The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders.

Neurological disorders present a wide range of symptoms and challenges in diagnosis and treatment. Cannabis sativa, with its diverse chemical composition, offers potential therapeutic benefits due to its anticonvulsive, analgesic, anti-inflammatory, and neuroprotective properties. Beyond cannabinoids, cannabis contains terpenes and polyphenols, which synergistically enhance its pharmacological effects. Various administration routes, including vaporization, oral ingestion, sublingual, and rectal, provide flexibility in treatment delivery. This review shows the therapeutic efficacy of cannabis in managing neurological disorders such as epilepsy, neurodegenerative diseases, neurodevelopmental disorders, psychiatric disorders, and painful pathologies. Drawing from surveys, patient studies, and clinical trials, it highlights the potential of cannabis in alleviating symptoms, slowing disease progression, and improving overall quality of life for patients. Understanding the diverse therapeutic mechanisms of cannabis can open up possibilities for using this plant for individual patient needs.

Exploring Beneficial Properties of Haskap Berry Leaf Compounds for Gut Health Enhancement.

This study investigates the potential of formulated systems utilising haskap berry leaf extracts and dextran as carriers, to modulate both antioxidant and enzymatic inhibitory activities and their impact on the growth of specific bacterial strains. The analysis of antioxidant capacity, assessed through ABTS, CUPRAC, DPPH, and FRAP assays, revealed varying but consistently high levels across extracts, with Extract 3 (loganic acid: 2.974 mg/g, chlorogenic acid: 1.125 mg/g, caffeic acid: 0.083 mg/g, rutin: 1.137 mg/g, and quercetin: 1.501 mg/g) exhibiting the highest values (ABTS: 0.2447 mg/mL, CUPRAC: 0.3121 mg/mL, DPPH: 0.21001 mg/mL, and FRAP: 0.3411 mg/mL). Subsequent enzymatic inhibition assays demonstrated a notable inhibitory potential against α-glucosidase (1.4915 mg/mL, expressed as acarbose equivalent), hyaluronidase (0.2982 mg/mL, expressed as quercetin equivalent), and lipase (5.8715 µg/mL, expressed as orlistat equivalent). Further system development involved integration with dextran, showcasing their preserved bioactive compound content and emphasising their stability and potential bioactivity. Evaluation of the dextran systems' impact on bacterial growth revealed a significant proliferation of beneficial strains, particularly the Bifidobacterium and lactobacilli genus (Bifidobacterium longum: 9.54 × 107 to 1.57 × 1010 CFU/mL and Ligilactobacillus salivarius: 1.36 × 109 to 1.62 × 1010 CFU/mL), suggesting their potential to modulate gut microbiota. These findings offer a foundation for exploring the therapeutic applications of haskap berry-based dextran systems in managing conditions like diabetes, emphasising the interconnected roles of antioxidant-rich botanical extracts and dextran formulations in promoting overall metabolic health.

Zein as an Effective Carrier for Hesperidin Delivery Systems with Improved Prebiotic Potential.

Hesperidin is a polyphenol derived from citrus fruits that has a broad potential for biological activity and the ability to positively modify the intestinal microbiome. However, its activity is limited by its low solubility and, thus, its bioavailability-this research aimed to develop a zein-based hesperidin system with increased solubility and a sustained release profile. The study used triple systems enriched with solubilizers to maximize solubility. The best system was the triple system hesperidin-zein-Hpß-CD, for which the solubility improved by more than six times. A significant improvement in the antioxidant activity and the ability to inhibit α-glucosidase was also demonstrated, due to an improved solubility. A release profile analysis was performed in the subsequent part of the experiments, confirming the sustained release profile of hesperidin, while improving the solubility. Moreover, the ability of selected probiotic bacteria to metabolize hesperidin and the effect of this flavonoid compound on their growth were investigated.

A suggestive seizure induction technique protocol in a short EEG in children and adolescents.

