Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

The aim of this study was to assess age- and sex-related differences in multiple sleep latency test (MSLT) results and in the performance of the Epworth Sleepiness Scale (ESS) at classifying objective hypersomnia (mean sleep latency (MSL) ≤ 8 min). We studied 480 consecutive adults (39.3 ± 15.3 years old [18-93], 67.7% female) who underwent hypersomnia evaluation. We fit linear regression models to investigate associations between age and sex and sleep latencies (mean and for every nap), after adjusting for total sleep time and sleep efficiency (on polysomnography), and REM-suppressing antidepressant effect. A logistic regression was performed to assess whether age and sex were associated with sleep-onset REM period (SOREMP) occurrence. ROC analysis assessed the diagnostic performance of ESS scores to identify a MSL ≤ 8 min in different age/sex groups. For every 10 years of age, there was 0.41 (95% CI 0.11-0.72, p = 0.008) min reduction in MSL. Objectively (MSL ≤ 8 min) sleepy patients had shortening of latencies in naps 4 and 5 with aging. Female sex was associated with a higher MSL only in patients with MSL > 8 min. A 2.4% reduction in the odds of SOREMP occurrence was observed for every year of age in objectively sleepy patients (p = 0.045). ESS scores had a better diagnostic performance in older (≥ 50 years old) men than younger (< 50 years old) women (p < 0.05). Older patients with objectively confirmed hypersomnia may be sleepier in later naps, possibly due to less restorative naps and/or circadian rhythm factors. Self-reported sleepiness is more predictive of objective sleepiness in older men than younger women.

Correction: Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

[This corrects the article DOI: 10.1007/s41105-024-00512-5.].

Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder.

STUDY OBJECTIVES: Accurate diagnosis of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is crucial due to its injury potential and neurological prognosis. We aimed to analyze visual and automated REM sleep without atonia (RSWA) diagnostic thresholds applicable in varying clinical presentations in a contemporary cohort of patients with iRBD using submentalis (SM) and individual bilateral flexor digitorum superficialis (FDS) and anterior tibialis electromyography limb recordings during polysomnography. METHODS: We analyzed RSWA in 20 patients with iRBD and 20 age-, REM-, apnea-hypopnea index-matched controls between 2017 and 2022 for phasic burst durations, density of phasic, tonic, and "any" muscle activity (number of 3-second mini-epochs containing phasic or tonic muscle activity divided by the total number of REM sleep 3-second mini-epochs), and automated Ferri REM atonia index (RAI). Group RSWA metrics were comparatively analyzed. Receiver operating characteristic curves determined optimized area under the curve (AUC) and maximized specificity and sensitivity diagnostic iRBD RSWA thresholds. RESULTS: All mean RSWA metrics were higher in patients with iRBD than in controls (P < .05), except for selected anterior tibialis measures. Optimized, maximal specificity AUC diagnostic cutoffs for coprimary outcomes were: SM "any" 6.5%, 14.0% (AUC = 92.5%) and combined SM+FDS "any" 15.1%, 27.4% (AUC = 95.8%), while SM burst durations were 0.72, and 0.72 seconds (AUC 90.2%) and FDS RAI = 0.930, 0.888 (AUC 92.8%). CONCLUSIONS: This study provides evidence for current quantitative RSWA diagnostic thresholds in chin and individual 4 limb muscles applicable in different iRBD clinical settings and confirms the key value of SM or SM+FDS to assure accurate iRBD diagnosis. Evolving iRBD recognition underscores the necessity of continuous assessment with future large, prospective, well-harmonized, multicenter polysomnographic analyses. CITATION: Leclair-Visonneau L, Feemster JC, Bibi N, et al. Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder. J Clin Sleep Med. 2024;20(2):279-291.

Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

BACKGROUND: Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. OBJECTIVE: Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. METHODS: We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. DISCUSSION: The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Spinal cord stimulation for gait impairment in Parkinson Disease: scoping review and mechanistic considerations.

OBJECTIVE: Advanced Parkinson's Disease (PD) is associated with Parkinson's Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. METHODS: We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. RESULTS: Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests.Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. CONCLUSIONS: Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.

Phase-Amplitude Coupling Localizes Pathologic Brain with Aid of Behavioral Staging in Sleep.

