Neurology -- Correspondence for Rossetti et al., 69 (3) 255-260

Correspondence published:

Status epilepticus. An independent outcome predictor after cerebral anoxia: Hartmut Meierkord, Martin Holtkamp (18 October 2007)

Reply from the authors: Andrea O. Rossetti, Giancarlo Logroscino (18 October 2007)

Status epilepticus: An independent outcome predictor after cerebral anoxia: Peter W. Kaplan, Yazmin Morales (19 September 2007)

Reply from the authors: Andrea O. Rossetti, Giancarlo Logroscino (19 September 2007)

Status epilepticus. An independent outcome predictor after cerebral anoxia 18 October 2007

Hartmut Meierkord,
Department of Neurology, Charité - Universitätsmedizin Berlin
Charitéplatz 1, 10117 Berlin, Germany,
Martin Holtkamp
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Re: Status epilepticus. An independent outcome predictor after cerebral anoxia

martin.holtkamp{at}charite.de Hartmut Meierkord, et al.

We read the report by Rossetti et al with interest. The authors addressed whether the prognosis of status epilepticus (SE) is determined by the underlying cause or if SE itself is independently associated with an increased mortality rate. [1]
The authors compared a group of patients with postanoxic encephalopathy combined with what they called “postanoxic status epilepticus” to patients suffering solely from postanoxic encephalopathy. While the idea is sound, the authors’ selection criteria are not convincing.
It has been shown that there is no single EEG pattern which is pathognomonic for SE if taken separately from the clinical features. Most cases of postanoxic encephalopathy are associated with EEG patterns that the authors accepted as indicative of additional “postanoxic SE”. Also, the presence of spontaneous burst suppression patterns was sufficient for the diagnosis of additional SE. However, this EEG finding commonly reflects severe diffuse brain injury.
Taken together, the diagnosis of SE in this study was based on EEG changes alone, at variance to the widely agreed-upon diagnostic criteria. [2] In addition, we disagree with this current approach for practical reasons because lax criteria may result in aggressive pharmacological treatment resulting merely in “EEG cosmetics”.
References
1. Rossetti AO, Logroscino G, Liaudet L, et al. Status epilepticus. An independent outcome predictor after cerebral anoxia. Neurology 2007;69:255-260.
2. Meierkord H, Holtkamp M. Non-convulsive status epilepticus in adults: clinical forms and treatment. Lancet Neurol 2007;6:329-339.
Disclosure: The authors report no conflicts of interest.

Reply from the authors 18 October 2007

Andrea O. Rossetti,
Service de Neurologie
CHUV BH-07, CH-1011 Lausanne, Switzerland,
Giancarlo Logroscino
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Re: Reply from the authors

andrea.rossetti{at}chuv.ch Andrea O. Rossetti, et al.

We thank Drs. Meierkord and Holtkamp for their comments. As they correctly point out, electrographical manifestations of status epilepticus (SE) are variable. We used a broad definition, relying on previously described EEG patterns in SE. [3] We added periodic discharges (PEDs) and spontaneous burst suppression because they are often associated with myoclonus. [4] In our ongoing prospective series, this occurs in about 90% of cases (unpublished data).
We agree with Meierkord and Holtkamp that SE diagnosis relies on clinical criteria. Our study was retrospective and we used uniform diagnostic criteria based on EEG rather than relying on reports of clinical manifestations that are often inconsistent. This is common in retrospective assessments.
Finally, while we understand that unjustified aggressive pharmacological treatment in postanoxic SE has to avoided, this study should be viewed as an attempt to better characterize the profile of patients that may benefit from a SE therapy even after cerebral anoxia. While this SE etiology has been historically shown to be fatal [5], exceptions do exist. [1,6]
When routine clinical and electrophysiological evaluations [7] are discordant in the assessment of the prognosis of awakening, our current policy is to administer SE treatment including anesthetics for 24-36 hours before re-evaluation. Three more patients in our series would have died without this therapeutic approach.
In our opinion, it would be wrong and ethically questionable to deny appropriate therapy to a subgroup of subjects that have the potential of awakening if treated. Currently, we are conducting a prospective study to better characterize prognostic factors of anoxic encephalopathy including the role of postanoxic status epilepticus.
References
3. Herman ST. The electroencephalogram in status epilepticus. In: Drislane FW, ed. Status epilepticus. A clinical perspective. Totowa, NJ: Humana Press, 2005:77–124.
4. Thömke F, Marx JJ, Sauer O, et al. Observations on comatose survivors of cardiopulmonary resuscitation with generalized myoclonus. BMC Neurology 2005;5:14. Accessed online September 18, 2007.
5. Wijdicks EFM, Parisi JE, Sharbrough FW. Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 1994;35:239–243.
6. Morris HR, Howard RS, Brown P. Early myoclonic status and outcome after cardiorespiratory arrest. J Neurol Neurosurg Psychiatry 1998;64:267–268.
7. Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2006;67:203–210.
Disclosure: The authors report no conflicts of interest.

Status epilepticus: An independent outcome predictor after cerebral anoxia 19 September 2007

Peter W. Kaplan,
Johns Hopkins University School of Medicine
B-123 Dept of Neurology, Johns Hopkins Bayview Med Ctr, 4940 Eastern Ave, Baltimore, 21224,
Yazmin Morales
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Re: Status epilepticus: An independent outcome predictor after cerebral anoxia

pkaplan{at}jhmi.edu Peter W. Kaplan, et al.

