Resilience predicts and modulates anxiety severity in people with epilepsy.

BACKGROUND: Anxiety is one of the most relevant psychiatric comorbidities in people with epilepsy (PwE). The role of resilience (RES) in the development of anxiety is not well understood. We purposed to better characterize RES impact on anxiety severity in PwE. MATERIALS AND METHODS: One hundred and seventy-six PwE underwent online surveys including a collection of socio-demographic, seizure-related, and psychological variables. PwE were grouped according to the data collected; anxiety levels were compared through non-parametric statistics. Hierarchical regression analysis (HRA) and logistic regression were performed to characterize RES contribute in predicting the presence and the severity of anxiety. Mediation/moderation analysis was performed to evaluate causal effects among RES, depression, and anxiety. RESULTS: Anxiety did not differ according to socio-demographic and seizure-related variables, exemption for the presence of drug-related adverse effects. Depression, RES, and sleep quality provided the major contribute on anxiety variance. The addiction of RES level in HRA and logistic regression provided a significant increase of R-squared value (p-value = 0.02) and of area under the curve (p-value = 0.03), respectively. RES modulated depression/anxiety relationship (p-value < 0.001), whereas depression did not mediate RES/anxiety correlation (p-value = 0.68). CONCLUSIONS: We demonstrated that RES is a significant independent predictor of anxiety in PwE and is able to modulate depression impact on anxiety. Moreover, we confirmed the relevance of depression and sleep quality on anxiety severity.

Determinants of medication adherence in people with epilepsy: A multicenter, cross-sectional survey.

OBJECTIVES: Poor medication adherence in people with epilepsy (PwE) increases mortality, hospitalization, and poor quality of life, representing a critical challenge for clinicians. Several demographic, clinical, and neuropsychological factors were singularly found associated with medication adherence in several studies, but the literature lacks a comprehensive study simultaneously assessing all these variables. METHODS: We performed a multicenter and cross-sectional study using online questionnaires with the following clinical scales: Morisky Medication Adherence Scale (MMAS-8), Quality of Life in Epilepsy Inventory 31 (QoLIE-31), Beck Depression Inventory-II (BDI-II), Generalized Anxiety Disorder-7 (GAD-7) and 14-item Resilience scale (RES14) in a population of 200 PwE. We used the ANOVA test and Spearman's correlation to evaluate the relationship between medication adherence and demographic, clinical (seizure frequency, number of anti-seizure medications), and neuropsychological characteristics. We trained separate machine learning models (logistic regression, random forest, support vector machine) to classify patients with medium-high adherence (MMAS-8 ≥ 6) and poor adherence (MMAS-8 < 6) and to identify the main features that influence adherence. RESULTS: Women were more adherent to medication (p-value = 0.035). Morisky Medication Adherence Scale -8 showed a direct correlation with RES14 (p-value = 0.001) and age (p-value = 0.001), while was inversely correlated with BDI-II (p-value = 0.001) and GAD-7 (p-value = 0.001). In our model, the variables mostly predicting treatment adherence were QoLIE-31 subitems, followed by age, resilience, anxiety, years of school, and disease duration. CONCLUSION: Our study confirms that gender, age, and neuropsychological traits are relevant factors in predicting medication adherence to PwE. Furthermore, our data provided the first evidence that machine learning on multidimensional self-report questionnaires could help to develop a decisional support system in outpatient epilepsy clinics.

Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: implications for cellular-based therapy.

Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc-mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc patients and 10 healthy controls (HC). Senescence was evaluated by assessing cell cycle, ß-galactosidase (ß-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions. Immunomodulatory abilities were studied co-culturing MSCs with peripheral blood mononuclear cells (PBMCs) and CD4(+) cells, in order to establish both their ability to block proliferation in mixed lymphocyte reaction and in regulatory T cells (Tregs) induction. SSc-MSC showed an increase of senescence biomarkers. Eighty per cent of MSCs were in G0-G1 phase, without significant differences between SSc and HC. SSc-MSCs showed an increased positive ß-Gal staining and higher p21 transcript level compared to HC cells. After doxorubicin, ß-Gal staining increased significantly in SSc-MSCs. On the contrary, doxorubicin abolished p21 activation and elicited p53 induction both in SSc- and HC-MSCs. Interleukin (IL)-6 and transforming growth factor (TGF)-ß-related transcripts and their protein levels were significantly higher in SSc-MSCs. The latter maintained their immunosuppressive effect on lymphocyte proliferation and induced a functionally regulatory phenotype on T cells, increasing surface expression of CD69 and restoring the regulatory function which is impaired in SSc. Increased activation of the IL-6 pathway observed in our cells might represent an adaptive mechanism to senescence, but preserving some specific cellular functions, including immunosuppression.

