Predicting seizures in untreated temporal lobe epilepsy using point-process nonlinear models of heartbeat dynamics.

Symptoms of temporal lobe epilepsy (TLE) are frequently associated with autonomic dysregulation, whose underlying biological processes are thought to strongly contribute to sudden unexpected death in epilepsy (SUDEP). While abnormal cardiovascular patterns commonly occur during ictal events, putative patterns of autonomic cardiac effects during pre-ictal (PRE) periods (i.e. periods preceding seizures) are still unknown. In this study, we investigated TLE-related heart rate variability (HRV) through instantaneous, nonlinear estimates of cardiovascular oscillations during inter-ictal (INT) and PRE periods. ECG recordings from 12 patients with TLE were processed to extract standard HRV indices, as well as indices of instantaneous HRV complexity (dominant Lyapunov exponent and entropy) and higher-order statistics (bispectra) obtained through definition of inhomogeneous point-process nonlinear models, employing Volterra-Laguerre expansions of linear, quadratic, and cubic kernels. Experimental results demonstrate that the best INT vs. PRE classification performance (balanced accuracy: 73.91%) was achieved only when retaining the time-varying, nonlinear, and non-stationary structure of heartbeat dynamical features. The proposed approach opens novel important avenues in predicting ictal events using information gathered from cardiovascular signals exclusively.

CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease.

OBJECTIVES: To investigate, in patients with Alzheimer's Disease (AD), the possible interplay linking alteration of neuronal energy metabolism, as measured via cerebrospinal fluid (CSF) lactate concentration, to severity of AD neurodegenerative processes and impairment of cognitive abilities. METHODS: In this study we measured and correlated CSF lactate concentrations, AD biomarker levels (τ-proteins and ß-amyloid) and Mini-Mental State Examination (MMSE) score in a population of drug-naïve patients with AD ranging from mild (MMSE≥21/30) to moderate-severe (MMSE<21/30) cognitive decline. They were compared to healthy controls and patients with vascular dementia (VaD). RESULTS: Patients with AD (n=145) showed a significant increase of CSF lactate concentration compared to controls (n=80) and patients with VaD (n=44), which was higher in mild (n=67) than in patients with moderate-severe AD (n=78). Moreover, we found, in either the whole AD population or both subgroups, a CSF profile in which higher CSF levels of t-τ and p-τ proteins corresponded to lower concentrations of lactate. CONCLUSIONS: We verified the occurrence of high CSF lactate levels in patients with AD, which may be ascribed to mitochondria impairment. Hypothesising that τ proteins may exert a detrimental effect on the entire cellular energy metabolism, the negative correlation found between lactate and τ-protein levels may allow speculation that τ toxicity, already demonstrated to have affected mitochondria, could also impair glycolytic metabolism with a less evident increase of lactate levels in more severe AD. Thus, we suggest a dynamic relationship between neuronal energy metabolism, τ proteins and cognitive decline in AD and propose the clinical potential of assessing CSF lactate levels in patients with AD to better define the neuronal brain metabolism damage.

Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia.

Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 ± 66.45 vs 170.81 ± 42.73 pg/mL) and ESS scores (7.45 ± 4.36 vs 3.84 ± 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD.

Anterior Microsurgical Approach to Ventral Lower Cervical Spine Meningiomas: Indications, Surgical Technique and Long Term Outcome.

Ventral lower cervical spinal meningiomas with posterior displacement of the spinal cord are rare and anterior approach has been rarely reported in the literature. The authors present their experience about eight patients operated through anterior microsurgical approach. Exposure of meningiomas was achieved through one or two corpectomies, according to meningioma extension. Tumour removal was performed thanks to the aid of a dedicated ultrasonic aspirator, and intraoperative evoked potentials were employed. Particular care was taken with the materials adopted for reconstruction of the anterior dural plane, to avoid postoperative cerebrospinal fluid leak. Vertebral fusion and stabilization were achieved by tantalum cage or titanium graft in case of one or two corpectomies respectively; anterior titanium plate fixed with screws was applied in all patients. Extent of tumour removal was related to the presence of a conserved arachnoidal plane between the tumour and the spinal cord: total removal was achieved in 2 patients, while gross total removal in the other six ones. Postoperative neurological outcome, which was favourable in all patients, was related mostly to preoperative neurologic status. No recurrence after total removal and no remnant growth after gross total removal occurred during an average follow-up period of 6, 7 years.

Sleep disorders in myotonic dystrophy type 2: a controlled polysomnographic study and self-reported questionnaires.

