In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis

ObjectiveHypokalaemic periodic paralysis (HypoPP) is caused by mutations of Ca_v1.1, and Na_v1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Na_v1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo.MethodsMVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP(n = 7), HypoPP (n = 10), and normal controls (n = 26).ResultsMuscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges.ConclusionsThe in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita.SignificanceMVRCs provide important in vivo data that complements expression studies of ion channel mutations.     

Burden of disease in pediatric narcolepsy: a claims-based analysis of health care utilization,costs, and comorbidities

BackgroundThis study analyzed a privately insured pediatric population with and without narcolepsy to determine the impact of pediatric narcolepsy on comorbidities, health care utilization, and cost. Additional analyses compared narcolepsy type 1 and type 2.MethodsThis retrospective cross-sectional study identified US patients with narcolepsy <18 years of age with ≥2 claims with a diagnosis code of narcolepsy using Truven MarketScan® data 2011 to 2015. Patients were matched to controls without narcolepsy. Comorbid conditions, health care utilization, and costs were measured by calendar year. P values are nominal, and no adjustments for multiplicity or multiple comparisons were made.ResultsA total of 1427 pediatric patients with narcolepsy were identified and matched with 4281 controls from 2011 to 2015. Patients with narcolepsy had more comorbid conditions (mean 5.8 vs 2.4, nominal P < 0.001). Respiratory diseases and mood disorders were more common in patients with narcolepsy than controls (57% vs 32% and 56% vs 14%, respectively; both nominal P < 0.001). Compared to controls, patients with narcolepsy underwent more diagnostic tests (electroencephalogram, EEG [0.13 vs 0.0053]) and brain computed tomography, CT/magnetic resonance imaging, MRI (0.26 vs 0.022; both nominal P < 0.001). Mean annual inpatient days (0.71 vs 0.15), emergency department visits (0.51 vs 0.15), and outpatient office visits (8.6 vs 2.3) were higher for patients with narcolepsy than controls (all nominal P < 0.001). Annual mean health care costs were higher for patients with narcolepsy versus controls ($15,797 vs $2449, nominal P < 0.001).ConclusionPediatric patients with narcolepsy had greater comorbidity, higher health care utilization, and higher costs than patients without narcolepsy.     

Neuropathy in sporadic inclusion body myositis: A multi-modality neurophysiological study

ObjectiveSporadic inclusion body myositis (sIBM) has been associated with neuropathy. This study employs nerve excitability studies to re-examine this association and attempt to understand underlying pathophysiological mechanisms.MethodsTwenty patients with sIBM underwent median nerve motor and sensory excitability studies, clinical assessments, conventional nerve conduction testing (NCS) and quantitative thermal threshold studies. These results were compared to established normal controls, or results from a normal cohort of older control individuals.ResultsSeven sIBM patients (35%) demonstrated abnormalities in conventional NCS, with ten patients (50%) demonstrating abnormalities in thermal thresholds. Median nerve motor and sensory excitability differed significantly in sIBM patients when compared to normal controls. None of these neurophysiological markers correlated significantly with clinical markers of sIBM severity.ConclusionA concurrent neuropathy exists in a significant proportion of sIBM patients, with nerve excitability studies revealing changes possibly consistent with axolemmal depolarization or concurrent neuronal adaptation to myopathy. Neuropathy in sIBM does not correlate with muscle disease severity and may reflect a differing tissue response to a common pathogenic factor.SignificanceThis study affirms the presence of a concurrent neuropathy in a large proportion of sIBM patients that appears independent of the severity of myopathy.     

