Effect of cognitive load on eye-target synchronization during smooth pursuit eye movement.

In mild traumatic brain injury (mTBI), the fiber tracts that connect the frontal cortex with the cerebellum may suffer shear damage, leading to attention deficits and performance variability. This damage also disrupts the enhancement of eye-target synchronization that can be affected by cognitive load when subjects are tested using a concurrent eye-tracking test and word-recall test. We investigated the effect of cognitive load on eye-target synchronization in normal and mTBI patients using the nonlinear dynamical technique of stochastic phase synchronization. Results demonstrate that eye-target synchronization was negatively affected by cognitive load in mTBI subjects. In contrast, eye-target synchronization improved under intermediate cognitive load in young (≤40years old) normal subjects.

Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) may be a useful index of microstructural changes implicated in diffuse axonal injury (DAI) linked to persistent postconcussive symptoms, especially in mild traumatic brain injury (TBI), for which conventional MR imaging techniques may lack sensitivity. We hypothesized that for mild TBI, DTI measures of DAI would correlate with impairments in reaction time, whereas the number of focal lesions on conventional 3T MR imaging would not. MATERIALS AND METHODS: Thirty-four adult patients with mild TBI with persistent symptoms were assessed for DAI by quantifying traumatic microhemorrhages detected on a conventional set of T2*-weighted gradient-echo images and by DTI measures of fractional anisotropy (FA) within a set of a priori regions of interest. FA values 2.5 SDs below the region average, based on a group of 26 healthy control adults, were coded as exhibiting DAI. RESULTS: DTI measures revealed several predominant regions of damage including the anterior corona radiata (41% of the patients), uncinate fasciculus (29%), genu of the corpus callosum (21%), inferior longitudinal fasciculus (21%), and cingulum bundle (18%). The number of damaged white matter structures as quantified by DTI was significantly correlated with mean reaction time on a simple cognitive task (r = 0.49, P = .012). In contradistinction, the number of traumatic microhemorrhages was uncorrelated with reaction time (r = -0.08, P = .71). CONCLUSION: Microstructural white matter lesions detected by DTI correlate with persistent cognitive deficits in mild TBI, even in populations in which conventional measures do not. DTI measures may thus contribute additional diagnostic information related to DAI.

Eye-target synchronization in mild traumatic brain-injured patients.

Eye-target synchronization is critical for effective smooth pursuit of a moving visual target. We apply the nonlinear dynamical technique of stochastic-phase synchronization to human visual pursuit of a moving target, in both normal and mild traumatic brain-injured (mTBI) patients. We observe significant fatigue effects in all subject populations, in which subjects synchronize better with the target during the first half of the trial than in the second half. The fatigue effect differed, however, between the normal and the mTBI populations and between old and young subpopulations of each group. In some cases, the younger (40 years old) normal subjects. Our results, however, suggest that further studies will be necessary before a standard of "normal" smooth pursuit synchronization can be developed.

Traumatic brain injury.

The decrease in mortality and improved outcome for patients with severe traumatic brain injury over the past 25 years can be attributed to the approach of "squeezing oxygenated blood through a swollen brain". Quantification of cerebral perfusion by monitoring of intracranial pressure and treatment of cerebral hypoperfusion decrease secondary injury. Before the patient reaches hospital, an organised trauma system that allows rapid resuscitation and transport directly to an experienced trauma centre significantly lowers mortality and morbidity. Only the education of medical personnel and the institution of trauma hospital systems can achieve further improvements in outcome for patients with traumatic brain injuries.

The effect of implementation of guidelines for the management of severe head injury on patient treatment and outcome.

