Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia.

BACKGROUND: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory α-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized α-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual α-peak-frequency-guided rTMS (αTMS) on treatment-refractory schizophrenia. METHODS: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this doubleblind, sham-controlled study. We randomized patients to a 3-week course of either active αTMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. RESULTS: We included 44 patients. After treatment, we observed a significantly higher PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the αTMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received αTMS compared with sham stimulation (p = 0.048). LIMITATIONS: The limited number of study participants included only male patients. Depression was not formally evaluated. CONCLUSION: Navigated αTMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual α-peak-frequency-guided rTMS in treatment-refractory schizophrenia. CLINICAL TRIAL REGISTRATION: NCT01941251; ClinicalTrials.gov.

Short- and long-interval intracortical inhibition in EPM1 is related to genotype.

OBJECTIVE: Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)-induced long-interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short-interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1. METHODS: TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3 ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed. RESULTS: The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho = 0.872; p < .001) and SICI (rho = 0.689; p = .006). SIGNIFICANCE: Our results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.

Cognitive functioning in progressive myoclonus epilepsy type 1 (Unverricht-Lundborg Disease, EPM1).

OBJECTIVE: The aim of this neuropsychological study of a large cohort of patients with progressive myoclonus epilepsy type 1 (Unverricht-Lundborg disease, EPM1) was to characterize the cognitive function of EPM1 patients and to explore the association between the disability caused by the disease and cognitive performance. METHOD: Sixty-eight genetically verified EPM1 patients homozygous for the expansion mutation in the CSTB gene (37 males and 31 females aged 35 ±â€¯11) participated in a neuropsychological assessment of intellectual ability, verbal memory, and executive and psychomotor function. The clinical evaluation comprised administering (and video-recording) the unified myoclonus rating scale (UMRS) to assess the severity of each patient's myoclonus. Forty-six healthy volunteers (19 males and 27 females aged 32 ±â€¯11) served as the control group for the neuropsychological tests. RESULTS: The cognitive performance of the EPM1 patient group was impaired. Verbal Intelligence Quotient (VIQ) was below the average range (VIQ < 85) in 49% of the patients; further, Performance Intelligence Quotient (PIQ) was below average in 75% of the patients. The patients performed worse than the controls in both immediate and delayed story recall (p = 0.001); however, in the word list learning task, the patients performed only slightly worse than the controls. The one-hour delayed recall of the learned words was similar in both groups, and the percentage of retained words and story contents did not differ between the patients and controls. The patients were impaired in all of the executive function tests as well as in the psychomotor speed tests (p < 0.001 for all). Also, the patients' simple psychomotor speed in the tapping task was significantly slowed in comparison to controls (p < 0.001). CONCLUSION: The patients had impaired performance in the majority of the cognitive measures; they showed the highest level of impairment in all the executive function tests and in the psychomotor speed tests. The measures of these cognitive domains are timed-therefore, it is clear that severe myoclonus limits patients' performance. In contrast, verbal memory, especially delayed recall, was the least affected cognitive domain.

Intra-night variation in apnea-hypopnea index affects diagnostics and prognostics of obstructive sleep apnea.

BACKGROUND: Diagnostics of obstructive sleep apnea (OSA) is based on apnea-hypopnea index (AHI) determined as full-night average of occurred events. We investigate our hypothesis that intra-night variation in the frequency of obstructive events affects diagnostics and prognostics of OSA and should therefore be considered in clinical practice. METHODS: Polygraphic recordings of 1989 patients (mean follow-up 18.3 years) with suspected OSA were analyzed. Number and severity of individual obstructive events were calculated hourly for the first 6 h of sleep. OSA severity was determined based on the full-night AHI and AHI for the 2 h when the obstructive event frequency was highest (AHI2h). Hazard ratios for all-cause, cardiovascular, and non-cardiovascular mortalities were calculated for different OSA severity categories based on the full-night AHI and AHI2h. RESULTS: Frequency and duration of obstructive events varied hour-by-hour increasing towards morning. Using AHI2h led to a statistically significant rearrangement of patients between the OSA severity categories. The use of AHI2h for severity classification showed clearer relationship between the OSA severity and mortality than the full-night AHI. CONCLUSIONS: Currently, the intra-night variation in frequency and severity of obstructive events is completely ignored by conventional, full-night AHI and considering this information could improve the diagnostics of OSA.

