Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-26T00:10:22.393Z Has data issue: false hasContentIssue false

Chapter 10 - Management of Status Epilepticus and Recurrent Seizures

from Part III - Practice of Neuromonitoring: Pediatric Intensive Care Unit

Published online by Cambridge University Press:  08 September 2022

Cecil D. Hahn
Affiliation:
The Hospital for Sick Children, University of Toronto
Courtney J. Wusthoff
Affiliation:
Lucile Packard Children’s Hospital, Stanford University
Get access

Summary

Status epilepticus is a life-threatening and time-sensitive emergency. Continuous EEG monitoring allows the detection of electrographic seizures and electrographic status epilepticus. Increasing evidence guides best practices for which patients to monitor for these conditions and appropriate duration of monitoring. The treatment of SE consists of benzodiazepines, non-benzodiazepines, antiepileptic drugs, and continuous infusions; cEEG monitoring is helpful in assessing the response to treatment. Interpretation of EEG after electrographic seizures requires care, as some patterns on the ictal-interictal continuum may be challenging. This chapter reviews current evidence regarding neuromonitoring and the management of status epilepticus and recurrent seizures.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abend, NS, Chapman, KE, Gallentine, WB, et al. Electroencephalographic monitoring in the pediatric intensive care unit. Curr Neurol Neurosci Rep. 2013;13(3):330.CrossRefGoogle ScholarPubMed
Lothman, E. The biochemical basis and pathophysiology of status epilepticus. Neurology. 1990;40(5 Suppl 2):1323.Google Scholar
Meldrum, BS, Horton, RW. Physiology of status epilepticus in primates. Arch Neurol. 1973;28(1):19.CrossRefGoogle ScholarPubMed
Lowenstein, DH, Bleck, T, Macdonald, RL. It’s time to revise the definition of status epilepticus. Epilepsia. 1999;40(1):120–2.Google Scholar
Tsuchida, TN, Wusthoff, CJ, Shellhaas, RA, et al. American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society critical care monitoring committee. J Clin Neurophysiol. 2013;30(2):161–73.CrossRefGoogle ScholarPubMed
Sanchez, SM, Carpenter, J, Chapman, KE, et al. Pediatric ICU EEG monitoring: current resources and practice in the United States and Canada. J Clin Neurophysiol. 2013;30(2):156–60.CrossRefGoogle ScholarPubMed
Loddenkemper, T, Goodkin, HP. Treatment of pediatric status epilepticus. Curr Treat Options Neurol. 2011;13(6):560–73.CrossRefGoogle ScholarPubMed
Chin, RF, Neville, BG, Scott, RC. A systematic review of the epidemiology of status epilepticus. Eur J Neurol. 2004;11(12):800–10.Google Scholar
DeLorenzo, RJ, Hauser, WA, Towne, AR, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46(4):1029–35.Google Scholar
Hesdorffer, DC, Logroscino, G, Cascino, G, Annegers, JF, Hauser, WA. Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology. 1998;50(3):735–41.Google Scholar
Abend, NS, Gutierrez-Colina, AM, Topjian, AA, et al. Nonconvulsive seizures are common in critically ill children. Neurology. 2011;76(12):1071–7.Google Scholar
Hosain, SA, Solomon, GE, Kobylarz, EJ. Electroencephalographic patterns in unresponsive pediatric patients. Pediatr Neurol. 2005;32(3):162–5.Google Scholar
Jette, N, Claassen, J, Emerson, RG, Hirsch, LJ. Frequency and predictors of nonconvulsive seizures during continuous electroencephalographic monitoring in critically ill children. Arch Neurol. 2006;63(12):1750–5.Google Scholar
Abend, NS, Dlugos, DJ. Nonconvulsive status epilepticus in a pediatric intensive care unit. Pediatr Neurol. 2007;37(3):165–70.Google Scholar
Alehan, FK, Morton, LD, Pellock, JM. Utility of electroencephalography in the pediatric emergency department. J Child Neurol. 2001;16(7):484–7.Google Scholar
