Dietary (Poly)phenols in Traumatic Brain Injury.

Traumatic brain injury (TBI) remains one of the leading causes of death and disability in young adults worldwide. Despite growing evidence and advances in our knowledge regarding the multifaceted pathophysiology of TBI, the underlying mechanisms, though, are still to be fully elucidated. Whereas initial brain insult involves acute and irreversible primary damage to the brain, the processes of subsequent secondary brain injury progress gradually over months to years, providing a window of opportunity for therapeutic interventions. To date, extensive research has been focused on the identification of druggable targets involved in these processes. Despite several decades of successful pre-clinical studies and very promising results, when transferred to clinics, these drugs showed, at best, modest beneficial effects, but more often, an absence of effects or even very harsh side effects in TBI patients. This reality has highlighted the need for novel approaches that will be able to respond to the complexity of the TBI and tackle TBI pathological processes on multiple levels. Recent evidence strongly indicates that nutritional interventions may provide a unique opportunity to enhance the repair processes after TBI. Dietary (poly)phenols, a big class of compounds abundantly found in fruits and vegetables, have emerged in the past few years as promising agents to be used in TBI settings due to their proven pleiotropic effects. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by a state-of-the-art summary of the studies that have evaluated the efficacy of (poly)phenols administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. The current limitations on our knowledge concerning (poly)phenol effects in TBI in the pre-clinical studies are also discussed.

Antiepileptic Drugs for Preventing Seizures in Patients with Chronic Subdural Hematoma.

Chronic subdural hematoma (CSH) is an accumulation of blood within the intracranial subdural space. It is associated with minor traumatic events and affects mostly the elderly. CSH can be effectively treated surgically with good outcomes, although the recurrence rate is high. Epileptic seizures are one of the major complications associated with CSH, either in the pre or postoperative period. The incidence rate of new onset seizures after CSH diagnosis ranges between 3% and 23%. However, the benefit of using prophylactic antiepileptic drugs in these patients is controversial with significant variations in clinical practice. It ranges from routine to total absence of use in this clinical context. The best current evidence does not allow any firm conclusion on whether such prophylactic treatment is effective, that is if it prevents the development of epileptic seizures. Furthermore, these drugs are associated with important adverse events. A systematic literature review found no controlled randomized trials evaluating the risk/benefit of the prophylactic use of anticonvulsants for people with CSH and retrospective studies showing contradictory results. Moreover, these observational studies are outdated and do not evaluate new generation drugs. Herein, we discuss the evidence for the use of antiepileptic drugs for preventing seizures in patients with CSH, with a particular focus on the subgroup of people most likely to benefit (such as the elderly and alcohol abusers), as well as the possible safety advantages of the new antiepileptic drugs.

Spontaneous pseudomeningocele associated with lumbar spondylolisthesis: A case report and review of the literature.

BACKGROUND: Pseudomeningocele, an extradural collection of cerebrospinal fluid (CSF), has only been rarely reported to occur spontaneously in conjunction with isthmic spondylolisthesis (with lysis) in the lumbar spine. CASE DESCRIPTION: A 68-year-old male presented with low back pain and neurogenic claudication of several years duration without any history of trauma, epidural spine injections, or spine surgery. Lumbosacral magnetic resonance imaging (MRI) revealed a grade-I L4-L5 isthmic spondylolisthesis with spinal canal narrowing and a posterior paravertebral collection consistent with CSF. The patient underwent a spinal decompression consisting of a complete L4 and partial L5 laminectomy, a bilateral L4-L5 instrumented fusion (due to the lysis defect), and closure of the CFS fistula. The histology analysis was compatible with a pseudomeningocele. CONCLUSION: Lumbar isthmic spondylolisthesis may lead to changes in the elastic properties of the underlying dura mater. Rarely, this may lead to meningeal tears and formation of a pseudomeningocele. Historically, one must always check for a prior epidural injection that could have resulted in this complication. Additionally, as most likely the case here, the lysis defect was responsible for the foraminal dural laceration resulting in the pseudomeningocele.

Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures.

BACKGROUND: Basilar skull fractures predispose patients to meningitis because of the possible direct contact of bacteria in the paranasal sinuses, nasopharynx or middle ear with the central nervous system (CNS). Cerebrospinal fluid (CSF) leakage has been associated with a greater risk of contracting meningitis. Antibiotics are often given prophylactically, although their role in preventing bacterial meningitis has not been established. OBJECTIVES: To evaluate the effectiveness of prophylactic antibiotics for preventing meningitis in patients with basilar skull fractures. SEARCH METHODS: We searched CENTRAL (2014, Issue 5), MEDLINE (1966 to June week 1, 2014), EMBASE (1974 to June 2014) and LILACS (1982 to June 2014). We also performed an electronic search of meeting proceedings from the American Association of Neurological Surgeons (1997 to September 2005) and handsearched the abstracts of meeting proceedings of the European Association of Neurosurgical Societies (1995, 1999 and 2003). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antibiotic versus placebo or no intervention. We also identified non-RCTs to perform a separate meta-analysis in order to compare results. DATA COLLECTION AND ANALYSIS: Three review authors independently screened and selected trials, assessed risk of bias and extracted data. We sought clarification with trial authors when needed. We pooled risk ratios (RRs) for dichotomous data with their 95% confidence intervals (CIs) using a random-effects model. We assessed the overall quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: In this update we did not identify any new trials for inclusion. We included five RCTs with 208 participants in the review and meta-analysis. We also identified 17 non-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with basilar skull fractures. Most trials presented insufficient methodological detail. All studies included meningitis in their primary outcome. When we evaluated the five included RCTs, there were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of the frequency of meningitis, all-cause mortality, meningitis-related mortality and need for surgical correction in patients with CSF leakage. There were no reported adverse effects of antibiotic administration, although one of the five RCTs reported an induced change in the posterior nasopharyngeal flora towards potentially more pathogenic organisms resistant to the antibiotic regimen used in prophylaxis. We performed a subgroup analysis to evaluate the primary outcome in patients with and without CSF leakage. We also completed a meta-analysis of all the identified controlled non-RCTs (enrolling a total of 2168 patients), which produced results consistent with the randomised data from the included studies.Using the GRADE approach, we assessed the quality of trials as moderate. AUTHORS' CONCLUSIONS: Currently available evidence from RCTs does not support prophylactic antibiotic use in patients with basilar skull fractures, whether there is evidence of CSF leakage or not. Until more research is available, the effectiveness of antibiotics in patients with basilar skull fractures cannot be determined because studies published to date are flawed by biases. Large, appropriately designed RCTs are needed.

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion.

UNLABELLED: OBJECT.: There is an unmet clinical need to develop neuroprotective agents for neurosurgical and endovascular procedures that require transient cerebral artery occlusion. The aim in this study was to explore the effects of a single dose of recombinant human erythropoietin (rhEPO) before middle cerebral artery (MCA) occlusion in a focal cerebral ischemia/reperfusion model. METHODS: Twenty-eight adult male Wistar rats were subjected to right MCA occlusion via the intraluminal thread technique for 60 minutes under continuous cortical perfusion monitoring by laser Doppler flowmetry. Rats were divided into 2 groups: control and treatment. In the treated group, rhEPO (1000 IU/kg intravenously) was administered 10 minutes before the onset of the MCA ischemia. At 24-hour reperfusion, animals were examined for neurological deficits, blood samples were collected, and animals were killed. The following parameters were evaluated: brain infarct volume, ipsilateral hemispheric edema, neuron-specific enolase plasma levels, parenchyma histological features (H & E staining), Fluoro-Jade-positive neurons, p-Akt and total Akt expression by Western blot analysis, and p-Akt-positive nuclei by immunohistochemical investigation. RESULTS: Infarct volume and Fluoro-Jade staining of degenerating neurons in the infarct area did not vary between groups. The severity of neurological deficit (p < 0.001), amount of brain edema (78% reduction in treatment group, p < 0.001), and neuron-specific enolase plasma levels (p < 0.001) were reduced in the treatment group. Perivascular edema was histologically less marked in the treatment group. No variations in the expression or localization of p-Akt were seen. CONCLUSIONS: Administration of rhEPO before the onset of 60-minute transient MCA ischemia protected the brain from this insult. It is unlikely that rhEPO pretreatment leads to direct neuronal antiapoptotic effects, as supported by the lack of Akt activation, and its benefits are most probably related to an indirect effect on brain edema as a consequence of blood-brain barrier preservation. Although research on EPO derivatives is increasing, rhEPO acts through distinct neuroprotective pathways and its clinical safety profile is well known. Clinically available rhEPO is a potential therapy for prevention of neuronal injury induced by transitory artery occlusion during neurovascular procedures.