The use of a suggestive seizure induction procedure (SSI) in medicine, particularly in the differential diagnosis of psychogenic nonepileptic epileptic seizures (PNES), is well documented. However, there is no description of standardized suggestion procedures used in children and adolescents. The research presents a standardized method of SSI with a cotton swab soaked in water. The protocol was developed based on of 544 placebo trials over ten years in a center for the differential diagnosis of children and adolescents. The protocol is a safe tool that allows inducing specific behavior in children and adolescents in whom there is a well-founded suspicion of PNES.

A Fisetin Delivery System for Neuroprotection: A Co-Amorphous Dispersion Prepared in Supercritical Carbon Dioxide.

Fisetin (FIS), a senolytic flavonoid, mitigates age-related neuroprotective changes. An amorphous FIS dispersion with a co-carrier was prepared using supercritical fluid extraction with carbon dioxide (scCO2). Characterisation, including powder X-ray diffraction and Fourier-transform infrared spectroscopy, confirmed amorphization and assessed intermolecular interactions. The amorphous FIS dispersion exhibited enhanced solubility, dissolution profiles, and bioavailability compared to the crystalline form. In vitro, the amorphous FIS dispersion demonstrated antioxidant activity (the ABTS, CUPRAC, DDPH, FRAP assays) and neuroprotective effects by inhibiting acetylcholinesterase and butyrylcholinesterase. FIS modulated gut microbiota, reducing potentially pathogenic gram-negative bacteria without affecting probiotic microflora. These improvements in solubility, antioxidant and neuroprotective activities, and gut microbiome modulation suggest the potential for optimising FIS delivery systems to leverage its health-promoting properties while addressing oral functionality limitations.

Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects.

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-ß-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and molecular dynamics studies were performed to assess the most preferable site of interactions between tested compounds and HP-ß-CD. The changes of physicochemical properties (solubility, dissolution rate, and permeability) were determined chromatographically. The impact of modification on biological activity was tested in an antioxidant study as well as with regards to inhibition of enzymes important in pathogenesis of neurodegenerative diseases. The results indicated improvement in solubility over 1000 and 2000 times for Hed and Het, respectively. Permeability studies revealed that Hed has difficulties in crossing biological membranes, in contrast with Het, which can be considered to be well absorbed. The improved physicochemical properties influenced the biological activity in a positive manner by the increase in inhibitory activity on the DPPH radical and cholinoesterases. To conclude the use of HP-ß-CD as a carrier in the formation of an amorphous inclusion complex seems to be a promising approach to improve the biological activity and bioavailability of Hed and Het.

The Systems of Naringenin with Solubilizers Expand Its Capability to Prevent Neurodegenerative Diseases.

BACKGROUND: Naringenin (NAR) is a flavonoid with excellent antioxidant and neuroprotective potential that is limited by its low solubility. Thus, solid dispersions with ß-cyclodextrin (ß-CD), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), hydroxypropylmethylcellulose (HPMC), and microenvironmental pH modifiers were prepared. METHODS: The systems formation analysis was performed by X-Ray Powder Diffraction (XRPD) and Fourier-transform infrared spectroscopy (FT-IR). Water solubility and dissolution rates were studied with a pH of 1.2 and 6.8. In vitro permeability through the gastrointestinal tract (GIT) and the blood-brain barrier (BBB) was assessed with the parallel artificial membrane permeability assay (PAMPA) assay. The antioxidant activity was studied with the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and cupric ion reducing antioxidant capacity (CUPRAC) assays, while in vitro enzymes studies involved the inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase. For the most promising system, in silico studies were conducted. RESULTS: NAR solubility was increased 458-fold by the solid dispersion NAR:HP-ß-CD:NaHCO3 in a mass ratio of 1:3:1. The dissolution rate was elevated from 8.216% to 88.712% in a pH of 1.2 and from 11.644% to 88.843% in a pH of 6.8 (within 3 h). NAR GIT permeability, described as the apparent permeability coefficient, was increased from 2.789 × 10-6 cm s-1 to 2.909 × 10-5 cm s-1 in an acidic pH and from 1.197 × 10-6 cm s-1 to 2.145 × 10-5 cm s-1 in a basic pH. NAR BBB permeability was established as 4.275 × 10-6 cm s-1. The antioxidant activity and enzyme inhibition were also increased. Computational studies confirmed NAR:HP-ß-CD inclusion complex formation. CONCLUSIONS: A significant improvement in NAR solubility was associated with an increase in its biological activity.

Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties.

Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, and their major secondary metabolites, in the context of searching for new therapies for CNS diseases, mainly glioblastoma multiforme (GBM). The extracts selected for the study were standardized for their content of salazinic acid, evernic acid, and (-)-usnic acid, respectively. The extracts and lichen metabolites were evaluated in terms of their anti-tumor activity, i.e., cytotoxicity against A-172 and T98G cell lines and anti-IDO1, IDO2, TDO activity, their anti-inflammatory properties exerted by anti-COX-2 and anti-hyaluronidase activity, antioxidant activity, and anti-acetylcholinesterase and anti-butyrylcholinesterase activity. The results of this study indicate that lichen-derived compounds and extracts exert significant cytotoxicity against GBM cells, inhibit the kynurenine pathway enzymes, and have anti-inflammatory properties and weak antioxidant and anti-cholinesterase properties. Moreover, evernic acid and (-)-usnic acid were shown to be able to cross the blood-brain barrier. These results demonstrate that lichen-derived extracts and compounds, especially (-)-usnic acid, can be regarded as prototypes of pharmacologically active compounds within the CNS, especially suitable for the treatment of GBM.

Fixed-Dose Combination of NSAIDs and Spasmolytic Agents in the Treatment of Different Types of Pain-A Practical Review.

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.

Permeability of Hypogymnia physodes Extract Component-Physodic Acid through the Blood-Brain Barrier as an Important Argument for Its Anticancer and Neuroprotective Activity within the Central Nervous System.

Lichen secondary metabolites are characterized by huge pharmacological potential. Our research focused on assessing the anticancer and neuroprotective activity of Hypogymnia physodes acetone extract (HP extract) and physodic acid, its major component. The antitumor properties were evaluated by cytotoxicity analysis using A-172, T98G, and U-138 MG glioblastoma cell lines and by hyaluronidase and cyclooxygenase-2 (COX-2) inhibition. The neuroprotective potential was examined using COX-2, tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activity tests. Moreover, the antioxidant potential of the tested substances was examined, and the chemical composition of the extract was analyzed. For physodic acid, the permeability through the blood-brain barrier using Parallel Artificial Membrane Permeability Assay for the Blood-Brain Barrier assay (PAMPA-BBB) was assessed. Our study shows that the tested substances strongly inhibited glioblastoma cell proliferation and hyaluronidase activity. Besides, HP extract diminished COX-2 and tyrosinase activity. However, the AChE and BChE inhibitory activity of HP extract and physodic acid were mild. The examined substances exhibited strong antioxidant activity. Importantly, we proved that physodic acid crosses the blood-brain barrier. We conclude that physodic acid and H. physodes should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially regarding the central nervous system diseases.

Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

Temporomandibular disorders in adolescents with headache.

BACKGROUND: Headache is a common complaint in all age groups and is a frequent cause of medical consultations and hospitalization. OBJECTIVES: The aim of this study was to evaluate the prevalence of bite and non-bite parafunctions as well as the signs and symptoms of temporomandibular disorder (TMD) in adolescents presenting with primary headaches. MATERIAL AND METHODS: Parents of adolescents presented with headaches to the Department of Developmental Neurology within a 12-month period were asked to complete a questionnaire developed by the authors of this study. Of the 1000 patients evaluated, 19 females and 21 males, aged 13 to 17 years, met the inclusion criterion - a confirmed clinical diagnosis of migraine or a tension headache according to the International Classification of Headache Disorders, 2nd edition. The diagnostic algorithm of the study group consisted of a full medical history, an assessment of the occurrence of bite habits and a physical examination based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). RESULTS: Bite and non-bite parafunctions were found in 36 of the study group patients. A significant difference (p = 0.0003) between the number of bite parafunctions and non-bite parafunctions was found in females but not in males. However, bite parafunctions were more frequent in boys compared to girls (p = 0.01). CONCLUSIONS: Our findings suggest that it may be useful for pediatricians and neurologists to include TMD dysfunctions as a part of a standard examination of adolescents presenting with persistent headaches.