Shahwan, A, Bailey, C, Shekerdemian, L, Harvey, AS. The prevalence of seizures in comatose children in the pediatric intensive care unit: a prospective video-EEG study. Epilepsia. 2010;51(7):1198–204.Google Scholar
Williams, K, Jarrar, R, Buchhalter, J. Continuous video-EEG monitoring in pediatric intensive care units. Epilepsia. 2011;52(6):1130–6.Google Scholar
Kirkham, FJ, Wade, AM, McElduff, F, et al. Seizures in 204 comatose children: incidence and outcome. Intensive Care Med. 2012;38(5):853–62.CrossRefGoogle ScholarPubMed
Abend, NS, Topjian, A, Ichord, R, et al. Electroencephalographic monitoring during hypothermia after pediatric cardiac arrest. Neurology. 2009;72(22):1931–40.Google Scholar
Tay, SK, Hirsch, LJ, Leary, L, et al. Nonconvulsive status epilepticus in children: clinical and EEG characteristics. Epilepsia. 2006;47(9):1504–9.Google Scholar
Greiner, HM, Holland, K, Leach, JL, et al. Nonconvulsive status epilepticus: the encephalopathic pediatric patient. Pediatrics. 2012;129(3):e748–55.CrossRefGoogle ScholarPubMed
Saengpattrachai, M, Sharma, R, Hunjan, A, et al. Nonconvulsive seizures in the pediatric intensive care unit: etiology, EEG, and brain imaging findings. Epilepsia. 2006;47(9):1510–18.Google Scholar
Topjian, AA, Gutierrez-Colina, AM, Sanchez, SM, et al. Electrographic status epilepticus is associated with mortality and worse short-term outcome in critically ill children. Crit Care Med. 2013;41(1):215–23.Google Scholar
Abend, NS. Electrographic status epilepticus in children with critical illness: epidemiology and outcome. Epilepsy Behav. 2015;49:223–7.Google Scholar
Abend, NS, Arndt, DH, Carpenter, JL, et al. Electrographic seizures in pediatric ICU patients: cohort study of risk factors and mortality. Neurology. 2013;81(4):383–91.Google Scholar
Claassen, J, Mayer, SA, Kowalski, RG, Emerson, RG, Hirsch, LJ. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology. 2004;62(10):1743–8.Google Scholar
Towne, AR, Waterhouse, EJ, Boggs, JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54(2):340–5.Google Scholar
Sanchez Fernandez, I, Abend, NS, Arndt, DH, et al. Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study. J Pediatr. 2014;164(2):339–46 e1-2.CrossRefGoogle Scholar
Loddenkemper, T, Syed, TU, Ramgopal, S, et al. Risk factors associated with death in in-hospital pediatric convulsive status epilepticus. PLoS ONE. 2012;7(10):e47474.Google Scholar
Maytal, J, Shinnar, S, Moshe, SL, Alvarez, LA. Low morbidity and mortality of status epilepticus in children. Pediatrics. 1989;83(3):323–31.CrossRefGoogle ScholarPubMed
Sanchez Fernandez, I, Abend, NS, Agadi, S, et al. Time from convulsive status epilepticus onset to anticonvulsant administration in children. Neurology. 2015;84(23):2304–11.Google Scholar
Coeytaux, A, Jallon, P, Galobardes, B, Morabia, A. Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR). Neurology. 2000;55(5):693–7.Google Scholar
Knake, S, Rosenow, F, Vescovi, M, et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia. 2001;42(6):714–18.Google Scholar
Martinos, MM, Yoong, M, Patil, S, et al. Early developmental outcomes in children following convulsive status epilepticus: a longitudinal study. Epilepsia. 2013;54(6):1012–19.Google Scholar
Raspall-Chaure, M, Chin, RF, Neville, BG, Scott, RC. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol. 2006;5(9):769–79.Google Scholar
Sahin, M, Menache, CC, Holmes, GL, Riviello, JJ. Outcome of severe refractory status epilepticus in children. Epilepsia. 2001;42(11):1461–7.Google Scholar
Payne, ET, Zhao, XY, Frndova, H, et al. Seizure burden is independently associated with short term outcome in critically ill children. Brain. 2014;137(Pt 5):1429–38.Google Scholar
Schreiber, JM, Zelleke, T, Gaillard, WD, et al. Continuous video EEG for patients with acute encephalopathy in a pediatric intensive care unit. Neurocrit Care. 2012;17(1):31–8.Google Scholar
