Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder.

Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small molecules capable of resetting and stabilizing clock genes to evaluate if they can rapidly relieve symptoms and sustain improvement.

The Mataró Stroke Registry: a 10-year registry in a community hospital.

INTRODUCTION: A prospective stroke registry leads to improved knowledge of the disease. We present data on the Mataró Hospital Registry. METHODS: In February-2002 a prospective stroke registry was initiated in our hospital. It includes sociodemographic data, previous diseases, clinical, topographic, etiological and prognostic data. We have analyzed the results of the first 10 years. RESULTS: A total of 2,165 patients have been included, 54.1% male, mean age 73 years. The most frequent vascular risk factor was hypertension (65.4%). Median NIHSS on admission: 3 (interquartile range, 1-8). Stroke subtype: 79.7% ischemic strokes, 10.9% hemorrhagic, and 9.4% TIA. Among ischemic strokes, the etiology was cardioembolic in 26.5%, large-vessel disease in 23.7%, and small-vessel in 22.9%. The most frequent topography of hemorrhages was lobar (47.4%), and 54.8% were attributed to hypertension. The median hospital stay was 8 days. At discharge, 60.7% of patients were able to return directly to their own home, and 52.7% were independent for their daily life activities. After 3 months these percentages were 76.9% and 62.9%, respectively. Hospital mortality was 6.5%, and after 3 months 10.9%. CONCLUSIONS: Our patient's profile is similar to those of other series, although the severity of strokes was slightly lower. Length of hospital stay, short-term and medium term disability, and mortality rates are good, if we compare them with other series.

Rapid assessment of transient ischaemic attack in a hospital with no on-call neurologist.

BACKGROUND: Risk of stroke soon after a transient ischaemic attack (TIA) is high. Urgent care can reduce this risk. Our aim is to describe and evaluate the efficacy of rapid assessment of TIA patients in a hospital without a neurologist available 24 hours a day. METHODS: In February 2007, we set up a protocol of rapid management of patients with symptoms consistent with acute TIA, with the aim of prioritising urgent care and reducing hospital admissions, without increasing risk of recurrences. We analyse our results since the protocol was implemented with particular focus on the analysis of delay in neurological and neurovascular assessment, percentage and reasons for hospitalisation, and stroke recurrence rates after 3 months. RESULTS: Four hundred and eleven patients were studied, with a final diagnosis of TIA in 282 (68.6%). Among other diagnoses, the most frequent were a vasovagal reaction (5.6%) and confusional syndrome (4.6%). Delay between emergency arrival and neurovascular assessment was <24h in 82% of the cases, and <48 h in 93%. After neurological evaluation, 28.7% of the patients were immediately admitted to hospital (most common causes: severe stenosis of a large artery and crescendo TIA). The incidence of ischaemic stroke in TIA patients was 3.55% after 3 months and 70% of them suffered the recurrence within the first week after the initial TIA. CONCLUSIONS: In a hospital without a neurologist available 24 hours a day, early assessment and management of TIA patients can be carried out in accordance with the guidelines, and may avoid hospitalisation in most cases without increasing recurrence rates.

Food borne-botulism during SARS-CoV-2 pandemic time. A case and a possible familial outbreak in Barcelona. / Botulismo alimentario durante la pandemia por el SARS-CoV-2. Descripción de un caso y de un posible brote familiar en Barcelona.

INTRODUCTION: Botulism is a potentially fatal neuroparalytic syndrome caused by Clostridium botulinum neurotoxin. The 25% are food-borne botulism cases. CASE REPORT: We describe a confirmed case of botulism attended in our hospital in September 2020, together with a second case in a patient's relative, suspected but not confirmed by laboratory tests. Clinical presentation consisted on general weakness, bilateral cranial palsy, mydriasis, and rapidly progressive tetraparesis in case 1, involving respiratory and swallowing function so she required hospitalization and support treatment. Non specific and transient symptoms occurred in case 2. SARS-CoV-2 infection was initially suspected in both cases due to pandemic situation in our country, ruled out by negative PCR. When B neurotoxin was detected in stool sample of patient 1 we confirmed the diagnosis of food-borne botulism probably linked to home-made conserved beans. CONCLUSION: Early clinical suspicion, together with laboratory and electromyography findings, and support treatment provided at hospital were crucial for favourable outcome. Being aware of this rare syndrom might contribute to its better management.

