Clinical risk factors in SUDEP

Objective We conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP). Methods The study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP). Results Experiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86–48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54–48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57–24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93–8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66–151.88), with AP estimated at 0.69 (CI 0.53–0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP. Conclusions Individuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

[1]  G. Cascino,et al.  Incidence and risk factors in sudden unexpected death in epilepsy , 2001, Neurology.

[2]  C. Binnie,et al.  A study of mortality after temporal lobe epilepsy surgery , 1999, Neurology.

[3]  Orrin Devinsky,et al.  Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention , 2016, The Lancet Neurology.

[4]  Orrin Devinsky,et al.  Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures , 2016, Epilepsia.

[5]  Philippe Ryvlin,et al.  Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy , 2017, Neurology.

[6]  Edouard Hirsch,et al.  ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology , 2017, Epilepsia.

[7]  Josemir W Sander,et al.  Do antiepileptic drugs or generalized tonic–clonic seizure frequency increase SUDEP risk? A combined analysis , 2012, Epilepsia.

[8]  Josemir W Sander,et al.  Combined analysis of risk factors for SUDEP , 2011, Epilepsia.

[9]  Neil Pearce,et al.  Case-control studies: basic concepts. , 2012, International journal of epidemiology.

[10]  Graeme J. Sills,et al.  Sudden unexpected death in epilepsy: A search for risk factors , 2007, Epilepsy & Behavior.

[11]  Sandor Beniczky,et al.  Wearable devices for sudden unexpected death in epilepsy prevention , 2018, Epilepsia.

[12]  P. Ryvlin,et al.  Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials , 2011, The Lancet Neurology.

[13]  Tomas Andersson,et al.  Calculating measures of biological interaction , 2005, European Journal of Epidemiology.

[14]  D. Thurman,et al.  Sudden unexpected death in epilepsy: Assessing the public health burden , 2014, Epilepsia.

[15]  R. Westerling,et al.  Unexplained differences between hospital and mortality data indicated mistakes in death certification: an investigation of 1,094 deaths in Sweden during 1995. , 2009, Journal of clinical epidemiology.

[16]  T. Tomson,et al.  Circumstances of SUDEP: A nationwide population‐based case series , 2018, Epilepsia.

[17]  A. Schulze-Bonhage,et al.  Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study , 2013, The Lancet Neurology.

[18]  Josemir W Sander,et al.  Case-control study of SUDEP , 2005, Neurology.

[19]  M. Sperling,et al.  A reappraisal of mortality after epilepsy surgery , 2016, Neurology.

[20]  M. Sperling,et al.  Long‐term surveillance of SUDEP in drug‐resistant epilepsy patients treated with VNS therapy , 2018, Epilepsia.

[21]  Rainer Surges,et al.  Who to target in sudden unexpected death in epilepsy prevention and how? Risk factors, biomarkers, and intervention study designs , 2016, Epilepsia.

[22]  J. Ludvigsson,et al.  External review and validation of the Swedish national inpatient register , 2011, BMC public health.

[23]  L. Nashef.  Sudden Unexpected Death in Epilepsy: Terminology and Definitions , 1997, Epilepsia.

[24]  L. Nilsson,et al.  Risk factors for sudden unexpected death in epilepsy: a case control study , 1999, The Lancet.

[25]  T. Tomson,et al.  The incidence of SUDEP , 2017, Neurology.

[26]  J. H. Cross,et al.  Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology , 2017, Epilepsia.

[27]  Josemir W Sander,et al.  Nocturnal supervision and SUDEP risk at different epilepsy care settings , 2018, Neurology.

[28]  M. Neovius,et al.  The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research , 2019, European Journal of Epidemiology.

[29]  J. Annegers,et al.  United States Perspective on Definitions and Classifications , 1997, Epilepsia.

[30]  Josemir W Sander,et al.  Sudden unexpected death in epilepsy: People with nocturnal seizures may be at highest risk , 2012, Epilepsia.

[31]  J. Duncan,et al.  From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy , 2016, Epilepsia.