Nocturnal seizures are associated with more severe hypoxemia and increased risk of postictal generalized EEG suppression.

Patients with epilepsy have 20-fold risk of sudden death when compared to the general population. Uncontrolled seizures is the most consistent risk factor, and death often occurs at night or in relation to sleep. We examined seizure-related respiratory disturbances in sleep versus wakefulness, focusing on periictal oxygen saturation. Respiratory measures were examined in 48 recorded seizures (sleep, n = 23, wake, n = 25) from 20 adult patients with epilepsy. Seizures from sleep were associated with lower saturation, as compared to seizures from wakefulness, both during ictal (sleep median = 90.8, wake median = 95.5; p < 0.01) and postictal periods (sleep median = 94.3, wake median = 96.9; p = 0.05). Compared to wake-related seizures, seizures from sleep were also associated with a larger desaturation drop (sleep median = -4.2, wake median = -1.2; p = 0.01). Postictal generalized electroencephalography (EEG) suppression (PGES) occurred more frequently after seizures from sleep (39%), as compared to wake-related seizures (8%, p = 0.01). Our findings suggest that nocturnal seizures may entail a higher sudden unexpected death in epilepsy (SUDEP) severity burden, as they are associated with more severe and longer hypoxemia events, and more frequently followed by PGES, both factors implicated in sudden death.

Treatment guidelines for Circadian Rhythm Sleep-Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part I. Physiology, assessment and therapeutic methods. / Standardy leczenia zaburzen rytmu okolodobowego snu i czuwania opracowane przez Polskie Towarzystwo Badan nad Snem i Sekcje Psychiatrii Biologicznej Polskiego Towarzystwa Psychiatrycznego. Czesc I. Fizjologia, metody oceny i oddzialywania terapeutyczne.

Majority of the physiological processes in the human organism are rhythmic. The most common are the diurnal changes that repeat roughly every 24 hours, called circadian rhythms. Circadian rhythms disorders have negative influence on human functioning. The aim of this article is to present the current understanding of the circadian rhythms physiological role, with particular emphasis on the circadian rhythm sleep-wake disorders (CRSWD), principles of their diagnosis and chronobiological therapy. The guidelines are based on the review of recommendations from the scientific societies involved in sleep medicine and the clinical experiences of the authors. Researchers participating in the preparation of guidelines were invited by the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association, based on their significant contributions in circadian rhythm research and/or clinical experience in the treatment of such disorders. Finally, the guidelines were adjusted to the questions and comments given by the members of both Societies. CRSWD have a significant negative impact on human health and functioning. Standard methods used to assess CRSWD are sleep diaries and sleep logs, while the actigraphy, when available, should be also used. The most effective methods of CRSWD treatment are melatonin administration and light therapy. Behavioral interventions are also recommended. Afourteen-day period of sleep-wake rhythm assessment in CRSWD enables accurate diagnosis, adequate selection of chronobiological interventions, and planning adequate diurnal timing of their application. This type of assessment is quite easy, low-cost, and provides valuable indications how to adjust the therapeutic approach to the circadian phase of the particular patient.

Treatment guidelines for Circadian Rhythm Sleep - Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part II. Diagnosis and treatment. / Standardy leczenia zaburzen rytmu okolodobowego snu i czuwania Polskiego Towarzystwa Badan nad Snem i Sekcji Psychiatrii Biologicznej Polskiego Towarzystwa Psychiatrycznego. Czesc II. Diagnoza i leczenie.

