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Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms.

The use of emergency electroencephalography (EEG) in clinical practice is limited in part due to the lack of commercially available EEG monitoring sets that are suitable for rapid and simple use. The aim of this study was to develop a rapid and simple-to-use disposable forehead EEG electrode set for routine use that is also suitable for long-term monitoring. The EEG set we developed consists of 12 hydrogel-coated electrodes (10 recording electrodes, plus a reference and ground electrode) attached to a solid polymer film. The developed EEG set was compared to the full conventional 10-20 electrode setup in terms of the ability to detect epileptiform abnormalities in two critically ill patients. The technical quality of the EEG signal from the newly developed electrode set was excellent, and status epilepticus was reliably detected with this EEG set. Electric performance testing showed that the impedance spectra of the developed EEG electrodes were comparable to those of three commercially available, disposable electrodes, and the noise level was lower than that of the commercial electrodes. The developed EEG set is also MRI and CT compatible and lacks any signs of imaging artefacts or heat induction. These promising results provide a reason to expect that the developed EEG set may be applicable to situations in which the full, conventional 10-20 electrode setup is not available.

Sleep apnea-hypopnea syndrome (SAHS) causes impairment of daytime functions and increases risk of cardiovascular diseases. Apnea-hypopnea index (AHI), currently used for the estimation of the severity of SAHS, does not contain information on the morphology or duration aspects of the breathing cessations and related oxygen desaturations. Longer breathing cessations and deeper desaturations may have more severe consequences than shorter and shallower ones. To address these issues, novel parameters containing information on the duration and morphology of breathing cessations and oxygen desaturations were calculated and evaluated on 160 male patients (40 patients in normal, mild, moderate and severe AHI severity categories). Obstruction and desaturation duration parameters consist of sum of event durations normalized with the total analysed time. Desaturation severity is a sum of desaturation event areas normalized with total analysed time and obstruction severity parameter is a sum of the products of apnea and hypopnea durations and related desaturation areas normalized with total analysed time. The median follow-up time of the patients was 183 months (range 154-215 months). The 40 patients in each category were further divided into subgroups A and B with lowest and highest novel parameter values, respectively. AHI showed no differences between the subgroups. Mortality was increased in subgroups B compared to subgroups A. The correlation of the novel parameters with AHI was only moderate and the parameter values were partially overlapping between the AHI severity categories. This suggests that patients with similar AHI may in fact suffer from SAHS of very different severity. Thus, the present results suggest that the novel parameters could bring new insight to the individual estimation of the severity of SAHS.

Obstructive sleep apnea (OSA) has been associated with an elevated rate of cardiovascular mortality. However, this issue has not been investigated in patients with elevated proneness to cardiovascular diseases. Our hypothesis was that OSA would have an especially adverse effect on the risk of cardiovascular mortality in Finnish individuals exhibiting elevated proneness for coronary heart diseases. Ambulatory polygraphic recordings from 405 men having suspected OSA were retrospectively analyzed. The patients were categorized regarding sleep disordered breathing into a normal group (apnea hypopnea index (AHI)

Sleep apnea-hypopnea syndrome (SAHS) is a complex public health problem causing increased risk of cardiovascular diseases. Traditionally, evaluation of the severity of the disease is based on Apnea-Hypopnea Index (AHI). It is defined as the average number of apnea and hypopnea events per hour during sleep. However, e.g. the total duration and the morphology of the recorded events are not considered when evaluating the severity of the disease. This is surprising, as increasing the length of apnea and hypopnea events will most likely lead to longer and deeper oxygen desaturation events. Obviously, this is physiologically more stressful and may have more severe health consequences than shorter and shallower desaturation events. Paradoxically, the lengthening of apnea and hypopnea events may even lead to a decrease in AHI and oxygen desaturation index (ODI). This raises the question of whether additional information is needed besides AHI and ODI for the evaluation of the severity of SAHS and its potential cardiovascular consequences. In the present paper, several novel parameters are introduced to bring additional information for evaluation of the severity of SAHS. Besides the number of events per hour, that AHI and ODI takes into account, the duration of the breathing cessations and the morphology of the oxygen desaturation events are considered as important factors that may influence the daytime fatigue and also the related cardiovascular problems. In this study diagnostic ambulatory polygraphy recordings of 19 male patients were retrospectively analysed. Importantly, the novel parameters showed significant variation amongst patients with similar AHI. For example, the correlation between AHI and the Obstruction severity-parameter was only moderate (r(2)=0.604, p0.001). This suggests that patients with similar AHI may exhibit significantly different cardiovascular stress related to the disease. It is suggested that the present novel parameters might provide additional information over the currently used parameters and support the evaluation of the severity of SAHS.

Obstructive sleep apnea (OSA) is diagnosed based on obstruction event incidence, albeit individual obstruction event severity is connected to increased mortality rate. Adjusted-AHI parameter, incorporating number and severity of obstruction events, has shown good potential, but is calculated using custom-made MATLAB(®) functions. To allow its clinical use, this study introduces the RemLogic™ plug-in. It is tested comparing adjusted-AHI values calculated with the plug-in and MATLAB(®) with a hundred patients. Furthermore, retrospective follow-up (mean ± SD = 194.1 ± 54.0 months) of 1128 working-age men was conducted to evaluate potential of adjusted-AHI to enhance diagnostic of OSA. Adjusted-AHI values were strongly correlated (r = 1.000, p0.001) and their average difference (mean ± SD) was minimal (0.08 ± 0.19%). Using adjusted-AHI to define OSA severity resulted in a higher hazard ratio of mortality in the severe OSA group and, for the first time, adjusted-AHI was found to explain independently the overall mortality and non-fatal cardiovascular events. Importantly, the present plug-in enables clinical use of adjusted-AHI, enhancing assessment of OSA severity.