The evaluation of sleep disturbances for Chinese frontline medical workers under the outbreak of COVID-19

ObjectiveTo evaluate sleep disturbances of Chinese frontline medical workers (FMW) under the outbreak of coronavirus disease 2019 (COVID-19), and make a comparison with non-FMW.MethodsThe medical workers from multiple hospitals in Hubei Province, China, volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status. Sleep disturbances were defined as PSQI>6 points or/and AIS>6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS, as well as prevalence of sleep disturbances between FMW and non-FMW.ResultsA total of 1306 subjects (801 FMW and 505 non-FMW) were enrolled. Compared to non-FMW, FMW had significantly higher scores of PSQI (9.3 ± 3.8 vs 7.5 ± 3.7; P < 0.001; Cohen's d = 0.47), AIS (6.9 ± 4.3 vs 5.3 ± 3.8; P < 0.001; Cohen's d = 0.38), anxiety (4.9 ± 2.7 vs 4.3 ± 2.6; P < 0.001; Cohen's d = 0.22) and depression (4.1 ± 2.5 vs 3.6 ± 2.4; P = 0.001; Cohen's d = 0.21), as well as higher prevalence of sleep disturbances according to PSQI > 6 points (78.4% vs 61.0%; relative risk [RR] = 1.29; P < 0.001) and AIS > 6 points (51.7% vs 35.6%; RR = 1.45; P < 0.001).ConclusionFMW have higher prevalence of sleep disturbances and worse sleep quality than non-FMW. Further interventions should be administrated for FMW, aiming to maintain their healthy condition and guarantee their professional performance in the battle against COVID-19.     

A prewarning sign for hearing loss by brainstem auditory evoked potentials during microvascular decompression surgery for hemifacial spasm

ObjectiveWe aimed to define the prewarning sign of brainstem auditory evoked potentials (BAEPs) associated with cerebellar retraction (CR) during microvascular decompression surgery for hemifacial spasm.MethodsA total of 241 patients with a latency prolongation of 1 ms or an amplitude decrement of 50% of wave V were analyzed. According to BAEPs before significant changes during CR, patients were classified into Groups A (latency prolongation of wave I [≥0.5 ms] without prolongation of the I–III interpeak interval [<0.5 ms]) and B (no latency prolongation of wave I [<0.5 ms] with prolongation of the I–III interpeak interval [≥0.5 ms]). BAEPs and postoperative hearing loss (HL) were compared between the two groups.ResultsGroup B comprised 160 (66.4%) patients. With maximal changes in wave V, latency prolongation (≥1 ms) with amplitude decrement (≥50%) was more common in Group B (p < 0.018). At the end of the operation, wave V loss was observed in 11 patients, including 10 patients from Group B. Five patients developed postoperative HL; all were from Group B.ConclusionsLatency prolongation of wave III during CR was associated with serious BAEPs changes and postoperative HL.SignificanceLatency prolongation of wave III is a significant prewarning sign.     

Evaluation of frequency-selective non-linear blending technique on brain CT in postoperative children with Moyamoya disease

ObjectiveTo evaluate whether a frequency-selective non-linear blending (BC) technique can improve tissue contrast and infarct detection on non-enhanced brain CT (NECT) in postoperative Moyamoya (MMD) patients.Materials and methodsFrom January 2010 to December 2017, 33 children (13 boys and 20 girls; mean age 9.1 ± 3.4 years) with MMD postoperatively underwent NECT followed by diffusion MRI. We compared the contrast-to-noise ratio (CNR) between gray matter (GM) and white matter (WM) in NECT and BC images and the CNR between the infarct lesion and adjacent normal-appearing brain in NECT and BC images using a paired t-test. We assessed image noise, GM-WM differentiation, artifacts, and overall quality using a Wilcoxon signed rank test. A McNemar two-tailed test was conducted to compare the diagnostic accuracy of infarct detection.ResultsThe CNR between GM and WM and the CNR of the infarct was better in BC images than in NECT images (3.9 ± 1.0 vs. 1.8 ± 0.6, P < 0.001 and 3.6 ± 0.3 vs. 1.9 ± 0.2, P < 0.001), with no difference in overall image quality observed. The sensitivity and specificity of infarct detection were 55.0% and 76.9% using NECT, and 70.0% and 69.2% using BC technique. The diagnostic accuracy of NECT and BC technique was 63.6% (21/33) and 69.7% (23/33), respectively.ConclusionThis study showed that the BC technique improved CNR and maintained image quality. This technique may also be used to identify ischemic brain changes in postoperative MMD patients by improving the CNR of the infarct lesion.     

Measuring the effects of first antiepileptic medication in Temporal Lobe Epilepsy: Predictive value of quantitative-EEG analysis

ObjectiveTo determine the quantitative EEG responses in a population of drug-naïve patients with Temporal Lobe Epilepsy (TLE) after Levetiracetam (LEV) initiation as first antiepileptic drug (AED). We hypothesized that the outcome of AED treatment can be predicted from EEG data in patients with TLE.MethodsTwenty-three patients with TLE and twenty-five healthy controls were examined. Clinical outcome was dichotomized into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG parameters were compared between healthy controls and patients with TLE at baseline (EEG^pre) and after three months of AED therapy (EEG^pre-post) and between SF and NSF patients. Receiver Operating Characteristic curves models were built to test whether EEG parameters predicted outcome.ResultsAED therapy induces an increase in EEG power for Alpha (p = 0.06) and a decrease in Theta (p < 0.05). Connectivity values were lower in SF compared to NSF patients (p < 0.001). Quantitative EEG predicted outcome after LEV treatment with an estimated accuracy varying from 65.2% to 91.3% (area under the curve [AUC] = 0.56–0.93) for EEG^pre and from 69.9% to 86.9% (AUC = 0.69–0.94) for EEG^pre-post.ConclusionsAED therapy induces EEG modifications in TLE patients, and such modifications are predictive of clinical outcome.SignificanceQuantitative EEG may help understanding the effect of AEDs in the central nervous system and offer new prognostic biomarkers for patients with epilepsy.     

Age-related changes in late synaptic inputs to corticospinal neurons and their functional significance: A paired-pulse TMS study

BackgroundRecent work suggests that the function of intracortical interneurons activated by transcranial magnetic stimulation (TMS) is modified in older adults, with the circuits generating short-interval intracortical facilitation (SICF) at longer intervals appearing to be particularly affected.ObjectiveTo use SICF to quantify age-related changes in the excitability and recruitment of late synaptic inputs to corticospinal neurons, and investigate if changes within these circuits contribute to altered motor performance in older adults.MethodsSICF was recorded with 3 different conditioning intensities in 23 young (23.0 ± 4.2 years) and 21 older (67.1 ± 1.1 years) adults. These measures were performed with conventional (posterior-anterior, PA) and reverse (anterior-posterior, AP) current directions using interstimulus intervals targeting late synaptic inputs to corticospinal neurons (3.5–5.3 ms).ResultsPeak SICF recorded with a PA current (SICF_PA) was reduced in older adults (P < 0.0001), and occurred at a longer latency (P < 0.05). Furthermore, there was reduced recruitment of SICF_PA in older adults (P < 0.0001), but this did not interact with the age-related shift in SICF_PA (P = 0.2). In addition, reduced performance on the Purdue pegboard was predicted by increased SICF_PA (P < 0.04) occurring at longer latencies (P < 0.04) in old but not young adults. For SICF recorded with an AP current (SICF_AP), facilitation was again reduced at longer latencies in older adults (P < 0.0001), but recruitment was not different between groups (P = 0.7) and was unrelated to motor function.ConclusionThese results suggest that there are age-related changes in late synaptic inputs to corticospinal neurons and that these changes influence fine motor performance.     

How does upper extremity Fugl-Meyer motor score relate to resting-state EEG in chronic stroke? A power spectral density analysis

