Potential of focal cortical dysplasia in migraine pathogenesis.

Focal cortical dysplasias are abnormalities of the cerebral cortex associated with an elevated risk of neurological disturbances. Cortical spreading depolarization/depression is a correlate of migraine aura/headache and a trigger of migraine pain mechanisms. However, cortical spreading depolarization/depression is associated with cortical structural changes, which can be classified as transient focal cortical dysplasias. Migraine is reported to be associated with changes in various brain structures, including malformations and lesions in the cortex. Such malformations may be related to focal cortical dysplasias, which may play a role in migraine pathogenesis. Results obtained so far suggest that focal cortical dysplasias may belong to the causes and consequences of migraine. Certain focal cortical dysplasias may lower the threshold of cortical excitability and facilitate the action of migraine triggers. Migraine prevalence in epileptic patients is higher than in the general population, and focal cortical dysplasias are an established element of epilepsy pathogenesis. In this narrative/hypothesis review, we present mainly information on cortical structural changes in migraine, but studies on structural alterations in deep white matter and other brain regions are also presented. We develop the hypothesis that focal cortical dysplasias may be causally associated with migraine and link pathogeneses of migraine and epilepsy.

The Use of CGH Arrays for Identifying Copy Number Variations in Children with Autism Spectrum Disorder.

Autism spectrum disorders (ASDs) encompass a broad group of neurodevelopmental disorders with varied clinical symptoms, all being characterized by deficits in social communication and repetitive behavior. Although the etiology of ASD is heterogeneous, with many genes involved, a crucial role is believed to be played by copy number variants (CNVs). The present study examines the role of copy number variation in the development of isolated ASD, or ASD with additional clinical features, among a group of 180 patients ranging in age from two years and four months to 17 years and nine months. Samples were taken and subjected to array-based comparative genomic hybridization (aCGH), the gold standard in detecting gains or losses in the genome, using a 4 × 180 CytoSure Autism Research Array, with a resolution of around 75 kb. The results indicated the presence of nine pathogenic and six likely pathogenic imbalances, and 20 variants of uncertain significance (VUSs) among the group. Relevant variants were more prevalent in patients with ASD and additional clinical features. Twelve of the detected variants, four of which were probably pathogenic, would not have been identified using the routine 8 × 60 k microarray. These results confirm the value of microarrays in ASD diagnostics and highlight the need for dedicated tools.

COVID-19 in pediatric palliative care patients: Multicenter, retrospective cohort study.

BACKGROUND: Studies have shown the risk factors for COVID-19 severity in children, including comorbidities, but information on the infection course in children with life-limiting conditions is sparse. AIM: To describe the effect of COVID-19 on pediatric patients receiving palliative care due to life-limiting conditions. DESIGN: We conducted retrospective cohort study. The WHO Clinical Progression Scale was used to measure COVID-19 severity. SETTING/PARTICIPANTS: Seven of the 24 invited pediatric palliative care centers participated in this study. We analyzed the medical records of children under palliative care with confirmed COVID-19 (January 2020-April 2022). RESULTS: Records of 60 patients with COVID-19 aged 0.24 to 21.6 years (mean (SD); 9.8 (6.6)) were collected. The largest group of patients with COVID-19 was children with congenital malformations and chromosomal abnormalities (42%); the most common manifestation was fever (85%). Bacterial coinfection was confirmed in 17 (28%) children. Fifteen (25%) children required hospitalization, including four admitted to the Intensive Care Unit. Mild COVID-19 was identified in 44 (73%) children, moderate in 11 (18%), severe in 3 (5%), and death in 2 (3%). Six of the 20 eligible children were vaccinated against SARS-CoV-2, followed by 16 mothers and fathers. CONCLUSION: In the study population initial presentation of COVID-19 was predominantly a mild; however, the small sample size precluded definitive conclusions. For children under palliative care, we should identify if they have an advance care plan for COVID-19, such as desires for intensive care support. Further studies are needed to define the short and long-term effects of COVID-19 in children with life-limiting conditions.

The Clinical and Epidemiological Profile of Paediatric-Onset Multiple Sclerosis in Poland.

