Primary versus secondary mechanical thrombectomy for anterior circulation stroke in children: An update.

This review of the literature on the use of mechanical thrombectomy (MT) in children with acute ischemic stroke from occlusion of the internal carotid artery and the proximal middle cerebral artery (MCA) compares the efficacy and safety of primary and secondary MT. We analyzed the data reported for 24 case reports from 20 relevant articles published up to 31 December 2016 and the data of a patient treated at our institution. Eighteen cases received primary MT and 7 received secondary MT. The proportions of complete MCA recanalization, small infarcts, and asymptomatic intracranial hemorrhage were similar in both MT groups (73% [11/15] vs. 67% [4/6], 58% [7/12] vs. 60% [3/5], and 15% [2/13] vs. 17% [1/6], respectively). The proportion of favorable neurological outcomes was higher for the primary MT group (69% [11/16] vs. 43% [3/7]). We found no substantial differences in efficacy and safety between primary and secondary MT for anterior circulation stroke in children.

Modulation of somatoparaphrenia following left-hemisphere damage.

Somatoparaphrenic symptoms after left-hemisphere damage are rare. To verify the potential role of body-related sensory (proprioceptive, visual, and somatosensory) manipulation in patients experiencing sensations of hand disownership, the symptoms of a patient suffering from right-hand somatoparaphrenia were monitored and clinical and neuropsychological variables were controlled. Four types of manipulation were administered: changes in spatial position of the hand, multisensory stimulation, and self-observation using video or mirrors. Multisensory visuo-tactile stimulation was efficacious in terms of reducing somatoparaphrenia, and changes in the position of the hand produced some positive effects. Third-person perspective self-observation did not, however, result in any changes.

Early secondary prevention after initially ineffective revascularization treatments for acute ischemic stroke due to tandem occlusion.

: The most effective treatment of patients with stroke due to tandem occlusion is still unclear. We report the case of a man with stroke due to tandem internal carotid artery/middle cerebral artery occlusion, who underwent initially ineffective intravenous thrombolysis (IVT) and endovascular treatment. Early anticoagulation with apixaban was started after 48 h of IVT, given a newly diagnosed nonvalvular atrial fibrillation. Spontaneous partial recanalization of the cervical internal carotid artery was noted, and carotid endarterectomy was performed 72 h after IVT and 8 h after the last dose of apixaban. Surgery was conducted without any complication and the patient was discharged 7 days after onset with a residual mild hemiparesis. This is the first report of urgent carotid endarterectomy in an anticoagulated patient receiving a direct oral anticoagulant. This case highlights the importance of an early multidisciplinary approach to achieve a successful treatment of stroke due to tandem occlusion.

Prognostic Importance of Lesion Location on Functional Outcome in Patients with Cerebellar Ischemic Stroke: a Prospective Pilot Study.

To date, few studies focused on prediction of functional recovery after cerebellar stroke. The main aim of this prospective pilot study was to determine the association between cerebellar lesion location and functional outcome in adults with acute cerebellar infarction. We examined 14 patients with first-ever unilateral cerebellar ischemic stroke within 7 days and at 90 days from the onset of stroke by means of the International Cooperative Ataxia Rating Scale. Cerebellar lesions were traced from magnetic resonance imaging performed within 72 h since stroke and region of interest were generated. The association between the International Cooperative Ataxia Rating Scale score and lesion location was determined with the voxel-based lesion-symptom mapping methods implemented in the MRIcro software. Colored lesion-symptom maps representing the z statistics were generated and overlaid onto the MNI-ICBM 152 linear probabilistic atlas of the human brain and the Johns Hopkins University white matter templates. Our results documented that injuries to the V, VI, VIIA Crus I, VIIA Crus II, VIIB, VIIIA, and VIIIB lobules and the middle cerebellar peduncle are significantly associated with the International Cooperative Ataxia Rating Scale (ICARS) score at 1 week after the onset of stroke. Furthermore, we found that injuries to the VI, VIIA Crus I, VIIA Crus II, VIIB, VIIIA, and VIIIB lobules, the dentate nucleus, and the middle cerebellar peduncle are significantly associated with the ICARS score at 3 months since the cerebellar stroke onset. The findings of this pilot study might improve prognostic accuracy of functional outcome in patients with acute cerebellar infarction.

Stroke etiologic subtype may influence the rate of hyperdense middle cerebral artery sign disappearance after intravenous thrombolysis.

