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Management in
Status epilepticus
Dr. Yotin Chinvarun M.D. Ph.D.
Comprehensive Epilepsy and Sleep disorder Program
Pramongkutklao hospital
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Case• F 31 years old with alteration of consciousness and low grade fever 5 day
PTA, the patient was found unconsciousness in her house
• Admitted at nearby hospital, low grade fever, stupor, CT and MRI brain was done
• LP showed no cell, normal protein and sugar, C/S negative
• Dx Acute encephalitis (DDx Herpes encephalitis)
• Rx: Acyclovir and Ampicillin IV
• CT brain and MRI brain were done
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Treatment• Repeated LP was performed, CSF analysis was normal
• Viral study from CSF was negative
• Rx – Valproate 800 mg q 6 hrs – LVT 500 mg q 6 hrs – Then, PB gr I 2-2-2, TPM 100 mg 1-1
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Progression• Autoimmune profile all normal
• U/S whole abdomen was normal
• Methylprednisolone had been given for 7 days
• Anti NMDA, GAD, VGKC: negative
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Why is Status Epilepticus is important ?
• Morbidity/mortality with some types of SE
• Medical emergency → Need for rapid and accurate diagnosis → Need for effective and safe treatment
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Status epilepticus: Mortality
DeLorenzo RJ, et al. Neurology. 1996;46:1029-1035.
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15
30
45
60
<1 1-‐4 5-‐9 10-‐15 16-‐39 40-‐59 60-‐79 80+
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1981 ILAE “Persists for a sufficient length of times or is repeated
frequently enough that recovery between attack does not occur”
Definition7
Status epilepticus: Definition by Time
• Duration of seizures not the sole cause of neuronal damage, etiology is strong determinant of whether injury develops, seizure type and patient’s age also play a role
• Recent clinical trend define SE with shorter and shorter times e.g. 20 minutes, The Veterans Affairs Cooperative Study used 10 minutes for generalized SE
• Lowenstein et al proposed “operational” definition of SE as 5 minutes of continuous seizures or “two or more discrete seizures with incomplete recovery of consciousness
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Definition of Status Epilepticus• Status epilepticus is present when an epileptic seizure is so frequently repeated or is so prolonged as to create a fixed and lasting condition (Gastaut, 1981)
• “There can be as many forms of SE as there are seizure types…” (Gastaut, 1983)
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Seizure type classification• Generalized SE
• Tonic clonic SE • Tonic SE • Clonic SE • Myoclonic SE • Absence SE • Atonic and akinetic SE
• Partial SE • Elementary partial SE • Complex partial SE
• Unilateral SE
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Status epilepticus: Epidemiologic data
• Operational definition; a seizure lasting >30 minutes or a series of seizures lasting >30 min without fully recovery
• Incidence of SE ranges between 18.1 and 41 cases per 100,000 population per year
• Approximately 60,000 to 195,000 cases /years in U.S.A. 40,000 deaths annually
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Status epilepticus and epilepsy
• 10-‐12% of patients with a first unprovoked seizure or newly diagnosed epilepsy present with SE
• 25-‐40% of SE occurs in patients with epilepsy
• 15-‐27% of patients with epilepsy will experience at least one episode of SE
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Who is at risk for SE
• Patients with acute symptomatic seizures
• Those with pre-‐existing neurological abnormalities
• The very young
• The very old
• Those with a history of prolonged seizures
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Classification of SE
Convulsive Nonconvulsive
Generalized Tonic-clonic Absence
Partial Partial motor (EPC) Complex partial
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Classification of SE Primary Generalized SE