Acute stroke and TIA patients have specific polygraphic features of obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is associated with increased risk for stroke, which is known to further impair respiratory functions. However, it is unknown whether the type and severity of respiratory events are linked to stroke or transient ischemic attack (TIA). Thus, we investigate whether the characteristics of individual respiratory events differ between patients experiencing TIA or acute ischemic stroke and matched patients with clinically suspected sleep-disordered breathing. METHODS: Polygraphic data of 77 in-patients with acute ischemic stroke (n = 49) or TIA (n = 28) were compared to age, gender, and BMI-matched patients with suspected sleep-disordered breathing and no cerebrovascular disease. Along with conventional diagnostic parameters (e.g., apnea-hypopnea index), durations and severities of individual apneas, hypopneas and desaturations were compared between the groups separately for ischemic stroke and TIA patients. RESULTS: Stroke and TIA patients had significantly shorter apneas and hypopneas (p < 0.001) compared to matched reference patients. Furthermore, stroke patients had more central apnea events (p = 0.007) and a trend for higher apnea/hypopnea number ratios (p = 0.091). The prevalence of OSA (apnea-hypopnea index ≥ 5) was 90% in acute stroke patients and 79% in transient ischemic attack patients. CONCLUSION: Stroke patients had different characteristics of respiratory events, i.e., their polygraphic phenotype of OSA differs compared to matched reference patients. The observed differences in polygraphic features might indicate that stroke and TIA patients suffer from OSA phenotype recently associated with increased cardiovascular mortality. Therefore, optimal diagnostics and treatment require routine OSA screening in patients with acute cerebrovascular disease, even without previous suspicion of OSA.

Polysomnographic scoring of sleep bruxism events is accurate even in the absence of video recording but unreliable with EMG-only setups.

PURPOSE: To determine the accuracy of scoring masticatory muscle activity (MMA) events in seven different polysomnography (PSG) setups. METHODS: Nineteen volunteers (13 females, 6 males, age 31.1 ± 12.9 years, 12 self-proclaimed bruxers) attended one-night PSG recording, supplemented with audio, video, and a separate frontal electroencephalography electrode set (FES). The same examiner scored the MMA events with seven different setups, with varying number of channels available: (1) one, (2) two, and (3) four EMG channels, (4) PSG without audio or video (PSG-N), (5) home PSG with FES and audio (FES-A), (6) PSG with audio (PSG-A), and (7) PSG with audio and video (PSG-AV). A subset (n = 10) of recordings was scored twice to determine intra-scorer reliability. MMA indices and accuracy of scoring the events in different setups were compared against PSG-AV. RESULTS: The intra-class correlation coefficient (ICC) between PSG-AV and PSG-A was high (0.940, p < 0.001) as well as for FES-A (0.927, p < 0.001), whereas for PSG-N, it was lower (0.835, p < 0.001); for setups with only EMG channels, coefficients were very low (ICC < 0.100 for all). Intra-examiner reliability was high (ICC > 0.939 for all setups), with the exception of PSG-N (ICC = 0.764, p = 0.002). When comparing against the MMA events scored in PSG-AV, the sensitivity of MMA event recognition for PSG-A was 78.5% and specificity 95.5%, which were substantially higher than sensitivity (52.0%) and specificity (87.2%) of PSG-N. CONCLUSIONS: MMA event scoring accuracy with PSG-A or FES-A is almost comparable to PSG-AV. Since precise event recognition is essential for accurate MMA scoring, it is evident that one cannot rely exclusively on EMG.

Facial nerve function and hearing after microsurgical removal of sporadic vestibular schwannomas in a population-based cohort.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor originating from the vestibulocochlear nerve. The optimal treatment strategy is debated, since surgery may result in iatrogenic facial nerve injury. We report the results of VS surgery in a population-based unselected cohort in a center with access to Cyber Knife (CK) radiosurgery. METHODS: We reviewed 117 consecutive operations and found 95 patients who had their primary operation due to vestibular schwannoma between 2001 and 2017. Facial nerve function was evaluated with the House-Brackmann (HB) scale and hearing with the EU classification. RESULTS: The population consisted of 37 males and 58 females with a median age of 54 years (range 19-79). One year after surgery 67% of patients had a good outcome (HB 1-2). The rate of good outcome was 90% if no facial nerve damage was observed during intraoperative monitoring, the size of the tumor was under 30 mm and no hydrocephalus was present. During the study period, the treatment strategy changed from total to near-total resection after the introduction of CK radiosurgery, which could be used as a second-line treatment in case of residual tumor regrowth. This resulted in an improvement of outcomes (0% HB 5-6) despite the larger tumor sizes (25 ± 14 mm vs. 31 ± 9 mm, p < 0.05). Hearing preservation rates did not increase. CONCLUSIONS: Near-total resection and subsequent CK radiosurgery in case of residual tumor regrowth during follow-up seems to provide a good outcome of facial nerve function even in large VSs.

