פרק 15 Chapter 15: Epilepsy and Other Seizure Disorders Flashcards
איזו מהתרופות האנטיאפילפטיות הבאות לא משפיעה על הפעילות
GABAergic
במוח
א. פנוברביטל
ב. קולונזפם
ג. ויגאבטרין
ד. פניטואין
ה. פרימדון
ד. פניטואין- חוסמת תעלות נתרן
Barbiturates and benzodiazepines are GABA agosints,
Vigabatrin - Irreversibly inhibits gamma-aminobutyric acid transaminase (GABA-T), increasing the levels of the inhibitory compound gamma amino butyric acid (GABA) within the brain
Phenytoin – Na channel
מה מהבאות יכולה להיות תופעת לוואי של למוטריג’ין?
א. היפונתרמיה
ב. אנמיה אפלסטית
ג. סינדרום סטיבן ג’ונסון
ד. הזיות ראייה
ה. היצרות של שדה הראייה
תשובה ג. סינדרום סטיבן ג’ונסון
מה מהבאות יכולה להיות תופעת לוואי של ויגאבאטרין?
א. היפונתרמיה
ב. אנמיה אפלסטית
ג. סינדרום סטיבן ג’ונסון
ד. הזיות ראייה
ה. היצרות של שדה הראייה
ה. היצרות של שדה הראייה
Table 15-5MECHANISMS AND USES OF THE MAIN ANTIEPILEPTIC DRUGS
כל הבאים יכולים לגרום לתסמונת של progressive myoclonic epilepsy
פרט ל-
1. Baltic myoclonus
2. Lafora body disease
3. adrenoleukodystrophy
4. ceroid lipoduscinosis
5. mitochondrial disease
- adrenoleukodystrophy
Myoclonic syndormes most often associated with ataxia.
inherited forms include:
* Infantile ospoclonus- myoclonus syndrome
* Lafora Body Polymyoclonus with epilepsy – Lafora Bodies – polyglucosan inclusions in dentate, brainstem, thalamic neurons. Seizures, myoclonic jerks, advanced myoclonus and ataxia, visual hallucinations, irritability, uninhibitiedbehaviour, failure of cognition. No abnormality of blood, CSF or urine. EEG diffuse slow waves. Skin and liver biopsies informative.
* Ceroid – AR, problem of fatty acids – mental regression, myocloinc seizures, ataxia, hypotonia, retinal degeneration. Diagnosis – sweat glands of skin
* juvenile GM2 Gangliosidosis – deficiency of hexosaminidase
* Late Gaucher with Polymyoclonus
Cherry Red Spot myoclonus syndrome (sialidosis, neuroaminidase deficiency)
* DRPLA
* Mitochondrial diseases include – MERRF – Myoclonic Epilepsy with Red Ragged Fibres
complex partial (AKA partial seizures with altered awarness)
מה זה FIRDA
FIRDAis a rhythmic 2 to 3 Hz delta frequency activity with an amplitude of 50–100 mv that predominates in the bilateral frontal regions of the waking adult electroencephalogram(EEG). The waves are usually regular with a sinusoidal pattern. FIRDA usually occurs in short bursts lasting 2 to 6 seconds and must be differentiated from slow eye blink artifact Figure 2. The electrooculogram (EOG) electrodes can aid in the differentiation of the two. FIRDA, unlike eye blink artifact, may have posterior field extension. It is attenuated by alerting or eye opening and accentuated by eye closure, hyperventilation, drowsiness, and stage N1 sleep. It disappears with the onset of Stage N2 sleep but may reappear during REM sleep. If diagnostic uncertainty is present, a full EEG montage should be used and the EEG recording should include 20 minutes during wakefulness, followed by 3 minutes of hyperventilation and standard intermittent light stimulation to adequately document FIRDA.
לפניך מספר דוגמאות של רצף התפשטות התקף אפילפטי ג’קסוני. איזה מהן אינה הגיוניד ומחשידה להתקף פסיכוגני ולא אפילפטי אמיתי:
א. מכף היד, לזרוע, לפנים
ב. מהפנים, לזרוע, לכף היד, לאצבעות
ג. מכף הרגל, לירך, לכף היד, לזרוע, לכתף
ד. מכף היד, לזרוע, לכתף, לירך, לכף הרגל
ה. מכף היד, לזרוע, התפשטות לפנים ובמקביל גם לאורך הרגל
ג. כף הרגל לירך לכף היד לזרוע לכתף- לא הגיוני מכיוון שלא מתפשט לפי ההומונקולוס.
