Continuous EEG monitoring in the intensive care unit.

The purpose and indications for continuous electroencephalography monitoring (CEEG) in intensive care unit (ICU) patients include seizure detection, monitoring the effects of treatment (including depth of sedation), grading and classification of EEG abnormalities, ischemia detection and prognostication. Practical considerations of ICU CEEG include: choice of montages (patterns of electrode placement and connections), EEG electrodes, recognition of artifacts, and the use of automated or computerized analysis. These aspects are reviewed, along with an identifcation of current advances and challenges for the future of CEEG in the ICU.

Reversible and irreversible cranial MRI findings associated with status epilepticus.

OBJECTIVE: There is limited information on neuroimaging changes in status epilepticus (SE). The objective of this study was to characterize the abnormalities associated with SE in cranial MRI of patients with SE. METHODS: A retrospective review of our records from 2001 to 2010 identified 203 patients with SE. Magnetic resonance imaging (MRI) changes considered were not attributable to any neurological disorder. RESULTS: Ten patients who met the inclusion criteria were found to have significant abnormalities. Magnetic resonance imaging findings included increased T2 signal changes in the gray and/or white matter with corresponding diffusion-weighted imaging (DWI) abnormalities (n=9). Apparent diffusion coefficient (ADC) values were both reduced (n=3) and increased (n=3). Other findings included changes affecting one hemisphere, a perilesional and homologous region, hippocampal changes, and findings in the thalamus, basal ganglia, brain stem, and cerebellum. CONCLUSIONS: Magnetic resonance imaging changes were diffuse. Notably, MRI changes were found to involve the brain stem, cerebellum, basal ganglia, and thalamus. Magnetic resonance imaging changes in the latter areas have not been previously well described. In addition, MRI changes tended to evolve after 1week; therefore, serial MRI is recommended in order to follow and highlight the MRI changes related to the neuroanatomic involvement seen in status epilepticus.

Disruptions of functional connectivity in the default mode network of comatose patients.

OBJECTIVE: To evaluate the possible role of the default mode network (DMN) in consciousness and assess the diagnostic or prognostic potential of DMN connectivity measures in the assessment of a patient group lacking cognitive awareness. METHODS: DMN connectivity was established using independent component analysis of resting-state fMRI data in patients with reversible (n = 2) and irreversible (n = 11) coma following cardiac arrest and compared to healthy controls (n = 12). RESULTS: A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness. CONCLUSIONS: The results suggest that the DMN is necessary but not sufficient to support consciousness. Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.

Involuntary craniofacial lingual movements in intensive care-acquired quadriplegia.

BACKGROUND: The syndrome of involuntary craniofacial lingual movements in the setting of acute intensive care-acquired quadriplegia (critical illness neuromyopathy) following sepsis-associated encephalopathy has not been previously described. We suggest a localization and treatment for this disabling condition. METHODS: Three patients (2 female) from our center were quadriplegic from critical illness neuromyopathy when they developed involuntary craniofacial lingual movements following sepsis-associated encephalopathy. RESULTS: Extensive investigations failed to identify an etiology for the abnormal movements. Movements were of large amplitude, of moderate speed, and semi-rhythmic in the jaw, tongue, and palate, persistent and extremely bothersome to all patients. Injection with Botulinum toxin type A was very beneficial. CONCLUSIONS: Involuntary craniofacial lingual movements in the setting of flaccid quadriplegia following sepsis-associated encephalopathy are consistent with focal craniofacial brainstem myoclonus and constitutes a new syndrome. Botulinum toxin type A treatment maybe helpful in treatment.

Recovery of awareness after hyperacute hepatic encephalopathy with "flat" EEG, severe brain edema and deep coma.

BACKGROUND: Hyperacute hepatic failure (HHF) has a high mortality rate that is most commonly due to severe cerebral edema. However, brain swelling and marked clinical and EEG suppression are potentially reversible, even though the same findings are associated with a very poor neurological outcome in anoxic-ischemic encephalopathy. METHODS: We present three cases that illustrate neurological recovery despite severe brain swelling and loss of EEG activity. RESULTS: All patients recovered conscious awareness, including one who transiently lost cranial nerve reflexes. CONCLUSIONS: Despite deep coma, markedly suppressed EEG and brain edema, aggressive control of ICP may lead to good recovery in acute hepatic failure.

