Syria civil war: Outcomes of humanitarian neurosurgical care provided to Syrian wounded refugees in Israel.

BACKGROUND: As an expected consequence of the civil war in Syria, emergent neurosurgical care for battlefield trauma has been provided for severely head-injured Syrians transferred to Northern Israel. METHODS: Sixty-six patients suffering from brain injury were brought to the border and then referred to the institution after initial resuscitation. Both the time and type of injury were recorded based on paramedic testimony, forensic material or on details provided by patients. A retrospective analysis of all medical charts and imaging material was performed. RESULTS: Most injuries were combat-related, either caused by blast (13.6%), shrapnel (24.2%), assault (28.8%) or gunshot wound (15.2%). Only a minority of patients (18.2%) suffered from injuries that were not directly caused by weapon. A total of 55 surgical procedures were performed in 46 out of 66 patients, including craniotomies in 40 patients, burr hole alone for placement of intraparenchymal intracranial pressure (ICP) sensor in nine instances and ventricle peritoneal shunt in two patients. Decompressive craniectomy was used only for the treatment of gunshot wound and was performed in eight out of 10 patients. The most common complication consisted in cerebrospinal fluid fistulas (16.7%). Post-operative infections occurred in seven patients (10.6%). Short-term outcomes were favourable in 60.7%, with a mortality rate of 4.5%. DISCUSSION: The present findings suggest that aggressive surgery and neuro-intensive care measures may lead to good functional results, even in the presence of seemingly devastating injuries in some selected patients.

Clinical applications of intracranial pressure monitoring in traumatic brain injury : report of the Milan consensus conference.

BACKGROUND: Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI. METHODS: A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants. The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features.

Skull base hemangiopericytomas.

OBJECTIVE: To retrospectively evaluate the clinical outcome of six patients with skull base hemangiopericytomas (HPCs) and that of a cohort of 37 similar patients identified by a systematic review of the literature. METHODS: The series constitutes of three men and three women with newly diagnosed skull base HPC who underwent multimodal treatment including surgery, external beam radiotherapy (EBRT) and pre-operative embolization. Furthermore, a systematic review off the literature identified 37 reports of primarily intracranial skull base HPCs. RESULTS: Four patients had a gross total resection (GTR) and two patients had a near total resection. Five patients were referred for adjuvant EBRT with a survival ranging from 15 to 47 months. All patients had an excellent outcome and resumed their previous activities. Literature review identified 37 additional patients with skull base HPC. Altogether, tumors were unevenly distributed above and below tentorium. GTR was achieved in half the patients, and 72.1% were referred to EBRT. Out of 37 reported patients in the literature, survival longer than 1 year was described in only 24. Within the combined cohort including the present series, survival was 83.6 months. CONCLUSIONS: The present series shows that a radical resection of HPC can be achieved under the difficult anatomical conditions of skull base surgery. Pre-operative arterial embolization may be instrumental to maintain a clear visual field and prevent excessive blood loss. Finally, the results of the present cohort suggest that EBRT may be useful for local growth control, as an effective palliative measure for skull base HPCs.

Improvement of cerebral metabolism mediated by Ro5-4864 is associated with relief of intracranial pressure and mitochondrial protective effect in experimental brain injury.

PURPOSE: To investigate the possible impact of reduction of mitochondrial membrane permeabilization by modulation of the 18 kDa translocator protein mediated by Ro5-4864 over post-traumatic cerebral edema and metabolic crisis. METHODS: Cerebral microdialysis and intracranial pressure (ICP) monitoring were performed in Sprague-Dawley rats treated by intraperitoneal injection of either dimethylsulfoxide (vehicle) or Ro5-4864 following cortical contusion and further correlated with quantitative assessment of mitochondrial damage, water content in the injured tissue, modified neurological severity score, and lesion size. RESULTS: Ro5-4864 resulted in a profound decrease in ICP that correlated with improved cerebral metabolism characterized by significantly higher glucose and pyruvate and lower lactate concentrations in the pericontusional area in comparison with vehicle-treated animals. Reduced ICP correlated with reduced water content in the injured tissue; improved metabolism was associated with reduced mitochondrial damage evidenced by electron microscopy. Both effects were associated with a profound and significant reduction in glycerol release and lesion size, and correlated with improved neurological recovery. CONCLUSIONS: The present study shows that Ro5-4864 has a favorable effect on the fate of injured brain, presumably mediated by improvement of metabolism. It further suggests that improvement of metabolism may contribute to ICP relief.