One form of focal frontal convulsion is the Jacksonian motor seizure, which begins with tonic and then clonic contraction of the fingers of one hand, the face on one side, or the muscles of one foot. Sometimes a series of clonic movements of increasing frequency build up to a tonic contraction. The characteristic feature is that the movements spread (march) from the part first affected to other contiguous muscles on the same side of the body. In its typical form, the seizure spreads from the hand, up the arm, to the face, and down the leg; or if the first movement is in the foot, the seizure marches up the leg, down the arm, and to the face, usually in a matter of 20 to 30 s. Rarely, the first muscular contraction is in the abdomen, thorax, or neck. In some cases, the one-sided seizure activity is followed by turning of the head and eyes to the convulsing side, occasionally to the opposite side, and then by a generalized seizure with loss of consciousness. Consciousness is not lost if the sensorimotor symptoms remain confined to one side
frontal lobe seizures
FRONTAL SEIZURES
Focal or partial motor seizures are attributable to a discharging lesion of the frontal lobe. The most common type, originating in the supplementary motor area, takes the form of a turning movement of the head and eyes to the side opposite the irritative focus, often associated with a tonic extension of limbs, also on the side contralateral to the affected hemisphere. This may constitutethe entire seizure, or it may be followed by generalized clonic movements. The frontal lobe, being so large, can give rise to numerous forms of seizure.
One form of focal frontal convulsion is the Jacksonian motor seizure, which begins with tonic and then clonic contraction of the fingers of one hand, the face on one side, or the muscles of one foot. Sometimes a series of clonic movements of increasing frequency build up to a tonic contraction. The characteristic feature is that the movements spread (march) from the part first affected to other contiguous muscles on the same side of the body. In its typical form, the seizure spreads from the hand, up the arm, to the face, and down the leg; or if the first movement is in the foot, the seizure marches up the leg, down the arm, and to the face, usually in a matter of 20 to 30 s. Rarely, the first muscular contraction is in the abdomen, thorax, or neck. In some cases, the one-sided seizure activity is followed by turning of the head and eyes to the convulsing side, occasionally to the opposite side, and then by a generalized seizure with loss of consciousness. Consciousness is not lost if the sensorimotor symptoms remain confined to one side
In addition to the typical Jacksonian Type, there are adversive, speech arrest, frontal, absence types, and a number of unusual disorders related to discharges from the supplementary motor area including hyperkinetic and postural tonic varieties. In practice, it is often difficult to distinguish such seizures from parasomnic (sleep related) events.
Vague and often indefinable visceral sensations arising in the thorax, epigastrium, and abdomen are among the most frequent of auras, as already indicated. Most often they have a temporal lobe origin, although *in several such cases the seizure discharge has been localized to the upper bank of the sylvian fissure, in the upper or middle frontal gyrus, or in the medial frontal area near the cingulate gyrus. *
התקף אפילפטי עם ביטוי של ריח שרוף הינו ממקור
טמפורלי
Olfactory hallucinations
דיווח על ריח ללא גירוי הוא תמיד ממקור מרכזי, phantosomia – הרגשת ריח שאף אחד לא מרגיש. לעיתים ביטוי של פרכוס עם ירידה בהכרה, וסימנים אפילפטיים נוספים, ממקור uncinate, uncinate fits.
Table 15-2
COMMON FOCAL SEIZURE PATTERNS
38 ילד בן 7 שמפרכס משינה ובEEG פעילות אפילפית צנטרו-טמפורלית. מה יהיה?
