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

AIM: To analyse the influence of apolipoprotein (APOE) epsilon4 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 epsilon4 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 epsilon4 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 epsilon4 allele than in those without it. More neurobehavioural disturbances are observed in APOE epsilon4 carriers than in APOE epsilon2 and epsilon3 carriers.

[Variability in the surgical indications for posttraumatic intradural lesions]. / Variabilidad en las indicaciones quirúrgicas de las lesiones intradurales postraumáticas.

INTRODUCTION: The surgical treatment of focal intradural lesions is still a matter of considerable debate. This is especially important in the decision to evacuate brain contusions. We present the results of a prospective observational study in which the main goal was to analyze intracenter variability in the indication for surgery in focal posttraumatic intradural lesions in a department of Neurosurgery of a University Hospital with a specialized neurotrauma unit. CLINICAL MATERIAL AND METHODS: Between May 1 and December 31, 2001, 32 patients with a closed traumatic brain injury and an intradural posttraumatic focal lesion were included. The patients studied were a subgroup included in the European multicenter observational study of the management of intradural lesions conducted under the aegis of the European Brain Injury Consortium (EBIC). RESULTS: Intradural lesions > 25 cc were immediately evacuated. Nine out of thirteen patients with lesions < 25 cc also underwent surgery due to intracranial hypertension or neuroworsening. In all patients in whom lesions were surgically evacuated, the postoperative CT-scan showed neuroradiological improvement of the signs of mass effect or midline shift. CONCLUSIONS: In our center, we found no evidence of significant variability in the indications for surgery in intradural lesions of more than 25 cc. However, significant differences were detected among neurosurgeons in the surgical indications for lesions below 25 cc. The small sample analyzed precludes generalization of these conclusions. The definitive results of the EBIC study will provide the neurosurgical community with a better understanding of variability in the management of these lesions.

Variabilidad en las indicaciones quirúrgicas de las lesiones intradurales postraumáticas / Variability in the surgical indications for posttraumatic intradural lesions

Introducción. El tratamiento de las lesiones focales intradurales continúa siendo motivo de controversia. Esto es especialmente importante en la decisión de evacuar contusiones cerebrales. Presentamos los resultados de un estudio prospectivo y observacional, cuyo objetivo ha sido analizar la variabilidad en las indicaciones quirúrgicas de lesiones focales intradurales postraumáticas en un servicio de neurocirugía perteneciente a un hospital universitario, dotado de una unidad especializada en neurotraumatología. Material y métodos. Entre el 1 de mayo y el 31 de diciembre de 2001, se incluyeron 32 pacientes con un traumatismo craneoencefálico (TCE) cerrado, con lesiones focales intradurales. Estos pacientes constituyen la aportación que nuestro centro realizó en el estudio multicéntrico y observacional sobre el manejo de lesiones intradurales dirigido por el European Brain Injury Consortium (EBIC). Resultados. Las lesiones intradurales de volumen > 25 cc. se evacuaron de forma inmediata al diagnóstico. Nueve de los 13 pacientes con lesiones 25 cc. Sin embargo, existen discrepancias en las indicaciones quirúrgicas de las lesiones con volumen < 25 cc. Los resultados definitivos del estudio del EBIC permitirán conocer mejor la variabilidad existente en el manejo de este tipo de pacientes

Introduction. The surgical treatment of focal intradural lesions is still a matter of considerable debate. This is especially important in the decision to evacuate brain contusions. We present the results of a prospective observational study in which the main goal was to analyze intracenter variability in the indication for surgery in focal posttraumatic intradural lesions in a department of Neurosurgery of a University Hospital with a specialized neurotrauma unit. Clinical material and methods. Between May 1 and December 31, 2001, 32 patients with a closed traumatic brain injury and an intradural posttraumatic focal lesion were included. The patients studied were a subgroup included in the European multicenter observational study of the management of intradural lesions conducted under the aegis of the European Brain Injury Consortium (EBIC). Results. Intradural lesions > 25cc were immediately evacuated. Nine out of thirteen patients with lesions < 25cc also underwent surgery due to intracranial hypertension or neuroworsening. In all patients in whom lesions were surgically evacuated, the postoperative CT-scan showed neuroradiological improvement of the signs of mass effect or midline shift. Conclusions. In our center, we found no evidence of significant variability in the indications for surgery in intradural lesions of more than 25 cc. However, significant differences were detected among neurosurgeons in the surgical indications for lesions below 25cc. The small sample analyzed precludes generalization of these conclusions. The definitive results of the EBIC study will provide the neurosurgical community with a better understanding of variability in the management of these lesions

