathic epilepsy. Sometimes the term secondary epilepsy was used for symptomatic epilepsy and primary epilepsy for idiopathic epilepsy.

IV. PRECIPITATING FACTORS

There are some kind of events that can provoke seizures. In people with seizures, the changes in chemical substance in the brain can induce seizures, such as: Sleep deprivated Emotional stress Infection Medicines Alcohol Hormonal changes Fatigue Fotosensitive

V. PATOPHYSIOLOGY2 The clinical neurophysiologic hallmark of focal-onset seizures is the focal interictal epileptiform spike or sharp wave. The cellular neurophysiologic correlate of an interictal focal epileptiform discharge in single cortical neurons is the paroxysmal depolarization shift (PDS). The PDS is characterized by a prolonged calcium-dependent depolarization that results in multiple sodium-mediated action potentials during the depolarization phase, and it is followed by a prominent after hyperpolarization, which is a hyperpolarized membrane potential beyond the baseline resting potential. Calcium-dependent potassium channels mostly mediate the after-hyperpolarization phase. When multiple neurons fire PDSs in a synchronous manner, the extracellular field recording shows an interictal spike. If the number of discharging neurons is more than several million, they can usually be recorded with scalp electrographic (EEG) electrodes. Calculations show that the interictal spikes need to spread to about 6 cm 2 of cerebral cortex before 2

they can be detected with scalp electrodes. Several factors may be associated with the transition from an interictal spike to an epileptic seizure. When any of the mechanisms that underlie an acute seizure become a permanent alteration, patients are assumed to then develop a propensity for recurrent seizures (ie, epilepsy). The mechanisms discussed below may coexist in different combinations to cause focal-onset seizures. If the mechanisms leading to a net increased excitability become permanent alterations, patients develop pharmacologically intractable focal-onset epilepsy. Current available medications were screened using acute models of focal-onset or generalized-onset convulsions. In clinical use, they are most effective at blocking the propagation of a seizure (ie, spread from the epileptic focus to secondary generalized tonic-clonic seizures). Further understanding of the mechanisms that permanently increase network excitability may lead to development of true antiepileptic drugs that alter the natural history of epilepsy. Mechanisms leading to decreased inhibition and those leading to increased excitation are discussed in this section. Mechanisms leading to decreased inhibition include the following:

Defective gamma-aminobutyric acid (GABA)A inhibition Defective GABA-B inhibition Defective activation of GABA neurons Defective intracellular buffering of calcium

Mechanisms leading to increased excitation include the following:

Increased activation of NMDA receptors Increased synchrony between neurons due to ephaptic interactions Increased synchrony and/or activation due to recurrent excitatory collaterals

VI. CLASSIFICATION2 PARTIAL SEIZURES (seizures beginning locally) A. Simple partial seizures (consciousness not impaired) 3

With motor symptoms With somatosensory or special sensory symptoms With autonomic symptoms With psychic symptoms

B. Complex partial seizures (with impairment of consciousness) Beginning as simple partial seizures and progressing to impairment of consciousness With impairment of consciousness at onset

C. Partial seizures secondary generalized GENERALIZED SEIZURES (bilaterally symmetrical and without local onset) A. Absence seizures B. Myoclonic seizures C. Clonic seizures D. Tonic seizures E. Tonic-clonic seizures F. Atonic seizures UNCLASSIFIED EPILEPTIC SEIZURES (inadequate or incomplete data)

