Neurosurgery for Refractory Schizophrenia: A Systematic Literature Review

Schizophrenia is a chronic and disabling psychiatric disease that can be refractory to conventional treatment. The present study aims to gather information about the circuitry related to schizophrenia to describe possible surgical targets, and to establish whether psychosurgery can be a safe and effective treatment option for refractory schizophrenia. A systematic review of the literature was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An electronic search was performed in the Pubmed and BVSalud databases using medical subject headings (MeSH) combined with Boolean operators. Out of the 724 studies retrieved, 13 were included in the review. Regarding leucotomy without a stereotactic approach, we found side effects such as irritability, nervous excitement, cases of disinhibition, and compromised normal social control. In other stereotactic procedures, there was some improvement, mainly regarding aggressiveness and positive symptoms; an anterior capsulotomy had an efficacy rate of 74% according to the Clinical Global Impression (CGI) rating scales. The only deep brain stimulation (DBS) case report found in our study described a significant improvement in the positive and negative symptoms. The use of a stereotactic approach enables psychosurgery to be a safe and effective treatment option in cases of refractory schizophrenia, improving the quality of life and the symptoms. Cognitive and negative symptoms remain a challenge in the treatment of schizophrenia, revealing that more targets in the circuitrymust be surgically explored. Furthermore,more clinical trials are needed to compare these many surgical techniques and targets, using a standard evaluation parameter. The results show that DBS has a promising future in the treatment of refractory schizophrenia.

Efecto de la amigdalotomía e hipotalamotomía unilateral en pacientes con agresividad refractaria / Effect of tonsillotomy and unilateral hypothalamotomy in patients with refractory aggressiveness

Resumen Antecedentes: El tratamiento neuroquirúrgico, aunque polémico, se considera un recurso útil en el tratamiento de enfermedades psiquiátricas crónicas como la agresividad refractaria. Objetivo: Evaluar los resultados clínicos y los efectos colaterales de la hipotalamotomía posteromedial (HPM) asociada a amigdalotomía en pacientes con agresividad refractaria. Método: Se realizó un ensayo clínico en pacientes con agresividad crónica y refractaria a tratamiento farmacológico. Se les realizó amigdalotomía central asociada a HPM mediante termocoagulación por radiofrecuencia. El grado de agresividad se cuantificó mediante la escala global de agresividad de Yudofsky. Los cambios postoperatorios en la conducta agresiva continuaron siendo evaluados cada 6 meses durante al menos 36 meses. Resultados: Se observó un cambio estadísticamente significativo de la conducta agresiva, a lo largo de 36 meses de seguimiento. Se describen los efectos colaterales de la asociación de ambos procedimientos, siendo el de mayor frecuencia la somnolencia y algunos casos de reducción en la conducta sexual. Conclusión: Las lesiones unilaterales simétricas y simultáneas del núcleo central de la amígdala y del hipotálamo posteromedial contralaterales a la dominancia motora dan el mismo efecto clínico en la reducción de la agresividad patológica que las lesiones bilaterales.

Abstract Background: Neurosurgical treatment, although controversial, is considered a useful resource in the treatment of chronic psychiatric diseases such as refractory aggressiveness. Objective: To evaluate the clinical results and side effects of posteromedial hypothalamotomy associated with amygdalotomy in patients with refractory aggressiveness. Method: A clinical trial was conducted in patients with chronic aggressiveness and refractory to pharmacological treatment. A central amygdalotomy associated with posteromedial hypothalamotomy was performed using thermo-coagulation by radiofrequency. The degree of aggressiveness was quantified by the Yudofsky's global scale of aggression. Postoperative changes in aggressive behavior continued to be evaluated every 6 months for at least 36 months. Results: A statistically significant change in aggressive behavior was observed during 36 months of follow-up. The collateral effects of the association of both procedures are described, the most frequent being drowsiness and some cases of reduction in sexual behavior. Conclusion: Symmetric and simultaneous unilateral lesions of the central nucleus of the amygdala and the posteromedial hypothalamus contralateral to motor dominance give the same clinical effect in the reduction of the pathological aggression that the bilateral lesions.

The Potential Usefulness of Magnetic Resonance Guided Focused Ultrasound for Obsessive Compulsive Disorders

Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.

The Potential Usefulness of Magnetic Resonance Guided Focused Ultrasound for Obsessive Compulsive Disorders

Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.

Psychosurgery: from ablation to neuromodulation / 上海交通大学学报（医学版）

Psychosurgery, the neurosurgical treatment for psychiatric disorders, has a long and controversial history. The review introduces the birth of psychosurgery, the rise and fall of the frontal lobotomy and the transition to the modern era of psychosurgery, due to the development of the stereotactic instruments, and the different psychosurgical procedures. Today, recent advances in neuromodulation may provide an opportunity for psychosurgery to become a more attractive option for the treatment of psychiatric diseases. Current states in China and prospects of psychosurgery are also discussed.

