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Sara CB Casagrande,1 Rubens G Cury,1 Eduardo JL Alho,2 Erich Talamoni Fonoff2 1Department of Neurology, School of Medicine, Movement Disorders Center, University of São Paulo, São Paulo, Brazil; 2Department of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil Abstract: Tourette’s syndrome (TS) is a neurodevelopmental disorder that comprises vocal and motor tics associated with a high frequency of psychiatric comorbidities, which has an important impact on quality of life. The onset is mainly in childhood and the symptoms can either fade away or require pharmacological therapies associated with cognitive-behavior therapies. In rare cases, patients experience severe and disabling symptoms refractory to conventional treatments. In these cases, deep brain stimulation (DBS) can be considered as an interesting and effective option for symptomatic control. DBS has been studied in numerous trials as a therapy for movement disorders, and currently positive data supports that DBS is partially effective in reducing the motor and non-motor symptoms of TS. The average response, mostly from case series and prospective cohorts and only a few controlled studies, is around 40% improvement on tic severity scales. The ventromedial thalamus has been the preferred target, but more recently the globus pallidus internus has also gained some notoriety. The mechanism by which DBS is effective on tics and other symptoms in TS is not yet understood. As refractory TS is not common, even reference centers have difficulties in performing large controlled trials. However, studies that reproduce the current results in larger and multicenter randomized controlled trials to improve our knowledge so as to support the best target and stimulation settings are still lacking. This article will discuss the selection of the candidates, DBS targets and mechanisms on TS, and clinical evidence to date reviewing current literature about the use of DBS in the treatment of TS. Keywords: deep brain stimulation, DBS, Tourette’s syndrome, tics &nbsp

The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.

Wellingson Silva Paiva,1 Erich Talamoni Fonoff,1 Marco Antonio Marcolin,2 Edson Bor-Seng-Shu,1 Eberval Gadelha Figueiredo,1 Manoel Jacobsen Teixeira11Division of Neurosurgery, Department of Neurology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil; 2Transcranial Magnetic Stimulation Laboratory, Institute of Psychiatry, School of Medicine, University of Sao Paulo, Sao Paulo, BrazilAbstract: Since the introduction of microscopic techniques, radical surgery for cavernous angiomas has become a recommended treatment option. However, the treatment of motor area cavernous angioma represents a great challenge for the surgical team. Here, we describe an approach guided by frameless neuronavigation and preoperative functional mapping with transcranial magnetic stimulation (TMS), for surgical planning. We used TMS to map the motor cortex and its relationship with the angioma. We achieved complete resection of the lesions in the surgeries, while avoiding areas of motor response identified during the preoperative mapping. We verified the complete control of seizures (Engel class 1A) in the patients with previous refractory epilepsy. Postsurgery, one patient was seizure-free without medication, and two patients required only one medication for seizure control. Thus, navigated TMS appears to be a useful tool, in preoperative planning for cavernous angiomas of the motor area.Keywords: neurosurgical procedures, brain mapping, neuronavigation

Francisco Nêuton de Oliveira Magalhães, Sandra Correia Soares, Jaqueline Melo Torres, Arthur Ungaretti, Mariana Fillipi Cacciacarro, Manoel Jacobsen Teixeira, Erich Talamoni FonoffPain Center and Division of Functional Neurosurgery, Department of Neurology, School of Medicine, University of São Paulo, São Paulo, BrazilIntroduction: In the last two decades, ozone has emerged as a treatment for low back pain, applied by means of minimally invasive techniques. Objective: The aim of this study is to assess the effect and safety of ozone therapy applied in the epidural space for chronic pain related to failed back surgery syndrome.Methods: The investigators studied 13 sequential patients of both sexes, between 18 and 70 years old, with persistent chronic pain (more than six months) in the lumbar region and in the lower limbs related to failed back surgery syndrome (FBSS). Pain was classified as neuropathic and non-neuropathic regarding the topography (lumbar and lower limb), based on the DN4 questionnaire. The patients received the ozone gas in the lumbar epidural space via spinal-sacral endoscopy. Clinical evaluation was performed before, immediately after (24 hours), and 1, 3, and 6 months after intervention with visual analog scale and Oswestry Disability Index (ODI).Results: Overall, the patients had 43.7% reduction of lumbar pain, 60.9% reduction in leg pain in six months followed by 44.0% of improvement in ODI. The reduction of pain and in the disability index was markedly greater in patients with non-neuropathic predominant pain, 95.2%, 80.6%, and 75.3% improvement in lumbar, leg pain, and ODI respectively, while neuropathic predominant pain patients experienced only 12.5%, 42.4%, and 20.9% improvement, also respectively. No neurological or infectious complications were observed acutely or during the follow-up. The present data suggests that epidural ozone might be a therapeutic option for persistent low back pain, especially in non-neuropathic predominant pain patients, but double-blind controlled studies are still required to prove its efficacy.Keywords: pain, failed back surgery syndrome, neuropathic pain, epiduroscopy, spinal endoscopy, ozone, minimally invasive surgery