ObjectiveWe investigated the potential added value of high-density resting-state EEG by addressing differences with healthy individuals and associations with Fugl-Meyer motor assessment of the upper extremity (FM-UE) scores in chronic stroke.MethodsTwenty-one chronic stroke survivors with initial upper limb paresis and eleven matched controls were included. Group differences regarding resting-state EEG parameters (Delta Alpha ratio (DAR) and pairwise-derived Brain Symmetry Index (BSI)) and associations with FM-UE were investigated, as well as lateralization of BSI and the value of different frequency bands.ResultsChronic stroke survivors showed higher BSI compared to controls (p < 0.001), most pronounced in delta and theta frequency bands (p < 0.0001; p < 0.001). In the delta and theta band, BSI was significantly negatively associated with FM-UE (both p = 0.008) corrected for confounding factors. DAR showed no differences between groups nor association with FM-UE. Directional BSI showed increased power in the affected versus the unaffected hemisphere.ConclusionsAsymmetry in spectral power between hemispheres was present in chronic stroke, most pronounced in low frequencies and related to upper extremity motor function deficit.SignificanceBSI is related to motor impairment and higher in chronic stroke patients compared to healthy controls, suggesting that BSI may be a marker of selective motor control.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

The histamine H1 receptor antagonist hydroxyzine enhances sevoflurane and propofol anesthesia: A quantitative EEG study

ObjectiveThe aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia.MethodsWe analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50–60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics.ResultsHydroxyzine increased the α bicoherence peaks in both sevoflurane anesthesia (mean difference, 11.2%; 95% confidence interval (CI), 7.6 to 14.8; P < 0.001) and propofol anesthesia (mean difference, 5.6%; 95% CI, 1.7 to 9.4; P = 0.008). Hydroxyzine increased the averaged δ bicoherence values in both sevoflurane anesthesia (mean difference, 5.5%; 95% CI, 2.1 to 8.8; P = 0.003) and propofol anesthesia (mean difference, 3.9%; 95% CI, 1.0 to 6.8; P = 0.011).ConclusionsHydroxyzine enhances both sevoflurane anesthesia and propofol anesthesia probably by facilitation of GABAergic neural circuit mechanisms.SignificanceThe findings provide a new insight into the role of histaminergic neurons during general anesthesia in humans.     

Whole-Brain Permeability Analysis on Admission Improves Prediction of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

PurposeTo evaluate the changes of blood-brain barrier permeability (BBBP) after aneurysmal subarachnoid hemorrhage (aSAH) and find out whether BBBP within 24 h after onset can further improve prediction of delayed cerebral ischemia (DCI).MethodsCT perfusion (CTP) was performed within 24 h after onset and in the DCI time window (DCITW). Whole brain average values of flow extraction product (mK^trans), qualitative and quantitative CTP parameters, and clinical data were compared between DCI and non-DCI groups. The changes of mK^trans were analysed using a Paired t test. Multivariate logistic regression analysis and ROC analyses were performed to identify predictors of DCI and evaluate the predictive performance.ResultsOne hundred and forty of 179 consecutive patients were included, 45 of whom (32%) developed DCI. mK^trans was higher in the DCI group both on admission and in the DCITW (P<0.001). mK^trans decreased significantly in the non-DCI group (P=0.003), but not in DCI group (P=0.285). Multivariate logistic regression analysis showed that mK^trans (OR=1.07, 95%CI: 1.03-1.11, P<0.001), World Federation of Neurosurgery Scale (OR=6.73, 95%CI: 1.09-41.41, P=0.040), Hunt-Hess grade (OR=0.16, 95%CI: 0.02-1.19, P=0.073), modified Fisher Score (OR=3.74, 95%CI: 1.30-10.75, P=0.014), and qualitative CTP (OR=4.31, 95%CI: 1.49-12.47, P=0.007) were independent predictors of DCI. The model with K^trans produced a larger AUC of 0.88 (95%CI: 0.81-0.95), with corresponding sensitivity and specificity of 84% and 86%, respectively.ConclusionBBBP measurement within 24 h after onset can improve the prediction of DCI. Early moderate BBB disruption may be reversible, whereas severe BBBP disruption indicates the risk of DCI.     

