Differentiating transcranial magnetic stimulation cortical and auditory responses via single pulse and paired pulse protocols: A TMS-EEG study

ObjectiveWe measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography).MethodsNineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS.ResultsCortical excitability indexed by area under the curve (AUC_(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η² = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η² = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition.ConclusionThe significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation.SignificanceOur study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.     

Delayed neonatal visual evoked potentials are associated to asymmetric growth pattern in twins

ObjectivesTo study the association between intrauterine growth and visual pathways maturation by neonatal visual evoked potentials (VEPs) in twins, in view of a possible prognostic role.MethodsSeventy-four twin neonates from 37 pregnancies were selected based on gestational age of more than 30 weeks and uneventful perinatal clinical course. Flash VEPs were recorded at the same postmenstrual age in each twin pair. The association between P2 latency and anthropometric variables at birth was analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins.ResultsAnalysis of differences within each twin pair highlighted that inter-twin difference in P2 latency was significantly related to difference in ponderal index (PI) (p = 0.048).Expressing the difference in latency as a categorical binary variable, the correlation was significant for both difference in PI, (median difference = −0.36, 95% CI −0.54 to −0.14, p = 0.001) and difference in body mass index (BMI), (median difference = −1.06, 95% CI −1.74 to −0.29, p = 0.006).ConclusionsLower values of PI and BMI differences are associated to delayed VEP latency in twin pairs.SignificanceVEP latency suggests reduced myelination of visual pathways when difference in growth pattern occurs in twins.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia

ObjectiveSensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias.MethodsParticipants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12–18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups.ResultsBeta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4–12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618).ConclusionIdiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups.SignificanceThe findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.     

Sleep positions in children with Down syndrome and obstructive sleep apnea

ObjectivesTo assess sleep positions in children with both Down syndrome (DS) and obstructive sleep apnea (OSA) and determine if there is a preferred sleep position by severity of apnea.MethodsA single-center retrospective review of patients with both DS and OSA was performed. Caregivers reported sleep position utilized greater than 50% of observed sleep time. Accuracy of this report was confirmed through review of hypnograms from polysomnography studies.ResultsEighty-two patients met inclusion criteria. Median body mass index (BMI) was 26.6 and 56% of patients had a prior tonsillectomy and/or adenoidectomy. The mean obstructive AHI (OAHI) was 25.33 with 90.4% having severe OSA, 9.6% having moderate OSA, and no patients having mild OSA. Reported sleep positions were skewed towards lateral/decubitus (82.9%) compared to prone (11.0%) and supine (6.1%). This was consistent with hypnogram data where 71% of total sleep time in lateral/decubitus positions compared to prone (13%) and supine (6%). The median changes in sleep position per patient was 5 (IQR: 3–6). Lower BMI (p < 0.001, 95% CI: 0.32–1.13) and tonsillectomy (p < 0.001, 95% CI: 7.7–18.19) were associated with lower OAHI. Sleep position was not associated with age (p = 0.19), sex (p = 0.66), race (p = 0.10), ethnicity (p = 0.68) nor history of tonsillectomy (p = 0.34). Preferred sleep position was not correlated with OAHI (p = 0.78, r = 0.03) or OSA severity (p = 0.72, r = 0.03).ConclusionsThis study highlights the possibility that children with DS may have preferential sleep positions that cater to optimized airflow in the context of OSA although further prospective study is needed.     

Objective measurement of limb bradykinesia using a marker-less tracking algorithm with 2D-video in PD patients

