Pediatric Migraine and Visual Cortical Excitability: A Prospective Observational Study with Sound-Induced Flash Illusions.

The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine.

Metalloproteinases and Tissue Inhibitors in Generalized Myasthenia Gravis. A Preliminary Study.

INTRODUCTION: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have recently been proposed as promising biomarkers in different immune-mediated disorders. We evaluated the plasma levels of MMP-9 and MMP-2 and their tissue inhibitors TIMP-1 and TIMP-2 in a patients' cohort with generalized myasthenia gravis (MG). METHODS: Plasma concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were evaluated in 14 patients with generalized MG and 13 age- and sex-matched healthy controls. The severity of disease was assessed by the modified Osserman classification. RESULTS: Compared to the healthy subjects, MG patients had increased plasma concentrations of MMP-9, but reduced plasma levels of MMP-2 and TIMP-1. MG patients also showed a positive correlation between MMP-2 concentrations and disease severity. An increase in MMP-9 levels and MMP-9/TIMP-1 ratio and a decrease in MMP-2 levels and MMP-2/TIMP-2 ratio were detected in patients with generalized MG. Higher levels of MMP-2 correlated with greater disease severity. DISCUSSION: Our preliminary findings suggest that MMPs and TIMPs could play a role in the pathogenesis of MG and might be associated with the risk of clinical deterioration.

Impact of COVID-19 in AChR Myasthenia Gravis and the Safety of Vaccines: Data from an Italian Cohort.

BACKGROUND AND AIMS: Patients with Myasthenia gravis (MG) are considered vulnerable as they may present with respiratory muscle weakness and because they are on immunosuppressive treatment; thereby, COVID-19 may have a detrimental effect on these patients. Vaccines against COVID-19 are currently available and it has been shown as they can prevent severe COVID-19 in vulnerable patients. Notwithstanding their efficacy, vaccine hesitancy has not been completely dispelled in the general population. Unfortunately, there is limited data about the safety of these vaccines in MG patients. The aims of this study are to evaluate the impact of COVID-19 in a MG cohort, the adherence to COVID-19 vaccination in Italy and vaccine safety in MG patients. METHODS: A retrospective cohort study of MG patients attending the Neuromuscular Clinic of the University Hospital "Paolo Giaccone" of Palermo, Italy, was performed. Patients underwent telephone interviews with a dedicated questionnaire on SARS-CoV-2 vaccination and infection. Vaccine safety was assessed though the evaluation of vaccine-related adverse events (AEs) and comparisons of MG-ADL scores before and after vaccination. Patient worsening was defined as two or more point increases in MG-ADL scores. RESULTS: From a total of 90 participants, 75 answered the questionnaire and 70.5% of them (n = 53) received the vaccine; ten patients did not receive vaccination and 3 patients were partially vaccinated. Among the vaccinated patients, about 45% (n = 24) experienced at least one AE, with a complete resolution within one week. No serious AEs and life-threatening conditions were observed. Globally, MG-ADL scores did not worsen after vaccination. Nine unvaccinated patients experienced SARS-CoV2 infection and four of them (44%) died-one patient required respiratory support, whereas three patients were asymptomatic. CONCLUSIONS: COVID-19 significantly impacted MG patients with an increase in mortality due to respiratory sequelae. Vaccines against SARS-CoV-2 showed good short-term safety in MG patients, who may take advantage of vaccination to avoiding life-threatening complications such as COVID-19 pneumonia.