[Use of teleradiology in the evaluation and management of head-injured patients. Results of a pilot study of a link between a district general hospital and a neurosurgical referral center]. / Aplicaciones de la telerradiología al cribaje y manejo de los pacientes con un traumatismo craneoencefálico. Resultados de un estuduo piloto de interconexión entre un hospital comarcal y un centro de referencia neuroquirúrgico.

UNLABELLED: Because of the centralization of neurosurgical services, many head-injured patients who are initially evaluated in district general hospitals need to be transferred to a high technology centre for neurosurgical assessment. However, after assessment, many of these patients are sent back to the original hospital. Establishing a teleradiological system between the two hospitals would eliminate these unnecessary transfers. OBJECTIVES: 1) to describe our initial experience and the results of a pilot study of the teleradiological link between a district general hospital and a tertiary hospital for neurosurgical assessment of head-injured patients, 2) to describe the infrastructure and the technological support required for this project, 3) to analyse the effects of the teleradiological link in both centers (referring and receiving), 4) to evaluate the effectiveness of the system in avoiding unnecessary transfers, and 5) to assess its effectiveness in improving the speed and the quality of transfers in head-injured patients. MATERIAL AND METHODS: In January 1998, the Neurotraumatology Unit of Vall d'Hebron University Hospital established a teleradiological link with the General Hospital of Vic for the neurosurgical evaluation of headinjured patients. The General Hospital of Vic sent the patients' clinical information by fax. CT scan images were digitalized, compressed and prepared for transmission with the StatView program, and were then transmitted by modem to the receiving center. The duty neurosurgeon viewed the images on a PC screen using MutiView software. After evaluating this clinical and radiological information the neurosurgeon sent a report back to the referring center recommending transfer or management (admission, observation, etc.). RESULTS: We analyse the results of our experience 5 years after the implantation of the teleradiological link. CONCLUSIONS: The use of teleradiology in the daily management of head-injured patients provides clear benefits and leads to a more rational use of resources, thus significantly reduces costs. The effectiveness of the system in reducing the interval between the injury and treatment in severe cases depends more on the infrastructure of the health system in each geographical area than on sophisticated telemedicine systems. These methods should be accompanied by other measures designed to hasten the transfer of selected patients.

Aplicaciones de la telerradiología 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 neuroquirúrgico / Use of teleradiology in the evaluation and management of head-injured patients. Results of a pilot study of a link between a district general hospital and a neurosurgical referral center

La centralización de los servicios de Neurocirugía condiciona que los pacientes que sufren un traumatismo craneal, y que son atendidos de forma inicial por centros comarcales, deban ser remitidos al hospital neuroquirúrgico para su valoración. Esto supone el desplazamiento de un número elevado de pacientes que, una vez valorados, regresan al centro emisor. La incorporación de la telerradiología puede limitar el traslado a aquellos casos que requieren una asistencia más especializada. Objetivos: 1) presentar la experiencia inicial y los resultados de un estudio piloto de interconexión telerradiológica entre un hospital comarcal y un hospital de tercer nivel para la valoración neuroquirúrgica de pacientes con un traumatismo eran eoencefálico (TCE), 2) describir la infraestructura y el soporte tecnológico necesario para este tipo de proyectos, 3) analizar las repercusiones del establecimiento de una conexión telerradiológica 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 neurotraumáticos. Material y Métodos: En enero de 1998, la Unidad de Neurotraumatología del Hospital Universitario Vall d'Hebron establece una conexión telerradiológica con el Hospital General de Vic para la valoración neuroquirúrgica de pacientes con un TCE. La información clínica de cada paciente se recibe por fax convencional. Las imágenes de la TC cerebral, que han sido digitalizadas, comprimidas y preparadas para su transmisión con el programa StatVieWTM, se trasmiten vía módem a nuestro centro. La visualización de estas imágenes se realiza en la pantalla de un PC convencional dotado del software MultiVieWTM. Después de valorada la exploración neurorradiológica, 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, observación etc.). Resultados: Analizamos los resultados de nuestra experiencia después de 5 años del inicio de este tipo de conexión telerradiológica. Conclusiones: La utilización de la telerradiología en el manejo diario de los pacientes con un TCE aporta un claro beneficio asistencial y supone una mayor racionalización de los recursos, redundando en un importante ahorro económico para el sistema sanitario. La efectividad del sistema en reducir los tiempos accidente-tratamiento en los casos graves, depende más de la infraestructura sanitaria de cada área geográfica que de sistemas sofisticados de telemedicina. La implementación de estos métodos debe ir acompañada de otras medidas de ámbito político/sanitario dirigidas a conseguir un traslado más rápido de los pacientes seleccionados (AU)