The Geriatric Scoring System (GSS) in meningioma patients--validation.

BACKGROUND: Meningiomas are the most common primary brain tumor, the incidence of which rises with age. The Geriatric Scoring System (GSS) was constructed in an attempt to answer which elderly subpopulation will benefit from a surgical intervention in terms of their overall physical and functional state of health. The GSS incorporates different prognostic indicators, both clinical and radiological, for risk stratification. OBJECTIVE: The purpose of the study was to validate the previously defined GSS for the evaluation and risk stratification of elderly patients suffering from intracranial meningioma. METHODS: One hundred and twenty patients aged over 65 years admitted to the RAMBAM Medical Center with meningiomas during the years 2005-2010 were characterized, forming an independent cohort. We report the presenting symptoms, chronic illness and radiological features, as well as perioperative and long-term follow-up results up to 5 years after the surgery. RESULTS: Nine outcome parameters were tested against the GSS score on admission. Survival, Barthel Index, Karnofsky Performance Scale (KPS), consciousness expressed by the Glasgow Coma Scale (GCS) [14] score 5 years after surgery, recurrence within and beyond 12 months of surgery, the length of hospitalization both overall and in a neurosurgical intensive care unit. A GSS score higher than 16 was associated with a significantly more favorable outcome. CONCLUSION: The present results suggest that common experience-based considerations may be optimized and implemented into a simple scoring system that in turn may allow for outcome prediction and evidence-based decision making.

Maternal cerebral blood flow during normal pregnancy: a cross-sectional study.

OBJECTIVE: Pregnancy is associated with substantial changes in the maternal circulatory physiology. Our aim was to investigate maternal cerebral blood flow (CBF) during normal pregnancies. STUDY DESIGN: We prospectively measured maternal CBF in 210 low-risk pregnant women at different gestational ages, and in 15 nonpregnant women. CBF was assessed by measuring blood flow volume in the internal carotid artery (ICA) by dual-beam angle-independent digital Doppler ultrasound. RESULTS: ICA blood flow volume increased during pregnancy from 318 mL/min ± 40.6 mL/min in the first trimester to 382.1 mL/min ± 50.0 mL/min during the third trimester, corresponding to CBF values of 44.4 and 51.8 mL/min(-1)/100 g(-1), respectively (P < .0001). CBF changes were associated with progressive decrease in cerebral vascular resistance and moderate increase in ICA diameter. CONCLUSION: Maternal CBF is gradually increasing during normal pregnancy. Vasorelaxing impact of estrogens and other factors on cerebral vessels may explain the changes in CBF during pregnancy.

Meningiomas in the elderly, the surgical benefit and a new scoring system.

OBJECTIVE: The purpose of the study was to define and identify prognostic indicators within an elderly population of patients suffering from intracranial meningiomas. The clinical presentation of the patient with meningioma is diverse, manifesting as a different clinical entity in the elderly patient compared to a similar type of tumor in a young patient. METHODS: Two hundred fifty patients aged over 65 years admitted to RAMBAM Medical Center with meningiomas from 1995-2005 were characterized. We report the presenting symptoms, chronic illnesses, perioperative and longterm follow-up results for a 5-year period. RESULTS: Based on univariate and multivariate analysis,significant prognostic indicators were identified and were implemented into a new geriatric scoring system (GSS)including tumor size and location, peritumoral edema,neurological deficits, Karnofsky score (Clancey J Neurosci Nurs 27:220, 1995; Crooks et al. J Gerontol 46:M139-M144, 1991), and associated diabetes, hypertension or lung disease. Seven outcome parameters were retrospectively tested using the scoring system, namely mortality,Barthel Index score (Mahoney and Barthel Md State Med J 14:61-65, 1965), Karnofsky score and consciousness expressed by the Glasgow Coma Scale score (Jennett and Bond Lancet 1:480-484, 1975) 5 years after surgery, as well as recurrence within and beyond 12 months. Age proved to inversely correlate with outcome. Morbidity and mortality were significantly lower in women. The extent of surgical resection (Simpson J Neurol Neurosurg Psychiatry 20:22-39, 1957) had no influence on functional outcome, although radical resection was associated with significantly lower mortality. Generally, a GSS score higher than 14 was associated with a significantly more favorable outcome. CONCLUSION: The present results suggest that common experience-based considerations may be optimized and implemented into a simple scoring system that in turn may allow for outcome prediction and evidence-based decision making

Neuroprotective effect of hyperbaric oxygen therapy in brain injury is mediated by preservation of mitochondrial membrane properties.