Cirugía de los trastornos del comportamiento: el estado del arte / Surgery for Behavioral Disorders: The state of the art

INTRODUCCIÓN: la cirugía de los trastornos del comportamiento (CTC) se está convirtiendo en un tratamiento más común desde el desarrollo de la neuromodulación. Podemos dividir su historia en 3 etapas: la primera comienza en los inicios de la psicocirugía y termina con el desarrollo de las técnicas estereotácticas, cuando comienza la segunda etapa. Ésta se caracteriza por la realización de lesiones estereotácticas. Nos encontramos transitando la tercera etapa, que comienza cuando la estimulación cerebral profunda (ECP) empieza a ser usada en CTC. OBJETIVO: el propósito de este artículo es realizar una revisión no sistemática de la historia, indicaciones actuales, técnicas y blancos quirúrgicos de la CTC. RESULTADOS: a pesar de los errores graves cometidos en el pasado, hoy en día, la CTC está renaciendo. Los trastornos psiquiátricos que más frecuentemente se tratan con cirugía y los blancos estereotácticos preferidos para cada uno de ellos son: cápsula interna/estriado ventral para trastorno obsesivo-compulsivo, cíngulo subgenual para depresión y complejo centromediano/parafascicular del tálamo para síndrome de Tourette. CONCLUSIÓN: los resultados de la ECP en estos trastornos parecen alentadores. Sin embargo, se necesitan más estudios randomizados para establecer la efectividad de la CTC. Debe tenerse en cuenta que una apropiada selección de pacientes nos ayudará a realizar un procedimiento más seguro así como también a lograr mejores resultados quirúrgicos, conduciendo a la CTC a ser más aceptada por psiquiatras, pacientes y sus familias. Se necesita mayor investigación en vários temas como: fisiopatología de los trastornos del comportamiento, indicaciones de CTC y nuevos blancos quirúrgicos

BACKGROUND: Surgery for behavioral disorders (SBD) is becoming a more commonly-used treatment since the development of neuromodulation techniques. We can divide the history of SBD into 3 stages: the first stage spanned from the dawn of psychosurgery to the initial development of stereotactic techniques. The second stage was characterized by the recognition of stereotactic lesions. We are currently traveling through the third stage, which began when deep brain stimulation (DBS) started to be used for SBD.OBJECTIVE: This article reviews the history, current indications, techniques and surgical targets of SBD. RESULTS: Despite serious errors committed in the past, SBD is now re-emerging as an accepted therapeutic approach. The psychiatric disorders that are most frequently treated by surgery and the preferred stereotactic targets for treating them are: the internal capsule/ventral striatum for obsessive-compulsive disorder; the subgenual cingulate for treatment-resistant depression; and the centromedianum/parafascicularis complex of the thalamus for Tourette syndrome. CONCLUSIONS: Early results for DBS in these disorders are encouraging. However, more randomized trials are needed to establish the effectiveness of SBD. It must be taken into account that ensuring proper patient selection will enhance both procedural safety and effectiveness, leading to SBD being more accepted by psychiatrists, patients and their families. Further research is needed in several areas, like the physiopathology of behavioral disorders, indications for SBD, and new surgical targets

Psicocirurgia para tratamento de transtorno obsessivo-compulsivo / Psychosurgery for the treatment of obsessive-compulsive disorder

O transtorno obsessivo-compulsivo (TOC) é uma patologia incapacitante tanto na esfera social como na ocupacional. Está associado a uma morbidade bastante alta quando comparado a outras condições psiquiátricas e estima-se atualmente uma prevalência de 2% a 3% na população. Alguns estudos sugerem uma provável relação com uma disfunção do córtex frontal e do cíngulo, envolvendo o circuito de Papez. Esse circuito parece mediar os sintomas ansiosos, visto que lesões cirúrgicas dessas áreas afetam a ansiedade geralmente associada ao TOC. A neurocirurgia ablativa para o tratamento de distúrbios psiquiátricos foi muito utilizada até o desenvolvimento de psicofármacos efetivos. Recentemente, com os avanços técnicos do procedimento cirúrgico, auxiliado pelo conhecimento neurofisiológico, a psicocirurgia tornou-se mais precisa e segura. Porém, sua indicação se restringe como uma alternativa ao tratamento de pacientes com TOC refratário à terapia comportamental e/ou medicamentosa.

The obsessive-compulsive disorder (OCD) is a both socially and occupationally incapacitating disease. It is associated with a quite high morbidity if compared to other psychiatric conditions and currently it is estimated a lifetime prevalence rate of 2% to 3%. Some studies suggest a probable relation with a dysfunction in the cingulate and the frontal cortex, involving the Papez circuit. Anxious symptoms seem to be mediated by that circuit, considering surgical lesions of these areas affect the anxiety usually associated with OCD. The ablative neurosurgery for the treatment of psychiatric disorders was widely used until the development of effective psychopharmacological medication. Recently, thanks to the technical advances of the surgical procedure, aided by the neurophysiological knowledge, the psychosurgery became more accurate and safer. Yet, its indication is restricted as an alternative treatment to refractory OCD patients.

