Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Comparison of direct MRI guided versus atlas-based targeting for subthalamic nucleus and globus pallidus deep brain stimulation.

PURPOSE: The subthalamic nucleus (STN) and globus pallidus internus (GPi) targets for deep brain stimulation (DBS) can be defined by atlas coordinates or direct visualisation of the target on MRI. The aim of this study was to evaluate geometric differences between atlas-based targeting and MRI-guided direct targeting. METHODS: One-hundred-nine Parkinson's disease or dystonia patients records who underwent DBS surgery between 2005 and 2016 were prospectively reviewed. MRI-guided direct targeting coordinates was used to implant 205 STN and 64 GPi electrodes and compared with atlas-based coordinates. RESULTS: The directly targeted coordinates (mean, SD, range) for STN were x: [9.9 ± 1.1 (7.1 - 13.2)], y: [-0.8 ± 1.1 (-4.2 - 2)] and z: [-4.7 ± 0.53 (-5.9 - -3.2)]. The mean value for the STN was 2.1 mm more medial (p < 0.0001), 1.2 mm more anterior (p < 0.0001) and 0.7 mm more ventral (p < 0.0001) than the atlas target. The targeted coordinates for GPi were x: [22.3 ± 2.0 (17.8 - 26.1)], y: [-0.2 ± 2.2 (-4.5 - 3.4)], z: [-4.3 ± 0.8 (-6.2 - -2.3)]. The mean value for the GPi was 2.2 mm (p < 0.001) more posterior and 0.3 mm (p < 0.01) more ventral than the atlas-based coordinates. CONCLUSION: MRI-guided targeting may be more accurate than atlas-based targeting due to individual variations in anatomy.

Chronic itch induced by thalamic deep brain stimulation: a case for a central itch centre.

BACKGROUND: Central itch syndrome has been previously described in conditions such as stroke. The neurophysiology of central itch syndrome has been investigated in non-human primates but remains incompletely understood. METHODS: We report an observational study of a rare case of severe central itch following thalamic deep brain stimulation and postulate the location of the central itch centre in humans. RESULTS: The patient was a 47-year-old female, with congenital spinal malformations, multiple previous corrective spinal surgeries and a 30-year history of refractory neuropathic pain in her back and inferior limbs. Following multidisciplinary pain assessment and recommendation, she was referred for spinal cord stimulation, but the procedure failed technically due to scarring related to her multiple previous spinal surgeries. She was therefore referred to our centre and underwent bilateral deep brain stimulation (DBS) of the ventral posterolateral nucleus of the thalamus for management of her chronic pain. Four weeks after switching on the stimulation, the patient reported significant improvement in her pain but developed a full body progressive itch which was then complicated with a rash. Common causes of skin eczema were ruled out by multiple formal dermatological evaluation. A trial of unilateral "off stimulation" was performed showing improvement of the itchy rash. Standard and normalized brain atlases were used to localize the active stimulating contact within the thalamus at a location we postulate as the central itch centre. CONCLUSIONS: Precise stereotactic imaging points to the lateral portion of the ventral posterolateral and posteroinferior nuclei of the thalamus as critical in the neurophysiology of itch in humans.

O-Arm Stereotactic Imaging in Deep Brain Stimulation Surgery Workflow: A Utility and Cost-Effectiveness Analysis.

