Gabriela Cardaioli

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Is ultrasound examination sufficient in the evaluation of patients with internal carotid artery severe stenosis or occlusion

Background and Purpose: Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade internal carotid artery (ICA) stenosis. Some authors have suggested that when ultrasound shows a stenosis 70–99%, CE can be performed without further imaging study. However, ultrasound findings that suggest an ICA occlusion, not confirmed by angiography but which instead show a near-occlusion usually benefit from CE. The objectives of this study are: (1) to evaluate how angiography-obtained information on intracranial arteries affects the treatment decision in patients with 70–99% ICA stenosis, and (2) to evaluate when a symptomatic ICA occlusion shown by ultrasound could actually be a patent artery and therefore benefit from CE. Materials and Methods: We prospectively collected the cerebral angiograms of 133 consecutive patients with TIA or non-disabling stroke due to large artery disease where ultrasound suggested a stenosis ≧70% or occlusion of symptomatic ICA; we calculated the frequency of intracranial vascular malformations and intracranial artery disease (IAD) located in the infraclinoid or supraclinoid portion of the ICA, and in the anterior or middle cerebral artery. Results: Ultrasound showed 31 ICA occlusions and 102 ICA with 70–99% stenosis. All the patients with an ICA stenosis 70–99% on ultrasound examination had the degree of stenosis confirmed by angiography. Two out of 31 patients did not have a complete occlusion but angiography showed a near-occlusion and consequently they underwent CE. Sixty-five (62.5%) out of 104 patients with patent ICA had IAD (mild 26.9%, moderate 21.2%, and severe 14.4%). Five patients (4.8%) had intracranial vascular malformations (4 aneurysms and 1 arteriovenous malformation). One patient had disabling stroke during angiography. Seven patients (6.7%) did not undergo CE after angiography (1 patient had an aneurysm >10 mm, 1 patient had a very tight stenosis of the basilar artery, 5 patients had intracranial stenosis more severe than the extracranial stenosis). Conclusions: In patients that on the basis of ultrasound examination can benefit from CE, information on intracranial arteries is necessary. Moreover, complete occlusion cannot be detected with certainty only by ultrasound examination.

CT angiography versus colour-Doppler US in acute dissection of the vertebral artery.

AbstractPurpose.Conventional digital subtraction angiography (DSA) still represents the criterion standard for the diagnosis of vertebral artery dissection (VAD), but the main drawbacks of this technique include invasiveness, patient discomfort and risk of complications. We evaluated the potential of multidetector computed tomography angiography (CTA) as a noninvasive tool providing highresolution images of the arterial lumen and wall by comparing the diagnostic accuracy of CTA and colour-Doppler ultrasonography (CDUS) in detecting acute VAD.Materials and methods. We retrospectively reviewed 15 cases of VAD in 15 patients (five men and ten women, age range 28–58 years) who came to our attention between August 2001 and September 2005. The diagnosis was made on the basis of appropriate clinical presentation, absence of atherosclerotic disease in the cerebrovascular circulation and evidence of distinctive CT features, which were subsequently confirmed by conventional angiography used as reference standard. All patients with a clinical suspicion of VAD underwent CDUS of the neck vessels prior to CTA. Accuracy, sensitivity and specificity of CDUS and CTA were expressed as percentages of agreement with the reference angiographic procedure. Interreader concordance for detection of VAD by CTA was calculated with the Cohen K value.Results.The CDUS examinations revealed ten out of 15 VAD, with a sensitivity of 66%, a specificity of 60%, a positive predictive value of 55.5% and a negative predictive value of 70.5%. In five cases, CDUS revealed nonspecific wall and flow alterations; in eight patients, high resistance obstructive flow; and in two patients, intimal flap with demonstration of the true and false lumen. CTA enabled the correct identification of all 15 VAD. The reported sensitivity, specificity, positive predictive value and negative predictive value were 100%, 95%, 93.7% and 100%, respectively. With regard to localisation of VAD, CTA showed 100% correlation with DSA. The differences in CTA and CDUS sensitivity (100% vs 66%), specificity (95% vs 60%), and overall diagnostic accuracy (97% vs 62.8%), assessed by cross tabulations and compared by using the McNemars two-sided test, were significant (p<0.05).Conclusions.Multidetector CTA is a sensitive technique for the diagnosis of VAD. Used as a complement to unenhanced brain CT, it has the advantage of being readily available and easy to perform.

Stroke related to carotid artery dissection in a young patient with Takayasu arteritis, systemic lupus erythematosus and antiphospholipid antibody syndrome.

Autoimmune diseases are rarely the cause of stroke even in the young age group in association with cervical artery dissection and collagen vascular diseases. Takayasu arteritis is a chronic, idiopathic, inflammatory disease that primarily affects large vessels, such as the aorta and its main branches. Takayasu arteritis rarely coexists with systemic lupus erythematosus, and only few cases have been reported in association with the presence of antiphospholipid antibodies. We describe a young patient with right internal carotid artery dissection and subsequent stroke who presented with all three syndromes. Although this patient met the diagnostic criteria for each syndrome, systemic lupus erythematosus, Takayasu arteritis and the antiphospholipid antibody syndrome, it remains unlikely that the three disorders are not related. We suggest a single disimmune disorder may have led to carotid artery dissection.