Abend, NS, Topjian, AA, Williams, S. How much does it cost to identify a critically ill child experiencing electrographic seizures? J Clin Neurophysiol. 2015;32(3):257–64.CrossRefGoogle ScholarPubMed
Abend, NS, Dlugos, DJ, Hahn, CD, Hirsch, LJ, Herman, ST. Use of EEG monitoring and management of non-convulsive seizures in critically ill patients: a survey of neurologists. Neurocrit Care. 2010;12(3):382–9.Google Scholar
Payne, ET, Hahn, CD. Continuous electroencephalography for seizures and status epilepticus. Curr Opin Pediatr. 2014;26(6):675–81.Google Scholar
Gutierrez-Colina, AM, Topjian, AA, Dlugos, DJ, Abend, NS. Electroencephalogram monitoring in critically ill children: indications and strategies. Pediatr Neurol. 2012;46(3):158–61.Google Scholar
Brophy, GM, Bell, R, Claassen, J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):323.CrossRefGoogle ScholarPubMed
Herman, ST, Abend, NS, Bleck, TP, et al. Consensus statement on continuous EEG in critically ill adults and children, part II: personnel, technical specifications, and clinical practice. J Clin Neurophysiol. 2015;32(2):96108.Google Scholar
Pensirikul, AD, Beslow, LA, Kessler, SK, et al. Density spectral array for seizure identification in critically ill children. J Clin Neurophysiol. 2013;30(4):371–5.Google Scholar
Stewart, CP, Otsubo, H, Ochi, A, et al. Seizure identification in the ICU using quantitative EEG displays. Neurology. 2010;75(17):1501–8.Google Scholar
Shah, DK, Mackay, MT, Lavery, S, et al. Accuracy of bedside electroencephalographic monitoring in comparison with simultaneous continuous conventional electroencephalography for seizure detection in term infants. Pediatrics. 2008;121(6):1146–54.CrossRefGoogle ScholarPubMed
Shellhaas, RA, Chang, T, Tsuchida, T, et al. The American Clinical Neurophysiology Society’s Guideline on Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol. 2011;28(6):611–17.Google Scholar
Hirsch, LJ, LaRoche, SM, Gaspard, N, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version. J Clin Neurophysiol. 2013;30(1):127.Google Scholar
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(2):7991.CrossRefGoogle ScholarPubMed
Ronner, HE, Ponten, SC, Stam, CJ, Uitdehaag, BM. Inter-observer variability of the EEG diagnosis of seizures in comatose patients. Seizure. 2009;18(4):257–63.Google Scholar
Brenner, RP, Schaul, N. Periodic EEG patterns: classification, clinical correlation, and pathophysiology. J Clin Neurophysiol. 1990;7(2):249–67.Google ScholarPubMed
Garzon, E, Fernandes, RM, Sakamoto, AC. Serial EEG during human status epilepticus: evidence for PLED as an ictal pattern. Neurology. 2001;57(7):1175–83.CrossRefGoogle ScholarPubMed
Treiman, DM, Walton, NY, Kendrick, C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res. 1990;5(1):4960.Google Scholar
Yemisci, M, Gurer, G, Saygi, S, Ciger, A. Generalised periodic epileptiform discharges: clinical features, neuroradiological evaluation and prognosis in 37 adult patients. Seizure. 2003;12(7):465–72.Google Scholar
Garcia-Morales, I, Garcia, MT, Galan-Davila, L, et al. Periodic lateralized epileptiform discharges: etiology, clinical aspects, seizures, and evolution in 130 patients. J Clin Neurophysiol. 2002;19(2):172–7.Google Scholar
Brenner, RP. Is it status? Epilepsia. 2002;43 (Suppl 3):103–13.Google Scholar
Fushimi, M, Matsubuchi, N, Sekine, A, Shimizu, T. Benign bilateral independent periodic lateralized epileptiform discharges. Acta Neurol Scand. 2003;108(1):55–9.Google Scholar
Koren, JP, Herta, J, Pirker, S, et al. Rhythmic and periodic EEG patterns of “ictal-interictal uncertainty” in critically ill neurological patients. Clin Neurophysiol. 2016;127(2):1176–81.Google Scholar
