Neurology International Open 2017; 01(03): E189-E203
DOI: 10.1055/s-0043-103383
Review
© Georg Thieme Verlag KG Stuttgart · New York

Nonconvulsive Status Epilepticus in Adults: Types, Pathophysiology, Epidemiology, Etiology, and Diagnosis

Stephan Rüegg
1   Department of Clinical Neurology, University Hospital Basel, Basel, Switzerland
› Author Affiliations
Further Information

Publication History

Publication Date:
04 September 2017 (online)

Abstract

Nonconvulsive status epilepticus (NCSE) is defined by permanent electroclinical nonconvulsive epileptic activity or a series of nonconvulsive seizures without recovery to baseline. This “silent” manifestation of lasting neurological symptoms, like aphasia, confusion, etc., impedes easily recognizing NCSE. The most important diagnostic step often is to consider the possibility of NCSE. NCSE can only be confirmed by an immediate EEG recording. Epidemiological studies show slight preponderance of convulsive status epilepticus (CSE) over NCSE (60:40%); however, this might result from lack of recognition of NCSE because of its very unspectacular manifestation. Regarding pathophysiology, the neuronal mechanisms are identical for both NCSE and CSE, but they spare the primary motor neurons. Permanent hyperexcitability may damage the neurons involved in NCSE the same way as the motor neurons in CSE. However, NCSE is spared from the life-threatening secondary pathophysiological sequelae of CSE (lactic acidosis, respiratory exhaustion, rhabdomyolsis, etc.). Nevertheless, autonomic dysregulation (arrhythmias (ventricular tachycardia/asystolia), apneas) may also expose the patient to substantial acute risks. There are a myriad of causes for NCSE and they are mainly medication errors (insufficient adherence or addition of new drugs with interactions) in patients with known epilepsy. In these patients and in those without known epilepsy, other causes include metabolic, toxic, structural (tumors, hemorrhages, ischemia), infectious, inflammatory, and autoimmune causes. Thus, it is germane to extensively search for the cause of the NCSE because the immediate and proper therapy of the underlying cause of, especially the acute symptomatic, forms of NCSE is at least as important as the antiictal treatment.