Low frequency brain rhythms facilitate communication across large spatial regions in the brain and high frequency rhythms are thought to signify local processing among nearby assemblies. A heavily investigated mode by which these low frequency and high frequency phenomenon interact is phase-amplitude coupling (PAC). This phenomenon has recently shown promise as a novel electrophysiologic biomarker, in a number of neurologic diseases including human epilepsy. In 17 medically refractory epilepsy patients undergoing phase-2 monitoring for the evaluation of surgical resection and in whom temporal depth electrodes were implanted, we investigated the electrophysiologic relationships of PAC in epileptogenic (seizure onset zone or SOZ) and non-epileptogenic tissue (non-SOZ). That this biomarker can differentiate seizure onset zone from non-seizure onset zone has been established with ictal and pre-ictal data, but less so with interictal data. Here we show that this biomarker can differentiate SOZ from non-SOZ interictally and is also a function of interictal epileptiform discharges. We also show a differential level of PAC in slow-wave-sleep relative to NREM1-2 and awake states. Lastly, we show AUROC evaluation of the localization of SOZ is optimal when utilizing beta or alpha phase onto high-gamma or ripple band. The results suggest an elevated PAC may reflect an electrophysiology-based biomarker for abnormal/epileptogenic brain regions.

Association of Polysomnographic Sleep Parameters With Neuroimaging Biomarkers of Cerebrovascular Disease in Older Adults With Sleep Apnea.

BACKGROUND AND OBJECTIVES: Our objective was to determine whether polysomnographic (PSG) sleep parameters are associated with neuroimaging biomarkers of cerebrovascular disease (CVD) related to white matter (WM) integrity in older adults with obstructive sleep apnea (OSA). METHODS: From the population-based Mayo Clinic Study of Aging, we identified participants without dementia who underwent at least 1 brain MRI and PSG. We quantified 2 CVD biomarkers: WM hyperintensities (WMHs) from fluid-attenuated inversion recovery (FLAIR)-MRI, and fractional anisotropy of the genu of the corpus callosum (genu FA) from diffusion MRI. For this cross-sectional analysis, we fit linear models to assess associations between PSG parameters (NREM stage 1 percentage, NREM stage 3 percentage [slow-wave sleep], mean oxyhemoglobin saturation, and log of apnea-hypopnea index [AHI]) and CVD biomarkers (log of WMH and log of genu FA), respectively, while adjusting for age (at MRI), sex, APOE ε4 status, composite cardiovascular and metabolic conditions (CMC) score, REM stage percentage, sleep duration, and interval between MRI and PSG. RESULTS: We included 140 participants with FLAIR-MRI (of which 103 had additional diffusion MRI). The mean ± SD age was 72.7 ± 9.6 years at MRI with nearly 60% being men. The absolute median (interquartile range [IQR]) interval between MRI and PSG was 1.74 (0.9-3.2) years. 90.7% were cognitively unimpaired (CU) during both assessments. For every 10-point decrease in N3%, there was a 0.058 (95% CI 0.006-0.111, p = 0.030) increase in the log of WMH and 0.006 decrease (95% CI -0.012 to -0.0002, p = 0.042) in the log of genu FA. After matching for age, sex, and N3%, participants with severe OSA had higher WMH (median [IQR] 0.007 [0.005-0.015] vs 0.006 [0.003-0.009], p = 0.042) and lower genu FA (median [IQR] 0.57 [0.55-0.63] vs 0.63 [0.58-0.65], p = 0.007), when compared with those with mild/moderate OSA. DISCUSSION: We found that reduced slow-wave sleep and severe OSA were associated with higher burden of WM abnormalities in predominantly CU older adults, which may contribute to greater risk of cognitive impairment, dementia, and stroke. Our study supports the association between sleep depth/fragmentation and intermittent hypoxia and CVD biomarkers. Longitudinal studies are required to assess causation.

Evaluating an under-mattress sleep monitor compared to a peripheral arterial tonometry home sleep apnea test device in the diagnosis of obstructive sleep apnea.

