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Patent foramen ovale (PFO) is the most common congenital cardiac abnormality found approximately in 25% of the adult population The pathophysiological role of paradoxical embolization through the PFO in ischemic stroke is well established. "Self-expanding double disk" and, more recently, suture-based "deviceless" systems are used for PFO closure in the setting of secondary prevention after ischemic stroke likely related to paradoxical embolization. Ultrasound plays a significant role in PFO assessment, indication to treatment, intra-procedural guidance, and follow-up for those undergoing PFO closure. Three different techniques are frequently used for these purposes: transesophageal echocardiography, transthoracic echocardiogram, and transcranial Doppler. In this review, advantages and limits of these techniques are discussed in detail to improve our skills in detection and treatment of this important condition by using ultrasound.

Background and purpose Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. Methods We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. Results We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. Conclusions GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

Background and purpose Stroke-associated pneumonia (SAP) affects 10 to 38% of patients in the acute phase of stroke. Stroke patients diagnosed with dysphagia have an 11-fold higher risk of developing SAP. Thus, identifying dysphagic patients through a highly accurate screening tool might be crucial in reducing the incidence of SAP. We present a case–control study designed to evaluate efficacy in reducing the risk of SAP between two swallowing screening tools, the classic water swallow test (WST) and a recently validated tool such as the GLOBE-3S (the Sapienza GLObal Bedside Evaluation of Swallowing after Stroke), which is a highly sensitive swallowing screening tool particularly accurate in detecting silent aspiration as well. Methods We analyzed the occurrence of dysphagia in 100 acute stroke patients distributed in two groups: half were screened with WST and the other half with GLOBE-3S. Results Dysphagia was diagnosed in 28 patients. The main result is that, among patients who passed the dysphagia screenings, none of those screened with the GLOBE-3S method developed pneumonia compared to 31.82% in the WST group. Discriminant function analysis (DFA) showed that NIH Stroke Scale (NIHSS) score and the dysphagia screening method (i.e., GLOBE-3S vs. WST) were the two main factors in the SAP’s predicting model and the only significant ones per se. Conclusions The new GLOBE-3S screening test can reduce the risk of SAP compared to WST.

Introduction: Since cognitive impairment (CI) occurs on average in 45% of multiple sclerosis (MS) patients, the early detection of patients “at risk” of CI is important in order to promptly apply preventive strategies. The aim of the present study was to investigate the prevalence and risk factors for CI in MS patients using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) as a screening test. Methods: During the 1-year period, CI was evaluated in 82 consecutives mild relapsing-remitting MS (EDSS ≤ 3.5) patients. Patients with 1 altered BICAMS test were defined “at risk.” Both “at risk” and CI patients underwent an extensive neuropsychological battery. Results: We found that: (i) 23% had CI, (ii), 25% were “at risk” of CI, and (iii) 76% of the “at risk” patients were already impaired at the NP assessment. In particular, the Symbol Digit Modalities Test was the most compromised (70% of “at risk” and 79% of CI patients). Patients with CI had more frequently an EDSS ≥ 2.5 (p = 0.05), lower education (p = 0.05), and relapses in the last 12 months (p = 0.03). Conclusions: CI is a significant issue in MS and integration of a screening test, such as the SDMT, into routine clinical practice could be of worth to identify “at risk” patients and to promote an early therapeutic intervention.

Recent evidence indicates that transcranial ultrasound stimulation (TUS) modulates sensorimotor cortex excitability. However, no study has assessed possible TUS effects on the excitability of deeper brain areas, such as the brainstem. In this study, we investigated whether TUS delivered on the substantia nigra, superior colliculus, and nucleus raphe magnus modulates the excitability of trigeminal blink reflex, a reliable neurophysiological technique to assess brainstem functions in humans. The recovery cycle of the trigeminal blink reflex (interstimulus intervals of 250 and 500 ms) was tested before (T0), and 3 (T1) and 30 min (T2) after TUS. The effects of substantia nigra-TUS, superior colliculus-TUS, nucleus raphe magnus-TUS and sham-TUS were assessed in separate and randomized sessions. In the superior colliculus-TUS session, the conditioned R2 area increased at T1 compared with T0, while T2 and T0 values did not differ. Results were independent of the interstimulus intervals tested and were not related to trigeminal blink reflex baseline (T0) excitability. Conversely, the conditioned R2 area was comparable at T0, T1, and T2 in the nucleus raphe magnus-TUS and substantia nigra-TUS sessions. Our findings demonstrate that the excitability of brainstem circuits, as evaluated by testing the recovery cycle of the trigeminal blink reflex, can be increased by TUS. This result may reflect the modulation of inhibitory interneurons within the superior colliculus.

