Erich Fonoff
@.fm.usp.br
Associate Professor
Faculdade de Medicina da University of São Paulo
RESEARCH, TEACHING, or OTHER INTERESTS
Medicine, Neurology (clinical)
Scopus Publications
Scopus Publications
Maria Gabriela S. Ghilardi, Ana Carolina P. Campos, Rubens G. Cury, Raquel C. R. Martinez, Rosana L. Pagano, and Erich T. Fonoff
Springer Science and Business Media LLC
AbstractPain control after deep brain stimulation (DBS) in Parkinson’s disease (PD) remains unclear. Following six months, subthalamic (STN)-DBS reduced sensory complaints related to parkinsonism and bodily discomfort, increasing central beta-endorphin level. Pallidal GPi-DBS decreased bodily discomfort and beta-endorphin levels. Unexplained pain by other conditions and bodily discomfort were negatively correlated with beta-endorphin levels. Thus, DBS regulates central opioids, and prioritizing STN is important for PD patients with significant sensory complications.
Wellingson Silva Paiva, Erich Talamoni Fonoff, Rhuann Pontes dos Santos Silva, Lucas Schiavao, André Russowsky Brunoni, César Cimonari de Almeida, and Carlos Carlotti Júnior
MDPI AG
Transcranial magnetic stimulation (TMS) represents a distinctive technique for non-invasive brain stimulation. Recent advancements in image processing have enabled the enhancement of TMS by integrating magnetic resonance imaging (MRI) modalities with TMS via a neuronavigation system. The aim of this study is to assess the efficacy of navigated TMS for cortical mapping in comparison to surgical mapping using direct electrical stimulation (DES). This study involved 30 neurosurgical procedures for tumors located in or adjacent to the precentral gyrus. The DES points were compared with TMS responses based on the original distances of vectorial modules. There was a notable similarity in the points obtained from the two mapping methods. The distances between the geometric centers of TMS and DCS were 4.85 ± 1.89 mm. A strong correlation was identified between these vectorial points (r = 0.901, p < 0.001). The motor threshold in TMS was highest in the motor cortex adjacent to the tumor compared to the normal cortex (p < 0.001). Patients with deficits exhibited excellent accuracy in both methods. In view of this, TMS demonstrated reliable and precise application in brain mapping, which is a promising method for preoperative functional mapping in motor cortex tumor surgery.
Ana Westenberger, Volha Skrahina, Tatiana Usnich, Christian Beetz, Eva-Juliane Vollstedt, Björn-Hergen Laabs, Jefri J Paul, Filipa Curado, Snezana Skobalj, Hanaa Gaber,et al.
Oxford University Press (OUP)
Abstract Estimates of the spectrum and frequency of pathogenic variants in Parkinson’s disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson’s disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10−34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10−35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10−4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10−14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.
Danielle V. Assis, Ana Carolina P. Campos, Amanda F. N. Paschoa, Talita F. Santos, Erich T. Fonoff, and Rosana L. Pagano
MDPI AG
Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1β in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased β-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic β-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic β-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.
Stefanie T. Jost, Agni Konitsioti, Philipp A. Loehrer, Keyoumars Ashkan, Alexandra Rizos, Anna Sauerbier, Maria Gabriela dos Santos Ghilardi, Franz Rosenkranz, Lena Strobel, Alexandra Gronostay,et al.
Elsevier BV
Artur M. Coutinho, Maria Gabriela Ghilardi, Ana Carolina P. Campos, Elba Etchebehere, Fernanda C. Fonoff, Rubens G. Cury, Rosana L. Pagano, Raquel C. R. Martinez, and Erich T. Fonoff
MDPI AG
Background: Parkinson’s disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. Results: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.
Flavia Venetucci Gouveia, Jurgen Germann, Gavin JB Elias, Alexandre Boutet, Aaron Loh, Adriana Lucia Lopez Rios, Cristina Torres Diaz, William Omar Contreras Lopez, Raquel Chacon Ruiz Martinez, Erich Talamoni Fonoff,et al.
eLife Sciences Publications, Ltd
Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas – together with patient age – were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.
Ana Carolina Pinheiro Campos, Raquel Chacon Ruiz Martinez, Aline Vivian Vatti Auada, Ivo Lebrun, Erich Talamoni Fonoff, Clement Hamani, and Rosana Lima Pagano
MDPI AG
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.