AIM: Circadian rhythm sleep-wake disorders (CRSWD) are a group of disorders, in which the timing of sleep and wakefulness significantly differs from a patient's expectations or socially acceptable times. The aimof the article is to present the current principles for the diagnosis and treatment of CRSWD in adults and children. METHOD: Guidelines proposed as CRSWD treatment standard are based on the recommendations from the scientific societies involved in the sleep research and medicine. Researchers participating in the guidelines preparation were invited by the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association based on their significant contribution to the circadian rhythm research and/or clinical experience in the treatment of these disorders. Finally, the guidelines were adjusted to the questions and comments given by the members of both Societies. RESULTS: Patients with endogenous CRSWD are often misdiagnosed and treated for insomnia or hypersomnia. Therefore, each patient reporting sleep-wake disorders should be interviewed about the quality of sleep and its timing during free days (e.g. weekends, holidays). Avalid CRSWD diagnosis can be also established by using sleep diaries/logs and actigraphy. The treatment of choice for CRSWD is chronotherapy, which involves melatonin application, light therapy, and behavioral interventions. Sleep disorders associated with shift work and time zone changes are a growing health problem. Interventions for these disorders should primarily focus on prevention. CONCLUSIONS: The main problem in the treatment of CRSWD is an invalid diagnosis. Hypnotics and/or psychostimulants are often used instead of chronotherapeutic interventions, what can alleviate symptoms but is not an effective treatment.

Concentration of Il-1ß, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate.

BACKGROUND: The aim of the study was the comparison of concentrations of IL-1ß, IL-2, IL-6 and TNFα before and after valproate (VPA) treatment in blood serum in patients with generalized seizures diagnosed and treated in the Department of Developmental Neurology, Poznan University of Medical Sciences from January 2006 to May 2007. METHODS: The analysis was conducted in a group of 21 patients with well controlled, generalized seizures (mean age 7.7±4.7 years) before and after 4-6 months of VPA therapy. Quantitative determination IL-1ß, IL-2, IL-6 and TNFα were performed with method of enzyme-linked immunosorbent assay (ELISA). The serum drug concentration was determined with the use of fluorescence-polarization-immunoassay system (FPIA). RESULTS: The concentration of IL-6 in blood serum of patients decreased significantly (p<0.001) after 4-6 months of VPA therapy, but concentration of IL-1ß (p=0.732), IL-2 (p=0.865), TNFα (p=0.079) did not change significantly. The serum concentration of VPA in all of patients was in therapeutic range (mean 77.53±19.71µg/ml). CONCLUSIONS: The serum level of pro-inflammatory IL-6 in patients with generalized epilepsy decreased in statistically significant way during VPA therapy, so the anti-inflammatory properties of VPA are also important for the effective control of seizure. Due to the incompatibility of reports on the influence of VPA on cytokine system in patients with generalized epilepsy, this problem needs more investigations, especially in the group of children.

Predicting diurnal and sleep/wake seizure patterns in paediatric patients of different ages.

AIM: To identify factors that influence diurnal and sleep/wake seizure timing in children undergoing tapered drug withdrawal in an epilepsy monitoring unit. METHODS: Medical charts of patients that underwent video-EEG were reviewed. Seizures were evaluated based on their occurrence in three-hour time intervals (bins) and between wakefulness and sleep. Patients were classified according to EEG localisation and age: infants (≤3 years), children (3-12 years), and adolescents (>12-21 years). Analysis utilising generalised estimating equations with a negative binomial distribution was performed. RESULTS: A total of 390 patients (188 girls; mean age: 9.2 years; SD: 6.0) had 1,754 seizures. Generalised seizures (109 patients; 490 seizures) occurred more during wakefulness (p<0.001) and during the day (p<0.001). Modelling revealed a greater occurrence of seizures at night with increasing age (p=0.046). Temporal lobe seizures (62 patients; 271 seizures) occurred overall more frequently during wakefulness (p=0.03). Frontal lobe seizures (41 patients; 184 seizures) occurred more frequently during wakefulness in infants (p<0.05) and more frequently during sleep in adolescents (p<0.0001). Adolescents with frontal lobe seizures were 3.6 times more likely to have seizures during sleep compared to other children (95% CI: 1.8-7.2). CONCLUSION: These findings are suggestive of changes in circadian rhythmicity that may alter seizure susceptibility in different age groups. The results may assist in prediction of periods of greatest seizure propensity.