Expression pattern of matrix metalloproteinases-2 and -9 and their tissue inhibitors in patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Matrix metalloproteinases (MMPs) are a heterogeneous family of endopeptidases that play a role in many physiological functions, including the immune response. An imbalance between the activity of MMPs and their physiological tissue inhibitors (TIMPs) has been proposed in the pathophysiology of different autoimmune disorders. We aimed to assess the plasmatic levels of MMP-2, MMP-9, and their inhibitors TIMP-1 and -2 in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). SUBJECTS AND METHODS: Twenty patients with CIDP and 20 age- and sex-matched healthy controls were enrolled. Plasma concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by the enzyme-linked immunosorbent assay. RESULTS: CIDP subjects had higher MMP-9 concentrations along with TIMP-1 downregulation when compared to controls, with the consequent increase in the MMP-9/TIMP-1 ratio (p<0.000002 for all measures). Conversely, the concentration of MMP-2 was lower in the CIDP group (p<0.01) without changes in the TIMP-2 concentration. The MMP-2/TIMP-2 ratio was decreased in the patients' group (p<0.02). DISCUSSION: We provide first preliminary evidence that the plasmatic pattern of MMPs and TIMPs is markedly altered in patients with CIDP. Future studies are needed to assess the potential usefulness of these new biomarkers in the clinical setting.

Multisensorial Perception in Chronic Migraine and the Role of Medication Overuse.

Multisensory processing can be assessed by measuring susceptibility to crossmodal illusions such as the Sound-Induced Flash Illusion (SIFI). When a single flash is accompanied by 2 or more beeps, it is perceived as multiple flashes (fission illusion); conversely, a fusion illusion is experienced when more flashes are matched with a single beep, leading to the perception of a single flash. Such illusory perceptions are associated to crossmodal changes in visual cortical excitability. Indeed, increasing occipital cortical excitability, by means of transcranial electrical currents, disrupts the SIFI (ie, fission illusion). Similarly, a reduced fission illusion was shown in patients with episodic migraine, especially during the attack, in agreement with the pathophysiological model of cortical hyperexcitability of this disease. If episodic migraine patients present with reduced SIFI especially during the attack, we hypothesize that chronic migraine (CM) patients should consistently report less illusory effects than healthy controls; drugs intake could also affect SIFI. On such a basis, we studied the proneness to SIFI in CM patients (n = 63), including 52 patients with Medication Overuse Headache (MOH), compared to 24 healthy controls. All migraine patients showed reduced fission phenomena than controls (P < .0001). Triptan MOH patients (n = 23) presented significantly less fission effects than other CM groups (P = .008). This exploratory study suggests that CM - both with and without medication overuse - is associated to a higher visual cortical responsiveness which causes deficit of multisensorial processing, as assessed by the SIFI. PERSPECTIVE: This observational study shows reduced susceptibility to the SIFI in CM, confirming and extending previous results in episodic migraine. MOH contributes to this phenomenon, especially in case of triptans.

Application of tRNS to improve multiple sclerosis fatigue: a pilot, single-blind, sham-controlled study.

We evaluated the effects of transcranial random noise stimulation (tRNS) on fatigue in 17 subjects with relapsing-remitting multiple sclerosis with low physical disability. Two different patient groups underwent real or sham stimulation for 10 days, targeting the primary motor cortex of the dominant side or contralateral to the most compromised limb. In the 'real group', beneficial effects were observed using the Modified Fatigue Impact Scale (p = 0.04; physical subscale: p = 0.03), the subscales 'change in health' (p = 0.006) and 'role limitations due to physical problems' (p = 0.001) of the Multiple Sclerosis Quality of Life-54, and by assessing the patient impression of perceived fatigue (p = 0.005).

The Unsolved Conundrum of Optimal Blood Pressure Target During Acute Haemorrhagic Stroke: A Comprehensive Analysis.

Intracerebral haemorrhage (ICH) is a devastating cerebrovascular disease, which accounts to 15% of all strokes. Among modifiable risk factors for ICH, hypertension is the most frequent. High blood pressure (BP) is detected in more than 75-80% of patients with ICH. Extremely elevated BP has been associated with early hematoma growth, a relatively frequent occurrence and powerful predictor of poor outcome in patients with spontaneous ICH. On the other hand, excessively low BP might cause cerebral hypoperfusion and ultimately lead to poor outcome. This review will analyse the most important trials that have tried to establish how far should BP be lowered during acute ICH. These trials have demonstrated either a small non-significant benefit (INTERACT-2, INTEnsive blood pressure Reduction in Acute Cerebral haemorrhage Trial) or no benefit (ATACH-2, Antihypertensive treatment of acute cerebral haemorrhage II study) when intensive systolic BP reduction was compared with modest or standard BP reduction. The more recent meta-analyses including studies investigating this issue yielded similar conclusions: aggressive BP control in the acute phase of ICH is not beneficial. For these reasons the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the management of arterial hypertension, do not recommend treatment to immediately lower BP in patients with acute ICH and systolic BP < 220 mmHg. Careful lowering of SBP to less than 180 mmHg via i.v. Infusion may be considered only in patients with SBP ≥ 220 mmHg.

