Increased hair cortisol and antecedent somatic complaints in children with a first epileptic seizure.

OBJECTIVE: Stress is the most frequent seizure-precipitating factor reported by patients with epilepsy, while stressful life events may increase seizure susceptibility in humans. In this study, we investigated the relations between both biological and behavioral measures of stress in children with a first epileptic seizure (hereafter called seizure). We hypothesized that hair cortisol, a biomarker of chronic stress reflecting approximately 3months of preceding exposure, might be increased in children with a first seizure. We also employed standardized questionnaires to examine presence of stress-related behavioral markers. METHODS: This was a cross-sectional clinical study investigating stress-related parameters in children with a first seizure (First Epileptic Seizure Group (FESG), n=22) in comparison to healthy children without seizures (Control Group, n=29). Within 24h after a first seizure, hair samples were collected from children for the determination of cortisol. In parallel, perceived stress and anxiety and depressive symptoms were examined with appropriate self- and parent-completed questionnaires, and history of stressful life events during the past year was recorded. Emotional and behavioral problems were also assessed by parent-reported validated and widely-used questionnaires. RESULTS: Higher hair cortisol measurements were observed in the FESG than control children (7.5 versus 5.0pg/mg respectively, p=0.001). The former were more likely to complain of somatic problems than the latter (59.8 vs. 55.4 according to DSM-oriented Scale, p=0.021); however, there were no differences in perceived stress and anxiety or depressive symptoms between the two groups. Using ROC analysis of hair cortisol measurements for predicting disease status, the maximum sensitivity and specificity were observed for a cut-off point of 5.25pg/mg. SIGNIFICANCE: Increased hair cortisol indicates chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis prior to the first seizure. This might have contributed to the epileptogenesis process and may help explain the higher incidence of antecedent somatic complaints in the first seizure group.

Parkinson's Disease Tremor Differentially Responds to Levodopa and Subthalamic Stimulation.

Background: Tremor in Parkinson's disease (PD) has an inconsistent response to levodopa and subthalamic deep brain stimulation (STN-DBS). Objectives: To identify predictive factors of PD tremor responsiveness to levodopa and STN-DBS. Material and Methods: PD patients with upper limb tremor who underwent STN-DBS were included. The levodopa responsiveness of tremor (overall, postural, and rest sub-components), was assessed using the relevant Unified Parkinson's Disease Rating Scale-III items performed during the preoperative assessment. Post-surgical outcomes were similarly assessed ON and OFF stimulation. A score for the rest/postural tremor ratio was used to determine the influence of rest and postural tremor severity on STN-DBS outcome. Factors predictive of tremor responsiveness were determined using multiple linear regression modeling. Volume of tissue activated measurement coupled to voxel-based analysis was performed to identify anatomical clusters associated with motor symptoms improvement. Results: One hundred and sixty five patients were included in this study. Male gender was negatively correlated with tremor responsiveness to levodopa, whereas the ratio of rest/postural tremor was positively correlated with both levodopa responsiveness and STN-DBS tremor outcome. Clusters corresponding to improvement of tremor were in the subthalamic nucleus, the zona incerta and the thalamus, whereas clusters corresponding to improvement for akinesia and rigidity were located within the subthalamic nucleus. Conclusion: More severe postural tremor and less severe rest tremor were associated with both poorer levodopa and STN-DBS response. The different locations of clusters associated with best correction of tremor and other parkinsonian features suggest that STN-DBS effect on PD symptoms is underpinned by the modulation of different networks.

Worldwide trends in mortality related to Parkinson's disease in the period of 1994-2019: Analysis of vital registration data from the WHO Mortality Database.

Background: Mortality due to Parkinson's disease (PD) and its long-term trends worldwide in recent decades remain unknown. No previous studies have simultaneously studied age- and sex-specific mortality trends at a population level worldwide. Insights gained from this study can help identify high-risk populations and inform healthcare service requirements for managing Parkinson's disease globally. Objectives: The aim of the study was to examine trends in mortality from Parkinson's disease by age-group and sex across countries all over the world. In this study, we used worldwide registry data to examine the temporal trends in PD mortality across most counties of the world from 1994 to 2019 using joinpoint regression. Results: In data from vital registration systems, huge variations in the patterns of deaths due to Parkinson's disease were observed both over time and between countries. Between 1994 and 2019, there was a significant increase in mortality rates globally in both men and women. In more detail, the mortality rate (per 100,000) in 1994 was 1.76 and reached 5.67 in 2019. Greater increases in mortality were seen in men than in women; and in older than in younger people. Conclusions: There has been a striking rising trend in Parkinson's disease mortality globally. Persistent age and sex disparities are found in Parkinson's disease mortality trends. Our findings may have important implications for future research, healthcare planning, and provision.

Association between white matter lesions and Parkinson's disease: an impact on Postural/Gait difficulty phenotype and cognitive performance.

BACKGROUND: White matter hyperintensities (WMHs) may be observed on Magnetic Resonance Imaging (MRI) in patients with Parkinson disease with or without vascular risk factors. Whether WMHs may influence motor and non-motor aspects of Parkinson disease is a subject of debate. The aim of this study is to evaluate the impact of WMH severity on various aspects of Parkinson disease in combination to the estimation of the impact of cerebrovascular risk factors. MATERIALS AND METHODS: We included a cohort of patients with Parkinson's disease who underwent MRI examination. The Fazekas visual rating scale was used to assess the severity and location of WMHs, and patient clinical characteristics were correlated with MRI data. RESULTS: All vascular risk factors were associated with higher Fazekas score in both periventricular and deep white matter. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were associated with lower scores in the ACE-R cognitive assessment scale (p < 0.001). Furthermore, PWMHs and DWMHs severity was associated with higher UPDRS motor score (p < 0.001), while the Postural Instability Gait Difficulty (PIGD) phenotype was correlated with higher burden of WMHs. CONCLUSIONS: Comorbid WMHs may contribute to multi-dimension dysfunction in patients with Parkinson disease and consequently the management of vascular risk factors may be crucial to maintain motor and non-motor functions in PD.

Clinically Silent Small Vessel Disease of the Brain in Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with increased risk of cerebrovascular disease. The aim of the present study was to investigate the association between the presence of the small vessel disease (SVD) of the brain in patients with OSAHS. The study included 24 patients with moderate to severe OSAHS and 34 healthy volunteers. All the subjects underwent magnetic resonance imaging (MRI) of the brain, in order to sought periventricular white matter (PVWM), deep white matter (DWM) and brainstem SVD. Among patients with OSAHS, 79.1% had SVD (grade 1-3, Fazekas score) in DWM and 91.7% in PVWM while 22.4% had brainstem-white matter hyperintensities (B-WMH). Patients with OSAHS had a much higher degree of SVD in the DWM and PVWM compared to the control group (p < 0.001). The multivariate analysis showed an independent significant association of OSAHS with SVD (DWM and PVWM) (p = 0.033, OR 95% CI: 8.66 (1.19-63.08) and: p = 0.002, OR 95% CI: 104.98 (5.15-2141)). The same analysis showed a moderate association of OSAHS with B-WMH (p = 0.050, OR 15.07 (0.97-234.65)). Our study demonstrated an independent significant association of OSAHS with SVD and a moderate association of OSAHS with B-WMH.