Migraine with aura and patent foramen ovale: myth or reality?

Several observational studies report that subjects with migraine with aura have a higher prevalence of right-to left shunt, commonly due to patent foramen ovale, and that patent foramen ovale is more prevalent in subjects with migraine with aura. Although migraine without aura has been less extensively studied, it does not seem to be associated with an increased prevalence of right-to left shunt. The mechanism that underlies the possible relationship between patent foramen ovale and migraine with aura remains speculative. The proposed mechanisms are migraine-triggering vasoactive chemicals bypassing the pulmonary filter and reaching the cerebral circulation and paradoxical microembolization. However, it is unclear, at this time, if there is a causal or comorbid association between the two conditions. In some families atrial shunts show a dominant inheritance that seems to be linked to inheritance of migraine with aura. Migraine with aura is an independent risk factor for ischemic stroke, and patent foramen ovale is present more frequently in patients with cryptogenic stroke than in controls. At this moment, there is no convincing evidence that excess stroke risk of migraine is simply mediated by patent foramen ovale through paradoxical embolism. Several non-controlled studies suggest that closure of the foramen ovale significantly reduces attack frequency in migraine patient, but the only prospective placebo-controlled trial does not support these results. Patent foramen ovale closure, at present, is not indicated as a treatment for migraine in clinical practice.

Validation of a simple method for atrial fibrillation screening in patients with stroke.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in adult and old people and represents a risk factor for stroke. Correct AF individuation bears strong relevance in primary and secondary stroke prevention. Our goal was to evaluate the reliability of a low-cost, non-invasive technology in detecting AF in acute stroke patients. AFib model BP3MQ1-2D (Microlife USA, Dunedin, FL) showed good accuracy in diagnosing AF in a general cardiologic outpatient population. We carried out an observational study in patients with recent stroke. We studied 207 subjects, 103 men, 104 women, mean age (±SD) 77.7 ± 11.34 years, who underwent a test by AFib device with indication of AF or lack of it. The golden standard was a 12-lead EKG done immediately and evaluated by a certified cardiologist. We computed estimates of Sensitivity and Specificity and their 95 % confidence intervals (CI). AF was present in 38 subjects from the sample of 207 (18.4 %). AFib correctly demonstrated AF in 34 and failed diagnosing AF in 4 cases; on the other hand, AFib correctly excluded AF in 167 and caused an erroneous diagnosis of AF in 2 cases. The Sensitivity was 0.895 (95 % CI 0.7597-0.958) and the Specificity was 0.988 (95 % CI 0.958-0.997). The AFib device global accuracy was 0.971 (95 % CI 0.938-0.987). This device was able to detect AF with high specificity and a good sensitivity. This device may be considered as an accurate tool in detecting AF in stroke patients.

Female reproductive steroids and neuronal excitability.

Oestrogen and progesterone have specific receptors in the central nervous system and are able to regulate neuronal development and plasticity, neuronal excitability, mitochondrial energy production, and neurotransmitter synthesis, release, and transport. On neuronal excitability, estradiol and progesterone seem to have an opposite effect, with estradiol being excitatory and progesterone and its derivative allopregnanolone being inhibitory. Estradiol augments N-methyl-D-aspartate-mediated glutamate receptor activity, while progesterone enhances gamma-aminobutyric acid-mediated chloride conductance. Sex steroid regulation of the balance of neuroexcitatory and neuroinhibitory activities may have a role in modulating clinical susceptibility to different neurological conditions such as migraine, catamenial epilepsy, premenstrual dysphoric disorder, and premenstrual syndrome.

Restless legs syndrome is not associated with migraine with aura: a clinical study.

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by "pure" migraine with aura (pMA). We recruited 63 patients (33 females and 30 males) affected by MA without other types of primary headache among all patients referred in five Italian headache centers in a 1-year period. The prevalence of RLS in pMA patients (9.5%) is similar to that observed in Italian headache-free subjects (8.3%). No significant differences were found between pMA patients with and without RLS about clinical features of MA attacks and systemic and psychiatric diseases were investigated. Moreover, no association appeared between RLS and familial cases of MA. Differently from migraine without aura, our data do not confirm the existence of an association between RLS and MA, not even when a genetic factor is involved.

