Administration of Denosumab Preserves Bone Mineral Density at the Knee in Persons With Subacute Spinal Cord Injury: Findings From a Randomized Clinical Trial.

Persons with neurologically motor-complete spinal cord injury (SCI) have a marked loss of bone mineral density (BMD) of the long bones of the lower extremities, predisposing them to fragility fractures, especially at the knee. Denosumab, a commercially available human monoclonal IgG antibody to receptor activator of nuclear factor-κB ligand (RANKL), may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty-six SCI participants with subacute motor-complete SCI were randomized to receive either denosumab (60 mg) or placebo at baseline (BL), 6, and 12 months. Areal bone mineral density (aBMD) by dual energy x-ray absorptiometry (DXA) at 18 months at the distal femur was the primary outcome and aBMD of the proximal tibia and hip were the secondary outcomes analyzed in 18 of the 26 participants (denosumab, n = 10 and placebo, n = 8). The metrics of peripheral QCT (pQCT) were the exploratory outcomes analyzed in a subsample of the cohort (denosumab, n = 7 and placebo n = 7). The mean aBMD (±95% CI) for the denosumab versus the placebo groups demonstrated a significant group × time interactions for the following regions of interest at BL and 18 months: distal femoral metaphysis = mean aBMD 1.187; 95% CI, 1.074 to 1.300 and mean aBMD 1.202; 95% CI, 1.074 to 1.329 versus mean aBMD 1.162; 95% CI, 0.962 to 1.362 and mean aBMD 0.961; 95% CI, 0.763 to 1.159, respectively (p < 0.001); distal femoral epiphysis = mean aBMD 1.557; 95% CI, 1.437 to 1.675 and mean aBMD 1.570; 95% CI, 1.440 to 1.700 versus mean aBMD 1.565; 95% CI, 1.434 to 1.696 and mean aBMD 1.103; 95% CI, 0.898 to 1.309, respectively (p = 0.002); and proximal tibial epiphysis = mean aBMD 1.071; 95% CI, 0.957 to 1.186 and mean aBMD 1.050; 95% CI, 0.932 to 1.168 versus mean aBMD 0.994; 95% CI, 0.879 to 1.109 and mean aBMD 0.760; 95% CI, 0.601 to 0.919, respectively (p < 0.001). Analysis of pQCT imaging revealed a continued trend toward significantly greater loss in total volumetric BMD (vBMD) and trabecular vBMD at the 4% distal tibia region, with a significant percent loss for total bone mineral content. Thus, at 18 months after acute SCI, our findings show that denosumab maintained aBMD at the knee region, the site of greatest clinical relevance in the SCI population. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

BACKGROUND: Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI). METHODS: One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4); 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5)] and 53 able-bodied (AB) subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package. RESULTS: Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01) and 112±8 mg/dl (p<0.05), respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05) and 55±4 µmol/l (p<0.05)]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P) and VAT volume or HOMA-IR was significant only in the ↓T5 group. CONCLUSIONS: Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB control groups. Thus, level of injury is an important determinate of the concentration of circulating triglyceride rich lipoproteins, which may play a role in the genesis of cardiometabolic dysfunction.

Assessing limb apraxia in traumatic brain injury and spinal cord injury.

People with traumatic brain injury (TBI) may demonstrate action planning disorders and limb apraxia. Many patients, who sustain a spinal cord injury (SCI), sustain a co-occurring TBI (11-29 percent of people with SCI) and therefore are at risk for limb apraxia. People with SCI and TBI (SCI/TBI) rely on powered assistive devices which amplify movement. Their ability to learn complex motor compensatory strategies, that is, limb praxis, is critical to function. We wished to identify methods of screening for apraxia in patients with SCI/TBI. We reviewed instruments available for limb praxis assessment, presenting information on psychometric development, patient groups tested, commercial/clinical availability, and appropriateness for administration to people with motor weakness. Our review revealed that insufficient normative information exists for apraxia assessment in populations comparable to SCI/TBI patients who are typically young adults at the time of injury. There are few apraxia assessment instruments which do not require a motor response. Non-motoric apraxia assessments would be optimal for patients with an underlying motor weakness.

Interdisciplinary communication in inpatient rehabilitation facility: evidence of under-documentation of spatial neglect after stroke.

PURPOSE: Spatial neglect commonly occurs after stroke and predicts poor rehabilitation outcomes. However, this disorder is under-recognized in clinical practices, which may result from the failure to document its presence. This study aimed to identify the predictors for documentation of spatial neglect in inpatient rehabilitation facilities. METHOD: We performed a comprehensive chart review to investigate whether the presence of spatial neglect was documented in 74 neglect patients' clinical notes recorded by physicians, nurses, or occupational therapists (OTs), or in team conference notes. Independent variables included neglect severity, length of stay, Functional Independence Measure at admission and discharge. RESULTS: Of the 74 neglect patients, 75.7% were documented by OTs, 63.5% by physicians, and 17.6% by nurses. Although 93.2% of neglect patients were recognized by at least one clinician group, only 31.1% were discussed in multidisciplinary team conferences. Neglect patients who were documented by physicians were more likely to be documented in team conferences. While no factors predicted whether a neglect patient would be documented by nurses or OTs, we found significant predictors for neglect documentation in physician and team conference notes. The odds of being documented by physicians were increasingly greater with poorer efficiency of cognitive rehabilitation (odds ratio = 0.70). The odds of being discussed in team conferences were increasingly greater with more severe neglect (odds ratio = 0.98), and with longer stay in hospitalization (odds ratio = 1.06). CONCLUSIONS: Multidisciplinary care may not involve as much interdisciplinary communication as needed to document important disease states. Stroke rehabilitation professionals should be able to recognize spatial neglect independently and document it consistently.

False localizing signs in traumatic brain injury.

BACKGROUND: Hemiparesis ipsilateral to a mass-occupying lesion can be due to Kernohan-Woltman Notch Phenomenon (KWNP). This syndrome implies a false-localizing sign because clinical findings lead the examiner to an incorrect neuroanatomical diagnosis. The contralateral crus cerebri (pyramidal tract) is pressed against the tentorial incisum and a resultant hemiparesis is found on the same side of the lesion. REVIEW: A detailed literature search of false-localizing signs is presented. CONCLUSIONS: Not infrequently, patients presenting to a physiatrist may have incomplete records. The existence of false localizing signs may point the physician towards the wrong underlying pathology.

Primary care practitioners' understanding of physiatric practice: effects on intention to refer.

OBJECTIVES: To learn what family practice and internal medicine physicians understand about the scope of practice of physical medicine and rehabilitation (PM&R) and to study what effect that understanding and various demographic variables have on their intention to refer to physiatrists. DESIGN: Survey-based. SETTING: National survey. PARTICIPANTS: One thousand internal medicine and family practice physicians were contacted, with 460 respondents. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Intention to refer patients to physiatrists using 13 case scenarios (10 appropriate referrals, 4 inappropriate referrals) and self-reported number of referrals per year associated with understanding of 7 skills of physiatrists analyzed by multiple logistic regression analyses. RESULTS: Although most respondents were likely to refer to physiatrists, a wide variation existed in the types of patients referred. Physicians with a greater understanding of the scope of physiatric practice were more likely to refer ( P =.003). Female physicians were more likely to refer than male physicians ( P =.003). CONCLUSIONS: There appears to be an association between an understanding of physiatric practice and primary care practitioners' willingness to refer to PM&R. Primary care physicians should be educated about the benefits of referring patients to physiatrists.