INTRODUCTION: Deep brain stimulation (DBS) surgery is an established treatment for movement disorders. Advances in neuroimaging techniques have resulted in improved targeting accuracy that may improve clinical outcomes. This study aimed to evaluate the safety and feasibility of using the Medtronic O-arm device for the acquisition of intraoperative stereotactic imaging, targeting, and localization of DBS electrodes compared with standard stereotactic MRI or computed tomography (CT). METHODS: Patients were recruited prospectively into the study. Routine frame-based stereotactic DBS surgery was performed. Intraoperative imaging was used to facilitate and verify the accurate placement of the intracranial electrodes. The acquisition of coordinates and verification of the position of the electrodes using the O-arm were evaluated and compared with conventional stereotactic MRI or CT. Additionally, a systematic review of the literature on the use of intraoperative imaging in DBS surgery was performed. RESULTS: Eighty patients were included. The indications for DBS surgery were dystonia, Parkinson's disease, essential tremor, and epilepsy. The globus pallidus internus was the most commonly targeted region (43.7%), followed by the subthalamic nucleus (35%). Stereotactic O-arm imaging reduced the overall surgical time by 68 min, reduced the length of time of acquisition of stereotactic images by 77%, reduced patient exposure to ionizing radiation by 24.2%, significantly reduced operating room (OR) costs per procedure by 31%, and increased the OR and neuroradiology suite availability. CONCLUSIONS: The use of the O-arm in DBS surgery workflow significantly reduced the duration of image acquisition, the exposure to ionizing radiation, and costs when compared with standard stereotactic MRI or CT, without reducing accuracy.

Adult giant cerebellar cavernous malformations: case report and review of the literature.

Cavernous malformations are vascular malformations that can occur anywhere in the central nervous system (CNS). Giant cavernous malformations (GCM) are extremely rare in adults, especially in the posterior fossa. Herein, we described a 48-year-old male who presented with vertigo and postural instability for three months. Neuroimaging revealed a 131.15 cm3 heterogeneous midline upper cerebellar lesion. After a suboccipital craniotomy, a gross total resection (GTR) was accomplished. Histopathologic examination revealed a huge cavernous malformation. Only 27 GCM adult cases were reported in the English-based literature. Only two patients had cerebellar lesions and, to the best of our knowledge, this is the first case of cerebellar vermis GCM. We concluded that cerebellar GCM (CGCM) in adults are exceedingly rare and indolent lesions. These lesions can radiologically and clinically mimic neoplastic lesions that have to be considered in the differential diagnosis. GTR is the mainstay of treatment and, whenever possible, should be attempted.

Deep Brain Stimulation of the Internal Pallidum in Lesch-Nyhan Syndrome: Clinical Outcomes and Connectivity Analysis.

BACKGROUND: Lesch-Nyhan syndrome (LNS) is a rare genetic disorder characterized by a deficiency of hypoxanthine-guanine phosphoribosyltransferase enzyme. It manifests during infancy with compulsive self-mutilation behavior associated with disabling generalized dystonia and dyskinesia. Clinical management of these patients poses an enormous challenge for medical teams and carers. OBJECTIVES: We report our experience with bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) in the management of this complex disorder. MATERIALS AND METHODS: Preoperative and postoperative functional assessment data prospectively collected by a multidisciplinary pediatric complex motor disorders team, including imaging, neuropsychology, and neurophysiology evaluations were analyzed with regards to motor and behavioral control, goal achievement, and patient and caregivers' expectations. RESULTS: Four male patients (mean age 13 years) underwent DBS implantation between 2011 and 2018. Three patients received double bilateral DBS electrodes within the posteroventral GPi and the anteromedial GPi, whereas one patient had bilateral electrodes placed in the posteroventral GPi only. Median follow-up was 47.5 months (range 22-98 months). Functional improvement was observed in all patients and discussed in relation to previous reports. Analysis of structural connectivity revealed significant correlation between the involvement of specific cortical regions and clinical outcome. CONCLUSION: Combined bilateral stimulation of the anteromedial and posteroventral GPi may be considered as an option for managing refractory dystonia and self-harm behavior in LNS patients. A multidisciplinary team-based approach is essential for patient selection and management, to support children and families, to achieve functional improvement and alleviate the overall disease burden for patients and caregivers.

Subthalamic Nucleus Deep Brain Stimulation in Post-Infarct Dystonia.

