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Priscila Aparecida Rodrigues,1 Ana Luiza Zaninotto,1,2 Iuri Santana Neville,1 Cintya Yukie Hayashi,1 André R Brunoni,3 Manoel Jacobsen Teixeira,1 Wellingson Silva Paiva1 1Department of Neurology, University of São Paulo, São Paulo, Brazil; 2Laboratory of Neuromodulation, Harvard Medical School, Boston, MA, USA; 3Institute of Psychiatry, University of São Paulo, São Paulo, BrazilCorrespondence: Priscila Aparecida RodriguesCaring - Clinic of Psychology and Neuropsychology, Avenue Vereador Narciso Yague, Guimarães, Number 1145 – Sala 1610, Mogi das Cruzes, São Paulo 08780-500, BrazilTel +55 1 199 654 2972Email pri.ar@outlook.comAbstract: Anxiety is currently one of the main mood changes and can impair the quality of life of the individual when associated with other neurological or psychiatric disorders. Neuromodulation has been highlighted as a form of treatment of several pathologies, including those involving anxiety symptoms. Among the neuromodulatory options with the potential to improve mood changes, we highlight repetitive transcranial magnetic stimulation (rTMS). rTMS is a viable therapeutical option for neuropsychiatric dysfunctions of high prevalence and is important for the understanding of pathological and neuropsychological adaptation processes. Even with this potential, and high relevance of intervention, we observe the scarcity of literature that covers this subject. The objective of this study was to carry out a survey of the current literature, using scientific databases for the last five years. We found 32 studies reporting the effects of rTMS on anxiety, 7 on anxiety disorders and 25 on anxiety symptoms as comorbidities of neurological or psychiatric disorders. This survey suggests the need for further studies using TMS for anxiety in order to seek strategies that minimize these anxiety effects on the quality of life of the victims of this disorder.Keywords: transcranial magnetic stimulation, anxiety disorders, review, treatment

João Gustavo Rocha Peixoto dos Santos, Wellingson Silva Paiva, Manoel Jacobsen Teixeira Department of Neurological Surgery, University of São Paulo School of Medicine, São Paulo, Brazil Abstract: The cost of traumatic brain injury (TBI) for public health policies is undeniable today. Even patients who suffer from mild TBI may persist with cognitive symptoms weeks after the accident. Most of them show no lesion in computed tomography or conventional magnetic resonance imaging, but microstructural white matter abnormalities (diffuse axonal lesion) can be found in diffusion tensor imaging. Different brain networks work together to form an important part of the cognition process, and they can be affected by TBI. The default mode network (DMN) plays an important central role in normal brain activities, presenting greater relative deactivation during more cognitively demanding tasks. After deactivation, it allows a distinct network to activate. This network (the central executive network) acts mainly during tasks involving executive functions. The salience network is another network necessary for normal executive function, and its activation leads to deactivation of the DMN. The use of red or near-infrared (NIR) light to stimulate or regenerate tissue is known as photobiomodulation. It was discovered that NIR (wavelength 800–900nm) and red (wavelength 600nm) light-emitting diodes (LEDs) are able to penetrate through scalp and skull and have the potential to improve the subnormal, cellular activity of compromised brain tissue. Based on this, different experimental and clinical studies were done to test LED therapy for TBI, and promising results were found. It leads us to consider developing different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. Keywords: traumatic brain injuries, diffuse axonal injury, low-level light therapy, neurologic manifestations, post-concussion syndrome, quality of life

Davi Fontoura Solla,1 Tatiana Saito Paiva,2 Marcia André,2 Wellingson Silva Paiva1,31Department of Neurology, University of Sao Paulo Medical School, 2Department of Surgery, Prosthesis, and Maxillofacial Traumatology, University of Sao Paulo Dentistry School, 3Neurology Center, Samaritano Hospital, Sao Paulo, BrazilIt was enlightening to read this comprehensive review of dental nanomaterials toxicity to the central nervous systems (CNSs) by Feng et al1 published in the International Journal of Nanomedicine. There are many potential applications of nanomaterials indentistry.2 Composite resins have been widely used in restorations of dental caries;3 however, it is estimated that approximately 50% of prepared restorations need to be remade, the secondary caries is one of the most frequent causes of failure,4 and the use of nanomaterials could decrease the incidence of these complications. Thus, the application of nanomaterials can bring numerous benefits in dentistry, especially in caries prevention; however, there is an important question about the safety of these materials for the nervous system. In the study by Feng et al1 a vast array of nanomaterials types and their major applications were outlined. View original article by Feng and colleagues.

