Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit

Objective: To assess risk factors and prognosis in patients with refractory status epilepticus (RSE). Methods: We retrospectively analysed all episodes of status epilepticus (SE) treated between 1993 and 2002 on the neurological intensive care unit (NICU) of the Charité-Universitätsmedizin Berlin. The predictive and prognostic features of RSE were compared with non-RSE (NRSE). All patients with “de novo” SE were followed up to identify the possible development of post-SE symptomatic epilepsy. Results: A total of 83 episodes fulfilled our criteria of SE. Of these 43% were refractory to first line anticonvulsants. The mean age of patients with SE was 53.3 (SD 19) years, with only two patients younger than 18 years. Encephalitis was significantly more often the primary cause in RSE (p<0.05), whereas low levels of antiepileptic drugs were significantly more often associated with NRSE (p<0.001). Hyponatraemia within the first 24 hours after onset of status activity was significantly more often associated with RSE (p<0.05). In RSE, compared with NRSE, significantly longer duration of seizure activity (p<0.001), more frequent recurrence of epileptic activity within the first 24 hours after the end of seizure activity (p<0.001), longer stay in the NICU and in hospital (p<0.001 and p<0.01, respectively), and more frequent development of symptomatic epilepsy (p<0.05) were seen. Conclusions: SE treated in the NICU is frequently refractory to first line anticonvulsant drugs. Encephalitis is a predictor for RSE, which is associated with markedly poor outcome, in particular, the development of post-SE symptomatic epilepsy. Thus prevention of this most severe form of SE should be the primary target of treatment of SE.

[1]  G. Mathern,et al.  Epilepsia , 1991, NEURO FUNDAMENTAL.

[2]  E. Serafetinides,et al.  ETIOLOGY AND PATHOGENESIS OF TEMPORAL LOBE EPILEPSY. , 1964, Archives of neurology.

[3]  J. Aicardi,et al.  Convulsive Status Epilepticus in Infants and Children , 1970, Epilepsia.

[4]  B. Meldrum,et al.  Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons. , 1973, Archives of neurology.

[5]  M. Aminoff,et al.  Status epilepticus: Causes, clinical features and consequences in 98 patients , 1980 .

[6]  C. A. Phillips,et al.  Herpes Simplex Encephalitis , 1966, Lancet.

[7]  R. Press,et al.  Proposal for Revised Clinical and ~lectro~nce~halo ~ra~hic Classification of Epileptic Seizures From the Commission on Classification and Terminology of the International League Against Epilepsy* , 1981 .

[8]  W. Hauser,et al.  Seizure recurrence after a first unprovoked seizure. , 1982, The New England journal of medicine.

[9]  R. Herndon,et al.  Brain dehydration and neurologic deterioration after rapid correction of hyponatremia. , 1989, Kidney international.

[10]  K. Yaffe,et al.  Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus , 1993, Neurology.

[11]  S. Shorvon,et al.  Tonic clonic status epilepticus. , 1993, Journal of neurology, neurosurgery, and psychiatry.

[12]  R. Delorenzo,et al.  Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. , 1993, JAMA.

[13]  D. Lowenstein,et al.  Status epilepticus at an urban public hospital in the 1980s , 1993, Neurology.

[14]  D. Lowenstein,et al.  Treatment of refractory generalized status epilepticus with continuous infusion of midazolam , 1994, Neurology.

[15]  J. Pellock,et al.  Determinants of Mortality in Status Epilepticus , 1994, Epilepsia.

[16]  M. C. McBride,et al.  Status epilepticus. , 2016, Pediatrics in review.

[17]  H. Farrar,et al.  Hyponatremia as the cause of seizures in infants: a retrospective analysis of incidence, severity, and clinical predictors. , 1995, Annals of emergency medicine.

[18]  G. Cascino.  Generalized convulsive status epilepticus. , 1996, Mayo Clinic proceedings.

[19]  W. Hauser,et al.  A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia , 1996, Neurology.

[20]  W. Hauser,et al.  Short‐Term Mortality After a First Episode of Status Epilepticus , 1997, Epilepsia.

[21]  W. Hauser,et al.  Incidence of status epilepticus in Rochester, Minnesota, 1965-1984 , 1998, Neurology.

[22]  J. Gastaut,et al.  Complex partial status epilepticus provoked by hyponatremia. , 1998, European neurology.

[23]  S. Tarlacı,et al.  Generalized tonic-clonic status epilepticus: causes, treatment, complications and predictors of case fatality , 1998, Journal of Neurology.

[24]  W. Hauser,et al.  Morbidity of Nonfebrile Status Epilepticus in Rochester, Minnesota, 1965–1984 , 1998, Epilepsia.

[25]  B. Uthman,et al.  A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. , 1998, The New England journal of medicine.

[26]  M. Stecker,et al.  Treatment of Refractory Status Epilepticus with Propofol: Clinical and Pharmacokinetic Findings , 1998, Epilepsia.

[27]  D. Lowenstein.  Status Epilepticus: An Overview of the Clinical Problem , 1999, Epilepsia.

[28]  D. Lowenstein,et al.  It's Time to Revise the Definition of Status Epilepticus , 1999, Epilepsia.

[29]  P Jallon,et al.  Incidence of status epilepticus in French-speaking Switzerland , 2000, Neurology.

[30]  W. Oertel,et al.  Incidence of Status Epilepticus in Adults in Germany: A Prospective, Population‐Based Study , 2001, Epilepsia.

[31]  E. Bertram,et al.  Propofol and Midazolam in the Treatment of Refractory Status Epilepticus , 2001, Epilepsia.

[32]  Manjit,et al.  Neurology , 1912, NeuroImage.

[33]  Susan T Herman,et al.  Epilepsy after brain insult: Targeting epileptogenesis , 2002, Neurology.

[34]  L. Marino.  Convergence of Complex Cognitive Abilities in Cetaceans and Primates , 2002, Brain, Behavior and Evolution.

[35]  S. Shorvon.  Does convulsive status epilepticus (SE) result in cerebral damage or affect the course of epilepsy--the epidemiological and clinical evidence? , 2002, Progress in brain research.

[36]  Wolfgang Löscher,et al.  Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy , 2002, Epilepsy Research.

[37]  Jan Claassen,et al.  Refractory status epilepticus: frequency, risk factors, and impact on outcome. , 2002, Archives of neurology.

[38]  Bagher Forghani,et al.  In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  I. Scheffer,et al.  Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t” , 2003, Journal of neurology, neurosurgery, and psychiatry.

[40]  K. Einhäupl,et al.  The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists , 2003, Journal of neurology, neurosurgery, and psychiatry.

[41]  C. Tonon,et al.  Incidence and Short‐term Prognosis of Status Epilepticus in Adults in Bologna, Italy , 2003, Epilepsia.

[42]  N. Fountain,et al.  Assessment of acute morbidity and mortality in nonconvulsive status epilepticus , 2003, Neurology.