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Background: Despite the acute infection's remission, COVID-19 is associated with clinically severe residual symptoms (i.e., post-COVID-19 syndrome). One of the most prevalent and incapacitating symptoms of the syndrome is fatigue, accompanied by cognitive impairment. Very few therapy options are effective for post-acute SARS-Cov-2 sequelae (PASC). There is a possibility that non-invasive brain stimulation methods could become successful and convenient treatment options for post-acute and chronic COVID-19. There are already the first clinical results for the use of transcranial direct current stimulation (tDCS) in the therapy of PASC. Our goal was to study the potential tDCS effect on cognitive impairment in patients with PASC. Method(s): We present a four-week, double-blind, randomized, placebo-controlled, parallel study with a 4-week active dorsolateral prefrontal cortex (DLPFC) tDCS (20 tDCS applications;anode on the F3;2 mA, 30 min/tDCS session). Patients were evaluated with tests measuring attention (digit span forward), working memory (digit span backward), and psychomotor speed (digit symbol substitution test) at baseline, after two weeks, and at the end of four weeks of treatment. The tests were chosen according to previous studies on the assessment of cognitive function in patients after COVID-19. Result(s): 15 out of 34 enrolled patients were included in Intention-to-treat (ITT) analysis. The treatment groups did not differ in age, gender, and baseline cognitive tests. There wasn't a significant difference in cognitive tests results between active DLPFC tDCS and sham tDCS after four weeks. However, the study is still in progress and the results will be updated. No major side effects were observed during and after the treatment. Supported by grant No. NU22-D-133 of the MH CR. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: cognitive symptoms, post-acute sequelae of SARS-Cov-2, transcranial direct current stimulation, dorsolateral prefrontal cortexCopyright © 2023
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Symposium title: The potential role of tDCS in the management of Post-Acute Sequelae of SARS-COV-2 (PASC) Symposium description: The novel SARS-CoV-2 virus has infected millions of people worldwide. Post-infectious symptoms, referred to as Post-Acute Sequelae of SARS-CoV-2 (PASC), affect a large and growing segment of survivors, lasting months or even years without recovery. With continuous COVID-19 infections, PASC is a growing problem for public health. Therefore, effective and accessible treatment options need to be evaluated urgently. PASC symptoms are multi-systemic and can vary by the individual in clinical presentation, and its underlying pathological mechanisms remain uncharacterized. tDCS is a well-tolerated and extensively characterized noninvasive neuromodulation technique, and is effective in targeting the neuropsychiatric symptoms that define PASC (i.e., fatigue, cognitive, pain, emotional) including in other post-viral conditions. In addition, tDCS may have a larger role in the management of persisting respiratory symptoms. We will provide an overview of the theoretical basis and work to date supporting tDCS as a tool for PASC management, and present initial findings from recently completed and ongoing clinical trials. When COVID-19 first emerged, many researchers were focused on its impact on the lungs. As we have learned more about SARS-CoV-2 and resulting COVID-19, we have discovered that patients present a greater complexity in the context of the neurotrauma and the pulmonary lesions can become an aggravation of the neuroinvasion of the coronavirus and originate from cerebral injury. Recently, it has been suggested that noninvasive brain stimulation could be a valuable tool for the management of the early and postacute phase of patients with COVID-19. This session will present the results of our investigation of the High-definition transcranial direct current stimulation effects during the acute and chronic recovery phase from COVID-19. The prognostic factors and clinical predictors that contribute to greater response to treatment will be presented and directions for future research will be discussed. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: HD-tDCS, Coronavirus disease, Noninvasive brain stimulation, Long COVID-19Copyright © 2023
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Introduction Since the start of the COVID-9 pandemic, inpatient hospital resources have become extremely limited. This has limited access to surgical care for patients, especially for elective surgeries. Deep brain stimulation (DBS) surgery has been known to be very safe with very low rates of serious complications but has typically been accompanied with an inpatient hospital stay. Performing DBS surgery as an outpatient procedure could preserve access to this important treatment option, even during medical scarcity. Methods From March 2020 to January of 2021, stage I DBS surgery was scheduled as outpatient surgery for 19 patients. DBS patients who were scheduled as inpatient admissions were included as a comparison. Cohorts were compared based on time until discharge, early surgical complications, readmissions, emergency department (ED) visits, as well as demographic patient characteristics. Results Eighteen patients underwent a DBS scheduled as an outpatient surgery were compared to 20 patients who were scheduled as inpatient surgeries. Only 1 patient scheduled as an outpatient surgery was admitted overnight. This was due to an asymptomatic hemorrhage seen on routine post op imaging. There were no significant differences between readmissions, ED visits, or complications between the groups. In the outpatient surgery group, there were 2 post op ED visits and no admissions. There were no symptomatic hemorrhages, surgical site infections, readmissions, or reoperations in the outpatient group. The post op admission time for the two groups was 3.72h (+/-1.11) vs 26.83h (+/-3.49) (p<0.0001). Conclusion Outpatient DBS surgery does not result in increases in readmissions or emergency visits. This could allow increased availability of DBS surgery during times of medical scarcity and lower the economic barriers to DBS surgery..