•Generalized convulsive status epilepticus (GCSE) • Absence status epilepticus (ASE) • Atypical absence status epilepticus (AASE) • Generalized atonic status epilepticus (GASE) • Generalized myoclonic SE • Generalized clonic SE • Generalized tonic SE • Electrical Status Epilepticus of sleep (ESES)
(Treiman, 1995)
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Classification of SE Partial SE
• Simple partial status epilepticus (SPSE) • Epilepsia partialis continua (EPC) • Rolandic status epilepticus (RSE)
• Complex partial status epilepticus (CPSE)
• Secondarily generalized convulsive status epilepticus (GCSE)
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Clinical features: Convulsive SE
• Generalized tonic-‐clonic seizures – Unconsciousness – Firstly, tonic, clonic, or tonic-‐clonic – With time, subtle motor involvement – Tonic status commonly in children e.g. LGS
• Clonic status: commonly in neonate
• Myoclonic status e.g. JME, Mitochondrial diseases, anoxic encephalopathy
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Clinical features: Convulsive SE
• Simple partial status epilepticus
• Epilepsia partialis continua
• Commonly in the Rasmussen’s encephalitis
• Others causes e. q. focal motor seizure (due to localized cerebral lesions), metabolic disturbances (nonketotic hyperglycemia)
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Non-‐convulsive SE
• NCSE is a term used to denote a range of conditions in which electrographic seizure activity is prolonged and results in non-‐convulsive clinical symptoms
• Note – no time limit set -‐ Emphasis on EEG patterns for diagnosis
-‐ NCSE is best viewed as a form of cerebral response dependent on: age, cerebral development/integrity, anatomical location, epilepsy syndrome
-‐ Diagnostic difficulties – ‘boundaries of SE’ -‐ EEG changes in acute cerebral damage (Coma with PLEDs)
-‐ Epileptic encephalopathies – differentiation of ictal vs interictal state
-‐ Epileptic behavioral changes with limbic but no scalp EEG change
-‐ EEG change in metabolic/drug induced encephalopathies
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Determination of NCSE• Altered consciousness or behavior from baseline for > 30
minutes without convulsive movements AND:
– Repetitive focal or generalized epileptiform activity (spikes, sharp waves, spike-‐and-‐wave, sharp-‐and-‐slow wave complexes) or rhythmic theta/delta activity at >2/sec
– Above EEG patterns at < 1/sec with improvement or resolution of epileptic activity and clinical state following injection of rapid onset AED (e.g.BZP)
– Temporal EEG evolution of epileptiform or rhythmic activity > 1/sec with change in location or frequency of rhythmic/epileptiform activity.
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NCSE: complex partial SE• Clinical pattern
– Usually recurrent, attacks can be prolonged
– EEG features-‐ variable, can be slight
– Anatomy-‐ often frontal (65%) rather than temporal (35%)
– Clinical features • Confusion or altered consciousness, range in severity (video), video 2, video 3
• Often fluctuates (cycling/discontinuous, vs continuous forms)
• Motor features (jerking, automatism)
• Behavioural/psychic changes – agitation, excitation, questing, sluggish, restless, retardation, questing
• Amnesia common
• EEG variable and inconsistent patterns
• Treatment with IV BZD only sometimes helpful. Response often incomplete. Other oral or IV AEDs may be effective. Anaesthesia seldom indicated
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The umlity of intravenous benzodiazepine
• Clear clinical improvement of following BZD: likely indicator of NCSE • Lack of clinical improvement following BZD
– Does not rule out NCSE – 15% of NCSE:-‐ resistant to BZD treatment
• Lagging clinical improvement in 28% of 54 NCSE paments (Shneker and Fountain 2003) – Delayed or masked by Rx itself – Prolonged posmctal state (especially in elderly) – Concurrent nonepilepmc encephalopathy, associated acute brain injury
• Resolumon of periodic discharges with BZD – Can occur in metabolic cause of periodic discharge (such as Triphasic wave)
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Myoclonic SE and Subtle SE
• Myoclonic SE in coma – Acute onset – in context of severe brain injury – usually anoxic (e.g. post cardiac arrest)
– Deep coma
