Yasunori Nagahama

Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: association with reduced risk of clinical vasospasm and delayed cerebral ischemia

OBJECTIVE Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients. METHODS Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression. RESULTS Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097-0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01-0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9). CONCLUSIONS The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

Bone flap elevation for intracranial EEG monitoring: technical note

Intracranial electroencephalography (iEEG) provides invaluable information in determining seizure focus and spread due to its high spatial and temporal resolution, which are not afforded by noninvasive studies. Electrodes of various types (e.g., grid, strip, and depth electrodes) and configurations are often used for optimum coverage of suspected areas of seizure onset and propagation. Given the fixed intracranial volume and added mass effect from placement of cortical electrodes, brain edema and postoperative deficits can occur. The authors describe a simple, inexpensive, and highly effective technique of bone flap replacement using standard titanium plates to expand the intracranial volume and minimize risks of brain compression and intracranial hypertension. Rectangular titanium plates are bent and placed in a way that secures the bone flap in a slightly elevated position relative to the adjacent calvaria during iEEG monitoring. The authors evaluated the degree of bone flap elevation and amount of volume created using this technique in 3 iEEG cases. They then compared these results with the bone flap elevation and volume created using linear titanium plates, a method they had used previously. The use of rectangular plates produced on average 6.6 mm of bone flap elevation, compared with only 1.8 mm of bone flap elevation with the use of linear plates, resulting in a statistically significant 261% increase in bone flap elevation (p ≤ 0.001). The authors suggest that rectangular plates may provide stronger resistance to scalp tension after myocutaneous skin closure compared with the linear plates and that subsidence of the bone flap likely occurred with the use of linear plates. In summary, the described technique utilizing rectangular plates creates significantly increased bone flap elevation compared with a similar method using linear plates, and it may reduce the risk of neurological deficits related to intracranial electrode placement.

Functional hemispherotomy in Rasmussen syndrome in the absence of classic MRI findings.

A 7-year-old previously healthy girl presented with a left-sided focal seizure without impaired consciousness and subsequently developed epilepsia partialis continua. Initial MRI was normal, and the subsequent images only showed a focal T2/FLAIR hyperintense area without cortical atrophy. She was diagnosed with Rasmussen syndrome by pathology and promptly treated with functional hemispherotomy. Rasmussen syndrome is a rare progressive neurological disorder, the only definitive cure for which is hemispheric disconnection. The disease presents a management dilemma, especially early in disease course without characteristic neuroimaging features. A high index of suspicion, multidisciplinary approach, and clear timely communication with the family are critical.

Catenin delta-1 (CTNND1) phosphorylation controls the mesenchymal to epithelial transition in astrocytic tumors.

Inactivating mutations of the TSC1/TSC2 complex (TSC1/2) cause tuberous sclerosis (TSC), a hereditary syndrome with neurological symptoms and benign hamartoma tumours in the brain. Since TSC effectors are largely unknown in the human brain, TSC patient cortical tubers were used to uncover hyperphosphorylation unique to TSC primary astrocytes, the cell type affected in the brain. We found abnormal hyperphosphorylation of catenin delta-1 S268, which was reversible by mTOR-specific inhibitors. In contrast, in three metastatic astrocytoma cell lines, S268 was under phosphorylated, suggesting S268 phosphorylation controls metastasis. TSC astrocytes appeared epithelial (i.e. tightly adherent, less motile, and epithelial (E)-cadherin positive), whereas wild-type astrocytes were mesenchymal (i.e. E-cadherin negative and highly motile). Despite their epithelial phenotype, TSC astrocytes outgrew contact inhibition, and monolayers sporadically generated tuberous foci, a phenotype blocked by the mTOR inhibitor, Torin1. Also, mTOR-regulated phosphokinase C epsilon (PKCe) activity induced phosphorylation of catenin delta-1 S268, which in turn mediated cell-cell adhesion in astrocytes. The mTOR-dependent, epithelial phenotype of TSC astrocytes suggests TSC1/2 and mTOR tune the phosphorylation level of catenin delta-1 by controlling PKCe activity, thereby regulating the mesenchymal-epithelial-transition (MET). Thus, some forms of TSC could be treated with PKCe inhibitors, while metastasis of astrocytomas might be blocked by PKCe stimulators.

