Seizure disorderin children new updated.pptx

Seizure disoder in children

1. SEIZURE DISORDER By: Gamachu Alemu And Amare Molla Modulator: Dr. Etabezahu

2. Definition A seizure is a transient occurrence of signs and/or symptoms(alteration in behavior, motor function, and/or autonomic function) resulting from abnormal excessive or synchronous neuronal activity in the brain The term transient is used as demarcated in time, with a clear start and finish “ provoked ” or “ unprovoked,” referring to whether they were precipitated by an acute causes that can affect brain excitability, such as an electrolyte imbalance , structural, inflammatory, or metabolic disorders of the brain , such as meningitis, encephalitis, acute stroke, or brain tumor

3. The term “symptomatic” refers to whether the seizures represent a symptom of a known chronic disorder, such as a structural, genetic, or metabolic abnormality. A remote symptomatic seizure is one that is considered to be secondary to a distant brain injury, such as an old stroke.

4. Characteristics of seizure Seizures are usually stereotyped (each one is like the previous one) random (occur at any time of the day or night), and are rarely precipitated by specific environmental, psychological, or physiological events. Some individuals have several different types of seizures, but most have one type that expresses itself in partial or complete form

5. Seizure disorder Is a general term that is usually used to include any 1 of several disorders, including epilepsy febrile seizures single seizures symptomatic seizures secondary to metabolic, infectious, or other etiologies (e.g., hypocalcemia, meningitis).

6. Reflex seizures(Stimulus-Precipitate seizures) precipitated by a sensory stimulus or activity Because no known reflex may be involved, more appropriate terms may be sensory-precipitated or stimulus-sensitive seizures Stimuli may be external (light, patterns, music, brushing teeth) or internal (math, reading, thinking, self-induced) people in the risk age-group are 5-25 yr. Patients tend to outgrow photosensitive or pattern-induced seizures in their 30s. Prevention: avoidance of stimuli watching tv at >8 ft, closing of one eyes in provocative situation

7. Epilepsy Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate seizures and by the neurobiologic , cognitive, psychological, and social consequences of this condition(conceptual definition) defined by any of the following conditions 1. At least two unprovoked (or reflex) seizures occurring > 24 h 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

8. epilepsy If categorized by etiology, epilepsies are grouped into Genetic epilepsy (idiopathic epilepsy): is the direct result of a known or presumed genetic defect(s) that is not causative of a brain structural or metabolic disorder other than the epilepsy. (i.e. childhood absence epilepsy, Dravet syndrome) structural epilepsy(symptomatic epilepsy): caused by an underlying structural brain disorder(i.e. old stroke, HIE, tuberous sclerosis) metabolic epilepsy immune epilepsy : immune-mediated central nervous system (CNS) inflammation. (i.e. Autoimmune encephalitides such as anti-NMDA receptor encephalitis and anti-LG1 limbic encephalitis ) Infectious epilepsy; chronic infectious conditions such as tuberculosis and HIV unknown epilepsy . (cryptogenic epilepsy): the underlying cause of the epilepsy is till unknown

9. Epilepsy Epileptic syndrome Is a disorder manifests 1 or more specific seizure types has a specific age of onset and a specific prognosis. Epileptic encephalopathy Is an epilepsy syndrome in which there is a severe EEG abnormality which result in cognitive and other impairments in the patient Developmental encephalopathy denotes a disorder in which the underlying etiology (e.g., a specific gene mutation) contributes to a developmental delay independently of the patient’s seizure burden and/or EEG abnormalities.

10. Causes of seizures Causes of seizures can be remembered by the four M’s and the four I’s • The four M’s 1 . Metabolic and electrolyte disturbances: hyponatremia, hypoglycemia or hyperglycemia, hypocalcemia, hypomagnesemia, uremia, thyroid storm, hyperthermia. 2. Mass lesions : brain metastases, primary brain tumors, hemorrhage. 3 . Missing drugs (Noncompliance) with anticonvulsants in patients with epilepsy. 4. Miscellaneous Hypertensive encephalopathy: severe hypertension can cause cerebral edema. Acute withdrawal from alcohol, benzodiazepines, barbiturates.

11. Causes of seizures • The four I’s 1. Intoxications : cocaine,lithium,theophylline , carbon monoxide poisoning. 2. Infections : malaria, bacterial or viral meningitis, encephalitis, brain abscess, sepsis. 3. Ischemia: stroke, TIA (common cause of seizure in elderly patients). 4. Increased ICP: for example, due to trauma

12. SEIZURE PRECIPITANTS More than 50% of subjects with epilepsy reported at least one precipitant Emotional stress sleep deprivation fatigue fever or illness flickering light Missing antiepileptic medication doses.(carbamazepine and oxcarbazepine, severe) menstruation.( catamenial epilepsy )

13. classification The International League Against Epilepsy (ILAE) operational classification of seizure types divides epileptic seizures into four categories based on the presumed mode of seizure onset Focal Generalized unknown unclassified

14. classification

15. Focal seizure the first clinical and electroencephalographic (EEG) changes suggest initial activation of a system of neurons limited to part of one cerebral hemisphere account for approximately 40% of seizures in children focal seizures with preserved awareness (previously called simple partial seizures) and focal seizures with impaired awareness (previously called complex partial seizures) also described as motor or nonmotor seizures

16. Focal Seizures can progress into secondary generalized seizures, called focal to bilateral tonic- clonic seizures, although less commonly the secondary generalized seizure may be tonic, clonic , or atonic.

17. manifestations Focal seizures can have motor and/or sensory components(physical symptoms), depending on which areas of what is termed eloquent cortex become involved otherwise it causes what is termed as the silent or noneloquent cortex Electrographic seizures or subclinical seizures . Subclinical electrographic seizures, particularly during sleep, can be associated with deterioration in development, behavior, attention, and learning Focal motor seizures produce rhythmic jerking ( clonic ) movements of the limb contralateral to the primary motor cortex involved.

