Publications by authors named "Arthur Cukiert"

50 Publications

Deep Brain Stimulation for Treatment of Refractory Epilepsy.

Neurol India 2021 Jan-Feb;69(1):42-44

Department of Neurosurgery, Epilepsy Surgery Program, Cliìnica Cukiert, São Paulo, Brazil.

Background And Introduction: Deep brain stimulation (DBS) has been increasingly used in the treatment of refractory epilepsy with remarkable safety. Experimental data demonstrated that electric current could modulate distinct brain circuits and decrease neuronal hypersynchronization seen in epileptic activity. The ability to carefully choose the most suitable anatomical target and precisely implant the lead is of extreme importance for satisfactory outcomes.

Objective: This video aimed to explore the targeting of the three most relevant nuclei in the treatment of refractory epilepsy.

Technique: Through a step-by-step approach, this video describes the surgical planning for DBS implantation in the anterior nucleus of the thalamus (ANT), the centromedian nucleus of the thalamus (CM), and the hippocampus (HIP).

Conclusion: Each of the discussed targets has its own pearls and pitfalls that should be considered for an adequate lead placement. Accurate planning of the surgical procedure is essential for achieving optimal results.
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http://dx.doi.org/10.4103/0028-3886.310083DOI Listing
March 2021

Deep Brain Stimulation for Treatment of Refractory Epilepsy.

Neurol India 2020 Nov-Dec;68(Supplement):S268-S277

Department of Neurosurgery, Epilepsy Surgery Program, Clínica Cukiert, São Paulo, Brazil.

Deep brain stimulation (DBS) has been used in the treatment of motor diseases with remarkable safety and efficacy, which abet the interest of its application in the management of other neurologic and psychiatric disorders such as epilepsy. Experimental data demonstrated that electric current could modulate distinct brain circuits and decrease the neuronal hypersynchronization seen in epileptic activity. The ability to carefully choose the most suitable anatomical target as well as to define the most reasonable stimulation parameters is highly dependable on the comprehension of the underlying mechanisms of action, which remain unclear. This review aimed to explore the relevant clinical data regarding the use of DBS in the treatment of refractory epilepsy.
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http://dx.doi.org/10.4103/0028-3886.302454DOI Listing
December 2020

Long-term seizure outcome during continuous bipolar hippocampal deep brain stimulation in patients with temporal lobe epilepsy with or without mesial temporal sclerosis: An observational, open-label study.

Epilepsia 2021 01 30;62(1):190-197. Epub 2020 Nov 30.

São Paulo Epilepsy Clinic, São Paulo, Brazil.

Objective: We present the findings related to seizure outcome during hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporal lobe epilepsy.

Methods: Twenty-five patients submitted to Hip-DBS were studied. All patients were evaluated with interictal and ictal electroencephalography (EEG) and high-resolution 1.5 T magnetic resonance imaging (MRI). The hippocampus was targeted directly on MRI using a posterior occipital burr hole approach. Bipolar continuous stimulation was ramped up until 3.0 V (300 µs, 130 Hz). Patients were considered responders if at least 50% seizure frequency reduction was obtained.

Results: Median age was 39 years; median follow-up time was 57 months (16 women). All patients had focal with impaired awareness seizure (FIAS) and 23 patients had focal aware seizure (FAS). Baseline median FAS and FIAS frequency was 8. Ictal EEG showed unilateral (n = 10) or bilateral (n = 15) seizure onset. MRI showed unilateral (n = 11) or bilateral (n = 8) mesial temporal sclerosis (MTS) and was normal in six6 patients. Fifteen patients were submitted to bilateral and 10 patients to unilateral Hip-DBS. Median reduction in FAS frequency was 66%. Eighteen patients with FAS were considered responders and five (21%) were free of FAS. Median FIAS frequency (n = 25) reduction was 91%. Twenty-two patients were considered responders and eight (32%) were free of FIAS. FIAS were significantly more reduced then FAS (P = .017). There was no relation between any contact's position within the hippocampus and outcome for either FAS (P = .727) or FIAS (P = .410). There was no difference in outcome in patients submitted to either unilateral or bilateral Hip-DBS regarding FAS (P = .978) or FIAS (P = .693).

Significance: Hip-DBS significantly reduced the frequency of both FAS and FIAS in this cohort of patients with refractory temporal lobe epilepsy. Hip-DBS might represent a good therapeutic option in such patients not amenable to resective surgery.
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http://dx.doi.org/10.1111/epi.16776DOI Listing
January 2021

Establishing criteria for pediatric epilepsy surgery center levels of care: Report from the ILAE Pediatric Epilepsy Surgery Task Force.

Epilepsia 2020 12 14;61(12):2629-2642. Epub 2020 Nov 14.

Department of Neurology, Nicklaus Children's Hospital, Miami, FL, USA.

Presurgical evaluation and surgery in the pediatric age group are unique in challenges related to caring for the very young, range of etiologies, choice of appropriate investigations, and surgical procedures. Accepted standards that define the criteria for levels of presurgical evaluation and epilepsy surgery care do not exist. Through a modified Delphi process involving 61 centers with experience in pediatric epilepsy surgery across 20 countries, including low-middle- to high-income countries, we established consensus for two levels of care. Levels were based on age, etiology, complexity of presurgical evaluation, and surgical procedure. Competencies were assigned to the levels of care relating to personnel, technology, and facilities. Criteria were established when consensus was reached (≥75% agreement). Level 1 care consists of children age 9 years and older, with discrete lesions including hippocampal sclerosis, undergoing lobectomy or lesionectomy, preferably on the cerebral convexity and not close to eloquent cortex, by a team including a pediatric epileptologist, pediatric neurosurgeon, and pediatric neuroradiologist with access to video-electroencephalography and 1.5-T magnetic resonance imaging (MRI). Level 2 care, also encompassing Level 1 care, occurs across the age span and range of etiologies (including tuberous sclerosis complex, Sturge-Weber syndrome, hypothalamic hamartoma) associated with MRI lesions that may be ill-defined, multilobar, hemispheric, or multifocal, and includes children with normal MRI or foci in/abutting eloquent cortex. Available Level 2 technologies includes 3-T MRI, other advanced magnetic resonance technology including functional MRI and diffusion tensor imaging (tractography), positron emission tomography and/or single photon emission computed tomography, source localization with electroencephalography or magnetoencephalography, and the ability to perform intra- or extraoperative invasive monitoring and functional mapping, by a large multidisciplinary team with pediatric expertise in epilepsy, neurophysiology, neuroradiology, epilepsy neurosurgery, neuropsychology, anesthesia, neurocritical care, psychiatry, and nursing. Levels of care will improve safety and outcomes for pediatric epilepsy surgery and provide standards for personnel and technology to achieve these levels.
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http://dx.doi.org/10.1111/epi.16698DOI Listing
December 2020

