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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by sleep, behavioral, memory, and cognitive deteriorations. Sleep disturbance (SD) is a major disease burden in AD, which has a reciprocal relationship with AD pathophysiology. It aggravates memory, behavioral, and cognitive complications in AD. Different studies have found that melatonin hormone levels reduce even in the pre-clinical stages of AD. Melatonin is the primary sleep-regulating hormone and a potent antioxidant with neuroprotective roles. The decrease in melatonin levels can thus promote SD and AD neuropathology. Exogenous melatonin has the potential to alleviate neuropathology and SD in AD by different mechanisms. Various studies have been conducted to assess the efficacy of exogenous melatonin to treat SD in AD. Though most of the studies suggest that melatonin is useful to ameliorate SD in AD, the remaining studies show opposite results. The timing, dosage, and duration of melatonin administration along with disease condition, genetic, environmental, and some other factors can be responsible for the discrepancies between the studies. More extensive trials with longer durations and higher dosage forms and studies including bright light therapy and melatonin agonists (ramelteon, agomelatine, and tasimelteon) should be performed to determine the efficacy of melatonin to treat SD in AD.

The association between thrombophilic alterations, migraine, and vascular events has been broadly investigated but not been completely clarified. In this cross-sectional, case-control study, we included consecutive outpatients diagnosed with migraine referring to a tertiary headache center. Migraine patients were matched to headache-free control subjects. All participants were evaluated for free protein S anticoagulant, functional protein C anticoagulant, homocysteine, and antiphospholipid antibodies (aPLs). History of ischemic stroke (IS) or transient ischemic attack (TIA), coronary heart disease, and peripheral venous thrombosis was also ascertained. We included 329 migraine patients and 329 control subjects (mean age 41 years, 77% women in both groups). Among migraine patients, 239 (72.6%) had migraine without aura and 90 (27.4%) had migraine with aura. Migraine patients had more frequently arterial hypertension, hypercholesterolemia, history of IS or TIA and, peripheral venous thrombosis compared to control subjects, whereas we found no differences in diabetes mellitus, BMI, and coronary heart disease between the two groups. At least one thrombophilic alteration was detected in 107 (32.5%) migraine patients and in 74 (22.5%) control subjects (OR = 1.66, 95% CI 1.17–2.35, p = 0.004). We identified an association of migraine with aPL positivity (OR = 2.6, 95% CI 1.5–4.7, p = 0.001) and with free protein S deficiency (OR = 4.7, 95% CI 1.6–14.0, p = 0.002), whereas we found no differences in protein C deficiency, APCR, and hyperhomocysteinemia between the two groups. Furthermore, aPL positivity and free protein S deficiency were more common in migraine patients with and without aura than in control subjects. We found that in migraine patients, aPL positivity was associated with both IS or TIA (OR = 5.6, 95% CI 1.5–20.4, p = 0.009) and with coronary heart disease (OR = 27.6, 95% CI 1.4–531.1, p = 0.028), whereas free protein S deficiency was associated with IS or TIA only (OR = 14.3, 95% CI 2.8–74.4, p = 0.002). Our research documented a significative higher prevalence of aPL positivity and protein S deficiency in migraineurs than in controls. Data also showed an association between these alterations and some vascular thrombotic events in migraine patients. We can argue that thrombophilic disorders associated with migraine may contribute to the occurrence of vascular events.