Brain Modulation by Electric Currents in Fibromyalgia: A Structured Review on Non-invasive Approach With Transcranial Electrical Stimulation.

Fibromyalgia syndrome (FMS) is a complex disorder where widespread musculoskeletal pain is associated with many heterogenous symptoms ranging from affective disturbances to cognitive dysfunction and central fatigue. FMS is currently underdiagnosed and often very poorly responsive to pharmacological treatment. Pathophysiology of the disease remains still obscure even if in the last years fine structural and functional cerebral abnormalities have been identified, principally by neurophysiological and imaging studies delineating disfunctions in pain perception, processing and control systems. On such basis, recently, neurostimulation of brain areas involved in mechanism of pain processing and control (primary motor cortex: M1 and dorsolateral prefrontal cortex: DLPFC) has been explored by means of different approaches and particularly through non-invasive brain stimulation techniques (transcranial magnetic and electric stimulation: TMS and tES). Here we summarize studies on tES application in FMS. The great majority of reports, based on direct currents (transcranial direct currents stimulation: tDCS) and targeting M1, showed efficacy on pain measures and less on cognitive and affective symptoms, even if several aspects as maintenance of therapeutical effects and optimal stimulation parameters remain to be established. Differently, stimulation of DLPFC, explored in a few studies, was ineffective on pain and showed limited effects on cognitive and affective symptoms. Very recently new tES techniques as high-density tDCS (HD-tDCS), transcranial random noise stimulation (tRNS) and tDCS devices for home-based treatment have been explored in FMS with interesting even if very preliminary results opening interesting perspectives for more effective, well tolerated, cheap and easy therapeutic approaches.

Atypical CIDP: diagnostic criteria, progression and treatment response. Data from the Italian CIDP Database.

OBJECTIVES: A few variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been described, but their frequency and evolution to typical CIDP remain unclear. To determine the frequency and characteristics of the CIDP variants, their possible evolution to typical CIDP, and treatment response. METHODS: We applied a set of diagnostic criteria to 460 patients included in a database of Italian patients with CIDP. Clinical characteristics and treatment response were reviewed for each patient. The Kaplan-Meier curve was used to estimate the progression rate from atypical to typical CIDP. RESULTS: At the time of inclusion, 376 (82%) patients had a diagnosis of typical CIDP while 84 (18%) had atypical CIDP, including 34 (7%) with distal acquired demyelinating symmetric neuropathy (DADS), 17 (4%) with purely motor, 17 (4%) with Lewis-Sumner syndrome (LSS) and 16 (3.5%) with purely sensory CIDP. Based on retrospective review of the symptoms and signs present at onset and for at least 1 year, 180 (39%) patients had an initial diagnosis compatible with atypical CIDP that in 96 (53%) patients evolved to typical CIDP. Mean disease duration was longer in patients evolving to typical CIDP than in those not evolving (p=0.0016). Patients with DADS and LSS had a less frequent response to immunoglobulin than those with typical CIDP, while patients with purely motor and sensory CIDP had a similar treatment response. CONCLUSIONS: The proportion of patients with atypical CIDP varies during the disease course. DADS and LSS have a less frequent response to intravenous immunoglobulin compared with typical CIDP, raising the possibility of a different underlying pathogenetic mechanism.

Intracortical facilitation within the migraine motor cortex depends on the stimulation intensity. A paired-pulse TMS study.

