Management of refractory complex partial seizures: current state of the art

Diagnosis of complex partial epilepsy is based on the clinical history, and laboratory tests, including EEG and neuroimaging studies, corroborate the diagnosis. The goal of epilepsy management is to make the patient completely seizure-free without drug-induced side effects, even in the patient with refractory complex partial seizures. Frequently this can be accomplished by choice of the optimal antiepileptic drug (AED) or a combination of drugs, the use of strategies to maximize the effectiveness of drug treatment, or by surgical removal of the seizure focus. Currently there are five “classical” first-line AEDs and 11 new AEDs available in the US and in many other countries for the treatment of localization-related epilepsy. The current state of the evidence is that no AED is clearly superior to other AEDs in the management of refractory complex partial seizures. Therefore the choice of which drug to use in an individual patient has to be based on other considerations, including the potential adverse reactions that may occur in that patient. There are a number of strategies for optimal use of AEDs in the management of refractory complex partial seizures. These include verification of the diagnosis of epilepsy and classification of specific seizure types, use of monotherapy if possible but polytherapy if necessary, starting with a low dose and raising it slowly but, until complete seizure control is achieved, pushing to the maximum tolerated dose, changing timing of dosing to reduce toxicity, using pharmacokinetic principles to fine-tune AED doses, adjusting dose for drug–drug interactions, and never giving up in the pursuit of better seizure control. Resection of the seizure focus can be curative in the majority of patients with seizures localized to one mesial temporal lobe. Success rates for resection of extratemporal seizure foci are lower. Vagus nerve stimulation (VNS) devices result in a significant reduction of seizure frequency in many patients, but patients rarely become completely seizure-free as a result of VNS device implantation. Management of refractory complex partial seizures continues to improve with the identification of new drugs and the development of new approaches to their control and cure

Gender Differences in Human Single Neuron Responses to Male Emotional Faces

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender€™s role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15/66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6/76) of neurons in women. A Fisher€™s exact test comparing the two ratios found a highly significant difference between the two (p \u3c 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala

Psychometric Evaluation and Design of Patient-Centered Communication Measures for Cancer Care Settings

Objective To evaluate the psychometric properties of questions that assess patient perceptions of patient-provider communication and design measures of patient-centered communication (PCC). Methods Participants (adults with colon or rectal cancer living in North Carolina) completed a survey at 2 to 3 months post-diagnosis. The survey included 87 questions in six PCC Functions: Exchanging Information, Fostering Health Relationships, Making Decisions, Responding to Emotions, Enabling Patient Self-Management, and Managing Uncertainty. For each Function we conducted factor analyses, item response theory modeling, and tests for differential item functioning, and assessed reliability and construct validity. Results Participants included 501 respondents; 46% had a high school education or less. Reliability within each Function ranged from 0.90 to 0.96. The PCC-Ca-36 (36-question survey; reliability=0.94) and PCC-Ca-6 (6-question survey; reliability=0.92) measures differentiated between individuals with poor and good health (i.e., known-groups validity) and were highly correlated with the HINTS communication scale (i.e., convergent validity). Conclusion This study provides theory-grounded PCC measures found to be reliable and valid in colorectal cancer patients in North Carolina. Future work should evaluate measure validity over time and in other cancer populations. Practice implications The PCC-Ca-36 and PCC-Ca-6 measures may be used for surveillance, intervention research, and quality improvement initiatives

Sparse and Distributed Coding of Episodic Memory in Neurons of the Human Hippocampus

Neurocomputational models hold that sparse distributed coding is the most efficient way for hippocampal neurons to encode episodic memories rapidly. We investigated the representation of episodic memory in hippocampal neurons of nine epilepsy patients undergoing intracranial monitoring as they discriminated between recently studied words (targets) and new words (foils) on a recognition test. On average, single units and multiunits exhibited higher spike counts in response to targets relative to foils, and the size of this effect correlated with behavioral performance. Further analyses of the spike-count distributions revealed that (i) a small percentage of recorded neurons responded to any one target and (ii ) a small percentage of targets elicited a strong response in any one neuron. These findings are consistent with the idea that in the human hippocampus episodic memory is supported by a sparse distributed neural code

Magmatic volatiles (H, C, N, F, S, Cl) in the lunar mantle, crust, and regolith: abundances, distributions, processes, and reservoirs

There have been many studies on magmatic volatiles (H, C, N, F, S, Cl) in and on the Moon within the last several years that have cast into question the post-Apollo view of lunar formation, the distribution and sources of volatiles in the Earth-Moon system, and the thermal and magmatic evolution of the Moon. However, these recent observations are not the first data on lunar volatiles. When Apollo samples were first returned, substantial efforts were made to undersand volatile elements and a wealth of data regarding volatile elements exists in this older literature. In this review paper we approach volatiles in and on the Moon using new and old data derived from lunar samples and remote sensing. From combining these data sets, we identified many points of convergence, although numerous questions remain unanswered

Mineralogy

The power of mineralogical analysis as a descriptive or predictive technique stems from the fact that only a few thousand minerals are known to occur in nature as compared to several hundred thousand inorganic compounds. Further, all of the known minerals have specific stability ranges in pressure, temperature, an composition. A specific knowledge of the mineralogy of a planets surface or interior therefore allows one to characterize the present or past conditions under which the minerals were formed or have existed. For the purposes of this paper, a slightly broader definition of mineralogy was adopted by including not only crystalline materials found on planetary surfaces, but also ices and classes that can benefit from in situ types of analyses. Both visual examination and the various spectroscopies available for robotic probes to planetary surfaces are discussed

Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy

Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration

Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy

Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration

Clinical follow-up rather than duplex surveillance after carotid endarterectomy

AbstractPurpose: The value of duplex surveillance and the significance of contralateral carotid disease after endarterectomy have been assessed.Methods: Three hundred five patients were observed prospectively after carotid endarterectomy for a median time of 36 months (range, 6 to 96 months), with duplex surveillance performed at 1 day; 1 week; 3, 6, 9, and 12 months; and then each year after endarterectomy.Results: Thirty patients (10%) had ipsilateral symptoms (13 strokes, 17 transient ischemic attacks [TIAs]) at a median time of 6 months (range, 0 to 60 months). Life table analysis demonstrated that ipsilateral stroke was equally common for patients who had ≥50% restenosis (3% at 36 months) and those who did not (6% at 36 months, p > 0.5). Twenty-three patients (8%) developed symptoms (stroke 5, TIA 14) attributable to the contralateral carotid artery at a median time of 9 months (range, 0 to 36 months) after endarterectomy. By life table analysis, 40% of patients with 70% to 99%, 6% with 50% to 69%, 1% with <50% contralateral internal carotid stenosis, and 5% with contralateral carotid occlusion at the time of endarterectomy had a contralateral TIA in the 36 months after endarterectomy ( p < 0.01). However, contralateral stroke was not significantly more common for patients with severe contralateral internal carotid stenosis demonstrated at the time of endarterectomy (<50% stenosis, 0%; 50% to 69%, 3%; 70% to 99%, 7%; occlusion, 6% stroke rate at 36 months). Seven of the 32 patients who developed progression of contralateral disease had a TIA, compared with 11 of 227 patients who did not develop progression of contralateral disease ( p < 0.01). None of the 12 patients who progressed from a <70% to a 70% to 99% contralateral stenosis had a stroke.Conclusions: After carotid endarterectomy restenosis is rarely associated with symptoms; contralateral stroke is rare and is not associated with progressive internal carotid artery disease suitable for endarterectomy. This study has shown no benefit from long-term duplex surveillance after carotid endarterectomy. Selective clinical follow-up of patients who have high-grade contralateral stenoses would appear more appropriate. (J Vasc Surg 1997;25:55-63.