 
  • References

  • 1 Maganti R, Gerber P, Drees C. et al. Nonconvulsive status epilepticus. Epilepsy Behav 2008; 12: 572-586
  • 2 Rosenow F, Knake S, Hamer HM. Nonkonvulsiver Status epilepticus. Modeerscheinung oder behandlungspflichtige Realität?. Nervenarzt 2012; 83: 1551-1558
  • 3 Fernández-Torre JL, Kaplan PW, Hernández-Hernández MA. New understanding of nonconvulsive status epilepticus in adults: treatments and challenges. Expert Rev Neurother 2015; 15: 1455-1473
  • 4 Beleza P, Rocha J, Pinho J. Diagnosis, etiology, and treatment of nonconvulsive status epilepticus, a semiological oriented review. Neurologist 2015; 19: 160-167
  • 5 Sutter R, Semmlack S, Kaplan PW. Nonconvulsive status epilepticus in adults – insights into the invisible. Nat Rev Neurol 2016; [epub ahead of print] April 11 DOI: 10.1038/nrneurol.2016.45.
  • 6 Shorvon S. What is nonconvulsive status epilepticus, and what are its subtypes?. Epilepsia 2007; 48 (Suppl. 08) S35-S38
  • 7 Trinka E, Cock H, Hesdorffer D. et al. A definition and classification of status epilepticus – report of the ILAE Task force on Classification of Status Epilepticus. Epilepsia 2015; 56: 1515-1523
  • 8 Sung CY, Chu NS. Status epilepticus in the elderly: etiology, seizures type, and outcome. Acta Neurol Scand 1989; 80: 51-56
  • 9 Cheng S. Non-convulsive status epilepticus in the elderly. Epileptic Disord 2014; 16: 385-394
  • 10 Sutter R, Fuhr P, Grize L. et al. Continuous video-EEG monitoring increases detection rate of nonconvulsive status epilepticus in the ICU. Epilepsia 2011; 52: 453-457
  • 11 Naeije G, Depondt C, Meeus C. et al. EEG patterns compatible with nonconvulsive status epilepticus are common in elderly patients with delirium: a prospective study with continuous EEG monitoring. Epilepsy Behav 2014; 36: 18-21
  • 12 Theodore WH, Porter RJ, Perry JK. Complex partial seizures: Clinical characteristics and differential diagnosis. Neurology 1983; 33: 1115-1121
  • 13 Theodore WH, Porter RJ, Albert P. et al. The secondarily generalized tonic-clonic seizure: A videotape analysis. Neurology 1994; 44: 1403-1407
  • 14 Jenssen S, Gracely EJ, Sperling MR. How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit. Epilepsia 2006; 47: 1499-1503
  • 15 Afra P, Jouny CC, Bergey GK. Duration of complex partial seizures: Intracranial EEG study. Epilepsia 2008; 49: 677-684
  • 16 Shinnar S, Berg AT, Moshé SL. et al. How long do new-onset seizures in children last?. Ann Neurol 2001; 49: 659-664
  • 17 Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia 1999; 40: 120-122
  • 18 Young GB, Jordan KG, Doig GS. An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: An investigation of variables associated with mortality. Neurology 1996; 47: 83-89
  • 19 Sloviter RS, Zappone CA, Bumanglag AV. et al. On the relevance of prolonged convulsive status epilepticus in animals to the etiology and neurobiology of human temporal lobe epilepsy. Epilepsia 2007; 48 (Suppl. 08) S6-S10 Erratum in: Epilepsia 2007; 48 2382
  • 20 Corsellis JA, Bruton CJ. Neuropathology of status epilepticus in humans. Adv Neurol 1983; 34: 129-139
  • 21 Gastaut H. A propos d’une classification symptomatologique des états de mal épileptiques. In: Gastaut H, Roger J, Loeb H. eds. Les états de mal épileptiques. Paris: Masson; 1967: 1-8
  • 22 Chong DJ, Hirsch LJ, Which EEG. patterns warrant treatment in the critically ill? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns. J Clin Neurophysiol 2005; 22: 79-91
  • 23 Bauer G, Trinka E. Nonconvulsive status epilepticus and coma. Epielpsia 2010; 51: 177-190
  • 24 Seeck M, Alberque C, Spinelli L. et al. Left temporal rhythmic electrical activity: A correlate for psychosis? A case report. J Neural Transm 1999; 106: 787-794
  • 25 Kuba R, Brázdil M, Rektor I. Postictal psychosis and its electrophysiological correlates in invasive EEG: A case report study and literature reveiw. Epilepsy Behav 2012; 23: 426-430
  • 26 Sutter R, Kaplan PW, Valença M. et al. EEG for diagnosis and prognosis of acute nonhypoxic encephalopathy: History and current evidence. J Clin Neurophysiol 2015; 32: 456-464
  • 27 Sutter R, Kaplan PW. Clinical, electroencephalographic, and neuroradiological outcome predictors in acute nonhypoxic encephalopathy: A nine-year cohort study. Clin EEG Neurosci 2016; 47: 61-68
