Normobaric hyperoxia--induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort-matched study

OBJECT: The effect of normobaric hyperoxia (fraction of inspired O2 [FIO2] concentration 100%) in the treatment of patients with traumatic brain injury (TBI) remains controversial. The aim of this study was to investigate the effects of normobaric hyperoxia on five cerebral metabolic indices, which have putative prognostic significance following TBI in humans. METHODS: At two independent neurointensive care units, the authors performed a prospective study of 52 patients with severe TBI who were treated for 24 hours with 100% FIO2, starting within 6 hours of admission. Data for these patients were compared with data for a cohort of 112 patients who were treated in the past; patients in the historical control group matched the patients in our study according to their Glasgow Coma Scale scores after resuscitation and their intracranial pressure within the first 8 hours after admission. Patients were monitored with the aid of intracerebral microdialysis and tissue O2 probes. Normobaric hyperoxia treatment resulted in a significant improvement in biochemical markers in the brain compared with the baseline measures for patients treated in our study (patients acting as their own controls) and also compared with findings from the historical control group. In the dialysate the glucose levels increased (369.02 +/- 20.1 micromol/L in the control group and 466.9 +/- 20.39 micromol/L in the 100% O2 group, p = 0.001), whereas the glutamate and lactate levels significantly decreased (p < 0.005). There were also reductions in the lactate/glucose and lactate/pyruvate ratios. Intracranial pressure in the treatment group was reduced significantly both during and after hyperoxia treatment compared with the control groups (15.03 +/- 0.8 mm Hg in the control group and 12.13 +/- 0.75 mm Hg in the 100% O2 group, p < 0.005) with no changes in cerebral perfusion pressure. Outcomes of the patients in the treatment group improved. CONCLUSIONS: The results of the study support the hypothesis that normobaric hyperoxia in patients with severe TBI improves the indices of brain oxidative metabolism. Based on these data further mechanistic studies and a prospective randomized controlled trial are warranted.

Vaccination with recombinant NcROP2 combined with recombinant NcMIC1 and NcMIC3 reduces cerebral infection and vertical transmission in mice experimentally infected with Neospora caninum tachyzoites

We investigated the protective potential of recombinant his-tagged antigens recNcMIC1, recNcMIC3 and recNcROP2, applied either as single vaccines or as vaccine combinations, in BALB/c mouse models for cerebral and fetal infection. Subsequently, mice were mated and challenged by i.p. inoculation of 2 x 10(6)Neospora caninum tachyzoites at day 7 of pregnancy. The mortality and morbidity of adult mice (non-pregnant and dams) and of the newborn pups was studied for a period of 40 days following birth. Vaccination of non-pregnant mice with recNcROP2 or combinations of recNcROP2 with recNcMIC antigens significantly reduced the numbers of mice suffering from clinical signs, and morbidity was completely prevented with the combination of all three antigens. Of the dams, the groups receiving either recNcROP2 alone or the combination of all three antigens did not exhibit any morbidity, the groups receiving ROP2 mixed with either MIC1 or MIC3 exhibited reduced numbers of deaths, and in the infection control group and the adjuvant group 50% and 43% of mice, respectively, succumbed to disease. For pups, the highest survival rates were noted for the groups receiving recNcROP2 (50%) and recNcROP2/NcMIC1/NcMIC3 (35%), while in the infection- and adjuvant- control groups all pups died, the latest at days 25 and 30, respectively. Quantification of parasite DNA by N. caninum-specific real-time PCR revealed consistently lower parasite burdens in brain tissue of pups from vaccinated groups compared with the controls. However, dense granule antigen 2 (GRA2) real-time reverse transcriptase-PCR on brain tissue of surviving pups (applied here to detect viable parasites) demonstrated that only the pups from the group vaccinated with all three antigens in combination appeared free of viable tachyzoites, while in all other groups viable parasites were still present. Serological analysis of humoral (total IgG, IgG1 and IgG2a) and serum cytokine (IL-4 and IFN-gamma) responses showed that this effect was associated with a Th-2-biased immune response, with a clearly elevated IL-4/IFN-gamma ratio in the mice receiving all three antigens in combination. In conclusion, a mixture of recombinant antigens representing important secretory micronemal and rhoptry proteins leads to a significant protection against vertical transmission of N. caninum in mice.