TITLE: Botulismo alimentario durante la pandemia por el SARS-CoV-2. Descripción de un caso y de un posible brote familiar en Barcelona.Introducción. El botulismo es un síndrome neuroparalítico hoy en día infrecuente, potencialmente fatal, causado por neurotoxinas de Clostridium botulinum. El origen es alimentario en el 25% de los casos. Caso clínico. Describimos el caso confirmado de botulismo alimentario en una paciente atendida en nuestro hospital en septiembre de 2020 y la sospecha de un segundo caso en un familiar de la paciente, no confirmado éste por las pruebas de laboratorio. La instauración en pocos días de una afectación bilateral de pares craneales, incluyendo disfagia, disnea y disartria, junto con midriasis y tetraparesia graves, precedida de diarrea, constituyó la presentación clínica en el primer caso; mientras que en su familiar cursó con síntomas inespecíficos y transitorios. Constatamos disautonomía consistente en hipotensión arterial en ambos casos. Teniendo en cuenta la situación pandémica en aquel momento, se descartó repetidamente la infección por SARS-CoV-2 antes de plantear alternativas diagnósticas. La neurotoxina B de C. botulinum fue detectada en las heces de la paciente, confirmando el diagnóstico de botulismo, que relacionamos con la ingesta de una conserva casera de alubias. Se completó el diagnóstico diferencial del cuadro descartando otras posibles etiologías. Conclusión. La sospecha clínica temprana, confirmada con los hallazgos de laboratorio y neurofisiológicos y que llevaron al manejo específico de la paciente, fueron cruciales para la evolución favorable. No fue necesario aplicar medidas de salud pública, a excepción de la notificación a sus allegados de la contaminación detectada. Conocer la existencia de esta patología puede contribuir a su pronóstico.

[Myths and evidence on the use of botulinum toxin: neuropharmacology and dystonia]. / Mitos y evidencias en el empleo de la toxina botulinica: neurofarmacologia y distonias.

INTRODUCTION: Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. AIM: To analyze and summarize different questions about the use of BTA in our clinical practice. DEVELOPMENT: A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia. A literature search at PubMed, mainly for English language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of neuropharmacology, such as mechanism of action, bioequivalence of the different preparations, immunogenicity, etc. were included. Regarding dystonia, the document included questions about methods of evaluation, cervical dystonia, blepharospasm, etc. CONCLUSION: This review does not pretend to be a guide, but rather a tool for continuous training of residents and specialists in neurology, about different specific areas of the management of BTA.

TITLE: Mitos y evidencias en el empleo de la toxina botulinica: neurofarmacologia y distonias.Introduccion. La toxina botulinica de tipo A (TBA) ha supuesto una verdadera revolucion terapeutica en neurologia, y en la actualidad es el tratamiento rutinario en las distonias focales y la espasticidad. Objetivo. Plantear, revisar y responder cuestiones controvertidas en relacion con la neurofarmacologia de la TBA y su uso en las distonias en la practica clinica habitual. Desarrollo. Un grupo de expertos en trastornos del movimiento reviso una lista de temas controvertidos relacionados con la farmacologia de la TBA y su uso en las distonias. Revisamos la bibliografia e incluimos articulos relevantes especialmente en ingles, pero tambien, si su importancia lo merece, en castellano y en frances, hasta junio de 2016. El documento se estructuro como un cuestionario que incluyo las preguntas que podrian generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. Incluimos preguntas sobre diferentes aspectos de la neurofarmacologia, especialmente el mecanismo de accion, la bioequivalencia de los diferentes preparados y la inmunogenicidad. En relacion con el subapartado de las distonias, se incluyeron aspectos sobre la evaluacion y el tratamiento de las distonias focales. Conclusiones. Esta revision no pretende ser una guia, sino una herramienta practica destinada a neurologos y medicos internos residentes interesados en esta area, dentro de diferentes ambitos especificos del manejo de la TBA.