Recent experimental data have shown that hyperbaric oxygen therapy (HBOT) was associated increased Bcl-2 expression at the injury site that correlated with reduced apoptosis. We hypothesized that HBOT mediated enhancement of Bcl-2 expression and increased intracellular oxygen bio-availability may both contribute to preserve mitochondrial integrity and reduce the activation of the mitochondrial pathway of apoptosis. For this purpose, a cortical lesion was created in the parietal cortex of Sprague-Dawley rats by dynamic cortical deformation (DCD) and outcome measures in non-treated animals were compared with that of HBOT treated rats. Morphological analysis showed a profound reduction in neuronal counts in the perilesional area and a marked rarefaction of the density of the axonal-dendritic network. In treated animals, however, there was a significant attenuation of the impact of DCD over perilesional neurons, characterized by significantly higher cell counts and denser axonal network. In mitochondria isolated from injured brain tissue, there was a profound loss of mitochondrial transmembrane potential (Deltapsi(M)) that proved to be substantially reversed by HBOT. This finding correlated with a significant reduction of caspases 3 and 9 activation in HBOT treated animals but not of caspase 8, indicating a selective effect over the intrinsic pathway of apoptosis. All together, our results indicate that the neuroprotective effect of HBOT may represent the consequence of preserved mitochondrial integrity and subsequent inhibition of the mPTP and reduction of the mitochondrial pathway of apoptosis.

Monitoring of cerebral metabolism: non-ischemic impairment of oxidative metabolism following severe traumatic brain injury.

OBJECTIVE: To investigate and compare the respective dynamics of cerebral blood flow (CBF) and metabolism in response to changes in neurological condition and intracranial pressure (ICP) in severe traumatic brain injury (TBI). METHODS: Eight-four patients with severe TBI were prospectively enrolled in this study. CBF was measured daily and global cerebral metabolic rates of oxygen (CMRO(2)), glucose (CMRGlc) and lactate (CMRLct) were calculated using arterial jugular differences. In addition, 33 patients had a second evaluation shortly after a significant change (>5 mmHg) in their ICP. RESULTS: Eight hundred and ninety-four evaluations were collected during a period ranging between 1 and 12 days (mean: 5.1 +/- 2.6 days). CBF was moderately but significantly decreased. Oppositely, CMRO(2) was profoundly reduced with evidence for critical metabolic failure (<1.2 ml/100 g/min) in 30.5% whereas only 8.5% of CBF measurements were lower than 20 ml/100 g/min. Furthermore, in 78 instances of a dynamic assessment performed following ICP increase (n = 20) or decrease (n = 58), CMRO(2) but not CBF proved to be significantly and inversely affected by ICP fluctuations. Finally, CMRO(2) and CMRLct correlated with GCS score in contrast with CBF. Both CBF and metabolic indices, however, correlated with neurological outcome. CONCLUSION: This study shows that cerebral metabolic failure following TBI is a common finding that is not of ischemic origin in most instances. Unlike frequently assumed, cerebral metabolism is not constrained within the narrow range of a static depression sustained for weeks but rather subject to significant variations in response to changes in ICP or neurological condition.

Post-traumatic cytotoxic edema is directly related to mitochondrial function.