Hippocampal deep brain stimulation: a therapeutic option in patients with extensive bilateral periventricular nodular heterotopia: a case report.

Epileptic Disord 2020 Oct;22(5):664-668

Clinica de Epilepsia de São Paulo, São Paulo, Brazil.

A female adult patient with extensive bilateral periventricular nodular heterotopia (PNH), who was referred for bilateral hippocampal deep brain stimulation (Hip-DBS), was investigated. She presented with daily focal aware and impaired-awareness seizures with automatism and weekly generalized tonic-clonic seizures. Her EEG showed bilateral independent ictal and interictal neocortical temporal lobe discharges and her MRI showed extensive, symmetric PNH. She was treated with bilateral Hip-DBS which led to a major decrease in her seizure frequency (one seizure per trimester). The outcome was stable over three years, and there was no additional neuropsychological deficits or device-related adverse effects. This is the first reported patient to be undergo long-term continuous Hip-DBS to treat bilateral PNH. DBS, a non-lesional, reversible, neuromodulatory technique, may prove to be a good therapeutic option in patients with extensive bilateral epileptogenic networks who present with temporal lobe epilepsy and who are usually considered poor candidates for resective surgery.
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http://dx.doi.org/10.1684/epd.2020.1206DOI Listing
October 2020

Impact of Cardiac-Based Vagus Nerve Stimulation Closed-Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective, Individual-Control Study.

Neuromodulation 2020 Oct 12. Epub 2020 Oct 12.

Department of Neurosurgery, São Paulo Epilepsy Clinic, São Paulo, SP, Brazil.

Objectives: We designed a prospective, individual-controlled study to evaluate the effect of cardiac-based VNS (cbVNS) in a cohort of patients with generalized epilepsy (GE).

Materials And Methods: Twenty patients were included. They were followed up for six months under regular VNS (rVNS) and subsequently for six months during cbVNS. Stimulation parameters were 500 μsec, 30 Hz, and up to 2.5 mA. Seizure frequency was documented after two, four, and six months during the rVNS and cbVNS phases. Patients with at least 50% seizure frequency reduction were considered responders. The total and relative amount of stimulation cycles generated by both rVNS and cbVNS activation were documented. Findings during rVNS were compared to baseline and cbVNS data were compared to those during rVNS.

Results: There was a significant decrease in mean seizure frequency (61% [95% CI, 48-74]; p < 0.001) during the rVNS phase compared to baseline. There was no additional significant (16% [95% CI, 4-35]; p = 0.097) mean seizure frequency reduction during cbVNS compared to the rVNS phase. Fifteen patients (75%) were considered responders after rVNS. Four patients (20%) were considered responders after six months of cbVNS. During the cbVNS phase, the mean total number of cycles/day was 346, 354, and 333 for months two, four, and six, respectively; the cycles generated by rVNS were 142, 138, and 146 for months two, four, and six, respectively; and cycles generated by cbVNS were 204, 215, and 186 for months two, four, and six, respectively. There was no relationship between the mean total number of cycles (-6[95% CI, -85 to 72]; p = 0.431), the mean number of auto-stimulation cycles (27[95% CI,-112 to 166]; p = 0.139), the mean number of regular cycles (-33[95% CI,-123 to 57]; p = 0.122), or the mean percentage of auto-stimulation cycles (13[95% CI,19- 45]; p = 0.109) and outcome during the cbVNS phase. Eight patients showed some decrease in seizure frequency during cbVNS.

Conclusions: rVNS was effective in reducing seizure frequency in patients with generalized epilepsy, but activation of the cbVNS feature did not add significantly to rVNS efficacy. On the other hand, although not statistically significant, 40% of the patients showed some reduction in seizure frequency, which might prove useful at an individual level.
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http://dx.doi.org/10.1111/ner.13290DOI Listing
October 2020

Seizure outcome during bilateral, continuous, thalamic centromedian nuclei deep brain stimulation in patients with generalized epilepsy: a prospective, open-label study.

Seizure 2020 Oct 10;81:304-309. Epub 2020 Sep 10.

São Paulo Epilepsy Clinic, São Paulo, Brazil.

Objective: We report on the seizure frequency and attention outcome during thalamic centromedian stimulation (CM-DBS) in patients with refractory generalized epilepsy (GE).

Methods: Twenty consecutive patients with GE who were submitted to CM-DBS and had at least one year of follow-up were prospectively studied. The CM was targeted bilaterally. Stimulation intensity was ramped up (bipolar, continuous, 130 Hz; 300μsec) until 4.5 V or until side effects developed. Contacts` position was determined on postoperative volumetric MRI scans. Attention was qualitatively evaluated using the SNAP-IV (Swanson, Nolan, and Pelham) questionnaire. Patients were considered responders during CM-DBS if an at least 50% seizure frequency reduction was obtained compared to baseline.

