Biophase equilibration times.

PubMed

Veng-Pedersen, P; Mandema, J W; Danhof, M

1991-09-01

Various methods for describing how quickly a drug equilibrates at the biophase are proposed. The biophase equilibration time (BET) is the time it takes the biophase drug level to reach a given percentage (p) of its predicted steady state in a drug administration that leads to a steady-state condition. The time to reach biophase equilibrium may be defined as the BET value for p = 95, and the 50% biophase equilibration time is obtained when p = 50. Biophase equilibration profiles (BEPs), obtained by plotting p versus BET, give a dynamic representation of the approach to equilibrium and may serve as an indicator of the rate of drug delivery to the biophase. A pharmacodynamic system analysis method is proposed to determine BETs and BEPs from the biophase conduction function. The approach is demonstrated using pharmacodynamic data from the CNS effect of amobarbital evaluated by an aperiodic analysis of EEG recordings. The relevance of the BET and/or BEP principles in optimal computer-controlled drug infusion, drug design, and evaluation of targeted drug delivery is discussed. Both vascular and extravascular drug administrations are considered in the analysis.

Simulating memory outcome before right selective amygdalohippocampectomy.

PubMed

Patrikelis, Panayiotis; Lucci, Giuliana; Siatouni, Anna; Zalonis, Ioannis; Sakas, Damianos E; Gatzonis, Stylianos

2013-01-01

In this paper we present the case of a left-sided speech dominant patient with right medial temporal sclerosis (RMTS) and pharmacoresistant epilepsy who showed improved verbal memory during intracarotid amobarbital test (IAT) at his right hemisphere as compared with his own performance before the drug injection (baseline), as well as after right selective amygdalohippocampectomy. We suggest that the defective verbal memory shown by this patient is due to abnormal activity of his right hippocampus that interfered with the function of his left hippocampus. This hypothesis was demonstrated by the fact that disconnection of the two hippocampi, either by anesthetisation or by resection of the right hippocampus, disengaged the left hippocampus and, consequently improved its function. This paper main objective is twofold: first to contribute to the field of neuropsychology of epilepsy surgery by emphasising on postoperative memory outcomes in right medial temporal lobe epilepsy (RMTLE) patients, particularly those undergoing amygdalohippocampectomy, as the pattern of memory changes after resection of the right temporal lobe is less clear; second, by focusing on memory performance asymmetries during IAT, and comparatively considering them with neuropsychological memory performance, because of their possible prognostic-simulating value.

Postictal aphasia and paresis: a clinical and intracerebral EEG study.

PubMed

Adam, C; Adam, C; Rouleau, I; Saint-Hilaire, J M

2000-02-01

We examined the lateralizing value of postictal language and motor deficits and studied their underlying mechanisms. The total sample consisted of 35 patients (26 temporals, 8 frontals, 1 parietal) with a good postsurgical outcome (Engel's class I and II). Postictal examination was blindly reviewed on videotapes. In 15 cases (29 seizures), postictal language manifestations were analyzed in relation with the diffusion of the epileptic discharge recorded by intracerebral EEG. Language dominance was determined by the intracarotid amobarbital test. Postictal aphasia was observed only when (1) seizure originated in the dominant hemisphere and (2) ictal activity spread to language areas (Wernicke and/or Broca areas). When the epileptic focus was in the nondominant hemisphere, no postictal aphasia was observed even if there was secondary generalization of ictal activity affecting the language areas of the dominant hemisphere. Postictal motor deficits also had a strong lateralizing value even when seizures were secondarily generalized. Postictal aphasia in temporal epilepsies and postical motor deficits in temporal and extra temporal epilepsies provided excellent lateralizing information. Postictal deficits appear to be the result of inhibitory mechanisms induced by previous ictal activity of the structures related to these functions.

Atypical cortical language organization in epilepsy patients: evidence for divergent hemispheric dominance for receptive and expressive language function.

