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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The World Health Organisation &#40;WHO&#41; estimates that diseases with psychiatric causes account for at least 20&#37; of disability worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Almost 10&#37; of chronic psychiatric patients are hospitalised due to episodes of aggressiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In Mexico&#44; psychiatric diseases have been treated with great indifference and their cost to the public underestimated&#44; allocating them just 2&#37; of total healthcare spending&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Irreducible neuroaggressive disorder &#40;IND&#41; is known by a number of names&#44; including&#58; aggressive&#8211;disruptive behaviour and pure aggressiveness&#46; It is currently defined as a specific condition of uncontrollable anger followed by secondary violence&#44; and includes persistent or recurrent verbal and physical attacks that are not provoked by stressful situations or provocations of any type&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">As a complaint&#44; neuroaggressive behavioural disorder presents serious difficulties in diagnosis&#44; and even more so in its treatment&#44; which is multidisciplinary and includes pharmacological measures&#44; concomitant therapies &#40;electroconvulsive therapy&#44; long-term hospitalisation or restraint&#41; and neurosurgery&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In our hospital&#44; an interdisciplinary group comprising neurologists&#44; neurosurgeons&#44; neurophysiologists&#44; paediatricians&#44; psychiatrists and neuropsychologists has been formed to study this group of patients&#44; from case selection to treatment and follow-up&#44; following international clinical and bioethical guidelines for the optimal treatment of these patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Functional neurosurgery for this disorder has been described for adult patients&#44; but very seldom in paediatric patients&#46; In countries like Japan and the United States&#44; between 1950 and 1960&#44; children with refractory aggressiveness were treated&#46; Freeman performed lobotomies in children&#44; inspired by the work of Egas Moniz&#44; who performed the first leucotomy&#44; introducing the surgical technique&#46; However&#44; in 1970&#44; American and Japanese paediatric psychiatrists indicated their disapproval of such procedures&#44; and they ceased to be performed in those countries&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> In 1970&#44; in Mississippi&#44; United States&#44; Orlando Andy presented a series of 30 patients between 6 and 49 years of age&#44; including adults with Parkinson&#39;s disease&#44; in whom he performed thalamotomy in hyperactive and aggressive paediatric patients&#44; with encouraging results&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">However&#44; psychosurgery fell into disuse in the 1970s due to social pressure&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> In the same decade&#44; Laitinen and Livingston&#44; in Finland and Canada&#44; published <span class="elsevierStyleItalic">Surgical approaches in psychiatry</span>&#44; mentioning the targets involved in each psychiatric disease and the best known combinations of the era&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Various surgical techniques exist for the treatment of aggressiveness&#58; amygdalotomy was described for the first time in 1966 by Narabayashi and Uno as a therapeutic option based on lesion of the temporal amygdala&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Also in 1966&#44; Sano et al&#46; described hypothalotomy for the first time&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> Cingulotomy was first described by Fulton and Jacobsen&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Capsulotomy involves the lesion of the anterior fibres of the internal capsule&#59; the technique was pioneered by Talairach in 1949<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> and later promoted by Leksell&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">13&#44;14</span></a> Good results were obtained in all anterior targets&#44; leading to the subsequent development of combinations of these&#44; which improved the functional outcome in patients&#46; All of these targets form part of the limbic system&#44; which is the foundation of human behaviour&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The objective of this article is to describe the safety and efficacy of the surgical targets used in paediatric patients with aggressiveness and disruptive behaviour in our institution&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Material and methods</span><p id="par0060" class="elsevierStylePara elsevierViewall">The population selected for treatment of irreducible neuroaggressive disorder was obtained using the following criteria&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Belonging to the health system of the <span class="elsevierStyleItalic">Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado</span> &#40;Public Sector Workers&#8217; Social Services and Security Institute &#91;ISSSTE&#93;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Displaying auto- or hetero-aggression&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Diagnosis and chronic nature &#40;at least 5 years&#41; expressed and in follow-up with two different psychiatrists simultaneously&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Informed Consent Form for the surgical procedure signed by the patient&#39;s family and the patient where applicable&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">At