Angelo Rafael Cunha de Azevedo, William Omar Contreras López, Paula Alejandra Navarro, Flavia Venetucci Gouveia, Jürgen Germann, Gavin J.B. Elias, Raquel Chacon Ruiz Martinez, Eduardo Joaquim Lopes Alho, and Erich Talamoni Fonoff
Neurosurgery Ovid Technologies (Wolters Kluwer Health)
BACKGROUND
Hemidystonia (HD) is characterized by unilateral involuntary torsion movements and fixed postures of the limbs and face. It often develops after deleterious neuroplastic changes secondary to injuries to the brain. This condition usually responds poorly to medical treatment, and deep brain stimulation often yields unsatisfactory results. We propose this study based on encouraging results from case reports of patients with HD treated by ablative procedures in the subthalamic region.
OBJECTIVE
To compare the efficacy of stereotactic-guided radiofrequency lesioning of the subthalamic area vs available medical treatment in patients suffering from acquired HD.
METHODS
This is an open-label study in patients with secondary HD allocated according to their treatment choice, either surgical or medical treatment; both groups were followed for one year. Patients assigned in the surgical group underwent unilateral campotomy of Forel. The efficacy was assessed using the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, Arm Dystonia Disability Scale, and SF-36 questionnaire scores.
RESULTS
Patients in the surgical group experienced significant improvement in the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, and Arm Dystonia Disability Scale (39%, 35%, and 15%, respectively) 1 year after the surgery, with positive reflex in quality-of-life measures, such as bodily pain and role-emotional process. Patients kept on medical treatment did not experience significant changes during the follow-up. No infections were recorded, and no neurological adverse events were associated with either intervention.
CONCLUSION
The unilateral stereotaxy-guided ablation of Forel H1 and H2 fields significantly improved in patients with HD compared with optimized clinical treatment.
Tiago Matheus Nordi, Rodrigo Henrique Gounella, Maximiliam Luppe, João Navarro Soares Junior, Erich Talamoni Fonoff, Eduardo Colombari, Murilo Araujo Romero, and João Paulo Pereira do Carmo
Electronics (Switzerland) MDPI AG
Deep-brain stimulation (DBS) is an emerging research topic aiming to improve the quality of life of patients with brain diseases, and a great deal of effort has been focused on the development of implantable devices. This paper presents a low-noise amplifier (LNA) for the acquisition of biopotentials on DBS. This electronic module was designed in a low-voltage/low-power CMOS process, targeting implantable applications. The measurement results showed a gain of 38.6 dB and a −3 dB bandwidth of 2.3 kHz. The measurements also showed a power consumption of 2.8 μW. Simulations showed an input-referred noise of 6.2 μVRMS. The LNA occupies a microdevice area of 122 μm × 283 μm, supporting its application in implanted systems.
Tamine T. C. Capato, Rubens G. Cury, Juliana Tornai, Erich T. Fonoff, Renata Guimarães, Manoel T. Jacobsen, Mônica S. Haddad, and Egberto R. Barbosa
Frontiers Media SA
In advanced stages of in Huntington's disease (HD) gait impairments and severe chorea are usually medication-refractory. The long-term effects on gait in HD of physiotherapy ICF-based management post- globus pallidus deep brain stimulation (GPi DBS) are not well-established. Physiotherapy has been recognized as an essential element in HD treatment. Here, we present a case report of a 56-year-old woman with HD on the advanced stage and severe chorea medication-refractory after GPi-DBS. We performed multidisciplinary motor assessments ICF-based to identify the disability at clinical and home-setting, including environmental and personal factors before and after GPi-DBS surgery and at 11-time points follow-up. The surgery was very successful and directly post GPi-DBS, there were a significant improvement in chorea and a substantial decrease in medication dose. A framework ICF- based physiotherapy protocol with external cues was developed to improve gait was delivered post-surgery and was continued three times/week during 18-months. Physiotherapy sessions consisted of a personalized protocol of exercises with functional movements, balance, and gait training with external cues. Improvements in gait were observed in 3-months post-intervention and were more expressive in 6-months follow-up. Our patient improved substantially HD motor symptoms and her quality of life after GPi-DBS intervention and a physiotherapy program ICF-based. The objective outcomes measures used to assess gait have served as endpoints to assessing the patient's motor profile during the pre-operative period. Assessments were helpful to verify the efficacy of the multidisciplinary intervention in long-term.ConclusionPeriodically assessing function and disability using outcome improvements may support clinicians' decisions about DBS, medication adjustments and guide physiotherapists to personalize the ICF-based intervention.
Denise Spinola Pinheiro and Erich Fonoff
Springer International Publishing
William Omar Contreras Lopez, Paula Alejandra Navarro, Flavia Venetucci Gouveia, Erich Talamoni Fonoff, Ivo Lebrun, Aline V.V. Auada, Eduardo Joaquim Lopes Alho, and Raquel C.R. Martinez
World Neurosurgery Elsevier BV
BACKGROUND
Intermittent Explosive Disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behaviour. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS.