Capsulotomia ventro-capsular e ventro-estriatal por raios gama no transtorno obsessivo-compulsivo: avaliação inicial da eficácia e perfil de eventos adversos / Ventral capsular and ventral striatal gamma capsulotomy in obsessive-compulsive disorder: initial assessment of efficacy and profile of adverse events

Inúmeros estudos têm demonstrado que o Transtorno Obsessivo-Compulsivo (TOC) costuma cursar com uma taxa de resposta a tratamentos variando entre cerca de 60 a 80% dos casos, por meio do emprego de medicamentos inibidores de recaptação de serotonina, ou da terapia comportamental. Encontramos, no entanto, uma parcela de indivíduos portadores desta enfermidade os quais não respondem às opções terapêuticas clássicas, evoluindo com grave comprometimento psicossocial. Radiocirurgias estereotáxicas, como a capsulotomia anterior por raios gama, são uma opção terapêutica para estes pacientes. Recentemente, um aperfeiçoamento da capsulotomia anterior por raios gama foi desenvolvido na Universidade de Brown, denominado capsulotomia ventro-capsular e ventro-estriatal por raios gama, utilizando-se de lesões menores e tendo melhor perfil de eventos adversos. Faltam no entanto estudos detalhando a eficácia e o perfil de eventos adversos desta técnica. O objetivo deste estudo foi determinar se a capsulotomia ventro-capsular e ventro-estriatal por raios gama no TOC é eficaz quanto à redução de sintomas obsessivo-compulsivos e melhora clínica global e qual o perfil de eventos adversos, e de alterações neuropsicológicas e de personalidade do procedimento. Selecionaram-se 14 pacientes com TOC refratário, e que foram submetidos a esta técnica cirúrgica no país, cinco dos quais fizeram parte de um estudo piloto inicial. Os outros nove pacientes participaram de um ensaio clínico randomizado, duplo-cego, no qual um grupo se submeteu a radiocirurgia verdadeira (grupo ativo), enquanto o outro grupo recebeu uma falsa radiocirurgia (grupo placebo). Anteriormente ao procedimento, todos realizaram uma detalhada avaliação clínica/psiquiátrica, além de uma extensa bateria de instrumentos de diagnóstico psiquiátrico, gravidade e evolução do TOC, melhora clínica global, sintomas depressivos/ansiosos, e alterações neuropsicológicas e de personalidade...

Several studies have demonstrated that good treatment responses in obsessive-compulsive disorder (OCD) are often obtained in 60 to 80 % of patients, whether employing serotonin reuptake inhibitors or behavior therapy. However, a subgroup of these patients does not respond to the conventional therapeutic options. Severe psychosocial impairments are meanwhile observed. Stereotactic radiosurgeries, such as Gamma Knife anterior capsulotomy is a treatment option for these subjects. A smaller Gamma Knife capsulotomy technique, termed ventral capsular and ventral striatal gamma capsulotomy, has been recently developed at Brown University, with few adverse events. On the other hand, there is a lack of studies describing the efficacy and adverse events associated to this new technique. The aim of this study was to determine whether ventral capsular and ventral striatal gamma capsulotomy is efficacious in terms of obsessive-compulsive symptoms reductions and clinical global improvements, as well as to report the profile of adverse events, and neuropsychological and personality changes associated to this procedure. Fourteen refractory OCD patients were selected to be submitted to this new radiosurgical technique. Five subjects were operated in an open, pilot study. The other nine patients took part in a double-blind, randomized controlled trial, consisting of an active group (which received true radiosurgery) and a placebo group (with sham radiosurgery patients). All subjects were previously evaluated by a preliminary clinical/psychiatric interview, as well as by extensive specific instruments regarding psychiatric diagnosis, OCD evolution and severity, clinical global improvements, anxiety/depression symptoms, and neuropsychological and personality changes. All patients were offered periodical follow-up visits for a minimum of one year. Regarding the pilot study, two of five patients (40%) responded to treatment after one year of follow-up, while three of five (60%)...