Occipital arteriovenous malformations and migraine

Background: Headache has been reported to be the first clinical presentation in several patients with cerebral arteriovenous malformations (AVMs). Headache associated with AVMs often shows characteristics of migraine with and without aura. Angiographic characteristics of AVMs, such as their location, could determine the ‘migraine-like’ features of attacks. Methods: We performed an observational study of the clinical and angiographic characteristics of a cohort of 40 consecutive patients with AVMs who had been admitted to our institute for endovascular embolization over a 4-year period. Headache was characterized according to ICHD-II criteria. The relationship between headaches and the angioarchitectural features of AVMs was also analysed. Results: Migraine-like headache was the first clinical manifestation in 22.5% of patients. The location of the malformation was significantly associated with migraine-like presentation (p = 0.03) and the occipital lobe was the predominant site. Conclusions: An occipital location may be linked with spreading depression, a pathogenic mechanism of migraine. Headache associated with arteriovenous malformations in the occipital lobe, although secondary in nature, could have clinical features similar to migraine.

A critical role of NO/cGMP/PKG dependent pathway in hippocampal post-ischemic LTP: modulation by zonisamide.

Abstract Nitric oxide (NO) is an intercellular retrograde messenger involved in several physiological processes such as synaptic plasticity, hippocampal long-term potentiation (LTP), and learning and memory. Moreover NO signaling is implicated in the pathophysiology of brain ischemia. In this study, we have characterized the role of NO/cGMP signaling cascade in the induction and maintenance of post-ischemic LTP (iLTP) in rat brain slices. Moreover, we have investigated the possible inhibitory action of zonisamide (ZNS) on this pathological form of synaptic plasticity as well as the effects of this antiepileptic drug (AED) on physiological activity-dependent LTP. Finally, we have characterized the possible interaction between ZNS and the NO/cGMP/PKG-dependent pathway involved in iLTP. Here, we provided the first evidence that an oxygen and glucose deprivation episode can induce, in CA1 hippocampal slices, iLTP by modulation of the NO/cGMP/PKG pathway. Additionally, we found that while ZNS application did not affect short-term synaptic plasticity and LTP induced by high-frequency stimulation, it significantly reduced iLTP. This reduction was mimicked by bath application of NO synthase inhibitors and a soluble guanyl cyclase inhibitor. The effect of ZNS was prevented by either the application of a NO donor or drugs increasing intracellular levels of cGMP and activating PKG. These findings are in line with the possible use of AEDs, such as ZNS, as a possible neuroprotective strategy in brain ischemia. Moreover, these findings strongly suggest that NO/cGMP/PKG intracellular cascade might represent a physiological target for neuroprotection in pathological forms of synaptic plasticity such as hippocampal iLTP.

Clinical Aspects and Management of Levodopa-Induced Dyskinesia

In Parkinsons disease, one of the most troublesome dilemmas is the treatment of levodopa-induced dyskinesia. After a few years, chronic treatment with levodopa is associated with the development of dyskinesias. Strategies to delay or to reduce dyskinesias are based on the change of levodopa dosing or the early use of dopamine agonists. Dopamine agonists with different pharmacological profile are available. Our paper was aimed to analyse the clinical impact and the management of dyskinesias with dopamine agonists.

Evidence of hydrogen sulfide involvement in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease whose pathophysiological deficits, causing impairment in motor function, are largely unknown. Here we propose that hydrogen sulfide (H2S), as a glial‐released inflammatory factor, contributes to ALS‐mediated motor neuron death.

Vertebral Artery Dissection and Hyperhomocysteinemia: A Case Report

In young adults, cervical artery dissection (CAD) is recognized as the second cause of stroke [1–3], justifying approximately 20% of acute cerebrovascular events before 45 years [4–7].The cause of CAD is still unknown in most cases. Except in anecdotal case reports, the most recognized predisposing factors are traumas and primary diseases of the arterial wall [8]. In 1969 McCully [9] hypothesized a possible link between increased plasma level of homocystein and vascular disease. Nowadays, we know that mild hyperhomocysteinemia, i.e. 12–14 Ìmol/l, is also an independent risk factor for vascular disease [10–12]. Among factors contributing to mild hyperhomocysteinemia the thermolabile form of the enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) is a quite common genetic abnormality that occurs in 4–10% of the general population as homozygous form [12–15]. The genetic base of thermolability has been detected as a C to T substitution at nucleotide 677 [12, 15] of the MTHFR gene. Homozygotes for the thermolabile form have a specific activity of F50% of normal while heterozygotes have F75% of normal subjects. We describe a case of vertebral artery dissection associated to hyperhomocysteinemia and homozygosity for the thermolabile form of MTHFR.

Multimodal Use of Computed Tomography in Early Acute Stroke, Part 2

Computed tomography (CT) scan remains the most widely technique in the cerebrovascular emergency, as it is largely available, minimally invasive, fast, cheap and reliable. Noncontrast enhanced CT (NeCT) imaging can show early signs of infarction in ischemic stroke; however, it could not show if the ischemic tissue is irreversibly damaged. CT perfusion (CTP) imaging has been shown to predict stroke location and size and can provide information about ischemic cerebral parenchyma not definitively compromised. CT angiography (CTA) could highlight stenosis or occlusion both in intracranial and extracranial vessels. By combining NeCT, CTP, and CTA the entire cerebrovascular axis can be imaged during acute stroke. Currently, the term “multimodal CT” indicates the combined use of these three techniques in order to obtain a complete picture of the extension of ischemic damage in acute stroke patients.