Experience of Subcutaneous Levetiracetam in Palliative Care.

BACKGROUND: Seizures are common in palliative care patients and its control is essential in the management of these patients as it helps to reduce suffering at the end of life. Subcutaneous levetiracetam has been used off-license for seizure control in palliative care. OBJECTIVE: The objective of the study was to describe our experience with subcutaneous levetiracetam in two hospitals in Bogota, Colombia. METHODS: We conducted a retrospective review of patients treated with subcutaneous levetiracetam in two hospitals in Colombia during 2019-2021. Data were extracted from medical records, and participants were followed up as outpatients. RESULTS: Twenty-one patients were included into the study. No severe adverse effects or rise in ictal frequency were documented. Twelve patients died during hospitalization and nine continued treatments as outpatients. The principal diagnosis was structural focal epilepsy. The daily dose of levetiracetam ranged from 1,000 mg to 3,000 mg, and the duration of treatment varied among subjects between 1 and 360 days. CONCLUSION: Subcutaneous levetiracetam was well tolerated and effective in controlling seizures in palliative care when oral administration or intravenous access was not an option. Randomized controlled trials are needed to elucidate the efficacy and tolerability of subcutaneous levetiracetam in clinical practice.

Dysautonomia in people with epilepsy: A scoping review.

BACKGROUND: Epilepsy is one of the most common neurological diseases and has high morbidity and mortality. Multiple methods for assessing dysautonomia have been reported; however, the patient characteristics and epilepsy features that drive any method selection are unclear. People with epilepsy (PWE) can experience sudden unexpected death in epilepsy (SUDEP) and one reason can be dysautonomia. If dysautonomia can be detected in PWE before a severe event, then it could complement and redirect patient treatment and monitoring. OBJECTIVE: To map the available literature on dysautonomia in PWE and describe patients' characteristics and methods used to evaluate dysautonomia. METHODS: We performed a scoping literature review. We searched PubMed, Scopus, Embase, and hand searched starting from the first registry in the literature until August 2019. Studies were independently assessed by three authors and two epileptologists. We present data in tables and summarize information according to the following structure: population, concepts, and context. RESULTS: Thirty-five studies were included in the analysis with epidemiological designs including case reports (23), cross-sectional studies (4), case‒controls (7), and cohort studies (1). A total of 618 patients were enrolled. Heart rate variability, arrhythmia, blood pressure, the tilt-table test, polysomnography, respiratory function, and magnetic resonance imaging were the methods most commonly used to assess dysautonomia in PWE. A detailed description of the heart rate variability assessment is presented. CONCLUSIONS: This review provides a broad description of the available literature identifying clinical findings, the most frequently reported assessment measurements of dysautonomia, in temporal lobe epilepsy and extratemporal epilepsies.

Ocular adverse events from pharmacological treatment in patients with multiple sclerosis-A systematic review of the literature.

PURPOSE: The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis. METHODS: A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis. RESULTS: A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon ß, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon ß was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case. CONCLUSIONS: Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42020106886.

Leptin: role over central nervous system in epilepsy.

Adipose tissue is a dynamic organ with different effects on the body. Many of these effects are mediated by leptin, a hormone strongly involved in regulation of feeding and energy metabolism. It has an important role as a mediator of neuronal excitatory activity and higher brain functions. The aim of this study was to review the association between leptin and cerebral neuronal function, in particular its anticonvulsant or convulsant effects and the possible therapeutic role for treating epilepsy. For this purpose, the databases Pubmed, Science Direct, Elsevier, ResearchGate and Scielo were searched to identify experimental studies, reviews and systematic review articles, published in English, Spanish or Portuguese. Experimental studies and the presence of leptin receptors in nervous system sites other than the hypothalamus suggest an influence on higher brain functions. Indeed several animal studies have demonstrated a role of these channels in epileptiform activity as both anticonvulsive and convulsive effects have been found. The reason for these discrepancies is unclear but provides clear evidence of a potential role of leptin and leptin therapy in epileptiform activity. The association between leptin and brain function demonstrates the importance of peripheral metabolic hormones on central nervous system and opens a new way for the development of novel therapeutic interventions in diseases like epilepsy. Nevertheless further investigations are important to clarify the dynamics and diverse actions of leptin on excitatory regulation in the brain.

Síndrome de Alicia en el país de las maravillas (AIWS). Reflexión / Alice in Wonderland Syndrome (AIWS). A reflection

Abstract The Alice in Wonderland syndrome is a rare clinical neurological condition, defined by the presence of perception disorders usually interpreted by the affected patient as rare metamorphosing and depersonalization phenomena. Due to its extremely rare occurrence and its surreal and sometimes psychedelic character, the syndrome has been associated with the phenomena experienced by Alice, the character in the classic and world-famous story by Lewis Carroll.