18. Occasionally after a seizure, there is persistent focal weakness or hemiparesis known as Todd palsy , which is strongly suggestive of a contralateral focal onset to the seizure

19. FOCAL AWARE SEIZURE awareness is not altered in the course of the seizure. The manifestation depend on the brain region involved. However, it may originate in silent areas, and the first clinical manifestations may reflect seizure spread to other brain regions These can take the form of sensory seizures (auras, called focal aware seizures) or brief motor seizures(tonic, clonic , or atonic seizures) Often there is a motor (Jacksonian) march Unlike tics, motor seizures are not under partial voluntary control; more often stereotyped and are less likely to manifest different types in a given patient

20. FOCAL AWARE SEIZURE FAS and auras may have important lateralizing and localizing value adversive head and eye movements to the contralateral side postictal (Todd) paralysis that can last minutes or hours, and sometimes longer. Auras are typically short in duration, lasting seconds to minutes. Are different from prodrome may occasionally be prolonged, in which case they are called aura continua , which is a form of focal nonconvulsive status epilepticus without impairment of consciousness

21. FOCAL SEIZURES WITH IMPAIRED AWARENESS transient impairment of awareness (very subtle, manifesting with slight confusion, fuzziness, or slowing of responses, to no response and amnesia) The patient might appear to react to some of the stimulation around him or her but does not later recall the epileptic event. The seizure starts with aura or loss of consciousness often a motionless stare, marks the onset of the period of impaired awareness

22. FOCAL WITH IMPAIRED AWARENESS are often preceded by an aura that is stereotypic for the patient. rising abdominal feeling déjà vu or déjà vécu , a sense of fear, complex visual hallucinations, simple visual experiences (occipital lobe) micropsia or macropsia (temporal lobe) generalized difficult-to-characterize sensations (frontal lobe), focal sensations (parietal lobe) An aura may be suspected in very young children if there is a change in behavior before seizures, such as interrupting an activity to seek out parents, or complaining of abdominal pain

23. FOCAL WITH IMPAIRED AWARENESS The impaired awareness is usually accompanied by automatisms The most common type of motor activity in this seizure type is automatism. Automatism: are involuntary, semi purposeful, automatic behaviors that have a wide range of manifestations. Pervasive Automatisms Inappropriate continuation of previously ongoing activity. Denovo Automatisms Start after seizure onset are called de novo automatisms.

24. FOCAL WITH IMPAIRED AWARENESS Oroalimentary automatisms Include lip smacking, chewing, swallowing, and other mouth movements. Ictal spitting and ictal drinking can be considered forms of oroalimentary automatisms. Manual or Pedal Automatisms Affecting the distal extremities Manual or pedal automatisms can be bilateral or unilateral. Gestural automatisms include extremity movements such as those used to enhance speech. Hyperkinetic automatisms imply an inappropriately rapid sequence of movements that predominantly involve axial and proximal limb muscles. The resulting motion can be thrashing, rocking, pelvic thrusting, kicking, or bicycling motions.

25. FOCAL WITH IMPAIRED AWARENESS More recently introduced categories for upper extremity automatisms are manipulative and non-manipulative Manipulative automatisms involve picking and fumbling motions, typically reflecting interaction with the environment. Non-manipulative automatisms tend to be rhythmic and do not involve interaction with the environment. Distal non-manipulative upper-extremity automatisms have been described with the acronym RINCH (rhythmic ictal nonclonic hand) movements

26. FOCAL WITH IMPAIRED AWARENESS Often there is salivation, dilation of the pupils, and flushing or color change FIAS commonly arise from the temporal lobe; the frontal lobe is the second most common site of seizure origin.

27. The patient is typically confused following the seizure, and the transition to full recovery of consciousness may range from seconds up to an hour or longer. Examination immediately following the seizure may show an anterograde amnesia or transient neurologic deficits (such as aphasia, hemi-neglect, or visual loss) caused by postictal inhibition of the cortical regions most involved in the seizure.

28. Focal to Bilateral Tonic- Clonic Seizures These seizures may start as focal aware or FIAS, or as GTC The transition to bilateral tonic- clonic activity usually involves versive head turning in a direction contralateral to the hemisphere of seizure onset

29. Focal to Bilateral Tonic- Clonic Seizures The bilateral tonic phase may be asymmetrical, with flexion on one side and extension on the other. This has been called figure-of-four posturing

30. Focal to Bilateral Tonic- Clonic Seizures The evolution from tonic to clonic activity is gradual phase of high-frequency tremor has been referred to as the tremulous or vibratory phase of the seizure. And sebsequentlry decrease in frequency The clonic activity may end on one side of the body first In addition, there may be a late head turn ipsilateral to the hemisphere of seizure origin After the motor activity stops, the individual is usually limp and has a loud snoring respiration often referred to as stertorous respiration

31. Focal Seizure Semiology in Relation to Localization Focal seizures of temporal lobe origin mesial temporal amygdalohippocampal origin. Starts with aura, an epigastric sensation frequently with a rising character. less commonly fear, anxiety, and other emotions, déjà vu and jamais vu, nonspecific sensations, and autonomic changes such as palpitation and gooseflesh. Olfactory and gustatory auras are uncommon and are more likely with tumoral mesial temporal lobe epilepsy

32. Focal seizures of temporal lobe origin FIAS may start with an aura or with altered consciousness. Automatisms are one of the most prominent manifestations are most commonly manipulative, with picking or fumbling. the contralateral upper extremity is commonly involved in dystonic posturing manipulative automatisms tend to be ipsilateral, Nonmanipulative automatisms tend to be contralateral, often preceding overt dystonic posturing. Well-formed ictal speech (nondominant temporal lobe origin.) Postictal aphasia is (dominant temporal lobe seizures )

33. Focal seizures of lateral temporal lobe origin much less common than those of mesial temporal origin. They cannot be reliably distinguished based on their semiology, Auditory auras are the most common auras referable to the lateral temporal cortex, usually implying involvement of the Heschl gyrus Visual hallucination and vertigo

34. Focal seizures of frontal lobe origin FAS can be motor with focal clonic activity, can originate in the motor cortex, or can be the result of spread to the motor cortex. Asymmetrical tonic seizures or postural seizures are usually related to involvement of the supplementary motor area in the mesial frontal cortex anterior to the motor strip. The best-known posturing pattern is the fencing posture in which the contralateral arm is extended and the ipsilateral arm is flexed When these seizures originate in the supplementary motor area, consciousness is usually preserved

