Inclusión de técnicas imagenológicas en la planificación neuroquirúrgica: integración de equipos multidisciplinarios / Inclusion of imaging techniques in neurosurgical planning: integration of multidisciplinary teams

Introducción: El tratamiento quirúrgico de las epilepsias consiste en lograr la resección del área lesional o epileptógena minimizando a la vez el déficit neurológico postquirúrgico. Las neuroimágenes se han constituido en una poderosa herramienta diagnóstica. El procesamiento de las mismas logran proveer relación topográfica entre la lesión, el área epileptogénica primaria y las áreas funcionales importantes de manera no invasiva. Objetivos: Estudiar la utilidad de incluir diferentes técnicas de imágenes en la evaluación prequirúrgica, planificación y resección quirúrgica de epilepsias. Materiales y Métodos: Se estudiaron 8 pacientes con diagnóstico de epilepsia con diversas técnicas imagenológicas, en resonador 3T y en tomógrafo helicoidal de 64 canales. Las imágenes fueron post-procesadas, corregistradas, fusionadas e incorporadas en el sistema de neuronavegación. La información resultante fue estudiada por un equipo multidisciplinario de físicos médicos y neurocirujanos. Resultados: Los casos presentados muestran que la incorporación e integración de las técnicas de imágenes facilitan la comprensión anatómica, metabólica y funcional del área lesional /epileptogénica y el tejido circundante. La cirugía guiada por imágenes colabora en la mejora de las limitaciones de los métodos “gold standard”, como son la electrocorticografía y la estimulación cortical eléctrica directa, disminuyendo la invasividad, el tamaño de la craneotomía, aumentando el área de resección de la lesión y brindando mayor seguridad en los resultados postquirúrgicos.

Utilidad del PET en la epilepsia no lesional del lóbulo temporal / Usefulnes of PET scan in non-lesional related temporal lobe epilepsy

Objective: to evaluate the usefulness of PET in patients with refractory non-lesional temporal lobe epilepsy. Material and methods: we present three patients with features of temporal lobe epilepsy refractory to medication, where highdefinition MRI was normal. Results: these patients had PET hypometabolism in the temporal areas related to clinical and neurophysiological findings. Two of these patients were implanted with subdural grids to confirm the diagnosis and the third was operated directly based on the findings of PET. Encourage the presentation of the importance in recent years is acquiring the PET. Conclusion: in those patients in clinical neurophysiology and epilepsy with suspected temporal lobe, but in the MRI images show no structural lesions, PET can play an important role defining the diagnosis.

Patología de las malformaciones del desarrollo cortical en pacientes con epilepsia refractaria: experiencia en un hospital pediátrico / Pathology of CDM in patients with refractory epilepsy: experience in a pediatric hospital

Las malformaciones del desarrollo cortical (MDC) comprenden un grupo heterogéneo de lesiones caracterizadas por una desorganización de la arquitectura normal de la corteza cerebral, que incluye desde cambios microscópicos sutiles a extensas lesiones que pueden comprometer un hemisferio entero o conformar síndromes genéticos definidos. Múltiples esquemas de clasificación han sido propuestos para catalogar pacientes con malformaciones del desarrollo en subgrupos, basados en criterios de imágenes y hallazgos patológicos. Sin embargo aun hoy, la bibliografía es muy confusa en cuanto a su nomenclatura y/o a los criterios utilizados para evaluar la reproducibilidad. En algunos casos puede ser difícil distinguir estas lesiones de un tumor (ganglioglioma o Tumor Neuroepitelial Disembrioplásico) por la posible coexistencia de ambas lesiones y la representatividad de las muestras. La utilización del tejido humano de las resecciones quirúrgicas provee una fundamental herramienta tanto para esclarecer la patogénesis como para futuras investigaciones. Nuestra experiencia en patología de la epilepsia relacionada con malformaciones del desarrollo a lo largo de 20 años en un hospital público pediátrico incluye patología del lóbulo temporal y extratemporal, con lesiones puras malformativas, patología dual y otras asociaciones.

