Promoting tear production: neurostimulation for dry eye / 中华实验眼科杂志

Dry eye syndrome is a common ocular surface disorder often caused by deficient or poor-quality tear production.There are numerous therapeutic approaches to address dry eye, however, there are quite a number of patients with unsatisfactory treatment results, and neurostimulation therapy has introduced an innovative solution to this challenge.This therapy involves stimulation of the nasal nerves to activate the lacrimal reflex pathway, thereby increasing tear secretion.Unlike traditional dry eye treatments, its unique capacity is to stimulate the natural production of tears, as opposed to simply supplementing tear components.Theoretically, this method may be more effective in restoring tear film stability.Neurostimulation is a promising alternative for the management of dry eye, with several designs successfully transitioning to commercialization after clinical trials.In clinical practice, neurostimulation can significantly promote immediate tear secretion after application.In addition, some studies have reported that long-term use of neurostimulation can relieve the symptoms and signs of dry eye in some research.Ophthalmologists and ophthalmic researchers are encouraged to pay attention to the application and investigation of neurostimulation therapy in dry eye management.Future research should focus on exploring the long-term effects of neurostimulation on dry eye symptoms and signs, how it can be integrated into existing dry eye treatment protocols, and promoting neurostimulation therapy to benefit more dry eye patients.

Recent advance in treatment of refractory epilepsy by reactive nerve stimulation / 中华神经医学杂志

Neuromodulation techniques as vagus nerve stimulation (VNS) and deep brain stimulation (DBS) play important roles in treating refractory focal epilepsy. In recent years, epileptogenic zone closed-loop responsive neurostimulator system (RNS) has been gradually put into clinical practice; in 2013, it was approved by U.S. Food and Drug Administration (FDA) as an adjuvant therapy for refractory epilepsy. This article reviews the development history, clinical application, anti-epileptic mechanism and future research directions of RNS to deepen the understanding of clinical workers.

Second Courses of Transcranial Magnetic Stimulation (TMS) in Major Depressive Episodes for Initial Responders and Non- Responders

@#Background: Transcranial Magnetic Stimulation (TMS) is effective in major depressive episodes (MDE). However, MDE may follow a chronic, relapsing course, and some individuals may not satisfactorily respond to a first course of TMS. Objective: To investigate the outcome of second courses of TMS. Method: A naturalistic investigation—we prospectively studied 30 MDE in-patients and routinely collected information, including pre- and post-treatment with Six-item Hamilton Depression Rating Scale (HAMD6), a six-item Visual Analogue Scale (VAS6) and the Clinical Global Impression-Severity (CGI-S). Two categories of patients were considered: i) those who had remitted with a first course, but relapsed, and ii) those who had not remitted with the first course. Results: Thirty individuals received a second TMS course. The mean time to the second course was 27.5 weeks. Based on the HAMD6, 26 (87%) achieved remission after the first course, and 22 (73%) achieved remission after the second course. Furthermore, based on the HAMD6 results, of the four patients who did not achieve remission with a first course, three (75%) did so with a second course. Conclusion: In MDE, a second course of TMS is likely to help those who remitted to a first course and then relapsed, as well as those who did not achieve remission with a first course.

C1-C4 Dorsal Column Stimulation for Refractory Occipital Neuralgia Treatment. Case Report

Introduction Refractory occipital neuralgia is a difficult medical condition, especially when the patient has already been submitted to occipital nerve neurectomy and radiofrequency rhizotomy. There is no case report of spinal cord stimulation in the C1- C4 cervical segments for this condition. Objective To evaluate if C1-C4 dorsal spinal cord stimulation is effective in a patient with refractory occipital neuralgia who was already submitted to neurectomy and rhizotomy. Methods After obtaining the approval from the Ethics Committee of one of our institutions, a unilateral laminectomy was performed between C3 and C4, and a neurostimulator lead was conducted until the posterior portion of the C1 arc was in full view. Then we performed an intraoperative test to evaluate the correspondence between pain location and stimulation-induced paresthesias. We could not put the subcutaneous lead for such condition because of the scar tissue of the area and the previous neurectomy. Results After one year of follow up, we noticed a dramatic improvement in pain control, as well as medication withdrawal. The score of the visual analogue scale was 9 before the surgery, and it dropped to 2 after 1 year of follow-up. Conclusion Spinal cord stimulation between the C1 and C4 cervical segments can be an option for selected cases of refractory occipital neuralgia, including those patients who have already been submitted to neurectomy or rhizotomy.