35. Usually occur at sleep and are very brief Hyperkinetic automatisms(AKA hypermotor seizures) with frenzied behavior and agitation can be confused with psychiatric diseases

36. Parietal lobe seizures Somatosensory seizures (tingling, pins and needles, numbness, burning, or pain, feeling of movement, vertigo, visual illusions) Occipital lobe Visual manifestations Positive: simple( e.g flashing of light) vs complex( e.g familiar face) Negative: ictal blindness or hemianopia

37. Generalized seizures are defined as seizures in which the first clinical changes indicate initial involvement of both hemispheres. Motor involvement, if present, is bilateral, as are the initial EEG changes. Consciousness is impaired in most generalized seizures, but not in all; for instance, brief myoclonic seizures and some atonic seizures may not be associated with any impairment of consciousness

38. Generalized Seizures ABSENCE SEIZURES Typical start at 5-8 yr of age Are very brief, but occurs up to hundreds of times per day. Do dot have aura or post ictal phase eyelid flutter or upward rolling of the eyes but typically not by the usually more florid automatisms seen in focal seizures with impaired awareness (absence seizures can have simple automatisms such as lip smacking or picking at clothing, and the head can very minimally fall forward).

39. immediate resumption of what the patient was doing before the seizure. Hyperventilation for 3-5 min can precipitate the seizures and the accompanying 3-Hz spike-and–slow-wave discharges The presence of eye closure eyelid myoclonia ( Jeavons syndrome) and periorbital, perioral, or limb myoclonic jerks (the latter called myoclonic absences) with the typical absence seizures usually predicts difficulty in controlling the seizures with medications. Early-onset absence seizures (<4 yr of age) or drug resistance should trigger evaluation for a glucose transporter defect,

40. Atypical absence seizures myoclonic components and longer lapse of conciousnes tone changes of the head (head drop) and body more difficult to treat They are precipitated by drowsiness usually accompanied by 1- to 2-Hz spike-and–slow-wave discharges usually associated with diffuse or multifocal structural abnormalities of the brain and therefore may accompany other signs of neurologic dysfunction such as mental retardation .

41. absence seizures Juvenile absence seizure are similar to typical absences Occur at a later age are accompanied by 4- to 6-Hz spike-and–slow-wave and polyspike -and–slow-wave discharges. These are usually associated with juvenile myoclonic epilepsy

42. True absence seizures ("petit mal") cannot be predictably interrupted by calling the child's name or by tactile stimulation, as can the staring spells or behavioral inattentiveness ("spacing out") commonly seen in children with attention deficit hyperactivity disorder (ADHD). Absence seizures often interrupt conversation or ongoing physical activity such as eating and play, whereas a pseudoabsence of inattention or "daydreaming" tend to occur during more sedentary activity ( eg , sitting at a school desk). Absence seizures usually occur multiple times during the day and last only a few (rarely more than 10 to 30) seconds

43. GENERALIZED MOTOR SEIZURES The most common generalized motor seizures are generalized tonic- clonic in adults but it is rare in new born Tonic phase usually starts with loss of consciousness and sudden sustained contraction of facial, axial, and limb muscle groups with a sudden cry secondary to contraction of the diaphragm and chest muscles against a partially closed glottis (the ictal cry ). upward rolling of the eyes The tonic contraction is maintained for seconds to 10s of seconds, during which time the child falls if standing, is apneic and may become cyanotic, may bite the sides of their tongue, and may pass urine

44. GENERALIZED MOTOR SEIZURES clonic phase begins when the tonic contraction is repeatedly interrupted by momentary relaxation as the seizure progresses, shows slowing of the rhythmic contractions until the seizure stops, usually 1-2 min later. Incontinence and a postictal period often follow

45. GENERALIZED MOTOR SEIZURES Post ictal period few minutes up to several hours with semicoma or obtundation and postictal sleepiness weakness ataxia hyper- or hyporeflexia headaches.

46. GENERALIZED MOTOR SEIZURES Generalized tonic, atonic, and astatic seizures often occur in severe generalized pediatric epilepsies. Generalized myoclonic seizures can occur in either benign or difficult-to-control generalized epilepsies Atonic seizure: Sudden loss of postural muscle tone lasting 1–2s. Consciousness is briefly impaired but there is usually no postictal confusion. Myclonic seizure: Sudden and brief muscle contraction that may involve one part of the body or the entire body. Metabolic disorders, degenerative CNS diseases, or anoxic brain injury.

47. GENERALIZED MOTOR SEIZURES Epileptic spasm(Previously ‘’unclassified’’) Briefly sustained flexion or extension of predominantly proximal muscles, including truncal muscles (‘’SELAAM seizure’’) Predominantly in infants. Hypsarhthymia on EEG.

48. BENIGN GENERALIZED EPILEPSIES Childhood absence epilepsy starts in mid-childhood and most patients outgrow it before adulthood. Chxd by typical absence seizures (TAS) appearing in otherwise healthy school-aged children. Approximately 25% of patients also develop generalized tonic- clonic seizures, half before and half after the onset of absences

49. DIAGNOSIS — Childhood absence epilepsy (CAE) a diagnosis of CAE requires all of the following: Age at onset of 4 to 10 years Normal neurological and developmental state Brief (4 to 20 sec) and frequent ( 10/ day) absence seizures, with abrupt and severe loss of consciousness Generalized rhythmic spikes or double spike wave discharges at around 3 Hz the following criteria are exclusionary for the diagnosis of CAE: Other seizure types preceding or observed during the active stage of typical absence seizures Massive and sustained eyelid, perioral, head or limb myoclonias Mild or no impairment of consciousness during the spike wave discharge Spike wave discharges of less than 4 seconds More than 3 spikes or spike wave fragmentation Visual or other sensory seizure precipitants

50. SEVERE GENERALIZED EPILEPSIES Severe generalized epilepsies are associated with intractable seizures and developmental delay Early myoclonic infantile encephalopathy Early infantile epileptic encephalopathy ( Ohtahara syndrome) myoclonic epilepsy of infancy (Dravet syndrome) West syndrome Lennox- Gastaut syndrome Myoclonic astatic epilepsy ( Doose syndrome) Progressive myoclonic epilepsies Nodding syndrome Landau- Kleffner syndrome Amenably treatable metabolic epilepsies

