Ictal infraslow activity in stereoelectroencephalography: Beyond the "DC shift".

OBJECTIVES: The significance of infraslow activity (ISA) in focal epilepsies is largely unknown. Recent work has demonstrated ictal ISA to be more widespread in expression than originally understood. Analysis of ISA by stereoelectroencephalography (SEEG) may help to clarify its localizing value, namely the focal versus widespread expression of ISA. METHODS: The ictal SEEG records for fifteen consecutive adult patients were retrospectively analyzed, using both conventional (1.6-70 Hz) and infraslow (0.01-0.1 Hz) bandpass filters. When justified, seizures were averaged in the infraslow band to clarify their stereotypy. Wavelets were used to quantify the time-frequency characteristics of ISA. RESULTS: All clinical seizures were found to possess ISA, and this was markedly invariant across seizures in a given patient. ISA showed biphasic peaks in power, both at ictal onset and offset, with this most prominent in the anatomical structures implicated by conventional analysis. In addition, ISA demonstrated an association with low voltage fast activity, and possessed a more restricted field than conventional activity. CONCLUSIONS: ISA is both widespread (anatomically distributed) and focal (closed electric field). Seizures possess an infraslow spatiotemporal signature. SIGNIFICANCE: Beyond representing a "focus" of paroxysmal activity, ISA must arise from a network process as a component of wideband ictal dynamics. How this relates to clinical definition of the epileptogenic zone requires further study.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed.

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.

BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. MATERIALS AND METHODS: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. RESULTS: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. CONCLUSIONS: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.

A magnetoencephalography study of multi-modal processing of pain anticipation in primary sensory cortices.

Pain anticipation plays a critical role in pain chronification and results in disability due to pain avoidance. It is important to understand how different sensory modalities (auditory, visual or tactile) may influence pain anticipation as different strategies could be applied to mitigate anticipatory phenomena and chronification. In this study, using a countdown paradigm, we evaluated with magnetoencephalography the neural networks associated with pain anticipation elicited by different sensory modalities in normal volunteers. When encountered with well-established cues that signaled pain, visual and somatosensory cortices engaged the pain neuromatrix areas early during the countdown process, whereas the auditory cortex displayed delayed processing. In addition, during pain anticipation, the visual cortex displayed independent processing capabilities after learning the contextual meaning of cues from associative and limbic areas. Interestingly, cross-modal activation was also evident and strong when visual and tactile cues signaled upcoming pain. Dorsolateral prefrontal cortex and mid-cingulate cortex showed significant activity during pain anticipation regardless of modality. Our results show pain anticipation is processed with great time efficiency by a highly specialized and hierarchical network. The highest degree of higher-order processing is modulated by context (pain) rather than content (modality) and rests within the associative limbic regions, corroborating their intrinsic role in chronification.

Complications of invasive video-EEG monitoring with subdural grid electrodes.

OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

Systems for producing precise movements of a joint over a wide range of speeds and displacements for tests of a static-position sense.

This report describes 3 types of apparatus that were used to produce precise movements of a joint over a wide range of speeds and angles. The designs feature an ability for ultra slow rotation of the joint (fractions of a degree per min) with a minimum of extraneous cues. Two designs use servo-controlled DC motors configured as velocity servos and a third design uses a galvanometer motor configured as a position servo. Originally designed for use with humans in studies of proprioception with the ankle and two joints of the index finger (the metacarpophalangeal joint and proximal interphalangeal joint), the apparatuses should be useful in a variety of applications where precise control of velocity and position is needed.

Effects of cheese extract and its fractions on enamel demineralization in vitro and in vivo in humans.

