Insomnia and menopause: a narrative review on mechanisms and treatments.

The menopausal transition is associated with an increased frequency of sleep disturbances. Insomnia represents one of the most reported symptoms by menopausal women. According to its pathogenetic model (3-P Model), different predisposing factors (i.e. a persistent condition of past insomnia and aging per se) increase the risk of insomnia during menopause. Moreover, multiple precipitating and perpetuating factors should favor its occurrence across menopause, including hormonal changes, menopausal transition stage symptoms (i.e. hot flashes, night sweats), mood disorders, poor health and pain, other sleep disorders and circadian modifications. Thus, insomnia management implies a careful evaluation of the psychological and somatic symptoms of the individual menopausal woman by a multidisciplinary team. Therapeutic strategies encompass different drugs but also behavioral interventions. Indeed, cognitive behavioral therapy represents the first-line treatment of insomnia in the general population, regardless of the presence of mood disorders and/or vasomotor symptoms (VMS). Different antidepressants seem to improve sleep disturbances. However, when VMS are present, menopausal hormone therapy should be considered in the treatment of related insomnia taking into account the risk-benefit profile. Finally, given its good tolerability, safety, and efficacy on multiple sleep and daytime parameters, prolonged-released melatonin should represent a first-line drug in women aged ≥ 55 years.

Bi-hemispheric transcranial direct current stimulation for upper-limb hemiparesis in acute stroke: a randomized, double-blind, sham-controlled trial.

BACKGROUND AND PURPOSE: Neuromodulation is a promising approach to increasing motor recovery in stroke; however, to date, there is a scarcity of evidence documenting the clinical potential of transcranial direct current stimulation (tDCS) administered in the acute phase of stroke. The present study aims to examine the clinical effects of a treatment involving the application of tDCS in the acute stage post-stroke. METHODS: This was a randomized, double-blind, sham-controlled trial. A cohort of 32 stroke patients with severe motor impairment underwent 5 days of treatment with real or sham bi-hemispheric tDCS over the motor cortex. During the treatment, tDCS was applied twice per day (two daily applications each of 15 min), starting 48 to 72 h after stroke onset. RESULTS: We found statistically significant improvements after both real and sham tDCS treatments in primary (hand grip strength, Motricity Index) and secondary (National Institutes of Health Stroke Scale score, Barthel Index) outcomes. Patients receiving real tDCS showed a larger improvement of upper-limb muscle strength at the end of treatment phase; this advantage was no longer present after 6 months. CONCLUSIONS: Transcranial direct current stimulation may be used to accelerate the rate of upper-limb motor recovery during the spontaneous recovery period.

Medical and endovascular treatments of symptomatic intracranial stenosis. A Bayesian network meta-analysis.

Intracranial stenosis is a well-established stroke risk factor with an increase of stroke recurrence or TIA up to 12.6% at 1 year. Treatments are different: medical and endovascular. We performed a multiple treatment comparison analysis to detect the best treatment in reducing the risk of stroke recurrence. We searched in Medline, Embase, Cochrane Central Register of Controlled Trials databases between 1979 and October 2017. Inclusion criteria were prospective randomized trials that evaluated patients with TIA or stroke due to intracranial stenosis and treated with different medical therapies and/or endovascular procedures. Primary endpoint was the recurrence of TIA or stroke in the territory of intracranial stenosis, while secondary endpoint was represented by any stroke or vascular death. Multiple treatment comparison meta-analysis based on a Bayesian fixed and random effects Poisson model was performed. Seven trials were included with a total of 1337 patients. At multiple treatment comparison, no significant differences between treatments were observed for both primary (median fixed effect standard OR: 0.40; 95%CI: 0.02-1.07) and secondary endpoints (median random effect standard OR: 1.17; 95%CI: 0.32-1.92). Treatment with aspirin alone ranked with high values both for primary and secondary endpoints (surface under the cumulative ranking curve of 70% and 82%, respectively). In patients with symptomatic intracranial stenosis, no differences between treatments were observed. However, aspirin alone was more effective than stenting in the reduction of TIA or stroke recurrences, with a better safety profile than oral anticoagulants.

Prehospital stroke scales and large vessel occlusion: A systematic review.