Background. Paediatric-onset MS (POMS) has a unique clinical profile compared to the more prevalent adult-onset MS. For this study, we aimed to determine the demographic and clinical characteristics of POMS in Poland as well as addressing some of its epidemiological aspects. Methods. A retrospective study was conducted based on the Polish Multiple Sclerosis Registry, considering a population of children and adolescents with MS (age ≤ 18 years). Data were collected by all 13 centres across Poland specializing in diagnosing and treating POMS. The actual course of the disease and its clinical properties were compared between child (≤12 years) and juvenile (>12 years) patients. MS onset and its prevalence were assessed at the end of 2019, stratified by age range. Results. A total of 329 paediatric or juvenile patients (228 girls, 101 boys) with a clinically definite diagnosis of MS, in conformity with the 2017 McDonald Criteria, were enrolled. For 71 children (21.6%), the first symptoms appeared before the age of 12. The female: male ratio increased with age, amounting to 1:1 in the ≤12 years group and to 2.9:1 in the >12 years group. In most cases, the disease had multi-symptomatic onset (31.3%), and its course was mostly of a relapsing−remitting character (95.7%). The initial Expanded Disability Status Score for both groups was 1.63 ± 1.1, whereas the annual relapse rate was 0.84 during the first 2 years. The time between the onset of symptoms and diagnosis was longer in the younger patients (8.2 ± 4.2 vs. 4.6 ± 3.6 months; p < 0.005). On 31 December 2019, the age-adjusted prevalence standardized to the European standard population was 5.19/100,000 (95% CI, 4.64−5.78). Significantly higher prevalence was noted in the 13−18 years group (7.12; 95% CI, 6.64−7.86) than in the 9−12 years group (3.41; 95% CI, 2.98−3.86) and the <9 years group (0.56; 95% CI, 0.46−0.64; p < 0.001). Conclusion. POMS commencing at the age of ≤12 years is rare, differing significantly from the juvenile-onset and adult MS in terms of clinical characteristics, course, and incidence, as stratified by gender.

Safety, tolerability, and efficacy of a widely available nusinersen program for Polish children with Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder with limited treatment options. Nusinersen is the first disease-modifying therapy to treat children and adults with SMA. This study aimed to review the safety, tolerability, and efficacy data of a nusinersen treatment program in Polish children. A total of 298 patients aged from 0 to 18 years were included in the nusinersen treatment program in Poland between March 1 and September 20, 2019. All patients were prospectively followed for at least one year. The mean age at treatment onset was 6.9 years. SMA type 1 symptoms were reported in 127 patients (43.5%), SMA type 2 symptoms in 68 cases (23.3%), and SMA type 3 in 93 patients (31.8%). No patient met the inefficiency criteria defined in the program. One year after treatment initiation, all patients assessed by the CHOP-INTEND scale had improved or remained stable. The mean change in CHOP-INTEND score was an increase of 8.9 points between baseline and after one-year treatment (p < 0.001). Except for 2 fatal cases, not related to the treatment, no serious adverse events were reported. The results of our study indicate that treatment with nusinersen is beneficial for children with SMA regardless of their age, baseline functional status, or the number of SMN2 gene copies. Therapy with nusinersen was effective and well tolerated by patients.

Pediatric-onset multiple sclerosis in Poland: A registry-based retrospective cohort study.