51. Febrile seizure Definition: are seizures 1.that occur between the ages of 6 and 60 mo (peak 12-18 mo ) 2. a temperature of 38°C (100.4°F) or higher 3. not the result of CNS infection or inflammation 4. Absence of metabolic abnormality that may produce convulsions 5. Occurs in the absence of a history of prior afebrile seizures . Febrile seizures are not considered a form of epilepsy

52. classification based on clinical features, Febrile seizures are divided into two categories 1. simple febrile seizure: a generalized, usually tonic- clonic last less than 15 minutes do not recur in a 24-hour period very short postictal state and usually return to their baseline normal behavior and consciousness within minutes of the seizure With no neurologic deficits (no pre, peri, postnatal brain damage with normal psychomotor development(AAP,1999)

53. Classification 2. Complex: focal onset (shaking limited to one limb or one side of the body) last longer than 15 minutes, or occur more than once in 24 hours associated with post ictal neurological abnormality or with previous neurologic deficit With no treatment(for duration)

54. Others Febrile status epilepticus is a febrile seizure lasting longer than 30 min. Febrile infection–related(refractory) epilepsy syndrome (FIRES): seen in previously healthy 3-15 age children(predominantly above 5) Male(mostly) associated with an encephalitis-like illness but without an identifiable infectious agent. This children experiences a nonspecific febrile illness followed by prolonged refractory status epilepticus

55. FIRES FIRES has biphasic presentation Acute phase: seizure activity lasting 1-12 weeks Chronic phase: refractory seizures cluster every 2-4 weeks, which is multifocal Treatment is difficult, refractory to antiepileptic drugs and 30% of cases end in death, 66-100% survivors have intellectual disability

56. FACTORS LEADING TO FEBRILE SEIZURES It have familiar tendency: In some family inherited as autosomal dominant. Genes associated with febrile seizures include SCN1A, SCN1B, SCN9A, and CPA6. a dysregulation between the proinflammatory IL-1 β, IL-6, and IL-8 cytokines and anti-inflammatory ILR-1A cytokines has been associated with febrile status epilepticus ILR-1A/IL-8 ratio tells the risk for developing mesial temporal lobe epilepsy later in life Iron deficiency is associated with an increased risk of febrile seizures

57. Febrile seizure associated epilepsies few epilepsy syndromes typically start with febrile seizures; these are: generalized epilepsy with febrile seizures plus (GEFS+), Severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome), temporal lobe epilepsy secondary to mesial temporal sclerosis. GEFS+ is an autosomal dominant syndrome. Onset, in early childhood, and remission is usually in mid childhood. It is characterized by multiple febrile seizures and by several subsequent types of afebrile generalized seizures with variable degrees of severity. Mutations in the SCN1A

58. Dravet syndrome is the most severe. It constitutes a distinct entity, onset is in infancy. It is initially characterized by febrile and afebrile unilateral clonic seizures that recur every 1 or 2 mo. Seizures subsequently start to occur with lower fevers and then without fever. During the second year of life, myoclonus, atypical absences, and focal seizures occur frequently and developmental delay usually follows. Mutations in the SCN1A gene are the most common cause of Dravet syndrome (causing ~ 80% of all cases) The majority of patients who had prolonged febrile seizures and encephalopathy after vaccination turn out to have Dravet syndrome mutations

59. prognosis Simple febrile seizures do not have an increased risk of mortality Complex febrile seizures may have an approximately 2-fold long-term increase in mortality rates, as compared with the general population, over the subsequent 2 yr , probably secondary to a coexisting pathology. Risk of recurrence: 30% of those experiencing a first episode, 50% after two or more episodes, and 50% of infants younger than 1 yr of age at febrile seizure onset.

60. Recurrence of febrile seizure

61. prognosis only 5% develop later epilepsy but 15% of epileptic patient have had febrile seizure

62. evaluation Each child who presents with a febrile seizure requires a detailed history and a thorough general and neurologic examination. Febrile seizures often occur in the context of otitis media; roseola and human herpesvirus (HHV) 6 infections; and infections with norovirus, enteroviruses, Shigella, or similar agents, making the evaluation more demanding. In patients with febrile status epilepticus, HHV-6B (more frequently) and HHV-7 infections account for 30% of the cases.

63. Lumbar Puncture for all infants younger than 6 mo of age who present with fever and seizure, if the child is ill-appearing, at any age if there are clinical signs or symptoms of concern. A lumbar puncture is an option in a child 6-12 mo of age who is deficient in Haemophilus influenzae type b and Streptococcus pneumoniae immunizations or for whom the immunization status is unknown. Optional for child who was taking antibiotic EEG EEG need not be performed as part of routine evaluation. It should generally be restricted to special cases in which epilepsy is highly suspected An EEG would not predict the future recurrence of febrile seizure or epilepsy rather used to delineate the type of epilepsy if an EEG is indicated, it is delayed until or repeated after more than 2 wk have passed..

64. Blood Studies are not routinely recommended in the workup of a child with a first simple febrile seizure. Unless we want to identify the cause of the fever If clinically indicated (e.g., dehydration), these tests should be performed Blood glucose should be measured A low sodium level is associated with a higher risk of recurrence of the febrile seizure within the following 24 hr

65. Imaging Not recommended for simple febrile seizure Can be done for complex seizure and febrile status epilepticus particularly if the child is neurologically abnormal

66. Treatment algorithm

67. Gelastic and dacrystic Gelastic seizure are often called laughing seizures, dacrystic is crying and weeping Mechanical laughing and giggling Both are focal seizures that originates from hypothalamus Gelastic is brief, lasts 10-30sec Develops in infancy and early childhood Common cause is hypothalamic hamartoma, temporal lobe if only dacrystic 50% experiences precocious puberty

68. Clinical manifestation Sudden starting and stopping of laughing Looks like forced to smile Grunting Lip smacking The patient looks that he/she is afraid and going t panic Uncontrolled crying Grimacing Sad facial expression Lacrimation Subjective feeling of sadness

69. Status epilepticus (SE) Status epilepticus (SE) is a medical emergency that should be anticipated in any patient who presents with an acute seizure. Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures……conceptual definition

70. This definition has 2 operational dimension T1: the time beyond which the seizure is considered continuous. Called abnormally prolonged seizure T2: The time after which there is a risk of long term consequences SE is defined as continuous convulsive activity or recurrent generalized convulsive seizure activity without regaining of consciousness (t 1 = 5 min, t 2 ≥ 30 min) for GTC for adu Focal with impaired awareness (t1 = 10 min, t2 = 30 min) absence SE (t1 = 10-15 min, t2 = unknown).