Introducción a la neurocirugía psiquiátrica

Resumen: La neurocirugía para tratar los trastornos psiquiátricos tiene sus primeros antecedentes modernos a mediados del siglo XIX con los trabajos de Buckhart, quien resecó parcialmente la corteza frontal de pacientes psiquiátricos. Aunque los resultados fueron alentadores en cuatro de seis casos, la muerte de uno y crisis convulsivas en otros dos frenaron el desarrollo de este procedimiento. En 1936, Egas Moniz y Almeida Lima efectuaron una sección de las fibras frontales en pacientes psiquiátricos con diversos diagnósticos, procedimiento que denominaron lobotomía prefrontal. El éxito de este tratamiento llevó a Moniz a obtener un premio Nobel en 1949. A su vez, esto alentó a Fulton y a Jacobsen a promover este tipo de procedimientos, denominados entonces "psicocirugía", en Estados Unidos. Desafortunadamente, la ausencia de un entendimiento adecuado de la fisiopatología y la sobreindicación de los procedimientos provocó que entre 1935 y 1950 se operaran alrededor de 20,000 pacientes en condiciones cuestionables y con importantes complicaciones. La aparición de los fármacos antipsicóticos y la falta de regulación y entendimiento de la neurocirugía psiquiátrica evitan nuevamente que este tratamiento se realice de manera científica y controlada. Aun así, Spiegel y Wacis iniciaron en 1946 la era de la neurocirugía estereotáctica que reduce el riesgo de complicaciones de la neurocirugía funcional. Cuatro procedimientos fueron aceptados entonces por la OMS para el tratamiento seguro y efectivo de enfermedades psiquiátricas. Estas cirugías incluyen la cingulotomía, la capsulotomía anterior, la tractotomía subcaudada y la leucotomía límbica (combinación de cingulotomía y tractotomía). Por otro lado, los trastornos psiquiátricos que han mostrado mejoría sustancial después de alguno de estos procedimientos neuroquirúrgicos son el trastorno depresivo mayor, el trastorno obsesivo-compulsivo, el trastorno bipolar, algunos trastornos de ansiedad, la adicción a sustancias y los trastornos impulsivos-agresivos. Es importante señalar que los criterios de inclusión a protocolos neuroquirúrgicos asistenciales o de investigación para mejorar los síntomas psiquiátricos han sido bien establecidos, y la selección de pacientes y los grupos neuroquirúrgicos deben ser supervisados por un comité de ética bien acreditado. Actualmente, las indicaciones para proponer como candidato a neurocirugía a un paciente son: Una enfermedad psiquiátrica diagnosticada de acuerdo con los criterios del DSM IV-R; evidencia de refractariedad (mejoría inferior a 50% de los síntomas) con los tratamientos convencionales; ésta debe ser avalada por dos psiquiatras. El padecimiento debe tener una duración de al menos cinco años. Además, un comité ético revisor de los protocolos quirúrgicos y de investigación debe evaluar a cada candidato al procedimiento o protocolo y cerciorarse de que el paciente o las personas responsables de él entiendan los criterios médicos y psiquiátricos para participar en el proceso; el comité supervisa también el proceso de consentimiento. Los procedimientos neuroquirúrgicos sólo podrán ser indicados en pacientes psiquiátricos con capacidad y ellos mismos aprobarán y firmarán un consentimiento informado. Las clínicas de neurocirugía psiquiátrica deberán trabajar estrechamente y contar con los siguientes especialistas: Un equipo de neurocirujanos estereotácticos con experiencia probada en neurocirugía psiquiátrica, neuromodulación, radiocirugía e investigación. Un equipo de psiquiatras con amplia experiencia en condiciones psiquiátricas y de investigación. Preferiblemente, ambos grupos deberán tener experiencia en neurocirugía psiquiátrica o contar con la asesoría de una clínica de neurocirugía psiquiátrica. La neurocirugía psiquiátrica deberá realizarse sólo para restaurar la función normal y aliviar al paciente de su angustia y sufrimiento. Los procedimientos deberán practicarse para mejorar la vida de los pacientes y nunca por motivos políticos, cuestiones legales o propósitos sociales. Finalmente, la neuromodulación ha demostrado ser una técnica útil y segura para el alivio de trastornos psiquiátricos debido a que sus efectos son reversibles y ajustables a cada paciente. Por lo mismo, en la actualidad se ha aplicado con éxito en el tratamiento de la depresión mayor, el trastorno obsesivo compulsivo y la enfermedad de Gilles de la Tourette.