Resumen El Síndrome de Alicia en el País de las Maravillas es una condición clínica neurológica de rara aparición, definida por la aparición de alteraciones en la percepción usualmente interpretadas por el paciente que las experimenta, como fenómenos extraños de metamorfosis y despersonalización. Por su naturaleza altamente inusual y su carácter surreal e incluso en ocasiones psicodélico, se ha relacionado al cuadro con los fenómenos experimentados por el personaje de Alicia, en la clásica y mundialmente reconocida historia de Lewis Carroll.

Oliver Sacks, maestro y divulgador de la Neurología: reflexión / Oliver Sacks, masterful teacher and spokesman of Neurology: A reflection / Oliver Sacks, mestre e divulgador da Neurologia: reflexão

RESUMEN Como es cierto sobre muchas ciencias, el conocimiento en medicina solía ser protegido con el máximo secreto, y solo quienes dedicaban sus vidas a sanar podían acceder a él. Hoy, en la era de la información, todos saben, y más importante, todas las personas quieren y buscan tener conocimiento sobre medicina. Es entonces cuando resulta crucial la existencia de científicos dispuestos y capaces de difundir el conocimiento técnico para todas las personas. En este propósito, Oliver Sacks no tenía igual. Con su estilo narrativo único y su contagiosa sonrisa, fue una luz para los pacientes y las personas que, a tientas en la oscuridad, buscaban respuestas y fue un ejemplo para todos en el campo de la neurociencia.

SUMMARY As is true about many sciences, knowledge in medicine used to be kept under the utmost secrecy, private only to those few persons that devoted their lives to healing. Today, however, in the era of information, everybody knows and, more importantly, everybody wants to know about medicine. It is then when the existence of scientists willing and able to divulge technical knowledge for all people becomes crucial. For this purpose there was none other like Oliver Sacks. With his unique tell-tale writing style and his contagious smile, he was a beacon for patients and people stumbling in the dark, looking for answers, and an example for everyone in the field of neuroscience.

RESUMO Como é verdade sobre muitas ciências, o conhecimento na medicina sempre fio muito protegido com muito segredo, e só quem dedicavam suas vidas a curar, podiam ter acesso a ele. Hoje, na era da informação, todos sabemos, e mais importante, todas as pessoas querem e buscam ter conhecimento sobre medicina. Ai então quando resulta crucial a existência de científicos dispostos e capazes de difundir o conhecimento técnico para todas as pessoas. Neste propósito, Oliver Sacks não tinha concorrência. Com seu estilo narrativo único e seu contagioso sorriso, foi uma luz para os pacientes e as pessoas que, estando na escuridão, buscavam respostas e foi um exemplo para todos no campo da neurociência.

Involvement of Astrocytes in Alzheimer's Disease from a Neuroinflammatory and Oxidative Stress Perspective.

Alzheimer disease (AD) is a frequent and devastating neurodegenerative disease in humans, but still no curative treatment has been developed. Although many explicative theories have been proposed, precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes in brain homeostasis they have become interesting targets for the study of AD. Changes in astrocyte function have been observed in brains from individuals with AD, as well as in AD in vitro and in vivo animal models. The presence of amyloid beta (Aß) has been shown to disrupt gliotransmission, neurotransmitter uptake, and alter calcium signaling in astrocytes. Furthermore, astrocytes express apolipoprotein E and are involved in the production, degradation and removal of Aß. As well, changes in astrocytes that precede other pathological characteristics observed in AD, point to an early contribution of astroglia in this disease. Astrocytes participate in the inflammatory/immune responses of the central nervous system. The presence of Aß activates different cell receptors and intracellular signaling pathways, mainly the advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, responsible for the transcription of pro-inflammatory cytokines and chemokines in astrocytes. The release of these pro-inflammatory agents may induce cellular damage or even stimulate the production of Aß in astrocytes. Additionally, Aß induces the appearance of oxidative stress (OS) and production of reactive oxygen species and reactive nitrogen species in astrocytes, affecting among others, intracellular calcium levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing the risk of excitotoxicity) and mitochondrial function. Excessive neuroinflammation and OS are observed in AD, and astrocytes seem to be involved in both. The Aß/NF-κB interaction in astrocytes may play a central role in these inflammatory and OS changes present in AD. In this paper, we also discuss therapeutic measures highlighting the importance of astrocytes in AD pathology. Several new therapeutic approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids and other natural phytochemicals have been explored in astrocytes, obtaining some promising results regarding cognitive improvements and attenuation of neuroinflammation. Novel strategies comprising astrocytes and aimed to reduce OS in AD have also been proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, and various antioxidatives such as resveratrol, tocotrienol, anthocyanins, and epicatechin, showing beneficial effects in AD models.

