Estimulação elétrica do nervo vago na terapia adjuvante ao tratamento farmacológico em crianças e adultos com epilepsia focal ou generalizada refratária a pelo menos dois esquemas com medicamentos anticonvulsivantes para epilepsia / Electrical stimulation of the vagus nerve in adjuvant therapy to pharmacological treatment in children and adults with focal or generalized epilepsy refractory to at least two regimens with anticonvulsant drugs for epilepsy

CONTEXTO: A epilepsia é uma desordem crônica neurológica prevalente, caracterizada por sinais e sintomas característicos (crises convulsivas) associados a descargas elétricas cerebrais anormais. O tratamento da epilepsia geralmente inclui o uso contínuo em longo prazo de medicamentos com efeito anticonvulsivante. Atualmente, os tratamentos disponíveis no SUS são aqueles preconizados pelo Protocolo Clínico e Diretrizes Terapêuticas (PCDT) de epilepsia. TECNOLOGIA: Estimulação elétrica do nervo vago com dispositivo implantável. PERGUNTA: A estimulação do nervo vago (ENV) com dispositivo implantável como terapia adjuvante ao tratamento farmacológico, em crianças e adultos com epilepsia focal ou generalizada refratária, a pelo menos dois esquemas com medicamentos anticonvulsivantes é eficaz e seguro, quando comparado à terapia padrão (conforme preconizado no PCDT de epilepsia)? EVIDÊNCIAS CIENTÍFICAS: A ENV é eficaz na redução de crises convulsivas em adultos e adolescentes com mais de 12 anos portadores de epilepsia parcial refratária, levando a redução de pelo menos 50% das crises em cerca de 30% dos casos. Ausência total de crises é obtida em menos de 10% dos casos. O benefício absoluto (diferença entre o grupo tratado com alta estimulação e o grupo com baixa estimulação) é de cerca de 15%, para redução de 50% de crises ou mais. Para os desfechos selecionados de eficácia e segurança, a qualidade geral da evidência é moderada em adultos e baixa em crianças. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Dependendo da taxa de difusão da tecnologia a estimativa de impacto orçamentário varia entre aproximadamente R$ 65 milhões e R$ 262 milhões no primeiro ano e entre R$ 371 milhões e R$ 1,5 bilhão ao longo dos próximos 5 anos. RECOMENDAÇÃO PRELIMINAR: De acordo com o exposto, a CONITEC em sua 60ª reunião, nos dias 04 e 05 de outubro de 2017, recomendou preliminarmente a não incorporação no SUS da estimulação do nervo vago com dispositivo implantável para tratamento de pacientes com epilepsia focal ou generalizada refratária a pelo menos dois esquemas de medicamentos anticonvulsivantes e não candidatos ao tratamento cirúrgico. A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: Foram recebidas 12 contribuições técnico-científicas e 40 contribuições de experiência ou opinião, sendo 100% discordantes ou parcialmente discordantes da recomendação preliminar da CONITEC em ambos os formulários. Os argumentos foram convergentes e se basearam principalmente na necessidade de tratamento para pacientes refratários a dois ou mais medicamentos, ou inelegíveis à cirurgia ressectiva. A maioria das contribuições técnico-científicas foram realizadas por profissionais de saúde. As contribuições de experiência ou opinião foram realizadas principalmente por profissionais de saúde, familiares, amigos ou cuidadores e por pacientes que relataram experiência com a ENV e descreveram a redução na frequência das crises epilépticas como efeito positivo. As contribuições relataram também experiência com os FAEs utilizados para o tratamento da doença, cujos eventos adversos foram apontados como efeitos negativos, apesar também terem sido apontados alguns efeitos positivos dos mesmos. A CONITEC solicitou ao grupo elaborador do PCDT de epilepsia os critérios de elegibilidade para uso de tratamento por estimulação do nervo vago em pacientes com epilepsia refratária, que foram apresentados na 64ª reunião em 07/03/2018. O plenário da CONITEC entendeu que houve argumentação suficiente para alterar sua recomendação inicial e recomendou a incorporação da estimulação do nervo vago para o tratamento da epilepsia refratária aos medicamentos e com contraindicação à cirurgia, em centros habilitados em neurocirurgia, devendo o procedimento incluir-se na relação CNRAC. Foi assinado o Registro de Deliberação nº 337/2018. RECOMENDAÇÃO FINAL: A estimulação elétrica do nervo vago também esteve em avaliação devido à solicitação por incorporação pela empresa fabricante do dispositivo gerador de pulso, para terapia adjuvante em pacientes pediátricos com epilepsia resistente a medicamentos, sem indicação para cirurgia ressectiva de epilepsia. A deliberação final da solicitação feita pela empresa ocorreu na 66ª reunião ordinária em 10 de maio de 2018, onde os membros da CONITEC deliberaram por unanimidade recomendar a criação de um procedimento para estimulação elétrica do nervo vago para terapia adjuvante em pacientes com epilepsia resistente a medicamentos, sem indicação para cirurgia ressectiva de epilepsia, em Centros e Unidades Habilitados conforme Protocolo de Uso. DECISÃO: Incorporar o procedimento para estimulação elétrica do nervo vago para terapia adjuvante em pacientes com epilepsia resistente a medicamentos, sem indicação para cirurgia ressectiva de epilepsia no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria nº 24 de 11 de setembro de 2018, publicada no DOU de 12/09/2018. A portaria de incorporação contemplou as duas indicações solicitadas.

