Search

Background: There is little and controversial information about changes in plasma concentrations (PCs) or clinical events during coadministration of antiseizure medications (ASMs) and direct oral anticoagulants (DOACs). We aimed to explore possible determinants of dosage class among DOACs trough PCs when ASMs are co-administered and the relative risks. We also provided some clinical examples of patients' management., Methods: Data on adult patients concomitantly treated with ASMs (grouped in enzyme-inducing [I-ASMs], non-inducing [nI-ASMs], and levetiracetam [LEV]) and DOACs with at least one measurement of DOACs' PC were retrospectively collected. The role of DOAC-ASM combinations in predicting PC class (ranging from I at ischemic/thromboembolic risk to IV at increased bleeding risk) was investigated by an ordered logit model, and the marginal probabilities of belonging to the four dosage classes were calculated., Results: We collected 46 DOACs' PCs out of 31 patients. There were 5 (10.9%) determinations in class I (4 out of 5 with concomitant I-ASMs) and 5 (10.9%) in class IV. The rivaroxaban/I-ASM combination was associated with lower DOAC dosages than rivaroxaban/LEV (OR: 0.00; 95% CI: 0.00-0.62). Furthermore, patient's probability of being in class I was approximately 50% with the rivaroxaban/I-ASM combination, while apixaban, dabigatran, and edoxaban had the highest cumulative probability of being in class II or III despite the ASM used., Conclusion: These preliminary results confirm the reduction of DOAC's PC by I-ASMs and suggest a better manageability of apixaban, dabigatran, and edoxaban independently from the concomitant ASM, whereas rivaroxaban seems the most liable to PC alterations with I-ASMs., (© 2023. The Author(s).)

Background: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke., Methods: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies., Results: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers., Conclusions: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution., (© 2021. The Author(s).)

Objective: Systematic reviews suggest that patent foramen ovale closure (PFOc) is performed percutaneously with low complication rates. We did a network meta-analysis (NMA) comparing devices for PFO closures, evaluating safety and efficacy of transcatheter PFOc in preventing neurological events in patients with stroke when compared with medical therapy (MT), and assessing risk of atrial fibrillation (AF)., Methods: We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) identifying six randomized controlled trials from 2012 until December 2019. We performed a Bayesian NMA; number-needed-to-treat and number-needed-to-harm were derived by applying the estimated odds ratios (ORs). The likelihood of being helped or harmed (LHH) was evaluated to estimate the risk-effectiveness balance., Results: The 3560 patients allocated to PFOc were less subject to a stroke than patients with MT. The overall ORs of PFOc versus MT were 0.41 with fixed-effects, and 0.22 with random-effects model. NMA proves that PFOc induces AF episodes significantly higher than MT, even when analysis is limited to only new episodes of "serious AF." LHH (0.68 fixed-effects, 0.79 random-effects) showed that strokes saved are less than cases of AFs added. By considering only serious AF, strokes saved are higher than serious AFs induced by the PFOc (LHH was 3.46 and 4.00 respectively)., Conclusions: NMA supported PFOc in patients with cryptogenic stroke, confirming that devices are better than MT, but increase the risk of AF by over 2/4 times (serious or unserious AF). Considering serious AFs (real risky clinical condition), patients have more advantages in being treated, since LHH is ≥ 3-4.

Autoimmune encephalitis associated with antibodies against neuronal surface targets (NSAE) are rare but still underrecognized conditions that affect adult and pediatric patients. Clinical guidelines have recently been published with the aim of providing diagnostic clues regardless of antibody status. These syndromes are potentially treatable but the choice of treatment and its timing, as well as differential diagnoses, long-term management, and clinical and paraclinical follow-up, remain major challenges. In the absence of evidence-based guidelines, management of these conditions is commonly based on single-center expertise.Taking into account different published expert recommendations in addition to the multicenter experience of the Italian Working Group on Autoimmune Encephalitis, both widely accepted and critical aspects of diagnosis, management and particularly of immunotherapy for NSAE have been reviewed and are discussed.Finally, we provide consensus-based practical advice for managing hospitalization and follow-up of patients with NSAE.

