Posteromedial Hypothalamic Deep Brain Stimulation for Refractory Aggressiveness in a Patient With Weaver Syndrome: Clinical, Technical Report and Operative Video.

BACKGROUND AND IMPORTANCE: Deep brain stimulation of the posteromedial hypothalamus (PMH DBS) appears to be an effective treatment for drug-resistant aggressiveness. Weaver syndrome (WS) is a rare genetic disorder in which patients develop some degree of intellectual disability and rarely severe behavioral alterations that may benefit from this procedure. CLINICAL PRESENTATION: We present the case of a 26-yr-old man diagnosed with WS presenting with uncontrollable self and heteroaggressiveness and disruptive behavior refractory to pharmacological treatment and under severe physical and mechanical restraining measures. The patient was successfully treated with bilateral PMH DBS resulting in affective improvement, greater tolerance for signs of affection, regularization in his sleep pattern and appetite disturbances at 12-mo follow-up. A detailed description and video of the procedure are presented, and a review of the clinical characteristics of WS and the utility and benefits of PMH DBS for refractory aggressiveness are reviewed. CONCLUSION: To our knowledge, this is the first case of refractory aggressiveness described in WS as well as the first patient with WS successfully treated with PMH DBS.

Effectiveness of Integrative Laughter Therapy to Reduce Anxiety, Improve Self-Esteem and Increase Happiness: A Naturalistic Study at a Day Hospital for Addictive Disorders.

Little is known about the effectiveness of laughter therapy as an adjunctive treatment for patients with addictive disorders. This study aims to evaluate the benefits of integrative laughter therapy (ILT) on levels of self-esteem, anxiety, and happiness in patients treated for addiction at a day hospital (DH). A prospective, naturalistic study with a pre-post design was conducted. All 185 participants received the standard, multicomponent treatment at the DH (treatment as usual; TAU). The participants were also invited to attend weekly ILT sessions. Upon completion of the 2-month DH treatment program, patients were classified according to their attendance at the ILT sessions: patients who attended ≥80% constituted the experimental group (TAU + ILT group) while those who attended <80% were considered controls. Although both groups achieved statistically significant increases in self-esteem and happiness with a decrease in trait anxiety, the improvement on these variables was significantly greater in the TAU + ILT group. Subject to the limitations inherent to quasi-experimental research, the findings of the present study suggest that the addition of an ILT module to the standard treatment in a DH for addictive disorders may yield greater improvement in self-esteem, anxiety, and happiness compared to TAU.

[Occipital nerve stimulation for refractory chronic migraine]. / Estimulación de nervios occipitales en el tratamiento de la migraña crónica refractaria.

INTRODUCTION: Occipital nerve stimulation (ONS) is an emerging and promising preventive treatment for refractory chronic migraine. AIM: To evaluate the mechanisms of actions, clinical studies, implantation techniques and inclusion criteria of the ONS as a preventive treatment for migraine. DEVELOPMENT: This work includes a non-systematic review of the literature on the above-mentioned aspects of ONS as a treatment for refractory chronic migraine. This disease affects approximately 2% of the population and results in a significant impairment in quality of life, economic burden and interference with labor and social activities. ONS is an emerging and promising therapy for the treatment of chronic migraine with greater than 50% pain reduction in most of open-label studies and published clinical trials. Although the mechanisms of action remain unknown, there seem to be a neuromodulation of the transmitted nociceptive trigeminal information in the trigeminal caudal nucleus, what could be explained by means of the Melzack and Wall pain gate theory. ONS is a safe and well tolerated treatment, and its most frequent side effects are usually local such as electrodes displacement or infections of the surgical incision. These complications do not usually require the electrodes withdrawal. CONCLUSIONS: ONS is an effective, well tolerated and safe treatment for the prevention of chronic migraine and could emerge as a useful option for those patients with medically refractory chronic migraine.

