Contact heat evoked potentials reveal distinct patterns of spinal cord impairment in degenerative cervical myelopathy beyond MRI lesions

Background: Magnetic resonance imaging may suggest spinal cord compression and structural lesions in degenerative cervical myelopathy (DCM) but cannot reveal functional impairments in spinal pathways. We aimed to assess the value of contact heat evoked potentials (CHEPs) in addition to MRI and hypothesized that abnormal CHEPs may be evident in DCM independent of MR-lesions and are related to dynamic mechanical cord stress.Methods: Individuals with DCM underwent neurologic examination including segmental sensory (pinprick, light touch) and motor testing. The presence or absence of hyperintense signal on T2-weighted MRI (T2-positive/negative) was assessed. Phase-contrast MRI was used to assess spinal cord motion as an indicator of dynamic mechanical stress. Dermatomal somatosensory evoked potentials and CHEPs were recorded after stimulation of dermatomes C6, C8, and T4 (CHEPs only) to assess spinal cord integrity.Results: Of 138 individuals included in this study (age 56 ± 13 years), 35% (N = 48) presented with T2-positive and 65% (N = 90) presented with T2-negative DCM. Abnormal CHEPs were present in T2-positive DCM (C6:41%; C8:32%; T4:24%) and T2-negative DCM (C6:35%; C8:54%; T4:26%). Multisegmental CHEP abnormalities at C6 and C8 were related to increased spinal cord motion (p = 0.030; ϵ2 = 0.072), and reduced upper extremity pinprick (p = 0.046; ϵ2 = 0.063) and motor scores (p = 0.005; ϵ2 = 0.108).Conclusions: CHEPs revealed distinct patterns of spinal cord impairment independent of structural T2-positive lesions, which were associated with measures of cord motion. CHEPs thus provide valuable complementary diagnostic insights into spinal cord integrity beyond MRI. This is especially important in incipient myelopathy to inform early diagnosis and timely interventions before the development of definite cord lesions

Potential thresholds of critically increased cardiac-related spinal cord motion in degenerative cervical myelopathy

Introduction: New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord.Methods: Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI- (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis.Results: MRI+ patients (N = 31; 36.9%) were more impaired compared to MRI- patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p Discussion: These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI- DCM patients

Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: A randomised, double-blind, multicentre, placebo-controlled, phase 2b trial

Background: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury.Methods: This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321.Findings: From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group.Interpretation: NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies

New Directions in the Development of Population Estimates in the United States?

The advent of a continuously updated Master Area File (MAF) following the 2000 census represents an information resource that can be tapped for purposes of developing timely, cost-effective, and precise population estimates for even the smallest of geographical units (e.g., census blocks). We argue that the MAF can be enhanced (EMAF) for these purposes. In support of our argument we describe a set of activities needed to develop EMAF, each of which is well within the current capabilities of the U.S. Census Bureau and discuss various costs and benefits of each. We also describe how EMAF would provide population estimates containing a wide range of demographic (e.g., age, race, and sex) and socio-economic characteristics (e.g., educational attainment, income, and employment). As such, it could largely negate and eliminate the need for many of the traditional demographic methods of population estimation and possibly reduce the number of sample surveys. We identify important challenges that must be surmounted in order to realize EMAF and make suggestions for doing so. We conclude by noting that the idea of the EMAF could be of interest to other countries with MAF files and strong administrative records systems that, like the United States, are facing the challenge of producing good population information in the face of increasing census costs

A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality

The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19

ESTIMATING HEALTH EXPECTANCY IN PRESENCE OF MISSING DATA: AN APPLICATION USING HID SURVEY

In this article we estimate health transition probabilities using longitudinal data collected in France for the survey on handicaps, disabilities and dependencies from 1998 to 2001. Life expectancies with and without disabilities are estimated using a Markov-based multi-state life table approach with two non-absorbing states: able to perform all activities of daily living (ADLs) and unable or in need of help to perform one or more ADLs, and the absorbing state of death. The loss of follow-up between the two waves induces biases in the probabilities estimates: mortality estimates were biased upwards; also the incidence of recovery and the onset of disability seemed to be biased. Since individuals were not missing completely at random, we correct this bias by estimating health status for drop-outs using a non parametric model. After imputation, we found that at the age of 70 disability-free life expectancy decreases by 0.5 years, whereas the total life expectancy increases by 1 year. The slope of the stable prevalence increases, but it remains lower than the slope of the cross sectional prevalence. The gender differences on life expectancy did not change significantly after imputation. Globally, there is no evidence of a general reduction in ADL disability, as defined in our study. The added value of the study is the reduction of the bias induced by sample attrition