Multimodal neurologic monitoring.

Neurocritical care has two main objectives. Initially, the emphasis is on treatment of patients with acute damage to the central nervous system whether through infection, trauma, or hemorrhagic or ischemic stroke. Thereafter, attention shifts to the identification of secondary processes that may lead to further brain injury, including fever, seizures, and ischemia, among others. Multimodal monitoring is the concept of using various tools and data integration to understand brain physiology and guide therapeutic interventions to prevent secondary brain injury. This chapter will review the use of electroencephalography, intracranial pressure monitoring, brain tissue oxygenation, cerebral microdialysis and neurochemistry, near-infrared spectroscopy, and transcranial Doppler sonography as they relate to neuromonitoring in the critically ill. The concepts and design of each monitor, in addition to the patient population that may most benefit from each modality, will be discussed, along with the various tools that can be used together to guide individualized patient treatment options. Major clinical trials, observational studies, and their effect on clinical outcomes will be reviewed. The future of multimodal monitoring in the field of bioinformatics, clinical research, and device development will conclude the chapter.

Partial recanalization of concomitant internal carotid-middle cerebral arterial occlusions promotes distal recanalization of residual thrombus within 24 h.

OBJECTIVES: Acute, simultaneous, concomitant internal carotid artery (ICA) and middle cerebral arteries (MCA) occlusions almost invariably lead to significant neurological disability if left untreated. Endovascular therapy is frequently the method of treatment in such situations but there remains a chance of incomplete recanalization. Successful recanalization of the proximal aspect of the occlusion may allow for endogenous thrombolysis and facilitate further endogenous recanalization of any residual MCA occlusion. METHODS: Consecutive patients with acute ischemic stroke undergoing endovascular therapy for tandem extracranial ICA-MCA or contiguous intracranial ICA-MCA occlusions were retrospectively analyzed. Rates of facilitated endogenous recanalization at 24 h (FER(24)) were compared by imaging within the immediate post-intervention 5-24 h period in those with proximal recanalization and in those without. RESULTS: 17 patients were included in the analysis. 12 patients had good initial proximal recanalization but a residual partial or total occlusion of the MCA while five patients failed any recanalization. Seven patients (58.3%) in the first group and none in the second had FER(24) on interval imaging after intervention (p=0.04). The probability of death and disability at discharge was less in patients with FER(24) than those without (p=0.05). CONCLUSIONS: More than half of all patients who present with both ICA and MCA occlusions who are only partially recanalized will undergo facilitated endogenous recanalization within the subsequent 24 h following intervention.

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.

Higher rates of mortality but not morbidity follow intracranial mechanical thrombectomy in the elderly.

BACKGROUND AND PURPOSE: Mechanical thrombectomy is a promising means of recanalizing acute cerebrovascular occlusions in certain situations. We sought to determine if increasing age adversely affects prognosis. MATERIALS AND METHODS: We reviewed all Merci thrombectomy cases and compared patients younger than 80 years of age with older individuals. We compared these 2 age groups with respect to recanalization rates, hospital LOS, hemorrhagic transformation, and death and disability on discharge. RESULTS: Elderly patients were more likely to die from their stroke than those younger than 80 years of age, regardless of recanalization success (48% versus 15%; OR, 5.5; 95% CI, 2.1-14.1). Among survivors, there was no difference in the probability of having a good functional outcome (mRS,

Metabolic crisis after traumatic brain injury is associated with a novel microdialysis proteome.