Neurorehabilitation with FORAMENRehab for attention impairment in children with epilepsy.

Epilepsy is a frequent neurological disorder in children and often accompanied with attention impairment. Still, few systematically controlled rehabilitation techniques for children exist. The aim of this study was to design and measure the impact of the FORAMENRehab computer-based intervention method for attention impairment rehabilitation in children with epilepsy. We chose the FORAMENRehab program because it allows separate training for different attention components based on individual needs. Forty-eight children participated in the study. At baseline, all patients underwent neuropsychological examination of attention with the NEPSY test battery. The study group consisted of 17 8- to 12-year-old children with partial epilepsy and attention impairment who received neurorehabilitation over 5weeks (10 sessions) with FORAMENRehab Attention module accompanied by a therapist. Two control groups were included: the first control group of 12 children with partial epilepsy and attention impairment (waiting-list) participated in assessments with baseline tasks before and after the five-week period and received no active training. Additionally, all patients participated in the follow-up assessment 1.31years later. The second control group consisted of 19 typically developing children who only participated in the first assessment. After the intervention, study group patients showed significant improvement in complex attention and tracking (P<0.025). To achieve the effect of intervention in children with partial epilepsy, 10 sessions tailored to individual levels of ability were the minimum. Three attention components - sustained, complex, and tracking - need selective and longer training for more effective remediation. Follow-up assessment revealed a long-term positive effect of intervention. After 1.31years, the study group had significantly improved in three out of the four attention components (P<0.025), whereas the waiting-list group showed improvement in only two aspects of one complex attention component. In conclusion, attention impairment rehabilitation with FORAMENRehab is effective for children with epilepsy. Rehabilitation should focus on training specific components of attention and follow an individual-based rehabilitation process.

Neuropsychological benefits of computer-assisted cognitive rehabilitation (using FORAMENRehab program) in children with mild traumatic brain injury or partial epilepsy: A pilot study.

INTRODUCTION: The number of children with different cognitive difficulties is constantly increasing. Still, too few evidence-based pediatric neurocognitive rehabilitation programs exist. The main aim of the study was to assess the efficiency and usability of computer-assisted FORAMENRehab program for training specific components of attention in children with mild traumatic brain injury (mTBI) and partial epilepsy (PE). The second aim was to specify short- and long-term effects of the intervention. METHODS: Eight children between the ages of 9-12 years with attention impairment (3 with PE and 5 with mTBI) and 18 healthy controls participated. FORAMENRehab Attention software, adapted by the authors, was used for intervention. Strict intervention protocol consisting of patients completing 10 sessions over a 6-week-period to train four components of attention (sustaining, focusing, dividing, tracking) was designed and applied. Follow-up assessments were conducted after the end of the last training and 1.63 years later. RESULTS: After the intervention patients' sustained and complex attention improved. Long-term follow-up revealed continuing positive rehabilitation effects. 100% compliance suggested that the used method is attractive for children. CONCLUSIONS: These preliminary results of the pilot study give reason to presume that the method is effective in attention impairment remediation. However, more thorough research is needed.