Cincinnati Prehospital Stroke Scale Implementation of an Urban County Severity-Based Stroke Triage Protocol: Impact and Outcomes on a Comprehensive Stroke Center

Background and purposeScreening scales are recommended to assist field-based triage of acute stroke patients to designated stroke centers. Cincinnati prehospital stroke scale (CPSS) is a commonly used prehospital stroke screening tool and has been validated to identify large vessel occlusion (LVO). This study addresses the impact of county-based CPSS implementation to triage suspected LVO patients to a comprehensive stroke center (CSC).Materials and methodsDekalb County in Atlanta, Georgia, implemented CPSS-based protocol with score of 3 and last seen normal time < 24 h mandating transfer to the nearest CSC if the added bypass time was <15 min. Frequency of stroke codes, LVO, IV-tPA use, and thrombectomy treatment were compared six months before and after protocol change (November 1, 2020).ResultsDuring the study period, 907 stroke patients presented to the CSC by EMS, including 289 (32%) with CPSS score 3. There was an increase in monthly ischemic stroke volume (pre-16 ± 2 vs.19 ± 3 p = 0.03), LVO (pre-4.3 ± 1.7 vs. post-7.0 ± 2.4; p = 0.03), EVT (pre-15% vs. post-30%; p = 0.001), without significant increase in stroke mimic volume or delay in mean time from last seen normal to IV-tPA (pre-165 ± 66, post-158 ± 49 min; p = 0.35). CPSS score 3 was associated with increased likelihood of LVO diagnosis (OR 8.5, 95% CI 5.0-14.4; p = 0.001) and decreased the likelihood of stroke mimics (OR 0.66, 95% CI 0.50-0.88; p = 0.004).ConclusionCPSS is a quick, easy to implement, and reliable prehospital severity scale for EMS to triage LVO to CSC without delaying IV-tPA treatment or significantly increasing stroke mimics.     

Assessing the impact of sodium oxybate treatment on functioning,productivity, and health-related quality of life in patients with narcolepsy: findings from the Nexus Narcolepsy Registry (waves 1–4)

BackgroundThe aim of this study was to evaluate the impact of different therapy regimens, including sodium oxybate (SXB)-containing regimens, on patient-reported outcomes (PROs) in people with narcolepsy.MethodsOnline surveys were used to collect information from persons with narcolepsy in the Nexus Narcolepsy Registry. Surveys contained questionnaires assessing self-reported sleep quality (SQ; via single question), daytime sleepiness and function (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire), health-related quality of life (HRQoL; 36-Item Short Form Health Survey [SF-36]), work productivity and impairment (Work Productivity and Activity Impairment: Specific Health Problem), and history of injuries or motor vehicle accidents. Treatment with SXB (including monotherapy or combination therapy; SXB group) was compared with non-SXB therapy (No SXB group). The P values presented are nominal, as there are no adjustments for multiplicity.ResultsFrom June 2015 through December 2017, 983 participants completed 1760 surveys. SQ and daytime functioning scores were better in the SXB group compared with the No SXB group (all P < 0.001). HRQoL scores were better for the SXB group compared with the No SXB group for the SF-36 Physical Component (P = 0.016), Mental Component (P < 0.001), and all 8 subscales. Additionally, PROs were better for the SXB group for presenteeism, overall work and activity impairment, and risk of motor vehicle accidents (all P ≤ 0.001).ConclusionBased on participants’ self-assessments, treatment regimens with SXB were associated with better outcomes than regimens not containing SXB across many PROs, including SQ, HRQoL, work and activities, and risk of traffic accidents.Clinicaltrials.gov identifierNCT02769780.     

Predictive value of electrically induced seizures for postsurgical seizure outcome