[Effectiveness and safety of levetiracetam in patients with essential tremor: data from an open 11-week follow-up trial]. / Eficacia y tolerabilidad del levetiracetam en pacientes con temblor esencial: datos de un ensayo abierto de 11 semanas de seguimiento.

INTRODUCTION: It is a well-known fact that a relatively high proportion of patients with essential tremor are resistant to a number of pharmaceuticals currently used to treat the condition. AIM: To assess the effectiveness and safety of levetiracetam (LEV) in patients who displayed little or no response or intolerable side effects under treatment with beta blockers or primidone, or who presented contraindications against beginning such treatments. PATIENTS AND METHODS: We conducted an open 11-week pilot study in patients with the characteristics described above. The main response measurements were based on the Fahn-Tolosa-Marin (FTM) tremor rating scale, accelerometric variables and side effects. The maximum dose of LEV was 3000 mg, which was reached by patients who did not benefit from lower doses, after one week's treatment with 1000 mg and four weeks' treatment with 2000 mg. RESULTS. The sample consisted of 14 patients with essential tremor, with a mean age of 70.08 (7.99) years and an average clinical history of 11.5 years. Although by the end of the study small decreases were observed on the FTM rating scale and in the amplitude of the tremor, none of the differences were significant. Six patients dropped out of the study because of a lack of effectiveness or to side effects. CONCLUSION: LEV did not produce any statistically significant modifications in any of the variables that were monitored in this group of patients.

[Myths and evidence on the use of botulinum toxin: spasticity in adults and in children with cerebral palsy]. / Mitos y evidencias en el empleo de la toxina botulinica: espasticidad del adulto y del nintilde;o con paralisis cerebral.

INTRODUCTION: Spasticity is a medical problem with a high incidence that significantly impact on the quality of life of patients and their families. AIM: To analyze and to answer different questions about the use of botulinum toxin type A (BTA) in our clinical practice. DEVELOPMENT: A group of experts in neurology develop a list of topics related with the use of BTA. Two big groups were considered: spasticity in adults and in children with cerebral palsy. A literature search at PubMed for English, French, and Spanish language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow for modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of spasticity in adults, such as methods for evaluating spasticity, infiltration techniques, doses, number of infiltration points, etc. Regarding spasticity in children with cerebral palsy, the document included questions about minimum age of infiltration, methods of analgesia, etc. CONCLUSIONS: This review is a tool for continuous training for neurologist and rehabilitation specialist and residents of both specialties, about different specific areas of the management of BTA.

TITLE: Mitos y evidencias en el empleo de la toxina botulinica: espasticidad del adulto y del nintilde;o con paralisis cerebral.Introduccion. La espasticidad es un problema medico frecuente que impacta de forma significativa en la calidad de vida de los pacientes y sus familias. Objetivo. Analizar y dar respuesta a diferentes cuestiones en el uso de la toxina botulinica tipo A (TBA) en nuestra practica clinica habitual. Desarrollo. Un grupo de expertos en neurologia elaboro una lista de temas relacionados con el uso de la TBA. Se consideraron dos grandes bloques: espasticidad del adulto y del nintilde;o con paralisis cerebral. Se realizo una revision de la bibliografia que incluyo los diferentes articulos publicados en espantilde;ol, ingles y frances hasta junio de 2016. El documento se estructuro como un cuestionario que incluyo las preguntas que, segun el criterio del panel, podrian generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. A continuacion, el texto final fue validado. Se incluyeron diferentes preguntas sobre diferentes aspectos de la espasticidad en adultos: evaluacion de la espasticidad, tecnicas de infiltracion, dosis, numero de puntos, etc. En cuanto a la espasticidad en los nintilde;os con paralisis cerebral, se analizaron preguntas como: edad minima de infiltracion, metodos de sedoanalgesia, etc. Conclusiones. Esta revision constituye una herramienta para neurologos, medicos rehabilitadores y residentes de ambas especialidades, dentro de diferentes ambitos especificos del manejo de la TBA.

[Clinical utility of outpatient videoelectroencephalogram monitoring]. / Utilidad clínica del videoelectroencefalograma en régimen ambulatorio.