Adicción y conciencia avatar / Addiction and Avatar Consciousness

El objetivo de este trabajo es entender el cambio de estado o dimensión de conciencia del paciente adicto. No es suficiente con el conocimiento del estado de conciencia consensuado pues aparece en muchos pacientes un nuevo estado de conciencia que le impele al consumo y quizá, si no tenemos capacidad de catalizar en ellos una conciencia unitiva, no consigamos mejorar los fracasos frecuentes que tenemos con muchos de estos pacientes

This work sets out to understand the change in the state or dimension of the addicted patient’s consciousness. Knowledge of the consensual state of consciousness is not enough, since a new state of consciousness appears in many patients, driving them to consumption, and we will quite possibly not manage to improve on the frequent failure rates that we find with many of these patients if we are unable to catalyse a unitive consciousness in them

Aura interruption: the Andrews/Reiter behavioral intervention may reduce seizures and improve quality of life - a pilot trial.

Patients with epilepsy frequently experience depression and emotional stress and these may function as seizure triggers in epileptogenic frontotemporal cortex, which serves in emotional processing. Eight patients enrolled in a pilot trial of a 6-month epilepsy-specific behavioral approach comprising counseling and relaxation to recognize and eliminate emotional seizure triggers. Potential participants with psychogenic seizures were excluded by long-term EEG and/or the MMPI profile. One participant became seizure free, another had an approximately 90% reduction in seizures, and two additional participants achieved a greater than 50% reduction in seizure frequency (total responder rate=50%), stable during 6 months of observation after the intervention. All completers showed marked and stable improvement of quality of life (Quality of Life in Epilepsy-89 inventory) and temporary improvement in the Profile of Mood States. An adequately powered randomized controlled trial is needed to confirm our findings, which suggest that behavioral approaches may hold promise for motivated patients with epilepsy.

Voluntary brain regulation and communication with electrocorticogram signals.

Brain-computer interfaces (BCIs) can be used for communication in writing without muscular activity or for learning to control seizures by voluntary regulation of brain signals such as the electroencephalogram (EEG). Three of five patients with epilepsy were able to spell their names with electrocorticogram (ECoG) signals derived from motor-related areas within only one or two training sessions. Imagery of finger or tongue movements was classified with support-vector classification of autoregressive coefficients derived from the ECoG signals. After training of the classifier, binary classification responses were used to select letters from a computer-generated menu. Offline analysis showed increased theta activity in the unsuccessful patients, whereas the successful patients exhibited dominant sensorimotor rhythms that they could control. The high spatial resolution and increased signal-to-noise ratio in ECoG signals, combined with short training periods, may offer an alternative for communication in complete paralysis, locked-in syndrome, and motor restoration.

Extraction and localization of mesoscopic motor control signals for human ECoG neuroprosthetics.

Electrocorticogram (ECoG) recordings for neuroprosthetics provide a mesoscopic level of abstraction of brain function between microwire single neuron recordings and the electroencephalogram (EEG). Single-trial ECoG neural interfaces require appropriate feature extraction and signal processing methods to identify and model in real-time signatures of motor events in spontaneous brain activity. Here, we develop the clinical experimental paradigm and analysis tools to record broadband (1Hz to 6kHz) ECoG from patients participating in a reaching and pointing task. Motivated by the significant role of amplitude modulated rate coding in extracellular spike based brain-machine interfaces (BMIs), we develop methods to quantify spatio-temporal intermittent increased ECoG voltages to determine if they provide viable control inputs for ECoG neural interfaces. This study seeks to explore preprocessing modalities that emphasize amplitude modulation across frequencies and channels in the ECoG above the level of noisy background fluctuations in order to derive the commands for complex, continuous control tasks. Preliminary experiments show that it is possible to derive online predictive models and spatially localize the generation of commands in the cortex for motor tasks using amplitude modulated ECoG.