Cerebral edema represents a major threat following traumatic brain injury. However, therapeutic measures for control of intracranial pressure alone have failed to restore cerebral metabolism and improve neurological outcome. Since mitochondrial damage results in ATP depletion and deactivation of membrane ionic pumps, we hypothesized that modulation of ATP bioavailability may directly affect cytotoxic edema. Intracranial pressure measurements were performed in Sprague-Dawley rats treated by intraperitoneal injection of dimethylsulfoxide (vehicle), cyclosporine A (CsA), or Oligomycin B (OligB) following cortical contusion and further correlated with water content, mitochondrial damage, and electron microscopic assessment of neuronal and axonal edema. As hypothesized, ultra-structural figures of edema closely correlated with intracranial pressure elevation, increased water content and mitochondrial membrane permeabilization expressed by loss of transmembrane mitochondrial potential. Further, mitochondrial damage evidenced ultra-structurally by figures of swollen mitochondria with severely distorted cristae correlated with both cytotoxic edema and mitochondrial dysfunction. Importantly, cerebral edema and mitochondrial impairment were significantly worsened by treatment with OligB, whereas a noticeable improvement could be observed in animals that received injections of CsA. Since OligB and CsA are responsible for symmetrical and opposite effects on oxidative metabolism, these findings support the hypothesis of a causative relationship between edema and mitochondrial function.

Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury.

The purpose of this study was to compare the relative effects of mannitol and hypertonic saline (HTS) on calpain activity, apoptosis and neuroinflammatory response induced by experimental cortical contusion. Four groups of 5 Sprague-Dawley male rats were submitted to focal brain injury produced by exposing the parietal cortex to dynamic cortical deformation. Groups were defined by rescucitation fluids administered 30 min post-injury as follows: group 1-0.9% normal saline 2 ml/kg; group 2-mannitol 20% 0.5 g/kg; group 3-HTS 2 ml/kg; group 4-HTS 4 ml/kg. At 72 h, animals were sacrificed. Paraffin-mounted sections of were stained for mu-Calpain, TUNEL, active caspase 3 and myeloperoxidase. There was no difference in the lesion size between the different groups. In contrast, there was a significant reduction in calpain and apoptosis activity and in the neuroinflammatory response in animals receiving HTS. Although mannitol proved to significantly decrease the neuroinflammatory response and calpain activity, it did not affect apoptosis, and its effect was significantly less than that of HTS. Importantly, the effect of HTS was mostly independent from the infused volume. Our results show that HTS promotes cell survival and reduces secondary brain damage following TBI. This protective effect was evidenced at rather small infused volumes, proved to encompass several cellular and molecular mechanisms involved in secondary cell death and could not be related to relief of intracranial pressure. These findings suggest that the high osmolality of HTS may have protective effects besides its impact on brain edema.

Neuroprotective anti-apoptosis effect of estrogens in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and functional disability in western countries, affecting mostly young patients. Despite intense and sustained efforts deployed for the development of new therapeutic strategies, no clinical benefit has been shown by any of the investigated compounds. Increasing attention has been drawn during the past two decades to the neuroprotective effects of estrogens, although most of the available data relate to ischemic brain injury. The purpose of the present study was to investigate the potential neuroprotective value of estrogens in TBI as a therapeutic modality. For this purpose, a contusion was created in the parietal cortex by dynamic cortical deformation in two groups of 10 Sprague-Dawley male rats. Following the injury, treated animals received conjugated estrogens for 3 days, using a subcutaneously implanted osmotic pump. Animals were then sacrificed, and TUNEL, anti-active Caspase 3, bcl-2, and bax labeling were performed in paraffin-embedded brain sections, allowing for comparative and quantitative analysis. In estrogen-treated animals, there was a marked and significant reduction of apoptosis in comparison with non-treated animals. The reduction in TUNEL and active Caspase 3 staining was similar and close to 50%. Optical analysis of histological slides prepared by bcl-2 labeling showed a significant increase in bcl-2 expression in estrogen-treated animals compared to non-treated animals. On the contrary, bax expression was not influenced by hormonal treatment, and no difference could be noticed between the two groups. These results support the potential therapeutic value of estrogens in TBI and further clarify their mode of action.

Monitoring of cerebral blood flow and metabolism in traumatic brain injury.