In order to isolate and identify the most active anti-cariogenic components(s) of aqueous cheese extract (CE), we separated it into low (LMW) (MW less than 500), medium (MMW) (500 less than MW less than 10,000), and high (HMW) (MW greater than 10,000) molecular weight fractions by means of the Amicon ultrafiltration system. These fractions were then tested in vitro with a bacterial system containing S. mutans, adapted from that of Turtola (1977). The LMW fraction reduced the demineralization caused by the fermentation of sucrose by 96% (p less than 0.001) as compared with the water control; this was not significantly different from a 50% concentration of the CE. The MMW and HMW fractions reduced demineralization by 36 and 42%, respectively. The concentrations of acid-soluble calcium and phosphorus in CE, LMW, MMW, and HMW were 1509 and 462, 991 and 310, 231 and 7, and 162 and 3 micrograms/mL, respectively. A solution containing the same levels of calcium and phosphorus as CE was somewhat more effective in reducing demineralization in vitro than was CE itself (p less than 0.01). In vivo, the addition of these same calcium and phosphorus levels to a 10% sucrose solution reduced its cariogenicity by 67% (p less than 0.001), as judged by the intra-oral cariogenicity test (ICT). Plaque calcium and phosphorus concentrations were significantly higher in the ICT plaque samples subjected to the sucrose-Ca,P solution (p less than 0.01) than in the sucrose control. The resting pH, minimum pH, and shape of the pH curves produced by the sucrose control and sucrose-Ca,P were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of water-soluble components of cheese on experimental caries in humans.

The effect of water-soluble components of extra-old Cheddar cheese on experimental caries was tested by means of the seven-day intraoral cariogenicity test (ICT). Two bovine enamel blocks were placed in each buccal flange of the dental appliances of five volunteers. One side of each appliance (experimental) was dipped in a 25% water extract of the cheese for five min, while the other side (control) was dipped in de-ionized water. Immediately thereafter, the appliance was returned to the subject's mouth, and two 60-second rinses with 10% sucrose were performed. These procedures were repeated six times per day. The cheese-extract dippings reduced the cariogenicity of the sucrose by an average of 55.7% (p less than 0.01), as assessed by enamel microhardness. Neither the mean resting pH nor the mean minimum pH in response to sucrose was significantly different between the experimental and control sides. The concentration of calcium was significantly higher in plaque from the experimental side (32.44 micrograms/mg) as compared with the control side (19.36 micrograms/mg, p less than 0.01). The concentration of plaque phosphorus was higher on the experimental side (12.90 micrograms/mg) than on the control side (9.61 micrograms/mg); however, the difference was not statistically significant. These results show that cheese has one or more water-soluble components which reduce experimental caries in human subjects.

Clinical trial in adults of an antimicrobial varnish for reducing mutans streptococci.

An abbreviated treatment with a chlorhexidine-containing varnish was compared with a similar treatment with a placebo varnish and with a prophylaxis alone for its effects on the numbers of detectable salivary mutants streptococci in 51 adults. The varnishes, applied once weekly for four weeks, were held in place with a covering layer of either of two polyurethane sealants (FluorProtector or Adhesit). On the first appointment, the varnish-sealant combination was applied to all tooth surfaces, but on succeeding appointments only the occlusal and approximal surfaces were covered. The chlorhexidine varnish, covered with either sealant, reduced the salivary mutans streptococci by an average of 3 logs (99.9%) in all of the 20 subjects treated, and below detectable levels for at least four weeks in nine of them. In the groups receiving placebo varnish-sealant combinations, the mean log number of mutans streptococci of the subjects was reduced only by approximately 0.5 log (32%), and none of the subjects experienced loss of their detectable mutans streptococci for four weeks, although one subject did so for three weeks. No significant difference between the effects of the two polyurethane sealants was observed. Treatment with a single prophylaxis had no effect on mutans streptococcus levels. Subjects treated with chlorhexidine varnish also experienced an increase in S. sanguis and a small decrease in yeasts. Loss of detectable mutans streptococci did not cause changes in the numbers of other micro-organisms examined, beyond those observed with chlorhexidine varnish treatment alone.

Epidural peg electrodes for the presurgical evaluation of intractable epilepsy.