Neuralgia occipital refratária é uma condição médica difícil, especialmente em pacientes submetidos previamente a neurectomia nos nervos occipitais e rizotomia por radiofrequência. Não há na literatura relato de estimulação da medula espinhal entre os níveis C1 e C4 para essa condição. Objetivos Avaliar se a estimulação da coluna dorsal da medula nos níveis C1 a C4 é eficaz no controle da dor em paciente com neuralgia occipital refratária já submetido a neurectomia e rizotomia. Métodos Após aprovação do Conselho de Ética de uma de nossas instituições, foi realizada laminectomia unilateral de C3 e C4, com posterior introdução do conjunto de eletrodos em placa, que foi posicionado até que a porção anterior do arco de C1 estivesse sob visão direta. Posteriormente, foi realizado um teste intraoperatório para avaliar a correspondência entre a área dolorosa e a parestesia induzida pela estimulação. Não possível optar pelo uso de eletrodo subcutâneo devido ao extenso tecido cicatricial secundário às cirurgias prévias. Resultados Melhora significativa da dor ocorreu ao longo de um ano de acompanhamento, com redução progressiva da dose da medicação. O valor da escala visual analógica no pré-operatório era 9, e após 1 ano de acompanhamento, reduziu para 2. Conclusão Estimulação da coluna dorsal da medula espinhal entre os seguimentos C1 e C4 pode, em casos selecionados, ser uma opção terapêutica na neuralgia occipital refratária, incluindo pacientes que já foram submetidos a neurectomia e rizotomia.

Utilidad de la estimulación intra-operatoria en cirugía de procesos expansivos intracraneanos bajo anestesia general / Usefulness of intraoperative stimulation in surgery of expansive intracranial processes under general anesthesia

Resumen Introducción: El método de estimulación cortical y subcortical intraoperatoria (ECIO) es una técnica que en la última década se ha extendido en todo el mundo gracias a los éxitos reportados. La misma ha contribuido a lograr resecciones amplias de tumores cerebrales en áreas elocuentes manteniendo la indemnidad funcional. Este trabajo tiene como objetivo mostrar los resultados de la ECIO en una serie de pacientes con lesiones cerebrales operados bajo anestesia general. Metodología: Se presenta una serie clínica de 11 pacientes con lesiones cerebrales que fueron intervenidos en el período de agosto 2013 a julio de 2016 en diferentes centros de salud del Uruguay por un mismo grupo de cirujanos. En todos se realizó ECIO bajo anestesia general y las lesiones estaban relacionadas a la vía piramidal, cortical o subcortical. Resultados: Fueron 6 mujeres (55%) y 5 hombres (45 %), en un rango de edad entre 30 y 65 años. La función motora fue conservada en 7 pacientes (63%), aunque 3 tuvieron una peoría transitoria (27%), con un déficit permanente (9%). Hubo 8 tumores primarios y 3 secundarios. La distribución topográfica fue: 5 frontales (45%), 1 rolándica, 4 parietales y 1 talámica. Luego de estimular se obtuvo respuesta motora 6 casos (55%). Se logró la resección completa en 7 casos (63%). Conclusiones: La ECIO permite mapear la vía piramidal y determinar la relación que establece con el proceso patológico. Esto impacta directamente en el grado de resección tumoral respetando la función motora, todo lo cual converge en una mejor calidad de vida del paciente.

Abstract: Introduction: The method of intraoperative cortical and subcortical stimulation (ICS) is a technique that in the last decade has spread worldwide thanks to the successes reported. It has contributed to wide resections of brain tumors in eloquent areas preserving their functional indemnity. This study aims to show the results of ICS in a series of patients with brain lesions operated under general anesthesia. Methods: A series of 11 patients with brain lesions were operated on in the period between august 2013 and july 2016 in different uruguayan health centers. The patients where operated on under general anestesia and all of the cases were lesions related to the pyramidal pathway, cortically or subcortically. Results: There were six women (55%) and five men (45%), ranging from 30 to 65 years of age. The motor function was preserved in 7 patients (63%). There were 8 primary and 3 secondary tumors. The topographic distribution was: 5 frontal (45%), 1 rolandic, 4 parietal, 1 thalamic. Stimulation for motor response was positive in 6 cases (55%). Complete resection was performed in 7 cases (65%). Conclusions : The ICS allows mapping of the pyramidal tract and determines the relationship established with the pathological process. This impacts directly on the extent of tumor resection respecting motor function, thus leading to a better quality of life for patients.