Irreversible brain injury following status epilepticus.

Described here is a patient with medically intractable generalized epilepsy who developed status epilepticus (SE) affecting his right cerebral hemisphere for about 48 hours, which led to irreversible injury to that hemisphere. His partial SE did not respond to the first-line therapies, repeated doses of midazolam, or continuous intravenous infusion of propofol. Extensive investigations failed to find a cause of his SE except for a low serum valproic acid. A minor trauma that he suffered 1 week prior to his SE was of questionable significance. Neurological examination, neuropsychological testing, electroencephalography, and magnetic resonance imaging all demonstrated striking abnormalities limited to the affected cerebral hemisphere that did not resolve with repeated testing. This case illustrates permanent focal brain injury following prolonged partial SE in a patient with previously known generalized seizure disorder.

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.

OBJECTIVE: To systematically review outcomes in comatose survivors after cardiac arrest and cardiopulmonary resuscitation (CPR). METHODS: The authors analyzed studies (1966 to 2006) that explored predictors of death or unconsciousness after 1 month or unconsciousness or severe disability after 6 months. RESULTS: The authors identified four class I studies, three class II studies, and five class III studies on clinical findings and circumstances. The indicators of poor outcome after CPR are absent pupillary light response or corneal reflexes, and extensor or no motor response to pain after 3 days of observation (level A), and myoclonus status epilepticus (level B). Prognosis cannot be based on circumstances of CPR (level B) or elevated body temperature (level C). The authors identified one class I, one class II, and nine class III studies on electrophysiology. Bilateral absent cortical responses on somatosensory evoked potential studies recorded 3 days after CPR predicted poor outcome (level B). Burst suppression or generalized epileptiform discharges on EEG predicted poor outcomes but with insufficient prognostic accuracy (level C). The authors identified one class I, 11 class III, and three class IV studies on biochemical markers. Serum neuron-specific enolase higher than 33 microg/L predicted poor outcome (level B). Ten class IV studies on brain monitoring and neuroimaging did not provide data to support or refute usefulness in prognostication (level U). CONCLUSION: Pupillary light response, corneal reflexes, motor responses to pain, myoclonus status epilepticus, serum neuron-specific enolase, and somatosensory evoked potential studies can reliably assist in accurately predicting poor outcome in comatose patients after cardiopulmonary resuscitation for cardiac arrest.

Myoclonic status epilepticus following repeated oral ingestion of colloidal silver.

The authors report a case of a 71-year-old man who developed myoclonic status epilepticus and coma after daily ingestion of colloidal silver for 4 months resulting in high levels of silver in plasma, erythrocytes, and CSF. Despite plasmapheresis, he remained in a persistent vegetative state until his death 5.5 months later. Silver products can cause irreversible neurologic toxicity associated with poor outcome.

Seizure identification by clinical description in temporal lobe epilepsy: how accurate are we?

OBJECTIVE: To determine the accuracy of the clinical history performed by epileptologists in the identification of seizures in patients with suspected temporal lobe epilepsy. METHODS: The clinical and EEG telemetry (EEGT) monitoring data of 88 patients with suspected refractory temporal lobe seizures referred for evaluation of epilepsy surgery were prospectively evaluated. All clinical events obtained by history in these patients were adjudicated as being a seizure or not by two blinded (without access to EEG data) independent epileptologists. Each clinical event was then matched with the corresponding clinical event recorded with EEG telemetry in the epilepsy monitoring unit (gold standard). Sensitivity, specificity, overall accuracy, predictive value, and interrater agreement for the clinical assessment were obtained. RESULTS: Of 357 clinically different events, 175 (49%) were reproduced in the epilepsy monitoring unit. Only 10 events were misidentified by history as being a seizure or not, resulting in an overall clinical accuracy of 94%. Epileptologists' sensitivity for seizure identification was 96% (95% CI 92, 98%) but specificity was only 50% (95% CI 22, 79%). Accuracy for complex partial seizures and generalized seizures was higher than for simple partial seizures (SPS). Misidentification occurred only with SPS and nonepileptic events. Agreement beyond chance among epileptologists was good. CONCLUSION: In this selected group of patients with temporal lobe epilepsy, seizure identification by clinical history is highly accurate. Epileptologists rarely miss seizures (high sensitivity) but more often overcall nonepileptic events as seizures (low specificity).