Results: Median age was 15.5 years (13 males). Median follow-up time was 2.55 years. EEG disclosed generalized spike-and wave discharges in all patients. MRI was normal in 10 patients, showed diffuse atrophy in 6 patients, and showed abnormalities in 4 patients (3 patients had bilateral cortical development abnormalities and one had unilateral hemispheric atrophy). Patients presented with daily multiple seizure types (8 to 66 per day; median: 37), including tonic, atonic, myoclonic, atypical absence and generalized tonic-clonic seizures. Mean DBS intensity was 4.3 V. An insertional effect was noted in 14 patients. CM-DBS was able to significantly reduce the frequency of tonic (p < 0.001), atypical absence seizures (p < 0.001), atonic seizures (p = 0.001) and bilateral generalized tonic-clonic seizures (p = 0.004). One patient became seizure-free. Ninety percent of the patients were considered responders (>50% seizure frequency reduction). All patients showed some improvement in attention. The mean number of items in which improvement was noted in the SNAP-IV questionnaire was 4.8. There was a significant relationship between overall seizure frequency reduction and improvement of attention (p = 0.033).

Discussion: This prospective, open label study included a large, homogeneous cohort and provided evidence on the efficacy of CM-DBS in reducing the seizure burden and increasing attention in patients with refractory generalized epilepsy.
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http://dx.doi.org/10.1016/j.seizure.2020.08.028DOI Listing
October 2020

How technology is driving the landscape of epilepsy surgery.

Epilepsia 2020 05 29;61(5):841-855. Epub 2020 Mar 29.

Neurology and Neurosurgery Clinic Sao Paulo, Clinica Neurologica Cukiert, Sao Paulo, Brazil.

This article emphasizes the role of the technological progress in changing the landscape of epilepsy surgery and provides a critical appraisal of robotic applications, laser interstitial thermal therapy, intraoperative imaging, wireless recording, new neuromodulation techniques, and high-intensity focused ultrasound. Specifically, (a) it relativizes the current hype in using robots for stereo-electroencephalography (SEEG) to increase the accuracy of depth electrode placement and save operating time; (b) discusses the drawback of laser interstitial thermal therapy (LITT) when it comes to the need for adequate histopathologic specimen and the fact that the concept of stereotactic disconnection is not new; (c) addresses the ratio between the benefits and expenditure of using intraoperative magnetic resonance imaging (MRI), that is, the high technical and personnel expertise needed that might restrict its use to centers with a high case load, including those unrelated to epilepsy; (d) soberly reviews the advantages, disadvantages, and future potentials of neuromodulation techniques with special emphasis on the differences between closed and open-loop systems; and (e) provides a critical outlook on the clinical implications of focused ultrasound, wireless recording, and multipurpose electrodes that are already on the horizon. This outlook shows that although current ultrasonic systems do have some limitations in delivering the acoustic energy, further advance of this technique may lead to novel treatment paradigms. Furthermore, it highlights that new data streams from multipurpose electrodes and wireless transmission of intracranial recordings will become available soon once some critical developments will be achieved such as electrode fidelity, data processing and storage, heat conduction as well as rechargeable technology. A better understanding of modern epilepsy surgery will help to demystify epilepsy surgery for the patients and the treating physicians and thereby reduce the surgical treatment gap.
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http://dx.doi.org/10.1111/epi.16489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317716PMC
May 2020

Deep brain stimulation - depression and obsessive-compulsive disorder.

Rev Assoc Med Bras (1992) 2018 Nov;64(11):963-982

Members of the Brazilian Society of Neurosurgery - Spine Department, São Paulo, SP, Brasil.

Objective: The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors.

Conclusions: The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.
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http://dx.doi.org/10.1590/1806-9282.64.11.963DOI Listing
November 2018

Chronic pain treatment with spinal cord neurostimulation.

Rev Assoc Med Bras (1992) 2018 Apr;64(4):299-306

Brazilian Medical Association.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.
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http://dx.doi.org/10.1590/1806-9282.64.04.299DOI Listing
April 2018

Seizure outcome after hippocampal deep brain stimulation in patients with refractory temporal lobe epilepsy: A prospective, controlled, randomized, double-blind study.

Epilepsia 2017 10 26;58(10):1728-1733. Epub 2017 Jul 26.

Mario Covas Hospital, Santo Andre, São Paulo, SP, Brazil.

Objective: We designed a prospective, randomized, controlled, double-blind study to evaluate the efficacy of hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporary lobe epilepsy (TLE).

Methods: Sixteen adult patients with refractory TLE were studied. Patient's workup included medical history, interictal and ictal electroencephalography (EEG), and high-resolution 1.5T magnetic resonance imaging (MRI). Patients were randomized on a 1:1 proportion to an active (stimulation on) or to a control (no stimulation) arm. After implantation, patients were allowed to recover for 1 month, which was followed by a 1-month titration (or sham) period. The 6-month blinded phase started immediately afterward. A postoperative MRI confirmed the electrode's position in all patients. All patients received bipolar continuous stimulation. Stimulus duration was 300 μs and frequency was 130 Hz; final intensity was 2 V. Patients were considered responders when they had at least 50% seizure frequency reduction.

Results: All patients had focal impaired awareness seizures (FIAS, complex partial seizures), and 87% had focal aware seizures (FAS, simple partial seizures). Mean preoperative seizure frequency was 12.5 ± 9.4 (mean ± standard deviation) per month. MRI findings were normal in two patients, disclosed bilateral mesial temporal sclerosis (MTS) in three, left MTS in five, and right MTS in six patients. An insertional effect could be noted in both control and active patients. In the active group (n = 8), four patients became seizure-free; seven of eight were considered responders and one was a nonresponder. There was a significant difference regarding FIAS frequency between the two groups from the first month of full stimulation (p < 0.001) until the end of the blinded phase (p < 0.001). This was also true for FAS, except for the third month of the blinded phase.