1. יעבור לו בבגרות
2. יהיו מיוקלוניות
3. מחלה פרוגסיבית
4. ירידה קוגנטיבית
- יעבור לו בבגרות
Benign epilepsy of childhood with centrotemporal spikes (rolandic epilepsy, sylvian epilepsy)
אפילפסיה מוטורית המופיעה בגיל ילדות, 5-9 ונעלמת לאחר מכן, תגובה טובה למונותרפיה,
EEG מאוד אבנורמלי,
ומבחינה קלינית פרכוס לילי המתחיל פוקאלי ועובר הכללה לתנועות טוניות קלוניות לאחר מכן תנועות קלוניות בצד אחד לרוב נראה פרכוס בפנים, פחות ביד או ברגל ובהתאם מערב את האזור הקורטיקלי באזור הרולנדי הנמוך או באזור הצנטרוטמפורל
—-
עוד מידע על סוגים נוספים של אפילפסיה בילדות
* Epilepsy with occipital spikes Panayiotopoulos
לרוב שפירה , מתחילה בילדות ונעלמת לקראת גיל בגרות, יראה פעילות אוקסיפיטלית ובהתאם הלוסינציות ראיה הן הנפוצות ביותר, אך ייתכן גם טיניטוס וורטיגו או תחושת תזוזה של העינים. לרוב נגרם ע”י הטרוטרופיה קורטיקלית.
שינה מעצימה את הספייקים בEEG
-
Infantile spasm (west syndrome)
תסמונת מיוחדת בכך שמופיעה לרוב לפני גיל שנה, לרוב פרכוסים קצרים בהם יש פלקסציה של כל הגוף ולעיתים פחות נפוצות אקסטנציה. רוב (אבל לא כל) המטופלים מראים שינויים נרחבים
EEG- Hypssarrythmia- multiple spikes and slow wave
, אך תרשים זה אינו אופייני רק לתסמונת זו ונמצא בהרבה אבנורמליות הקשורות להתפתחות המוח, במידה וההדמיות תקינות, נמצא כי מקור הבעיה היא התפתחות לא תקינה של הקורטקס.
מגיב מעולה ל ACTH, סטרואידים ובנזו’ (בעיקר קלונקס)
אלו שמקורם מטוברוס סקלוריס מגיבים טוב למעכבי
** GABA (vigabartin)**
חלקם יתפתחו לתסמונת לנוקס גשטאוט עם פרוגנוזה לא טובה.
Table 15-1
INTERNATIONAL CLASSIFICATION OF EPILEPTIC SEIZURES
Electroclinical syndromes
Table 15-3
MONOGENIC EPILEPTIC DISORDERS
GABA RECEPTOR
איזו תעלה פגועה בתסמונת
DRAVET
תעלת נתרן SCN1A
common monogenic epileptic disorders
* Sodium Channel
Dravet- Benign familial neonatal convulsion
-
Potassium:
EA1 with partial epilepsy -
Ach:
AD nocturnal frontal seizures - GABA:
- JME
- Familial generalised seizures with febrile seizures plus
- GLUT1 transport deficiency – repsonsive to ketogenic diet
-
Calcium:
EA2 with spike wave seziures
———–
Tuberous sclerosis – Tuberin and Hamartin
Unverricht – Lundborg – Cystatin B
Lafora – Laforin
DRPLA – Atrophin 1
Gaucher – Beta-Glucocerebrosidase
פרונטלי
AD Nocturnal frontal lobe epilepsy
ACH RECEPTOR
באיזה שלב של הפרכוס הסכנה מוגברת ל
SUDEP
בשלב הפוסט איקטאלי
Sudden unexplained death in epilepsy
SUDEP מיוחס לאלו שנפטרים מסיבה לא ברורה (לרוב בשינה)
באופן מפתיע מתרחש בגיל הבגרות יותר מאשר ילדות
גורמי סיכון – היסטוריה של פרכוסים טונים קלונים, עלייה בתדירות הפרכוסים, חוסר הצלחה בטיפול, רמות סאבטראפויטיות של תרופות אנטי אפילפטיות, בגרות מוקדמת, אפילפסיה ממושכת ופיגור התפתחותי.
בילדים – אפילפסיה קשה לטיפול, פיגור התפתחותי, סינדרומים מסויים כמו טוברוס סקלרוזיס.
מנגנון לא ברור – כאמור מתרחש בשינה, במצב פוסטאיקטלי נצפו בעבר הפרעות קצב או שינויי קארדיאלים אחרים אולם אינם מסוכנים, ייתכן שמדובר ב”כיבוי גזע המוח” וצבירה של פחמן דו חמצני והיפוקסיה.