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Introduction: According to WHO, there are more than 300,000,000 people worldwide suffering from depression. It is the world's leading cause of disability and contributes significantly to the overall global burden of disease. 30% of the patients are refractory, being possible candidates for surgical treatment by means of Deep Brain Stimulation (DBS). We present the follow up at 22 months of a patient with Treatment Refractory Depression (TRD) operated on with a new combination of targets. Materials / Methods: The diagnostic criteria used are those established by Mayberg et al: DSM IV-TR criteria for major depressive disorder with a major depressive episode of at least 1 year duration, with a minimum score of 20 on the 17-item Hamilton Depression Scale (HAM-D). Result(s): 55-year-old male. HAM-D: 26-point. It was decided to simultaneously implant Area 25 (SCG/Cg 25) and the Inferior Thalamic Peduncle (ITP) in order to contemplate the synergistic effect of stimulation of both structures. On December 5, 2018, it was successfully implanted, with previously published techniques, using a deep brain micro register system and stereotactic planning to define the coordinates of each selected target for the implantation of the four tetrapolar electrodes, model 6145 (Abbott) for Area 25 and model 6149 for ITP (Abbott). The electrode implanted in Area 25 was kept lit for 3 months, then only the corresponding to the ITP for an additional 3 months, and finally the four electrodes simultaneously maintaining the stimulation parameters reported in the literature. Post-surgical HAM-D scales were performed, with the following results: * Exclusively Area 25 (21/03/19) = 10 points * Exclusively ITP (13/06/19) = 9 points * Area 25 + ITP (08/08/19) = 14 points. * Area 25 + ITP (19/12/19) = 5 points. * Area 25 + ITP (08/10/20) = 5 points. Discussion(s): The possibility of multiple targets is technically possible and appropriate in very well selected cases. Conclusion(s): The patient showed a statistically significant improvement. Despite maintaining a rating of 5, it is worth mentioning that the patient refers feeling "better" than the previous year considering the time of year (spring), and the burden of the COVID-19 pandemic. This confirms some reports that mention the maintenance of the effect in the long term, even at 8 years, or even an improvement after almost two years can be seen. We consider that the synergism obtained by simultaneous stimulation of both targets could be more effective in terms of control of the depressive state at the long term. Supplemental Data: none. Learning Objectives: 1- To present a new therapeutic modality of multitargeting DBS for major depression. 2- To demonstrate that the combination of surgical targets is a possible option in carefully selected patients. 3- To demonstrate that the therapeutic effect is maintained over the time. Keywords: depression, deep brain stimulation, Area 25, inferior thalamic peduncle, multitargeting Copyright © 2022
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Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.