Background. The increase of the optic nerve sheath diameter (ONSD) is a reliable, noninvasive sonographic marker of intracranial hypertension. Aim of the study was to demonstrate the efficacy of ONSD evaluation, when monitoring neurocritical patients, to early identify malignant intracranial hypertension in patients with brain death (BD).Methods. Data from ultrasound ONSD evaluation have been retrospectively analyzed in 21 sedated critical patients with neurological diseases who, during their clinical course, developed BD. 31 nonneurological controls were used for standard ONSD reference.Results. Patients with neurological diseases, before BD, showed higher ONSD values than control group (CTRL: RT0.45±0.03 cm; LT0.45±0.02 cm; pre-BD: RT0.54±0.02 cm; LT0.55±0.02 cm;p<0.000) even without intracranial hypertension, evaluated with invasive monitoring. ONSD was further significantly markedly increased in respect to the pre-BD evaluation in neurocritical patients after BD, with mean values above 0.7 cm (RT0.7±0.02 cm; LT0.71±0.02 cm;p<0.000), with a corresponding dramatic raise in intracranial pressure. Logistic regression analysis showed a strong correlation between ONSD and ICP (R0,895,p<0.001).Conclusions. ONSD is a reliable marker of intracranial hypertension, easy to be performed with a minimal training. Routine ONSD daily monitoring could be of help in Intensive Care Units when invasive intracranial pressure monitoring is not available, to early recognize intracranial hypertension and to suspect BD in neurocritical patients.

Background. We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment.Methods. We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment.Results. Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-a [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence.Conclusions. These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis.EU Clinical trialis registered with EudraCT Number:2005-000996-16; Sponsor Protocol Number: 694/30.06.04.

Background Therapeutic management of Chronic Migraine (CM), often associated with Medication Overuse Headache (MOH), is chiefly empirical, as no biomarker predicting or correlating with clinical efficacy is available to address therapeutic choices. The present study searched for neurophysiological correlates of Greater Occipital Nerve Block (GON-B) effects in CM. Methods We recruited 17 CM women, of whom 12 with MOH, and 19 healthy volunteers (HV). Patients had no preventive treatment since at least 3 months. After a 30-day baseline, they received a bilateral betamethasone-lidocaine GON-B of which the therapeutic effect was assessed 1 month later. Habituation of visual evoked potentials (VEP) and intensity dependence of auditory evoked potentials (IDAP) were recorded before and 1 week after the GON-B. Results At baseline, CM patients had a VEP habituation not different from HV, but a steeper IDAP value than HV (p = 0.01), suggestive of a lower serotonergic tone. GON-B significantly reduced the number of total headache days per month (− 34.9%; p = 0.003). Eight out 17CM patients reversed to episodic migraine and medication overuse resolved in 11 out of 12 patients. One week after the GON-B VEP habituation became lacking respect to baseline (p = 0.01) and to that of HV (p = 0.02) like in episodic migraine, while the IDAP slope significantly flattened (p

The aim of this study is to investigate the influence of Mozart's music on brain activity through spectral analysis of the EEG in young healthy adults (Adults), in healthy elderly (Elderly) and in elderly with Mild Cognitive Impairment (MCI). EEG recording was performed at basal rest conditions and after listening to Mozart's K448 or "Fur Elise" Beethoven's sonatas. After listening to Mozart, an increase of alpha band and median frequency index of background alpha rhythm activity (a pattern of brain wave activity linked to memory, cognition and open mind to problem solving) was observed both in Adults and in Elderly. No changes were observed in MCI. After listening to Beethoven, no changes in EEG activity were detected. This results may be representative of the fact that said Mozart's music is able to "activate" neuronal cortical circuits related to attentive and cognitive functions.

Background and Purpose: About half of the dysphagic stroke patients have persistent swallowing dysfunction after 7 days from symptom onset. The aim of the study was to evaluate incidence, prognosis, clinical and neuroradiological correlates of post-stroke dysphagia. Methods: We prospectively examined consecutive patients with acute ischemic or hemorrhagic stroke. Patients' clinical and neuroradiological data were collected. Swallowing function was assessed by the water swallow test upon admission and after 14 days; patients were then classified as persistent dysphagic, non-persistent dysphagic or non-dysphagic. Results: We recruited 275 patients, 121 of whom were dysphagic upon admission and 254 patients attended follow-up at 14 days; 141 never presented dysphagia, 21 had a non-persistent pattern of dysphagia and 92 had a persistent one. Stroke type, leukoaraiosis degree, previous cognitive impairment and stroke severity upon admission independently predicted the occurrence of dysphagia after stroke and its persistence as well. At receiver operating characteristic (ROC) analysis, the National Institutes of Health Stroke Scale (NIHSS) score of 11.5 was the best predictive value of persistent dysphagia, with a specificity of 90.1% and a sensitivity of 72.4%. Conclusion: Stroke severity is an important predictor of a persistent pattern of dysphagia, with a suggested NIHSS cutoff value of ≥12. An independent correlation was observed with leukoaraiosis and with previous cognitive impairment.

