Evaluation of Pain in Adults With Childhood-Onset Disabilities and Communication Difficulties

Adults with childhood-onset disabilities, particularly those with central nervous system impairment, commonly experience pain. Because many such individuals have difficulties in communication, caregivers and medical professionals must identify and interpret non-verbal behaviors as indicators of pain. This process is challenging and can lead to poor outcomes through delayed or incorrect diagnosis and treatment. Most research in the evaluation of pain in individuals with neurologic impairment has focused on the pediatric population, and evidence-based guidelines do not exist for adults. The purpose of this paper is to review current recommendations for pain assessment in adults with communication impairment. This approach includes guidance for history-taking, pharmacologic review, physical examination, and the judicious use of laboratory and imaging tests. Finally, we discuss adult-specific diagnoses to consider when evaluating pain in adults with childhood-onset disabilities and communication difficulties.

Parsing Fabry Disease Metabolic Plasticity Using Metabolomics

Background: Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal α-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype–phenotype correlation. FD could involve kidney, heart or central nervous system impairment that significantly decreases life expectancy. The advent of omics technologies offers the possibility of a global, integrated and systemic approach well-suited for the exploration of this complex disease. Materials and Methods: Sixty-six plasmas of FD patients from the French Fabry cohort (FFABRY) and 60 control plasmas were analyzed using liquid chromatography and mass spectrometry-based targeted metabolomics (188 metabolites) along with the determination of LysoGb3 concentration and GalA enzymatic activity. Conventional univariate analyses as well as systems biology and machine learning methods were used. Results: The analysis allowed for the identification of discriminating metabolic profiles that unambiguously separate FD patients from control subjects. The analysis identified 86 metabolites that are differentially expressed, including 62 Glycerophospholipids, 8 Acylcarnitines, 6 Sphingomyelins, 5 Aminoacids and 5 Biogenic Amines. Thirteen consensus metabolites were identified through network-based analysis, including 1 biogenic amine, 2 lysophosphatidylcholines and 10 glycerophospholipids. A predictive model using these metabolites showed an AUC-ROC of 0.992 (CI: 0.965–1.000). Conclusion: These results highlight deep metabolic remodeling in FD and confirm the potential of omics-based approaches in lysosomal diseases to reveal clinical and biological associations to generate pathophysiological hypotheses.

Complementarity of pain assessment instruments in children with central nervous system impairment

ABSTRACT Objective: To evaluate the complementarity of the revised Face, Legs, Activity, Cry, Consolability scale and of the Inventory of Pain Behavior in Neurological Disability for the assessment of pain in children with severe neurological impairment. Method: Cross-sectional study conducted in pediatric units of a university hospital in the southern region of Brazil. The sample consisted of 26 children with severe neurological impairment, hospitalized from January to August 2019, and their caregivers. The data were analyzed by descriptive statistics; Kappa Coefficient, Fisher’s Exact Test and Spearman’s Coefficient were used (p≤0,05). Results: Most children primary diagnosis was cerebral palsy (80.8%). Pain was present in 50.0% of children with the application of the scale and in 34.6% with that of the inventory. Considering the two instruments, there was good agreement (84.6%) between respondents (k=0.692; 95% CI 0.437-0.967; p=0.000). Conclusion: The instruments can be used complementarily to assess pain in children with this profile.

Age-Related Deficits in Binocular Vision Are Associated With Poorer Inhibitory Control in Healthy Older Adults

A robust association between reduced visual acuity and cognitive function in older adults has been revealed in large population studies. The aim of this work was to assess the relation between stereoacuity, a key aspect of binocular vision, and inhibitory control, an important component of executive functions. Inhibition was tested using the antisaccade task in older adults with normal or reduced stereopsis (study 1), and in young adults with transiently reduced stereopsis (study 2). Older adults with reduced stereopsis made significantly more errors on the antisaccade task in comparison to those with normal stereopsis. Specifically, there was a significant correlation between stereoacuity and antisaccade errors (r = 0.27, p = 0.019). In contrast, there were no significant differences in antisaccade errors between the normal and reduced stereopsis conditions in the young group. Altogether, results suggest that the association between poorer stereopsis and lower inhibitory control in older adults might arise due to central nervous system impairment that affects the processing of binocular disparity and antisaccades. These results add to a growing body of literature, which highlights the interdependence of sensory and cognitive decline in older adults.

Arsenic Neurotoxicity in Humans

Arsenic (As) contamination affects hundreds of millions of people globally. Although the number of patients with chronic As exposure is large, the symptoms and long-term clinical courses of the patients remain unclear. In addition to reviewing the literature on As contamination and toxicity, we provide useful clinical information on medical care for As-exposed patients. Further, As metabolite pathways, toxicity, speculated toxicity mechanisms, and clinical neurological symptoms are documented. Several mechanisms that seem to play key roles in As-induced neurotoxicity, including oxidative stress, apoptosis, thiamine deficiency, and decreased acetyl cholinesterase activity, are described. The observed neurotoxicity predominantly affects peripheral nerves in sensory fibers, with a lesser effect on motor fibers. A sural nerve biopsy showed the axonal degeneration of peripheral nerves mainly in small myelinated and unmyelinated fibers. Exposure to high concentrations of As causes severe central nervous system impairment in infants, but no or minimal impairment in adults. The exposure dose–response relationship was observed in various organs including neurological systems. The symptoms caused by heavy metal pollution (including As) are often nonspecific. Therefore, in order to recognize patients experiencing health problems caused by As, a multifaceted approach is needed, including not only clinicians, but also specialists from multiple fields.

Dolutegravir Cerebrospinal Fluid Diffusion in HIV-1–Infected Patients with Central Nervous System Impairment

This study aimed to determine dolutegravir cerebrospinal fluid (CSF) diffusion in 13 patients with HIV-related cerebral impairment enrolled in a real-life observational study. Dolutegravir median (range) CSF concentration [9.6 (3.6–22.8) ng/mL] reached CSF therapeutic concentrations whatever the blood-brain barrier status and diffused in correlation with the albumin quotient (P = .0186).