The diagnostic yield of pediatric polysomnography based on the professional background of referring physicians.

INTRODUCTION: Polysomnography (PSG) is the gold standard in diagnosis of sleep-disordered breathing but is labor intensive and expensive. We assessed PSG outcomes based on physician specialty and whether prior referral to sleep clinics reduces costs for children with sleep problems. METHODS: Retrospective analysis of PSGs was performed by demographics, physician specialization, PSG indication, and results. Average costs of evaluating PSGs ordered by primary care physicians (PCPs) versus initial referral to sleep specialists were compared. RESULTS: A total of 493 PSGs were performed between June 2010 and December 2010. Most referrals came from sleep physicians (31%), otolaryngologists (24%), and PCPs (18%). Forty-four percent PSGs ordered by PCPs were normal versus 22% by sleep physicians (odds ratio = 2.8, P < .05). Average cost of PSGs ordered by PCPs was $3053.54/patient versus $917.85/patient for sleep specialist referral. CONCLUSION: PSGs ordered by PCPs were more likely to be normal than PSGs by sleep physicians. Sleep clinic assessment before PSGs may assist in appropriate service utilization, improve delivery of care, and reduce health care costs by using these tests appropriately.

Cardiopulmonary complications during pediatric seizures: a prelude to understanding SUDEP.

PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is an important, unexplained cause of death in epilepsy. Role of cardiopulmonary abnormalities in the pathophysiology of SUDEP is unclear in the pediatric population. Our objective was to assess cardiopulmonary abnormalities during epileptic seizures in children, with the long-term goal of identifying potential mechanisms of SUDEP. METHODS: We prospectively recorded cardiopulmonary functions using pulse-oximetry, electrocardiography (ECG), and respiratory inductance plethysmography (RIP). Logistic regression was used to evaluate association of cardiorespiratory findings with seizure characteristics and demographics. KEY FINDINGS: We recorded 101 seizures in 26 children (average age 3.9 years). RIP provided analyzable data in 78% and pulse-oximetry in 63% seizures. Ictal central apnea was more prevalent in patients with younger age (p = 0.01), temporal lobe (p < 0.001), left-sided (p < 0.01), symptomatic generalized (p = 0.01), longer duration seizures (p < 0.0002), desaturation (p < 0.0001), ictal bradycardia (p < 0.05), and more antiepileptic drugs (AEDs; p < 0.01), and was less prevalent in frontal lobe seizures (p < 0.01). Ictal bradypnea was more prevalent in left-sided (p < 0.05), symptomatic generalized seizures (p < 0.01), and in brain magnetic resonance imaging (MRI) lesions (p < 0.1). Ictal tachypnea was more prevalent in older-age (p = 0.01), female gender (p = 0.05), frontal lobe (p < 0.05), right-sided seizures (p < 0.001), fewer AEDs (p < 0.01), and less prevalent in lesional (p < 0.05) and symptomatic generalized seizures (p < 0.05). Ictal bradycardia was more prevalent in male patients (p < 0.05) longer duration seizures (p < 0.05), desaturation (p = 0.001), and more AEDs (p < 0.05), and was less prevalent in frontal lobe seizures (p = 0.01). Ictal and postictal bradycardia were directly associated (p < 0.05). Desaturation was more prevalent in longer-duration seizures (p < 0.0001), ictal apnea (p < 0.0001), ictal bradycardia (p = 0.001), and more AEDs (p = 0.001). SIGNIFICANCE: Potentially life-threatening cardiopulmonary abnormalities such as bradycardia, apnea, and hypoxemia in pediatric epileptic seizures are associated with predictable patient and seizure characteristics, including seizure subtype and duration.