BackgroundQuantitative measurement of parkinsonian motor symptoms is crucial in clinical practice and in research. However, the widely used Unified PD Rating Scale (UPDRS) part III is based on a semi-quantitative evaluation with high inter- and intra-rater variability. Sensor-based measurements have been widely studied but are limited for their accessibility.MethodsWe analyzed 2D-RGB videos recording finger tapping and leg agility tests in 29 PD patients with a marker-less deep-learning based tracking algorithm. The tracking performance was validated with an accelerometer. Four parameters (mean amplitude, mean interpeak interval, amplitude variability and interpeak interval variability) were calculated from the position tracking.ResultsThe performance of the video-tracking was in good agreement with the accelerometer-based tracking (Intra-class correlation coefficient > 0.9 for the peak amplitude, and >0.6 for the interpeak interval). The video-tracking successfully captured variable aspects of limb bradykinesia that have a distinct correlation with the general parkinsonian motor symptoms and gait. In the finger-tapping task, the mean amplitude (R = −0.6, p = 2.4 × 10⁻⁶), amplitude variability (R = 0.36, p = 0.0092), mean interpeak interval (R = 0.34, p = 0.014), and interpeak interval variability (R = 0.66, p = 1.4 × 10⁻⁷) was significantly correlated with the UPDRS scores. In leg agility test, the mean amplitude (R = −0.58, p = 1.7 × 10⁻⁵), mean interpeak interval (R = 0.37, p = 0.0088) and interpeak interval variability (R = 0.7, p = 6.2 × 10⁻⁸) were significantly correlated with the UPDRS scores, but not with amplitude variability (R = 0.17, p = 0.26). Limb rigidity was significantly correlated with the interpeak interval (R = 0.40, p = 0.0036) and its variability (R = 0.59, p = 4.2 × 10⁻⁶) in the leg agility test.ConclusionThe video-based tracking could objectively measure limb bradykinesia in PD patients.     

Valproate but not levetiracetam slows the EEG alpha peak frequency – A pharmaco-EEG study

ObjectiveStudies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF).MethodsWe retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients’ APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level.ResultsThe APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = −0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = −0.17 ± 0.18 across patients, p = 0.4072).ConclusionsOur results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment.SignificanceOur study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.     

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies.MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS.ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events.ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction.SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.     

Monitoring of patients with brainstem hemorrhage: A simultaneous study of quantitative electroencephalography and transcranial Doppler

ObjectiveTo explore whether quantitative electroencephalography (QEEG) and transcranial Doppler (TCD) can be used to evaluate patients with acute severe brainstem hemorrhage (ASBH).MethodsWe prospectively enrolled patients with ASBH and assessed their mortality at the 90-day follow-up. The patients' demographic data, serological data, and clinical factors were recorded. Quantitative brain function monitoring was performed using a TCD-QEEG recording system attached to the patient’s bedside.ResultsThirty-one patients (55.3 ± 10.6 years; 17 men) were studied. Mortality at 90 days was at 61.3%. There was no significant difference in TCD-related parameters between the survival group and the death group (p > 0.05). Among the QEEG-related indexes, only the (delta + theta)/(alpha + beta) ratio (DTABR) (odds ratio 11.555, 95%confidence interval 1.413–94.503, p = 0.022) was an independent predictor of clinical outcome; the area under the ROC curve of DTABR was 0.921, cut-off point was 3.88, sensitivity was 79%, and specificity was 100%.ConclusionsIn patients with ASBH, QEEG can effectively inform the clinical prognosis regarding 90-day mortality, while TCD cannot.SignificanceQEEG shows promise for informing the mortality prognosis of patients with ASBH.     

Paired-pulse navigated TMS is more effective than single-pulse navigated TMS for mapping upper extremity muscles in brain tumor patients

ObjectiveSingle-pulse navigated transcranial magnetic stimulation (sp-nTMS) is used for presurgical motor mapping in patients with motor-eloquent lesions. However, recently introduced paired-pulse nTMS (pp-nTMS) with biphasic pulses could improve motor mapping.MethodsThirty-four patients (mean age: 56.0 ± 12.7 years, 53.0% high-grade glioma) with motor-eloquent lesions underwent motor mapping of upper extremity representations and nTMS-based tractography of the corticospinal tract (CST) by both sp-nTMS and pp-nTMS with biphasic pulses for the tumor-affected hemisphere before resection.ResultsIn three patients (8.8%), conventional sp-nTMS did not provide motor-positive points, in contrast to pp-nTMS that was capable of generating motor maps in all patients. Good concordance between pp-nTMS and sp-nTMS in the spatial location of motor hotspots and center of gravity (CoG) as well as for CST tracking was observed, with pp-nTMS leading to similar motor map volumes (585.0 ± 667.8 vs. 586.8 ± 204.2 mm³, p = 0.9889) with considerably lower resting motor thresholds (35.0 ± 8.8 vs. 32.8 ± 7.6% of stimulator output, p = 0.0004).ConclusionsPp-nTMS with biphasic pulses may provide motor maps even in highly demanding cases with tumor-affected motor structures or edema, using lower stimulation intensity compared to sp-nTMS.SignificancePp-nTMS with biphasic pulses could replace standardly used sp-nTMS for motor mapping and may be safer due to lower stimulation intensity.     