Shasha Li,1,2 Ana Luiza Zaninotto,2,3 Iuri Santana Neville,4 Wellingson Silva Paiva,4 Danuza Nunn,2 Felipe Fregni21Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Spaulding Neuromodulation Center, Harvard Medical School, Boston, MA, USA; 3Division of Psychology, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil; 4Division of Neurosurgery, University of São Paulo Medical School, São Paulo, São Paulo, BrazilAbstract: Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery.Keywords: traumatic brain injury, brain stimulation, neuroplasticity

Wellingson Silva Paiva,1 Angelica Duarte Correia,2 Suely Kazue Marie2 1Division of Neurological Surgery, 2Laboratory of Medical Investigation 15, Department of Neurology, University of São Paulo Medical School, Sao Paulo, BrazilWe read with great interest the recent study by Lozano et al1 published in the Neuropsychiatric Disease and Treatment. The recovery after traumatic brain injury (TBI) is related to severity of the initial injury (primary injury) and the presence of secondary injury.2 Evidences suggest that inflammation, oxidative stress, excitotoxicity, apoptosis, and neuroendocrine responses play an important role in the development of secondary brain injury.3 Therefore, an important part in the management of patients with TBI is trying to minimize the occurrence of deleterious secondary lesions. Lozano et al’s1 paper focused on the role of neuroinflammation in brain injury.Although some studies have described experimental drugs which may eventually have neuroprotective effects in patients with TBI,2–4 there is currently no approved pharmacological treatment for neuroinflammatory effects of the acute phase of the injury. The dissociation between experimental data with positive results and consecutive clinical trials with negative results leads to a dilemma for the treatment of patients with TBI. And, we agree with Lozano et al1 that further clarification of the neuroinflammatory mechanisms could be the basis for addressing the gap between bench and clinical results to provide better treatment and reduce death and sequelae of TBI.View original paper by Lozano and colleagues.

Wellingson Silva Paiva, Almir Ferreira de Andrade, Eberval Gadelha Figueiredo, Robson Luis Amorim, Marcelo Prudente, Manoel Jacobsen Teixeira Division of Neurosurgery, University of São Paulo Medical School, São Paulo, Brazil Background: Pneumocephalus (PNC) is defined as a pathological collection of gas within the cranial cavity. The authors studied the effects of hyperbaric oxygenation (HBO2) therapy on a group of patients with PNC, comparing them with a control group to determine the relative impact on pneumocephalus volume, clinical symptoms, and duration of hospitalization.Methods: Twenty-four patients with PNC treated at our hospital were consecutively studied. These patients were divided into a treated group (n=13) and a control group (n=11). Thirteen patients (treated group) were treated with HBO2 therapy sessions in a monoplace hyperbaric chamber at 2.5 atmospheres with 100% oxygen concentration. The control group was treated with normobaric oxygenation.Results: Clinical improvement was seen in all patients. In the treated group, a decrease of the gas bubble was observed on the computerized tomography scan after each session of HBO2. The treated group also experienced a lower rate of meningitis compared with the control group. The length of hospital stay was significantly higher in the control group compared with the treated group.Conclusions: HBO2 therapy in selective cases may lead to clinical and radiological improvement in patients with PNC.Keywords: cerebrospinal fluid leakage, head injury, meningitis&nbsp