Significance: Hip-DBS was effective in significantly reducing seizure frequency in patients with refractory TLE in the active group, as compared to the control group. Fifty-percent of the patients in the active group became seizure-free. The present study is the larger prospective, controlled, double-blind study to evaluate the effects of Hip-DBS published to date.
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http://dx.doi.org/10.1111/epi.13860DOI Listing
October 2017

Introduction-Pediatric epilepsy surgery techniques.

Epilepsia 2017 04;58 Suppl 1:7-9

Hospital Brigadeiro, Epilepsy Clinic of de Sao Paulo, Sao Paulo, Brazil.

This supplement includes the proceedings from the Pediatric Epilepsy Surgery Techniques Meeting held in Gothenburg (July 4-5, 2014), which focused on presentations and discussions regarding specific surgical technical issues in pediatric epilepsy surgery. Pediatric epilepsy neurosurgeons from all over the world were present and active in very fruitful and live presentations and discussions. These articles represent a synopsis of the areas and subjects dealt with there.
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http://dx.doi.org/10.1111/epi.13677DOI Listing
April 2017

Deep brain stimulation targeting in refractory epilepsy.

Epilepsia 2017 04;58 Suppl 1:80-84

Department of Neurosciences and Rehabilitation, Tampere University Hospital, Tampere, Finland.

Deep brain stimulation has been used in increasing frequency to treat refractory epilepsy. Different targets have been tried, and different epileptic syndromes have been addressed in different ways. We describe the current targeting techniques for the structures presently most often implanted, namely the anterior nucleus of the thalamus, the centromedian nucleus of the thalamus, and the hippocampus.
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http://dx.doi.org/10.1111/epi.13686DOI Listing
April 2017

Commentary: Anterior Nucleus Deep Brain Stimulation for Refractory Epilepsy: Insights Into Patterns of Seizure Control and Efficacious Target.

Authors:
Arthur Cukiert

Neurosurgery 2016 06;78(6):812

Clinica de Epilepsia de Sao Paulo and Department of Neurosurgery, ABC Faculty of Medicine, São Paulo, Brazil.

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http://dx.doi.org/10.1227/NEU.0000000000001243DOI Listing
June 2016

Commentary: Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy.

Authors:
Arthur Cukiert

Neurosurgery 2016 09;79(3):354-5

*Clinica de Epilepsia de Sao Paulo, Sao Paulo, Brazil; ‡Department of Neurosurgery, ABC Faculty of Medicine, Sao Paulo, Brazil.

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http://dx.doi.org/10.1227/NEU.0000000000001215DOI Listing
September 2016

Technical aspects of pediatric epilepsy surgery: Report of a multicenter, multinational web-based survey by the ILAE Task Force on Pediatric Epilepsy Surgery.

Epilepsia 2016 Feb 8;57(2):194-200. Epub 2016 Jan 8.

Center for Neuroscience and Behavioral Health, Children's National Health System, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, U.S.A.

Surgical techniques may vary extensively between centers. We report on a web-based survey aimed at evaluating the current technical approaches in different centers around the world performing epilepsy surgery in children. The intention of the survey was to establish technical standards. A request was made to 88 centers to complete a web-based survey comprising 51 questions. There were 14 questions related to general issues, 13 questions investigating the different technical aspects for children undergoing epilepsy surgery, and 24 questions investigating surgical strategies in pediatric epilepsy surgery. Fifty-two centers covering a wide geographic representation completed the questionnaire. The median number of resective procedures per center per year was 47. Some important technical practices appeared (>80% of the responses) such as the use of prophylactic antibiotics (98%), the use of high-speed drills for bone opening (88%), nonresorbable material for bone flap closure (85%), head fixation (90%), use of the surgical microscope (100%), and of free bone flaps. Other questions, such as the use of drains, electrocorticography (ECoG) and preoperative withdrawal of valproate, led to mixed, inconclusive results. Complications were noted in 3.8% of the patients submitted to cortical resection, 9.9% hemispheric surgery, 5% callosotomy, 1.8% depth electrode implantation, 5.9% subdural grids implantation, 11.9% hypothalamic hamartoma resection, 0.9% vagus nerve stimulation (VNS), and 0.5% deep brain stimulation. There were no major differences across regions or countries in any of the subitems above. The present data offer the first overview of the technical aspects of pediatric epilepsy surgery worldwide. Surprisingly, there seem to be more similarities than differences. That aside many of the evaluated issues should be examined by adequately designed multicenter randomized controlled trials (RCTs). Further knowledge on these technical issues might lead to increased standardization and lower costs in the future, as well as definitive practice guidelines.
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http://dx.doi.org/10.1111/epi.13292DOI Listing
February 2016

Vagus Nerve Stimulation for Epilepsy: An Evidence-Based Approach.

Authors:
Arthur Cukiert

Prog Neurol Surg 2015 4;29:39-52. Epub 2015 Sep 4.

Epilepsy Surgery Program, Clinica de Epilepsia de Sao Paulo and Department of Neurology and Neurosurgery, ABC Faculty of Medicine, Sao Paulo, Brazil.