Abstract: Recent background in neurosurgery for psychiatric disorders can be placed in the mid XIXth century. Buckhartd made partial resection of frontal cortex in 6 psychiatric patients, with successful results in 4 of them, but important side effects prevented the development of this scientific approach. In 1936 Egas Moniz and Almeida Lima performed a new neuro-psychiatric technique for treatment of several psychiatric disorders, named prefrontal lobotomy. Results of this treatment won Moniz a Nobel Prize in 1949, and encouraged Freeman and Watts to further develop this kind of surgery in United States of America. Unfortunately, the knowledge about pathophysiology was not sufficient to make a precise indication of surgery in this patients. Between 1935 and 1950, nearly 20,000 surgeries were performed in doubtful conditions, showing important side effects. On the other hand, the emergency of new drugs for the treatment of psychiatric disorders along with the absence of regulation stopped development of "psychosurgery". However, in 1946 Spiegel and Wacis started stereotactic age of neurosurgery, thus reducing risk and complication of this procedures. Nowadays, World Health Organization accepted four neurosurgery procedures for psychiatric disorders: cingulotomy, anterior capsulotomy, subcaudate tractotomy and limbic leucotomy (a combination of cingulotomy and subcaudate tractotomy). Best results for this kind of surgery are shown for affective disorders (major depression disorder, bipolar disorder, anxiety disorders) and obsessive compulsive disorder. Besides, in clinical research protocols the inclusion criteria for neurosurgical procedures in psychiatry have been well defined. Both patients' selection and medical team must be monitored by ethics committee. Currently, the requirements to consider a patient as a candidate for psychiatric neurosurgery are: Clear psychiatric diagnosis in accordance to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM.IV-TR). Evidence of refractivity (improved of symptoms inferior to 50%) to conventional treatments provided by two different psychiatrists. A minimum of 5 years of evolution in symptoms. The ethics committee must monitor surgical and research protocols in a case by case basis. The Committee will made sure that patient and relatives understand medic and psychiatric inclusion criteria. Neurosurgical procedures will only be indicated when the patient is able to understand and accept any details presented to him or her in a formal Consent Form. Neurosurgery psychiatric clinical teams should be integrated by: Stereotactic neurosurgeons whose have experience in psychiatric neurosurgery, neuromodulation, radiosurgery and clinical issues. A psychiatric team with ample experience in psychiatric conditions and research protocols. In case both teams of specialists are not experienced enough in the field of psychiatric neurosurgery, they must look for technical advice from other neurosurgical psychiatric centers. Psychiatric neurosurgery can only be performed to recover healthy conditions and relief suffering. These interventions must always be performed with the sole objective of improving patients quality of life and they must never be used for political, legal or social purposes. Finally, Neuromodulation has shown to be a useful and safe tool in relief of psychiatric disorders. Neuromodulation's effects are reversible and they can adjusted to patient. Nowadays, Neuromodulation is being used in patients with major depression, obsessive compulsive disorder and Tourette's illness.

