Status Epilepticus

Briana Witherspoon

DNP, ACNP-BC

Objectives

• Define Status Epilepticus

• Describe the pathophysiology of SE

• Discuss the etiology of SE

• Discuss the treatment of SE

• Identify complications and outcomes associated with SE

Case Study

• M.K. -19 yo female with memory difficulties x 3 months

• Acute onset of visual and auditory hallucinations ending in confrontation with campus police

• Taken to local hospital

– No recollection of outburst

– CTH unremarkable

– Brain MRI ordered

Case Study

• While on MRI table M.K. has a generalized seizure lasting approximately 30 seconds

• Post seizure M.K. is noted to be unresponsive

– STAT team is called

• Upon arrival of the STAT team M.K. has a second generalized seizure

– requires intubation for airway protection

Question # 1

Does M.K. meet the criteria for Status Epilepticus?

a. Yes

b. No

c. Not sure

Criteria for SE

• Old (30 minute rule) vs New (NOW!)

• TIME is BRAIN

• ≥5 minutes of continuous seizures OR ≥2 discrete seizures between which there is incomplete recovery of consciousness

Neurocritical Care, 2012

Status Epilepticus

• Categorized electroclinically (focal or generalized)

– Morbidity

– Identify etiology

• Classified as Convulsive and Nonconvulsive

SE Chart

Convulsive

• Convulsions associated with rhythmic jerking of the extremities

• Types

– Generalized (most common)

• Myoclonic

• Clonic

• Tonic

• Tonic –Clonic

– Partial

• Simple

• Complex

Nonconvulsive

• Sz activity seen on EEG without clinical findings

• Types

– Partial (simple and complex)

– Absence

– Others (rare)

• Diagnosed based on

– Etiology

– EEG findings

• Captures 56% of seizures in first hour

• 88% of seizures in first 24h

– Clinical status of patientUpToDate, 2015Sutter et al, 2013

Neurocritical Care, 2012

Status Fast Facts

• First described on tablets from 718-612 BC

• Incidence: 7-41 cases per 100,000 adults per year

• $4 billion per year in healthcare costs (U.S.)

• Incidence rates peak in children < 1 year of age and adults > 60 years

• 10% of adults with epilepsy will have status epilepticus

• Mortality rate can be around 20%, especially if treatment is not initiated quickly

– Highest mortality occurs with anoxic and cerebrovascular causes

– Seizure duration is greatest predictor of mortality. SE lasting > 1 hour has significantly higher mortality

Lancet Neurol, 2006

More Facts

• In Neuro Intensive Care Units, up to 1/3 of patients will have nonconvulsive seizures and most of these will be in nonconvulsive status epilepticus (Jordon KG 1994)

• In Medical Intensive Care Units, up to 10% of patients undergoing continuous EEG monitoring have nonconvulsive seizures (Towne

AR et al 2000)

Case Study

• M.K. arrives to the ICU intubated but starts to have a third seizure shortly after arrival

• cEEG immediately obtained and reveals an abnormal generalized rhythmic delta activity consistent with SE

Question #2

What medication class is considered first line for the treatment of seizures?

A. Neuromuscular blocking agents

B. Benzodiazepines

C. General anesthetics

D. AEDs that affect voltage- dependent sodium channels

E. None of the above

Give a Benzo!

• No Access = No Excuse

– IV: lorazepam, midazolam, diazepam

– IM: midazolam

– Intranasal: midazolam

– PR: diazepam

• Diazepam crosses BBB, short acting, stable at room temperature

• Midazolam extremely short acting, multiple route administration

• Lorazepam ? Best benzo, long acting

Randomized, Double-blind study that compared IV lorazepam, IV diazepam, and placebo

205 patients total • 66 patients in lorazepam arm (59% seizure cessation)• 68 patients in diazepam arm (43% seizure cessation)• 71 Patients in placebo arm ( 21% seizure cessation)

5 year Multi-center, Double-blind study that compared IV diazepam + IV phenytoin, IV lorazepam, IV phenobarbital, and IV phenytoin

Included both convulsive (384 patients) and non-convulsive SE (134 patients)

lorazepam 65%phenobarbital 58%diazepam + phenytoin 56%phenytoin 44%

Large (N= 893), Double-blind, Randomized trial comparing IM midazolam to IV lorazepam

73% (IM midazolam) vs 63% (IV lorazepam) seizure cessation

Next Steps

• ? Time dependent loss of synaptic GABA receptors

• Window of effective anticonvulsant therapy is NARROW

• Treatment algorithms

– Prevents neuronal injury

– Maximizes cerebral O2 supply

– Decrease morbidity/mortality

Neurol Lancet, 2006

Next Steps

Neurol Lancet, 2006

Complications

• Cardiac arrhythmias

• Hypotension

• Hypoventilation/Hypoxia

• Aspiration pneumonitis

• Neurogenic pulmonary edema

• Metabolic lactic acidosis

• Hyperthermia

• Cardiac injury 2/2 catecholamine releaseUpToDate, 2015

Case Study

• 2 mg IV lorazepam administered STAT and Fosphenytoin load is ordered with improvement in EEG

• STAT Neurology consult placed

• MRI without abnormalities

• Family arrives to bedside

Case Study

• No prior seizure history

• Memory issues and personality changes x3 months

• No home meds or prior medical history

• Parents deny recent fever, chills, malaise

Why??

Seizure = Sign

Pathophysiology

• A seizure can be caused by any process that disrupts the cell membrane stability of a neuron

• The point at which the cell membrane becomes destabilized and an uncontrolled electrical discharge begins is known as the seizure threshold

• Lower the seizure threshold = more prone to seizures

UptoDate, 2015

Etiology

50% of seizures/SE are acute symptomatic

– Stroke

– Trauma

– Cerebral hypoxia

– Infection

– Tumor

Etiology

• AED noncompliance or use of drugs that lower seizure threshold

• Substance withdrawal

• Metabolic derangements

• Infectious cause

• Autoimmune/Paraneoplastic

Question # 4

What diagnostics and labs should be obtained?

A. CBC

B. BMP

C. UDS

D. CXR

E. LP

F. Pan cultures

G. Others?

• CBC, BMP, EKG, UDS, TFT, LFTs, Ammonia all unremarkable

• CXR shows widened mediastinum

• Blood, urine, sputum cultures (-)

• LP performed

– Nucs 0

– Glu 58 mg/dl

– Protein 40 mg/dl

– PCR negative for HSV

Etiology?

• Brain Injury/Insult

• AED noncompliance or use of drugs that lower seizure threshold

• Metabolic

• Infectious

• Autoimmune/Paraneoplastic Encephalitis

Autoimmune and Paraneoplastic Encephalitis

• Neoplastic Lung CA

• Anti-body Specific Syndromes

– Antibodies to intracellular antigens

• Ma2-associated encephalitis Testicular tumors

• Anti-CRMP5 encephalomyelitis NSCLC & Thymomas

– Antibodies to synaptic proteins

• Anti-NMDA receptor encephalitis

• Several others

Anti- NMDA Encephalitis

• Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis

– Psychiatric symptoms

– Seizures

– Memory deficits

– Dyskinesias

• IgG antibodies to NMDAR found in serum or CSF

• Think teratoma !!

• Treatment resection of tumor, IV IG, glucocorticoids

Case Study

• CSF (+) for Anti-NMDA

• CT of C/A/P shows mediastinal mass

• Resection with pathology confirmation

• Discharged from hospital to rehab after ~ 3 weeks

• 6 months follow up M.K. was back to attending classes

• Deficitmild short term memory deficits

Outcomes

• 20% mortality with first episode of GCSE

• 69-81% mortality for SE + anoxia

• Etiology = most important predictor of outcome

• Approximately 10-50% of survivors have residual neurological deficits

• Significant risk for recurrent seizures or SE

Neurology, 2007UpToDate, 2015

Summary

• Status Epilepticus is life threatening and seizures should be stopped as quickly as possible

• Remember sometimes status seizures are not obvious, symptoms can be very subtle or may only present as altered mental status

• Give a Benzo!

• Remember your ABCs

• Consult Neurology STAT

• Identify the cause as quickly as possible to improve outcomes

Questions??

References

Alderedge, B., Gelb, A. et al. A comparison of lorazepam, diazepam and placebo for the treatment of out of hospital status epilepticus. N Engl J Med 2001; 345:631

Brophy, G., Bell, R., Claassen, J., et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3

Chen, J., Wasterlain, C. Status epilepticus: Pathophysiology and management in adults. Neurol Lancet 2006; 5:3

Dalmau, J., Rosenfield, M. Paraneoplastic and autoimmune encephalitis. August 2015. http://www.uptodate.com

Drislane, F., Convulsive status epilepticus in adults: Treatment and prognosis. April 2015. http://www.uptodate.com

Gaspard, N., Jirsch, J., Hirsch, L. Nonconvulsive status epilepticus. April 2015. http://www.uptodate.com

Hauser, W. Status epilepticus: Epidemiologic considerations. Neurology 1990; 40:9.

Hesdorffer, D., Logroscino, G., Cascino, G., Hauser, W. Recurrence of afebrile status epilepticus in a population-based study in Rochester, Minnesota. Neurology 2007; 69(1):73

Lowenstein, D., Bleck, T., Macdonald, R. It’s time to revise the definition of status epilepticus. Epilepsia 1999; 40:120

Silbergleit, R., Durkalski, V., et al. Intramuscular versus intravenous therapy for prehospital status epilepticus N Engl J Med 2012; 366:591

Sutter, R., Stevens R., Kaplan P. Continuous Electroencephalographic monitoring in critically ill patients: Indications, limitations, and strategies. CCM Journal. 2013, 41(4) 1124-1132

Treiman, D., et al. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 1998; 339:792.