Ana Luiza Zaninotto,1 Vinícius Monteiro de Paula Guirado,2 Beatriz Baldivia,1 Monica Domiano Núñes,1 Robson Luis Oliveira Amorim,2 Manoel Jacobsen Teixeira,2 Mara Cristina Souza de Lucia,1 Almir Ferreira de Andrade,2 Wellingson Silva Paiva2 1Divisionof Psychology, Hospital das Clínicas, 2Divisionof Neurosurgery, University of São Paulo Medical School, São Paulo, Brazil Background: Diffuse axonal injury (DAI), a common cause of neurological sequelae in patients with traumatic brain injury (TBI), is considered one of the most prevalent forms of primary neuronal injury in patients with severe TBI. Cognitive deficits induced by DAI can persist over time, especially following moderate or severe injuries. The aim of the present study was to compare verbal fluency (VF) performance at6and12months after the trauma in a same group of patients with DAI. Methods: Eighteen patients with moderate to severe DAI and17healthy volunteers were enrolled. All DAI participants had sustained a TBI at least6months prior to the start of the study, were between18and50years of age, and had at least4years of education. The VF test was administered within an extensive neuropsychological test battery. We evaluated the same patients at6months (DAI1group) and12months (DAI2group) and compared the results of neuropsychological tests with a control group of healthy volunteers who were matched to patients for sex, age, and educational level. Results: In comparison to controls, the DAI1group produced significantly fewer words. The DAI2group produced significantly more semantic words than DAI1(P

Fernanda Coelho,1 Arthur Maynart Oliveira,2 Wellingson Silva Paiva,2 Fabio Rios Freire,1 Vanessa Tome Calado,1 Robson Luis Amorim,2 Iuri Santana Neville,2 Almir Ferreira de Andrade,2 Edson Bor-Seng-Shu,3 Renato Anghinah,1 Manoel Jacobsen Teixeira21Neurorehabilitation Group, Division of Neurology, 2Division of Neurosurgery, 3Neurosonology and Cerebral Hemodynamics Group, University of São Paulo Medical School, São Paulo, BrazilAbstract: Decompressive craniectomy is an established procedure to lower intracranial pressure and can save patients' lives. However, this procedure is associated with delayed cognitive decline and cerebral hemodynamics complications. Studies show the benefits of cranioplasty beyond cosmetic aspects, including brain protection, and functional and cerebrovascular aspects, but a detailed description of the concrete changes following this procedure are lacking. In this paper, the authors report a patient with trephine syndrome who underwent cranioplasty; comprehensive cognitive and cerebral hemodynamic evaluations were performed prior to and following the cranioplasty. The discussion was based on a critical literature review.Keywords: cranioplasty, decompressive craniotomy, perfusion CT, traumatic brain injury, cognition, neuropsychological test

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

Rita de Cassia Almeida Vieira,1 Daniel Vieira de Oliveira,2 Manoel Jacobsen Teixeira,2 Wellingson da Silva Paiva2 1Nursing School, 2Division of Neurological Surgery, University of Sao Paulo, Sao Paulo, BrazilWe read with great interest the paper by Ślusarz et al1 published in the Patient Preference and Adherence. The functional recovery after traumatic brain injury (TBI) is related to the severity of the brain lesion and the time after TBI. The consequences of brain damage remain beyond the acute phase, extending and modifying for a long period after the traumatic event.2 Knowing the functional recovery after TBI is relevant to evaluating the results of new techniques and treatments to minimize the severity of the disability. As a result, the pathophysiology of disability after TBI and the mechanisms involved in functional recovery are the subject of investigations, which provide the foundation to direct rehabilitation programs and guide the development of individualized therapy after TBI.3 Ślusarz et al’s1 article focused on the role of establishing the relationships between measurements by the Glasgow Coma Scale (GCS) and the scales used for the assessment of functional capacity of TBI patients.Vieworiginal paper byŚlusarz et al.