[First tier measures in the treatment of intracranial hypertension in the patient with severe craniocerebral trauma. Proposal and justification of a protocol]. / 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.

The management of severe head injuries in general and that of high intracranial pressure (ICP) in particular are among the most challenging tasks in neurocritical care. One of the difficulties still faced by clinicians is that of reducing variability among centers when implementing management protocols. The purpose of this paper is to propose a standardized protocol for the management of high ICP after severe head injury, consistent with recently published clinical practice guidelines and other clinical evidence such as that provided by the systematic reviews of the Cochrane Collaboration. Despite significant advances in neuromonitoring, deeper insight into the physiopathology of severe brain trauma and the many therapeutic options available, standardized protocols are still lacking. Recently published guidelines provide sketchy recommendations without details on how and when to apply different therapies. Consequently, great variability exists in daily clinical practice even though different centers apply the same evidence-based recommendations. In this paper we suggest a structured protocol in which each step is justified and integrated into an overall strategy for the management of severe head injuries. The most recent data from both the preliminary and definitive results of randomized clinical trials as well as from other sources are discussed. The main goal of this article is to provide neurotraumatology intensive care units with a unified protocol that can be easily modified as new evidence becomes available. This will reduce variation among centers when applying the same therapeutic measures. This goal will facilitate comparisons in outcomes among different centers and will also enable the implementation of more consistent clinical practice in centers involved in multicenter clinical trials.

[The use of moderate hypothermia in the treatment of patients with severe craniocerebral trauma]. / Reflexiones sobre el uso de la hipotermia moderada en el tratamiento del paciente con un traumatismo craneoencefálico grave.

Traumatic brain injury initiates several metabolic processes that can increase the primary injury. It is well established that in severe head injuries, posttraumatic secondary insults, such as brain hypoxia, hypotension or anemia, exacerbate neuronal injury and lead to a poorer outcome. Experimental and clinical evidence suggests that moderate hypothermia (32-34 degrees C), may limit some of these deleterious secondary metabolic responses. Recent laboratory studies and prospective controlled clinical trials of induced moderate hypothermia for relatively short periods (24-48 h) in patients with severe head injury, have demonstrated good intracranial pressure control and better outcome when compared with patients maintained in normothermia and given conventional treatment. Despite its proven clinical role in neuroprotection, hypothermia research has been inconstantly followed for various reasons. In this paper we review the mechanisms of neuroprotection in hypothermia, the different preclinical and clinical studies that favor its use as a neuroprotector in severe head injury or in patients in whom high intracranial pressure is refractory to first tier measures. The evidence that favors hypothermia is discussed. We also discuss the negative results of the still unpublished multicentre trial on prophylactic moderate hypothermia developed in the USA. The main problem with moderate hypothermia is the lack of a systematic methodology to induce and maintain it. Also, optimal duration of its use and the methodology and timing for rewarming have not been determined. Consequently, the results of different trials are difficult to analyze and compare. However, most evidence suggests that hypothermia provides remarkable protection against the adverse effects of neuronal damage that is exacerbated by secondary injury. Further prospective controlled trials with clearly defined methodology are needed before this method is implemented in daily clinical practice. The most important task for the years to come may be to focus on refining this procedure, defining the optimal time of cooling and rewarming and to optimize the methods of rapidly inducing and maintaining low temperature. It is also essential to define the most appropriate method and velocity of the rewarming phase, in which many successfully controlled patients deteriorate and die.

