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Biomedical subjects

I Osorio

Publications and source records attributed to I Osorio.

At least 19 recordsLinked to original sources

Electrical and thermal behavior of non-ferrous noble metal electrodes exposed to MRI fields.

MRI is a valuable tool in invasive epilepsy surgery evaluation. However, its use is limited due to concerns that under those conditions it may injure the brain. This study investigates the thermal and electrical behavior of electrodes exposed to MRI fields, using a phantom brain implanted with depth and grid electrodes. Voltages and temperatures were measured during various MRI scan sequences at electrodes whose numbers and orientations were varied in a pre-specified manner. Maximum SAR recorded during the scans was 1.5 W/kg. Temperature changes and DC voltages were negligible. Peak-to-peak voltage induction depended on the position, number of electrodes, MRI modality and sequence. Voltages exceeded 40 V at 63.6 MHz, only when electrode wires formed loops, reaching peak values of 72 V at RF. Estimated charge densities due to leakage currents were well within the safety limit for neural tissue, which is 30 microC/cm(2), even at the highest voltages. Although in the absence of loops, voltages and charge densities recorded in this study were, under most conditions within safe limits for brain tissue, their dependence on: a) the physical dimensions of electrode arrays; b) their position/orientation in reference to each other and to the plane of the magnetic field, and c) the MR sequence and slice thickness, may make these observations and conclusions not generalizable and thus not directly applicable to other conditions with regard to safety risks assessment.

Brain↗

Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: a controlled study.

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chemically-induced seizures in rats were compared with control groups receiving no stimulation (NoS), left sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 130 min. Seizures were scored visually and the temporal variation of their probability P(s) across the stimulation cycle was measured statistically. P(s) was significantly different (P<0.01) for all groups: LSNS had the highest and MA-LVNS the lowest seizure probability; LVNS and NoS had intermediate values. While LVNS blocked seizures, it also precipitated them, explaining why its anti-seizure effect was only slightly greater than NoS. Neither LVNS nor MA-LVNS induced changes in cortical rhythms ('activation') associated with decreased P(s), unlike LSNS which increased cortical rhythm synchrony and with it, P(s). LVNS alone induced marked bradycardia and moderate hypoxemia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitated seizures, while LVNS both suppressed and facilitated them. The anti-seizure effect of LVNS was small and may have, in part, been due to a hemodynamically-induced deficit in energy substrates. The effects of MA-LVNS on seizure duration and P(s) raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.

Animals↗

Spectrum of clinical and histopathologic responses to intracranial electrodes: from multifocal aseptic meningitis to multifocal hypersensitivity-type meningovasculitis.

PURPOSE: We sought to characterize and compare the histopathologic and clinical changes elicited by subdural and depth electrodes in subjects undergoing epilepsy surgery evaluation. METHODS: A retrospective review of clinical records, imaging and histopathologic studies of epilepsy surgery cases requiring subdural strips and depth electrodes for localization of epileptogenic tissue was performed between 1993 and 1999. Forty-nine subjects had a combination of subdural and depth, whereas 10 had depth electrodes only. Histopathologic changes were classified as mild, moderate, or severe based on the density, extent, and composition of the inflammatory infiltrate. RESULTS: Subdural electrodes induced a clinical picture of transient aseptic meningitis; histopathologically, the infiltrates were moderate in degree in the majority (73%) and severe in the remainder (27%), with T cells and eosinophils infiltrating the cortex and arteriolar walls (hypersensitivity-type response). Depth electrodes alone caused minimal or no symptoms of meningeal irritation; the cellular response elicited by these electrodes was mild in five and moderate in the remaining five cases; severe inflammation was not observed in this group. Although the proportion of small clinically silent hematomas was larger in cases with depth (five of 59) compared with subdural electrodes (one of 49), microhemorrhages were considerably more numerous with subdural than with depth electrodes. CONCLUSIONS: These results suggest that the spectrum of brain responses to foreign bodies is wide, ranging from self-limited physiologic to hypersensitivity-type reactions of varying severity. Subdural strips elicited more intense inflammation than did depth electrodes. The histopathologic extent of the reaction to either type of electrodes could not be precisely defined because of the retrospective nature of this study. History of allergy to latex or previous craniotomies are probable risk factors for the hypersensitivity-type reaction. Surgical outcome, excellent in the majority, was independent of the severity or type of inflammation, and there have not been neurologic or systemic sequelae.