Dystonia secondary to cerebral infarcts presents months to years after the initial insult, is usually unilateral and causes significant morbidity. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is established as the most frequent target in the management of the dystonic symptoms. We report our experience with subthalamic nucleus (STN) DBS in 3 patients with post-infarct dystonia, in whom GPi DBS was not confidently possible due to the presence of striatal infarcts. Two patients had unilateral STN DBS implantation, whereas the third patient had bilateral STN DBS implantation for bilateral dystonic symptoms. Prospectively collected preoperative and postoperative functional assessment data including imaging, medication and neuropsychology evaluations were analyzed with regard to symptom improvement. Median follow-up period was 38.3 months (range 26-43 months). All patients had clinically valuable improvements in dystonic symptoms and pain control despite variable improvements in the Burke-Fahn-Marsden dystonia rating scores. In our series, we have demonstrated that STN DBS could be an alternative in the management of post-infarct dystonia in patients with abnormal striatal anatomy which precludes GPi DBS. A multidisciplinary team-based approach is essential for patient selection and management.

Fixed-Life or Rechargeable Battery for Deep Brain Stimulation: A Prospective Long-Term Study of Patient's Preferences.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for movement disorders. We have previously shown that in our practice, the majority of adult patients prefer fixed-life implantable pulse generators (IPGs), although rechargeable batteries are increasingly used. The aim of this study was to evaluate patients' long-term satisfaction with their choice of battery and factors that influence their decision. METHODS: Thirty patients with DBS were given a questionnaire to assess long-term satisfaction and experience with the type of battery they had chosen. RESULTS: Twenty-six patients completed the survey. The mean age was 67.7 ± 7.3 years, and mean follow-up was 18.0 ± 7.2 months. The indications for DBS were Parkinson's disease (76.9%), tremor (11.5%) and dystonia (11.5%). Eleven patients (42.5%) had chosen the rechargeable battery. All patients were still happy with their choices and would not change the type of battery if they had the chance to do so. However, in patients who chose the fixed-life battery, concern about the size of battery rose from 6.7% pre-operatively to 60% on long-term post-operative follow-up. In patients who chose the rechargeable battery, concern about the need to recharge the battery did not change, remaining low postoperatively. Interestingly, even though the main reason cited for choosing the fixed-life battery was the convenience and concern about forgetting to recharge the battery, patients who had chosen a rechargeable IPG did not experience this problem. CONCLUSION: Patients and caregivers should be involved in the choice of battery, as each type of IPG has its own advantages and disadvantages. Long-term evaluation of patient's experience and satisfaction with battery of choice revealed that size of the IPG, need for further replacement surgeries and need for recharging remain matters of major concern. Although preoperatively often underestimated, the size of the battery seems to be an important factor in long-term satisfaction.

Pediatric neurosurgery during the COVID-19 pandemic: update and recommendations from the Brazilian Society of Pediatric Neurosurgery.

OBJECTIVES: Coronavirus disease (COVID-19) is a potentially severe respiratory illness that has threatened humanity globally. The pediatric neurosurgery practice differs from that of adults in that it treats children in various stages of physical and psychological development and contemplates diseases that do not exist in other areas. The aim of this study was to identify the level of knowledge and readiness of the healthcare providers, as well as to evaluate new preventive practices that have been introduced, psychological concerns, and the impact of the COVID-19 pandemic on pediatric neurosurgical units in Brazil. METHODS: Pediatric neurosurgeons were given an online questionnaire developed by the Brazilian Society of Pediatric Neurosurgery to evaluate the impact of the COVID-19 pandemic on their clinical practice. RESULTS: Of a cohort of 110 active members of the Brazilian Society of Pediatric Neurosurgery, 76 completed the survey (69%). Ninety-six percent were aware of the correct use of and indication for the types of personal protective equipment in clinical and surgical practices, but only 73.7% of them had unrestricted access to this equipment. Ninety-eight percent of participants agreed or strongly agreed that the pandemic had affected their pediatric neurosurgical practice. The COVID-19 pandemic interfered with outpatient care in 88% of the centers, it affected neurosurgical activity in 90.7%, and it led to the cancellation of elective neurosurgical procedures in 57.3%. Concerning the impact of COVID-19 on surgical activity, 9.2% of the centers had less than 25% of the clinical practice affected, 46.1% had 26%-50% of their activity reduced, 35.5% had a 51%-75% reduction, and 9.2% had more than 75% of their surgical work cancelled or postponed. Sixty-three percent affirmed that patients had been tested for COVID-19 before surgery. Regarding the impact of the COVID-19 pandemic on the mental health of those interviewed, 3.9% reported fear and anxiety with panic episodes, 7.9% had worsening of previous anxiety symptoms, 60.5% reported occasional fear, 10.5% had sadness and some depressive symptoms, and 2.6% reported depressive symptoms. CONCLUSIONS: The COVID-19 pandemic has posed unprecedented challenges to healthcare services worldwide, including neurosurgical units. Medical workers, pediatric neurosurgeons included, should be aware of safety measures and follow the recommendations of local healthcare organizations, preventing and controlling the disease. Attention should be given to the psychological burden of exposure to SARS-CoV-2 in healthcare workers, which carries a high risk of anxiety and depression.