OBJECTIVE: To analyze the utility of outpatient videoelectroencephalogram (VEEG) in a general neurology department to detect an ictal event. PATIENTS AND METHODS: One hundred and five patients with ictal phenomenology of unknown etiology, suspicion of pseudoseizures, refractory epilepsy with very frequent seizures, underwent outpatient VEEG monitoring from 30 minutes to five hours of duration, between June 1, 1999 and June 30, 2003. Patient medication was not modified to perform the recording. RESULTS: Among the 105 outpatient VEEG monitoring, 33 clinical pathologic events were identified; these comprised 14 epileptic seizures, 12 pseudoseizures, four syncopes, and three non epileptic abnormal movements. Outpatient VEEG monitoring duration was as follows: 30 minutes in 12 patients, between 30 minutes and two hours in another 12, and more than two hours in 9. In 19 patients, the VEEG recording allowed a definitive diagnosis; in one case, it changed the epileptic seizure type, and in 11 patients, it helped to better characterize the epileptic seizure type. CONCLUSION: Although the percentage of pathologic events during an outpatient VEEG monitoring of 30 minutes to five hours of duration is low, its clinical repercussion is very important and the added cost is low.

Cerebral hypothyroidism in rats with adult-onset iodine deficiency.

Rats fed chronically a low iodine diet may have low serum T4 and high circulating TSH, despite normal serum T3. As the brain depends to a great extent on intracellular generation of T3 from T4 for its total and nuclear T3, we have carried out two experiments to determine whether the brain of iodine-deficient rats may become hypothyroid, despite normal serum T3 levels. In both experiments we confirmed previous data, showing that the pituitary and liver of iodine-deficient rats with very low plasma T4 levels are hypothyroid as compared to those of animals receiving the same diet supplemented with KI, though not as markedly as animals which had undetectable circulating levels of both T4 and T3 as a consequence of chronic ingestion of KC1O-4, or of surgical thyroidectomy. We have further found that the nuclear T3 content was decreased in the brain of iodine-deficient rats, as compared with the animals on the iodine-supplemented diet. The nuclear to plasma ratios of labeled T3 showed that the uptake of this hormone into liver and brain nuclei is not decreased in the iodine-deficient rats as compared with those on the iodine-supplemented diet. This finding indicates that the decreased liver and brain nuclear T3 contents of iodine-deficient rats are likely to be a consequence of the marked reduction of their T4 pool, leading to decreased amounts of intracellularly generated T3. The number of spines on shafts of pyramidal neurons from the visual cortex of iodine-deficient rats was lower than that of rats fed the same diet supplemented with KI. Their distributions along the shaft were also not the same. Such changes might well be an index of cerebral hypothyroidism, as they are similar to those found after thyroidectomy of adult rats. It is concluded from the present findings that normal circulating T3 levels may not be sufficient to maintain brain euthyroidism in rats fed a diet iodine deficient enough to result in very low circulating T4 levels.

[Cryptogenic infarct. A follow-up period of 1 year study]. / Infartos criptogénicos. Estudio de 1 año de seguimiento.

OBJECTIVE: To analyze the outcome of patients with a cryptogenic infarct (CI) after a follow-up period of 1 year. METHODS: From our prospective registry of stroke, during a 4-year period, we've identified 121 consecutive patients with a CI (15.1% of all infarcts). They have been followed up for 1 year and we have registered stroke recurrence, cardiovascular events and other incidences. RESULTS: Mean age 70.6 years-old, 53% male. Middle cerebral artery (MCA) was the most often involved territory (52 cases), 70% of them with cortical involvement. No patient died during admission, 95.8% received antiplatelet therapy and 4.1% oral anticoagulant. Fourteen patients were lost of follow-up. During 1-year period, atrial fibrillation (AF) was detected in 7 patients (6.54%), their mean age was 75 years-old, in 5 of them the CI was in MCA territory (4 with cortical involvement, 1 only deep infarct). Three patients (2.76%) suffered a recurrent ischemic stroke, in weeks 15, 16 and 44 after the CI. In all 3 cases the infarct was considered cryptogenic again. Two patients suffered a myocardial infarction and 4 died during follow-up period. CONCLUSION: In our series rate of stroke recurrence and cardiovascular events after a CI was low. An 11% of patients with a CI involving cortical MCA territory developed FA during the following year.