Manoel Jacobsen Teixeira, Eloy Rusafa Neto, José Cláudio Marinho da Nóbrega, Jairo Silva dos Ângelos, Miguel San Martin, Bernardo Assumpção de Monaco, Erich Talamoni FonoffDepartment of Neurology, Division of Functional Neurosurgery of the Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Optimal treatment of oncologic pain is a challenge to all professionals who deal with cancer and its complications. The management of upper abdominal pain is usually difficult and it is often refractory to conservative therapies. In this context, celiac plexus neurolysis (CPN) appears to be an important and indispensable tool because it alleviates pain, gives comfort to patients and is a safe procedure. In this study, the importance of CPN is reviewed by a retrospective study of 74 patients with pain due to upper abdominal cancer. Almost all cases evaluated (94.6%) had an excellent result after CPN and the majority of side effects were transitory.Keywords: pain, celiac plexus, alcohol neurolysis, cancer

Matheus Schmidt Soares, Wellingson Silva Paiva, Eda Z Guertzenstein, Robson Luis Amorim, Luca Silveira Bernardo, Jose Francisco Pereira, Erich Talamoni Fonoff, Manoel Jacobsen Teixeira Division of Neurosurgery, Hospital das Clínicas, University of Sao Paulo Medical School, Sao Paulo, Brazil Abstract: Following the early studies of Moniz and Lima, psychosurgery had considerable scientific credibility until the advent of modern antipsychotics in the mid 1950s. Thereafter, psychosurgery was almost abandoned in large medical centers as a common treatment for schizophrenia, although is still used for some affective and anxiety disorders. We reviewed relevant papers cited in the Medline/Index Medicus, Cochrane, and Scielo databases from 1930 to 2012. In our review of the literature, we show from recent studies that there are still many patients with schizophrenia who have serious deficits even after being treated with current noninvasive therapies. The value of psychosurgery remains controversial. There are no data available to support the use of stereotactic procedures for schizophrenia. Well designed controlled trials are needed to establish the effectiveness of psychosurgery in patients with schizophrenia. Keywords: psychosurgery, schizophrenia, treatment, stereotactic techniques

Eduardo Santamaria Carvalhal Ribas, Wellingson Silva Paiva, Natali Cordeiro Pinto, Lin Tchia Yeng, Massako Okada, Erich Talamoni Fonoff, Maria Cristina Chavantes, Manoel Jacobsen TeixeiraPain Center, Department of Neurology, Hospital das Clínicas School of Medicine, University of São Paulo, BrazilAbstract: Debilitating stump pain following amputation surgery is a major problem when it affects the patient's quality of life, often making the patient totally dependent on others for their day-to-day care. Attempts have been made to treat those patients through pharmacological, psychological, and physical therapies, but in many cases these fail to relieve the pain. This article focuses on three patients with chronic, intense, and debilitating stump pain who were previously treated with pain medications, but with little success. These patients underwent nine sessions of low-intensity laser therapy (LILT) to the stump – this is a new treatment that has been used to treat other pain disorders. All patients reported a decrease in the intensity of their pain and increased ability to perform daily living activities during a 4-month follow-up.Keywords: pain, laser therapy, amputation stumps

Wellingson S Paiva1, Erich T Fonoff1, Marco A Marcolin2, Hector N Cabrera1, Manoel J Teixeira11Division of Functional Neurosurgery, Hospital das Clinicas, 2TMS Laboratory of the Psychiatry Institute, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Transcranial magnetic stimulation (TMS) is a promising method for both investigation and therapeutic treatment of psychiatric and neurologic disorders and, more recently, for brain mapping. This study describes the application of navigated TMS for motor cortex mapping in patients with a brain tumor located close to the precentral gyrus.Materials and methods: In this prospective study, six patients with low-grade gliomas in or near the precentral gyrus underwent TMS, and their motor responses were correlated to locations in the cortex around the lesion, generating a functional map overlaid on three-dimensional magnetic resonance imaging (MRI) scans of the brain. To determine the accuracy of this new method, we compared TMS mapping with the gold standard mapping with direct cortical electrical stimulation in surgery. The same navigation system and TMS-generated map were used during the surgical resection procedure.Results: The motor cortex could be clearly mapped using both methods. The locations corresponding to the hand and forearm, found during intraoperative mapping, showed a close spatial relationship to the homotopic areas identified by TMS mapping. The mean distance between TMS and direct cortical electrical stimulation (DES) was 4.16 ± 1.02 mm (range: 2.56–5.27 mm).Conclusion: Preoperative mapping of the motor cortex with navigated TMS prior to brain tumor resection is a useful presurgical planning tool with good accuracy.Keywords: transcranial magnetic stimulation, cortical mapping, brain tumor, motor cortex

Bernardo Assumpção de Monaco, Erich Talamoni Fonoff, Manoel Jacobsen TeixeiraDivision of Functional Neurosurgery, Department of Neurology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, BrazilAbstract: The treatment of uncomplicated osteoma consists of an en bloc resection, or curettage, of the tumor, followed by cranioplasty. Here, we present a case report of a patient treated for a parietal osteoma, followed by a calcium phosphate cranioplasty, with early resorption after 3 months, which was presented by a sinking flap above the resection area. This case suggests that synthetic cranioplasty should be preferred, even in small skull-gap areas.Keywords: cranioplasty, bone cement, osteoma, calcium phosphate, resorption