Adolescent↗

Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans.

PURPOSE: The purpose of this study was to determine if stimulation of the left vagus nerve (LVNS) with the neurocybernetic prosthesis (NCP) in humans is, as claimed in the literature, without cardiac chronotropic actions. METHODS: We analyzed 228 h of ECG recorded from five subjects with intractable epilepsy who had not benefited from LVNS, for effects on instantaneous heart rate (IHR) and heart rate variability (HRV). RESULTS: There were two main cardiac responses: (a) bradycardia, and (b) tachycardia during the first half, followed by bradycardia during the second half of stimulation (biphasic response). Multiphasic responses characterized by alternating bradycardia and tachycardia were rarely observed. HRV was either increased or decreased depending on the subject and on the stimulation parameters. HRV as a function of HR also showed high interindividual variability, and interestingly, in one case behaved paradoxically, increasing at higher and decreasing at lower heart rates. CONCLUSIONS: LVNS at high intensities has complex effects on IHR and HRV, which show large interindividual variability. These spectra of cardiac responses reflect the interplay of autonomic, visceral, and somatic sensory afferences and the role of central structures in their integration. These findings also point to the need for more comprehensive studies of cardiac function in humans implanted with the NCP, using sensitive methods for data processing and analysis such as those developed for this study.

Adult↗

Observations on the application of the correlation dimension and correlation integral to the prediction of seizures.

The authors reexamine the correlation integral and the related correlation dimension in the context of EEG analysis with application to seizure prediction. They identify dependencies of the correlation integral and the correlation dimension on frequency and amplitude of the signal, which may result in a reinterpretation of the dynamic importance of these measures and may cast doubts on their predictive abilities for certain classes of seizures. The relevance, for clinical and research purposes, of the distinction between retrospective and prospective inference (prediction) is addressed briefly. The authors point to the need for further research, consisting of long time series, containing multiple seizures, and for the development of objective prediction criteria.

Cerebral Cortex↗

Stochastic modeling and prediction of experimental seizures in Sprague-Dawley rats.

Most seizure prediction methods are based on nonlinear dynamic techniques, which are highly computationally expensive, thus limiting their clinical usefulness. The authors propose a different approach for prediction that uses a stochastic Markov chain model. Seizure (Ts) and interictal (Ti) durations were measured from 11 rats treated with 3-mercaptopropionic acid. The duration of a seizure Ts was used to predict the time (Ti2) to the next one. Ts and Ti were distributed bimodally into short (S) and long (L), generating four probable transitions: S --> S, S --> L, L --> S, and L --> L. The joint probability density f (Ts, Ti2) was modeled, and was used to predict Ti2 given Ts. An identical model predicted Ts given the duration Ti1 of the preceding interictal interval. The median prediction error was 3.0 +/- 3.5 seconds for Ts (given Ti1) and 6.5 +/- 2.0 seconds for Ti2 (given Ts). In comparison, ranges for observed values were 2.3 seconds < Ts < 120 seconds and 6.6 seconds < Ti < 782 seconds. These results suggest that stochastic models are potentially useful tools for the prediction of seizures. Further investigation of the probable temporal interdependence between the ictal and interictal states may provide valuable insight into the dynamics of the epileptic brain.

3-Mercaptopropionic Acid↗

An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short-term clinical trials, and to multidimensional statistical analysis of therapeutic efficacy.

Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety-in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in-hospital "closed-loop" trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable.

Anticonvulsants↗

Network system for automated seizure detection and contingent delivery of therapy.

