Effectiveness of deep brain stimulation on refractory aggression in pediatric patients with autism and severe intellectual disability: meta-analytic review.

Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator's bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies' quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior.

OBJECTIVES: The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug-resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). METHODS: Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp-DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases-FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self-harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). RESULTS: All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow-up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. SIGNIFICANCE: In well-selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts.

[Resection of frontal lobe epileptogenic foci identified after corpus callosotomy: long term results]. / Resección de focos epileptogénicos frontales identificados tras la callosotomía: resultados a largo plazo.

OBJECTIVES: To analyse the results of resective surgery in patients in whom it was possible to identify a frontal epileptogenic focus through corpus callosotomy. MATERIAL AND METHODS: Data from patients suffering drug-resistant epilepsy showing persistence of disabling seizures after undergoing corpus callosotomy and subsequent treatment with frontal lobe resective surgery were prospectively reviewed. Classifications according to Engel's scale before and after each intervention were evaluated, as were the percentages of seizure reduction. Additionally, the satisfaction of family members with surgical outcomes was also assessed. RESULTS: Eleven patients were identified. After a median follow-up period of 7 years (IQR: 3-8 years), 63.6% of patients showed improvement of seizures according to Engel's scale, 27.2% remained unchanged and one worsened. One patient was categorised as class i, 8 as class ii, one as class iii and one as class iv. The percentage reduction in the number of seizures was over 90% in 54.5% of patients, between 50% and 90% in 36.4% and less than 50% in 9.1%. Family satisfaction was reported as good or excellent in 90.9% of cases. CONCLUSIONS: In addition to providing better seizure control, corpus callosotomy also appears to be a diagnostic tool allowing the identification of potential targets for resective surgery. Therefore, it should be considered upon suspicion of a frontal epileptogenic focus which could be surgically treated.

Deep brain stimulation may be a viable option for resistant to treatment aggression in children with intellectual disability.

INTRODUCTION: Deep brain stimulation (DBS) is a surgical technique used to manage aggression in patients who do not improve despite the use of appropriate drug treatment. OBJECTIVE: The objective of this study is to assess the impact of DBS on aggressive behavior refractory to the pharmacological and behavioral treatment of patients with Intellectual Disabilities (ID). METHODS: A follow-up was conducted on a cohort of 12 patients with severe ID, undergoing DBS in posteromedial hypothalamic nuclei; evaluated with the Overt Aggression Scale (OAS), before the intervention, at 6, 12, and 18 months of medical follow-up. RESULTS: After the surgical procedure, there was a significant reduction in the aggressiveness of patients in the follow-up medical evaluation at 6 months (t = 10.14; p < 0.01), 12 months (t = 14.06; p < 0.01), and 18 months (t = 15.34; p < 0.01), respect to the initial measurement; with a very large effect size (6 months: d = 2.71; 12 months: d = 3.75; 18 months: d = 4.10). From 12 months onward, emotional control stabilized and is sustained at 18 months (t = 1.24; p > 0.05). CONCLUSION: DBS in posteromedial hypothalamic nuclei may be an effective treatment for the management of aggression in patients with ID refractory to pharmacological treatment.

[Vagus nerve stimulation therapy in patients with drug-resistant epilepsy and previous corpus callosotomy]. / Terapia con estimulación del nervio vago en pacientes con epilepsia fármaco-resistente y callosotomía previa.

OBJECTIVE: To analyse the results of vagus nerve stimulation in patients with drug-resistant epilepsy and previous corpus callosotomy. MATERIALS AND METHODS: We prospectively reviewed data from patients with drug-resistant epilepsy who showed persistence of disabling seizures after undergoing corpus callosotomy, in whom it was not possible to identify an epileptogenic focus and who were subsequently treated with vagus nerve stimulation. Variables analysed included: age, gender, aetiology of epilepsy, frequency and characteristics of the crises and Engel scale classification, before and after vagal stimulator implant. Furthermore, the percentage differences in seizure frequency changes were also calculated. RESULTS: Four patients were identified: two male and two female. The total seizure frequency had decreased between 20% and 81% after corpus callosotomy in three patients and one of them did not show any favourable response (Engel IVB). Following implantation of the stimulator they became reduced to between 57% and 100% after a mean follow-up period of 8.3 months (range: 3 to 12 months). Generalised seizures decreased between 71.4% and 100%, and focal seizures between 57.7% and 100%. CONCLUSIONS: Vagus nerve stimulation therapy proved to be an alternative for the reduction of seizure frequency in patients with drug-resistant epilepsy who suffered disabling seizures despite undergoing corpus callosotomy as primary surgery.

