[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.

Ablative stereotactic neurosurgery for irreducible neuroaggressive disorder in pediatric patients. / Neurocirugía estereotáctica ablativa para trastorno neuroagresivo irreductible en pediátricos.

INTRODUCTION AND OBJECTIVES: The irreducible neuroaggressive disorder (IND) is a well-described entity known to be associated with impulsive and aggressive behavior. 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 analyze the efficacy and safety of the different described targets for this disorder in pediatric patients. MATERIALS AND METHODS: Eight pediatric 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 Agressive 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 pediatric patients with IND treated with lesional stereotactic therapy.

Clinical features and evolution of the gelastic seizures-hypothalamic hamartoma syndrome.

Gelastic seizures, usually with onset in early infancy, are the hallmark manifestation of hypothalamic hamartoma. This seizure type is directly generated by hamartoma itself, intrinsically epileptogenic because of its anatomofunctional organization. Other types of seizures, focal or generalized, may appear during the evolution, probably resulting from mechanisms of secondary epileptogenesis. Nevertheless, the clinical expression and the severity of the syndrome, ranging from a focal drug-resistant epilepsy to a catastrophic generalized encephalopathy with severe cognitive and behavioral impairments, depends on the size and the site of attachment of the hamartoma. Early suspicion, timely diagnosis, and appropriate treatment are mandatory to reverse a potential catastrophic evolution of this condition.

Hypothalamic hamartoma: Neuropathology and epileptogenesis.

Hypothalamic hamartomas (HHs) are congenital malformations of the ventral hypothalamus resulting in treatment-resistant epilepsy and are intrinsically epileptogenic for the gelastic seizures that are the hallmark symptom of this disorder. This paper reviews the neuropathologic features of HHs associated with epilepsy, with an emphasis on characterizing neuron phenotypes and an ultimate goal of understanding the cellular model of ictogenesis occurring locally within this tissue. We also present previously unpublished findings on Golgi staining of HH. The microarchitecture of HH is relatively simple, with nodular clusters of neurons that vary in size and abundance with poorly defined boundaries. Approximately 80-90% of HH neurons have an interneuron-like phenotype with small, round soma and short, unbranched processes that lack spines. These neurons express glutamic acid decarboxylase and likely utilize γ-aminobutyric acid (GABA) as their primary neurotransmitter. They have intrinsic membrane properties that lead to spontaneous pacemaker-like firing activity. The remaining HH neurons are large cells with pleomorphic, often pyramidal, soma and dendrites that are more likely to be branched and have spines. These neurons appear to be excitatory, projection-type neurons, and have the functionally immature behavior of depolarizing and firing in response to GABA ligands. We hypothesize that the irregular neuronal clusters are the functional unit for ictogenesis. Further research to define and characterize these local networks is required to fully understand the cellular mechanisms responsible for gelastic seizures.

Emotional functioning: Long-term outcomes after pediatric epilepsy surgery.

OBJECTIVE: Children with epilepsy are at a high risk for developing symptoms of anxiety and depression. By improving seizure control, epilepsy surgery has the potential to improve patients' anxiety and depression symptoms. Few studies have assessed the long-term outcomes of anxiety and depressive symptoms after pediatric epilepsy surgery while using an appropriate control group. This study examined anxiety and depressive symptoms 4-11 years after surgery in surgical patients and in a control group of nonsurgical patients with pediatric-onset epilepsy. METHODS: Seventy-three surgical patients with a mean age of 19.87 (standard deviation [SD] 4.46, range 10.08-28.50) and 40 nonsurgical controls with a mean age of 20.31 (SD 4.01, range 12.08-27.25) completed the study measures. Patients completed the Child Depression Inventory II/Beck Depression Inventory II and State Trait Anxiety Inventory for Children/State Trait Anxiety Inventory and parents completed the Child Behavior Checklist/Adult Behavior Checklist to assess the patients' anxiety and depressive symptoms. Baseline measurements of affective symptoms (Child Behavior Checklist) were retrieved from the patients' medical records. RESULTS: Patient-reported affective functioning was obtained at the follow-up visit only. Patient-reported depressive symptoms and state and trait anxiety were similar for both groups. Based on parent reports at follow-up, patients with seizures were found to have significantly more depressive problems and anxious/depressed symptoms, and marginally more withdrawn symptoms relative to patients without seizures. SIGNIFICANCE: Seizure status was related to the presence of affective symptoms, irrespective of whether the patient had undergone surgery. In addition, parents and not patients reported the presence of anxiety and depressive symptoms, which indicates the importance of obtaining multiple informants to assess affective symptomatology.