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain.MethodsForty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.ResultsPain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095–3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques.ConclusionsHigh-frequency rTMS appeared superior to iTBS for neuropathic pain relief.SignificanceAdequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.     

High frequency oscillations relate to cognitive improvement after epilepsy surgery in children

ObjectiveTo investigate how high frequency oscillations (HFOs; ripples 80–250 Hz, fast ripples (FRs) 250–500 Hz) and spikes in intra-operative electrocorticography (ioECoG) relate to cognitive outcome after epilepsy surgery in children.MethodsWe retrospectively included 20 children who were seizure free after epilepsy surgery using ioECoG and determined their intelligence quotients (IQ) pre- and two years postoperatively. We analyzed whether the number of HFOs and spikes in pre- and postresection ioECoGs, and their change in the non-resected areas relate to cognitive improvement (with ≥ 5 IQ points increase considered to be clinically relevant (=IQ+ group) and < 5 IQ points as irrelevant (=IQ− group)).ResultsThe IQ+ group showed significantly more FRs in the resected tissue (p = 0.01) and less FRs in the postresection ioECoG (p = 0.045) compared to the IQ− group. Postresection decrease of ripples on spikes was correlated with postoperative cognitive improvement (correlation coefficient = −0.62 with p = 0.01).ConclusionsPostoperative cognitive improvement was related to reduction of pathological HFOs signified by removing FR generating areas with subsequently less residual FRs, and decrease of ripples on spikes in the resection edge of the non-resected area.SignificanceHFOs recorded in ioECoG could play a role as biomarkers in the prediction and understanding of cognitive outcome after epilepsy surgery.     

Elevated Hypoperfusion Intensity Ratio (HIR) observed in patients with a large vessel occlusion (LVO) presenting in the evening

BackgroundCircadian variability has been implicated in timing of stroke onset, yet the full impact of underlying biological rhythms on acute stroke perfusion patterns is not known. We aimed to describe the relationship between time of stroke onset and perfusion profiles in patients with large vessel occlusion (LVO).MethodsA retrospective observational study was conducted using prospective registries of four stroke centers across North America and Europe with systematic use of perfusion imaging in clinical care. Included patients had stroke due to ICA, M1 or M2 occlusion and baseline perfusion imaging performed within 24h from last-seen-well (LSW). Stroke onset was divided into eight hour intervals: (1) Night: 23:00-6:59, (2) Day: 7:00-14:59, (3) Evening: 15:00-22:59. Core volume was estimated on CT perfusion (rCBF <30%) or DWI-MRI (ADC <620) and the collateral circulation was estimated with the Hypoperfusion Intensity Ratio (HIR = [Tmax>10s]/[Tmax>6s]). Non-parametric testing was conducted using SPSS to account for the non-normalized dependent variables.ResultsA total of 1506 cases were included (median age 74.9 years, IQR 63.0-84.0). Median NIHSS, core volumes, and HIR were 14.0 (IQR 8.0-20.0), 13.0mL (IQR 0.0-42.0), and 0.4 (IQR 0.2-0.6) respectively. Most strokes occurred during the Day (n = 666, 44.2%), compared to Night (n = 360, 23.9%), and Evening (n = 480, 31.9%). HIR was highest, indicating worse collaterals, in the Evening compared to the other timepoints (p = 0.006). Controlling for age and time to imaging, Evening strokes had significantly higher HIR compared to Day (p = 0.013).ConclusionOur retrospective analysis suggests that HIR is significantly higher in the evening, indicating poorer collateral activation which may lead to larger core volumes in these patients.     

Inflammation in children with neuromuscular disorders and sleep disordered breathing

IntroductionPaediatric obstructive sleep apnoea is associated with systemic inflammation and co-morbidities. We assessed whether sleep disordered breathing (SDB) due to neuromuscular weakness was associated with elevated airway and systemic pro-inflammatory cytokines.MethodsConsecutive neuromuscular children (age 5–18years) underwent overnight full polysomnography and morning collection of serum and breath condensate, analysed for cytokines (Interleukin-10, Interleukin-6, Interleukin-1β, Tumour Necrosis Factorα, high-sensitivity C-Reactive Protein, Intercellular and Vascular Adhesion Molecules ICAM-1, VCAM-1). Cytokine levels were related to Oxygen desaturation index (ODI), desaturation>4%/h, and levels of transcutaneous carbon dioxide overnight (tcCO2≥6.7 kPa > 2% sleep).ResultsA total of 23 patients were included, median age 12.6 years (IQR 8.7–14.6). ODI>3/h was associated with higher breath and serum IL-6 (p = 0.02). Children with elevated CO₂ overnight had higher ICAM-1 and VCAM-1. CO₂ levels correlated with serum ICAM-1 (rs0.570, p = 0.026) and VCAM-1 (rs0.76, p = 0.001).DiscussionSDB in neuromuscular children is associated with raised serum IL-6, VCAM-1, ICAM-1. This may predispose these children to future cardiovascular and other co-morbidities.     

Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms

ObjectiveTo investigate the diagnostic utility of high frequency oscillations (HFOs) via scalp electroencephalogram (EEG) in infantile spasms.MethodsWe retrospectively analyzed interictal slow-wave sleep EEGs sampled at 2,000 Hz recorded from 30 consecutive patients who were suspected of having infantile spasms. We measured the rate of HFOs (80–500 Hz) and the strength of the cross-frequency coupling between HFOs and slow-wave activity (SWA) at 3–4 Hz and 0.5–1 Hz as quantified with modulation indices (MIs).ResultsTwenty-three patients (77%) exhibited active spasms during the overnight EEG recording. Although the HFOs were detected in all children, increased HFO rate and MIs correlated with the presence of active spasms (p < 0.001 by HFO rate; p < 0.01 by MIs at 3–4 Hz; p = 0.02 by MIs at 0.5–1 Hz). The presence of active spasms was predicted by the logistic regression models incorporating HFO-related metrics (AUC: 0.80–0.98) better than that incorporating hypsarrhythmia (AUC: 0.61). The predictive performance of the best model remained favorable (87.5% accuracy) after a cross-validation procedure.ConclusionsIncreased rate of HFOs and coupling between HFOs and SWA are associated with active epileptic spasms.SignificanceScalp-recorded HFOs may serve as an objective EEG biomarker for active epileptic spasms.     

The impact of obstructive sleep apnea on bronchiolitis severity in children with Down syndrome

ObjectivesAcute bronchiolitis commonly causes respiratory failure in children ≤2 years, and is particularly severe in those with Down syndrome (DS). Obstructive sleep apnea (OSA), common in DS, is also associated with respiratory complications. However, it is unknown whether OSA is associated with worse outcomes in children with and without DS, hospitalized with bronchiolitis. We hypothesized that in children with bronchiolitis, OSA is associated with worse outcomes in those with DS, independent of DS-related comorbidities.MethodsHospital discharge records of children with bronchiolitis aged ≤2 years were obtained for 1997–2012 from the Kid's Inpatient Database. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were non-invasive mechanical ventilation (NIMV), length of hospital stay, and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for DS-associated comorbidities.ResultsThere were 928,961 hospitalizations for bronchiolitis. The DS group with bronchiolitis (n = 8697) was more likely to have OSA [241 (2.77%) vs 1293 (0.14%), p < 0.001] compared to the non-DS group (n = 920,264). Multivariable logistic regression showed that OSA was associated with IMV (adjusted odds ratio [OR], 3.32 [95% CI 2.54–4.35], p < 0.0001) in all children with bronchiolitis; and in those with DS, it was associated with IMV (adjusted OR, 2.34 [95% CI 1.38–3.97], p = 0.002), NIMV (adjusted OR, 8.21 [95% CI 4.48–15.04], p < 0.0001) and IACH (adjusted β, 0.18 [95% CI 0.02–0.34], p = 0.031).ConclusionsOSA is independently associated with assisted ventilation in all children hospitalized with bronchiolitis, regardless of DS-associated comorbidities in those with DS. The severity of bronchiolitis in children with DS may be driven by the high prevalence of OSA.     