BACKGROUND AND PURPOSE: Time sensitivity for pharmacological and mechanical arterial recanalization in acute ischemic stroke influences the choice of the reference hospital. The accurate selection and identification of patients with high probability of a large vessel occlusion (LVO) in the prehospital setting improve the rationalization of the transport in the more suitable centers. Aim of this analysis was to determine the diagnostic accuracy of prehospital stroke scales detecting LVO. MATERIAL AND METHODS: Studies were searched into MEDLINE, EMBASE, and CINHAL databases between January 1990 and September 2017. Principal measurements of the meta-analysis were the overall accuracy level, sensitivity, and specificity of prehospital stroke scales. RESULTS: Nineteen scoring systems were included in the analysis coming from 13 studies. A total of 9824 patients were considered. Although a higher heterogeneity was observed in the analysis, three scores showed better results in predicting a LVO (the stroke Vision, Aphasia, Neglect assessment, the National Institute of Health Stroke scale and the Los Angeles Motor Scale). We observed significant differences of overall accuracy only for scores including hemineglect as cortical neurological sign (P < .05). CONCLUSIONS: This meta-analysis suggests that some prehospital scoring systems including cortical signs showed better accuracy to predict stroke due to LVO. However, the assessment of these signs could be difficult to investigate by paramedics and personnel of Emergency Medical Services, and for this reason, further prospective evaluations are needed.

The organisation of the acute ischemic stroke management: key notes of the Italian Neurological Society and of the Italian Stroke Organization.

The main aim of acute ischemic stroke treatment is the as much possible prompt, safe and effective arterial recanalisation, in order to restore reperfusion into the ischemic brain area. The procedures obtaining this result are rapidly evolving and in the last years, we observed new evidences that affirmed the therapeutical benefit of the concomitant treatment using endovenous thrombolysis and mechanical thrombectomy in selected patients with ischemic stroke. However, all treatments are time-sensitive and the main limitation for their application is represented by the time. For this reason, the optimisation of the acute stroke management that includes a pre-hospital and an in-hospital phase is essential to reduce the avoidable delay, increasing the number of patients potentially treatable. The purpose of this document is to define the main elements and to suggest the principal key points constituting the optimal pathway of stroke management in Italian care settings, in line with the recommendations coming from the current national and international guidelines.

HLA-DRB1*15 association with multiple sclerosis is confirmed in a multigenerational Italian family.

Environmental and genetic factors seem to play a pathogenetic role in multiple sclerosis (MS). The genetic component is partly suggested by familial aggregation of cases; however, MS families with affected subjects over different generations have rarely been described. The aim of this study was to report clinical and genetic features of a multigenerational MS family and to perform a review of the literature on this topic. We describe a multigenerational Italian family with six individuals affected by MS, showing different clinical and neuroradiological findings. HLA-DRB1* typing revealed the presence of the DRB1*15:01 allele in all the MS cases and in 4/5 non-affected subjects. Reports on six multigenerational MS families have previously been published, giving similar results. The HLA-DRB1*15:01 allele was confirmed to be linked to MS disease in this family; moreover, its presence in non-affected subjects suggests the involvement of other susceptibility factors in the development and expression of the disease, in accordance with the complex disease model now attributed to MS.

Headache in subarachnoid hemorrhage and headache attributed to intracranial endovascular procedures.

Headache is a critical problem in the emergency setting. In this paper we briefly review the epidemiological data regarding headache in Subarachnoid Hemorrhage (SAH), considering the role of headache as a warning symptom and the other clinical manifestation of SAH. We have also introduced a recent clinical entity, represented by headache associated to intracranial endovascular procedures (IEPs).

Stroke care in young patients.

The aims of this study were (i) to evaluate the clinical features of a consecutive series of young patients with ischemic stroke and (ii) to assess the changes in the clinical management of these patients over the study period. All consecutive cases of young adults aged 16 to 44 years, with ischemic stroke, that were admitted between 2000 and 2005 in 10 Italian hospitals were included. We retrospectively identified 324 patients. One or more vascular risk factors were present in 71.5% of the patients. With respect to the diagnostic process, an increase in the frequency of cerebral noninvasive angiographic studies and a decrease in the use of digital subtraction angiography were observed (P < 0.001 and P = 0.03, resp.). Undetermined causes decreased over 5-year period of study (P < 0.001). The diagnosis of cardioembolism increased. Thrombolysis was performed for 7.7% of the patients. PFO closure (8%) was the most frequently employed surgical procedure. In conclusion, the clinical care that is given to young patients with ischemic stroke changed over the study period. In particular, we detected an evolution in the diagnostic process and a reduction in the number of undetermined cases.