INTRODUCTION: Connectivity within the primary motor cortex can be measured using the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates the effect of a first conditioning stimulus on the motor evoked potential (MEP) elicited by a second test stimulus when different interstimulus intervals are used. Aim of the present study was to provide, in patients suffering from migraine without aura (MwoA), additional information on intracortical facilitation (ICF), short intracortical inhibition (SICI), and long intracortical inhibition (LICI), using different intensities of the test stimulus (TS). METHODS: We enrolled 24 patients with episodic MwoA and 24 age- and sex-matched healthy volunteers. Both patients and controls were randomly assigned to two different experimental groups: the first group underwent evaluation of ICF, while in the second group we assessed SICI and LICI. All these measures were assessed by using three different suprathreshold intensities of the TS (110%, 130% and 150% of the resting motor threshold, RMT). Interstimulus intervals (ISIs) of 10 ms were used for testing ICF, while SICI and LICI were carried out by using 2 ms and 100 ms ISIs respectively. All migraine patients underwent the experimental protocol while in the interictal pain-free state. RESULTS: A main finding of the study was that an increased ICF could be seen in migraineurs as compared to the healthy subjects only by using a 110% intensity of the TS. Instead, no significant differences were observed between patients and controls as regards both measures of intracortical inhibition. CONCLUSION: We show that hyperresponsivity of the glutamatergic intracortical circuits can be detected in the migraine motor cortex only by applying a low suprathreshold intensity of stimulation. Our results strengthen the notion that, to be reliable, the assessment of cortical excitability in migraine should always include evaluation of the cortical response to different stimulation intensities.

Mild cognitive impairment in Parkinson's disease: the Parkinson's disease cognitive study (PACOS).

Approximately 30% of Parkinson's disease (PD) patients show impaired cognitive performance, which is suggestive of Mild Cognitive Impairment (MCI), representing a predictor of dementia, especially when present at diagnosis. The objective of the study was to evaluate the frequency and clinical predictors of MCI in a large hospital-based cohort of PD patients. We collected cross-sectional data from the Parkinson's disease cognitive impairment study (PACOS), a multicenter study involving two Movement Disorder centers, which are located in south Italy. The PD subjects were diagnosed according to the UK Brain Bank criteria and they underwent an extensive neuropsychological assessment. PD-MCI was diagnosed according to the Movement Disorder Society task force criteria for MCI. PD severity was evaluated in accordance with the Unified PD Rating Scale-Motor Examination (UPDRS-ME) and the Hoehn and Yahr scales. The study included 659 PD patients (57.5% men; mean age 67.0 ± 9.7 years), with a mean disease duration of 3.8 ± 4.6 years and a mean UPRDS-ME score of 25.8 ± 12.3. PD-MCI was diagnosed in 261 (39.6%) subjects and in 82 (31.7%) of 259 newly diagnosed patients (disease duration ≤ 1 year). An amnestic MCI multidomain phenotype was the most frequent MCI subtype (39.1% of the overall sample and 43.9% in newly diagnosed PD). A positive significant association between MCI, age and motor scores was found at multivariate logistic regression analysis, while a negative association was observed between educational level and MCI. In conclusion and in agreement with the literature data, the prevalence of MCI recorded in the PACOS sample was approximately 40 and 32% amongst newly diagnosed patients.

Preliminary experience with a transcranial magnetic resonance-guided focused ultrasound surgery system integrated with a 1.5-T MRI unit in a series of patients with essential tremor and Parkinson's disease.