Employment outcomes following resective epilepsy surgery.

PURPOSE: Analyze determinates of employment changes from before to 2 years after surgery in refractory focal epilepsy patients. METHODS: Preoperative employment was prospectively assessed in 375 adults with refractory epilepsy. Two-year postsurgical employment status was obtained for 299; factors potentially associated with employment status change among subgroups unemployed and employed at baseline were analyzed. RESULTS: Presurgical employment status was full-time (n = 148, 39.5%), part-time (n = 26, 6.9%), disabled and unemployed (n = 100, 26.7%), unemployed (n = 44, 11.7%), and other (n = 57, 15.2%). Those with and without 2-year follow-up did not differ on baseline characteristics (all p > 0.10). Two years after surgery, 42.8% were employed full-time and 12.4%, part-time. Among those unemployed before surgery, better seizure outcome was associated with gaining employment at 2 years (p = 0.03). CONCLUSIONS: Net employment gains were modest 2 years after surgery and higher with better seizure outcomes, reinforcing the need for optimizing surgical candidate selection, long-term follow-up studies, and postsurgical vocational rehabilitation.

Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes.

PURPOSE: The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike-waves during slow sleep (CSWS) and Landau-Kleffner syndromes, which are two rare epileptic syndromes occurring in children. METHODS: We enrolled seven young adults, five who had a CSWS syndrome, and two, a Landau-Kleffner syndrome in childhood. We evaluated their intellectual level as well as their oral and written language and executive functions. RESULTS: This study confirmed that the epilepsy associated with these syndromes has a good prognosis. Only one patient still had active epilepsy. However, the neuropsychological disorders particular to each syndrome persisted. Only two patients had followed a normal pathway in school. Three of the five patients with a CSWS syndrome during childhood remained globally and nonselectively mentally deficient. We found no evidence of the persistence of a dysexecutive syndrome in this study group. The intellectual functions of the two patients with Landau-Kleffner syndrome were normal; however, their everyday lives were disrupted by severe, disabling language disturbances. We discuss the role of some prognostic factors such as the location of the interictal electric focus and the age at onset of CSWS. CONCLUSIONS: These two epileptic syndromes of childhood are very similar in many respects, but their clinical outcomes in adulthood are different.

The effectiveness of cognitive rehabilitation for attention deficits in focal seizures: a randomized controlled study.

PURPOSE: Cognitive deficits are one of the major limiting factors in the everyday life functioning of patients with focal seizures. Although cognitive rehabilitation methods have been successfully applied to patients with other central nervous system (CNS) lesions, these methods have not yet been evaluated in cognitively impaired patients with epilepsy. The present study evaluated the effectiveness of two commonly used methods for attention deficits: (a) the Retraining Method, aimed at retraining impaired cognitive functions; and (b) the Compensation Method, aimed at teaching compensatory strategies while taking neuronal loss for granted. METHODS: Fifty adult outpatients with focal seizures and attention impairments receiving carbamazepine (CBZ) monotherapy were randomly assigned to the Retraining Method, the Compensation Method, or to a waiting-list control group. Established and self-reported neuropsychological outcomes and self-reported quality of life of these groups were evaluated at pretraining, posttraining, and at a 6-month follow-up measurement point and were completed by 44 patients. RESULTS: Neuropsychological outcomes related to training, self-reported neuropsychological outcomes, and quality of life at the 6-month follow-up measurement point improved both in the Retraining Method group (n = 19) and the Compensation Method group (n = 17) relative to the waiting-list control group (n = 8). The Compensation Method was more effective in improving self-reported neuropsychological outcomes and quality of life, especially for patients with less education. The patients with active epilepsy benefited more from both methods than did the seizure-free patients. CONCLUSIONS: These data show that cognitive rehabilitation programs are effective for patients with focal seizures and attention deficits and should, therefore, be incorporated into comprehensive care programs.

Patient satisfaction and epilepsy surgery.