Effect of corpus callosotomy on attention deficit and behavioral problems in pediatric patients with intractable epilepsy.

To evaluate the effect of corpus callosotomy (CC) on attention deficit and behavioral problems in pediatric patients with intractable epilepsy, we retrospectively investigated sequential patients who had undergone CC to control seizures. Between August 2005 and April 2010, a total of 15 patients aged between 3.1 and 17.9 years underwent CC at our institute. All the patients experienced either drop attacks or head nodding, which were considered to be therapeutic targets of CC. A standardized instrument, the Child Behavior Checklist (CBCL), was used to assess behavioral and emotional problems before and after surgery. On postoperative EEGs, 8 (53%) showed improvement and 7 (47%) showed no change in epileptiform discharges. The Attention Problems scale and total score on the CBCL significantly improved in patients whose postoperative EEGs showed improvement. In addition to amelioration of target seizures, CC can improve attention impairments in association with improvement in the postoperative EEG.

Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 1. Clear lens extraction and refractive lens exchange.

INTRODUCTION: A subpopulation of children with high myopia and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated using lensectomy alone (clear lens extraction), or lensectomy with simultaneous implantation of an intraocular lens (refractive lens exchange). METHODS: Clinical course and outcome data were collated prospectively in a group of 13 children (mean age 10.4 years, range 1 to 18 years) with neurobehavioral disorders exacerbated by chronic noncompliance with spectacle wear, causing profoundly low functional vision. Myopia in the 26 eyes ranged from -14.25 to -26.00 D (mean -19.1 D). Goal refraction was approximately +1 D. Correction was achieved by lensectomy alone in 10 eyes, and lensectomy with intraocular lens implantation in 16 eyes. Primary posterior capsulectomy/subtotal vitrectomy was performed during the primary procedure in 11 eyes (42%). Mean follow-up was 4.5 years (range 1.3 to 7.5 years). RESULTS: Myopia correction averaged 19.9 D. Eighty-one percent (21 eyes) were corrected to within +/-2 D of goal refraction and the remaining 19% (5 eyes) to within +/-4 D. Uncorrected acuity improved substantially (ie, an average 2 log units) in all 26 eyes, with commensurate gains in behavior and environmental visual interaction in 85% [corrected] of children (11/13) [corrected] Myopic regression averaged -0.16 D/year. Capsular regrowth and/or opacification necessitated vitrector or YAG-laser membranectomy in 13 [corrected] eyes (50%) [corrected] Focal retinal detachment (successfully repaired) occurred after eye contusion in one eye (4%) with cicatricial retinopathy of prematurity. CONCLUSIONS: Bilateral refractive lensectomy is effective for improving functional vision in neurobehaviorally impaired children who have high myopia (beyond the range of excimer laser correction: see companion publication) and difficulties wearing glasses. Posterior capsule regrowth/opacification is common, necessitating secondary membranectomy. Further study is indicated to determine the long-term safety of this procedure in similar pediatric populations.

Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 2. Laser-assisted subepithelial keratectomy (LASEK).