– Myoclonic jerking, ocular movements
– EEG shows PLED/BiPLEDs/other spikes
– Rx controversial – anaesthetic AEDs vs none
– Poor prognosis >80% death rate
– Not clear to what extent this is a form of SE or whether the EEG changes simply are a reflection of severe brain damage
• Subtle SE clinical features – Deep coma in the aftermath of a GTCS or SE
– Myiclonic jerking, ocular movement
– EEG shows PLEDs BiPLEDs/other spikes
– Rx anaesthetic AEDs or BZD
– Prognosis good
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NCSE-‐ABI Brain Damage:The Clock is Ticking
• Seizure duration and delay to Dx are major determinants of mortality, independent of etiology (Young et al, 1996; DeLorenzo et al, Neurology 1998)
• 36% if < 30 min vs 75% if >24 hrs delay
• 10% if < 10 hrs vs 85% if >20 hrs duration
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Survival in Status Epilepticus by Duration of Seizure Survival
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NCSE causes neurological morbidity and mortality, related to
• Adverse systemic metabolic and physiologic effects
• Brain injury caused by an acute insult that may induce NCSE
• Direct neuronal damage from the abnormal electrical activities
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NCSE-‐ABI Increases Brain Damage: Biochemical Evidence
• Increased excitotoxic cell injury metabolites:
– Brain glutamate: exceeds the concentration for excitotoxic cell death and swelling (Vespa et al. J Neurosurg 1998)
– Excitotoxic cell membrane peroxidation products; e.g., glycerol (Vespa et al. Acta Neurochir Suppl 2002)
– Lactate/pyruvate ratio suggesting ischemic cascade activation (Vespa et al. JCN 2005)
– Serum neuronal enolase: highest levels in combined SE and ABI (DeGiorgio et al. Neurology 1999)
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NCSE-‐Acute Brain Injury (ABI) Increases Mortality
•Clinical Evidence
– 57% vs 9% NCS alone (Young et al, Neurology, 1996)
– 46% vs 16% remote brain injury (Young et al, ibid)
– In Acute Ischemic Stroke 39% vs 14% AIS alone. AIS + SE mortality is synergistic and not merely additive (Waterhouse et al. Epilepsia 1998.)
– Preventing NCSE in experimental AIS: 70% lower mortality (Williams, et al. J. Pharmacol Exp Ther 2004)
– In ICH, assoc with cerebral edema and midline shift, independently predicts mortality (Vespa et al. Neurology 2003)
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Status Epilepticus NMDA receptor activation
Seizure-induced neuronal loss
Reduced GABAA
receptor function
Neuronal Dysfunction Sustaining SE
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Neuronal injury and network reorganization
• Recently, evidence that prolonged febrile seizures and episode of SE produce hippocampal cell loss and shrinkage
• Seizure-‐induced presumably excitotoxic pathology includes – neuronal loss – reactive gliosis – aberrant synaptic reorganization
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The pathology of status epilepticus (SE)31
Treatment
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Treatment of SE
• Assessment and control airway • Monitor vital signs • Conduct pulse oximetry and monitor cardiac function • IV fluid replacement • Administer glucose if suspect hypoglycemia • Start anticonvulsant
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Treatment• Goal to prompt cessation of seizure activity
• Should be easy to administer
• Have immediate and long-‐lasting antiseizure activity
• Least effect particularly to cardiovascular and pulmonary function and level of consciousness
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Current medications35
The ideal IV AED in Status Epilepticus
• Easy to administer
• Quick onset of action
• Long duration of action
• Good safety & tolerability profile
• No drug interactions
• Smooth transition to oral treatment
Currently available IV AEDs
•Benzodiazepines• Diazepam• Lorazepam• Midazolam• Clonazepam
•Phenytoin, FPHT
•Valproate
•Levetiracetam
•Lacosamide
•Barbiturates• Thiopental, Pentobarbital
•Propofol
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Treatment
▪ Prehospital treatment with IV benzodiazepine improves outcome and reduces morbidity1
