Status epilepticus

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Synonyms and keywords: Persistent Seizure, Refractory Seizure, Resistant Seizure

Overview

Status epilepticus is a life-threatening neurological medical emergency caused by the prolongation of a seizure that fails to terminate due to an imbalance between excitatory and inhibitory neurotransmitters/mechanisms in the brain. It is defined as a seizure lasting 5 minutes or more, or a recurrent seizure without a recovery phase. In 1983 Gastaut identified status epilepticus as, “when an epileptic seizure is so frequently repeated or so prolonged as to create a fixed and lasting condition”. There is no established system for the classification of status epilepticus. status epilepticus may be caused by epilepsy, stroke, infection, metabolic imbalance, cerebral trauma or cerebrovascular accidents, hypoxia, eclampsia, and drug toxicity. Status epilepticus must be differentiated from other disorders that may mimic the clinic presentation such as neuroleptic malignant syndrome, psychogenic nonepileptic seizures, delerium tremens, low blood sugar, and movement disorders. The incidence of status epilepticus is approximately 7 to 40 cases per 100,000/year. Common risk factors in the development of status epilepticus include inadequate control of epilepsy, hypoglycemia, stroke, alcohol use, metabolic abnormalities, anoxia, hypoxia, tumors, and infections. Common complications of status epilepticus include cardiac dysrhythmia, metabolic derangements, autonomic dysfunction, neurogenic pulmonary edema, hyperthermia, rhabdomyolysis, and aspiration pneumonia. Brain injury can be minimized by; airway patency, adequate oxygenation/circulation, prevention of hypoglycemia, maintaining optimum body temperature, termination of a seizure by antiepileptic drugs. Lorazepam is a preferred benzodiazepine due to its low lipid solubility, rapid onset, long duration of action and high affinity to GABA receptor. Diazepam can be administered if lorazepam is not available or there is no IV access.

Historical Perspective

  • In 1983 Gastaut identified status epilepticus as, “when an epileptic seizure is so frequently repeated or so prolonged as to create a fixed and lasting condition”.[1]
  • In 2001, 2005 Shorvon defined it as “a term used to denote a range of conditions in which electrographic seizure activity is prolonged for 30 minutes or more and results in nonconvulsive clinical symptoms”.[2]
  • Status epilepticus was included in the classification of seizures of the International League Against Epilepsy of 1970 and 1981.[3]

Classification

  • There is no established system for the classification of status epilepticus.
  • However, various types of status epilepticus may occur as any kind of seizure may evolve into a status epilepticus can.[4]
    • Generalized Convulsive Status Epilepticus(GCSE), seizures last more that five minutes with tonic-clonic movement. It is the most common neurological emergency.[5]
    • Non-convulsive Status Epilepticus can be identified on electroencephalogram(EEG) with no motor convulsive activity (e.g persistent absence seizure)
    • Focal seizure affecting a group of muscle with/without loss of consciousness.
    • Myoclonic status epilepticus with prolonged jerks and epileptiform discharges on EEG.
    • Refractory status epilepticus, continuous seizure not responding to treatment.[6] [7]

Pathophysiology

  • Seizures occur due to an imbalance between excitatory and inhibitory neurotransmitters/mechanisms in the brain.
  • Excitatory neurotransmitters are glutamate, aspartate, and acetylcholine.
  • Inhibitory neurotransmitters include GABA.
  • The disturbance in calcium ion-dependent potassium ion current and magnesium blockade of N-methyl-d-aspartate (NMDA) play a role in the prolongation of seizures.
  • Status epilepticus occurs due to failure in termination of seizure.
  • Prolonged status epilepticus is more likely to develop resistance to drugs and have poor prognosis.

Causes

Differentiating Status epilepticus from other Diseases

Epidemiology and Demographics

  • The incidence of status epilepticus is approximately 7 to 40 cases per 100,000/year.
  • Status epilepticus seems to be more common in males.

Risk Factors

Screening

  • There is insufficient evidence to recommend routine screening for status epilepticus.