Autoimmunity is believed to play an important causative role in the pathogenesis of epilepsy. There are evidences for the presence of autoantibodies in patients with epilepsy. To date, many studies have assessed the presence of antiphospholipid antibodies (aPLs) in epilepsy patients, though the relationship has been inconclusive.The aim of this systematic review and meta-analysis was to evaluate the presence of aPLs in epileptic patients as compared to healthy controls.Five electronic databases (PubMed, Web of Science, Embase, Scopus and Google Scholar) were searched systematically. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). L'Abbé plots were generated to visually inspect heterogeneity while publication bias was evaluated via visualization of contour- enhanced funnel plots, and Begg's and Egger's tests.Based on the inclusion criteria, 14 studies were selected involving 1248 epilepsy patients and 800 healthy controls. The majority of epilepsy was categorised as generalised or partial and none had comorbidity with autoimmune diseases. Significant presence of both anticardiolipin (aCL) antibodies (OR: 5.16, 95% CI: 3.21-8.28, p 0.00001) and anti-β2- glycoprotein I (anti-β2-GPI) antibodies (OR: 2.95, 95% CI: 1.07-8.11, p = 0.04) exhibited comorbid association with epilepsy patients as compared to healthy controls. Subgroup analyses revealed that presence of aCL antibodies was more specifically observed in paediatrics (OR: 4.57, 95% CI: 2.57-8.15, p 0.00001) than adults (OR: 4.24, 95% CI: 1.80-10.01, p = 0.001). The odds of aCL antibody presence was higher in partial epilepsy patients (OR: 7.88, 95% CI: 3.23-19.24, p 0.00001) than that of generalised (OR: 3.76, 95% CI: 2.15-6.59, p 0.00001) and in Asian epileptic patients (OR: 9.56, 95% CI: 2.69-33.95, p = 0.0005) than Europeans (OR: 4.35, 95% CI: 2.74-6.92, p 0.00001). The presence of anti-β2-GPI antibodies was significant in paediatric (OR: 6.44, 95% CI: 1.39-29.89, p = 0.02) and African population with epilepsies (OR: 10.59, 95% CI: 1.22-92.25, p = 0.03). NOS of the majority of the studies (11/14) indicated a high methodological quality. No substantial heterogeneity was observed either from the quantitative analysis or from the L'Abbé plots while no significant publication bias was detected from funnel plots; Begg's and Egger's tests.Since none of the epilepsy subjects exhibited any comorbid autoimmune disorders, significant presence of aCL and anti-β2-GPI antibodies indicate towards their contribution in immune-mediated general pathogenesis of epilepsy.

Alpha-lipoic acid (ALA) is known to lower insulin resistance (IR), which is common among migraineurs. To assess the effect of ALA on headache in migraineurs with IR, we performed an exploratory study on a cohort of patients with migraine, followed at our Headache Center. The 32 patients took ALA 400 mg b.i.d. for 6 months in addition to their on-going treatment. The percentage of patients with a reduction of at least 50% of the attacks was 0.53 (confidence interval [95% CI] 0.36-0.70) at 2 months, 0.56 (0.39-0.73) at 4 months, and 0.69 (0.53-0.85) at 6 months. The incidence rate ratio of attacks at 6 months versus baseline was 0.48 (0.43-0.53, P .001), corresponding to a mean (95% CI) number of attacks of 5 (4-6) versus 11 (10-12). The number of days of treatment in the previous month was 7.7 (6.8-8.7) at baseline, 5.4 (4.6-6.2) at 2 months, 5.3 (4.5-6.1) at 4 months, and 4.3 (3.6-5.0) at 6 months. Baseline and 120-min glucose and insulin and quantitative insulin sensitivity check index (QUICKI) and the Stumvoll index did not change at 6 months versus baseline. This exploratory study shows that the administration of ALA may be associated with a reduction in the number of attacks and the days of treatment in migraineurs with IR. A randomized controlled trial is needed to test this possibility.

Background.: Migraine is a diffuse and disabling disease. Its pathophysiology is complex and involves both central and peripheral dysfunctions. Objective.: This review will discuss the pathogenesis of migraine from the origin of the neuro-inflammatory theory, to the modern pathophysiological model and the latest therapies. Methods.: PUBMED and EMBASE (up to May 2019) were searched for: migraine, inflammation, immunomodulation. An additional search was carried out from the bibliography of previous review articles. Results.: Migraine was thought to be mainly a vascular disorder, according to the so-called “vascular theory”. Based on animal models, a new hypothesis called “the neuro-inflammatory” was conceived at the end of the 20th century. The growing knowledge about the trigeminovascular system and its role in the inflammatory-pain pathway, allowed to identify other specific neurotransmitters, such as the Calcitonin Gene-Related Peptide and Pituitary Adenylate Cyclase-Activating Peptide. Evidence was provided that the inflammatory-pain system could become sensitised and, due to this sensitisation, the pain could also perpetuate, even in the absence of any triggers of the migraine attack. At last, brain immune cells modification during cortical spreading depression in migraine was demonstrated, along with the existence and function of the glymphatic system. The better comprehension of the immune system abnormalities allowed the development of new immunomodulating drugs: the monoclonal antibodies against the CGRP or the CGRP receptor. Moreover, new insights into the molecular mechanism of CGRP, and the function of C-fibres and Aδ-fibres, highlighted the mechanism of action of Botulinum Toxin type A in the treatment of chronic migraine.