PubMed

Eliashiv, Dawn S; Kurelowech, Lacey; Quint, Patti; Chung, Jeffrey M; Otis, Shirley M; Gage, Nicole M

2014-06-01

The central goal of presurgical language mapping is to identify brain regions that subserve cortical language function to minimize postsurgical language deficits. Presurgical language mapping in patients with epilepsy presents a key challenge because of the atypical pattern of hemispheric language dominance found in this population, with higher incidences of bilateral and right-biased language dominance than typical. In this prospective study, we combine magnetoencephalography with a panel of tasks designed to separately assess receptive and expressive function to provide a sensitive measure of language function in 15 candidates for resective surgery. We report the following: 4 of 15 patients (27%) showed left hemisphere dominance across all tasks, 4 of 15 patients (27%) showed right hemisphere dominance across all tasks, and 7 of 15 (46%) showed discordant language dominance, with right-dominant receptive and left-dominant expressive language. All patients with discordant language dominance showed this right-receptive and left-expressive pattern. Results provide further evidence supporting the importance of using a panel of tasks to assess separable aspects of language function. The clinical relevance of the findings is discussed, especially about current clinical operative measures for assessing language dominance, which use single hemisphere procedure (intracarotid amobarbital procedure and awake intraoperative stimulation) for determining language laterality.

The history of barbiturates a century after their clinical introduction

PubMed Central

López-Muñoz, Francisco; Ucha-Udabe, Ronaldo; Alamo, Cecilio

2005-01-01

The present work offers an analysis of the historical development of the discovery and use of barbiturates in the field of psychiatry and neurology, a century after their clinical introduction. Beginning with the synthesis of malonylurea by von Baeyer in 1864, and up to the decline of barbiturate therapy in the 1960s, it describes the discovery of the sedative properties of barbital, by von Mering and Fischer (1903), the subsequent synthesis of phenobarbital by this same group (1911), and the gradual clinical incorporation of different barbiturates (butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, etc). We describe the role played in therapy by barbiturates throughout their history: their traditional use as sedative and hypnotic agents, their use with schizophrenic patients in so-called “sleep cures” (Klaesi, Cloetta), the discovery of the antiepileptic properties of phenobarbital (Hauptmann) and their use in the treatment of epilepsy, and the introduction of thiobarbiturates in intravenous anesthesia (Lundy, Waters). We also analyze, from the historical perspective, the problems of safety (phenomena of dependence and death by overdose) which, accompanied by the introduction of a range of psychoactive drugs in the 1950s, brought an end to barbiturate use, except in specific applications, such as the induction of anesthesia and the treatment of certain types of epileptic crisis. PMID:18568113

Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Qun; Yin, Guotian; Stewart, Sarah

2010-07-09

Ischemia damages the mitochondrial electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Mitochondrial damage resulting from ischemia, in turn, leads to cardiac injury during reperfusion. The goal of the present study was to localize the segment of the ETC that produces the ischemic mitochondrial damage. We tested if blockade of the proximal ETC at complex I differed from blockade distal in the chain at cytochrome oxidase. Isolated rabbit hearts were perfused for 15 min followed by 30 min stop-flow ischemia at 37 {sup o}C. Amobarbital (2.5 mM) or azide (5 mM) was used tomore » block proximal (complex I) or distal (cytochrome oxidase) sites in the ETC. Time control hearts were buffer-perfused for 45 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated. Ischemia decreased cytochrome c content in SSM but not in IFM compared to time control. Blockade of electron transport at complex I preserved the cytochrome c content in SSM. In contrast, blockade of electron transport at cytochrome oxidase with azide did not retain cytochrome c in SSM during ischemia. Since blockade of electron transport at complex III also prevented cytochrome c loss during ischemia, the specific site that elicits mitochondrial damage during ischemia is likely located in the segment between complex III and cytochrome oxidase.« less

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

PubMed

Spritzer, Scott D; Hoerth, Matthew T; Zimmerman, Richard S; Shmookler, Aaron; Hoffman-Snyder, Charlene R; Wellik, Kay E; Demaerschalk, Bart M; Wingerchuk, Dean M

2012-09-01

Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.

Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy.

PubMed

O'Rourke, D M; Saykin, A J; Gilhool, J J; Harley, R; O'Connor, M J; Sperling, M R

1993-04-01

We examined the relationship of preoperative unilateral memory function and quantitative hippocampal histology in patients undergoing anterior temporal lobectomy for the treatment of complex partial seizures. Recognition memory (objects, words, figures) was assessed preoperatively for each hemisphere by the intracarotid amobarbital procedure in 23 patients (mean age at the time of operation, 30.2 yr; standard deviation, 9.2; mean age at the time of seizure onset, 12.3 yr; standard deviation, 8.6) without tumor. Memory scores were the total number of items recognized, adjusted for guessing. Histological examination of the anterior 20 to 30 mm of hippocampal tissue was accomplished in all patients. The degree of unilateral memory impairment ipsilateral to the seizure focus was significantly correlated with decreased neuronal density in the hilar (r = 0.66, P < 0.001) and dentate granule (r = 0.61, P < 0.002) regions, but not in the CA1 (r = 0.10, P = not significant) or CA2-3 (r = 0.35, P = not significant) regions. Memory performance with the contralateral hemisphere was not significantly correlated with ipsilateral hippocampal densities. These data support the role of the hippocampus in human memory and show further evidence of hippocampal subfield specificity in the relationship between memory performance and neuronal cell loss. Further studies of the dentate granule and hilar regions in relation to human memory are warranted.

Use of Preoperative Functional MRI to Predict Verbal Memory Decline After Temporal Lobe Epilepsy Surgery

PubMed Central

Binder, Jeffrey R.; Sabsevitz, David S.; Swanson, Sara J.; Hammeke, Thomas A.; Raghavan, Manoj; Mueller, Wade M.

2010-01-01

Purpose Verbal memory decline is a frequent complication of left anterior temporal lobectomy (L-ATL). The goal of this study was to determine whether preoperative language mapping using functional magnetic resonance imaging (fMRI) is useful for predicting which patients are likely to experience verbal memory decline after L-ATL. Methods Sixty L-ATL patients underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language and memory lateralization, and pre- and postoperative neuropsychological testing. Demographic, historical, neuropsychological, and imaging variables were examined for their ability to predict pre- to postoperative memory change. Results Verbal memory decline occurred in over 30% of patients. Good preoperative performance, late age at onset of epilepsy, left dominance on fMRI, and left dominance on the Wada test were each predictive of memory decline. Preoperative performance and age at onset together accounted for roughly 50% of the variance in memory outcome (p < .001), and fMRI explained an additional 10% of this variance (p ≤ .003). Neither Wada memory asymmetry nor Wada language asymmetry added additional predictive power beyond these noninvasive measures. Discussion Preoperative fMRI is useful for identifying patients at high risk for verbal memory decline prior to L-ATL surgery. Lateralization of language is correlated with lateralization of verbal memory, whereas Wada memory testing is either insufficiently reliable or insufficiently material-specific to accurately localize verbal memory processes. PMID:18435753

Dynamics of hemispheric dominance for language assessed by magnetoencephalographic imaging.

PubMed

Findlay, Anne M; Ambrose, Josiah B; Cahn-Weiner, Deborah A; Houde, John F; Honma, Susanne; Hinkley, Leighton B N; Berger, Mitchel S; Nagarajan, Srikantan S; Kirsch, Heidi E

2012-05-01

The goal of the current study was to examine the dynamics of language lateralization using magnetoencephalographic (MEG) imaging, to determine the sensitivity and specificity of MEG imaging, and to determine whether MEG imaging can become a viable alternative to the intracarotid amobarbital procedure (IAP), the current gold standard for preoperative language lateralization in neurosurgical candidates. MEG was recorded during an auditory verb generation task and imaging analysis of oscillatory activity was initially performed in 21 subjects with epilepsy, brain tumor, or arteriovenous malformation who had undergone IAP and MEG. Time windows and brain regions of interest that best discriminated between IAP-determined left or right dominance for language were identified. Parameters derived in the retrospective analysis were applied to a prospective cohort of 14 patients and healthy controls. Power decreases in the beta frequency band were consistently observed following auditory stimulation in inferior frontal, superior temporal, and parietal cortices; similar power decreases were also seen in inferior frontal cortex prior to and during overt verb generation. Language lateralization was clearly observed to be a dynamic process that is bilateral for several hundred milliseconds during periods of auditory perception and overt speech production. Correlation with the IAP was seen in 13 of 14 (93%) prospective patients, with the test demonstrating a sensitivity of 100% and specificity of 92%. Our results demonstrate excellent correlation between MEG imaging findings and the IAP for language lateralization, and provide new insights into the spatiotemporal dynamics of cortical speech processing. Copyright © 2012 American Neurological Association.

Effects of hemisphere speech dominance and seizure focus on patterns of behavioral response errors for three types of stimuli.

PubMed

Rausch, R; MacDonald, K

1997-03-01

We used a protocol consisting of a continuous presentation of stimuli with associated response requests during an intracarotid sodium amobarbital procedure (IAP) to study the effects of hemisphere injected (speech dominant vs. nondominant) and seizure focus (left temporal lobe vs. right temporal lobe) on the pattern of behavioral response errors for three types of visual stimuli (pictures of common objects, words, and abstract forms). Injection of the left speech dominant hemisphere compared to the right nondominant hemisphere increased overall errors and affected the pattern of behavioral errors. The presence of a seizure focus in the contralateral hemisphere increased overall errors, particularly for the right temporal lobe seizure patients, but did not affect the pattern of behavioral errors. Left hemisphere injections disrupted both naming and reading responses at a rate similar to that of matching-to-sample performance. Also, a short-term memory deficit was observed with all three stimuli. Long-term memory testing following the left hemisphere injection indicated that only for pictures of common objects were there fewer errors during the early postinjection period than for the later long-term memory testing. Therefore, despite the inability to respond to picture stimuli, picture items, but not words or forms, could be sufficiently encoded for later recall. In contrast, right hemisphere injections resulted in few errors, with a pattern suggesting a mild general cognitive decrease. A selective weakness in learning unfamiliar forms was found. Our findings indicate that different patterns of behavioral deficits occur following the left vs. right hemisphere injections, with selective patterns specific to stimulus type.

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy

PubMed Central

Szaflarski, Jerzy P.; Gloss, David; Binder, Jeffrey R.; Gaillard, William D.; Golby, Alexandra J.; Holland, Scott K.; Ojemann, Jeffrey; Spencer, David C.; Swanson, Sara J.; French, Jacqueline A.; Theodore, William H.

2017-01-01

Objective: To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. Methods: An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. Results and recommendations: The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case. PMID:28077494

Temporal lobe epilepsy: analysis of patients with dual pathology.

PubMed

Salanova, V; Markand, O; Worth, R

2004-02-01

To determine the frequency and types of dual pathology in patients with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and surgical outcome. A total of 240 patients with TLE underwent temporal resections following a comprehensive pre-surgical evaluation. Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe gliosis in association with another lesion (dual pathology). Eighteen of 37 patients with dual pathology had heterotopia of the temporal lobe, nine had cortical dysplasia, four had cavernous angiomas or arteriovenous malformations, one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic resonance imagings, 91.3% had abnormal positron emission tomography scans, and 96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed impaired memory of the epileptogenic side in 72% of the patients. Twenty patients had left and 17 had right-sided en bloc temporal resections, including the lesion and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years). 15.4% had dual pathology. The dual pathology was almost exclusively seen in patients whose lesions were congenital, or occurred early in life, suggesting that the hippocampus is more vulnerable and more readily develops HS in early childhood. Resections, including the lateral and mesial temporal structures led to a favorable outcome with no mortality and little morbidity.

Implementation of Intraoperative Neurophysiological Monitoring during Endovascular Procedures in the Central Nervous System.

PubMed

Martinez Piñeiro, Alicia; Cubells, Carles; Garcia, Pablo; Castaño, Carlos; Dávalos, Antonio; Coll-Canti, Jaume

2015-03-01

Intraoperative monitoring (IOM) has been used in different surgical disciplines since the 1980s. Nonetheless, regular routine use of IOM in interventional neuroradiology units has only been reported in a few centers. The aim of this study is to report our experience, 1 year after deciding to implement standardized IOM during endovascular treatment of vascular abnormalities of the central nervous system. Basic recordings included somatosensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs). Corticobulbar motor-evoked potentials and flash-visual-evoked potentials were also recorded depending on the topography of the lesion. Intra-arterial provocative tests (PTs) with amobarbital and lidocaine were also performed. All patients except 1 were under total intravenous anesthesia. Clinical outcome was assessed prospectively and correlated with IOM events. Twelve patients and 15 procedures were monitored during the inclusion period. Significant IOM events were detected during 3 of the 15 procedures (20%). We observed temporary MEP changes in 2 cases which resolved after interruption of the embolization or application of corrective measures, leaving no postoperative neurological deficits. In 1 case, persistent SEP and MEP deterioration was detected secondary to a frontal hematoma, resulting in mild sensory-motor deficit in the right upper extremity after the procedure. Overall, 12 PTs (4 spinal cord and 8 brain abnormalities) were performed using lidocaine and sodium amytal injections. One positive result occurred after the injection of lidocaine. No false negatives were detected. IOM may provide continuous real-time data about the functional status of eloquent areas and pathways of the central nervous system in patients under general anesthesia. It therefore allows us to detect early neurological damage in time to perform specific actions that may prevent irreversible neurological deficits.

Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy.

PubMed

DeSalvo, Matthew N; Tanaka, Naoaki; Douw, Linda; Leveroni, Catherine L; Buchbinder, Bradley R; Greve, Douglas N; Stufflebeam, Steven M

2016-10-01

Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. (©) RSNA, 2016 Online supplemental material is available for this article.

Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy

PubMed Central

Tanaka, Naoaki; Douw, Linda; Leveroni, Catherine L.; Buchbinder, Bradley R.; Greve, Douglas N.; Stufflebeam, Steven M.

2016-01-01

Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. © RSNA, 2016 Online supplemental material is available for this article. PMID:27467465

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

PubMed

Szaflarski, Jerzy P; Gloss, David; Binder, Jeffrey R; Gaillard, William D; Golby, Alexandra J; Holland, Scott K; Ojemann, Jeffrey; Spencer, David C; Swanson, Sara J; French, Jacqueline A; Theodore, William H

2017-01-24

To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case. © 2017 American Academy of Neurology.

Detection and management of the neuroleptic malignant syndrome.

PubMed

Bond, W S

1984-01-01

Two patients who developed the neuroleptic malignant syndrome (NMS) are described, and pertinent literature is reviewed. A 30-year-old man developed NMS, apparently as a result of haloperidol treatment of chronic undifferentiated schizophrenia. Treatment with cooling blankets, acetaminophen, dantrolene sodium, and bromocriptine mesylate decreased abnormal vital signs, but catatonia continued. After 30 treatments with electroconvulsive therapy over a one-month period, the patient's catatonia was resolved, and he was discharged on no medication with the schizophrenia in remission. The second patient was a 22-year-old woman who developed NMS after five weeks of therapy with haloperidol and thiothixene for an acute episode of abnormal behavior. She did not respond to therapy with cooling blankets, acetaminophen, antibiotics, and amobarbital sodium. Dantrolene sodium therapy produced no improvement except for some relief of muscular rigidity. Electroconvulsive therapy (22 treatments over one month) successfully decreased the patient's elevated liver enzymes and leukocyte count, but periodic temperature elevations and catatonia continued. Prompt diagnosis and treatment of NMS are essential, as the mortality rate is 20%. Acute lethal catatonia and malignant hyperthermia are considered in differential diagnosis. Both central and peripheral pathophysiologic mechanisms are probably involved in NMS, and most cases are seen in patients with psychiatric illness. Onset of NMS does not seem related to duration of neuroleptic therapy and, in susceptible persons, additional factors may be required to trigger onset of NMS. Symptoms, including diffuse muscular rigidity, akinesia, and fever, develop within 24-72 hours. Neurologic symptoms may develop or worsen, and leukocytosis and elevated levels of liver enzymes occur. Death can result from respiratory or cardiovascular failure, and rhabdomyolysis can lead to acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Temporal lobe epilepsy: when are invasive recordings needed?

PubMed

Diehl, B; Lüders, H O

2000-01-01

Temporal lobe epilepsy (TLE) is the most common type of medically intractable partial epilepsy amenable to surgery. In the majority of cases, the underlying pathology in temporal lobe epilepsy is mesial temporal sclerosis (MTS). Whereas historically invasive recordings were required for most epilepsy surgeries, indications have dramatically changed since the introduction of high-resolution MRI, which uncovers structural lesions in a high percentage of cases. No invasive recordings are required to perform a temporal lobectomy in patients with intractable epilepsy who have structural imaging suggesting unilateral MTS and concordant interictal and ictal surface EEG recordings, functional imaging, and clinical findings. Invasive testing is needed if there is evidence of bitemporal MTS on structural imaging and/or electrophysiologically, and additional information from functional imaging, neuropsychology, and the intracarotid amobarbital (Wada) test also does not help to lateralize the epileptogenic zone. Depth electrodes can be particularly helpful in this setting. However, no surgery is indicated, even without invasive recordings, if bitemporal-independent seizures are recorded by surface EEG and all additional testing is inconclusive. Other etiologies of TLE such as a tumor, vascular malformation, encephalomalacia, or congenital developmental abnormality account for about 30% of all patients who undergo epilepsy surgery. Epilepsy surgery is indicated after limited electrophysiologic investigations if neuroimaging and electrophysiology converge. However, approaches for resection in lesional temporal lobe epilepsy vary among centers. Completeness of resection is crucial and invasive recordings may be needed to guide the resection by mapping eloquent cortex and/or to determine the extent of the non-MRI-visible epileptogenic area. Specific approaches for the different pathologies are discussed because there is evidence that the relationship between the lesions visible on MRI and the epileptogenic zone varies among lesions of different pathologies, and therefore variable surgical strategies must be applied.

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

PubMed

Mozaffari, Mahmood S; Baban, Babak; Liu, Jun Yao; Abebe, Worku; Sullivan, Jennifer C; El-Marakby, Ahmed

2011-03-01

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Effectiveness of four different clinical fMRI paradigms for preoperative regional determination of language lateralization in patients with brain tumors.

PubMed

Zacà, Domenico; Nickerson, Joshua P; Deib, Gerard; Pillai, Jay J

2012-09-01

Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) has demonstrated its capability to provide comparable results to gold standard intracarotid sodium amobarbital (Wada) testing for preoperative determination of language hemispheric dominance. However, thus far, no consensus has been established regarding which fMRI paradigms are the most effective for the determination of hemispheric language lateralization in specific categories of patients and specific regions of interest (ROIs). Forty-one brain tumor patients who performed four different language tasks-rhyming (R), silent word generation (SWG) sentence completion, and sentence listening comprehension (LC)-for presurgical language mapping by fMRI were included in this study. A statistical threshold-independent lateralization index (LI) was calculated and compared among the paradigms in four different ROIs for language activation: functional Broca's (BA) and Wernicke's areas (WA) as well as larger anatomically defined expressive (EA) and receptive (RA) areas. The two expressive paradigms evaluated in this study are very good lateralizing tasks in expressive language areas; specifically, a significantly higher mean LI value was noted for SWG (0.36 ± 0.25) compared to LC (0.16 ± 0.24, p = 0.009) and for R (0.40 ± 0.22) compared to LC (0.16 ± 0.24, p = 0.001) in BA. SWG LI (0.28 ± 0.19) was higher than LC LI (0.12 ± 0.16, p = 0.01) also in EA. No significant differences in LI were found among these paradigms in WA or RA. SWG and R are sufficient for the determination of lateralization in expressive language areas, whereas new semantic or receptive paradigms need to be designed for an improved assessment of lateralization in receptive language areas.

A study of the risk of mental retardation among children of pregnant women who have attempted suicide by means of a drug overdose.