Academic and professional paths of narcoleptic patients: the Narcowork study

Objective/BackgroundTo study educational and professional pathways of narcoleptic patients and examine demographic, disease-related and environmental factors associated with a better academic and professional prognosis.Patients/MethodsIn sum, 69 narcoleptic patients (51 narcolepsy type 1 and 18 narcolepsy type 2, age 42.5 ± 18.2 years) were enrolled in this pilot monocentric cross-sectional study with a comparison group (80 age- and sex-matched controls) between October 2017 and July 2018 in Lyon Center for Sleep Medicine. They completed questionnaires about their academic and professional trajectories and specific scales of quality of life (EuroQol quality of life scale EQ-5D-3L), depression (beck depression inventory, BDI), sleepiness (Epworth Sleepiness Scale, ESS) and narcoleptic symptoms severity (narcolepsy severity scale, NSS).ResultsNo difference in grade repetition or final obtained diploma was observed between patients and controls, but patients evaluated their academic curricula as more difficult (45.5% vs 16.9%, p = 0.0007), complained for more attentional deficits (75% vs 22.1%, p < 0.0001), and had needed more educational reorientation (28.6% vs 9.9%, p = 0.01). Even if no difference was observed in occupational category and professional status, patients expressed significantly less satisfaction about their work. Patients had more signs of depression [OR severe depression = 4.4 (1.6–12.6), p = 0.02] and their quality of life was significantly decreased (67.3 ± 18.4 vs 80.6 ± 13.2, p = 0.0007) as compared to controls. Multivariate analysis showed that a more favorable professional career was associated with a better quality of life.ConclusionsEducational and professional pathways do not seem to be significantly impaired in narcoleptic patients, but their experience and quality of life are affected. These findings may allow to reassure patients and should lead to a more comprehensive management of the disease.Clinical trial registrationNarcowork, https://clinicaltrials.gov/ct2/show/NCT03173378, N° NCT03173378.     

Development and validation of the hypersomnia-specific beliefs scale

Objective/BackgroundPatients with Central hypersomnia, especially Narcolepsy type 1 and Idiopathic Hypersomnia (NT1 and IHS) often have psychological frustration in their daily lives. We aimed to develop the first scale of hypersomnia-specific beliefs (HSB).Patients/methodsWe developed the HSB scale consisting of three factors (“aversion toward doze”, “hypersensitivity toward others” reactions about my doze”, and “sense of defeat caused by doze”) with 12 items through interviews to 11 patients with NT1 and IHS. Validity and reliability of the HSB were evaluated cross-sectionally with 166 patients with NT1 and IHS and 375 controls. Simultaneously, scores of patient health questionnaire −2(PHQ-2), mini-Social Phobia Inventory (mini-SPIN), and Epworth Sleepiness Scale (ESS) were obtained.ResultsThis 3-factor model had enough fitness (χ2 = 60.25, df = 51, p = 0.18, TLI = 0.99, CFI = 0.99, RMSEA = 0.03), Cronbach's α coefficient being 0.90. The intraclass correlation coefficient was 0.76. Also, the area under the receiver operating characteristic curve (AUC = 0.88) confirmed good discrimination ability. A cut-off score of 38 resulted in a sensitivity of 90% and a specificity of 75%. Multiple linear regression analyses showed that these scales were independently associated with the HSB score; the PHQ-2 (β = 0.24, p = 0.002), mini-SPIN (β = 0.29, p < 0.001) and ESS (β = 0.15, p = 0.048).ConclusionsOur data suggest that the HSB scale measured beliefs in NT1 and IHS patients with good validity, reliability, and discrimination ability. The HSB scale assesses the negative beliefs specific to patents with NT1 and IHS. This scale could be applied to the development of novel psychotherapeutic approach to patients with NT1 and IHS.     