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

Fernando Roberto de Vasconcelos, Almir Ferreira de Andrade, Manoel Jacobsen Teixeira, Wellingson Silva Paiva Division of Neurological Surgery, Department of Neurology, University of São Paulo Medical School, São Paulo, BrazilWe read with great interest the recent study by Sun et al1 published in Neuropsychiatric Disease and Treatment. Intracranial hypertension (ICH) remains the most common cause of death in patients with traumatic brain injury (TBI).1 After the trauma, secondary injuries arise due to perfusion and molecular changes that begin after the moment of the trauma resulting from the interaction of intracerebral and extracerebral factors, which add to the neuronal injury. Hypotension, hypoglycemia, hypercapnia, respiratory hypoxia, anemic hypoxia, and electrolyte disturbances are the main factors associated with secondary injury, which can lead to ICH and cerebral hypoxia, thereby worsening the morbidity and death rates associated with brain injury.1,2 In this paper, the authors have discussed the multimodality intracranial monitoring carried out in 62 severe TBI patients, with evidence of hypothermia as a therapeutic strategy to adequately control intracranial pressure (ICP).View the original paper by Sun and colleagues.

Ana Luiza Zaninotto,1 Tatiana Saito Paiva,2 Marcia André,2 Beatriz Silva Mattos,2 Wellingson Silva Paiva3 1Division of Psychology, Clinics Hospital at University of São Paulo Medical School, 2Department of Surgery, Prosthesis, and Maxillofacial Trauma, University of Sao Paulo Dentistry School, 3Division of Neurological Surgery, Department of Neurology, University of São Paulo Medical School, São Paulo, BrazilRecently, we read publications relating to helping students to improve their scientific thinking and writing;1,2 in which Sørensen wrote a brilliant paper entitled “I-determinants for successful PhD or postdoctoral outcome”.3 There is a new world in clinical and experimental research with many challenges for training new researchers. There is notable intensification of the International Scientific Cooperation, requiring more systematic programs for PhD students and research fellow training. In this paper, the author describes his extensive experience relating on how to identify the characteristics of PhD students and postdoctoral fellows that can successfully perform the training program and became an independent researcher.View original paper by Sørensen.

Wellingson Silva Paiva, Douglas Alexandre França Bezerra, Robson Luis Oliveira Amorim, Eberval Gadelha Figueiredo, Wagner Malago Tavares, Almir Ferreira De Andrade, Manoel Jacobsen TeixeiraIntensive Care Unit, Division of Neurosurgery, Hospital Das Clinicas, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Sodium disorders are the most common and most poorly understood electrolyte disorders in neurological patients. The aim of this study was to determine the incidence of sodium disorders and its association with different traumatic brain injuries. This prospective study was conducted in 80 patients diagnosed with moderate and severe traumatic brain injuries. All patients underwent cerebral computed tomography. Incidence of sodium disorders, presence of injuries in the first computed tomography after traumatic brain injury, and level of consciousness were analyzed. Patients that presented other potential causes of sodium disorders and systemic trauma were excluded from the study. The incidence of sodium disturbances was 45%: 20 patients presented hypernatremia and 16 hyponatremia. Refers to all patients with sodium disturbances 53% were detected in the first sample. We recorded at least one measurement

Wellingson Silva Paiva,1 Luiz Eugênio Mello21Division of Neurosurgery, School of Medicine, University of São Paulo, 2Department of Physiology, Federal University of São Paulo, São Paulo, BrazilWe have read with great interest the recent paper by Szaflarski et al1 published in Neuropsychiatric Disease and Treatment. Patients suffering from traumatic brain injury (TBI) have three times greater risk than the general population to have epilepsy. This makes the TBI one of the most important causes of secondary epilepsy.2 In the paper by Szaflarski et al1 the authors highlighted the epidemiological relevance of this topic and describe the therapeutic options in detail.View original paper by Szaflarski and colleagues.

Thiago Mazzoli Moraes,1 Almir Ferreira de Andrade,2 Wellingson Silva Paiva2,3 1Division of Psychology, 2Division of Neurosurgery, University of São Paulo Medical School, São Paulo, SP, Brazil; 3Neurology Center, Samaritano Hospital, São Paulo, SP, BrazilWe read with great interest the recent study by Botella et al1published in the journal Neuropsychiatric Disease and Treatment. Virtual reality (VR) technology has allowed for the neuropsychological rehabilitation in patients with many neurological diseases including stroke and traumatic brain injury.2,3Read the original paper byBotella et al&nbsp