TITLE: Estimulacion de nervios occipitales en el tratamiento de la migraña cronica refractaria.Introduccion. La estimulacion de nervios occipitales (ENO) es un tratamiento preventivo de la migraña cronica refractaria que esta adquiriendo una importancia creciente en los ultimos años. Objetivo. Evaluar el mecanismo de accion, estudios clinicos, tecnica de implantacion y criterios de inclusion de la ENO en el tratamiento preventivo de la migraña. Desarrollo. Se realiza una revision no sistematica de la bibliografia sobre los aspectos anteriormente expuestos en la ENO como tratamiento para la migraña cronica. Esta patologia afecta aproximadamente al 2% de la poblacion y da lugar a una importante disminucion de la calidad de vida e interferencia con las actividades laborales y sociales. La ENO es una terapia emergente y prometedora para el tratamiento de la migraña cronica que ha demostrado una disminucion superior al 50% en el dolor en la mayoria de los estudios abiertos y ensayos clinicos publicados. Aunque el mecanismo de accion es desconocido, parece existir una neuromodulacion de la informacion nociceptiva trigeminal en el nucleo caudal del trigemino explicada mediante la teoria de la puerta de entrada de Melzack y Wall. La ENO es un tratamiento seguro y bien tolerado, y los efectos secundarios son habitualmente locales, como desplazamiento de los electrodos o infecciones de la herida quirurgica, que habitualmente no requieren su retirada. Conclusiones. La ENO es un tratamiento eficaz, bien tolerado y seguro en la prevencion de la migraña cronica, y supone una opcion util para aquellos pacientes con migraña cronica refractaria a los tratamientos medicos convencionales.

Primary central neurocytoma of the mesencephalic tectum in a pediatric patient.

PURPOSE: Neurocytomas are tumors or neuronal differentiation, typically located within the supratentorial ventricular system. The extraventricular location is uncommon. A limited number of cases involving the brainstem have been reported and may be misdiagnosed as brainstem gliomas. Furthermore, midbrain neurocytomas are extremely rare, and no similar cases in pediatric patients have been reported in the literature to date. Brainstem location of neurocytomas often precludes gross total removal of the lesion, and in these cases, adjuvant therapies may be helpful. METHODS: We report a case of a 16-year-old child who presented with signs and symptoms of increased intracranial pressure. The magnetic resonance imaging study demonstrated the presence of a primary mesencephalic tectum lesion causing obstructive hydrocephalus. The patient underwent emergent ventriculoperitoneal shunt implantation, resolving the hydrocephalus and the clinical symptoms. The lesion was partially removed through a suboccipital craniotomy and supracerebellar infratentorial approach to the mesencephalic tectum, without intraoperative complications. RESULTS: Histological examination of the lesion was consistent with the diagnosis of extraventricular neurocytoma. The patient was referred to the oncology department for additional treatment with Gamma Knife radiosurgery. CONCLUSIONS: Although brainstem neurocytoma is rare, this case demonstrates that it should be included in the differential diagnosis of brainstem gliomas. Because of brainstem tumor location, complete surgical removal may be challenging or not possible, with a high risk of postoperative neurological deficits. Adjuvant therapies may prevent local tumor growth in cases of tumor remnants or recurrences following microsurgery in selected cases.

Lack of cytotoxic and genotoxic effects of Minthostachys verticillata essential oil: studies in vitro and in vivo.

Minthostachys verticillata (peperina) is an aromatic and medicinal plant with several uses and ethnobotanical properties. Numerous studies have demonstrated that its essential oil (Mv-EO) presents antimicrobial capacity and shows immunomodulating and anti-allergic properties in human cell lines. Thus, the goal of this study was to investigate the main chemical composition, analyzed by GC-FID, and the cyto-genotoxic effects of Mv-EO, using Vero cells, human PBMCs and mice bone marrow cells. The Mv-EO was rich in pulegone 60.5% and menthone 18.2%. Our results clearly show that Mv-EO is not cyto-genotoxic in vitro nor in vivo. It not induced cytotoxic effects, as indicated by trypan blue dye exclusion and NRU assays both in Vero cells and human PBMCs. In addition, Mv-EO (100-1000 µg/mL) not induced apoptotic effects on human PBMCs, as indicated by Hoechst staining and DNA fragmentation analysis by agarose gel electrophoresis. The in vivo assay showed that Mv-EO (25-500 mg/kg) not increased the frequency of micronucleus in bone marrow cells of mice. Further, the ratio of polychromatic/normochromatic erythrocytes was not modified. These findings suggest that Mv-EO appears to be safe as a therapeutic agent.