Surgery for low-grade glioma infiltrating the central cerebral region: location as a predictive factor for neurological deficit, epileptological outcome, and quality of life

OBJECT A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life. METHODS Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution. RESULTS For the central cohort, the median extent of resection was 92% (range 80%-97%), and for the frontal cohort, the median extent of resection was 93% (range 83%-98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001). CONCLUSIONS Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.

The effect of inner speech on arterial CO2 and cerebral hemodynamics and oxygenation: a functional NIRS study

The aim of the present study was (i) to investigate the effect of inner speech on cerebral hemodynamics and oxygenation, and (ii) to analyze if these changes could be the result of alternations of the arterial carbon dioxide pressure (PaCO2). To this end, in seven adult volunteers, we measured changes of cerebral absolute [O2Hb], [HHb], [tHb] concentrations and tissue oxygen saturation (StO2) (over the left and right anterior prefrontal cortex (PFC)), as well as changes in end-tidal CO2 (PETCO2), a reliable and accurate estimate of PaCO2. Each subject performed three different tasks (inner recitation of hexameter (IRH) or prose (IRP) verses) and a control task (mental arithmetic (MA)) on different days according to a randomized crossover design. Statistical analysis was applied to the differences between pre-baseline, two tasks, and four post-baseline periods. The two brain hemispheres and three tasks were tested separately. During the tasks, we found (i) PETCO2 decreased significantly (p < 0.05) during the IRH ( ~ 3 mmHg) and MA ( ~ 0.5 mmHg) task. (ii) [O2Hb] and StO2 decreased significantly during IRH ( ~ 1.5 μM; ~ 2 %), IRP ( ~ 1 μM; ~ 1.5 %), and MA ( ~ 1 μM; ~ 1.5 %) tasks. During the post-baseline period, [O2Hb] and [tHb] of the left PFC decreased significantly after the IRP and MA task ( ~ 1 μM and ~ 2 μM, respectively). In conclusion, the study showed that inner speech affects PaCO2, probably due to changes in respiration. Although a decrease in PaCO2 is causing cerebral vasoconstriction and could potentially explain the decreases of [O2Hb] and StO2 during inner speech, the changes in PaCO2 were significantly different between the three tasks (no change in PaCO2 for MA) but led to very similar changes in [O2Hb] and StO2. Thus, the cerebral changes cannot solely be explained by PaCO2.

End-tidal CO2 pressure: an important parameter for a correct interpretation of changes in cerebral hemodynamics and oxygenation measured with functional near infrared spectrophotometry (fNIRS)

The aim of the present study was to investigate the effects of different speech tasks (recitation of prose (PR), alliteration (AR) and hexameter (HR) verses) and a control task (mental arithmetic (MA) with voicing of the result) on endtidal CO2 (ET-CO2), cerebral hemodynamics; i.e. total hemoglobin (tHb) and tissue oxygen saturation (StO2). tHb and StO2 were measured with a frequency domain near infrared spectrophotometer (ISS Inc., USA) and ET-CO2 with a gas analyzer (Nellcor N1000). Measurements were performed in 24 adult volunteers (11 female, 13 male; age range 22 to 64 years) during task performance in a randomized order on 4 different days to avoid potential carry over effects. Statistical analysis was applied to test differences between baseline, 2 recitation and 5 recovery periods. The two brain hemispheres and 4 tasks were tested separately. Data analysis revealed that during the recitation tasks (PR, AR and HR) StO2 decreased statistically significant (p < 0.05) during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. tHb showed a significant decrease during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased significantly. A significant decrease in ET-CO2 was found during all 4 tasks with the smallest decrease during the MA task. In conclusion, we hypothesize that the observed changes in tHb and StO2 are mainly caused by an altered breathing during the tasks that led a lowering of the CO2 content in the blood provoked a cerebral CO2 reaction, i.e. a vasoconstriction of blood vessels due to decreased CO2 pressure and thereby decrease in cerebral blood volume. Therefore, breathing changes should be monitored during brain studies involving speech when using functional near infrared spectroscopy (fNIRS) to ensure a correct interpretation of changes in hemodynamics and oxygenation.