The authors describe an integrated bedside system for real-time seizure detection and automated delivery of electrical stimulation directly to the brain of subjects undergoing invasive epilepsy surgery evaluation. These stimulations were triggered by specific detections following a prespecified pattern. The system uses a commercially available EEG unit, two personal computers, two Grass S-12 stimulators, and other custom-built units to enable interfacing between these components. To date, more than 9,500 hours of electrocorticographic data have been acquired, displayed, and analyzed, and more than 900 closed-loop stimulations for seizure blockage have been delivered safely and reliably to eight subjects with intractable epilepsy. This system generates on-line reports containing information about seizures that provide the epileptologist with timely, valuable data while allowing adaptation of the algorithm detection parameters to improve its performance if necessary. Additionally, it can control the output of any therapeutic device and administrate automatically cognitive tests or radioactive tracers for neuroimaging purposes. This network system, which can be replicated at a relatively low cost by others, is proof of concept for a portable or implantable device that could serve identical functions. Widespread availability of this type of system will advance the fields of clinical and basic epilepsy rapidly and considerably.

Cerebral Cortex↗

Refractory idiopathic absence status epilepticus: A probable paradoxical effect of phenytoin and carbamazepine.

PURPOSE: To compare the frequency of seizures and status epilepticus and their response to first-line drugs in patients with idiopathic generalized epilepsies receiving carbamazepine or phenytoin to those receiving other drugs or no treatment. METHODS: We performed a retrospective chart review of all cases of idiopathic generalized epilepsies treated by the authors between 1985 and 1994. We compared seizure frequency and mean intravenous benzodiazepine dose required to control absence status epilepticus, intraindividually in subjects on carbamazepine or phenytoin before and after discontinuation of these compounds, and interindividually to subjects without treatment or receiving other drugs. RESULTS: Bouts of absence or tonic-clonic status epilepticus and seizures in subjects treated with phenytoin or carbamazepine at therapeutic concentrations were considerably more frequent and proved intractable to treatment with valproic acid or benzodiazepines, compared with a cohort of subjects also with idiopathic generalized epilepsies, but naive to, or receiving subtherapeutic or therapeutic doses of other agents. CONCLUSIONS: Our observations strongly suggest that therapeutic concentrations of phenytoin and carbamazepine exacerbate idiopathic generalized epilepsies. Subjects in whom absence is one of the seizure types seem at a particularly high risk for responding paradoxically. These findings underscore the value of accurate classification of seizures and particularly the syndromic approach to diagnosis and point to the potential for iatrogenic complications with indiscriminate use of antiseizure drugs.

Acute Disease↗

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Electric Stimulation Therapy↗

Plasma glucose alone does not predict neurologic dysfunction in hypoglycemic nondiabetic subjects.

STUDY OBJECTIVE: To assess the value of plasma glucose concentration alone as a predictor of neurologic dysfunction in nondiabetic subjects with normal baseline neurologic examination and electroencephalographic (EEG) findings. METHODS: Neurologic function and EEG results were evaluated in 17 subjects before and during insulin-induced hypoglycemia using relevant and reliable clinical tools for bedside use. RESULTS: Hypoglycemia (mean nadir concentration, 30 mg/dL) was without effect on level of consciousness or cranial nerve, motor, sensory, vestibulocerebellar, language, or simple visuospatial functions. Attention was minimally impaired in all subjects, but memory in only 3. EEG results remained normal in 5 subjects; minimal to moderate nonspecific changes occurred in the rest. All patients manifested signs of sympathetic stimulation from hypoglycemia, including tremor, tachycardia, and diaphoresis. The manifestations of neuroglycopenia did not correlate significantly with nadir plasma glucose or duration of hypoglycemia. CONCLUSION: Moderately severe hypoglycemia of short duration can be neurologically occult, or subtle inattention can be its first and only clinical manifestation. Our findings are at variance with reports in the emergency medicine literature in which marked deficits are universally present at glucose concentrations equal to those attained in this study. This discrepancy suggests that the expression of neuroglycopenia is multifactorially determined and that plasma glucose concentration alone does not predict neurologic dysfunction in nondiabetic subjects with normal baseline neurologic examinations.

Adult↗

Least squares acceleration filtering for the estimation of signal derivatives and sharpness at extrema.

