On temporal scale-free non-periodic stimulation and its mechanisms as an infinite improbability drive of the brain's functional connectogram.

Rationalized development of electrical stimulation (ES) therapy is of paramount importance. Not only it will foster new techniques and technologies with increased levels of safety, efficacy, and efficiency, but it will also facilitate the translation from basic research to clinical practice. For such endeavor, design of new technologies must dialogue with state-of-the-art neuroscientific knowledge. By its turn, neuroscience is transitioning-a movement started a couple of decades earlier-into adopting a new conceptual framework for brain architecture, in which time and thus temporal patterns plays a central role in the neuronal representation of sampled data from the world. This article discusses how neuroscience has evolved to understand the importance of brain rhythms in the overall functional architecture of the nervous system and, consequently, that neuromodulation research should embrace this new conceptual framework. Based on such support, we revisit the literature on standard (fixed-frequency pulsatile stimuli) and mostly non-standard patterns of ES to put forward our own rationale on how temporally complex stimulation schemes may impact neuromodulation strategies. We then proceed to present a low frequency, on average (thus low energy), scale-free temporally randomized ES pattern for the treatment of experimental epilepsy, devised by our group and termed NPS (Non-periodic Stimulation). The approach has been shown to have robust anticonvulsant effects in different animal models of acute and chronic seizures (displaying dysfunctional hyperexcitable tissue), while also preserving neural function. In our understanding, accumulated mechanistic evidence suggests such a beneficial mechanism of action may be due to the natural-like characteristic of a scale-free temporal pattern that may robustly compete with aberrant epileptiform activity for the recruitment of neural circuits. Delivering temporally patterned or random stimuli within specific phases of the underlying oscillations (i.e., those involved in the communication within and across brain regions) could both potentiate and disrupt the formation of neuronal assemblies with random probability. The usage of infinite improbability drive here is obviously a reference to the "The Hitchhiker's Guide to the Galaxy" comedy science fiction classic, written by Douglas Adams. The parallel is that dynamically driving brain functional connectogram, through neuromodulation, in a manner that would not favor any specific neuronal assembly and/or circuit, could re-stabilize a system that is transitioning to fall under the control of a single attractor. We conclude by discussing future avenues of investigation and their potentially disruptive impact on neurotechnology, with a particular interest in NPS implications in neural plasticity, motor rehabilitation, and its potential for clinical translation.

Epilepsy as a dynamical system, a most needed paradigm shift in epileptology.

The idea of the epileptic brain being highly excitable and facilitated to synchronic activity has guided pharmacological treatment since the early twentieth century. Although tackling epilepsy's seizure-prone feature, by tonically modifying overall circuit excitability and/or connectivity, the last 50 years of drug development has not seen a substantial improvement in seizure suppression of refractory epilepsies. This review presents a new conceptual framework for epilepsy in which the temporal dynamics of the disease plays a more critical role in both its understanding and therapeutic strategies. The repetitive epileptiform pattern (characteristic during ictal activity) and other well-defined electrographic signatures (i.e., present during the interictal period) are discussed in terms of the sequential activation of the circuit motifs. Lessons learned from the physiological activation of neural circuitry are used to further corroborate the argument and explore the transition from proper function to a state of instability. Furthermore, the review explores how interfering in the temporally dependent abnormal connectivity between circuits may work as a therapeutic approach. We also review the use of probing stimulation to access network connectivity and evaluate its power to determine transitional states of the dynamical system as it moves towards regions of instability, especially when conventional electrographic monitoring is proven inefficient. Unorthodox cases, with little or no scalp electrographic correlate, in which ictogenic circuitry and/or seizure spread is temporally restricted to neurovegetative, cognitive, and motivational areas are shown as possible explanations for sudden death in epilepsy (SUDEP) and other psychiatric comorbidities. In short, this review presents a paradigm shift in the way that we address the disease and is aimed to encourage debate rather than narrow the rationale epilepsy is currently engaged in. This article is part of the Special Issue "NEWroscience 2018".