Cardioembolic stroke is generally caused by intracranial artery occlusion. Clots may be identified in the intracranial vessels by means of conventional neuroimaging in the acute phase. High-resolution ultrasonography may show some features suggestive of cardiac emboli when occluding extracranial carotid arteries. We describe a patient with cardioembolic ischemic stroke in the right hemisphere in whom a left internal carotid artery stenosis paradoxically protected the ipsilateral hemisphere from distal intracranial embolism. The patient also presented multiple acute ischemic embolic lesions in the right middle cerebral artery territory and in the right occipital lobe, which was fed by the posterior cerebral artery, anomally originating from the right carotid siphon. Interestingly, the left internal carotid artery--which showed a severe preexisting stenosis--was occluded by the cardiac clot, whereas the right internal carotid artery only presented a moderate stenosis that had probably allowed the clots to pass. Therefore, the severe left internal carotid artery stenosis may have blocked the cardiac embolus, preventing it from reaching the ipsilateral hemisphere.

Background: Intra- and extracranial internal carotid artery dissections (ICD) are two different pathological conditions. Extracranial dissection is considered to be among the most frequent causes of stroke in the young and the segment generally reopens in 2 out of 3 cases, completely or partially, within 6 months. Intracranial ICD (IICD) is considered a rare occurrence in stroke and, accordingly, there are few systematic published data. However, it is a clinically significant condition that may cause severely disabling ischemic stroke or subarachnoid hemorrhage. In the past, sole availability of invasive imaging methods for its detection may have induced an underreporting. The aim of the study was to analyze ultrasound findings, timing and predictors of recanalization in patients with IICD. Methods: IICD acute patients admitted to our Stroke Unit were submitted to carotid sonographic seriated monitoring, daily for the 1st week after symptom onset, at day 14, at month 1 and every 3 months thereafter up to a follow-up of 4 years. Contrast carotid ultrasound was performed in patients with persistent occlusion after month 1. Results: Fourteen acute patients with IICD were enrolled. Extracranial internal carotid patency was observed in 8 patients at first ultrasound scans; all of these showed complete intracranial recanalization within the 1st week and oral anticoagulants were withdrawn after 6 months. Conversely, in 6 patients retrograde extracranial internal carotid thrombosis was immediately observed, since the first ultrasound scans. In 4 of these the occlusion persisted after 4 years while 2 of them had only a partial recanalization, with evidence at contrast ultrasound of still late remodeling processes in the extracranial thrombus up to 2 years after the first observation; for this reason, in these 2 patients anticoagulation was not discontinued, while in the 4 patients with persistent, stable, occlusion, therapy was suspended 1 year after the diagnosis. Conclusions: Identification of the site of dissection - i.e. extra- versus intracranial - is fundamental in clinical studies for outcome and prognosis evaluation. Carotid ultrasound strict surveillance is important to monitor eventual recanalization in patients with ICD, even in a late phase. Retrograde internal carotid thrombosis seems to be correlated with persistent occlusion and partial recanalization. Remodeling of thrombotic material in the internal carotid artery may, however, continue for up to 2 years. In these cases, contrast ultrasound evidence of thrombus morphological changes may support the decision to continue anticoagulation.

Background Air–saline transcranial Doppler is nowadays the first-choice examination to identify right-to-left shunt. To increase right-to-left shunt detection in echocardiography, cardiologists also use air–gelatin mixtures, which are more stable, more echogenic, and easier to be prepared. Aim We assessed the sensitivity of air–gelatin compared with air–saline for transcranial Doppler right-to-left shunt detection. Methods Air–saline transcranial Doppler, during unilateral middle cerebral artery monitoring at rest and after Valsalva maneuver, was performed in patients referred to our neurosonology laboratory for right-to-left shunt detection. The same transcranial Doppler protocol was repeated with air–gelatin. To consider transcranial Doppler positive for cardiac right-to-left shunt, at least one embolic signal had to be detected within 20″ from contrast injection. Later signals were interpreted of pulmonary origin. Trans-thoracic echocardiography was repeated with both air–saline and air–gelatin. Results A total of 97 patients were enrolled; 46 had negative transcranial Doppler for cardiac right-to-left shunt with both air–saline and air–gelatin; out of these, four patients with air–saline plus two more patients with air–gelatin presented late, isolated microemboli, slightly more numerous with air–gelatin: these were interpreted as pulmonary shunts and confirmed with trans-thoracic echocardiography. In 28 patients with already early positive air–saline transcranial Doppler at rest, air–gelatin induced a marked right-to-left shunt increase, facilitating its visualization at trans-thoracic echocardiography. In 23 patients in whom air–saline transcranial Doppler was negative at rest and positive for cardiac right-to-left shunt only after Valsalva maneuver, air–gelatin was able to reveal shunt also at rest. Conclusions Air–gelatin increases right-to-left shunt detection sensitivity with transcranial Doppler in particular at rest, even in patients in whom air–saline mixture fails to identify the shunt. The choice of air–gelatin mixture should be considered for multicentric, clinical, and research trials.

