Wavelet analysis of heart rate variability related to nocturnal frontal lobe epilepsy seizures

Introduction: Nocturnal frontal lobe epilepsy (NFLE) is a distinct syndrome of partial epilepsy whose clinical features comprise a spectrum of paroxysmal motor manifestations of variable duration and complexity, arising from sleep. Cardiovascular changes during NFLE seizures have previously been observed, however the extent of these modifications and their relationship with seizure onset has not been analyzed in detail. Objective: Aim of present study is to evaluate NFLE seizure related changes in heart rate (HR) and in sympathetic/parasympathetic balance through wavelet analysis of HR variability (HRV). Methods: We evaluated the whole night digitally recorded video-polysomnography (VPSG) of 9 patients diagnosed with NFLE with no history of cardiac disorders and normal cardiac examinations. Events with features of NFLE seizures were selected independently by three examiners and included in the study only if a consensus was reached. Heart rate was evaluated by measuring the interval between two consecutive R-waves of QRS complexes (RRi). RRi series were digitally calculated for a period of 20 minutes, including the seizures and resampled at 10 Hz using cubic spline interpolation. A multiresolution analysis was performed (Daubechies-16 form), and the squared level specific amplitude coefficients were summed across appropriate decomposition levels in order to compute total band powers in bands of interest (LF: 0.039062 - 0.156248, HF: 0.156248 - 0.624992). A general linear model was then applied to estimate changes in RRi, LF and HF powers during three different period (Basal) (30 sec, at least 30 sec before seizure onset, during which no movements occurred and autonomic conditions resulted stationary); pre-seizure period (preSP) (10 sec preceding seizure onset) and seizure period (SP) corresponding to the clinical manifestations. For one of the patients (patient 9) three seizures associated with ictal asystole were recorded, hence he was treated separately. Results: Group analysis performed on 8 patients (41 seizures) showed that RRi remained unchanged during the preSP, while a significant tachycardia was observed in the SP. A significant increase in the LF component was instead observed during both the preSP and the SP (p<0.001) while HF component decreased only in the SP (p<0.001). For patient 9 during the preSP and in the first part of SP a significant tachycardia was observed associated with an increased sympathetic activity (increased LF absolute values and LF%). In the second part of the SP a progressive decrease in HR that gradually exceeded basal values occurred before IA. Bradycardia was associated with an increase in parasympathetic activity (increased HF absolute values and HF%) contrasted by a further increase in LF until the occurrence of IA. Conclusions: These data suggest that changes in autonomic balance toward a sympathetic prevalence always preceded clinical seizure onset in NFLE, even when HR changes were not yet evident, confirming that wavelet analysis is a sensitive technique to detect sudden variations of autonomic balance occurring during transient phenomena. Finally we demonstrated that epileptic asystole is associated with a parasympathetic hypertonus counteracted by a marked sympathetic activation

Impact of rare variants in autosomal dominant hypercholesterolemia causing genes.

PURPOSE OF REVIEW: The systematic analysis of the major candidate genes in autosomal dominant hypercholesterolemia (ADH) and the use of next-generation sequencing (NGS) technology have made possible the discovery of several rare gene variants whose pathogenic effect in most cases remains poorly defined. RECENT FINDINGS: One major advance in the field has been the adoption of a set of international guidelines for the assignment of pathogenicity to low-density lipoprotein receptor (LDLR) gene variants based on the use of softwares, complemented with data available from literature and public databases. The clinical impact of several novel rare variants in LDLR, APOB, PCSK9, APOE genes have been reported in large studies describing patients with ADH found to be homozygotes/compound heterozygotes, double heterozygotes, or simple heterozygotes. In-vitro functional studies have been conducted to clarify the effect of some rare ApoB variants on LDL binding to LDLR and the impact of a rare ApoE variant on the uptake of VLDL and LDL by hepatocytes. SUMMARY: The update of the ADH gene variants database and the classification of variants in categories of pathogenicity is a major advance in the understanding the pathophysiology of ADH and in the management of this disorder. The studies of molecularly characterized patients with ADH have emphasized the impact of a specific variant and the variable clinical expression of different genotypes. The functional studies of some variants have increased our understanding of the molecular bases of some forms of ADH

