Cerebral haemodynamics in early puerperium: A prospective study.

AIM: Prospective study on 900 consecutive puerperae to assess normal values and range of the blood flow velocity in the middle cerebral artery in both hemispheres. MATERIAL AND METHOD: M1 and M2 segments of both middle cerebral arteries were assessed in all subjects within 96 hours of delivery. Mean flow velocity was recorded after adjusting for insonation angle. Lindegaard index (LI = middle cerebral artery-Internal Carotid Artery mean flow velocity ratio) was calculated whenever the mean flow velocity exceeded 100 cm/second. Asymmetry indexes were calculated inter hemispherically for M1 and M2 segments separately. RESULTS: Mean flow velocities were 74 ± 17 and 72 ± 17 in right and 73 ± 17 and 72 ± 17 cm/second in the left M1 and M2, respectively. A total of 136 subjects (12.1%) exceeded the threshold of 100 cm/second, but LI was consistently <3 in all of them. Mean flow velocity was inversely and independently correlated to haemoglobin levels and to parity. Mean asymmetry indexes were 0.25 ± 23 in M1 and 0.45 ± 25 in M2. CONCLUSION: Mean flow velocity in the middle cerebral artery of healthy subjects in early puerperium is higher than in age-matched non-puerperal women and may exceed the threshold of 100 cm/second with no evidence of intracranial spasm, because of blood loss during delivery. Mean flow velocity is independently correlated with parity. Right-to-left mean flow velocity asymmetry may reach 50% as a consequence of a transient imbalance in vascular tone regulation.

Is the search for right-to-left shunt still worthwhile?

OBJECTIVES: Patent foramen ovale (PFO) is a common disembryogenic defect with well-attested prevalence but dubious etiopathogenetic linkage with cryptogenic stroke and different clinical conditions. Transcranial color-coded Doppler (TCCD) assures high accuracy in diagnosing right-to-left shunt (RLS) and its functional aspects. Aim of the study was to evaluate RLS prevalence and degree in subjects submitted to TCCD for conditions theoretically associated or caused by paradoxical embolism to the brain. METHODS: PFO assessment, performed in 10 major diagnostic categories and a control group, followed a standardized protocol with a 10 or 20 microbubbles (MB) cutoff to identify any or only large RLS, respectively. RESULTS: Among 2113 patients, a significant larger RLS prevalence was found in stroke (53.3%), TIA (45.7%) and migraine with aura (39.7%) when compared with non-migraineurs controls (25.5%). RLS degree was significantly higher in stroke and TIA patients: The ROC curve from MB load data helped to identify new cutoff values for both normal breathing (42 MB) and Valsalva (139 MB) tests. From logistic regression, a family history for PFO, ASA, and male gender appeared independent predictors of a RLS. By contrast, RLS seemed independent of white matter abnormalities presence on brain neuroimaging or stroke mimics. CONCLUSIONS: In addition to recently defined criteria, genetically determined inheritable traits and epidemiologic characteristics (male gender) should be taken into account when assessing PFO and related cerebrovascular risk profile. A newly defined threshold in TCCD MB count is suggested to discriminate shunts related to stroke and TIA from innocent ones.

Neuropathy in eosinophilic granulomatosis with polyangiitis: a comparison study of 24 cases with or without prior leukotriene antagonist exposure.

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome (CSS), is a systemic vasculitis affecting almost exclusively patients with asthma. Neuropathy is the presenting feature in 55-75 % of cases. An increased incidence of the syndrome has been reported in asthmatics treated with leukotriene antagonists (LTAs). The causal relation is still debated. We retrospectively examined clinical, biochemical, histological features, and outcome of patients referred between 1990 and 2006 for sural nerve biopsy affected by neuropathy related to EGPA. We identified 24 patients, 6 treated with LTA montelukast (T-group) and 18 not treated (NT-Group). All had chronic asthma; in T-group neuropathy developed from 1 to 150 days after starting montelukast. Demographic features as well as asthma duration and pre-onset treatment were remarkably similar, with the only exception of a statistically nonsignificant larger involvement of the nasal mucosa in T group. Nerve biopsy revealed in both group an axonal neuropathy. At follow-up, all within the T-group and most within the NT-group improved clinically; neurophysiological parameters remained stable, improved or worsened in the same proportion within the two groups. Only 2 NT and no T-patient had stopped steroid treatment before the appearance of the peripheral neuropathy, making withdrawal overall unlikely as a causative factor of the onset of neuropathy. In summary, the temporal relationship between montelukast administration and the onset of neuropathy, would make the latter more likely as an "adverse drug reaction". Despite this, no significant clinical neither neurophysiological differences were noted between the two groups.

