Alessandro Davoli

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.

Electrophysiological Effects of Trace Amines on Mesencephalic Dopaminergic Neurons

Trace amines (TAs) are a class of endogenous compounds strictly related to classic monoamine neurotransmitters with regard to their structure, metabolism, and tissue distribution. Although the presence of TAs in mammalian brain has been recognized for decades, until recently they were considered to be by-products of amino acid metabolism or as “false” neurotransmitters. The discovery in 2001 of a new family of G-protein-coupled receptors (GPCRs), namely trace amines receptors, has re-ignited interest in TAs. In particular, two members of the family, trace amine receptor 1 (TA1) and trace amine receptor 2 (TA2), were shown to be highly sensitive to these endogenous compounds. Experimental evidence suggests that TAs modulate the activity of catecholaminergic neurons and that TA dysregulation may contribute to neuropsychiatric disorders, including schizophrenia, attention deficit hyperactivity disorder, depression and Parkinsons disease, all of which are characterized by altered monoaminergic networks. Here we review recent data concerning the electrophysiological effects of TAs on the activity of mesencephalic dopaminergic neurons. In the context of recent data obtained with TA1 receptor knockout mice, we also discuss the mechanisms by which the activation of these receptors modulates the activity of these neurons. Three important new aspects of TAs action have recently emerged: (a) inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. While the first two effects have been well documented in our laboratory, the direct activation of GIRK channels by TA1 receptors has been reported by others, but has not been seen in our laboratory (Geracitano et al., 2004). Further research is needed to address this point, and to further characterize the mechanism of action of TAs on dopaminergic neurons.

Endovascular Stroke Treatment of Acute Tandem Occlusion: A Single-Center Experience

PURPOSE To evaluate outcomes and prognostic factors in patients with acute ischemic stroke caused by tandem internal carotid artery/middle cerebral artery occlusion undergoing endovascular treatment. MATERIALS AND METHODS Characteristics of consecutive patients with tandem occlusion (TO) were extracted from a prospective registry. Collateral vessel quality on pretreatment computed tomographic (CT) angiography was evaluated on a 4-point grading scale, and patients were dichotomized as having poor or good collateral flow. Outcome measures included successful reperfusion according to Thrombolysis In Cerebral Infarction score, good outcome at 3 months defined as a modified Rankin scale score ≤ 2, symptomatic intracranial hemorrhage (ICH; sICH), and mortality. RESULTS A total of 72 patients with TO (mean age, 65.6 y ± 12.8) were treated. Intravenous thrombolysis was performed in 54.1% of patients, and a carotid stent was inserted in 48.6%. Successful reperfusion was achieved in 64% of patients, and a good outcome was achieved in 32%. sICH occurred in 12.5% of patients, and the overall mortality rate was 32%. Univariate analysis demonstrated that good outcome was associated with good collateral flow (P = .0001), successful reperfusion (P = .001), and lower rate of any ICH (P = .02) and sICH (P = .04). On multivariate analysis, good collateral flow (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.04-0.75; P = .01) and age (OR, 1.08; 95% CI, 1.01-1.15; P = .01) were the only predictors of good outcome. The use of more than one device for thrombectomy was the only predictor of sICH (OR, 10.74; 95% CI, 1.37-84.13; P = .02). CONCLUSIONS Endovascular treatment for TO resulted in good outcomes. Collateral flow and age were independent predictors of good clinical outcomes at 3 months.

Efficacy and Safety of Mechanical Thrombectomy in Older Adults with Acute Ischemic Stoke

To evaluate the safety and efficacy of endovascular therapy in elderly adults treated for acute ischemic stroke.

Mechanical thrombectomy of acute ischemic stroke with a new intermediate aspiration catheter: preliminary results

Background and purpose To report clinical and procedural outcomes of acute ischemic stroke patients after endovascular treatment with the new thromboaspiration catheter AXS Catalyst 6. Methods Patients with anterior and posterior circulation stroke were selected. Successful reperfusion defined as a Thrombolysis in Cerebral Infarction (TICI) score ≥2 b and 3-month functional independence defined as a modified Rankin Scale (mRS) ≤2 were the main efficacy outcomes. Symptomatic intracranial hemorrhage and mortality were the main safety outcomes. Results 107 patients were suitable for analysis. Mean age was 73.18±12.62 year and median baseline NIHSS was 17 (range: 3–32). The most frequent site of occlusion was the middle cerebral artery (MCA) (60.7%). 76.6% of patients were treated with AXS Catalyst 6 alone without the need for rescue devices or thromboaspiration catheters. Successful reperfusion was achieved in 84.1%, functional independence in 47.6%, symptomatic intracranial hemorrhage occurred in 3.7%, and mortality in 21.4%. Conclusions Endovascular treatment with AXS Catalyst 6 proved to be safe, technically feasible, and effective. Comparison analyses with other devices for mechanical thrombectomy are needed.

Transient parkinsonism after unilateral midbrain stroke: a compensatory intervention from the healthy side?