Malformations of cortical development (MCD) comprise a heterogeneousgroup of lesions characterized by a disruption of the normal architecture of the cerebral cortex, ranging from subtlemicroscopic lesions to large lesions that can compromise an entire hemisphere or shape defined genetic syndromes. Multiple classification schemes have been proposed to catalogue patients with developmental malformations in subgroups based on criteria and pathological images. But even now, literature is very confusing in their classification and / or the criteria used to assess reproducibility. In some cases it may be difficult to distinguish these lesions from a tumor (ganglioglioma orDysembryoplastic Neuroepithelial Tumor) for the possible coexistenceof both lesions and representativeness of the samples. The use of human tissue for surgical resection provides afundamental tool both to clarify the pathogenesis and for future research. Our experience in pathology of epilepsy associated with malformations of the development over 20 years in a public pediatric hospital includes temporal lobe and extratemporal pathology, pure malformations, dual pathology and other associations.

Malformación del desarrollo cortical: nuestra experiencia acerca de 150 casos / Cortical development malformations (CDM): our experience on 150 cases

Objetivo Realizar una evaluación retrospectiva de 150 pacientes de una serie de 570 (26.3%), operados por epilepsia refractaria con diagnóstico de algún tipo de malformación del desarrollo cortical (MDC), desde 1988 a noviembre de 2009. Material y método. 118 niños y 32 adultos; 69 localización temporal (42 niños, 27 adultos) y 81 extratemporal (76 niños y 5 adultos). La evaluación prequirúrgica incluye: características clínico-semiológicas de las crisis epilépticas, EEG de superficie, video EEG, TC y/o RM y evaluación neuropsicológica. Población: varones: 86; mujeres 64; edad, media de 6.7 años (rango: 6 m – 18.9 a) en los niños y media de 31.3 años (rango: 19-59 a) en los adultos. Evolución de epilepsia: media de 4.9 años para los niños (rango: 1 mes a 17 años) y media de 13.8 (rango: 2 meses a 50 años). Aspectos clínicos: tipos de crisis: pudiendo un mismo paciente presentar más de una de ellas, vinculadas a la localización, CPS, ausencias, crisis tónicas, automatismos, crisis versivas, CPC, anopsia transitoria, “drop attacks”, “Startle epilepsia”, escotoma, automatismos masticatorios, crisis clónicas, fotopsia, desviación ocular, “head attacks”. Imágenes: la TC fue normal en 5, y se realizó IRM en todos a partir de 1996

Objective: To evaluate the surgical results in a group of patients with epilepsy associated with cortical development malformations (CDM). Method: A retrospective study in 150 patients of a series of 570 patients (26.3%) who have undergone surgery for intractable epilepsy with a diagnosis of CDM, since 1988. Clinical features,scalp EEG, video EEG, CT scan, MRI and neuropsychological evaluation were assessed. Population: males: 86 patients, females: 64; mean age, children: 6.7 years (range: 0,5-18.9) and adults: 31.3 years (range: 19-59); mean evolution of epilepsy, children: 4.9 years (range: 1mo-17 yr.), adults: 13.8 years (range: 2mo-50 yr.). Clinical manifestations: CPS, absences,tonic crises, automatisms and versive crises, CPS, transitory anopsia, drop attacks and Startle epilepsy, scotoma, masticatory automatisms, clonic crises, photopsia, eye deviation and head attacks. Imaging: CT scan was normal in 5, and MRI was performed since 1996. Twenty of 150 (13.3%) required chronic intracranial electrodes implantation. Surgical procedures: resectives: lesionectomies 63 (wide lesionectomy, 17 and + MST, 5), standard anterior temporal lobectomies (SATL) 37, anteromesial resections (Spencer) 9, corticectomies 11(+MST, 1),amigdalo- hippocampectomies 3, anatomic hemispherectomy 1, lobectomy1 and polectomies 4; disconnecting procedures: functional hemispherectomies (FH) 10, hemispherotomy 4, hemi-hemispherectomy 1, multiple subpial transection (MST) 1 and 2 callosotomies...

