Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability.

OBJECTIVE: Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (St O2 ) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood. METHODS: We investigated the reproducibility of fdNIRS measurements. We measured cortical hypoxia in pwMS, and the relationships between St O2 , neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of St O2 measured at 1-week intervals for 4 weeks, and at 8 weeks and ~1 year. RESULTS: We show that fdNIRS parameters were highly reproducible in 7 healthy control participants measured over 6 days (p > 0.05). There was low variability between and within subjects. In line with our previous findings, we show that 33% of pwMS (n = 88) have cortical microvascular hypoxia. Over 8 weeks and at ~1 year, St O2 values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and St O2 . This conclusion should be revisited as only a small proportion of the relapsing-remitting MS group (21%) was cognitively impaired. INTERPRETATION: The fdNIRS parameters have high reproducibility and repeatability, and we have demonstrated that hypoxia in MS is a chronic condition, lasting at least a year. The results show a weak relationship between cognitive functioning and oxygenation, indicating future study is required. ANN NEUROL 2023;94:1067-1079.

NIRS Studies Show Reduced Interhemispheric Functional Connectivity in Individuals with Multiple Sclerosis That Exhibit Cortical Hypoxia.

Many with multiple sclerosis (MS) have low cortical microvascular oxygen levels (hypoxia), which have been previously proposed to exacerbate inflammation in MS. We do not know if hypoxia impacts or relates to brain function. We hypothesise that within the MS population, those who have hypoxia may show reduced brain functional connectivity (FC). We recruited 20 MS participants and grouped them into normoxic and hypoxic groups (n = 10 in each group) using frequency-domain near-infrared spectroscopy (fdNIRS). Functional coherence of the haemodynamic signal, quantified with functional near-infrared spectroscopy (fNIRS) was used as a marker of brain function and was carried out during resting-state, finger-tapping, and while completing two neurocognitive tasks. Reduced FC was detected in the hypoxic MS group. fNIRS measures of haemodynamic coherence in MS could be a biomarker of functional impairment and/or disease progression.

Advanced diffusion MRI and image texture analysis detect widespread brain structural differences between relapsing-remitting and secondary progressive multiple sclerosis.

Introduction: Disease development in multiple sclerosis (MS) causes dramatic structural changes, but the exact changing patterns are unclear. Our objective is to investigate the differences in brain structure locally and spatially between relapsing-remitting MS (RRMS) and its advanced form, secondary progressive MS (SPMS), through advanced analysis of diffusion magnetic resonance imaging (MRI) and image texture. Methods: A total of 20 patients with RRMS and nine patients with SPMS from two datasets underwent 3T anatomical and diffusion tensor imaging (DTI). The DTI was harmonized, augmented, and then modeled, which generated six voxel- and sub-voxel-scale measures. Texture analysis focused on T2 and FLAIR MRI, which produced two phase-based measures, namely, phase congruency and weighted mean phase. Data analysis was 3-fold, i.e., histogram analysis of whole-brain normal appearing white matter (NAWM); region of interest (ROI) analysis of NAWM and lesions within three critical white matter tracts, namely, corpus callosum, corticospinal tract, and optic radiation; and along-tract statistics. Furthermore, by calculating the z-score of core-rim pathology within lesions based on diffusion measures, we developed a novel method to define chronic active lesions and compared them between cohorts. Results: Histogram features from diffusion and all but one texture measure differentiated between RRMS and SPMS. Within-tract ROI analysis detected cohort differences in both NAWM and lesions of the corpus callosum body in three measures of neurite orientation and anisotropy. Along-tract statistics detected cohort differences from multiple measures, particularly lesion extent, which increased significantly in SPMS in posterior corpus callosum and optic radiations. The number of chronic active lesions were also significantly higher (by 5-20% over z-scores 0.5 and 1.0) in SPMS than RRMS based on diffusion anisotropy, neurite content, and diameter. Conclusion: Advanced diffusion MRI and texture analysis may be promising approaches for thorough understanding of brain structural changes from RRMS to SPMS, thereby providing new insight into disease development mechanisms in MS.

