[Treatment of refractory aggressiveness by amygdalotomy and posteromedial hypothalamotomy by radiofrequency]. / Tratamiento de la agresividad refractaria mediante amigdalotomia e hipotalamotomia posteromedial por radiofrecuencia.

INTRODUCTION: Since, under certain circumstances, defensive or attacking behaviours display a pattern of motor dominance, as observed in subjects who participate in contact or fighting sports, aggressive behaviour was considered to have a dominant motor pattern. With the aim of preventing the functional problems reported with bilateral lesion procedures involving both the central nucleus of the amygdala and the posteromedial hypothalamus, the decision was made to combine them; thus, an amygdalotomy of the central nucleus of the amygdala and a posteromedial hypothalamotomy were to be performed simultaneously and unilaterally, on the basis of the motor dominance of the patient determined by means of the Edinburgh test. PATIENTS AND METHODS: This study describes the surgical experience in a series of nine patients diagnosed with refractory neuroaggressive syndrome. As part of the study protocol, a magnetic resonance brain scan was performed to rule out the presence of neoplasms, vascular diseases, infections and degenerative disorders. The degree of aggressiveness was quantified using Yudofsky's Overt Aggression Scale. Additionally, manual dominance was determined by means of the Edinburgh test. RESULTS AND CONCLUSIONS: Good control of aggressiveness was seen immediately. In some cases it was necessary to reduce the antipsychotic or benzodiazepine medication, as it was seen to increase aggressiveness. Only one case required a second surgical intervention. Follow-up was achieved in 100% of the cases at 24 months and 78% at 36 months.

TITLE: Tratamiento de la agresividad refractaria mediante amigdalotomia e hipotalamotomia posteromedial por radiofrecuencia.Introduccion. Dado que, en algunas circunstancias, las conductas defensivas o de ataque muestran un patron de dominancia motora, tal como se observa en los sujetos dedicados a los deportes de contacto o de lucha, se considero que la conducta agresiva tiene un patron motor dominante. Con el fin de evitar los problemas funcionales descritos con los procedimientos de lesion bilateral tanto del nucleo central de la amigdala como del hipotalamo posteromedial, se decidio combinarlos; es decir, realizar amigdalotomia del nucleo central de la amigdala e hipotalamotomia posteromedial de manera unilateral y simultanea, basandose en la dominancia motora del paciente mediante la prueba de Edimburgo. Pacientes y metodos. Este estudio muestra la experiencia quirurgica en una serie de nueve pacientes con el diagnostico de sindrome neuroagresivo resistente al tratamiento farmacologico. Dentro del protocolo de estudio, se les realizo resonancia magnetica cerebral para descartar la presencia de neoplasias, enfermedades vasculares, infecciones y trastornos degenerativos. El grado de agresividad se cuantifico mediante la escala global de agresividad de Yudofsky. Adicionalmente, se determino la dominancia manual a traves de la prueba de Edimburgo. Resultados y conclusiones. El buen control de la agresividad se observo de modo inmediato. En algunos casos fue necesario reducir la medicacion de antipsicoticos o benzodiacepinas, ya que aumentaban la agresividad. Solo un caso requirio una segunda cirugia. Se logro seguimiento del 100% de los casos en 24 meses y del 78% en 36 meses.

Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display co-occurring repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on valproic acid (VPA)-induced autism model mice. Human ASCs were injected into the neonatal pups (P2 or P3) intraventricularly and then we evaluated major behavior symptoms of ASD. VPA-treated mice showed increased repetitive behaviors, decreased social interactions and increased anxiety but these autistic behaviors were ameliorated through transplantation of hASCs. In addition, hASCs transplantation restored the alteration of phosphatase and tensin homolog (PTEN) expression and p-AKT/AKT ratio in the brains of VPA-induced ASD model mice. The decreased level of vascular endothelial growth factor (VEGF) and interleukin 10 (IL-10) by VPA were rescued in the brains of the hASC-injected VPA mice. With these results, we experimentally found hASCs' therapeutic effects on autistic phenotypes in a ASD model mice for the first time. This animal model system can be used to elucidate further mechanisms of therapeutic effects of hASCs in ASD.

Evaluation of bilateral cingulotomy and anterior capsulotomy for the treatment of aggressive behavior.

BACKGROUND: Agressiveness is a psychiatric symptom that may be part of schizophrenia, mental retardation, drug abuse and other conditions. Surgical treatment remains controversial and few therapeutic options are available. We undertook this study to perform a prospective analysis on the efficacy and safety of bilateral cingulotomy and anterior capsulotomy in the treatment of aggressiveness behavior. METHODS: We studied 25 patients with a primary diagnosis of aggressiveness refractory to conventional treatment. Subjects were clinically evaluated with the Mayo-Portland adaptability inventory and the Global Assessment of Functioning score. Lesions were placed stereotactically in both targets and confirmed by postoperative magnetic resonance imaging. Significant changes were evaluated with Wilcoxon test after 3 and 6 months. RESULTS: According to inclusion and exclusion criteria, only 12 patients were finally included and surgical treated. Lesions significantly decreased using the Mayo-Portland adaptability inventory and the Global Assessment of Functioning score (p <0.002) at 3 and 6 months follow-up. Only five patients showed either mild or transitory postsurgical complications. CONCLUSIONS: Combined bilateral anterior capsulotomy and cingulotomy successfully reduced aggressiveness behavior and improved clinical evaluations. These effects were obtained with fewer complications than previously described targets.