OBJECTIVE Transcranial magnetic resonance-guided focused ultrasound surgery (tcMRgFUS) is one of the emerging noninvasive technologies for the treatment of neurological disorders such as essential tremor (ET), idiopathic asymmetrical tremor-dominant Parkinson's disease (PD), and neuropathic pain. In this clinical series the authors present the preliminary results achieved with the world's first tcMRgFUS system integrated with a 1.5-T MRI unit. METHODS The authors describe the results of tcMRgFUS in a sample of patients with ET and with PD who underwent the procedure during the period from January 2015 to September 2017. A monolateral ventralis intermedius nucleus (VIM) thalamic ablation was performed in both ET and PD patients. In all the tcMRgFUS treatments, a 1.5-T MRI scanner was used for both planning and monitoring the procedure. RESULTS During the study period, a total of 26 patients underwent tcMRgFUS thalamic ablation for different movement disorders. Among these patients, 18 were diagnosed with ET and 4 were affected by PD. All patients with PD were treated using tcMRgFUS thalamic ablation and all completed the procedure. Among the 18 patients with ET, 13 successfully underwent tcMRgFUS, 4 aborted the procedure during ultrasound delivery, and 1 did not undergo the tcMRgFUS procedure after stereotactic frame placement. Two patients with ET were not included in the results because of the short follow-up duration at the time of this study. A monolateral VIM thalamic ablation in both ET and PD patients was performed. All the enrolled patients were evaluated before the treatment and 2 days after, with a clinical control of the treatment effectiveness using the graphic items of the Fahn-Tolosa-Marin tremor rating scale. A global reevaluation was performed 3 months (17/22 patients) and 6 months (11/22 patients) after the treatment; the reevaluation consisted of clinical questionnaires, neurological tests, and video recordings of the tests. All the ET and PD treated patients who completed the procedure showed an immediate amelioration of tremor severity, with no intra- or posttreatment severe permanent side effects. CONCLUSIONS Although this study reports on a small number of patients with a short follow-up duration, the tcMRgFUS procedure using a 1.5-T MRI unit resulted in a safe and effective treatment option for motor symptoms in patients with ET and PD. To the best of the authors' knowledge, this is the first clinical series in which thalamotomy was performed using tcMRgFUS integrated with a 1.5-T magnet.

Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient.

Thiamine (vitamin B1) deficiency is a common condition in alcohol abusers, which can lead to damage of both the peripheral and the central nervous systems. Here we describe the case of an alcoholic patient who presented with acute onset of ataxia, severe weakness of the four limbs, and hypoesthesia and dysesthesia of the distal portion of the upper and lower extremities. The clinical picture also included mental confusion and amnesia. A diagnosis of Wernicke-Korsakoff syndrome was made based on clinical symptoms and brain RMI findings. Electromyography and electroneurography revealed signs of subacute axonal sensory-motor polyneuropathy that were compatible with a rare acute presentation of beriberi. Patient immediately received parenteral thiamine administration, which resulted in rapid clinical amelioration of ataxia and confusion and also in a significant improvement of motor and sensory deficits. The association between Wernicke-Korsakoff syndrome and acute axonal polyneuropathy is a very rare condition that could make less recognizable the clinical picture of a thiamine deficiency. However, the diagnosis of thiamine deficiency should be suspected in every alcoholic patient presenting with acute onset symptoms of central and/or peripheral nervous system involvement. This because the immediate replacement treatment can be life-saving and reverse the clinical symptoms.

Anodal transcranial direct current stimulation over the right hemisphere improves auditory comprehension in a case of dementia.

BACKGROUND: Noninvasive transcranial stimulation methods have been increasingly employed in order to improve cognitive performance in neurological patients. In previous studies with both stroke patients and healthy subjects, noninvasive stimulation of temporal-parietal regions and their homologue produced an improvement in linguistic tasks. OBJECTIVE: The aim of the current study was to evaluate if anodal transcranial direct current stimulation (tDCS) over Brodmann areas 39/40 (angular and supramarginal gyri) could promote the recovery of linguistic functions, in particular comprehension and naming, in a single patient affected by dementia. METHODS: Three preliminary explorative single sessions (right-side anodal, left-side anodal and sham tDCS) were carried out (Experiment 1). This procedure allows targeting the more effective site of stimulation for the treatment. Subsequently, we carried out a five-days tDCS treatment on the selected hemisphere (Experiment 2). RESULTS: We report verb comprehension amelioration after 5 days of anodal tDCS over the right BAs 39/40 compared with the placebo tDCS. This result is maintained until two weeks after the end of the 5-days treatment. CONCLUSIONS: Our findings provide new evidence for the therapeutic use of tDCS in degenerative diseases, suggesting that an explorative study can be useful for targeting the more appropriate stimulation site, and confirm the involvement of right-sided areas associated with language activities.