Reflexiones sobre el uso de la hipotermia moderada en el tratamiento del paciente con un traumatismo craneoencefálico grave / Reflections on the use of moderate hypothermia in the management of severely head injured patients

En los traumatismos craneoencefálicos se desencadenan una serie de alteraciones metabólicas que incrementan las lesiones primarias sufridas de forma inmediata al impacto. Es un hecho suficientemente demostrado que en los traumatismos craneoencefálicos graves, los insultos postraumáticos intra o extracraneales tales como la hipoxia cerebral, la hipotensión arterial o la anemia, exacerban la lesión neuronal y condicionan un peor pronóstico de aquellos pacientes que los sufren. La evidencia, tanto experimental como clínica, sugiere que la hipotermia moderada (32-34°C) puede limitar el efecto nocivo de estas anomalías metabólicas. Estudios experimentales y estudios clínicos controlados de hipotermia moderada, inducida durante periodos relativamente cortos de tiempo (24-48 h), demuestran que esta es efectiva en el control de la hipertensión intracraneal y en mejorar el pronóstico cuando se comparan los resultados con grupos control en los que se utilizó la normotermia y las medidas terapéuticas convencionales. A pesar del probado efecto neuroprotector de la hipotermia, los trabajos clínicos sobre el tema han sido desarrollados, estudiados y seguidos de una forma inconstante por diversas razones. En este trabajo, revisamos los mecanismos neuroprotectores de la hipotermia, así como la evidencia clínica y experimental que demuestra su efecto neuroprotector en los pacientes con un TCE grave o en aquéllos que presentan hipertensión intracraneal refractaria a medidas de primer nivel. Se discuten también los resultados negativos del estudio multicéntrico de la hipotermia moderada profiláctica en TCE graves efectuado en EEUU y cuyos resultados no han sido todavía publicados. El principal problema que persiste en la aplicación terapéutica de la hipotermia moderada es la falta de una metodología sistemática para su inducción y mantenimiento. Del mismo modo, la duración óptima de la fase hipotérmica, el momento más adecuado y la metodología para iniciar el recalentamiento no han sido homogéneos en los diferentes estudios analizados. Por ello, los resultados entre diferentes centros son difíciles de comparar y analizar. Sin embargo, la mayor parte de datos disponibles sugieren que la hipotermia es altamente efectiva como neuroprotector contra los efectos adversos de la lesión neuronal traumática y en el tratamiento de las lesiones secundarias. Sin embargo, es necesario la realización de estudios clínicos prospectivos con una metodología homogénea y bien definida antes de implementar esta medida en la práctica clínica diaria. El esfuerzo más importante en los próximos años debe dirigirse a refinar la metodología, a definir el momento y el método óptimo de enfriamiento y recalentamiento, y a tratar de optimizar la metodología consiguiendo tiempos de inducción más rápidos. También es fundamental, definir el momento más apropiado y la velocidad de recalentamiento, ya que es en esta fase del tratamiento donde muchos de los pacientes adecuadamente controlados, deterioran clínicamente y en algunos casos, mueren (AU)

Lesión postraumática de la arteria carótida.Valoración del diagnóstico clinicorradiológico / Posttraumatic lesion of the carotid artery. Evaluation of the clinico-radiological diagnosis