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.

We first review the clinical presentation and current therapeutic approaches available for treating Unverricht-Lundborg disease (ULD), a progressive myoclonus epilepsy. Next, we describe the identification of disease causing mutations in the gene encoding cystatin B (CSTB). A Cstb-deficient mouse model, which recapitulates the key features of ULD including myoclonic seizures, ataxia, and neuronal loss, was generated to shed light on the mechanisms contributing to disease pathophysiology. Studies with this model have elucidated the diverse biological roles for Cstb from functioning as a protease inhibitor, to regulating glial activation, oxidative stress, serotonergic neurotransmission, and hyperexcitability. These findings set the stage for future studies that may open avenues to improved therapeutic approaches.

Objective: We investigated the feasibility of delayed computed tomography (CT) arthrography for evaluation of human knee cartilage in vivo. Especially, the diffusion of contrast agent out of the joint space and the optimal time points for imaging were determined. Design: Two patients were imaged using delayed CT arthrography and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) techniques. Results: Two hours after injection, the concentration of contrast agent in the joint space was still high enough (20% to 24.5% of the initial concentration at 0 minutes) to allow delayed CT arthrography. The half-life of the contrast agent in the joint space varied from 30 to 60 minutes. The contrast agent concentration in patellar and femoral cartilage reached the maximum after 30 and 60 minutes, respectively. According to dGEMRIC, there were no differences between patients. However, in delayed CT arthrography, the penetration of the contrast agent was higher in the osteoarthritic knee cartilage. Conclusions: Contrast agent remained in the joint space long enough to enable delayed CT arthrography of cartilage. After 30 minutes, the normalized contrast agent concentration was higher in the cartilage of the osteoarthritic knee in comparison with the healthy knee. To conclude, delayed CT arthrography exhibited potential for use in the clinical evaluation of cartilage integrity.

Introduction Transcranial magnetic stimulation (TMS) is used for assessing the excitability of cortical neurons and corticospinal pathways by determining the subject-specific motor threshold (MT). However, the MT is dependent on the TMS instrumentation and exhibits large variation. We hypothesized that between-subject differences in scalp-to-cortex distance could account for the variation in the MT. Computational electric field (EF) estimation could theoretically be applied to reduce the effect of anatomical differences, since it provides a more direct measure of corticospinal excitability. Methods The resting MT of the thenar musculature of 50 healthy subjects (24 male and 26 female, 22–69 years) was determined bilaterally at the primary motor cortex with MRI-navigated TMS using monophasic and biphasic stimulation. The TMS-induced maximum EF was computed at a depth of 25 mm from the scalp (EF 25 mm ) and at the individual depth of the motor cortex (EF cortex ) determined from MRI-scans. Results All excitability parameters (MT, EF 25 mm and EF cortex ) correlated significantly with each other ( p cortex at MT intensity was 95 ± 20 V/m for biphasic and 120 ± 24 V/m for monophasic stimulation. The MT did not correlate with the anatomical scalp-to-cortex distance, whereas the coil-to-cortex distance was found to correlate positively with the MT and negatively with EF cortex ( p Discussion In healthy subjects, the scalp-to-cortex distance is not a significant determinant of the MT, and thus the use of EF cortex does not offer substantial advantages. However, it provides a purposeful and promising tool for studying non-motor cortical areas or patient groups with possible disease-related anatomical alterations.

Background: The clinical benefits of intensive stroke rehabilitation vary individually. We used multimodal functional imaging to assess the relationship of clinical gain and imaging changes in patients with chronic stroke whose voluntary motor control improved after constraint-induced movement therapy (CIMT). Methods: Eleven patients (37.6 ± 36.8 months from stroke) were studied by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and behavioral assessment of hand motor control (Wolf Motor Function Test) before and after 2 weeks of CIMT. Individual and group-level changes in imaging and behavioral parameters were investigated. Results: Increase in fMRI activation in the sensorimotor areas was greater amongst those subjects who had poor hand motor behavior before therapy and/or whose motor behavior improved notably because of therapy than amongst subjects with relatively good motor behavior already before therapy. The magnitude of CIMT-induced changes in task-related fMRI activation differed between lesioned and non-lesioned hemispheres, and the fMRI laterality index was different for paretic and non-paretic hand tasks. The corticospinal conduction time in TMS was significantly decreased after CIM therapy. Conclusions: Alterations in sensorimotor cortical activations (fMRI) and corticospinal conductivity (TMS) were observed after intensive rehabilitation in patients with chronic stroke. Activation and functional changes in fMRI and TMS correlated significantly with the degree of clinical improvement in hand motor behavior. The present data advance the understanding of the functional underpinnings of motor recovery, which may be obtained even years after the stroke.

Patients with Unverricht-Lundborg disease, also referred to as progressive myoclonus epilepsy type 1, exhibit widespread motor symptoms and signs in addition to epileptic seizures, which suggest abnormal excitability of the primary motor pathways. To explore the plasticity of the sensory-motor cortex, we employed a modern neurophysiological method, the paired associative stimulation protocol, which resembles the concept of long-term potentiation of experimental studies. Seven patients with genetically verified Unverricht-Lundborg disease and 13 healthy control subjects were enrolled in the study to characterize cortical sensory-motor plasticity. In the study protocol, peripheral electric median nerve stimulation preceded navigated transcranial magnetic stimulation targeted to the representation area of thenar musculature on the contralateral primary motor cortex. The protocol consisted of 132 transcranial magnetic stimulation trials at 0.2 Hz, preceded by peripheral sensory stimulation at 25 ms. Motor-evoked potential amplitudes were analyzed at baseline and after the paired associative stimulation protocol at an intensity of 130% of the individual motor threshold. The patients with Unverricht-Lundborg disease exhibited an average decrease of 15% in motor-evoked potential amplitudes 30 minutes after paired associative stimulation, whereas in the control subjects, a significant increase (101%) was observed (P < .05), as expected. The results indicate a lack of normal cortical plasticity in Unverricht-Lundborg disease, which stresses the role of abnormal motor cortical functions or sensorimotor integration as possible pathophysiological contributors to the motor symptoms. The impaired cortical plasticity may be associated with the previously reported structural and physiological abnormalities of the primary motor cortex.

