Citations

Object The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation–evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM). Methods The WINCS was used for FSCV, which consisted of a triangle wave scanned between −0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 μm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ~ 50 μm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra. Results The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV. Conclusions Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.

Object The purpose of this study was to evaluate the incidence of seizures or epileptiform abnormalities on electroencephalography (EEG) studies in patients undergoing surgical treatment for acute subdural hematoma (SDH). Methods This was a retrospective study of 134 consecutive patients with acute or acute-on-chronic SDH who underwent surgical treatment at the authors' institution between January 2004 and July 2008. Detailed information was collected regarding baseline clinical data (including preexistent functional impairment); Glasgow Coma Scale (GCS) sum scores before and 24 hours after surgery; presence of clinical seizures; EEG findings; and functional outcome on discharge and up to the 6-month follow-up. All brain CT scans were reviewed to calculate SDH volume and midline shift. The Glasgow Outcome Scale (GOS) score was used for functional assessment, and GOS scores of 1–3 were considered indicative of poor outcome. Univariate and multivariate logistic regression analyses were performed to identify statistical associations. Results Clinical seizures or epileptiform changes on EEG were observed during the acute postoperative period in 33 patients (25%). Preexistent functional impairment and seizures/epileptiform EEG findings after surgery were independently associated with poor functional outcome upon hospital discharge (p < 0.001 for both). Preexistent functional impairment (p < 0.001), lower GCS score before surgery (p = 0.04), and lower GCS score 24 hours after surgery (p = 0.007), but not seizures/epileptiform EEG findings, were independently associated with poor functional recovery at 1- to 6-month follow-up evaluations. Seizures/epileptiform EEG findings had a strong association with lower GCS scores after surgery (p = 0.01), and they were more common in patients who underwent evacuation by craniotomy (p = 0.02). Conclusions Epileptic complications are common after acute SDH evacuation, and should be suspected in patients with an unanticipated depressed level of consciousness after surgery. Seizures worsen early functional outcome, but delayed favorable recovery is possible. Therefore, one should be cautious when discussing prognosis in the early postoperative period of patients with epileptic complications.

Abstract Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610–6)

Chordoma is a tumor of the axial skeleton that is distinctly uncommon in children and adolescents. Previous observations have suggested that chordomas in pediatric patients differ from adult chordomas in presentation, morphology, and behavior. This study examines the clinical and histologic features of chordomas in young patients (≤25 years old). All cases from the Mayo Clinic files were graphed according to age and a bimodal distribution was observed. The 35 cases representing the youngest population were selected for review. Histopathology ranged from low cellularity tumors with lobulated architecture and abundant myxoid matrix (conventional chordoma), to those with varying amounts of chondroid matrix (chondroid chordoma), to more cellular tumors (atypical chordoma), and finally to neoplasms with high-grade spindle-cell differentiation (dedifferentiated chordoma). Over an average follow-up period of 129 months (range 1 to 501 months), there were 13 deaths (37%) and 3 patients with metastasis. This survival rate was slightly better than the reported mortality rate for adults with chordoma, but there was a subset of young patients (those with atypical chordoma) that had a significantly worse survival rate, suggesting that histologic subtyping may be predictive of prognosis.

SummaryThe relationship between allergic airway inflammation and pneumococcal pneumonia is not well understood. We assessed susceptibility to experimental pneumococcal pneumonia in mice with and without allergic airway inflammation. Susceptibility to pneumococcal pneumonia was evaluated by challenging mice with a bioluminescent Streptococcus pneumoniae strain after sensitization with ovalbumin (OVA), with subsequent monitoring of pneumococcal infection using real-time photonic imaging. Of 46 OVA-sensitized mice challenged with pneumococci, 13 (28%) developed imaging findings consistent with pneumococcal pneumonia. In comparison, 28 (57%) of 49 non-sensitized control mice developed pneumococcal pneumonia (P = 0·005). While none of the control group developed meningitis (0%, none of 28), two mice in the OVA-sensitized group developed meningitis (15·4%, two of 13) (P = 0·09). The mean bacterial count in the lung was significantly lower in the OVA-sensitized than the non-sensitized group (8·26 ± 0·69 versus 9·21 ± 0·67 log10 colony-forming units (CFU)/g, P = 0·002). There was a trend towards the mean bacterial count in the spleen being higher in the OVA-sensitized versus the non-sensitized group (8·14 ± 0·89 versus 7·45 ± 1·07 log10 CFU/g, P = 0·071). A high level of interleukin (IL)-4 in lung homogenates was associated with risk of pneumococcal infection independent of sensitization with OVA (odds ratio: 49·7, 95% confidence interval 2·92-846·5, per increment of 1·0 pg/ml). In the murine model studied, acute allergic airway inflammation reduced susceptibility to pneumococcal pneumonia. IL-4 may increase the risk of pneumococcal pneumonia independently of allergic airway inflammation.