Intracranial EEG for seizure focus localization: evolving techniques, outcomes, complications, and utility of combining surface and depth electrodes

OBJECTIVEIntracranial electroencephalography (iEEG) provides valuable information that guides clinical decision-making in patients undergoing epilepsy surgery, but it carries technical challenges and risks. The technical approaches used and reported rates of complications vary across institutions and evolve over time with increasing experience. In this report, the authors describe the strategy at the University of Iowa using both surface and depth electrodes and analyze outcomes and complications.METHODSThe authors performed a retrospective review and analysis of all patients who underwent craniotomy and electrode implantation from January 2006 through December 2015 at the University of Iowa Hospitals and Clinics. The basic demographic and clinical information was collected, including electrode coverage, monitoring results, outcomes, and complications. The correlations between clinically significant complications with various clinical variables were analyzed using multivariate analysis. The Fisher exact test was used to evaluate a change in the rate of complications over the study period.RESULTSNinety-one patients (mean age 29 ± 14 years, range 3-62 years), including 22 pediatric patients, underwent iEEG. Subdural surface (grid and/or strip) electrodes were utilized in all patients, and depth electrodes were also placed in 89 (97.8%) patients. The total number of electrode contacts placed per patient averaged 151 ± 58. The duration of invasive monitoring averaged 12.0 ± 5.1 days. In 84 (92.3%) patients, a seizure focus was localized by ictal onset (82 cases) or inferred based on interictal discharges (2 patients). Localization was achieved based on data obtained from surface electrodes alone (29 patients), depth electrodes alone (13 patients), or a combination of both surface and depth electrodes (42 patients). Seventy-two (79.1%) patients ultimately underwent resective surgery. Forty-seven (65.3%) and 18 (25.0%) patients achieved modified Engel class I and II outcomes, respectively. The mean follow-up duration was 3.9 ± 2.9 (range 0.1-10.5) years. Clinically significant complications occurred in 8 patients, including hematoma in 3 (3.3%) patients, infection/osteomyelitis in 3 (3.3%) patients, and edema/compression in 2 (2.2%) patients. One patient developed a permanent neurological deficit (1.1%), and there were no deaths. The hemorrhagic and edema/compression complications correlated significantly with the total number of electrode contacts (p = 0.01), but not with age, a history of prior cranial surgery, laterality, monitoring duration, and the number of each electrode type. The small number of infectious complications precluded multivariate analysis. The number of complications decreased from 5 of 36 cases (13.9%) to 3 of 55 cases (5.5%) during the first and last 5 years, respectively, but this change was not statistically significant (p = 0.26).CONCLUSIONSAn iEEG implantation strategy that makes use of both surface and depth electrodes is safe and effective at identifying seizure foci in patients with medically refractory epilepsy. With experience and iterative refinement of technical surgical details, the risk of complications has decreased over time.

Deep brain stimulation hardware–related infections: 10-year experience at a single institution

OBJECTIVEDeep brain stimulation is an effective surgical treatment for managing some neurological and psychiatric disorders. Infection related to the deep brain stimulator (DBS) hardware causes significant morbidity: hardware explantation may be required; initial disease symptoms such as tremor, rigidity, and bradykinesia may recur; and the medication requirements for adequate disease management may increase. These morbidities are of particular concern given that published DBS-related infection rates have been as high as 23%. To date, however, the key risk factors for and the potential preventive measures against these infections remain largely uncharacterized. In this study, the authors endeavored to identify possible risk factors for DBS-related infection and analyze the efficacy of prophylactic intrawound vancomycin powder (VP).METHODSThe authors performed a retrospective cohort study of patients who had undergone primary DBS implantation at a single institution in the period from December 2005 through September 2015 to identify possible risk factors for surgical site infection (SSI) and to assess the impact of perioperative (before, during, and after surgery) prophylactic antibiotics on the SSI rate. They also evaluated the effect of a change in the National Healthcare Safety Networks definition of SSI on the number of infections detected. Statistical analyses were performed using the 2-sample t-test, the Wilcoxon rank-sum test, the chi-square test, Fishers exact test, or logistic regression, as appropriate for the variables examined.RESULTSFour hundred sixty-four electrodes were placed in 242 adults during 245 primary procedures over approximately 10.5 years; most patients underwent bilateral electrode implantation. Among the 245 procedures, 9 SSIs (3.7%) occurred within 90 days and 16 (6.5%) occurred within 1 year of DBS placement. Gram-positive bacteria were the most common etiological agents. Most patient- and procedure-related characteristics did not differ between those who had acquired an SSI and those who had not. The rate of SSIs among patients who had received intrawound VP was only 3.3% compared with 9.7% among those who had not received topical VP (OR 0.32, 95% CI 0.10-1.02, p = 0.04). After controlling for patient sex, the association between VP and decreased SSI risk did not reach the predetermined level of significance (adjusted OR 0.32, 95% CI 0.10-1.03, p = 0.06). The SSI rates were similar after staged and unstaged implantations.CONCLUSIONSWhile most patient-related and procedure-related factors assessed in this study were not associated with the risk for an SSI, the data did suggest that intrawound VP may help to reduce the SSI risk after DBS implantation. Furthermore, given the implications of SSI after DBS surgery and the frequency of infections occurring more than 90 days after implantation, continued follow-up for at least 1 year after such a procedure is prudent to establish the true burden of these infections and to properly treat them when they do occur.

