Practical Closed-Loop Strategies for Deep Brain Stimulation: Lessons From Chronic Pain

Deep brain stimulation (DBS) is a plausible therapy for various neuropsychiatric disorders, though continuous tonic stimulation without regard to underlying physiology (open-loop) has had variable success. Recently available DBS devices can sense neural signals which, in turn, can be used to control stimulation in a closed-loop mode. Closed-loop DBS strategies may mitigate many drawbacks of open-loop stimulation and provide more personalized therapy. These devices contain many adjustable parameters that control how the closed-loop system operates, which need to be optimized using a combination of empirically and clinically informed decision making. We offer a practical guide for the implementation of a closed-loop DBS system, using examples from patients with chronic pain. Focusing on two research devices from Medtronic, the Activa PC+S and Summit RC+S, we provide pragmatic details on implementing closed- loop programming from a clinician’s perspective. Specifically, by combining our understanding of chronic pain with data-driven heuristics, we describe how to tune key parameters to handle feature selection, state thresholding, and stimulation artifacts. Finally, we discuss logistical and practical considerations that clinicians must be aware of when programming closed-loop devices.

Towards long term monitoring: Seizure detection with reduced electroencephalogram channels

Epilepsy is a prevalent condition characterised by recurrent, unpredictable seizures. The diagnosis of epilepsy is by surface electroencephalography (EEG), a time-consuming and uncomfortable process for patients. The diagnosis of seizures using EEG over a brief monitoring period has variable success, dependent on patient tolerance and seizure frequency. Further, the availability of hospital resources and hardware and software specifications inherently limit the capacity to perform long-term data collection whilst maintaining patient comfort. The application and maintenance of the standard number of electrodes restrict recording time to a maximum of approximately ten days. This limited monitoring period also results in limited data for machine learning models for seizure detection and classification. This work examines the literature on the impact of reduced electrodes on data accuracy and reliability in seizure detection. Here we present two electrode ranking models, demonstrating the decline in seizure detection performance associated with reducing electrodes. We assert the need for further research in electrode reduction to advance solutions toward portable, reliable devices that can simultaneously provide patient comfort, long-term monitoring and contribute to multi-modal patient care solutions.

Intracavernosal ephedrine for management of intraoperative penile erection during urological procedure under general anesthesia

Intraoperative penile tumescence during urological procedure can occur after regional or general anesthesia. It is a rare event but can cause delay or defer of the surgery. Pathophysiology of intraoperative erection is mainly due to autonomic imbalance during anesthesia. Various physical and pharmacological management of tumescence have been tried with variable success and complication. We injected ephedrine 15 mg intracavernous resulting immediate de-tumescence and minimum complication.

A Systematic Review of Scientific Studies and Case Reports on Music and Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a severe psychiatric disorder, which can be associated with music-related symptoms. Music may also be used as an adjunct treatment for OCD. Following the PRISMA guidelines, we performed a systematic literature review exploring the relationship between music and OCD by using three online databases: PubMed, the Web of Science, and PsycINFO. The search terms were “obsessive compulsive disorder”, “OCD”, “music”, and “music therapy”. A total of 27 articles were utilised (n = 650 patients/study participants) and grouped into three categories. The first category comprised case reports of patients with musical obsessions in patients with OCD. Most patients were treated with selective serotonin reuptake inhibitors (SSRIs) or a combination of an SSRI and another pharmacological or a non-pharmacological treatment, with variable success. Studies on the music perception of people with OCD or obsessive-compulsive personality traits represented the second category. People with OCD or obsessive-compulsive personality traits seem to be more sensitive to tense music and were found to have an increased desire for harmony in music. Three small studies on music therapy in people with OCD constituted the third category. These studies suggest that patients with OCD might benefit from music therapy, which includes listening to music.

AIP1, Encoding the Small Subunit of Acetolactate Synthase, Is Partially Responsible for Resistance to Hypoxic Stress in Arabidopsis thaliana

Flooding is a significant stress to land plants, depriving them of essential oxygen. Plants have evolved diverse strategies with variable success to survive flooding. Similar strategies have been described in organisms from other kingdoms. Several fungal species can successfully survive a low-oxygen environment by increasing their branched-chain amino acid (BCAA) contents. BCAAs may act as alternative electron acceptors in the respiratory chain under an oxygen-limited environment. The key and first enzyme for BCAA biosynthesis is acetolactate synthase (ALS). We identified two homologous genes encoding the small subunit of ALS in Arabidopsis (Arabidopsis thaliana). We determined that ALS INTERACTING PROTEIN1 (AIP1), which encodes the small subunit of ALS, is strongly expressed in all organs and highly expressed under submergence and low-oxygen stresses. We also showed that the overexpression of AIP1 confers tolerance to low-oxygen stress. These results indicate that ALS may play an essential role under prolonged flooding or oxygen deficiency in Arabidopsis.

Effects of background food on alternative grain uptake and zinc phosphide efficacy in wild house mice

BACKGROUND: House mice (Mus musculus) cause significant, ongoing losses to grain crops in Australia, particularly during mouse plagues. Zinc phosphide (ZnP) coated grain is used for control, but with variable success. In a laboratory setting, we tested if mice would (1) switch from consumption of one grain type to another when presented with an alternative, and (2) consume ZnP-treated grains when presented as a choice with a different grain. RESULTS: Mice readily switched from their background grain to an alternative grain, preferring cereals (wheat or barley) over lentils. Mice readily consumed ZnP-coated barley grains. Their mortality rate was significantly higher (86%, n=30) in the presence of a less-favoured grain (lentils) compared to their mortality rate (47%, n=29; and 53%, n=30) in the presence of a more-favoured grain (wheat and barley, respectively). Mice died between 4-112 h (median = 18 h) after consuming one or more toxic grains. Independent analysis of ZnP-coated grains showed variable toxin loading indicating that consumption of a single grain would not guarantee intake of a lethal dose. There was also a strong and rapid behavioural aversion if mice did not consume a lethal dose on the first night. CONCLUSIONS: The registered dose rate of 25 g ZnP/kg wheat; ~ 1 mg ZnP/grain in Australia needs to be re-evaluated to determine what factors may be contributing to variation in efficacy. Further field research is also required to understand the complex association between ZnP dose, and quantity and quality of background food on efficacy of ZnP baits.

