Subdural hematoma, retinal hemorrhage, and fracture triad as a clinical predictor for the diagnosis of child abuse.

OBJECTIVE: Nonaccidental trauma (NAT) is a major cause of traumatic death during infancy and early childhood. Several findings are known to raise the index of clinical suspicion: subdural hematoma (SDH), retinal hemorrhage (RH), fracture, and external trauma. Combinations of certain injury types, determined via statistical frequency associations, may assist clinical diagnostic tools when child abuse is suspected. The present study sought to assess the statistical validity of the clinical triad (SDH + RH + fracture) in the diagnosis of child abuse and by extension pediatric NAT. METHODS: A retrospective review of The University of Arizona Trauma Database was performed. All patients were evaluated for the presence or absence of the components of the clinical triad according to specific International Classification of Diseases (ICD)-10 codes. Injury type combinations included some variation of SDH, RH, all fractures, noncranial fracture, and cranial fracture. Each injury type was then correlated with the ICD-10 codes for child abuse or injury comment keywords. Statistical analysis via contingency tables was then conducted for test characteristics such as sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: There were 3149 patients younger than 18 years of age included in the quantitative analysis, all of whom had at least one component of the clinical triad. From these, 372 patients (11.8%) had a diagnosis of child abuse. When compared to a single diagnosis of either SDH, RH, all fractures, noncranial fracture, or cranial fracture, the clinical triad had a significantly greater correlation with the diagnosis of child abuse (100% of cases) (p < 0.0001). The dyad of SDH + RH also had a significantly greater correlation with a child abuse diagnosis compared to single diagnoses (88.9%) (p < 0.0001). The clinical triad of SDH + RH + fracture had a sensitivity of 88.8% (95% CI 87.6%-89.9%), specificity of 100% (95% CI 83.9%-100%), and positive predictive value of 100% (95% CI 99.9%-100%). The dyad of SDH + RH had a sensitivity of 89.1% (95% CI 87.9%-90.1%), specificity of 88.9% (95% CI 74.7%-95.6%), and positive predictive value of 99.9% (95% CI 99.6%-100%). All patients with the clinical triad were younger than 3 years of age. CONCLUSIONS: When SDH, RH, and fracture were present together, child abuse and by extension pediatric NAT were highly likely to have occurred.

Outcomes following therapeutic intervention of post-traumatic vasospasm: A systematic review and meta-analysis.

BACKGROUND: Vasospasm occurrence following traumatic brain injury may impact neurologic and functional recovery of patients, yet treatment of post-traumatic vasospasm (PTV) has not been well documented. This systematic review and meta-analysis aims to assess the current evidence regarding favorable outcome as measured by Glasgow Outcome Scale (GOS) scores following treatment of PTV. METHODS: A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality; occurrence of PTV; rate of favorable outcome following each treatment modality; and follow-up duration. Treatments evaluated were calcium channel blockers (CCBs), endovascular intervention, and dopamine-induced hypertension. Outcomes were compared via the random-effects analysis. RESULTS: Fourteen studies with 1885 PTV patients were quantitatively analyzed: 982 patients who received tailored therapeutic intervention and 903 patients who did not receive tailored therapy. For patients undergoing treatment, the rate of favorable outcome was 57.3 % (500/872 patients; 95 % CI 54.1 - 60.6 %) following administration of CCBs, 94.1 % (16/17 patients; 95 % CI 82.9 - 100.0 %) following endovascular intervention, and 54.8 % (51/93 patients; 95 % CI 44.7 - 65.0 %) following dopamine-induced hypertension. Of note, the endovascular group had the highest rate of favorable outcome but was also the smallest sample size (n = 17). Patients who received tailored therapeutic intervention for PTV had a higher rate of favorable outcome than patients who did not receive tailored therapy: 57.7 % (567/982 patients; 95 % CI 54.1 - 60.8 %) versus 52.0 % (470/903 patients; 95 % CI 48.8 - 55.3 %), respectively. CONCLUSIONS: The available data suggests that tailored therapeutic intervention of PTV results in a favorable outcome. While endovascular intervention of PTV had the highest rate of favorable outcome, both CCB administration and dopamine-induced hypertension had similar lower rates of favorable outcome.

Three-Dimensional Printing in Neurosurgery Residency Training: A Systematic Review of the Literature.