Autonomic dysfunction in mild cognitive impairment: a transcranial Doppler study.

OBJECTIVES: The contribution of early microvascular and autonomic derangements to the pathogenesis of mild cognitive impairment (MCI) is unclear. Aim of this study is to evaluate cerebrovascular reactivity (CVR) and cardiac autonomic function in patients with MCI by means of transcranial Doppler (TCD). MATERIAL AND METHODS: Fifteen patients with MCI and 28 controls underwent carotid ultrasound and TCD evaluation, including assessment of mean flow velocity (MFV) in the middle cerebral artery at baseline, after CO(2) inhalation and after hyperpnoea. End-tidal CO(2) , mean arterial blood pressure (MAP), heart rate (HR), and respiratory rate were monitored throughout the procedure, and CVR was calculated. RESULTS: MAP, end-tidal CO(2) , and MFV variations during hypercapnia and hyperventilation showed no between-group differences. CVR was similar in controls and MCI (2.30 vs 2,39, respectively, P = 0.767). HR significantly increased in hypercapnia (+9.4%, P < 0.0001) and hyperventilation (+18.7%, P < 0.0001) in controls, while in MCI it significantly increased in hyperventilation (+10.4%, P = 0.002), but not in hypercapnia (+1.1%, P = 0.635). CONCLUSIONS: This study demonstrates that patients with MCI have a normal CVR, but they exhibit signs of autonomic dysfunction after CO(2) challenge. Should this finding be confirmed in larger studies, HR response to CO(2) challenge could become a marker of MCI.

Cerebral distribution of white matter lesions in migraine with aura patients.

OBJECTIVE: The objective of the study was to compare the cerebral distribution of white matter lesions (WMLs) between migraine patients with different aura symptoms. METHODS: Migraine with aura (MA) patients were consecutively enrolled as part of the Shunt-Associated Migraine (SAM) study. According to clinical symptoms, aura was classified as motor, aphasic, sensory, visual or vertebrobasilar. Standard and FLAIR (fluid attenuated inversion recovery) T(2)-weighted MRI sequences were inspected for WMLs by three independent raters blinded to clinical data. WMLs were assessed in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Schelten's scale. Interobserver agreement was good to excellent (k = 0.64 to 0.96, p < .0001). RESULTS: One hundred and eighty-five patients (77% women) were included. Aura symptoms were classified as visual in 172 (99%) patients, sensory in 76 (42%), aphasic in 54 (30%), motor in 39 (21%) and vertebrobasilar in 17 (9%) patients. One hundred and four patients (57%) exhibited more than one type of aura. D-WMLs were mainly detected in the frontal lobes (86%). There was no association between type of aura and the presence of WMLs in any cerebral location. CONCLUSION: Aura symptoms do not influence the cerebral distribution of WMLs associated with migraine disease.

Evaluating endothelial function of the common carotid artery: an in vivo human model.