71. Status epilepticus convulsive status epilepticus (generalized tonic, clonic , or tonic- clonic ), nonconvulsive status epilepticus ( a confusional state, dementia, hyperactivity with behavioral problems, fluctuating mental status, hallucinations, paranoia, aggressiveness ) myoclonic status epilepticus epilepsia partialis continua neonatal status epilepticus

72. The incidence of SE ranges between 10 and 60 per 100,000 SE is most common in children younger than 5 yr of age, (> 100 per 100,000 children) Febrile status epilepticus is the most common type of SE in children

73. Refractory status epilepticus is SE that has failed to respond to therapy, at least two medications (such as a benzodiazepine and another medication). Previously minimum duration of 30 min, 60 min, or even 2 hr was cited. Super refractory status epilepticus is SE that has failed to resolve within 24 hr or more despite therapy that includes a continuous infusion such as midazolam and/ or pentobarbital

74. New-onset refractory status epilepticus (NORSE) has been identified as a distinct entity that can be caused by almost any of the causes of SE in a patient without prior epilepsy. It also is often of unknown etiology, presumed to be encephalitic or postencephalitic, can last several weeks or longer, and often, but not always, has a poor prognosis Devastating epileptic encephalopathy in school-age children (DESC), also called fever-induced refractory epileptic encephalopathy in school age children (FIRES), is a syndrome of refractory SE that is associated with acute febrile infections, appears to be parainfectious in nature, and appears to be highly drug resistant but is often responsive to the ketogenic diet

75. classification For classification of SE we propose the following four axes: 1 Semiology 2 Etiology 3 EEG correlates 4 Age

76. Axis 1: Semiology The two main taxonomic criteria are: 1. The presence or absence of prominent motor symptoms 2 The degree (qualitative or quantitative) of impaired consciousness Those forms with prominent motor symptoms and impairment of consciousness may be summarized as convulsive SE as opposed to the nonconvulsive forms of SE (NCSE)

77. Axis 2: Etiology known” or “symptomatic” is used for SE caused by a known disorder, which can be structural, metabolic, inflammatory, infectious, toxic, or genetic.

78. Causes of status epilepticus 1 Cerebrovascular diseases a Ischemic stroke b Intracerebral bleeding c Subarachnoid bleeding d Subdural hematoma 2 CNS infections a Acute bacterial meningitis b Chronic bacterial meningitis c Acute viral encephalitis (including , herpes simplex encephalitis, human herpesvirus 6) d Progressive multifocal leukoencephalopathy (PML) e Cerebral toxoplasmosis f Tuberculosis g Neurocysticercosis h Cerebral malaria i Atypical bacterial infections j HIV-related diseases k Prion diseases (Creutzfeldt-Jakob disease, CJD) l Protozoal infections m Fungal diseases n Subacute sclerosing panencephalitis o Progressive Rubella encephalitis 3 Neurodegenerative diseases b Corticobasal degeneration c Frontotemporal dementia 4 Intracranial tumors a Glial tumors b Meningioma c Metastases d Lymphoma e Meningeosis neoplastica f Ependymoma g Primitive neuroectodermal tumor (PNET)

79. 5 Cortical dysplasias a Focal cortical dysplasia (FCD) II, tuberous sclerosis complex (TSC), b Ganglioglioma, gangliocytoma d Subcortical band heterotopia spectrum e Lissencephaly f Familial and sporadic polymicrogyria g Familial and sporadic schizencephaly h Infratentorial malformations (e.g., dentate dysplasia, mamillary dysplasia, etc.) 6 Head trauma a Closed head injury b Open head injury c Penetrating head injury 7 Alcohol related a Intoxication b Alcohol withdrawal c Late alcohol encephalopathy with seizures d Wernicke encephalopathy 8 Intoxication a Drugs b Neurotoxins c Heavy metals 9 Withdrawal of or low levels of antiepileptic drugs 10 Cerebral hypoxia or anoxia 11 Metabolic disturbances

80. 12 Autoimmune disorders causing SE a Multiple sclerosis b Paraneoplastic encephalitis c Hashimoto’s encephalopathy d Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis e Anti–voltage–gated potassium channel receptor encephalitis (including anti–leucine–rich glioma inactivated 1 encephalitis) f Anti-glutamic acid decarboxylase antibody associated encephalitis g Anti–alpha–amino–3–hydroxy–5– methylisoxazole – 4–propionic acid receptor encephalitis h Seronegative autoimmune encephalitis i Rasmussen encephalitis j Cerebral lupus (systemic lupus erythematosus) k CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome l Adult-onset Still’s disease m Goodpasture syndrome n Thrombotic thrombocytopenic purpura ( Moschcowitz syndrome, Henoch Sch€ onlein purpura) 13 Mitochondrial diseases causing SE a Alpers disease b Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) c Leigh syndrome d Myoclonic encephalopathy with ragged red fibers (MERRF) e Neuropathy, ataxia, and retinitis pigmentosa (NARP)

81. 4 Chromosomal aberrations and genetic anomalies a Ring chromosome 20 b Angelman syndrome c Wolf- Hirshhorn syndrome d Fragile X syndrome e X-linked mental retardation syndrome h Down syndrome (trisomy 21) a Sturge-Weber syndrome 16 Metabolic disorders a Porphyria c Wilson disease d Adrenoleukodystrophy f Cobalamin C/D deficiency g Ornithine transcarbamylase deficiency h Hyperprolinemia u Carnitine palmitoyltransferase deficiency v Succinic semialdehyde dehydrogenase deficiency 17 Others a Familial hemiplegic migraine b Infantile onset spinocerebellar ataxia (SCA) c Wrinkly skin syndrome d Neurocutaneous melanomatosis e Neuroserpin mutation f Wolfram syndrome g Autosomal recessive hyperekplexia h Cockayne syndrome i Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) j Robinow syndrome k Malignant hyperpyrexia