least two years of well-documented pharmacological treatment with at least four incisive or first-line drugs&#44; with adequate doses and durations&#44; with no reduction in symptoms&#44; including neuroleptics&#44; anticonvulsants&#44; selective serotonin reuptake inhibitors&#44; benzodiazepines&#44; beta blockers&#44; lithium and combinations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Any comorbid condition causing aggressiveness that is under control &#40;for example&#44; Prader&#8211;Willi syndrome&#44; Dandy&#8211;Walker syndrome&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">The patient must attend preparatory preoperative consultations on all occasions in order to ensure adequate follow-up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Patients with and without psychomotor retardation were included&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Patients refractory to standard non-pharmacological treatments&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall">The presence of any disease outside the surgical target that might be causing the IND was ruled out using MRI&#44; VEEG&#44; EEG&#44; hormone testing and clinical examinations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0115" class="elsevierStylePara elsevierViewall">The clinimetric Overt Aggression Scale &#40;OAS&#41; was used with global weighting for an aggressiveness score greater than 5 out of a maximum of 21 points&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a></p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">The main criterion was irreducible hetero- or auto-aggression that was resistant or refractory to treatment based on the ICD-10 and DSM-IV-TR&#44; as well as a high score on the OAS &#40;more than 5 points&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Failure to attend preparatory preoperative consultations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">The patient or his&#47;her family member does not agree to sign the Informed Consent Form when the procedure is explained&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Tumour lesion that includes the surgical target&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Desertion or non-compliance during the process&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Death of the patient during the study and&#47;or treatment period&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Systemic or focalised medical disease that in itself causes psychiatric symptoms&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Pregnancy confirmed by a beta-human chorionic gonadotropin test&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Associated medical condition that might put the patient at risk&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">All cases were presented and reviewed thoroughly by the multidisciplinary team in functional neurosurgery ordinary meetings in order to review the patient&#39;s clinical condition&#44; as well as imaging and electroencephalographic studies&#44; to establish clinical correlation&#44; the current status of each patient and to select the best treatment for each&#46;</p></li></ul></p><p id="par0175" class="elsevierStylePara elsevierViewall">This protocol was approved by the ethics and biosafety committees of the ISSSTE Centro M&#233;dico Nacional 20 de Noviembre for compliance with the official Mexican regulations in force&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Since its approval&#44; 41 patients of various ages have been operated on&#59; the subpopulation selected was 8 children &#40;patients under 18 years of age&#41; who met the severity&#44; resistance and chronicity criteria&#46; They were accepted by the committee for surgical treatment as a final therapeutic measure&#44; as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Surgical technique</span>&#58; 3T magnetic resonance imaging &#40;MRI&#41; was used to extract T1 and T2 sequences in the axial plane as DICOM images&#46; After administering a local anaesthetic&#44; a Leksell stereotactic frame was put in place&#46; Once the frame was in place&#44; a head computed tomography &#40;CT&#41; scan was performed with contrast with the gantry at 0 degrees&#46; A surgical plan was then created using the AtlasSpace and ImageMerge version 3&#46;0 software&#44; merging the MRI and CT images to determine the following volumes&#58; amygdaloid nuclear complex &#40;ANC&#41;&#44; left and right anterior cingulum&#44; anterior limb of the left and right internal capsule and posterior hypothalamus&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The selection of neurosurgical targets was based on&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Neuroanatomical abnormalities&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Presence of intellectual disability&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Associated psychiatric comorbidities&#46;</p></li></ul></p><p id="par0210" class="elsevierStylePara elsevierViewall">References for the surgical targets were taken from the following works&#58; for the posterior hypothalamus&#44; the procedure was performed as described by the Italian<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> and Spanish<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a> group&#59; for the ANC it was performed as described by Langevin<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a> and Mpakopoulou<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a>&#59; for the cingulum and capsule&#44; the procedure was performed as described by Mexican groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The amygdaloid nuclear complex was identified using a T2 MRI sequence in an image merged with CT&#44; and