BACKGROUND AND AIMS: Flow mediated dilation (FMD) of peripheral conduit arteries is a well-established tool to evaluate endothelial function. The aims of this study are to apply the FMD model to cerebral circulation by using acetazolamide (ACZ)-induced intracranial vasodilation as a stimulus to increase common carotid artery (CCA) diameter in response to a local increase of blood flow velocity (BFV). METHODS AND RESULTS: In 15 healthy subjects, CCA end-diastolic diameter and BFV, middle cerebral artery (MCA) BFV and mean arterial blood pressure (MBP) were measured at basal conditions, after an intravenous bolus of 1g ACZ, and after placebo (saline) sublingual administration at the 15th and 20th minute. In a separate session, the same parameters were evaluated after placebo (saline) infusion instead of ACZ and after 10 microg/m(2) bs and 300 microg of glyceryl trinitrate (GTN), administered sublingually, at the 15th and 20th minute, respectively. After ACZ bolus, there was a 35% maximal MCA mean BFV increment (14th minute), together with a 22% increase of mean CCA end-diastolic BFV and a CCA diameter increment of 3.9% at the 3rd minute (p=0.024). There were no MBP significant variations up to the 15th minute (p=0.35). After GTN administration, there was a significant increment in CCA diameter (p<0.00001). CONCLUSIONS: ACZ causes a detectable CCA dilation in healthy individuals concomitantly with an increase in BFV. Upon demonstration that this phenomenon is endothelium dependent, this experimental model might become a valuable tool to assess endothelial function in the carotid artery.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and right-to-left shunt: lack of evidence for an association in a prevalence study.

BACKGROUND/AIMS: Up to more than 50% of cryptogenetic stroke patients and patients with migraine with aura (MA) are found to have a right-to-left shunt (RLS), which is usually due to a patent foramen ovale. Moreover, both MA and stroke are cardinal features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Notch3 mutations have been suggested to induce an abnormally high incidence of atrial septal defects in a family harbouring an Arg141Cys pathogenetic mutation. We sought to determine the prevalence of RLS in CADASIL patients with different Notch3 mutations, both with and without migraine as a clinical feature. METHODS: Subjects with a molecular diagnosis of CADASIL were tested for the presence of an RLS by means of contrast-enhanced transcranial Doppler (TCD). The diagnosis of migraine was made according to the 2004 International Headache Classification. RESULTS: Sixteen CADASIL patients were tested; 6 had MA. Four patients displayed an RLS on contrast-enhanced TCD examination. Three of these patients had MA. Both patients with Arg141Cys displayed a large RLS. CONCLUSION: We conclude that RLS is not necessarily linked to CADASIL as a comorbidity factor. Nevertheless, there could be a relation between RLS and specific Notch3 mutations, such as Arg141Cys.

Predictors of carotid clamping intolerance during endarterectomy that would be wise to apply to stenting procedures.

BACKGROUND AND PURPOSE: Carotid artery stenting procedures are increasingly being performed with devices such as the MO.MA or the Parodi system that involve endovascular clamping of the common carotid artery, thus exposing the ipsilateral hemisphere to the risk of hypoperfusion. The aim of the present study was to look for predictors of carotid clamping intolerance by means of transcranial Doppler. PATIENTS AND METHODS: We analysed the findings of an earlier Italian multicentre prospective study (SCITEA, Italian Cooperative Study of Transcranial Doppler in Carotid Endarterectomy) in which 513 consecutive patients (males/females 397/116, mean age 67 +/- 7 years, mean carotid stenosis 81 +/- 11%, NASCET method) scheduled to undergo carotid endarterectomy had been investigated non-invasively with transcranial Doppler, and we correlated the data obtained preoperatively with the need to insert a shunt during surgery as an index of intolerance to carotid clamping. RESULTS: Four hundred and thirty-nine patients (85.6%) underwent surgery without and 74 (14.4%) with the insertion of a shunt. Patients who needed a shunt (intolerant) had a significantly higher decrement in mean flow velocity in the ipsilateral middle cerebral artery (MCA) after compression of the ipsilateral common carotid artery (71.8 +/- 22 vs. 30.6 +/- 24%) and were significantly more likely to have non-recruitable collateral pathways (75 vs. 18%). Logistic regression analysis confirmed that an MCA decrement of >85% (p = 0.005) and no potential collateralization (p = 0.011) were independent predictors of clamping intolerance. Combining the results of both compression tests (MCA decrement and collateral recruitment) yielded a sensitivity of 64%, a specificity of 99%, a positive predicted value of 88%, a negative predicted value of 95% and an overall accuracy of 95% in predicting shunt insertion. CONCLUSIONS: The preoperative assessment of recruitable collaterals and of maximal decrement in MCA mean flow velocity after carotid compression are useful predictors of carotid clamping intolerance. The criteria derived from carotid endarterectomy need to be applied and validated in a prospective series of patients undergoing carotid artery stenting procedures.

