Migraine is an extremely common disorder. The underlying mechanisms of this chronic illness interspersed with acute symptoms appear to be increasingly complex. An important aspect of migraine heterogeneity is comorbidity with other neurological diseases, cardiovascular disorders, and psychiatric illnesses. Depressive disorders are among the leading causes of disability worldwide according to WHO estimation. In this review, we have mainly considered the findings from general population studies and studies on clinical samples, in adults and children, focusing on the association between migraine and psychiatric disorders (axis I of the DSM), carried over after the first classification of IHS (1988). Though not easily comparable due to differences in methodology to reach diagnosis, general population studies generally indicate an increased risk of affective and anxiety disorders in patients with migraine, compared to non-migrainous subjects. There would also be a trend towards an association of migraine with bipolar disorder, but not with substance abuse/dependence. With respect to migraine subtypes, comorbidity mainly involves migraine with aura. Patients suffering from migraine, however, show a decreased risk of developing affective and anxiety disorders compared to patients with daily chronic headache. It would also appear that psychiatric disorders prevail in patients with chronic headache and substance use than in patients with simple migraine. The mechanisms underlying migraine psychiatric comorbidity are presently poorly understood, but this topic remains a priority for future research. Psychiatric comorbidity indeed affects migraine evolution, may lead to chronic substance use, and may change treatment strategies, eventually modifying the outcome of this important disorder.

A retrospective study was conducted on 1300 women suffering from migraine without aura referred to the Headache Centers of Parma and Pavia from 1984 to 1990. All the data concerning their reproductive life, and the modifications induced by it on the course of headache were obtained from record-charts. Migraine frequently started at menarche (10.7%); in 60% of cases the migraine attacks occurred mostly or exclusively in the perimenstrual period, in 67% of cases disappeared during pregnancy, and in 24.1% significantly (P < 0.0001) worsened with "pill" intake. This study also designated a migraine subgroup which is more influenced by changes in sexual hormones, i.e. migraine with onset at menarche. This form of migraine shows more frequently a menstrual periodicity, and usually improves during pregnancy. Furthermore, menstrual migraine patients show social and cultural characteristics with distinguish them from other women.

Abstract:Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. The chemokine stromal cell-derived factor 1, (SDF1), binds to the seventransmembrane G protein-coupled CXCR4 receptor and acts to modulate cell migration, differentiation, and proliferation. CXCR4 and SDF1 are reported to be expressed in various tissues including brain. Here we show that SDF1 and CXCR4 are expressed in cultured cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In cortical astrocytes, prolonged treatment with lipopolysaccharide induced an increase of SDF1 expression and a down-regulation of CXCR4, whereas treatment with phorbol esters did not affect SDF1 expression and down-modulated CXCR4 receptor expression. We also demonstrated the ability of human SDF1␣ (hSDF1␣) to increase the intracellular calcium level in cultured astrocytes and cortical neurons, whereas in the same conditions, cerebellar granule cells did not modify their intracellular calcium concentration. Furthermore, in cortical astrocytes, the simultaneous treatment of hSDF1␣ with the HIV-1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.

In the past, little or no attention was paid to cognitive disorders associated with depression (a condition sometimes termed pseudodementia). However, recent years have seen a growing interest in these changes, not only because of their high frequency in acute-stage depression, but also because they have been found to persist, as residual symptoms (in addition to affective and psychomotor ones), in many patients who respond well to antidepressant treatment. These cognitive symptoms seem to impact significantly not only on patients’ functioning and quality of life, but also on the risk of recurrence of depression. Therefore, over the past decade, pharmacological research in this field has focused on the development of new agents able to counteract not only depressive symptoms, but also cognitive and functional ones. In this context, novel antidepressants with multimodal activity have emerged. This review considers the different issues, in terms of disease evolution, raised by the presence of cognitive disorders associated with depression and considers, particularly from the neurologist’s perspective, the ways in which the clinical approach to cognitive symptoms, and their interpretation to diagnostic and therapeutic ends, have changed in recent years. Finally, after outlining the pharmacodynamics and pharmacokinetics of the first multimodal antidepressant, vortioxetine, it reports the main results obtained with the drug in depressed patients, also in consideration of the ever-increasing evidence on its different mechanisms of action in animal models.

Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.

The administration of nitroderivatives in cluster headache (CH) sufferers is the most reproducible experimental paradigm to induce spontaneous-like pain attacks. Previous uncontrolled studies have reported that the local use of anaesthetic agents in the area of the sphenopalatine fossa is able to extinguish nitroglycerin (NTG)-induced pain in CH. The present study, carried out according to a double-blind placebo-controlled design, included 15 CH patients, six with episodic CH (mean +/- SD age of 36.8+/-5.6 years), and nine with chronic CH (37.8+/-10.4 years). Patients had undergone a standard NTG test (0.9 mg sublingually), during which the intensity of pain was scored using a visuoanalogic scale (VAS, range 0-10). Nine patients (two with the episodic form, seven with the chronic form) experienced a typical, spontaneous-like attack on the usual side, occurring in all cases within 45 min. In these patients, the test was repeated with an interval of 2 days, and once pain intensity reached 5 on the VAS, a 10% solution of cocaine hydrochloride (1 ml, mean amount per application 40-50 mg), or 10% lidocaine (1 ml), or saline was applied using a cotton swab in the area corresponding to the sphenopalatine fossa, under anterior rhinoscopy. This was done in both the symptomatic and the non-symptomatic side, for 5 min. Treatments were always performed randomly, in separate sessions. All patients responded promptly to both anaesthetic agents, with complete cessation of induced pain occurring after 31.3+/-13.1 min for cocaine and 37.0+/-7.8 min for lidocaine (M+/-SD). In the case of saline application, pain severity increased thereafter, and extinction of the provoked attacks occurred with a latency of 59.3+/-12.3 min (P<0.01 and P<0.01 vs. cocaine and lidocaine, respectively, Mann-Whitney U-test). While further suggesting that the sphenopalatine ganglion participates in the mechanisms of pain, these findings indicate that the local administration of the anaesthetic agents cocaine and lidocaine is effective on NTG-induced CH attacks, and may be used in the symptomatic treatment of this disorder.

During the recent coronavirus disease 2019 (COVID-19) outbreak in Northern Italy, we observed a 57-year-old man developing acute motor-sensory axonal neuropathy, a variant of Guillain-Barré syndrome (GBS), 12 days after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Similarly to other bacterial and viral infections, dysregulation of the immune system due to post-infectious mechanisms, such as the molecular mimicry, could lead to an indirect damage of the peripheral nervous system related to SARS-CoV-2. GBS causes motor dysfunctions that are not easily recognizable in non-neurological settings or in patients requiring ventilatory assistance. Several reports also suggested that GBS and Miller Fisher syndrome (MFS) could be neurological complications of COVID-19. Therefore, we performed a review of the 29 articles so far published, describing 33 GBS cases and five MFS cases associated with SARS-CoV-2 infection. We recommend awareness of this rare, but treatable, neurological syndrome, which may also determine a sudden and otherwise unexplained respiratory deterioration in COVID-19 patients.

Migraine is a common and highly disabling neurological disorder associated with a high socioeconomic burden. Effective migraine management depends on adequate patient education: to avoid unrealistic expectations, the condition must be carefully explained to the patient soon as it is diagnosed. The range of available acute treatments has increased over time. At present, abortive migraine therapy can be classed as specific (ergot derivatives and triptans) or non-specific (analgesics and non-steroidal anti-inflammatory drugs). Even though acute symptomatic therapy can be optimised, migraine continues to be a chronic and potentially progressive condition. In addition to the drugs officially approved for migraine prevention by international governmental regulatory agencies, numerous different agents are commonly used for this indication, showing various levels of evidence of efficacy and tolerability. Guidelines published in recent years, based on evidence-based medicine data on migraine prophylaxis, are a useful source of guidance, especially for primary care physicians and neurologists without specific expertise in headache medicine. Although the field of pharmacological migraine prevention has seen few advances in recent years, potential novel approaches are now being developed. This review looks at emerging pharmacological strategies for acute and preventive migraine treatment that are nearing or have already entered the clinical trial phase. Specifically, it discusses preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the serotonin 5-HT1F receptor, nitric oxide synthase, and acid-sensing ion channel blockers.