Spinal Cauda Equina Stimulation for Alternative Location of Spinal Cord Stimulation in Intractable Phantom Limb Pain Syndrome: A Case Report

Phantom limb pain is a phenomenon in which patients experience pain in a part of the body that no longer exists. In several treatment modalities, spinal cord stimulation (SCS) has been introduced for the management of intractable post-amputation pain. A 46-year-old male patient complained of severe ankle and foot pain, following above-the-knee amputation surgery on the right side amputation surgery three years earlier. Despite undergoing treatment with multiple modalities for pain management involving numerous oral and intravenous medications, nerve blocks, and pulsed radiofrequency (RF) treatment, the effect duration was temporary and the decreases in the patient's pain score were not acceptable. Even the use of SCS did not provide completely satisfactory pain management. However, the trial lead positioning in the cauda equina was able to stimulate the site of the severe pain, and the patient's pain score was dramatically decreased. We report a case of successful pain management with spinal cauda equina stimulation following the failure of SCS in the treatment of intractable phantom limb pain.

Impacto del manejo con neuroestimulación en un paciente con síndrome doloroso complejo y cambios tróficos severos. Reporte de caso / Impact of the use of neurostimulation for the management of a patient with complex pain syndrome and severe trophic changes. Case report

Introducción: Causas frecuentes de síndrome doloroso regional complejo (SDRC) son el trauma y la cirugía en extremidades. Algunos casos resultan demuy difícil manejo a pesar de la utilización de altas dosis de analgésicos, antiinflamatorios y terapia física lo cual motiva la búsqueda de terapias intervencionistas que frenen su progresión. Descripción del caso y resultados: Presentamos el caso de un paciente a quien se le diagnosticó SDRC tipo i con cambios tróficos severos y marcada limitación funcional, que fue manejado con múltiples terapias farmacológicas y bloqueos nerviosos sin mejoría evidente, a quien posteriormente se decidió realizar una prueba con neuroestimulación, la cual fue favorable. Meses después se obtuvo una mejoría sustancial ya que presentó mejoría del dolor «de un 100%¼; disminución del edema y retorno progresivo al aspecto normal de la mano, recuperación parcial de la fuerza y disminución de su limitación funcional, explicable por la adición de esta terapia de manera definitiva. Conclusión: La neuroestimulación ejerce un impacto notable sobre la evolución del SDRC con cambios tróficos en pacientes con pobre respuesta al manejo farmacológico indicado. El inicio temprano de esta intervención facilita la recuperación funcional y psicológica al paciente que, usualmente, se encuentra en una etapa productiva de su vida.

Introduction: Limb trauma and surgery are frequent causes of complex regional pain syndrome (CRPS). Some cases are very difficult to manage despite the use of high-dose analgesics, anti-inflammatory agents and physical therapy; hence the need to look for interventional therapies to slow its progression. Case description and results: We present the case of a patient diagnosed with CRPS type I with severe trophic changes and marked functional limitation, managed with multiple pharmacological therapies and nerve blocks without apparent improvement. The patient decided to try neurostimulation with favourable results and substantial improvement months later reported as «100% improvement¼ of pain; reduced oedema; progressive recovery of the normal appearance of the hand; partial recovery of strength, and improved function attributable to the use of this additional therapy. Conclusion: Neurostimulation has a noticeable impact on the course of the complex regional pain syndrome accompanied by trophic changes in patients with a poor response to there commended pharmacological management. Early initiation of this intervention facilitates functional and psychological recovery of the patients, who are usually in the productive stage of their lives.

