Evoked versus spontaneous high frequency oscillations in the chronic electrocorticogram in focal epilepsy.

OBJECTIVE: Spontaneous high frequency oscillations (HFOs; ripples 80-250Hz, fast ripples (FRs) 250-500Hz) are biomarkers for epileptogenic tissue in focal epilepsy. Single pulse electrical stimulation (SPES) can evoke HFOs. We hypothesized that stimulation distinguishes pathological from physiological ripples and compared the occurrence of evoked and spontaneous HFOs within the seizure onset zone (SOZ) and eloquent functional areas. METHODS: Ten patients underwent SPES during 2048Hz electrocorticography (ECoG). Evoked HFOs in time-frequency plots and spontaneous HFOs were visually analyzed. We compared electrodes with evoked and spontaneous HFOs for: percentages in the SOZ, sensitivity and specificity for the SOZ, percentages in functional areas outside the SOZ. RESULTS: Two patients without spontaneous FRs showed evoked FRs in the SOZ. Percentages of evoked and spontaneous HFOs in the SOZ were similar (ripples 32:33%, p=0.77; FRs 43:48%, p=0.63), but evoked HFOs had generally a lower specificity (ripples 45:69%, p=0.02; FRs 83:92%, p=0.04) and higher sensitivity (ripples 85:70%, p=0.27; FRs 52:37%, p=0.05). More electrodes with evoked than spontaneous ripples were found in functional (54:30%, p=0.03) and 'silent' areas (57:27%, p=0.01) outside the SOZ. CONCLUSIONS: SPES can elicit SOZ-specific FRs in patients without spontaneous FRs, but activates ripples in all areas. SIGNIFICANCE: SPES is an alternative for waiting for spontaneous HFOs, but does not warrant exclusively pathological ripples.

High frequency oscillations and high frequency functional network characteristics in the intraoperative electrocorticogram in epilepsy.

OBJECTIVE: High frequency oscillations (HFOs; > 80 Hz), especially fast ripples (FRs, 250-500 Hz), are novel biomarkers for epileptogenic tissue. The pathophysiology suggests enhanced functional connectivity within FR generating tissue. Our aim was to determine the relation between brain areas showing FRs and 'baseline' functional connectivity within EEG networks, especially in the high frequency bands. METHODS: We marked FRs, ripples (80-250 Hz) and spikes in the electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We assessed 'baseline' functional connectivity in epochs free of epileptiform events within these recordings, using the phase lag index. We computed the Eigenvector Centrality (EC) per channel in the FR and gamma band network. We compared EC between channels that did or did not show events at other moments in time. RESULTS: FR-band EC was higher in channels with than without spikes. Gamma-band EC was lower in channels with ripples and FRs. CONCLUSIONS: We confirmed previous findings of functional isolation in the gamma-band and found a first proof of functional integration in the FR-band network of channels covering presumed epileptogenic tissue. SIGNIFICANCE: 'Baseline' high-frequency network parameters might help intra-operative recognition of epileptogenic tissue without the need for waiting for events. These findings can increase our understanding of the 'architecture' of epileptogenic networks and help unravel the pathophysiology of HFOs.

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

OBJECTIVE: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS: We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). RESULTS: Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. CONCLUSION: Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SIGNIFICANCE: Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network.

Missing patients in a regional trauma registry: incidence and predictors.

BACKGROUND: Trauma systems have data registries in order to describe and evaluate (the quality of) trauma care. If results between centres and countries (benchmarking) are to be compared, data has to be accurate, reliable and complete. All trauma registries deal with incompleteness. A contributor to incompleteness of the data is failure to include patients that fulfil the criteria; the so-called missing patients. The aim of this study is to assess the number of missing patients in our regional trauma registry and to identify predictors for being missing from the trauma registry. METHODS: A random sample was taken. Four calendar weeks from 2012 were selected and medical files of all consecutive presentations to the emergency department or trauma room during those weeks were studied. Patients who were already correctly included in the trauma registry were assigned to the 'included' group and patients who should have been but were not to the 'missing' group. Multivariable logistic regression analysis was performed to identify predictors for being missed from the trauma registry. RESULTS: Of a total of 338 patients, 50 (15%) were identified as missing. Characteristics of the missing patients did not differ substantially from the included patients. Transfer to another hospital after initial assessment and presentation in a Level 3 hospital compared to a Level 1 hospital were independent predictors for being missed from the trauma registry, with an adjusted odds ratio of 5.86 (95% CI: 2.08-16.52) and 6.64 (95% CI: 1.86-23.78), respectively. CONCLUSIONS: Overall, 15% of the patients who met the inclusion criteria of the trauma registry were not included in the registry. Special attention should be paid to patients who are transferred to other hospitals in the network after initial assessment and to registration in Level 3 hospitals.

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery.

OBJECTIVE: Removal of brain tissue showing high frequency oscillations (HFOs; ripples: 80-250Hz and fast ripples: 250-500Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG). METHODS: HFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes. RESULTS: Ripple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p=0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex. CONCLUSIONS: Our observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex. SIGNIFICANCE: Fast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.

Characterization of microsatellite loci in the myco-heterotrophic plant Monotropa hypopitys (Ericaceae) and amplification in related taxa.