Summary Objectives To describe normal and pathological findings with three-dimensional (3D) ultrasound of the carotid bifurcation. Methods Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. Volume 3D scans were performed manually, on the axial plane, and the software presented the volume rendering from the inward blood flow signal detected with the Power Color Mode. Results Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinkings) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. Conclusions 3D ultrasound is a feasible technique. It can improve carotid axis general imaging through a global image presentation “at a glance”, visualizing caliber variations and vessels course. Imaging of stenosis from inward flow can be provided, but complete stenosis characterization requires the assessment of plaque morphology and vessel wall.

Summary The identification of vulnerable and unstable carotid atherosclerotic lesions is up-to-date an important topic of research, in order to adopt the adequate strategy for preventing cerebrovascular events. Plaque inflammation, presence of adventitial vasa vasorum, intimal angiogenesis and plaque neovascularization have been identified in histological studies as indicators of the instability of the atheroma of carotid arteries in cerebrovascular patients and of coronary arteries in cardiovascular patents. Consequently, the identification “in vivo” of these pathophysiological aspects has been objective for the development of new imaging techniques. Ultrasound of carotid arteries, with ultrasound contrast agents, is not only able to provide an enhanced visualization of the arterial lumen and plaque morphology, but also allows to directly visualize adventitial vasa-vasorum and carotid plaque neovascularization. This technique and its clinical implications in the unstable plaque identification are discussed in the present paper.

Introduction Cerebral vascular response via local and reflex adjustments is part of the integrated response to hypoxia and is coupled with changes in systemic vascular resistances that allow a redistribution of blood flow toward the brain. The cerebral vascular response in airmen exposed to simulated high altitude is not clear, thus we sought to investigate this aspect. Methods Four healthy military airmen were exposed to simulated high altitude in a hypobaric chamber according to a standard training protocol. Blood saturation (SpO2) and blood flow velocity with transcranial Doppler from the left middle cerebral artery (Vm) were continuously recorded. Pulsatility Index (PI), resistance index (RI), and systolic/diastolic ratio (S/D ratio) were computed. Alternate hypoxia-hyperoxia trials for 2 and 1 min, respectively, were used to assess the cerebrovascular response. Results Acute hypoxia induced an increase in Vm that promptly recovered when the oxygen supply was restored (mean increase of 5.5% at 18,000 ft and 17.2% at 25,000 ft). Alternate hypoxia-hyperoxia at 25,000 and 18,000 ft elicited changes in both SpO2 and Vm. In hypoxia, PI significantly decreased (mean decrease o" 25.6% at 18,000 ft and 39.5% at 25,000 ft), as did RI (mean decrease of 18.7% at 18,000 ft and 34.4% at 25,000 ft), while S/D ratio increased. Discussion The standard altitude training protocol induced a transient cerebrovascular response. The response was as expected, with hypoxia-induced vasodilation and opposite changes when breathing pure oxygen.

Late-onset absence status epilepticus (ASE) may be observed in adult and elderly patients as a late complication of idiopathic generalized epilepsy or de novo, usually related to benzodiazepines withdrawal, alcohol intoxication or psychotropic drugs initiation, but without history of epilepsy. EEG may be highly heterogeneous, varying from the 3 to 3.5Hz spike-wave discharges typical of idiopathic generalized epilepsy to asymmetric irregular sharp and slow wave complexes. We report the clinical and neurophysiologic 14 years follow-up of a now 86 years-old woman, in whom we observed – at the age of 72 – an idiopathic late-onset ASE, with a good clinical response to lamotrigine monotherapy, but with the persistence over years of the same interictal 3–3.5Hz spike-wave epileptic activity at EEG. This case is singular because, with the available long follow-up, indicates that idiopathic generalized epilepsy may also occur in the elderly, with a late-onset ASE presentation. In this condition, it is particularly important to underline the essential role of EEG (urgent and ambulatory) for the diagnosis, management and monitoring of the disease.

Non-ketotic hyperglycaemia is an endocrine emergency characterised by elevated blood glucose levels and high plasma osmolarity. While hypoglycaemia-induced seizures are usually generalised, hyperglycaemia-induced seizures are often focal and secondary to the presence of brain lesions. Moreover, in the few studies in which language disorders of epileptic origin have been reported as a clinical manifestation of non-ketotic hyperglycaemia, the disorders were usually not isolated but were followed by partial motor seizures. We describe a patient who presented with non-convulsive partial status epilepticus and whose only sign was a fluctuating language disorder induced by non-ketotic hyperglycaemia. There were no accompanying brain lesions and the patient responded optimally to diazepam. Neurophysiological EEG evaluation was fundamental for the diagnosis.

