Edoardo Vicenzini

Contrast Carotid Ultrasound for the Detection of Unstable Plaques with Neoangiogenesis: A Pilot Study

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 microm) 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.

Detection of Carotid Adventitial Vasa Vasorum and Plaque Vascularization With Ultrasound Cadence Contrast Pulse Sequencing Technique and Echo-Contrast Agent

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.

Cerebrovascular Reactivity in Degenerative and Vascular Dementia: A Transcranial Doppler Study

Background: An impairment of cerebral microvessels is reported both in normal ageing and in senescence-associated processes, as well as in Alzheimer’s disease (AD) and vascular dementia (VaD). The aim of this study was to explore cerebral hemodynamics by transcranial Doppler in VaD and AD, compared with age-matched control subjects. Methods: Transcranial Doppler was investigated in all patients in the basal condition. Cerebral vasoreactivity to hyper- and hypocapnia was evaluated with CO2 mixture inhalation followed by hyperventilation. Results: We studied 60 AD and 58 VaD patients and 62 nondemented controls. Both AD and VaD subjects showed lower flow velocities (FV) and higher pulsatility indices (PI) as compared with controls. Lower total vasomotor reactivity and lower response to hypercapnia were observed in the AD and VaD groups as compared with controls. AD and VaD patients did not show significant differences in FV, PI values or cerebral vasoreactivity. Conclusions: Reduced FV and increased PI with a significant vasoreactivity reduction in VaD and AD patients are indicators of impairment of cerebral microvasculature circulation in both diseases. The identification of vascular function impairment in all kinds of dementia could be of help in identifying patients who would thus benefit more from specific therapeutic approaches.

Delayed poststroke dementia: A 4-year follow-up study

Objective: To assess patients who have had a stroke for the subsequent development of poststroke dementia (PSD) and to determine if the characteristics of delayed PSD (dPSD) vary in the long-term follow-up. Methods: Nondemented patients were followed from 6 months after stroke onset for 4 years. Dementia was diagnosed by International Classification of Diseases-10 criteria; dementia etiology was diagnosed by the National Institute of Neurological and Communication Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association and National Institute of Neurologic Disorders and Stroke/Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria. Neuroimaging and neuropsychological tests were repeated annually. Results: During a 2-year period, 191 stroke patients were enrolled. By the end of the follow-up period, 41 (21.5%) patients had developed dementia. At the Cox regression analysis, dPSD was associated with cortical atrophy (hazard ratio [HR] = 3.4, 95% CI 1.5 to 7.9), age (HR = 3.3, 95% CI 1.4 to 7.8), and multiple ischemic lesions (HR = 2.5, 95% CI 1.2 to 4.8). The Kaplan-Meier analysis showed a significant difference between the incidence of dPSD subtypes (log-rank test; p = 0.002). Conclusions: During the 4-year follow-up, the incidence of dementia increased gradually, shifting from an Alzheimer disease-type picture in the first years to a vascular dementia type later in years 2 to 4.

Clinical, Cognitive, and Neurophysiologic Correlates of Short-Term Treatment with Carbamazepine, Oxcarbazepine, and Levetiracetam in Healthy Volunteers

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.

Monitoring After the Acute Stage of Stroke A Prospective Study

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.

Imaging of carotid plaque angiogenesis.

Currently, characterization of the vulnerable plaque is a hot research topic as a more adequate strategy for preventing cerebrovascular events is being sought. Histological studies have recognized that plaque inflammation and the presence of adventitial vasa vasorum, intimal angiogenesis and plaque neovascularization are strong predictors of instability in atheromatous lesions of cerebrovascular and cardiovascular patients. The in vivo study of these features has been the focus of development of several new radiological imaging methods. Carotid ultrasound, with ultrasound contrast agents, is not only able to provide an enhanced assessment of the arterial lumen and plaque morphology with an improved resolution of the carotid intima-media thickness, but also to directly visualize adventitial vasa vasorum and plaque neovascularization. This technique and its future clinical implications are discussed in the present review.

EEG patterns and epileptic seizures in acute phase stroke.

Background: The rate of early post-stroke epileptic seizures ranges from 2 to 33%. This wide range is likely due to differences in study design, patient selection and type of neurophysiological monitoring. Electroencephalography (EEG), which is not used in the routine work-up of acute stroke, is the best neurodiagnostic technique for detecting epileptic activity, especially in patients with non-convulsive post-stroke epileptic activity. The aim of this study was to analyze patterns on EEGs performed within 24 h of stroke onset, and to investigate correlations between these patterns and the occurrence of early epileptic seizures and status epilepticus (SE), vascular risk factors, stroke subtypes and short-term outcome. Methods: We prospectively studied 232 patients (mean age 71 ± 12 years; 177 ischemic strokes and 55 hemorrhagic). EEG recording was performed within 24 h from hospitalization. The follow-up lasted 1 week. Results: Fifteen patients (6.5%) had early seizures within 24 h; 10 of these patients had focal SE with or without secondary generalization. EEG revealed sporadic epileptiform focal abnormalities in 10% and periodic lateralized epileptiform discharges (PLEDs) in 6%. SE was recorded in 71.4% of patients with PLEDs. At the multivariate analysis, only early epileptic manifestations (p < 0.001) were independently associated with PLEDs. Conclusions: Our study confirms that seizures are not frequent in the early phase of acute stroke and occur prevalently as focal SE at onset. EEG may help to detect specific patterns, such as PLEDs, that are closely related to early seizures. EEG monitoring should be performed in order to detect purely electrographic seizures.

Combined pharmacological and short-term psychodynamic psychotherapy for probable medication overuse headache: a pilot study

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.

Clinical and Electroencephalographic Effects of Topiramate in Patients with Epilepsy and Healthy Volunteers

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.