Post-acute sensory neurological sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: the COVID-PN observational cohort study.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause neurological sequelae after the resolution of symptomatic COVID-19 illness, but the occurrence of peripheral neuropathy symptoms and cranial nerve dysfunction is unknown. This study aimed to characterize the occurrence and severity of pain and peripheral neuropathy symptoms in patients with SARS-CoV-2 infection. An observational cohort study included adults tested for a SARS-CoV-2 infection at an academic medical center (assigned as CV+ or control, based on test results). Thirty to 90 days after the index SARS-CoV-2 test, patients completed a web-based questionnaire assessing pain, peripheral neuropathy-related sensory symptoms, and symptoms in the distribution of cranial nerves (current symptoms, symptoms at testing and 2 weeks thereafter). Univariate analyses compared the outcomes between the groups. Multivariable analysis was used to determine the odds for neuropathy symptoms after adjusting for key baseline variables. A total of 1556 participants were included: 542 CV+ patients and 1014 control subjects. CV+ patients reported a higher occurrence of peripheral neuropathy symptoms in the extremities anytime within 90 days postinfection (28.8% vs 12.9%, odds ratio [OR] [95% confidence interval] = 2.72 [2.10-3.54]), as well as such symptoms persisting up to 90 days after infection (6.1% vs 1.9%, OR = 3.39 [1.91-6.03]). The occurrence of pain in the extremities was higher in the CV+ group (24.2% vs 9.8%, OR = 2.95 [2.21-3.91]). SARS-CoV-2 infection was also associated with higher occurrence of peripheral neuropathy symptoms, after adjusting for the history of chronic pain and neuropathy (OR = 3.19 [2.37-4.29]). The results suggest that SARS-CoV-2 infection was independently associated with an increased risk of pain and peripheral neuropathy symptoms.

Characterization of Patients With and Without Painful Peripheral Neuropathy After Receiving Neurotoxic Chemotherapy: Traditional Quantitative Sensory Testing vs C-Fiber and Aδ-Fiber Selective Diode Laser Stimulation.

Painful chemotherapy induced peripheral neuropathy (CIPN) is a common complication of chemotherapy with drugs such as taxanes and platinum compounds. Currently, no methods are available for early detection of sensory changes that are associated with painful CIPN, nor are there biomarkers that are specific to painful CIPN. This study aimed to compare Diode Laser fiber type-selective stimulator (DLss), a method to selectively stimulate cutaneous C and Aδ fibers, to traditional quantitative sensory testing (QST) in determining psychophysical differences between patients with painful CIPN and a control group. Sensory testing was performed on the dorsal mid-foot of 20 patients with painful neuropathy after taxane- or platinum-based chemotherapy, and 20 patients who received similar neurotoxic chemotherapy, without painful CIPN. In a multivariable analysis, C-fiber to Aδ fiber detection threshold ratio, measured by DLss, was significantly different between the groups (P <.05). While QST parameters such as warmth detection threshold were different between the groups in univariate analyses, these findings were likely attributable to group differences in patient age and cumulative chemotherapy dose. PERSPECTIVE: In this study, fiber-specific DLss test showed potential in identifying sensory changes that are specific for painful neuropathy, encouraging future testing of this approach as a biomarker for early detection of painful CIPN. TRIAL REGISTRATION: The study was approved by the Washington University Institutional Review Board (#201807162) and registered at ClinicalTrials.gov (NCT03687970).

Cohort study protocol to characterize the incidence and severity of neuropathic pain in patients with severe acute respiratory syndrome coronavirus 2 infection.

INTRODUCTION AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has resulted in patients experiencing symptoms that include neurological dysfunction. As many viral infections are associated with neuropathy, the aim of the study is to characterize the incidence and severity of neuropathic pain in patients with COVID-19. METHODS: A cohort study will be conducted in adult (≥18 years) patients who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Washington University/Barnes-Jewish Hospital. Participants who are deceased, with incomplete test results, or who cannot be contacted will be excluded. Approximately 1320 participants will be recruited in a 1:2 ratio of those with a positive-to-negative SARS-CoV-2 test result. Each participant will be invited to complete a survey to assess their symptoms related to neuropathy, 30 to 90 days after their initial SARS-CoV-2 test. Survey responses, demographics, and clinical data from the electronic health record will be used for analysis. The primary outcome is the incidence of new symptoms of neuropathic pain. The self-reported DN4 and Neuropathic Pain Symptom Inventory questionnaires (Appendix 1, http://links.lww.com/PR9/A103) will be used for neuropathic pain screening and severity assessment, respectively. Exploratory analyses will be performed to investigate other potential clinical endpoints and trends. RESULTS/CONCLUSION: Similar to previous coronavirus infections, an increased incidence of new-onset neuropathic pain after COVID-19 disease is expected, along with an increase in the severity experienced by patients with COVID-19 with pre-existing chronic pain. Comprehensive understanding of how COVID-19 affects the nervous system can provide a better framework for managing pain in this disease.

Spatial and Frequency-specific Electrophysiological Signatures of Tonic Pain Recovery in Humans.

The objective of this study was to comprehensively investigate patterns of brain activities associated with pain recovery following experimental tonic pain in humans. Specific electrophysiological features of pain recovery may either be monitored or be modulated through neurofeedback (NF) as a novel chronic pain treatment. The cold pressor test was applied with simultaneous electroencephalogram (EEG) recording. EEG data were acquired, and analyzed to define: (1) EEG power topography patterns of pain recovery; (2) source generators of pain recovery at cortical level; (3) changes in functional connectivity associated with pain recovery; (4) features of phase-amplitude coupling (PAC) as it relates to pain recovery. The novel finding of this study is that recovery from pain was characterized by significant theta power rebound at the left fronto-central area. The sources of theta power over-recovery were located in the left dorsolateral prefrontal cortex (DLPFC), cingulate cortex, left insula and contralateral sensorimotor cortex. These effects were paralleled by theta band connectivity increase within hemispheres in a prefrontal-somatosensory network and interhemispherically between prefrontal and parietal areas. In addition, this study revealed significant reduction in PAC between theta/alpha and gamma oscillations during recovery period following tonic pain. These findings have largely been replicated across two identical sessions. Our study emphasizes the association between pain recovery and left lateral prefrontal theta power rebound, and significant over-recovery of functional connectivity in prefrontal-sensorimotor neural network synchronized at theta frequencies. These findings may provide basis for chronic pain treatment by modulating neural oscillations at theta frequencies in left prefrontal cortex.