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Cortisol-induced effects on human cortical excitability

BACKGROUND Cortisol may fulfill all criteria for a neuromodulator. However, it is not known whether it may rapidly influence motor system activity in humans. OBJECTIVE Circulating cortisol levels were manipulated by administration of a single intravenous dose of hydrocortisone or saline solution, on separate days, to study changes in corticospinal and motor cortical excitability. METHODS Motor-evoked potentials (MEPs) to single- and paired-pulse transcranial magnetic stimulation from the resting first dorsal interosseous muscle, and cortisol plasma levels were assessed before and after either a bolus of 20 mg of hydrocortisone or saline solution in seven healthy subjects. RESULTS Mean cortisol plasma level rapidly rose, peaked between 5 and 10 minutes after hydrocortisone injection, to slowly decay afterward. Mean MEP amplitude significantly increased from preinjection levels, and mean standard deviation of MEPs significantly increased between 8-12 minutes postinjection. Short-intracortical inhibition, tested during the same period, was significantly decreased. No significant changes in the above measures were observed after saline solution administration. CONCLUSIONS Our results suggest that high circulating levels of cortisol rapidly increase corticospinal excitability and reduce gamma aminobutyric acid activity, as measured by short-intracortical inhibition, in humans. These effects, lasting about 10 minutes, were observed within 15 minutes from the pharmacological intervention. They are therefore compatible with a nongenomic mechanism. These findings are important in view of the notion that a decrease in intracortical gamma aminobutyric acid activity appears to be a prerequisite for motor learning and plastic processes in the human motor cortex.

Relationship between the modified Rankin Scale and the Barthel Index in the process of functional recovery after stroke.

OBJECTIVE The modified Rankin Scale (mRS) and the Barthel Index (BI) are the most common clinimetrical instruments for measuring disability after stroke. This study investigated the relationship between the BI and the mRS at multiple time points after stroke. The BI, which is a widely used instrument for longitudinal follow-up post-stroke, was used as reference to determine the effect of time on the sensitivity of the mRS in differentiating functional recovery. METHODS Ninety-two patients with first stroke and hemispheric brain lesion were evaluated using the BI and mRS at 10 days, 3 and 6 months. The Kruskal-Wallis test was applied to examine median differences in BI among the mRS levels at 10 days, 3 and 6 months with Dunns correction for multigroup comparison. The Mann and Whitney test was used to compare median differences in BI scores between two aggregations of mRS grades (mRS=0-2, mRS=3-5) at the same time periods after stroke. RESULTS BI score distribution amongst mRS grades overlapped at 10 days, differentiating only between extreme grades (no disability vs severe disability). At 3 months, independent patients with slight disability could be distinguished from dependent patients with marked disability. At 6 months, grade 2 and 3 overlapped no more, differentiating independence (class 0-2) from dependence (class 3-5). The largest transition to an independent functional status occurred from grade 4, at 3 months. CONCLUSION Maximum sensitivity of mRS in differentiating functional recovery is reached at six months post-stroke.

Normative Reference Values of Right Heart in Competitive Athletes: A Systematic Review and Meta-Analysis

Training-induced right ventricular (RV) enlargement is frequent in athletes. Unfortunately, RV dilatation is also a common phenotypic expression and one of the diagnostic criteria of arrhythmogenic RV cardiomyopathy (ARVC). The current echocardiographic reference values derived from the general population can overestimate the presence of RV dilatation in athletes. We performed a meta-analysis of the literature to derive the proper reference values for assessing RV enlargement in competitive athletes. We conducted systematic review of English-language studies in the MEDLINE, Scopus, and Cochrane databases investigating RV size and function by echocardiography and by cardiac magnetic resonance (CMR) in competitive athletes. In total, 6,806 and 740 competitive athletes were included for the echocardiographic and CMR quantification of the RV, respectively. In this review, we present normal reference values for RV size and function to be applied in competitive athletes according to the disciplines practiced. The reference ranges reported in this review suggest that physicians should be aware that application of the current recommendations for normal population could be misleading when evaluating athletes. We suggest using these normative reference values, obtained in competitive athletes, to avoid the potential for mistakenly concluding, in this specific population, that RV size or function are abnormal.

Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism.

In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care.

Eye fixations identification based on statistical analysis - Case study

Eye movement is the most simple and repetitive movement that enable humans to interact with the environment. The common daily activities, such as watching television or reading a book, involve this natural activity which consists of rapidly shifting our gaze from one region to another. The identification of the main components of eye movement during visual exploration such as fixations and saccades, is the objective of the analysis of eye movements in various contexts ranging from basic neuro sciences and visual sciences to virtual reality interactions and robotics. However, many of the algorithms that detect fixations present a number of problems. In this article, we present a new fixation identification algorithm based on the analysis of variance and F-test. We present the new algorithm and we compare it with the common fixations algorithm based on dispersion. To demonstrate the performance of our approach we tested the algorithm in a group of healthy subjects.