OBJECTIVE
To evaluate efficacy and safety of pHyp-DBS using eight-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters.
METHODS
A prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with eight-contact directional electrodes. Follow-up was performed at 3, 6 and 12 months after surgery.
RESULTS
Four patients (3 men, mean age 27 ± 2.8 yr) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one has co-diagnosis of infantile autism and the fourth presents with drug-resistant epilepsy. There was a marked increase in the levels of GABA and glycine during intraoperative stimulation. The average improvement in aggressive behaviour in the last follow-up was 6 points (Δ: 50%, p= 0.003) while also documenting an important improvement of the SF-36 in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed.
CONCLUSIONS
This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with refractory Intermittent Explosive Disorder and to demonstrate the corresponding mechanism of action through increases in GABA and glycine concentration in the pHyp.
Clement Hamani, Erich T Fonoff, Daniella C Parravano, Valquiria A Silva, Ricardo Galhardoni, Bernardo A Monaco, Jessie Navarro, Lin T Yeng, Manoel J Teixeira, and Daniel Ciampi de Andrade
Brain Oxford University Press (OUP)
Abstract Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active (‘on’) or sham (‘off’) stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2–68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.
Flavia Venetucci Gouveia, Jürgen Germann, Gavin JB. Elias, Clement Hamani, Erich Talamoni Fonoff, and Raquel Chacon Ruiz Martinez
Brain Stimulation Elsevier BV
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Flavia Venetucci Gouveia, Jürgen Germann, Gabriel A. Devenyi, Erich T. Fonoff, Rosa M. C. B. Morais, Helena Brentani, M. Mallar Chakravarty, and Raquel C. R. Martinez
Frontiers in Human Neuroscience Frontiers Media SA
Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.
Eduardo Joaquim Lopes Alho, Erich T. Fonoff, Ana Tereza Di Lorenzo Alho, József Nagy, and Helmut Heinsen
Brain Structure and Function Springer Science and Business Media LLC
Flavia Venetucci Gouveia, Jürgen Germann, Rosa de Morais, Erich Talamoni Fonoff, Clement Hamani, Eduardo Joaquim Alho, Helena Brentani, Ana Paula Martins, Gabriel Devenyi, Raihaan Patel,et al.
Neurosurgery Oxford University Press (OUP)
Abstract BACKGROUND Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. OBJECTIVE To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. METHODS This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). RESULTS Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. CONCLUSION These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.
Carolina Pinto de Souza, Daniel Boari Coelho, Débora da Silva Fragoso Campos, Maria Gabriela dos Santos Ghilardi, Edrin Claro de Oliveira Vicente, Carelis González-Salazar, Marcondes Cavalcante França Junior, Orlando Graziani Povoas Barsottini, José Luiz Pedroso, and Erich Talamoni Fonoff
Parkinsonism and Related Disorders Elsevier BV
Yanan Sui, Ye Tian, Wai Kin Daniel Ko, Zhiyan Wang, Fumin Jia, Andreas Horn, Dirk De Ridder, Ki Sueng Choi, Ausaf A. Bari, Shouyan Wang,et al.
Frontiers in Neurology Frontiers Media SA
Deep brain stimulation (DBS) is one of the most important clinical therapies for neurological disorders. DBS also has great potential to become a great tool for clinical neuroscience research. Recently, the National Engineering Laboratory for Neuromodulation at Tsinghua University held an international Deep Brain Stimulation Initiative workshop to discuss the cutting-edge technological achievements and clinical applications of DBS. We specifically addressed new clinical approaches and challenges in DBS for movement disorders (Parkinson's disease and dystonia), clinical application toward neurorehabilitation for stroke, and the progress and challenges toward DBS for neuropsychiatric disorders. This review highlighted key developments in (1) neuroimaging, with advancements in 3-Tesla magnetic resonance imaging DBS compatibility for exploration of brain network mechanisms; (2) novel DBS recording capabilities for uncovering disease pathophysiology; and (3) overcoming global healthcare burdens with online-based DBS programming technology for connecting patient communities. The successful event marks a milestone for global collaborative opportunities in clinical development of neuromodulation to treat major neurological disorders.