Esclerosis temporal mesial: paradigma de la epilepsia de resolución quirúrgica: 2da. parte / Temporary mesial sclerosis: Surgical resolution epilepsy paradigm 2nd. Part*

Objective. To describe the Mesial Temporal Lobe Sclerosis (MTS), in relation to its anatomical, clinical, iconographic, neurophysiologic, neuro psychologic, and surgical aspects, in reference to the epilepsy cases that needed a surgical resolution. Additionally, it’s realized a statistical analysis of our series and its results.Material and methods. From the series of 469 patients (115 adults and 354 children) operated on between 1989 and 2007, at National Pediatrics . Dr. Juan Garrahan, FLENI, Dr. Cosme Argerich, and Prof. Dr. R. Rossi Hospitals; who harbored RefractoryEpilepsy ; were analyzed 91 cases (19,4%) with the diagnosis of MTS; 38 patients belong to the pediatric group and 53 were adults. Results. The results were evaluated by the Engel score. Applying this classification, our population of patients showed thenext pattern of distribution: 69 (75,8%) are in Engel’s class IA, from this group, 36 (52,2%) are children, and 33 (47,8%), adults; 4 adults patients;( 4,4%) are in Engel’s class IB, 3 patients (3,3%) in Engel’s class IC; 1 (in Engel’s class ID(1,1%); 4 adults in Engel’s class IIA (4,4%); 5 in Engel’s class IIB (5;5%) and 3 (3,3%) in Engel’s class IVA; from then, one patient was a child, and underwent the implantation of VNS, the rest were adults. One adult patient committed suicide, one year after surgery (was in Engel’s class IA). One patient is on his first post operative year,and then couldn’t been included in statistical analysis, because follow up wasn’t enough. Conclusion. The MTS is the paradigm of Refractory Epilepsy inthe adult population, and in the pediatric subgroup involved a significant percentage: the presurgical evaluation must be exhaustive for adequate selection of cases. The extent of resection should be done with high degree of selectivity. The early diagnosis and treatment can obtain a high index of good results without ictal phenomena and the absence of necessity of antiepileptic drugs.

Epilepsia refractaria del lobulo temporal secundaria a patología dual: Nuestra experiencia acerca de 32 casos / Refractory temporal lobe epilepsy secondary to dual pathology: Review of 32 cases

Classical dual pathology is the coexistence of temporal mesial sclerosis (TMS) and an ipsilateral extra-hippocampal lesion. The aim of this presentation is to increase the awareness of the existence of this pathology as well as variants as a cause of refractory temporal lobe epilepsy and its difficult pre-op diagnosis. Of the 32 cases here presented, 19 were adults and 13 children. Adults: 17 had TMS + cortical dysplasia (CD) and of the remaining patients, 1 had TMS + oligodendroglioma and 1 TMS+ ganglioglioma. Children: pathology findings were: A) TMS + malformation of cortical development 6; B) TMS + CD + ganglioglioma 2; TMS + ganglioglioma + post-infectious sequelae 1 (“triple pathology”) and C) CD associated with low-grade glioma 1 and with MAV 1.Surgical techniques: LATS and the Spencer variant were the most commonly used techniques. Results: Patients in both groups are in Engel Class I and II. Conclusion: The good results in this series can be attributed to the complete resection of these entities.

Hemisferectomías y hemi-hemisferectomías: nuestra experiencia acerca de 49 casos / Hemispherectomy and hemi-hemispherectomy: Review of 49 cases

Objective. To review the results of hemispherectomy in the treatment of refractive epilepsy. Methodology. Analytic retrospective cohort study including every patient presenting refractive epilepsy to pharmacologic therapy, operated with hemispherectomy techniques from 1988 to 2008 (n=49). Of 507 patients, operated for refractive epilepsy in the last 20 years, in 49 cases we used any kind of hemispherectomy techniques (9,7%). The male/female relationship was 1.13-1, with 53% males and 47% females. The mean age was 8±5 years old, minimum 4 months and maximum 19 years old. The epilepsy time evolution was 3±2 years. The age of initial presentation was 3±1 years old. The more frequent pathologies were: Rasmussen encephalopathy (30,6%) and secuelar lesions (34,7%). Results. The results were evaluated with the Engel score. Using this classification, our patients were distributed in this manner: 40 patients (81,6%) were in class I of Engel; 4 patients (8,2%) in class II of Engel and 5 patients (10,2%) en Engel III and IV. 88% (43 cases) without complications, 4% (2 cases) present hematomas and the same occur with hydrocephalus and postoperative meningitis. One patient died a few days posterior to surgery because of hematologic complications. Conclusion. The hemispherectomy for the management of refractive epilepsy is a safe procedure with high positive results and small morbimortality in selective pathologies.