With the increase in survivors after cardio-respiratory arrest, clinicians must balance a meaningful survival against the realities of ICU care. Studies like Rossetti et al’s are paramount in determining the need for life support and examine the validity of postanoxic status epilepticus-EEG (PSE) as a predictor of outcome. [1]
Poor outcome has been established in post-anoxic coma (even after hypothermia treatment) for somato-sensory evoked potentials (SSEPs), neuron-specific enolase, or a flat EEG. [2] This prognostic information enables clinicians and patients' families to make informed decisions on withdrawal of care. [3]
Rossetti et al investigated PSE as an independent predictor of outcome and found that 32/35 died; all those with ventricular fibrillation (VF) without hypothermia, and those hypothermia-treated patients with non-VF or VF with a brief period before restoration of spontaneous cardiac activity [ROSCA]. Survivors with VF were those treated with hypothermia.
There is uncertainty regarding EEG with PSE as a predictor of bad outcome unless other features of EEG are noted. This is illustrated by the following case:
A 42-year-old man with cardiac arrest had ROSCA after about 40 minutes. Examination showed a GCS of 3. After a tonic-clonic seizure he received lorazepam, levetiracetam and 24 hours of hypothermia therapy. Five days later (24 hours after stopping propofol), GCS remained 3. He had intact brainstem reflexes, facial myoclonus and vertical nystagmus.
After several hours, EEG showed bilateral epileptiform discharges with intervening background alpha/theta activity, indicating PSE. Facial myoclonus resolved by day 13 after further lorazepam and levetiracetam.
With no clinical improvement (despite preservation of brainstem reflexes), the lack of response to noxious stimulation and the EEG pattern of SE by day 6, ventilation support was withdrawn and the patient breathed spontaneously. On day 19 he spoke brief sentences. By day 22 he gave the season, year, city and state and followed commands, said hello, smiled and waved.
Despite approximately 42 minutes of VF arrest, PSE, GCS 3, but with hypothermia and AEDs, the patient returned to a conscious interactive state over days. The EEG showed background brain activity suggesting preservation of brain activity, and possibly seizures obscured the patient’s responsiveness and lowered the GCS rating invalidating its applicability in this setting.
This survival after hypothermia with two cases from Rossetti indicate that prospective studies are warranted to better categorize those characteristics of PSE, electrographic or nonconvulsive seizures (amount, frequency and prevalence of background activity; reactivity to stimuli) that signal a favorable outcome. [4]
References
1. Rossetti AO, Logroscino G, Liaudet L, et al. Status epilepticus: An independent outcome predictor after cerebral anoxia. Neurology 2007;69:255-260.
2. Zandbergen EGJ, Hijdra A, Koelman JHTM, et al for the PROPAC study group. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006;66:62-68.
3. Geocadin RG, Buitrago M, Torbey MT, Chandra-Strobos N, Williams MA, Kaplan PW. Neurological prognostication and withdrawal of life sustaining therapies in patients resuscitated from cardiac arrest. Neurology 2006;67:105-108.
4. Kaplan PW. Electroencephalographic Criteria for Nonconvulsive Status Epilepticus. Epilepsia 2007: (in press).
Disclosure: The authors report no conflicts of interest.

Reply from the authors 19 September 2007

Andrea O. Rossetti,
Service de Neurologie, CHUV
BH-07, CH-1011 Lausanne, Switzerland,
Giancarlo Logroscino
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Re: Reply from the authors

andrea.rossetti{at}chuv.ch Andrea O. Rossetti, et al.

We thank Drs. Kaplan and Morales for their valuable comments. As they correctly point out, in spite of earlier claims of an absolute mortality related to postanoxic status epilepticus (PSE) [5], some exceptions have been reported in the last 10 years. [1,6].
Their patient was in a “gray zone” on admission. He showed ventricular fibrillation at the beginning of resuscitation (which is better than asystole) but had a long time to restoration of spontaneous cardiac rhythm. Hypothermia, which is potentially beneficial in the presence of VF [7], was applied but he did not regain consciousness after weaning from propofol, and he had persisting myoclonus for 2 weeks. However, his EEG disclosed some theta-alpha background. After several days, somewhat surprisingly, he regained consciousness. He probably had normal cortical somatosensory evoked potentials.
This case highlights two important features that are unfortunately not always used in clinical practice, especially by physicians not familiar with EEG (perphaps due to the lack of evidence-based guidelines). However, these issues are important in fine tuning strategies on withdrawal of supportive care.
First, postanoxic catastrophic myoclonus is generally transient, lasting only 24-48 hours. [8] Conversely, postanoxic “Lance and Adams” myoclonus, which is compatible with restoration of consciousness, typically arises in the days and weeks following the initial event. Second, many patients with “catastrophic” PSE lack a background EEG activity, displaying burst-suppression or generalized periodic patterns on a flat background. [8], (personal communication, C. Fisher, Lyon, France). Alternatively, subjects who do awaken often show some background activity as in the case of Kaplan and Morales. We are now prospectively investigating this aspect in Lausanne.
Before opting for supportive care withdrawal, which is actually a definite decision on the potential survival, it is mandatory to be intimately convinced of the bad prognosis of the patient. When dealing with complex biological phenomena occurring in human beings, a comfortable decision may be met only when several elements coming from different directions converge to the very same point. The more elements one can rely upon, the better the decision will be.
References
5. Wijdicks EFM, Parisi JE, Sharbrough FW. Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 1994;35:239–243.
6. Morris HR, Howard RS, Brown P. Early myoclonic status and outcome after cardiorespiratory arrest. J Neurol Neurosurg Psychiatry 1998;64:267–268.
7. Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 2006;34:1865- 1873.
8. Thömke F, Marx JJ, Sauer O, et al. Observations on comatose survivors of cardiopulmonary resuscitation with generalized myoclonus. BMC Neurology 2005;5:14.
Disclosure: The authors report no conflicts of interest.