Claassen, J. How, I treat patients with EEG patterns on the ictal-interictal continuum in the neuro ICU. Neurocrit Care. 2009;11(3):437–44.Google Scholar
Wilkes, R, Tasker, RC. Pediatric intensive care treatment of uncontrolled status epilepticus. Crit Care Clin. 2013;29(2):239–57.CrossRefGoogle ScholarPubMed
Glauser, T, Shinnar, S, Gloss, D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):4861.Google Scholar
Abend, NS, Loddenkemper, T. Pediatric status epilepticus management. Curr Opin Pediatr. 2014;26(6):668–74.Google Scholar
Chin, RF, Neville, BG, Peckham, C, et al. Wade, A, Bedford, H, Scott, RC. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol. 2008;7(8):696703.Google Scholar
Alldredge, BK, Gelb, AM, Isaacs, SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631–7.Google Scholar
Appleton, R, Macleod, S, Martland, T. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2008(3):CD001905.Google Scholar
Sathe, AG, Tillman, H, Coles, LD, et al. Underdosing of benzodiazepines in patients with status epilepticus enrolled in established status epilepticus treatment trial. Acad Emerg Med. 2019;26(8):940–3.Google Scholar
Chin, RF, Verhulst, L, Neville, BG, Peters, MJ, Scott, RC. Inappropriate emergency management of status epilepticus in children contributes to need for intensive care. J Neurol Neurosurg Psychiatry. 2004;75(11):1584–8.Google Scholar
Chamberlain, JM, Kapur, J, Shinnar, S, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020;395(10231):1217–24.Google Scholar
Dalziel, SR, Borland, ML, Furyk, J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2125–34.Google Scholar
Lyttle, MD, Rainford, NEA, Gamble, C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019; 393(10186):2135–45.Google Scholar
Agarwal, P, Kumar, N, Chandra, R, et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16(6):527–32.Google Scholar
Malamiri, RA, Ghaempanah, M, Khosroshahi, N, et al. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Eur J Paediatr Neurol. 2012;16(5):536–41.Google Scholar
Alvarez, V, Januel, JM, Burnand, B, Rossetti, AO. Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam. Epilepsia. 2011;52(7):1292–6.Google Scholar
Misra, UK, Kalita, J, Patel, R. Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology. 2006;67(2):340–2.Google Scholar
Goodkin, HP, Yeh, JL, Kapur, J. Status epilepticus increases the intracellular accumulation of GABAA receptors. J Neurosci. 2005;25(23):5511–20.CrossRefGoogle ScholarPubMed
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(34):7724–33.Google Scholar
Naylor, DE, Liu, H, Niquet, J, Wasterlain, CG. Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus. Neurobiol Dis. 2013;54:225–38.Google Scholar
Mazarati, AM, Baldwin, RA, Sankar, R, Wasterlain, CG. Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. Brain Res. 1998;814(1–2):179–85.CrossRefGoogle ScholarPubMed
Goodkin, HP, Liu, X, Holmes, GL. Diazepam terminates brief but not prolonged seizures in young, naive rats. Epilepsia. 2003;44(8):1109–12.Google Scholar
Eriksson, K, Kalviainen, R. Pharmacologic management of convulsive status epilepticus in childhood. Expert Rev Neurother. 2005;5(6):777–83.Google Scholar
DeLorenzo, RJ, Garnett, LK, Towne, AR, et al. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia. 1999;40(2):164–9.Google Scholar
Logroscino, G, Hesdorffer, DC, Cascino, GD, et al. Long-term mortality after a first episode of status epilepticus. Neurology. 2002;58(4):537–41.Google Scholar
Sanchez Fernandez, I, Gainza-Lein, M, Abend, NS, et al. Factors associated with treatment delays in pediatric refractory convulsive status epilepticus. Neurology. 2018;90(19):e1692-e701.Google Scholar
Lowenstein, DH, Alldredge, BK. Status epilepticus at an urban public hospital in the 1980s. Neurology. 1993; 43 (3 Pt 1): 483–8.Google Scholar
Sutter, R, Kaplan, PW, Ruegg, S. Outcome predictors for status epilepticus–what really counts. Nat Rev Neurol. 2013;9(9):525–34.Google Scholar