Accuracy of detecting enlargement of aneurysms using different MRI modalities and measurement protocols

In BriefTo reliably assess the individual and agreement rates of accurately detecting intracranial aneurysm enlargement, the authors performed this study using flow phantom models and generally used MRI modalities. The results of this study suggest that the detection rate of at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or different measurement protocols.

Red man syndrome caused by vancomycin powder

Red man syndrome (RMS) is a well-known hypersensitivity reaction caused by intravenous administration of vancomycin, with symptoms ranging from flushing, erythematous rash, pruritus, mild to profound hypotension, and even cardiac arrest. RMS has not previously been described from local application of vancomycin powder in a surgical wound, a technique increasingly utilized for infection prophylaxis in many surgical disciplines including neurosurgery. We describe the first reported case of RMS as a result of local intra-wound application of vancomycin powder for infection prophylaxis. A 73-year-old male with a history of Parkinsons disease underwent 2-stage deep brain stimulation implantation surgeries. Vancomycin powder was applied locally in the surgical wounds for infection prophylaxis during both of the surgeries. The patient developed a well-demarcated, geometric erythematous pruritic rash following the second surgery that was clinically diagnosed as RMS and resolved without sequelae.

Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging

Background: Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood. Methods: The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects. Results: In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed. Conclusions: With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

Temporal lobe asymmetry in FDG-PET uptake predicts neuropsychological and seizure outcomes after temporal lobectomy

OBJECTIVE The objective of this study was to determine whether preoperative [18F]fludeoxyglucose (FDG)-positron emission tomography (PET) asymmetry in temporal lobe metabolism predicts neuropsychological and seizure outcomes after temporal lobectomy (TL). METHODS An archival sample of 47 adults with unilateral temporal lobe epilepsy who underwent TL of their language-dominant (29 left, 1 right) or nondominant (17 right) hemisphere were administered neuropsychological measures pre- and postoperatively. Post-TL seizure outcomes were measured at 1year. Regional FDG uptake values were defined by an automated technique, and a quantitative asymmetry index (AI) was calculated to represent the relative difference in the FDG uptake in the epileptic relative to the nonepileptic temporal lobe for four regions of interest: medial anterior temporal (MAT), lateral anterior temporal (LAT), medial posterior temporal (MPT), and lateral posterior temporal (LPT) cortices. RESULTS In language-dominant TL, naming outcomes were predicted by FDG uptake asymmetry in the MAT (r=-0.38) and LPT (r=-0.45) regions. For all patients, visual search and motor speed outcomes were predicted by FDG uptake asymmetry in all temporal regions (MPT, r=0.42; MAT, r=0.34; LPT, r=0.47; LAT, r=0.51). Seizure outcomes were predicted by FDG uptake asymmetry in the MAT (r=0.36) and MPT (r=0.30) regions. In all of these significant associations, greater hypometabolism in regions of the epileptic temporal lobe was associated with better postoperative outcomes. CONCLUSIONS Our results support the conclusion that FDG uptake asymmetry is a useful clinical tool in assessing risk for cognitive changes in patients being considered for TL.