Medical treatment of seizures yields a satisfactory response in 75-80% of the patients; resective epilepsy surgery is a therapeutic option for those patients who are refractory to drug therapy, but there is still a considerable portion (20-30%) of patients who are ineligible for surgery or failed surgery. Vagus nerve stimulation (VNS) might be an option for these very refractory patients. We carried out an evidence-based search to identify the best evidence presently available related to the use of VNS. We used multiple searchable databases (primary: PubMed-MEDLINE, EMBASE, LILACS, and SciELO; secondary: Cochrane Library) and a standard structured approach know as the PICO scheme: P (patient), I (intervention), C (comparison), and O (outcome). Publications were selected based on study design, PICO components, language, and availability of full text. For study design, we included papers designed as 'randomized controlled trials'; these trials were evaluated according to the Jadad score; the type II error was not used while selecting studies to avoid further limitations. Twenty-eight papers were selected, all from PubMed-MEDLINE. The search results showed that patients older than 12 years with refractory partial seizures (with or without generalization) may benefit from VNS. Children might also benefit, but might need different stimulation parameters. We also noted that higher stimulation settings are associated with increased occurrence of hoarseness, throat pain, cough, and dyspnea. The available randomized controlled trials and cohorts made it clear that VNS is a useful palliative procedure in adult patients with partial epilepsy, and a 50-60% reduction in seizure frequency might be expected in at least 50% of the patients. VNS is a useful palliative procedure in patients with refractory epilepsy. As our practical experience and understanding of the mechanism of action of VNS increase, more homogeneous patient populations that might respond better to VNS are being recognized, such as children with secondary generalized epilepsy and some types of reflex epilepsy.
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http://dx.doi.org/10.1159/000434654DOI Listing
July 2016

Seizure Outcome After Battery Depletion in Epileptic Patients Submitted to Deep Brain Stimulation.

Neuromodulation 2015 Aug 29;18(6):439-41; discussion 441. Epub 2015 Apr 29.

Hospital Brigadeiro, São Paulo, SP, Brazil.

Objective: We studied patients treated with chronic DBS in whom there was depletion of the generator's battery, in order to get insight on the modulatory potential of chronic DBS in refractory epilepsy.

Material: Nine adult patients with refractory epilepsy treated with at least three years of deep brain stimulation (DBS), and who were followed up for at least six months after battery depletion were studied. One patient was treated with hippocampal DBS (Hip-DBS), two to centro-median DBS (CM-DBS) and six to anterior nucleus stimulation (AN-DBS).

Results: Two patients did not have seizure's frequency modification after battery depletion; the other seven patients had seizure frequency increase, including those three patients that were seizure-free. Five of those seven patients who had seizure frequency increase after battery's depletion had seizure's frequency lower than their pre-DBS baseline seizure frequency; two of such patients returned to their pre-DBS baseline seizure frequency.

Conclusions: In the majority of the patients, three years of chronic DBS did not show a permanent effect on epileptogenesis. On the other hand, the post-battery depletion seizure's frequency was usually much lower than the baseline (pre-DBS) seizure's frequency, suggesting that there was actual network neuromodulation.
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http://dx.doi.org/10.1111/ner.12290DOI Listing
August 2015

Superior turbinectomy: role for a two-surgeon technique in endoscopic endonasal transsphenoidal surgery--technical note.

Neurol Med Chir (Tokyo) 2015 23;55(4):345-50. Epub 2015 Mar 23.

Department of Neurosurgery, Osaka Neurological Institute.

We describe a practical technique of superior turbinectomy followed by posterior ethmoidectomy as a less invasive procedure for two-surgeon technique on endoscopic endonasal transsphenoidal surgery. After identification of the superior turbinate and the sphenoid ostium, the inferior third portion of the superior turbinate was coagulated and resected. This partial superior turbinectomy procedure exposed the posterior ethmoidal sinus. Resection of the bony walls between the sphenoid and posterior ethmoid sinuses provided more lateral and superior exposure of the sphenoid sinus. This technique was performed in 56 patients with midline skull base lesions, including 49 pituitary adenomas and 7 other lesions. Meticulous manipulation of instruments was performed in all cases without surgical complications such as permanent hyposmia/anosmia or nasal bleeding. Our findings suggested that the partial superior turbinectomy followed by retrograde posterior ethmoidectomy is a simple and safe technique providing a sufficient surgical corridor for two-surgeon technique to approaching midline skull base regions, mainly involving pituitary adenomas.
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http://dx.doi.org/10.2176/nmc.tn.2014-0159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628182PMC
December 2016

c-FOS expression after hippocampal deep brain stimulation in normal rats.

Neuromodulation 2014 Apr 7;17(3):213-7; discussion 216-7. Epub 2013 Oct 7.

Neurologia Experimental, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.

Objectives: We studied the effects of Hip-deep brain stimulation (DBS) on the expression of the inducible transcription factor c-FOS in the brain of normal rats.

Materials And Methods: Ten Wistar rats were anesthetized, and nine were implanted with epidural and hippocampal electrodes for brain activity recording; one animal was used as sham. Bipolar stimulating electrodes were implanted in the left hippocampus. Three animals were used as control (implanted but not stimulated), one as sham (not implanted, not stimulated), and six as the study group. Stimulation was carried out using square wave pulses with 0.8V, 300 μsec, and 130 Hz (∼25μC/cm2) on the left hippocampus through the implanted bipolar hippocampal lead. Three animals were submitted to a one-hour and three to a six-hour stimulation session. Immunohistochemistry was employed to visualize c-FOS distribution in the rat's brain. The presence of seizures and electrocorticographic findings also were observed.

Results: In animals submitted to both one-hour or six-hour unilateral hippocampal stimulation sessions, there was a significant bilateral overexpression of c-FOS in the hippocampus proper, dentate gyrus, and hylus. In the CA1 and CA3 regions, although activation was bilateral, c-FOS hyperexpression prevailed at the stimulated side over time; this was not true for the hilar and dentate gyrus regions where a more symmetric activation occurred over time. A significant c-FOS activation occurred after one hour of Hip-DBS in the ipsilateral amygdala; there was no contralateral amygdala activation, and by six hours, no amygdala activation was noted. No c-FOS activation was noted in other brain areas.

Discussion: Our data showed that unilateral Hip-DBS was able to cause widespread and persistent bilateral activation of the normal rat limbic system, although in some, nuclei activation prevailed over the stimulated side. Cortical activation outside the limbic system was not noted. Our data represent a first approach to study the mechanistic paradigm involved in Hip-DBS.
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http://dx.doi.org/10.1111/ner.12122DOI Listing
April 2014

Seizure outcome after hippocampal deep brain stimulation in a prospective cohort of patients with refractory temporal lobe epilepsy.