Disappearance of hyperdense middle cerebral artery sign (HMCAS) on non-contrast brain computed tomography (CT) scan is a reliable sign of arterial recanalization after intravenous (IV) thrombolysis for ischemic stroke. We aimed to assess whether stroke etiologic subtype may influence the rate of HMCAS disappearance and the clinical outcome after IV thrombolysis. We conducted a retrospective analysis of data prospectively collected from 1031 consecutive stroke patients treated with IV thrombolysis. Outcome measures were HMCAS disappearance on follow-up CT scan within 22-36 h of IV thrombolysis, neurologic improvement (NIH Stroke Scale [NIHSS] ≤4 points from baseline or NIHSS score of 0) at 7 days, and modified rankin scale (mRS) ≤1 at 3 months. Of 256 patients with HMCAS on admission CT scan, 125 had a cardioembolic stroke, 67 a stroke due to large-artery atherosclerosis (LAA), 58 a stroke of undetermined etiology, and six a stroke secondary to carotid artery dissection. HMCAS disappearance occurred in 145 (56.6 %) patients, neurologic improvement in 122 (55.0 %) patients, and mRS ≤1 in 64 (32.8 %) patients. Compared with cardioembolic stroke patients, patients with stroke due to LAA had lower odds ratios (OR) for HMCAS disappearance (OR 0.29, 95 % CI 0.15-0.58, p < 0.001), neurologic improvement (OR 0.42, 95 % CI 0.22-0.82, p = 0.011), and mRS ≤1 (OR 0.18, 95 % CI 0.06-0.52, p = 0.002). No significant differences in outcome measures were found between cardioembolic strokes and strokes of undetermined etiology. This study suggests that stroke due to LAA is associated with lower rates of HMCAS disappearance, neurologic improvement, and mRS ≤1 after IV thrombolysis, compared with cardioembolic stroke.

Cortical and spinal excitability in patients with multiple sclerosis and spasticity after oromucosal cannabinoid spray.

BACKGROUND: Delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) has been recently approved for the management of treatment-resistant multiple sclerosis (MS) spasticity. Although the symptomatic relief of Sativex® on MS-spasticity has been consistently demonstrated, the pathogenetic implications remain unclear and the few electrophysiological studies performed to address this topic yielded controversial results. We therefore aimed to investigate the mechanisms underpinning the modulation of spastic hypertonia by Sativex®, at both central and spinal levels, through an extensive neurophysiological battery in patients with MS. METHODS: Nineteen MS patients with treatment-resistant spasticity were recruited. Before and after 4weeks of treatment with Sativex® patients were clinically assessed with the Modified Ashworth Scale (MAS) and underwent a large neurophysiological protocol targeting measures of excitability and inhibition at both cortical [e.g., intracortical facilitation (ICF), short (SICI) and long (LICI) intracortical inhibition, cortical silent period (CSP)] and spinal level [e.g., H-reflex, H/M ratio and recovery curve of the H-reflex (HRC)]. A group of 19 healthy subjects served as controls. RESULTS: A significant reduction of the MAS score after 4weeks of Sativex® treatment was detected. Before treatment, an increase in the late facilitatory phase of HRC was recorded in patients compared to the control group, that normalised post treatment. At central level, SICI and LICI were significantly higher in patients compared to healthy subjects. After therapy, a significant strengthening of inhibition (e.g. reduced LICI) and a non-significant facilitation (e.g. marginally increased ICF) occurred, suggesting a modulatory effect of Sativex® on different pathways, predominantly of inhibitory type. Sativex® treatment was well tolerated, with only 3 patients complaining about dizziness and bitter taste in their mouth. DISCUSSION: Our results confirm the clinical benefit of Sativex® on spastic hypertonia and demonstrate that it might modulate both cortical and spinal circuits, arguably in terms of both excitation and inhibition. We suggest that the clinical benefit was likely related to a net increase of inhibition at cortical level that, in turn, might have influenced spinal excitability.

Bilateral internal carotid artery dissection associated with prior syphilis: a case report and review of the literature.