A Quality Improvement Project to Determine the Effect of Aromatherapy on Postoperative Nausea and Vomiting in a Short-Stay Surgical Population.

Postoperative nausea and vomiting (PONV) is a major concern for short-stay surgical patients because it can delay discharge and cause preventable postoperative complications, which in turn can increase hospital costs. Evidence suggests that aromatherapy effectively reduces PONV, either as a monotherapy or in conjunction with pharmacologic antiemetics. This quality improvement project investigated the effectiveness of aromatherapy in reducing PONV in a short-stay surgical population. The outcome of this project supported the hypothesis that the administration of blended aromatherapy would result in a significant decrease in patients' self-reported ratings of nausea. This finding suggests that aromatherapy is an appropriate adjunct therapy for decreasing patient nausea and vomiting in this short-stay surgical unit and may help prevent discharge delays in this population.

Implications of Maple Syrup Urine Disease in Newborns.

Maple syrup urine disease (MSUD) is an inherited metabolic disorder that affects the body's ability to metabolize amino acids. If left untreated, it places newborns at risk for life-threatening health problems, including episodes of illness called metabolic crisis. Newborn screening for MSUD should ideally be done within the first 24 to 48 hours after birth. With proper screening, along with genetic counseling, nutritional counseling, primary care follow-up, and ongoing monitoring, newborns with MSUD can typically go on to live healthful lives. Nurses play a key role in supporting families with a diagnosis of MSUD.

Clinical utility of the mini-mental status examination when assessing decision-making capacity.

The main objectives of this study were to examine the relationship between cognitive deficits, as measured by the Mini-Mental Status Examination (MMSE), and decision-making capacity and to determine whether the sensitivity and specificity of the MMSE varied based upon the patient population assessed. Using a sample size of 152 patients and varying cutoff scores, the MMSE demonstrated extremely poor sensitivity. In contrast, the MMSE had excellent specificity when scores of 19 or less were obtained. In our sample, not one patient, regardless of diagnosis, was deemed to have capacity if their MMSE score was below 20. However, reliance on the MMSE for scores above 19 would too frequently lead to misclassification and incorrect assumptions about a patient's decision-making abilities. Although a score below 20 consistently yielded findings of incapability in our sample, it remains our opinion that the MMSE should not be used as a stand-alone tool to make determinations related to capacity, especially when considering the complexities associated with capacity evaluations and the vital areas, such as executive functioning and individual values and beliefs, which are omitted by the MMSE.

Sensory temporal processing in adults with early hearing loss.

This study examined tactile and visual temporal processing in adults with early loss of hearing. The tactile task consisted of punctate stimulations that were delivered to one or both hands by a mechanical tactile stimulator. Pairs of light emitting diodes were presented on a display for visual stimulation. Responses consisted of YES or NO judgments as to whether the onset of the pairs of stimuli was perceived simultaneously or non-simultaneously. Tactile and visual temporal thresholds were significantly higher for the deaf group when compared to controls. In contrast to controls, tactile and visual temporal thresholds for the deaf group did not differ when presentation locations were examined. Overall findings of this study support the notion that temporal processing is compromised following early deafness regardless of the spatial location in which the stimuli are presented.

Temporal judgments, hemispheric equivalence, and interhemispheric transfer in adolescents with attention deficit hyperactivity disorder.