Necrotizing Otitis Externa: A Disease Barely Known to Neurosurgeons

Necrotizing otitis externa (NOE), also known as malignant otitis externa (MOE), is a severe and rare infectious disease of the external auditory canal (EAC). Without treatment, it may progress to skull base involvement. The bacteria Pseudomonas aeruginosa is the most common causative agent (90% of the cases), and affects immunocompromised subjects, particularly diabetic patients. Severe chronic otalgia, otorrhea, and cranial nerve palsy are the most common clinical presentations. Patients with NOE are frequently referred to neurosurgery because of the neurological impairment and skull base compromise. The definitive diagnosis is frequently elusive, requiring a high index of suspicion. Several laboratorial tests, imaging modalities, and the histologic exclusion of malignancy may be required. An early diagnosis and aggressive treatment reduce morbidity and mortality. We present four NOE cases to illustrate the spectrum of clinical presentation and complementary exams. According to the literature, more effort for early diagnosis and treatment is required, and neurosurgeons play an important role in this task.

C1-C4 Dorsal Column Stimulation for Refractory Occipital Neuralgia Treatment. Case Report

Introduction Refractory occipital neuralgia is a difficult medical condition, especially when the patient has already been submitted to occipital nerve neurectomy and radiofrequency rhizotomy. There is no case report of spinal cord stimulation in the C1- C4 cervical segments for this condition. Objective To evaluate if C1-C4 dorsal spinal cord stimulation is effective in a patient with refractory occipital neuralgia who was already submitted to neurectomy and rhizotomy. Methods After obtaining the approval from the Ethics Committee of one of our institutions, a unilateral laminectomy was performed between C3 and C4, and a neurostimulator lead was conducted until the posterior portion of the C1 arc was in full view. Then we performed an intraoperative test to evaluate the correspondence between pain location and stimulation-induced paresthesias. We could not put the subcutaneous lead for such condition because of the scar tissue of the area and the previous neurectomy. Results After one year of follow up, we noticed a dramatic improvement in pain control, as well as medication withdrawal. The score of the visual analogue scale was 9 before the surgery, and it dropped to 2 after 1 year of follow-up. Conclusion Spinal cord stimulation between the C1 and C4 cervical segments can be an option for selected cases of refractory occipital neuralgia, including those patients who have already been submitted to neurectomy or rhizotomy.

Neuralgia occipital refratária é uma condição médica difícil, especialmente em pacientes submetidos previamente a neurectomia nos nervos occipitais e rizotomia por radiofrequência. Não há na literatura relato de estimulação da medula espinhal entre os níveis C1 e C4 para essa condição. Objetivos Avaliar se a estimulação da coluna dorsal da medula nos níveis C1 a C4 é eficaz no controle da dor em paciente com neuralgia occipital refratária já submetido a neurectomia e rizotomia. Métodos Após aprovação do Conselho de Ética de uma de nossas instituições, foi realizada laminectomia unilateral de C3 e C4, com posterior introdução do conjunto de eletrodos em placa, que foi posicionado até que a porção anterior do arco de C1 estivesse sob visão direta. Posteriormente, foi realizado um teste intraoperatório para avaliar a correspondência entre a área dolorosa e a parestesia induzida pela estimulação. Não possível optar pelo uso de eletrodo subcutâneo devido ao extenso tecido cicatricial secundário às cirurgias prévias. Resultados Melhora significativa da dor ocorreu ao longo de um ano de acompanhamento, com redução progressiva da dose da medicação. O valor da escala visual analógica no pré-operatório era 9, e após 1 ano de acompanhamento, reduziu para 2. Conclusão Estimulação da coluna dorsal da medula espinhal entre os seguimentos C1 e C4 pode, em casos selecionados, ser uma opção terapêutica na neuralgia occipital refratária, incluindo pacientes que já foram submetidos a neurectomia e rizotomia.

Endoscopic Sural Nerve Removal in Obstetric Brachial Plexopathy Using Basic Endoscopy Instruments: Technical Note

Introduction The sural nerve (SN) is commonly used for grafting following resection of a neuroma-in-continuity in neonatal brachial plexus lesions (NBPL). The main drawbacks of the current open techniques are large scars and contractures in the late postoperative stage, which may, in severe cases, cause equinovarus contractures. Objective To describe the feasibility and the technical aspects of endoscopic SN harvesting with the use of basic endoscopy instruments and small incisions. Methods Prospective observational study of NBPL subjected to endoscopic nerve harvesting between February of 2012 and February of 2014 in a consecutive series. Patients were operated at the Felício Rocho Hospital (Hospital Felício Rocho) and the Clinical Hospital, Federal University of Minas Gerais (Hospital das Clínicas UFMG), Belo Horizonte/MG, in Brazil. The study outcomes assessed were: scar size, presence or absence of contractures in the calf, bleeding volume (measured by the number of gauzes used) and number of incisions. Only patients with a follow-up longer than 6 months were included. Results Seven patients were selected and twelve endoscopic nerves were endoscopically harvested. The average surgery time was 45 minutes. Nine SNs were harvested through two incisions, and three nerves through three incisions. The estimated bleeding was less than 5ml and there were no complications or contractures during the follow-up period of 6 months to 4 years. Conclusion Sural nerve harvesting in children with NBPL is feasible and it offers the advantage of needing only two or three small incisions using basic endoscopy instruments.