BACKGROUND: To examine if the metabolic distress after traumatic brain injury (TBI) is associated with a unique proteome. METHODS: Patients with severe TBI prospectively underwent cerebral microdialysis for the initial 96 h after injury. Hourly sampling of metabolism was performed and patients were categorized as having normal or abnormal metabolism as evidenced by the lactate/pyruvate ratio (LPR) threshold of 40. The microdialysate was frozen for proteomic batch processing retrospectively. We employed two different routes of proteomic techniques utilizing mass spectrometry (MS) and categorized as diagnostic and biomarker identification approaches. The diagnostic approach was aimed at finding a signature of MS peaks which can differentiate these two groups. We did this by enriching for intact peptides followed by MALDI-MS analysis. For the biomarker identification approach, we applied classical bottom-up (trypsin digestion followed by LC-MS/MS) proteomic methodologies. RESULTS: Five patients were studied, 3 of whom had abnormal metabolism and 2 who had normal metabolism. By comparison, the abnormal group had higher LPR (1609 +/- 3691 vs. 15.5 +/- 6.8, P < 0.001), higher glutamate (157 +/- 84 vs. 1.8 +/- 1.4 microM, P < 0.001), and lower glucose (0.27 +/- 0.35 vs. 1.8 +/- 1.1 mmol/l, P < 0.001). The abnormal group demonstrated 13 unique proteins as compared with the normal group in the microdialysate. These proteins consisted of cytoarchitectural proteins, as well as blood breakdown proteins, and a few mitochondrial proteins. A unique as yet to be characterized peptide was found at m/z (mass/charge) 4733.5, which may represent a novel biomarker of metabolic distress. CONCLUSION: Metabolic distress after TBI is associated with a differential proteome that indicates cellular destruction during the acute phase of illness. This suggests that metabolic distress has immediate cellular consequences after TBI.

Recanalization rates decrease with increasing thrombectomy attempts.

BACKGROUND AND PURPOSE: Use of the Merci retriever is increasing as a means to reopen large intracranial arterial occlusions. We sought to determine whether there is an optimum number of retrieval attempts that yields the highest recanalization rates and after which the probability of success decreases. MATERIALS AND METHODS: All consecutive patients undergoing Merci retrieval for large cerebral artery occlusions were prospectively tracked at a comprehensive stroke center. We analyzed ICA, M1 segment of the MCA, and vertebrobasilar occlusions. We compared the revascularization of the primary AOL with the number of documented retrieval attempts used to achieve that AOL score. For tandem lesions, each target lesion was compared separately on the basis of where the device was deployed. RESULTS: We identified a total of 97 patients with 115 arterial occlusions. The median number of attempts per target vessel was 3, while the median final AOL score was 2. Up to 3 retrieval attempts correlated with good revascularization (AOL 2 or 3). When >or=4 attempts were performed, the end result was more often failed revascularization (AOL 0 or 1) and procedural complications (P = .006). CONCLUSIONS: In our experience, 3 may be the optimum number of Merci retrieval attempts per target vessel occlusion. Four or more attempts may not improve the chances of recanalization, while increasing the risk of complications.

Endovascular mechanical clot retrieval in a broad ischemic stroke cohort.

BACKGROUND AND PURPOSE: Our aim was to describe an expanded experience with endovascular mechanical embolectomy in a broad group of patients, including those not meeting entry criteria for the MERCI multicenter trials. METHODS: We performed an analysis of all patients with ischemic stroke treated with the Merci Clot Retrieval Device at a single academic center outside of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trials. RESULTS: Twenty-four patients were treated with the device. Nine were MERCI trial ineligible: 4 received intravenous (IV) tissue plasminogen activator (tPA), 1 received IV tPA and was younger than 18 years of age, and 4 had time-to-treatment of longer than 8 hours. Mean age was 64 years (range, 14-89 years; 42% women). Median National Institutes of Health Stroke Scale (NIHSS) score was 21 (range, 11-30). Median symptoms-to-procedure-start time was 303 minutes (range, 85-2385 minutes). Recanalization (Thrombolysis in Myocardial Infarction, 2-3) was achieved in 15/24 (63%). In device-only patients, recanalization occurred in 10/16. In patients who failed IV tPA undergoing rescue embolectomy, recanalization was achieved in 4/5. Three patients unresponsive to device therapy received rescue intra-arterial tPA/abciximab; recanalization was achieved in 2/3. Recanalization was achieved in 3/4 patients in whom treatment was started longer than 8 hours after symptom onset. Asymptomatic hemorrhage occurred in 38%; symptomatic hemorrhage, in 8%. Three device fractures occurred; none worsened clinical outcome. In-hospital mortality was 17%; 90-day mortality, 29%. Good 90-day functional outcome (modified Rankin Scale,

Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome.