The pathogenesis underlying cluster headache remains an unresolved issue. Although both the autonomic system and the hypothalamus play a central role, the modality of their involvement remains largely unknown. It is, also, unknown why the duration of the pain attacks is so brief and why their onset and termination are abrupt and extremely painful. This review summarizes the evidence to date accumulated in favor of a possible role of anomalies in the metabolism of tyrosine, tryptophan, and arginine in these unresolved issues.

This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

The primary aim of this study (TA-CH, Tryptophan Amine in Chronic Headache) was to investigate a possible role of tryptophan (TRP) metabolism in chronic migraine (CM) and chronic tension-type headache (CTTH). It is not known if TRP metabolism plays any role in CM and/or CTTH. Plasma levels of serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), metabolite of 5-HT, and tryptamine (TRY) were tested in 73 patients with CM, 15 patients with CTTH and 37 control subjects. Of these, plasmatic TRY was significantly lower in CM (p < 0.001) and in CTTH (p < 0.002) patients with respect to control subjects, while 5-HIAA levels in plasma were within the same range in all groups. 5-HT was undetectable in the plasma of almost all subjects. Our results support the hypothesis that TRP metabolism is altered in CM and CTTH patients, leading to a reduction in plasma TRY. As TRY modulates the function of pain matrix serotonergic system, this may affect modulation of incoming nociceptive inputs from the trigeminal endings and posterior horns of the spinal cord. We suggest that these biochemical abnormalities play a role in the chronicity of CM and CTTH.

Patients with chronic migraines are often refractory to medical treatment. Therefore, they might need other strategies to modulate their pain, according to their level of disability. Neuromodulation can be achieved with several tools: meditation, biofeedback, physical therapy, drugs and electric neurostimulation (ENS). ENS can be applied to the central nervous system (brain and spinal cord), either invasively (cortical or deep brain) or non-invasively [cranial electrotherapy stimulation, transcranial direct current stimulation and transcranial magnetic stimulation]. Among chronic primary headaches, cluster headaches are most often treated either through deep brain stimulation or occipital nerve stimulation because there is a high level of disability related to this condition. ENS, employed through several modalities such as transcutaneous electrical nerve stimulation, interferential currents and pulsed radiofrequency, has been applied to the peripheral nervous system at several sites. We briefly review the indications for the use of peripheral ENS at the site of the occipital nerves for the treatment of chronic migraine.

AIDA Cefalee is a database for the management of headache patients developed on behalf of the Italian Neurological Association for Headache Research (ANIRCEF). The system integrates a diagnostic expert system able to suggest the correct ICHD-II diagnosis once all clinical characteristics of a patient's headache have been collected. The software has undergone a multicentre validation study to assess: its diagnostic accuracy; the impact of using the software on visit duration; the userfriendliness degree of the software interface; and patients' acceptability of computer-assisted interview. Five Italian headache centres participated in the study. The results of this study validate AIDA Cefalee as a reliable diagnostic tool for primary headaches that can improve diagnostic accuracy with respect to the standard clinical method without increasing the time length of visits even when used by operators with basic computer experience.

Recent studies have suggested that abnormalities of dopamine and trace amines (tyramine, octopamine, and synephrine), products of tyrosine metabolism, may constitute the metabolic events that predispose to the occurrence of cluster headache (CH) and migraine attacks. This hypothesis is supported by the following evidences: the discovery of trace amine associated receptors (TAARs), expressed on the olfactory epithelium, amigdala, hypothalamus, periacqueductal gray, and the biochemical anomalies of dopamine and trace amines. The possible effects of these biochemical abnormalities on TAARs and dopamine receptors, located in different areas of CNS, may explain the behaviour (restlessness, anxiety and, at times, hypersexuality) and the autonomic signs during the painful attacks of CH, and the premonitory symptoms of migraine crisis (thirst, craving, yawning, alteration of smell, depression etc.).

The pain of cluster headache attacks is severe, excruciating and selectively responsive to subcutaneous sumatriptan. Serious cardiovascular events attributed to sumatriptan are extremely rare and have most often been reported in patients at significant cardiovascular risk, or in overt cardiovascular disease. They also have occurred, however, in patients without evidence of cardiovascular disease. We describe a 42-year-old man with episodic cluster headache without history of coronary artery disease who was admitted to our coronary care unit for acute myocardial infarction after 3 h of subcutaneous injection of sumatriptan. During hospitalisation cluster headache attacks were successfully treated with e.v. indomethacin.