The -670G>A polymorphism in the FAS gene promoter region influences the susceptibility to systemic sclerosis.

OBJECTIVE: To evaluate the role of the single-nucleotide polymorphism (SNP) at position -670 in the FAS gene promoter (FAS-670G>A) in influencing the susceptibility, clinical features and severity of systemic sclerosis (SSc). METHODS: 350 white Italian SSc patients (259 with limited cutaneous SSc (lcSSc) and 91 with diffuse cutaneous SSc (dcSSc)) and 232 healthy individuals were studied. Patients were assessed for the presence of autoantibodies (anticentromere, anti-topoisomerase I (anti-Scl-70) antibodies), interstitial lung disease (ILD), pulmonary arterial hypertension and scleroderma renal crisis. FAS-670G>A SNP was genotyped by PCR restriction fragment length polymorphism assay. Serum levels of soluble FAS (sFAS) were analysed by ELISA. RESULTS: A significant difference in FAS-670 genotype distribution was observed between SSc patients and healthy individuals (p = 0.001). The frequency of the FAS-670A allele was significantly greater in SSc than in controls (p = 0.001). No significant difference in genotype distribution and allele frequencies was observed between lcSSc and dcSSc, although a greater frequency of the FAS-670A allele was found in dcSSc. The FAS-670AA genotype significantly influenced the predisposition to SSc (OR 1.97, 95% CI 1.35 to 2.88, p = 0.001) and to both lcSSc (OR 1.84, 95% CI 1.23 to 2.75, p = 0.003) and dcSSc (OR 2.37, 95% CI 1.41 to 3.99, p = 0.001). FAS-670A allele frequency was greater, although not significantly, in anti-Scl-70 antibody-positive dcSSc and ILD dcSSc. sFAS was significantly higher in patients and controls carrying the FAS-670AA genotype compared with those carrying the FAS-670GG genotype (p = 0.003 in SSc, p = 0.004 in controls). CONCLUSION: The FAS-670A allele is significantly associated with susceptibility to SSc, suggesting a role for a genetic control of apoptosis in the pathogenesis of the disease.

Impairment of endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair. METHODS: MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit-fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed. RESULTS: MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell-derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential less than that in controls. CONCLUSION: Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.

Differential expression of tissue kallikrein in the skin of systemic sclerosis.

Systemic sclerosis (SSc) is characterised by ischemic damage, impaired angiogenesis and skin fibrosis. Tissue kallikrein (t-kallikrein) is involved through kinins in inflammation, vasorelaxation and angiogenesis. T-kallikrein is synthetised by endothelial, smooth muscle, and inflammatory cells and, in skin, also by dark cells of the sweat glands, where it is involved in sweat formation. Our aim was to analyse, by immunohistochemistry and RT-PCR, the expression of t-kallikrein in the skin of patients with different SSc subsets, limited (lSSc) and diffuse (dSSc), and phases, early and advanced. Skin biopsies were taken from 18 SSc patients and 10 controls. Immunohistochemistry was performed on paraffin sections with an antibody against human urinary t-kallikrein. For RT-PCR, cDNA from skin biopsies was amplified using primers specific for human t-kallikrein. In the control skin, dark cells of the secretory units of sweat glands showed immunopositivity for t-kallikrein as well as blood vessels. In the lSSc skin, immunoreactivity was observed only in some glands, with weak staining in the advanced phase. In early lSSc skin, immunoreactivity was observed in microvessel walls and in the inflammatory infiltrate. In dSSc skin, dark cells of the glandular fundus units, and the few remaining vessels showed scarcity (early phase) or lack (advanced phase) of immunoreactivity for t-kallikrein. RT-PCR confirmed a decrease of t-kallikrein mRNA levels from early to advanced phase in SSc subsets, reaching its lowest level in advanced dSSc. In conclusion, immunohistochemical and biomolecular results indicate that t-kallikrein is decreased in the skin of SSc patients and decreases progressively from the early to advanced phase of lSSc and dSSc. The decreased expression of t-kallikrein may be involved in the impairment of the sweating process, vessel functionality and angiogenesis.