Eduardo Joaquim Lopes Alho, Erich Talamoni Fonoff, and Helmut Heinsen
Elsevier
Tiago Mateus Nordi, V. M. Barbosa, R. H. Gounella, Godfred Asan, Maximiliam Luppe, Joao Navarro, Soares Junior, J. P. Carmo, Erich Talamoni Fonoff, and Eduardo Colombari
IEEE
Deep-Brain Stimulation (DBS) is an emerging area to improve the life of patients with brain deceases and one with the most dynamic research towards implantable devices. This paper presents an electronic circuit to generate mild current pulses for application on Deep-Brain Stimulation (DBS). This circuit can generate current pulses with arbitrary shapes in the range of -514µA to +514µA, with a variable frequency up to at least 130Hz, and minimum pulse duration of 90µs. The simulations showed a power consumption of 1.7mW for currents with symmetric shapes and 1.2V. This circuit was designed in a low-power TSMC 65nm CMOS process, targeting implantable devices.
Ana Carolina P. Campos, Miriã B. Berzuíno, Gabriela R. Barbosa, Helena M. R. C. Freire, Patricia S. Lopes, Danielle V. Assis, Erich T. Fonoff, and Rosana L. Pagano
Cells MDPI AG
Persistent pain is a prevalent symptom of Parkinson’s disease (PD), which is related to the loss of monoamines and neuroinflammation. Motor cortex stimulation (MCS) inhibits persistent pain by activating the descending analgesic pathways; however, its effectiveness in the control of PD-induced pain remains unclear. Here, we evaluated the analgesic efficacy of MCS together with serotonergic and spinal glial modulation in an experimental PD (ePD) rat model. Wistar rats with unilateral striatal 6-OHDA and MCS were assessed for behavioral immobility and nociceptive responses. The immunoreactivity of dopamine in the substantia nigra and serotonin in the nucleus raphe magnus (NRM) and the neuronal, astrocytic, and microglial activation in the dorsal horn of the spinal cord were evaluated. MCS, without interfering with dopamine loss, reversed ePD-induced immobility and hypernociception. This response was accompanied by an exacerbated increase in serotonin in the NRM and a decrease in neuronal and astrocytic hyperactivation in the spinal cord, without inhibiting ePD-induced microglial hypertrophy and hyperplasia. Taken together, MCS induces analgesia in the ePD model, while restores the descending serotonergic pathway with consequent inhibition of spinal neurons and astrocytes, showing the role of MCS in PD-induced pain control.
Bruna Luiza Roim Varotto, Raquel Chacon Ruiz Martinez, Flavia Venetucci Gouveia, Geiza Fernanda Antunes, Gisele Maria de Campos Fabri, Gerson Ballester, Reynaldo Antequera, Silvia Regina Dowgan Tesseroli de Siqueira, Erich Talamoni Fonoff, Manoel Jacobsen Teixeira,et al.
Frontiers in Neurology Frontiers Media SA
Periodontal disease (PD) is an infectious-inflammatory oral disease that is highly prevalent among adolescence and adulthood and can lead to chronic orofacial pain and be associated with anxiety, stress and depression. This study aimed to identify anxiety-like behaviors in the ligature-induced murine preclinical model of PD in different phases of the disease (i.e., acute vs. chronic). Also, we investigated orofacial mechanical allodynia thresholds and superficial cortical plasticity along the orofacial motor cortex in both disease phases. To this aim, 25 male Wistar rats were randomly allocated in acute (14 days) or chronic (28 days) ligature-induced-PD groups and further divided into active-PD or sham-PD. Anxiety-like behavior was evaluated using the elevated plus maze, mechanical allodynia assessed using the von Frey filaments test and superficial motor cortex mapping was performed with electrical transdural stimulation. We observed increased anxiety-like behavior in active-PD animals in the acute phase, characterized by decreased number of entries into the open arm extremities [t(1,7) = 2.42, p = 0.04], and reduced time spent in the open arms [t(1,7) = 3.56, p = 0.01] and in the open arm extremities [t(1,7) = 2.75, p = 0.03]. There was also a reduction in the mechanical allodynia threshold in all active-PD animals [Acute: t(1,7) = 8.81, p &lt; 0.001; Chronic: t(1,6) = 60.0, p &lt; 0.001], that was positively correlated with anxiety-like behaviors in the acute group. No differences were observed in motor cortex mapping. Thus, our findings show the presence of anxiety-like behaviors in the acute phase of PD making this a suitable model to study the impact of anxiety in treatment response and treatment efficacy.
Haidar S. Dafsari, Maria Gabriela dos Santos Ghilardi, Veerle Visser-Vandewalle, Alexandra Rizos, Keyoumars Ashkan, Monty Silverdale, Julian Evans, Raquel C.R. Martinez, Rubens G. Cury, Stefanie T. Jost,et al.
Brain Stimulation Elsevier BV