Fabry disease in patients with migraine with aura.

Anderson-Fabry disease (AFD) is an X-linked recessive lysosomal disease caused by alpha-galactosidase A (alpha-gal) deficiency, causing progressive glycosphingolipid storage in various organ systems. Headache is a frequent symptom. Cerebral magnetic resonance imaging (MRI) often shows multiple white matter lesions (WML), like those seen in patients affected by migraine, in particular with aura (MA). To our knowledge, there are no reports about the prevalence of AFD in patients with MA. The objective of the study was to determine AFD prevalence, as assessed by alpha-gal activity and genetic tests, in MA patients. We evaluated 73 consecutive patients followed by the Headache Centre of our Department with a diagnosis of MA. They were screened for migraine characteristics and cerebrovascular risk factors. Gaseous contrast transcranial Doppler was used to diagnose right-to-left shunt and MRI to detect WML. All patients underwent blood test to evaluate peripheral alpha-gal activity and to identify alpha-gal gene mutations. Of 73 consecutive screened subjects (59 females, 14 males; mean age 38.3 +/- 11.8 years), the known GLA pathologic mutation p.[Asp313Tyr] was found in a 38-year-old woman, with a history of MA, deep venous thrombosis and abdominal pain. Cerebral MRI showed small WML. This is the first study reporting AFD prevalence in a cohort of MA patients. We found a relatively high prevalence (about 1.37%) among the examined patients, even if this finding needs to be confirmed in a larger sample. Despite this high prevalence, it seems not necessary to screen systematically all MA patients for AFD, but since it is a treatable genetic disorder, it is worthwhile to consider it for the subgroup of patients presenting WML and other typical AFD symptoms.

Carotid Stenting and Mechanical Thrombectomy in Patients with Acute Ischemic Stroke and Tandem Occlusions: Antithrombotic Treatment and Functional Outcome.

BACKGROUND AND PURPOSE: There is no consensus on the optimal antithrombotic medication for patients with acute ischemic stroke with anterior circulation tandem occlusions treated with emergent carotid stent placement and mechanical thrombectomy. The identification of factors influencing hemorrhagic risks can assist in creating appropriate therapeutic algorithms for such patients. This study aimed to investigate the impact of medical therapy on functional and safety outcomes in patients treated with carotid stent placement and mechanical thrombectomy for tandem occlusions. MATERIALS AND METHODS: A multicenter retrospective study on prospectively collected data was conducted. Only patients treated with carotid stent placement and mechanical thrombectomy for tandem occlusions of the anterior circulation were included. Univariate and multivariate analyses were performed on preprocedural, procedural, and postprocedural variables to assess factors influencing clinical outcome, symptomatic intracranial hemorrhage, stent patency, and successful intracranial vessel recanalization. RESULTS: Ninety-five patients with acute ischemic stroke and tandem occlusions were included. Good clinical outcome (mRS ≤ 2) at 3 months was reached by 33 (39.3%) patients and was associated with baseline ASPECTS ≥ 8 (OR = 1.53; 95% CI, 1.16-2.00), ≤2 mechanical thrombectomy attempts (OR = 0.71; 95% CI, 0.55-0.99), and the absence of symptomatic intracranial hemorrhage (OR = 0.13; 95% CI , 0.03-0.51). Symptomatic intracranial hemorrhage was associated with a higher amount of intraprocedural heparin, ASPECTS ≤ 7, and ≥3 mechanical thrombectomy attempts. No relationships among types of acute antiplatelet regimen, intravenous thrombolysis, and symptomatic intracranial hemorrhage were observed. Patients receiving dual-antiplatelet therapy after hemorrhagic transformation had been ruled out on 24-hour CT were more likely to achieve functional independence and had a lower risk of symptomatic intracranial hemorrhage. CONCLUSIONS: During carotid stent placement and mechanical thrombectomy for tandem occlusion treatment, higher intraprocedural heparin dosage (≥3000 IU) increased symptomatic intracranial hemorrhage risk when the initial ASPECTS was ≤7, and mechanical thrombectomy needs more than one passage for complete recanalization. Antiplatelets antiplatelets use were safe, and dual-antiaggregation therapy was related to better functional outcomes.