STUDY OBJECTIVES: To evaluate whether or not the apnea-hypopnea index (AHI) from a peripheral arterial tonometry (PAT) home sleep apnea test (HSAT) is equivalent to the AHI provided by the mean of one, three, or seven nights from the Withings Sleep Analyzer (WSA) under-mattress device. METHODS: We prospectively enrolled patients with suspected OSA in whom a PAT-HSAT was ordered. Eligible patients used the WSA for seven to nine nights. PAT data were scored using the device's intrinsic machine learning algorithms to arrive at the AHI using both 3% and 4% desaturation criteria for hypopnea estimations (PAT3%-AHI and PAT4%-AHI, respectively). These were then compared with the WSA-estimated AHI (WSA-AHI). RESULTS: Of 61 patients enrolled, 35 completed the study with valid PAT and WSA data. Of the 35 completers 16 (46%) had at least moderately severe OSA (PAT3%-AHI ≥ 15). The seven-night mean WSA-AHI was 2.13 (95%CI = - 0.88, 5.14) less than the PAT3%-AHI, but 5.64 (95%CI = 2.54, 8.73) greater than the PAT4%-AHI. The accuracy and area under the receiver operating curve (AUC) using the PAT3%-AHI ≥ 15 were 77% and 0.87 and for PAT4%-AHI ≥ 15 were 77% and 0.85, respectively. The one-, three-, or seven-night WSA-AHI were not equivalent to either the 3% or 4% PAT-AHI (equivalency threshold of ± 2.5 using the two one-sided t-test method). CONCLUSIONS: The WSA derives estimates of the AHI unobtrusively over many nights, which may prove to be a valuable clinical tool. However, the WSA-AHI over- or underestimates the PAT-AHI in clinical use, and the appropriate use of the WSA in clinical practice will require further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04778748.

Patient values and preferences regarding prognostic counseling in isolated REM sleep behavior disorder.

STUDY OBJECTIVES: Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. METHODS: One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. RESULTS: Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. CONCLUSIONS: Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients' values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity.

Introduction: Sleepiness has been associated with cognitive decline and dementia in the elderly. Older adults with excessive daytime sleepiness appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. However, it remains unclear whether sleepiness is similarly associated with other biomarkers of Alzheimer's disease (AD), axonal integrity, and inflammation, which may also contribute to neurodegeneration and cognitive decline. Methods: In this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years) from the Mayo Clinic Study of Aging, a population-based cohort from Olmsted County (MN), who underwent CSF quantification of AD biomarkers (Aß42, p-tau, p-tau/Aß42) in addition to at least one of the following biomarkers [neurofilament light chain (NfL) interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α)]. We fit linear regression models to assess associations between sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and CSF biomarkers, controlling for age, sex, APOε4 status, body mass index, hypertension, dyslipidemia, and prior diagnosis of obstructive sleep apnea. Results: Higher ESS scores were associated with higher CSF IL-6 and NfL, but not with the other CSF biomarkers. For every ESS score point increase, there was a 0.009 ([95% CI 0.001-0.016], p = 0.033) increase in the log of IL-6 and 0.01 ([95% CI 0.002-0.018], p = 0.016) increase in the log of NfL. A sensitivity analysis showed an association between ESS scores and log of p-tau/Aß42 only in participants with an abnormal ratio (>0.023), highly predictive of amyloid positivity. For every ESS score point increase, there was a 0.006 ([95% CI 0.001-0.012], p = 0.021) increase in the log of CSF p-tau/Aß42. Conclusion: Sleepiness was associated with greater CSF IL-6 and NfL levels, which could contribute to neurodegeneration or alternatively cause sleepiness. Higher NfL levels may result from sleep disruption and/or contribute to sleepiness via disturbed connectivity or damage to wake-promoting centers. Associations between sleepiness and p-tau/Aß42 in participants with abnormal ratio suggest that amyloid positivity contributes to vulnerability to sleep disturbance, which may further amyloid accumulation in a feed-forward loop process. Prospective studies of these markers are needed to determine cause-effect relationships between these associations.

Sleep and Epilepsy: a Focused Review of Pathophysiology, Clinical Syndromes, Co-morbidities, and Therapy.

A healthy brain requires balancing of waking and sleeping states. The normal changes in waking and sleeping states result in neurophysiological conditions that either increase or decrease the tendency of seizures and interictal discharges to occur. This article reviews the manifold and complex relationships between sleep and epilepsy and discusses treatment of the sleep-related epilepsies. Several forms of epilepsy predominantly or exclusively manifest during sleep and seizures tend to arise especially from light NREM sleep. Diagnostic interictal epileptiform discharges on the electroencephalogram are also most likely to be activated during deep NREM sleep stage N3. Epileptiform discharges and antiepileptic medications may in turn detrimentally impact sleep. Co-morbid sleep disorders also have the potential to worsen seizure control. Sleep has an important key association with sudden unexpected death in epilepsy (SUDEP). Further research is necessary to understand the complex relationships between sleep and epileptic disorders and their treatments.