Decompressive craniectomy for severe traumatic brain injury in children: analysis of long-term neuropsychological impairment and review of the literature.

OBJECTIVE: The effectiveness of decompressive craniectomy (DC) in the context of neurocritical care in adult patients has been recently under debate. The aim of our study was to evaluate the impact of decompressive craniectomy in severe traumatic brain injury (TBI) in children, focusing on short and long-term neurological and neuropsychological outcomes. METHODS: Retrospective review of the medical records of children admitted at a level I trauma center, between January 2012 and December 2015, submitted to DC due to severe TBI. Additionally, an extensive review of literature on this subject was carried out. RESULTS: Sixteen patients underwent DC for TBI at our institution during the evaluated period. 62.5% were males and the mean age was 12 years. Road traffic accident (RTA) was the main mechanism of trauma (62.5%). Average Glasgow Coma Scale (GCS) at admission was 5.2, whereas 75% of the patients presented with pathological pupillary reaction. Initial computed tomography (CT) showed skull fractures in 62.5% and acute subdural hemorrhage (ASH) in 56.3% of the patients. The mean intracranial pressure (ICP) was 27.2 mmHg prior to surgery, and the mean time window between admission and DC was 36.3 h. Unilateral DC was performed in 68.8% of the cases. The average Glasgow Outcome Scale (GOS) at 6-month follow-up was 3.7, whereas 70% of the survivors presented good recovery (GOS 4-5). Abnormal pupillary reaction at hospital admission increased 3-fold the risk of long-term neuropsychological disturbances. Follow-up evaluation revealed cognitive abnormality in 55.6% of the patients. The overall mortality at 6-month follow-up was 37.5%. CONCLUSION: The present study indicates towards a potential benefit of DC in children with severe TBI; nevertheless, our data demonstrated a high incidence of neuropsychological impairment in the long-term follow-up. Psychological and cognitive assessment should be computed in prognosis evaluation in future prospective studies.

The role of coagulopathy on clinical outcome following traumatic brain injury in children: analysis of 66 consecutive cases in a single center institution.

INTRODUCTION: Head injury is a significant economic, social, and medical problem in developing countries and remains one of the leading causes of pediatric morbidity and mortality. The association of traumatic brain injury and coagulopathy in children is linked with an increase in mortality and poor functional outcomes. However, its impact on long-term outcome has not been discussed in the literature so far. OBJECTIVES: The aim of this paper was to investigate the effect of coagulopathy diagnosed by routine laboratory tests on neurological outcome following traumatic brain injury in children. METHODS: A retrospective review was carried out using medical records of children with a traumatic brain injury admitted at a level I trauma center, between January 2013 and December 2016, submitted to any neurosurgical procedures. Statistical analysis was performed accordingly to identify factors predicting unfavorable or favorable outcomes at 1- and 6-month follow-ups. Data regarding age, gender, trauma mechanism, Glasgow Coma Scale at admission and at discharge, highest and lowest stable intracranial pressure, serum glucose and coagulation assessment, radiological findings, and length of stay were analyzed. RESULTS: We identified 66 children with surgical head trauma. Mean age was 10.9 years (ranges from 3 months to 17 years), with male predominance (77.3%). Common mechanisms were road traffic accidents (66.7%), falls (19.7%), and blunt trauma (10.6%). Brain edema was detected in 68.2% of the patients, surgical fractures or intracranial bleeding in 75.8%. ICP monitoring was performed in 24.2% of the patients, and of these, 18.7% underwent consecutive decompressive craniectomy. Mean length of in-patient treatment was 16.3 ± 28.2 days. At 1- and 6-month follow-ups, favorable outcome was detected in 71.2 and 78.7% of the patients, respectively. The mortality rate was 12.1%. Routine coagulation assessments such as prothrombin time, fibrinogen levels, and thrombocyte count upon admission were potential prognostic variables identified. CONCLUSIONS: The present study concluded that a trauma-related coagulopathy is an important predictor of unfavorable neurological outcome following TBI in pediatric patients. Initial GCS score, age, and neuroradiological findings, such as severe brain edema and different types of intracranial bleeding, correlated with GOS in the first 6 months following TBI. Sustained intracranial hypertension also predicted unfavorable outcome and death in this series.