White matter lesions in migraine and right-to-left shunt: a conventional and diffusion MRI study.

Subjects with migraine with aura (MA) have a high prevalence of white matter lesions (WMLs) on magnetic resonance imaging (MRI). Moreover, right-to-left shunt (RILES), mainly due to patent foramen ovale, is frequently associated with MA. The aim of this study was to clarify the relationship between RILES and WML in MA. We enrolled 87 consecutive subjects affected by MA. Patients were screened for migraine characteristics and cerebrovascular risk factors. Transcranial Doppler was used to diagnose RILES and MRI with T2-weighted and diffusion-weighted imaging (DWI) to evaluate presence, number and volume of WMLs. RILES was present in 45% of patients. We did not detect any DWI hyperintense lesion; WMLs were present in 61% of patients on T2-weighted images. Presence of WMLs did not correlate with any migraine clinical feature, whereas the presence, number and volume of WMLs increased with subjects' age. There was no significant difference in the total volume and number of WMLs in the group with and without RILES. In conclusion, RILES does not increase the likelihood of finding WMLs in migraineurs.

Stroke due to atrial fibrillation and the attitude to prescribing anticoagulant prevention in Italy. A prospective study of a consecutive stroke population admitted to a comprehensive stroke unit.

BACKGROUND: Several studies have reported that oral anticoagulant prophylaxis (OAC) is under-used in patients with atrial fibrillation (AF). OBJECTIVE: This study investigated the attitude to prescribing OAC in patients with AF observed in an Italian Stroke Unit (SU) and the severity of ischemic stroke due to AF in comparison with that of other etiologies. METHODS: We prospectively studied a continuous series of acute stroke patients admitted to our SU from January 1, 2003 to December 31, 2005. Using Multiple Logistic Regression, we analyzed factors associated with the non-use of OAC and with poor prognosis. RESULTS: Of 400 consecutive ischemic stroke patients, 103 (25.75 %) had AF; this group was older (mean age+/-sd= 79.74 +/- 10.15 years vs. 73.49 +/- 12.72; P = 0.0000045) and their strokes were more severe (NIHSS median value = 10 vs. 7, P < 0.002) in comparison with the group of patients whose strokes were due to other etiologies. Only 27.27% of patients with known AF, and without contraindications, were under OAC before the onset of stroke. The main independent factor associated with the non-use of OAC was old age. Moreover, AF proved to be a significant independent predictor of poor prognosis in our stroke population. CONCLUSIONS: The results of this study indicate a marked under- use of OAC prophylaxis in AF subjects in Italy. Campaigns to raise awareness and to improve the implementation of guidelines on stroke prevention strategies are strongly recommended, not least because stroke due to AF has a worse prognosis.

Absence of hemispheric dominance for mental rotation ability: a transcranial Doppler study.

Mean blood flow velocity (MFV) of the middle cerebral arteries was monitored in 19 healthy, adult, right-handed subjects during the resting phase and the execution of a series of neuropsychological tests: two right/left discrimination tasks, two mental rotation paradigms (the Ratcliff's test and a cube comparison test) and a phonemic fluency task, which was utilised as an internal control. In the group as a whole, the Ratcliff's test was associated with a significant bilateral increase in MFV versus both the resting state (right: p < .000001, left: p < .000001) and right/left discrimination tasks (task 1: right: p = .003, left: p = .005; task 2: right: p = .001, left: p = .001). The cube comparison in turn produced a significant increase in MFV versus both the baseline conditions (right: p < .000001, left: p < .000001) and the Ratcliff's test (right: p = .01, left: p = .002). As expected, the fluency task was associated with a significant asymmetric increase in cerebral perfusion (left > right: p = .0001). Increasing task difficulty (right/left discrimination < Ratcliffs test < cube comparison) was paralleled by a roughly proportional rise in MFV values (right: r = .424, p < .01; left: r = .331, p = .01). In conclusion, we were able to demonstrate that (1) in addition to the amount of MFV variation due to right/left discrimination (when required), mental rotation per se causes a bihemispheric activation irrespective of the experimental paradigm; (2) the MFV variation is proportional to the difficulty of the tasks.