INTRODUCTION: A subpopulation of children with high myopia and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated bilaterally using excimer laser technology. METHODS: Clinical course and outcome data were collated prospectively in a group of 9 children (mean age, 10.2 years; range, 3-16 years) with neurobehavioral disorders exacerbated by chronic noncompliance with spectacle wear, causing profoundly low functional vision. Myopia in the 18 eyes ranged from -3.75 to -11.5 D (mean -16.6 D) and the desired refraction was approximately +1D. Correction was achieved by bilateral laser-assisted subepithelial keratectomy (ie, LASEK) performed under brief general anesthesia. Mean follow-up was 17 months (range, 6-36 months). RESULTS: Myopia correction averaged 7.9 D. Eighty-nine percent (16/18 eyes) were corrected to within +/-1 D of goal refraction. Uncorrected acuity improved postoperatively in all 18 eyes, with commensurate gains in behavior and environmental visual interaction in 88% (15/17 children). Myopic regression averaged approximately 0.8 d/year. the only complication encountered was mild (1+) corneal haze in 35% of treated eyes. DISCUSSION/CONCLUSIONS: Bilateral excimer laser surgery is effective for improving functional vision substantially in highly myopic, neurobehaviorally impaired children who have difficulties wearing glasses. Myopic regression is common. Further study is indicated to determine the long-term safety of these and alternative refractive procedures in similar pediatric populations.

Improvement of aggressive and antisocial behavior after resection of temporal lobe tumors.

Seizures associated with temporal lobe tumors may rarely manifest as episodic aggressive behavior. We describe 2 cases involving pediatric patients who presented with histories of unusually aggressive and antisocial behavior. Magnetic resonance imaging identified right mesial temporal lobe masses in both patients. After craniotomy for tumor removal, both patients were seizure-free and had marked reductions in their aggressive behavior. Tumors in the temporal lobe may be associated with behavioral problems, including aggression and rage attacks, which can be alleviated with surgical intervention. It is important to distinguish this subgroup of pediatric patients from those with alternative diagnoses such as attention-deficit/hyperactivity disorder or oppositional defiant disorder.

Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence.

Hemispherectomy has been performed in the treatment of epilepsy in association with hemiplegia for over 50 years. However, the optimal timing of surgery with respect to age at presentation and the influence of underlying pathology on outcome is only slowly emerging. This study reports on the clinical course and outcomes of 33 children who underwent hemispherectomy at Great Ormond Street Hospital, London, between 1991 and 1997. Age at surgery was 0.33-17 years (median 4.25) with 1-8 years follow-up (median 3.4). The underlying pathology was developmental in 16 (10 hemimegalencephaly, two polymicrogyria, two focal cortical dysplasia, one diffuse cortical dysplasia and one microdysgenesis), acquired in 11 (six middle cerebral artery infarct, three post encephalitis/trauma, and one each of hemiconvulsion-hemiplegia epilepsy and perinatal ischaemic insult) and progressive in six children (four Rasmussen encephalitis, two Sturge-Weber syndrome). At follow-up, 52% were seizure free, 9% experienced rare seizures, 30% showed >75% reduction in seizures and 9% showed <75% seizure reduction or no improvement. Seizure freedom was highest in those with acquired pathology (82%), followed by those with progressive pathology (50%) and those with developmental pathology (31%). However, seizure freedom, rare seizures or >75% reduction in seizures occurred in 100% of those with progressive pathology, 91% of those with acquired and 88% of those with developmental pathology, indicating a worthwhile seizure outcome in all groups. Hemiplegia remained unchanged following surgery in 22 out of 33 children, improved in five and was worse in six. No significant cognitive deterioration or loss of language occurred, and four children showed significant cognitive improvement. Behavioural improvement was reported in 92% of those who had behaviour problems pre-operatively.

Multiple subpial transection in Landau-Kleffner syndrome.

We have considered multiple subpial transection (MST) as a treatment option for Landau-Kleffner syndrome (LKS) for the past 6 years. The effect of this technique on language and cognitive ability, behaviour, seizures, and EEG abnormalities is analysed here. Five children (4 males, 1 female; aged 5.5 to 10 years) underwent MST with sufficiently detailed pre- and postoperative data for analysis. Behaviour and seizure frequency improved dramatically after surgery in all children. Improvement in language also occurred in all children, although none improved to an age-appropriate level. All five had electrical status epilepticus in sleep (ESES) before surgery, which was eliminated by the procedure. One child has had an extension of his MST due to the recurrence of ESES and accompanying clinical deterioration with good effect. An attempt is made to set the effect of MST against the natural history of the condition. MST is an important treatment modality in LKS, although the timing of this intervention and its effect on final language outcome remains to be defined.