OBJECTIVE: To determine whether early seizures that occur frequently after intracerebral hemorrhage (ICH) lead to increased brain edema as manifested by increased midline shift. METHODS: A total of 109 patients with ischemic stroke (n = 46) and intraparenchymal hemorrhage (n = 63) prospectively underwent continuous EEG monitoring after admission. The incidence, timing, and factors associated with seizures were defined. Serial CT brain imaging was conducted at admission, 24 hours, and 48 to 72 hours after hemorrhage and assessed for hemorrhage volume and midline shift. Outcome at time of discharge was assessed using the Glasgow Outcome Scale score. RESULTS: Electrographic seizures occurred in 18 of 63 (28%) patients with ICH, compared with 3 of 46 (6%) patients with ischemic stroke (OR = 5.7, 95% CI 1.4 to 26.5, p < 0.004) during the initial 72 hours after admission. Seizures were most often focal with secondary generalization. Seizures were more common in lobar hemorrhages but occurred in 21% of subcortical hemorrhages. Posthemorrhagic seizures were associated with neurologic worsening on the NIH Stroke Scale (14.8 vs 18.6, p < 0.05) and with an increase in midline shift (+ 2.7 mm vs -2.4 mm, p < 0.03). There was a trend toward increased poor outcome (p < 0.06) in patients with posthemorrhagic seizures. On multivariate analysis, age and initial NIH Stroke Scale score were independent predictors of outcome. CONCLUSION: Seizures occur commonly after ICH and may be nonconvulsive. Seizures are independently associated with increased midline shift after intraparenchymal hemorrhage.

PET investigation of post-traumatic cerebral blood volume and blood flow.

Hemodynamic changes following traumatic brain injury (TBI) may reflect cellular damage leading to secondary injury. The purpose of this study was to investigate the regional hemodynamic parameters acutely after TBI among regions in and around contusions. Sixteen patients (11 male, 5 female) showing evidence of contusion on CT and 18 normal volunteers (12 male, 6 female) underwent positron emission tomography (PET) with O-15 CO and O-15 H2O to estimate cerebral blood volume (CBV) and cerebral blood flow (CBF), respectively. A flow to volume ratio (FVR = CBF/CBV) was also calculated as an index of vasodilatation. The hemodynamic parameters were compared among contusion, pericontusion, and remote areas. Globally, hemodynamic parameters did not differ between patients and normal volunteers, and did not correlate with intracranial pressure (ICP). Regionally, contusional and pericontusional areas showed significantly lower CBF and FVR compared with normal volunteers, while CBV did not differ significantly. The correlation between CBF and CBV was significant (r = 0.37, p < 0.01). Remote areas did not show a significant difference in any of the PET parameters. In conclusion, regional brain edema is likely to occur in contusion and pericontusion areas, while some of the contusional tissue may show vascular engorgement.

Metabolic suppressive therapy as a treatment for intracranial hypertension--why it works and when it fails.

Thirty years after its first description metabolic suppressive therapy is still controversial in patients with intractable intracranial hypertension. In this study high dose propofol was used to induce metabolic suppression. The effects on intracranial pressure (ICP) and the cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlc) are reported. A total of 28 studies were performed on 14 head injured patients. A Xenon133 cerebral blood flow (CBF) and a CO2-reactivity (CO2R) test were performed prior to induction of metabolic suppression. The following parameters were continuously monitored: EEG, etCO2, SjvO2, ICP, MAP and bilateral MCA flow velocity (VMCA). PCO2 was obtained before and during propofol-induced EEG burst-suppression in arterial and jugular-venous blood. CMRO2, CMRGlc and Metabolic Ratio (MR = CMRO2/CMRGlc) were calculated. MR < 0.6 was defined as relative hyperglycolysis. ICP decreased by 24.1 +/- 29.0% during burst-suppression. Arterial, jugular-venous and etCO2 also decreased. Multiple regression analysis revealed that CO2 was the strongest predictor for ICP. Lower baseline ICP and normal CO2 reactivity were predictors for normal metabolic suppression reactivity. In studies with normal metabolic ratio, ICP reduction was associated with a reduction in CMRO2. In studies with hyperglycolysis, ICP reduction was poor but CMRGlc decreased significantly. In conclusion, intact CO2R, normal or only moderately elevated ICP and normal MR are predictive of ICP reduction with high dose propofol after head injury.

Is CPP therapy beneficial for all patients with high ICP?