Síntomas neurológicos de fístula carotídeo carvenosa: reporte de caso / Neurological symptoms of cavernous carotid fistula: case report

RESUMEN Las fístulas carótido-cavernosas son comunicaciones anormales entre la arteria carótida interna o externa; o alguna de sus ramas (sistema arterial) y el seno cavernoso (sistema venoso); el espectro de presentación de esta entidad es muy variable, sin embargo existe un gran número de pacientes en los cuales los síntomas neurológicos conllevan a sospecha clínica. Los síntomas pueden variar desde cefalea de intensidad variable, síntomas de origen auditivo, tinitus, hipoacusia y vértigo hasta manifestaciones que son clínicamente evidenciables y signos derivados de congestión orbitaria como proptosis, quemosis, soplos orbitarios y pérdida de la visión, causas que motivan un diagnóstico y tratamiento oportuno. Se realiza reporte de un caso de un paciente de 60 años de edad que acude al servicio hospitalario de la Fundación Centro Colombiano y Enfermedades Neurológicas FIRE, con cefalea de 2 meses de evolución, consulta por diplopía binocular, dolor ocular bilateral, inyección conjuntival, secreción purulenta, epifora bilateral, vértigo con miositis orbitaria aguda, fístula carótido-cavernosa en ojo derecho y parálisis del sexto par craneal izquierdo. La panangiografía cerebral reporta fístula carótida-cavernosa indirecta tipo B de Barrow por aferencias del tronco meningohipofisiario derecho e izquierdo por lo que es llevado a terapia endovascular con obliteración exitosa de la fístula.

SUMMARY Carotid-cavernous fistulas are abnormal communications between the internal or external carotid artery or one of its branches (arterial system) and the cavernous sinus (venous system). The spectrum of presentation of this entity is very variable. However, patients may consult for headache and symptoms derived from orbital congestion such as proptosis, chemosis, orbital murmurs and loss of vision. They require timely diagnosis and treatment. We present the case of a 60 year old patient with a history of acute orbital myositis, carotid-cavernous fistula in the right eye, paralysis of the sixth left cranial nerve and a 2 month old headache who consults for binocular diplopia, bilateral ocular pain, conjunctival injection, purulent secretion outflow, bilateral epiphora, sensation of hallucination of movement with gait and photophobia. Cerebral panangiography reports remnant of Barrow's b-type indirect carotid-cavernous fistula by right and left meningohypophysis trunks. The pacient taken to endovascular therapy with successful fistula obliteration.

Epilepsia estructural por síndrome de Dyke Davidoff Masson: un caso infrecuente de epilepsia refractaria / Structural epilepsy due to Dyke Davidoff Masson syndrome: an infrequent case of refractory epilepsy

RESUMEN El síndrome de Dyke Davidoff Masson es una infrecuente condición neurológica, caracterizada por crisis epilépticas, alteración cognoscitiva y compromiso neurológico variable en el examen físico. En los estudios de imágenes por tomografia y resonancia magnética cerebral se observa principalmente hemiatrofia cerebral con compromiso de los senos y la calota. Existe en la actualidad menos de 100 artículos publicados en la base de datos Pubmed. Se realiza revisión de la literatura existente y reporte de un caso de paciente masculino de 21 años de edad con epilepsia refractaria, retardo mental y hemiparesia derecha en el cual se realiza resonancia magnética cerebral 1,5 Tesla que concluye el diagnóstico por imágenes.