Natural History, Complications, and Prognosis

  • Common complications of status epilepticus include cardiac dysrhythmia, metabolic derangements, autonomic dysfunction, neurogenic pulmonary edema, hyperthermia, rhabdomyolysis, and aspiration pneumonia. [12]
  • Permanent neurologic damage can occur with prolonged status epilepticus.
  • Prognosis of status epilepticus depends upon the underlying cause, age, and medical condition of the patient. Overall mortality rate of status epilepticus is 7%–39%.[13]
  • Approximately 10 to 30% of patients with underlying brain condition who have status epilepticus die within 30 days.[10]
  • Patients with epilepsy and who develop status epilepticus have increased mortality risk. However, stabilizing condition and optimal maintenance of medication, sleep, stress factors and stimulants plays an important role in improving prognosis. [8]

Diagnosis

Diagnostic Study of Choice

  • There are no established criteria for the diagnosis of status epilepticus. However clinical manifestation, duration, EEG findings can aid in the diagnosis and identification of the underlying cause.

History and Symptoms

  • Status epilepticus is identified as a seizure lasting more than 5 mins or recurrent seizures without a recovery period.
  • Patient may have a recent history of infection with fever, head trauma, alteration in medication, sleep deprivation, alcohol use/withdrawal.
  • Past medical history of the patient could include stroke, prior seizures, meningitis, encephalitis.

Physical Examination

  • Consciousness may be impaired.
  • Rhythmic tonic-clonic movement may be present in patients with generalized convulsive status epilepticus. Non-convulsive status epilepticus may appear on an EEG.
  • In the post-ictal period focal neurological deficit may be present.
  • In suspected drug use, look for needle marks.
  • Presence of [[papilledema[[ could suggest a brain mass/abscess.

Laboratory Findings

  • There are no diagnostic laboratory findings associated with status epilepticus.
  • However, electrolyte, BUN, creatinine, glucose, LFT, toxicology, pregnancy test(in women of child-bearing age) and medication level should be checked to identify the underlying cause.

Electrocardiogram

  • There are no ECG findings associated with status epilepticus.

X-ray

  • There are no x-ray findings associated with status epilepticus.

Echocardiography or Ultrasound

CT scan

  • There are no CT scan findings associated with status epilepticus.
  • In patients with a previous history of stroke may appear on CT scan.

MRI

  • Variable MRI changes have been noticed in patients with status epilepticus but it is not present in every patient.
  • The findings suggest cytotoxic and vasogenic edema due to prolonged seizure activity.

Other Imaging Findings

  • There are no other imaging findings associated with status epilepticus.

Other Diagnostic Studies

  • Electroencephalogram (EEG) is very important in recognizing and classifying the type of status epilepticus supported by clinical semiology.

Treatments

Medical Therapy

  • Brain injury can be minimized by; airway patency, adequate oxygenation/circulation, prevention of hypoglycemia, maintaining optimum body temperature, termination of a seizure by antiepileptic drugs.
  • For tonic-clonic status epilepticus treatment should be initiated in 5 minutes. For focal status epilepticus treatment should be initiated in 10 minutes.[14]
  • Benzodiazepines are the antiepileptic drug of choice for initial managment. [10] Lorazepam is a preferred benzodiazepine due to its low lipid solubility, rapid onset, long duration of action and high affinity to GABA receptor. Diazepam can be administered if lorazepam is not available or there is no IV access.
  • Other antiepileptic drugs like fosphenytoin, phenytoin, levetiracetam, and valproic acid can be co-administered.
  • Status epilepticus is considered refractory to benzodiazepine if two rounds of the medication fail to terminate the seizure.
  • In case of refractory status epilepticus continuous intravenous (IV) infusion of midazolam, pentobarbital, or propofol should be administered.[15]
  • For status epilepticus induced by eclampsia in pregnant women, magnesium sulfate is the drug of choice.

Surgery

  • Surgical intervention is not recommended for the management of status epilepticus.
  • However, the underlying cause of status epilepticus including the brain abscess or brain tumor could benefit from a surgical procedure.

Primary Prevention

Secondary Prevention

  • There are no established measures for the secondary prevention of status epilepticus.
  • Patients with a prior episode of status epilepticus can prevent future episodes by controlling the aforementioned risk factors.