טיפול יעיל מוריד את הסיכוי ל SUDEP!
Several factors have emerged as risks from population-based and cohort case controlled studies; the postictal period immediately after a tonic clonic seizure, increasing seizure frequency (including three generalized seizures in the preceding year), lack of successful treatment (i.e., patients not in remission as documented in a 40-year follow-up of childhood epilepsy by Sillanp and Shinnar), or subtherapeutic levels of antiepileptic drugs, the period of early adulthood, long-standing epilepsy, and mental retardation.
Most instances of SUDEP occur when the patient is unattended or during sleep
בחולה עם אירועים חשודים לפרכוס עולה חשד שמדובר ב-
PNES.
מה יתמוך באירוע אורגני?
1. תרשים אינטראיקטלי פתולוגי
2. פרכוס שנמשך מעל 10 דקות
3. אובדן שליטה על סוגרים
4. נשיכת לשון לטרלית
- נשיכת לשון לטרלית
Gabapentin
תרופות רבות יכולות לגרום לפרכוסים, בפרט לנוכח אי ספיקה כלייתית
אנטיביוטיקות - אימיפנם, פניצילין, לינזוליד, צפהפים
פסיכאטרי – טריציקליים, בופופריון,ליתיום – בפרט לנוכח לזיה פוקאלית
מעכבי תעלות – לידוקאין
ברונכודילאטטורים – אמינופילין
נרקוטיקה – טרמדול
פרופפול באופן פרדוקסלי יכול לגרום להפרעות מיוקלוניות.
מי מהבאים הוא
hepatic inhibitor?
1. carbamazepine
2. phenytoin
3. valproic acid
4. phenobarbital
5. topamax
valproic acid
בגלל שאין לו מטבוליט אפוקסיד- עושה פחות תופעות לוואי
- Carbamazepine This drug causes many of the same side effects as phenytoin, but to a slightly lesser degree. Mild leukopenia is common, and there have been rare instances of pancytopenia, hyponatremia (inappropriate antidiuretic hormone [ADH]), and, rarely, diabetes Insipidus as idiosyncratic reactions. It is advisable therefore, that a complete blood count be done before or soon after treatment is instituted and that counts are rechecked regularly.
-
Oxcarbazepine, a more recently introduced analogue of carbamazepine, has fewer of these side effects than the parent drug, especially marrow toxicity. Unlike carbamazepine, which is converted to an epoxide metabolite, oxcarbazepine is rapidly converted to its monohydroxy derivative (MHD), which is the main active metabolite.
the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interaction.
however Hyponatremia has been reported in 3 percent of patients taking oxcarbazepine. Should drowsiness or increasedseizure frequency occur, this complication should be suspected. Although hypona- tremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine.
מטופלתלאחרטיפולבלמוטריגיןמפתחתפריחה.לאיזותרופהאפשרלהחליף?
א.פנוברביטל
ב.קרבהמזפין
ג.פניטואין
ד. קפרה
קפרה
מטופל מאושפז בטיפול נמרץ , כעבור 3 ימים מפתחפנקראטיטיסוהיפרטריגליצרידמיה.איזו תרופה אחראית לכך ?
1. פניטואין
2. בנזודיאזפין
3. פרופופול
4. מידאזולם
פרופופול יכול להוביל לפנקראטיטיס והיפרטריגליצרידמיה
Propofol syndrome – היפרטריגלצירמיה, פנקראטיטיס אקוטית ושוק עם אצידוסיס.
טיפול בסטטוס אפילפטיקוס
GABA transaminase inhibitor (VIGABATRIN)
Vigabatrin- Irreversibly inhibits gamma-aminobutyric acid transaminase (GABA-T), increasing the levels of the inhibitory compound gamma amino butyric acid (GABA) within the brain. Duration of effect is dependent upon rate of GABA-T resynthesis.
Vigabatrin can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, vigabatrin also can damage the central retina and may decrease visual acuity.
The onset of vision loss from vigabatrin is unpredictable and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years.
Symptoms of vision loss from vigabatrin are unlikely to be recognized by the patients or caregivers before vision loss is severe. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function.
The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss.
