Non convulsive status Epileticus Dr AMINA H Harharah

Non convulsive status Epileticus Dr. AMINA H. Harharah Non covulsive satus epilepticus 1

Status Epilepticuc Status epilepticus (SE) is a major clinical problem, frequently occurring in childhood, with a high potential for morbidity. The condition is subdivided into convulsive and nonconvulsive forms (CSE and NCSE, respectively), and the seizures can be generalized or partial. . Non covulsive satus epilepticus 2

Non convulsive status epilepticus is difficult to diagnose in children as it can present with altered mental status and change in behaviour. It is important to rule out other serious differential diagnoses. It may be one of the most frequently missed diagnoses in patients with altered neurologic function. . Non covulsive satus epilepticus 3

Historical Background Non covulsive satus epilepticus 4

One of the first detailed accounts of NCSE or ‘automatisme ambulatoire’, was by Charcot in 1888, who described a patient who got into trouble with the law because he had boarded a train without a valid ticket. Lennox in 1949 described a boy aged 11 years who had occasional days of being confused, when he was able to eat but not to converse. periods of what he then termed ‘petit mal’ status Non covulsive satus epilepticus 5

NCSE represents a prolonged state of seizure(s) (status epilepticus— SE) without marked motor manifestations. NCSE typically encompasses an ictal impairment of cognition, subtle facial or limb twitches, eyes-open mutism, head or eye deviation, automatisms, and behavioral change. Non covulsive satus epilepticus 6

NCSE has traditionally been considered to occur less frequently and to be less harmful than CSE. Increasing evidence, however, indicates that NCSE is under diagnosed, particularly in children, and might not be as benign as was previously thought. Non covulsive satus epilepticus 7

NCSE has been defined as a cognitive or behavioral change that lasts for at least 30 minutes, with evidence of seizures on electroencephalogram (EEG). Some authors believe that a more-precise definition of NCSE should include "unequivocal electrographic seizure activity, rhythmic electrographic discharges with clinical seizures, and clinical or electrographic response to treatment". Non covulsive satus epilepticus 8

The recognition of a significant cognitive or behavioral change is often challenging, if not impossible, in children, particularly in: - Very young - Children with pre-existing Developmental delay - Those with intractable recurrent seizures treated with multiple medications—all categories that carry a relatively high risk for NCSE. Non covulsive satus epilepticus 9

The following criteria have been suggested for the diagnosis of NCSE in children : "clear and persistent clinical change in behavior (which includes changes in cognition, memory, arousal or motor behavior), confirmed by comparisons with previous functioning observations and/or by neuropsychological examination, in the presence of continuous paroxysmal electrographic activity, and in the absence of clonic, tonic or tonic–clonic Non covulsive satus epilepticus 10 seizures”

Classification Non covulsive satus epilepticus 11

Classification based on the age at which NCSE occurs has recently been suggested 1. NCSE occurring in the neonatal and infantile epilepsy syndromes 1 a. West syndrome 1 b. Ohtahara syndrome 1 c. Severe myoclonic encephalopathy of infancy (SMEI; Dravet syndrome) 1 d. NCSE in other forms of neonatal or infantile epilepsy Non covulsive satus epilepticus 12

2. NCSE occurring only in childhood 2 a. NCSE in Early-onset benign childhood occipital epilepsy (Panayiotopoulos syndrome) 2 b. NCSE in other forms of childhood epileptic encephalopathies, syndromes and etiologies, e. g. , Ring chromosome X and other karyotype abnormalities, Angelman , Rett syndrome, myoclonicastatic epilepsy, other childhood myoclonic encephalopathies. 2 c. Electrical status epilepticus in slow wave sleep (ESES) Non covulsive satus epilepticus 13 2 d. Landau-Kleffner syndrome

3. NCSE occurring in both childhood and adult life With epileptic encephalopathy 3 a. NCSE in the Lennox-Gastautsynd i. Atypical absence status epilepticus ii. Tonic–status epilepticus 3 b. Other forms of NCSE in patients with learning disability or disturbed cerebral development (cryptogenic or symptomatic) Non covulsive satus epilepticus 14

Without epileptic encephalopathy 3 c. Typical absence status epilepticus in idiopathic generalized epilepsy 3 d. Complex partial status epilepticus: 3 e. NCSE in the postictal phase of tonic –clonic seizures 3 f Subtle Status epilepticus (myoclonic SE occurring in the late stage of convulsive SE) 3 g. Aura continua Non covulsive satus epilepticus 15

4. NCSE occurring in late adult life 4 a. De novo absence status epilepticus of late onset 5. Boundary syndromes 5 a. Some cases of epileptic encephalopathy. 5 b. Some cases of coma due to acute brain injury with epileptiform EEG changes. 5 c. Some cases of epileptic behavioral disturbance or psychosis. 5 d. Some cases of drug induced or metabolic confusional state with Non covulsive satus epilepticus 16 epileptiform EEG changes.