Resultados de la cirugía de epilepsia en esclerosis tuberosa / Results of surgical treatment of epilepsy in tuberous sclerosis patients

Objective. We review our experience with surgical treatment in tuberous sclerosis and refractory epilepsy. Method. Between june 1995 and june 2008 , surgery was performed in 12 patients with tuberous sclerosis and refractory epilepsy. Median age: 6 years (r=6 months-19 years). 6 males and 6 females. Epilepsy began during the first year of life. They have been studied with RMI and video-EEG. Two patients were studied with intracranial electrodes. Electrocorticography was performed in 7, somatosensory evoked potentials in 2 and cortical stimulation in 1. Epileptogenic region was frontal in 4, temporal in 3, parietal in 2, occipital in 1 and bilateral in 2. Surgical procedures were resection of the epileptogenic regions and associated tuber(s) in 6, temporal lobectomy in 1, callosotomy in 1, parietal lobectomy in 1, frontal polectomy and vagus nerve stimulation in 1. A second surgery was performed in 1 case. Results. The outcome of seizures was classified with Engel’s outcome classification: 7 patients were in class I , 2 in class II and III . Callosotomy and vagus nerve stimulation were performed in 2 patients who had multifocal abnormality , seizure freedom was achieved in more than 60%.

Esclerosis temporal mesial: paradigma de la epilepsia de resolución quirúrgica / Mesial temporal sclerosis: paradigm of surgically treatable epilepsy

Objetivo. Describir la esclerosis temporal mesial (ETM) es sus aspectos anatómicos, fisiopatológico, clínico, imagenológico, neurofisiológico, neuropsicológico y quirúrgico; y su relación con la epilepsia de resolución quirúrgica. Luego analizar estadísticamente nuestra casuística y resultados. Materiales y métodos. De los 469 (115 adultos y 354 niños) pacientes intervenidos quirúrgicamente por presentar epilepsia entre los años 1989-2007 en el Hospital Dr. Juan P. Garraham, FLENI, Hospital Dr. Cosme Argerich y Hospital Prof. Dr. Rodolfo Rossi, se analizar 91 pacientes (19.4%) con el diagnóstico de ETM; 38 de los cuales (41.75%) son niños y 53 (58.25%) adultos. Resultados. Los resultados son evaluados mediante el score de Engel. Aplicando esta clasificación, nuestra población tiene la siguiente distribución; 69 pacientes (75.8%) se encuentran en clase IA de Engel, de ellos 36 son niños (52.2%) y 33 adultos (47.8%); 4 pacientes adultos se encuentran en Engel IB (4.4%), 3 en Engel IC (3.3%), 1 adulto en Engel ID (1.1%), 4 adultos en Engel IIA (4.4%), 5 adultos en Engel IIB (5.5%) y 3 pacientes en Engel IVA (3.3%) de ellos 1 niño a quien posteriormente se le implantó un estimulador del nervio vago y los 2 restantes adultos. Un paciente adulto se suicidó luego de un año de la cirugía (en clase IA de Engel). Un paciente se encuentra durante su primer año postoperatorio por lo cual no puede ser incluido aún en la estadística de resultados. Conclusión. La ETM es el paradigma de la epilepsia refractaria en al población adulta y la causa de un porcentaje significativo de pacientes pediátricos sometidos a cirugía. La evolución prequirúrgica debe ser exhaustiva para lograr la selección del paciente. La resección quirúrgica debe ser realizada con la mayor selectividad posible. El diagnóstico y tratamiento precoz permite lograr un alto índice de curación.

Esclerosis temporomesial en adultos: revisión del síndrome y evalución de resultados / Mesial temporal sclerosis in adults: Revision of the syndrome and assessment of results