[Surgical management of asymptomatic carotid artery stenosis. Authors' experience, problems and prospectives]. / La chirurgia della stenosi carotidea asintomatica. Nostra esperienza, problemi e prospettive.

BACKGROUND: Some trials have demonstrated effectiveness of carotid endarterectomy (CEA) for preventing stroke in patients with severe symptomatic carotid stenosis. Although some researches, indication to surgery for asymptomatic carotid stenosis is debated up today. Based on personal experience and literature, the main problems of CEA for asymptomatic stenosis are discussed. DESIGN: Retrospective study. SETTING: Section of Vascular Surgery, University Department. PATIENTS: CEA was performed in a consecutive series of 63 cases with asymptomatic stenosis (59 patients, 40 males and 19 females, ages ranging from 46 to 80 years, mean 67.9). INTERVENTIONS: CEA was performed under general anesthesia, with primary closure of arteriotomy in 37 cases and patch angioplasty using PTFE in 24, using eversion technique in 2 cases. Pruitt-Inahara shunt was used in 10/63 cases (15.9%), according to the mean velocity of the middle cerebral artery at carotid clamping/mean velocity of the middle cerebral artery pre-clamping ratio x 100 equal to or lesser than 15%, evaluated with transcranial Doppler, or stump pressure lesser than 50 mmHg, when transcranial Doppler examination was not possible. MEASURES: Operative mortality and postoperative morbidity. RESULTS: Operative mortality plus postoperative stroke were 1.6% (1/63). Operative mortality was precisely 0.0%. Postoperative complications were two: one was a neurologic deficit (monoparesis of the arm) and the other was myocardial ischemia. CONCLUSIONS: Four main problems have been shown in CEA for asymptomatic stenosis: 1. Identification of asymptomatic stenosis: 2. Assessment of risk for stroke: 3. Role of CEA: 4. Questions about surgical treatment. For the first problem, it is important to consider possible indicators for carotid stenosis (contralateral carotid stenosis, coronary artery disease, aortic aneurysm, peripheral arterial disease, etc.). With regard to the second problem, it is important to know the natural history of the carotid stenosis, which shows a stroke rate of 1-2% per year. Regarding the third problem, the role of CEA is conditioned by: trials, patient conditions, lesion characteristics and ability of the surgeon. Further studies should identify some groups of patients (with severe carotid stenosis, dyshomogeneous plaque, progression of plaque, etc.), who can profit from CEA. Finally (fourth problem), CEA for asymptomatic carotid stenosis carries all common problems of carotid surgery (preoperative assessment, evaluation of cerebral ischemia due to carotid clamping, shunt, closure of arteriotomy, etc.). Some of these problems can receive ultimate solutions from some studies in next years.

Right-to-left shunt does not increase white matter lesion load in migraine with aura patients.

BACKGROUND: White matter lesions (WMLs) are commonly found on brain MRI of migraine patients. Migraine with aura (MA+) is associated with an increased frequency of right-to-left shunt (RLS) mostly due to patent foramen ovale. The relationship between WML load and RLS in MA+ is currently unknown. METHODS: MA+ patients were consecutively enrolled as part of the Shunt Associated Migraine (SAM) study. Patients underwent a standardized headache and vascular risk factors questionnaire, contrast-enhanced transcranial Doppler, blood coagulation tests, and brain MRI. RLS was categorized into four grades: no shunt, <10 microbubbles (mb), >10 mb single spikes pattern, and >10 mb shower/curtain pattern. Standard and fluid-attenuated inversion recovery T2-weighted MRI sequences were inspected for WMLs by three independent raters blinded to RLS grade. WML load was scored in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Scheltens scale. Interobserver agreement was good to excellent (kappa = 0.64 to 0.96, p < 0.0001). WML load was then correlated between patients with and without RLS. RESULTS: One hundred eighty-five patients (77% women) were included. PV-WML load was similar between patients with and without RLS. D-WML load decreased in patients with RLS (p = 0.045). On logistic regression analysis, only age was associated with WMLs (p < 0.001). CONCLUSIONS: The presence of right-to-left shunt does not increase white matter lesion load in patients who have migraine with aura.