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.

Is migraine associated with right-to-left shunt a separate disease? Results of the SAM study.

Migraine with aura (MA) is associated with the persistence of patent foramen ovale (PFO) in about 50% of cases, and migraineurs tend to have larger shunts than controls, suggesting that right-to-left shunt (RILES) determined by PFO could play a role in triggering migraine attacks. Moreover, some preliminary reports have suggested that PFO closure may give relief to both migraine and aura attacks. The aim of this study was to clarify if shunt-associated migraine (SAM) has clinical features that allow a distinction from shunt-unrelated migraine (SUM), in a prospective, multicentre, observational study (SAM study). We enrolled consecutive MA patients, who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. All were systematically screened for RILES with transcranial Doppler, and for coagulation disorders. Overall, 460 patients were included; the SUM and SAM classes comprised 58% and 42% of patients, respectively. SAM patients were significantly younger (34.1 +/- 10 vs. 37.1 +/- 11 years), had a more frequent family history of migraine (76% vs. 66%) and a higher frequency of sensory symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of SAM with other cardiac abnormalities and with coagulation disorders. The SAM study suggests that the effect of RILES on migraine features is not relevant. The higher family history of migraine in SAM suggests a possible genetic linkage between migraine and RILES.

Silent brain embolism during transcatheter closure of patent foramen ovale: a transcranial Doppler study.

The aim of this report is to quantify the amount of spontaneous microembolism detected in brain vessels by transcranial Doppler (TCD) during transcatheter closure of right-to-left shunt (RLS). We examined 29 patients who had had a stroke or a transient ischaemic attack (17 females and 12 males; mean age 45+/-15 years). They all underwent TCD monitoring during the procedure and microembolic signals (MES) were recorded. Detection of MES was distributed as follows: during femoral catheterisation in 8 patients (25%), during atrial catheterisation in 5 patients (17%), during transeptal crossing in 14 patients (48%), during left disc opening in 28 patients (96%) and during right disc opening in 7 patients (24%). The highest rates of MES were observed during left disc opening and less during transeptal crossing with an average count of 31 (range 3-135) and 3 (range 1-18) respectively. Brain embolism occurs throughout the procedure after femoral catheterisation for PFO closure. Our results indicate that the majority of MES reached the brain during the opening of the left disc in the left atrium: 28/29 patients exhibited MES with an average of 31 (3-135), thus supporting the notion that gas embolism accounted for the findings.

Migraine: traditional or "innovative" treatment? A preliminary case-control study.

The aim of this preliminary case-control study was to compare, in patients with migraine and PFO, transcatheter closure of PFO vs. medical treatments. Twelve patients were treated with antimigraine drugs and twelve underwent percutaneous transcatheter closure. All patients were followed-up for 12 months. Our preliminary results seem to confirm that, compared to medical treatment, PFO closure is by far more effective in reducing both frequency, duration and intensity of migraine attacks. Furthermore, the occurrence of prodromal aura is almost abolished.

Does transcatheter closure of patent foramen ovale really "shut the door?" A prospective study with transcranial Doppler.