Introducción. Las lesiones vasculares postraumáticas de la arteria carótida (LPAC) son poco frecuentes pero tienen una elevada morbimortalidad por lo cual es importante su diagnóstico y tratamiento precoz. Objetivo. Revisar los hallazgos clínicos y radiológicos de la LPAC con la hipótesis de que existen signos que permiten su diagnóstico precoz. Pacientes y métodos. Estudio retrospectivo de 9 pacientes (p) con LPAC. Resultados. La causa fue un accidente de tráfico (4 p), precipitación (1p) o un movimiento brusco cervical aislado (4 p). La clínica inicial era de dolor cervical (1 p), hipoacusia (1p), síndrome de Claude-Bernard-Horner (4 p) o síntomas de un ataque vascular cerebral (6 p). La TC craneal mostraba un infarto cerebral de arteria cerebral media (6 p), una hemorragia subaracnoidea (1 p) o era normal (3 p). El diagnóstico de la lesión vascular se realizó mediante resonancia magnética (9 p), arteriografía (5 p) y ecografía-Doppler (4 p). Las lesiones vasculares fueron: estenosis grave por trombosis mural (3 p), oclusión por trombosis completa (4 p) y pseudoaneurisma (2p).Conclusiones. La LPAC se debe sospechar tras un traumatismo craneofacial-cervical cuando ha habido un movimiento cervical brusco, cuando existe un síndrome de Claude-Bernard-Horner o cuando se demuestra un infarto cerebral de arteria cerebral media (AU)

Relevancia de las alteraciones morfoestructuralesdetectadas en la microvascularización de la corteza cerebral en pacientes fallecidos por traumatismo craneoencefálico grave / Importance of morphostructural changes observed in cortical microvessels in patients died after a severe head injury

Introducción. El desarrollo de lesiones secundarias en los traumatismos craneoencefálicos graves es un factor determinante en su supervivencia. Las lesiones principales son la isquemia cerebral y la hipertensión intracraneal, en cuya fisiopatología puede desempeñar un papel fundamental la lesión del endotelio de los microvasos de la corteza cerebral. Objetivo. El presente trabajo pretende determinar cuáles son las alteraciones morfológicas que se observan en la microvascularización de la corteza cerebral en dichos pacientes. Material y métodos. Hemos estudiado 15 cerebros procedentes de sujetos que habían fallecido tras un traumatismo craneoencefálico grave. El estudio se ha llevado a cabo mediante la obtención de moldes de corrosión vascular y el posterior análisis con microscopio electrónico de barrido, y a través de la utilización de técnicas de inmunocitoquímica y la técnica de TUNEL sobre muestras de tejido que fueron analizadas mediante microscopio láser confocal. Resultados y conclusiones. Las principales alteraciones estructurales se hallaron en las arteriolas y capilares de los estratos vasculares medio y profundo de la corteza cerebral. Los moldes de corrosión mostraban vasos con pliegues longitudinales, superficie excavada y una importante disminución de su luz. La tinción inmunocitoquímica del endotelio demostró también la presencia de pliegues, un engrosamiento del endotelio con cuerpos citoplásmicos redondeados y disminución de la luz vascular. La técnica de TUNEL fue positiva para algunas células endoteliales. Estas alteraciones pueden ser el reflejo de una situación de daño celular del endotelio en la microcirculación de estos pacientes. Esta lesión y el daño funcional secundario de la barrera hematoencefálica podrían desempeñar un papel importante en el desarrollo de las lesiones secundarias (AU)

Cerebral hemodynamic effects of 7.2% hypertonic saline in patients with head injury and raised intracranial pressure.

The aim of the present study was to investigate the acute effects of 7.2% hypertonic saline (HS) on intracranial pressure (ICP), cerebral and systemic hemodynamics, serum sodium, and osmolality in 14 patients with moderate and severe traumatic brain injury (Glasgow Coma Scale < or =13) and raised ICP (>15 mm Hg) within the first 72 h postinjury. After CO2 reactivity and autoregulation were tested, each patient received a 15-min infusion of 7.2% HS (1,232 mEq/L, volume 1.5 mL/kg). ICP, serial hemodynamics, cerebral blood flow (CBF) estimated from cerebral arteriovenous oxygen content difference (AVDO2), and laboratory variables, including serum osmolality, electrolytes, urea, and creatinine were collected before infusion (T0) and at 5, 30, 60, and 120 min after (T5, T30, T60, T120). Urine output was measured 2 h before infusion and at T120. While CO2 reactivity was preserved in all patients, autoregulation was preserved in only four. ICP decreased to about 30% of base line (p = 0.0001) during the whole study period. During the first hour after infusion, cerebral perfusion pressure (p< or =0.04) and cardiac index (CI; p< or =0.01) increased, while systemic vascular resistance index fell (p< or =0.05). Heart rate increased (p< or =0.04) during the first 30 min. Pulmonary artery occlusion pressure (PAOP) increased (p = 0.004) at T5. There were no significant changes in mean arterial blood pressure (MABP), urine output, and estimated CBF. A significant positive correlation (r = 0.75; p = 0.02) between ICP and serum osmolality was found at T5. The administration of 7.2% HS in patients with traumatic brain injury significantly reduces ICP without significant changes in relative global CBF (expressed as 1/AVDO2), increases CI and transiently increases PAOP, without changing MABP and urine output. The correlation between changes in osmolality and ICP supports the hypothesis that HSS may in part decrease ICP by means of an osmotic mechanism.