BackgroundThe occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear.AimThe aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals.MethodsA comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence.ResultsCohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p ConclusionHigher frequency of comorbidity between aPLs and headache was observed in healthy individuals and patient cases. Therefore, experimental studies are warranted to evaluate the aPLs-induced pathogenic mechanism of headache.

Background and Objective: Migraine and systemic autoimmune diseases are 2-3-fold more common in women and various studies have reported an association between the two pathologies. Methods: This review takes into account epidemiological studies involving migraine and systemic lupus erythematosus, antiphospholipid syndrome, Sjogren's syndrome, and other diffuse connective tissue diseases. This scientific literature analysis consists of the main articles found in Medline with a search up to April 2017. Results: Many epidemiological studies were carried out on patients suffering from systemic lupus erythematosus. Results showed that headache and migraine are more prevalent in systemic lupus erythematosus patients compared to controls, especially migraine with aura. Patients with Lupus and migraine show a higher lupus activity and association with Raynaud and/or antiphospholipids in these populations are contradictory. There are not enough data to establish an association between antiphospholipid syndrome and migraine. However, data are more consistent between antiphospholipid carrier condition and migraine. Systemic sclerosis is a rare disease, for this reason the amount of available data on this disorder are scanty. However, some studies reported an association between headache, migraine and systemic sclerosis, especially where gliotic brain lesions and Raynaud are coexisting. Finally, large propensity cohort population based studies suggested that systemic autoimmune diseases are more frequent in patients suffering from migraine. Conclusion: An attempt at explaining the possible link between these disorders and migraine is discussed at the end of the review. Several autoimmune alterations are shared by most autoimmune diseases and headache types. Endothelial dysfunction is the only alteration that is common among all these disorders.

Background Headache is a widespread disorder in children, but little is known about the headache prevalence in northwest Italy, on less frequent migraine equivalents, family history, and treatment habits in children. Method This is an epidemiologic population–based study of a representative sample of children aged 3 to 11 years, conducted in Alba, Italy. We used a self-administered questionnaire to acquire information on gender, age, headache, possible migraine equivalents, family history for various diseases, and treatment habits. Results We distributed the questionnaire to 1152 children, and a total of 649 questionnaires were successfully completed. In the preschool age, 10.3% (seven boys and nine girls) of children suffered from headache. In school-age children, the prevalence of headache was 31.4% (75 boys and 80 girls; 27% in 6 year olds and 41% at age 9 years). We found a significant correlation between headache and abdominal pain in the entire sample and with cyclic vomiting syndrome and dizziness in school-age children only. Headache correlated significantly with a family history of headache, thyroid diseases, diabetes, hypertension, and vascular diseases. Headache was treated with drugs, primarily paracetamol, in 60 of the 171 (35%) children who reported headache and in 61% of the children with migraine; no subjects were treated with triptans. Conclusions Headache is widespread in children, with a high prevalence of associated symptoms and family history for many other headache-related disorders.