BACKGROUND AND PURPOSE: There is a paucity of data available regarding the occurrence of sleep disorders in myotonic dystrophy type 2 (DM2). In this study the sleep-wake cycle and daytime sleepiness were investigated in DM2 patients and compared with results from healthy subjects and myotonic dystrophy type 1 (DM1) patients. METHODS: Twelve DM2 outpatients, 12 age- and sex-matched healthy controls and 18 DM1 patients were recruited. Subjective quality of sleep was assessed by means of the Pittsburgh Sleep Quality Index (PSQI). Both the Epworth Sleepiness Scale and the Daytime Sleepiness Scale were performed in order to evaluate excessive daytime sleepiness (EDS). All participants underwent polysomnographic monitoring over 48 h as well as the Multiple Sleep Latency Test. RESULTS: Sleep efficiency was < 90% in 12/12 DM2 patients, and significantly reduced when compared with controls or with DM1. Decreased sleep efficiency was associated with sleep-disordered breathing in seven out of 12 DM2 patients and/or periodic limbs movements of sleep (PLMS) in three out of eight patients. Six DM2 patients showed REM sleep without atonia, whereas none of the controls or DM1 patients showed REM sleep dysregulation. The global PSQI score was higher in DM2 patients than in controls and DM1 patients. CONCLUSIONS: Sleep quality in DM2 patients is poorer than in DM1 patients and controls. Sleep apnea is the most common sleep disorder in DM2 patients. Obstructive sleep apnea and sleep fragmentation may represent the main cause of EDS, whereas PLMS is a frequent finding in DM1.

Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies.

Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterized by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified, myotonic dystrophy type 1 (DM1 or Steinert's Disease) and myotonic dystrophy type 2 (DM2). Myotonic dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in DM1 are common and include sleep-disordered breathing (SDB), periodic limb movements (PLMS), central hypersomnia, and REM sleep dysregulation (high REM density and narcoleptic-like phenotype). Interestingly, drowsiness in DM1 seems to be due to a central dysfunction of sleep-wake regulation more than SDB. To date, little is known regarding the occurrence of sleep disorders in DM2. SDB (obstructive and central apnoea), REM sleep without atonia, and restless legs syndrome have been described. Further polysomnographic, controlled studies are strongly needed, particularly in DM2, in order to clarify the role of sleep disorders in the myotonic dystrophies.

Spasticity as an ictal pattern due to excitotoxic upper motor neuron damage.

We describe the case of a man who presented with spasticity and aphasia related to continuous electroencephalographic epileptic activity in the left frontal-temporal regions. Magnetic resonance imaging (MRI) documented in diffusion-weighted images (DWI) two areas of restricted diffusion in the left frontal and temporal cortex. After starting treatment with levetiracetam 3000 mg/day there was progressive recovery of the clinical picture as well as the gradual disappearance of the electroencephalographic seizure activity and the vanishing of areas of restricted diffusion in brain MRI. Based on the clinical, EEG and MRI data, we hypothesized that both aphasia and spasticity represented ictal signs. To our knowledge, this is the first case report of ictal spasticity.

Evaluation of the performances of different P300 based brain-computer interfaces by means of the efficiency metric.

The aim of this paper is to show how to use the Efficiency, a brain-computer interface (BCI) performance indicator, to evaluate the performances of a wide range of BCI systems. Unlike the most used metrics in the BCI research field, the Efficiency takes into account the penalties and the strategies to recover errors and this makes it a reliable instrument to describe the behavior of real BCIs. The Efficiency is compared with the accuracy and the information transfer rate, both in the Wolpaw and Nykopp definitions. The comparison covers four widely used classifiers and different stimulation sequences. Results show that the Efficiency is able to predict if the communication will not be possible, because the time spent to correct mistakes is longer than the time needed to generate a correct selection, and therefore it provides a much more realistic evaluation of a system. It can also be easily adapted to evaluate different applications, so it reveals a more general and versatile indicator for BCI systems.

Sleep disorders in adult-onset myotonic dystrophy type 1: a controlled polysomnographic study.

BACKGROUND: Sleep disturbances and excessive daytime somnolence are common and disabling features in adult-onset myotonic dystrophy type 1 (DM1). METHODS: Our study used questionnaires, ambulatory polysomnography and the multiple sleep latency test to evaluate sleep-wake cycle and daytime sleepiness in unselected adult-onset DM1 patients. We recruited 18 patients affected by adult-onset DM1 and 18 matched controls. RESULTS: Sleep efficiency was <90% in 16/18 patients, and it was significantly reduced when compared with controls. Reduced sleep efficiency was associated with abnormal respiratory events (5/18 patients) and/or periodic limb movements (11/18 patients). The Periodic Limb Movement Index was significantly increased in DM1 versus controls. A significantly lower mean MSLT sleep latency was detected in DM1 versus controls, but it did not reach pathological levels. CONCLUSIONS: Our controlled study demonstrated sleep alterations in unselected consecutive DM1 patients. Periodic limb movements in sleep are commonly associated with sleep disturbance in adult-onset DM1, and it may represent a marker of CNS neurodegenerative processes in DM1.

Study of the time-varying cortical connectivity changes during the attempt of foot movements by spinal cord injured and healthy subjects.

