Maria Etchepare

Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis

Objective: To determine whether nonconvulsive electrographic post‐traumatic seizures result in increases in intracranial pressure and microdialysis lactate/pyruvate ratio. Design: Prospective monitoring with retrospective data analysis. Setting: Single center academic neurologic intensive care unit. Patients: Twenty moderate to severe traumatic brain injury patients (Glasgow Coma Score 3–13). Measurements and Main Results: Continuous electroencephalography and cerebral microdialysis were performed for 7 days after injury. Ten patients had seizures and were compared with a matched cohort of traumatic brain injury patients without seizures. The seizures were repetitive and constituted status epilepticus in seven of ten patients. Using a within‐subject design, post‐traumatic seizures resulted in episodic increases in intracranial pressure (22.4 ± 7 vs. 12.8 ± 4.3 mm Hg; p < .001) and an episodic increase in lactate/pyruvate ratio (49.4 ± 16 vs. 23.8 ± 7.6; p < .001) in the seizure group. Using a between‐subjects comparison, the seizure group demonstrated a higher mean intracranial pressure (17.6 ± 6.5 vs. 12.2 ± 4.2 mm Hg; p < .001), a higher mean lactate/pyruvate ratio (38.6 ± 18 vs. 27 ± 9; p < .001) compared with nonseizure patients. The intracranial pressure and lactate/pyruvate ratio remained elevated beyond postinjury hour 100 in the seizure group but not the nonseizure group (p < .02). Conclusion: Post‐traumatic seizures result in episodic as well as long‐lasting increases in intracranial pressure and microdialysis lactate/pyruvate ratio. These data suggest that post‐traumatic seizures represent a therapeutic target for patients with traumatic brain injury.

Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury

Objective:To determine that intensive glycemic control does not reduce microdialysis glucose concentration brain metabolism of glucose. Design:Prospective monitoring followed by retrospective data analysis of cerebral microdialysis and global brain metabolism. Setting:Single center, academic neurointensive care unit. Patients:Forty-seven moderate to severe traumatic brain injury patients. Interventions:A nonrandomized, consecutive design was used for glycemic control with loose insulin (n = 33) for the initial 2 yrs or intensive insulin therapy (n = 14) for the last year. Measurements and Main Results:In 14 patients treated with intensive insulin therapy, there was a reduction in microdialysis glucose by 70% of baseline concentration compared with a 15% reduction in 33 patients treated with a loose insulin protocol. Despite this reduction in microdialysis glucose, the global metabolic rate of glucose did not change. However, intensive insulin therapy was associated with increased incidence of microdialysis markers of cellular distress, namely elevated glutamate (38 ± 37% vs. 10 ± 17%, p < .01), elevated lactate/pyruvate ratio (38 ± 37% vs. 19 ± 26%, p < .03) and low glucose (26 ± 17% vs. 11 ± 15%, p < .05, and increased global oxygen extraction fraction. Mortality was similar in the intensive and loose insulin treatment groups (14% vs. 15%, p = .9), as was 6-month clinical outcome (p = .3). Conclusions:Intensive insulin therapy results in a net reduction in microdialysis glucose and an increase in microdialysis glutamate and lactate/pyruvate without conveying a functional outcome advantage.

Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study.

Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. Levels of glucose, lactate, pyruvate, glutamate, and urea were analyzed hourly. The 6-month Glasgow Outcome Scale extended (GOSe6) score was assessed for each patient. In regions of increased glucose utilization defined by positron emission tomography, the extracellular glucose concentration was less than 0.2 mmol/l. Extracellular glucose values were less than 0.2 mmol during postinjury days 0 to 7 in 19% to 30% of hourly samples on each day. Transient decreases in glucose levels occurred with electrographic seizures and nonischemic reductions in cerebral perfusion pressure and jugular venous oxygen saturation. Glutamate levels were elevated in the majority of low-glucose samples, but the lactate/pyruvate ratio did not indicate focal ischemia. Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.

Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy.

Objective: To determine if posttraumatic nonconvulsive electrographic seizures result in long-term brain atrophy. Methods: Prospective continuous EEG (cEEG) monitoring was done in 140 patients with moderate to severe traumatic brain injury (TBI) and in-depth study of 16 selected patients was done using serial volumetric MRI acutely and at 6 months after TBI. Fluorodeoxyglucose PET was done in the acute stage in 14/16 patients. These data were retrospectively analyzed after collection of data for 7 years. Results: cEEG detected seizures in 32/140 (23%) of the entire cohort. In the selected imaging subgroup, 6 patients with seizures were compared with a cohort of 10 age- and GCS-matched patients with TBI without seizures. In this subgroup, the seizures were repetitive and constituted status epilepticus in 4/6 patients. Patients with seizures had greater hippocampal atrophy as compared to those without seizures (21 ± 9 vs 12 ± 6%, p = 0.017). Hippocampi ipsilateral to the electrographic seizure focus demonstrated a greater degree of volumetric atrophy as compared with nonseizure hippocampi (28 ± 5 vs 13 ± 9%, p = 0.007). A single patient had an ictal PET scan which demonstrated increased hippocampal glucose uptake. Conclusion: Acute posttraumatic nonconvulsive seizures occur frequently after TBI and, in a selected subgroup, appear to be associated with disproportionate long-term hippocampal atrophy. These data suggest anatomic damage is potentially elicited by nonconvulsive seizures in the acute postinjury setting.

Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability.

