Functional Recovery Despite Status Epilepticus in Post-Anoxic Coma
Abstract & Commentary
By Nicholas D. Schiff, MD, Associate Professor of Neurology and Neuroscience, Center for the Advanced Study of Brain Injury, Weill Cornell Medical College. Dr. Schiff reports that he receives grant and research support and is a retained consultant for Intelect Medical, Inc.; and is an inventor of patented technology through Cornell.
Synopsis: Postanoxic status epilepticus does not necessarily imply irreversible and fatal brain injury.
Source: Rossetti AO, Oddo M, Liaudet L, et al. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology 2009;72:744-749.
Coma following cardiac arrest generally carries a grave prognosis and a majority of patients will not survive or recover function above the level of vegetative state.1 A new report by Rosetti and colleagues importantly emphasizes that prognosis in coma may be uncertain even in circumstances that appear to strongly predict poor outcome following cardiac arrest. The investigators report on a small cohort of six patients treated with hypothermia who recovered consciousness with varying degrees of functional recovery despite the presence of post-anoxic status epilepticus (PSE).
PSE is a clinical indicator positively associated with poor outcome in anoxic coma and often used to limit aggressive care in the early stages of treatment following cardiac arrest. All patients in the Rosetti study received mild hypothermia (external cooling to 33° C) for 24 hours with passive rewarming over 6-12 hours. Intact brainstem reflexes were present within 36 hours for all patients (measured off sedation with core temperature greater than 35°C), but motor response was inconsistent. The EEG in all six patients showed background activity and reactivity (using the gross measures of a 10 microvolt amplitude threshold and any identifiable change with external stimulation). Additionally, somatosensory evoked potential (SSEP) measurements obtained from five of the patients showed intact cortical responses. Functional recovery at six months for the cohort ranged from full recovery and return to work (1), moderate disability (3), to severe disability (2). One patient remained in a minimally conscious state at 18 days after arrest prior to death from multi-organ failure.
The six patients in this observational study were drawn from two groups, one studied retrospectively (three patients from a group of 107 patients) and another prospectively (three patients from a group of 74 patients). Collectively, the subjects represented about 10% of all patients with PSE in both groups. The majority of patients studied prospectively with electroclinical myoclonic PSE (23/24) did not awaken, whereas two of four patients with only EEG evidence of PSE recovered (a statistically significant difference).
The authors cite prior series reported in the literature of patients with status epilepticus and myoclonus following cardiac arrest that found small numbers of patients showing significant improvements. In case reports of patients similar to those discussed by Rosetti and colleagues who achieved good recovery despite PSE, brainstem function also remained intact.2,3 Collectively, the current and earlier studies support the conclusion that if indicators of preserved neuronal integrity (such as brainstem reflexes, EEG activity/reactivity and SSEPs) are present, PSE should be aggressively treated. Although electroclinical PSE carried a very poor prognosis in their overall study, the dissociation of clinical and electrical evidence of functional preservation is clearly important and demonstrates the limitations of using PSE a proxy for neuronal death following anoxic injury.
Commentary
From this report it is not clear whether hypothermia changed the underlying distribution of patients with PSE who show clinical indicators of preserved neuronal function. Nonetheless, the application of new interventions, particularly the increasingly widespread use of hypothermia, is likely to change current outcome predictors. To date, strong prospective negative indicators in the setting of anoxic/hypoxic-ischemic encephalopathy have been based on early clinical assessments and are well correlated with natural history and anatomic pathology.4,5 While existing measures do not reflect the potential impact of interventions such as hypothermia to alter the natural history of recovery, the present report suggests that these traditional indirect measures from clinical evaluation and electrical assessments will continue to be important indicators. Based on the findings of Rosetti, clinicians should consider the evaluation of prognosis of coma following cardiac arrest in the context of treatments received and track clinical examinations closely. Moreover, the report suggests avoiding the summary withdrawal of care based on single factors such as PSE as a guide to outcomes of vegetative state or death. As more aggressive therapeutic interventions are applied early, this approach will become increasingly unreliable.
References
1. Booth CM, Boone RH, Tomlinson G, et al. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA 2004;291:870-879.
2. Golby A, McGuire D, Bayne L. Unexpected recovery from anoxic-ischemic coma. Neurology 1995;45:1629-1630.
3. Goh WC, Heath PD, Ellis SJ, et al. Neurological outcome prediction in a cardiorespiratory arrest survivor. Br J Anaesth 2002;88:719-722.
4. Adams JH, Graham DI, Jennett B. The neuropathology of the vegetative state after acute insult. Brain 2000;123:1327-1338.
5. Posner J, Saper C, Schiff N, et al. Plum and Posner's Diagnosis of Stupor and Coma (4th Ed.). New York; Oxford University Press: 2007.
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