Topo-kinesthetic memory in chronic headaches. A new test for chronic patients: preliminary report

The objective of this study was to establish if chronic headaches with medication overuse can modify a topo\u2013kinesthetic memory test. Nineteen patients with medication overuse headache (MOH), 13 patients with chronic tension\u2013type headache (CTTH) without medication use and a group of "normal" subjects underwent a topo\u2013kinesthetic memory test at T0 and after one month (T1); a control group of healthy volunteers was also tested to establish the baseline in our experimental setting. After one month, in the MOH patients there was a reduction of medication overuse from 3.3\ub12.65 to 1.1\ub12.23 (p<0.01), but no significant reduction in headache frequency and severity index, quality of life, anxiety and depression scores. The navigation time at T0 was 14.3\ub14.97, 27.9\ub110.12, 34.3\ub115.38 and 7.5\ub12.33, 10.1\ub12.95, 11.4\ub13.21 for control, MOH and CTTH with closed and open eyes, respectively (p<0.02). At T1, the MOH patients reached performances with open eyes similar to the healthy controls, while with closed eyes the navigation test reached times similar to those of CTTH patients. The topokinesthetic memory test seems both able to discriminate MOH and CTTH from healthy volunteers and to be related to pain scores but is not influenced by the use of drugs

Italian guidelines for primary headache: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105-190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedic

Safety and efficacy of natalizumab in children with multiple sclerosis.

OBJECTIVE: To describe the effect of natalizumab in the treatment of subjects with active multiple sclerosis (MS) treated before the age of 18 years. METHODS: Nineteen pediatric subjects with MS (mean age 14.6 +/- 2.2 years, mean number of attacks 5.2 +/- 1.9 during the pretreatment phase of 27.7 +/- 19.7 months, median pretreatment Expanded Disability Status Scale score [EDSS] 2.5, range 1.0-5.0) were treated with natalizumab at the dose of 300 mg every 28 days. After treatment initiation, patients were reassessed clinically every month; brain MRI was performed at baseline and every 6 months. RESULTS: Patients received a median number of 15 infusions (range 6-26). A transient reversible worsening of preexisting symptoms occurred in 1 subject during and following the first infusion. All the patients remained relapse-free during the whole follow-up. The median EDSS decreased from 2.5 to 2.0 at the last visit (p < 0.001). EDSS remained stable in 5 cases, decreased by at least 0.5 point in 6 cases, and decreased by at least 1 point in 8 cases. At baseline, the mean number of gadolinium-enhancing lesions was 4.1 (range 1-20). During the follow-up, no gadolinium-enhancing lesions were detected (p = 0.008); 3 patients developed new T2-visible lesions at month 6 scan but the overall number of T2 lesions remained stable during the subsequent follow-up. Transient and mild side effects occurred in 8 patients. CONCLUSIONS: Natalizumab was well-tolerated in all subjects. A strong suppression of disease activity was observed in all subjects during the follow-up. Classification of evidence: This study provides Class IV evidence that natalizumab, 300 mg IV once every 28 days, decreased EDSS scores in pediatric patients with MS over a mean treatment period of 15.2 months

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Cadmium effects on human fetal spinal cord

The biological effects of Cadmium (Cd) on the central nervous system is poorly understood; it is thought that during brain development, when the blood-brain barrier is not well established, Cd may enter the brain and exerts its toxic effects. It has also been suggested that several diseases such as Parkinson disease, amyotrophic lateral sclerosis (ALS) as well as malformations such as spina bifida and forelimb ectrodactyly may be related to Cd exposure. In this study we evaluated the role of Cd in affecting motor neurons and glial cells of the ventral horns of human fetal spinal cord. Sections of human fetal spinal cord (9-12 weeks) were exposed for 24 h to 10 and 100 μM CdCl2 . Morphology was evaluated by Haematoxilyn-Eosin staining; distribution and number of motor neurons as well as of glial cells were studied by immunohistochemistry and by Western blot; apoptosis were investigated by TUNEL assay and by Western blot. The cell density in the ventral horns, after CdCl2 treatments, appeared dramatically decreased and the number of apoptotic cells became higher in comparison to control specimens as demonstrated by the high expression level of three different apoptotic markers (NGFR p75, caspase 8 and PARP). The number and the distribution of motor neurons, expressing β tubulin III and positive to choline acetyltransferase, appeared significantly decreased after the treatment with different concentrations of CdCl2 . Activation and increase of glial cells were confirmed by the high expression level of Glial Fibrillary Acidic Protein (GFAP). In this study we demonstrate the role of Cd, one of the most diffuse environmental pollutant linked to industrial development, in inducing apoptosis of motor neurons in the ventral horns of human fetal spinal cord. Motor neurons death is accompanied by a surrounding intense glyosis leading to a significant overthrow of the morphological architecture of spinal cord during its development

Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats

PURPOSE: Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model. METHODS: Subgroups of OVX Sprague–Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson’s trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR. RESULTS: Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001–10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis. CONCLUSIONS: Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery