Search

Deep brain stimulators (DBS) may fail for a multitude of reasons. We present a 79-year-old Parkinson's disease patient who suffered a DBS failure following impulse generator (IPG) replacement surgery due to the IPG flipping within an expanded capsular pocket. This creation of the pocket was unintentional, and the pocket formed around an undiagnosed postoperative hemorrhage. The syndrome could be considered “Twiddler-like” because it resulted in device flipping. There were, however, many characteristic differences between our case and classical Twiddler's syndrome. DBS neurostimulator failure due to hematoma induced device flipping should be suspected when device interrogation is impossible or there are abnormally high impedances across multiple DBS lead contacts. A plain film X-ray series should be ordered and can be useful in providing radiological evidence of device flipping. In cases like ours the extensive braiding encountered in Twiddler's syndrome may be absent. Anchoring the IPG to a deep fascial layer as well as the use of an antimicrobial pouch are two methods that may be employed to prevent or to treat this complication.

Natural gas can be collected from hydrate deposits by exchange with CO2, but the ensuing mixed hydrates and the path to a complete exchange are not fully understood. Here, computational analyses of neutron pair distribution functions of CH4, CO2 and mixed CH4-CO2 hydrates at 10 K reveal that the behavior of mixed gas species cannot be interpolated from properties of pure compounds.

BackgroundAdult lead encephalopathy is a rare but critical condition to recognize in modern healthcare settings. Few reports have described the medical and neurosurgical management of severe adult lead encephalopathy.Case PresentationA 22 year old woman presented with severe headache, anemia, vomiting, 40-lb weight loss, and constipation. At the time of presentation, she had extensive colonic radiopaque material and a serum lead concentration of 87 mcg/dl (normal

Background: The centromedian-parafascicular (Cm-Pf) complex of the thalamus is a common deep brain stimulation (DBS) target for treatment of Tourette syndrome (TS). Currently, there are no standardized functional intraoperative neurosurgical targeting approaches. Collectively, these issues have led to variability in DBS lead placement. Therefore, more defined methods are needed to improve targeting accuracy. Objective: The objective of this observational study was to develop and to verify a functional mapping task capable of differentiating the Cm-Pf region from the nearby ventral intermediate (Vim) nucleus region of the thalamus. The overarching goal was to improve the reproducibility of DBS targeting in the Cm-Pf region. Methods: Seven TS patients completed a modified Go/NoGo task (five in the post-operative setting and two in the intra-operative setting). Post-operative neural signals from Cm-Pf region were collected using sensing-enabled implanted neural stimulators, and intraoperative neural signals from the Cm-Pf region were collected using an external amplifier. Event-related potential (ERP) features were identified by using the grand-average of stimulus onset signals derived from the postoperative participants. These features were correlated with anatomical locations for the specific electrode recordings. The same features were extracted from the intraoperative patients in order to verify electrode positions in the operating room environment. Results: Two features – a positive and a negative deflection – were identified in the average ERP from the post-operative participants. The peak amplitudes of both features were significantly correlated with the electrode depth position (p = 0.025 for positive deflection and p = 0.039 for negative deflection). The same result was reproduced intra-operatively in the two most recent patients, where more ventral electrode contacts revealed stronger peak amplitudes in comparison to the dorsal electrode contacts. Conclusion: This process was used to physiologically confirm accurate lead placement in the operating room setting. The modified Go/NoGo task elicited robust neural responses in the Cm-Pf region however the signal was not present in the Vim nucleus region of thalamus along the DBS electrode trajectory. We conclude that the differences in ERP responses may be a potentially novel LFP based functional approach for future targeting of the Cm-Pf complex for TS DBS.

IntroductionDeep brain stimulation (DBS) is a proven, effective tool in the treatment of movement disorders. Expansion of indications for DBS into the realm of neuropsychiatric disorders, especially obsessive–compulsive disorder (OCD), has gained fervent interest, although data on appropriate clinical utilization remains limited.MethodsA retrospective, naturalistic study followed nine severely affected OCD patients (average YBOCs score before implantation 34.2 ± 2.5) treated with DBS of ventral capsule/ventral striatum, with average follow up of 54.8 months.ResultsWith chronic stimulation (years), a majority of the patients achieved significant benefits in obsessive–compulsive and depressive symptoms. Six patients experienced periods of OCD remission following implantation. Four of the six responders required more than 12 months to achieve response. Relief of major depressive symptoms occurred in four out of six patients with documented co-morbid depression. Settings required to achieve efficacy were higher than those typically utilized for movement disorders, necessitating increased impulse generator (IPG) battery demand. We found patients benefited from conversion to a rechargeable IPG to prevent serial operations for IPG replacement. For patients with rechargeable IPGs, the repetitive habit of recharging did not appear to aggravate or trigger new obsessive–compulsive behaviors or anxiety symptoms.ConclusionsOur study supports and builds upon other research suggesting that DBS for OCD in a real-world setting can be implemented successfully and provide long-term benefit for severely affected OCD patients. Optimal patient selection and DBS programming criteria are discussed. The use of rechargeable IPGs appears to be both cost effective and well-tolerated in this population.

Spinal Epidural Lipomatosis (SEL) is an uncommon but previously characterized ailment typified by excessive overgrowth epidural adipose tissue. This overgrowth may lead to compression of local tissue including the underlying thecal space and nervous tissues. Common causes are medication induced (particularly glucocorticoid administration) and obesity. Prompt recognition of the diagnosis and initiation of treatment, be it medication stoppage or surgical decompression is imperative. In this report we describe the case of a 51-year-old female who presented with back and leg pain. She was diagnosed with SEL due to obesity with noted compression of the underlying nervous tissue noted on MRI. The patient was successfully treated with a course of weight loss with remarkable clinical and noted resolution of thecal sac compression on follow up MRI. Early consideration of this entity can increase the likelihood of timely diagnosis and successful treatment. Keywords: Spinal epidural lipomatosis, Conservative management, Obesity, Glucocorticoids, Weight loss, Epidural adipose

Abstract: Idelalisib, a first-in-class oral inhibitor of phosphatidylinositol-3-kinase δ, has shown considerable antitumor activity as a monotherapy in recurrent indolent non-Hodgkin lymphoma (iNHL). To evaluate the safety and activity of idelalisib in combination with immunotherapy, chemotherapy, or both, 79 patients with relapsed/refractory iNHL were enrolled based on investigator preference in 3 treatment groups. Patients received continuous idelalisib in combination with (1) rituximab (IR; 375 mg/m2 weekly × 8 doses), (2) bendamustine (IB; 90 mg/m2 per day × 2, for 6 cycles), or (3) both bendamustine and rituximab at aforementioned doses (IBR; monthly × 6 cycles). Patients had a median age of 61 years, a median of 3 prior therapies, and 46% had refractory disease. The overall response rate was 75% (22% complete response) for IR, 88% (36%) for IB, and 79% (43%) for IBR. The median progression-free survival was 37.1 months overall: 29.7 months for IR, 32.8 for IB, and 37.1 months for IBR. The median duration of response was 28.6 months in the IR group and has not been reached in the IB and IBR groups. The most common grade ≥3 adverse events and laboratory abnormalities were neutropenia (41%), pneumonia (19%), transaminase elevations (16%), diarrhea/colitis (15%), and rash (9%). The safety and efficacy reflected in these early data, however, stand in contrast with later observations of significant toxicity in subsequent phase 3 trials in frontline chronic lymphocytic leukemia and less heavily pretreated iNHL patients. Our findings highlight the limitations of phase 1 trial data in the assessment of new regimens. This trial was registered at www.clinicaltrials.gov as #NCT01088048 (an extension study was registered at www.clinicaltrials.gov as #NCT01090414).

Introduction: Intradural spinal cord stimulation (SCS) may offer significant therapeutic benefits for those with intractable axial and extremity pain, visceral pain, spasticity, autonomic dysfunction and related disorders. A novel intradural electrical stimulation device, limited by the boundaries of the thecal sac, CSF and spinal cord was developed to test this hypothesis. In order to optimize device function, we have explored finite element modeling (FEM).Methods: COMSOL®Multiphysics Electrical Currents was used to solve for fields and currents over a geometric model of a spinal cord segment. Cathodic and anodic currents are applied to the center and tips of the T-cross component of the electrode array to shape the stimulation field and constrain charge-balanced cathodic pulses to the target area.Results: Currents from the electrode sites can move the effective stimulation zone horizontally across the cord by a linear step method, which can be diversified considerably to gain greater depth of penetration relative to standard epidural SCS. It is also possible to prevent spread of the target area with no off-target action potential.Conclusion: Finite element modeling of a T-shaped intradural spinal cord stimulator predicts significant gains in field depth and current shaping that are beyond the reach of epidural stimulators. Future studies with in vivo models will investigate how this approach should first be tested in humans.

Extreme body mass index (BMI) values (i.e., above the 97th and below the 3rd percentiles) are inaccurately represented on the Centers for Disease Control and Prevention’s growth curves, which may limit the utility of BMI percentile and BMI z-score for capturing changes in clinical outcomes for patients at extreme weights. Modeling child obesity severity based upon the percentage of BMI in excess of the 95th percentile (BMI95pct) has been proposed as an improved metric to better capture variability in weight at extreme ends of growth curves, which may improve our understanding of relationships between weight status and changes in clinical outcomes. However, few studies have evaluated whether the use of BMI95pct would refine our understanding of differences in clinical psychosocial constructs compared to previous methods for categorization. This cross-sectional study evaluated child obesity severity based on BMI95pct to examine potential group differences in a validated, obesity-specific measure of Health-Related Quality of Life (HRQoL). Four hundred and sixty-five children with obesity completed Sizing Me Up, a self-report measure of HRQoL. Children were classified into categories based on BMI95pct (i.e., class I: ≥100% and

We prove that, within the class of pair potential Hamiltonians, the excess entropy is a universal, temperature-independent functional of the density and pair correlation function. This result extends Henderson’s theorem, which states that the free energy is a temperature dependent functional of the density and pair correlation. The stationarity and concavity of the excess entropy functional are discussed and related to the Gibbs–Bugoliubov inequality and to the free energy. We apply the Kirkwood approximation, which is commonly used for fluids, to both fluids and solids. Approximate excess entropy functionals are developed and compared to results from thermodynamic integration. The pair functional approach gives the absolute entropy and free energy based on simulation output at a single temperature without thermodynamic integration. We argue that a functional of the type, which is strictly applicable to pair potentials, is also suitable for first principles calculation of free energies from Born–Oppenheimer molecular dynamics performed at a single temperature. This advancement has the potential to reduce the evaluation the free energy to a simple modification to any procedure that evaluates the energy and the pair correlation function.

This article is premised on the current (2015–2016) developments in South Africa whereby the country’s youth are increasingly engaging in discourses of South Africa’s post-colonial condition and the need for decolonisation. But how do the history textbooks that they use in schools construct this contentious post-colonial period? On this basis, the main objective is to examine the temporal representation of post-colonial Africa in South African history textbooks. Critical discourse analysis was applied on a sample of four National Curriculum Statement-aligned textbooks with a focus on sections that covered content on post-colonial Africa. The findings from the textual analysis show that the temporal notion of post-colonial Africa is not clearly framed within a particular period. The ambiguity of the temporal notion, a fundamental concept in history, stems from the fact that the lexicalisations used as time markers in the textbooks cannot be linked to one particular date, resulting in a post-colonial Africa whose beginning and – more specifically – end cannot be unambiguously determined. The textbooks also sometimes refer to the post-colonial period as singular, whereas in other cases they describe the period as consisting of different phases. I conclude that such ambiguity reveals a loophole in educating the learners about a period whose circumstances they are trying to not only engage but also transform.