  • 28 Lado FA, Moshé SL. How do seizures stop?. Epilepsia 2008; 49: 1651-1664
  • 29 Meldrum BS. Concept of activity-induced cell death in epilepsy: Historical and contemporary perspectives. Prog Brain Res 2002; 135: 3-11
  • 30 Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci 2005; 25: 7724-7733
  • 31 Goodkin HP, Joshi S, Mitchedlishvili Z. et al. Subunit-specific trafficking of GABA(A) receptors during status epilepticus. J Neurosci 2008; 28: 2527-2538
  • 32 Hunt DL, Castillo PE. Synaptic plasticity of NMDA receptros: Mechanisms and functional implications. Curr Opin Neurobiol 2012; 22: 496-508
  • 33 Naylor DE, Liu H, Niquet J. et al. Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus. Neurobiol Dis 2013; 54: 225-238
  • 34 Holzer FJ, Seeck M, Korff CM. Autoimmunity and inflammation in status epilepticus: from concepts to therapies. Expert Rev Neurother 2014; 14: 1181-1202
  • 35 Vezzani A, Dingledine R, Rossetti AO. Immunity and inflammation in status epilepticus and its sequelae possibilities for therapeutic application. Expert Rev Neurother 2015; 15: 1081-1092
  • 36 Fabene PF, Navarro Mora G, Martinello M. et al. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat Med 2008; 14: 1377-1383
  • 37 Henshall DC. MicroRNAs in the pathophysiology and treatment of status epilepticus. Front Mol Neurosci 2013; 6: 37 10.3389/fnmol.2013.00037
  • 38 Worrell GA, Cranstoun SD, Echauz J. et al. Evidence of self-organized criticality in human epileptic hippocampus. Neuroreport 2002; 13: 2017-2021
  • 39 Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res 1990; 5: 49-60
  • 40 Shorvon S. the management of status epilepticus. J Neurol Neurosurg Psychiatry 2001; 70 Suppl2 II22-II27
  • 41 Sloviter RS. Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science 1987; 235: 73-76
  • 42 Young GB, Jordan KG. Do nonconvulsive seizures damage the brain? – Yes. Arch Neurol 1998; 55: 117-119
  • 43 Aminoff MJ. Do nonconvulsive seizures damage the brain? – No. Arch Neurol 1998; 55: 119-120
  • 44 Wasterlain CG, Fujikawa DG, Penix L. et al. Pathopyhsiological mechanisms of brain damage from status epilepticus. Epilepsia 1993; 34 (Suppl. 01) S37-S53
  • 45 Krumholz A, Sung GY, Fisher RS. et al. Complex partial status epilepticus accompanied by serious morbidity and mortality. Neurology 1995; 45: 1499-1504
  • 46 Fujikawa DG, Itabashi HH, Wu A. et al. Status epilepticus-induced neuronal loss in humans without systemic complications of epilepsy. Epilepsia 2000; 41: 981-991
  • 47 Parmar H, Lim SH, Tan NCK. et al. Acute symptomatic seizures and hippocampus damage: DWI and MRS findings. Neurology 2006; 66: 1732-1735
  • 48 Bauer G, Gotwald T, Dobesberger J. et al. Transient and permanent magnetic resonance imaging abnormalities after complex partial status epilepticus. Epilepsy Behav 2006; 8: 666-671
  • 49 Vespa PM, McArthur DLXu Y. et al. Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology 2010; 75: 792-798
  • 50 van der Lende M, Surges R, Sander JW. et al. Cardiac arrhythmias during after epileptic seizures. J Neurol Neurosurg Psychiatry 2016; 87: 69-74
  • 51 Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology 2015; 85: 1332-1341
  • 52 Thomas P, Valton L, Genton P. Absence and myoclonic status epilepticus.precipitated by antiepileptic drugs in idiopathic generalized epilepsy. Brain 2006; 129: 1281-1292
  • 53 Thomas P, Beaumanoir A, Genton P. et al. “de novo” absence status of late onset: report of 11 cases. Neurology 1992; 42: 104-110
  • 54 Pandis D, Scarmeas N. Seizures in Alzheimerdisease: clinical and epidemiological data. Epilepsy Curr 2012; 12: 184-187
  • 55 Nicastro N, Assal F, Seeck M. From here to epilepsy: The risk of seizure in patients with Alzheimer’s disease. Epileptic Disord 2016; 16: 1-12
  • 56 Amatniek JC, Hauser WA, DelCastillo-Castaneda C. et al. Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia 2006; 47: 867-872
  • 57 Scarmeas N, Honig LS, Choi H. et al. Seizures in Alzheimer’s disease: Who, when, and how common?. Arch Neurol 2009; 66: 992-997
  • 58 Irizarry MC, Jin S, He F. et al. Incidence of new-onset seizures in mild to moderate Alzheimer disease. Arch Neurol 2012; 69: 368-372
  • 59 Sherzai D, Losey T, Vega S. et al. Seizures and dementia in the elderly: Nationwide inpatient sample 1999– 2008. Epilepsy Behav 2014; 36: 53-56