Peripheral nerve blockade as an exclusive approach to obturator nerve block in anterior cruciate ligament reconstructive surgery / 대한마취과학회지

BACKGROUND: Obturator nerve block plays an additive role on the quality of analgesia for knee surgery. Since the use of dual guidance increases the success rate of nerve blocks, we investigated the feasibility of performing anterior cruciate ligament reconstruction under dual-guided blockade of obturator with femoral and sciatic nerves. Furthermore, we propose a novel method for the assessment of obturator nerve block. METHODS: Fifty-seven patients undergoing anterior cruciate ligament repair were studied. Neurostimulating needles were guided out-of-plane by ultrasound. To induce the obturator nerve block, 10 ml of ropivacaine 0.5% were injected after eliciting contractions of adductor longus, brevis and magnus followed by block assessment for 30 minutes by examining the patient lift and left down the leg. RESULTS: The sonographic recognition of obturator nerve was easy and quick in all cases. Time for applying the block was 119.9 +/- 79.2 sec. Assessing this block with lifting-leaving down the leg gave satisfactory results in 24.0 +/- 5.07 min. After performing femoral-sciatic blocks, the inflation of tourniquet resulted in VAS score of > 0 in 2/57 patients and operation in 12/57. Total dose of fentanyl was 120.1 +/- 64.6 microg and of midazolam 1.86 +/- 0.8 mg. In 6 patients propofol was administered for sedation and 1 of them required ventilation with laryngeal mask airway, converting the anesthesia technique to general anesthesia. CONCLUSIONS: Our data suggest that anterior cruciate ligament reconstruction can be performed under obturator-femoral-sciatic blocks. Identification of obturator nerve with ultrasound is easy and the block can be assessed by observing how the patient lifts and leaves down the leg.

Deep Brain Stimulation for the Treatment of Medically Intractable Epilepsy: a Review on Clinical Application

It has been suggested that epileptic seizures can be interrupted by deep brain stimulation (DBS) of various deep brain structures which may exert a therapeutic control on seizure generators or correspond to ictal onset zone themselves. Several groups have used DBS in drug-resistant epilepsy cases for which resective surgery cannot be applied. The promising subcortical brain structures are anterior and centromedian nucleus of the thalamus, subthalamic nucleus, and other nuclei to treat epilepsy in light of previous clinical and experimental data. Recently two randomized trials of neurostimulation for controlling refractory epilepsy employed the strategies to stimulate electrodes placed on both anterior thalamic nuclei or near seizure foci in response to electroencephalographically detected epileptiform activity. However, the more large-scale, long-term clinical trials which elucidates optimal stimulation parameters, ideal selection criteria for epilepsy DBS should be performed before long.

Deep Brain Stimulation for the Treatment of Medically Intractable Epilepsy: a Review on Clinical Application / 대한간질학회지

It has been suggested that epileptic seizures can be interrupted by deep brain stimulation (DBS) of various deep brain structures which may exert a therapeutic control on seizure generators or correspond to ictal onset zone themselves. Several groups have used DBS in drug-resistant epilepsy cases for which resective surgery cannot be applied. The promising subcortical brain structures are anterior and centromedian nucleus of the thalamus, subthalamic nucleus, and other nuclei to treat epilepsy in light of previous clinical and experimental data. Recently two randomized trials of neurostimulation for controlling refractory epilepsy employed the strategies to stimulate electrodes placed on both anterior thalamic nuclei or near seizure foci in response to electroencephalographically detected epileptiform activity. However, the more large-scale, long-term clinical trials which elucidates optimal stimulation parameters, ideal selection criteria for epilepsy DBS should be performed before long.

Revisión de la literatura médica sobre el manejo de las depresiones resistentes/refractarias al tratamiento / Literature review on management of treatment-resistant depression