Modulation of anticipatory emotion and perception processing by cognitive control.

Strategies of cognitive control are helpful in reducing anxiety experienced during anticipation of unpleasant or potentially unpleasant events. We investigated the associated cerebral information processing underlying the use of a specific cognitive control strategy during the anticipation of affect-laden events. Using functional magnetic resonance imaging, we examined differential brain activity during anticipation of events of unknown and negative emotional valence in a group of eighteen healthy subjects that used a cognitive control strategy, similar to "reality checking" as used in psychotherapy, compared with a group of sixteen subjects that did not exert cognitive control. While expecting unpleasant stimuli, the "cognitive control" group showed higher activity in left medial and dorsolateral prefrontal cortex areas but reduced activity in the left extended amygdala, pulvinar/lateral geniculate nucleus and fusiform gyrus. Cognitive control during the "unknown" expectation was associated with reduced amygdalar activity as well and further with reduced insular and thalamic activity. The amygdala activations associated with cognitive control correlated negatively with the reappraisal scores of an emotion regulation questionnaire. The results indicate that cognitive control of particularly unpleasant emotions is associated with elevated prefrontal cortex activity that may serve to attenuate emotion processing in for instance amygdala, and, notably, in perception related brain areas.

Individual differences in inhibitory control - relationship between baseline activation in lateral PFC and an electrophysiological index of response inhibition

The capacity to inhibit inappropriate responses is crucial for goal-directed behavior. Inhibiting such responses seems to come more easily to some of us than others, however. From where do these individual differences originate? Here, we measured 263 participants' neural baseline activation using resting electroencephalogram. Then, we used this stable neural marker to predict a reliable electrophysiological index of response inhibition capacity in the cued Continuous Performance Test, the NoGo-Anteriorization (NGA). Using a source-localization technique, we found that resting delta, theta, and alpha1 activity in the left middle frontal gyrus and resting alpha1 activity in the right inferior frontal gyrus were negatively correlated with the NGA. As a larger NGA is thought to represent better response inhibition capacity, our findings demonstrate that lower levels of resting slow-wave oscillations in the lateral prefrontal cortex, bilaterally, are associated with a better response inhibition capacity.

Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke - a longitudinal MRI study using arterial spin labeling perfusion

BACKGROUND Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. OBJECTIVE To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. METHODS Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. RESULTS Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. CONCLUSIONS Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information.

Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study

BACKGROUND Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound. MATERIALS AND METHODS Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann-Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons. RESULTS In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5-fold to 344.5 (59-1019) during CVVHD (P<0.001). The number of solid CME was low in all groups (non-ICU group: 2 [0-5.5]; ICU group CVVHD-free interval: 1.5 [0-14.25]; ICU group during CVVHD: 7 [3-27.75]). CONCLUSIONS This observational pilot study shows that CVVHD was associated with a higher gaseous but not solid CME burden in critically ill patients. Although the differentiation between gaseous and solid CME remains challenging, our finding may support the hypothesis of microbubble generation in the CVVHD circuit and its transpulmonary translocation toward the intracranial circulation. Importantly, the impact of gaseous and solid CME generated during CVVHD on brain integrity of critically ill patients currently remains unknown and is highly debated.

