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Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20-30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case.

The treatment of psychiatric patients presents significant challenges to the clinical community, and a multidisciplinary approach to diagnosis and management is essential to facilitate optimal care. In particular, the neurosurgical treatment of psychiatric disorders, or \"psychosurgery,\" has held fascination throughout human history as a potential method of influencing behavior and consciousness. Early evidence of such procedures can be traced to prehistory, and interest flourished in the nineteenth and early twentieth century with greater insight into cerebral functional and anatomic localization. However, any discussion of psychosurgery invariably invokes controversy, as the widespread and indiscriminate use of the transorbital lobotomy in the mid-twentieth century resulted in profound ethical ramifications that persist to this day. The concurrent development of effective psychopharmacological treatments virtually eliminated the need and desire for psychosurgical procedures, and accordingly the research and practice of psychosurgery was dormant, but not forgotten. There has been a recent resurgence of interest for non-ablative therapies, due in part to modern advances in functional and structural neuroimaging and neuromodulation technology. In particular, deep brain stimulation is a promising treatment paradigm with the potential to modulate abnormal pathways and networks implicated in psychiatric disease states. Although there is enthusiasm regarding these recent advancements, it is important to reflect on the scientific, social, and ethical considerations of this controversial field.

Abstract BACKGROUND Obsessive compulsive disorder (OCD) is a complex neuropsychiatric disease characterized by obsessions and compulsions. Deep brain stimulation (DBS) has demonstrated efficacy in improving symptoms in medically refractory patients. Multiple targets have been investigated. OBJECTIVE To systematically review the current level and quality of evidence supporting OCD-DBS by target region with the goal of establishing a common nomenclature. METHODS A systematic literature review was performed using the PubMed database and a patient/problem, intervention, comparison, outcome search with the terms “DBS” and “OCD.” Of 86 eligible articles that underwent full-text review, 28 were included for review. Articles were excluded if the target was not specified, the focus on nonclinical outcomes, the follow-up period shorter than 3 mo, or the sample size smaller than 3 subjects. Level of evidence was assigned according to the American Association of Neurological Surgeons/Congress of Neurological Surgeons joint guideline committee recommendations. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Selected publications included 9 randomized controlled trials, 1 cohort study, 1 case-control study, 1 cross-sectional study, and 16 case series. Striatal region targets such as the anterior limb of the internal capsule, ventral capsule/ventral striatum, and nucleus accumbens were identified, but stereotactic coordinates were similar despite differing structural names. Only 15 of 28 articles included coordinates. CONCLUSION The striatal area is the most commonly targeted region for OCD-DBS. We recommend a common nomenclature based on this review. To move the field forward to individualized therapy, active contact location relative to stereotactic coordinates and patient specific anatomical and clinical variances need to be reported.

Abstract BACKGROUND Models have been developed for predicting ideal contact and amplitude for subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Pulse-width is generally varied to modulate the size of the energy field produced. Effects of varying frequency in humans have not been systematically evaluated. OBJECTIVE To examine how altered frequencies affect blood oxygen level-dependent activation in PD. METHODS PD subjects with optimized DBS programming underwent functional magnetic resonance imaging (fMRI). Frequency was altered and fMRI scans/Unified Parkinson Disease Rating Scale motor subunit (UPDRS-III) scores were obtained. Analysis using DBS-OFF data was used to determine which regions were activated during DBS-ON. Peak activity utilizing T-values was obtained and compared. RESULTS At clinically optimized settings (n = 14 subjects), thalamic, globus pallidum externa (GPe), and posterior cerebellum activation were present. Activation levels significantly decreased in the thalamus, anterior cerebellum, and the GPe when frequency was decreased (P < .001). Primary somatosensory cortex activation levels significantly decreased when frequency was increased by 30 Hz, but not 60 Hz. Sex, age, disease/DBS duration, and bilaterality did not significantly affect the data. Retrospective analysis of fMRI activation patterns predicted optimal frequency in 11/14 subjects. CONCLUSION We show the first data with fMRI of STN DBS-ON while synchronizing cycling with magnetic resonance scanning. At clinically optimized settings, an fMRI signature of thalamic, GPe, and posterior cerebellum activation was seen. Reducing frequency significantly decreased thalamic, GPe, and anterior cerebellum activation. Current standard-of-care programming can take up to 6 mo using UPDRS-III testing alone. We provide preliminary evidence that using fMRI signature of frequency may have clinical utility and feasibility. Graphical Abstract Graphical Abstract

