Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial

ObjectivesLittle evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity.MethodsTwenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2.ResultsAt T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016).At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group.ConclusionstDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections.SignificanceThis study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.     

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.     

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.     

Gold Coast diagnostic criteria increase sensitivity in amyotrophic lateral sclerosis

ObjectiveThis study evaluates diagnostic accuracy of the proposed ‘Gold Coast’ (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS).MethodsFive European centres retrospectively sampled consecutive patients referred for electromyography on suspicion of ALS. Patients were classified according to the GC criteria, the revised El Escorial (rEE) criteria and the Awaji (AW) criteria without and with the ‘Possible’ category (+ Poss). Reference standard was ALS confirmed by disease progression at follow-up.ResultsOf 404 eligible patients 272 were diagnosed as ALS, 94 had mimicking disorders, 35 were lost for follow-up, and three had insufficient data. Sensitivity for the GC criteria was 88.2% (95% CI: 83.8-91.8%), which was higher than for previous criteria, of which the AW + Poss criteria reached the highest sensitivity of 77.6% (95% CI: 72.2–82.4%) (p < 0.001). Specificity was high for all criteria. The increase in sensitivity for the GC criteria was mainly due to the inclusion of 28 patients with progressive muscular atrophy (PMA).ConclusionsThe simpler GC criteria increase the sensitivity, primarily due to considering PMA as a form of ALS with high specificity preserved.SignificanceThis validation study supports that GC criteria should be used in clinical practice and may be used for inclusion in trials.     

Cortico-cortical evoked potential by single-pulse electrical stimulation is a generally safe procedure

ObjectiveCortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs.MethodsWe retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures.ResultsOut of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18–82 pairs per patient, ADs and clinical seizures were induced in 0–4 and 0–3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058).ConclusionAlthough caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation.SignificanceCCEP is safe under the established protocol.     

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.     

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.     

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.     

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.     

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.     

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.     

Quantitative electroencephalography characteristics of tilt-induced neurally-mediated syncope among youth

ObjectiveTo characterize the quantitative electroencephalographic (QEEG) patterns associated with tilt-induced syncope in youth.MethodsSeveral QEEG parameters were analyzed. Data were calculated for peak or nadir changes with syncope for amplitude-EEG, fast Fourier transform (FFT) power in several frequency ranges, 8–13 Hz/1–4 Hz frequency ratio, and FFT edge.ResultsChanges in QEEG parameters were present among all patients with tilt-induced syncope (n = 76). These changes included increases in the low frequency FFT power (1–4 Hz range), decreases in the power ratio (8–13 Hz/1–4 Hz) and decreases in the FFT edge (95%, 1–18 Hz). All patients had suppression of EEG amplitudes that closely followed loss of consciousness. Asymmetry indices demonstrated cerebral hemisphere lateralization at multiple periods during the evolution of syncope, but the side of lateralization did not differ from 0.5 probability.ConclusionsQEEG parameters can be used to characterize EEG changes associated with tilt-induced, neurally-mediated syncope.SignificanceQEEG may serve as a useful tool for the study of syncope neurophysiology, and the modeling of changes with syncope may improve our understanding of other neurologic disorders caused by defects in cerebral perfusion.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

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.     

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.     

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.     

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.     

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.     

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.     

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.