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) is increasingly being performed and monitored with transthoracic or transesophageal echocardiography, whereas contrast-enhanced transcranial Doppler (ce-TCD), which probably represents the most suitable tool to quantify right-to-left shunt (RLS) in the brain vessels, has been systematically overlooked. Our goal is to prospectively assess efficacy and safety of PFO transcatheter closure using ce-TCD. METHODS: A total of 140 consecutive patients (mean age, 46+/-13 years; male/female ratio, 63/77) with PFO-related large RLS and no other recognized cause of focal cerebral ischemia underwent transcatheter closure. TCD was done preoperatively and 1 month after the procedure in all patients, after 3 months in 120, after 6 months in 112, and after 1 year in 104 patients. RESULTS: Implantation was successful in all patients. During Valsalva strain, a large shunt was still detectable in 31 of 140 (22%), 15 of 120 (13%), 9 of 112 (8%), and 9 of 104 (9%) patients at the 1-, 3-, 6-, and 12-month visits, respectively. Periprocedural and postprocedural complications included atrial fibrillation in 8% and scintillating scotomata in 6% of patients. During the 1-year follow-up period, only 1 transient ischemic attack was recorded in a patient with paroxysmal atrial fibrillation and complete PFO closure. CONCLUSIONS: Transcatheter PFO closure in patients with cryptogenic stroke and large RLS may be less successful than reported previously. TCD appears the ideal tool to follow up the closure process and to identify early, during follow-up, those patients who will be left with a significant shunt. Atrial fibrillation is more common than believed previously and may underlie the occurrence of further cerebrovascular events despite complete PFO closure. Irritative visual phenomena may occur as a consequence of nickel toxicity.

Transcranial Doppler and risk of recurrence in patients with stroke and patent foramen ovale.

The importance of patent foramen ovale (PFO) in stroke of unknown cause remains disputed, as PFO may be present in up to 20% of normal people and in a high proportion of patients with non-vascular disorders. Recent evidence suggests that the amount of right-to-left shunt (RLS) may be the crucial factor for stroke occurrence and relapse. The aim of the study was to assess predictors of recurrence in PFO-related stroke patients with particular emphasis on amount of shunting. Patients less than 61 years old who had been admitted for a PFO-related stroke within the previous 5 years, were re-evaluated on a follow-up visit. The clinical syndrome, residual disability, vascular risk factors and number of relapses as the index event were assessed. RLS sizing was semi-quantitatively performed with saline-enhanced transcranial Doppler (TCD), by assuming a cut-off of more or less 10 bubbles recorded in the cerebral vessels as a criterion to discriminate large versus small shunt, respectively. Thereafter patients were prospectively followed-up for a median time of 23 months. Total follow-up was 61 months. Fifty-nine patients (M/F = 23/36, mean age 43 +/- 13) were studied. Overall there were 23 relapses in 13 patients. The amount of shunting was the only significant independent variable associated with relapse: at the end of the follow-up period the recurrence rate was 0.66 and 8.2% per patient per year in patients with small and large shunt, respectively. This difference was statistically significant (chi2 = 10.39, P = 0.0012; OR 17.05, 95% CI 2.10-755.22). In patients with PFO-related stroke, the amount of RLS as assessed with TCD is the only independent predictor of relapse. PFO sizing is mandatory in patients with PFO.

Transient global amnesia: a clinical and sonographic study.

BACKGROUND: The aetiology of transient global amnesia (TGA) is still unknown. The aim of this study was to identify potential risk factors for TGA, vascular risk factors, the role of patent foramen ovale (PFO) and of retrograde jugular venous flow. METHODS: 138 subjects entered the study, including 48 patients with TGA, 42 age-matched patients with transient ischaemic attack (TIA) and 48 controls. PFO was studied by contrast transcranial duplex sonography. Retrograde jugular venous flow was tested with air contrast ultrasound venography (ACUV). RESULTS: TGA patients and controls showed a lower prevalence for vascular risk factors than TIA patients. No statistical difference was found between the 3 groups with regard to PFO. ACUV detected jugular valve incompetence in 72.9% TGA, 35.7% TIA and 39.5% controls (TGA vs. TIA and TGA vs. controls p < 0.01). CONCLUSIONS: TGA patients have fewer vascular risk factors than TIA patients. Paradoxical embolism due to PFO as a cause of TGA is not confirmed in our study. Cerebral venous hypertension due to incompetence of the internal jugular valve may play a role in the pathogenesis of TGA.