Bilateral internal carotid artery dissection is a rare entity, and its presentation may include cerebral ischemia. We describe the case of a 69-year-old man with ischemic stroke and radiological evidence of intimal flap of both internal carotid arteries suggestive for dissection. During the hospitalization, our patient was found positive for a previous syphilis infection. We conducted a review of the literature, with evidence of a few cases of ischemic stroke presumably related to a prior syphilis. The absence of major cardiovascular risk factors in our patient leads us to believe that an etiopathogenetic link may exist between these two conditions.

The Representation of Objects in Apraxia: From Action Execution to Error Awareness.

Apraxia is a well-known syndrome characterized by the sufferer's inability to perform routine gestures. In an attempt to understand the syndrome better, various different theories have been developed and a number of classifications of different subtypes have been proposed. In this article review, we will address these theories with a specific focus on how the use of objects helps us to better understand upper limb apraxia. With this aim, we will consider transitive vs. intransitive action dissociation as well as less frequent types of apraxia involving objects, i.e., constructive apraxia and magnetic apraxia. Pantomime and the imitation of objects in use are also considered with a view to dissociating the various different components involved in upper limb apraxia. Finally, we discuss the evidence relating to action recognition and awareness of errors in the execution of actions. Various different components concerning the use of objects emerge from our analysis and the results show that knowledge of an object and sensory-motor representations are supported by other functions such as spatial and body representations, executive functions and monitoring systems.

The etiologic subtype of intracerebral hemorrhage may influence the risk of significant hematoma expansion.

BACKGROUND: Intracerebral hemorrhage (ICH) growth is an important independent predictor of clinical deterioration and outcome. Little is known about the association between etiology of ICH and occurrence of hematoma expansion (HE). The aim of the present study was to assess whether ICH etiologic subtype may influence the risk of significant HE. METHODS: We conducted an analysis on retrospectively collected data of 424 consecutive patients with ICH, who were admitted to the Verona General Hospital, from March 2011 to December 2014. Using the SMASH-U (Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined) classification, we identified the ICH etiologic subtypes. Outcome measure was significant HE (an absolute increase in ICH volume>12.5 mL or >50%) within 48 h. RESULTS: Significant HE occurred in 11/57 (19.3%) Amyloid, 7/14 (50%) Structural, 31/57 (54.4%) Medication, 25/44 (56.8%) in Systemic, 62/139 (44.6%) Hypertensive, and 21/68 (30.9%) Undetermined ICH. Baseline ICH volume (OR 1.011 per mL, 95% CI 1.006-1.017, p<0.001) and onset-to-baseline CT time (OR 0.919 per hour, 95% CI 0.852-0.990, p=0.027) were predictors of significant HE. Compared with Amyloid ICH, ORs for significant HE were higher in patients with Structural ICH (OR 1.430, 95% CI 1.060-1.948, p=0.023), Medication ICH (OR 4.344, 95% CI 1.382-13.653, p=0.012), Systemic ICH (OR 1.796, 95% CI 1.070-3.015, p=0.027), and Hypertensive ICH (OR 3.081, 95% CI 1.426-6.655, p=0.004). CONCLUSION: Our study shows that Structural, Medication, Systemic, and Hypertensive ICH were the etiologic subtypes associated with a higher risk of significant HE, compared with Amyloid ICH patients.

Regulation of IL-8 gene expression in gliomas by microRNA miR-93.

BACKGROUND: Different strategies have been proposed to target neoangiogenesis in gliomas, besides those targeting Vascular Endothelial Growth Factor (VEGF). The chemokine Interleukin-8 (IL-8) has been shown to possess both tumorigenic and proangiogenic properties. Although different pathways of induction of IL-8 gene expression have been already elucidated, few data are available on its post-transcriptional regulation in gliomas. METHODS: Here we investigated the role of the microRNA miR-93 on the expression levels of IL-8 and other pro-inflammatory genes by RT-qPCR and Bio-Plex analysis. We used different disease model systems, including clinical samples from glioma patients and two glioma cell lines, U251 and T98G. RESULTS: IL-8 and VEGF transcripts are highly expressed in low and high grade gliomas in respect to reference healthy brain; miR-93 expression is also increased and inversely correlated with transcription of IL-8 and VEGF genes. Computational analysis showed the presence of miR-93 consensus sequences in the 3'UTR region of both VEGF and IL-8 mRNAs, predicting possible interaction with miR-93 and suggesting a potential regulatory role of this microRNA. In vitro transfection with pre-miR-93 and antagomiR-93 inversely modulated VEGF and IL-8 gene expression and protein release when the glioma cell line U251 was considered. Similar data were obtained on IL-8 gene regulation in the other glioma cell line analyzed, T98G. The effect of pre-miR-93 and antagomiR-93 in U251 cells has been extended to the secretion of a panel of cytokines, chemokines and growth factors, which consolidated the concept of a role of miR-93 in IL-8 and VEGF gene expression and evidenced a potential regulatory role also for MCP-1 and PDGF (also involved in angiogenesis). CONCLUSION: In conclusion, our results suggest an increasing role of miR-93 in regulating the level of expression of several genes involved in the angiogenesis of gliomas.