BACKGROUND: The use of three-dimensional (3D) printing in neurosurgery has become more prominent in recent years for surgical training, preoperative planning, and patient education. Several smaller studies are available using 3D printing; however, there is a lack of a concise review. This article provides a systematic review of 3D models in use by neurosurgical residents, with emphasis on training, learning, and simulation. METHODS: A structured literature search of PubMed and Embase was conducted using PRISMA guidelines to identify publications specific to 3D models trialed on neurosurgical residents. Criteria for eligibility included articles discussing only neurosurgery, 3D models in neurosurgery, and models specifically tested or trialed on residents. RESULTS: Overall, 40 articles were identified that met inclusion criteria. These studies encompassed different neurosurgical areas including aneurysm, spine, craniosynostosis, transsphenoidal, craniotomy, skull base, and tumor. Most articles were related to brain surgery. Of these studies, vascular surgery had the highest overall, with 13 of 40 articles, which include aneurysm clipping and other neurovascular surgeries. Twenty-two articles discussed cranial plus tumor surgeries, which included skull base, craniotomy, craniosynostosis, and transsphenoidal. Five studies were specific to spine surgery. Subjective outcome measures of neurosurgical residents were most commonly implemented, of which results were almost unanimously positive. CONCLUSIONS: 3D printing technology is rapidly expanding in health care and neurosurgery in particular. The technology is quickly improving, and several studies have shown the effectiveness of 3D printing for neurosurgical residency education and training.

Peripheral Nerve Stimulation for Refractory Trigeminal Pain: Recent Single-Institution Case Series With Long-Term Follow-Up and Review of the Literature.

BACKGROUND: Peripheral neurostimulation (PNS) for medically refractory trigeminal pain is an emerging alternative to traditional surgical approaches, with safety and efficacy demonstrated in several retrospective series and a prospective trial currently in progress. Many existing studies suffer from relatively small numbers and short or inconsistent follow-up, making balanced treatment assessment difficult. MATERIALS AND METHODS: Consecutive cases of trial and permanent placement of trigeminal branch stimulation electrodes by a single surgeon from May 2014 through January 2019 were retrospectively reviewed from a prospectively collected database, following the PROCESS guidelines for surgical case series. Outcomes were assessed at six months and at last follow-up. RESULTS: Ninteen patients underwent trial electrode placement, with 15 patients undergoing permanent system placement. The most common diagnoses were idiopathic trigeminal neuralgia Type 2 (N = 8) and trigeminal neuropathic pain (N = 7). Median follow-up was 14 months (range 6-58 months). At last follow-up, 12 of 15 implanted patients (80%) were still receiving stimulation, with mean (median) pain reduction of 52.3% (47.5%). Infection and revision rates were high, although erosion and migration, which have typically plagued trigeminal PNS surgery, did not occur. Implanted systems were well-tolerated, with excellent cosmetic outcomes and high patient satisfaction that proved durable over long follow-up. CONCLUSIONS: We present a single-institution series of PNS for complex craniofacial pain involving the trigeminal nerve. The procedure is safe, effective and durable over at least one year in the large majority of a well-selected patient population.

Altered expression of signaling pathways regulating neuronal excitability in hippocampal tissue of temporal lobe epilepsy patients with low and high seizure frequency.

Despite recent advances in our understanding of synaptic transmission associated with epileptogenesis, the molecular mechanisms that control seizure frequency in patients with temporal lobe epilepsy (TLE) remain obscure. RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean = 4 seizure/month) versus high (HSF, mean = 60 seizures/month) seizure frequency identified 979 genes with ≥2-fold change in transcript abundance (FDR-adjusted p-value ö0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE.

Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy.

Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value < 0.05, FDR <0.05). Network and pathway analyses identified differential activation of pathways involved in lipid metabolism, morphology of oligodendrocytes, inflammatory response, and development of astrocytes. These results suggest that pre-operative leukocyte expression profiles have prognostic value for seizure outcome following SLAH.

Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy.

Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post-operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of zinc finger protein 852 (ZNF852), CUB domain-containing protein 2 (CDCP2), proline-rich transmembrane protein 1 (PRRT1), hypothetical LOC440200 (FLJ41170), RNA probe 8047763, RNA probe 8126238, RNA probe 8113489, RNA probe 8092883, RNA probe 7935228, RNA probe 806293, and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH.