To characterize the behaviour of primary motor cortex and to determine appropriate measurement parameters for short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) by paired-pulse transcranial magnetic stimulation (TMS) with the aid of MRI-based neuronavigation.Paired-pulse TMS was targeted to the optimal cortical representation sites of the abductor pollicis brevis (APB) muscle in 48 healthy right-handed volunteers. Motor evoked potentials (MEPs) were recorded from the APB and abductor digiti minimi (ADM) muscles. The conditioning stimulus (CS) intensities were 80% and 90% and the test stimulus was 120% of the resting motor threshold (rMT). The interstimulus intervals (ISIs) were 3, 7, 13, 22 and 28 ms.Inhibition was observed at 3 ms with a CS of 80%. Facilitation emerged at ISIs of 7 and 13 ms with both CS intensities, more prominently with 90%. At ISI of 22 ms, facilitation was observed in ADM (p0.01) but not in APB. No uniform amplitude change was observed at ISI of 28 ms. For both muscles, MEP latencies were shortened (p0.01) at ISIs of 3 and 7 ms and prolonged (p0.01) at 28 ms.Inhibition is most prominent at ISI of 3 ms and CS of 80% of rMT, whereas CS of 90% of rMT and ISIs of 7 and 13 ms are preferable for facilitation. Latencies appear to be stable and independent indicators of both phenomena should be taken into account.Both the latency and amplitude of MEPs are important parameters when paired-pulse paradigms are used in clinical studies.

Purpose Unverricht–Lundborg disease (EPM1) is the most common form of progressive myoclonus epilepsies. The genetic background is a homozygous dodecamer repeat extension mutation in the cystatin B (CSTB) gene. However, mutations occurring in a compound heterozygous form with the expansion mutation have also been reported. In Finland, we have found five EPM1 patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutation in the CSTB gene (chEPM1). There are no previous clinical or neurophysiological studies on these patients. Thus, we aimed to characterize possible functional alterations in primary motor cortical areas. Methods Five chEPM1 patients were compared with homozygous patients and healthy controls. All patients underwent a clinical evaluation to characterize the severity of the symptoms. Navigated transcranial magnetic stimulation (TMS) was used to study cortical excitability by determining the motor thresholds (MT), silent periods (SP) and motor evoked potential (MEP) characteristics. Continuous electroencephalography (EEG) was recorded during the measurements. Voxel-based MRI morphometry (VBM) was used to study differences in gray matter volume. Results The chEPM1 patients exhibited an inhibitory cortical tonus reflected as elevated MTs and prolonged SPs. EEG showed spontaneous focal epileptiform activity in centro-temporal and parietal areas in addition to more widespread and generalized discharges. VBM revealed loss of gray matter volume in primary motor cortical areas and thalami. Discussion The chEPM1 patients exhibited functional and structural changes in primary motor cortical areas. The functional changes are more profound as compared to homozygous patients, suggesting a neurophysiological background for the more severe clinical symptoms.

Objective Intracortical inhibition (SICI) and facilitation (ICF) in the human motor cortex can be measured using a paired pulse transcranial magnetic stimulation (ppTMS) protocol. Recently, a technical device has been introduced, which allows recording electroencephalographic (EEG) responses to TMS of a given scalp site. The latency, amplitude and scalp topography of such responses are considered a reflection of cortico-cortical connectivity and functional state. The aim of the present study is to better characterize the neuronal circuits underlying motor cortex connectivity as well as the mechanisms regulating its balance between inhibition and facilitation by means of EEG navigated-ppTMS coregistration. Methods Sub-threshold and supra-threshold single and ppTMS of the left primary motor cortex were carried out during a multi-channel EEG recording on 8 healthy volunteers; the between-pulse intervals used in the paired pulse trials were 3 (for SICI) and 11 ms (for ICF). Motor evoked potentials (MEPs) from the opposite hand were simultaneously recorded. Results Single and ppTMS induced EEG responses characterized by a sequence of negative deflections peaking at approximately 7, 18, 44, 100 and 280 ms alternated with positive peaks at approximately 13, 30, 60 and 190 ms post-TMS. Moreover, ppTMS modulated both EEG evoked activity and MEPs. Amplitude variability of EEG responses was correlated with – and therefore might partially explain – amplitude variability of MEPs. Interpretation EEG-ppTMS is a promising tool to better characterize the neuronal circuits underlying cortical effective connectivity as well as the mechanisms regulating the balance between inhibition and facilitation within the human cortices and the corticospinal pathway.

Background/Aims: Unverricht-Lundborg disease (EPM1) is caused by mutations in the cystatin B (CSTB) gene. Most patients are homozygous for the expanded dodecamer repeat mutation alleles, but 9 other EPM1-associated mutations have also been identified. We describe the clinical, cognitive and imaging characteristics of 5 Finnish EPM1 patients who are compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutations. Methods: Five compound heterozygous patients and 21 patients homozygous for the expansion mutation, participating in an ongoing nationwide clinical and molecular genetics study, were evaluated using the Unified Myoclonus Rating Scale test and comprehensive neuropsychological testing. All patients underwent MR imaging. The MR data were also compared with those of 24 healthy control subjects. Results: Age at onset of symptoms was significantly lower in the compound heterozygotes than in the homozygous EPM1 patients. They also had severer myoclonus and drug-resistant tonic-clonic seizures. Moreover, they had lower cognitive performance. In MRI a voxel-based morphometry analysis of primary and premotor cortex, supplementary motor cortex and thalami revealed gray matter volume loss when compared with the healthy controls, similar to patients homozygous for the expansion mutation. Conclusion: Patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutations seem to have a severer form of EPM1 than patients homozygous for the expansion mutation. These findings have implications for counseling of EPM1 patients with different genetic defects.