Cerebrospinal fluid shunts in the management of behavioural problems in Sanfilippo syndrome (MPS III).

UNLABELLED: Severe behavioural disturbance is a very common feature of Sanfilippo syndrome (mucopolysaccharidosis III, MPSIII), and one of the more difficult aspects of the disease to treat. We describe a series of six patients with MPS III who had cerebrospinal shunts inserted in an attempt to ameliorate behaviour that had proved refractory to conventional treatment. Symptoms improved significantly in all six but removal of the shunt was necessitated in one patient due to shunt blockage and infection. CONCLUSION: Our experience suggests cerebrospinal fluid shunting should be formally evaluated as an adjunct to conventional forms of treatment of extreme behavioural disturbance in MPS III.

The role of hemispherectomy in the treatment of holohemispheric hemimegaloencephaly.

The role of hemispherectomy in treating holohemispheric hemimegaloencephaly, a unilateral brain malformation, is still not well defined. The authors describe the cases of five infants presenting with intractable seizures, progressive neurological deficits, and severe developmental delay. Electroencephalography (EEG) showed generalized polyspikes from the megaloencephalic hemisphere and progressive slowing on the opposite side in all children; contralateral seizure spikes occurred in three children. Three of the five children underwent hemispherectomy for intractable seizures before 2 years of age, after which the seizures subsided completely in two children and improved remarkably in the third. Preoperative Wada testing proved useful in evaluating pharmacologically the effect of hemispherectomy on contralateral polyspikes. Postoperative EEG revealed the absence of polyspikes in the operated hemisphere and decreased slowing on the contralateral side. Psychomotor development in the surgically treated infants exceeded that of the children not undergoing hemispherectomy. Of the two children treated medically, one died at 4 years of age in status epilepticus and the other (now 5 years old) has frequent seizures and severe developmental delay. Based on these results, hemispherectomy appears to be a useful procedure for controlling seizures and improving psychomotor development in children with hemimegaloencephaly involving the entire hemisphere. Surgery in infancy can prevent or minimize seizure foci and encephalopathic changes that may develop in the contralateral hemisphere. Staging the procedure and exercising meticulous hemostasis make surgery relatively safe in infants who otherwise may have significant blood loss associated with increased blood flow to the megaloencephalic hemisphere.

Intractable seizures, compulsions, and coprolalia: a pediatric case study.

A 10-year-old girl with intractable complex partial seizures developed aphasia, coprolalia, and repetitive motor behaviors involving touching, sexual touching, and aggressive acts. Her symptoms subsided following surgical resection of a left anterior temporal lobe ganglioglioma and control of seizures. Possible neurobehavioral implications of the reversibility of this patient's symptoms are discussed.

Stereotactic operation in behaviour disorders. Amygdalotomy and hypothalamotomy.

After a survey of the anatomical and physiological basis of operative treatment of behaviour disorders by stereotactic lesions in the amygdala and the posterior medial hypothalamus the author describes his own experiences with 603 operations for control of conservatively untreatable aggressiveness. In 481 cases bilateral amygdalotomies and in 122 mostly secondary posteromedian hypothalamotomies have been performed. Initially excellent or moderate improvement was achieved in 76%. After a follow-up of more than three years this figure only slightly decreased to 70%. The group of patients who did not positively respond (30%) needs further study to discover the reasons for failure.

Why hemispherectomy?

A series of ten cases of infantile hemiplegia with behaviour disorders and with of without fits treated by unilateral stereotactic amygdalotomy is described. Out of the eight cases with fits good releif was seen in six and amelioration of the seizures in two. The behavioural disorders were well controlled in all the patients. When this procedure is compared with hemispherectomy, it is felt that operation of stereotactic amygdalotomy can be done as the procedure of first choice. Some hypotheses have been advanced to explain the modus operandi of the operation.