Abstract. Phosphatidylinositol 3-kinase-delta (PI3Kδ) signaling is critical for proliferation, survival, homing, and tissue retention of malignant B cells. Idelalisib, a selective oral inhibitor of PI3Kδ, has shown considerable single-agent activity in patients with heavily pretreated chronic lymphocytic leukemia (CLL). This study evaluated the safety and clinical activity of idelalisib in combination with bendamustine (IB) or rituximab (IR) or both (IBR) in patients with relapsed or refractory (R/R) CLL. Idelalisib was given continuously at 100 or 150 mg twice daily in combination with rituximab (375 mg/m2 weekly × 8 doses), bendamustine (70 or 90 mg/m2, days 1 and 2 every 4 weeks × 6 cycles) or BR (rituximab, 375 mg/m2 every 4 weeks and bendamustine, 70 mg/m2, days 1 and 2 every 4 weeks × 6 cycles). The primary endpoint was safety; secondary endpoints included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Fifty-two patients (median age 64 years) with a median of 3 prior therapies were enrolled. ORR was 84.6% (89.5% IR group, 77.8% IB group, and 86.7% IBR group). The overall median PFS was 25.6 months, and median DOR was 26.6 months. The most common grade ≥3 adverse events (≥10% of patients) were pneumonia (19.2%), diarrhea (13.5%), and febrile neutropenia (17.3%). Idelalisib-based combination therapy with bendamustine and/or rituximab was highly active, resulting in durable tumor control in patients with heavily pretreated R/R CLL. However, its tolerability profile suggests that these regimens should be used cautiously in this patient population. ClinicalTrials.gov ID: NCT01088048.

Spontaneous spinal subdural hematoma (sSDH) is a rare condition outright. Moreover, cases that occur spontaneously in the absence of an identifiable etiology are considerably less common and remain poorly understood. Here, we present the case of a 43-year-old man with spontaneous sSDH presenting with acute onset low back pain and paraplegia. Urgent magnetic resonance imaging identified a dorsal SDH from T8 to T11 with compression of the spinal cord. Emergent T8–T10 laminectomies with intradural exploration and hematoma evacuation were performed. However, despite prompt identification and appropriate action, the patient’s recovery was modest and significant disability remained at discharge. This unique and unusual case demonstrates that spontaneous sSDH requires prompt surgical treatment to minimize associated morbidity and supports the association between the presence of severe neurological deficits upon initial presentation with less favorable outcomes. We performed a comprehensive systematic review of spontaneous sSDH of unknown etiology, which demonstrates that emergent surgical intervention is indicated for patients presenting with severe neurological deficits and the presence of these deficits is predictive of poor neurological outcome. Furthermore, conservative management should be considered in patients presenting with mild neurological deficits as spontaneous resolution followed by favorable neurological outcomes is often observed in these patients.

Graham Ellis,1 Trudi Marshall,2 Claire Ritchie2 1Medicine for the Elderly, Monklands Hospital, Airdrie, Scotland, UK; 2Kirklands Hospital, Bothwell, Scotland, UK Abstract: Changing global demography is resulting in older people presenting to emergency departments (EDs) in greater numbers than ever before. They present with greater urgency and are more likely to be admitted to hospital or re-attend and utilize greater resources. They experience longer waits for care and are less likely to be satisfied with their experiences. Not only that, but older people suffer poorer health outcomes after ED attendance, with higher mortality rates and greater dependence in activities of daily living or rates of admission to nursing homes. Older people’s assessment and management in the ED can be complex, time consuming, and require specialist skills. The interplay of multiple comorbidities and functional decline result in the complex state of frailty that can predispose to poor health outcomes and greater care needs. Older people with frailty may present to services in an atypical fashion requiring detailed, multidimensional, and increasingly multidisciplinary care to provide the correct diagnosis and management as well as appropriate placement for ongoing care or admission avoidance. ­Specific challenges such as delirium, functional decline, or carer strain need to be screened for and managed appropriately. Identifying patients with specific frailty syndromes can be critical to identifying those at highest risk of poor outcomes and most likely to benefit from further specialist interventions. Models of care are evolving that aim to deliver multidimensional assessment and management by multidisciplinary specialist care teams (comprehensive geriatric assessment). Increasingly, these models are demonstrating improved outcomes, including admission avoidance or reduced death and dependence. Delivering this in the ED is an evolving area of practice that adapts the principles of geriatric medicine for the urgent-care environment. Keywords: ED, frailty, models of care