neuroablation was performed on a 9<span class="elsevierStyleHsp" style=""></span>mm line with a 3<span class="elsevierStyleHsp" style=""></span>mm space for 90<span class="elsevierStyleHsp" style=""></span>s at 80<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; as shown in <a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#46; The target in the hypothalamus was located in the <span class="elsevierStyleItalic">X</span>-axis plane&#44; 2&#8211;4<span class="elsevierStyleHsp" style=""></span>mm from the wall of the third ventricle and 2<span class="elsevierStyleHsp" style=""></span>mm below the midpoint of the commissure&#44; corresponding to Sano&#39;s ergometric region&#44; in a CT merged with a T2 MRI sequence in three planes&#58; coronal&#44; axial and sagittal&#44; applying stimulation at 2<span class="elsevierStyleHsp" style=""></span>Hz and assessing the sympathetic response&#46; Neuroablation was performed at 80<span class="elsevierStyleHsp" style=""></span>&#176;C for 90<span class="elsevierStyleHsp" style=""></span>s as shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#46; The anterior limb of the internal capsule was identified using a T2 MRI sequence merged with CT in the axial plane&#44; 15<span class="elsevierStyleHsp" style=""></span>mm anterior to the anterior commissure&#44; 15<span class="elsevierStyleHsp" style=""></span>mm lateral to the midline and 2<span class="elsevierStyleHsp" style=""></span>mm below the line of the commissure&#46; Ablation was then performed at 80<span class="elsevierStyleHsp" style=""></span>&#176;C for 90<span class="elsevierStyleHsp" style=""></span>s&#46; The cingulum was identified in a T2 MRI sequence merged with CT in the coronal and sagittal planes&#44; locating the anterior third of the corpus callosum as the inferior margin or basal midline&#46; Ablation was performed at 80<span class="elsevierStyleHsp" style=""></span>&#176;C for 90<span class="elsevierStyleHsp" style=""></span>s&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0220" class="elsevierStylePara elsevierViewall">Once the coordinates of the surgical targets had been obtained&#44; under general anaesthesia and in supine decubitus position with slight flexion of the head&#44; precoronal trepanation was performed to insert the electrode&#59; the ablation was then carried out&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The patients were treated in two surgical procedures&#44; with an interval of at least 12 weeks between each one&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The inferential statistical analysis was performed using the Wilcoxon signed rank test for the OAS prior to surgery and at 6 months of follow-up&#46; The statistically significant differences were established with an alpha error &#60;0&#46;05&#46; Complications were recorded as percentages&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Results</span><p id="par0235" class="elsevierStylePara elsevierViewall">The average age was 13 years and 2 months&#44; with a range from 8 to 17 years and a mean of 14 years&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The time of evolution of the aggressiveness was 4&#8211;13 years&#44; with a mean of 8&#46;62 years&#59; the age of onset was 3&#8211;7 years with a mean of 4&#46;37&#59; 37&#46;5&#37; were female and 62&#46;5&#37; were male&#46; Six patients had a profound mental retardation&#44; one had a mild mental retardation and one had no mental retardation&#46; There was one patient with sequelae of Dandy&#8211;Walker syndrome&#44; while the other seven did not have preoperative anatomical alterations&#46; Four patients presented auto-aggression and four presented hetero-aggression&#46; Measurements were taken prior to surgery &#40;baseline&#41; and at 6 months after surgery&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0245" class="elsevierStylePara elsevierViewall">All ablations were immediately verified by postoperative MRI&#44; as shown in <a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">An improvement of 39&#46;29&#37; was observed in the overall score measured by the OAS between the baseline result and that obtained during follow-up&#46; Statistical analysis of theses scores was performed using the Wilcoxon signed rank test and revealed a statistically significant difference&#44; with a <span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0156&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Follow-up CT and MRI images were taken for all patients&#46; These confirmed the correct location of the lesions&#44; with the characteristics described above in the amygdaloid nuclear complex&#44; the posterior hypothalamus&#44; the anterior limb of the internal capsule and the cingulum&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Evidence of complications was found in 37&#46;5&#37; of the population&#46; These were transitory&#44; the patient with paresis recovering after two weeks and the two patients with hypersomnia recovering after one month&#59; there were no deaths that could be attributed to the procedure&#46; Of the two deaths recorded&#44; one was due to pneumonia at four months after the surgery&#44; and the other due to trauma at five months after the surgery &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0265" class="elsevierStylePara elsevierViewall">From the 1950s onwards&#44; neurosurgical treatment significantly decreased due to pharmacological advances and its then unfavourable reputation&#44; in spite of the good progress that was later made in stereotaxy&#44; such as the stereotactic device designed by Todd and Wells in the 1970s&#44; which served as a basis for the design of the Cosman&#8211;Roberts&#8211;Wells system&#44; which together with the Leksell