Abnormalities of Na/K ATPase in migraine with aura.

It has been previously shown from our laboratory that abnormal functioning of Na/K ATPase can cause spreading depression, the likely mechanism of migraine aura. We used lymphocytes to investigate whether or not membrane Na/K ATPase is altered in migraine with aura patients. Lymphocytes were prepared from such patients, aged 20-45 years, and from age-matched healthy volunteers (controls). The binding of 3H- ouabain was studied using increasing concentrations (0.5-25 nm) of this radioligand, specific for Na/K-ATPase. We studied 19 migraine with aura patients and 22 healthy volunteers, matched for age and sex. B(max) (fmol/mg protein) and K(D) (nM) were not different between patients and controls. However, their ratio (B(max)/K(D)) was higher in patients than in controls. B(max) was (mean +/- SD) 270 +/- 110 fmol/mg protein in controls, and 360 +/- 230 in migraine with aura patients (P = 0.10, t-test). K(D) was (mean +/- SD) 2.8 +/- 1.5 nm in controls, and 2.9 +/- 3.2 nm in migraine with aura patients (P = 0.88, t-test). B(max)/K(D) was (mean +/- SD) 120 +/- 78 in controls, and 210 +/- 190 in migraine patients (P = 0.046, t-test). Moreover, no control patient had a B(max)/K(D) ratio greater than 398, while three migraine patients had ratios of 417, 572 and 722, respectively. Ouabain binding is affected by Na/K ATPase structure (K(D)) and expression (B(max)). While these parameters were not altered in migraine with aura patients, the difference in their ratio suggests an imbalance between the enzyme's ouabain affinity and its expression, with higher-affinity subtypes being more expressed than normal. Moreover, single patients had values quite different from the control population. Our data suggest that (i) ouabain binding to lymphocyte membranes may be a useful tool in the diagnosis of migraine with aura and (ii) Na/K ATPase abnormalities may be involved in migraine aura.

White blood cell count and erythrocyte sedimentation rate correlate with outcome in patients with acute ischemic stroke.

We studied white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) in 241 consecutive patients with acute ischemic stroke. White cell count was elevated in 20% of the patients, ESR was elevated in 68%. Each increase significantly correlated with outcome, as evaluated by either lesion size at CT scan or by score at the Rankin disability scale at the time of discharge. This correlation was stronger for WBC count than for ESR. These routine blood tests may be useful adjuncts in determining stroke prognosis.

Cluster headache and right-to-left shunt on contrast transcranial Doppler: a case-control study.

The authors evaluated the prevalence of right-to-left shunt in 40 subjects with cluster headache (CH) vs 40 subjects without primary headaches or cerebrovascular disease. The diagnosis of shunt was made by means of transcranial Doppler with contrast medium. A shunt was found in 17 CH patients (42.5%) and in 7 controls (17.5%) (p = 0.029; OR = 3.48; 95% CI = 1.13 to 10.69).

Silent cerebral infarcts in patients with ischemic infarction.

Silent cerebral infarcts occur in patients with chronic nonvalvular atrial fibrillation and asymptomatic or symptomatic carotid stenosis. There is not a well-defined prevalence of asymptomatic lesions in patients with transient ischemic attack or completed strokes. We attempted to determine the occurrence rate of silent brain infarction in a hospital population, including a comparison of the risk factors with those of symptomatic infarction and an evaluation of the relevance of infarction size and location.

Microembolic signals with serial transcranial Doppler monitoring in acute focal ischemic deficit. A local phenomenon?