A 69-year-old man was admitted in our department because of acute onset of left hemiparesis. The neurological examination, apart from the weakness and hypoesthesia in left limbs (NIHSS, National Institute of Health Stroke Scale = 5), also revealed moderate extrapyramidal signs, definitely absent before admission. Indeed patient had an abnormal diminution of facial expression, moderately impaired speech, mild bradykinesia on the right side proven with finger-tapping, open–close and prono-supination hand movements and foot-tapping. Brain magnetic resonance imaging (MRI), performed few days after the onset, showed an ischemic lesion of the right portion of midbrain with involvement of right cerebral peduncle. Therefore, patient was properly cared for the stroke, thus he had a normal clinical course and was discharged in a week. The observed extrapyramidal syndrome was further investigated by a SPECT with the presynaptic dopamine transporter (DAT) ligand ioflupane-123 (DaTscan) performed about 1 month after the clinical onset. The SPECT revealed a reduced tracer distribution in right striatum consistent with the ischemic lesion in the right substantia nigra (SN). Conversely, normal values of tracer’s uptake were measured in left striatum (Fig. 1). Patient was kept under observation and 1 year later, after rehabilitation, he clinically improved. He had minimal pyramidal signs on the left side, whereas bradykinesia and rigidity on the right body side were not-detectable. In face of this change, a new DaTscan was performed. The tracer uptake was found still more reduced in the right striatum, the affected side; contrarily in left striatum, the healthy side, was found unexpectedly increased (Fig. 2). This case allows us to reflect on two main points that call into question the lateralization of functions in basal ganglia (BG) circuits: (I) the unilateral lesion of SN was able to induce a not lateralized parkinsonian syndrome, partially masked by the hemiparesis; (II) the changes observed in the two brain SPECTs correlated with the clinical evolution may indicate an adaptation of the nigrostriatal pathway in the uninjured side. The research studies on Parkinson’s disease (PD) have shown how the unilateral nigrostriatal damage may induce several modifications in activity of both BG due or to the decrease of dopaminergic tone or even aimed to preserve this tone relatively constant. Breit et al. have observed, in the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD, that contralateral subthalamic nucleus (STN) and substantia nigra pars reticulate (SNr) were hyperactive in a similar fashion to the corresponding nuclei on the lesioned side; they also suggested that the Peduncle Pontine Nucleus (PPN) of the lesioned side, because of its pronounced crossing efferent projections, should be at the origin of these changes in the contralateral hemisphere [1]. Nikolaus et al. using a small animal positron emission tomography, investigated the changes in striatal dopamine D2 receptor density before and after 6-OHDA T. Schirinzi (&) A. Davoli M. Pierantozzi G. Sancesario Neurology, Department of System Medicine, University of Rome Tor Vergata, Viale Oxford 1, 00133 Rome, Italy e-mail: t.schirinzi@yahoo.com

Letter by Sallustio et al Regarding Article, “Endovascular Thrombectomy and Stroke Physicians: Equity, Access, and Standards”

We read with great interest the editorial by Davis et al1 recently published in Stroke . We totally agree with the authors about shortage of neurointerventionists. It is undoubted that health systems throughout the world have been taken by surprise and unprepared by the astonishing news of 2015. Health systems and, most of all, economies differ deeply between different countries. Despite cost savings in the social service sector deriving from treating stroke with thrombectomy,2 few improvements have been reached in terms of availability of neurointerventionists during the last 2 years. The need for much more thrombectomy performers is going to quickly and further increase in light of the recent results of the Diffusion-weighted imaging or computerized tomography perfusion …

Pretreatment predictors of malignant evolution in patients with ischemic stroke undergoing mechanical thrombectomy

Background Few data exist on malignant middle cerebral artery infarction (MMI) among patients with acute ischemic stroke (AIS) after endovascular treatment (ET). Numerous predictors of MMI evolution have been proposed, but a comprehensive research of patients undergoing ET has never been performed. Our purpose was to find a practical model to determine robust predictors of MMI in patients undergoing ET. Methods Patients from a prospective single-center database with AIS secondary to large intracranial vessel occlusion of the anterior circulation, treated with ET, were retrospectively analyzed. We investigated demographic, clinical, and radiological data. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. Results 98 patients were included in the analysis, 35 of whom developed MMI (35.7%). No differences in the rate of successful reperfusion and time from stroke onset to reperfusion were found between the MMI and non-MMI groups. The following parameters were identified as independent predictors of MMI: systolic blood pressure (SBP) on admission (p=0.008), blood glucose (BG) on admission (p=0.024), and the CTangiography (CTA) Alberta Stroke Program Early CT Score (ASPECTS) (p=0.001). A scoreof ≤5 in CTA ASPECTS was the best cut-off to predict MMI evolution (sensitivity 46%; specificity 97%; positive predictive value 78%; negative predictive value 65%). Conclusions in our study a clinical and radiological features-based model was strongly predictive of MMI evolution in AIS. High SBP and BG on admission and, especially, a CTA ASPECTS ≤5 may help to make decisions quickly, regardless of time to treatment and successful reperfusion.

Transient MR-angiography changes associated with morphological alterations in epileptic seizure: A short case series

• MRI is extremely helpful in detecting structural brain abnormalities associated with seizures