Classification The term NCSE encompasses several conditions that differ widely in their etiology, prognosis and management: Absence SE Myoclonic SE Complex partial SE Simple partial SE SE in coma SE in patients with learning difficulties. Atypical absence SE Autonomic SE. Non covulsive satus epilepticus 17

Absence status epilepticus Absence SE is characterized by a prolonged confusion state, but agitation, violent behavior and hallucinations can occasionally occur. Associated automatisms, blinking, and jerks of the face and limbs might also be observed. Absence SE has a strong tendency to recur. In childhood, absence SE is almost exclusively noted in patients with known idiopathic generalized epilepsies. Non covulsive satus epilepticus 18

Absencestatus epilepticus in a 6 -year-old child who presented with unresponsiveness with subtle twitching of the corner of the mouth. The electroencephalogram m shows continuous rhythmic generalized spike-and-wave discharges with frontal predominance. Non covulsive satus epilepticus 19

FIG. 1. Rapid generalized epileptiform spikes and slow waves following a few seconds of a normal EEG. Non covulsive satus epilepticus 20

Myoclonic status epilepticus It is characterized by continuous, usually generalized, myoclonias of cortical origin. The inclusion of myoclonic SE in the category of nonconvulsive SE is controversial, because myoclonias might be considered as convulsions. Myoclonic manifestations might be subtle, however, and they frequently go unnoticed in patients with chronically disturbed cognitive functioning Non covulsive satus epilepticus 21

Complex partial status epilepticus Differentiation of complex partial SE from absence SE is difficult to achieve on clinical grounds alone. patients in complex partial SE are confused, and clear lateralizing signs might be missing. Criteria for the clinical diagnosis of complex partial SE have been summarized as follows: "recurrent complex partial seizures without full recovery of consciousness between seizures or continuous 'epileptic twilight state' with cycling between unresponsive and partially responsive phases“. . Non covulsive satus epilepticus 22

Symptoms of complex partial SE can include amnesia, aphasia, bizarre behavior and hemiparesis. EEG is essential to make a correct diagnosis: the ictal abnormalities are focal and include spike-and-slow waves, polyspikes and rhythmical slowing. A secondary generalization might occur, potentially leading to diagnostic confusion. Non covulsive satus epilepticus 23

Periodic discharges of nonconvulsive status epilepticus following convulsive status epilepticus Non covulsive satus epilepticus 24

Periodic discharges of nonconvulsive status epilepticus following convulsive status epilepticus. A 10 -year-old girl presented in convulsive status epilepticus, and this electroencephalogram was obtained after convulsions resolved but while she was still unresponsive. There are right hemisphere periodic sharp waves with a slow repetition rate Non covulsive satus epilepticus 25

Periodic lateralized epileptiform discharges in nonconvulsive status epilepticus Non covulsive satus epilepticus 26

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Bilateral PLEDs (rhythmic 1 Hz spikeand-wave discharges) in a 12 -year-old girl. 3 Fp 1–F 3 F 3–C 3 C 3–P 3 P 3–O 1 Fp 2–F 4 F 4–C 4 C 4–P 4 P 4–O 2 Fp 1–F 7 F 7–T 3 T 3–T 5 T 5–O 1 Fp 2–F 8 F 8–T 4 T 4–T 6 T 6–O 2 Fz–Cz Cz–Pz EKG–Ref Non covulsive satus epilepticus 28

NCSE with learning difficulties It is diagnosed mainly in children. It encompasses several pediatric conditions that share variable degrees of developmental delay and continuous or near-continuous electrographic epileptic activity. Non covulsive satus epilepticus 29

It is commonly divided into electrical SE during sleep (ESES), atypical absence SE, and tonic SE. ESES is characterized by diffuse 1. 5– 3. 5 Hz spike-and-wave discharges occurring in 85– 100% of non-rapid eye movement sleep, usually associated with various pediatric epilepsy syndromes, such as typical or atypical benign epilepsy with centrotemporal spikes, Landau–Kleffner syndrome, and epileptic encephalopathy with continuous spike-and-wave discharges Non covulsive satus epilepticus 30 during sleep.

Autonomic status epilepticus Most cases of autonomic SE have been observed in Panayiotopoulos syndrome, the most important clinical manifestations of which include nausea, vomiting, pupillary abnormalities, and cardiorespiratory and thermal alterations. Despite the fact that some of these episodes end in convulsions, they are considered to be autonomic NCSE because of the large predominance Non ofcovulsive vegetative features. 31 satus epilepticus

Electrographic criteria for nonconvulsive status epilepticus. Non covulsive satus epilepticus 32

• Frequent or continuous focal electrographic seizures with ictal patterns that change in amplitude frequency or localization • Frequent or continuous generalized spikeand-waves in patients without a prior history of epilepsy • Frequent or continuous generalized spikeand-waves, significantly different in amplitude or frequency as compared to previous findings, in patients with a history of epileptic encephalopathy Periodic lateralized epileptiform discharges (PLEDs) in comatose patients after convulsive status epilepticus Non covulsive satus epilepticus 33