Abnormal motor cortical adaptation to external stimulus in Unverricht-Lundborg disease (progressive myoclonus type 1, EPM1).

Unverricht-Lundborg disease (EPM1) is associated with progressive functional and anatomic changes in the thalamus and motor cortex. The neurophysiological mechanisms behind the impaired thalamocortical system were studied through short-term adaptation of the motor cortex to transcranial magnetic stimulation (TMS) via repetition suppression (RS) phenomenon. RS is considered to be related to neural processing of external stimuli. We hypothesized that this neural processing is progressively impaired in EPM1 from adolescence to adulthood. Eight adult patients with EPM1 (age: 40 ± 13 yr), six adolescent patients with EPM1 (age: 16 ± 1 yr), and ten adult controls (age: 35 ± 12 yr) were studied using navigated TMS and RS study protocol including trains of four repeated stimuli with intertrain interval of 20 s and interstimulus interval of 1 s. Changes in RS were investigated from adolescence to adulthood in EPM1 by comparing with adult controls. In controls, the RS was seen as 50-55% reduction in motor response amplitudes to TMS after the first stimulus. RS was mild or missing in EPM1. RS from first to second stimulus within the stimulus trains was significantly stronger in adolescent patients than in adult patients ( P = 0.046). Abnormal RS correlated with the myoclonus severity of the patients. In agreement with our hypothesis, neural processing of external stimuli is progressively impaired in EPM1 possibly due to anatomically impaired thalamocortical system or inhibitory tonus preventing sufficient adaptive reactiveness to stimuli. Our results suggest that RS abnormality might be used as a biomarker in the therapeutic trials for myoclonus. NEW & NOTEWORTHY Unverricht-Lundborg disease (EPM1) is associated with impaired thalamocortical function, which we studied in 8 adult and 6 adolescent patients and in 10 adult controls through repetition suppression (RS) of the motor cortex. We hypothesized that neural processing is progressively impaired in EPM1 from adolescence to adulthood. RS was normal in controls, whereas it was mild or missing in EPM1. Stronger RS was seen in adolescent patients than in adult patients correlating with the myoclonus severity.

Screen-printed ambulatory electrode set enables accurate diagnostics of sleep bruxism.

Currently, definite diagnosis of sleep bruxism requires polysomnography. However, it is restrictedly available, and too cumbersome and expensive for the purpose. The aim of this study was to introduce an ambulatory electrode set and evaluate its feasibility for more cost-effective diagnostics of sleep bruxism. Six self-assessed bruxers (one male, five females; aged 21-58 years) and six healthy controls (four males, two females, aged 21-25 years) underwent a standard polysomnographic study and a concurrent study with the ambulatory electrode set. Bruxism events, cortical arousals and sleep stages were scored for the two montages separately in a random order, and obtained sleep parameters were compared. In addition, the significance of video recording and sleep stage scoring for the diagnostic accuracy of ambulatory electrode set was determined. Ambulatory electrode set yielded similar diagnoses as standard polysomnography in all subjects. However, compared with standard polysomnography the median (interquartile range) tonic bruxism event index was significantly higher in the control group [+0.38 (+0.08 to +0.56) events per hour, P = 0.046], and the phasic bruxism event index was significantly lower in the bruxer group [-0.44 (-1.30 to +0.07) events per hour, P = 0.046]. Exclusion of video recording and both video recording and sleep stage scoring from analysis increased overestimation of the tonic bruxism event index in the control group +0.86 (+0.42 to +1.03) and +1.19 (+0.55 to +1.39) events per hour, P = 0.046 and P = 0.028, respectively], resulting in one misdiagnosed control subject. To conclude, ambulatory electrode set is a sensitive method for ambulatory diagnostics of sleep bruxism, and video recording and sleep stage scoring help reaching the highest specificity of sleep bruxism diagnostics.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Severity of individual obstruction events is gender dependent in sleep apnea.