Summary. Background: It has been observed that migraineurs show a higher risk of thrombosis and that the most frequent symptom reported by patients with antiphospholipid syndrome is headache, especially migraine. Objectives: The aim of our research was to evaluate the prevalence of antiphospholipid antibodies (aPL) in a random cohort of migraineurs. Patients/Methods: This analytic, comparative case study was performed to evaluate the prevalence of antiphospholipid antibodies by comparing a population of migraineurs with and without aura with sex- and age-matched controls. Both the diagnosis of migraine and the laboratory diagnosis of aPL positivity were made on the basis of the most recent international guidelines. Results: Between September 2008 and August 2009, we recruited 284 consecutive patients (225 women and 59 men, 203 without aura and 81 with aura) and 225 controls (174 women and 51 men). Positivity for at least one test for aPL (LAC, ACA IgG or antis2GLP1 IgG) was detected and confirmed in 12% (n = 33) of patients and in 3% (n = 7) of controls (odds ratio, 4.08; confidence interval, 1.77–9:39; P = 0.0004). Two of the patients had triple positivity for aPL (LAC, ACA and antis2GLP1) and one had double positivity (LAC and antis2GLP1); none of the controls showed multiple positivity. Conclusions: Our data show that migraineurs have a significantly higher prevalence of antiphospholipid antibodies, and point towards the fact that the two conditions may be comorbid or even that migraine may be an early sign for identifying patients with aPL positivity.

Background.— Migraine is a complex biochemical dysfunction attributed to a disorder of the trigeminal and hypothalamic pathways. Impairment of glucose metabolism has been reported in migraine, but data are scanty and inconsistent. Objective.— The main aim was to verify whether migraineurs have abnormalities of the glucose and insulin metabolism.We also studied correlations between blood glucose and insulin and between insulin levels and migraine severity. Patients and methods.— Patients with migraine or headache other than migraine, and healthy volunteers were included. All had general blood tests and a standard oral glucose tolerance test after a 12-hour fast, and glucose and insulin were measured. Results.— Over a 6-month period, we recruited 84 migraineurs (73 women, 11 men), 25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls (24 women, 2 men). Multivariate analysis confirmed a significant difference between groups for glucose levels (P

The possible relationship between Guillain-Barre syndrome (GBS) and cancer is still controversial and the existence of a paraneoplastic GBS remains unconfirmed. To better define whether there is a relationship between GBS and malignancy, we compared the observed and the expected number of patients with tumours in a population-based cohort of subjects with GBS. Clinical differences between GBS patients with or without malignancies were analysed. Data were obtained from the Piemonte and Valle d'Aosta Register for GBS (PARGBS) (years 1990-1998). GBS was diagnosed according to NINCDS criteria. The number of expected cases of malignancy in the PARGBS population was calculated using the incidence rate of all types of cancer (ICD codes 140-208) in Piemonte [1985-1987], and in the most important town of this region, that is Turin (years 1993-1997). In the nine-year period, 435 incident patients with GBS were found. Nine of them developed cancer in the six months preceding or following GBS; in seven of them, the diagnosis of cancer and GBS was concomitant. The expected number of malignant tumours was 3.7 (using the incidence in Piemonte) and 3.8 (using the incidence in Turin); therefore, the odds ratios were 2.43 (95 % CI, 1.11-4.62) and 2.37 (95% CI, 1.09-4.50), respectively (p