Summary Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long-term outcomes of consecutive true MRI-negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI-negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high-resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12-month follow-up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR-negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI-negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long-term also remain stable. Modern imaging techniques could further improve the postsurgical seizure-free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.

Introduction Short-latency afferent inhibition (SAI) is a phenomenon in which transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs) are decreased in amplitude due to preceding electrical stimulation of the peripheral nerve, such as the median nerve at the wrist. If the nerve is stimulated around 21 ms before giving the TMS pulse to the cortical representation area of a muscle innervated by the same nerve, the resulting MEP amplitude is smaller than without electrical stimulation. On the contrary, if the nerve is stimulated 30 ms before giving the TMS pulse, there is no effect in MEP amplitude in healthy humans. In some movement disorders, such as in writer’s cramp, the 30 ms stimulation may, however, result in facilitation of the MEP amplitude. SAI is thought to reflect the sensorimotor interaction and cholinergic activity of the cerebral cortex and is likely mediated by the GABA A receptor subtype bearing the α 1-subunit. In this study, we evaluated the effects of repetitive TMS (rTMS) therapy on SAI in treatment-resistant depression (TRD). Methods Two patient groups received either active (12 patients) or sham (12 patients) rTMS daily for 27 days. During treatment, excitatory 10 Hz stimulation was applied on the left and inhibitory 1 Hz on the right dorsolateral prefrontal cortex. Before and after the treatment, SAI was measured from right abductor pollicis brevis muscle by using time-intervals of 21 ms and 30 ms between the electric stimulation of the right median nerve at the wrist and TMS of the left motor cortex. Furthermore, baseline MEPs were recorded before and after the treatment. Results Before the treatment, the 21 ms SAI was inhibitory (p = 0.001) whereas the 30 ms SAI was facilitatory (p = 0.023) in TRD patients. After treatment in the active group, the baseline MEPs decreased in amplitude (p = 0.030), the 21 ms SAI MEPs stayed the same (p = 0.299) and the 30 ms SAI MEPs decreased (p = 0.047) compared to pre-treatment amplitudes. In the sham group, treatment did not induce any changes (p ⩾ 0.188). Conclusion rTMS treatment modulates the sensorimotor interaction of TRD patients.

Introduction Obstructive sleep apnea (OSA) is a common disease with severe health consequences most commonly treated with continuous positive airway pressure (CPAP) device. However, the adherence to CPAP treatment is often limited and the usage of the CPAP device can be only around 4 h per night after 1 month usage ( Chai-Coetzer et al., 2013 ). Possibly for this reason the benefits of the CPAP usage in terms of cardiovascular outcomes are not always obvious ( McEvoy et al., 2016 ). The severity of OSA is estimated with apnea-hypopnea-index (AHI) together with daytime symptoms. AHI may vary hour by hour during the night. In the current study, the aim was to investigate whether there is a difference in AHI during the first 4 h of sleep (possible CPAP adherence) and during the worst 4 h during the night. Methods 2002 ambulatory polygraphic recordings of suspected OSA patients were evaluated. The patients were divided into normal, mild, moderate and severe OSA categories based on their total AHI. Total AHI, AHI during the first 4 h and AHI during the worst 4 h during the recording were analyzed. AHI during the first and the worst 4 h were then compared. Wilcoxon signed ranks test was used to estimate the statistical significance of the differences. p Results There were 972, 508, 260 and 262 patients in normal, mild, moderate and severe OSA categories, respectively. We found a trend of increasing AHI towards the end of the night. The median total AHI in these categories were 1.5, 8.7, 20.7 and 47.6 events/h, respectively. The median differences between the AHI during the worst 4 h and the first 4 h of the recording were 0.8, 4.8, 10.4 and 9.8 events/h ( p Conclusion There were statistically and clinically significant differences between the median AHI values of the worst 4 h and the first 4 h of the night in all OSA severity categories. CPAP adherence has been reported to be around 4 h per night ( Chai-Coetzer et al., 2013 ) and the CPAP usage is probably typically focused on the first hours from the beginning of the night. For these reasons the benefits of the CPAP usage are probably not as linear as the simple time of adherence indicates. With limited adherence time, CPAP treatment is not always able to prevent severe cardiovascular outcomes ( McEvoy et al., 2016 ). If the CPAP usage could be directed to the worst hours of the night at the same adherence level it might provide better treatment results. The total AHI would decrease more when CPAP would be used during the worst hours instead the first hours of the night.

Summary Purpose: Appropriate treatment of generalized convulsive refractory status epilepticus (RSE) requires general anesthesia in the intensive care unit (ICU) with continuous electroencephalography (cEEG) monitoring. During out of office hours and weekends, cEEG monitoring is not always available. The Bispectral Index (BIS) monitor can be used to assess the hypnotic component of general anesthesia. We conducted a study to evaluate the feasibility of using the BIS monitoring to assess the burst suppression (BS) pattern during propofol anesthesia in RSE. Methods: Ten adult patients with RSE admitted to the ICU were monitored simultaneously with cEEG and BIS monitoring. We compared the BIS and suppression ratio (SR) values with the EEG burst suppression pattern when the depth of anesthesia was titrated to the BS level monitoring by cEEG. Results: We found an excellent correlation between the cEEG burst rate per minute and the BIS (r2 = −0.9; p