Extreme climatic events, including drought, are predicted to increase in intensity, frequency, and geographic extent as a consequence of global climate change. In general, to grow crops successfully in the future, growers will need to adapt to less available water and to take better advantage of the positive effects of drought. Fortunately, there are positive effects associated with drought. Drought stimulates the secondary metabolism, thereby potentially increasing plant defences and the concentrations of compounds involved in plant quality, particularly taste and health benefits. The role of drought on the production of secondary metabolites is of paramount importance for fruit crops. However, to manage crops effectively under conditions of limited water supply, for example by applying deficit irrigation, growers must consider not only the impact of drought on productivity but also on how plants manage the primary and secondary metabolisms. This question is obviously complex because during water deficit, trade-offs among productivity, defence, and quality depend upon the intensity, duration, and repetition of events of water deficit. The stage of plant development during the period of water deficit is also crucial, as are the effects of other stressors. In addition, growers must rely on relevant indicators of water status, i.e. parameters involved in the relevant metabolic processes, including those affecting quality. Although many reports on the effects of drought on plant function and crop productivity have been published, these issues have not been reviewed thus far. Here, we provide an up-to-date review of current knowledge of the effects of different forms of drought on fruit quality relative to the primary and secondary metabolisms and their interactions. We also review conventional and less conventional indicators of water status that could be used for monitoring purposes, such as volatile compounds. We focus on fruit crops owing to the importance of secondary metabolism in fruit quality and the importance of fruits in the human diet. The issue of defence is also briefly discussed.

Directional deep brain stimulation (DBS) technology aims to address the limitations, such as stimulation-induced side effects, by delivering selective, focal modulation via segmented contacts. However, DBS programming becomes more complex and time-consuming for clinical feasibility. Local field potentials (LFPs) might serve a functional role in guiding clinical programming. In this pilot study, we investigated the spectral dynamics of directional LFPs in subthalamic nucleus (STN) and their relationship to motor symptoms of Parkinson's disease (PD). We recorded intraoperative STN-LFPs from 8-contact leads (Infinity-6172, Abbott Laboratories, Illinois, United States) in 8 PD patients at rest. Directional LFPs were referenced to their common average and time-frequency analysis was computed using a modified Welch periodogram method. The beta band (13-35 Hz) features were extracted and their correlation to preoperative UPDRS-III scores were assessed. Normalized beta power (13-20 Hz) and normalized peak power (13-35 Hz) were found to be higher in anterior direction despite lack of statistical significance ( > 0.05). Results of the Spearman correlation analysis demonstrated positive trends with bradykinesia/rigidity in dorsoanterior direction ( = 0.659, = 0.087) and with axial scores in the dorsomedial direction ( = 0.812, = 0.072). Given that testing all possible combinations of contact pairs and stimulation parameters is not feasible in a single clinic visit, spatio-spectral LFP dynamics obtained from intraoperative recordings might be used as an initial marker to select optimal contact(s).

Abstract BACKGROUND Secondary to the complex care, involved specialty providers, and various etiologies, chronic pelvic pain patients do not receive holistic care. OBJECTIVE To compare our general and neuromodulation cohorts based on referrals, diagnosis, and therapy and describe our neuromodulation patients. METHODS A multidisciplinary team was established at our center. The intake coordinator assessed demographics and facilitated care of enrolled patients. Outcomes were compared using minimal clinical important difference of current Numerical Rating Scale (NRS) between patients with neuropathic pain who received neuromodulation and those who did not. The neuromodulation cohort completed outcome metrics at baseline and recent follow-up, including NRS score (best, worst, and current), Oswestry Disability Index (ODI), Beck Depression Inventory, and Pain Catastrophizing Scale. RESULTS Over 7 yr, 233 patients were referred to our consortium and 153 were enrolled. A total of 55 patients had neuropathic pain and 44 of those were managed medically. Eleven underwent neuromodulation. A total of 45.5% patients of the neuromodulation cohort were classified as responders by minimal clinically important difference compared to 26.6% responders in the control cohort at most recent follow-up (median 25 and 33 mo, respectively). Outcome measures revealed improvement in NRS at worst (P = .007) and best (P = .025), ODI (P = .014), and Pain Catastrophizing Scale Rumination (P = .043). CONCLUSION Eleven percent of patients were offered neuromodulation. There were more responders in the neuromodulation cohort than the conservatively managed neuropathic pain cohort. Neuromodulation patients showed significant improvement at 29 mo in NRS best and worst pain, disability, and rumination. We share our algorithm for patient management. Graphical Abstract Graphical Abstract