  • 60 Beyenburg S, Elger CE, Reuber M. Acute confusion or altered mental state: Consider nonconvulsive status epilepticus. Gerontology 2007; 53: 388-396
  • 61 Noebels J. A perfect storm: Converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation. Epilepsia 2011; 52 (Suppl. 01) S39-S46
  • 62 Feddersen B, Rémi J, Einheilig M. et al. Parkinson’s disease: Less epileptic seizures, more status epilepticus. Epilepsy Res 2014; 108: 349-354
  • 63 DeLorenzo RJ, Hauser WA, Towne AR. et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996; 46: 1029-1035
  • 64 Hesdorffer DC, Logroscino G, Cascino G. et al. Incidence of status epilepticus in Rochester, Minnestoa 1965– 1984. Neurology 1998; 50: 735-741
  • 65 Coeytaux A, Jallon P, Galobardes B. et al. Incidence of status epilepticus in French-speaking Switzerland (EPISTAR). Neurology 2000; 55: 693-697
  • 66 Knake S, Rosenow F, Vescovi M. et al. Incidence of status epilepticus in adults in Germany: A prospective, population-based study. Epilepsia 2001; 42: 714-718
  • 67 Vignatelli L, Tonon C, D’Alessandro R. Bologna Group for the Study of Status Epilepticus. Incidence and short-term prognosis of status epilepticus in adults in Bologna. Italy. Epilepsia 2003; 44: 964-968
  • 68 Rüegg S. Non-convulsive status epilepticus in adults: An overview. Schweiz Arch Neurol Psychiatrie 2008; 159: 53-83
  • 69 Rudin D, Grize L, Schindler C. et al. High prevalence of nonconvulsive and subtle status epilepticus in an ICU of a tertiary care center: A three-year observational study. Epilepsy Res 2011; 96: 140-150
  • 70 Privitera M, Hoffman M, Moore JL. Jester D. EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness. Epilepsy Res 1994; 18: 155-166
  • 71 Alroughani R, Javidan M, Qasem A. et al. Non-convulsive status epilepticus: the rate of occurrence in a general hospital. Seizure 2009; 18: 38-42
  • 72 Towne AR, Waterhouse E, Boggs JG. et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000; 54: 340-345
  • 73 Sutter R, Rüegg S, Kaplan PW. Epidemiology, diagnosis, and management of nonconvulsive status epilepticus – opening Pandora’s box. Neurol Clin Pract 2012; 2: 275-286
  • 74 Kaplan PW. EEG criteria for nonconvulsive status epilepticus. Epilepsia 2007; 48 (Suppl. 08) S39-S41
  • 75 Beniczky S, Hirsch LJ, Kaplan PW. et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia 2013; 54 (Suppl. 06) S28-S29
  • 76 Sutter R, Kaplan PW. Electroencephalographic criteria for nonconvulsive status epilepticus: Synopsis and comprehensive survey. Epilepsia 2012; 53 (Suppl. 03) 1-51
  • 77 Hirsch LJ, LaRoche SM, Gaspard N. et al. American Clinical Neurophysiological Society’s Standardized Critical Care EEG Terminology: 2012 version. J Clin Neurophysiol 2013; 30: 1-27
  • 78 Hauf M, Slotboom J, Nirkko A. et al. Cortical regional hyperperfusion in nonconvulsive status epilepticus measured by dynamic brain perfusion CT. Am J Neuroradiol 2009; 30: 693-698
  • 79 Masterson K, Vargas MI, Delavelle J. Postictal deficit mimicking stroke: Role of perfusion CT. J Neuroradiol 2009; 36: 48-51
  • 80 Winkler DT, Fluri F, Fuhr P. et al. Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome. Stroke 2009; 40: 1522-1525
  • 81 Lansberg MG, O’Brien MW, Norbash AM. et al. MRI abnormalities associated with partial status epilepticus. Neurology 1999; 52: 1021-1027
  • 82 Flacke S, Wüllner U, Keller E. et al. Reversible changes in echo planar perfusion- and diffusion-weighted MRI in status epilepticus. Neuroradiology 2000; 42: 92-95
  • 83 Szabo K, Poepel A, Pohlmann-Eden B. et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain 2005; 128: 1369-1376
  • 84 Huang YC, Weng HH, Tsai YT. et al. Periictal magnetic resonance imaging in status epilepticus. Epilepsy Res 2009; 86: 72-81
  • 85 Katramados AM, Burdette D, Patel SC. et al. Periictal diffusion abnormalities of the thalamus in partial status epilepticus. Epilepsia 2009; 50: 265-275
  • 86 Canas N, Breia P, Soares P. et al. The elctroclinical-imagological spectrum and long-term outcome of transient periictal MRI abnormalities. Epilepsy Res 2010; 91: 240-252
  • 87 Cartagena AM, Young GB, Lee DH. et al. Reversible and irreversible cranial MRI findings associated with status epilepticus. Epilepsy Behav 2014; 33: 24-30