ObjectiveTo determine whether semiological similarity of electrically induced seizures (EIS) and spontaneously occurring habitual seizures (SHS) is associated with postsurgical seizure outcome in patients undergoing invasive video-EEG monitoring (VEM) before resective epilepsy surgery.MethodsData of patients undergoing invasive VEM were retrospectively reviewed and included if at least one EIS and SHS during VEM occurred and the brain region in which EIS were elicited was resected. Seizure outcome was evaluated at three follow-up (FU) visits after surgery (1, 2 years and last available FU) according to the classification by Engel and the International League Against Epilepsy (ILAE). The level of semiological similarity of EIS and SHS was rated blinded to the surgical outcome. Statistics were done using Fisher’s exact test and a mixed linear-logistic regression model.Results65 patients were included. Postsurgical seizure freedom was achieved in 51% (ILAE class 1) and 58% (Engel class I) at last FU (median 36 months). Patients with identical EIS and SHS displayed significantly better postsurgical seizure outcomes (ILAE class 1 at last FU: 76% vs. 31%, p < 0.001; Engel class I: 83% vs. 39%, p < 0.001).ConclusionEIS are useful to confirm the location of the epileptogenic zone. A high level of similarity between EIS and SHS is associated with a favorable postsurgical seizure outcome.SignificanceEIS may be used as an additional predictor of postsurgical outcome when counselling patients to proceed to resective epilepsy surgery.     

The Nexus Narcolepsy Registry: methodology,study population characteristics,and patterns and predictors of narcolepsy diagnosis

Objective/backgroundThe real-world experience of people with narcolepsy is not well understood.Patients/methodsThe Nexus Narcolepsy Registry (NCT02769780) is a longitudinal, web-based patient registry of self-reported data from adults with physician-diagnosed narcolepsy. Surveys were electronically distributed every 6 months; the current analysis reports registry population demographics, narcolepsy diagnosis journey, and predictors of diagnostic delays.ResultsThe registry population included in this analysis (N = 1024) was predominantly female (85%) and White (92%), with a mean age of 37.7 years. Most participants had education/training beyond high school (93%). Mean (median) reported ages at narcolepsy symptom onset, first consultation for symptoms, and narcolepsy diagnosis were 18.1 (16), 26.4 (24), and 30.1 (28) years, respectively. A majority (59%) of participants reported ≥1 misdiagnosis, and 29% reported consulting ≥5 physicians before narcolepsy diagnosis. More than half (56%) of participants’ first consultations for narcolepsy symptoms were with a general practitioner, whereas the diagnosing clinician was usually a sleep specialist (64%) or neurologist (27%). Pediatric symptom onset was associated with a longer mean interval to first consultation than adult symptom onset (10.7 and 4.6 years, respectively; P < 0.001) and a longer mean interval between first consultation and diagnosis (4.5 and 2.2 years, respectively; P < 0.001). Overall, mean (95% CI) time from symptom onset to diagnosis was 11.8 (11.1–12.5) years.ConclusionsThe Nexus Narcolepsy Registry data indicate that onset of narcolepsy symptoms frequently occurs in childhood or adolescence. In many individuals, the diagnostic process is long and involves multiple physicians and frequent misdiagnosis.     

Effect of partial and total sleep deprivation on serum testosterone in healthy males: a systematic review and meta-analysis

BackgroundCurrently, there is no consensus on the effect of sleep deprivation on male serum testosterone. This systematic review and meta-analysis aimed to determine the association between partial/total sleep deprivation and male serum testosterone level.MethodsThe literature related to sleep deprivation and male serum testosterone in the PubMed, Embase, and Cochrane Library databases were searched from their inception to July 15, 2021. Data were pooled using the Stata 15 software. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs).ResultsEighteen studies involving 252 men were included in the systematic review and meta-analysis. The findings revealed that short-term partial sleep deprivation had no significant effect on male serum testosterone (SMD = −0.22; 95% CI: −0.5, 0.06; P = 0.13), while total sleep deprivation reduced the male testosterone levels (SMD = −0.64; 95% CI: −0.87, −0.42; P < 0.001). According to the intervention duration of total sleep deprivation, subgroup analysis was conducted by a fixed-effects model. The results revealed that the serum testosterone was significantly decreased after 24 h total sleep deprivation (SMD = − 0.67; 95% CI = − 0.93, −0.42, P < 0.001), as well as 40–48 h total sleep deprivation (SMD = − 0.74; 95% CI = − 1.22, −0.26, P = 0.002).ConclusionsThis meta-analysis revealed that total sleep deprivation (more than or equal to 24 h) reduces the male testosterone levels, while short-term partial sleep deprivation has no significant effect on male serum testosterone. Sleep duration plays a pivotal role in maintaining male serum testosterone levels.     