The authors retrospectively analysed two groups of consecutive patients who were similarly matched for brain injury severity. From a total of 39 severe head injury patients, 23 were treated according to the Guidelines for the Management of Severe Head Injury with intracranial pressure (ICP) monitoring ("Guidelines group"). Such an approach allowed the maintenance of ICP within normal values, especially in patients with intraventricular ICP monitoring allowing the release of cerebrospinal fluid (CSF) from the ventricular system. In the Guidelines group only two patients were administered barbiturates, after all other means of ICP lowering had been exhausted. The second group consisted of 16 patients who were not monitored for ICP ("non-Guidelines group"). In this group, management consisted of the prophylactic administration of barbiturates, high dose osmotic diuretics and hyperventilation usually at levels below 25 mm Hg. In the Guidelines group the mortality rate was 30% compared to 44% in the non-Guidelines group. Almost twice as many patients achieved a "favourable" (good recovery and moderate disability) outcome (49%) compared to the non-Guidelines treated patients (25%). Furthermore, there was a 32% decrease in severe neurological disabilities in those patients in the Guidelines group. It seems that the implementation of "Guidelines" in the treatment of severe head injury, based on the result of our clinical study, reduces death and disability rates in patients with severe head injury. The administration of therapy based on the "Guidelines principles" and monitoring of ICP, can minimise the application of those therapeutic modalities (barbiturate coma and prolonged hyperventilation) which, in addition to favourable effects, may also have harmful effects on patients with severe head injury.

Early white blood cell dynamics after traumatic brain injury: effects on the cerebral microcirculation.

Increasing clinical and experimental evidence suggests that traumatic brain injury (TBI) elicits an acute inflammatory response. In the present study we investigated whether white blood cells (WBC) are activated in the cerebral microcirculation early after TBI and whether WBC accumulation affects the posttraumatic cerebrovascular response. Twenty-four anesthetized rabbits had chronic cranial windows implanted 3 weeks before experimentation. Animals were divided into four experimental groups and were studied for 7 hours (groups I, IIa, and III) or 2 hours (group IIb). Intravital fluorescence videomicroscopy was used to visualize WBC (rhodamine 6G, intravenously), pial vessel diameters, and blood-brain barrier (BBB) integrity (Na+-fluorescein) at 6 hours (groups I, IIa, and III) or 1 hour (group IIb) after TBI. Group I (n = 5) consisted of sham-operated animals. Groups IIa (n = 7) and IIb (n = 5) received fluid-percussion injury at 1 hour. Group III (n = 7) received fluid-percussion injury and 1 mg/kg anti-adhesion monoclonal antibody (MoAb) "IB4" 5 minutes before injury. Venular WBC sticking, intracranial pressure (ICP), and arterial vessel diameters increased significantly for 6 hours after trauma. IB4 reduced WBC margination and prevented vasodilation. Intracranial pressure was not reduced by treatment with IB4. Blood-brain barrier damage occurred at 1 hour but not at 6 hours after TBI and was independent of WBC activation. This first report using intravital videomicroscopy to study the inflammatory response after TBI reveals upregulated interaction between WBC and cerebral endothelium that can be manipulated pharmacologically. White blood cell activation is associated with pial arteriolar vasodilation. White blood cells do not induce BBB breakdown less than 6 hours after TBI and do not contribute to posttraumatic ICP elevation. The role of WBC more than 6 hours after TBI should be investigated further.

Hypertonic/hyperoncotic saline attenuates microcirculatory disturbances after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) induces an acute inflammatory response characterized by early recruitment of inflammatory cells (white blood cells). Rapid resuscitation of TBI with hypertonic saline/dextran (HS/DEX) yields promising results in clinical and experimental studies. The purpose of this paper was to test the hypothesis that HS/DEX exerts its effects in part through a modulation of the acute inflammatory response to TBI. METHODS: Rabbits equipped with chronic cranial windows underwent fluid-percussion injury and were followed up for 6 hours. Intravital fluorescence videomicroscopy technique was used to visualize white blood cell trafficking and to measure pia vessel diameters and venular shear rates. Three groups were studied: sham (group I, n = 5), trauma (group II, n = 7), and trauma and 4 mL/kg 7.2% NaCl/10% dextran 60 IV over 5 minutes at 10 minutes after TBI (group III, n = 7). RESULTS: TBI in groups II and III led to significant increases of intracranial pressure. Arteriolar diameters after trauma increased by 17 +/- 8% at 6 hours in group II. Infusion of HS/DEX completely prevented this secondary diameters increase. At 6 hours, the increase of "sticking" white blood cells in group III was reduced by approximately 90% compared with group II. CONCLUSIONS: Whether the anti-inflammatory effect of HS/DEX plays a role in reducing delayed brain damage (> 6 hours after TBI) or other systemic complications of TBI arises as an important question and should be investigated further.

Treatment of refractory intracranial hypertension in severe traumatic brain injury with repetitive hypertonic/hyperoncotic infusions.