VII.CLINICAL MANIFESTATION 1. Partial Seizures Simple partial seizures The patient does not lose consciousness, and therefore is able to tell what happened, but the experience may be so strange that he may not be able to express himself properly. What happens is dependent on the location of the affected area. In motor seizures, the focus is in the primary motor cortex. There are twitchings, starting in a distal part of the extremity, or in the face. The 4

twitching may remain there, or spread up the whole extremity and even become completely generalized. The spreading is called a Jacksonian march (named after Huglings Jackson 1835 - 1911). The sensory seizures have their focus in the post central gyrus (primary sensory cortex). There might be feelings of tingling, pins and needles, cold or heat, or numbness of a limb. Sometimes there may be strange feelings with visual signs, or hearing or smelling sensations. The autonomic seizures are associated with foci in the temporal lobe. There maybe: a sensation rising from the epigastrium to the throat, palpitations, sweating or flushing. The psychic symptoms may consist of changes in mood, memory, or thought (thinking). There may be distorted perceptions (time, space, or person) or problems with language. Structured hallucinations could occur (music, scenes). These simple partial seizures are usually only recognized as epileptic seizures when they develop into generalized seizures. Complex partial seizures Here the patient has impaired consciousness, there is no complete loss of consciousness, he is slightly aware of what is going on, but he cannot respond to anything, neither can he change his behaviour during an attack. There is an aura, a strange feeling in the stomach rising up to the throat and head, or a sensation of light, smell, sound or taste. The seizure may occur with changes in perception, e.g., of time (time seems to pass too slowly or too fast), of light or sound or space. The surroundings may suddenly seem completely strange and different in scale (things seem larger or smaller than usual), or there is dj vu (a sensation of things having happened before). These feelings can cause the patient a great deal of anxiety. 5

2. Generalized seizures Grandmal (Tonic Clonic Seizures) The patient loses consciousness, falls down, sometimes with a scream, and develops a generalized stiffness (the tonic phase). Breathing stops, as all the muscles of the trunk are in spasm, and the patient becomes cyanotic, the head is retracted, the arms flexed and the legs extended. After a while, this tonic phase is followed by the clonic phase, when the muscles alternately contract and relax, resulting in clonic movements. With this jerking the patient might bite his tongue, pass urine, or sometimes stool. The clonic phase may last several minutes. When all the jerking stops and the patient regains consciousness, he may feel very tired with a headache and confusion. He has no memory of what happened, and may find himself on the floor in a strange position. Often he falls into a deep sleep.

Absence Seizure (Petit Mal) These are short periods of loss of consciousness lasting only a few seconds (not more than half a minute). They are of sudden onset, there are usually no, or only minimal motor manifestations. There is a blank stare, brief upward rotation of the eyes, an interruption of ongoing activity. The child is unresponsive when spoken to. It is suddenly over, and the child continues what he was doing before the seizure came. The child has no memory of these seizures. They should not be confused with brief complex partial seizures. Myoclonic These seizures consist of sudden, brief, shock-like muscle contractions, either occurring in one limb, or more widespread and bilateral. They may be single jerks, or jerks repeated over longer periods.

Clonic These seizures are generalized seizures, where the tonic component is not present, only repetitive clonic jerks (clonic jerks are repetitive rhythmic flexing and streching of limbs). When the frequency diminishes the amplitude of the jerks do not. Tonic Tonic seizures are sudden sustained muscle contractions, fixing the limbs in some strained position. There is immediate loss of consciousness. Often there is a deviation of the eyes and head towards one side, sometimes rotation of the whole body. They are seen mainly in paediatric practice. Atonic There is a sudden loss of muscle tone causing the head or a limb to drop, and often the patient falls suddenly to the floor. They are therefore also called drop attacks. There is loss of consciousness, a sudden onset and no post-ictal phase. The patient stands up and continues what he was doing. The seizure is very short, only seconds, but may occur several times a day. The patients often present with scars or fresh wounds on chin, cheek or forehead, or the back of the head. A protective helmet is recommended for these patients. 3. Unclasified Epileptic Seizures This category includes all seizures which cannot be classified because of inadequate or incomplete data, or seizures that defy classification in the categories as presently defined.

VIII.