Cortical gene expression correlates of temporal lobe epileptogenicity.

INTRODUCTION: Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency. METHODS: Baseline seizure frequency was used as a clinical measure of epileptogenicity. Twenty-four patients in high or low seizure frequency groups (median seizures/month) underwent anterior temporal lobectomy with amygdalohippocampectomy for intractable TLE. RNA was isolated from the lateral temporal cortex and submitted for expression analysis. Genes significantly associated with baseline seizure frequency on likelihood ratio test were identified based on >0.90 area under the ROC curve, P value of <0.05. RESULTS: Expression levels of forty genes were significantly associated with baseline seizure frequency. Of the seven most significant, four have been linked to other neurologic diseases. Expression levels associated with high seizure frequency included low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB (POZ) domain containing 11, Thanatos-associated protein domain containing 8 and Heparin sulfate (glucosamine) 3-O-sulfotransferase 3A1. CONCLUSIONS: This study describes novel associations between forty known genes and a clinical marker of epileptogenicity, baseline seizure frequency. Four of the seven discussed have been previously related to other neurologic diseases. Future investigation of these genes could establish new biomarkers for predicting epileptogenicity, and could have significant implications for diagnosis and management of temporal lobe epilepsy, as well as epilepsy pathogenesis.

Use of a stop-flow programmable shunt valve to maximize CNS chemotherapy delivery in a pediatric patient with acute lymphoblastic leukemia.

BACKGROUND: The requirement for frequent intraventricular drug delivery in the setting of shunt dependence is particularly challenging in the treatment of central nervous system infection, neoplastic disease, and hemorrhage. This is especially relevant in the pediatric population where both hematogenous malignancy requiring intrathecal drug delivery and shunt-dependent hydrocephalus are more prevalent. Intrathecal and intraventricular chemotherapy agents can be prematurely diverted in these shunt-dependent patients. CASE DESCRIPTION: We report the use of a stop-flow programmable shunt valve to maximize delivery of intraventricular chemotherapy in a child with acute lymphoblastic leukemia and disseminated intravascular coagulation who presented with spontaneous intracerebral and intraventricular hemorrhages. The patient then developed posthemorrhagic hydrocephalus and eventually progressed to shunt dependence but still required frequent intraventricular chemotherapy administration. A ventriculoperitoneal shunt, equipped with a valve that allows for near cessation of cerebrospinal fluid flow (Certas(®), Codman, Raynham, MA), and a contralateral Ommaya reservoir were inserted to maximize intraventricular dissemination of chemotherapy. CONCLUSIONS: To the best of our knowledge, this is the first reported case of the use of a high-resistance programmable valve being used to virtually cease cerebrospinal fluid flow through the distal catheter temporarily in order to maximize intraventricular drug dissemination in a pediatric patient with acute lymphoblastic leukemia.

Spinal cord stimulation with implanted epidural paddle lead relieves chronic axial low back pain.

INTRODUCTION: Spinal cord stimulation (SCS) provides significant relief for lumbosacral radiculopathy refractory to both medical and surgical treatment, but historically only offers limited relief for axial low back pain (LBP). We aim to evaluate the response of chronic axial LBP treated with SCS using a surgically implanted epidural paddle lead. MATERIALS AND METHODS: This is a retrospective review of a consecutive series of patients with exclusive LBP or predominant LBP associated with lower extremity (LE) pain evaluated and treated with SCS using an implanted paddle lead within the dorsal thoracic epidural space. Baseline LBP, and if present LE pain, were recorded using the visual analogue scale (VAS) at an initial evaluation. At a follow-up visit (a minimum of 12 months later), LBP and LE pain after a spinal cord stimulator implantation were again recorded using the VAS. Patients were also asked to estimate total LBP pain relief achieved. RESULTS: Patients with either exclusive (n=7) or predominant (n=2) axial LBP were treated with SCS by implantation of a paddle lead at an average spine level of T9. The baseline VAS score for LBP was 7.2; after a follow-up of 20 months, the score decreased to 2.3 (P=0.003). The LE pain VAS score decreased from 7.5 to 0.0 (P=0.103). Patients also reported a subjective 66.4% decrease of their LBP at follow-up. There were no surgical complications. CONCLUSIONS: Axial LBP is refractory to many treatments, including SCS. SCS using a surgically implanted paddle electrode provides significant pain relief for chronic axial LPB, and is a safe treatment modality.

Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1.

BACKGROUND: Patients with brain tumors suffer significant thrombotic morbidity and mortality. In addition to increased thrombin generation via tumor release of tissue factor-bearing microparticles and hyperfibrinogenemia, brain tumors and surrounding normal brain likely generate endogenous carbon monoxide (CO) via the hemeoxygenase-1 (HO-1) system. CO has been shown to enhance plasmatic coagulation via formation of carboxyhemefibrinogen (COHF). Thus, our goals in this study were to determine whether patients with brain tumors had increased HO-1 upregulation/CO production, plasmatic hypercoagulability, and formation of COHF. METHODS: Patients with brain tumors (N = 20) undergoing craniotomy had blood collected for determination of carboxyhemoglobin as a marker of HO-1 activity, plasmatic hypercoagulability (defined as clot strength > 95% confidence interval value of normal subject plasma), and COHF formation (determined with a thrombelastograph-based assay). Plasma obtained from commercially available normal subjects (N = 30) was used for comparison with brain tumor patient samples. RESULTS: Brain tumor patients had carboxyhemoglobin concentrations of 1.5% ± 0.5% (mean ± SD), indicative of HO-1 upregulation. Compared with normal subject plasma, brain tumor patient plasma had significantly (P < 0.0001) greater clot formation velocity (5.2 ± 1.5 vs 9.5 ± 2.3 dynes/cm/s, respectively) and significantly (P = 0.00016) stronger final clot strength (166 ± 28 vs 230 ± 78 dynes/cm, respectively). Ten of the brain tumor patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal subjects, and 12 of the brain tumor patients had COHF formation. Five of the brain tumor patients in the hypercoagulable subgroup had COHF formation. Last, 5 of the hypercoagulable patients had primary brain tumors, whereas the other 5 patients had metastatic tumors or an inflammatory mass lesion. CONCLUSIONS: A subset of patients with brain tumors has increased endogenous CO production, plasmatic hypercoagulability, and COHF formation. Future investigation of the role played by HO-1 derived CO in the pathogenesis of brain tumor-associated thrombophilia is warranted.

Current management and surgical outcomes of medically intractable epilepsy.

Epilepsy is one of the most common neurologic disorders in the world. While anti-epileptic drugs (AEDs) are the mainstay of treatment in most cases, as many as one-third of patients will have a refractory form of disease indicating the need for a neurosurgical evaluation. Ever since the first half of the twentieth century, surgery has been a major treatment option for epilepsy, but the last 10-15 years in particular has seen several major advances. As shown in relatively recent studies, resection is more effective for medically intractable epilepsy (MIE) than AED treatment alone, which is why most clinicians now endorse a neurosurgical consultation after approximately two failed regimens of AEDs, ultimately leading to decreased healthcare costs and increased quality of life. Temporal lobe epilepsy (TLE) is the most common form of MIE and comprises about 80% of epilepsy surgeries with the majority of patients gaining complete seizure-freedom. As the number of procedures and different approaches continues to grow, temporal lobectomy remains consistently focused on resection of mesial structures such as the amygdala, hippocampus, and parahippocampal gyrus while preserving as much of the neocortex as possible resulting in optimum seizure control with minimal neurological deficits. MIE originating outside the temporal lobe is also effectively treated with resection. Though not as successful as TLE surgery because of their frequent proximity to eloquent brain structures and more diffuse pathology, epileptogenic foci located extratemporally also benefit from resection. Favorable seizure outcome in each of these procedures has heavily relied on pre-operative imaging, especially since the massive surge in MRI technology just over 20 years ago. However, in the absence of visible lesions on MRI, recent improvements in secondary imaging modalities such as fluorodeoxyglucose positron emission computed tomography (FDG-PET) and single-photon emission computed tomography (SPECT) have lead to progressively better long-term seizure outcomes by increasing the neurosurgeon's visualization of supposed non-lesional foci. Additionally, being historically viewed as a drastic surgical intervention for MIE, hemispherectomy has been extensively used quite successfully for diffuse epilepsies often found in pediatric patients. Although total anatomic hemispherectomy is not utilized as commonly today, it has given rise to current disconnective techniques such as hemispherotomy. Therefore, severe forms of hemispheric developmental epilepsy can now be surgically treated while substantially decreasing the amount of potential long-term complications resulting from cavitation of the brain following anatomical hemispherectomy. Despite the rapid pace at which we are gaining further knowledge about epilepsy and its surgical treatment, there remains a sizeable underutilization of such procedures. By reviewing the recent literature on resective treatment of MIE, we provide a recent up-date on epilepsy surgery while focusing on historical perspectives, techniques, prognostic indicators, outcomes, and complications associated with several different types of procedures.

