Citations

Accurate antemortem diagnosis of parkinsonism is primarily based on clinical evaluation with limited biomarkers. We evaluated the diagnostic utility of quantitative rapid eye movement (REM) sleep without atonia analysis in the submentalis and anterior tibialis muscles in parkinsonian patients (53 synucleinopathy, 24 tauopathy). Receiver operating characteristic curves determined REM sleep without atonia cutoffs distinguishing synucleinopathies from tauopathies. Elevated submentalis muscle activity was highly sensitive (70–77%) and specific (95–100%) in distinguishing synucleinopathy from tauopathy. In contrast, anterior tibialis synucleinopathy discrimination was poor. Our results suggest that elevated submentalis REM sleep without atonia appears to be a potentially useful biomarker for presumed synucleinopathy etiologies in parkinsonism. ANN NEUROL 2019;86:969–974

Abstract Study Objectives Values for normative REM sleep without atonia (RSWA) remain unclear. Older age and male sex are associated with greater RSWA, and isolated elevated RSWA has been reported. We aimed to describe normative RSWA and characterize isolated RSWA frequency in adults without REM sleep behavior disorder (RBD). Methods We visually quantified phasic, “any,” and tonic RSWA in the submentalis (SM) and anterior tibialis (AT) muscles, and the automated Ferri REM Atonia Index during polysomnography in adults without RBD aged 21–88. We calculated RSWA percentiles across age and sex deciles and compared RSWA in older (≥ 65) versus younger (<65) men and women. Isolated RSWA (exceeding diagnostic RBD cutoffs, or >95th percentile) frequency was also determined. Results Overall, 95th percentile RSWA percentages were SM phasic, any, tonic = 8.6%, 9.1%, 0.99%; AT phasic and “any” = 17.0%; combined SM/AT phasic, “any” = 22.3%, 25.5%; and RAI = 0.85. Most phasic RSWA burst durations were ≤1.0 s (85th percentiles: SM = 1.07, AT = 0.86 seconds). Older men had significantly higher AT RSWA than older women and younger patients (all p < 0.04). Twenty-nine (25%, 18 men) had RSWA exceeding the cohort 95th percentile, while 17 (14%, 12 men) fulfilled diagnostic cutoffs for phasic or automated RBD RSWA thresholds. Conclusions RSWA levels are highest in older men, mirroring the demographic characteristics of RBD, suggesting that older men frequently have altered REM sleep atonia control. These data establish normative adult RSWA values and thresholds for determination of isolated RSWA elevation, potentially aiding RBD diagnosis and discussions concerning incidental RSWA in clinical sleep medicine practice.

Mary Broadfoot Walker (1888-1974) was the first to demonstrate the ‘Mary Walker effect’ describing the weakness of other muscle groups following release of the arteriovenous occlusion of an unrelated exercising muscle group in patients with myasthenia gravis, which led to the search for a circulating causative agent for myasthenia gravis. She was the first to clearly demonstrate that strength temporarily improved in patients with myasthenia gravis with physostigmine or Prostigmin (neostigmine). This dramatic treatment response has been erroneously termed the ‘Mary Walker effect'. Further, she noted hypokalaemia during attacks of weakness in familial periodic paralysis, pioneering treatment with potassium chloride. Although Mary Walker practiced in a nonacademic setting and trained at a time when women were not allowed to train alongside men, she was the first to convincingly demonstrate three life-changing treatments in the field of neuromuscular medicine, a feat that few physicians of any era can claim.

SummaryObjectiveWe aimed to determine the frequency of probable obstructive sleep apnea (pOSA) in refractory epilepsy monitoring unit inpatients and clinical features associated with pOSA, including risk for sudden unexpected death in epilepsy (SUDEP).MethodsWe prospectively recruited 49 consecutive adult patients admitted to the Mayo Clinic Epilepsy Monitoring Unit with focal, generalized, or unclassified epilepsy syndromes. pOSA was identified using oximetric oxyhemoglobin desaturation index (ODI) and the Sleep Apnea–Sleep Disorders Questionnaire (SA‐SDQ) and STOP‐BAG screening tools. Revised SUDEP Risk Inventory (rSUDEP‐7) scores were calculated, and epilepsy patients with and without pOSA were compared with Wilcoxon signed‐rank tests. Correlation and regression analyses were utilized to determine relationships between pOSA and rSUDEP‐7 scores.ResultsThirty‐five percent of patients had pOSA, with a mean ODI of 11.3 ± 5.1/h (range = 5.1‐22.8). Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration, with higher SA‐SDQ and STOP‐BAG scores (all P < 0.05). Median rSUDEP‐7 score was 3 ± 1.4 (range = 0‐6). Higher rSUDEP‐7 scores were positively correlated with higher ODI (P = 0.036). rSUDEP‐7 score ≥ 5 was associated with pOSA by ODI, SA‐SDQ, and STOP‐BAG questionnaire criteria (P < 0.05).SignificanceOur pilot study identified a high frequency of pOSA in refractory epilepsy monitoring patients, finding that pOSA patients were older and heavier, with higher screening symptoms for sleep apnea and more frequent focal seizures with a longer epilepsy duration. We also found a possible association between OSA and SUDEP risk. Identification and treatment of OSA in patients with epilepsy could conceivably provide a novel approach toward preventing the risk of SUDEP. Future studies with polysomnography are needed to confirm predictive features for OSA in epilepsy populations, and to determine whether OSA is associated with SUDEP risk.