DIAGNOSIS3

The diagnosis of seizures is based on the clinical history. Because many types of seizures are associated with impairment of consciousness, patients are unaware of their occurrence; thus, the history as related by a witness is of high importance. The clinical diagnosis can be confirmed by abnormalities on the interictal electroencephalogram (EEG), but these abnormalities could be present in otherwise healthy individuals, and their absence does not exclude the diagnosis of epilepsy. Recurrent seizing (minimal of two times) with the epileptiform pattern on EEG. Anamnesa Physical and neurological examination Advanced examination Laboratory findings Brain imaging EEG

IX. TREATMENT

PHENOBARBITONE, if it is the only available drug in a dispensary or health centre, then all patients with epilepsy might be started with phenobarbitone treatment. This medicine is no longer advocated in the developed world, but it is still a useful, effective and cheap anticonvulsant But if there is no improvement, or even a worsening of the condition, the dosage should not be increased beyond 120 mg daily, and the patient referred to a clinic or hospital where other anticonvulsants are available. VALPROATE has been marketed since 1966. The main indications are the generalized absences, myoclonic seizures, and the drop attacks. It is also used for the GTCS occurring after awakening. And if necessary it might be used for all other seizure types. When phenobarbitone cannot be used as prophylaxis for febrile convulsions, valproate can be used instead. It has a short half-life time. Although its pharmacodynamic action in the central nervous system exceeds its presence in serum, it should be given three times daily in order to avoid high peak concentrations. The specific side-effects are increase in body weight, loss of hair, 9

and gastric irritation. The effect on the foetus is more serious, as spina bifida might occur. The risk of spina bifida is reduced by supplementing folate in all women at risk of being pregnant. CARBAMAZEPINE is a drug marketed after 1960. The main indication is for complex partial seizures. But it is also effective for other partial seizures and for all GTCS. It is not effective for generalized absences and myoclonic seizures. In the beginning of the treatment drowsiness and dizziness occur, and occur again when the dosage becomes too high. Then there might be also double vision and ataxia. It does not have a long halflife time and therefore it cannot be given once daily. It should be given twice daily and when combined with other drugs it must be given three times daily.

PHENYTOIN is also a very effective anticonvulsant for partial and GTCS and seizures during sleep. The main problem is the small margin between the therapeutic level and the level where the metabolizing enzyme gets saturated and the serum level rises steeply to reach toxic values. Increments should be not larger than 50 mg to prevent toxic side-effects. The side-effects are drowsiness, gum hypertrophy and hirsutism, and when the dosage is too high ataxia and nystagmus. Besides these reversible cerebellar signs at high dosage, it has been suggested that a permanent cerebellar syndrome may also result from chronic therapy. A mild subclinical neuropathy is common after prolonged phenytoin therapy, but may occur with other drugs too. If toxicity has appeared, the dosage should be omitted for one day and then restarted on a lower level. If at all possible, a change-over to another anticonvulsant could be made to prevent further mishaps.

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CHAPTER II CASE ILLUSTRATION

A 51 year old woman came to neurology policlinic of M. Djamil Hospital in April 1st, 2013 with chief complaint: epilepsy control. History of current illness: Patient was first admitted in Internal Medicine and consulted to neurology for her epilepsy. Patient had seizures 7 days ago. The first seizures happened suddenly when the patient just woke up in the morning from her sleep, it happened once, started with freezing for about 10s then seizing in her whole body, lasted for about 2 minutes, the patient was unconcious during the attack. Patient was brought by the family to the emergency room of M. Djamil Hospital. In the ER, the second seizure occurred, lasted for about 1 minutes, and patient was unconscious. About 5 minutes after that, patient gained her conciousness and vomited 2 times. Patient was hospitalized in Internal Medicine for one day. Fever (-), headache (-), and she didnt wet her pants during seizures.

History of previous illness: Epilepsy since 3 months ago, controlled with phenitoin. DM since 5 years ago, well controlled, normoweight. No history of hypertension, stroke, heart disease, meningitis, and head trauma.

History of family illness: 11

 No history of epilepsy, DM, hypertension, stroke, heart disease in the family.

Economical and social status: Pasien is a housewife, physical activity is quite enough, doesnt smoke, drink coffee or alcohol.