Abstract BACKGROUND In 2020, the Guidelines Task Force conducted another systematic review of the relevant literature on deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) to update the original 2014 guidelines to ensure timeliness and accuracy for clinical practice. OBJECTIVE To conduct a systematic review of the literature and update the evidence-based guidelines on DBS for OCD. METHODS The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies as used to search PubMed and Embase for relevant literature. The updated search included studies published between 1966 and December 2019. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed and relevant full-text articles were retrieved and graded. Of 864 articles, 10 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update. RESULTS Seven studies were included in the original guideline, reporting the use of bilateral DBS as more effective in improving OCD symptoms than sham treatment. An additional 10 studies were included in this update: 1 class II and 9 class III. CONCLUSION Based on the data published in the literature, the following recommendations can be made: (1) It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD (level I). (2) Clinicians may use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patients with medically refractory OCD (level II). There is insufficient evidence to make a recommendation for the identification of the most effective target. The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/deep-brain-stimulation-obsessive-compulsive-disord.

Chronic spinal cord injury (SCI) causes major disruption of ejaculatory function in men. Ejaculation is a reflex and the spinal generator for ejaculatory reflexes in the rat has been located in the lumbosacral spinal cord. The effects of SCI on the rat spinal ejaculation generator and ejaculatory reflexes remain understudied. The first goal of the current study was to establish the effects of chronic SCI on the function of the spinal ejaculation generator. Male rats received a contusion injury of the spinal cord at spinal level T6–T7. Ejaculatory reflexes elicited by electrical stimulation of the dorsal penile nerve (DPN) were evaluated in injured and control rats at 4–6 weeks following SCI. SCI males demonstrated significant reductions in bursting of the bulbocavernosus muscle (BCM), an indicator for expulsion phase of ejaculation, and in seminal vesicle pressure (SVP) increases, an indicator for the emission phase of ejaculation, following DPN stimulation. Thus, contusion SCI resulted in long-term impairment of ejaculatory reflexes. The D3 agonist 7-hydroxy-2-(di-N-propylamino) tetralin (7OHDPAT) facilitates ejaculation in spinal cord intact rats, thus the second goal of the current study was to test whether subcutaneous infusions of 7OHDPAT can facilitate ejaculatory reflexes in rats with chronic SCI. Male rats received a contusion injury at T6–T7 and effects of systemic administration of 7OHDPAT (1 mg/kg) were tested 4–5 weeks following injury. Results showed that 7OHDPAT administration facilitated ejaculatory reflexes in SCI males with or without DPN stimulation, provided that supraspinal inputs to the lumbar cord were severed by transection just prior to evaluating the reflex. Thus, 7OHDPAT administration in SCI males was able to overcome the detrimental effects of SCI on ejaculatory reflexes.

Over the past two decades, the United States has experienced a rise of opioid misuse, with a significant increase in drug overdose deaths– many of these deaths have been attributed to prescription opiate misuse. Given this epidemic, numerous specialties have created enhanced recovery after surgery protocols to decrease opiate usage post-operatively and some specialties have even created guidelines advising how many morphine milligram equivalents per day are recommended at discharge. The neurosurgical literature is lacking on best practices for discharge opiate prescribing. The goal of this review is to assess opiate prescribing practices at discharge for both cranial and spine neurosurgical patients, and to determine if neurosurgeons are over-prescribing opiates to their patients. A systematic literature review was performed according to PRISMA guidelines. After searching PubMed, Cochrane, and Embase, a total of 288 abstracts were identified, 71 studies underwent full text review and 23 were included in this study. Studies that quantified opiate usage (number of pills prescribed, morphine equivalents, prescription refills) were included. The range of opiate prescribing varied and there was a tendency to both over-prescribe and under-prescribe; therefore, no conclusions could be made. This review underscores the need to take individual patient pain needs into account and shows the need for higher quality literature that can help formulate guideline creation.