Conditions associated with NCSE in children Non covulsive satus epilepticus 34

Although rare, NCSE is found in a wide variety of situations in childhood these conditions can be grouped in three separate categories: 1 - Acute neurological injuries 2 - Specific childhood epilepsy syndromes with prominent tendency for NCSE 3 - Nonprogressive encephalopathies Non covulsive satus epilepticus 35

Acute neurological injuries: NCSE in children often occurs as a consequence of one of a variety of Acute or subacute neurological injuries, such as stroke, encephalitis. Exacerbation of a chronic metabolic encephalopathy. Trauma Intoxication. Non covulsive satus epilepticus 36

Specific epilepsy syndromes Children with epilepsy are at risk of presenting with NCSE for two main reasons. 1 - Certain antiepileptic drugs, such as levetiracetam, lamotrigine, valproate and tiagabine, have been associated with NCSE. Tonic SE induced by benzodiazepines, sometimes subtle enough to be considered as a nonconvulsive. Non covulsive satus epilepticus 37

2 - Several pediatric epilepsy syndromes show a prominent tendency for NCSE. These include Dravet syndrome, myoclonic– astatic epilepsy, malignant migrating partial seizures in infancy, and LGS. Non covulsive satus epilepticus 38

Dravet syndrome (severe myoclonic epilepsy in infancy) Is a severe form of epilepsy that begins in infancy. It is associated with mutations in the gene that encodes the sodium channel. Infants with Dravet syndrome often have prolonged febrile convulsions at disease onset, but afebrile focal seizures, atypical absence seizures and myoclonic seizures might follow at a later stage. NCSE occurs in at least 40% of cases usually after the age of 2 years. Non covulsive satus epilepticus 39

Myoclonic–astatic epilepsy Is characterized by isolated myoclonias and epileptic falls or head drops, often preceded by subtle myoclonias of the limbs, that begin in infancy. NCSE frequently occurs in this condition, and takes the form of stupor associated with perioral or distal muscle twitching and repeated head nods, all lasting for several hours. Non covulsive satus epilepticus 40

Malignant migrating partial seizures in infancy Infants with this condition develop normally before the onset of seizures, which usually begin during the first 6 months of life. The seizures are focal and nearly continuous, and they shift from one area of the brain to the next, giving the appearance of migration. Clinical manifestations can be very subtle, with behavioral arrest. Non covulsive satus epilepticus 41

Although not often formally described as NCSE, patients with this syndrome have prolonged and nearly continuous electroclinical seizures with subtle manifestations and altered responsiveness. Non covulsive satus epilepticus 42

Lennox–Gastaut syndrome Is characterized by multiple seizure types, almost invariably including nocturnal tonic seizures and atypical absences, in patients with severe developmental delay and interictal diffuse slow spike-and-wave discharges on EEG. Non covulsive satus epilepticus 43

NCSE occurs in 50– 75% Subtle tonic SE with progressive attenuation of motor manifestations and prolonged obtundation with myoclonias are two forms of NCSE also observed in this syndrome. Non covulsive satus epilepticus 44

Nonprogressive encephalopathies Myoclonic SE can occur in various nonprogressive encephalopathies one of the best-recognized being Angelman syndrome. Non covulsive satus epilepticus 45

Angelman syndrome is a genetically determined disorder, Children with this condition have: Developmental delay Mild facial dysmorphism Ataxia Hypotonia Cheerful disposition Non covulsive satus epilepticus 46

The interictal EEG often shows a characteristic pattern that is sometimes referred to as 'notched' delta. The pattern can occur without any clear clinical manifestations, but affected children might have prolonged periods of altered responsiveness with admixed myoclonias and eye blinking timelocked with the rhythmic EEG activity. Non covulsive satus epilepticus 47

Ring chromosome 20 epilepsy syndrome Is a rare entity, the most important clinical characteristics of which include repeated episodes of NCSE. onset of seizures ranged from 1 day to 14 years. Most of the patients had convulsions that were very difficult to treat in addition to prolonged confusional states. Non covulsive satus epilepticus 48

EEG show asymmetric high-voltage slow waves with occasional spikes, predominantly in frontal regions Non covulsive satus epilepticus 49

Treatment of nonconvulsive status epilepticus. Non covulsive satus epilepticus 50

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Conclusion Non covulsive satus epilepticus 52

Cognitive or behavioral change for at least 30 minutes, with evidence of seizures on electroencephalogram • The diagnosis is difficult and requires a high index of suspicion • Lack of agreement on diagnostic criteria • Observed in various childhood epilepsy syndromes, encephalopathies and acute conditions • Data scarce regarding diagnosis, treatment and outcome. Further studies analyzing the EEG features and clinical presentation, especially the very young, are needed Non covulsive satus epilepticus 53

Criteria for Diagnosis of NCSE 1. Diminished level of consciousness or other neurologic deficit 2. EEG: typical discrete seizures or continuous discharges 3. Response to anticonvulsants: clinical and EEG (controversial, often after long delay) Non covulsive satus epilepticus 54

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