PHYSICAL EXAMINATION GENERALIZE STATE General appearance Conciousness Nutritional status Blood pressure Pulse Respiration rate Temperature INTERNAL STATE Skin KGB Head Eyes ENT : no abnormality detected : no abnormality detected : no abnormality detected : anemis (-), icteric (-) : no abnormality detected : moderate illness : composmentis cooperative : good : 130/80 mmHg : 74x/i : 20x/i : 36,8C

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 Neck Pulmo I : symetrical

: JVP = 5 - 2 cmH2O

P : fremitus left = right P : sonor A : vesikuler, ronkhi -/-, wheezing -/ Cor I: ictus cant be inspected P : iktus was palpable at medially 1 finger to LMCS RIC V P : cardiomegali (-) A : reguler, murmur(-) Abdomen I : perut tidak membuncit P : hepar and lien werent palpable P : thympani A: bising usus (+) normal Alat kelamin Tangan Tungkai dan kaki NEUROLOGICAL STATE GCS15 : E4M6V5 Meningeal signs : nuchal rigidity (-), Brudzinsky I (-), II (-), Kernig (-) 13 : unchecked : no abnormality detected : no abnormality detected

 Increasing intracranial pressure signs: projectile vomitting (-), progressive headache (-) Cranial nerves : N. I N. II N. III, IV, VI : olfactory was good : visual field was normal : pupils were isochor, round shape, 3 mm/ 3 mm, light reflex

(+/+), eyes movement were free to all direction N. V : opening the mouth, jaw movement, bite function, and

chewing can be done N. VII same N. VIII N. IX N. X N. XI can be done N. XII Motoric : Upper extremity: active, strength 555/555, eutonus, eutrofi Lower extremity: active, strength 555/555, eutonus, eutrofi Sensoric Exteroceptive Proprioceptive : good : good 14 : tounge was symmetrical : hearing functions are good : vomit reflex (+) : voice and articulation are normal, heart rate is normal : head turning to the right and left, and lifting of the shoulder : facial curves are normal, plica nasolabialis left and right are the

 Autonomic function : urination, defecation, and secretion of sweat are normal Reflexes Physiologic reflex: Reflex of biceps ++/++ Reflex of KPR ++/++ Reflex of triceps ++/++ Refleks of APR ++/++ Pathological reflex: Hoffman Trommer reflex -/ Babinsky reflex -/DIAGNOSIS : Clinical Diagnosis Topic Diagnosis Eiology Diagnosis THERAPY : Fenitoin 3 x 100 mg (po) Clobazam 3 x 10 mg (po) ADVANCED EXAMINATION : Electro Encephalography Result: EEG abnormal III with general epileptiform discharge. : epilepsi : intrakranial : idiopatik

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CHAPTER III DISCUSSION

A female patient entered the neurology outpatient dept. for an epilepsy control. From the anamnesis, patient had seizure 7 days ago, and was not conscious throughout the seizure. Seizure happened at her whole body. This is the second attack, while her first came on December 2012. Patient does not have any history of brain infection or trauma to the head. No abnormality was found hrough the physical examination. Her EEG showed that she had an abnormal III with general epileptiform discharge. From the anamnesis and physical examination we can conclude that the diagnosis is an idiopathic epilepsy because does not have any history of disease that may presipitate the seizure. Patient was given fenitoin 3 x 100mg and clobazam 3 x 10mg as her medication.

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LITERATURE

Goetz, Christopher G. 1999. Textbook of Clinical Neurology. W. B. Sanders Company: Pennsylvania. Harsono. 2008. Buku Ajar Neurologi Klinis. Gajah Mada University Press: Yogyakarta. http://emedicine.medscape.com/article/1184846-overview tanggal 3 April 2013. Tanu, Ian. 2007. Farmakologi dan Terapi. Fakultas Kedokteran Universitas Indonesia: Jakarta. Dekker, P.A. 2002. Epilepsy: A Manual for Medical and Clinical Officers in Africa. WHO: Geneva. diakses pada

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