Women Stroke Association Statement on Stroke.

We describe the current and future objectives of the Women Stroke Association, a nonprofit multidisciplinary organization promoting research awareness on medical, psychological, and social issues concerning women affected by cerebrocardiovascular disease. In this paper, we deal with only cerebrovascular disease, whereas cardiovascular disorders will be addressed in a future paper. Gender differences in the clinical presentation of cerebrovascular diseases have been repeatedly suggested, and some treatment options may not be as effective and safe in men and women. For many years, women have either been underrepresented or excluded from randomized clinical trials, and the majority of therapeutic research has been carried on predominantly male populations. Furthermore, gender differences have been shown to contribute to different responses to cerebrovascular drugs in women when compared with men, regarding pharmacokinetics, pharmacodynamics, and physiology. In this statement, we discuss main research fields relevant to Women Stroke Association's mission and commitment, highlighting opportunities and critical from the women's health perspective. Future directions and goals of the Women Stroke Association arise from these considerations and represent the association's commitment to combating stroke.

Cerebral transverse sinus morphology as detected by MR venography in patients with chronic migraine.

OBJECTIVE: To clarify the frequency and characteristics of altered transverse sinus morphology in a series of consecutive patients with chronic migraine. BACKGROUND: As terminology, neuroradiological techniques and patient selection differ widely across various studies, reliable, reproducible information is lacking on the frequency of cerebral transverse sinus asymmetry as measured by cerebral magnetic resonance venography in patients with chronic migraine. METHODS: We assessed the frequency and characteristics of transverse sinus asymmetries and their correlation with the chronic migraine phenotype in a blind, cross-sectional magnetic resonance venographic study in a series of 83 consecutive patients with chronic migraine. RESULTS: After excluding mild (≤ 10%) physiological differences in transverse sinus diameter, we found magnetic resonance venographic evidence of altered transverse sinus morphology in 50.6% of the patients: 16.9% had moderate transverse sinus asymmetry (≤ 50%), 24.1% severe asymmetry (>50%), and 9.6% aplasia. Among the tested risk factors for migraine chronification, analgesic consumption, anxiety, and high systolic blood pressure were more frequent in patients with transverse sinus aplasia than in those without. CONCLUSIONS: Advanced magnetic resonance venographic techniques used in strictly selected subjects disclose transverse sinus asymmetries in as many as 50.6% of patients with chronic migraine, even when mild differences in physiological caliber are excluded. The unexpected correlation between transverse sinus aplasia and some risk factors for migraine chronification requires confirmation in larger studies.

Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. METHOD: We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. RESULTS: Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. CONCLUSION: The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

Changes in magnetic resonance imaging disease measures over 3 years in mildly disabled patients with relapsing-remitting multiple sclerosis receiving interferon ß-1a in the COGnitive Impairment in MUltiple Sclerosis (COGIMUS) study.

BACKGROUND: Conventional magnetic resonance imaging (MRI) has improved the diagnosis and monitoring of multiple sclerosis (MS). In clinical trials, MRI has been found to detect treatment effects with greater sensitivity than clinical measures; however, clinical and MRI outcomes tend to correlate poorly. METHODS: In this observational study, patients (n = 550; 18-50 years; relapsing-remitting MS [Expanded Disability Status Scale score ≤4.0]) receiving interferon (IFN) ß-1a therapy (44 or 22 µg subcutaneously [sc] three times weekly [tiw]) underwent standardized MRI, neuropsychological and quality-of-life (QoL) assessments over 3 years. In this post hoc analysis, MRI outcomes and correlations between MRI parameters and clinical and functional outcomes were analysed. RESULTS: MRI data over 3 years were available for 164 patients. T2 lesion and T1 gadolinium-enhancing (Gd+) lesion volumes, but not black hole (BH) volumes, decreased significantly from baseline to Year 3 (P < 0.0001). Percentage decreases (baseline to Year 3) were greater with the 44 µg dose than with the 22 µg dose for T2 lesion volume (-10.2% vs -4.5%, P = 0.025) and T1 BH volumes (-7.8% vs +10.3%, P = 0.002). A decrease in T2 lesion volume over 3 years predicted stable QoL over the same time period. Treatment with IFN ß-1a, 44 µg sc tiw, predicted an absence of cognitive impairment at Year 3. CONCLUSION: Subcutaneous IFN ß-1a significantly decreased MRI measures of disease, with a significant benefit shown for the 44 µg over the 22 µg dose; higher-dose treatment also predicted better cognitive outcomes over 3 years.

3 Tesla is twice as sensitive as 1.5 Tesla magnetic resonance imaging in the assessment of diffuse axonal injury in traumatic brain injury patients.