system&#44; laid the groundwork for the procedures we use today&#46; Likewise&#44; with the technological progress in stereotactic systems&#44; high-precision neuronavigation&#44; neuroimaging and surgical technique&#44; these use of these resources for the benefit of our patients has become more accessible&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">It is still not possible to attribute a psychiatric disease to a specific anatomical region&#44; so treating a surgical target does not cure the disease but merely treats the most significant symptom&#44; as can be seen in our study&#46; Similarly&#44; this paper aims to offer the possibility of a surgical means to treat patients with IND that is refractory to conventional treatment&#46; Each patient must be appropriately selected using strict inclusion and exclusion criteria&#44; under the supervision of a multidisciplinary team&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">The dysfunctional neural unit&#44; circuit or region causes changes in behaviour&#44; and the amygdaloid nuclear complex plays a fundamental role in these circuits&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Narabayashi conducted the first study on amygdalectomy in 60 patients&#44; demonstrating that in 51 &#40;85&#37;&#41; patients emotional excitability improved and behaviour and social adaptation normalised postoperatively&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">21</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Persistent improvement has been reported during long-term follow-up &#40;3 years&#41; in 67&#46;5&#37; of patients treated with bilateral amygdalectomy&#44; as well as good long-term outcomes in paediatric patients &#40;5&#8211;13 years&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">10&#44;22</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">In a meta-analysis&#44; Mpakopoulou et al&#46; analysed 13 case series that used the amygdala as a target in adults&#44; finding a long-term improvement of 33&#8211;100&#37;&#44; with complications ranging from 0&#37; to 42&#37;&#44; without compromising higher brain functions&#44; thereby according great value to this method for carefully selected patients with IND&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">IND is associated with other behavioural alterations including anxiety&#44; addiction and other mood disorders&#46; Treatment was usually started in a context of concomitant epilepsy and electroencephalographic alterations&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a> Even these comorbidities&#44; especially epilepsy&#44; showed improvement following this surgical treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">23&#44;24</span></a> The mortality rate is reportedly very low &#40;3&#46;8&#37;&#41;&#44; and the deaths reported are due to causes unrelated to the surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">Ideally deep brain stimulation&#44; as described by Franzini et al&#46;&#44; has been used for patients with IND&#44; with a series reported of seven cases with mental retardation and aggressiveness who received implants in the bilateral posterior hypothalamus with significant improvements in OAS scores&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Although deep brain stimulation is reversible and adjustable&#44; in our environment it was not possible to use it&#44; partly due to the behaviour of the patients themselves&#44; the lack of family support for the treatment and above all the availability of economic resources&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Franzini et al&#46;&#44; in a series of eight patients with associated mental retardation&#44; reported improvement in six patients &#40;75&#37;&#41; following stimulation of the posterior hypothalamus&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> These results were studied over the long term by Torres et al&#46;&#44; in another case series with six patients who were monitored for an average of 3&#46;5 years and assessed using the Inventory for Client and Agency Planning general aggressiveness score&#46; Significant improvement was reported in auto- and hetero-aggression&#44; as well as improvements in other factors such as sleep patterns&#44; dietary changes and frequency of seizures where there was concomitant epilepsy&#44; without apparent significant adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">Other less studied targets include the cingulum and the internal capsule&#46; Two case series have been reported by a Mexican group&#46; The first studied 12 patients who underwent capsulotomy and cingulotomy and were followed up at 3 and 6 months using the Mayo-Portland Adaptability Inventory and the Global Assessment of Functioning Scale&#44; finding improvement on both scales&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a></p><p id="par0320" class="elsevierStylePara elsevierViewall">A later paper by the same group reported 10 cases&#44; this time with follow-up at 6 months and 4 years&#44; with assessment using the OAS and the Global Assessment of Functioning Scale&#44; finding improvement at 6 months of follow-up on both scales&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a> As for other surgical targets&#44; as reported in the literature&#44; the surgical region itself presented complications in some 50&#37; of cases&#44; the most common being transitory hyperphagia&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">19&#44;20</span></a> Our series did not coincide with that study with regard to hyperphagia as a surgical complication&#44; although we did also encounter complications within the range reported in the literature&#44; all of which were reversible&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">There