Ipilimumab toxicity presented as a monophasic, multifocal, asymmetric polyradiculoneuropathy involving roots and peripheral and cranial nerves. Ipilimumab may produce a polyradiculoneuropathy with disruption of the blood-nerve barrier due to a microvasculopathy.
Background
The association between autonomic dysfunction and long‐COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long‐COVID syndrome in a large population are lacking.
Objective
To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long‐COVID syndrome.
Methods
We administered the Composite Autonomic Symptom Score 31 (COMPASS‐31) questionnaire to a sample of post‐COVID‐19 patients who were referred to post‐COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long‐COVID syndrome. Participants were asked to complete the COMPASS‐31 questionnaire referring to the period of more than 4 weeks after acute COVID‐19.
Results
We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS‐31 score was 26.29 (0–76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS‐31 score and long‐COVID duration (
p
< 0.001) and a positive correlation between orthostatic intolerance domain score and post‐COVID duration (
p
< 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (
p
= 0.004). Two hundred forty‐seven patients (76.7%) had a high score of COMPASS‐31 >16.4. Patients with COMPASS‐31 >16.4 had a longer duration of long‐COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks,
p
< 0.001).
Conclusions
Symptoms of dysautonomia are common in long‐COVID syndrome. The most common COMPASS‐31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.
Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS.
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