Diffuse axonal injury (DAI), associated with deafferentation and functional rearrangement, probably plays a role in the chronic phase of traumatic brain injury (TBI). DAI with a haemorrhagic component can be quantified using magnetic resonance imaging (MRI) thanks to the iron-based susceptibility effect of haemosiderin, which increases with magnetic field strength. The aim of this work was to compare conventional 1.5 Tesla and 3 Tesla MRI in the assessment of DAI in TBI patients. Eighteen TBI patients were submitted, in random order, to a 1.5T and a 3T MRI examination using standard gradient echo sequences. Both scans were always performed on the same day. DAI lesions with a haemorrhagic component were manually segmented and classified by anatomical location. The Wilcoxon and ANOVA tests were used for statistical analysis, significance being set at p<0.05. The results of this study showed that 3T MRI is almost twice as sensitive as 1.5T MRI in assessing DAI in terms of lesion number and volume. Differences between the two scanners were not significant in the posterior cranial fossa. High-field MRI enhances the assessment of DAI and may help to increase understanding of the mechanisms underlying subacute and chronic clinical, cognitive and behavioural changes in TBI patients.

Contrast echocardiography and migraine in divers with patent foramen ovale.

BACKGROUND: It has been proposed that the patent foramen ovale (PFO) may be associated with migraine, in particular migraine with aura. However, it is not clear whether paradoxical embolism triggers crises of headache. Cerebral embolization is provoked in subjects with PFO through contrast echocardiography, a safe method to diagnose the presence of foramen ovale pervium. METHODS: Twenty-four men practicing diving, an activity characterized by increased prevalence of PFO and migraine, underwent trans-thoracic echocardiography with contrast solution, composed of saline and air mixture and checked for the occurrence of migraine in the following 24 hours. RESULTS: A PFO (five of minimal size, i.e. visible only during Valsalva, one of small and two of medium size) was detected in 8/24 divers (33%). No one reported headache over the 24 hours after the procedure. DISCUSSION: Our preliminary data suggest that cerebral micro-embolism, provoked by contrast echocardiography, does not systematically trigger migraine crises when a minimal-to-medium sized patent foramen ovale is present.

Olfactory hallucinations as a manifestation of hidden rhinosinusitis.

The exact anatomical origin of olfactory epileptic seizures is controversial. Partial seizures can be an uncommon manifestation of brain tumours involving the medial temporal lobe and the orbitofrontal structures or as a marker of mesial temporal sclerosis. We present a patient suffering from olfactory hallucinations associated with inflammatory tissue in the anterior ethmoidal cells, in the right fronto-ethmoidal recess and in the maxillary sinus. Our report supports the opinion that the involvement of the olfactory bulb is crucial for developing so-called uncinate fits and is independent of other causes.

Spastic paraplegia with thinning of the corpus callosum and white matter abnormalities: further mutations and relative frequency in ZFYVE26/SPG15 in the Italian population.

Spastic paraplegia with thinning of the corpus callosum (ARHSP-TCC) is a relatively frequent form of complicated hereditary spastic paraplegia in which mental retardation and muscle stiffness at onset are followed by slowly progressive paraparesis and cognitive deterioration. Although genetically heterogeneous, ARHSP-TCC is frequently associated with mutations in the SPG11 gene, on chromosome 15q. However, it is becoming evident that ARHSP-TCC can also be the clinical presentation of mutations in ZFYVE26 (SPG15), as shown by the recent identification of eight families with a variable phenotype. Here, we present an additional Italian ARHSP-TCC patient harboring two new, probably loss-of-function mutations in ZFYVE26. This finding, together with the report of a mutation in another Italian family, provides confirmation that ZFYVE26 is the second gene responsible for ARHSP-TCC in the Italian population.

Relationship between supratentorial arachnoid cyst and chronic subdural hematoma: neuroradiological evidence and surgical treatment.

OBJECT: Arachnoid cysts are relatively common congenital intracranial mass lesions that arise during the development of the meninges. They can be complicated by the formation of an ipsilateral chronic subdural hematoma (CSDH) after minor cranial trauma. Treatment of these coexisting conditions remains controversial. In this study the authors describe the anatomical, clinical, and neuroradiological features and outcome in a series of patients whose CSDH associated with arachnoid cysts were managed surgically by draining the hematoma alone and leaving the cyst intact. The authors based this surgical management on histological and neuroradiological observations concerning these associated medical conditions. METHODS: A series of 8 patients with CSDHs associated with arachnoid cysts underwent surgery to drain the hematoma though a bur hole. The arachnoid cyst was left intact. Postoperative follow-up included CT scanning and T1- and T2-weighted MR imaging. RESULTS: Clinical, anatomical, and radiological observations suggest that because separate membranes cover arachnoid cysts and the related hematoma, arachnoid cysts remain unaffected by the subdural bleeding. In the present study, these observations received support from the neuroimaging appearances, suggesting that arachnoid cysts related to hematoma contained only blood breakdown products from the hematoma that had filtered through the reciprocal dividing membranes. CONCLUSIONS: Arachnoid cysts associated with SDH are anatomically separate conditions whose neurological symptoms respond to surgical drainage of the CSDH alone.

Complications in major depressive disorder therapy: a review of magnetic resonance spectroscopy studies.