is another surgical target reported in the literature with good results&#44; although only in one single reported case in a 19-year-old patient with mental retardation in whom deep brain stimulation was performed in the right orbitofrontal cortex&#44; obtaining good results at 2 weeks and 7 years from the procedure in impulse control and emotional control as measured by the OAS&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">There is one case study on stereotactic neuroablation conducted in China that reports low morbidity when operating on both amygdaloid nuclear complexes simultaneously with very wide ablation diameters on horizontal bitemporal trajectory&#44; offering knowledge that differs from traditional studies&#46; In our group&#44; we do not recommend bilateral lesion of this target due to reports in the literature relating to the development of Kl&#252;ver&#8211;Bucy syndrome&#46; Moreover&#44; some details of the study are unclear with regard to patient selection and follow-up time&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">28&#44;29</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">Our study is in line with international literature&#44; which shows a benefit in adult patients treated with this type of neurosurgical therapy&#44; observing satisfactory outcomes in children&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Nevertheless&#44; we encountered difficulties in the paucity of standardised definitions and measurement tools for this disease and the lack of clinically randomised international studies on either adult or paediatric patients in order to perform comparative analyses&#46; Another limitation of the study itself was in achieving patient adherence and follow-up&#44; as well as difficulties locating family members&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">The definitive effectiveness of these surgical procedures is difficult to establish&#44; as previous studies contain technical and methodological deficiencies that do not allow for the interpretation or analysis of information on safety and surgical response in the different targets treated&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">Our results showed improvement in all patients with the various combinations of surgical targets used in our study&#44; with the amygdala being the most used&#44; in 7 of the 8 patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions</span><p id="par0355" class="elsevierStylePara elsevierViewall">For the treatment of IND&#44; patients showed improvement in post-surgical OAS scores&#44; and the most satisfactory results &#40;improvement greater than 40&#37;&#41; had the inclusion of the amygdaloid nuclear complex in their surgical targets in common&#46; The only adverse events reported were transitory&#46; Through these procedures&#44; we achieved significant improvement&#44; thereby increasing the quality of life of the patients treated and&#44; consequently&#44; of their families&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">All of the literature makes reference to surgical targets based on adult patients&#46; To date&#44; this study is the only and largest case series reported in paediatric patients with IND treated with stereotactic neurosurgery&#46; It is therefore considered to be a pioneer on the subject&#44; and encourages the conduct of new clinical trials with higher numbers of cases&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0365" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "sec0030"
          "titulo" => "Conflicts of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-01-04"
    "fechaAceptado" => "2018-05-10"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1041367"
          "palabras" => array:4 [
            0 => "Irreducible neuroaggressive disorder"
            1 => "Neurosurgery"
            2 => "Ablation"
            3 => "Stereotactic"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1041366"
          "palabras" => array:4 [
            0 => "Trastorno neuroagresivo irreductible"
            1 => "Neurocirug&#237;a"
            2 => "Ablaci&#243;n"
            3 => "Estereot&#225;ctico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The irreducible neuroaggressive disorder &#40;IND&#41; is a well-described entity known to be associated with impulsive and aggressive behaviour&#46; While various studies have assessed available pharmacological and non-pharmacological treatment regimens&#44; patients with IND continue to pose a major threat to themselves and society&#46; While targeted stereotactic therapy for IND has gained traction in recent years&#44; there is a paucity of information describing comparative effectiveness of different validated anatomic regions&#46; In this paper&#44; we discuss the surgical results for patients with IND following targeted lesional therapy with a special focus on selection criteria and operative methods&#46; The objective is to analyse the efficacy and safety of the different described targets for this disorder in paediatric patients&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Eight paediatric patients met strict criteria for IND and were enrolled in this study&#46; Electroencephalography &#40;EEG&#41;&#44; video electroencephalography &#40;VEEG&#41; and magnetic resonance imaging &#40;MRI&#41; were performed in all patients prior to surgery&#46; Irreducible neuroagressive symptom was approached by lesional therapy based on most described targets for this disorder and assessed by the Overt Aggression Scale &#40;OAS&#41; pre-operatively and 6 months following surgery&#44; using Wilcoxon test for statistical analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results and