Gian Piero Pelliccioli

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.

Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis.

Abstract We aimed to increase confidence in the combined use of MRI and proton MR spectroscopy (1H-MRS) in diagnosis of amyotrophic lateral sclerosis (ALS). We investigated 12 patients with ALS, seven definite and five probable, taking into account clinical measures of motor neuron function. On T2-weighted images we found high signal in the corticospinal tract in six and low signal in the primary motor cortex in seven of the 12 patients. Atrophy of the precentral gyrus was apparent in all the patients apart from one with probable ALS. Absolute quantification of cerebral metabolites using 1H-MRS demonstrated a significantly lower mean concentration of N-acetylaspartate (NAA) in the precentral gyrus of patients with probable and definite ALS (8.5 ± 0.62) than in control subjects (10.4 ± 0.71; P < 0.001). NAA concentration in primary motor cortex correlated with Norris scale scores (r = 0.30; P < 0.0001) but not with the ALS Functional Rating Scale score or disease duration. Significantly lower levels of NAA were detected in patients with low signal in the motor cortex than in those without (P < 0.01). Mean choline (Cho) and creatine (Cr) values did not differ between patients with ALS and controls.

Recanalization of Cervical Artery Dissection: Influencing Factors and Role in Neurological Outcome

Background and Purpose: Generally, the prognosis for cervical artery dissection (CAD) is uncertain. The recanalization rate of CAD can be up to 85% within 3 months. This study evaluates the variables that might affect recanalization and the role of recanalization as a predictor for neurological outcome. Patients and Results: This study prospectively included 38 patients with acute stroke following occlusion due to CAD (18 males, 20 females, median age 50.5 years, range 16–82). Vertebral and carotid dissections were equally distributed (19 carotid dissections). The recanalization rate was influenced by the presence of hypertension (p = 0.001). Outcomes were dependent on infarct location. Patients with lateral medullary infarction returned to functional independence (p = 0.026), while patients with deep hemispheric infarction tended to have a disabling stroke (p = 0.068). The presence of good collaterals seemed to influence functional independence (p = 0.03). Conclusion: There seemed to be no relationship between outcome and the rate of recanalization following CAD. Recanalization appeared to be a spontaneous mechanism, which could have depended on the intrinsic condition of the vessels. Finally, neurological outcome was dependent on lesion localization and the presence of good collaterals.

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.

Abnormalities in the cerebrospinal fluid levels of endocannabinoids in Multiple Sclerosis

Objective: Endocannabinoids (eCBs) play a role in the modulation of neuroinflammation, and experimental findings suggest that they may be directly involved in the pathogenesis of multiple sclerosis (MS). The objective of our study was to measure eCB levels in the cerebrospinal fluid (CSF) of patients with MS. Patients and methods: Arachidonoylethanolamine (anandamide, AEA), palmotylethanolamide (PEA), 2-arachidonoylglycerol (2-AG) and oleoylethanolamide (OEA) levels were measured in the CSF of 50 patients with MS and 20 control subjects by isotope dilution gas-chromatography/mass-spectrometry. Patients included 35 patients with MS in the relapsing-remitting (RR) form of the disease, 20 in a stable clinical phase and 15 during a relapse, and 15 patients with MS in the secondary progressive (SP) form. Results: Significantly reduced levels of all the tested eCBs were found in the CSF of patients with MS compared to control subjects, with lower values detected in the SP MS group. Higher levels of AEA and PEA, although below those of controls, were found in the CSF of RR MS patients during a relapse. Higher levels of AEA, 2-AG and OEA were found in patients with MRI gadolinium-enhancing (Gd+) lesions. Discussion: The present findings suggest the presence of an impaired eCB system in MS. Increased CSF levels of AEA during relapses or in RR patients with Gd+ lesions suggest its potential role in limiting the ongoing inflammatory process with potential neuroprotective implications. These findings provide further support for the development of drugs targeting eCBs as a potential pharmacological strategy to reduce the symptoms and slow disease progression in MS.

Multiple cranial nerve palsies in a patient with internal carotid artery dissection.

nunciation of the letter ‘S’. The patient also described experiencing a severe dysgeusia without involvement of the motor part of cranial nerve VII and moderate right facial pain. A few days later, the patient had sudden transient (1-hour) rotatory vertigo associated with nausea and aggravated by head movements. At this time, i.e. 10 days after the first symptoms, the patient was admitted to hospital. Neurological examination showed a right syndrome of lower cranial nerve palsies with dysphonia, pharyngeal and tongue paresis (IX, X, XII), horizontal nystagmus with the rapid phase on the left (presumably due to the involvement of the cranial nerve VIII) without acoustic impairment, slight left limb sensory disturbances and diminished reflexes – especially of the lower limbs. Magnetic resonance imaging (MRI) of the brain with diffusion-weighted images was performed, and any involvement of the brainstem was excluded. Duplex ultrasound examination was normal. Electromyography and lumbar puncture excluded a neuropathy, while MRI of the pharynx and hypopharynx excluded compressive diseases. During hospitalization, the patient had a sudden, mild reduction in visual acuity in the right eye lasting for 2 days, most likely due to transient ischemic optic neuropathy. The ocular fundus was normal. Seven days after admission, because of the occurDear Sir, The incidence of spontaneous cervical artery dissection is approximately 5 per 100,000 per year [1] . It is estimated that internal carotid artery (ICA) dissection is responsible for 5% of all ischemic strokes and for 25% of strokes in the young [2, 3] . With ongoing progress in neuroimaging techniques, a wider spectrum of clinical presentations regarding ICA dissection has been reported. In more than 90% of patients, ICA dissection causes carotid territory ischemia, local signs and/or symptoms on the dissection side, whereas the remaining ICA dissections are clinically asymptomatic. Cranial nerve palsy is reported in 8–16% of patients having ICA dissection [4] . Here, we report on a patient with right ICA dissection and ipsilateral multiple cranial nerve deficits (cranial nerves II, V, VII, VIII, IX, X and XII).

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.

Spiral computed tomography angiography (SCTA) and color coded duplex ultrasound (CCDUS): two complementary diagnostic techniques for assessment of extracranial cerebral artery stenosis.

Atherosclerotic lesions of the extracranial cerebral arteries account for ischemic stroke in over half of all cases. The risk of stroke associated with symptomatic carotid artery disease is related to the severity of the stenosis. Results of the two major clinical trials, North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST), showed that patients with symptomatic carotid artery disease may benefit from carotid endarterectomy. Therefore, detection and quantification of stenosis are essential. Discrepancies in the angiographic criteria used in both NASCET and ECST trials resulted in continued controversy about the most accurate method of measuring carotid artery stenosis. Moreover, to avoid complications related to the angiography procedure, a good evaluation of vessel wall and plaque composition need to be considered. Both SCTA and CCDUS are non invasive techniques that could overcome angiographic complications and give detailed information on stenosis grading and plaque characteristics. They have been used to evaluate carotid stenosis as a single or combined methods.