Effectiveness of cerebral hemispherotomy for improving behavioral disorders associated with intractable post-traumatic seizures.

A 25-year-old man presented with intractable post-traumatic seizures after suffering cerebral contusion in a traffic accident at age 5 years. Cerebral hemispherotomy was performed to transect the neuronal fibers to interrupt connections between seizure foci in wide areas of the brain, and to minimize the resected brain parenchyma. His seizures resolved and behavioral disorders improved, which had been impaired since age 8 years. Increased glucose metabolism in the normal frontal lobe detected by interictal fluorodeoxyglucose-positron emission tomography was correlated with the improvements in behavioral disorders. These findings suggest that the effects of seizures may be reversible in brain areas connected with, but remote from, the epileptogenic cortex.

Global improvement in intellectual and neuropsychological functioning after removal of a suprasellar cystic craniopharyngioma.

This is a case report of a patient who presented with cognitive and behavioral decline and underwent surgery for removal of a suprasellar craniopharyngioma. Previous studies have reported memory impairments in the presence of craniopharyngioma, but information is lacking regarding the impact of craniopharyngioma on other brain functions as well as on intellectual abilities. In this study, comprehensive neuropsychological testing, including intellectual testing, was conducted 9 to 14 days before surgery and 16 to 22 days after surgery. Results before surgery demonstrated average intellectual abilities, which were decreased from premorbid estimates, and diffuse neuropsychological impairments. Postoperatively, significant improvement in both intellectual abilities and neuropsychological test scores was observed. These results suggest that craniopharyngiomas can be associated with impairments in intellectual abilities and in brain functions aside from memory. The results are contrasted with those of previous reports, and implications for future research are discussed.

Stereotaxy and behavioural disorders.

A series of 35 selected non senile patients was investigated with stereotactic brain biopsies in frontal and temporal lobes including the rhinencephalon. Results of neuropathological studies are confronted with clinical proposals. Alzheimer's disease is diagnosed in about 10% of the cases under 50 years of age, but more than 50% after 50. In the whole series only 10 clinical diagnoses (29%) were confirmed by neuropathological findings, 14 cases (40%) were fully corrected, 5 out of 7 undefined demented patients were specified but 6 cases (17%) remained unspecified because only nonspecific gliosis was found. Thus stereotactic biopsies were without real interest in 10 confirmed diagnosis (29%), of relatively poor interest in 6 nonspecific gliosis (17%), but of great interest in 19 cases (40% corrected + 14% specified = 54%). It can be considered from a general point of view that in our series more than 50% of diagnoses benefit definitively by stereotactic brain biopsies bearing in mind that the clinical diagnosis fails in one case out of two. It is clearly demonstrated that this stereotactic methodology has a significantly higher score than conventional biopsies.

The role of stereotactic amygdalotomy in the treatment of temporal lobe epilepsy associated with behavioral disorders.

The efficacy of bilateral stereotactic amygdalotomy for the treatment of aggressive behavioral disorders has been evaluated in a retrospective study of 67 cases. In addition 4 cases with complex partial seizures accompanied by aggressive outbursts revealing a unilateral epileptogenic focus in the amygdala or periamygdala region during preoperative stereoelectroencephalographic (SEEG) evaluation received a unilateral stereotactic amygdalotomy. Long-term follow-up of these 4 cases shows that 3 patients had considerable improvement in seizure frequency and severity as well as behavioral disturbances. The results in the remaining patients evaluated by surface EEG were inconclusive.

Social implications of the "dyscontrol syndrome" (neuropsychiatric correlates).

The recent literature contains numerous publications which have tried to stimulate a new and biologically oriented approach to the problem of violence. Experimental brain research indicates that biologically important predatory and aggression responses have multiple representations in the nervous system. However, knowledge gained so far concerning emotional brain function in violent persons with brain disease, or from experimental research, can only infrequently be applied to combat the violence-triggering mechanisms in the brains of the non-diseased. In the hope of determining the neurological basis of aggression, the present author studied the brains of forty-two patients whose clinical history indicated definite aggressive behaviour. Results are reported and discussed. It is also the aim of this paper to discuss the social implications of the surgical treatment of patients with a "dyscontrol syndrome" whose investigations do not reveal definite evidence of "hard" signs and symptoms of brain pathology.