SUMMARY Dyke Davidoff Masson syndrome is an uncommon neurological condition, characterized by epileptic seizures, cognitive impairment, and variable neurological compromise on physical examination. In the studies of images by tomography and cerebral magnetic resonance, cerebral hemiatrophy with sinus and calotte involvement is observed. There are currently less than 100 articles published in the published database. We review the existing literature and report a case of a 21-year-old male patient with refractory epilepsy, mental retardation and right hemiparesis in which a magnetic resonance test is performed, 1.5 tesla, which concludes the diagnostic imaging.

Trombosis de senos venosos cerebrales, una manifestación inusual de déficit de proteína S en paciente joven / Cerebral venous sinus thrombosis, an unusual manifestation of protein s deficiency in young patients

Resumen La trombosis venosa cerebral (TSVC) es un tipo de accidente cerebrovascular (ACV) que involucra el lado venoso de la circulación cerebral, incluye trombosis de los senos venosos durales y/o de las venas corticales y profundas del cerebro, es una causa poco común 0,5-1 % de todos los accidentes cerebrovasculares, con una prevalencia estimada en el rango entre 0. 22 a 1,23 / 100.000 / año. Los factores de riesgo para TSVC, están generalmente divididos en riesgos adquiridos (por ejemplo: cirugía, trauma, embarazo, puerperio, síndrome antifosfolípido, cáncer, hormonas exógenas) y los riesgos genéticos (trombofilia hereditaria). Los factores de riesgo más ampliamente estudiados para TSVC incluyen estados protrombóticos, las trombofilias heredadas asociadas con TSVC incluyen deficiencias de antitrombina, proteína C, proteína S (PS), mutación del factor V Leiden y la mutación del gen 20210 de protrombina. La prevalencia del déficit de PS, oscila entre un 0,02 y un 0,03 % en la población general y aumenta hasta un 2 % en pacientes no seleccionados con trombosis. Con una mortalidad cercana al 9 %. El manejo es usualmente médico. Se cita el caso de una paciente de 28 años de edad, con cuadro clínico de cefalea de 1 mes de evolución, con hallazgos en neuroimagen de trombosis de senos transverso y sigmoideo izquierdo con déficit de proteína S.

Summary Cerebral venous thrombosis (TSVC) is a type of stroke (CVA) involving the venous side of the cerebral circulation, including thrombosis of the dural venous sinuses and / or cortical and deep veins of the brain, is a rare cause 0.5-1% of all strokes, with an estimated range between 0. 22 to 1.23 / 100,000 / year prevalence. Risk factors for TSVC, are generally divided into acquired risks (eg, surgery, trauma, pregnancy, postpartum, antiphospholipid syndrome, cancer, exogenous hormones) and genetic risks (hereditary thrombophilia). The most widely studied factors TSVC risk include prothrombotic states, inherited thrombophilia associated with deficiencies TSVC include antithrombin, protein C, protein S (PS), mutation of factor V Leiden mutation and prothrombin 20210 gene. The prevalence of PS deficit ranges between 0.02 and 0.03% in the general population and increases up to 2% in unselected patients with thrombosis. With close to 9% mortality. The operation is usually doctor. It cites the case of a 28-year-old, with clinical symptoms of headache 1 month of evolution with neuroimaging findings transverse sinus thrombosis and left sigmoid with protein S deficiency.

Epilepsia y síndrome dismórfico asociado a cromosomopatía hereditaria ligada al cromosoma X, tipo micro-duplicación / Epilepsy and dysmorphic syndrome associated with hereditary chromosomopathy linked to X chromosome, micro-duplication type

Resumen Los hallazgos de síndromes dismórficos asociados a cromosomopatía ligada a X y epilepsia son de presentación infrecuente. Presentamos un caso de alteración genética en un paciente masculino, con microduplicación ligada al cromosoma X MECP2 y antecedente familiar de hermano con fenotipo similar, que comparten línea sanguínea materna, de diferentes padres. El síndrome dismórfico ligado a cromosoma X MECP2 (methyl-CpG-binding protein2), causan grave retraso mental, encefalopatía epiléptica e infecciones recurrentes del aparato respiratorio y consecuentemente pueden además tener una epilepsia resistente al manejo farmacológico.