Migraine is a widespread disorder thataffects about 18% of the people, in 2/3 ofcases women (1).The concept that migraine could berelated to some vascular diseases, such asmyocardial infarction or a stroke, havegrown over the years, mainly in migrainewith aura (2–6). In the last decades, severalstudies have been carried out to under-stand if and what the linkage could be.Among these studies, we have found manyresearches on thrombophilic disorders. Inthiscontext,thestudiesfocusonalterationsof coagulation factors, coagulation pro-teins,homocysteine with MTHFR variants,andauto-immunedisordersof coagulationsuch as anti-phospholipid antibodies. Theavailable data are sometimes difficult tointerpret. The first problem we meet is thatthrombophilic disorders usually have a lowprevalence, so we need larger sample stud-ies to reach significant results. The secondproblem could be how to correctly selectthe proper study population,because somedeficits could be inherited and some othersacquired,andresultscouldchangedepend-ing on contextual factors such as preg-nancyoranti-coagulantorestroprogestinictherapy. The third problem, mainly deal-ing with auto-immune coagulative disor-ders,couldbedifferentlaboratorymethodsand the different positivity criteria used.Another problem is that the prevalence ofthe coagulative deficit could change withage, so we find variable results in study-ing children or adults. Therefore, we needto calculate properly the sample size ofthe study population. Another chance tostudy the correlation between migraineand thrombophilic disorders could be byusing the data collected through spe-cific disease database. The main Interna-tional Disease Database is the EuropeanRegister on anti-phospholipid syndrome(APS). These data show that the first andmost frequent symptom of the syndromeis a headache, probably a migraine con-sidering the reported descriptions (7, 8).Headaches are so important in APS tolead expert hematologists to recommendcarrying out tests for anti-phospholipidantibodies (aPL) in all patients present-ing severe headaches (9). The Italian Reg-istry of Rare Diseases is another impor-tant source of information. It was activatedby the National Health Institute (NHI)almost 10years ago, through the creationof Regional Registries. In the last Data-base Report of Rare Diseases’ 2013 data-base of the Piedmont Region, we find howthe number of the diagnosis of a throm-bophilic disease performed in an headachecenter is equal or higher than the onerecorded by those centers taking care ofpatients who had experienced a throm-botic event (10). Articles published morerecently correlate migraine and throm-bophilic alterations, so we can presumethey could be co-morbid.Coagulative factors II, V, VII, VIII, IX,and von Willebrand have been studied inmigraineurs. The correlation between fac-tor II mutations and migraine has beenstudied throughout several smaller studies,always with negative results (11, 12). Onlyrecently,a population based study reporteda higher prevalence of factor II mutationin women suffering from migraine, but aselection bias could be suspected becausethis population had been selected amongwomen with a positive family history ofvenous and arterial thrombosis (13). Wecan find a few reports of deficit of fac-tor VII, which seems to be non-relevant(14, 15), and of factors von Willebrand,VIII e IX, and various platelet alloantigens(11, 16), topics that would be interestingto investigate further. Most authors studiedthe alterations of factor V in migraineurs,and also in these studies the sample sizeseem to be unrepresentative, and resultsare controversial (11, 15, 17–20). Further-more, some authors considered homozy-gous mutation alone, while others consid-ered both homozygous and heterozygousmutation. Among the coagulative factors,the V seems to be the most interestingone, but larger and better designed stud-ies are required, with more severe selectionof inclusion criteria.Still little is known on deficit of coagu-lation proteins C and S. The main prob-lem of studying protein C deficit is itslow prevalence, which is around 0.4%, thatrequires larger sample sizes to study anddetect any significant difference in preva-lence between migraineurs and healthycontrols. The few available studies are toosmall to clearly understand this topic (11,18, 19). The prevalence of protein S deficitis higher, but this type of deficit is morecomplex to understand and diagnose. Firstof all, laboratory methods that are usedshould be clearly defined, such as the sen-sitivity of the laboratory kit used andwhat type of protein S was dosed, and isit the total or only the free protein, allelements needed to make a proper diag-nosis of the type of defect (genetic oracquired). It would be better to distinguishinherited from acquired types of deficit,because of the different clinical relevanceand etiopathogenesis. Inherited deficits areeasiertodetectandthelevelofproteinScanbe stable over time, on the contrary of theacquired deficits. It is also very importantto consider and exclude iatrogenic deficits,such as those due to anti-coagulant orestroprogestinic therapy,or the physiologic

Sneddon’s syndrome is a rare vascular disease affecting mainly skin and brain arterioles leading to their occlusion due to excessive endothelial proliferation. The two main features of this syndrome are livedo reticularis and lacunar subcortical infarcts. Here, we describe the case of a 64-year-old woman presenting with a 4-year history of a throbbing, bilateral, parieto-occipital headache associated with facial pain, but without any other accompanying symptom. The pain, initially misdiagnosed as atypical trigeminal neuralgia, worsened up to chronic daily and such severely disabling headache that she was constrained to bed. She presented with reduced cognitive functions, diffuse and severe livedo reticularis, severe myalgias and mild stiffness. All diagnostic test for different diseases were performed and other diseases excluded except for Sneddon’s syndrome. Her symptoms were reduced firstly using acetylsalicylic acid, then ticlopidine 250 mg bid was begun and then Pentoxyphillin, resulting in a significant improvement of symptoms with the disappearance of headache. Her worsening in the first year was characterized by obsessive-compulsive behaviours, body-image misperceptions and panic attacks, improved for a period using olanzapine. Considering this case, we remark the importance of using headache classification to avoid diagnostic errors, secondly, we describe an atypical manifestation of Sneddon’s syndrome and therapeutic efficacy of using ticlopidine and pentoxyphillin.