Induced blood pressure elevation has become a popular treatment for intracranial hypertension. However, there remains a concern that in some patients blood pressure elevation will further elevate ICP. This study was conducted to test the hypothesis that increasing MAP decreases ICP. A total of 47 studies were performed on 23 intubated patients with head injury. MAP and SjvO2 were continuously monitored. MAP was raised significantly by 13.8 (5.9) mmHg (t-test; p < 0.0001) using phenylephrine infusion. The percent change ICP per mmHg increase in MAP (% delta ICP/mm Hg MAP) was calculated. Pearson correlation coefficient, t-test and logistic regression analysis were used for statistical evaluation. Increasing MAP resulted in a decrease in ICP in 38.3% and in an increase in ICP in 61.7% out of 47 studies. The following characteristics were seen in patients in whom a decrease in ICP was associated with an increase in MAP: High GCS (r = -0.61; p = 0.004) and low SjvO2 ((2 = 4.89; p = 0.027). In patients with lower GCS and high SjvO2 an increase in MAP resulted in an increase in ICP. We concluded that in the majority of studies increasing MAP was followed by an increase in ICP. CPP therapy has a selective indication in patients with high GCS, low SjvO2 and increased ICP.

Can hyperventilation improve cerebral microcirculation in patients with high ICP?

Gosling's pulsatility index (PI) is generally thought to reflect cerebrovascular resistance. Hyperventilation and increased intracranial pressure (ICP) usually increase PI. In this study, the effect of hyperventilation on PI was assessed in head injured patients with and without elevated ICP. A total of 73 hyperventilation studies were conducted on 20 intubated TBI patients. EtCO2, ICP, MCA flow velocity and MCA PI bilaterally were recorded simultaneously. Hemispheric CO2-Reactivity (hCO2R) was calculated. Only studies with a baseline ICP < 15 or > 30 mm Hg were included for analysis. With hyperventilation pCO2 decreased on average from 33.54.2 to 26.84.8 mmHg. PI increased significantly in patients with baseline ICP < 15 mmHg (11.8%; p < 0.0001) but decreased significantly if baseline ICP was > 30 mm Hg (12.21%; p = 0.0013). High baseline ICP, low initial GCS and impaired hCO2R were associated with the decrease of PI. Hyperventilation unexpectedly reduced PI in patients with high ICP. Because decreased PI suggests decreased CVR, it is postulated that hyperventilation in the setting of raised ICP improves cerebral microcirculation.

Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage.

BACKGROUND: It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. OBJECTIVE: To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. METHOD: Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. RESULTS: Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. CONCLUSIONS: A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.

Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury.

Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we studied the correlation between CMRglc and the level of consciousness within the first month following human traumatic brain injury. Forty-three FDG-PET scans obtained on 42 mild to severely head-injured patients were quantitatively analyzed for the determination of regional cerebral metabolic rate of glucose (CMRglc). Reduction of cerebral glucose utilization, defined as a CMRglc of < or =4.9 mg/100 g/min, was present regionally in 88% of the studies. The prevalence of global cortical CMRglc reduction was higher in severely head-injured patients (86% versus 67% mild-moderate), although the absolute magnitude was similar across the injury severity spectrum (mean CMRglc 3.9 +/- 0.6 mg/100 g/min). The level of consciousness, as measured by the Glasgow Coma Scale, correlated poorly with the global cortical CMRglc value (r = 0.08; p = 0.63). With regards to severity of head injury, this correlation was worst for the severely injured (r = -0.11; p = 0.58) and better for the mildly injured patients (r = 0.50; p = 0.07). In most cases, intraparenchymal hemorrhagic lesions were associated with either focal CMRglc reduction or elevation. It is concluded that the etiologies of CMRglc reduction are likely multifactorial given the complex nature of traumatic brain injury and that the reduction of CMRglc represents a fundamental pathobiologic state following head injury that is not tightly coupled to level of consciousness.

Endovascular treatment and neurointensive care of ruptured aneurysms.

The acute management of aneurysmal SAH requires a comprehensive approach entailing acute critical care and stabilization, occlusion of the aneurysm, and intensive care management of acute neurologic complications. The development of endovascular treatment of aneurysms has added an important, less-invasive treatment to the regimen available in treating aneurysms. An integrated approach of providing critical care before, during, and after the occlusion of the aneurysm is an important concept that should be the goal. Debate and controversy remains regarding which aneurysms are best suited to endovascular treatment or to surgical treatment; an evolving experience and clinical trials will provide further guidance. Nonetheless, some aneurysms may require both surgery and endovascular treatment. Finally, close neurologic observation and directed specialized monitoring techniques are required for providing directed critical care in the acute period after SAH.

Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring.