This study investigated temporal processing abilities, hemispheric asymmetry, interhemispheric transfer, and stimulant medication effects in adolescents with attention deficit hyperactivity disorder (ADHD). Pairs of light emitting diodes in a visual half-field display (i.e., bilateral and unilateral presentations) were presented to examine medication effects, temporal judgments, hemispheric asymmetry, and interhemispheric transfer in male adolescents with ADHD and matched controls on age and gender. Participants responded (YES/NO) whether pairs of spatially separated diodes were illuminated simultaneously. Stimulant medication did not have an affect on temporal judgments, hemispheric equivalence, or interhemispheric transfer. No group differences in temporal judgments in any of the paired conditions were revealed. Both the ADHD and control groups demonstrated hemispheric equivalence for temporal judgments. Unexpectedly, the ADHD group demonstrated significantly faster interhemispheric transfer times when compared to the control group. The overall findings indicate that the reported deficit in time perception among individuals with ADHD may be restricted to tasks that involve response inhibition, reaction time, and/or motor movements (e.g., replicate durations of stimuli by pressing a lever).

Sensory temporal thresholds and interhemispheric transfer times in multiple sclerosis: a preliminary study of a new outcome measure.

This preliminary study investigated the potential of a cerebral lateralization technique that measures both, temporal judgements to sensory stimuli and interhemispheric transfer time (IHTT), as an outcome measure in multiple sclerosis (MS). Tactile stimulation was delivered to one or both hands by mechanical tactile stimulators. Pairs of light emitting diodes were presented to hemifields for visual stimulation. Response consisted of a binary forced-choice (YES/NO) judgement as to the simultaneity of the onset of pairs of stimuli. Both tactile and visual temporal thresholds were significantly higher in MS patients than controls in every presentation condition. IHTT estimates (threshold differences between unilateral and bilateral presentations) for the tactile and visual tasks were also significantly longer in patients than controls. Age correlated with sensory temporal thresholds for the control group only. These findings suggest that this technique may be a useful outcome measure in MS. We hypothesize that myelin injury slows central conduction therefore impairing the ability to judge the onset of sensory stimuli and increasing IHTTs.

Age- and sex-related differences in temporal judgments to visual stimuli: support for hemispheric equivalence.

Light-emitting diodes in avisual half-field display were employed to examine hemispheric asymmetries in temporal resolution among young and older adults. Participants judged whether pairs of spatially separated diodes were illuminated simultaneously. No visual field threshold differences emerged for either age group, thus supporting hemispheric equivalence. Older adults had significantly higher thresholds than did younger adults, regardless of spatial location. The results further revealed that older females had significantly higher thresholds than did older males, younger males, and younger females. The results further revealed sex differences, favoring females, when interhemispheric transfer times (IHTTs) were examined for a central bilateral presentation. However, sex effects were not revealed when IHTTs were examined for a peripheral bilatepresentation, indicating a disadvantage forolder females.

Gaze pursuit and arm control of adolescent males diagnosed with attention deficit hyperactivity disorder (ADHD) and normal controls: evidence of a dissociation in processing visual information of short and long duration.

Three-dimensional kinematic analysis of line of gaze, arm and ball was used to describe the visual and motor behaviour of male adolescents diagnosed with attention deficit hyperactivity disorder (ADHD). The ADHD participants were tested when both on (ADHD-On) and off (ADHD-Off) their medication and compared to age-matched normal controls in a modified table tennis task that required tracking the ball and hitting to cued right and left targets. Long-duration information was provided by a pre-cue, in which the target was illuminated approximately 2 s before the serve, and short-duration information by an early-cue illuminated about 350 ms after the serve, leaving approximately 500 ms to select the target and perform the action. The ADHD groups differed significantly from the control group in both the pre-cue and early-cue conditions in being less accurate, in having a later onset and duration of pursuit tracking, and a higher frequency of gaze on and off the ball. The use of medication significantly reduced the gaze frequency of the ADHD participants, but surprisingly this did not lead to an increase in pursuit tracking, suggesting a barrier was reached beyond which ball flight information could not be processed. The control and ADHD groups did not differ in arm movement onset, duration and velocity in the short-duration early-cue condition; in the long-duration pre-cue condition, however, the ADHD group's movement time onset and arm velocity differed significantly from controls. The results show that the ADHD groups were able to process short-duration information without experiencing adverse effects on their motor behaviour; however, long-duration information contributed to irregular movement control.