conclusions</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The average patient age was 13 years 2 months&#46; 7 of the 8 patients enrolled had intellectual disabilities&#44; 1 patient suffered neurologic sequelae referable to Dandy&#8211;Walker syndrome and 7 patients had no preoperative anatomical alterations&#46; Following surgery&#44; patients with IND noted improvement in their OAS&#46; On average&#44; the OAS improved by 39&#46;29&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0156&#41;&#44; a figure similar in comparison to studies assessing treatment of IND in adult patients&#46; The most satisfactory results were achieved in patients whose ablative therapy involved the Amygdala in their targets&#46; There were no deaths or permanent neurological deficits attributable to procedure&#46; To the author&#39;s knowledge&#44; this is the largest series described in the literature for paediatric patients with IND treated with lesional stereotactic therapy&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results and conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducci&#243;n y objetivos</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El trastorno neuroagresivo irreductible &#40;TNI&#41; es una entidad bien descrita asociada con comportamiento impulsivo y agresivo&#46; Es un dilema tanto para el tratamiento farmacol&#243;gico como para el no farmacol&#243;gico en la psiquiatr&#237;a moderna&#44; implicando un riesgo individual y social importante&#46; A pesar de los avances en la terapia estereot&#225;ctica dirigida para TNI persiste una ausencia de informaci&#243;n cuando se compara la eficacia de los diferentes blancos anat&#243;micos validados&#46; En el presente trabajo se describen los resultados quir&#250;rgicos de los pacientes con TNI tratados con cirug&#237;a estereot&#225;ctica ablativa&#44; con enfoque en los criterios de selecci&#243;n y m&#233;todos utilizados en nuestra instituci&#243;n&#46; El objetivo es analizar la eficacia y seguridad de los diferentes blancos estereot&#225;cticos m&#225;s utilizados para agresividad irreductible en ni&#241;os&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Materiales y m&#233;todos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Seleccionamos a 8 pacientes pedi&#225;tricos con TNI bajo un estricto protocolo&#46; Se les realiz&#243; electroencefalograma&#44; videoelectroencefalograma y resonancia magn&#233;tica previo a la cirug&#237;a&#46; El s&#237;ntoma neuroagresivo irreductible fue tratado con cirug&#237;a estereot&#225;ctica hacia los blancos cerebrales m&#225;s descritos para agresividad&#44; y posteriormente evaluado mediante la <span class="elsevierStyleItalic">Overt Agressive Scale</span> en el prequir&#250;rgico y a los 6 meses de seguimiento&#44; usando el test de Wilcoxon para el an&#225;lisis estad&#237;stico&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Resultados y conclusiones</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La edad promedio de los pacientes fue de 13 a&#241;os y 2 meses&#44; 7 de los 8 pacientes incluidos ten&#237;an discapacidad intelectual&#44; un paciente ten&#237;a secuelas neurol&#243;gicas por s&#237;ndrome de Dandy Walker y 7 pacientes no ten&#237;an alteraciones anat&#243;micas preoperatorias&#46; Despu&#233;s de la cirug&#237;a los pacientes mostraron mejor&#237;a en la escala <span class="elsevierStyleItalic">Overt Agressive Scale</span> con un promedio de 39&#44;29&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0156&#41;&#44; lo cual se encuentra dentro del rango descrito para TNI en adultos&#46; Los resultados m&#225;s satisfactorios tuvieron en com&#250;n la inclusi&#243;n del complejo nuclear amigdalino dentro de los blancos quir&#250;rgicos&#46; No hubo muertes ni secuelas permanentes atribuibles al procedimiento&#46; La presente serie es la m&#225;s grande descrita en la literatura hasta el momento para pacientes pedi&#225;tricos con TNI tratados con ablaci&#243;n estereot&#225;ctica&#46;</p></span>"
        "secciones" => array:3 [
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            "identificador" => "abst0020"
            "titulo" => "Introducci&#243;n y objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Materiales y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Resultados y conclusiones"
          ]
        ]
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    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Hern&#225;ndez Salazar M&#44; Zarate M&#233;ndez A&#44; Meneses Luna O&#44; Ledesma Torres L&#44; Paniagua Sierra R&#44; S&#225;nchez Moreno MC&#44; et al&#46; Neurocirug&#237;a estereot&#225;ctica ablativa para trastorno neuroagresivo irreductible en pedi&#225;tricos&#46; Neurocirugia&#46; 2018&#59;29&#58;296&#8211;303&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Population included in the study&#46;</p>"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Patient number 4&#58; postoperative image of the frontal operculum and sylvian aqueduct showing a circumscribed hyperintense image in the basolateral region of the amygdaloid nuclear complex&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Patient number 5&#58; postoperative image of the sylvian aqueduct and cerebral peduncle showing a circumscribed hypointense image in the basolateral region of the left amygdaloid nuclear complex&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Patient number 2&#44; with Dandy&#8211;Walker syndrome&#44; mental retardation and hydrocephaly controlled with a ventriculoperitoneal shunt&#58; postoperative axial T2 MRI image of the basal third ventricle showing a circumscribed hyperintense image on the edge of the left posterior hypothalamus&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Patient