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

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

Chronic deep brain stimulation of the medial forebrain bundle reverses depressive-like behavior in a hemiparkinsonian rodent model.

Preclinical and clinical evidence suggests that depression might be associated with a dysfunction in the reward/motivation circuitry. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has been shown in a recent clinical trial to provide a prompt and consistent improvement of depressive symptoms in treatment-resistant patients. In order to better understand the underlying mechanisms of neuromodulation in the context of depression, the effects of chronic bilateral MFB-DBS were assessed in a combined rodent model of depression and Parkinson's disease. Female Sprague-Dawley rats received unilateral 6-OHDA injection in the right MFB and were divided into three groups: CMS-STIM, CMS-noSTIM and control group. The CMS groups were submitted to chronic unpredictable mild stress (CMS) protocol for 6 weeks. MFB-DBS was applied only to the CMS-STIM group for 1 week. All groups were repeatedly probed on a series of behavioral tasks following each intervention, and to a postmortem histological analysis. CMS led to an increase in immobility in the forced swim test, to a decrease in sucrose solution consumption in the sucrose preference test, as well as to an increased production of ultrasonic vocalizations in the 22 kHz range, indicating increased negative affect. MFB-DBS reversed the anhedonic-like and despair-like behaviors. The results suggest that unilateral dopamine depletion did not preclude MFB-DBS in reversing depressive-like and anhedonic-like behavior in the rodent. Further understanding of the importance of hemispheric dominance in neuropsychiatric disorders is essential in order to optimize stimulation as a therapeutic strategy in these diseases.

The impact of surgical resection of giant supratentorial brain tumor in pediatric patients: safety and neurological outcome evaluated in 23 consecutive cases.

OBJECTIVE: This study aims to evaluate the impact of gross total resection of giant supratentorial brain tumors (GSBT) on survival and neurological outcome in a consecutive single-center pediatric series. METHODS: Clinical data of 23 patients under 18 years of age operated with GSBT (≥5 cm in diameter) were reviewed to determine epidemiological aspects, clinical presentation, associated factors, histopathological features, and outcome. Volumetric measurements were performed on magnetic resonance imaging or computed tomography scans obtained at the time of the initial surgical procedure. RESULTS: The group included 23 patients (mean age 4.5 years). Signs and symptoms of raised intracranial pressure were present in 19 patients (82.6%). The most frequent tumor location was the parietal lobe in 19 patients (82.6%), and the mean tumor volume was 208 cm(3). Gross total or radical resection was achieved in all patients. Histopathological analysis revealed malignant brain tumors in 18 cases (78.2%). The most common neoplasm was choroid plexus carcinoma in seven (30.4 %). Mean intraoperative blood transfusion volume was 51.2 ml/kg. Chemotherapy and/or radiotherapy were performed as adjuvant treatment in 16 patients (69.5%). Mean length of follow-up was 36.7 months. Tumor malignancy grade significantly correlated with recurrence of the disease (P = 0.03) and death (P = 0.01), as opposed to tumor location, size, and extension to the ventricles. CONCLUSIONS: Our clinical experience suggests that tumor mass reduction by en bloc surgery seems to be an effective approach in pediatric patients with GSBT, relieving symptoms related to raised intracranial pressure and providing a better response to adjuvant treatment.