Sanchez Fernandez, I, Abend, NS, Agadi, S, et al. Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG). Seizure. 2014;23(2):8797.Google Scholar
Rossetti, AO, Lowenstein, DH. Management of refractory status epilepticus in adults: still more questions than answers. Lancet Neurol. 2011;10(10):922–30.Google Scholar
Koul, R, Chacko, A, Javed, H, Al Riyami, K. Eight-year study of childhood status epilepticus: midazolam infusion in management and outcome. J Child Neurol. 2002;17(12):908–10.Google Scholar
Lambrechtsen, FA, Buchhalter, JR. Aborted and refractory status epilepticus in children: a comparative analysis. Epilepsia. 2008;49(4):615–25.Google Scholar
Lewena, S, Pennington, V, Acworth, J, et al. Emergency management of pediatric convulsive status epilepticus: a multicenter study of 542 patients. Pediatr Emerg Care. 2009;25(2):83–7.Google Scholar
Zaw, W, Knoppert, DC, da Silva, O. Flumazenil’s reversal of myoclonic-like movements associated with midazolam in term newborns. Pharmacotherapy. 2001;21(5):642–6.Google Scholar
Meierkord, H, Boon, P, Engelsen, B, et al. EFNS guideline on the management of status epilepticus in adults. Eur J Neurol. 2010;17(3):348–55.Google Scholar
Krishnamurthy, KB, Drislane, FW. Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus. Epilepsia. 1999;40(6):759–62.Google Scholar
Claassen, J, Hirsch, LJ, Emerson, RG, Mayer, SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia. 2002;43(2):146–53.Google Scholar
Kang, BS, Jung, KH, Shin, JW, et al. Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus. J Clin Neurosci. 2015;22(5):854–8.Google Scholar
Hocker, SE, Britton, JW, Mandrekar, JN, Wijdicks, EF, Rabinstein, AA. Predictors of outcome in refractory status epilepticus. JAMA Neurol. 2013;70(1):72–7.CrossRefGoogle ScholarPubMed
Friedman, D, Claassen, J, Hirsch, LJ. Continuous electroencephalogram monitoring in the intensive care unit. Anesth Analg. 2009;109(2):506–23.CrossRefGoogle ScholarPubMed
Ferlisi, M, Shorvon, S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012;135(Pt 8):2314–28.Google Scholar
Gaspard, N, Foreman, B, Judd, LM, et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia. 2013;54(8):1498–503.Google Scholar
Nabbout, R, Mazzuca, M, Hubert, P, et al. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia. 2010;51(10):2033–7.Google Scholar
Fung, EL, Chang, SK, Yam, KK, Yau, PY. Ketogenic diet as a therapeutic option in super-refractory status epilepticus. Pediatrics and Neonatol. 2015;56(6):429–31.CrossRefGoogle ScholarPubMed
Corry, JJ, Dhar, R, Murphy, T, Diringer, MN. Hypothermia for refractory status epilepticus. Neurocrit Care. 2008;9(2):189–97.Google Scholar
Lin, JJ, Lin, KL, Hsia, SH, Wang, HS. Therapeutic hypothermia for febrile infection-related epilepsy syndrome in two patients. Pediatr Neurol. 2012;47(6):448–50.Google Scholar
Vendrame, M, Loddenkemper, T. Surgical treatment of refractory status epilepticus in children: candidate selection and outcome. Semin Pediatr Neurol. 2010;17(3):182–9.Google Scholar
Greiner, HM, Tillema, JM, Hallinan, BE, et al. Corpus callosotomy for treatment of pediatric refractory status epilepticus. Seizure. 2012;21(4):307–9.Google Scholar
Petit-Pedrol, M, Armangue, T, Peng, X, et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol. 2014;13(3):276–86.Google Scholar
Suleiman, J, Brilot, F, Lang, B, Vincent, A, Dale, RC. Autoimmune epilepsy in children: case series and proposed guidelines for identification. Epilepsia. 2013;54(6):1036–45.Google Scholar
Abend, NS, Wusthoff, CJ, Goldberg, EM, Dlugos, DJ. Electrographic seizures and status epilepticus in critically ill children and neonates with encephalopathy. Lancet Neurol. 2013;12(12):1170–9.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×