Rapid resuscitation of clinical and experimental traumatic brain injury (TBI) with hypertonic saline (HS) has been shown to improve neurological function and decrease intracranial pressure (ICP). The purpose of the present study was to test the efficacy of administration of HS (7.5%) combined with 6% hydroxyethyl starch (molecular weight 200,000/0.60-0.66; HHES) for the treatment of intracranial hypertension refractory to standard therapy in patients with severe TBI. With approval of the Institutional Ethics Committee six consecutive patients with severe TBI (GCS < 8) between 22 and 47 years of age (mean 32) who met the inclusion criteria (therapy resistant ICP > 25 mmHg, cerebral perfusion pressure (CPP) < 60 mmHg, plasma-Na+ < 150 mOsm and > 4 hours since the last HS/HHES treatment) were prospectively enrolled in the study. Patients received between one and ten bolus infusions of maximal 250 ml HS/HHES at a rate of 20 ml/min. A total of 32 infusions were given. ICP and CPP before treatment were 45 +/- 15 and 52 +/- 18 mmHg, respectively. Administration of HS/HHES significantly lowered ICP to 25 +/- 14 mmHg and improved CPP to 72 +/- 16 mmHg at 30 min without affecting arterial blood pressure or blood gases. Plasma sodium normalized within 30 min. HS/HES might become an interesting addition to conventional treatment maneuvers currently used for ICP therapy. It reduces otherwise therapy-resistant intracranial hypertension without negatively affecting blood pressure, blood gases and cerebral perfusion.

Hypertonic/hyperoncotic saline reliably reduces ICP in severely head-injured patients with intracranial hypertension.

Hypertonic saline (HS) has been shown to decrease intracranial pressure (ICP) and cerebral water content in experimental models of traumatic brain injury (TBI). The purpose of the present study was to test the efficacy of administration of HS (7.5%) combined with 6% hydroxyethyl starch (molecular weight 200.000/0.60-0.66; HHES) for the treatment of therapy-resistant intracranial hypertension in patients with severe TBI. Six patients with severe TBI (GCS < 8) who met the inclusion criteria (therapy resistant ICP > 25 mmHg, cerebral perfusion pressure (CPP) < 60 mmHg, plasma-Na+ < 150 mOsm and > 4 hours since the last HS/HHES treatment) were prospectively enrolled in the study and received between one and ten bolus infusions of maximal 250 ml HS/HHES at a rate of 20 ml/min. A total of 32 infusions were given. Administration of HS/HHES significantly lowered ICP by 44% and improved CPP by 38% to well above 70 mmHg at 30 min without affecting arterial blood pressure or blood gases. Plasma sodium normalized within 30 min. Experimental studies from our laboratory indicate that the ICP lowering effect is primarily due to dehydration of brain tissue and that cerebral blood volume remains largely unaffected by HS. In summary, HS/HHES reduces otherwise therapy-resistant intracranial hypertension and improves cerebral perfusion even after repeated administration without negatively affecting blood pressure or causing a rebound ICP increase.

Blood-brain barrier breakdown occurs early after traumatic brain injury and is not related to white blood cell adherence.

The time course of blood-brain barrier (BBB) breakdown after traumatic brain injury (TBI) has important implications for therapy. This study was conducted in order to test post-traumatic BBB dysfunction in a model of fluid-percussion induced TBI in rabbits at 1 and 6 hours after TBI and relate it to white blood cell (WBC) activation. Ten anesthetized rabbits had chronic cranial windows implanted three weeks prior to experimentation. Fluid-percussion injury (3.5 atm.) was induced and animals were followed for 1 or 6 h. Intravital fluorescence videomicroscopy was used to assess BBB permeability and WBC adhesion to pial venules. Na(+)-fluorescein was infused continuously over 30 min at either 30 min (Group I, n = 5) or 5.5 h (Group II, n = 5) after TBI. Microvascular permeability in individual postcapillary venules was assessed qualitatively at 1 and 30 min after start of infusion. TBI led to a transient mean arterial blood pressure (MAP) surge after trauma and a progressive increase in the number of sticking WBCs per mm2 vessel wall. Na(+)-fluorescein extravasation was observed in 4 out of 5 Group I animals and in none of Group II. BBB breakdown was not associated with WBC sticking. We conclude that after fluid-percussion injury the BBB is damaged at 1 h post-trauma and that its function is restored 6 h later. Increased WBC sticking at 6 h is not associated with BBB breakdown. Whether WBCs may cause vascular permeability changes at a later point needs further investigation.