Radiocirugía psiquiátrica con Gamma Knife

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Abstract: Today, psychosurgery is a minimally invasive and highly selective treatment performed only on some patients with severe, refractory treatment, affective, anxious, or obsessive-compulsive disorders. Recent advancements in technology and functional neuroanatomy as well as economic pressures to lower the cost of caring for the chronically ill may provide an opportunity for psychosurgery to become a more attractive option in the treatment of psychiatric disease. In recent years, the rapid adoption of computer-based techniques for surgical planning and visualization and image-guided surgery have made possible a number of impressive advances in functional neurosurgery. Magnetic resonance imaging (MRI) allows for the acquisition of highly detailed structural information of soft tissues in the brain. Minute pathological alterations can be visualized even before they are detected by other means. Stereotaxic atlases based on this information are now used to achieve an extraordinary precision in the placement of electrodes and probes and to plan the operation. Functional imaging is currently possible with special metabolic markers and MRI, as well as computerized techniques for the mathematical processing and visualization of images. Thus, non-invasive evaluation of brain function can be performed with extraordinary precision and sensitivity. Bloodless stereotaxic surgery without opening the skull (even the patient's head does not need to be shaved) is possible thanks to a revolutionary technique called radiosurgery. The destruction of nervous or vascular tissue inside the brain is achieved by projecting thin and powerful beams of ionizing radiation, which come from several angles around the patient's head. These beams produced by sources of radioactive cobalt (the "gamma knife" developed in the 60's by the Swedish neurosurgeon Lars Leksell). With this modality, radiation energy concentrates in a single small point inside the brain. Gamma Knife radiosurgery was first used in our country in 1996 to treat patients diagnosed with treatment-refractory psychiatric diseases. This treatment modality requires a multidisciplinary effort on the part of psychiatrists, neuropsychologists, neurologists, neurosurgeons and medical physicists. This should also be in accordance with the psychiatric neurosurgical protocol and ethics code of Medica Sur, as well as following the guidelines established by the National Nuclear Regulatory Commission and the Radiosurgery and Stereotaxic Radiotherapy Section of the Mexican College of Neurological Surgery. Ten patients have been treated with several procedures like cingulotomy, anterior capsulotomy, subcaudate tractotomy and limbic leukotomy in order to aid them in obsessive-compulsive disorder, major depression, pathological aggression, and Asperger and Tourette Syndromes. In this paper we disclose our experience with follow-ups ranging from six months to seven years in accordance with the most usual evaluation scales for mental disease and multiaxial evaluation framework of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). In our cases, the most common indications have been refractory obsessive-compulsive disorder (OCD), pathologic aggression and major depression after at least two years of treatment and with the involvement of at least two psychiatrists. According to the basal diagnosis, psychological tests are used by the neuropsychology specialist from our group and /or the neuropsychologists who have given medical treatment along with the psychiatrists. Six males and four females were treated with an age range of 13 to 52 years, and an average age of 28.2 years. The first patient had impulsive disorder and hetero-aggression, with a history of two bilateral prefrontal lobotomies with no stereotaxic planning and without a good response. The patient had gamma radiosurgery with bilateral anterior capsulotomy and continued his antipsychotic treatment. For two years, the patient had a good response and was able to go back to his wife and mother. After those two years, he developed a hypersexuality syndrome that led to a divorce from his wife and the patient was lost to clinical follow-up. The second patient was an adolescent with corpus callosum lipoma and hetero-aggression and compulsive syndrome refractory to medical treatment including carbamazepine levels above the therapeutic level. Three persons had to continuously watch him at home during 24 hours a day. He had a history of bilateral stereotaxic cingulotomy with thermocoagulation without a good response. Under general anesthesia, a gamma bilateral stereotaxic capsulotomy was performed. After 2 months of latency period and three years of follow-up, the hetero-aggression has been under control. Carbamazepine treatment is still used. The third patient had physical hetero-aggression towards his parents for more than seven years. He underwent gamma radiosurgery for bilateral capsulotomy and after a latency period of three months and a three year follow-up the patient has had no aggression episodes. The fourth patient had hetero-aggression since his teenage years, with a course of more than 6 years of this disorder and major depression with suicidal attempts. He had an electroconvulsive therapy session that led to a minor improvement lasting 2 months. Gamma radiosurgery was used for a limbic leukotomy in the cingula and the anterior arm of the internal capsules. His aggressiveness has significantly improved and his depression has been fluctuating under medical supervision. The patient has anxiety crisis that the patient's mother helps to control by giving him marijuana. The fifth patient had OCD of more than 10 years of course and a predominance of contamination fobias and bleeding hands because of frequent washing. She was treated with bilateral gamma capsulotomy and after two months of latency she stopped using gloves and after two years of follow-up the fobias have disappeared and has been able to work with no limitations in a company office. The sixth adolescent patient is the son of a neurosurgeon colleague and has symptoms of hetero and self-aggression, impulsivity and destructive behavior associated with mental retardation. The patient underwent a bilateral anterior capsulotomy under general anesthesia. The suggested treatment protocol was to combine the procedure with bilateral limbic leukotomy and hypothalamic procedure in a second surgical stage to control the self-aggression outbreaks. The patient had significant improvement of his impulsivity during the first two months and before the end of his minimum latency period of 6 to 8 months developed a zone of radionecrosis. He had an open cingulotomy after five months of radiosurgery in another hospital and his current clinical course is unknown. The seventh patient with Asperger and Tourette syndrome and impulsivity and hetero-aggression had a bilateral anterior gamma capsulotomy with significant improvement and after one year of follow-up he had a less severe clinical recurrence and underwent bilateral gamma cingulotomy to complete limbic leukotomy. He has early shown improvement but his follow-up is only two months. The eighth patient had schizophrenic disorder displayed as impulsivity crisis, obsessive ideas and hetero-aggression towards his family fluctuating with periods of depression. He had a limbic leukotomy and has good control of his aggression and is still under medical treatment as most of the patients are. The nineth patient in the series had major depression, suicidal attempts and chronic anxiety refractory to medical treatment. She was operated two years before and had a bilateral capsulotomy by thermocoagulation and because her clinical picture prevailed, she had bilateral anterior capsulotomy with gamma knife. In her six month follow-up, her anxiety has improved, and she has had no new major depression crisis and her follow-up neuropsychological tests are pending to be made in her home town.

La neurocirugía en los trastornos de la alimentación: ¿una alternativa posible?