A new electrode design for the extradural recording of electrical brain activity is described. Epidural peg electrodes are implantable mushroom-shaped composites of Silastic elastomer and a stainless steel or platinum disc. These electrodes are useful for the preoperative mapping of seizure foci in some patients who have cranial defects or severe muscle artifacts on scalp recordings. They are also used for canvassing wide areas of cortex to determine whether a seizure is focal in origin, arises diffusely from a hemisphere, or has a bilateral origin. Advantages of epidural peg electrodes over screw and other types of epidural electrodes include low risk of infection or hemorrhage and improved patient comfort.

Deformities of the forearm in patients who have multiple cartilaginous exostosis.

Thirty-five patients who had multiple cartilaginous exostosis and deformities of the wrist and forearm were evaluated to determine the natural history and prognostic factors for the deformities. Radial and ulnar shortening were correlated linearly (r2 = 0.86), showing that both bones of the forearm were symmetrically involved. The angular growth abnormality of the distal aspect of the radius was correlated with radial shortening (r2 = 0.53) and ulnar shortening (r2 = 0.61), but it had no correlation with negative variance of the ulnar (r2 = 0.30). Carpal slip was an independent factor, with no correlation with any of the factors studied. The ulnar tether theory for deformities of the wrist in patients who have multiple cartilaginous exostosis was not substantiated by this study.

Tumor necrosis factor and chemotherapeutic agents. Potentiation of cytotoxicity with interferon gamma.

This study examined combinations of the recombinant human cytokines, tumor necrosis factor alpha and interferon gamma, with doxorubicin and dactinomycin as well as other drugs on six squamous cell carcinoma cell lines of head and neck origin using the 3(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide proliferation assay. Interferon gamma significantly enhanced the cytotoxicity of tumor necrosis factor alpha with dactinomycin on all six cell lines investigated, while in four of six cell lines the cytotoxicity of tumor necrosis factor alpha with doxorubicin was significantly augmented by interferon gamma. Additional experiments showed no effect with either cytokine in combination with cisplatin, fluorouracil, methotrexate, or etoposide. These data demonstrate that human recombinant cytokines in concert with certain drugs improve in vitro cytotoxicity and may have a potential for improving in vivo therapy.

EView--a workstation-based viewer for intensive clinical electroencephalography.

We describe a workstation-based EEG viewer that satisfies the requirements for high-volume clinical EEG review. It currently supports two 24-h four-bed epilepsy monitoring units and a network of routine, intraoperative, and intensive care monitors, providing paperless review of over 5000 pages/day by a staff of clinical neurophysiologists. The design takes advantage of the development environment, processing and graphics resources, and networking capabilities of high-performance UNIX workstations. The user interface and operational infrastructure have been tailored to the demands of clinical neurophysiologists requiring rapid access to large volumes of EEG waveform data in a large clinical neurophysiology laboratory. This paper describes the functional requirements, system architecture, and implementation details of the current system.

An arrhythmia detector and heart rate estimator for overnight polysomnography studies.

We present an algorithm for automatic on-line analysis of the electrocardiography (ECG) channel acquired during overnight polysomnography (PSG) studies. The system is independent of ECG morphology, requires no manual initialization, and operates automatically throughout the night. It highlights likely occurrences of arrhythmias and intervals of bad signal quality while outputting a continual estimate of heart rate. Algorithm performance is validated against standard ECG databases and PSG data. Results demonstrate a minimal false negative rate and a low false positive rate for arrhythmia detection, and robustness over a wide range of noise contamination.

Accumulation of nifedipine after multiple doses.