Homocysteine increases in the acute phase of ischaemic stroke and from the acute to the convalescent phase, suggesting that hyper-homocysteinaemia may be a consequence rather than a causal factor. Therefore we measured homocysteine plasma levels in stroke patients in order to investigate possible correlations of homocysteine with stroke severity and clinical outcome. Further we looked for eventual differences in stroke subtypes. We prospectively studied plasma homocysteine levels in acute stroke patients admitted to the stroke unit of our department. Seven hundred and seventy-five ischaemic stroke patients, 39 cerebral haemorrhages and 421 healthy control subjects have been enrolled. Stroke severity and clinical outcome were measured with the Scandinavian Stroke Scale, the Rankin Scale and the Barthel Index. Stroke severity by linear stepwise regression analysis was not an independent determinant of plasma homocysteine levels. Homocysteine was not correlated with outcome measured by the Barthel Index. Mean plasma homocysteine of both ischaemic and haemorrhagic stroke was significantly higher than controls (p<0.05). Homocysteine had an adjusted odds ratios (OR) of 4.2 (95% CI 2.77-6.54) for ischaemic stroke and of 3.69 (95% CI 1.90-7.17) for haemorrhagic stroke. Compared with the lowest quartile, the upper quartile was associated with an adjusted OR of ischaemic stroke due to small artery disease of 17.4 (95% CI 6.8-44.3). Homocysteine in the acute phase of stroke was not associated with stroke severity or outcome. Elevated plasma homocysteine in the acute phase of stroke was associated with both ischaemic and haemorrhagic stroke. Higher levels are associated with higher risk of small artery disease subtype of stroke.

We briefly summarise biochemical anomalies of serotonin, norepinephrine, glutamic and aspartic acids, the main neurotransmitters of inhibitory and excitatory neuronal circuitries, found in primary headaches and their relationship with pathogenesis of migraine and cluster headache (CH). In addition, the high levels of circulating tyramine, octopamine and synephrine (elusive amines), recently reported in both migraine types and CH, are discussed in relation to the other "classic" amines findings. In particular it is suggested how abnormal levels of elusive amines may participate in the pathophysiology of migraine and CH acting through their specific trace amine receptors and alpha and beta receptors. The possible hypothesis that emerges from the analysis of these biochemical findings is that an imbalance of systems, with opposite neurophysiological functions related to the pain and other yet unknown functions, may constitute the biochemical phenotype of migraine with and without aura, and CH.

Workplace disability due to migraine has not been extensively researched in non-English speaking countries. We assessed the repercussions of headache, and particularly of migraine, on work in a sample of employees from an Italian company (Bulgari). Information was obtained through a self-answering questionnaire in "all headaches" sufferers, and through direct interview in migraine sufferers (diagnosis according to IHS criteria). Headache frequency, pain intensity and headache-related disability were higher in migraineurs than in "all headaches" sufferers. About a quarter of migraineurs missed at least one day in the three months prior to the interview due to headache, and around 10% lost two or more days over the same period. Moore than 50% of migraineurs reported 1-7 days per month at work with headache, with reduction in productivity level by 50% or more in 15% of respondents. Our data confirmed that headaches, and particularly migraine, cause a considerable reduction in workplace productivity. Workplace interventions to effectively manage migraine are needed.

The main aim of this study is to look for early clinical markers of cerebral venous thrombosis (CVT). As headache represents the major clinical manifestation at presentation we focused our attention on this symptom. We present the preliminary results of a prospective multicentric study that includes cases diagnosed as CVT in the participating centres. We have so far studied 35 patients (5 males and 30 females) from the ages of 18 to 78. The most frequent manifestation was headache (77.1%). It was more frequently localised (66.7%) and continuous (77.8%). The onset of pain was mostly acute-subacute (38.5%-50.0%) and the intensity moderate-severe (37.0%-51.9%). On univariate analysis, we found a positive correlation between CVT, acute headache onset (p=0.001) and severe headache (p=0.004). These preliminary results seem in accordance with our previous findings in the retrospective study, suggesting that CVT is more often associated with acute-onset headache of severe intensity.