Curcuminoids limit neutrophil-mediated reperfusion injury in experimental stroke by targeting the endothelium.

OBJECTIVE: We sought to test the hypothesis that turmeric-derived curcuminoids limit reperfusion brain injury in an experimental model of stroke via blockade of early microvascular inflammation during reperfusion. METHODS: Male Sprague Dawley rats subjected to MCAO/R were treated with turmeric-derived curcuminoids (vs. vehicle) 1 hour prior to reperfusion (300 mg/kg ip). Neutrophil adhesion to the cerebral microcirculation and measures of neutrophil and endothelial activation were assayed during early reperfusion (0-4 hours); cerebral infarct size, edema, and neurological function were assessed at 24 hours. Curcuminoid effects on TNFα-stimulated human brain microvascular endothelial cell (HBMVEC) were assessed. RESULTS: Early during reperfusion following MCAO, curcuminoid treatment decreased neutrophil rolling and adhesion to the cerebrovascular endothelium by 76% and 67% and prevented >50% of the fall in shear rate. The increased number and activation state (CD11b and ROS) of neutrophils were unchanged by curcuminoid treatment, while increased cerebral expression of TNFα and ICAM-1, a marker of endothelial activation, were blocked by >30%. Curcuminoids inhibited NF-κB activation and subsequent ICAM-1 gene expression in HBMVEC. CONCLUSION: Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.

Treatment of chronic, intractable pain with a conventional implantable pulse generator: a meta-analysis of 4 clinical studies.

OBJECTIVE: To provide further short-term (6 mo) and long-term (1 y) evidence for the use of spinal cord stimulation (SCS) with a conventional implantable pulse generator in the management of chronic, intractable pain. MATERIALS AND METHODS: We conducted a meta-analysis of 4 prospective, multicenter studies that collected outcome data from patients implanted with SCS to treat chronic pain of the trunk and/or limbs (Genesis IPG system). Two of these were conducted as long-term studies lasting 1 year, and 2 as shorter term studies lasting 6 months. A total of 300 patients from 28 investigational sites were prospectively evaluated for efficacy at 3 months after implant and safety at 6 months after implant. None of the sites participated in more than one study. Outcome measures included patient-reported percent of pain relief, patient satisfaction, quality of life improvement, pain evaluation (0 to 10 rating), pain relief rating, Short-Form McGill Pain Questionnaire, visual analog scale, the Short Form-36, and the total number of adverse events (AEs). RESULTS: At 3 months after implantation of the permanent system, 75.4% of the patients (190/252) reported a 50% or greater pain relief as determined by the patient-reported degree of pain relief. Similarly, assessment of patient satisfaction with SCS therapy showed that 86.1% of patients (217/252) in all 4 studies were satisfied or very satisfied with the therapy at 3 months. In the 2 long-term studies, 80.9% of patients (140/173) were satisfied or very satisfied with the therapy at the 1-year evaluation point. Quality-of-life (QoL) data indicated that at 3 months after implant, 77.8% of patients (196/252) reported QoL as improved or greatly improved. Similarly, QoL was improved or greatly improved for 74.0% patients in the long-term study at 1 year (128/173). In the safety analysis, AEs were reviewed for all 4 studies. A total of 190 AEs were reported in 117 of 300 patients during all studies. CONCLUSIONS: This analysis provides further evidence of the safety and effectiveness of SCS in treating chronic intractable pain of the trunk and/or limbs. Specifically, it underscores a high level of effectiveness and acceptable safety concerns in the use of nonrechargeable SCS devices.

A multicenter, single-blind, prospective randomized trial to evaluate the safety of a polyethylene glycol hydrogel (Duraseal Dural Sealant System) as a dural sealant in cranial surgery.

OBJECTIVE: Incisional cerebrospinal fluid (CSF) leakage after cranial surgery is a significant cause of morbidity due to poor wound healing and infection, meningitis, and pseudomeningocele formation. Many common dural closure techniques, such as sutures, autologous grafts, gelatin or collagen sponges, and fibrin glues, are used to achieve watertight closure, although none are US Food and Drug Administration approved for this use. DuraSeal Dural Sealant System is a polyethylene glycol (PEG) hydrogel approved by the U.S. Food and Drug Administration for obtaining watertight dural closure when applied after standard dural suturing. This multicenter, prospective randomized study further evaluated the safety of a PEG hydrogel compared with common dural sealing techniques. METHODS: A total of 237 patients undergoing elective cranial surgery at 17 institutions were randomized to dural closure augmented with the PEG hydrogel or a control "standard of care" dural sealing technique after Valsalva maneuver demonstrated an intraoperative nonwatertight dural closure. Data were collected on complications resulting in unplanned postoperative interventions or reoperations, surgical site infections, CSF leaks, and other neurological complications within 30 days. Surgeons also provided data on the ease of use of the dural sealing techniques, as well as preparation and application times. RESULTS: The incidences of neurosurgical complications, surgical site infections, and CSF leaks were similar between treatment and control groups, with no statistically significant difference between the measures. In the PEG hydrogel group (n = 120), the incidence of neurosurgical complications was 5.8% (n = 7), the incidence of surgical site infections was 1.7% (n = 2), and the incidence of CSF leak was 0.8% (n = 1). In the control group (n = 117), the incidence of neurosurgical complications was 7.7% (n = 9), the incidence of surgical site infection was 2.6% (n = 3), and the incidence of CSF leak was 1.7% (n = 2). Sealant preparation time was less than 5 minutes in 96.6% of the PEG hydrogel group compared with 66.4% of controls (P < 0.001). The dural augmentation was applied in less than 1 minute in 85.7% of the PEG hydrogel group compared with 66.4% of the control group (P < 0.001). CONCLUSIONS: The PEG hydrogel dural sealant used in this study has a similar safety profile to commonly used dural sealing techniques when used as dural closure augmentation in cranial surgery. The PEG hydrogel dural sealant demonstrated faster preparation and application times than other commonly used dural sealing techniques.

Peripheral nerve stimulation for trigeminal neuropathic pain.

Facial pain is a complex disease with a number of possible etiologies. Trigeminal neuropathic pain (TNP) is defined as pain caused by a lesion or disease of the trigeminal branch of the peripheral nervous system resulting in chronic facial pain over the distribution of the injured nerve. First line treatment of TNP includes management with anticonvulsant medication (carbamazepine, phenytoin, gabapentin, etc.), baclofen, and analgesics. TNP, however, can be a condition difficult to adequately treat with medical management alone. Patients with TNP can suffer from significant morbidity as a result of inadequate treatment or the side effects of pharmacologic therapy. TNP refractory to medical management can be considered for treatment with a growing number of invasive procedures. Peripheral nerve stimulation (PNS) is a minimally invasive option that has been shown to effectively treat medically intractable TNP. We present a case series of common causes of TNP successfully treated with PNS with up to a 2 year follow-up. Only one patient required implantation of new electrode leads secondary to electrode migration. The patients in this case series continue to have significant symptomatic relief, demonstrating PNS as an effective treatment option for intractable TNP. Though there are no randomized trials, peripheral neuromodulation has been shown to be an effective means of treating TNP refractory to medical management in a growing number of case series. PNS is a safe procedure that can be performed even on patients that are not optimal surgical candidates and should be considered for patients suffering from TNP that have failed medical management.

Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris in an immunocompetent girl.

BACKGROUND: Balamuthia mandrillaris is a recently recognized cause of a rare, devastating infection, granulomatous amoebic encephalitis (GAE). Presenting symptoms of GAE are nonspecific and can last for months before becoming clinically significant. Once the infection involves the central nervous system, death often results within days to weeks. A high degree of clinical suspicion is needed to correctly diagnose this infection because definitive diagnostic tests are presently limited, and even then there are only sparse data concerning effective treatment. The importance of early diagnosis is emphasized because delay likely contributes to the extremely high mortality with this infection. METHODS: This study presents a previously healthy, immunocompetent 2-year-old female patient who succumbed to GAE secondary to B. mandrillaris, with the intention of raising awareness of this devastating infection. RESULTS: Balamuthia amoebic encephalitis is a devastating form of amoebic encephalitis that is increasingly reported in the literature. CONCLUSIONS: GAE should be considered for a patient with atypical encephalitis and single or multiple lesions with surrounding edema evident on neurodiagnostic imaging.

Establishment of primary cultures of human brain microvascular endothelial cells to provide an in vitro cellular model of the blood-brain barrier.

We describe a method for generating primary cultures of human brain microvascular endothelial cells (HBMVECs). HBMVECs are derived from microvessels isolated from temporal tissue removed during operative treatment of epilepsy. The tissue is mechanically fragmented and size filtered using polyester meshes. The resulting microvessel fragments are placed onto type I collagen-coated flasks to allow HBMVECs to migrate and proliferate. The overall process takes less than 3 h and does not require specialized equipment or enzymatic processes. HBMVECs are typically cultured for approximately 1 month until confluent. Cultures are highly pure ( approximately 97% endothelial cells; approximately 3% pericytes), are reproducible, and show characteristic brain endothelial markers (von Willebrand factor, glucose transporter-1) and robust expression of tight and adherens junction proteins as well as caveolin-1 and efflux protein P-glycoprotein. Monolayers of HBMVECs show characteristically high transendothelial electric resistance and have proven useful in multiple functional studies for in vitro modeling of the human blood-brain barrier.

Time from ictal subdural EEG seizure onset to clinical seizure onset: an electrocorticographic time factor associated with temporal lobe epileptogenicity.

Long-term subdural video/electroencephalographic (EEG) monitoring was performed in a series of patients with medically intractable complex partial seizures, in a study of diagnostic accuracy, to test the hypothesis that the time from ictal subdural EEG seizure onset to clinical seizure onset (ECOT) is correlated with temporal lobe epileptogenicity and confirm measures of validity of ECOT for predicting seizure-free outcome following anterior temporal lobectomy and amygdalohippocampectomy (ATL/AH). In 34 patients with refractory temporal lobe epilepsy, subdural EEG monitoring localized the ictal epileptogenic focus to a single temporal lobe. In each patient, ECOT was analysed for correlation with temporal lobe epileptogenicity as measured by seizure interval in hours. Patients in whom ECOT was equal to or less than the mean (i.e. subdural EEG seizure onset preceding clinical seizure onset by at least 11.7 seconds) had a significantly greater likelihood of becoming seizure-free following ATL/AH compared to patients in whom ECOT was greater than the mean (i.e. subdural EEG seizure onset preceding clinical seizure onset by less than 11.7 seconds) (x(2) = 5.78, p<0.05). The validity of ECOT for predicting seizure-free outcome following ATL/AH is confirmed to have sensitivity of 55.0%, specificity of 85.7%, false positive rate of 15.4%, false negative rate of 42.9%, diagnostic value of 84.6% and diagnostic accuracy of 67.6%. In addition, a significant correlation, described by a second order polynomial relationship, was found between the natural exponential function of ECOT and seizure interval [f(x=0.415x(2) -25.554x + 267.036, r= 0.731, df= 32, t =6.05, p<0.001, where f(x)=e(ECOT) and x= seizure interval). This result provides the epileptologist with a quantitative tool capable of predicting seizure interval based on ECOT. The capability of ECOT to predict seizure interval may allow the patient and epileptologist to anticipate future seizure onset based on ECOT, potentially facilitating accurate timing of ictal seizure focus localization techniques and clinical intervention to abort seizure onset using various available central and peripheral nervous system stimulation therapeutic strategies. The results suggest a relationship between ECOT and seizure interval. Fundamental pathophysiologic processes involved in the transition from ictal EEG to clinical seizure onset may be responsible for temporal lobe epileptogenicity.

Predicting functional gains in a stroke trial.

BACKGROUND AND PURPOSE: A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment. METHODS: Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains. RESULTS: Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment. CONCLUSIONS: Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention.