Neuropharmacological aspects of cognitive neurorehabilitation in epilepsy.

The role of CNS neuromodulators in cognitive neurorehabilitation can be related to two main issues: 1) the negative impact on cognition of drug categories prescribed for different neurologic symptoms, such as spasticity, extrapyramidal symptoms, or epileptic seizures; 2) their possible role in neuroprotection and amelioration of the cognitive status of the patient, especially attention and memory. This paper reviews different pharmacological aspects of cognitive neurorehabilitation in epilepsy

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Poetry by Rhys Trimbl

Treatment of psychoses in patients with epilepsy: an update.

Psychotic disorders represent a relatively rare but serious comorbidity in epilepsy. Current epidemiological studies are showing a point prevalence of 5.6% in unselected samples of people with epilepsy going up to 7% in patients with temporal lobe epilepsy, with a pooled odds ratio of 7.8 as compared with the general population. This is a narrative review of the most recent updates in the management of psychotic disorders in epilepsy, taking into account the clinical scenarios where psychotic symptoms occur in epilepsy, interactions with antiepileptic drugs (AEDs) and the risk of seizures with antipsychotics. Psychotic symptoms in epilepsy can arise in a number of different clinical scenarios from peri-ictal symptoms, to chronic interictal psychoses, comorbid schizophrenia and related disorders to the so-called forced normalization phenomenon. Data on the treatment of psychotic disorders in epilepsy are still limited and the management of these problems is still based on individual clinical experience. For this reason, guidelines of treatment outside epilepsy should be adopted taking into account epilepsy-related issues including interactions with AEDs and seizure risk. Second-generation antipsychotics, especially risperidone, can represent a reasonable first-line option because of the low propensity for drug-drug interactions and the low risk of seizures. Quetiapine is burdened by a clinically significant pharmacokinetic interaction with enzyme-inducing drugs leading to undetectable levels of the antipsychotic, even for dosages up to 700 mg per day

The functional neuroimaging correlates of psychogenic versus organic dystonia

The neurobiological basis of psychogenic movement disorders remains poorly understood and the management of these conditions difficult. Functional neuroimaging studies have provided some insight into the pathophysiology of disorders implicating particularly the prefrontal cortex, but there are no studies on psychogenic dystonia, and comparisons with findings in organic counterparts are rare. To understand the pathophysiology of these disorders better, we compared the similarities and differences in functional neuroimaging of patients with psychogenic dystonia and genetically determined dystonia, and tested hypotheses on the role of the prefrontal cortex in functional neurological disorders. Patients with psychogenic (n = 6) or organic (n = 5, DYT1 gene mutation positive) dystonia of the right leg, and matched healthy control subjects (n = 6) underwent positron emission tomography of regional cerebral blood flow. Participants were studied during rest, during fixed posturing of the right leg and during paced ankle movements. Continuous surface electromyography and footplate manometry monitored task performance. Averaging regional cerebral blood flow across all tasks, the organic dystonia group showed abnormal increases in the primary motor cortex and thalamus compared with controls, with decreases in the cerebellum. In contrast, the psychogenic dystonia group showed the opposite pattern, with abnormally increased blood flow in the cerebellum and basal ganglia, with decreases in the primary motor cortex. Comparing organic dystonia with psychogenic dystonia revealed significantly greater regional blood flow in the primary motor cortex, whereas psychogenic dystonia was associated with significantly greater blood flow in the cerebellum and basal ganglia (all P < 0.05, family-wise whole-brain corrected). Group × task interactions were also examined. During movement, compared with rest, there was abnormal activation in the right dorsolateral prefrontal cortex that was common to both organic and psychogenic dystonia groups (compared with control subjects, P < 0.05, family-wise small-volume correction). These data show a cortical-subcortical differentiation between organic and psychogenic dystonia in terms of regional blood flow, both at rest and during active motor tasks. The pathological prefrontal cortical activation was confirmed in, but was not specific to, psychogenic dystonia. This suggests that psychogenic and organic dystonia have different cortical and subcortical pathophysiology, while a derangement in mechanisms of motor attention may be a feature of both conditions

Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus.</p> <p>Case presentation</p> <p>Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus.</p> <p>Conclusions</p> <p>In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.</p

Neonatal Oral Imitation in Patients with Severe Brain Damage

Background: Neonates reproduce facial movements in response to an adult model just after birth. This neonatal oral imitation usually disappears at about 2- to 3-months of age following the development of cortical control. There is controversy relating to the nature and neural basis of such neonatal imitation. To address this issue, we studied the relationship between oral imitation, primitive reflexes, and residual voluntary movement in patients with severe brain damage. Methods: Six male and six female patients with cerebral palsy, from 4 to 39 years, were included in this study. Oral imitation was examined when they were awake and looked at the experimenter. Patients were evaluated as performing oral imitation when they opened their mouth repeatedly without visual feedback regarding their own behavior in response to the experimenter’s oral movement. Tongue or lip protrusion was not examined because none of patients were able to do those behaviors due to their physical disability. Rooting and sucking reflexes were also investigated as representatives of primitive reflexes. Results: Six patients (50%) performed oral imitation. Mouth opening was not observed repeatedly in response to other facial expression without opening the mouth such as surprise or smile, excluding the possibility of nonspecific oral reaction. They exhibited little voluntary movement of their extremities. Half of them also manifested at least one primitive reflex. N

The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research

The evolution of rotating stars

First, we review the main physical effects to be considered in the building of evolutionary models of rotating stars on the Upper Main-Sequence (MS). The internal rotation law evolves as a result of contraction and expansion, meridional circulation, diffusion processes and mass loss. In turn, differential rotation and mixing exert a feedback on circulation and diffusion, so that a consistent treatment is necessary. We review recent results on the evolution of internal rotation and the surface rotational velocities for stars on the Upper MS, for red giants, supergiants and W-R stars. A fast rotation is enhancing the mass loss by stellar winds and reciprocally high mass loss is removing a lot of angular momentum. The problem of the ``break-up'' or $\Omega$-limit is critically examined in connection with the origin of Be and LBV stars. The effects of rotation on the tracks in the HR diagram, the lifetimes, the isochrones, the blue to red supergiant ratios, the formation of W-R stars, the chemical abundances in massive stars as well as in red giants and AGB stars, are reviewed in relation to recent observations for stars in the Galaxy and Magellanic Clouds. The effects of rotation on the final stages and on the chemical yields are examined, as well as the constraints placed by the periods of pulsars. On the whole, this review points out that stellar evolution is not only a function of mass M and metallicity Z, but of angular velocity $\Omega$ as well.Comment: 78 pages, 7 figures, review for Annual Review of Astronomy and Astrophysics, vol. 38 (2000

Peptidases compartmentalized to the Ascaris suum intestinal lumen and apical intestinal membrane

The nematode intestine is a tissue of interest for developing new methods of therapy and control of parasitic nematodes. However, biological details of intestinal cell functions remain obscure, as do the proteins and molecular functions located on the apical intestinal membrane (AIM), and within the intestinal lumen (IL) of nematodes. Accordingly, methods were developed to gain a comprehensive identification of peptidases that function in the intestinal tract of adult female Ascaris suum. Peptidase activity was detected in multiple fractions of the A. suum intestine under pH conditions ranging from 5.0 to 8.0. Peptidase class inhibitors were used to characterize these activities. The fractions included whole lysates, membrane enriched fractions, and physiological- and 4 molar urea-perfusates of the intestinal lumen. Concanavalin A (ConA) was confirmed to bind to the AIM, and intestinal proteins affinity isolated on ConA-beads were compared to proteins from membrane and perfusate fractions by mass spectrometry. Twenty-nine predicted peptidases were identified including aspartic, cysteine, and serine peptidases, and an unexpectedly high number (16) of metallopeptidases. Many of these proteins co-localized to multiple fractions, providing independent support for localization to specific intestinal compartments, including the IL and AIM. This unique perfusion model produced the most comprehensive view of likely digestive peptidases that function in these intestinal compartments of A. suum, or any nematode. This model offers a means to directly determine functions of these proteins in the A. suum intestine and, more generally, deduce the wide array functions that exist in these cellular compartments of the nematode intestine

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201