Background: Mannitol infusion is widely used in clinical practice to reduce perilesional edema in intracerebral hemorrhage (ICH), though no controlled studies have yet provided evidence of its effects on clinical outcome or on cerebral blood flow impairment following the event. The aim of our study was to evaluate blood flow velocity changes in the middle cerebral arteries (MCA) after a mannitol bolus in patients with ICH. Methods: Transcranial Doppler bilateral monitoring was performed for 90 min in 20 patients with ICH, during 100 ml mannitol bolus i.v. administration. The MCA mean flow velocities (MFVs) and pulsatility index (PI) were recorded. Results: When the ‘healthy’ and the ‘affected’ hemispheres were compared, we observed higher MCA MFV and lower PI on the affected side than on the contralateral side, both at baseline and during the experiment. After the mannitol bolus, we observed a significant MFV increase, starting at the end of the infusion and lasting longer than 60 min in the MCA on the affected side alone. The PI increased after mannitol administration on the healthy side alone. Conclusions: A single bolus of mannitol modified cerebral hemodynamics in our patients with ICH, increasing flow velocities on the affected MCA. This effect may be a consequence of reduced edema in the perilesional areas. The increased PI on the unaffected side may be indicative of preserved pulsatility in the healthy hemisphere.

Spontaneous bilateral internal carotid artery dissection has frequently been described in the literature as a cause of stroke. In more than half of the patients with internal carotid artery dissection, recanalization occurs early after the event and is unusual later than 6 months after onset of the dissection. We describe a patient with ischemic stroke due to left internal carotid artery occlusion in the extracranial segment. The patient was treated with anticoagulants and early vessel recanalization did not occur. Ten months later, he developed contralateral internal carotid occlusion in the intracranial tract, which was followed by early complete recanalization. Anticoagulation therapy was continued and, 16 months after the initial event, the left internal carotid artery unexpectedly also reopened. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2011

Objectives To evaluate whether contrast ultrasonography can be used to distinguish asymptomatic from symptomatic carotid plaques and provide insight into underlying pathophysiological differences. Design Contrast Carotid ultrasound was performed in both symptomatic and asymptomatic patients referred for carotid endarterectomy. Materials and methods Of 77 consecutive patients referred for carotid artery evaluation, 64 underwent carotid endarterectomy for asymptomatic cerebrovascular disease and 9 underwent urgent surgery for acute neurological deficits with hemiparesis. The endarterectomy specimens were assessed immunohistologically. Results In all 9 patients undergoing urgent surgery, contrast ultrasonography showed the accumulation of diffuse microbubble contrast at the base of the carotid plaque. This pattern was observed only in 1/64 of the patients undergoing surgery for asymptomatic carotid disease. Immunohistologically staining of the endarterectomy specimens showed that the area of microbubble contrast at the base of the symptomatic plaques was associated with an increased number of small diameter (20–30 μm) microvessels staining for vascular endothelial growth factor (VEGF). Conclusions Contrast carotid ultrasonography may allow the identification of microvessels with neoangiogenesis at the base of carotid plaques, and differentiate symptomatic from asymptomatic plaques.

Over the past 20 years, conventional ultrasonography has identified features of the "unstable" carotid plaque. Histological studies have recognized that plaque inflammation and neoangiogenesis play a pivotal role in the developing of the vulnerable plaque. Hence, the growing interest on the biological activities of atherosclerotic lesions leading to cere- brovascular events. The presence of adventitial vasa vasorum and the occurrence of plaque vascularization have been con- sidered as predictors of unstable lesions in cerebrovascular and/or cardiovascular patients. The advent of ultrasound con- trast agents has represented a fundamental step in the up-to-date functional evaluation in several fields with minimally in- vasive procedures. Contrast specific ultrasound modalities are currently used with excellent results in oncology, in cardi- ology and in vascular diseases. Contrast carotid ultrasound is an emerging imaging technique, able to depict in vivo new functional information on plaque activity and vascularization that may add further new data on the actual condition and future cerebrovascular risk. Further studies will provide a better clarification of the degree of neo-angiogenesis. A future strategy could be represented by the monitoring of plaque neoangiogenesis in order to detect the possible pharmacological effects on plaque remodeling.

We studied the effects of short-term psychodynamic psychotherapy (STPP) and pharmacological therapy in 26 consecutive patients with probable medication overuse headache (pMOH). Patients underwent a standard in-patient detoxification protocol, lasting a mean of 7 days. Eleven patients overused non-steroidal anti-inflammatory drugs (NSAIDs), five a combination of NSAIDs and triptans, four triptans, four a combination of NSAIDs, and three triptans and ergot derivates. Preventive therapy was initiated during detoxification. The STPP protocol comprised the Brief Psychodynamic Investigation (BPI) and psychoanalysis-inspired psychotherapy. All patients (groups A and B) underwent the BPI and pharmacological therapy. Half of the patients (group B) also not randomly underwent psychoanalysis-inspired psychotherapy. We found a significant interaction between time and group for headache frequency and medication intake. At 12-month follow-up, a statistically greater decrease in headache frequency and medication intake was observed in group B than in group A ( P = 0.0108 and P = 0.0097, respectively). The relapse rate was much lower in group B patients at both 6 and 12 months [15.3%, odds ratio (OR) 0.11, P = 0.016, and 23%, OR 0.18, P = 0.047, respectively] than in group A. The risk of developing chronic migraine (CM) during follow-up was higher in group A than in group B at 6 (OR 2.0, P = 0.047) and 12 months (OR 2.75, P = 0.005). Our study suggests that STPP in conjunction with drug withdrawal and prophylactic pharmacotherapy relieves headache symptoms in pMOH, reducing both long-term relapses and the burden of CM.