The aim of the present study was to investigate the course of cerebral blood flow (CBF) and metabolism in traumatic brain injury (TBI) patients and to specifically characterize the changes in lactate and glucose indices in the acute post-traumatic period with regard to neurological condition and functional outcome. For this purpose, 55 consecutive TBI patients (mean age 37 +/- 17 years, mean GCS 6.8 +/- 3.2) were prospectively and daily evaluated. Global CBF, cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc), and lactate (CMRLct) were calculated using arterial jugular differences. In all patients, CBF was moderately decreased during the first 24 h in comparison with normal subjects although this relative oligemia was more pronounced in patients with poor outcome (p = 0.0007). Both CMRO2 and CMRGlc were significantly depressed and correlated to outcome (p < 0.0001, p = 0.0088). CMRLct analysis revealed positive values (lactate uptake) during the first 48 h, especially in patients with favorable outcome. Both CMRO2 and CMRLct correlated with GCS (p = 0.0001, p = 0.0205). CMRLct levels showed an opposite correlation with CBF in patients with favorable and poor outcome. In the former group, correlation analysis exhibited a negative slope with evidence for increasing lactate uptake associated with lower CBF values (r = -0.1940, p = 0.0242). On the contrary, in patients with adverse outcome, CMRLct values demonstrated a weak though opposite correlation with CBF (r = 0.0942, p = 0.2733). The present data emphasize the clinical significance of monitoring of cerebral blood flow and metabolism in TBI and provide evidence for metabolic coupling between astrocytes and neurons.

Basilar vasospasm diagnosis: investigation of a modified "Lindegaard Index" based on imaging studies and blood velocity measurements of the basilar artery.

BACKGROUND AND PURPOSE: Numerous studies have shown that cerebral vasospasm is one of the leading causes of death and neurological disability after subarachnoid hemorrhage. Most of these studies, however, have focused on anterior circulation vessels. Since the introduction of the transcranial Doppler (TCD), increasing attention has been given to basilar artery (BA) vasospasm, especially in traumatic subarachnoid hemorrhage. As shown for the anterior circulation, however, the significance of elevated flow velocities (FVs) in the posterior vessels may be ambiguous, so vasospasm may not be reliably differentiated from hyperemia. The purpose of the present study was to evaluate the potential additional value of an intracranial/extracranial FV ratio in the posterior circulation to cope with this shortcoming of the TCD in the diagnosis of BA vasospasm. METHODS: FV in the extracranial vertebral artery (VA) was measured in 20 healthy volunteers. Normative values of an intracranial/extracranial VA FV ratio (IVA/EVA) and a BA/extracranial VA FV ratio (BA/EVA) were calculated. Thirty-four patients with subarachnoid hemorrhage were then evaluated with TCD and CT angiography (CTA). The value of the IVA/EVA and BA/EVA ratios in the diagnosis and assessment of vertebrobasilar vasospasm was investigated. RESULTS: The extracranial VA could be insonated in all subjects at depths ranging from 45 to 55 mm. The average FV for the extracranial VA was 26 cm/s. The ratios between intracranial and extracranial VA FVs were 1.6 on both sides, whereas the ratio between the BA FVs and the mean extracranial VA FVs was slightly higher at 1.7. Fourteen patients (41.2%) had CTA evidence of BA vasospasm. Vasospasm was severe in 7 patients, moderate in 1, and mild in the remaining. An FV threshold of 80 cm/s was indicative of BA vasospasm in 92.8% with 3 false-positive results that could be related to vertebrobasilar hyperemia. Comparative analysis between CTA and TCD findings showed that BA/EVA was >2 in all patients with BA vasospasm (100% sensitivity) and < 2 in all but 1 patient without BA vasospasm (95% specificity). Furthermore, the BA/EVA ratio showed a close correlation with BA diameter (r=-0.8139, P<0.0001) and was >3 in all patients with severe vasospasm. CONCLUSIONS: The results of the present study showed that the BA/EVA ratio may contribute to an improved discrimination between BA vasospasm and vertebrobasilar hyperemia and enhance the accuracy and reliability of TCD in the diagnosis of BA vasospasm. Our data further suggest that the BA/EVA ratio may provide an approximation of vasospasm severity and help in identifying patients who are likely to suffer from hemodynamically significant vasospasm.

Hyperbaric oxygen therapy for reduction of secondary brain damage in head injury: an animal model of brain contusion.