Major depressive disorder (MDD) is a prevalent and costly disease that is usually associated with high rates of disability. The target for the treatment of MDD is to achieve and maintain remission or complete control of depressive symptoms by the choice of an effective antidepressant. Sometimes, despite evidence based-treatment, it is possible that the patient does not have a favorable response. Although there is an increasing number of antidepressants available to treat depression, approximately half of the patients do not respond and two-thirds do not achieve remission after first-line treatment. In these cases we refer to treatment-resistant depression (TRD) as is defined in an article in this issue of Salud Mental. The TRD is one of the most complex conditions in psychiatry from the therapeutic point of view due to different definitions, algorithms, and response criteria, especially in Latin America where the procedures based on regional needs and consensus are scarce and not always based on evidence. It was conducted a systematic review using several databases such as MEDLINE, PsycINFO, EMBASE, the Cochrane Library and LILACS from 1949 to March 2011 crossing terms which allowed the inclusion of relevant articles in the management of the TRD. Unfortunately, the original publications in Latin America are often based on TRD case report, so the results and conclusions of this review have been based entirely on Anglo-Saxon scientific production. The therapeutic strategies used in the TRD are many, and include combinations of antidepressants or other psychotropic agents, in some cases addition of psychotherapy and, in extreme cases, neurostimulation techniques such as electroconvulsive therapy (ECT). The study Sequenced Treatment Alternatives to Relieve Depression (STAR-D) is the largest trial of treatment for MDD conducted in real practice settings, and the first to study remission as a measure of pre-defined primary outcome. It consists of four different stages of resistance. It is clear that there are diminishing remission rates as the number of treatment trials increases. The strategies include: antidepressant dose optimization, addition of medications like thyroid hormone, lithium, or nutritional supplements, a combination of antidepressants, and addition of second-generation antipsychotics (SGAs). Evidence suggests that remission rates can be from 25% to 50%, although with some differences among the drugs recommended. Evidence supports the use of SGAs for increasing the level of remission of new-generation antidepressants, although neither the profit nor the long-term benefits of this strategy have been well established. Neuro-modulation techniques include ECT, repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT remains a first line option for the treatment of DRT with response rates ranging from 50% to 89%. Finally, the effectiveness of cognitive-behavioral therapy (CBT) in the management of the DRT could be a useful alternative when practiced in conjunction with any of the pharmacological strategies. However, further studies are needed to recommend it as first line treatment.