A Sonographic Quantitative Cutoff Value of Cerebral Venous Outflow in Neurologic Diseases: A Blinded Study of 115 Subjects

BACKGROUND AND PURPOSE: The autonomic nervous system maintains constant cerebral venous blood outflow in changing positions. Alterations in cerebral autoregulation can be revealed by postural changes at quantitative color Doppler sonography. The aim of this study was to reach an optimal cutoff value of the difference between the cerebral venous blood outflow in the supine and seated positions that can discriminate healthy controls from patients with multiple sclerosis and those with other neurologic diseases and to evaluate its specificity, sensitivity, and diagnostic accuracy. MATERIALS AND METHODS: One hundred fifteen subjects (54 with MS, 31 healthy controls, 30 with other neurologic diseases) underwent a blinded quantitative color Doppler sonography evaluation of cerebral venous blood outflow in the supine and sitting positions. An optimal difference value between the supine and sitting positions of the cerebral venous blood outflow cutoff value was sought. RESULTS: The difference value between supine and sitting positions of the cerebral venous blood outflow was ≤ 503.24 in 38/54 (70.37%) patients with MS, 9/31 (29.03%) healthy controls, and 13/30 (43.33%) subjects with other neurological diseases. A difference value between supine and sitting positions of the cerebral venous blood outflow at a 503.24 cutoff reached a sensitivity at 70.37%, a 70.96% specificity, a 80.85% positive predictive value, and a 57.89% negative predictive value; the quantitative color Doppler sonography parameters yielded significant differences. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 assessed the significant difference between MS versus other neurological diseases. CONCLUSIONS: Alteration of cerebral venous blood outflow discriminated MS versus other neurologic diseases and MS versus healthy controls. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 was statistically associated with MS.

Ocular-Motor Profile and Effects of Memantine in a Familial Form of Adult Cerebellar Ataxia with Slow Saccades and Square Wave Saccadic Intrusions

Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°–18°) and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly), but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich’s, in which saccadic intrusions are prominent.

Automatic eye fixations identification based on analysis of variance and covariance

Eye movement is the simplest and repetitive movement that enables humans to interact with the environment. The common daily activities, such as reading a book or watching television, involve this natural activity, which consists of rapidly shifting our gaze from one region to another. In clinical application, the identification of the main components of eye movement during visual exploration, such as fixations and saccades, is the objective of the analysis of eye movements: however, in patients affected by motor control disorder the identification of fixation is not banal. This work presents a new fixation identification algorithm based on the analysis of variance and covariance: the main idea was to use bivariate statistical analysis to compare variance over x and y to identify fixation. We describe the new algorithm, and we compare it with the common fixations algorithm based on dispersion. To demonstrate the performance of our approach, we tested the algorithm in a group of healthy subjects and patients affected by motor control disorder.

Predictors of long-term recovery in complex activities of daily living before discharge from the stroke unit.

BACKGROUND AND PURPOSE There is a need for individuating those post-stroke patients who may benefit from an optimal and customised rehabilitation plan aiming at early reintegration in community life participation. This study investigated whether the gain of independence in complex Activities of Daily Living (ADL) may be predicted before the discharge from the stroke unit using simple bedside determinants. METHODS In 104 first-ever stroke patients with no previous disability, ten determinants at 10 days after stroke were selected. Multivariable logistic regression analysis was applied to identify the prognostic determinants able to predict independence in complex ADL, as measured by modified Rankin Scale grade ≤2. RESULTS The model shows that having a Barthel Index ≥9, a Motricity Index- Upper Limb ≥75, an age ≤70 and being a male resulted in 100% probability of achieving independence in complex ADL. If three of the four determinants were present, the probability was more than 90%. With the presence of two of the four determinants, the probability ranged from 87% to 28%. With the presence of only one determinant, the probability was 13%. CONCLUSIONS Accurate prediction of independence in complex ADL can be made before the discharge from the stroke unit. The strength of the paretic upper limb, age, gender, and the ability of performing basic ADL are the significant variables. The probability of favorable prognosis depends on the presence and on the robustness of each single determinant.

Cerebral Circulation Time is Prolonged and Not Correlated with EDSS in Multiple Sclerosis Patients: A Study Using Digital Subtracted Angiography

Literature has suggested that changes in brain flow circulation occur in patients with multiple sclerosis. In this study, digital subtraction angiography (DSA) was used to measure the absolute CCT value in MS patients and to correlate its value to age at disease onset and duration, and to expand disability status scale (EDSS). DSA assessment was performed on eighty MS patients and on a control group of forty-four age-matched patients. CCT in MS and control groups was calculated by analyzing the angiographic images. Lesion and brain volumes were calculated in a representative group of MS patients. Statistical correlations among CCT and disease duration, age at disease onset, lesion load, brain volumes and EDSS were considered. A significant difference between CCT in MS patients (mean = 4.9s; sd = 1.27s) and control group (mean = 2.8s; sd = 0.51s) was demonstrated. No significant statistical correlation was found between CCT and the other parameters in all MS patients. Significantly increased CCT value in MS patients suggests the presence of microvascular dysfunctions, which do not depend on clinical and MRI findings. Hemodynamic changes may not be exclusively the result of a late chronic inflammatory process.