Choline-acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the human infant dorsal motor nucleus of the Vagus (DMNV), and alterations according to sudden infant death syndrome (SIDS) category.

Amongst other molecules, the cholinergic system consists of choline-acetyltransferase (ChAT, - synthesis enzyme), acetylcholinesterase (AChE - primary hydrolysis enzyme), and butyrylcholinesterase (BuChE - secondary hydrolysis enzyme). In the brainstem, the Dorsal Motor Nucleus of The Vagus (DMNV) has high cholinergic expression and is a region of interest in the neuropathology of sudden infant death syndrome (SIDS). SIDS is the unexpected death of a seemingly healthy infant, but postmortem brainstem abnormalities suggesting altered cholinergic regulation have been found. This study aimed to determine the percentage of positive ChAT and AChE neurons within the infant DMNV through immunohistochemistry at the three levels of the brainstem medulla (caudal, intermediate, and rostral), to investigate whether the proportion of neurons positive for these enzymes differs amongst the diagnostic subgroups of SIDS compared to those with an explained cause of Sudden unexpected death in infancy (eSUDI), and whether there were any associations with SIDS risk factors (male gender, cigarette smoke exposure, co-sleeping/bed sharing, and prone sleeping). Results showed that ChAT-positive neurons were lower in the rostral DMNV in the SIDS II cohort, and within the caudal and intermediate DMNV of infants who were exposed to cigarette smoke. These findings suggest altered cholinergic regulation in the brainstem of SIDS infants, with potential contribution of cigarette smoke exposure, presumably via the nicotinic acetylcholinergic receptor system.

Sleep dysfunction associated with worse chemotherapy-induced peripheral neurotoxicity functional outcomes.

PURPOSE: Sleep problems are commonly reported by cancer survivors; however, knowledge of the impact of chemotherapy-induced peripheral neurotoxicity (CIPN) on sleep quality remains limited. In this study, we explored the impact of CIPN on sleep quality, as well as identified clinical characteristics associated with poor sleep quality. METHODS: Participants were assessed cross-sectionally post-neurotoxic chemotherapy. CIPN severity was graded using a range of questionnaires that assessed CIPN severity and quality of life, as well as neurological grading scales. Sleep quality was assessed using a self-rated questionnaire (Pittsburgh Sleep Quality Index, PSQI). Participants with poor sleep quality were further grouped according to whether sleep impairment was due to CIPN or other factors. RESULTS: Among 77 participants who reported CIPN, 75% (n = 58) reported poor sleep quality. Of those, 41% (n = 24) reported CIPN as contributing to sleep impairment, while 59% (n = 34) reported other causes. Participants with CIPN-induced sleep impairments had higher CIPN severity across all outcome measures, as well as greater neuropathic pain (all p < 0.05). Furthermore, participants with CIPN-induced sleep impairments reported worse impact of neuropathy on physical and social functioning, as well as emotional well-being (all p < 0.05). CONCLUSIONS: Participants with CIPN-induced poor sleep quality reported worse scores across all CIPN severity measures. This emphasises the negative impacts of CIPN symptoms on quality of life of chemotherapy-treated patients and highlights the importance of sleep quality assessment in cancer survivors.

Upper-limb dysfunction in cancer survivors with chemotherapy-induced peripheral neurotoxicity.

INTRODUCTION: Upper-limb symptoms are often reported in the context of chemotherapy-induced peripheral neurotoxicity (CIPN), but objective quantification of functional deficits is often lacking. We examined and compared a range of neurophysiological and functional assessments of the upper-limb in the assessment of CIPN severity. METHODS: Cross-sectional assessment of neurotoxic chemotherapy-treated patients was undertaken using patient-reported and clinically-graded CIPN measures. Upper-limb functional assessments comprised of assessing fine motor skills, sensory perception, and neurophysiological measures of the median nerve. Group comparisons between participants who reported absence or presence of upper-limb functional deficits were investigated. RESULTS: 60 participants who were 11.5 (IQR = 4.0-26.0) months post-neurotoxic chemotherapy treatment reported CIPN. 65% (n = 39) reported upper-limb CIPN symptoms. Reduction in fine motor skills, sensory perception and median nerve SNAP amplitudes were associated with higher CIPN severity. Participants who self-reported presence of upper-limb functional deficits had worse CIPN severity across all measures, compared to participants who reported no upper-limb functional deficits. CONCLUSIONS: Participants who reported upper-limb symptoms and functional deficits had worse CIPN severity and quality-of-life. There is a high burden of upper-limb dysfunction long after neurotoxic chemotherapy treatment cessation. Focus on research into supportive care and rehabilitation options to improve upper-limb function is warranted to improve patient quality-of-life.