82. Axis 3: Electroencephalographic correlates Currently there are no evidence-based EEG criteria for SE. EEG patterns in SE can be described : 1 Location: generalized (including bilateral synchronous patterns), lateralized, bilateral independent, multifocal. 2 Name of the pattern : Periodic discharges, rhythmic delta activity or spike-and-wave/sharp-and-wave plus subtypes. 3 Morphology: sharpness, number of phases (e.g., triphasic morphology), absolute and relative amplitude, polarity. 4 Time-related features : prevalence, frequency, duration, daily pattern duration and index, onset (sudden vs. gradual), and dynamics (evolving, fluctuating, or static). 5 Modulation: stimulus-induced vs. spontaneous. 6 Effect of intervention (medication) on EEG

83. Axis 4: Age 1 Neonatal (0 to 30 days). 2 Infancy (1 month to 2 years). 3 Childhood (> 2 to 12 years). 4 Adolescence and adulthood (> 12 to 59 years). 5 Elderly (≥ 60 years).

84. mechanism 1. failure of desensitization of AMPA glutamate receptors 2. reduction of GABA-mediated inhibition as a result of intracellular internalization of GABA A receptors During SE, there is an increased cerebral metabolic rate and a compensatory increase in cerebral blood flow that, after approximately 30 min, is not able to keep up with the increases in cerebral metabolic rate. This contributes to neuronal injury resulting from SE

85. investigation Glucose complete blood count Sodium, calcium, magnesium, basic metabolic panel continuous EEG ruling out pseudo–status epilepticus or other movement disorders type of SE distinguish between postictal depression and later stages of SE in which the clinical manifestations are subtle (e.g., minimal myoclonic jerks) or absent (electroclinical dissociation), can help in monitoring the therapy, particularly in patients who are paralyzed and intubated.

86. Blood and spinal fluid cultures, toxic drug screens, and Tests for inborn errors of metabolism are often needed Neuroimaging must be considered after the child has been stabilized, especially if it is indicated by the clinical manifestations

87. Therapy All patients with SE, even the ones who respond, need to be admitted to the intensive care unit for completion of therapy and monitoring. The goal is to stop electrographic seizure activity before reducing the therapy.(flattening of electrical activities for 8-20 sec)

88. potential side effect is respiratory depression If seizures persist 5 min after the initial benzodiazepine dose, a second dose of the drug should be given Valproate should avoided in patients younger than 2 yr of age and in those with hepatic dysfunction or mitochondrial disease.

89. Approach to the child with seizure disorder Emergency support There is a risk of aspiration and injury positioning the patient on his or her side clearing the mouth if it is open loosening tight clothes or jewelry gently extending the head if possible, insertion of an airway by a trained professional. The mouth should not be forced open with a foreign object (this could dislodge teeth, causing aspiration) or with a finger in the mouth (this could result in serious injury to the examiner’s finger)

90. HISTORY a careful history is the cornerstones of an accurate diagnosis. A detailed account of the child's behavior preceding, during, and following a "spell" is critical. This may require a follow-up visit with witnesses who actually saw the "seizure.“ remember to include the child in the conversion

91. HISTORY Characterization of the abnormal body movement o Duration o Mode of onset and its progression o Frequency o Time of occurrence o State of consciousness o Generalized or focal onset ▪ If it is focal from which part, does it start from face or extremity.

92. HISTORY Aura:▪ It could be visual, olfactory, auditory, déjà vu, tingling, chest tightness, epigastric pain, fear. o Child behavior before the event like cyanosis, urine on cloth. o Vocalization o Posture of the patient o Automatism: ▪ Example: -chewing, salivation, dilation of pupils, flushing, lip smacking, picking at clothes. o Postictal state ▪ Sleep, headache, hemi paresis, aphasia.

93. Setting in which episodes occur: Most seizures occur at random and without warning ●Was the child taking medication (prescription and over-the-counter) or herbal substances prior to the seizure? o Similarly, a history of cognitive regression can suggest a degenerative or metabolic disease. History of personality change or symptoms of increased intracranial pressure can suggest an intra- cranial tumor.

94. o Any evidence of active CNS infection. o Any history of trauma. • Risk factor for the underlying cause • Previous similar attack • Family history • Immunization history • Detailed prenatal history (asphyxia, jaundice, meningitis) • Detailed developmental history

95. PHYSICAL EXAMINATION Dysmorphic features and other congenital anomalies,  eye examination.(congenital ocular defects,retinal changes associated with neurocutaneous and neurodegenerative disorders, increased icp ) abdominal examination(hepatosplenomegaly, suggesting a storage disease) A cardiac examination, including an ECG skin examination(café-au-lait spots of neurofibromatosis, the nevi of the linear nevus syndrome, swirling hypopigmentation of Ito syndrome, ash leaf spots of tuberous sclerosis)

96. investigation ELECTROENCEPHALOGRAM — Virtually every child with recurrent seizures should have an EEG awake and while sleeping. It should be obtained as soon as possible (the first 24 hours after a seizure or within time frame when the seizure usually occurs) Up to 30 to 50 percent of children with epilepsy will be "EEG-negative.

97. NEUROIMAGING MRI is more sensitive than CT for detecting brain malformations and dysplastic lesions, as well as subtle temporal lobe pathology, particularly in the hippocampus, a common site of seizure onset Gadolinium contrast is not routinely requested, but is used when tumor, vascular malformation, inflammation, or infection is suspected A CT scan is often used for emergency department is better than MRI in identifying calcifications associated with congenital infections(cytomegalovirus and toxoplasmosis

98. LABORATORY TESTING RPG CBC ESR, CRP Arterial blood gas and pH Electrolyte panels Organ function test(liver, renal)

99. A lumbar puncture is only indicated if there is reason to suspect an infectious or inflammatory etiology (e.g., if the patient is febrile). Toxicology screening should similarly be restricted to specific clinical circumstances Serum and CSF autoantibodies ( eg , anti-N-methyl-D-aspartate receptor [NMDAR] antibodies Chromosomal karyotype

100. TREATMENT COUNSELING educating the family and the child about the disease, its management, and the limitations it might impose and how to deal with them. Avoiding precipitants, Restrictions on driving (in adolescents), swimming, and certain sports are usually necessary