OBJECT: The early pathophysiological features of traumatic brain injury observed in the intensive care unit (ICU) have been described in terms of altered cerebral blood flow, altered brain metabolism, and neurochemical excitotoxicity. Seizures occur in animal models of brain injury and in human brain injury. Previous studies of posttraumatic seizures in humans have been based principally on clinical observations without a systematic approach to electroencephalographic (EEG) recording of seizures. The purpose of this study was to determine prospectively the incidence of convulsive and nonconvulsive seizures by using continuous EEG monitoring in patients in the ICU during the initial 14 days post-injury. METHODS: Ninety-four patients with moderate-to-severe brain injuries underwent continuous EEG monitoring begin-ning at admission to the ICU (mean delay 9.6+/-5.4 hours) and extending up to 14 days postinjury. Convulsive and nonconvulsive seizures occurred in 21 (22%) of the 94 patients, with six of them displaying status epilepticus. In more than half of the patients (52%) the seizures were nonconvulsive and were diagnosed on the basis of EEG studies alone. All six patients with status epilepticus died, compared with a mortality rate of 24% (18 of 73) in the nonseizure group (p<0.001). The patients with status epilepticus had a shorter mean length of stay (9.14+/-5.9 days compared with 14+/-9 days [t-test, p<0.031). Seizures occurred despite initiation of prophylactic phenytoin on admission to the emergency room, with maintenance at mean levels of 16.6+/-2.8 mg/dl. No differences in key prognostic factors (such as the Glasgow Coma Scale score, early hypoxemia, early hypotension, or 1-month Glasgow Outcome Scale score) were found between the patients with seizures and those without. CONCLUSIONS: Seizures occur in more than one in five patients during the 1st week after moderate-to-severe brain injury and may play a role in the pathobiological conditions associated with brain injury.

Continuous EEG monitoring in the intensive care unit: early findings and clinical efficacy.

The assessment of the neurocritical care patient involves serial assessment of neurologic status using bedside clinical examination and a variety of periodic neurophysiologic testing. Continuous electroencephalographic (CEEG) monitoring in the intensive care unit offers a unique means to track neurologic function directly and regionally. CEEG is becoming more widespread with a growing but small body of literature. The purpose of this paper is to outline the current experience with intensive care unit CEEG monitoring. The basic methods and caveats are discussed. We review the underlying rationale for using CEEG which is that secondary neurologic injury commonly occurs in the intensive care unit and at times is hard to detect. CEEG has a proven role in detecting secondary injuries, namely seizures and brain ischemia. The basic tenets of establishing clinical effectiveness for CEEG in the ICU are discussed while acknowledging a need for further study of clinical effectiveness. We review our initial clinical experience of CEEG in 300 patients and outline the clinical efficacy in terms of cost reduction and improvement in outcome (P < 0.01) using CEEG. Finally, several controversial aspects of CEEG are enumerated, and the need for additional study to answer these pressing questions is presented.

Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study.

Experimental traumatic brain injury studies have shown that cerebral hyperglycolysis is a pathophysiological response to injury-induced ionic and neurochemical cascades. This finding has important implications regarding cellular viability, vulnerability to secondary insults, and the functional capability of affected regions. Prior to this study, posttraumatic hyperglycolysis had not been detected in humans. The characteristics and incidence of cerebral hyperglycolysis were determined in 28 severely head injured patients using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). The local cerebral metabolic rate of glucose (CMRG) was calculated using a standard compartmental model. In six of the 28 patients, the global cerebral metabolic rate of oxygen (CMRO2) was determined by the simultaneous measurements of arteriovenous differences of oxygen and cerebral blood flow (xenon-133). Hyperglycolysis, defined as an increase in glucose utilization that measures two standard deviations above expected levels, was documented in all six patients in whom both FDG-PET and CMRO2 determinations were made within 8 days of injury. Five additional patients were found to have localized areas of hyperglycolysis adjacent to focal mass lesions. Within the 1st week following the injury, 56% of patients studied had presumptive evidence of hyperglycolysis. The results of this study indicate that the metabolic state of the traumatically injured brain should be defined differentially in terms of glucose and oxygen metabolism. The use of FDG-PET demonstrates that hyperglycolysis occurs both regionally and globally following severe head injury in humans. The results of this clinical study directly complement those previously reported in experimental brain-injury studies, indicating the capability of imaging a fundamental component of cellular pathophysiology characteristic of head injury.