PURPOSE: In obstructive sleep apnea (OSA), severity of individual obstruction events is connected to increased mortality rate and it can be significantly different in patients with similar apnea-hypopnea index (AHI). However, possible gender-dependent variation in severity of obstruction events in different OSA categories is unknown. We investigated whether the severity of obstruction events differs between genders with similar AHI and if this difference varies between OSA categories. METHODS: Polygraphic recordings of 2057 consecutive patients with suspected OSA were reanalyzed and those with AHI ≥5/h were included for further analysis (n male = 893 and n female = 197). Statistical significance of differences in AHI, apnea index, hypopnea index, oxygen desaturation index, obstruction severity parameter, and severity of individual obstruction events between genders were evaluated using the Mann-Whitney U (MWU) test as well as the general linear model (GLM) univariate analysis adjusted for age, BMI, smoking, daytime sleepiness, snoring, and heart failure. RESULTS: Apneas were 16.9 and 19.6% longer (MWU p ≤ 0.015, GLM p ≤ 0.036) and desaturation areas were 15.4 and 23.7% larger (MWU p ≤ 0.024, GLM p ≤ 0.053) in males compared to females with moderate and severe OSA, respectively. In contrast, hypopneas were 9.1% shorter (MWU p = 0.001, GLM p ≤ 0.001) and desaturation areas were 6.0% smaller (MWU p = 0.114, GLM p = 0.025) in men with mild OSA. The apnea index was 433.3 and 313.1% higher (MWU p ≤ 0.001, GLM p ≤ 0.043) and the hypopnea index was 12.2 and 17.8% lower (MWU p ≤ 0.001, GLM p = 0.002, p = 0.083) in males with mild and moderate OSA, respectively. CONCLUSION: As severity of individual obstruction events was significantly different in males and females, the overall severity of OSA may not be similar despite the similarity in AHI.

Peri-apneic hemodynamic reactions in obstructive sleep apnea.

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. Little is known on acute peri-apneic hemodynamic alterations due to apneas. We assessed these rapid changes and how duration of apnea might contribute to them. Eight patients with severe OSA were studied with polysomnography including continuous blood pressure monitoring. Peri-apneic hemodynamic alterations, heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance, were assessed in short (<20s) and long (>27s) apneas. Systolic and diastolic blood pressure along with heart rate elevated significantly in both apneas. These changes occurred within first 10 beats immediately after apnea. In contrast to short apneas long apneas caused sudden increase of 0.7l in cardiac output. Acute and pronounced peri-apneic hemodynamic alterations were seen during both short and long apneas. These described rapid hemodynamic changes might escape autoregulatory mechanisms of several organs, thus making OSA patients vulnerable to acute cardiovascular events.

Sensorimotor cortex excitability and connectivity in Alzheimer's disease: A TMS-EEG Co-registration study.

Several studies have shown that, in spite of the fact that motor symptoms manifest late in the course of Alzheimer's disease (AD), neuropathological progression in the motor cortex parallels that in other brain areas generally considered more specific targets of the neurodegenerative process. It has been suggested that motor cortex excitability is enhanced in AD from the early stages, and that this is related to disease's severity and progression. To investigate the neurophysiological hallmarks of motor cortex functionality in early AD we combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We demonstrated that in mild AD the sensorimotor system is hyperexcitable, despite the lack of clinically evident motor manifestations. This phenomenon causes a stronger response to stimulation in a specific time window, possibly due to locally acting reinforcing circuits, while network activity and connectivity is reduced. These changes could be interpreted as a compensatory mechanism allowing for the preservation of sensorimotor programming and execution over a long period of time, regardless of the disease's progression. Hum Brain Mapp 37:2083-2096, 2016. © 2016 Wiley Periodicals, Inc.

Assessment of the suitability of using a forehead EEG electrode set and chin EMG electrodes for sleep staging in polysomnography.

Recently, a number of portable devices designed for full polysomnography at home have appeared. However, current scalp electrodes used for electroencephalograms are not practical for patient self-application. The aim of this study was to evaluate the suitability of recently introduced forehead electroencephalogram electrode set and supplementary chin electromyogram electrodes for sleep staging. From 31 subjects (10 male, 21 female; age 31.3 ± 11.8 years), sleep was recorded simultaneously with a forehead electroencephalogram electrode set and with a standard polysomnography setup consisting of six recommended electroencephalogram channels, two electrooculogram channels and chin electromyogram. Thereafter, two experienced specialists scored each recording twice, based on either standard polysomnography or forehead recordings. Sleep variables recorded with the forehead electroencephalogram electrode set and separate chin electromyogram electrodes were highly consistent with those obtained with the standard polysomnography. There were no statistically significant differences in total sleep time, sleep efficiency or sleep latencies. However, compared with the standard polysomnography, there was a significant increase in the amount of stage N1 and N2, and a significant reduction in stage N3 and rapid eye movement sleep. Overall, epoch-by-epoch agreement between the methods was 79.5%. Inter-scorer agreement for the forehead electroencephalogram was only slightly lower than that for standard polysomnography (76.1% versus 83.2%). Forehead electroencephalogram electrode set as supplemented with chin electromyogram electrodes may serve as a reliable and simple solution for recording total sleep time, and may be adequate for measuring sleep architecture. Because this electrode concept is well suited for patient's self-application, it may offer a significant advancement in home polysomnography.