Purpose Quantitative analysis of epileptiform discharges (EDs) before and after the initiation of an antiepileptic treatment is a useful tool to objectively documentate the efficacy of an antiepileptic drug (AED). Aim of this study was to evaluate the effect of levetiracetam (LEV) on EDs, monitored with ambulatory EEG (A/EEG), in a limited series of patients with generalized epilepsy. Methods We performed 24h A/EEG recording in basal condition and at follow-up after LEV therapy in 21 adult epileptic patients. Eleven received LEV as monotherapy and 10 as add-on. For each patient we quantified total epileptic activity considering the following parameters: total number, total duration, maximal duration and median duration of EDs. Self-reported information on the effect of LEV on clinical seizures was also collected, to determine the electro-clinical correlation. Results A high variability of the response to LEV was observed in the monotherapy group, without statistical differences for all the parameters investigated. A significant reduction of the total number of seizures (113.6 vs. 41.2; p =.01) was observed in patients in add-on therapy. The modifications of epileptiform EEG abnormalities did not necessarily correlate with the self-reported clinical impressions. Discussion The quantification of EDs monitored by A/EEG provides a useful objective support for evaluating the neurophysiologic profile and the real efficacy of an antiepileptic treatment. In our patients LEV was able to significantly reduce the EDs only in add-on therapy. Further larger studies are necessary to clarify the effects of LEV on electro-clinical features of generalized epilepsy.

Backgrounds: Erectile dysfunction (ED) is not only evidence of diffuse atherosclerosis but also an index of early endothelial damage. We investigated cerebrovascular reactivity, expression of early arterial damage, in patients with isolated ED (ED+) and controls (ED–). Materials and Methods: Fifteen ED+ and 15 ED– subjects, matched for age (ED+: 58±6, ED–: 59 ± 4 years) and vascular risk factors, were submitted to carotid duplex ultrasound and transcranial Doppler. Cerebrovascular reactivity was assessed on both middle cerebral arteries simultaneously calculating (a) the total vasomotor range (VMR) measured after breath holding and hyperventilation and (b) the rate of change (VMR/CO2) after breath holding. Results: Carotid Duplex scanning showed a light carotid stenosis only in 3 (2 in the ED+ and 1 in the ED– group). No differences were observed in intima-media thickness between ED+ and ED–. Slightly slower mean middle cerebral artery flow velocities were observed in ED+ with respect to ED–. ED+ patients showed a reduced VMR (p < 0.001) and a slower VMR/CO2 rate of change (p < 0.001) compared to ED–. Conclusions: The reduced reactivity in patients with isolated ED may represent a marker of early cerebral vasomotor dysfunction due to subclinical endothelial damage.

Background and Purposes— In the early stage of stroke, the occurrence of neurologic and medical complications is associated with clinical deterioration. Previous studies were focused on the first week after stroke onset. The aim of this study was to evaluate the impact of complications on clinical outcome in patients with stroke in the early subacute stage. Methods— We prospectively evaluated the influence on the outcome of complications feasible (MC) and not feasible for monitoring (NMC) in all patients with stroke admitted consecutively in our subacute stroke unit. Patients were divided into three classes according to stroke severity evaluated by the National Institutes of Health Stroke Scale score. A change in the National Institutes of Health Stroke Scale score group from admission to discharge was considered clinically significant. Results— We included 261 patients. Sixty percent of patients had complications (105 MC, 118 NMC). Hyperthermia (OR=14.12; 95% CI: 6.01 to 33.20), urinary infections (OR=4.92; 95% CI: 2.19 to 11.04), hypertension (OR=2.86; 95% CI: 1.21 to 6.76), hypoxia (OR=15.75; 95% CI: 6.73 to 36.84), and neuroradiologic damage progression (OR=58.31; 95% CI, 19.48 to 174.55) were associated with a change to a more severe class at discharge and with a higher risk of mortality. Conclusions— A high percentage of patients can develop both MC and NMC during this subacute stage of stroke. The occurrence of complications influences outcome and raises the question about the need for a prolonged stay in a dedicated ward for patients with stroke.