Deep brain stimulation of the globus pallidus internus or ventralis intermedius nucleus of thalamus for Holmes tremor.

Holmes tremor (HT) is a difficult-to-treat, very disabling symptomatic condition which characteristically appears weeks to years after a brain lesion. It features a unique combination of rest, action, and postural tremors. Pharmacotherapy is mostly not effective. Chronic deep brain stimulation (DBS) of ventralis intermedius nucleus (Vim) of thalamus has been described as being the best surgical approach in singular case series; various authors observe, however, cases with partial responses only; therefore, alternatives are still needed. We report ten patients with HT unresponsive to best medical therapy who underwent DBS in our center from March 2002 to June 2012. Based in our previous experience dealing with cases of unsatisfactory Vim intraoperative tremor control and in order to optimize surgical results, presurgical target planning included two Nuclei: Vim and posteroventral Globus pallidus internus (GPi) (Espinoza et al. 2010; Espinoza et al. Stereotact Funct Neurosurg 90(suppl 1):1-202, p 61, 2012). Definitive chosen target was decided after single-cell microelectrode recording, intraoperative test stimulation, thresholds for stimulation-induced adverse effects and best clinical response compared to baseline status. Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) was used to evaluate outcome. The electrode was implanted in the nucleus with the best tremor suppression achievement; on the other hand, GPi DBS was initially decided if one of the following conditions was present: (a) If Vim nucleus anatomy was grossly altered; (b) when intraoperative tremor control was unsatisfactory despite Vim high-intensity stimulation; or (c) if unaffordable side effects or even tremor worsening occurred during intraoperative macrostimulation. Seven patients received definitive Gpi DBS implantation, while three patients received Vim DBS. In all observed cases, we observed an improvement on the TRS. In two cases where Vim thalamic anatomy was altered by the pathological insult GPI was planned from the beginning, and same was true in two additional cases where the Gpi nucleus showed major alterations allowing only Vim planning. Over all cases, the average improvement in tremor was of 2.55 points on the TRS or a 64 % increase in measured results; with a minimum of 1 point (25 %) improvement in one case and a maximum of 4 points (100 % improvement) also in one case. All the results were sustained at 2 years follow-up. One case with predominant resting component, implanted in the GPi, achieved the maximum possible tremor reduction (from 4 to 0 points, meaning 100 % tremor reduction); in the nine resting cases, the average reduction was of 3 points (or 75 %). DBS demonstrated in this case series adequate tremor control in 10 patients unresponsive to medical therapy. Presurgical planning of two targets allowed choosing best optimal response. Gpi stimulation could be considered as an alternative target for cases in which thalamic anatomy is considerably altered or Vim intraoperative stimulation does not produce satisfactory results.

Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats.

Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinson's disease (PD) cases refractory to medication. Cell transplantation is a tissue-restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival. Our experiment investigates the impact of a partial subthalamotomy prior to ventral mesencephalic (VM) embryonic cell transplantation on dopaminergic cell survival and functional outcome. Unilateral dopamine depletion was carried out in rats, via medial forebrain bundle (MFB) injection of 6-hydroxydopamine, and half of the animals went on to receive unilateral excitotoxic lesions of the STN/Zone Incerta (ZI) causing partial lesion of these structures on the same side as the MFB lesion. All MFB-lesioned animals, with or without the STN/ZI lesion, received striatal ipsilateral embryonic VM cell grafts. The data suggest that the STN/ZI lesion could boost the dopamine cell survival in the grafts by 2.6-fold compared with the control grafted-only group. Moreover, performance on the drug-induced rotation and the spontaneous behavior tests were ameliorated on the STN/ZI-lesioned group to a significantly greater extent than the grafted-only group. These data suggest that the STN/ZI partial lesion optimized the striatal environment, promoting an improvement in cell survival. Further studies are needed to see whether the synergy between STN modulation via deep brain stimulation and cell therapy might have clinical applications in the management of PD.

Vagus nerve stimulation in pediatric patients: Is it really worthwhile?

Vagus nerve stimulation (VNS) seems to be effective in the management of selected cases of pharmacoresistant epilepsy in children. This was a case-control prospective study of children with refractory epilepsy submitted to vagal nerve stimulator implantation and a control group with epilepsy treated with antiepileptic drugs. Patients under 18years of age who underwent clinical or surgical treatment because of pharmacoresistant epilepsy from January 2009 to January 2012 were followed and compared with an age-matched control group at final evaluation. Statistically significant differences were observed considering age at epilepsy onset (VNS group - 1.33±1.45years; controls - 3.23±3.11; p=0.0001), abnormal findings in neurological examination (p=0.01), history of previous ineffective epilepsy surgery (p=0.03), and baseline seizure frequency (p=0.0001). At long-term follow-up, 55.4% of the patients in the VNS group had at least 50% reduction of seizure frequency, with 11.1% of the patients presenting 95% reduction on seizure frequency. Also, a decrease in traumas and hospitalization due to seizures and a subjective improvement in mood and alertness were observed. The control group did not show a significant modification in seizure frequency during the study. In this series, VNS patients evolved with a statistically significant reduction of the number of seizures, a decreased morbidity of the seizures, and the number of days in inpatient care. In accordance with the current literature, VNS has been proven to be an effective alternative in the treatment of pediatric patients with drug-resistant epilepsy.

Epidermoid cyst mimicking an intrinsic brainstem tumor.

OBJECTIVE: To describe an atypical clinical and radiological presentation of a brainstem epidermoid cyst in a child and to provide a review of the medical literature on brainstem epidermoid cysts in children. MATERIAL AND METHOD: Review of medical records and operative notes of an unusual case of a patient with a brainstem epidermoid cyst. MEDLINE literature search using the terms brainstem, epidermoid cyst and children. RESULTS: Gross total resection of the cyst was achieved. The patient had an uneventful recovery. CONCLUSION: Epidermoid cysts are rare tumors of the brain and children. The management of these tumors can be quite challenging. A good clinical and neuroradiological evaluation pre-operatively is fundamental for a successful surgical treatment. Surgical resection should be as radical as possible without putting the patient's neurological status into risk.

Pediatric meningiomas: a single-center experience with 15 consecutive cases and review of the literature.

OBJECTIVE: The goal of this study was to determine the epidemiology, clinical presentation, associated factors, pathological features, and treatment outcome of pediatric meningiomas in a single-center institution. METHODS: Clinical data of 15 patients under 18 years of age operated on for meningiomas from January 1994 to December 2010 were reviewed. RESULTS: The study group included nine males and six females (mean age of 13 years at surgery). The most common symptoms at presentation were headaches in 6 out of 15 (40 %), raised intracranial pressure in 3 out of 15 (20 %), and seizures in 3 out of 15 (20 %). Sole operated tumors were found in 12 out of 15 (80 %), whose location is as follows: parasagittal in 4 out of 12 (33.3 %), 2 in the convexity (16.6 %), 2 at the skull base (16.6 %), and 4 in other sites (33.3 %). Six children presented with radiation-induced (RT) meningiomas and five had evidence of neurofibromatosis type 2 (NF2). Three patients had multiple meningiomas (all of them had NF2). Simpson's grade I excision was achieved in 12 out of 15 (80 %). On histopathology, 11 out of 15 (73.3 %) were grade I and 4 out of 15 (26.6 %) were grade II (all of them atypical). Five tumors (33.3 %) recurred, four of which had RT or NF2. During the mean follow-up period of 5 years, 12 out of 15 (80 %) had a good outcome (GOS=5). CONCLUSIONS: Childhood meningiomas are uncommon lesions with a slight male predominance. Absence of large series with long follow-up precludes any definite conclusions on the clinical course and outcome of these tumors. Associated factors (such as RT and NF2), location, and extent of excision appear to be more important than histopathological grade in predicting outcome.