Effect of oxygen desaturation threshold on determination of OSA severity during weight loss.

PURPOSE: Weight loss leads to improvement of obstructive sleep apnea (OSA), based on frequency of respiratory events (apnea-hypopnea index, AHI). However, AHI does not incorporate the severity of individual obstruction events. The American Academy of Sleep Medicine suggests two alternative oxygen desaturation thresholds (ODT) for scoring of hypopneas. We hypothesize that lowering the ODT level increases the determined impact of weight loss on OSA severity. We investigate this during weight change with AHI and adjusted AHI. Adjusted AHI is a novel parameter incorporating both severity and number of the events. METHODS: Ambulatory polygraphic data of 54 OSA patients (F 15/M 39, 51.7 ± 8.4 years), divided into weight loss (>5 %, n = 20), control (weight change 0-5 %, n = 26), and weight gain (>5 %, n = 8) groups, were evaluated at baseline and after 5-year follow-up. Effect of ODT (ODT2%-ODT6%) on AHI and adjusted AHI was investigated. RESULTS: The greatest changes in AHI (decrease in weight loss group and increase in weight gain group) were observed with ODT2%. Changes in AHI diminished with increasing ODT. In weight loss group, adjusted AHI showed a similar but non-significant trend. In contrast, the higher ODT was used in weight gain group, the greater increase in adjusted AHI resulted. Using adjusted AHI instead of AHI, led to a smaller number of patients (20 vs. 55 %, ODT3%) whose OSA severity category improved along weight loss. CONCLUSIONS: Weight loss significantly reduced AHI. This reduction was highly dependent on selected ODT. The change in adjusted AHI did not occur in the same extent. This was expected as the more severe events which tend to remain during the weight loss have greater importance in adjusted AHI, while the event severity is neglected in AHI.

Forehead EEG electrode set versus full-head scalp EEG in 100 patients with altered mental state.

BACKGROUND: Acute EEG is vastly underutilized in acute neurological settings. The most common reason for this is simply the fact that acute EEG is not available when needed or getting EEG is delayed as it requires trained technicians and equipment to be properly recorded. We have recently described a handy disposable forehead EEG electrode set that is suitable for acute emergency EEG recordings. The specific objective in this study was to assess the forehead electrode's utility when the clinical demand was to exclude SE. PATIENTS AND METHODS: One hundred consecutive acute neurological patients (53 women, 47 men, age: 18-90 years) with unexplained altered mental state were studied with acute emergency EEG to rule out SE. Electroencephalographic recordings were obtained simultaneously with forehead EEG electrode and routine 10-20 system full-head scalp electrodes to clarify the clinical usefulness of forehead EEG electrode in this setting. Electroencephalographic recordings were interpreted blindly by three experienced clinical neurophysiologists first only based on forehead EEG and then by full-head EEG. RESULTS: Ninety-six out of the 100 patients did not show EEG evidence of SE. There was 100% agreement with forehead and routine EEG. Four out of the 100 patients showed EEG evidence of SE in routine EEG, with 50% agreement between different electrode types. The forehead EEG missed two cases because the EEG findings supporting SE were restricted to the posterior parts of the brain. MAJOR CONCLUSIONS: With a forehead EEG set, the sensitivity of detecting NCSE was 50%. There were no false positive cases yielding a specificity of 100%. Patients with AMS can benefit from forehead EEG recording in prehospital, hospital, and ICU settings. Since EEG recording can be started within a few minutes with the forehead EEG set, it will significantly reduce the delay in treatment of SE. This article is part of a Special Issue entitled "Status Epilepticus".

Morbidity and mortality risk ratios are elevated in severe supine dominant OSA: a long-term follow-up study.