Source imaging of seizure onset predicts surgical outcome in pediatric epilepsy

ObjectiveTo assess whether ictal electric source imaging (ESI) on low-density scalp EEG can approximate the seizure onset zone (SOZ) location and predict surgical outcome in children with refractory epilepsy undergoing surgery.MethodsWe examined 35 children with refractory epilepsy. We dichotomized surgical outcome into seizure- and non-seizure-free. We identified ictal onsets recorded with scalp and intracranial EEG and localized them using equivalent current dipoles and standardized low-resolution magnetic tomography (sLORETA). We estimated the localization accuracy of scalp EEG as distance of scalp dipoles from intracranial dipoles. We also calculated the distances of scalp dipoles from resection, as well as their resection percentage and compared between seizure-free and non-seizure-free patients. We built receiver operating characteristic curves to test whether resection percentage predicted outcome.ResultsResection distance was lower in seizure-free patients for both dipoles (p = 0.006) and sLORETA (p = 0.04). Resection percentage predicted outcome with a sensitivity of 57.1% (95% CI, 34–78.2%), a specificity of 85.7% (95% CI, 57.2–98.2%) and an accuracy of 68.6% (95% CI, 50.7–83.5%) (p = 0.01).ConclusionIctal ESI performed on low-density scalp EEG can delineate the SOZ and predict outcome.SignificanceSuch an application may increase the number of children who are referred for epilepsy surgery and improve their outcome.     

Characterization of EEG-based functional brain networks in myotonic dystrophy type 1

ObjectiveIn the autosomal dominant, multisystem, chronic progressive disease myotonic dystrophy type 1 (DM1), cognitive deficits may originate from disrupted functional brain networks. We aimed to use network analysis of resting-state electro-encephalography (EEG) recordings of patients with DM1 and matched unaffected controls to investigate changes in network organization in large-scale functional brain networks and correlations with cognitive deficits.MethodsIn this cross-sectional study, 28 adult patients with genetically confirmed DM1 and 26 age-, sex- and education-matched unaffected controls underwent resting-state EEG and neuropsychological assessment. We calculated the Phase Lag Index (PLI) to determine EEG frequency-dependent functional connectivity between brain regions. Functional brain networks were characterized by applying concepts from graph theory and compared between-groups. Network topology was evaluated using the minimum spanning tree (MST). We evaluated correlations between network metrics and neuropsychological tests that showed statistically significant between-group differences.ResultsFunctional connectivity estimated as whole-brain median PLI for DM1 patients versus healthy controls was higher in theta band (0.141 [0.050] versus 0.125 [0.018], p = 0.029), and lower in the upper alpha band (0.154 [0.048] versus 0.182 [0.073], p = 0.038), respectively. Functional MST-constructed networks in DM1 patients were significantly dissimilar from healthy controls in the delta, (p = 0.009); theta, (p = 0.009); lower alpha, (p = 0.036); and upper alpha, (p = 0.008) bands. In evaluation of local MST network measures, trends toward networks with higher global integration in the theta band and lower global integration in the upper alpha band were observed. Compared to unaffected controls, DM1 patients performed worse on tests of attention, motor function, executive function and visuospatial memory. Visuospatial memory correlated with the global median PLI in the upper alpha band; the Stroop interference test correlated with betweenness centrality in this band.ConclusionThis study supports the hypothesis that brain changes in DM1 give rise to disrupted functional network organization, as modelled with EEG-based networks. Further study may help unravel the relations with clinical brain-related DM1 symptoms.SignificanceEEG network analysis has potential to help understand brain related DM1 phenotypes.FundingThis work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 305697 (OPTIMISTIC) and the Marigold Foundation.