————
שאר המסיחים בשאלה
Carbonic Anhydrase – Topiramate
Ca – Ethosuximide, Gabapentin
Na – Phenytoin, Carbamazepine, Lamotrigine
בת 30, התקפי אפילפסיה חלקים. מטופלת ב
Vigabatrin.
המנגנון פעולה הספציפי לתרופה זו:
- חסם מנגנון Reuptake של GABA
- מגרה ישירות קולטן GABA
- מגביר שחרור GABA מהסינפסות
- מדכא פירוק של GABA
- מגביר סינתזה של GABA
מדכא פירוק של GABA
Two other drugs, gabapentin and vigabatrin, were synthesized specifically to enhance the intrinsic inhibitory system of GABA
* Vigabatrin is an irreversible inhibitor of GABA aminotransferase (GABA-T), the enzyme responsible for the degradation of GABA. It may also inhibit the vesicular GABA transporter. Vigabatrin produces a sustained increase in the extracellular concentration of GABA in the brain. This leads to some desensitization of synaptic GABAA receptors but prolonged activation of nonsynaptic GABAA receptors that provide tonic inhibition. A decrease in brain glu- tamine synthetase activity is probably secondary to the increased GABA concentrations. It is effective in a wide range of seizure models.Vigabatrin is no longer used in adults because of the side effect or retinal damage.
* Gabapentin is chemically similar to GABA, but its anticonvulsant mechanism is not known; it has an apparent effect on calcium channels. It is moderately effective in partial and secondary generalized seizures and has the advantage of not being metabolized by the liver
* Tiagabine is considered to be an inhibitor of GABA reuptake
ילד בן 6 החל להתלונן על הפרעות בשדה הראיה. ברקע–סובל מ-
West syndrome .
איזו תרופה שניתנת בתסמונת זו עלולה לגרום להפרעה זו?
א. felbamate
ב. vigabatrin
ג. topiramate
ד. zonisamide
ב. vigabatrin
Vigabatrin can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, vigabatrin also can damage the central retina and may decrease visual acuity.
TOPOMAX
Topiramate Has been associated with acute myopia and secondary angle-closure glaucoma in adults and children, typically within 1 month of initiation
vigabatrin is notable for causing retinal degeneration and a concentric restriction of the visual fields in almost half of exposed patients
Acute angle-closure (closed-angle or narrow-angle) glaucoma produces symptoms such as eye pain, headaches, halos around lights, dilated pupils, vision loss, red eyes, nausea and vomiting.
Topiramate, has much the same mode of action and probably a broader effectiveness as tiagabine.
Although no idiosyncratic reactions have been noted, dose-related adverse effects occur most frequently in the first 4 weeks and include somnolence, fatigue, dizziness, cognitive slowing, paresthesias, nervousness, and confusion. Acute myopia and glaucoma may require prompt drug withdrawal. It will rarely
cause serious dermatologic side effects, especially if used with valproate, and appears to induce renal stones in 1.5 percent of patients. Angle-closure glaucoma has also been reported as a complication. A minor problem has been the development of hyperchloremic metabolic acidosis.
אוקסקרבזפין- בהנחה ויש פה מחשבה שמדובר גם על DRAVET
Lennox gastaut syndrome –
מופיע בעיקר בסביב גיל 2-6, מלוווה בפרכוסים אטונים, טונים קלונים וחלקיים, כאן המטופל נופל. מופיע עם ירידה אינלקטאולית
EEG** אופייני לגל זיז האורך 1-2 לשניה (איטי).**
לעיתים טרם הופעת התסמונת היה אינפנטייל ספאזם עם היפסאריטמיה (אמפליטודה גבוהה עם קצב קאוטי) ועצירה של קצב התפתחותי –
שלושת אלו (אינפנטייל ספאזם + היפסראריטמיה + פגיעה בהתפתחות) הם הטריאדה ע”ש West syndrome.
לרוב מיוחס להפרעה קונגניטלית – פציעה סביב הלידה או הפרעה מטבולית בגיל המוקדם –** פרוגנוזה רעה**. בגיל המבוגר קשה מאוד לשליטה ולטיפול.