Cerebral contusions are one the most frequent traumatic lesions and the most common indication for secondary surgical decompression. The purpose of this study was to investigate the physiology of perilesional secondary brain damage and evaluate the value of hyperbaric oxygen therapy (HBOT) in the treatment of these lesions. Five groups of five Sprague-Dawley rats each were submitted to dynamic cortical deformation (DCD) induced by negative pressure applied to the cortex. Cerebral lesions produced by DCD at the vacuum site proved to be reproducible. The study protocol entailed the following: (1) DCD alone, (2) DCD and HBOT, (3) DCD and post-operative hypoxia and HBOT, (4) DCD, post-operative hypoxia and HBOT, and (5) DCD and normobaric hyperoxia. Animals were sacrificed after 4 days. Histological sections showed localized gross tissue loss in the cortex at injury site, along with hemorrhage. In all cases, the severity of secondary brain damage was assessed by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase 3-positive cells in successive perilesional layers, each 0.5 mm thick. Perilesional TUNEL positive cells suggested the involvement of apoptosis in group 1 (12.24% of positive cells in layer 1). These findings were significantly enhanced by post-operative hypoxia (31.75%, p < 0.001). HBOT significantly reduced the severity and extent of secondary brain damage expressed by the number of TUNEL positive cells in each layer and the volume of the lesion (4.7% and 9% of TUNEL positive cells in layer 1 in groups 2 and 4 respectively, p < 0.0001 and p < 0.003). Normobaric hyperoxia also proved to be beneficial although in a lesser extent. This study demonstrates that the vacuum model of brain injury is a reproducible model of cerebral contusion. The current findings also suggest that HBOT may limit the growth of cerebral contusions and justify further experimental studies.

Role of multisection CT angiography in the evaluation of vertebrobasilar vasospasm in patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Optimal means for assessing cerebral vasospasm, mainly at the vertebrobasilar system, have not been established. The purpose of this study was to evaluate the role of multisection CT angiography (MCTA) in the detection and quantification of vertebrobasilar vasospasm (VBS) indicated on transcranial Doppler (TCD) imaging in patients with subarachnoid hemorrhage (SAH). METHODS: Forty-three MCTA studies of the vertebrobasilar arteries were performed with a multisection spiral CT scanner in 36 patients with SAH. Parameters used were 1-mm collimation, 0.625Q pitch, 120 kV, and 250 mAs. Contrast material was injected (80-100 mL, 3 mL/s) after a 15-20-second delay. Postprocessing of the vertebrobasilar system was performed by using maximum intensity projection and volume-rendering reconstruction. Vessel diameter was measured at different intracranial locations along the vertebral and basilar arteries perpendicular to their long axis by using curved reformatted multiplanar reformation. TCD imaging of the posterior circulation was performed within 24 hours. RESULTS: MCTA demonstrated narrowed arteries compatible with VBS in 13 patients, consistent with TCD findings. Despite TCD recordings of high flow velocity in three other patients, MCTA did not reveal vasospasm but did show wide arteries feeding arteriovenous malformations in two and normal-sized arteries in one. VBS in two patients was identified on MCTA but overlooked during TCD imaging. Twenty patients had normal findings on both TCD and MCTA studies. CONCLUSION: Cerebral MCTA is recommended as a reliable, rapid, and minimally invasive diagnostic method, one complementary to TCD imaging for assessing VBS in patients with SAH.

Posttraumatic basilar artery vasospasm.

BACKGROUND: During the past decade, vasospasm following posttraumatic subarachnoid hemorrhage (tSAH) has drawn increasing attention. However, despite accumulating evidence linking this phenomenon with poorer outcome, the clinical significance of posttraumatic vasospasm is still debated and often disputed, so that no definite therapeutic attitude has yet been adopted. Recent attention has been drawn to basilar vasospasm, suggesting a negative influence on neurologic outcome. The aim of the present study was the evaluation of basilar vasospasm as an independent factor of secondary brain damage following posttraumatic hemorrhage. METHODS: Daily transcranial Doppler (TCD) evaluations were conducted in 93 consecutive patients with tSAH. Basilar artery (BA) vasospasm was defined by blood flow velocity (FV) higher than 85 cm/s for at least 2 consecutive days. RESULTS: Thirty-two patients (34.4%) had BA FVs higher than 85 cm/s. In those patients, the ratio between BA FV and mean vertebral artery FV was higher than 2.5 and below 2 and those without TCD signs of vasospasm. Using multivariate logistic regression analysis, BA vasospasm proved to independently influence neurologic outcome. CONCLUSIONS: BA vasospasm severe enough to compromise cerebral blood flow to the brainstem, although uncommon, may nevertheless have a potential deleterious effect on neural tissue sensitized by trauma. The present results suggest that specific imaging procedures and eventually therapeutic measures should be conducted in the presence of significant BA vasospasm.