[Knowledge about stroke symptoms and attitude towards them in the population]. / Reconocimiento de los síntomas del ictus y respuesta frente a ellos en la población.

INTRODUCTION: To know the meaning of stroke symptoms and to perceive them as an emergency is a decisive factor to reduce hospital admission delay. The aim of the study is to analyze the degree of recognition of stroke symptoms by the patients, their attitude towards them, and which factors contribute to a better knowledge on cerebrovascular diseases. METHODS: A total of 292 patients diagnosed of stroke were studied prospectively, following a protocol designed for data collection that included 76 variables. Univariate and multivariate analyses were conducted to identify which variables were independently associated with a better interpretation of stroke symptoms and emergency perception. RESULTS: Only 34% of all patients recognized they were suffering a stroke. The background that was independently associated with a better interpretation of symptoms included previous stroke (odds ratio [OR]: 3.97), institutionalized subjects (old people's home) (OR: 3.20), motor symptoms (OR: 1.92) and more serious stroke (OR: 1.05). Only 31% of all patients, 41% of whom had recognized stroke symptoms, decided to go immediately to hospital or call for an ambulance. Variables that were independently associated with a better perception of emergency included cardioembolic stroke (OR: 2.62), not having hypertension (OR: 0.48) and a correct interpretation of stroke symptoms (OR: 0.62). CONCLUSION: Only 14% of all patients have a good knowledge about stroke and correctly act when it occurs. It is necessary to develop education programs aimed at the population that emphasize the emergency when symptoms suggesting stroke appear.

[Intracranial stenosis. Study and follow-up of 38 patients]. / Estenosis intracraneales. Estudio y seguimiento de 38 pacientes.

INTRODUCTION: To describe vascular risk factors of patients harboring intracranial arterial stenosis (IAS) as well their final outcome. METHODS: We reviewed clinical reports of all patients admitted to our Institution from April 1, 1999 to November 30, 2001 with the diagnosis of IAS. Diagnosis was made by means of magnetic resonance angiography (MRA) or four-vessels digital subtraction angiography. Thirty-eight patients harboring 56 IAS were identified. Mean follow-up was 18 months. Two control groups were selected: one was a group of 44 patients with stroke and embolic cardiopathy (EC) and the other was a group of 67 patients with stroke and extracranial stenosis without IAS. RESULTS: Mean age was 69.7 years, with male preponderance (76.3 %). Seventeen cases (44.7 %) had associated extracranial carotid stenosis greater than 50 %. Multiple IAS were found in 12 patients. Diabetes mellitus was significantly more frequent in the IAS group than in both control groups. On the other hand, cigarette smoking was more common in the IAS group with respect to the EC group. IAS was symptomatic in 25 cases, whereas in 13 patients IAS was found in the work-up for cerebral ischemia in another territory. From the group of symptomatic patients, 22 (88 %) had a Rankin scale 2 or lower on discharge and, in the long term follow-up, their incidence rate of recurrent ischemic stroke was 15 per 100 patients/year. CONCLUSIONS: Diabetes mellitus was the most specific risk factor for IAS. IAS was multiple in 32% of patients and in extracranial stenosis from moderate to severe degree was found in 44.7% of the cases. Stroke secondary to IAS caused a low dependency level at discharge. Incidence rate of recurrent ischemic stroke was 15 % patients/ year.

Incidencia de enteroparasitosis en escolares de la ciudad de Cochabamba, area fiscal / Incidence of enteroparasitic infection in public school children of the city of Cochabamba

La necesidad de contar con datos estadisticos actuales sobre la prevalencia de enteroparasitos en la poblacion del Departamento de Cochabamba, ha impulsado la realizacion del presente estudio que ha tenido como universo a ninos de 5 a 12 anos que concurren a las escuelas de ciclo basico fiscal del area urbana. El principal objetivo fue el de conocer la mencionada prevalencia para facilitar la planificacion de medidas preventivas por quienes estan encargados de la proteccion de la salud. De los resultados encontrados resalta que la Entamoeba Histolitica se encuentra en un 17// de los casos estudiados, 14// para Himenolepsia nana, 12// Giardia intestinalis y un 5// de Ascaris lumbricoides.