Despite its favorable outcome in up to 90% of patients, epilepsy is still considered to carry a higher than normal risk of morbidity and accidents. Knowledge of the everyday life risks (illnesses, acc

Objective To evaluate the clinical characteristics and outcome of non-invasive ventilation (NIV) in an epidemiological based series of amyotrophic lateral sclerosis (ALS) patients. Methods The study was performed using data from the Piemonte and Valle d9Aosta Register for ALS, a prospective epidemiological register enrolling all ALS incident cases in two Italian regions. Results Among the 1260 patients incident in the period 1995–2004, 259 (20.6%) underwent NIV. Young male patients and subjects attending the tertiary ALS centres were more likely to undergo NIV. There was a progressive significant increase in the use of NIV during the study but was limited to patients attending the ALS tertiary centres. Median survival after NIV was 289 days (95% CI 255 to 333). Conclusions In an epidemiological setting, NIV represents an increasingly utilised option for the treatment of respiratory disturbances in ALS and has favourable effects on survival, in particular among patients followed by tertiary ALS centres. Sociocultural factors, such as age, gender and marital status, strongly influence the probability of undergoing NIV. Efforts should be made to remove these obstacles in order to spread the use of NIV in all ALS patients with respiratory failure.

Contexte: Certaines publications font etat d'alterations vasculaires a l'IRM du cerveau chez les migraineux et d'une relation entre des variantes de l'hexagone de Willis et les infarctus cerebraux lacunaires. Nous avons examine les anomalies de tout l'hexagone de Willis et leur relation aux lesions vasculaires du cerveau chez des migraineux afin d'identifier un mecanisme vasculaire possible dans la migraine. Methode: Nous avons effectue une etude de cohorte controlee chez des patients migraineux, ayant consulte de facon consecutive a notre clinique de cephalee, et chez des temoins non migraineux pour etudier l'hexagone de Willis par angio IRM cerebrale. Les donnees ont ete analysees par les methodes statistiques suivantes: l'ANOVA, le critere de Scheffe et le test t de Student. Resultats: Nous avons recrute 270 patients migraineux, soit 204 sans aura (MSA) et 66 avec aura (MAA), et 159 temoins. Cent huit migraineux (40%) et 34 temoins (21,4%) etaient porteurs d'une variante anatomique. Nous avons constate une association significative entre la MSA et les variantes anatomiques (RR = 2,4 ; IC a 95% 1,5 a 3,9) et entre la MAA et les variantes anatomiques (RR = 3,2 ; IC a 95% 1,6 a 4,1). Les variantes posterieures unilaterales avec hypoplasie basilaire sont associees statistiquement avec la MAA seulement par rapport aux temoins (RR = 9,2 ; IC a 95% 2,3 a 37,2). Trente-trois pour cent des patients atteints de MSA et 24% de ceux atteints de MAA ont une lesion au cerveau, dont 2% de lesions sous-tensorielles. Nous n'avons pas constate d'association statistique entre la presence de variantes de l'hexagone de Willis et la presence de lesions ischemiques a l'IRM (RR = 1,5 ; IC a 95% 0,68 a 1,94) ou de lesions lacunaires sous-tensorielles (RR = 1,58 ; IC a 95% 0,48 a 5,24). Conclusions: Les variantes anatomiques de l'hexagone de Willis sont significativement plus frequentes chez les patients migraineux. Les anomalies posterieures sont plus frequentes dans la MAA, ce qui est en faveur d'un mecanisme vasculaire provoquant des changements dans le flux sanguin cerebral, stimulant ainsi une depression se propageant au cortex.