Advanced magnetic resonance imaging techniques, such as proton magnetic resonance spectroscopy (H-MRS), have helped to further understanding of the pathophysiology of major depressive disorder (MDD) and to shed light on mechanisms underlying the therapeutic response. Potential complications of MDD therapy constitute an important area of research. Interruption of the absorption of serotonin reuptake inhibitors (SSRIs) is associated with discontinuation syndrome, while electroconvulsive therapy (ECT) can lead to transient and persistent anterograde amnesia. This paper reviews studies, since 1994, that have used H-MRS to evaluate adverse effects and complications of MDD treatment, either with ECT or SSRIs. Three articles have been published on adverse effects and complications of MDD treatment and H-MRS. Two focused on the ECT-induced memory deterioration and showed no sign of hippocampal atrophy in MDD patients with a residual memory deterioration after ECT, but a significant mean increase of the signal from Cho-containing compounds bilaterally, possibly due to an alteration of membrane turnover in the hippocampal region. The third paper showed that placebo-day Cho/Cr metabolite ratios were decreased in subjects with discontinuation syndrome, a finding that possibly reflects the dynamics of rostral anterior cingulate function. In spite of the limits deriving from the small number of papers published, our review demonstrated that H-MRS could be a useful instrument not only in evaluating therapy efficacy, but also for offering new insights into mechanisms underlying MDD treatments.

Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis.

Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-beta-1a; Rebif 44 microg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance. We validated IL-10 up-regulation, which is in accordance with previous reports, and other novel changes that underscore the capacity of IFN-beta to impair antigen presentation and migration of inflammatory elements into the central nervous system (up-regulation of filamin B and down-regulation of IL-16 and rab7). Overall, gene expression changes became less pronounced after 3 months of therapy, suggesting a homeostatic response to IFN-beta. This may be of use for the design of new treatment schedules.

Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis.

OBJECTIVES: The aim of this study was to identify clinical, magnetic resonance imaging (MRI) and biological markers predictive of long-term clinical response to interferon beta (IFN beta) therapy in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Sixty-eight patients treated with IFN beta were followed over a 6-year period. Relapse rate and disability progression were evaluated throughout the study. We considered suboptimal clinical response to be either the presence of sustained disability progression, or more than two relapses. Baseline and 12-month demographic, clinical and MRI findings, as well as the development of neutralizing antibodies (NAbs) against IFN beta during the first year of therapy were analyzed as predictors of long-term clinical outcome. RESULTS: "Black holes" on MRI were the best baseline predictor of disability progression (odds ratio [OR] 6.8; p < 0.001). At 1 year, both male gender (OR 4.9; p = 0.009) and NAbs (OR 7.3; p = 0.003) were independently associated with a high risk of developing subsequent disability. The presence of gadolinium enhancement, both at baseline (OR 4.7; p = 0.005) and on the 1-year MRI scan (OR 7.9; p = 0.002), was the unique variable associated with the number of relapses over the study period. CONCLUSIONS: Variables assessable within the first year of treatment significantly influence relapse rate and disability progression in patients with RRMS treated with IFN beta. These findings may help clinicians to make decisions regarding therapy regimen over time, and highlight the need for a prognostic algorithm.

Fast detection of diffuse axonal damage in severe traumatic brain injury: comparison of gradient-recalled echo and turbo proton echo-planar spectroscopic imaging MRI sequences.

BACKGROUND AND PURPOSE: Diffuse axonal injury (DAI) is a common type of primary neuronal injury in patients with severe traumatic brain injury (TBI), and is frequently accompanied by tissue tear hemorrhage. T2-weighted gradient-recalled echo (GRE) sequences are more sensitive than T2-weighted spin-echo images for detection of hemorrhage. The purpose of this study is to compare turbo Proton Echo Planar Spectroscopic Imaging (t-PEPSI), an extremely fast sequence, with GRE sequence in the detection of DAI. METHODS: Twenty-one patients (mean age 26.8 years) with severe TBI occurred at least 3 months earlier, underwent a brain MR Imaging study on a 1.5-T scanner. A qualitative evaluation of the t-PEPSI sequences was performed by identifying the optimal echo time and in-plane resolution. The number and size of DAI lesions, as well as the signal intensity contrast ratio (SI CR), were computed for each set of GRE and t-PEPSI images, and divided according to their anatomic location as lobar and/or deep brain. RESULTS: There was no significant difference between GRE and t-PEPSI sequences in the detection of the total number of DAI lesions (291 vs. 230, respectively). GRE sequence delineated a higher number of DAI in the temporal lobe compared to the t-PEPSI sequence (74 vs. 37, P < .004), while no differences were found for the other regions. The SI CR was significantly lower with the t-PEPSI than the GRE sequence (P < .00001). CONCLUSION: Owing to its very short scan time and high sensitivity to the hemorrhage foci, the t-PEPSI sequence may be used as an alternative to the GRE to assess brain DAI in severe TBI patients, especially if uncooperative and medically unstable.