1. Alldredge BK, et al. N Engl J Med. 2001;345:631-637. Erratum in: N Engl J Med. 2001;345:1860.
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Initial Therapy
▪ Outpatient therapy – Rectal diazepam gel – 0.2 mg/kg – Intranasal/buccal midazolam – 10 mg
▪ Inpatient/emergency department therapy – IV lorazepam 2 mg q 5-‐10 minutes, maximum 10 mg – IV fosphenytoin (18 mg/kg load, level >20 μg/mL)
▪ Maximize phenytoin – Additional load of 10 mg/kg – Desired serum level of 25 to 30 μg/mL
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• Should be prompt administer after diagnosed as SE
• Choice of AED based on the rapid onset and half-‐life of AED
• Prospective blinded studied, comparing Lorazepam, Phenytoin, Diazepam with Phenytoin, and Phenobarbital;-‐ all were equally effective
• Except the Lorazepam was superior to PHT when seizures were assessed 20 min after drugs administration
Treatment42
• Benzodiazepines; diazepam, lorazepam, or clonazepam
• Phenytoin; 20-‐25 minutes used for the drug to attain its maximal effect
• Hypotension occur 30-‐50%, cardiac arrhythmias 2%
• Fosphenytoin a water-‐soluble form of PHT (half life 15 min) can be administered at phenytoin-‐equivalent, rate can be up to 150 mg/min, less side effects of infusion-‐site reaction
Treatment43
• Phenobarbital; using when benzodiazepine or PHT failed, dosage 20mg/kg (at a rate 50-‐75 mg/min)
• Be careful about depression of respiratory function
• BP and level of consciousness
• Can be use as 3rd line with high dosage to induced “Barbiturate coma”
Treatment44
• Valproate used intravenously treatment of SE
• Case series suggest useful for variety of seizure types
• Loading dose 15 mg/kg and maintenance of 1 mg/kg/h, stopped seizures within 30 minute in 80% of cases
• Valproate IV also been successful in children
• Well tolerated and causes less cardiovascular instability than does IV phenytoin, non-‐sedative
Treatment45
When does SE become refractory
• No standard definition
• Most authors have considered SE refractory when adequate does of a benzodiazepine and phenytoin fail to terminate SE – Others required Phenobarbital as well
• Duration of SE prior treatment
• Effects of treatment sequence
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Agents commonly recommended for refractory SE treatment
• High dose Barbiturates (“Barbiturate coma”) • Thiopental • Phenobarbital
• High dose benzodiazepines • Midazolam • Lorazepam • Diazepam
• Propofol
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Drug treatment
• Midazolam • (0.2mg /kg slowly administer followed by 0.75-‐10 microgram/min
• Propofol • (1-‐2 mg/kg /hour), maintain infusion of these drugs for 12-‐24 hours
• Thiopental and pentobarbital • 10-‐15 mg/kg IV administer over a period of one hour followed by 0.5-‐1 mg/kg/hour
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Carbamazepine, Oxcarbazepine, Topiramate, and Levetiracetam
• These antiseizure medications often added to the acute AED regimen with the intention of providing adequate maintenance AED coverage to pre-‐ vent SE recurrence when infusion therapy is withdrawn
• In the setting of SE, these medications generally titrated quickly up
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Carbamazepine, Oxcarbazepine, Topiramate, and Levetiracetam
• The use of carbamazepine in SE primarily as maintenance antiseizure medication
• A parenteral formulation is not yet available. Typical daily doses in the setting of SE are up to 1600 mg/d
• Oxcarbazepine is used in the same way as carbamazepine
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Carbamazepine, Oxcarbazepine, Topiramate, and Levetiracetam
• Topiramate has been reported to be effective when administered enterally in the setting of SE
• Topiramate can be administered by nasogastric tube or rectally, is generally well tolerated except for mild sedation, and can be quickly titrated to dose ranges of up to 1600 mg/d
• Levetiracetam can now be administered parenterally as well as by nasogastric tube – Typical daily doses of levetiracetam in the setting of SE are up to 5000 mg/d.
– Main advantage of levetiracetam in the setting of acute seizures and SE is ease of administration, rapid titration, easy transition to use as a maintenance AED, and few drug−drug interactions
– However, limited data on its efficacy in SE in humans
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Other AEDs• Other maintenance AEDs is growing and includes lamotrigine, gabapentin,
zonisamide, pre-‐ gabalin, felbamate, methsuximide, ethosuximide, acetazolamide, primidone, tiagabine, and vigabatrin.