Summary The findings of dysmorphic syndromes associated with X-linked chromosomopathy and epilepsy are infrequent. It is a case of genetic alteration in a male patient, with X-linked microduplication MECP2 and familiar history of a sibling with similar phenotype, which compares the maternal blood line of different parents. X-linked dysmorphic syndrome MECP2 (methyl-CpG2 binding protein), causing severe mental retardation, epileptic encephalopathy and recurrent infections of the respiratory tract and consecutively also have epilepsy resistant to pharmacological management.

Discapacidad física en la práctica clínica diaria en pacientes con esclerosis múltiple tratados con interferón beta-1b / Physical disability in daily clinical practice in multiple sclerosis patients treated with interferon beta-1b

IntroduccIón: la esclerosis múltiple (EM) es la enfermedad crónica discapacitante del sistema nervioso central más frecuente en adultos jóvenes y se caracteriza por la acumulación de grados variables de discapacidad física.objetIvos: determinar la progresión de discapacidad física en pacientes diagnosticados con esclerosis múltiple tratados con interferón beta-1b. Establecer adherencia al tratamiento y seguridad.MaterIales y Métodos: estudio observacional realizado en 9 centros neurológicos de la Costa Atlántica Colombiana en pacientes con esclerosis múltiple remitente recidivante (EMRR), secundaria progresiva (EMSP) o síndrome clínicamente aislado (SCA) tratados con interferón beta-1b. Se determinó la discapacidad física mediante 5 evaluaciones clínicas por medio de la escala expandida del estado de discapacidad (EDSS) de Kurtzke.resultados: se incluyeron 83 pacientes, media de edad de 43,4 años (61.5% mujeres). 71,1% de pacientes diagnosticados con EMRR, 20.1% EMSP y 4,8% SCA. La media en la escala EDSS permaneció inferior a 4 (inicial 3.7 y final 3.5, p=0.712). No se encontraron diferencias entre los puntajes iniciales, ni a 24 meses de observación en pacientes con EMRR (media3.7 vs 3.4 p=0.424) ni en el grupo EMSP (media4.0 vs 4.2, p=0.660). Se presentaron 17 suspensiones de tratamiento. 8.4% de los pacientes presentaron eventos adversos, 4 fueron catalogados como serios. Se registraron 2 muertes.conclusIón: el estado funcional de los pacientes con EM tratados con interferón beta-1b permaneció estable sin presentar cambios significativos, en pacientes con EMRR y EMSP.

Fisiopatología del estatus epiléptico / Pathophysiology of status epilepticus

El Estatus Epiléptico (EE) es una emergencia neurológica con una incidencia de 20/100.000 habitantes y unamortalidad del 3 al 40% dependiendo de etiología, tipo de estatus y la duración.La comprensión de la fisiopatología del EE es incompleta en la actualidad y un único mecanismo como causa espoco probable; lo que parece estar más claro es la participación del sistema límbico como estructura fundamentalen el desarrollo y mantenimiento del mismo.Los elementos claves del desarrollo del EE incluyen un desequilibrio entre la excitabilidad e inhibición neuronalcon alteración de la comunicación que da lugar a hipersincronía de poblaciones neuronales. Una mejor compresiónde estos mecanismos pudiese prevenir el desarrollo de un EE de difícil control y sus consecuencias como dañocerebral, epileptogénesis e incluso muerte.Esta revisión discute las descripciones fisiopatológicas del estatus convulsivo en el contexto de la mejor evidenciaactual disponible.

Enfermedad de FAHR una causa infrecuente de calcificaciones cerebrales / Fahr disease an infrequent cause of brain calcifications

Se ilustra el caso de una paciente con episodios convulsivos, movimientos anormales y déficit cognitivo de varios meses de evolución. En la tomografía axial computarizada se evidenciaron lesiones ganglio basales, paraventriculares, sustancia blanca y cerebelo; clínicamente presentó síntomas típicos de la enfermedad de Fahr y con estudios de laboratorio complementarios se descartaron otras causas.

This is the case of an patient with convulsive episodes, abnormal movements and cognitive deficit of several months of evolution. The axial computed tomography demonstrated injuries ganglion basal, paraventriculares,white substance and cerebellum; presenting clinical symptoms of Fahr’s disease and with laboratory studies thatreject other pathologies of similar characteristics.