A family of finite impulse-response (FIR) filters is derived which estimate the second derivative or "acceleration" of a digitized signal. The acceleration is obtained from parabolas that are continuously fit to the signal using a least squares optimization criterion. A closed-form solution for the filter coefficients is obtained. The general approach is computationally simple, can be performed in real-time, and is robust in the presence of noise. An important application of the method, that of measuring sharpness in biologic signals, is presented using the electroencephalogram (EEG) and electrocardiogram (EKG) signals as examples. Furthermore, the design method is extended to derive FIR filters for estimating derivatives of arbitrary order in digital signals of biologic or other origins.

Algorithms↗

Real-time automated detection and quantitative analysis of seizures and short-term prediction of clinical onset.

PURPOSE: We describe an algorithm for rapid real-time detection, quantitation, localization of seizures, and prediction of their clinical onset. METHODS: Advanced digital signal processing techniques used in time-frequency localization, image processing, and identification of time-varying stochastic systems were used to develop the algorithm, which operates in generic or adaptable "modes." The "generic mode" was tested on (a) 125 partial seizures (each contained in a 10-min segment) involving the mesial temporal regions and recorded using depth electrodes from 16 subjects, and (b) 205 ten-minute segments of randomly selected interictal (nonseizure) data. The performance of the algorithm was compared with expert visual analysis, the current "gold standard." RESULTS: The generic algorithm achieved perfect sensitivity and specificity (no false-positive and no false-negative detections) over the entire data set. Seizure intensity, a novel measure that seems clinically relevant, ranged between 35.7 and 6129. Detection was sufficiently rapid to allow prediction of clinical onset in 92% of seizures by a mean of 15.5 s. CONCLUSIONS: This algorithm, which was implemented with a personal computer, represents a definitive step toward rapid and accurate detection and prediction of seizures. It may also enable development of intelligent devices for automated seizure warning and treatment and stimulate new study of the dynamics of seizures and of the epileptic brain.

Algorithms↗

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Adolescent↗

Childhood caffeine tic syndrome.

OBJECTIVE: To determine whether caffeine ingestion was temporally correlated with tics in 2 healthy children. METHODS: Two first-degree cousins were observed over a period of approximately 3 years, and the presence and absence of tics was recorded and correlated with consumption of or abstinence from caffeinated foods or beverages. RESULTS: Appearance and disappearance of tics were closely and clearly temporally correlated with ingestion and elimination of caffeine in the cousins' diets. CONCLUSIONS: Our observations suggest that caffeine may precipitate tics in susceptible children.

Beverages↗

The roles of semantic networks and search efficiency in verbal fluency performance in intractable temporal lobe epilepsy.

Two competing hypotheses (i.e., disruption of semantic networks vs. search inefficiency) concerning the mechanisms underlying impaired semantic verbal fluency in temporal lobe epilepsy (TLE) were tested within a single paradigm. Reports that semantic verbal fluency is more impaired in left than right TLE groups were confirmed by the findings that the left TLE group produced fewer words on a supermarket fluency task than did the normal control (NC) group, and that the performance of the right TLE group was intermediate to that of the left TLE and NC groups. Because both TLE groups generated fewer words per category of supermarket items sampled, and produced a higher ratio of category labels relative to category exemplars than did the NC group, it can be surmised that TLE disrupts semantic memory networks. The findings did not support the competing hypothesis that reduced semantic verbal fluency in TLE is a manifestation of inefficient search/retrieval strategies, possibly associated with distal frontal lobe pathophysiology. Specifically, the TLE and NC groups did not differ significantly in their mean number of perseverations, intrusions, or search efficiency (operationalized as the ratio of the number of shifts between categories to the number of categories sampled).

Adult↗

Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria: report of two cases.

We report the clinical, radiologic, and postmortem findings in two patients with paroxysmal nocturnal hemoglobinuria (PNH) who developed cerebral venous thromboses (CVTs). In contrast with those in most published cases, our patients did not have focal neurologic signs. Antemortem diagnosis of CVT had been made by MR cerebral venograms. We conclude that (1) PNH should be considered in any patient with stroke associated with iron deficiency anemia, hemolysis, hemoglobinuria, or hemosiderinuria; (2) PNH should be in the differential diagnosis of CVT; (3) the latter could present without focal neurologic signs; and (4) MR cerebral venography may be a reliable diagnostic alternative to cerebral angiography when CVT is suspected.

Cerebral Angiography↗