Christine A. C. Wijman

The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on “research and technology” of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and “omics” research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care.

Background and Purpose—: Knowledge on the natural history and clinical impact of perihematomal edema (PHE) associated with intracerebral hemorrhage is limited. We aimed to define the time course, predictors, and clinical significance of PHE measured by serial magnetic resonance imaging. Methods—: Patients with primary supratentorial intracerebral hemorrhage ≥5 cm ³ underwent serial MRIs at prespecified intervals during the first month. Hematoma (H _v ) and PHE (E _v ) volumes were measured on fluid-attenuated inversion recovery images. Relative PHE was defined as E _v /H _v . Neurologic assessments were performed at admission and with each MRI. Barthel Index, modified Rankin scale, and extended Glasgow Outcome scale scores were assigned at 3 months. Results—: Twenty-seven patients with 88 MRIs were prospectively included. Median H _v and E _v on the first MRI were 39 and 46 cm ³ , respectively. Median peak absolute E _v was 88 cm ³ . Larger hematomas produced a larger absolute E _v ( r ² =0.6) and a smaller relative PHE ( r ² =0.7). Edema volume growth was fastest in the first 2 days but continued until 12±3 days. In multivariate analysis, a higher admission hematocrit was associated with a greater delay in peak PHE ( P =0.06). Higher admission partial thromboplastin time was associated with higher peak rPHE ( P =0.02). Edema volume growth was correlated with a decline in neurologic status at 48 hours (81 vs 43 cm ³ , P =0.03) but not with 3-month functional outcome. Conclusions—: PHE volume measured by MRI increases most rapidly in the first 2 days after symptom onset and peaks toward the end of the second week. The timing and magnitude of PHE volume are associated with hematologic factors. Its clinical significance deserves further study.

Background and Purpose— The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method— Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest. Results— Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema. Conclusion— The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

Before the use of hypothermia as a treatment for comatose post-cardiac arrest patients, several prognostic variables were widely accepted as reliable and valid for the prediction of poor outcome. Recent studies using hypothermia have reported on patients with recovery of consciousness in spite of absent or extensor motor responses after 3 days, absent bilateral cortical N20 responses after 24 h, serum neuron-specific enolase levels greater than 33 μg/L, and early myoclonus status epilepticus. Hypothermia and its associated use of sedative and paralytic agents may delay neurologic recovery and affect the optimal timing of prognostic variables. Recent developments in brain imaging may provide additional objective prognostic information and deserve further study. Pending the results of future validation studies in patients treated with hypothermia, we recommend that irreversible management decisions not be made based on a single prognostic parameter, and, if there is uncertainty, these decisions be delayed for several days to allow for repeated testing.

Background: The optimal diagnostic evaluation for spontaneous intracerebral hemorrhage (ICH) remains controversial. In this retrospective study, we assessed the utility of early magnetic resonance imaging (MRI) in ICH diagnosis and management. Methods: Eighty-nine (72%) of 123 patients with spontaneous ICH underwent a brain CT and MRI within 30 days of ICH onset. Seventy patients with a mean age of 62 ± 15 years were included. A stroke neurologist and a general neurologist, each blinded to the final diagnosis, independently reviewed the admission data and the initial head CT and then assigned a presumed ICH cause under 1 of 9 categories. ICH cause was potentially modified after subsequent MRI review. The final ‘gold standard’ ICH etiology was determined after review of the complete medical record by an independent investigator. Change in diagnostic category and confidence and the potential impact on patient management were systematically recorded. Results: Mean time to MRI was 3 ± 5 days. Final ICH diagnosis was hypertension or cerebral amyloid angiopathy (CAA) in 50% of patients. After MRI review the stroke neurologist changed diagnostic category in 14%, diagnostic confidence in an additional 23% and management in 20%, and the general neurologist did so in 19, 21 and 21% of patients, respectively. MRI yield was highest in ICH secondary to ischemic stroke, CAA, vascular malformations and neoplasms, and did not differ by age, history of hypertension, hematoma location or the presence of intraventricular hemorrhage. Conclusions: The results of this study suggest potential additive clinical benefit of early MRI in patients with spontaneous ICH.