Objective: To describe the presentation and the management of the Mesial Temporal Sclerosis (ETM) in adult patients and to evaluate the results of the presented series. Description: the authors selectioned 3 cases among 53 adults who underwent surgical treatment with ETM diagnosis. Case 1: female patient, 32 years old. Antecedents of complex partial crisis since 6 years old, some of the crisis related to febrile episodes. Aura related like unpleasent gastroesophageal sensation, break of contact, right hand dystonia, cephalic turn to right and oroalimentary and manual automatism. RMI and EEG-video: injury compatible with left ETM. Case 2: male patient, 24 years old. Antecedents of complex partial crisis since 13 years old. Breack of contact, verbal automatisms (repeats unintelligible sounds) and sensation of postictal sikness. RMI: increase of signal (FLAIR) in both hippocampus, impressing right atrophy. EEG-video with profund electrodes implanted: start of the crisis on a right mesial temporal level. Case 3: female patient, 21 years old. Antecedents of complex partial crisis since 12 years old. Complex partial crisis with bimanual and oroalimentary automatisms with an episode of generalization. RMI and EEG-video: injury compatible with right ETM. Intervention: case 1 and 2 were resolved by the realization of an anteromesial resection of Spencer. In case 3 a selective amygdalo hippocampectomy was practiced. Conclusion: ETM is the paradigm of the refractory epilepsy in an adult population. Precocious diagnosys and treatment allow to obtain a high index of cure with small amount of significant sequels.

El desarrollo e implementación de la resonancia magnética intraoperatoria en neurocirugía (remain) y su aplicación en 83 intervenciones en la Argentina / Development of REMAIN for neurosurgery and application in 83 operative intervention in Argentina

Objective: To show implementation and development of an operating room in which we operated 83 patients using intraoperative MRI (REMAIN). Method: We used a side-opening-magnet, 0.23 Tesla, installed in a surgical area specially designed with all the advances of the modern operating rooms. Results: A great variety of neuro-surgical procedures can be made with REMAIN controls. The obtained images are clear, without devices and with an excellent definition of the anatomical structures and the pathology, that allows the neurosurgeon to make more precise and safer interventions. Conclusions: The images of REMAIN in a surgical scope, make possible that injuries can be identified and located with absolute precision. It is particularly useful in determining with exactitude the tumor-like limits, optimizing the surgical approaches, obtaining complete extirpations of brain injuries and controlling the possible intraoperative complications.

Use of ultrasonic aspiration for dural opening in re-do epilepsy surgery: a preliminary report

Dural detachment from the brain in cranial reoperations has been accomplished previously by selective coagulation and cutting of brain cutting procedures led the authors ultrasonic aspiration during tumor surgery or brain cutting procedures led the authors to speculate that detachment of the duramater from the brain tumors by appling the Cavitron ultrasonic surgical aspirator (CUSA) to the brain-duramater interface could be used to reduce bleeding and facilitate dural opening during cranial re-operations. Thus, the use of ultrasonic aspiration and its effects on brain separation from the duramater were examined. Ten patients underwent a second craniotomy for epilepsy surgery (5 cases of extended temporal lobectomy and 5 cases of extended extratemporal lesionectomy). Intraoperative use of the CUSA during dural opening produced immediate blanching of the duramater and enhanced visualization of the cortical surface without distortion of the brain anatomy. Incremental dural opening and brain visualization is achieved by careful application of ultrasonic aspiration directly into the brain-dura limit, producing immediate regional dural devascularization. Use of this technique reduces cortical and dural bleeding and enhances the ease and effectiveness of brain visualization

Functional hemispherectomy variant a report of twenty one cases / Functional hemispherectomy variant a report of twenty one cases

Objective and importance: Although Rasmussen´s hemispherectomy is a proven effective technique, the reduction in surgical time and in blood volume los during its performance is crucial. This is achieved by means of the tecnichal variant intended to disconnect instead of to remove the temporal lobe. Clinical representation: We present 21 children operated between 1997 and 2004 in whom a functional hemisfactory (FH) variant was performed. The clinical manifestations included the following crises: hemianopsia, versive crises, abscences, CPC and tonic crises, with secondary generalization in some of the children. Intervention: The proposed variant is a sort of combination of Rasmussen´s hemispherectomy and Delalande´s hemispherectomy, involving disconnection and isolation of the temporal lobe. This is achieved at cortical level by prolonging the incision of the mesial aspect of the occipital lobe by intraventricular route is extended towards the fornix to reach the free border of the cerebellar tentorium. The juncture of both incisions disconnects the neocortex from the temporal lobe, as well as the parahippocampal gyrus and the hippocampus itself. Since aprevious complete callosotomy, a temporal stem section and amigdala suction had been performed, the temporal lobe remains in situ, but nonfunctional. Conclusion: It is the autor conviction that Rasmussen´s hemipherectomy is a valid procedure given its proven efficacy. We believe that the proposed technical variant is particularly useful for neurosurgeons that are in training in the field of epilepsy surgery, as a priori stage to the use of more restricted disconnecting techniques