Objectives: The association between obstructive sleep apnea (OSA) and mortality or serious cardiovascular events over a long period of time is not clearly understood. The aim of this observational study was to estimate the clinical effectiveness of continuous positive airway pressure (CPAP) treatment on an outcome variable combining mortality, acute myocardial infarction (AMI), and cerebrovascular insult (CVI) during a follow-up period of 15.5 years (186 ± 58 months). Methods: The data set consisted of 978 patients with an apnea-hypopnea index (AHI) ≥5.0. One-third had used CPAP treatment. For the first time, a data-driven causal Bayesian network (DDBN) and a hypothesis-driven causal Bayesian network (HDBN) were used to investigate the effectiveness of CPAP. Results: In the DDBN, coronary heart disease (CHD), congestive heart failure (CHF), and diuretic use were directly associated with the outcome variable. Sleep apnea parameters and CPAP treatment had no direct association with the outcome variable. In the HDBN, CPAP treatment showed an average improvement of 5.3 percentage points in the outcome. The greatest improvement was seen in patients aged ≤55 years. The effect of CPAP treatment was weaker in older patients (>55 years) and in patients with CHD. In CHF patients, CPAP treatment was associated with an increased risk of mortality, AMI, or CVI. Conclusions: The effectiveness of CPAP is modest in younger patients. Long-term effectiveness is limited in older patients and in patients with heart disease (CHD or CHF).

Progressive myoclonus epilepsies (PMEs) comprise a heterogeneous group of conditions characterized by an imbalance between excitatory and inhibitory neuronal mechanisms. The aim of this study was to assess the function of the motor cortex in Unverricht-Lundborg disease (ULD), progressive myoclonus epilepsy type 1 (EPM1).Genetically verified EPM1 patients (n=24) were studied and compared with healthy subjects (n=24). MRI-navigated transcranial magnetic stimulation (TMS) was used to study the function of the motor cortex. Motor threshold (MT) and cortical silent period (SP) were used as parameters to evaluate cortical excitability. Peripheral muscle responses were recorded at the thenar and hypothenar using on-line electromyography (EMG).The normal shortening of SP duration with age was not evident in EPM1. Thus, older patients exhibited significantly prolonged SPs in comparison to healthy control subjects (p0.05). The MTs, measured as both stimulator output percentage and induced electric field strength (EF), were significantly higher in EPM1 patients than in control subjects (p0.001). The stimulation of the thenar caused a co-activation in the hypothenar with significantly higher amplitudes as compared to controls (p0.05).The prolongation of the SPs with age in EPM1 patients suggests a prevailing inhibitory tonus of the primary motor cortex (M1) as possible reactive mechanism to the disease. Antiepileptic drugs may contribute to the increased MT but do not affect the SP. The results and methodology of this study can lead to a better understanding of the pathophysiology and progression of EPM1.

Navigated transcranial magnetic stimulation (TMS) is a tool for targeted, noninvasive stimulation of cerebral cortex. Transcranial stimuli can depolarize neurons and evoke measurable effects which are unique in two ways: the effects are caused directly and without a consciousness of the subject, and, the responses from peripheral muscles provide a direct measure for the integrity of the whole motor pathway. The clinical relevance of the method has not always been fully exposed because localizing the optimal stimulation site and determining the optimal stimulation strength have been dependent on time-consuming experimentation and skill. Moreover, in many disorders it has been uncertain, whether the lack of motor responses is the result of true pathophysiological changes or merely because of unoptimal stimulation. We characterized the muscle responses from human primary motor cortex system by navigated TMS to provide normative values for the clinically relevant TMS parameters on 65 healthy volunteers aged 22 to 81 years. We delivered focal TMS pulses on the primary motor area (M1) and recorded muscle responses on thenar and anterior tibial muscles. Motor threshold, latencies and amplitudes of motor-evoked potentials, and silent period duration were measured. The correction of the motor-evoked potential latency for subjects' height is provided. In conclusion, we provide a modified baseline of TMS-related parameters for healthy subjects. Earlier such large-scale baseline material has not been available.

Am J Phys Med Rehabil 2008;87;992-997. Objective: The purpose of this study was to assess clinical and neurophysiological changes after 6 mos of transcutaneous electrical stimulation in patients with unresolved facial nerve paralysis. Design: A pilot case series of 10 consecutive patients with chronic facial nerve paralysis either of idiopathic origin or because of herpes zoster oticus participated in this open study. All patients received below sensory threshold transcutaneous electrical stimulation for 6 mos for their facial nerve paralysis. The intervention consisted of gradually increasing the duration of electrical stimulation of three sites on the affected area for up to 6 hrs/day. Assessments of the facial nerve function were performed using the House-Brackmann clinical scale and neurophysiological measurements of compound motor action potential distal latencies on the affected and nonaffected sides. Patients were tested before and after the intervention. Results: A significant improvement was observed in the facial nerve upper branch compound motor action potential distal latency on the affected side in all patients. An improvement of one grade in House-Brackmann scale was observed and some patients also reported subjective improvement. Conclusions: Transcutaneous electrical stimulation treatment may have a positive effect on unresolved facial nerve paralysis. This study illustrates a possibly effective treatment option for patients with the chronic facial paresis with no other expectations of recovery.

Obstructive sleep apnea syndrome (OSAS) is a major public health problem. The golden reference for diagnosing OSAS is the sleep-laboratory based polysomnography (PSG). However, screening of population for OSAS may be practical and cost efficient only through ambulatory home recordings. In this work we aimed to design, construct and evaluate a novel ambulatory device for these recordings. The device was designed to record breathing movements, nasal and oral flow, position, snore, blood oxygen saturation and heart rate. The first part of clinical evaluation was done by recording 19 patients simultaneously with the novel device and with clinical reference instrumentation at a sleep laboratory. In the simultaneous recordings, no statistically significant difference was detected in the apnea-hypopnea index. All patients were correctly diagnosed, as compared to the reference instrumentation, with the novel ambulatory device. The second part of clinical evaluation was conducted through 323 ambulatory home recordings of which 275 (193 males and 82 females) were of diagnostically acceptable quality. A total of 106 and 169 recordings were successfully conducted with the novel device and a commercial ambulatory device, respectively. Both devices showed similar diagnostic capability in detecting sleep apnea. The novel device was found clinically applicable, technically reliable and sensitive for the diagnostics of OSAS.

Cerebral stroke is a major cause for long-term disability in the elderly and it is often manifested in hemiparesis of the upper extremity. Constraint-induced movement therapy (CIMT), an intensive 2 week rehabilitation program, improves affected upper limb motor abilities in subjects with stroke. Intensive training has also been suggested to modify neural function. We wanted to find out if there are changes in cortical excitabihlity in subjects with chronic stroke after CIMT.Participants were 13 subjects with stroke who fulfilled the entry criteria for the CIMT program. The motor function of the affected arm and hand was assessed using a structured motor behavior test (WMFT). The cortical excitability changes were assessed in regard to involuntary and voluntary motor control, former with transcrania magnetic stimulation (TMS) and latter with movement-related cortical potentials (MRCP).The motor abilities of the affected arm improved after 2 week rehabilitation (total time in WMFT shortened 36%). The motor-evoked potential (MEP) amplitudes were unchanged following the stimulation of the non-affected hemisphere; however, the MEP amplitudes of lateral stimulation locations increased significantly in the affected side after the intervention. The power spectra of MRCPs revealed reduced peak frequency over the supplementary motor area when the affected hand was moved. However, no changes occurred when the healthy hand was moved.We show changes in cortical electrical excitability while performing both involuntary and voluntary movements after 2 weeks of CIMT in subjects with chronic stroke. These changes may be seen as a sign of neural reorganization instigated by the intervention.

Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

Summary Purpose Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder. Cases tend to be sporadic. We elucidate the characteristics of an inherited r(20) mosaicism by describing the clinical features of three family members: a mother and her two children. Results The mosaicism rate of the mother was 10% and that of the children 40%. The mother experienced her first epileptic seizures at 24 years of age. Epilepsy was diagnosed two years later. After an unstable period lasting 3 years, she has been seizure-free for 13 years on a combination of valproate and lamotrigine. She has normal intelligence with full working capacity. The daughter exhibited her first epileptic seizures at the age of 7 years and she continues to have seizures weekly. The first epileptic seizures in the son were observed at 5 years of age. The son's epilepsy has been drug resistant from the onset, and a vagal nerve stimulator (VNS) has been ineffective. Psychomotor development was normal in both children up to the onset of epilepsy. Learning difficulties increased throughout school age and both children needed special educational programs. Neuropsychological evaluations have shown deterioration of cognitive levels. Both children had behavioural problems during school age but no longer in adolescence. All three subjects are nondysmophic, normocephalic and of normal growth. Conclusion In this family the phenotype of r(20) mosaicism seems to be more severe in the successive generation along with a greater level of mosaicism. The aggravated clinical picture in inherited r(20) mosaicism concerned the onset of epilepsy, drug responsiveness, the cognitive level and behavioural features.

Background Navigated transcranial magnetic stimulation (nTMS) has become established as an accurate noninvasive technique for mapping the functional motor cortex for the representation areas of upper and lower limb muscles but not yet for facial musculature. Objective To characterize the applicability and clinical impact of using nTMS to map cortical motor areas of facial muscles in healthy volunteers and neurosurgical tumor patients. Methods Eight healthy volunteers and 12 patients with tumor were studied. The motor threshold (MT) was determined for the abductor pollicis brevis and mentalis muscles. The lateral part of the motor cortex was mapped with suprathreshold stimulation intensity, and motor evoked potentials were recorded from several facial muscles. The patient protocol was modified according to the clinical indication. Results In all healthy subjects, motor evoked potentials were elicited in the mentalis (mean latency, 13.4 milliseconds) and orbicularis oris (mean latency, 12.6 milliseconds) muscles. At 110% of MT of the mentalis, the motor evoked potentials of facial muscles were elicited mainly in the precentral gyrus but also from one gyrus anterior and posterior to it. The cortical areas applicable for mapping were limited by an artifact attributable to direct peripheral nerve stimulation. The mapping protocol was successful in 10 of 12 tumor patients at locating the representation area of the lower facial muscles. The MT of the facial muscles was significantly higher than that of the abductor pollicis brevis. Conclusion nTMS is an applicable and clinically beneficial noninvasive method to preoperatively map the cortical representation areas of the facial muscles in the lower part of the face. Instead of using the MT of the abductor pollicis brevis, the stimulus intensity during mapping should be proportioned to the MT of a facial muscle.

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".

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. 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. 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. 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.