El trastorno depresivo mayor (TDM) es una enfermedad costosa y prevalente que suele asociarse con altas tasas de discapacidad funcional. La meta para el tratamiento del TDM es lograr y mantener la remisión o el control completo de los síntomas depresivos por medio de la elección de un antidepresivo efectivo. Entre los factores a considerar para el logro de la remisión en pacientes deprimidos con los diferentes tratamientos disponibles, se incluyen su mecanismo de acción, el nivel de tolerabilidad, su facilidad de uso, su costo (directo e indirecto), la historia del tratamiento del paciente y su familia y algunas peculiaridades culturales que influyen en la adhesión al tratamiento y en la patoplastia clínica. En ocasiones, a pesar de un tratamiento ceñido a la evidencia, cabe la posibilidad de que el paciente no tenga una respuesta favorable al mismo. Aunque un número creciente de agentes antidepresivos está disponible para tratar la depresión, aproximadamente la mitad de los pacientes no responden y hasta dos tercios no logran la remisión después del tratamiento de primera línea. En estos casos nos referimos a la depresión refractaria/ resistente al tratamiento (DRT) tal como es definida en un artículo publicado en este número de la revista (Tamayo JM et al., 2011). La DRT es una de las condiciones más complejas en psiquiatría desde el punto de vista terapéutico debido a diferentes definiciones, algoritmos y criterios de respuesta que hacen difícil ofrecer alternativas eficaces, especialmente en América Latina donde los procedimientos basados en las necesidades regionales o el consenso son escasos y no siempre basados en la evidencia. Para este proyecto se llevó a cabo una revisión sistematizada utilizando varias bases de datos como MEDLINE, PsycINFO, EMBASE, the Cochrane Library y LILACS desde 1949 hasta marzo de 2011, cruzando términos por medio de un sistema de búsqueda predefinido que permitió incluir artículos relevantes en relación al manejo de las DRT. Desafortunadamente, las publicaciones originales en América Latina sobre la DRT suelen basarse en el reporte de casos por lo que los resultados y conclusiones de esta revisión han debido basarse en su totalidad en la producción científica anglosajona. Las estrategias terapéuticas utilizadas para la DRT son múltiples e incluyen combinaciones entre antidepresivos o con otros agentes psicotrópicos, en algunos casos adición de psicoterapia y en casos extremos técnicas de neuroestimulación como la TEC. El Estudio Secuenciado de Alternativas de Tratamiento para Aliviar la Depresión (STAR-D, por sus siglas en inglés) es el mayor ensayo de tratamiento del TDM llevado a cabo en entornos de práctica real, y el primero en estudiar la remisión como una medida de resultado primaria y predefinida. Está conformado por cuatro etapas diferentes de resistencia/refractariedad. Queda claro que hay rendimientos decrecientes a medida que el número de intentos de tratamiento aumenta. Pero cuando los pacientes siguen en tratamiento durante las cuatro fases que componen el STAR-D, aproximadamente el 67% alcanza la remisión. Las estrategias psicofarmacológicas incluyen cambio de antidepresivo en respondedores parciales luego de optimización de dosis, adición de medicamentos no antidepresivos como hormona tiroidea, litio o suplementos nutricionales, combinación de antidepresivos y adición de antipsicóticos de segunda generación (ASG). En general, se puede afirmar que los diversos estudios tienden a corroborar un incremento de las tasas de mejorías y remisiones después de seguir alguna de las estrategias terapéuticas mencionadas. Sin embargo, ningún estudio ha evaluado adecuadamente a los pacientes que no han respondido a múltiples cursos y combinaciones de terapias de medicamentos. En particular, respecto a las terapias de aumento, la evidencia sugiere que se pueden lograr tasas de remisión entre 25% y 50%, aunque con algunas diferencias entre los medicamentos recomendados. El uso del litio y de la hormona tiroidea, por ejemplo, si bien se basa en niveles de evidencia aceptables, se apoya en estudios pequeños, con diseños objetables y en pacientes menos refractarios que los que suelen incluirse en los estudios actuales. De todas las estrategias farmacológicas para aumentar la respuesta a los antidepresivos de nueva generación, la evidencia apoya con más frecuencia el uso de los ASG, aunque ni la rentabilidad ni el beneficio a largo plazo de esta estrategia han sido bien establecidos. Las técnicas de neuromodulación incluyen la TEC, la estimulación magnética transcraneana repetitiva (EMTr), la estimulación cerebral profunda (ECP) y la terapia de estimulación del nervio vago (ENV). La TEC sigue siendo una opción de primera línea para el tratamiento de la DRT con tasas de respuesta que van desde el 50% al 89%. Desafortunadamente, las estrategias de neuroestimulación, si bien suelen ser eficaces, especialmente la TEC y la ECP, son invasivas, costosas y deben relegarse como segunda línea de tratamiento en pacientes que no responden a las estrategias farmacológicas para la DRT. Finalmente, la eficacia de la terapia cognitivo-comportamental (TCC) en el manejo de las DRT podría ser una alternativa útil cuando se practica conjuntamente con alguna de las estrategias farmacológicas. Sin embargo, la eficacia de la psicoterapia en pacientes con DRT no ha sido fehacientemente demostrada y se requieren más estudios para recomendarla como primera línea de tratamiento. En cuanto al manejo a largo plazo de pacientes con DRT, el estudio STAR-D muestra que las tasas de remisión, cercanas al 67% luego de varias estrategias, se reducen al 45% cuando se incluyen en el análisis los pacientes que abandonan el estudio. Esto sugiere que el orden de administración de las alternativas terapéuticas aconsejadas hasta hoy necesita ser revaluado. Se requiere, pues, encontrar un tratamiento más rápido y más eficaz en el logro de la remisión en pacientes con TDM y estudios preliminares propenden por el uso temprano de la combinación de antidepresivos desde el inicio en pacientes con depresiones graves y caractersticas que sugieran un alto riesgo de resistencia/refractariedad.

Permanent Peripheral Nerve Stimulation for Chronic Occipital Neuralgia: Case reports / 대한통증학회지

This report presents the application of occipital nerve stimulation in two patients with severe and disabling bilateral occipital neuralgia. Pain persisted despite the use of several procedures and the administration of medication in the patients. The patients underwent peripheral nerve stimulation for the treatment of headache. Peripheral nerve stimulation was accomplished via implantation of a subcutaneous electrode to stimulate the peripheral nerve in the occipital area. The patients reported a 90% improvement in overall pain. These cases illustrate the possible utilization of peripheral nerve stimulation for the treatment of occipital neuralgia.