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 microg/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.

[Post-traumatic lesion of the carotid artery. Evaluation of the clinico-radiological diagnosis]. / Lesión postraumática de la arteria carótida. Valoración del diagnóstico clinicorradiológico.

INTRODUCTION: Posttraumatic vascular lesions of the carotid artery (PLCA) are infrequent but have a high morbid-mortality, so early diagnosis and treatment is important. OBJECTIVE: To review the clinical and radiological findings of the PLCA with the hypothesis that there are signs which permit early diagnosis. PATIENTS AND METHODS: A retrospective study of 9 patients (p) with PLCA. RESULTS: The cause was road traffic accident (4p), fall (1p) or a single abrupt cervical movement (4p). The initial clinical feature was cervical pain (1p), deafness (1p), Claude-Bernard-Horner syndrome (4p) or symptoms of a cerebral vascular accident (6p). Cranial CT showed a cerebral infarct in the territory of the middle cerebral artery (6p), subarachnoid hemorrhage (1p) or normal (3p). Diagnosis of the vascular lesion was made using magnetic resonance (9p), arteriography (5p) and echo-Doppler (4p). The vascular lesions were: severe stenosis due to a mural thrombosis (3p), complete obstruction due to thrombosis (4p) and pseudoaneurysm (2p). CONCLUSIONS: PLCA should be suspected following craniofacial-cervical trauma when there was an abrupt neck movement, a Claude-Bernard-Horner syndrome is present or a cerebral infarct in the territory of the middle cerebral artery is shown.

False autoregulation (pseudoautoregulation) in patients with severe head injury. Its importance in CPP management.

False autoregulation has been described as an alteration of autoregulation in which the apparent maintenance of a constant cerebral blood flow (CBF) when increasing cerebral perfusion pressure (CPP) is due to an increase in brain tissue pressure. The objective of our study was to investigate how often false autoregulation occurred in patients with a severe head injury. In forty-six patients with a moderate or severe head injury autoregulation was studied using arteriojugular differences of oxygen (AVDO2) to estimate changes in CBF after inducing arterial hypertension with phenylephrine. Changes in mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and AVDO2 were calculated before and after inducing hypertension. Ninety-five episodes of provoked hypertension were studied in 46 patients. In 28 tests (29.5%) a constant or even reduced CBF was detected simultaneously with a median increase in parenchymal ICP of 8.5 mm Hg (false autoregulation). In this group the median of the induced increase in MABP was 20.6 mm Hg with a median increase in CPP of 11.5 mm Hg. From our data we can conclude that false autoregulation is frequently found in patients after a severe head injury. Increasing MABP to obtain a better CPP in these patients is not beneficial because CBF is not modified or may even be reduced.

[Importance of morphostructural changes observed in cortical micro-vessels in patients who died after a severe head injury]. / Relevancia de las alteraciones morfoestructurales detectadas en la microvascularización de la corteza cerebral en pacientes fallecidos por traumatismo craneoencefálico grave.