This study was designed to describe patients' experience with surgical treatment of epilepsy in terms of whether it was useful or had negative effects and to assess associations between experienced utility (satisfaction), experienced negative effects (dissatisfaction), and selected objective outcome measures. An evaluation of patients' satisfaction and dissatisfaction was conducted retrospectively by questionnaires for all patients surgically treated for epilepsy in Norway between 1949 and 1988. One hundred sixteen patients (74.3%) replied. Overall, 75% of the surgically treated patients reported that treatment had been useful, and 20% reported that the treatment had negative effects. The experience of satisfaction with treatment was strongly associated with a favorable seizure outcome, more severe underlying disease, improvements in working ability, being in regular work or education postoperatively, and not having disability pensions postoperatively. The experience of dissatisfaction with treatment was significantly associated with neurologic deficit and decreased working ability. There was overall agreement between subjectively reported satisfaction with treatment and success measured objectively. The experiences of useful effects and negative effects of the operation could not be represented by a single-dimension scale. Seizure outcome played a more important role in terms of reported useful effects, and neurologic deficit played a more important role in reported negative effects. In both categories, effects on social, occupational, emotional, and behavioral aspects played an important role.

Therapeutic recreation programmes for children with epilepsy.

Amongst children with epilepsy, research has shown that most have a negative self-concept and consequently a low level of self-esteem. This elusive concept of the self is constantly being assessed and reassessed by each child throughout the process of social development. Early literature has suggested that children with disabilities, especially chronic medical or biological disabilities, typified by epilepsy and diabetes, are more susceptible to the development of psychopathology and negative self-concepts. This paper reports that intervention in the form of therapeutic recreation programmes can help rectify this problem of negative self-concept and low self-esteem in children with epilepsy. The Piers-Harris Self Concept Scale, a Self Report Inventory on six dimensions of self-concept, was assessed both pre- and post-therapeutic recreational intervention to show significant improvement in the child's self-concept and acceptance of their epilepsy. Educational components within the programme have demonstrated significant learning and increased treatment compliance--particularly with long-term medications. The Adolescent Psychosocial Seizure Inventory, an adolescent version of the Washington Psycho-Social Seizure Inventory (WPSI), both of which have been validated as a reliable clinical assessment for use in Australia, has provided further evidence to suggest that improvements occur in children's self-concept as a consequence of therapeutic recreation, however use of this protocol appears limited to adolescents over the age of 13 years.

University students with epilepsy: a study of social aspects.

Improved control of epilepsy has permitted an increasing number of young persons with epilepsy to attend university. This study was designed to assess the impact of epilepsy on their education, employment, family and social life. We studied fifteen randomly selected full time university students, aged 20-28 years, who had a well documented history of partial or generalized epilepsy. One third still had seizures, over 90% were taking antiepileptic medication and all were followed by a neurologist. Interviews were conducted according to a standard open-ended questionnaire lasting 1.5 hours. After an initial adjustment period, most did not feel that epilepsy constituted a handicap to their education. They learned about epilepsy, did independent research and one quarter chose careers in the health sciences. Most reported occasional negative experiences, but were reluctant to interpret this as evidence of discrimination. All felt that they had had equal opportunities at school and at work. They were selective about imparting knowledge about their seizures to students, staff and employers, but did not hide their epilepsy. Subjects had high vocational aspirations and academic motivation reflecting good intelligence and previous educational achievements. Their positive attitude, enthusiasm and denial of difficulties were striking. This reflects improved seizure control as well as family and social support in this group of young people.

Pre- and postoperative rehabilitation related to epilepsy surgery.

A short review is presented of the mental impairment and personality deficits of persons with severe epilepsy and of their consequences, that require psychosocial and occupational rehabilitation, as well as of some aspects of health economics related to epilepsy surgery. It is concluded that detailed studies on the psychosocial outcome of epilepsy surgery are rather rare in the vast literature on epilepsy surgery, a situation that needs to be changed in order to promote better understanding of the therapeutic and palliative surgical treatment of epilepsy, to develop and broaden it, and to motivate more financial support from health authorities.