Witnessed apneas are associated with elevated tau-PET levels in cognitively unimpaired elderly.

OBJECTIVE: To assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau. METHODS: From the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly ≥65 years of age with both AV-1451 tau-PET and Pittsburgh compound B (PiB)-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the entorhinal and inferior temporal cortices as our regions of interest (ROIs) because they are highly susceptible to tau accumulation. PET signal was scaled to the cerebellum crus to calculate standardized uptake value ratio (SUVR). We fit linear models to assess the association between regional tau and witnessed apneas while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global PiB. RESULTS: Forty-three participants (14.7%) were found to have witnessed apneas during sleep. The report of witnessed apneas was associated with higher tau-PET SUVR elevation in our ROIs: 0.049 SUVR (95% confidence interval [CI] 0.010-0.087, p = 0.015) in the entorhinal cortex and 0.037 SUVR (95% CI 0.006-0.067, p = 0.019) in the inferior temporal cortex after controlling for confounders. CONCLUSION: We identified a significant association between witnessed apneas in CU elderly and elevated tau-PET signal in tau-susceptible brain regions. These results suggest a plausible mechanism that could contribute to cognitive impairment and the development of Alzheimer disease. Longitudinal observations are necessary to determine direction of causality.

Brain age from the electroencephalogram of sleep.

The human electroencephalogram (EEG) of sleep undergoes profound changes with age. These changes can be conceptualized as "brain age (BA)," which can be compared to chronological age to reflect the degree of deviation from normal aging. Here, we develop an interpretable machine learning model to predict BA based on 2 large sleep EEG data sets: the Massachusetts General Hospital (MGH) sleep lab data set (N = 2532; ages 18-80); and the Sleep Heart Health Study (SHHS, N = 1974; ages 40-80). The model obtains a mean absolute deviation of 7.6 years between BA and chronological age (CA) in healthy participants in the MGH data set. As validation, a subset of SHHS containing longitudinal EEGs 5.2 years apart shows an average of 5.4 years increase in BA. Participants with significant neurological or psychiatric disease exhibit a mean excess BA, or "brain age index" (BAI = BA-CA) of 4 years relative to healthy controls. Participants with hypertension and diabetes have a mean excess BA of 3.5 years. The findings raise the prospect of using the sleep EEG as a potential biomarker for healthy brain aging.

Association of Excessive Daytime Sleepiness With Longitudinal ß-Amyloid Accumulation in Elderly Persons Without Dementia.

Importance: Aging is associated with excessive daytime sleepiness (EDS), which has been linked to cognitive decline in the elderly. However, whether EDS is associated with the pathologic processes of Alzheimer disease remains unclear. Objective: To investigate whether EDS at baseline is associated with a longitudinal increase in regional ß-amyloid (Aß) accumulation in a cohort of elderly individuals without dementia. Design, Setting, and Participants: This prospective analysis included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota. Of 2900 participants, 2172 (74.9%) agreed to undergo carbon 11-labeled Pittsburgh compound B positron emission tomography (PiB-PET). We included 283 participants 70 years or older without dementia who completed surveys assessing sleepiness at baseline and had at least 2 consecutive PiB-PET scans from January 1, 2009, through July 31, 2016, after excluding 45 (13.7%) who had a comorbid neurologic disorder. Main Outcomes and Measures: Excessive daytime sleepiness was defined as an Epworth Sleepiness Scale score of at least 10. The difference in Aß levels between the 2 consecutive scans (ΔPiB) in Aß-susceptible regions (prefrontal, anterior cingulate, posterior cingulate-precuneus, and parietal) was determined. Multiple linear regression models were fit to explore associations between baseline EDS and ΔPiB while adjusting for baseline age, sex, presence of the apolipoprotein E ε4 allele, educational level, baseline PiB uptake, global PiB positivity (standardized uptake value ratio ≥1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, and diabetes), reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans. Results: Of the initial 283 participants, mean (SD) age was 77.1 (4.8) years; 204 (72.1%) were men and 79 (27.9%) were women. Sixty-three participants (22.3%) had EDS. Baseline EDS was significantly associated with increased regional Aß accumulation in the anterior cingulate (B coefficient = 0.031; 95% CI, 0.001-0.061; P = .04), posterior cingulate-precuneus (B coefficient = 0.038; 95% CI, 0.006-0.069; P = .02), and parietal (B coefficient = 0.033; 95% CI, 0.001-0.065; P = .04) regions. Association of EDS with longitudinal Aß accumulation was stronger in participants with baseline global PiB positivity in the anterior cingulate (B coefficient = 0.065; 95% CI, 0.010-0.118; P = .02) and cingulate-precuneus (B coefficient = 0.068; 95% CI, 0.009-0.126; P = .02) regions. Conclusions and Relevance: Baseline EDS was associated with increased longitudinal Aß accumulation in elderly persons without dementia, suggesting that those with EDS may be more vulnerable to pathologic changes associated with Alzheimer disease. Further work is needed to elucidate whether EDS is a clinical marker of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. Early identification of patients with EDS and treatment of underlying sleep disorders could reduce Aß accumulation in this vulnerable group.