Valproic acid (900 to 2,400 mg/d) will reduce the frequency of spells in approximately half the cases. The newer drugs—lamotrigine, topiramate, vigabatrin—are each effective in approximately 25 percent of cases. Clonazepam also has had limited success. In the special case of Dravet syndrome, a disorder of the sodium channel, antiepileptic drugs that block that same channel are avoided.
Table 15-7
CHOICES OF ANTIEPILEPTIC DRUGS IN CHILDHOOD SEIZURE DISORDERS
Table 15-6
PHARMACOLOGIC ASPECTS OF ANTIEPILEPTIC DRUGS
Table 15-4
CAUSES OF RECURRENT SEIZURES IN DIFFERENT AGE GROUPS
Table 15-8
APPROACH TO THE TREATMENT OF STATUS EPILEPTICUS IN ADULTS
Cystatin B
Unverricht-Lundborg progressive myoclonic epilepsy
Unverricht-Lundborg disease is an AR inheritance disease caused by an increase in size of the CSTB gene. One region of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is normally repeated two or three times within the gene and is called a dodecamer repeat. Most people with this disorder have more than 30 repeats of the dodecamer sequence in both copies of the CSTB gene. A small number of people with Unverricht-Lundborg disease carry other mutations.
The increased number of dodecamer repeats in the CSTB gene seems to interfere with the production of the cystatin B protein. Levels of cystatin B in affected individuals are only 5 to 10 percent of normal, and cathepsin levels are significantly increased. These changes are believed to cause the signs and symptoms of Unverricht-Lundborg disease, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder.
The beginning is marked by polymyoclonus as an isolated phenomenon, but later is associated with dementia and other signs of progressive neurologic disease. An outstanding feature of the latter is a remarkable sensitivity of the myoclonus to stimuli of all sorts. If a limb is passively or actively displaced, the resulting myoclonic jerk may lead, through a series of progressively larger and more or less synchronous jerks, to a generalized convulsive seizure.
MRI תקין
The diagnosis of the condition is based on the clinical history and EEG, which shows generalized irregular 4- to 6-Hz spike-and-wave activity occurring in bursts. The EEG is most likely to record discharges after awakening.
JME is predominantly a lifelong condition, with less than 25% of patients seizure free off medication in long-term follow-up.
However, the majority of patients can have seizure remission with medication therapy. The prognosis for seizure freedom is lowest in individuals with Childhood Abscence Epilepsy leading to JME and in individuals who have all three seizure types: generalized myoclonic, generalized tonic-clonic, and generalized absence seizures.
Valproate appears to be the most effective medication for all three seizure types, but its teratogenicity and some adverse effects limit its use in women of childbearing age.
Seizures may be aggravated by several AEDs that are specific for partial epilepsy.
מוטציה ברצפטור הניקוטיני ל
ACH
חסר בבי 12
-
Idiosyncratic:
Rash,
fever,
lymphadenopathy,
eosinophilia and other blood dyscrasias,
Polyarteritis
Choreoathetosis (rare) - Overdose:
- ataxia*,
diplopia, and
stupor. - The prolonged use of phenytoin:
hirsutism (mainly in young girls),
hypertrophy of gums (may improve if folate acid administered),
coarsening of facial features.
peripheral neuropathy and
a form of cerebellar degeneration; - An antifolate effect on blood
- interference with vitamin K metabolism for which reason pregnant women taking phenytoin (and in fact most other antiepileptic
drugs) should be given folate supplementation and
vitamin K before delivery and the newborn infant also
should receive vitamin K to prevent bleeding. -
Phenytoin should not be used together with:
disulfiram (Antabuse),
chloramphenicol,
sulfamethizole,
phenylbutazone, or
cyclophosphamide,
use of either phenobarbital or phenytoin is not advisable in patients receiving warfarin because of risk of bleeding.
מה מנגנון הפעולה העיקרי של phenytoin ?