Motor cortex tRNS improves pain, affective and cognitive impairment in patients with fibromyalgia: preliminary results of a randomised sham-controlled trial.

OBJECTIVES: Fibromyalgia (FM) is a clinical syndrome characterised by widespread musculoskeletal pain, chronic fatigue, cognitive deficits, and sleep and mood disorders. The effectiveness of most pharmacological treatments is limited, and there is a need for new, effective and well-tolerated therapies. It has recently been shown that transcranial direct-current stimulation (tDCS) of the motor cortex reduces pain, and that tDCS of the dorso-lateral prefrontal cortex (DLPFC) improves anxiety, depression and cognitive impairment in FM patients. The new technique of transcranial random noise stimulation (tRNS) using randomly changing alternating currents has very recently been shown to improve working memory and pain in limited series of patients with FM or neuropathic pain. The aim of this study was to investigate the clinical effects of primary motor cortex (M1) tRNS in FM patients. METHODS: Twenty female FM patients aged 26-67 years were randomised to undergo active (real) or placebo (sham) tRNS sessions on five days a week (Monday-Friday) for two weeks. Each patient was evaluated before and after treatment using a visual analogue scale (VAS), the Fibromyalgia Impact Questionnaire (FIQ), the Hospital Anxiety and Depression Scale (HADS), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT), the Forward and Backward Digit Span test, and the FAS verbal fluency test. RESULTS: In comparison with sham treatment, active tRNS of M1 induced a general improvement in the clinical picture of FM, with a significant reduction in pain, depression, anxiety and FIQ scores and a significant improvement in TMT (A), RAVLT and FAS scores. CONCLUSIONS: These findings suggest that tRNS of M1 can be very effective in relieving FM symptoms. Unlike motor cortex tDCS, it seems to counteract both pain and cognitive disturbances, possibly because the invoked mechanism of stochastic resonance synchronises neural firing and thus leads to more widespread and lasting effects.

Effects of More-Affected vs. Less-Affected Motor Cortex tDCS in Parkinson's Disease.

Objective: To evaluate therapeutic potential of different montages of transcranial direct current stimulation (tDCS) in Parkinson's Disease (PD) patients with asymmetric motor symptoms. Materials and Methods: Fourteen patients with asymmetric PD underwent, while on treatment, seven separate sessions including electrophysiological and clinical evaluation at baseline and after anodal, cathodal and sham tDCS of the primary motor cortex (M1) of the two hemispheres. Changes in motor cortical excitability were evaluated by transcranial magnetic stimulation (TMS). Effects on motor symptoms were assessed by testing finger tapping (FT) and upper limb bradykinesia, and by using the Italian validated Movement Disorder Society revision of the Unified PD Rating Scale (MDS-UPDRS). Results: Only anodal tDCS of the more-affected M1 (contralateral to the more-affected body side) and cathodal tDCS of the less-affected M1 (contralateral to the less-affected body side) were able to induce significant changes in cortical excitability, i.e., facilitation and inhibition of the motor evoked potentials respectively. The motor performances of both hands significantly improved after anodal tDCS of the more-affected M1, as well as after cathodal tDCS of the less-affected one. Conclusion: Our findings support the potential usefulness of tDCS as add-on treatment for asymmetric PD, also providing interesting clues on the possible pathophysiological role played by an asymmetric activation of homologous motor cortical areas in PD.

Relation between sexual dysfunctions and epilepsy, type of epilepsy, type of antiepileptic drugs: a prospective study.