INTRODUCTION: The development of secondary lesions in traumatic head injuries seems to be a determinative factor for the survival of these patients. Endothelium damage of cortical microvessels could be fundamental in the main secondary lesions as cerebral ischemia and intracranial hypertension. OBJECTIVES: To investigate which are the main morphological changes that can be observed in cortical microvessels from these patients. MATERIAL AND METHODS: We have studied 15 fresh human brains from subjects died after a severe head injury. The study has been carried out by scanning electron microscopy of vascular corrosion casts and confocal microscopy of histological sections after immunocytochemistry, as well as detection of apoptosis by TUNEL technique. RESULTS AND CONCLUSIONS: The most significant structural alterations were observed mainly on arterioles and capillaries of the middle and deep vascular zones of the cerebral cortex. Corrosion casts showed vessels with longitudinal folds, sunken surface with craters and flattened vessels with reduced lumen. Histological sections immunostained with MAS-336 also showed vessels with longitudinal folds and thinning of their vascular lumen, the presence of cytoplasmic round bodies and a thickening of endothelial cell membrane. TUNEL method revealed a positive staining of some endothelial cells. The structural alterations observed seem to reveal a situation of cellular damage of endothelium in the human cortical microvessels from these patients. It can be thought that this kind of lesions, as well as the secondary functional injury of the blood brain barrier, could play an important role in the development of secondary damage.

Interhemispheric supratentorial intracranial pressure gradients in head-injured patients: are they clinically important?

OBJECT: It is generally accepted that the intracranial compartment behaves as a unicameral space in which intracranial pressure (ICP) is uniformly distributed. However, this concept has been challenged many times. Although there is general agreement on the existence of craniospinal and suprainfratentorial gradients, the existence of interhemispheric gradients is still a matter of debate. The object of this study was to reexamine the issue of interhemispheric supratentorial ICP gradients in patients with head injuries and the clinical significance of these gradients in their management. METHODS: The authors present the results of a prospective study conducted in 50 head-injured patients to determine the clinical significance of supratentorial ICP gradients. In each case a concurrent bilateral frontal intraparenchymatous device was implanted within the 6-hour window after computerized tomography (CT) scanning. According to CT criteria, each patient was categorized into one of three different groups: 1) diffuse lesions, in which no unilaterally measured volumes greater than 25 ml were present and the midline shift was 3 mm or less; 2) Focal A, in which added hemispheric volumes were greater than 25 ml and midline shift was 3 mm or less; and 3) Focal B, in which all patients with a midline shift greater than 3 mm were included. From the results of the entire group the authors were able to distinguish four different patterns of supratentorial ICP. In Pattern I, the intracranial compartment behaved as a true unicameral space with similar mean ICPs and pulse amplitudes in both hemispheres; in Pattern II, different mean ICPs and amplitudes were observed although ICP increases or decreases were congruent; and in Pattern III, patients with different mean ICPs, different ICP amplitudes, and no congruent increases or decreases of ICP were included. All (15 cases) but one patient with a diffuse lesion presented with ICP Pattern I. Fifteen patients with focal lesions showed a Type II pattern, whereas only one patient presented with a Type III pattern. In 10 patients, of whom all but one presented with a focal lesion, transient gradients that disappeared in less than 4 hours were also observed. CONCLUSIONS: In many patients with focal lesions, clinically important interhemispheric ICP gradients exist. In this subset, transient gradients that disappear with time are frequently observed and may indicate an increase in the size of the lesion. The clinical relevance of such gradients is discussed and guidelines for adequately monitoring ICP are suggested to optimize head injury management and to avoid suboptimal or even harmful care in patients with mass lesions.

Cerebral hemodynamic changes during sustained hypocapnia in severe head injury: can hyperventilation cause cerebral ischemia?