References

  1. Gastaut H. Classification of status epilepticus. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status epilepticus. New York: Raven Press, 1983:15–35.
  2. Shorvon S. The management of status epilepticus. J Neurol Neurosurg Psychiatry 2001;70 (Suppl 2):ii22–27
  3. "A Proposed International Classification of Epileptic Seizures". Epilepsia. 5 (4): 297–306. 1964. doi:10.1111/j.1528-1157.1964.tb03337.x. ISSN 0013-9580.
  4. . doi:10.1001/archneur.1973.00490190028002. Check |doi= value (help). Missing or empty |title= (help)
  5. Scott, R. C; Surtees, R. A H; Neville, B. G R (1998). "Status epilepticus: pathophysiology, epidemiology, and outcomes". Archives of Disease in Childhood. 79 (1): 73–77. doi:10.1136/adc.79.1.73. ISSN 0003-9888.
  6. Won, Sae‐Yeon; Dubinski, Daniel; Sautter, Lisa; Hattingen, Elke; Seifert, Volker; Rosenow, Felix; Freiman, Thomas; Strzelczyk, Adam; Konczalla, Juergen (2019). "Seizure and status epilepticus in chronic subdural hematoma". Acta Neurologica Scandinavica. 140 (3): 194–203. doi:10.1111/ane.13131. ISSN 0001-6314.
  7. Harrison's Manual of Medicine 19th Edition
  8. 8.0 8.1 8.2 Stasiukynienė, Virginija; Pilvinis, Vidas; Reingardienė, Dagmara; Janauskaitė, Liuda (2009). "Epileptic seizures in critically ill patients". Medicina. 45 (6): 501. doi:10.3390/medicina45060066. ISSN 1010-660X.
  9. 9.0 9.1 9.2 Langenbruch, Lisa; Krämer, Julia; Güler, Sati; Möddel, Gabriel; Geßner, Sophia; Melzer, Nico; Elger, Christian E.; Wiendl, Heinz; Budde, Thomas; Meuth, Sven G.; Kovac, Stjepana (2019). "Seizures and epilepsy in multiple sclerosis: epidemiology and prognosis in a large tertiary referral center". Journal of Neurology. 266 (7): 1789–1795. doi:10.1007/s00415-019-09332-x. ISSN 0340-5354.
  10. 10.0 10.1 10.2 Al-Mufti, Fawaz; Claassen, Jan (2014). "Neurocritical Care". Critical Care Clinics. 30 (4): 751–764. doi:10.1016/j.ccc.2014.06.006. ISSN 0749-0704.
  11. Fountain, Nathan B. (2000). "Status Epilepticus: Risk Factors and Complications". Epilepsia. 41 (s2): S23–S30. doi:10.1111/j.1528-1157.2000.tb01521.x. ISSN 0013-9580.
  12. Sutter, Raoul; Dittrich, Tolga; Semmlack, Saskia; Rüegg, Stephan; Marsch, Stephan; Kaplan, Peter W. (2018). "Acute Systemic Complications of Convulsive Status Epilepticus—A Systematic Review". Critical Care Medicine. 46 (1): 138–145. doi:10.1097/CCM.0000000000002843. ISSN 0090-3493.
  13. Towne, Alan R.; Pellock, John M.; Ko, Daijin; DeLorenzo, Robert J. (1994). "Determinants of Mortality in Status Epilepticus". Epilepsia. 35 (1): 27–34. doi:10.1111/j.1528-1157.1994.tb02908.x. ISSN 0013-9580.
  14. Trinka, Eugen; Cock, Hannah; Hesdorffer, Dale; Rossetti, Andrea O.; Scheffer, Ingrid E.; Shinnar, Shlomo; Shorvon, Simon; Lowenstein, Daniel H. (2015). "A definition and classification of status epilepticus - Report of the ILAE Task Force on Classification of Status Epilepticus". Epilepsia. 56 (10): 1515–1523. doi:10.1111/epi.13121. ISSN 0013-9580.
  15. Harrison's Manual of Medicine 19th Edition