Anticonvulsants for preventing seizures in patients with chronic subdural haematoma.

BACKGROUND: Anticonvulsant therapy is sometimes used prophylactically in patients with chronic subdural haematoma, although the benefit is unclear. OBJECTIVES: To assess the effects of prophylactic anticonvulsants in patients with chronic subdural haematoma, in both the pre- and post-operative periods. SEARCH METHODS: We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), PubMed, LILACS, and the databases clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, and Current Controlled Trials. The search was through 27th March 2013. SELECTION CRITERIA: Randomised controlled trials comparing any anticonvulsant versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Three authors screened the search results to identify relevant studies. No studies met the inclusion criteria for the review. MAIN RESULTS: No randomised controlled trials were identified. AUTHORS' CONCLUSIONS: No formal recommendations can be made about the use of prophylactic anticonvulsants in patients with chronic subdural haematoma based on the literature currently available. There are no randomised controlled trials on this topic, and non-controlled studies have conflicting results. There is an urgent need for well-designed randomised controlled trials.

Dermoid tumor of the lateral wall of the cavernous sinus.

BACKGROUND: Congenital intracranial dermoid tumors are very rare. The location of these dermoid lesions in the cavernous sinus and the complexity of the operative procedure for these lesions have been noted by several authors. Dermoid tumors originating in the cavernous sinus are usually interdural, and thus blurred vision is an uncommon presentation. CASE DESCRIPTION: Herein we report the first incidental case of a cavernous sinus dermoid cyst in a 21-year-old woman. CONCLUSIONS: A literature review was done and the possible treatments and approaches for this lesion are discussed. We consider that surgical treatment is indicated in most incidental cavernous sinus dermoid lesions due to the possible symptoms related to compression or rupture leading to chemical meningitis.

One hundred and one dysembryoplastic neuroepithelial tumors: an adult epilepsy series with immunohistochemical, molecular genetic, and clinical correlations and a review of the literature.

Simple and complex forms of dysembryoplastic neuroepithelial tumors (DNTs) are readily recognizable but forms with diffuse growth pattern, and hybrid tumors, that is, mixed DNT and ganglioglioma (DNT/GG), are more contentious entities. Rare DNTs have shown aggressive behavior. We reviewed cortical growth patterns, immunophenotype (including CD34, nestin and calbindin), genetic profile, and outcome in 101 DNT in adults. Simple (n = 18), complex (n = 31), diffuse (n = 35) DNT, and mixed DNT/GG (n = 17) showed no difference in age of onset, associated seizure type, or outcome (67.5% free from seizure; mean follow-up, 6 years). CD34 was seen in 61%, calbindin in 57%, and nestin in 86% of all DNT types; these markers were less common in simple DNT. Peritumoral cortical changes (Layer I hypercellularity [61%], satellite nodules [51.6%]) were frequent, but dyslamination (cortical dysplasia) was not identified. Molecular genetic abnormalities identified in 17 cases were IDH1 mutation (n = 3), 1p/19q loss (n = 10), isolated loss 9q (n = 2), and PTEN loss (n = 3), which were not associated with tumor type or location, higher cell proliferation, or distinguishing clinical features (mean age of epilepsy onset, 9 years; age at surgery = 31 years; 69% free from seizure); none had progression on magnetic resonance imaging (mean follow-up, 6 years). No single feature was predictive of seizure-free outcome, but there was a trend for better outcome in CD34-positive tumors (p = 0.07). One case has shown transformation to a higher grade. This study supports the existence of a range of subtypes of DNT some with overlapping features with ganglioglioma; molecular genetic abnormalities were not predictive of atypical behavior.

Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures.

BACKGROUND: Basilar skull fractures (BSF) predispose patients to meningitis because of the possible direct contact of bacteria in the paranasal sinuses, nasopharynx or middle ear with the central nervous system (CNS). Cerebrospinal fluid (CSF) leakage has been associated with a greater risk of contracting meningitis. Antibiotics are often given prophylactically, although their role in preventing bacterial meningitis is not established. OBJECTIVES: To evaluate the effectiveness of prophylactic antibiotics for preventing meningitis in patients with BSF. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1966 to February 2011), EMBASE (1974 to February 2011) and LILACS (1982 to February 2011). We also performed an electronic search of meeting proceedings from the American Association of Neurological Surgeons (1997 to September 2005) and handsearched the abstracts of meeting proceedings of the European Association of Neurosurgical Societies (1995, 1999 and 2003). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antibiotic versus placebo or no intervention. We also identified non-RCTs to perform a separate meta-analysis to compare results. DATA COLLECTION AND ANALYSIS: At least two authors independently appraised trial quality and extracted data for each trial. MAIN RESULTS: We identified five RCTs and 17 non-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with BSF. Most trials presented insufficient methodological detail. All studies included meningitis in their primary outcome. Overall, we evaluated 208 participants from the five RCTs that were considered suitable for inclusion in the meta-analysis. There were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of the frequency of meningitis, all-cause mortality, meningitis-related mortality, and need for surgical correction in patients with CSF leakage. There were no reported adverse effects of antibiotic administration, although one of the five RCTs reported an induced change in the posterior nasopharyngeal flora towards potentially more pathogenic organisms resistant to the antibiotic regimen used in prophylaxis. We performed a subgroup analysis to evaluate the primary outcome in patients with and without CSF leakage. We also completed a meta-analysis of all the identified controlled non-RCTs (enrolling a total of 2168 patients), producing results consistent with the randomised data. AUTHORS' CONCLUSIONS: Currently available evidence from RCTs does not support prophylactic antibiotic use in patients with BSF, whether there is evidence of CSF leakage or not. Until more research is completed, the effectiveness of antibiotics in patients with BSF cannot be determined because studies published to date are flawed by biases. Large, appropriately designed RCTs are needed.

Antibiotic prophylaxis for surgical introduction of intracranial ventricular shunts: a systematic review.

OBJECT: Systemic antibiotics and antibiotic-impregnated shunt (AIS) systems are often used to prevent shunt infection. The authors conducted a systematic review to evaluate its effectiveness of antibiotics in patients who underwent placement of intracranial ventricular shunts. METHODS: The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, and the meeting proceedings from the American Association of Neurological Surgeons and from the European Association of Neurosurgical Societies until June 2005. Randomized and quasi-randomized trials comparing the use of prophylactic antibiotics (either systemic or AIS systems) in intracranial ventricular shunt procedures with placebo or no antibiotics were included in the review. RESULTS: Seventeen trials involving 2134 patients were included. Results from the meta-analysis showed that the use of systemic antibiotic prophylaxis for internal shunts was associated with a decrease in shunt infection (odds ratio 0.51; 95% confidence interval 0.36-0.73). The authors found no significant differences between the subgroups evaluated in type of internal shunt (ventriculoperitoneal/ventriculoatrial), age, or duration of the administration of antibiotics. CONCLUSIONS: The authors found a benefit of systemic prophylactic antibiotics in preventing shunt infection, regardless of the patient's age and the type of internal shunt used. The benefit of its use after the first 24 hours postoperatively remains uncertain. Future trials should be conducted to evaluate the effectiveness of different regimens of systemic antibiotics rather than placebo, namely single preoperative dose versus multiple doses. It should also be mandatory to evaluate the effectiveness of systemic prophylactic antibiotics for external ventricular drains. Evidence suggests that antibiotic-impregnated catheters reduce the incidence of shunt infection, although more well-designed clinical trials are needed.