Spectral analysis of visual potentials evoked by pattern-reversal checkerboard in juvenile patients with headache.

Changes in visual evoked potentials, mainly affecting the amplitude of the major positive wave, are referred to by many authors and are related to the pathophysiological basis of primary headache. We performed both transient pattern-reversal visual evoked potentials and spectral analysis by means of fast Fourier transform of 8-Hz steady-state pattern-reversal visual evoked potentials in 34 children affected with migraine (14 with aura, 20 without aura), and compared them with 14 patients with tension-type headache and 10 healthy subjects. The amplitude of the response to the transient stimulation (P100) was higher and the latency shorter in the patients with headache compared with the controls, but the difference was not statistically significant. The absolute power of the first harmonic (1F) obtained by the spectral analysis of the steady-state stimulation was increased in all the patients with headache compared with the controls, and the increase was significant in patients with migraine. These data seem to confirm the hypothesis of abnormal processing of visual input in migraineurs and could be interpreted as neurophysiological support for the theory that different headache types are related conditions. Furthermore, the spectral analysis of steady-state pattern-reversal visual evoked potentials could be proposed as a test to diagnose migraine.

[Hemicrania and photosensitive epilepsy in pediatric age]. / Emicrania ed epilessia fotosensibile in età pediatrica.

OBJECTIVE: Photosensitive epilepsy is joined to headache. Aim of the present study was the follow up of children suffering from headaches in order to verify if headache can be the only symptom of epileptic photosensitivity. PATIENTS AND METHODS: Thirteen children affected by headache were examined. They were screened on the basis of photosensitivity showed on the EEG. During following 6 patients had seizures. RESULTS: Antiepileptic drugs (VPA, CBZ, CZM) improved seizures and headache. In the others patients migraine therapy improved epileptic photosensitivity on the EEG. CONCLUSIONS: Headache can be the only symptom of epileptic photosensitivity. Migraine and photosensitive epilepsy in childhood are of particular interest because of growing features of occipital lobe. This has therapeutic significance.

Visual evoked potentials and serum magnesium levels in juvenile migraine patients.

Changes in visual evoked potentials and decreased intracellular magnesium levels have been separately described in patients affected by migraine both during the attacks and in the interictal periods. An inverse correlation between increased P100 amplitude and lowered serum magnesium levels was found in children suffering from migraine with and without aura in a headache-free period. A 20-day treatment with oral magnesium pidolate seemed to normalize the magnesium balance in 90% of patients. After treatment, the reduced P100 amplitude confirmed the inverse correlation with the serum magnesium level. These data seem to suggest the hypothesis that higher visual evoked potential amplitude and low brain magnesium level can both be an expression of neuronal hyperexcitability of the visual pathways related to a lowered threshold for migraine attacks.

Geomagnetic activity, humidity, temperature and headache: is there any correlation?

Meterological factors influence several biological functions. Geomagnetic activity (GMA) can be considered a trigger factor of migraine attacks. We studied the possible relationship between 40 migraine patients and some meteorological factors: humidity, temperature and geomagnetic activity in particular. All frequency changes of geomagnetic activity, temperature and humidity values are recorded daily. The study was performed from March to June 1988 over a geographically small area in order to avoid climatic and environmental influences. Our results indicate a significant correlation between geomagnetic activity and migraine attack frequency. Controversial opinions concerning the modalities of data collection and the possible relationships between environment and headache raise the need of further studies.

Neurological complications of Schoenlein-Henoch syndrome: contribution of MR to the diagnosis. Case report.

In the protean clinical pattern of the Schoenlein-Henoch syndrome the central and peripheral nervous system signs and symptoms are of most uncertain epidemiological importance and of most debatable physiopathological status. In the case reported the contribution of nuclear magnetic resonance to the diagnosis proved to be greater than that of computed tomography because it imaged the CNS lesions.