Seizure 2014 Jan 16;23(1):6-9. Epub 2013 Aug 16.

Clinica de Epilepsia de Sao Paulo, Epilepsy Surgery Program, Sao Paulo, SP, Brazil.

Purpose: In this study, we present the results obtained from a series of patients with refractory temporal lobe epilepsy (r-TLE) who underwent hippocampal deep brain stimulation (Hip-DBS).

Methods: Nine consecutive adult patients were studied. Low-frequency and high-frequency stimulation was carried out immediately after the insertion of each electrode. Chronic continuous high-frequency stimulation was used during treatment. The mean follow-up time was 30.1 months. The mean age of the patients was 37.2 years. The MRI scan was normal in three patients; four patients had bilateral mesial temporal sclerosis (MTS), and two had unilateral MTS.

Results: The patients with unilateral MTS received unilateral implantation and experienced a 76% and an 80% reduction in seizure frequency after Hip-DBS. All patients with normal MRI scans were implanted bilaterally. Two of these patients received unilateral activation of the electrodes and experienced a 97% and an 80% reduction in seizure frequency; the third patient had bilateral activation of the device and was a non-responder. All patients with bilateral MTS were implanted bilaterally. Three of these patients received unilateral activation of the device and experienced a 66%, a 66% and a 100% reduction in seizure frequency after Hip-DBS; one patient had bilateral electrode activation, and was a non-responder. Whenever present, generalised tonic-clonic seizures disappeared completely after Hip-DBS.

Conclusions: Although performed on a relatively small number of patients, Hip-DBS was safe and effective in our patients with r-TLE. Seven of the nine patients were considered responders. Hip-DBS might represent a useful therapeutic option in patients with refractory temporal lobe epilepsy who were not candidates for resective surgery or have had previous failed procedures.
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http://dx.doi.org/10.1016/j.seizure.2013.08.005DOI Listing
January 2014

A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy.

Neuromodulation 2013 Nov-Dec;16(6):551-6; discussion 556. Epub 2013 Jun 5.

Introduction: We report the outcome after vagus nerve stimulation (VNS) in children with secondary generalized epilepsy.

Methods: Twenty-four consecutive children with Lennox-Gastaut or Lennox-like syndrome under the age of 12 years by the time of surgery, who were implanted with a vagus nerve stimulator and had at least two years of postimplantation follow-up, were prospectively included in the study. The generator was turned on using 0.25 mA, 30 Hz, 500 μsec, 30 sec "on," 5 min "off" stimuli parameters; current was then increased by 0.25 mA every two weeks, until 3.5 mA was reached or adverse effects were noted.

Results: Magnetic resonance imaging was normal or showed atrophy in 13 children. Six children got an end-of-study (24 months) postimplantation video-electroencephalogram, and their findings were similar to those before VNS. Quality of life and health measures improved in up to 50% (mean = 25%) in 20 children. Attention was noted to improve in 21 out of the 24 children. Final intensity parameters ranged from 2 to 3.5 mA (mean = 3.1 mA). An implantation effect was noted in 14 out of the 24 children, and lasted a mean of 20.2 days. There were 47 seizure types among the 24 children. An at least 50% seizure frequency reduction was noted in 35 seizure types and 17 seizure types disappeared after VNS. Atypical absence, myoclonic and generalized tonic-clonic seizures were significantly reduced by VNS; tonic and atonic seizures did not improve. Transient seizure frequency worsening was noted in ten of the 24 children, at a mean of 3.1 mA.

Discussion: Our study showed that VNS was effective in reducing atypical absence, generalized tonic-clonic, and myoclonic seizures (but not atonic or tonic seizures) in children with Lennox-Gastaut or Lennox-like syndrome. A concomitant improvement in attention level and quality of life and health also was noted. Secondary generalized epilepsy represents a subset of good candidates for VNS.
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http://dx.doi.org/10.1111/j.1525-1403.2012.00522.xDOI Listing
September 2014

Long-term outcome after callosotomy or vagus nerve stimulation in consecutive prospective cohorts of children with Lennox-Gastaut or Lennox-like syndrome and non-specific MRI findings.

Seizure 2013 Jun 13;22(5):396-400. Epub 2013 Mar 13.

Clinica de Epilepsia de Sao Paulo, Epilepsy Surgery Program, Sao Paulo, SP, Brazil.

Purpose: There is currently no resective (potentially curative) surgical option that is useful in patients with Lennox-Gastaut syndrome. Palliative procedures such as callosotomy (Cx), vagus nerve stimulation (VNS) or deep brain stimulation have been offered. We compared the outcomes after Cx or VNS in two consecutive prospective cohorts of patients with generalised epilepsy.

Methods: Twenty-four patients underwent callosotomy from 2006 to 2007 (Group 1); 20 additional patients were submitted to VNS from 2008 to 2009 (Group 2). They had generalised epilepsy of the Lennox-Gastaut or Lennox-like type. They were submitted to a neurological interview and examination, interictal and ictal video-EEG, high resolution 1.5T MRI, and cognitive and quality of life evaluations. The two-year post-operative follow-up results were evaluated for each patient.

Results: The final mean stimuli intensity was 3.0 mA in the Group 2 patients. Seizure-free patients accounted for 10% in Group 1 and none in Group 2. Ten and sixteen percent of the Group 1 and 2 patients, respectively, were non-responders. Improvements in attention and quality of life were noted in 85% of both Group 1 and 2 patients. Rupture of the secondary bilateral synchrony was noted in 85% of Group 1 patients; there was no EEG modification after VNS in Group 2. Both procedures were effective regarding the control of atypical absences and generalised tonic-clonic seizures. Both procedures were not effective in controlling tonic seizures. Callosotomy was very effective in reducing the frequency of atonic seizures, but VNS was ineffective. In contrast, callosotomy was not effective in reducing myoclonic seizures, whereas VNS was.