Intrauterine fetal death followed by shoulder dystocia and birth by modified posterior axillary sling method: a case report

Background Various manoeuvres such as McRoberts position, suprapubic pressure, rotational methods, posterior arm extraction and all-four position (HELPERR) have been proposed for relieving shoulder dystocia with variable success. Posterior axillary sling method using a rubber catheter was proposed in 2009 but has not been widely used. We modified this method using ribbon gauzes and a long right-angle forceps and report a successful case. Case presentation A 44 years old parity one Chinese woman with a history of a caesarean delivery and poorly controlled type 2 diabetes mellitus was admitted to the Accident and Emergency Department for advanced stage of labour at term. Upon arrival, intrauterine fetal demise was diagnosed with severe asynclitism causing obstruction at the perineum. Episiotomy resulted in birth of the fetal head. The fetal posterior right shoulder, however, remained very high up in the pelvis and HELPERR methods failed to extract the shoulders. We then tied two long ribbon gauzes together, and guided its knot to the anterior aspect of the posterior axilla. By using a long right-angle forceps (24 cm long) to grasp the knot on the posterior side of the axilla and pulling it through, a sling was formed. Traction was then applied through the sling to simultaneously pull and rotate the posterior shoulder. A stillbirth of 3488 g was finally extracted. Conclusions We modified the sling method by using two ribbon gauzes, tied together and a right-angle forceps with several advantages. Compared to a rubber catheter, ribbon gauze with a knot can be easily held between the fingers for easy guidance past the fetal axilla. It is also thin, non-elastic and stiff enough to ensure a good grip for traction. The long and slim design of the right-angle forceps makes it easy to pass through a narrow space and reach the axilla high up in the pelvis. We emphasize simultaneous traction and rotation, so that the shoulders are delivered through the wider oblique pelvic outlet dimension.

Clinical features, pathophysiology and therapy of Poor Graft Function Post Allogeneic Stem Cell Transplantation

Poor graft function (PGF) defined by the presence of multi-lineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (alloSCT). Inducers or potentiators of allo-immunity such as CMV reactivation and graft versus host disease (GVHD) are associated with the development of PGF, however more clinical studies are required to establish further risk factors and describe outcomes of PGF. The pathophysiology of PGF can be conceptualized as dysfunction related to the number or productivity of the stem cell compartment, defects in bone marrow microenvironment components such as mesenchymal stromal cells and endothelial cells, or immunological suppression of post alloSCT haematopoiesis. Treatment strategies focused on improving stem cell number and function and microenvironment support of haematopoiesis have been attempted with variable success. There has been limited use of immune manipulation as a therapeutic strategy, but emerging therapies hold promise. This review details the current understanding of the causes of PGF and methods of treatment to provide a framework for clinicians managing this complex problem.

Exploring how people with chronic pain understand their pain: a qualitative study

Objectives A fundamental principle of pain management is educating patients on their pain using current neuroscience. However, current pain neurophysiology education (PNE) interventions show variable success in improving pain outcomes, and may be difficult to integrate with existing understanding of pain. This study aimed to investigate how people with chronic pain understand their pain, using qualitative exploration of their conceptualisations of pain, and how this understanding accommodated, or resisted, the messages of PNE. Methods Twelve UK adults with chronic pain were recruited through advertisements on online pain networks. Semi-structured interviews were conducted remotely, with responses elicited using the Grid Elaboration Method (GEM) and then a PNE article. Participants’ grid elaborations and responses to PNE were analysed using thematic analysis (TA). Results Three main themes were extracted from participants' grid elaborations: communicating pain, explaining pain and living with pain. These themes incorporated varied, inconsistent sub-themes: of pain as simultaneously experiential and conceptual; in the body and in the mind; diagnosable and inexplicable; manageable and insuperable. Generalised, meta-level agreement was identified in participants' PNE responses, but with doubts about its practical value. Conclusions This study shows that people understand pain through inconsistent experiential models that may resist attempts at conceptual integration. Participants' elaborations showed diverse and dissonant conceptualisations, with experiential themes of restricted living; assault on the self; pursuit of understanding pain and abandonment of that pursuit. Responses, although unexpectedly compatible with PNE, suggested that PNE was perceived as intellectually engaging but practically inadequate. Experiential disconfirmation may be required for behavioural change inhibited by embedded fears and aversive experiences. Ethical committee number UCL REC# 17833/003.

The continued relevance of Deep Brain Stimulation for chronic pain

For the millions of patients experiencing chronic pain despite pharmacotherapy, deep brain stimulation (DBS) provides a beacon of hope. Over the past decade the field has shifted away from DBS towards other forms of neuromodulation, particularly spinal cord stimulation (SCS). DBS for pain is still performed, albeit off-label in US and UK, and experiences variable success rates. SCS is an extremely useful tool for the modulation of pain but is limited in its application to specific pain aetiologies. We advocate use of DBS for pain, for patients for whom pharmacology has failed and for whom spinal cord stimulation is inadequate. DBS for chronic pain is at risk of premature neglect. Here we outline how this has come to pass, and in the process argue for the untapped potential for this procedure.