Involvement of the mitochondrial benzodiazepine receptor in traumatic brain injury: therapeutic implications.

Traumatic brain injuries represent the leading cause of death and morbidity in young adults in western countries, and are responsible for a major social and economical burden. For decades, the mainstay of neurotrauma management has been represented by control of post-traumatic edema. With the emergence of a better understanding of the underlying cellular mechanisms responsible for the generation of secondary brain damage, the hope for the "magic bullet" has prompted the development of novel drugs that have repeatedly failed to significantly improve outcome of head-injured patients. During the past decade, mitochondrial functional and structural impairment has emerged as a pivotal event in the pathway of cell to secondary death. Extensive research has identified a vast range of deleterious signals that are generated and integrated at the mitochondrial level resulting in impairment of major mitochondrial functions such as calcium homeostasis, free radicals generation and detoxification, energy production and neurosteroidogenesis. Mitochondria have therefore emerged as a potential therapeutic target. Within the spectrum of major mitochondrial structural components, the 18 kDa translocator protein (TSPO) has shown important and relevant functions such as steroid synthesis and modulation of the mitochondrial permeability transition that may substantially affect the fate of injured cells. This review summarizes the potential therapeutic implications of TSPO modulation in traumatic brain injury in the view of the current knowledge on this intriguing mitochondrial complex.

Mitochondrial targeting for development of novel drug strategies in brain injury.

For years, therapeutic approach to brain injury has been mostly physiological in essence, either based on revascularization of ischemic tissue in stroke or decompression of the swollen brain in neurotrauma. Despite tremendous efforts for the development of new strategies, translational research targeting specific cellular pathophysiological processes triggered by the injury has provided deceiving results. During the past decade, disruption of mitochondrial function and structural integrity has emerged as a pivotal event in the generation of cell damage. Following the injury, a vast array of deleterious signals are generated and integrated at the mitochondrial level resulting in impairment of three major mitochondrial functions: calcium homeostasis, free radicals generation and detoxification and energy production. Increasing understanding of the biochemical complexity of these events has led to the development of new therapeutic strategies targeting mitochondrial damage that has shown encouraging data in various models of injury. Importantly, translational efforts have been already initiated with promising preliminary data in several phase II clinical studies. In this review, we will briefly describe the process of mitochondrial damage and dysfunction following brain injury and discuss the various therapeutic strategies aiming at mitochondrial protection.

Mitochondrial damage: a target for new therapeutic horizons.

Traumatic brain injury (TBI) represents a leading cause of death and morbidity, as well as a considerable social and economical burden in western countries, and has thus emerged as a formidable therapeutic challenge. Yet despite tremendous efforts enlightening the mechanisms of neuronal death, hopes for the "magic bullet" have been repeatedly deceived, and TBI management has remained focused on the control of increased intracranial pressure. Indeed, impairment of cerebral metabolism is traditionally attributed to impaired oxygen delivery mediated by reduced cerebral perfusion in the swollen cerebral parenchyma. Although intuitively appealing, this hypothesis is not entirely supported by physiological facts and does not take into consideration mitochondrial dysfunction that has been repeatedly reported in both human and animal TBI. Although the nature and origin of the events leading to mitochondrial damage may be different, most share a permeabilization of mitochondrial membrane, which therefore may represent a logical target for new therapeutic strategies. Therefore, the proteins mediating these events may represent promising targets for new TBI therapies. Furthermore, mimicking anti-apoptotic proteins, such as Bcl-2 or XIAP, or inhibiting mitochondrial pro-apoptotic proteins, such as Smac/DIABLO, Omi/HTRA2, and ARTS (septin 4 isoform 2) may represent useful novel therapeutic strategies. This review focuses on mechanisms of the mitochondrial membrane permeabilization and its consequences and discusses the current and possible future therapeutic implications of this key event of neuronal death.