101. TREATMENT

102. Medical therapy is generally the first-line treatment after the diagnosis of epilepsy has been made. Its goal should be complete seizure freedom in the absence of medication side effects. The treating physician must have a low threshold for reevaluating the diagnosis when therapy fails, particularly when the diagnosis of epilepsy is based on history alone without supportive EEG or imaging data TREATMENT

103. Mechanisms of AED

104. Focal onset Seizures For partial-onset seizures, carbamazepine or phenytoin may be used first, but newer drugs have clear pharmacokinetic advantages, particularly absence of enzyme induction Although oxcarbazepine and topiramate are the only ones with official FDA indications, lamotrigine, gabapentin, and levetiracetam have clinical trial evidence supporting their use as initial monotherapy. A large community-based study found that lamotrigine was significantly better than carbamazepine, gabapentin, and topiramate and had a nonsignificant advantage compared to oxcarbazepine with respect to time to treatment failure

105. However, lamotrigine requires slow titration and would not be an appropriate first choice when a rapid onset of action is needed. When rapid therapeutic effect is required, oxcarbazepine and levetiracetam may be the drugs of choice because they can be started at an effective dose. Topiramate also requires slow titration. Because of its cognitive adverse effects, it is not generally the first drug of choice unless comorbidities (e.g., migraine, obesity) favor its use

106. Generalized onset Seizures For generalized-onset seizures, the initial AED is dependent on the seizure type(s). For pure generalized absence seizures, ethosuximide is the first drug of choice, based on the recent comparative trial in which it had the best balance of efficacy and tolerability Valproate was equally effective and may be the best choice if there are concomitant generalized tonic- clonic seizures or generalized myoclonic seizures because ethosuximide efficacy is limited to generalized absence seizures

107. West syndrome is best treated with hormonal therapy in the form of either ACTH injections , of (75 units/m2 BID IM) for 2 wks and tapered over 2, or possibly, oral steroids vigabatrin Dravet syndrome is usually treated with benzodiazepines such as clobazam and with valproate. The ketogenic diet can also be useful

108. Initiating Therapy For all epilepsy indications, treatment is initiated with an AED monotherapy. In the absence of urgency, it is preferable to start at a low dose and titrate slowly, even for AEDs that can be started at a higher effective dose. to build tolerance to adverse effects such as sedation Two approach 1 . start with maintenance dose : as zonisamide , phenobarbital, phenytoin, or valproate, 2. Start with low dose and gradually increase: oxcarbazepine, carbamazepine, topiramate, and perampanel Other can work eitherway : levetiracetam and gabapentin

109. If a medication fails due to lack of efficacy, then we may choose either replacement monotherapy or adjunctive therapy with another medication. If the initial therapy has been completely ineffective, then replacement monotherapy is the best choice. If the initial therapy was partially effective, adjunctive therapy may be a consideration. If medication failure is due to lack of tolerability, then replacement monotherapy is the clearly preferable option.

110. Replacement monotherapy usually requires initially adding the new AED before withdrawing the old agent However, overnight switch is possible for some AEDs such as carbamazepine and oxcarbazepine Adjunctive therapy should take into consideration any possible interactions between the medications in question When adding a new AED, the doses used are often affected by the background medications.

111. Adjunctive therapy All AEDs are approved for adjunctive therapy Consider possible interactions the doses of new AED are often affected by the background medications Some have of synergistic effect.(lamotrigine and valproate, lamotrigine and levetiracetam )

112. On the other hand, mechanism of action may be a predictor of adverse effects from pharmacodynamic interactions. For example, dizziness, ataxia, and diplopia are more likely when combining lacosamide with another agent that acts on the sodium channel The neurologist will often need to reduce the dose of the initial AED when adding a second AED with a similar mechanism of action.

113. Patients with drug resistance epilepsy Reconsider the diagnosis treatable metabolic disorders that can manifest as drug-resistant epilepsy include pyridoxine-dependent and pyridoxal-responsive epilepsy; cerebral folate deficiency; other vitamin-responsive conditions (such as biotin/thiamine–responsive basal ganglia disease and riboflavin-responsive epilepsy); neurotransmitter disorders; Biotinidase deficiency; glucose transporter 1 deficiency (responds to the ketogenic diet); serine synthesis defects; creatine deficiency syndromes; untreated phenylketonuria; developmental delay, epilepsy, and neonatal diabetes; and hyperinsulinemia–hyperammonemia.

114. Seizure aggravation with AED Seizure aggravation may occur with a number of medications This is most common in generalized epilepsy, where AEDs such as carbamazepine, oxcarbazepine, phenytoin, tiagabine, gabapentin, or vigabatrin may increase the number of seizures or provoke the appearance of new seizure types (myoclonic or absence seizures) at a therapeutic level.

115. Seizure aggravation with AED any AED may cause a paradoxical increase in seizures in some patients.( levetiracetam) May also occur in the setting of AED-induced encephalopathy or with sedation. For example, seizures may be exacerbated with valproate-induced encephalopathy, and sedative AEDs may exacerbate tonic seizures in patients with Lennox- Gastaut syndrome.

116. Monitoring For the older AEDs, before starting treatment, baseline laboratory studies, including complete blood count, platelets, liver enzymes, and possibly kidney function tests and urinalysis, are often obtained and repeated periodically. These laboratory studies are usually initially checked once or twice during the 1st mo , then every 3-4 mo thereafter Laboratory monitoring is more relevant early on but yield of significant adverse effects is low and the costs may be high.