Background Chronic headache (CM) occurs in 2-5% of the general population, often associated with medication-overuse headache (MOH), and comorbid psychiatric disorders [1,2]. Among therapeutic approaches, psychotherapeutic interventions may be effective, either alone or associated with pharmacological therapies. As we previously showed, the short-term psychodynamic psychotherapy (STPP), plus drug therapy, is more effective in patients with probable MOH to reduce headache symptoms and relapse rate than drug therapy alone [3]. Moreover, STPP alone is not inferior to valproate in CM, as preventive therapy [4]. According to psychodinamic diagnosis (BPI) some psychodynamic profiles with poor ability to process the emotional content or low mentalizing level (i.e., pre-psychosis, psychosis and borderline) could be at risk of developing chronic headaches. The aim of the present study was to identify the most frequent psychodynamic profiles in CM and test the effective of STPP in those patients with no record of psychiatric disorders.

Joint hypermobility syndrome (JHS) and Ehlers–Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine with or without aura is considered the most common form of headache in JHS/EDS-HT. In this population of chronically ill patients, we investigated whether migraine characteristics were different from those of a control population of migraine patients. The study was carried out on 33 selected JHS/EDS-HT patients, diagnosed according to current criteria. Sixty-six migraine subjects matching age and gender were consecutively selected as controls (MO group) among patients attending our Headache Clinic. JHS/EDS-HT and MO were screened for a series of headache characteristics, such as frequency, intensity, age of onset, level of disability, use of rescue and prophylactic medications. Differences between the two groups were tested by using independent group comparisons. Results showed that in JHS/EDS-HT: (1) migraine has an earlier onset (12.6 vs 17 years of age; p = 0.005); (2) the rate of migraine days/month is higher (15 vs 9.3 days/month; p = 0.01); (3) accompanying symptoms are usually more frequent; (4) HIT-6 and MIDAS scores are higher (p = 0.04 and p = 0.03); (5) efficacy of rescue medication is almost identical, although, total drug consumption is significantly lower (p

We performed an observational EEG study in 43 patients with neurally-mediated syncope in basal condition and during hyperventilation (HV), and compared it with 32 healthy controls. On blind analysis at rest, EEG was classified as normal in 47% of patients (vs. 94% of controls, P < 0.001). More abundant and pronounced delta–theta activities and alpha slowing were found in patients than in control subjects on both visual inspection and quantitative spectral analysis. During prolonged HV, the EEG remained normal in 21% of patients only. Slow activities became more evident in patients than in control subjects, and intermittent rhythmic delta activity appeared in 40% of syncopal patients. These “pseudoparoxysmal” EEG changes differed from the common slowings induced by HV in adult subjects and were not observed in our control subjects. Moreover, these distinctive EEG changes, a common finding in syncopal patients, could not be confused with epileptiform activity of any kind. Further studies will clarify the pathophysiology of these EEG modifications.

BACKGROUND The adverse effects of the antiepileptic drugs (AEDs) originally developed are well known, while those of the newer AEDs remain unclear. OBJECTIVE To investigate clinical, cognitive, and neurophysiologic effects of carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. METHODS A double-blind crossover study was conducted in 10 volunteers. Eight-day treatment with carbamazepine, oxcarbazepine, levetiracetam, or placebo was administered in random order. Drug doses were titrated gradually to the daily target doses on day 7: carbamazepine 800 mg, oxcarbazepine 1200 mg, and levetiracetam 1500 mg. At baseline and at the end of each treatment period, participants underwent cognitive and neurophysiologic assessment. A washout period of 14 days between treatment periods was conducted. RESULTS More adverse events were self-reported with carbamazepine (63%) than the other treatments (oxcarbazepine 12%, levetiracetam 20%, placebo 5%; p < 0.001 between the 4 groups). Carbamazepine induced the greatest motor slowing (p = 0.002), followed by oxcarbazepine (p = 0.01). Levetiracetam left baseline motor speed unchanged. All AEDs increased attention span from baseline values as shown on the Stroop test. Quantitative electroencephalogram (EEG) analysis showed that carbamazepine significantly increased the delta–theta power and reduced the frequency of alpha rhythm; oxcarbazepine induced smaller changes than carbamazepine. Levetiracetam did not change any EEG measurements. On color visually evoked potential (VEP) tests, carbamazepine induced a constant slowing of P1 latency, while oxcarbazepine induced changes only after the blue–black pattern. All color VEP measures for volunteers receiving levetiracetam were almost unchanged. CONCLUSIONS After short-term treatment in healthy volunteers, carbamazepine induced major clinical and neurophysiologic changes. Oxcarbazepine was better tolerated than carbamazepine. Levetiracetam interfered least with clinical and neurophysiologic test results.

Summary Contrast Enhanced Carotid Ultrasonography (CCU) is capable of detecting angiogenesis within the carotid plaque as a potential index of plaque vulnerability. However, due to a lack of standard of examination technique and documentation, results are not sufficiently, reliably comparable. To improve this situation and in order to support wide acceptance of this promising technique, experts in this field met in the Consensus conference in May 22, 2011, held during the 16th ESNCH Meeting (20–23 May 2011) in Munich, Germany, to discuss the limitations and problems and to determine guidelines for its proper use in scientific investigations and clinical practice. The main results of this conference are presented here. The discussion is still in progress and individual conclusions may not reflect the opinion of all participants. It aims to provide a basis for a later comprehensive consensus statement.