Obstructive sleep apnea (OSA) is a public health problem with severe health consequences. The current OSA severity estimation is based on the average number of breathing cessation and desaturation events per hour of sleep, neglecting the individual event characteristics. The aim of the current study was to evaluate desaturation event morphology in de- ceased and matched control patients with severe OSA. 12 deceased and 12 AHI, age, BMI and follow-up time matched alive control patients with severe OSA were analyzed. Desaturation event durations, depths, and areas of the deceased and alive control patients were compared. Also the effect of different baseline level selection in the desaturation depth analysis was investigated. Patient demographics, apnea-hypopnea-index (AHI) and oxygen-desaturation-index (ODI) did not differ statistically significantly between the groups. The average oxygen saturation levels were statistically significantly lower 89.8% vs. 93.2% ( p =0.002) in the deceased patients compared to the alive controls. The median desaturation event duration 31.8s vs. 25.9s ( p =0.017), depth 15.0% vs. 9.5% ( p =0.006) and area 349.9s% vs. 201.4s% ( p

To study prospectively the effects of propofol anesthesia on seizure control, hemodynamics and course of intensive care in patients with refractory status epilepticus.Prospective observational study in the general intensive care unit in a tertiary university hospital.Ten patients with refractory status epilepticus.Patients received propofol anesthesia aiming to burst suppression EEG pattern for 12 h.Dose of propofol, quality of burst suppression EEG, hemodynamics and the course of intensive care were recorded. Clinical and electrophysiological seizures terminated quickly, but maintaining burst suppression EEG pattern required incremental doses of propofol. Despite high doses of propofol, recovery from anesthesia was fast.High doses of propofol are needed in the treatment of refractory status epilepticus. The maintenance of continuous-burst suppression is difficult, and vigilant titrating of dosage of propofol is necessary under continuous EEG monitoring.

Human temporal lobe epilepsy (TLE) is associated with cellular alterations (eg, hilar cell death, neurogenesis, and granule cell dispersion) in the dentate gyrus but their underlying molecular mechanism are not known. We previously demonstrated increased expression of cystatin C, a protease inhibitor linked to both neurodegeneration and neurogenesis, during epileptogenesis in the rat hippocampus. Here, we investigated cystatin C expression in the dentate gyrus in chronic epilepsy and its association with neuronal loss and neurogenesis. In both rats with epilepsy and human patients with TLE, cystatin C expression was increased in glial cells in the molecular layer of the dentate gyrus, being most prominent in cases with granule cell dispersion. In patients with TLE, high cystatin C expression associated with greater numbers of polysialylated neural cell adhesion molecule-positive newborn cells in the molecular layer, although the overall number was decreased, indicating that the newborn cells migrate to abnormal locations in the epileptic dentate gyrus. These data thus demonstrate that cystatin C expression is altered during the chronic phase of epilepsy and suggest that cystatin C plays a role in network reorganization in the epileptic dentate gyrus, especially in granule cell dispersion and guidance of migrating newborn granule cells.

Hemiparesis is the most common deficit after cerebral stroke. Constraint-induced movement therapy (CIMT) is a new neurorehabilitation method that emphasizes task-relevant repetitive training for the stroke hand. Twelve chronic stroke patients were studied with single-photon emission computerized tomography at rest before and after the two-week CIMT period. Increased perfusion was found in motor control related areas. The specific areas with an increase in perfusion in the affected hemisphere were in the precentral gyrus, premotor cortex (Brodmann's area 6 (BA6)), frontal cortex, and superior frontal gyrus (BA10). In the nonaffected hemisphere, perfusion was increased in the superior frontal gyrus (BA6) and cingulate gyrus (BA31). In the cerebellum increased perfusion was seen bilaterally. The brain areas with increased perfusion receive and integrate the information from different sensory systems and plan the movement execution. Regional cerebral perfusion decreased in the lingual gyrus (BA18) in the affected hemisphere. In the nonaffected frontal cortex, two areas with decreased perfusion were found in the middle frontal gyrus (BA8/10). Also, the fusiform gyrus (BA20) and inferior temporal gyrus (BA37) in the non-affected hemisphere showed decreased perfusion. Intensive movement therapy appears to change local cerebral perfusion in areas known to participate in movement planning and execution. These changes might be a sign of active reorganization processes after CIMT in the chronic state of stroke.

We report an illustrative case of presurgical evaluation for epilepsy surgery, where the three-dimensional reconstructed magnetic resonance imaging played a pivotal role in determining the exact location of the subdural strip electrodes in temporomesial area. The tip of one the frontal strip electrodes was actually recording the temporopolar ictal activity. This contributed conclusively to the decision for surgical treatment and to the excellent outcome.

To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up.Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy.46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (por = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome.Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

Objectives Unverricht-Lundborg disease, or progressive myoclonus epilepsy type 1 (EPM1), affects cortical excitability and inhibition, and neuroanatomy of the thalamocortical system. Stimulus sensitive myoclonus with potentially disabling features associates with EPM1. Our objective was to assess neurophysiological adaptation in EPM1 to further understand the role of the impaired thalamocortical system in the characteristic features of the disease. Methods Eight EPM1 patients and 10 controls were studied using navigated transcranial magnetic stimulation (nTMS). We studied adaptation of motor cortex to excitatory external stimuli using nTMS with repetition suppression (RS) study-protocol adapted from our previous study [1] . Results We found that the reactivity and adaptation to external stimuli was highly abnormal in EPM1 patients compared to healthy controls. EPM1 group exhibited no RS effect (F = 1.07, p = 0.385), while such effect was observed in controls (F = 53.01, p 0.001 ). In controls, the RS effect was seen as 50–55% reduction in motor evoked potentials of the right hand after the first stimulus in RS stimulus protocol. Conclusions Neural processing of stimuli received by the motor cortex is severely impaired in EPM1. This may be due to anatomic changes seen in the thalamocortical system, potentially impairing connective control between the thalamic nuclei and the cortex. Significance The abnormal adaption to external stimuli observed in the present study may contribute to the expression of the EPM1’s motor symptoms. This study helps to further understand the neurophysiological appearance of EPM1 in common neural functions.