Hyperventilation (HV) is routinely used in the management of increased intracranial pressure (ICP) in severe head injury. However, this treatment continues to be controversial because it has been reported that long-lasting reduced cerebral blood flow (CBF) due to profound sustained hypocapnia may contribute to the development or deterioration of ischemic lesions. Our goal in this study was to analyze the effects of sustained hyperventilation on cerebral hemodynamics (CBF, ICP) and metabolism (arterio jugular differences of lactates = AVDL). CO2-reactivity and CBF was estimated using AVDO2 (arteriojugular differences of oxygen content). Global cerebral ischemia and increased anaerobic metabolism were considered according to AVDO2 and AVDL respectively. Thirty-three patients with severe and moderate head injury and increased ICP were included. Within 72 hours after accident, patients were hyperventilated for a period of 4 hours. During this time jugular oxygen saturation (SjO2), arterial oxygen saturation (SaO2), ICP, mean arterial blood pressure (MABP), AVDO2 and AVDL were recorded. In our study, most patients preserved CO2-reactivity (88.2%). In these cases HV was very effective in lowering ICP. Our findings showed that this reduction was due to a CBF decrease. According to basal AVDO2 twenty-five patients (75.7%) were considered as hyperemic and eight (24.2%) as not hyperemic. Global ischemia and increased anaerobic metabolism were detected in one case in the non-hyperemic group. According to AVDO2 and AVDL, no adverse effects were found during four hours of HV in hyperemic patients. Nevertheless, AVDO2 and AVDL are global measurements and might not detect regional ischemia surrounding focal lesions such as contusions and haematomas. We suggest that monitoring of AVDO2 or other haemometabolic variables should be mandatory when sustained HV is used in the management of head injury patients.

Effects on intracranial pressure of fentanyl in severe head injured patients.

Despite opioids are routinely used for analgesia in head injured patients, the effects of such drugs on ICP and cerebral hemodynamics remain controversial. Cerebrovascular autoregulation (CAR) could be an important factor in the ICP increases reported after opioid administration. In order to describe the effects on intracranial pressure of fentanyl and correlated such effects with autoregulation status, we studied 30 consecutive severe head injury patients who received fentanyl (2 micrograms/kg) intravenously over one minute. Prior to study, CAR was assessed. Monitoring included MAP, HR, SaO2, ETCO2, SjO2 and ICP. Changes in cerebral blood flow (CBF) were estimated from relative changes in AVDO2. Patients mean GCS was 5.7 +/- 1.7 (mean +/- STD) and mean ICP on admission was 23.8 +/- 16.3 mmHg. Fentanyl caused significant increases in ICP and decreases in MAP and CPP, but CBF remained unchanged when estimated by AVDO2. In patients with preserved CAR (34.5%), opioid-induced ICP increase was greater (but not statistically significant) than in those with impaired CAR (65.5%). We conclude than fentanyl moderately increased ICP and decreased MAP and CPP. Our data suggests that in patients with preserved CAR, potent opioids could cause greater increases of ICP, probably due to activation of the vasodilatadory cascade.

Early ischaemia after severe head injury. Preliminary results in patients with diffuse brain injuries.

Ischaemic brain lesions still have a high prevalence in fatally head injured patients and are the single most important cause of secondary brain damage. The present study was undertaken to explore the acute phase of severely head injured patients in order to detect early ischaemia using Robertson's approach of estimating cerebral blood flow (CBF) from calculated arterio-jugular differences of oxygen (AVDO2), lactates (AVDL), and the lactate-oxygen index (LOI). Twenty-eight cases with severe head injury were included (Glasgow Coma Scale Score below or equal to 8). All patients but one had a non-missile head injury. All the patients had a diffuse brain injury according to the admission CT scan. ICP measured at the time of admission was below 20 mmHg in 17 cases (61%). All patients were evaluated with the ischaemia score (IS) devised in our center to evaluate risk factors for developing ischaemia. Mean time from injury to the first AVDO2/AVDL study was 23.9 +/- 9.9 hours. According to Robertson's criteria, 13 patients (46%) had a calculated LOI (-AVDL/AVDO2) value above or equal to 0.08 and therefore an ischaemia/infarction pattern in the first 24 hours after the accident. Of the 15 patients without the ischaemia/infarction pattern, in three cases the CBF was below the metabolic demands and therefore in a situation of compensated hypoperfusion. No patient in our series had hyperaemia. Comparing different variables in ischaemic and non-ischaemic patients, only arterial haemoglobin and ischaemia score (IS) was significantly different in both groups. The ischaemia score had mean of 4.3 +/- 1.7 in the ischaemic group and 2.7 +/- 1.4 in non-ischaemic patients (p = 0.01). It is concluded that ischaemia is highly prevalent in the early period after severe head injury. Factors potentially responsible of early ischaemia are discussed.