Angel Garnacho

Influence of APOE polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury

Aim: To analyse the influence of apolipoprotein (APOE) ε4 status on the cognitive and behavioural functions usually impaired after moderate and severe traumatic brain injury (TBI). Methods: In all, 77 patients with TBI selected from 140 consecutive admissions were genotyped for APOE. Each patient was subjected to neuropsychological and neurobehavioural assessment at least 6 months after injury. Results: Performance of participants carrying the ε4 allele was notably worse on verbal memory (Auditory Verbal Learning Test), motor speed, fine motor coordination, visual scanning, attention and mental flexibility (Grooved Pegboard, Symbol Digit Modalities Test and part B of the Trail Making Test) and showed considerably more neurobehavioural disturbances (Neurobehavioral Rating Scale—Revised) than the group without the ε4 allele. Conclusions: In particular, performance on neuropsychological tasks that are presumed to be related to temporal lobe, frontal lobe and white matter integrity is worse in patients with the APOE ε4 allele than in those without it. More neurobehavioural disturbances are observed in APOE ε4 carriers than in APOE ε2 and ε3 carriers.

Cerebral hemodynamic effects of morphine and fentanyl in patients with severe head injury: absence of correlation to cerebral autoregulation.

Background The current study investigates the effects of morphine and fentanyl upon intracranial pressure and cerebral blood flow estimated by cerebral arteriovenous oxygen content difference and transcranial Doppler sonography in 30 consecutive patients with severe head injury in whom cerebrovascular autoregulation previously had been assessed. Methods Patients received morphine (0.2 mg/kg) and fentanyl (2 &mgr;g/kg) intravenously over 1 min but 24 h apart in a randomized fashion. Before study, carbon dioxide reactivity and autoregulation were assessed. Intracranial pressure, mean arterial blood pressure, and cerebral perfusion pressure were repeatedly monitored for 1 h after the administration of both opioids. Cerebral blood flow was estimated from the reciprocal of arteriovenous oxygen content difference and middle cerebral artery mean flow velocity using transcranial Doppler sonography. Results Although carbon dioxide reactivity was preserved in all patients, 18 patients (56.7%) showed impaired or abolished autoregulation to hypertensive challenge, and only 12 (43.3%) had preserved autoregulation. Both morphine and fentanyl caused significant increases in intracranial pressure and decreases in mean arterial blood pressure and cerebral perfusion pressure, but estimated cerebral blood flow remain unchanged. In patients with preserved autoregulation, opioid-induced intracranial pressure increases were not different than in those with impaired autoregulation. Conclusions The authors conclude that both morphine and fentanyl moderately increase intracranial pressure and decrease mean arterial blood pressure and cerebral perfusion pressure but have no significant effect on arteriovenous oxygen content difference and middle cerebral artery mean flow velocity in patients with severe brain injury. No differences on intracranial pressure changes were found between patients with preserved and impaired autoregulation. Our results suggest that other mechanisms, besides the activation of the vasodilatory cascade, also could be implicated in the intracranial pressure increases seen after opioid administration.

Influence of extraneurological insults on ventricular enlargement and neuropsychological functioning after moderate and severe traumatic brain injury

Extraneurological insults secondary to TBI such as hypotension or hypoxia have been associated with mortality and morbidity. The purpose of this study was to investigate the influence of systemic complications on both neuropsychological outcome and cerebral atrophy. Fifty-seven patients selected from 122 consecutive admissions were studied. Data on the type and severity of injury as well as other systemic insults were collected prior to and during the first 3 days of hospitalization. These data included the presence or absence of a hypoxic episode during the pre-hospital period, the presence and degree of hypoxia, hypercapnia, anemia, hypotension and intracranial hypertension, pupillary reactivity, Glasgow Coma Scale score and coma duration. From the last control CT scan image, performed 6 months post-injury, four different indexes of ventricular dilatation were calculated. Neuropsychological assessment at 6 months included tests of verbal and visual memory, visuoconstructive functions, fine motor speed, and frontal lobe functions. Our results showed that hypoxia and hypotension were related to neuropsychological outcome and long-term ventricular enlargement. Hypoxic episodes prior to hospitalization were related to third ventricle dilatation and to adverse neurological and cognitive outcomes, especially to attention, motor speed, mental flexibility, fluency and verbal memory impairments, suggesting fronto-striatal and hippocampal dysfunction. We conclude that the effect of extraneurological insults on brain structure and function may be as important as the severity of the primary injury.

Medidas de primer nivel en el tratamiento de la hipertensión intracraneal en el paciente con un traumatismo craneoencefálico grave. Propuesta y justificación de un protocolo

Resumen El manejo de los traumatismos craneoencefalicos graves en general y de aquellos que presentan una hipertension intracraneal en particular, es uno de los desafios mas importantes en el manejo del paciente neurocritico. Una de las principales dificultades con las que aun se enfrentan los clinicos es la de intentar reducir la variabilidad que todavia existe entre centros en la implementacion de protocolos de tratamiento en estos pacientes. El objeto de este articulo es proponer un protocolo estandarizado para el manejo de la hipertension intracraneal en los traumatismos craneoencefalicos graves (TCEG), que siga las directrices propuestas por las guias de practica clinica recientemente publicadas y tambien otra evidencia clinica, como la aportada por las revisiones sistematicas de la Colaboracion Cochrane. A pesar de los avances significativos en la neuromonitorizacion que han permitido profundizar en la fisiopatologia de los TCEG, y de las diversas opciones terapeuticas disponibles, aun no existen protocolos estandarizados para el tratamiento de estos pacientes. Aunque las guias de practica clinica, recientemente publicadas, ofrecen recomendaciones generales, no aportan detalles explicitos sobre como y cuando aplicar estas recomendaciones terapeuticas. Como consecuencia, existe todavia una gran variabilidad en la practica clinica diaria incluso entre aquellos centros que aplican las mismas medidas terapeuticas. En este articulo se propone un protocolo estructurado, en el que cada paso se justifica e integra dentro de una estrategia global para el manejo de los traumatismos craneoencefalicos graves. Se discuten los datos disponibles mas recientes, procedentes de ensayos clinicos controlados tanto preliminares como definitivos, asi como de otras fuentes. El principal objetivo de este articulo es dotar a las unidades de neurocriticos de un protocolo unificado que pueda ser facilmente modificado a medida que se disponga de nueva informacion basada en evidencia clase I o II. Esto permite reducir la variabilidad que existe entre centros que aplican las mismas medidas terapeuticas. Por otra parte, este protocolo puede facilitar la comparacion de los resultados neurologicos entre diferentes hospitales haciendo mas facil a su vez la implantacion de una practica clinica mas uniforme en aquellos centros implicados en estudios clinicos multicentricos.