Background Different amyotrophic lateral sclerosis (ALS) phenotypes have been recognised, marked by a varying involvement of spinal and bulbar upper and lower motor neurons. However, the differential characteristics of these phenotypes are still largely unknown. Objective To define the epidemiology and outcome of ALS phenotypes in a population based setting. Methods All ALS cases incident in two Italian regions were prospectively collected from 1995 to 2004 in an epidemiological register. Cases were classified according to established ALS phenotypes: classic, bulbar, flail arm, flail leg, pyramidal, respiratory, pure lower motor neuron (PLMN) and pure upper motor neuron (PUMN). Results ALS phenotype were determined in 1332 out of 1351 incident patients (98.6%). Classic and bulbar phenotypes had similar mean annual incidence rates. Gender specific incidence rates showed a male preponderance in respiratory, flail arm, classic and PLMN phenotypes; in all other phenotypes, men and women had similar incidence rates. Age at onset was significantly lower in pyramidal, PLMN and PUMN phenotypes and higher in the bulbar phenotype. The best outcomes were observed in PUMN, pyramidal, PLMN and flail arm phenotypes and the worst in respiratory and bulbar phenotypes. Conclusions Our epidemiological findings suggest that ALS phenotypes carry distinctive and easily distinguishable clinical and prognostic characteristics, strongly related to a complex interplay between gender and age. The categorisation of ALS patients according to more homogenous clinical groups is relevant in identifying biological markers for ALS and should be considered for the design of clinical trials.

Many factors should be considered when an episodic migraine worsens and becomes chronic. Prolactin (PRL) was linked to the origin of pain in patients with microprolactinomas who developed different types of headaches. Our team carried out studies on 27 patients with a background of episodic headaches that became chronic. The patients were evaluated by means of a general examination, a neurological examination and a hormonal profile. Of the 27 patients, 7 of them had an increased level of prolactinaemia. All the patients were women, ranging from 17 to 57 years of age. Four of them had a pure form of migraine without aura, whereas 3 patients had both migraines without aura and tension–type headaches. They suffered from headache for a period ranging from 3 to 32 years and their headache became chronic 4–12 months prior to the visit. Their headache did not change in type, but only in severity and frequency. Two patients had no symptoms referable to high PRL levels; 4 patients had irregular menses or amenorrhoea. One of these patients also suffered galactorrhoea and two of these patients had a microprolactinoma at MRI; one patient was using estroprogestinic drugs, so her menstrual alteration could not be considered. The patients were followed–up for a period of 6–16 months. Six patients responded favourably after being treated with cabergoline, although some had already tried other drugs, which, however, had no effect on their headache. One patient improved after ceasing to take estroprogestinic, in spite of increased levels of PRL. Therefore, on this basis, PRL levels should always be considered when headache worsens. It is an adjunctive worsening factor, which can be easily eliminated.

We determined the incidence, risk factors, and short-term mortality of stroke in a well-defined area of southern Italy, i. e. the city of Vittoria, Sicily (58 833 inhabitants). The medical recores of the local hospitals and the outpatient files of the local neurologist referring to the calendar year 1991 were retrospectively investigated. Stroke was defined according to standard criteria and classified as first-ever (FE) and recurrent (R). Risk factors for stroke were diagnosed from medical history, laboratory and instrumental findings, and in the presence of specific treatments. Short-term mortality was assessed as 30-day case-fatality rate. The sample included 120 cases (61 men) aged 34-94 years, 89 of whom (48 men) had a FE stroke. The overall annual crude incidence rate of FE stroke was 165.3 per 100 000 (men, 178.4; women 152.2); for FE and R stroke together it was 222.9 (men, 226.8; women 219.1). The standardized rates were 245.3 (FE stroke) and 321.9 (FE and R stroke). The age-specific rates for FE stroke were 9.4 (55 years), 262.2 (55-64 years), 645.2 (65-74 years), 2019.7 (75-84 years), and 3246.8 (or =85 years). The corresponding values for FE and R stroke were 11.7, 412.0, 887.1, 2565.5, and 4220.8. In patients with FE stroke, cerebral infarction was the main type. Hypertension, diabetes and cardiac disorders were the commonest risk factors, with similar distribution among FE and R stroke. The 30-day case-fatality rate was 28% for FE and R stroke and 38% for FE stroke. Compared to other reports, the incidence of stroke in Vittoria was lower in the youngest but higher in the oldest age groups. Although the small sample size and possibility of misdiagnoses may partly explain our findings, the roles of different dietary, social, and genetic factors in the local population warrant investigation.