PubMed

Petik, Dora; Czeizel, Barbara; Banhidy, Ferenc; Czeizel, Andrew E

2012-01-01

The aim of the study was to estimate the effect on the fetal development of high doses of prescription drugs taken as a suicide attempt during pregnancy. Pregnant women were identified among self-poisoned females in the toxicological inpatient clinic in Budapest between 1960 and 1993. Congenital abnormalities, intrauterine development based on birth weight and post-conceptional age, mental retardation, cognitive-behavioral status were compared in exposed children born to mothers who had attempted suicide by means of a drug overdose during pregnancy with their siblings, born either before or after the affected pregnancy, as sib controls. Of a total of 1 044 pregnant women, 74 used the combination of amobarbital, glutethimide and promethazine (Tardyl®, one of the most popular drugs for treatment of insomnia in Hungary) for suicide attempt. Of these 74 women, 27 delivered live-born babies. The mean dose of Tardyl® used for suicide attempts was 24 times the usually prescribed clinical dose. The rate of congenital abnormalities and intrauterine retardation was not higher in exposed children than in their sib controls. However, of the 27 exposed children, eight (29.6%) were mentally retarded (X²₁=79.7, p= Sig) while mental retardation did not occur among 46 sib controls. These exposed children were born to mothers who attempted suicide with Tardyl® between the 14th and 20th post-conceptional weeks. The components of Tardyl® used separately for a suicide attempt during pregnancy were not associated with a higher risk of mental retardation. Therefore the high doses of Tardyl® associated with the high risk for mental retardation may be due to the interaction of its three drug components. The findings of the study showed that the high doses of a drug containing three components may be associated with a significantly increased risk for mental retardation without any structural defects, whereas each of these three component drugs taken alone was not associated with this adverse effect.

The impact of sex and language dominance on material-specific memory before and after left temporal lobe surgery.

PubMed

Helmstaedter, C; Brosch, T; Kurthen, M; Elger, C E

2004-07-01

Recent findings raised evidence that in early-onset left temporal lobe epilepsy, women show greater functional plasticity for verbal memory than men. In particular, women with lesion- or epilepsy-driven atypical language dominance show an advantage over men. The question asked in this study was whether there is evidence of sex- and language dominance-dependent late, i.e. adult age, plasticity for verbal memory when epilepsy surgery is performed in these patients. Pre- and 1-year postoperative memory performance was evaluated in 169 patients (94 males and 75 females) who underwent left temporal lobe surgery and who had WADA testing of hemispheric language dominance prior to surgery. Verbal memory and figural memory were assessed by list-learning paradigms. According to the Bonn intracarotid amobarbital test (IAT) protocol, patients were categorized into left dominant or atypically dominant (right, incomplete left or right, and bilateral dominant) groups. Results were controlled for the hypothesized sex differences. Thirty-four percent of men and 47% of women displayed patterns of atypical language dominance. Atypical dominance was related to an early onset of epilepsy. Men showed a larger time window for development of atypical dominance but, differently from women, the pattern of atypical dominance was more strictly determined by the age at onset of epilepsy. Atypically dominant women showed better verbal memory than typically dominant women or men. After surgery, right dominant patients had better verbal memory outcome than patients with bilateral or left language dominance who showed significant memory loss. No effect of sex on verbal memory change was found. Figural memory deteriorated in men and improved in women, when they were not left dominant. Seizure outcome had no effect on performance changes. It was concluded that better preserved verbal memory in atypically dominant women before surgery indicates greater benefit from atypical dominance in women than men with regard to the initial damage associated with left hemisphere epilepsy. Later in life, when epilepsy surgery causes additional damage, no such sex difference is observed, indicating that the women's advantage over men is fixed to an early time window in life. Postoperative changes in figural memory suggest dynamics in crowding and suppression patterns. Whether this reflects late plasticity and compensation needs further demonstration. For clinical practice, it is important to note that incomplete right hemisphere and bilateral language dominance do not protect against verbal memory loss after left-sided temporal lobe surgery. Copyright 2004 Guarantors of Brain

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy.

PubMed

Szaflarski, Jerzy P; Allendorfer, Jane B

2012-05-01

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization. Copyright © 2012 Elsevier Inc. All rights reserved.