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Abstract: Composition and quantity of food in-taken varies considerably between one meal and another, or between one day and the following. Non biological factors -such as emotional, social, day time, feasibility in the type of food, and cost- are, among others, factors that in some way affect the degree of energy in-take by food, which generally is not related with daily energy expenditure. These phenomena represent an active process of regulation that is characterized by the balance between signs that stimulate hunger, called orexigenics and those that produce satiation to stop in-take, called anorexigenics, that promotes the stability in the quantity of corporal energy manifested as fat. In this feeding regulatory process there are many molecular signs that participate and regulate the in-take of behaviour food for homeostasis. There are two hypothalamic centers related with the food in-take control: the hunger centre in the lateral hypothalamus and the satiation centre in the ventromedial nucleus. In this control many impulses participate, regulated by substances called neurotransmitters, such as: neuropeptide Y, galanine, orexines for the hunger centre and nor epinephrine, serotonin, and dopamine for the satiation centre. Insulin reaches the brain through circulation and acts reducing the contribution of energy, it was the first hormonal sign that was implicated in weight control by CNS. The second identified hormone, secreted by the adiposity, was leptin. Both hormones circulate in levels proportional to the corporal fat and get to the CNS in proportion to its plasmatic concentrations. Receptors as leptin and insulin are expressed by brain neurons involved in the contribution of energy, and the administration of any of both peptides directly to the brain, reduce the in-take of food. The lack of any of these hormones produces the opposite. Leptin has a more important role than insulin in the control of the energetic homeostasis in the CNS. For example, the lack of leptin causes severe obesity with hyperfagia that persists regardless the levels of elevated insulin. In contrast, obesity isn't induced by the lack of insulin. Insulin has a critic role to promote the storage of fat and the synthesis of leptin through the fat cellule. The neuropeptide Y, produced in the arcuate nucleus of the hypothalamus has an anabolic effect. The gene of expression and secretion of this peptide in the hypothalamus increases during depletion, in the storage of corporal fat and/or when the signs of leptin/insulin are decreased in the brain. Leptin inhibits the gene of expression of the neuropeptide Y in the arcuate nucleus and the genetic "knockout" of the NPY reduces hyperfagia and obesity in mice ob/ob, indicating that the total response to the lack of leptin requires the signs of the NPY. Other substances like the Agouti protein (AGRP), the orexines (hypocretines A and B) and the concentrations of the melancortin hormone have been added to the molecule candidate list with anabolic effects. Also in the adjoining neurons of the arcuate nucleus, are originated anorexigenic peptides like alfa-MSH (a derivated of the pro-opiomelancortin, POMC) and CART (transcript protein related with cocaine and amphetamine). Both types of neurons (NPY/AGRP and POMC/CART) coexpress the leptin receptors. In those situations in which the levels of leptin or insulin are low, the NPY/AGRP neurons activate and the POMC/CART are inhibited. This suggests that the main site of adiposity signs transformation is a neuronal response in the arched nucleus. The link between the lateral hypothalamus and the elevated centers of the brain that regulate hunger and satiation is a very important aspect of the regulation system. There have been typified two types of neuropeptides linked to neurons, that appear to be exclusively of the lateral hypothalamus area: the concentrated melanin hormone (MCH) and the orexines. At the lateral zone, there have been specified two types of hypothalamic neuropeptides, the orexines A and B, also known as hypocretines 1 and 2, which are cellular bodies of the hypothalamus, especially at the lateral hypothalamus and the perifornical area, which stimulate the appetite in an independent way to other neuropeptides known. On the other hand, the orexines A and B derive (by proteolysis) of a common precursor, and are capable of activating their two respective receptors that work in conjunction with proteins G. The central administration of orexines stimulates the in-take and production of orexines' increase with fasting. These neuropeptides match with the hypocretines described by other authors, with expression in late ral hypothalamus, arched nucleus, septal nucleus and forebrain. Monoaminergic neurotransmitters. Noradrenalin Noradrenalin is synthesized in different areas of the brain such as the dorsal nucleus of the vague and the locus coeruleus.Noradrenalin shares the same place with NPY and the injection of both inside the preventricular nucleus increase the in-take of food. The repeated injection can result in weight increase; leptin can inhibit noradrenalin secretion. Dopamine Critic dependence of the in-take of food in the CNS is given by the dopamine sign, which is implicated in the voluntary lack of the food in-take. Motor alterations associated with the lack of dopamine affect also the alimentary behavior. The dopamine effect over the alimentary behavior varies depending of the studyied area. For example the routes of dopamine in the mesolimbic area contribute to the reward of the in-take of savory food. SerotoninThe 5HT2c receptor of serotonin is implicated in the decrease of the in-take of food and the weight increase, due to its effect in the impulse of the satiation centre. To maintain the homeostasis of normal energy it is necessary that the serotonin sign be intact. New alternative hypothesis. On one hand, the knowledge of regulation of the appetite-satiety neuroendocrine cycle, and on the other, the new techniques of neuromodulation through stereotaxic surgery, allow to offer an extraordinarily interesting field of research in certain patients with feeding disorders of difficult control and with an increase in the mortality risk. The alternative of controlling specific centers of hunger/satiation regulation, is still a hypothesis, though there are some data that allow us to assume that it could be feasible and we will mention them after. Current experience. Stereotaxic (Latin: stereo, three-dimensional; taxis, positioning) is a modern technique of neurosurgery that allows the localization and precise access to intra-cerebral structures, through a small orifice in the skull. If we have identified the places that regulate the intake of food or satiety, it is feasible that through this technique we can stimulate or inhibit this function and offer the patient an alternative that in theory could be feasible. Some of its possible advantages will be that we are talking about a minimum invasive surgery, generally performed using local anesthesia; patients need a minimum hospitalization stay and surgical risks are minimized. This allows us to predict in the majority of the patients a satisfactory evolution of weight decrease. The current experience of stereotaxic used in eating disorders is null; everything about it is hypothetic. However, the use of this proceeding for other accepted indications where there is previous experience, has allowed us to obtain interesting data of the evolution of these patients that shows indirectly, that the procedure has influenced in the corporal weight. We present these indirect results, which motivate us to continue considering its possible use in patients that show the approved profile according to an ethic committee properly authorized. In depression or bipolar disorder cases, the use of the stereotaxic surgery applying electrodes in the bottom pedunculo thalamic region (ITP), independently that they show an improve in their basal alteration, the patients show a weight increase, inferring a relationship of this area and the one of the hypothalamus for the appetite/satiation control, situation that hypothetically could benefit patients with anorexia nervosa or bulimia. In the cases with Parkinson Disease, the stereotaxic procedure has been made in the pre-lemniscal (RAPRL) or the subtalamic region (STN) in a unilateral or bilateral way, and although the response hasn't been uniform, the weight changes showed a decrease, making this a possible alternative to be used in some patients with morbid obesity according to the inclusion criteria. Final comments. The expectative of stereotaxic surgery in handling patients with difficult to control feeding disorders or with high risk of morbid-mortality, is shown as an hypothesis, that should consider the specific rules of good clinical practices and adjust to the rules of an approved ethics committee, for these procedures.