Objective: To establish whether chronic alcoholism and alcohol consumption are risk factors for developing a first symptomatic epileptic seizure. Methods: Multicentre case-control study of 293 patients (160 men, 133 women) with a first seizure symptomatic (either acute or remote) of head trauma, stroke, or brain tumour, matched to 444 hospital controls for centre, sex, age (±5 years), and underlying pathology. Results: The risk of first seizure in alcoholics was no higher than in non-alcoholics for men (odds ratio 1.2, 95% confidence interval 0.4 to 3.2) or women (1.5, 0.1 to 54.4). The odds ratio (both sexes) was 1.2 (0.8 to 1.7) for an average intake of absolute alcohol of 1‐25 g/day, 0.9 (0.5 to 1.5) for 26‐50 g/day, 1.6 (0.8 to 3.0) for 51‐100 g/day, and 1.4 (0.5 to 3.5) for >100 g/day. Conclusions: We found no evidence of an association between alcohol use or alcoholism and a first symptomatic seizure.

Migraine is a complex biochemical dysfunction attributed to a disorder of the trigeminal and hypothalamic pathways. Impairment of glucose metabolism has been reported in migraine, but data are scanty and inconsistent.The main aim was to verify whether migraineurs have abnormalities of the glucose and insulin metabolism. We also studied correlations between blood glucose and insulin and between insulin levels and migraine severity.Patients with migraine or headache other than migraine, and healthy volunteers were included. All had general blood tests and a standard oral glucose tolerance test after a 12-hour fast, and glucose and insulin were measured.Over a 6-month period, we recruited 84 migraineurs (73 women, 11 men), 25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls (24 women, 2 men). Multivariate analysis confirmed a significant difference between groups for glucose levels (P.0001), but no significant time interaction. The differences were mostly between migraine and healthy controls (P.0001) and to a lesser extent between other headaches and healthy controls (P.05). A significant difference between groups was also found for insulin (P.0001), with a significant time interaction. The difference was confirmed for migraine compared to other headaches (P.0001) and healthy controls (P.0001).Blood glucose levels may be high in headache patients, but do not seem to be specific to migraineurs. Insulin levels were higher in migraineurs, and seemed specific to this group. These findings are in keeping with recent reports on the effects of insulin on brain functions and lend support to the possibility that insulin is involved in the pathogenesis of migraine.

Nineteen patients with mild or moderate chronic respiratory insufficiency, mean age, 63.3 y., have been investigated with pulmonary function tests, clinical examination and somatosensory (SEPs), visual (VEPs) and brainstem auditory (BAEPs) evoked potentials. Nineteen age and sex matched subjects acted as controls. None of the subjects had conditions known to affect the central nervous system (CNS). SEP N20 latency was significantly prolonged in 7 out of 19 patients and its mean value in the patients' group was significantly higher (21.02 vs 19.49 msec p0.001). VEP P100 latency was prolonged in the patients' group in 16/38 and 15/38 eyes with spatial frequencies of 30' and 15' of arc respectively. The P100 mean value was also significantly prolonged in the patients' group for both eyes and spatial frequencies (108.08 vs 101.87 msec p0.001 and 115.82 vs 107.63 msec p0.001 for spatial frequencies of 30' and 15' respectively). No significant difference was evident with BAEPs The data seem to support the hypothesis of a subclinical involvement of CNS in these cases, with preferential damage to the newer phylogenetic structures.