In patients with an impaired state of consciousness, EEG is fundamental, a correct neurological work-up. Cephalosporins have been identified as a case of triphasic waves' (TW) reversible encephalopathy. We report a case of an acute reversible encephalopathy with TWs during treatment with cefoperazone. We report the occurrence and regression of a confusional state with TWs encephalopathy at EEG after the administration of cefoperazone for urinary tract infection in a patient admitted for syncope. In conclusion, cefoperazone should be considered as a cause of toxic encephalopathy with EEG TWs, when there is a temporal relationship with its administration; EEG monitoring is useful in the neurological follow-up.

Background and Purpose— Adventitial vasa vasorum and plaque vascularization have been established as predictors of unstable atheromasic lesions in cerebro- and cardiovascular patients. Ultrasound contrast agents provide reliable information on tissue perfusion and microcirculation. We used contrast ultrasound duplex scanning to identify carotid plaque vascularization. Methods— Contrast carotid duplex scanning was performed in 23 patients with plaques of different degree of stenosis and echogenicity. Results— Plaque vascularization was detected in the fibrous and fibro-fatty tissue and not observed in the calcific nor in the necrotic and hemorrhagic tissue. Constantly, a small vessel was observed under ulcerations. Conclusions— Carotid contrast ultrasound imaging appears to be an emerging technique for identifying plaque angiogenesis. Further studies are needed to clarify the role of plaque angiogenesis for assessing cerebrovascular risk and to monitor effects of therapies aimed to plaque remodelling.

Cardioembolic stroke is generally caused by intracranial artery occlusion. Clots may be identified in the intracranial vessels by means of conventional neuroimaging in the acute phase. High-resolution ultrasonography may show some features suggestive of cardiac emboli when occluding extracranial carotid arteries. We describe a patient with cardioembolic ischemic stroke in the right hemisphere in whom a left internal carotid artery stenosis paradoxically protected the ipsilateral hemisphere from distal intracranial embolism. The patient also presented multiple acute ischemic embolic lesions in the right middle cerebral artery territory and in the right occipital lobe, which was fed by the posterior cerebral artery, anomally originating from the right carotid siphon. Interestingly, the left internal carotid artery--which showed a severe preexisting stenosis--was occluded by the cardiac clot, whereas the right internal carotid artery only presented a moderate stenosis that had probably allowed the clots to pass. Therefore, the severe left internal carotid artery stenosis may have blocked the cardiac embolus, preventing it from reaching the ipsilateral hemisphere.

Summary Background and purpose The early identification of ischemic stroke pathophysiology may lead to different diagnostic and therapeutical strategies. In 1/3 of patients, stroke is related to carotid disease, when a vulnerable plaque evolves with surface rupture and local apposition of highly embolic/thrombotic material. This being a rapidly evolving dynamic process, the value of its early identification may be underestimated. With the diffusion of high-resolution ultrasound equipments, the possibility of identifying these features of plaque vulnerability has become easily available. These plaque characteristics have to be always considered in the patient management, in order to avoid further worsening of neurological conditions or to prevent recurrent events, and to choose the appropriate strategies. Methods Early ultrasonography was performed with high frequency probes (9, 15, 18 MHz) in patients admitted to emergency area for acute ischemic symptomatology from carotid stenosis. Results In 8 patients admitted to the emergency area few hours after the onset of neurological symptoms, we detected peculiar plaque characteristics closely related to the neurological events and at high risk of further embolic events with local thrombosis, surface plaque rupture and carotid floating thrombi. All these cases were successfully submitted to emergency carotid endarterectomy repair. Conclusions Timing of carotid endarterectomy has always been debated in stroke patients’ clinical management, depending on several factors. All imaging techniques contribute to the identification of plaque morphology features, but early admission of stroke patients to the emergency areas and early US have a crucial leading role in detecting plaque rupture and dynamic changes in real-time. Peculiar characteristics of high unstable plaques allow the identification of those lesions at particularly high risk of further embolic events according to their fragile characteristics that may benefit from early surgery.

Maria Fabrizia Giannoni1, Edoardo Vicenzini2, Claudia Monaco3 and Piergiorgio Cao4 1Vascular Ultrasound Investigation Unit, Vascular Surgery, Department “P. Stefanini”, Sapienza University of Rome, 2Department of Neurology and Psychiatry, Sapienza University of Rome, 3Kennedy Institute of Rheumatology, Imperial College, London, 4Vascular Surgery, Department of Cardioscience, S. Camillo-Forlanini Hospital, Rome, 1,2,4Italy 3UK

Objectives: Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. Methods: Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. Results: Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. Conclusions: 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course ‘at a glance’. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.