INTRODUCTION: The aim of this study was to evaluate the incidence of sexual dysfunctions in males with epilepsy, the type of epilepsy, the frequency of seizures, the type of antiepileptic drugs (AEDs), the serum hormonal profile and the presence of psychiatric comorbidity. METHODS: Sixty-one patients focused on type of epilepsy, frequency of seizures, AEDs, hormonal profile and presence of mood disorders. We excluded all patients with severe neurologic and psychiatric impairment and patient who were not able to fill questionnaires. Mean age was 31.2 years (range 18-50 years); 31 patients (50.8%) had an idiopathic generalised epilepsy and 30 (49.2%) a focal epilepsy; among them, latter 18 (60%) had probably symptomatic type and 12 (40%) symptomatic type. Sexual functions were evaluated by "International Inventory of Erectile Function" questionnaire. RESULTS: Out of 61 enrolled patients, 22 (36.7%) showed sexual dysfunctions: erectile dysfunctions in 14 (23%), orgasmic dysfunctions in (11.5%) and sexual drive dysfunctions in 12 (19.7%). Out of 61 patients, 36 were subjected to blood measurement of sexual hormones and 21 (58.3%) showed hormonal modifications. CONCLUSIONS: Sexual dysfunction are present in 36.7% of enrolled males with epilepsy; there is any association between sexual dysfunctions and various AEDs in the treatment, except for carbamazepine (CBZ); there is not any association between sexual dysfunctions and frequency of seizures; hormonal changes are associated with sexual dysfunction in males with epilepsy treated with AEDs but not with the orgasmic dysfunction; there is not any association between hormonal changes and type of AEDs, except for CBZ; depression is associated with sexual dysfunctions.

Seizure following the Use of the COX-2 Inhibitor Etoricoxib.

We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

New frontiers in anticoagulation: non vitamin-K oral anticoagulants in stroke prevention.

INTRODUCTION: Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists. New evidences have suggested their use in treatment of elderly people, in patients with renal insufficiency or with antiphospholipid antibody syndrome. In addition, the use of antidotes, which rapidly reverse the anticoagulant effect of the NOACs, could be useful in bleeding, during emergency procedures, or in case of overdose.

Excessive Daytime Sleepiness and Sleep Disorders in a Population of Patients with Epilepsy: a Case-Control Study.

BACKGROUND AND PURPOSE: There are several primary causes for excessive daytime sleepiness (EDS) and sleep disorders in patients with epilepsy. Up to now, studies in the literature report conflicting data in terms of both prevalence and aetiology. The aim of our study was therefore to evaluate the prevalence of EDS and some sleep disorders in a population of patients with epilepsy treated with no more than two antiepileptic drugs (AEDs). We also investigated the role of the depression of mood as a variable that can negatively affect EDS. METHODS: We prospectively and consecutively recruited 99 patients with a diagnosis of epilepsy, sleep disorders and EDS, belonging to the Centre for Epilepsy of the Department of Experimental Biomedicine and Clinical Neurosciences of the University of Palermo. 61.6% of patients recruited were suffering from focal epilepsy, and 38.3% from generalized epilepsy. 68.6% were undertaking monotherapy and 27.2% were drug resistant. Patients were matched for sex and age (+/- 5 years) with 96 non epileptic controls recruited from high school students, college students, relatives and friends of the medical team that conducted the study. EDS was found in 11.1% of patients with epilepsy. Clinical evaluation of sleep disorders was performed using validated questionnaires to investigate excessive daytime sleepiness (EDS), insomnia, Restless Legs Syndrome (RLS) and Obstructive Sleep Apnoea Syndrome (OSAS). In a second phase of the study, 43 of the investigated patients and 34 controls - after giving their consent - underwent a polysomnographic examination by "Compumedics Somtè". RESULTS: Our study shows a statistically significant difference between cases and controls with regard to the prevalence of RLS (p = 0.022) and severity of OSAS with an increased risk in moderate-severe forms of epilepsy (odd ratio [OR] 2.5) most significantly associated with male gender (p = 0.04) and focal epilepsy (OR 3.8) with PSG seizures (0.02). Moreover, a statistically significant difference was demonstrated about mood disorders (p = 0.001) among patients with epilepsy and non epileptic controls. Sleepiness in patients with epilepsy seems to be particularly related to both the depression of mood (p = 0.01) and the presence of OSAS (p = 0.03), as well as to a higher mean age (p = 0.006) and a longer duration of illness (p = 0.04). CONCLUSIONS: Our results confirm that drowsiness trouble frequently complained by patients with epilepsy, is particularly related not only to the presence of OSAS but also to the depression of mood.