Zero-Temperature Properties of the Quantum Dimer Model on the Triangular Lattice

Using exact diagonalizations and Green's function Monte Carlo simulations, we have studied the zero-temperature properties of the quantum dimer model on the triangular lattice on clusters with up to 588 sites. A detailed comparison of the properties in different topological sectors as a function of the cluster size and for different cluster shapes has allowed us to identify different phases, to show explicitly the presence of topological degeneracy in a phase close to the Rokhsar-Kivelson point, and to understand finite-size effects inside this phase. The nature of the various phases has been further investigated by calculating dimer-dimer correlation functions. The present results confirm and complement the phase diagram proposed by Moessner and Sondhi on the basis of finite-temperature simulations [Phys. Rev. Lett. {\bf 86}, 1881 (2001)].Comment: 10 pages, 16 figure

Autonomic dysfunction in progressive supranuclear palsy

Background: The degree of involvement of the autonomic nervous system in progressive supranuclear palsy (PSP) has been investigated in several studies, often providing conflicting results. There is a need for a better characterization of autonomic dysfunction in PSP, to enhance our understanding of this highly disabling neurodegenerative disease including patients’ needs and possibly be of value for clinicians in the differential diagnosis among Parkinsonian syndromes. Methods: We applied a systematic methodology to review existing literature on Pubmed regarding autonomic nervous system involvement in PSP. Results: PSP reported quite frequently symptoms suggestive of autonomic dysfunction in all domains. Cardiovascular autonomic testing showed in some cases a certain degree of impairment (never severe). There was some evidence suggesting bladder dysfunction particularly in the storage phase. Dysphagia and constipation were the most common gastrointestinal symptoms. Instrumental tests seemed to confirm sudomotor and pupillomotor disturbances. Conclusions: PSP patients frequently reported visceral symptoms, however objective testing showed that not always these reflected actual autonomic impairment. Further studies are needed to better delineate autonomic profile and its prognostic role in PSP

A mathematical model of levodopa medication effect on basal ganglia in parkinson’s disease: An application to the alternate finger tapping task

Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system. The present work aims at interfacing this neurocomputational model with a compartmental model of levodopa, to propose a general model of medicated Parkinson's disease. Levodopa effect on the striatum was simulated with a two-compartment model of pharmacokinetics in plasma joined with a motor effect compartment. The latter is characterized by the levodopa removal rate and by a sigmoidal relationship (Hill law) between concentration and effect. The main parameters of this relationship are saturation, steepness, and the half-maximum concentration. The effect of levodopa is then summed to a term representing the endogenous dopamine effect, and is used as an external input for the neurocomputation model; this allows both the temporal aspects of medication and the individual patient characteristics to be simulated. The frequency of alternate tapping is then used as the outcome of the whole model, to simulate effective clinical scores. Pharmacokinetic-pharmacodynamic modeling was preliminary performed on data of six patients with Parkinson's disease (both “stable” and “wearing-off” responders) after levodopa standardized oral dosing over 4 h. Results show that the model is able to reproduce the temporal profiles of levodopa in plasma and the finger tapping frequency in all patients, discriminating between different patterns of levodopa motor response. The more influential parameters are the Hill coefficient, related with the slope of the effect sigmoidal relationship, the drug concentration at half-maximum effect, and the drug removal rate from the effect compartment. The model can be of value to gain a deeper understanding on the pharmacokinetics and pharmacodynamics of the medication, and on the way dopamine is exploited in the neural circuitry of the basal ganglia in patients at different stages of the disease progression

Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A-V deficiency due to a novel mutation in the APOA5 gene