• Although used in chronic epilepsy, these agents are rarely used in SE owing to slow titration or lack of evidence for clinical efficacy in the setting of SE
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EFNS guideline: Management of status epilepticus in adults
• The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is
• Intravenous (i.v.) administration of 4-8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin.
• If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended.
• The initial therapy of non-convulsive SE depends on type and cause.
Complex partial SE is initially treated in the same manner as GCSE.
• However, if it turns out to be refractory, further non-anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics.
H. Meierkord, et. al. Eur J Neurol. 2010, 17: 348–355
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EFNS guideline: Management of status epilepticus in adults
• Pharmacological treatment for refractory GCSE and subtle status epilepticus – In generalized convulsive and subtle SE, proceed immediately to the infusion of anesthetic
doses of midazolam, propofol or barbiturates
– Because of poor evidence, cannot recommend which anaesthetic substances should be the drug of choice.
– Recommends titration against EEG burst suppression pattern with propofol and barbiturates. If midazolam is given, seizure suppression is recommended, maintained for at least 24 hours. Simultaneously, initiation of the chronic medication (GPP)
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EFNS guideline: Management of status epilepticus in adults
• Pharmacological treatment for refractory NCSE – In complex partial SE, the time that has elapsed until termination of status is less
critical compared to GCSE
– Thus, general anesthesia due to its possible severe complications should be postponed and non-‐anaesthetizing anticonvulsants may be tried initially (GPP)
• Phenobarbital: 20 mg/kg i.v., administration of additional boluses requires intensive care conditions
• Valproic acid: i.v. bolus of 25–45 mg/kg is administered followed by maximum rates up to 6 mg/kg/min
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Case: Bursts suppression by using Barbiturate
Using too much barbiturate may casing fatal complication
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Novel Therapeutic Approaches in Highly Refractory Status Epilepticus
• Most effective way to terminate RSE is to successfully treat the underlying cause
• it is important to treat any active underlying disease processes in conjunction with treatment of the SE
• However, many causes of SE are actually static or remote from the active episode of SE, such as an old stroke
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What does a clinician do when patient remains in SE despite pharmacologic suppression of seizures by coma-‐
inducing agents?• Re-‐evaluate identified underlying cause particularly metabolic,
inflammatory, infectious, or iatrogenic causes
• Ensure that imaging studies, using MRI, positron emission tomography (PET), and single-‐photon emission computed tomography (SPECT), if available
• Be certain that the electrographic seizure activity is abolished while the patient is receiving infusion therapy.
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What does a clinician do when patient remains in SE despite pharmacologic suppression of seizures by coma-‐
inducing agents?• Ensure that adequate levels of maintenance AEDs
• If an infusion therapy does not work, then another should be tried – If infusion therapy regimen does not terminate SE after initial 12-‐ to 24-‐
hour, then it is unlikely to be successful after a 48-‐ or 72-‐hour period. – The regimen should be changed, and the underlying etiology should be
identified and treated.
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Surgical Intervention• Although rarely undertaken, surgery plausible option where electrographic
SE remains focal, particularly if there is evidence causal structural lesion
• The same criteria can be extended to acute setting of refractory focal SE., however, consideration of postoperative deficits and prospect of long-‐term seizure freedom should be weighed against the risks associated with ongoing focal SE
• Identification of a structural lesion or functional region requires correlation of EEG with MRI and functional (usually PET or SPECT) imaging
• Reports of successful treatment of refractory focal SE by surgical removal of an underlying structural lesion, particularly in the pediatric – Surgery generally lesionectomy, partial or complete lobectomy
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Case
• Girl 4 year old
• Presenting with seizures, spastic quadriparesis, right facial palsy
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Progression
• Patient developed status epilepticus
• Rx: VPA IV, FosPHT • Current med: VPA, LTG, PHT, TPM, Rivotril
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Case
• F 88 years old
• Presenting with dizziness, headache and ataxia
• Later on, had alteration of consciousness
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Case
• Surgical partial tumor removal
• Pathological finding: CNS lymphoma
• cEEG was done
• Rx as NCSE – Fosphenytoin IV 100 mg q 8 hrs
– LVT IV 2,000 mg per day
– PGB 600 mg/day
• Rx with XRT
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Case
• Patient was diagnosed as Highly Refractory NCSE
• Patient on come state, pupil 2 mm, no reflex was noted, on respirator
• Rx with XRT
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Multiple Continuous Infusion Therapy
• if a single-‐agent infusion therapy is not effective on the first trial, it generally remains ineffective thereafter.