BACKGROUND: Epidemiologic data on pediatric-onset multiple sclerosis (POMS) in Central and Eastern Europe are limited. The aim of this study was to determine the incidence, prevalence and the clinical features of POMS in Poland. METHODS: Registry-based retrospective study was conducted among Polish children population (age ≤ 18 years), between 1 January 2010 and 31 December 2019. A total of 329 pediatric or juvenile patients fulfilled the International Pediatric MS Study Group (IPMSSG) criteria for MS, reported to the Polish Multiple Sclerosis Registry, were considered for estimation of age- and sex-specific prevalence (per 100,000 persons), and incidence rates (per 100,000 person-years). The demographic data, clinical presentation and treatment strategies also were investigated. RESULTS: On December 31, 2019 in the database were collected data of 329 patients up to 18 years with POMS diagnosis (101 boys and 228 girls; mean age 15.3 ± 3.8 years). The age-adjusted prevalence standardized to the European Standard Population was 5.19/100,000 (95% confidence interval (CI), 4.64-5.78). A significantly higher prevalence was recorded in girls (7.41; 95% CI, 6.48-8.44) than in boys (3.08; 95% CI, 2.50-3.74; P<0.001). The mean annual standardized incidence in Poland between 2015 - 2019 was 0.77 (95%CI, 0.45-1.02) per 100,000 person-years. The highest overall standardized incidence 1.06 (95%CI, 0.82-1.34) was noted in 2018. Most of patients (95.7%) had relapsing-remitting disease with polysymptomatic onset in one-thirds of the cases, and 82.3% were treated with disease-modifying drugs. Family history of MS was reported in 26 cases (7.9%). CONCLUSION: In this first report of registry-based study from Poland an increasing prevalence and incidence of POMS was found during the last years. This temporal trend corroborate the findings of studies conducted elsewhere.

Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis.

Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for APOA1 and A2M genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet-platelet and platelet-leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for APOA1 and A2M genes.

Flavonoids as a Natural Enhancer of Neuroplasticity-An Overview of the Mechanism of Neurorestorative Action.

Neuroplasticity is a complex physiological process occurring in the brain for its entire life. However, it is of particular importance in the case of central nervous system (CNS) disorders. Neurological recovery largely depends on the ability to reestablish the structural and functional organization of neurovascular networks, which must be pharmacologically supported. For this reason, new forms of therapy are constantly being sought. Including adjuvant therapies in standard treatment may support the enhancement of repair processes and restore impaired brain functions. The common hallmark of nerve tissue damage is increased by oxidative stress and inflammation. Thus, the studies on flavonoids with strong antioxidant and anti-inflammatory properties as a potential application in neuro intervention have been carried out for a long time. However, recent results have revealed another important property of these compounds in CNS therapy. Flavonoids possess neuroprotective activity, and promote synaptogenesis and neurogenesis, by, among other means, inhibiting oxidative stress and neuroinflammation. This paper presents an overview of the latest knowledge on the impact of flavonoids on the plasticity processes of the brain, taking into account the molecular basis of their activity.

Palliative sedation at home for terminally ill children with cancer.

CONTEXT: The presence of symptoms that are difficult to control always requires adjustment of treatment, and palliative sedation (PS) should be considered. OBJECTIVES: We analyzed our experience in conducting PS at home for terminally ill children with cancer during a seven-year period. METHODS: We performed a retrospective analysis of medical records of children with cancer treated at home between the years 2005 and 2011. RESULTS: We analyzed the data of 42 cancer patients (18% of all patients); in 21 cases, PS was initiated (solid tumors n = 11, brain tumors [5], bone tumors [4], leukemia [1]). Sedation was introduced because of pain (n = 13), dyspnea (9), anxiety (5), or two of those symptoms (6). The main drug used for sedation was midazolam; all patients received morphine. There were no significant differences in the dose of morphine or midazolam depending on the patient's sex; age was correlated with an increase of midazolam dose (R = 0.68; P = 0.005). Duration of sedation (R = 0.61; P = 0.003) and its later initiation (R = 0.43; P = 0.05) were correlated with an increase of the morphine dose. All patients received adjuvant treatment; in patients who required a morphine dose increase, metoclopramide was used more often (P = 0.0002). Patients did not experience any adverse reactions. Later introduction of sedation was associated with a marginally higher number of intervention visits and a significantly higher number of planned visits (R = 0.53; P = 0.013). CONCLUSION: Sedation may be safely used at home. It requires close monitoring and full cooperation between the family and hospice team. Because of the limited data on home PS in pediatric populations, further studies are needed.

Perinatal palliative care: barriers and attitudes of neonatologists and nurses in Poland.