Traumatic clivus epidural hematoma: case report and review of the literature.

BACKGROUND: Traumatic clival epidural hematoma is an extremely rare reported entity. CASE DESCRIPTION: We describe the case of a 26-year-old woman involved in a car accident who presented with a Glasgow Coma Scale score of 13, bilateral abducens palsy, bilateral numbness on the mandibular territory of the trigeminal nerve, and left hypoglossal palsy. Radiological examinations revealed a clival epidural hematoma. The patient was managed conservatively, with clinical improvement of her neurological condition. This is the first traumatic clival epidural hematoma reported in an adult. From a review of the literature, we found only 8 cases. CONCLUSION: The pathophysiology of these hematomas is still a subject of debate; occipitoatlantoaxial ligamentous instability may play a role in it. In one third of the cases, bilateral cranial nerve palsies were associated. Apparently, they have a benign outcome.

Aggressive intracranial and extra-cranial epithelioid hemangioendothelioma: a case report and review of the literature.

Epithelioid hemangioendothelioma is a rare tumor of intermediate malignancy. Twelve intracranial cases have been well documented. We report an intra- and extra-cranial single mass epithelioid hemangioendothelioma. We describe the case of a 27-year-old male who presented a left temporal and retroauricular pain and an intra and extra-cranial mass extending to the left infratemporal fossa. The neoplasm was isointense with gray matter in both T1 and T2-weighted images, showing marked nodular gadolinium enhancement. About 90% of the tumor was surgically removed. The neoplasm was fibrous, well defined and arose from the left temporal artery branches. Recovery was uneventful. The histological diagnosis was epithelioid hemangioendothelioma. Enhanced magnetic resonance scan was repeated at 3 and 6 months after surgery, showing an increasing mass volume extending to the surrounding tissues, including intracranially, infratemporal fossa and left orbit. The patient died 8 months after the initial diagnosis. Epithelioid hemangioendotheliomas can be very aggressive tumors, presenting initially at an intra- and extra-cranial location, due to its fast growth. From our review of the literature, they seem to have an equal gender distribution (M : F = 7 : 6) and tend to affect people under the age of 30 (10/13). We report a unique and extremely aggressive tumor. The rarity of reports and the continuous spectrum of differentiation, ranging from borderline to highly malignant are obstacles to identifying initial therapeutic protocols and the adjunctive therapy after surgery.

Intrinsic hematoma of the oculomotor nerve: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Intrinsic oculomotor nerve hematoma is an exceptional cause of third nerve palsy. This case report illustrates the clinical, radiological, and intraoperative relevance of this rare pathological finding. CLINICAL PRESENTATION: A 25-year-old woman with a 12-year history of gross total resection of cerebellar medulloblastoma and posterior whole-brain radiotherapy presented with complete left oculomotor palsy. Magnetic resonance imaging revealed a left-sided, perimesencephalic cistern, small, round lesion with a fluid level. Digital subtraction angiography demonstrated no evidence of vascular abnormalities. INTERVENTION: A pterional craniotomy was performed, and the left oculomotor nerve was exposed. A blackish intrinsic lesion was detected in its cisternal segment near the uncus. The lesion was incised, and liquid compatible with a subacute noncoagulated hematoma was drained. Three months after surgery, the patient had partial recovery from diplopia and extraocular muscle function. CONCLUSION: We reviewed the literature and found four cases of oculomotor nerve intrinsic hematoma. These cases were all associated with hematological diseases, trauma, or solid tumors, and, as a group, these patients had poor outcomes. In the present report, the possibility of radiotherapy-induced vasculopathy as a predisposing factor is discussed. Surgical removal of an intrinsic nerve hematoma is probably helpful in the functional recovery of these patients.