Discussion: Callosotomy might be preferred as the primary treatment in children with Lennox-Gastaut syndrome, and no specific findings on MRI if atonic seizures prevail in the patient's clinical picture; when myoclonic seizures prevail, the same might hold true in favour of VNS. When atypical absence or generalised tonic-clonic seizures are the main concern, although both procedures carry similar effectiveness, VNS might be considered a good option as an initial approach, taking into account the adverse event profile. Patients should be advised that both procedures are not very effective in the treatment of tonic seizures.
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http://dx.doi.org/10.1016/j.seizure.2013.02.009DOI Listing
June 2013

Neuropsychological and quality of life assessment in patients with Parkinson's disease submitted to bilateral deep brain stimulation in the subthalamic nucleus.

Dement Neuropsychol 2012 Oct-Dec;6(4):260-265

MD, Neurosurgeon in Chief-Movement Disorders Unit - Department of Neurosurgery of Hospital "Euriclydes de Jesus Zerbini", São Paulo SP, Brazil.

Deep brain stimulation (DBS) has been widely used to control motor symptoms and improve quality of life in patients with Parkinsons disease (PD). Recently, DBS in the subthalamic nucleus (STN) has become the preferred target for patients with mixed motor symptoms. Despite resultant motor and quality of life improvements, the procedure has been associated with cognitive decline, mainly in language skills, and also with psychiatric symptoms.

Objective: To evaluate the influence of DBS in the STN on cognition, mood and quality of life.

Methods: We studied 20 patients with PD submitted to DBS in the STN from May 2008 to June 2012 with an extensive battery of cognitive tests including memory, language, praxis, executive functions and attention assessments; the Parkinson's Disease Quality of Life Questionnaire (PDQ-39); and the Hospital Anxiety and Depression Scale (HAD), were applied both before and after the surgery. Data was analyzed using SPSS version 17.0 and results compared using the paired Student's test.

Results: A total of 20 patients with pre and post-operative assessments were included. A statistically significant improvement was found in total score and on subscales of mobility, activities of daily living and emotional well-being from the PDQ-39 (P=0.009, 0.025, 0.001 and 0.034, respectively). No significant difference was found on the cognitive battery or mood scale.

Conclusion: DBS in the SNT improved quality of life in PD with no negative impact on cognitive skills and mood.
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http://dx.doi.org/10.1590/S1980-57642012DN06040010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619338PMC
December 2017

Brain electrical activity after acute hippocampal stimulation in awake rats.

Neuromodulation 2013 Mar-Apr;16(2):100-4. Epub 2012 Aug 6.

Neurologia Experimental, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.

Objective: We describe the electrocorticographic findings after hippocampal stimulation in normal awake rats.

Methods: Six male Wistar rats were implanted bilaterally with neocortical and hippocampal electrodes. The animals were submitted to hippocampal low- and high-frequency stimulation.

Results: Recruiting responses were seen in the ipsilateral hippocampus after unilateral low-frequency (6 Hz) hippocampal stimulation with low voltage (0.3 V). These recruiting responses could be seen at the contralateral hippocampus with slightly higher voltage (0.5 V) and over the ipsilateral neocortex with stimulation with 1.2 V. Bilateral neocortical recruiting responses were noted at stimuli voltage of 1.5 V. There were no recruiting responses after high-frequency stimulation (130 Hz). A dorsal column (DC) shift, characterized by baseline oscillation without brain activity modification, was noted in all animals after hippocampal stimulation with frequency higher than 60 Hz. The increase of stimulation frequency from 6 to 130 Hz (1.2 V, 300 µ sec) showed progressive reduction in the amplitude and disappearance of the time-locked recruiting responses, especially from around 60 Hz.

Conclusions: Bilateral hippocampal and cortical recruiting responses were easily obtained in all animals after low-frequency hippocampal unilateral stimulation. High-frequency stimulation did not give rise to recruiting response, although a DC shift was noted. The fact that unilateral hippocampal stimulation might lead to bilateral limbic system modulation suggested that unilateral stimulation might be enough in many situations. Our findings suggested that high-frequency stimulation was more likely to be effective than low-frequency stimulation regarding the potential inactivation of the hippocampus. These findings might prove relevant to the determination of the adequate parameters for stimulation using hippocampal deep brain stimulation (DBS) in the future. An increase in our knowledge on the physiologic mechanisms underlying DBS might be translated into more rational clinical approaches.
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http://dx.doi.org/10.1111/j.1525-1403.2012.00491.xDOI Listing
September 2013

Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation.

Seizure 2011 Dec 22;20(10):748-53. Epub 2011 Jul 22.

Department of Neurology & Neurosurgery, Epilepsy Surgery Program, Hospital Brigadeiro, São Paulo, Brazil.

Purpose: Deep brain stimulation (DBS) has been used in an increasing frequency for treatment of refractory epilepsy. Acute deep brain macrostimulation intraoperative findings were sparsely published in the literature. We report on our intraoperative macrostimulation findings during thalamic and hippocampal DBS implantation.

Methods: Eighteen patients were studied. All patients underwent routine pre-operative evaluation that included clinical history, neurological examination, interictal and ictal EEG, high resolution 1.5T MRI and neuropsychological testing. Six patients with temporal lobe epilepsy were submitted to hippocampal DBS (Hip-DBS); 6 patients with focal epilepsy were submitted to anterior thalamic nucleus DBS (AN-DBS) and 6 patients with generalized epilepsy were submitted to centro-median thalamic nucleus DBS (CM-DBS). Age ranged from 9 to 40 years (11 males). All patients were submitted to bilateral quadripolar DBS electrode implantation in a single procedure, under general anesthesia, and intraoperative scalp EEG monitoring. Final electrode's position was checked postoperatively using volumetric CT scanning. Bipolar stimulation using the more proximal and distal electrodes was performed. Final standard stimulation parameters were 6Hz, 4V, 300μs (low frequency range: LF) or 130Hz, 4V, 300μs (high frequency range: HF).