number 1&#58; postoperative T1 contrast MRI of the columns of the fornix and carotid bifurcation showing two hypointense signals with a hyperintense centre in both cinguli above the corpus callosum&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age at onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Time of evolution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Type of aggressiveness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Psychomotor retardation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pre-surgical medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Post-surgical medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Targets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Previous OAS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Current OAS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Auto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Profound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Carbamazepine&#44; haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Carbamazepine&#44; risperidone&#44; fluoxetine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bilateral cingulum<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>left amygdala&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;85&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Auto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Profound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Carbamazepine&#44; risperidone&#44; fluoxetine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44; escitalopram&#44; carbamazepine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Left unilateral posterior hypothalamus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Auto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Profound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Haloperidol&#44; fluoxetine&#44; olanzapine&#44; magnesium valproate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Olanzapine&#44; fluoxetine&#44; magnesium valproate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bilateral cingulum&#44; left amygdala&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hetero&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Risperidone&#44; valproate&#44; methylphenidate&#44; atomoxetine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44; risperidone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st surgery 26&#47;09&#47;2014&#58; bilateral cingulotomy&#44; left amygdala&#44;<br>2nd surgery&#58; 24&#47;04&#47;2015&#58; left amygdala&#44; left posterior hypothalamus&#44; bilateral internal capsule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#46;63&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Auto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Profound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44; quetiapine&#44; clonazepam&#44; magnesium valproate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Valproate&#44; fluoxetine&#44; quetiapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Left amygdala&#44; left posterior hypothalamus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#46;53&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hetero&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oxcarbamazepine&#44; fluoxetine&#44; biperiden&#44; haloperidol&#44; risperidone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No medication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Left amygdala&#44; bilateral internal capsule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#46;82&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hetero&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Profound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Risperidone&#44; magnesium valproate&#44; fluoxetine&#44; clonazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Risperidone&#44; magnesium valproate&#44; fluoxetine&#44; clonazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st surgery 21&#47;11&#47;2006 bilateral posterior hypothalamus&#44;<br>2nd surgery 25&#47;04&#47;2015 bilateral posterior hypothalamus and left amygdala&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hetero&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Profound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Risperidone&#44; magnesium valproate&#44; fluoxetine&#44; clonazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Risperidone&#44; magnesium valproate&#44; fluoxetine&#44; clonazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st surgery 12&#47;04&#47;2006 bilateral anterior cingulum and left amygdala&#44;<br>2nd surgery 14&#47;11&#47;2006 bilateral posterior hypothalamus&#44; left amygdalectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
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Journal Information
Vol. 29. Issue 6.
Pages 296-303 (November - December 2018)
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Vol. 29. Issue 6.
Pages 296-303 (November - December 2018)
Clinical Research
Ablative stereotactic neurosurgery for irreducible neuroaggressive disorder in pediatric patients
Neurocirugía estereotáctica ablativa para trastorno neuroagresivo irreductible en pediátricos
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Manuel Hernández Salazara, Antonio Zarate Méndeza, Oscar Meneses Lunaa, Lucía Ledesma Torresa, Ramón Paniagua Sierrab, Mary Carmen Sánchez Morenoa, Juan Leonardo Serrato Avilaa,
Corresponding author
jls_avila@hotmail.com

Corresponding author.
a Centro Médico Nacional 20 Noviembre, ISSSTE, Mexico City, Mexico
b Centro Médico Nacional Siglo XXI, Hospital de Especialidades, Mexico City, Mexico
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Table 1. Study group characteristics.