117. Adverse reactions Virtually all AEDS can produce sleepiness, ataxia, nystagmus, and slurred speech Stevens- johnson -like syndrome: lamotrigine Rickets(bone mineralization): enzyme inducers(phenytoin, carbamazepine, primidone) Hyperammonemia: valproate Hepatic injury: valproate, children(<2) Suicidal ideation and action for adolescents

118. Discontinuation of AED Discontinuation of AEDs is usually indicated when children are free of seizures for at least 2 yr. In more severe syndromes, prolonged period of seizure freedom with treatment is often warranted before AEDs are withdrawn, if withdrawal is attempted at all. In self-limited (benign) epilepsy syndromes, the duration of therapy can often be as short as 6 mo 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

119. Older age of epilepsy onset, longer duration of epilepsy, presence of multiple seizure types, The need to use more than one AED are all factors associated with a higher risk of seizure relapse after AED withdrawal AED therapy should be discontinued gradually; often over a period of 3-6 mo. Abrupt discontinuation can result in withdrawal seizures or in status epilepticus.(phenobarbital and benzodiazepines) Seizure before 2-3 month is due to drug withdrawal, is after 2 to 3 month is relapse

120. EPILEPSY SURGERY If a patient has failed three drugs, the chance of achieving seizure freedom using AEDs is generally < 10%. Therefore, proper evaluation for surgery is necessary as soon as patients fail two or three AEDs usually within 2 yr of the onset of epilepsy and often sooner than 2 yr. Performing epilepsy surgery in children at an earlier stage (e.g., < 5 yr of age) allows transfer of function in the developing brain

121. Indications for surgery proof of resistance to AEDs used at maximum, tolerably nontoxic doses; absence of expected unacceptable adverse consequences of surgery properly defined epileptogenic zone

122. Epilepsy surgery is often used to treat drug-resistant epilepsy of a number of etiologies, including cortical dysplasia, tuberous sclerosis, polymicrogyria, hypothalamic hamartoma, Landau- Kleffner syndrome, and hemispheric syndromes, such as Sturge-Weber syndrome, hemi- megalencephaly , and Rasmussen encephalitis. metabolic or degenerative problems are not candidates for resective epilepsy surgery

123. Focal resection Hemispherectomy multiple subpial transection corpus callosotomy Vagus nerve stimulation Responsive neurostimulation (RNS) Focal resection and hemispherectomy result in a high rate (50–80%) of seizure freedom

124. SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP) Most common epilepsy related death, 17% risk factors include polytherapy with more than three AEDs, male gender, young age at epilepsy onset, developmental delay, poor AED compliance, nocturnal seizure Patients are usually found dead in their bed in a prone position with evidence suggesting a recent seizure. Respiratory, cardiogenic, and mixed respiratory/cardiogenic mechanisms have been hypothesized to cause SUDEP

125. Conditions That Mimic Seizures The misdiagnosis of epilepsy is estimated to be as high as 5–40 Often all that is needed to differentiate nonepileptic paroxysmal disorders from epilepsy is a careful and detailed history in addition to a thorough exam sometimes EEG or more advanced testing may be necessary.

126. Nonepileptic paroxysmal disorders can be classified according to the age at presentation and the clinical manifestations: (1) syncope and other generalized paroxysms, (2) movement disorders and other paroxysmal movements and postures, (3) oculomotor and visual abnormalities and visual hallucinations, and (4) sleep-related disorders

127. SYNCOPE AND OTHER GENERALIZED PAROXYSMS Apnea Apneic episodes (cessation of breathing > 20 sec) is usually not due to an epileptic seizure, apnea is the sole manifestation. premature children during active sleep and are believed to be due to brainstem immaturity bradycardia A few jerks may occur, but the baby does not convulse

128. Apnea epileptic seizure should be suspected if apnea is accompanied by eye closure or opening, eye deviation mouth movement hypertension tachycardia.

129. Breath-holding spells common events in infants and young children from six months to six years of age. Most children (80 to 90 %) have their first episode before 18 months of age dysfunction of the autonomic nervous system. Iron deficiency anemia is more prevalent in children with breath-holding spells compared with controls

130. Breath-holding spells The two clinical types of breath-holding spells are cyanotic and pallid. The pallid breath-holding spell , is caused by reflex vagal-cardiac bradycardia and asystole. The cyanotic, or blue, breath-holding spell , which does not occur during inspiration but results from prolonged expiratory apnea and intrapulmonary shunting A history of any provocation ( eg , head injury, crying), as this is typical for breath-holding spells. video-EEG monitoring can be helpful in difficult cases

131. Breath-holding spells Triggers Injury (such as even a minor bump on the head), pain frustration particularly with surprise Education( how to handle more severe spells, CPR, avoid triggering factors ) and reassurance of the parents because it is self-limited and are outgrown within a few years. If recurrent: check for anemia and ECG anticholinergic and AED for anoxic seizure

132. Neonatal Jitteriness and Clonus jitteriness consists of recurrent tremors. manifest as equal backward-and-forward movements of the limbs Occurring spontaneously, by touch or loud sounds. suppressed by stimulus removal or by relaxing the affected limbs, the lack of autonomic symptoms

133. Hyperekplexia (Stiff Baby Syndrome) Hyperekplexia is a rare, sporadic or dominantly inherited disorder with neonatal onset It is characterized by a triad of generalized stiffness, nocturnal myoclonus, Later a pathologic startle reflex. Bathing sudden awakening Auditory or tactile stimuli can induce attacks

134. difficulty in swallowing choking spells hip dislocations umbilical or inguinal hernias Delayed motor development A specific diagnostic sign can be elicited by tapping the nose, which produces a non fatigable startle reflex with head retraction.

135. Paroxysmal Dyskinesias These disorders are characterized by sudden attacks that consist of choreic , dystonic, ballistic, or mixed movements. Consciousness is preserved and patients may be able to perform a motor activity, such as walking, despite the attack. The variability in the pattern of severity and localization between different attacks may also help in differentiating them from seizures

136. Motor Tics These are movements that are under partial control, An urge to do them and with subsequent relief. exacerbated by emotions Simple tics, which occur at some time in about one in five children, involve one or two muscle groups; complex tics involve multiple tics or muscle groups; and Tourette syndrome consists of multiple motor tics(>2), vocal tics for more than a year, must start before age of 18(mostly 4-6) Persistent motor or vocal tic but not both for >1 Provisional tic disorder <1 PANDAS and PANS

137. Psychogenic non-epileptic seizures Psychogenic non-epileptic seizures Most are the result of somatoform disorder, with a variety of reported traumatic antecedents, particularly sexual or physical abuse in women A higher prevalence in women (70%–80%) Common features Side-to-side turning of the head, Asymmetric and large-amplitude shaking movements of the limbs, Twitching of all four extremities without loss of consciousness, and Pelvic thrusting Often last longer than epileptic seizures and may wax and wane over minutes to hours.