The myco-heterotroph Monotropa hypopitys is a perennial, circumboreally distributed herb of significant importance in studies of nonphotosynthetic plant biology. To address a deficiency in our knowledge of myco-heterotroph population genetics, 11 microsatellite markers were developed using a cost-effective, nonradioactive protocol. Multiplex reactions revealed polymorphism in the red and yellow colour forms of M. hypopitys with an average of 2.69 alleles per primer. Many primers additionally amplified in the congener Monotropa uniflora and five other closely related genera. This is the first report of microsatellite primer development and amplification in the Monotropoideae (Ericaceae).

Ketamine sedation for pediatric gastroenterology procedures.

BACKGROUND: Although the dissociative sedative ketamine is used commonly for pediatric procedural sedation in other settings, the safety of this agent in pediatric gastroenterology is not well-studied. A 5-year experience with ketamine sedation for pediatric gastroenterology procedures was reviewed to document the safety profile of this agent and to identify predictors of laryngospasm during esophagogastroduodenoscopy (EGD). METHODS: The study was a retrospective consecutive case series of children receiving ketamine administered by pediatric gastroenterologists skilled in basic airway management to facilitate pediatric gastrointestinal procedures during a 5-year period. Patient's records were reviewed to determine indication, dosage, adverse effects, drugs, inadequate sedation, and recovery time for each sedation. A multiple logistic regression analysis was performed to identify predictors of laryngospasm during EGD. Outcome measures were descriptive features of sedation, including adverse effects and predictors of laryngospasm during EGD. RESULTS: During the study period pediatric gastroenterologists administered ketamine 636 times, primarily for EGD (86%) and primarily by the intravenous route (98%). The median loading dose and total dose were 1.00 mg/kg and 1.34 mg/kg, respectively. Inadequate sedation was noted in seven (1.1%) procedures. Adverse effects included transient laryngospasm (8.2%), emesis (4.1%), recovery agitation (2.4%), partial airway obstruction (1.3%), apnea and respiratory depression (0.5%), and excessive salivation (0.3%). There were no adverse outcomes attributable to ketamine. Nearly half (46%) the subjects had severe underlying illness (American Society of Anesthesiologists (ASA] class > or =3). All instances of laryngospasm occurred during EGD (9.5% incidence), and the only independent predictor of laryngospasm in this sample was decreasing age. The incidence of laryngospasm was 13.9% in preschool-aged (< or =6 years) children and was 3.6% in school-aged (>6 years) children (difference 10.3%, 95% confidence intervals 5.5-14.9%). No dose relationship was noted with laryngospasm, and the risk did not increase with underlying illness. CONCLUSION: Pediatric gastroenterologists skilled in ketamine administration and basic airway management can effectively administer this drug to facilitate gastrointestinal procedures. Transient laryngospasm occurred in 9.5% of children receiving ketamine for EGD, and its incidence was greater in preschool than in school-aged children.

Chest radiography in infant cardiac allotransplantation.

Heart transplants were performed in seven infants at Loma Linda University Medical Center from 1985 to 1987. Five of these seven patients survived. In this report, the radiographic appearance of the chest is presented before surgery, immediately after surgery, and during a documented episode of rejection. The most current available chest radiograph is also presented. Acute rejection was confirmed by clinical, echocardiographic, and ECG findings. The only pulmonary infection encountered was mycoplasma pneumonitis. Four patients developed gastrointestinal rotavirus infections and were shown to have dilated proximal small-bowel folds on upper gastrointestinal studies. At the time of this writing, the prognosis for the five surviving infants is good. We conclude that the radiographs of infants who have received heart transplants show an unusual cardiac contour and slight cardiomegaly. Increasing cardiomegaly can alert one to early rejection. Prominent folds in the small bowel are of uncertain origin and significance, but they may be related to infection resulting from immunosuppression.

Rapid high-performance liquid chromatography assay for salivary and serum caffeine following an oral load. An indicator of liver function.

A rapid isocratic reversed-phase high-performance liquid chromatography (HPLC) system for the quantitative measurement of serum and salivary caffeine is described. The best separation of caffeine from other methylxanthines was achieved by chromatography on an ODS-Hypersil column using a solvent system of 0.1 M ammonium acetate pH 4.6-acetonitrile (85:15, v/v). The effluent was monitored at 280 nm. Caffeine was extracted from diluted serum and saliva samples (10-500 microliter) by adsorption on a small Bond-Elut C18 cartridge and recovered by elution with methanol. Thermospray HPLC-mass spectrometry conditions were optimized to afford a means of directly identifying caffeine in samples. The positive-ion mass spectrum was characterized by an intense protonated molecular ion, MH+, at m/z 195 and negligible fragmentation. When the mass spectrometer was operated in selected ion monitoring mode, caffeine could be detected in less than 1 microliter of serum and saliva at a concentration of 1 microgram/ml. Caffeine (3.5 mg/kg body wt.) was administered orally to healthy adults, children, and newborn infants, and to patients with liver disease. The clearance rate and half-life were determined as a test of liver function. A prolongation in the elimination of caffeine was observed in patients with liver disease and, although there was some overlap in the values obtained for patients with noncirrhotic liver disease and healthy persons, the oral caffeine load test may usefully serve as a dynamic assessment of liver function in the serial follow-up of patients with liver disease.