Introdução O nervo sural é a melhor opção para enxertia nas reconstruções microcirúrgicas da plexopatia braquial obstétrica. O método clássico aberto com incisão longitudinal desde o tornozelo até a fossa poplítea ou em incisões em degraus possuem as desvantagens de cicatrizes amplas e contraturas em equinovarus (pé torto). Atualmente, o emprego de endoscópios específicos para a retirada de enxertia de nervos e vasos mostra resultados satisfatórios em relação ao encurtamento do tempo cirúrgico e à redução no tamanho das incisões, mas tem como inconveniente o alto custo de aquisição e manutenção. Objetivo Discutir a viabilidade e descrever nota técnica da retirada do nervo sural utilizando instrumental básico de endoscopia e pequenas incisões. Métodos Estudo observacional prospectivo em pacientes com plexopatia braquial obstétrica submetidos a retirada do nervo sural por endoscopia no período de fevereiro de 2012 a fevereiro de 2014 no Hospital Felicio Rocho e no Hospital das Clinicas UFMG, Belo Horizonte/MG, Brasil. Resultados Sete pacientes foram selecionados e foram retirados doze nervos surais por endoscopia. O tempo médio da cirurgia foi de 45 minutos. Nove nervos surais foram retirados por duas incisões, e três nervos foram retirados por três incisões. O sangramento foi inferior a 5ml e não houve complicações no pós-operatório imediato e tardio em acompanhamento entre 6 meses e 4 anos. Não foram observadas contraturas no período observacional. Conclusão O nervo sural pode ser retirado utilizando duas ou três pequenas incisões por meio de instrumental endoscópico básico em crianças com plexopatia braquial obstétrica.

Punção liquórica cervical lateral em C1-C2: um procedimento de grande utilidade em pacientes vítimas de trauma ­ Relato de série de casos / Lateral Cervical Spinal Puncture at c1-c2: A Useful Procedure in Trauma Patients - Report of a Series of Cases

A punção liquórica cervical lateral no espaço C1-C2 foi descrita a partir de uma modificação da técnica utilizada para cordotomia percutânea anterolateral. Neste artigo, é descrita uma série de 14 pacientes vítimas de trauma, submetidos à punção liquórica cervical lateral. Todos os procedimentos foram realizados para pesquisa de meningite bacteriana. Presença de escara lombar e occipital, fratura instável de coluna vertebral, tração ou imobilização ortopédica e ventilação mecânica controlada foram os principais motivos para se optar pela punção liquórica cervical lateral. A taxa de sucesso foi de 93%. Não foram evidenciadas maiores complicações per ou pósprocedimento. A punção liquórica cervical lateral se mostrou um método eficaz para obtenção de líquor em pacientes vítimas de trauma, pois não requer mudança de decúbito ou angulação da cabeceira, o que evita complicações em pacientes entubados e com fratura instável de coluna vertebral. Estudos prévios sugerem que a punção liquórica cervical lateral deve ser o método de escolha em pacientes vítimas de trauma com restrição de mobilização.

The lateral cervical spinal puncture at C1-C2 was described from a modification of the technique used for percutaneous anterolateral cordotomy. In this article, we describe a series of 14 patients of multiple trauma victims who underwent lateral cervical spinalpuncture. All procedures were performed as a screening for bacterial meningitis. Low back and occipital ulcer, unstable spinal fractures, orthopedic traction or immobilization and ventilated patients were the main reasons to opt for the lateral cervical spinal puncture over standard techniques of liquor puncture. The success rate was 93%. There was not major complication per or post procedural. The lateral cervical spinal puncture proved to be an effective method of obtaining liquor in victims of trauma because it does not requires changing position or rotation of the head, preventing complications in patients with orotraqueal tube and unstable spinal fractures. Previous studies suggest that the lateral cervical spinal puncture should be the method of choice in trauma patients with restriction of mobilization.