Intracranial pressure monitoring techniques.

In patients requiring ICP monitoring, a ventricular catheter connected to an external strain gauge transducer or catheter-tip pressure transducer device is the most accurate and reliable method of monitoring ICP, and enables therapeutic CSF drainage. Clinically significant infections or hemorrhage associated with ICP devices causing patient morbidity are rare and should not deter the decision to monitor ICP. Parenchymal catheter-tip pressure transducer devices measure ICP, similar to ventricular ICP pressure, but have the potential for significant measurement differences and drift due to the inability to recalibrate. These devices are advantageous when ventricular ICP is not obtained or if there is obstruction in the fluid coupling. Subarachnoid or subdural fluid-coupled devices and epidural ICP devices are currently less accurate.

The square-wave approach to impedance measurement of brain tissue water dynamics.

Electrical properties of living soft tissue have been used to analyze their structure and function. Presently, the 'admittance locus' method, with the sine-wave signal of changing frequency, is the most informative continuous method for analyzing extra-and intracellular water content in brain tissue. Using the square-wave signal in lieu of the sine-wave signal, we can avoid cumbersome and costly measurements and facilitate real-time data processing. An isolation-calibration device was developed for the present study in order to condition and stabilize electrical current through the brain cortex. This device was also used for impedance calibration before and after the experiments. We propose a simple algorithm for data analysis on the basis of equivalent circuit approach, which allows to develop a computer program for data processing. Preliminary experiments on rat brains were carried out with a 0.2-0.5 mm stainless-steel tetrapolar electrode system. These studies showed good linearity between stimulating currents (I = 5-30 microA) through the external electrodes in the brain cortex and a drop in voltage which was measured by 2 inner electrodes. The results of the device and the program accuracy tests allow us to choose the optimal range for the working current. We can recommend this method for usage in animal experiments.

Survey of critical care management of comatose, head-injured patients in the United States.

OBJECTIVE: This survey was designed to study current practices in the monitoring and treatment of patients with severe head injury in the United States. DATA SOURCES: The collected data represent answers to telephone interviews of nurse managers, clinical specialists, and staff nurses specializing in neurotrauma care at 277 randomly selected hospitals from a total pool of 624 trauma centers. Overall, 261 (94%) centers participated in the survey. Of the participating centers, 219 (84%) were providers of care for severely head-injured patients. In order to assess reliability and account for differences among respondents, personnel from 40 (15%) centers were resurveyed 6 months later and a different nursing professional was interviewed, although the questions remained the same. DATA EXTRACTION: The largest group of respondents came from level I centers (49%), followed by level II (32%) and level III (2%). Thirty-four percent of the surveyed hospitals had a designated neurologic/neurosurgical intensive care unit, and 24% of all units surveyed were under the direction of either a neurosurgeon or a neurologist. Twenty-eight percent of the centers routinely performed intracranial pressure monitoring, while 7% of the centers reported never using this technique. The use of ventriculostomy catheters for intracranial pressure monitoring was employed in 72% of the centers, but cerebrospinal fluid drainage was utilized by only 44% of the hospitals. The percentage of patients who had their intracranial pressure monitored was significantly higher in level I trauma centers and at hospitals that treated larger numbers of severely head-injured patients (15 to 30 patients per month, which represented 15% of the hospitals surveyed). Hyperventilation and osmotic diuretics were used in 83% of centers to reduce intracranial hypertension. The administration of barbiturates was reported in 33% of the units as a treatment for intracranial hypertension. Corticosteroids were used more than half of the time in 64% of trauma centers. Twenty-nine percent of the centers reported aiming for PaCO2 values of < 25 torr (< 3.3 kPa). CONCLUSIONS: The survey data indicate that there is a considerable variation in the management of patients with severe head injury in the United States. The establishment of guidelines for the management of head injury based on available scientific data and moderated by practical and financial considerations may lead to improvement in the standard of care.

Critical care of children with acute brain injury.