OBJECTIVE: To identify barriers and personnel attitudes towards realization of palliative care principles in neonatological units. STUDY DESIGN: An anonymous questionnaire was posted to all heads of departments and head nurses of all the 27 neonatological units in the Lodz area. RESULTS: We received 46 (85%) questionnaires. Final analysis comprised 42 properly filled-in questionnaires (by 22 doctors and 20 nurses). In case of prenatal diagnosis of a lethal defect, 77.27% of doctors and 65% of nurses opted for informing the mother also about the possibility of pregnancy continuation and organization of palliative care after delivery. Most of respondents accepted conditions for abortion pointed by the Polish law. The most common barriers pointed out by both groups were insufficient knowledge of the personnel on palliative medicine and family preference for life sustaining treatment. CONCLUSIONS: Understanding attitudes of personnel towards palliative care and identification of barriers are a starting point for future efforts to improve the system of neonatological care.

Who receives home-based perinatal palliative care: experience from Poland.

CONTEXT: The current literature suggests that perinatal palliative care (PPC) programs should be comprehensive, initiated early, and integrative. So far there have been very few publications on the subject of home-based PC of newborns and neonates. Most publications focus on hospital-based care, mainly in the neonatal intensive care units. OBJECTIVE: To describe the neonates and infants who received home-based palliative care in Lodz Region between 2005 and 2011. METHODS: A retrospective review of medical records. RESULTS: 53 neonates and infants were admitted to a home hospice in Lodz Region between 2005 and 2011. In general, they are a growing group of patients referred to palliative care. Congenital diseases (41%) were the primary diagnoses; out of 53 patients 16 died, 20 were discharged home, and 17 stayed under hospice care until 2011. The most common cause of death (56%) was cardiac insufficiency. Neurological symptoms (72%) and dysphagia (58%) were the most common clinical problems. The majority of children (45%) had a feeding tube inserted and were oxygen dependent (45%); 39 families received psychological care and 31 social supports. CONCLUSIONS: For terminally ill neonates and infants, perinatal palliative care is an option which improves the quality of their lives and provides the family with an opportunity to say goodbye.

The impact of pediatric palliative care education on medical students' knowledge and attitudes.

PURPOSE: Most undergraduate palliative care curricula omit pediatric palliative care (PPC) issues. Aim of the study was to evaluate the pilot education programme. METHODS: All 391 students of Faculty of Medicine (FM) and 59 students of Division of Nursing (DN) were included in anonymous questionnaire study. Respondents were tested on their knowledge and attitude towards PPC issues before and at the end of the programme and were expected to evaluate the programme at the end. RESULTS: For final analysis, authors qualified 375 double forms filled in correctly (320 FM and 55 DN). Before the programme, students' knowledge assessed on 0-100-point scale was low (FM: median: 43.35 points; 25%-75%: (40p-53.3p); DN: 26.7p; 13.3p-46.7p), and, in addition, there were differences (P < 0.001) between both faculties. Upon completion of the programme, significant increase of the level of knowledge in both faculties was noted (FM: 80p; 73.3-100; DN: 80p; 66.7p-80p). Participation in the programme changed declared attitudes towards some aspects of withholding of special procedures, euthanasia, and abortion. Both groups of students positively evaluated the programme. CONCLUSIONS: This study identifies medical students' limited knowledge of PPC. Educational intervention changes students' attitudes to the specific end-of-life issues. There is a need for palliative care curricula evaluation.

Pediatric palliative care education for medical students: development and evaluation of a pilot program.

UNLABELLED: In Poland, medical curricula cover palliative care for adults, not for children. This paper evaluates feedback of students who participated in a pilot pediatric palliative care education program. METHOD: An anonymous questionnaire was designed for the students; they were asked to assess each aspect of the program on a scale of 0 to 6 (0 denoted complete dissatisfaction; 6, complete satisfaction). RESULTS: 207 students participated in the program, 197 evaluated it, and 160 formed the research data group. More than 50 percent gave the program 5 points (mean +/- SD; 4.91 +/- 0.9). A total of 79 students (44 percent) assessed the material as 51 to 75 percent new, and 56 students (31 percent) placed it between 76 and 100 percent. A majority indicated that the material would be most useful to them in their future clinical work. Most respondents (78 percent) stated that pediatric palliative care should be included in the pediatrics curriculum. The contribution of the program instructors was given a high score (on average, 5.26 +/- 0.52). CONCLUSION: The pediatric palliative care education program was feasible, and it was well received by the students who undertook it.