Improving thrombolysis for acute ischemic stroke in Lombardia stroke centers.

The purpose of this study is to identify which factors are able to limit or hamper the access to systemic thrombolysis (evTPA) in Lombardia to define corrective interventions. We analyzed 1,015 patients with ischemic stroke admitted to emergency departments (ED) participating to the Lombardia Stroke Unit Registry and eligible for evTPA; 303 (29.9%) patients were treated with evTPA (evTPA+ group) and 712 (70.1%) were not (evTPA- group). We collected case-mix and stroke care process variables.The evTPA+ group was characterized by a shorter ED arrival time, a greater neurological impairment, a more chance to be admitted to ED linked to comprehensive stroke center (CSC) and a shorter waiting time to access to diagnostic procedures. The chance to be treated with evTPA was greater if neurological evaluation anticipated neuroimaging (p = 0.0003). The multivariate analysis confirmed that the admission to ED linked to CSC (OR: 2.50, 95% CI: 1.39-4.48, p < 0.0001) and neurological evaluation performed before neuroimaging (OR: 2.34, 95% CI: 1.35-4.04, p = 0.002) increased the probability to receive rtPA. The evTPA treatment is strictly dependent on pre-hospital and ED care process phases and strongly influenced by the degree of stroke severity. Door-to-needle time is shorter in patients with a greater stroke severity and a shorter ED arrival time. A 24-h/week availability of the neurologist in ED can increase the percentage of thrombolysis optimizing the selection of patients and the timing of the diagnostic procedures.

Migraine and small vessel diseases.

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies affecting small cerebral vessels, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy and hereditary infantile hemiparesis, retinal arteriolar tortuosity and leucoencephalopathy. Moreover, several studies have reported an association between migraine and white matter lesions or clinically silent infarct-like abnormalities in the posterior circulation. In this review, we focus on genetic vasculopathies associated with migraine and speculate about the pathophysiological mechanism that can explain this comorbidity.

Thunderclap headache and benign angiopathy of the central nervous system: a common pathogenetic basis.

Thunderclap headache (TCH) is a head pain that begins suddenly and is severe at onset; TCH might be the first sign of different neurological illnesses, and primary TCH is diagnosed when no underlying cause is discovered. Patients with TCH who have evidence of reversible, segmental, cerebral vasoconstriction of circle of Willis arteries and normal or near-normal results on cerebrospinal fluid assessment are thought to have reversible cerebral vasoconstriction syndrome (RCVS). Herein, we discuss the differential diagnosis of TCH and offer pathophysiological considerations for TCH and RCVS.

An atypical case of spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is a well-known clinical syndrome associated with the typical magnetic resonance imaging findings of pachymeningeal enhancement, downward cerebral displacement and subdural fluid collections. Atypical clinical presentations are not infrequent and often misdiagnosed. We report a case of SIH presenting with thunderclap headache and CT scan evocative of subarachnoid hemorrhage. We discuss the unusual presentation of this patient and the differential diagnosis of this case.

Migraine and cerebrovascular disease.

The association between migraine and stroke is complex and bidirectional. Epidemiological studies suggest that migraine may be a risk factor for stroke; magnetic resonance studies suggest that white matter abnormalities may be more frequent in migraine patients than in controls; and stroke may occur during the course of a migraine with aura (MA) attack (migrainous stroke). However, the relationship between migraine, aura and stroke is complex and mechanisms other than a direct cause/effect relationship are possible. Migraine aura may be the consequence, rather than the cause of cerebral ischaemia. Furthermore both MA and stroke may be secondary to a third underlying condition. In this review we analyse data regarding the relationship between migraine and stroke considering 3 aspects: (1) migraine as a risk factor for stroke, (2) migraine as a cause of stroke and (3) migraine and cerebral ischaemia sharing a common cause.

Two symptomatic cases of cluster headache associated with internal carotid artery dissection.