Functional Neurosurgery for Psychiatric Disease / 대한정신약물학회지

Despite a long and controversial history, psychosurgery has persisted as a modern treatment option for some severe, medically intractable psychiatric disorders. The empirical basis of psychosurgery is weak because of the lack of well-designed investigations. Several carefully conducted studies in which independent evaluation has been made, however, show convincingly that highly selective stereotactic operations on the brain can benefit some carefully selected, chronically ill psychiatric patients with a low rate of unwanted side effects. The goal of this article is to review the current state of psychosurgery. In this review, the definition of psychosurgery, patient selection criteria, and anatomical and physiological rationales for anterior cingulotomy, subcaudate tractotomy, anterior capsulotomy, limbic leukotomy, vagus nerve stimulation and deep brain stimulation are discussed.

Psychosurgical Treatment of Obsessive-Compulsive Disorder and Related Ethical Issues / 대한정신약물학회지

Several case reports suggest that neurosurgical operations can improve symptoms in patients with severe treatment-refractory obsessive-compulsive disorder (OCD). However, it is unclear which procedure is best and which may produce the most side-effects. We also review recent ethical issues related to the procedures. We review the literature on the efficacy and complications of frequently used neurosurgical procedures that are used to treat refractory OCD and related ethical issues. Since the vast majority of patients who underwent surgery were severely and chronically disabled, it is likely that these procedure were of assistance in alleviating some of their symptoms. It is currently impossible to determine which surgical procedure is the best for a particular patient. Since the psychosurgery is reported as effective in the area of human behavior and psychopathology, the indication for operation demand strict ethical process. Recent studies report that strict informed consent and the evaluation for competence to decide whether to get operation with free will should be taken so as to stress the autonomy of patients for the treatment. Despite a lack of controlled data and inconsistencies in the literature, it appears that when nonsurgical treatments have failed to improve OCD symptoms significantly in severely ill patients, at least partial relief can be obtained by some people with OCD by neurosurgery. Results of cumulative studies strongly support the need for continued research in this area.

Surgical Experience of Stereotactic Psychosurgery for Psychiatric Diseases

The authors report surgical experiences in patients with severe psychiatric illness refractory to all other conventional treatments. All 5 patients in this series were referred from their own psychiatrists. One patient with aggressive-conductive disorder, who was cared for in a closed ward, underwent bilateral amygdalotomy and bifrontal leucotomy. Four patients with obsessive-compulsive disorder were treated by limbic leucotomy, which is a combination of subcaudate tractotomy and anterior cingulotomy. Target points were selected according to the individual symptoms of each patients. Target construction was performed under ventriculogram or computerized tomographic guidance, using a Hitchcock stereotactic frame. All the procedures were performed under local anesthesia, except for the patient with aggressive-conductive disorder for whom the surgery had to be performed under general anesthesia because of the incooperative nature of the patient. The result of each surgery was good without serious complication. During the follow-up period, all the patients were freed from disturbing symptoms and successfully returned to their premorbid social life. Psychosurgery can be helpful in certain patients with severe, chronic, disabling, and treatment-refractory psychiatric illness.

Surgical Experience of Stereotactic Psychosurgery for Psychiatric Diseases

The authors report surgical experiences in patients with severe psychiatric illness refractory to all other conventional treatments. All 5 patients in this series were referred from their own psychiatrists. One patient with aggressive-conductive disorder, who was cared for in a closed ward, underwent bilateral amygdalotomy and bifrontal leucotomy. Four patients with obsessive-compulsive disorder were treated by limbic leucotomy, which is a combination of subcaudate tractotomy and anterior cingulotomy. Target points were selected according to the individual symptoms of each patients. Target construction was performed under ventriculogram or computerized tomographic guidance, using a Hitchcock stereotactic frame. All the procedures were performed under local anesthesia, except for the patient with aggressive-conductive disorder for whom the surgery had to be performed under general anesthesia because of the incooperative nature of the patient. The result of each surgery was good without serious complication. During the follow-up period, all the patients were freed from disturbing symptoms and successfully returned to their premorbid social life. Psychosurgery can be helpful in certain patients with severe, chronic, disabling, and treatment-refractory psychiatric illness.