Table 2. Transitory adverse effects in 3 patients.
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Abstract
Introduction and objectives

The irreducible neuroaggressive disorder (IND) is a well-described entity known to be associated with impulsive and aggressive behaviour. While various studies have assessed available pharmacological and non-pharmacological treatment regimens, patients with IND continue to pose a major threat to themselves and society. While targeted stereotactic therapy for IND has gained traction in recent years, there is a paucity of information describing comparative effectiveness of different validated anatomic regions. In this paper, we discuss the surgical results for patients with IND following targeted lesional therapy with a special focus on selection criteria and operative methods. The objective is to analyse the efficacy and safety of the different described targets for this disorder in paediatric patients.

Materials and methods

Eight paediatric patients met strict criteria for IND and were enrolled in this study. Electroencephalography (EEG), video electroencephalography (VEEG) and magnetic resonance imaging (MRI) were performed in all patients prior to surgery. Irreducible neuroagressive symptom was approached by lesional therapy based on most described targets for this disorder and assessed by the Overt Aggression Scale (OAS) pre-operatively and 6 months following surgery, using Wilcoxon test for statistical analysis.

Results and conclusions

The average patient age was 13 years 2 months. 7 of the 8 patients enrolled had intellectual disabilities, 1 patient suffered neurologic sequelae referable to Dandy–Walker syndrome and 7 patients had no preoperative anatomical alterations. Following surgery, patients with IND noted improvement in their OAS. On average, the OAS improved by 39.29% (p=.0156), a figure similar in comparison to studies assessing treatment of IND in adult patients. The most satisfactory results were achieved in patients whose ablative therapy involved the Amygdala in their targets. There were no deaths or permanent neurological deficits attributable to procedure. To the author's knowledge, this is the largest series described in the literature for paediatric patients with IND treated with lesional stereotactic therapy.

Keywords:
Irreducible neuroaggressive disorder
Neurosurgery
Ablation
Stereotactic
Resumen
Introducción y objetivos

El trastorno neuroagresivo irreductible (TNI) es una entidad bien descrita asociada con comportamiento impulsivo y agresivo. Es un dilema tanto para el tratamiento farmacológico como para el no farmacológico en la psiquiatría moderna, implicando un riesgo individual y social importante. A pesar de los avances en la terapia estereotáctica dirigida para TNI persiste una ausencia de información cuando se compara la eficacia de los diferentes blancos anatómicos validados. En el presente trabajo se describen los resultados quirúrgicos de los pacientes con TNI tratados con cirugía estereotáctica ablativa, con enfoque en los criterios de selección y métodos utilizados en nuestra institución. El objetivo es analizar la eficacia y seguridad de los diferentes blancos estereotácticos más utilizados para agresividad irreductible en niños.

Materiales y métodos

Seleccionamos a 8 pacientes pediátricos con TNI bajo un estricto protocolo. Se les realizó electroencefalograma, videoelectroencefalograma y resonancia magnética previo a la cirugía. El síntoma neuroagresivo irreductible fue tratado con cirugía estereotáctica hacia los blancos cerebrales más descritos para agresividad, y posteriormente evaluado mediante la Overt Agressive Scale en el prequirúrgico y a los 6 meses de seguimiento, usando el test de Wilcoxon para el análisis estadístico.

Resultados y conclusiones

La edad promedio de los pacientes fue de 13 años y 2 meses, 7 de los 8 pacientes incluidos tenían discapacidad intelectual, un paciente tenía secuelas neurológicas por síndrome de Dandy Walker y 7 pacientes no tenían alteraciones anatómicas preoperatorias. Después de la cirugía los pacientes mostraron mejoría en la escala Overt Agressive Scale con un promedio de 39,29% (p=0,0156), lo cual se encuentra dentro del rango descrito para TNI en adultos. Los resultados más satisfactorios tuvieron en común la inclusión del complejo nuclear amigdalino dentro de los blancos quirúrgicos. No hubo muertes ni secuelas permanentes atribuibles al procedimiento. La presente serie es la más grande descrita en la literatura hasta el momento para pacientes pediátricos con TNI tratados con ablación estereotáctica.

Palabras clave:
Trastorno neuroagresivo irreductible
Neurocirugía
Ablación
Estereotáctico

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