Cluster headache is a clinical entity characterised by strictly unilateral head pain attacks accompanied by ipsilateral autonomic phenomena. We report two patients who had pain episodes mimicking cluster headache attacks, and who experienced a total or partial Horner's syndrome ipsilaterally to pain, persisting for 48 h after the last attack. A dissection of the ipsilateral internal carotid artery at the extra-intracranial passage was present in both cases. These cases highlight the need for extensive neuroradiological investigation in cluster headache patients when atypical features are present.

Platelet glutamate uptake and release in migraine with and without aura.

Glutamate may play an important role in the pathogenesis of migraine: glutamate release in the brain may be involved in the development of spreading depression and increased concentrations of this amino acid have been reported in plasma and platelets from migraine patients. Here we assessed platelet glutamate uptake and release in 25 patients affected by migraine with aura (MA) and 25 patients affected by migraine without aura (MoA), comparing the results with a group of 20 healthy matched controls. Both glutamate release from stimulated platelets and plasma concentrations of the amino acid were assessed by high-performance liquid chromatography, and were increased in both types of migraine, although more markedly in MA. Platelet glutamate uptake, assessed as 3H-glutamate intake, was increased in MA, while it was reduced in MoA with respect to the control group. These results support the view that MA might involve different pathophysiological mechanisms from MoA and, specifically, up-regulation of the glutamatergic metabolism. Understanding these dysfunctional pathways could lead to new, possibly more successful therapeutic approaches to the management of migraine.

The complications of migraine with aura.

Migraine with aura is a common disorder in industrialised countries, affecting up to 5% of the adult population. Although migraine aura is usually a benign disorder, in rare instances it can be the cause of serious neurologic complications. The most common is migrainous stroke, defined as a persistent neurologic deficit following the aura with evidence of brain infarction at neuroimaging and lack of alternative explanations. The most likely pathogenic mechanism is brain ischaemia induced by cortical spreading depression, but other possibilities, such as intracranic arterial dissection or embolism through patent foramen ovale need to be considered. Other complications are migraine-related seizures, which are probably caused by neuronal hyperexcitability in migraineurs, and persistent auras without infarction. These disorders are of both clinical and scientific interest, as they throw light on the complex and not yet fully understood relationship between migraine with aura, stroke and epilepsy.

Hemodynamic instability after extracranial carotid stenting.

OBJECTIVE: Hemodynamic instability (hypertension, hypotension and bradycardia) is a well-known complication of carotid endarterectomy. Carotid angioplasty and stenting (CAS) is becoming a valuable alternative treatment for patients with severe carotid stenosis and increased surgical risk. CAS implies instrumentation of the carotid bulb, so baroceptor dysfunction may provoke hemodynamic instability. The aim of this work was to calculate the incidence of this complication and to detect factors to predict it. METHODS: Medical records and angiograms of 51 consecutive patients submitted to CAS for severe atherosclerotic stenosis (40 cases) or postsurgical restenosis (11 cases) were retrospectively reviewed in order to detect the occurrence of intra- and post-procedural hypertension (systolic blood pressure >160 mmHg), hypotension (systolic blood pressure <90 mmHg) and bradycardia (heart rate <60 beats/min). The relationship between clinical, procedural and angiographic factors and the occurrence of hemodynamic instability was assessed with univariate and multivariate analysis (logistic regression). RESULTS: Transient mild systolic post-procedural hypertension occurred in five cases (10%); preprocedural hypertension, asymptomatic stenosis and ipsilateral post-surgical restenosis predicted this. Hypotension with bradycardia also occurred in five cases (10%), one with neurological sequelae. Transient periprocedural bradycardia occurred in 19 cases (37%). Severe bradycardia without hypotension arose in one case only. Factors predicting post-procedural hypotension included the presence of a fibrous plaque and the ratio between the pre- and post-stenting diameter of the internal carotid artery. Peri-procedural bradycardia predicted post-procedural bradycardia. None of these factors were confirmed by multivariate analysis as a significant prognostic predictor. CONCLUSION: Mild systolic hypertension may occur after CAS, but is resolved by medical treatment. Prolonged hypotension and bradycardia may also arise and this can be dangerous because it may cause neurological deterioration due to hypoperfusion. These complications cannot be predicted by clinical, procedural, and angiographic factors.