THE RELATIONSHIP BETWEEN THE RHEOENCEPHALOGRAM AND CEREBRAL BLOOD FLOW

The rheoencephalogram (REG) is the change in the electrical impedance of the head that occurs with each heart beat. Without knowledge of the relationship between cerebral blood flow (Q) and the REG, the utility of the REG in the study of the cerebral vasculature is greatly limited. The hypothesis is that the relationship between the REG and Q when venous outflow is nonpulsatile is^ (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)^ where K is a proportionality constant and Q is the mean Q.^ Pulsatile CBF was measured in the goat via a chronically implanted electromagnetic flowmeter. Electrodes were implanted in the ipsilateral cerebral hemisphere, and the REG was measured with a two electrode impedance plethysmograph. Measurements were made with the animal's head elevated so that venous flow pulsations were not transmitted from the heart to the cerebral veins. Measurements were made under conditions of varied cerebrovascular resistance induced by altering blood CO(,2) levels and under conditions of high and low cerebrospinal fluid pressures. There was a high correlation (r = .922-.983) between the REG calculated from the hypothesized relationship and the measured REG under all conditions.^ Other investigators have proposed that the REG results from linear changes in blood resistivity proportional to blood velocity. There was little to no correlation between the measured REG and the flow velocity ( r = .022-.306). A linear combination of the flow velocity and the hypothesized relationship between the REG and Q did not predict the measured REG significantly better than the hypothesized relationship alone in 37 out of 50 experiments.^ Jacquy proposed an index (F) of cerebral blood flow calculated from amplitudes and latencies of the REG. The F index was highly correlated (r = .929) with measured cerebral blood flow under control and hypercapnic conditions, but was not as highly correlated under conditions of hypocapnia (r = .723) and arterial hypotension (r = .681).^ The results demonstrate that the REG is not determined by mean cerebral blood flow, but by the pulsatile flow only. Thus, the utility of the REG in the determination of mean cerebral blood flow is limited. ^

A case-control study of the risk factors for eclampsia

Objective. To study the risk factors for eclampsia, a rare but significant complication of pregnancy.^ Target population. All deliveries at or after the 20th week of gestation that took place between January 1, 1977 and March 1992, and between January 1990 and April 1992 at two hospitals in Houston, Texas, respectively.^ Study population. Sixty-six confirmed cases of eclampsia, and 2 groups of randomly selected controls: Non-preeclamptic and preeclamptic deliveries matched to cases on hospital and month of delivery on a 1:4 ratio.^ Exclusions. Women with chronic hypertension, gestational epilepsy, a previous history of epilepsy, and convulsions attributed to encephalitis, meningitis, cerebral tumor, and intracerebral bleeding, and women without a definite diagnosis of preeclampsia/eclampsia.^ Results. Eclampsia developed in 0.52-0.93/1000 deliveries. Fifty-six percent of seizures occurred in the antepartum period, 2% as early as 20 weeks of gestation and 39% between 37 and 42 weeks. Twenty-nine percent and 15% occurred in the postpartum and late postpartum periods, respectively, 8% as late as one week postpartum. A different set of risk factors was involved in the development of eclampsia in non-preeclamptic women than in the progression from preeclampsia to eclampsia. Factors involved in the development of eclampsia included, in addition to twin pregnancy and family history of pregnancy-induced hypertension, fewer than 3 prenatal care visits, urinary tract infections, primigravidity, obesity, black ethnicity, diabetes mellitus, and age $\le$20 years. Risk factors involved in the progression from preeclampsia to eclampsia included fewer than 3 of prenatal care visits, and age $\le$20 years. Protective factors were magnesium sulfate administration prior to seizure, history of abortions and longer gestational age. Having less than 3 prenatal care visits and being less than or equal to 20 years of age were predictors of eclampsia, whether of its development or progression from preeclampsia. Once preeclampsia is diagnosed, primigravid, diabetic, black, or obese women and those with urinary tract infections did not appear to exhibit any increased risk for the progression to eclampsia. The administration of magnesium sulfate was especially protective, followed by a positive history of abortions, 3 or more prenatal care visits, and longer gestational age. The protective effect of MgSO$\sb4$ was only slightly diminished when cases were restricted to the 65% who had a diagnosis of preeclampsia. The progression from preeclampsia to eclampsia may be largely preventable through adequate prenatal care and presumably the administration of magnesium sulfate. (Abstract shortened by UMI.) ^

Importancia del control postural para las A.V.D. en personas con secuelas neurológicas

El ser humano tiene la necesidad de adaptarse a la actividad que se propone, a sus propios desajustes por el movimiento y a los cambios internos. Todo en un entorno determinado y para que ocurra, el cuerpo debe estar preparado para anticiparse, mantenerse y reaccionar ante estas situaciones. Las personas con secuelas neurológicas tienen dificultades para mantenerse en una posición estática y más aún en poder pasar de una postura a otra. No solamente tienen problemas para tomar objetos o levantarse de una silla; por ejemplo, sino que presentan serios inconvenientes para mantener el equilibrio y controlar la postura para poder alcanzar cualquiera de las maniobras referidas anteriormente; de lo que se desprende, que el desarrollo de un buen control postural es requisito indispensable para cualquier manejo de las actividades de la vida diaria (A.V.D.). Y la atención, entendida como uno de los procesos cognitivos que hay que activar para que todo esto suceda, juega un papel importante en éste reaprendizaje motriz. Todas estas habilidades motoras necesitan aprenderse y luego llevarlas al plano de la automatización con un mínimo de dirección consciente. La corteza cerebral necesita relajarse y ocuparse de las estrategias y no tanto ya de la postural, al menos que se requiera una corrección