• It is not known whether combinations of these infusions are more effective or safer. If hypotension is a major problem, then infusion rate of pentobarbital can be lessened if midazolam is commenced
• Different modes of action may enhance the chance of terminating SE
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Ketamine
• Potent NMDA antagonist has been used in some institutions in RSE
• Loading dose of 2 mg/kg, followed by an infusion of 10 to 50 μg/kg/min.
• Limited data are available
• Evidence that excessive NMDA excitatory receptor-‐mediated transmission is an important mechanism of persistent neuronal firing, may explain ineffectiveness of GABA agonists
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Ketamine
• Adverse effects relate to its use as an analgesic, such as – Hallucinations and other transient psychotic sequelae
– Associated with cardiovascular stimulation and a rise in arterial pressure and heart rate and should be used with caution in patients with systemic or intracranial hypertension.
– Cerebellar damage has been reported after longer-‐term use
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Lidocaine Infusion
• A number of reports of successful use of lidocaine in the setting of RSE
• Should not be used in patients with coexisting sinoatrial disorders
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Inhalation Anesthetics
• There have been several case reports of successful use of inhalation anesthetics in the setting of RSE including isoflurane and desflurane
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Paraldehyde
• Important therapy in the past but is now rarely used because of difficulties in administration
• Associated unwanted adverse effects.
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Allopregnanolone (SAGE 547)• Allopregnanolone (SAGE 547): Intravenous allosteric modulator
of both synaptic and extra synaptic GABAA receptors
• Effective AEDs when prolonged seizure activity has become resistant to benzodiazepine treatment.
• A novel agent designed to treat super-‐refractory status epilepticus (SRSE) proving successful in 71% of patients (20 patients 2>2 years of age diagnosed with SRSE)
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Direct Brain Stimulation
• Surface and deep brain stimulation devices are being developed for use in focal and generalized epilepsies,
• Their use has not been reported in humans in the setting of SE
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Transcranial Magnetic Stimulation
• Transcranial magnetic stimulation has similarly been evaluated in animal models of focal SE
• However, has not yet been reported to be helpful in human SE
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Electroconvulsive Therapy• Owing to its potent anticonvulsant actions, electro-‐ convulsive therapy has
been proposed as an intervention for SE
• It may seem illogical to administer a proconvulsive stimulus in SE, but after coming inhibitory state after a convulsion induced by electroconvulsive therapy may, in theory, be beneficial to patients in SE.
• Has not been evaluated in a rigorous fashion by clinical trial.
• However, it seem to be not helpful in the management of refractory SE
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Diagnostic Tools in Refractory Status Epilepticus
• Advances in diagnostic techniques in the setting of difficult-‐to-‐control SE have been digital EEG recording and novel imaging approaches – Continuous digital EEG monitoring allows for easier data acquisition,
reformatting, storage, and application of seizure-‐screening software tools such as event detection and spectral analysis.
– Continuous video recording in conjunction with EEG facilitates interpretation, principally by facilitating artifact rejection and assessing the clinical correlation of paroxysmal EEG activity or events.
– Imaging plays a role in the management of SE such as • MRI brain
– Exclude neurosurgical causes for seizures – Peri-‐ictal structural changes
• Both ictal SPECT, FDG-‐PET, can provide valuable data in focal seizures
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Peri-‐ictal structural changes
• Remote – Occurrence of migratory T2 and lesions on diffusion-‐weighted imaging, appearing in remote cortical areas
– Often reversible
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Peri-‐ictal structural changes
• Categorized as local or remote
• Local – Include a swollen cortical ribbon with loss of grey− white matter
differentiation. – Increased T2 signal intensity due to edema occurs in areas of cortex and
adjacent subcortical white matter. – The local T2-‐ weighted changes may be associated with MRI evidence of
restricted diffusion, which are bright on diffusion-‐weighted imaging and dark on apparent diffusion coefficient maps
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Outcome
• Factors contribute to the morbidity and mortality associated with SE are – Underlying etiology, – Age – Duration of the SE.