BACKGROUND AND PURPOSE: The occurrence of microembolic signals (MES) in patients with transient ischemic attack (TIA) or stroke has already been described, but the diagnostic and prognostic value of this finding is still debated. METHODS: We evaluated 90 consecutive patients admitted for their first hemispheric TIA or ischemic stroke within 72 hours of onset. All of them underwent 30-minute bilateral transcranial Doppler monitoring of middle cerebral arteries, within 72 hours of onset. The monitoring was repeated after an additional 24 hours and after 7 days. We then classified the episodes in the following etiologic categories: cardioembolic, atherothrombotic, small-vessel disease, mixed cases, unknown origin, and other causes. RESULTS: We included 75 patients, with a mean interval of registration of 32.04 +/- 19.39 hours. There were 9 patients with MES (12%). All MES were recorded only on the symptomatic middle cerebral artery, and the majority were recorded during the first or the second registration. No statistically significant difference was found in risk factors and hematologic parameters. Five patients (56%) had atherothrombotic episodes, 3 patients (33%) had cardioembolic episodes, and 1 patient (11%) had a protein S deficit. No patient with MES had small-vessel disease (P = .01). CONCLUSIONS: MES are an infrequent finding in patients with TIA or ischemic stroke within 72 hours of onset, but they can be recorded more easily with serial registration. In our patients, MES were found only on the symptomatic middle cerebral artery and were present in atherothrombotic and cardioembolic episodes but not in small-vessel disease.

Value of early variables as predictors of short-term outcome in patients with acute focal cerebral ischemia.

Reliable, simple and safe criteria are needed for the early prediction of short-term outcome in patients with acute ischemic stroke. The aim of our study was to evaluate, in terms of their individual and combined power, the prognostic value of a few widely available clinical and instrumental variables obtained during the acute phase. The study involved 351 consecutive patients who were examined within 48 hours of their first ischemic stroke. Eight variables were chosen: age, initial level of consciousness, limb paresis, arterial blood pressure, glycemia, the results of electrocardiography and electroencephalography, and the infarct size revealed by computed tomography. Mortality and disability were evaluated on Day 30, when the variables that significantly correlated with disability were the severity of limb paresis, electroencephalographic abnormalities, infarct size and (less significantly) the level of consciousness and hyperglycemia. There was no statistical correlation with blood pressure. Logistic analysis confirmed only infarct size, the severity of limb paresis and electroencephalographic abnormalities as independent variables. The variables that significantly correlated with early death were the severity of limb paresis, infarct size, electrocardiographic abnormalities, the level of consciousness, electroencephalographic abnormalities and hyperglycemia. More intriguingly, logistic analysis confirmed only the electroencephalographic and electrocardiographic abnormalities as independent variables. The predictive prognostic value of limb paresis, infarct size, the level of consciousness and hyperglycemia is well known, but we would like to stress the fact that only a few independent variables are predictive of early death (electroencephalographic and electrocardiographic abnormalities) and poor recovery (infarct size, the severity of limb paresis, electroencephalographic abnormalities). The prognostic value of electroencephalography may express the potential involvement of dynamic non-structural phenomena, such as penumbra ischemica and diaschisis.

Asymptomatic cerebral infarctions in patients with ischemic stroke.

We studied 383 consecutive patients with stroke and ischemic lesions on CT scan for the presence of symptomatic cerebral infarction (SCI) and asymptomatic cerebral infarction (ACI). We evaluated risk factors as well as volume, site and number of the lesions. ACIs occurred in 34% of the cases (130/383); 88% of ACIs were lacunes and internal borderzone infarctions, with a volume of less than 2 ml. Larger infarctions were asymptomatic in 27 patients (20.8%); 114 (68.7%) out of 166 patients with two or more SCIs (68.7%) had one or more ACIs. Infarctions in the lateral middle cerebral artery (MCA) territory were SCIs, in the medial MCA territory ACIs. Independent risk factors for ACI were age above 70 years and smoking; cardioembolism prevailed in SCI, small vessel disease in ACI; high levels of disability prevailed in SCIs.

Bilateral ophthalmoplegia: an unusual sign of the top of the basilar artery syndrome.

Bilateral ophthalmoplegia may be an unusual sign of vertebrobasilar ischemia. We report the cases of two patients (75 and 73 years old), who suddenly developed drowsiness, bilateral ophthalmoplegia with bilateral ptosis and mild right hemiparesis. In both patients, MRI revealed bilateral thalamic and midbrain infarcts, ECG showed the presence of atrial fibrillation and Doppler study of the extracranial and intracranial vertebral arteries found no significant alterations. Ischemia involving the midbrain and thalamic paramedian regions may cause bilateral ophthalmoplegia and consciousness disturbances. In these two cases, the most plausible etiologic mechanism was cardiac embolism, and the prognosis for bilateral ocular palsy was poor.