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Objective: To assess the utility of the recently FDA approved Virtual Clinic platform that enables clinicians to remotely make programming changes in DBS patients. Background: DBS in Parkinson's disease and Essential tremor requires multiple in-person programming sessions for therapy optimization and management. Until recently, this was only possible through inperson clinic sessions which place time, travel and fiscal burdens on patients and caregivers limiting their access to care. This has an even greater bearing on patients that are dependent on caregivers, need to take time off from work or are concerned about exposure during COVID-19. The recent FDA approved NeuroSphere™ Virtual Clinic enables clinicians for the first time to remotely make programming changes over the internet to help DBS patients. Methods: 34 patients provided signed written consent to Abbott or verbal consent to the Clinician to be enrolled. The enrolled Abbott Infinity™ IPGs were securely mapped to authorized Clinicians. Software on programming devices was upgraded without requiring any hardware or firmware changes. Patients initiated remote sessions and Clinicians securely connected to the IPGs using unique logins and multi-factor authentication. Stimulation changes were synchronized with integrated video and a failsafe mechanism ensured continuity of therapy in case of network failure. Results: Of the 34 patients programmed remotely, 74% benefited from stimulation changes, 26% from side effects resolution, 9% from battery status check, 6% were out of the country when they needed intervention, 29% completed routine follow-up. The use of this platform has allowed seamless virtual patient visits reducing the patient burdens related to access to care as well as increasing throughput in our clinic. We have also billed for these sessions for reimbursement in the US using the Telemedicine modifier code (95). The average time to establish a session has been less than 1 minute with no perceptible difference in system checks and stimulation changes. Remote programming is both clinically viable and valuable to patients, caregivers and clinicians. Conclusion: Remote programming is both clinically viable and valuable to patients, caregivers and clinicians.
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Objective: The COVID-19 pandemic created unique challenges for neuropsychological assessment of DBS candidates due to physical distancing and safety requirements. Existing literature has demonstrated guidelines and feasibility of neuropsychological measures administered via teleconference, but none to our knowledge have assessed implementation, feasibility, clinical utility, and acceptance of home-to-home TeleNP in determining candidacy for DBS in Parkinson's disease (PD) patients. Background: PD is the second most common neurodegenerative disorder and DBS surgery offers significant improvement in motor symptoms and quality of life for medication refractory patients. Since neuropsychologists play an essential role in evaluating cognitive and behavioral changes that impact decisions on DBS surgical candidacy, adapting current practices is critical for continuity of care. Design/Methods: PD patients [n=72, M =63.3(8.76), 65.3% male, M =14.7(2.93), 50.7% Hispanic, 58.3% tested in English/41.7% in Spanish) underwent neuropsychological (global cognition, language, memory, attention, processing speed, visuospatial ability) and emotional assessments via home-to-home TeleNP between May 2020 and August 2021. Independent t-tests were conducted to assess TeleNP discriminability of cognitive and emotional function in surgical candidates. Results: To date, 66 candidates were approved for DBS (44 completed surgery, 17 are pending, 5 opted not to proceed), and 6 were not surgical candidates due to neurocognitive and/or severe psychiatric disorders. Surgical candidate mean neuropsychological scores were average across all domains, with normal to mild mood symptoms. The non-selected group differed by education but not age, and was significantly different (p≤.006) in overall cognition [MoCA t(70)=3.62], age edu working memory [WAIS-IV DS t(70)=3.15], phonemic fluency [COWAT FAS t(70)=2.85], verbal reasoning [WAIS-IV SI t(67)=3.38], perceptual reasoning [WAIS-IV MR t(70)=3.02], depression [BDI-2 t(68)=3.47], and anxiety [BAI t(70)=2.88]. Conclusions: TeleNP is a successful platform for assessing DBS surgical candidacy safely in English and Spanish speaking PD patients and offers potential for providing high quality screening for those with physical limitations, reduced access to transportation, or are living in remote areas.