א. Sodium channel inhibitor
ב. SV2A modulation
ג. AMPA inhibition
ד. GABA potentiation
Sodium channel inhibitor
א. אפשר להשתמש בדפלפט
Many antiepileptic medications also seem to be safe for the baby during breast-feeding in that only small amounts are excreted in lactated milk. The degree of penetration into breast milk is dependent on the extent of protein binding. Highly bound drugs do not appear in substantial concentrations and the converse is true. Relatively safe agents include carbamazepine, which is found to be 40 percent of the mother’s serum concentration, resulting in a neonatal blood level that is below the conventionally detectable amount. Phenytoin is excreted at 15 percent of maternal serum concentration, and valproate, being highly protein bound, is virtually absent in breast milk. No adverse effects have been attributed to these small amounts of these drugs. Those that appear in intermediate concentrations include levetiracetam, oxcarbazepine, tiagabine, vigabatrin, gabapentin, and topiramate. Drugs considered risky for the infant because of high concentrations in breast milk include phenobarbital, primidone, ethosuximide, zonisamide, and benzodiazepines. The risks of using this last group of drugs in the postpartum period must be weighed against the sedating effects of the medication on the neonate
מההתרופההגורמתל
neural tube defect
בשכיחות הגבוהה ביותר ?
א.קרבמזפין
ב.ולפרואט
ג.פניטואין
ד.קפרה
ב. ולפרואט
The risk of neural tube defects is also slightly increased by anticonvulsants during pregnancy, and greatest for the use of valproate
הסיכון בטרטוגניות של תרופות אנטיאפילפטיות ביחס לאוכלוסיה הוא כ-2%
valproate during pregnancy.
The most common teratogenic effects have been cleft lip and cleft palate, but infrequently also a subtle facial dysmorphism (“fetal anticonvulsant syndrome”), similar to the fetal alcohol syndrome. The risks are highest with Valproate.
In general, the risk of major congenital defects is low; it increases to 4 to 5 percent in women taking anticonvulsant drugs during pregnancy, in comparison to 2 to 3 percent in the overall population of pregnant women.
פניטואין
If a woman with seizure disorder has been off epilepsy medications for a time before getting pregnant and seizes during the pregnancy, the best choice of medication currently may be phenytoin for its advantage in rapid seizure control, or levetiracetam. Exposure of the fetus late in gestation poses few teratogenic risks. If a woman discovers she is pregnant while on an antiepileptic drug, changing medications is unlikely to reduce the chances of
birth defects, even for valproate, but this drug retains the risk of lower IQ in the child. The special case of eclamptic seizures is managed by infusion of magnesium. Epileptic women of childbearing age should be advised that higher doses of the estradiol component of birth control agents are required or they may be exposed to the issues of becoming pregnant while antiepileptic medications.
Figure 15-1. ILAE proposal for terminology for organization of seizures and epilepsies 2010 classification of seizures. (From http://www.ilae.org/Visitors/Centre/ctf/ documents/ILAEHandoutV10_000.pdf.)
Figure 15-2. ILAE proposal for revised terminology for organization of seizures and epilepsies 2010 electroclinical syndromes and other epilepsies grouped by specificity of diagnosis. (From http://www.ilae.org/Visitors/Centre/ctf/documents/ILAEHandoutV10_000.pdf.)
Figure 15-3. The distribution of the main types of epilepsy by age. The overrepresentation of absence and myoclonic seizures in childhood and of complex partial seizures in older individuals is evident. Complex partial=focal with dyscognitive features; simple partial=focal without dyscognitive features. (Adapted from Hauser and Annegers and the texts of Engel and of Pedley.)
Figure 15-4. Medial temporal sclerosis.
A. T1-weighted MRI in the coronal plane, showing reduced volume of the left hippocampus (shown by arrow) and secondary enlargement of the adjacent temporal horn of the lateral ventricle.
B. Coronal T2-FLAIR image showing abnormal hyperintense signal within the left hippocampus (shown by arrow).
Figure 15-5. Distribution of the main causes of epilepsy at different ages. Evident is the prevalence of congenital causes in childhood and the emergence of cerebrovascular disease in older patients. (Adapted from several sources including Hauser and Annegers and the texts of Engel and Pedley.)
Figure 15-6.
Schematic depiction of sites and mechanisms of action of antiepileptic drugs on excitatory and inhibitory synapses. GABA, gamma amino butyric acid; GAD: glutamic acid decarboxylase; GATI: GABA transporter (also known as SLC6A1). (Adapted by permission of Nature Publishing Group and authors from Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 9:68–82, 2010.)