In this study we estimated time-varying cortical connectivity patterns from a group of Spinal Cord Injured (SCI) patients during the attempt to move a paralyzed limb. These data were compared with the time-varying connectivity patterns estimated in a control group during the real execution of the movement by using time-varying Partial Directed Coherence. Connectivity was estimated from high resolution EEG recordings with the use of realistic head modelling and the linear inverse estimation of the cortical activity in a series of Regions of Interest of the cortex (ROIs). The experimental evidences obtained support the conclusion that the SCI population involved a larger cortical network than those generated by the healthy subjects during the task performance. Such network differs for the involvement of the parietal cortices, which increases in strength near to the movement imagination onset for the SCI when compared to the normal population. Such details about the temporal evolution of the connectivity patterns cannot be obtained with the application of the standard estimators of connectivity.

Estimation of the cortical activity from simultaneous multi-subject recordings during the prisoner's dilemma.

One of the most challenging questions open in Neuroscience today is the characterization of the brain responses during social interaction. A major limitation of the approaches used in most of the studies performed so far is that only one of the participating brains is measured each time. The "interaction" between cooperating, competing or communicating brains is thus not measured directly, but inferred by independent observations aggregated by cognitive models and assumptions that link behavior and neural activation. In this paper, we present the results of the simultaneous neuroelectric recording of 5 couples of subjects engaged in cooperative games (EEG hyperscanning). The simultaneous recordings of couples of interacting subjects allows to observe and model directly the neural signature of human interactions in order to understand the cerebral processes generating and generated by social cooperation or competition. We used a paradigm called Prisoner's dilemma derived from the game theory. Results collected in a population of 10 subjects suggested that the most consistently activated structure in social interaction paradigms is the orbitofrontal region (roughly described by the Brodmann area 10) during the condition of competition.

Single-epoch analysis of interleaved evoked potentials and fMRI responses during steady-state visual stimulation.

OBJECTIVE: Aim of the study was to record BOLD-fMRI interleaved with evoked potentials for single-epochs of visual stimulation and to investigate the possible relationship between these two measures. METHODS: Sparse recording of fMRI and EEG allowed us to measure BOLD responses and evoked potentials on an epoch-by-epoch basis. To obtain robust estimates of evoked potentials, we used blocks of contrast-reversing visual stimuli eliciting steady-state visual evoked potentials (SSVEPs). For each block we acquired one volume of fMRI data and we then tested for co-variations between SSVEPs and fMRI signals. Our analyses tested for frequency-specific co-variation between the two measurements that could not be explained by the mere presence/absence of the visual stimulation. RESULTS: Condition-specific single-epoch SSVEPs and fMRI responses were observed at occipital sites. Combined SSVEPs-fMRI analysis at the single-epoch level did not reveal any significant correlation between the two recordings. However, both signals contained stimulation-specific linear decreases that may relate to neuronal habituation. CONCLUSIONS: Our findings demonstrate robust estimation of single-epoch evoked potentials and fMRI responses during interleaved recording, using visual steady-state stimulation. SIGNIFICANCE: Single-epochs analysis of evoked potentials and fMRI signals is feasible for interleaved SSVEPs-fMRI recordings.

Estimation of effective and functional cortical connectivity from neuroelectric and hemodynamic recordings.

In this paper, different linear and nonlinear methodologies for the estimation of cortical connectivity from neuroelectric and hemodynamic measurements are reviewed and applied on common data set in order to highlight similarities and differences in the results. Different effective and functional connectivity methods were applied to motor and cognitive data sets, including structural equation modeling (SEM), directed transfer function (DTF), partial directed coherence (PDC), and direct directed transfer function (dDTF). Comparisons were made between the results in order to understand if, for a same dataset, effective and functional connectivity estimators can return the same cortical connectivity patterns. An application of a nonlinear method [phase synchronization index (PSI)] to similar executed and imagined movements was also reviewed. Connectivity patterns estimated with the use of the neuroelectric information and of the information from the multimodal integration of neuroelectric and hemodynamic data were also compared. Results suggests that the estimation of the cortical connectivity patterns performed with the linear methods (SEM, DTF, PDC, dDTF) or with the nonlinear method (PSI) on movement related potentials returned similar cortical networks. Differences in cortical connectivity were noted between the patterns estimated with the use of multimodal integration and those estimated by using only the neuroelectric data.

ICTAL aphasia as manifestation of partial status epilepticus in a long-lasting misdiagnosed symptomatic epilepsy: an emblematic case.

Magnetic Resonance Imaging (MRI) represents the procedure of choice for detection of anatomical lesions in epilepsy. Vascular malformations in central nervous system, such as cavernoma, can cause symptomatic epilepsy. We describe a case of ictal aphasia as manifestation of a partial status epilepticus probably due to a mutual interaction between a recent bleeding cavernoma and a concomitant reduction of antiepileptic treatment in a long-lasting misdiagnosed symptomatic epilepsy. We conclude that MRI is a mandatory diagnostic method to identify structural abnormalities underlying epilepsy in all patients affected by recurrent focal seizures independent of the duration of epilepsy.