APOA5 encodes a novel apolipoprotein (apo A-V) which appears to be a modulator of plasma triglyceride (TG). In apoA5 knock out mice plasma TG level increases almost fourfold, whereas in human APOA5 transgenic mice it decreases by 70%. Some SNPs in the APOA5 gene have been associated with variations in plasma TG in humans. In addition, hypertriglyceridaemic (HTG) patients have been identified who carried rare nonsense mutations in the APOA5 gene (Q139X and Q148X), predicted to result in apo A-V deficiency. In this study we report a 17-year-old male with high TG and low high density lipoprotein cholesterol (HDL-C), who at the age of two had been found to have severe HTG and eruptive xanthomas suggesting a chylomicronaemia syndrome. Plasma postheparin LPL activity, however, was normal and no mutations were found in LPL and APOC2 genes. The sequence of APOA5 gene revealed that the patient was homozygous for a point mutation (c.289 C&gt;T) in exon 4, converting glutamine codon at position 97 into a termination codon (Q97X). Apo A-V was not detected in patient's plasma, indicating that he had complete apo A-V deficiency. The administration of a low-fat and low-oligosaccharide diet, either alone or supplemented with ω-3 fatty acids, started early in life, reduced plasma TG to a great extent but had a negligible effect on plasma HDL-C. Loss of function mutations of APOA5 gene may be the cause of severe HTG in patients without mutations in LPL and APOC2 genes

Mathematical modeling and parameter estimation of levodopa motor response in patients with Parkinson disease

Parkinson disease (PD) is characterized by a clear beneficial motor response to levodopa (LD) treatment. However, with disease progression and longer LD exposure, drug-related motor fluctuations usually occur. Recognition of the individual relationship between LD concentration and its effect may be difficult, due to the complexity and variability of the mechanisms involved. This work proposes an innovative procedure for the automatic estimation of LD pharmacokinetics and pharmacodynamics parameters, by a biologically-inspired mathematical model. An original issue, compared with previous similar studies, is that the model comprises not only a compartmental description of LD pharmacokinetics in plasma and its effect on the striatal neurons, but also a neurocomputational model of basal ganglia action selection. Parameter estimation was achieved on 26 patients (13 with stable and 13 with fluctuating LD response) to mimic plasma LD concentration and alternate finger tapping frequency along four hours after LD administration, automatically minimizing a cost function of the difference between simulated and clinical data points. Results show that individual data can be satisfactorily simulated in all patients and that significant differences exist in the estimated parameters between the two groups. Specifically, the drug removal rate from the effect compartment, and the Hill coefficient of the concentration-effect relationship were significantly higher in the fluctuating than in the stable group. The model, with individualized parameters, may be used to reach a deeper comprehension of the PD mechanisms, mimic the effect of medication, and, based on the predicted neural responses, plan the correct management and design innovative therapeutic procedures

Cognitive function in peripheral autonomic disorders

aims of the current study were 1) to evaluate global cognitive function in patients with autonomic failure (AF) of peripheral origin and 2) to investigate the effect of a documented fall in blood pressure (BP) fulfilling the criteria for orthostatic hypotension (OH) on cognitive performances

Switching on the deep brain stimulation: Effects on cardiovascular regulation and respiration.

BACKGROUND: Objective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. METHODS: Systolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. RESULTS: In supine resting condition switching on the DBS induced no significant changes (p>0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1 min or 10 heartbeats as a sample for analysis. CONCLUSIONS: Switching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions

Heart Rate Variability as a Tool for Seizure Prediction: A Scoping Review

: The most critical burden for People with Epilepsy (PwE) is represented by seizures, the unpredictability of which severely impacts quality of life. The design of real-time warning systems that can detect or even predict ictal events would enhance seizure management, leading to high benefits for PwE and their caregivers. In the past, various research works highlighted that seizure onset is anticipated by significant changes in autonomic cardiac control, which can be assessed through heart rate variability (HRV). This manuscript conducted a scoping review of the literature analyzing HRV-based methods for detecting or predicting ictal events. An initial search on the PubMed database returned 402 papers, 72 of which met the inclusion criteria and were included in the review. These results suggest that seizure detection is more accurate in neonatal and pediatric patients due to more significant autonomic modifications during the ictal transitions. In addition, conventional metrics are often incapable of capturing cardiac autonomic variations and should be replaced with more advanced methodologies, considering non-linear HRV features and machine learning tools for processing them. Finally, studies investigating wearable systems for heart monitoring denoted how HRV constitutes an efficient biomarker for seizure detection in patients presenting significant alterations in autonomic cardiac control during ictal events