Cirugia en dos tiempos en epilepsia refractaria. Utilidad de los electrodos intracraneanos cronicos. Experiencia en poblacion pediatrica y adulta / Two steps surgery in refractory epilepsy. Usefulnes of chronic intracranial electrodes. Experience in pediatric and adult population

Objetivo: Comunicar la utilidad de la cirugia en dos tiempos con implante de electrodos intracraneales para definir el area epileptogenica primaria. Metodos: se analizaron las historias clinicas de 41 pacientes, 28 niños y 13 adultos estudiados mediante el implante de electrodos intracraneanos con el objetivo de determinar el area epileptogenica primaria (AEP) cuando no fue posible identificarla por estudios no invasivos. Se realizaron cirugias resectivas / desconexion y se analizo evolucion con la Escala de Engel. Resultados: Poblacion pediatrica: se definio lateralidad y el area epileptogenica primaria (AEP) en 26 de 28 casos. El estimulo cortical permitio localizar el area motora en 4 pacientes. En 2 pacientes no pudo definirse lateralidad del AEP. Poblacion adulta: en 12 de 13 pacientes pudo establecerse lataralidad y localizacion del AEP; en un paciente no se logro. A pesar de la dificultad de localizar el AEP en el 14 por ciento de los niños y 16 por ciento de los adultos esta metodologia permitio tratar quirurgicamente ambas poblaciones con una evolucion en Engel I y II del 84 y 72 por ciento respectivamente. El seguimiento promedio fue en la poblacion pediatrica de 6 años y en la poblacion adulta de 6 años y 8 meses. Conclusion: la cirugia en dos tiempos con implante de electrodos intracraneamos es muy util para el diagnostico y tratamiento de epilepsias refractarias complejas en las que la imagen, clinica y video EEG son incongruentes

Neuronavegacion en cirugias intracraneales / Neuronavigation in intracranial surgeries

Objectives: to present our experience with Neuronavigation system in intracranial surgery. Material and Methods: The use of neuronavigation system was evaluated in 104 consecutive patients operated on during the period September 1999 - April 2003 (Range of age: 5 months - 75 years). Surgical procedures included the remotion of brain tumor, arteriovenous malformation, cavernous angiomas and epilepsy surgeries. The neuronavigation system is the Elekta Insight View Scope (Elekta Instrumental). Results: The additional time required for preoperative organization of the Neuronavigation system was 30 minutes. There were no differences during the registration process related to the surgical position (prone, supine and park-bench). The reference system planning of the surgical approach, to guide endoscopical procedures, perform smaller craniotomies, localize deep-seated subcortical lesions, identify the boundaries of low grade tumors and evaluate the extent of resection in epilepsy surgeries. Conclusion: Neuronavigation system improves the surgical approach of intracranial surgeries allowing to short the operating time, define the less invasive trajector, and identify the margins of low grade lesions

Traumatismo encefalocraneano en la infancia / Brain trauma in childhood

Con el objetivo de intentar una mejor comprensión y un más racional manejo de los niños con traumatismo de cráneo (TEC) que consultan en el área de emergencia, se analiza la población atendida entre enero y junio de 1996. La población incluye 1022 niños. Los TEC se clasificaron en leves, moderados y graves según el SCG y la situación clínica. Fueron leves 920 pacientes, moderados 58 y graves (4.3 por ciento). De los TEC leves, fueron ambulatorios el 62.7 por ciento. El resto, 279, requirió ingreso a observación por presentar signos neurológicos anormales y/o fractura o hundimiento de cráneo. El tiempo medio de permanencia en observación fue de 13.3 horas (rango: 4 a 48 horas). Se efectuaron TC de cerebro en el 14.1 por ciento de la población total, se encontraron lesiones intracraneanas en le 1.7% del total de pacientes con TEC leve. Este pequeño porcentaje de lesiones en niños con TEC leves debe alertar el pediatra ante el riesgo de su potencial agravamiento. Concluimos que el mayor porcentaje de pacientes presentó TEC leve. La observación clínica de los pacientes con riesgo potencial es imprescindible. Debe ser manejados inicialmente por el pediatra, con el obvio entrenamiento que esto requiere. El neurocirujano debe ser consultado ante situaciones de empeoramiento. La prevención continúa siendo el primer tratamiento.