Apoptosis and mutagenicity induction by a characterized aqueous extract of Baccharis articulata (Lam.) Pers. (Asteraceae) on normal cells.

In a previous study we have demonstrated that cold aqueous extract of Baccharis articulata (Ba-CAE) induced the death of human peripheral blood mononuclear cells (PBMCs) and exerted low mutagenic effects on mice at 6h after administration. The aim of this work was to investigate whether the PBMCs death induced by Ba-CAE is due to apoptosis, and whether this extract exerts mutagenic effects on mice at 24 and 48h after administration. In addition, Ba-CAE was chemically characterized. PBMCs from healthy volunteers were exposed to extract (10, 20, 40, 80, 160, 320, 640 and 1280µg/mL) for 18-24h. Cell viability was determined by staining of trypan blue dye exclusion method. Apoptosis was determined by Hoechst 33258 staining, TUNEL, and DNA fragmentation analysis by agarose gel electrophoresis. BALB/c mice were injected with extract (1800, 900 and 450mg/kg) and sacrificed at 24 and 48h postinjection. Bone marrow samples were used to assess chromosome mutations by the micronucleus test. The extract induced PBMCs death by apoptosis and increased the frequency of micronuclei in bone marrow. The phytochemical study of Ba-CAE showed the presence of flavones as luteolin and acacetin, caffeoylquinic acids as chlorogenic acid, and tannins.

[Neurosurgical techniques for the neuromodulation of pain]. / Técnicas neuroquirúrgicas de neuromodulación del dolor.

Neuromodulation for treating pain goes back to the times of the ancient Egyptians, who applied natural electric currents to modulate the painful sensation. Since then, this concept has been developed in parallel with the scientific and technological development, and various forms of neuromodulation with different indications and characteristics have originated. Chronic pain may produce significant disability, which leads to important physical, social and psychological consequences. Peripheral nerve, spinal cord, deep brain and motor cortex stimulation are safe and effective techniques that control pain and improve quality of life in selected patients.

Study of antiviral and virucidal activities of aqueous extract of Baccharis articulata against Herpes suis virus.

Baccharis articulata is native of América and traditionally used for the treatment of digestive disorders and urinary infections. Cytotoxicity of aqueous extracts of B. articulata was investigated in Vero cells. As the maximal non cytotoxic concentration has been established, this concentration has been used to evaluate antiviral and virucidal activities against Herpes suis virus type 1, member of the same subfamily of Herpes simplex virus. Aqueous extracts of B. articulata exhibited more than 95% of virucidal activity. These findings support their potential application as a disinfectant or antiseptic with low toxicity and provide a valuable knowledge to ethnopharmacology properties of Baccharis articulata.

[Thalamic deep brain stimulation for refractory epilepsy]. / Estimulación cerebral profunda talámica para la epilepsia resistente.

Epilepsy is a neurological disorder that affects 1-2% of the population. Despite the available treatments (drug therapy, resective surgery, vagus nerve stimulation), there is a significant subgroup of patients that continues to have disabling seizures. The indications of deep brain stimulation are exponentially growing, and there is a wide experience with deep brain stimulation (DBS) for the treatment of abnormal movements. DBS for epilepsy may be a new therapy for the subgroup of patients that remain disabled despite other treatments. Experiments with animal models, and the new advances in our knowledge about the neurophysiological processes that govern the genesis of epilepsy, have led to the selection of various brain targets for stimulation. The thalamus is a fundamental relay centre in the corticothalamic and corticostriatal thalamocortical circuits, and it has been studied with this purpose. Studies on epileptic patients have shown various degrees of effectiveness; however, controlled studies do not permit definitive conclusions about the role of DBS in the treatment of epilepsy. Probably a better patient selection would lead to more decisive conclusions. Further randomised studies are needed to draw reliable conclusions and scientific evidence on the effectiveness of DBS for refractory epilepsy.

High dosage of ascorbic acid and alpha-tocopherol is not useful for diminishing oxidative stress and DNA damage in healthy elderly adults.