Cervical flexion myelopathy after valproic acid overdose.

STUDY DESIGN: Case report and literature review of cervical flexion myelopathies. OBJECTIVE: To increase awareness that prolonged extreme neck flexion, in association with profound muscular relaxation, can produce a severe cervical myelopathy. SUMMARY OF BACKGROUND DATA: Similar case reports of cervical myelopathies have been documented in the neurosurgical literature after intraoperative prolonged neck flexion, and after forcible prolonged neck flexion during a robbery. To the authors' best knowledge, this is the first report of a cervical flexion myelopathy after a medication overdose, and the only clinical-pathologic correlation. METHODS: Retrospective case report with clinical, radiographic, and postmortem data available for analysis. RESULTS: A transverse myelopathy at the sixth cervical level developed in a 25-year-old woman after an overdose of valproic acid in a suicide attempt. She was found in the sitting position, with her neck in extreme flexion, where she had been for an estimated 18 hours. Magnetic resonance imaging showed that her cervical cord was enlarged, maximally at C6, with prominent paraspinal soft tissue swelling. The patient died of pulmonary embolism and pneumonia. Pathologic findings included transverse spinal cord necrosis at C6; central gray matter necrosis extended to several segments below this. CONCLUSION: Prolonged extreme neck flexion, in association with profound muscular relaxation, can produce a severe myelopathy that is at least partly related to compromise of the spinal cord's microcirculation.

Solvent-induced collapse of alpha-synuclein and acid-denatured cytochrome c.

The effects of solution conditions on protein collapse were studied by measuring the hydrodynamic radii of two unfolded proteins, alpha-synuclein and acid-denatured ferricytochrome c, in dilute solution and in 1 M glucose. The radius of alpha-synuclein in dilute solution is less than that predicted for a highly denatured state, and adding 1 M glucose causes further collapse. Circular dichroic data show that alpha-synuclein lacks organized structure in both dilute solution and 1 M glucose. On the other hand, the radius of acid-denatured cytochrome c in dilute solution is consistent with that of a highly denatured state, and 1 M glucose induces collapse to the size and structure of native cytochrome c. Taken together, these data show that alpha-synuclein, a natively unfolded protein, is collapsed even in dilute solution, but lacks structure.

Continuous EEG monitoring in a patient with massive carbamazepine overdose.

The authors report a woman who took a massive overdose (OD) of carbamazepine (CBZ). On admission she was unconscious with absent brainstem reflexes and multifocal stimulus-sensitive myoclonus. Continuous EEG recordings showed a burst-suppression pattern with bursts containing only generalized spikes accompanying myoclonic activity. Myoclonus and EEG bursts were both spontaneous and stimulus induced. With treatment, the serum CBZ concentration declined, and the EEG became more continuous and rhythmic without epileptiform discharges. Unfortunately, the patient died from adult respiratory distress syndrome. Autopsy revealed that cortical and subcortical structures were normal without neuronal necrosis or eosinophilia. Massive CBZ OD may produce a reversible encephalopathy that includes cortical hyperexcitability, a profound burst-suppression EEG pattern, and cranial nerve areflexia. Continuous EEG monitoring is helpful in managing seizures that occur as a complication of CBZ OD, after the course of recovery or worsening, and in providing assistance with prognosis.

Improved outcomes in stroke thrombolysis with pre-specified imaging criteria.