Importancia del control postural para las A.V.D. en personas con secuelas neurológicas

El ser humano tiene la necesidad de adaptarse a la actividad que se propone, a sus propios desajustes por el movimiento y a los cambios internos. Todo en un entorno determinado y para que ocurra, el cuerpo debe estar preparado para anticiparse, mantenerse y reaccionar ante estas situaciones. Las personas con secuelas neurológicas tienen dificultades para mantenerse en una posición estática y más aún en poder pasar de una postura a otra. No solamente tienen problemas para tomar objetos o levantarse de una silla; por ejemplo, sino que presentan serios inconvenientes para mantener el equilibrio y controlar la postura para poder alcanzar cualquiera de las maniobras referidas anteriormente; de lo que se desprende, que el desarrollo de un buen control postural es requisito indispensable para cualquier manejo de las actividades de la vida diaria (A.V.D.). Y la atención, entendida como uno de los procesos cognitivos que hay que activar para que todo esto suceda, juega un papel importante en éste reaprendizaje motriz. Todas estas habilidades motoras necesitan aprenderse y luego llevarlas al plano de la automatización con un mínimo de dirección consciente. La corteza cerebral necesita relajarse y ocuparse de las estrategias y no tanto ya de la postural, al menos que se requiera una corrección

Importancia del control postural para las A.V.D. en personas con secuelas neurológicas

El ser humano tiene la necesidad de adaptarse a la actividad que se propone, a sus propios desajustes por el movimiento y a los cambios internos. Todo en un entorno determinado y para que ocurra, el cuerpo debe estar preparado para anticiparse, mantenerse y reaccionar ante estas situaciones. Las personas con secuelas neurológicas tienen dificultades para mantenerse en una posición estática y más aún en poder pasar de una postura a otra. No solamente tienen problemas para tomar objetos o levantarse de una silla; por ejemplo, sino que presentan serios inconvenientes para mantener el equilibrio y controlar la postura para poder alcanzar cualquiera de las maniobras referidas anteriormente; de lo que se desprende, que el desarrollo de un buen control postural es requisito indispensable para cualquier manejo de las actividades de la vida diaria (A.V.D.). Y la atención, entendida como uno de los procesos cognitivos que hay que activar para que todo esto suceda, juega un papel importante en éste reaprendizaje motriz. Todas estas habilidades motoras necesitan aprenderse y luego llevarlas al plano de la automatización con un mínimo de dirección consciente. La corteza cerebral necesita relajarse y ocuparse de las estrategias y no tanto ya de la postural, al menos que se requiera una corrección

Clasificación de sujetos según el control motor de la extremidad superior en Neurorrehabilitación Funcional

El presente trabajo propone la aplicación de las redes neuronales artificiales (RNA) en la comparación del movimiento de la extremidad superior entre sujetos con Daño Cerebral Adquirido y sujetos sanos. La finalidad de esta comparación es clasificar a los sujetos según su control motor para posteriormente emitir una valoración funcional del movimiento como parte de un método de evaluación objetiva en neurorrehabiliatación funcional de extremidad superior. Para realizar esta comparación se propone un método en el que se aplica un pre-procesado a los datos usando análisis de componentes principales (ACP) para reducir la dimensión de los mismos y entrenar la red. Fueron evaluadas diferentes estructuras de redes. El resultado obtenido con el método propuesto fue de un 95.65% de exactitud en la clasificación. Este resultado permite certificar el uso de las RNAs como una opción viable para la evaluación disfuncional del movimiento de sujetos sanos y con DCA. Esta investigación puede ser considerada como un estudio piloto para investigaciones en mayor profundidad que corroboren estos resultados.