Objective:Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we assessed the temporal pattern and the correlation of functional and metabolic recovery following human traumatic brain injury. Design and Subjects:Fifty-four patients with injury severity ranging from mild to severe were studied. Thirteen of these patients underwent both an acute and delayed FDG-PET study. Results:Analysis of the pooled global cerebral metabolic rate of glucose (CMRglc) values revealed that the intermediate metabolic reduction phase begins to resolve approximately one month following injury, regardless of injury severity. The correlation, in the 13 patients studied twice, between the extent of change in neurologic disability, assessed by the Disability Rating Scale (DRS), and the change in CMRglc from the early to late period was modest (r = −0.42). Potential explanations for this rather poor correlation are discussed. A review of the pertinent literature regarding the use of PET and related imaging modalities, including single photon emission tomography (SPECT) for the assessment of patients following traumatic brain injury is given. Conclusion:The dynamic profile of CMRglc that changes following traumatic brain injury is seemingly stereotypic across a broad range and severity of injury types. Quantitative FDG-PET cannot be used as a surrogate technique for estimating degree of global functional recovery following traumatic brain injury.

Early Nonischemic Oxidative Metabolic Dysfunction Leads to Chronic Brain Atrophy in Traumatic Brain Injury

Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury. Regional lobar assessments comprised oxidative metabolism and glucose metabolism. Acute MRI showed a preponderance of hemorrhagic lesions with few irreversible ischemic lesions. Global and regional chronic brain atrophy occurred in all patients by 6 months, with the temporal and frontal lobes exhibiting the most atrophy compared with the occipital lobe. Global and regional reduction in cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose were observed. The extent of metabolic dysfunction was correlated with the total hemorrhage burden on initial MRI (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with CMRO2 and CBF. Lobar values of OEF were not in the ischemic range and did not correlate with chronic brain atrophy. Chronic brain atrophy is regionally specific and associated with regional reductions in oxidative brain metabolism in the absence of irreversible ischemia.

Tight glycemic control increases metabolic distress in traumatic brain injury: a randomized controlled within-subjects trial.

Objective:To determine the effects of tight glycemic control on brain metabolism after traumatic brain injury using brain positron emission tomography and microdialysis. Design:Single-center, randomized controlled within-subject crossover observational trial. Setting:Academic intensive care unit. Methods:We performed a prospective, unblinded randomized controlled within-subject crossover trial of tight (80–110 mg/dL) vs. loose (120–150 mg/dL) glycemic control in patients with severe traumatic brain injury to determine the effects of glycemic control on brain glucose metabolism, as measured by [18F] deoxy-D-glucose brain positron emission tomography. Brain microdialysis was done simultaneously. Measurements and Main Results:Thirteen severely injured traumatic brain injury patients underwent the study between 3 and 8 days (mean 4.8 days) after traumatic brain injury. In ten of these subjects, global brain and gray matter tissues demonstrated higher glucose metabolic rates while glucose was under tight control as compared with loose control (3.2 ± 0.6 vs. 2.4 + 0.4, p = .02 [whole brain] and 3.8 ± 1.4 vs. 2.9 ± 0.8, p = .05 [gray matter]). However, the responses were heterogeneous with pericontusional tissue demonstrating the least state-dependent change. Cerebral microdialysis demonstrated more frequent critical reductions in glucose (p = .02) and elevations of lactate/pyruvate ratio (p = .03) during tight glycemic control. Conclusion:Tight glycemic control results in increased global glucose uptake and an increased cerebral metabolic crisis after traumatic brain injury. The mechanisms leading to the enhancement of metabolic crisis are unclear, but delivery of more glucose through mild hyperglycemia may be necessary after traumatic brain injury.

Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduced levels of extracellular cerebral glutamate and unchanged lactate pyruvate ratios

IntroductionIntracerebral hemorrhage (ICH) is a devastating form of stroke commonly resulting in severe morbidity and high mortality. Secondary brain injury often occurs in the days following the initial hemorrhage and is associated with significant neurological deterioration. The neurochemistry associated with secondary injury is poorly understood The purpose of this study is to characterize the neurochemical changes, in perihematomal tissue during frameless minimally invasive evacuation of spontaneous hematomasMethodsThis is a nonrandomized prospective microdialysis study of 12 consecutive patients undergoing Frameless Stereotactic Aspiration and Thrombolysis (FAST) of deep ICHs. Hourly glucose, lactate, pyruvate, and glutamate were measured in the perihematomal tissue of patients undergoing minimally invasive hematoma evacuation. Analyte concentrations were compared to evaluate the natural history of perihematomal neurochemistry and to identify changes potentially related to secondary injury.ResultsBrain hematoma volumes were reduced 87% during FAST and National Institute of Health Stroke Scale (NIHSS) scores were improved from an average of 19 at admission to 12.6 at time of discharge from the, intensive care unit. Glutamate average values decreased from the first 24 hours of measurement (12 mmol/L±6) to the final 24-hour epoch (5 mmol/L±6). Glutamate reduction showed a significant linear (p=0.0007) and quadratic (p<0.05) trend during hematoma drainage. Lactate pyruvate ratios (LPR), a common marker of ischemia, were unchanged.ConclusionsThis study reports that elevated levels of glutamate are found in the perihematomal region after ICH and are decreased during hematoma drainage. Conversely, ischemic LPRs are not found in perihematomal regions and were unchanged during hematoma drainage. These data suggest that excitotoxicity related to glutamate may have an important impact on secondary injury. The data failed to support the role of ischemia in secondary perihematomal damage.

Contrast agent dose effects in cerebral dynamic susceptibility contrast magnetic resonance perfusion imaging

To study the contrast agent dose sensitivity of hemodynamic parameters derived from brain dynamic susceptibility contrast MRI (DSC‐MRI).