BACKGROUND: A 1995 National Institute of Neurological Disorders (NINDS) study found benefit for intravenous tissue plasminogen activator (tPA) in acute ischemic stroke (AIS). The symptomatic intracranial hemorrhage (SICH) rate in the NINDS study was 6.4%, which may be deterring some physicians from using this medication. METHODS: Starting December 1, 1998, patients with AIS in London, Ontario were treated according to NINDS criteria with one major exception; those with approximately greater than one-third involvement of the idealized middle cerebral artery (MCA) territory on neuroimaging were excluded from treatment. The method used to estimate involvement of one-third MCA territory involvement bears the acronym ICE and had a median kappa value of 0.80 among five physicians. Outcomes were compared to the NINDS study. RESULTS: Between December 1, 1998 and February 1, 2000, 30 patients were treated. Compared to the NINDS study, more London patients were treated after 90 minutes (p<0.00001) and tended to be older. No SICH was observed. Compared to the treated arm of the NINDS trial, fewer London patients were dead or severely disabled at three months (p=0.04). Compared to the placebo arm of the trial, more patients made a partial recovery at 24 hours (p=0.02), more had normal outcomes (p=0.03) and fewer were dead or severely disabled at three months (p=0.004). CONCLUSIONS: The results of the NINDS study were closely replicated and, in some instances, improved upon in this small series of Canadian patients, despite older are and later treatment. These findings suggest that imaging exclusion criteria may optimize the benefits of tPA.

Ethics in the intensive care unit with emphasis on medical futility in comatose survivors of cardiac arrest.

Medical futility refers to situations or cases in which treatment offers no meaningful benefit to the patient. Brain death does not pose a management problem because patients are considered to be dead. Management of other cases requires sequential considerations. First, the prognosis must be established with certainty. Then, if it is determined that there is no possibility of the patient regaining conscious awareness, a level of care should be decided through discussions involving the physician and significant others. Usually there is a consensus that high-level intensive care is not justified to maintain such a low quality of life. When the patient's advance directives or the substitute decision maker's request differs from the physician's recommendations, there are methods of resolving the issues that respect ethical and legal principles.

The EEG in coma.

The EEG allows insight into thalamocortical function in comatose patients when this is inaccessible clinically. A single EEG can help with broad diagnostic categorization whereas continuous or serial EEG provides monitoring for unstable and potentially treatable conditions and for monitoring the effects of therapy. The EEG plays a supplemental role in establishing the prognosis in disease states that are capable of causing neuronal death. The most prevalent and problematic of these conditions involves survivors of cardiac arrest who are initially in coma with intact brainstem reflexes. In such patients single EEGs are of 100% specificity for no possibility of recovery of consciousness only for essentially complete generalized suppression (<10 microV) after the first day of the arrest. Several other generalized patterns, including less marked suppression, burst-suppression, epileptiform activity, periodic complexes, and alpha-theta coma patterns, usually but not invariably indicate a poor outcome. Serial EEGs, continuous raw and automated "trending," testing of reactivity, and the inclusion of multiple variables hold promise for an improved role in the prognostic determination in these patients.

Effects of morphine on the electroencephalograms of neonates: a prospective, observational study.

OBJECTIVES: Although opiates have been reported to profoundly alter the EEG and cause seizures in full-term and premature newborn babies, no prospective study has systematically studied the effects of morphine on the EEG of normal neonates. METHODS: A prospective observational study was conducted on 20 neurologically and metabolically normal newborn babies of > or =26 weeks post-conceptional age, with EEG recordings performed while on and off morphine infusions. RESULTS: The recordings performed while the babies were on morphine were all abnormal; the principal abnormalities consisted of prolonged periods of electrical quiescence (PPEQs) and excessive interictal epileptiform activity. After the morphine was discontinued, the PPEQs resolved and the EEG background rhythms were normal for age, but 5 continued to have excessive sharp transients. All babies did well clinically and did not require anti-epileptic drug therapy. CONCLUSIONS: Morphine produces a profound, largely reversible alteration of all neonatal EEGs at various post-conceptional ages. The study has implications for caution in formulating conclusions regarding the clinical significance of EEGs of critically ill neonates on morphine infusions.