Severe neurologic illness and injury in children may occur in a wide range of clinical and environmental settings. The majority of children who sustain traumatic brain injury will achieve a good outcome if intensive care is directed toward preventing secondary injury. The most important aspect of care is ensuring adequate oxygenation, ventilation, and perfusion. Together with standard supportive care, the aggressive use of intraventricular pressure monitoring and CSF drainage to treat intracranial hypertension can attenuate or prevent continuing brain injury. Sustained hyperventilation, aggressive diuresis, hypothermia, and induction of barbiturate coma are reserved for children for whom the first tier of therapy is not effective.

A method for monitoring intracranial temperature via tunneled ventricular catheter: technical note.

A simple technique for monitoring intracerebral temperature in humans via a ventricular catheter is described. This differs from a previously described method by enabling such measurements to be accomplished with a commercially available thermistor, a standard ventricular catheter, and common hospital supplies. In contrast to the earlier device, this system allows for the subcutaneous tunneling of the distal ventricular catheter. This is an easily assembled and cost-effective technique with which to conduct investigations on human intracerebral temperature.

Traumatic injury induces interleukin-6 production by human astrocytes.

The brain is being evaluated as a de novo source of cytokines. Because recent evidence indicates that interleukin-6 (IL-6) may influence blood-brain barrier function and vascular permeability, we have sought to determine whether mechanical injury can directly induce in situ cerebral IL-6 production. Adult human astrocyte cultures were subjected to mechanical injury by the in vitro method of fluid percussion barotrauma, developed in our laboratory. Serial supernatant samples were collected for 8 h and evaluated for IL-6 activity using a proliferation assay employing the dependent B cell hybridoma cell line, B9. At optimum injury, the IL-6 level became significantly (P < 0.0001, analysis of variance) elevated from baseline 2 h after trauma and continued to increase over the observation period. Our study shows that following mechanical injury human astrocytes produce IL-6, which may contribute to post-traumatic cerebrovascular dysfunction. Elucidating the precise role of intracerebral cytokines is essential to our understanding of the mechanism responsible for post-traumatic cerebrovascular dysfunction.

A square signal wave method for measurement of brain extra- and intracellular water content.

Brain tissue electrical impedance is a commonly used method to evaluate the dynamics of brain edema. We have found the square wave impedance method simpler and more cost-effective than the currently used sine wave impedance method. This square wave method avoids the necessity for expensive frequency control and amplitude-phase measuring devices as well as simplifying on-line data processing. In our experiments the electrical impulse was generated by a pulse generator of Macintosh data acquisition system. The signal (I = 11 muA, t = 2-20 ms) was delivered every 2-3 s external electrodes of a tetrapolar system through a specially designed isolation-calibration device. This electrode system was inserted into the cerebral cortex of experimental animals (rat). The cerebral cortex was found to have linear electrical properties in the 5-30 muA range. Our impedance measurement system was tested in calibration trials, and showed system reliability and accuracy. The system was also tested in pilot experiments, in vivo, in a rat brain osmotic edema model.

Traumatic brain injury, hemorrhagic shock, and fluid resuscitation: effects on intracranial pressure and brain compliance.

Intracranial hypertension following traumatic brain injury is associated with considerable morbidity and mortality. Hemorrhagic hypovolemia commonly coexists with head injury in this population of patients. Therapy directed at correcting hypovolemic shock includes vigorous volume expansion with crystalloid solutions. It is hypothesized that, following traumatic brain injury, cerebrovascular dysfunction results in rapid loss of brain compliance, resulting in increased sensitivity to cerebrovascular venous pressure. Increased central venous pressure (CVP) occurring with vigorous crystalloid resuscitation may therefore contribute to the loss of brain compliance and the development of intracranial hypertension. The authors tested this hypothesis in miniature swine subjected to traumatic brain injury, hemorrhage, and resuscitation. Elevated CVP following resuscitation from hemorrhage to a high CVP significantly worsened intracranial hypertension in animals with concurrent traumatic brain injury, as compared to animals subjected to traumatic brain injury alone (mean +/- standard error of the mean: 33.0 +/- 2.0 vs. 20.0 +/- 2.0 mm Hg, p < 0.05) or to animals subjected to the combination of traumatic brain injury, hemorrhage, and resuscitation to a low CVP (33.0 +/- 2.0 vs. 24.0 +/- 2.0 mm Hg, p < 0.05). These data support the hypothesis that reduction in brain compliance can occur secondary to elevation of CVP following resuscitation from hemorrhagic shock. This may worsen intracranial hypertension in patients with traumatic brain injury and hemorrhagic shock.