PURPOSE: Obstructive sleep apnoea (OSA) is a common public health problem. Sleeping position dependency has been related to OSA, and around half of OSA patients suffer from positional OSA where majority of the respiratory events occur in supine position. The consequences of supine dominant OSA have not been thoroughly investigated in long-term follow-up studies. The aim of the study was to retrospectively investigate the effects of supine dominant OSA on morbidity and mortality risk ratios during long-term follow-up and compare the findings with a non-supine OSA group at different OSA severities. METHODS: Ambulatory polygraphic recordings of 793 patients with median follow-up time of 194.5 months were retrospectively analysed. The risk ratios of morbidity and mortality of supine dominant OSA and non-supine OSA patients were compared. RESULTS: Supine dominant OSA patients, having majority of the obstruction events occurring in supine position, showed higher mortality and morbidity risk ratios in severe OSA category than the non-supine OSA patients. In severe category, the observed risk ratios were statistically significant. CONCLUSIONS: The increased risk ratios of mortality and morbidity found further emphasises that supine OSA might have more severe health consequences than non-positional OSA especially in severe OSA. Severe OSA occurring in supine position was shown to be more deleterious than non-supine OSA based on long-term mortality and morbidity evidence.

Effect of different oxygen desaturation threshold levels on hypopnea scoring and classification of severity of sleep apnea.

PURPOSE: Recently, there has been a debate about the rules used to score hypopnea events. The purpose of this study was to examine the effect of different oxygen desaturation threshold (ODT) levels on the apnea-hypopnea index (AHI) and on a recently introduced parameter, adjusted AHI. Adjusted AHI incorporates the severity of individual breathing cessation events. We also aimed to clarify the impact of the different ODT levels on the current classification of obstructive sleep apnea (OSA) severity. METHODS: Ambulatory polygraphic recordings of 68 patients (19 F/49 M, median age 53.2 years, AHI ≥5) were analyzed retrospectively. Hypopneas were defined as ≥30% drop in airflow for ≥10 s associated with ≥2% oxygen desaturation (ODT2%), and after that, using stricter ODT criteria (ODT3%-ODT8%). RESULTS: Compared to ODT4%, the ODT3% resulted in 5.6 events/h higher median conventional AHI, but only 1.5 events/h higher median adjusted AHI. A significant rearrangement of patients between the clinical severity categories took place when using different ODTs. When assessing with ODT3% instead of ODT4%, the portion of the patients with moderate or severe OSA (AHI ≥15) raised from 29.4 to 73.5% using conventional AHI, but only marginally, i.e., from 73.5 to 77.9%, using the adjusted AHI. CONCLUSIONS: The conventional AHI was found to be susceptible even to minor changes in ODT level which may lead to substantial variability in AHI-based classification of disease severity. Since the adjusted AHI comprises information on severity of individual breathing cessations, it reduces the variability related to ODT levels used in hypopnea scoring and can increase the accuracy of estimation of OSA severity.

A Handy EEG Electrode Set for patients suffering from altered mental state.

Although electroencephalography (EEG) is an important diagnostic tool for investigating patients with unexplained altered mental state (AMS), recording of emergency EEG is not a clinical routine. This is mainly due to the cumbersome electrode solutions. A Handy EEG Electrode Set consists of ten EEG, two EOG, two ground and two commutative reference hydrogel-coated silver wire electrodes attached to a thin polyester carrier film. The clinical usefulness of the Handy EEG Electrode Set was tested in 13 patients (five females, eight males) with AMS. EEG recordings were conducted at the same time with a standard 10-20 electrode set. The registration in the first patient case without the behind-ear electrodes (T9 and T10), indicated that these electrodes are very crucial to provide clinically relevant information from posterior regions of brain. In following 12 cases, the sensitivity and specificity for detecting EEG abnormality based on the Handy EEG Electrode Set recordings were 83 and 100 %, respectively. The Handy EEG Electrode Set proved to be easy to use and to provide valuable information for the neurophysiological evaluation of a patient suffering from AMS. However, further studies with larger number of patients are warranted to clarify the true diagnostic accuracy and applicability of this approach.

Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy.

OBJECTIVE: Recessive LAMC3 mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed LAMC3 variant. METHODS: All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re-evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes. RESULTS: Among our study population of 323 DEE patients we recognized three patients with similar homozygous LAMC3 c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic LAMC3 c.4231-12C>G variant on another allele. All these patients have severe epilepsy and either bilateral agyria-pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox-Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. LAMC3 c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population. SIGNIFICANCE: Only a few patients with epilepsy caused by LAMC3 homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.