Propofol Frenzy: Clinical Spectrum in 3 Patients.

Postsedation neuroexcitation is sometimes attributed to intravenous injection of the sedative-hypnotic drug propofol. The movements associated with these events have strongly suggested convulsive activity, but they rarely have been comprehensively evaluated. We present video recordings of 3 healthy young patients who underwent elective surgery under conscious sedation and emerged from sedation with transient but repetitive violent motor activity and impaired consciousness. These manifestations required considerable mobilization of multiple health care workers to protect the patient from inflicting harm. All patients received propofol, and all fully recovered without adverse sequelae. We postulate that these movements are propofol related. Importantly, we found no evidence of seizures clinically or electrographically.

Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults.

Excessive daytime sleepiness (EDS) and fatigue increases with age. The aim of this study was to investigate the association between EDS and fatigue with cortical thickness and hippocampal volume in cognitively normal, late middle-aged and older adults. We performed a cross-sectional observational study of 1374 cognitively-normal subjects aged 50 years and older who had a structural MRI. Regional cortical thickness and hippocampal volume were measured. Multiple linear regression models were fit to explore associations between EDS and fatigue and structural MRI measures in different brain regions, adjusting for multiple covariates. EDS was defined as Epworth Sleepiness Scale ≥10. Fatigue severity was assessed with the Beck Depression Inventory-2. 208 participants had EDS, 27 had significant fatigue, and 11 had both. Participants with EDS or fatigue had significantly lower cognitive scores, more disturbed sleep, and medical comorbidities. The presence of EDS was associated with both global and regional atrophy, whereas fatigue was more associated with frontal and temporal changes. Cortical thinning predicted by EDS and fatigue was maximal in the temporal region with average reduction of 34.2 µm (95% CI, -54.1, -14.3; P = 0.001) and 90.2 µm (95% CI, -142.1, -38.2; P = 0.001), respectively. Fatigue was also associated with hippocampal volume reduction of -374.2 mm3 (95% CI, -670.8, -77.7; P = 0.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and 9 additional years of aging, respectively. EDS and fatigue were associated with cortical thickness reduction primarily in regions with increased age-susceptibility, which may indicate accelerated brain aging.

Absent quadriceps reflex with distant toe flexor response: An underrecognized neurological sign.

As opposed to finger flexion response upon tapping the styloid process with absent brachioradialis reflex (inverted brachioradialis reflex), toe flexion response upon patellar percussion with absent quadriceps reflex is a quite underrecognized neurological sign, and has been reported only once in the literature. Similar to the inverted brachioradialis reflex, this sign can also be useful for neurological localization. We hereby report a patient presenting with signs and symptoms of lumbar radiculopathy in the setting of an anterior epidural mass compressing the cauda equina at L2-L4, without evidence of myelopathy. Upon examination, the patient had bilateral absent quadriceps reflexes with a right toe flexor response when the right patella was percussed. An absent quadriceps reflex with distant toe flexor response is proposed as a lower extremity equivalent of the inverted brachioradialis reflex, likely localizing to L3-L4 levels. Spindle hypersensitivity due to lack of reciprocal inhibition from antagonist muscles is hypothesized as a possible underlying mechanism. Further observations should help clarify the most common underlying etiology (radicular vs. radiculomyelopathy). Neurologists should be able to recognize this sign, as it can be helpful for neurological localization.