Real-time feedback on mobile application use for emergency management affects the door-to-needle time and functional outcomes in acute ischemic stroke

ObjectivesTime from onset to reperfusion affects mortality and favorable outcomes in patients with acute ischemic stroke (AIS). To evaluate effects of a real-time feedback mobile application on critical time intervals and functional outcomes in stroke emergency management.MethodsWe recruited patients with clinically suspected acute stroke from December 1st, 2020 until July 30st, 2022. All Patients had a non-contrast computed tomography (CT) and were included only if they had AIS. We divided the patients into two groups based on the date of availability on mobile application: pre-APP group and post-APP group. Onset to Door time (ODT), Door to Imaging Time (DIT), Door to Needle Time (DNT), Door to Puncture Time (DPT), Door to Recanalization Time (DRT), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were compared between two groups.ResultsWe retrospectively enrolled 312 AIS patients who were assigned into the pre-APP group (n = 159) and post-APP group (n = 153). The median ODT time and median admission NIHSS score were not significantly different between the two groups at baseline assessment. The median (IQR) DIT [44 (30-60) min vs 28 (20-36) min, P < 0.01] and DNT [44 (36.25-52) min vs 39 (29-45) min, P = 0.02] both decreased significantly in two groups. However, median DPT and DRT time showed no significant differences. The proportion of mRS score of 0 to 2 at day 90 was significantly higher in the post-App group than in the pre-App group, at 82.4% and 71.7%, respectively (dominance ratio OR=1.84, 95% CI: 1.07 to 3.16, P = 0.03).ConclusionThe present findings indicate that the real-time feedback of stroke emergency management used by a mobile application have potential for shortening the DIT and DNT time and improve the prognosis of stroke patients.     

Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study

ObjectivePatients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment.MethodsPatients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients.ResultsWe enrolled 25 MuSK-MG patients (20 females), aged 16–79 years at the study time, with disease duration ranging 0.6–48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005).ConclusionsCholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease.SignificanceR-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is.     

Middle cerebral arterial bifurcation aneurysms are associated with bifurcation angle and high tortuosity

PurposeTo investigate the association of middle cerebral artery (MCA) bifurcation aneurysms with bifurcation morphology.Materials and methods205 patients were enrolled, including 61 patients with MCA bifurcation aneurysms and 144 non-aneurysmal subjects. Aneurysmal cases were divided into types C (aneurysm neck on extension of the parent artery centerline) and D (deviating neck). The radius of the parent artery M1 (R_P) and bilateral branches (R_S and R_L, respectively), smaller (φ_S) and larger (φ_L) lateral angles, bifurcation angle, and arterial tortuosity from parent vessel to bilateral branches (T_S and T_L, respectively) were analyzed. Logistic regression and receiver operator characteristic (ROC) curve analysis were performed to identify risk factors and predictive values for MCA aneurysm presence and types.ResultsIn aneurysmal MCA bifurcations, bifurcating angle, T_S, T_L and R_L were significantly larger (P<0.01), while φ_S was significantly smaller (P<0.001) than those in controls. The bifurcation angle, T_S and LogitP were better morphological parameters for predicting MCA aneurysm presence with the AUC of 0.795, 0.932 and 0.951, respectively. Significant (P<0.05) differences were observed in the bifurcation angle, φ_L, R_P, R_L and T_L between types C and D aneurysmal bifurcations. T_L was an independent factor in discriminating types C from D aneurysms with an AUC of 0.802.ConclusionsBifurcation angle and arterial tortuosity from the parent artery to the branch forming a smaller angle with the parent artery have a higher value in distinguishing MCA aneurysmal from non-aneurysmal ones, and the tortuosity from the parent artery to the contralateral branch is the best indicator for distinguishing types C from D aneurysmal bifurcations.