Normobaric Hyperoxia in Traumatic Brain Injury: Does Brain Metabolic State Influence the Response to Hyperoxic Challenge?

This study sought to investigate whether normobaric hyperoxia (NH) improves brain oxygenation and brain metabolism in the early phase of severe and moderate traumatic brain injury (TBI) and whether this effect occurs uniformly in all TBI patients. Thirty patients (9 women and 21 men) with a median initial Glasgow Coma Score (GCS) of 6 (range, 3-12) were monitored using a brain microdialysis (MD) catheter with a brain tissue oxygen sensor (PtiO(2)) placed in the least-injured hemisphere. The inspired oxygen fraction was increased to 100% for 2 h. Patients were divided into two groups: Group 1: patients with baseline brain lactate ≤3 mmol/L and Group 2: patients with baseline brain lactate >3 mmol/L, and therefore increased anaerobic metabolism in the brain. In Group 1, no significant changes in brain metabolic parameters were found after hyperoxic challenge, whereas a significant increase in glucose and a decrease in the lactate-pyruvate ratio (LPR) were found in Group 2. In this latter group of patients, brain glucose increased on average by 17.9% (95% CI, +9.2% to +26.6%, p<0.001) and LPR decreased by 11.6% (95% CI, -16.2% to -6.9%, p<0.001). The results of our study show that moderate and severe TBI may induce metabolic alterations in the brain, even in macroscopically normal brain tissue. We observed that NH increased PaO(2) and PtiO(2) and significantly decreased LPR in patients in whom baseline brain lactate levels were increased, suggesting that NH improved the brain redox state. In patients with normal baseline brain lactate levels, we did not find any significant changes in the metabolic variables after NH. This suggests that the baseline metabolic state should be taken into account when applying NH to patients with TBI. This maneuver may only be effective in a specific group of patients.

Aplicaciones de la telerradiologia al cribaje y manejo de los pacientes con un traumatismo craneoencefálico. Resultados de un estudio piloto de interconexión entre un hospital comarcal y un centro de referencia neuroquirurgico

Resumen La centralizacion de los servicios de Neurocirugia condiciona que los pacientes que sufren un traumatismo craneal, y que son atendidos de forma inicial por centros comarcales, deban ser remitidos al hospital neuroquirurgico para su valoracion. Esto supone el desplazamiento de un numero elevado de pacientes que, una vez valorados, regresan al centro emisor. La incorporacion de la telerradiologia puede limitar el traslado a aquellos casos que requieren una asistencia mas especializada. Objetivos : 1) presentar la experiencia inicial y los resultados de un estudio piloto de interconexion telerradiologica entre un hospital comarcal y un hospital de tercer nivel para la valoracion neuroquirurgica de pacientes con un traumatismo craneoencefalico (TCE), 2) describir la infraestructura y el soporte tecnologico necesario para este tipo de proyectos, 3) analizar las repercusiones del establecimiento de una conexion telerradiologica en los centros implicados (emisor y receptor), 4) evaluar la efectividad del sistema para evitar traslados innecesarios y 5) evaluar la efectividad en mejorar la rapidez y calidad en el traslado de los pacientes neurotraumaticos. Material y Metodos En enero de 1998, la Unidad de Neurotraumatologia del Hospital Universitario Vali d’Hebron establece una conexion telerradiologica con el Hospital General de Vic para la valoracion neuroquirurgica de pacientes con un TCE. La informacion clinica de cada paciente se recibe por fax convencional. Las imagenes de la TC cerebral, que han sido digitalizadas, comprimidas y preparadas para su transmision con el programa StatView™, se trasmiten via modem a nuestro centro. La visualizacion de estas imagenes se realiza en la pantalla de un PC convencional dotado del software MultiView™. Despues de valorada la exploracion neurorradiologica, el neurocirujano de guardia emite el informe pertinente al hospital emisor con las indicaciones a seguir respecto al traslado del paciente o su tratamiento (ingreso, observacion etc.). Resultados Analizamos los resultados de nuestra experiencia despues de 5 anos del inicio de este tipo de conexion telerradiologica. Conclusiones La utilizacion de la telerradiologia en el manejo diario de los pacientes con un TCE aporta un claro beneficio asistencial y supone una mayor racionalizacion de los recursos, redundando en un importante ahorro economico para el sistema sanitario. La efectividad del sistema en reducir los tiempos accidente-tratamiento en los casos graves, depende mas de la infraestructura sanitaria de cada area geografica que de sistemas sofisticados de telemedicina. La imple-mentacion de estos metodos debe ir acompanada de otras medidas de ambito politico/sanitario dirigidas a conseguir un traslado mas rapido de los pacientes seleccionados.