• Secondary factors that likely contribute to the outcome from SE include – sepsis, anoxia, duration of infusion therapy, and comorbid ICU-‐ related
medical complications
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Outcome• Inpatient mortality linked to
– potentially fatal etiologies,
– increasing age,
– severely impaired consciousness when first evaluated
• Patients with underlying anoxic brain injury, vascular lesions, tumors, and infections fare worse than patients whose SE was provoked by alcohol, drug withdrawal, or noncompliance with AED therapy
• Numerous reports of survival even after very prolonged hospital courses for SE, particularly in children.
• However, many patients will have persistent refractory epilepsy and functional deficits
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Outcome
Holtkamp M et al, 2005, Rossetti AO et al. 2005
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Problem Areas in Intensive Care Unit Management of Status Epilepticus
• Management of SE is frequently difficult. “Status epilepticus” is not a single entity but is a heterogenous collection of electroclinical syndromes with wide ranging etiologies, some benign and some malignant, and with varied clinical outcomes
• SE is often treated by the same management algorithm within the same institution
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Post-‐anoxic Status Epilepticus
• A specific electroclinical state resulting from diffuse cortical damage
• Postanoxic state varies in severity from electro-‐ cerebral silence to diffuse nonreactive alpha and theta-‐range activity (“alpha coma” and “theta coma”) to burst−suppression pattern or frequent generalized epileptiform discharges
• EEG findings may reflect activity of the residual islands of viable cerebral cortex
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Postanoxic Status Epilepticus
• Patient may or may not exhibit myoclonus.
• Such myoclonic status that arises in patients after an anoxic insult is usually transient (evolving into motionless coma) and invariably has a dismal outcome
• Presence of myoclonus may confer a worse prognosis than electrographic SE without clinical manifestations
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Post-‐anoxic Status Epilepticus
• Reasonable course of action is to institute a clearly defined course (24-‐48 hours) of IV propofol or midazolam sufficient to abolish the myoclonus and to suppress EEG
• This can be performed in conjunction with other interventions such as head-‐ cooling and administering neuroprotective agents
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Potential Mistakes in the Management of Status Epilepticus
• Relate to the early recognition and prompt use of appropriate doses of appropriate first-‐ and second-‐line AEDs
• Potential mistakes include – Assuming seizure activity has terminated when overt convulsive activity
has stopped but the patient remains obtunded – Failure to administer appropriate loading doses of AEDs in proportion to
the patient’s weight – Failure to recognize nonepileptic seizures or pseudostatus
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Potential Mistakes in the Management of Status Epilepticus
• Potential errors in an ICU setting include – Mis-‐ labeling of paroxysmal clinical behaviors as seizures – Underutilization or overutilization of diagnostic EEG monitoring – Lack of recognition of NCSE or metabolic encephalopathy – Failure to initiate adequate amounts of maintenance AED therapy – Inappropriate delay in switching from an ineffective treatment regimen
(manifesting as ongoing seizure activity on EEG monitoring) to another regimen
– Use anaesthetic agents too much casing fatal complication
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Conclusion• Initial management of SE is now well established, but the management of
advanced or refractory SE remains difficult proposition
• However, advances in our understanding of SE as well as both diagnostic and monitoring tools offer the prospect of better clinical outcomes in the future
• Early recognition and intervention in SE is far more likely to succeed than any delayed intervention.
• Ensuring an appropriate dose of a first-‐ and second-‐line AEDs
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Conclusion• All ED, neurology, and ICU personnel should be well versed in the initial
management of SE
• Neurologists are ideally placed to manage SE, particularly those with a knowledge of EEG, and should be consulted early
• Because of high morbidity and mortality associated with SE, physicians and staff must be aggressive in the management of SE.
• Finally, surgery should be considered a potential therapeutic option in refractory focal SE.
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