AIM: To determine the useful dosage of ascorbic acid and alpha-tocopherol against oxidative stress and DNA damage in the elderly. METHODS: A double-blind controlled clinical assay carried out in a sample of 66 healthy subjects divided into three age-paired random groups with 22 subjects in each group. Group A received placebo and group B was administered 500 mg of ascorbic acid and 400 IU of alpha-tocopherol, whereas group C received 1,000 mg of ascorbic acid and 400 IU of alpha-tocopherol for a 6-month period. The following measurements were performed before and after the 6-month treatment period: thiobarbituric acid reactive substances (TBARS); total antioxidant status (TAS); superoxide dismutase (SOD), and glutation peroxidase (GPx) and DNA damage by comet assay. RESULTS: After 6 months, group B subjects exhibited an increase in SOD and GPx enzyme levels; however, this was not statistically significant (p > 0.05). Likewise, TBARS and TAS concentrations remained unchanged (p > 0.05). In addition, in group C the decrease in TBARS and increase in SOD, GPx, and TAS were not statistically significant (p > 0.05). Similarly, average DNA migration showed no significant differences with high-dosage ascorbic acid and alpha-tocopherol. CONCLUSION: These findings suggest that administration of 1,000 mg of ascorbic acid plus 400 IU of alpha-tocopherol for 6 months is not useful for diminishing oxidative stress and DNA damage in healthy elderly adults.

Quantitative stereological evaluation of the gracile and cuneate nuclei and their projection neurons in the rat.

Stereological methods were employed to estimate the volume and neuron numbers of the rat dorsal column nuclei (DCN). These methods were applied to Nissl-stained sections from control animals and cases that received injections of horseradish peroxidase in the thalamus, the cerebellum, or the spinal cord. Additional cases received combinations of fluorescent tracers in the same structures, to examine whether some of the retrogradely labeled neurons sent collaterals to different targets. The mean volume of the DCN is 0.81 mm(3) (range 0.65-1.10 mm(3)), of which 3%, 39%, and 59% correspond, respectively, to the nucleus of Bischoff (Bi), the gracile (Gr), and the cuneate (Cu) nuclei. Within Cu, the middle division (CuM) is the largest (42%), followed by the rostral (CuR; 36%) and caudal (CuC; 22%) divisions. The mean total number of neurons in the DCN is 16,000 (range 12,400-19,500), of which 2.4%, 34.0% and 63.6% correspond, respectively, to Bi, Gr, and Cu. Within Cu, CuM contains 48% of all neurons, and 27% correspond to CuR and 25% to CuC. Interanimal variability is moderate for the whole DCN and Cu but increases when individual nuclei are considered. About 80% of DCN neurons project to the thalamus, 3% to the spinal cord, and 7% to the cerebellum. Thalamic-projecting cells are more numerous in CuM and Gr (83%), and relatively less common in Bi and CuC (72-74%). Most of the DCN neurons projecting to the spinal cord appear in CuC and CuM. Two-thirds of the neurons projecting to the cerebellum are located in CuR, 20% in CuM, and 15% in Gr. A small fraction of neurons projects simultaneously to spinal cord and thalamus.

La equidad en materia de salud vista con enfoque etnico / Equity in health as seen from an ethnic focus

In this day and age, public policies that aim to improve equity cannot limit themselves to seeking greater access for all to the job market; the lack of equity is also reflected in unequal access to health services, to education, and to political representation. In order to understand and attempt to correct this unequal access, an approach is needed that takes into account all the sociodemographic factors that shape inequality in the Region of the Americas, most notably sex, ethnic origin, and race. This paper is the product of a request by the Member States of the Pan American Health Organization for PAHO to make known the influence that race, ethnic origin, and sex have on the state of health and on access to health care services. The paper examines how racial discrimination and other forms of intolerance, the low socioeconomic and educational level of certain ethnic and racial groups, and cultural beliefs exert a decisive influence on individuals' search for health care and their possibilities of enjoying good health. This subject is particularly important this year, when the United Nations is holding its World Conference against Racism, Racial Discrimination, Xenophobia and Related Intolerance (AU)