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Objective: Describe clinical characteristics of COVID-19 in patients with Parkinson's disease (PD). Background: Individuals with PD have an increased risk of severe illness and poor outcomes in the context of COVID-19, though more research is needed. Design/Methods: We retrospectively analyzed clinical data from 18 consecutive patients with PD and COVID-19 presenting to a suburban hospital in the Northwest United States. Results: Our sample was predominantly male (61%) with a mean age of 71. The most common presenting symptoms of COVID-19 were cough (72%), fever (61%), and shortness of breath (50%). The most common comorbid conditions were hypertension (50%), obstructive sleep apnea (33%), dementia (33%), cardiovascular disease (22%), diabetes mellitus (22%), and lung disease (11%). Two patients (11%) had a history of deep brain stimulation, one of whom was also on an apomorphine pump trial. Two patients were asymptomatic with one testing positive on routine screening following an outbreak at her residential facility and the other testing positive prior to a sleep study. The latter received monoclonal antibody infusion as part of FDA emergency use authorization. Six patients (33%) required hospitalization. Eight patients (44%) had exacerbation of underlying PD symptomology. Five of six patients with PD dementia presented with encephalopathy. Two patients presented with increased tremor, one with increased lightheadedness, and one with increased falls. Two patients died. Both deceased patients had PD dementia and presented with encephalopathy. Conclusions: In this cohort of 18 patients with PD and COVID-19, 44% experienced exacerbation of PD symptomology including encephalopathy in those with dementia, tremor, lightheadedness, and falls. Both mortalities were associated with baseline dementia and encephalopathy as a presenting symptom. The results of our study further highlight the risk of severe illness and poor outcomes in those with PD and COVID-19. These findings will be helpful for treating physicians, researchers, individuals with PD and their carepartners.
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Internet gaming addiction (IGA) is a growing concern among adolescents, exacerbated by recent COVID-19 restrictions. The World Health Organization has recently included IGA in the 11th International Classification of Diseases. However, the validity and reliability of the proposed criteria are subjected to controversy 1. Despite growing neurobiological evidence in IGA, most systematic reviews have focused on adults or mixed adult/adolescent populations. Therefore, this systematic review explored the neuroimaging literature in adolescents with IGA. Altogether, 2263 primary studies were identified from PubMed, CINAHL Plus, PsycINFO, and Web of Science. After applying inclusion and exclusion criteria (appropriate title, , comparison group used within study, English-language, neuroimaging, and mean age under 18), 25 articles were included in this review. Functional and structural brain alterations in IGA were noted across several imaging modalities, including electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), and structural magnetic resonance imaging (MRI). Compared with healthy controls, adolescents with IGA demonstrated functional impairment in emotional regulation, reward-seeking, inattention and, inhibition control circuits, leading to increased risky decision making. Structural changes in gray and white matter were noted due to repetitive brain stimulation associated with visual, auditory, and spatial working memory. With regards to brain region processing self-concept, adolescents utilize the medial prefrontal region while having game character thoughts, compared to adults who utilize the left angular gyrus 2. In conclusion, adolescents with IGA showed common neurological findings consistent with other behavioral addictions and psychiatric disorders. Future studies are needed for potential neuroimaging markers that apply to diagnosis and informing treatment.
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COVID-19 presented a renewed awareness of the importance of smell, including the striking impact of smell loss on daily functioning, as well as the lack of available evidencebased interventions to improve smell. While medical and surgical treatments exist for inflammatory-related smell loss, interventions to treat loss due to other etiologies are limited. Given the role of the intranasal trigeminal system in smell function, we conducted a proof-of-concept study to determine the effects of electrical stimulation of the trigeminal nerve (TNS) on sensitivity to phenyl ethyl alcohol (PEA) and guaiacol (GUA), 2 odorants with low and high trigeminal properties, respectively. TNS is an emerging form of “bottom-up” brain stimulation in which low-level electrical current is delivered to superficial trigeminal nerve branches innervating the face and forehead. Twenty healthy adults (8M/12F, 27±8.1 years old) were recruited from MUSC and the surrounding community to participate in this double-blind, placebo-controlled, pilot. PEA and GUA thresholds were determined at baseline, immediately postintervention, and again 30-min post-intervention. In a randomized cross-over design, participants received active and sham TNS on separate visits. Results indicated a significant stimulation x odor x time interaction (F[2,76]=3.56, p=.024, η 2=.093). Detection of GUA, but not PEA, was significantly enhanced by active, but not sham, TNS (16% and 9% increase from baseline at the 1st and 2nd follow-up time points respectively). TNS is safe, noninvasive, inexpensive, and easy to administer, rendering it highly scalable. Future study should determine the full effects and durability of TNS on smell function across different stimulation parameters, odorants, and patient populations.