The single and multiple dose pharmacokinetics of oral nifedipine capsules, 10 mg, have been examined in five patients with peripheral vasospasm. After a single dose, nifedipine was rapidly absorbed in three and slowly absorbed in two patients. Mean bioavailability parameters included a tmax of 2.9 h, a Cmax of 33.3 ng ml-1 and a AUC0-8 h of 113.3 ng h ml-1. After multiple dosing with either 10 or 20 mg every 8 h for 10 days the mean tmax at steady state was 2.1 h while the mean dose-corrected (to 10 mg) Cmax and AUC0-8 h were 51.9 ng ml-1 and 146.9 ng h ml-1, respectively. The mean elimination rate constant was 0.173 h-1 after both single and multiple doses. The mean extent of accumulation of nifedipine, defined as the ratio of AUC0-8 h (steady state)/AUC0-8 h (single dose), was 1.3; we concluded that nifedipine accumulates in the body when it is administered every 8 h. This should be taken into account when predicting steady state serum concentrations and haemodynamic effects of nifedipine from single dose kinetic data.

Immediate closure of traumatic upper arm and forearm injuries with the latissimus dorsi island myocutaneous pedicle flap.

This paper reports the authors' experience with latissimus dorsi island pedicle flaps in the acute treatment of massive arm injuries. Seven patients with upper arm injuries and four patients with forearm injuries were treated with latissimus dorsi pedicle flaps. All cases involved massive soft-tissue loss and open fractures. Primary healing of wounds occurred without complications in 10 of 11 patients; the eleventh developed a wound infection. There were no instances of flap loss or vascular complications. This report compares and discusses surgical management options and details the importance of robust, immediate soft-tissue coverage for optimal functional recovery. Contrary to traditional thought, delay in definitive wound closure may be unnecessary when aggressive debridement is followed by acute flap closure.

Effect on caries of self-application of a zirconium silicate paste containing 9% stannous fluoride.

A 2-year clinical trial was conducted using an adolescent population from a low-fluoride area to evaluate the anticaries effect of self-applications of zirconium silicate paste containing 9% stannous fluoride. tthree study groups totaling 464 children, with an initial average of 12.8 years, completed the study. The control group brushed with a non-fluoride zirconium silicate paste (tzircate Prophylaxis Paste) once each year: the first experimental group brushed with zirconium silicate paste containing 9% stannous fluoride (Zircate Treatment Paste) once each year; and the second experimental group brushed every 6 months with Zircate Treatment Paste. After 2 year, the DMFT and DMFS increments were virtually identical for the control group and the group that received one application of fluoride paste per year. The group that received two applications of fluoride paste per year had a DMTF increment that was about 24% less than that of the control group; however, the DMFS increment was only 5% less. These differences were not statistically significant at the P=.05 level.

Polymerase chain reaction amplification of herpes simplex viral DNA from the geniculate ganglion of a patient with Bell's palsy.

Bell's palsy is the most common cause of facial paralysis. In this study, we demonstrate the presence of herpes simplex viral type 1 (HSV-1) genomic DNA in the geniculate ganglion of a patient who had Bell's palsy. This association suggests that in this patient, HSV-1 may have caused Bell's palsy. If HSV-1 is a cause of Bell's palsy, treatment with acyclovir may be beneficial. Additional studies should be done to establish the prevalence of HSV-1 as an etiologic agent of Bell's palsy.

A new method of determining patellar position.

A new ratio has been devised which allows direct measurement of the position of the patella in relationship to the femur. The range of normal values is from 0.56 to 0.76.

How competent do our graduates feel?

As part of a review of the undergraduate curriculum to assess its relevance for a future general practitioner, a survey of self-perceived competency at graduation based on the competency list developed by the Association of Canadian Faculties of Dentistry was circulated to recent graduates and the graduating class. The overall response was 67.5 percent, and revealed that approximately 70 percent of the respondents felt well prepared in approximately 69 percent of the competencies. These were the common "bread and butter" items of dentistry, such as basic restorative dentistry, examination, diagnosis, treatment planning, local anaesthesia, and scaling. Those areas reported as less well-prepared for included financial and personnel management, performance of soft-tissue biopsies, and management of chronic orofacial pain. Clarification of the raw survey results in focus groups was needed to uncover specific details that could lead to remedial action in problem areas.