Key Findings: Bilateral recruiting response (RR) was obtained after unilateral stimulation in all patients submitted to AN and CM-DBS using LF stimulation. RR was widespread but prevailed over the fronto-temporal region bilaterally, and over the stimulated hemisphere. HF stimulation led to background slowing and a DC shift. The mean voltage for the appearance of RR was 4V (CM) and 3V (AN). CM and AN-DBS did not alter inter-ictal spiking frequency or morphology. RR obtained after LF Hip-DBS was restricted to the stimulated temporal lobe and no contralateral activation was noted. HF stimulation yielded no visually recognizable EEG modification. Mean intensity for initial appearance of RR was 3V. In 5 of the 6 patients submitted to Hip-DBS, an increase in inter-ictal spiking was noted unilaterally immediately after electrode insertion. Intraoperative LF stimulation did not modify temporal lobe spiking; on the other hand, HF was effective in abolishing inter-ictal spiking in 4 of the 6 patients studied. There was no immediate morbidity or mortality in this series.

Significance: Macrostimulation might be used to confirm that the hardware was working properly. There was no typical RR derived from each studied thalamic nuclei after LF stimulation. On the other hand, absence of such RRs was highly suggestive of hardware malfunction or inadequate targeting. Thalamic-DBS (Th-DBS) RR was always bilateral after unilateral stimulation, although they somehow prevailed over the stimulated hemisphere. Contrary to Th-DBS, Hip-DBS gave rise to localized RR over the ipsolateral temporal neocortex, and absence of this response might very likely be related to inadequate targeting or hardware failure. Increased spiking was seen over temporal neocortex during hippocampal electrode insertion; this might point to the more epileptogenic hippocampal region in each individual patient. We did not notice any intraoperative response difference among patients with temporal lobe epilepsy with or without MTS. The relationship between these intraoperative findings and seizure outcome is not yet clear and should be further evaluated.
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http://dx.doi.org/10.1016/j.seizure.2011.07.003DOI Listing
December 2011

Speech preservation using a non-linear paradigm for determination of the extent of neocortical resection in patients with mesial temporal sclerosis submitted to cortico-amygdalo-hippocampectomy (CAH).

Seizure 2011 Oct 2;20(8):612-5. Epub 2011 Jul 2.

Epilepsy Surgery Program, Hospital Brigadeiro, São Paulo, SP, Brazil.

Rationale: The rationale for using a non-linear (proportional) paradigm for determining the extent of the neocortex to be removed in temporal lobe resection was based on anatomical and intra-operative cortical mapping findings. We present our results regarding speech preservation in patients submitted to CAH using the central artery as an anatomical landmark for determining the posterior border of neocortical resection.

Methods: Two hundred and fifty consecutive right-handed patients with left unilateral mesial sclerosis were studied. All patients were submitted to CAH under general anesthesia and without intraoperative electrocorticography. The posterior border of the lateral neocortical resection was defined by a line perpendicular to the temporal axis at the level of the central artery.

Results: Seven patients had transient (1-3 weeks; mean=9 days) receptive speech disturbance. There was no permanent speech deficit. Imaging documented edema or contusion at the posterior temporal cortical border in all patients who had transient speech deficits. The mean extent of cortical resection was 3.9 cm in adults and 3.1cm in kids.

Discussion: This is the first report in the literature discussing the use of a non-linear paradigm to determine the extent of lateral neocortical removal in this patient population. We found no permanent speech disturbances in this series. The non-linear approach used in this series proved to be safe and effective to avoid post-operative speech disorders. It was able to compensate for different brain and head sizes, and allowed smaller neocortical removal when compared to traditional linear approaches.
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http://dx.doi.org/10.1016/j.seizure.2011.06.002DOI Listing
October 2011

Outcome after cortico-amygdalo-hippocampectomy in patients with temporal lobe epilepsy and normal MRI.

Seizure 2010 Jul 21;19(6):319-23. Epub 2010 May 21.

Epilepsy Surgery Program, Hospital Brigadeiro, São Paulo, SP, Brazil.

Rationale: We describe seizure and neuropsychological outcome obtained after CAH in patients with TLE and normal MRI evaluated in the modern imaging era.

Methods: Forty-five adult consecutive patients with TLE and normal MRI were studied. All patients had neuropsychological testing, interictal and ictal EEG recordings and MRI. They were divided into two groups: Group 1 (n=18), included patients in whom non-invasive neurophysiological evaluation was lateralizing and Group 2 (n=27) included patients with non-lateralizing neurophysiological data who were submitted to invasive recordings.

Results: Seventy-seven percent of the Group 1 patients were rated as Engel I; 11% were rated as Engel II and 11% as Engel III. In Group 2, there were 57% of patients seizure-free, 26% in Engel II and 14% in Engel III. Pre-operatively, mean general IQ was 82 and 78 in Groups 1 and 2, respectively; post-operatively, mean general IQ was respectively 86 and 71. Some degree of verbal memory decline was noted in all patients submitted to dominant temporal lobe resection in both Groups 1 and 2. At last follow-up visit, 22% of Group 1 and 11% of Group 2 patients were receiving no antiepileptic drugs (AED).

Conclusions: Our data showed that patients with TLE and normal MRI could get good surgical results after CAH although 60% of them would need invasive recordings and their results regarding seizure control and cognition were worse than those obtained in patients with MRI defined temporal lobe lesions. Caution should be taken in offering dominant temporal lobe resection to this subset of patients.
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http://dx.doi.org/10.1016/j.seizure.2010.04.012DOI Listing
July 2010