Vías de señalización mTOR y AKT en epilepsia / Signaling pathways mTOR and AKT in epilepsy

Introducción. La vía de señalización AKT/mTOR es un eje central en la regulación celular, especialmente en las enfermedades neurológicas. En la epilepsia, se ha evidenciado su alteración dentro de su proceso fisiopatológico. Sin embargo, aún no se han descrito todos los mecanismos de estas rutas de señalización, las cuales podrían abrir la puerta hacia nuevas investigaciones y estrategias terapéuticas, que finalmente permitan desarrollar tratamientos efectivos en enfermedades neurológicas como la epilepsia. Objetivo. Revisar las asociaciones existentes entre las rutas de señalización intracelular de mTOR y AKT en la fisiopatología de la epilepsia. Desarrollo. La epilepsia es una enfermedad neurológica con un alto impacto epidemiológico en el mundo, por lo cual es de sumo interés la investigación de los componentes fisiopatológicos que puedan generar nuevos tratamientos farmacológicos. En esta búsqueda se han involucrado diferentes rutas de señalización intracelular en neuronas, como determinantes epileptógenos. Los avances en esta materia han permitido incluso la implementación de nuevas estrategias terapéuticas exitosas y que abren el camino hacia nuevas investigaciones. Conclusiones. Mejorar los conocimientos respecto al papel fisiopatológico de la vía de señalización mTOR/AKT en la epilepsia permite plantear nuevas investigaciones que ofrezcan nuevas alternativas terapéuticas para el tratamiento de la enfermedad. El uso de inhibidores de mTOR ha surgido en los últimos años como una alternativa eficaz en el tratamiento de algunos tipos de epilepsias, pero es evidente la necesidad de seguir en la búsqueda de nuevas terapias farmacológicas involucradas en estas vías de señalización (AU)

Introduction. The signaling pathway AKT/mTOR is a central axis in regulating cellular processes, particularly in neurological diseases. In the case of epilepsy, it has been observed alteration in the pathophysiological process of the same. However, they have not described all the mechanisms of these signaling pathways that could open the opportunity to new research and therapeutic strategies. Aim. To review existing partnerships between intracellular signaling pathways AKT and mTOR in the pathophysiology of epilepsy. Development. Epilepsy is a disease with a high epidemiological impact globally, so it is widely investigated regarding the pathophysiological components thereof. In that search they have been involved different intracellular signaling pathways in neurons, as determinants epileptogenic. Advances in this field have even allowed the successful implementation of new therapeutic strategies and to open the way to new research in the field. Conclusions. Improving knowledge about the pathophysiological role of the signaling pathway mTOR/AKT in epilepsy can raise new investigations regarding therapeutic alternatives. The use of mTOR inhibitors, has emerged in recent years as effective in treating this disease entity alternative however is clear the necessity of continue the research for new drug therapies (AU)

Gilles de la Tourette y su síndrome / Gilles de la Tourette and his syndrome

Georges Albert Brutus Edouard Gilles de la Tourette nació y se crio dentro de una época esplendorosa de Francia. Se destacó por sus méritos como estudiante y fue educado para que tuviera una brillante carrera como médico. Su paso por el hospital Pitie-Salpêtrière fue algo fundamental en su vida, ya que allí conoció al profesor Jean-Martin Charcot quien le brindó la oportunidad y las herramientas para estudiar su pasión, la Neurología, de una manera amplia la y dedicarse a otros casos interesantes dedicados a la mente humana. Gracias a esto pudo describir la patología que hoy nos compete como el síndrome de La Tourette. Su estudio y su incansable curiosidad permitieron además involucrarse no sólo con este síndrome sino que ayudó a hacer múltiples descripciones de otras patologías e incursionó en el nuevo campo del hipnotismo. Sin embargo, su muerte prematura, debido a una enfermedad hoy en día curable, hizo que se truncara la maravillosa mente de este neurólogo que, muy seguramente, hubiese aportado más conocimiento de la época a nuestro saber actual.

Georges Albert Edouard Brutus Gilles de la Tourette was born and raised in an era of French splendor; he was an outstanding student, educated to have a brilliant career as a doctor. Passing through the Pitie-Salpetriere hospital was critical in his life, there were the place where he had the opportunity to meet Professor Jean-Martin Charcot, who would be his colleague and friend throughout his life. Charcot gave him the opportunity and the tools to study his passion, neurology, in a comprehensive manner, and to pursue interesting cases dedicated to the study of the human mind. It was thanks to this that he could so aptly describe the disease that concerns us today as Tourette’s syndrome. His study and tireless curiosity also allowed him to get involved not only with this syndrome but helped him make multiple descriptions of other diseases and to enter the new field of hypnotism. But his premature death, due to an illness which would have been curable today, cut short this brilliant career; otherwise, he would, most certainly, have contributed a lot more to our current knowledge of neurology.