Objectives Despite the poorly known mechanism of action, high-frequency rTMS targeted somatotopically to M1, is beneficial to treat therapy-resistant chronic neuropathic pain in about half of the patients. According to previous literature hand motor representation area is diminished in chronic pain. We hypothesized that face motor map is altered in chronic pain and will be restored after rTMS treatment. Another aim was to find the different patterns of plastic cortical reshaping. Methods 13 patients with severe unilateral, chronic atypical facial pain were examined before therapy (2 five-day rTMS treatment courses (2400 or 3600 pulses daily), separated by 6 weeks), and 4–5 days after the last treatment session. Motor mapping was performed at 105% rMT of the mentalis muscle using a grid (2 stimuli per square) to determine the extent of representation area on the hemisphere contralateral to painful side. Mapping was analyzed for hotspot, center-of-gravity (CoG) and representation area, calculated using spline-interpolation method. Patient scored the effect of treatment using patient global impression of change (PGIC). Results The hotspots and CoGs were located in anatomically expected areas. In group level, the rTMS did not cause any shift in mediolateral or anteroposterior axis, or affect the extent of representation areas. However, there were several patients in whom the area significantly largened or became more compact/dense after the treatment. Noteworthly, the motor map of facial muscles was surprisingly small in four patients, whereof three scored high benefit. Discussion The face motor maps in patients with chronic facial pain are variable in size. There was a trend of rTMS increasing the motor map. In some patients the face motor map was clearly diminished and mainly, these patients responded to treatment well. This may be related to enhanced cortical plasticity. Conclusion nTMS motor mapping is a feasible method to study neuronal plasticity in chronic pain and enlighten the effects of rTMS. However, larger amount of patient is needed to draw conclusions about patterns of cortical plasticity. Significance Motor map area may be a biomarker for treatment response in chronic facial pain.

Introduction Repetitive TMS (rTMS) targeted to primary motor cortex (M1) has been proven effective in treating pharmacoresistant chronic neuropathic pain. However, the mechanisms of action of rTMS are so far unknown. Better efficacy has been shown when rTMS is targeted to adjacent cortical area ( Lefaucheur et al., 2006 ), though somatotopic targeting is also commonly used. Previously, smaller hand motor representation area of the painful side has been shown in chronic pain ( Krause et al., 2006 ). Objectives We hypothesized that the motor map plasticity would be changed after two 5-days rTMS treatment sessions separated by 6 weeks. Therapy was targeted to the somatotopic facial M1 using neuronavigated TMS. Patients and methods Three patients with severe unilateral, chronic atypical facial pain were enrolled in the study. High-frequency rTMS (10 Hz or 20 Hz, 2400 or 3600 pulses per session, 90% of the resting motor threshold, rMT) was targeted to functional motor representation area of the mentalis muscle. Hotspots and rMTs were determined for face and hand on both hemispheres. Silent period duration was measured on the hand muscle. Mapping was performed at 105% of the rMT of the mentalis muscle to determine the center-of-gravity (CoG) on the hemisphere contralateral to painful side. A grid with 5 mm spacing was used and two stimuli were applied per square. Results rTMS sessions did not significantly change the hand or face rMTs on either hemisphere. In all three patients, the representation area of the mentalis muscle has expanded in anterior-posterior direction. Correspondingly, the CoG of the mentalis muscle moved posteriorly (Fig. 1). Silent period duration was increased in the third patient showing the largest shift of the CoG. Patients 2 and 3 benefitted from the treatment Download : Download high-res image (302KB) Download : Download full-size image . Conclusion These preliminary results suggest that rTMS induces changes in the motor map plasticity measurable 4–11 days after last rTMS session. Plastic changes may be related to normalized corticospinal inhibition.

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. 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. 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. 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.

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.

Background Navigated transcranial magnetic stimulation (nTMS) is a modern precise method to activate and study cortical functions noninvasively. We hypothesized that a combination of nTMS and functional magnetic resonance imaging (fMRI) could clarify the localization of functional areas involved with motor control and production of speech. New method Navigated repetitive TMS (rTMS) with short bursts was used to map speech areas on both hemispheres by inducing speech disruption during number recitation tasks in healthy volunteers. Two experienced video reviewers, blinded to the stimulated area, graded each trial offline according to possible speech disruption. The locations of speech disrupting nTMS trials were overlaid with fMRI activations of word generation task. Results Comparison with existing methods: Speech disruptions were produced on both hemispheres by nTMS, though there were more disruptive stimulation sites on the left hemisphere. Grade of the disruptions varied from subjective sensation to mild objectively recognizable disruption up to total speech arrest. The distribution of locations in which speech disruptions could be elicited varied among individuals. On the left hemisphere the locations of disturbing rTMS bursts with reviewers’ verification followed the areas of fMRI activation. Similar pattern was not observed on the right hemisphere. Conclusions The reviewer-verified speech disruptions induced by nTMS provided clinically relevant information, and fMRI might explain further the function of the cortical area. nTMS and fMRI complement each other, and their combination should be advocated when assessing individual localization of speech network.

The aim of this study was to evaluate neurophysiological features of M1 excitability and plasticity in Subcortical Ischemic Vascular Dementia (SIVD), by means of TMS mapping technique. Seven SIVD and nine AD patients, along with nine control subjects were tested. The M1 excitability was studied by resting thresholds, area and volume of active cortical sites for forearm and hand’s examined muscles. For M1 plasticity, coordinates of the hot-spot and the center of gravity (CoG) were evaluated. The correlation between the degree of hyperexcitability and the amount of M1 plastic rearrangement was also calculated. Multivariate analysis of excitability measures demonstrated similarly enhanced cortical excitability in AD and SIVD patients with respect to controls. SIVD patients showed a medial and frontal shift of CoG from the hot-spot, not statistically different from that observed in AD. A significant direct correlation was seen between parameters related to cortical excitability and those related to cortical plasticity. The results suggest the existence of common compensatory mechanisms in different kind of dementing diseases supporting the idea that cortical hyperexcitability can promote cortical plasticity. This study characterizes neurophysiological features of motor cortex excitability and plasticity in SIVD, providing new insights on the correlation between cortical excitability and plasticity.

Background: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. Methods: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. Results: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. Conclusions: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic-clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.