Background Therapeutic hypothermia is commonly used in comatose survivors’ post-cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors perform accurately after hypothermia treatment. Methods Post-CPR comatose survivors were prospectively enrolled. Six outcome predictors [pupillary and corneal reflexes, motor response to pain, and somatosensory-evoked potentials (SSEP) >72 h; status myoclonus, and serum neuron-specific enolase (NSE) levels 72 h predicted poor outcome with a 100% specificity both in hypothermia and normothermia patients. In contrast, absent corneal reflexes >72 h, motor response extensor or absent >72 h, and peak NSE >33 ng/ml <72 h predicted poor outcome with 100% specificity only in non-sedated patients, irrespective of prior treatment with hypothermia. Conclusions Sedative medications are commonly used in proximity of the 72-h neurological examination in comatose CPR survivors and are an important prognostication confounder. Patients treated with hypothermia are more likely to receive sedation than those who are not treated with hypothermia.

Background and Purpose— Diffusion-weighted magnetic resonance imaging of the brain is a promising technique to help predict functional outcome in comatose survivors of cardiac arrest. We aimed to evaluate prospectively the temporal-spatial profile of brain apparent diffusion coefficient changes in comatose survivors during the first 8 days after cardiac arrest. Methods— Apparent diffusion coefficient values were measured by 2 independent and blinded investigators in predefined brain regions in 18 good- and 15 poor-outcome patients with 38 brain magnetic resonance imaging scans and were compared with those of 14 normal controls. The same brain regions were also assessed qualitatively by 2 other independent and blinded investigators. Results— In poor-outcome patients, cortical structures, in particular the occipital and temporal lobes, and the putamen exhibited the most profound apparent diffusion coefficient reductions, which were noted as early as 1.5 days and reached a nadir between 3 and 5 days after the arrest. Conversely, when compared with normal controls, good-outcome patients exhibited increased diffusivity, in particular in the hippocampus, temporal and occipital lobes, and corona radiata. By qualitative magnetic resonance imaging readings, 1 or more cortical gray matter structures were judged to be moderately to severely abnormal in all poor-outcome patients except for the 3 patients imaged within 24 hours after the arrest. Conclusions— Brain diffusion-weighted imaging changes in comatose, postcardiac arrest survivors in the first week after the arrest are region and time dependent and differ between good- and poor-outcome patients. With increasing use of magnetic resonance imaging in this context, it is important to be aware of these relations.

Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.

Objective: Outcome prediction is challenging in comatose postcardiac arrest survivors. We assessed the feasibility and prognostic utility of brain diffusion‐weighted magnetic resonance imaging (DWI) during the first week.Methods: Consecutive comatose postcardiac arrest patients were prospectively enrolled. AWI data of patients who met predefined specific prognostic criteria were used to determine distinguishing apparent diffusion coefficient (ADC) thresholds. Group 1 criteria were death at 6 months and absent motor response or absent pupillary reflexes or bilateral absent cortical responses at 72 hours or vegetative at 1 month. Group 2 criterion was survival at 6 months with a Glasgow Outcome Scale score of 4 or 5 (group 2A) or 3 (group 2B). The percentage of voxels below different ADC thresholds was calculated at 50 × 10⁻⁶ mm²/sec intervals.Results: Overall, 86% of patients underwent DWI. Fifty‐one patients with 62 brain DWIs were included. Forty patients met the specific prognostic criteria. The percentage of brain volume with an ADC value less than 650 to 700 × 10⁻⁶mm²/sec best differentiated between Group 1 and Groups 2A and 2B combined (p < 0.001), whereas the 400 to 450 × 10⁻⁶mm²/sec threshold best differentiated between Groups 2A and 2B (p = 0.003). The ideal time window for prognostication using DWI was between 49 and 108 hours after the arrest. When comparing DWI in this time window with the 72‐hour neurological examination, DWI improved the sensitivity for predicting poor outcome by 38% while maintaining 100% specificity (p = 0.021).Interpretation: Quantitative DWI in comatose postcardiac arrest survivors holds promise as a prognostic adjunct. Ann Neurol 2009;65:394–402