Behavioral and neural correlates of visual emotion discrimination and empathy in mild cognitive impairment.

Emotional and social cognitive deficits were investigated in a group of 24 individuals with mild cognitive impairment (MCI) and 24 healthy controls. Empathic and visual emotional responses were collected, analyzed and correlated to brain structural imaging data by means of: (i) a pictorial matching-to-sample task with facial and non-facial stimuli; (ii) self-reported questionnaires for cognitive and affective emotional components, and alexithymia; (iii) in-depth assessment of cognitive functions. Results indicated that visual processing of faces in MCI individuals did not benefit from fearful emotional content which in healthy controls facilitates stimulus' recognition (emotional enhancement effect). This implicit visuo-emotional disorder was specific for the faces, did not generalize to other categories, and did not correlate to explicit measures of empathy. Thus, our main finding indicates that in MCI individuals, deficits in visual recognition of facial emotions may arise already in the earliest stages of memorization, during the visual encoding of facial emotions. Voxel-based morphometry revealed its association with atrophy in frontal and occipito-temporal regions, mostly involving the anterior medial prefrontal cortex (P<0.05, multiple-comparison correction). Neural evidences were corroborated by clinical scores showing significant correlation between reduction of Emotion Enhancement Effect and deficits in frontal/executive functions. Crucially, the disorder did not appear to be related to the number of impaired cognitive domains (single or multiple-domain MCI) but rather to the involvement of frontal brain networks and frontal/executive functions. This suggests that in prodromal stages of dementia, frontal symptoms may represent a significant signal of emotional recognition disorders.

The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. OBJECTIVE: The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. METHODS: Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. RESULTS: Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The preoperative "central" track (which corresponds to ideal STN targeting) proved to be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical target was confirmed by MER data in 76% of tracks in Group A, and in 75% of tracks in Group B (p < 0.001, univariate and multivariate analysis). CONCLUSION: 3T MRI appears to be a useful tool in STN-DBS preoperative targeting. Neurophysiologic testing remains fundamental to determine lead deepness (and prevent clinical side effects.

Yield of ultra-rapid carotid ultrasound and stroke specialist assessment in patients with TIA and minor stroke: an Italian TIA service audit.

In Italy the vast majority of TIA and minor strokes are seen in the A&E. Early diagnosis and management of TIA and minor stroke in this setting is habitually difficult and often lead to cost-ineffective hospital admissions. We set up an ultra-rapid TIA service run by neurovascular physicians based on early specialist assessment and ultrasound vascular imaging. We audit the clinical effectiveness and feasibility of the service and the impact of this service on TIA and minor strokes hospital admissions. We compared the rate of TIA and minor stroke admissions/discharges in the year before (T0) and in the year during which the TIA service was operating (T1). At T1 57 patients had specialist evaluation and 51 (89.5 %) of them were discharged home. Two (3.5 %) patients had recurrent symptoms after discharge. Seven had a pathological carotid Doppler ultrasound. Four of them had hospital admission and subsequent carotid endoarterectomy within a week. Taking the whole neurology department into consideration at T1 there was a 30-41 % reduction in discharges of patients with TIA or minor stroke. Taking the stroke unit section into consideration at T1 there was a 25 % reduction in admissions of patients with NIHSS score <4 and 40 % reduction in admissions of patients with Barthel Index above 80. The model of TIA service we implemented based on ultra-rapid stroke physician assessment and carotid ultrasound investigation is feasible and clinically valid. Indirect evidence suggests that it reduced the rate of expensive TIA/minor stroke hospital admissions.

Repeated intravenous thrombolysis after recurrent stroke. A case series and review of the literature.

BACKGROUND: The likelihood of severe disability and death increases with each recurrent stroke. Repeated intravenous (IV) thrombolysis remains one of the therapeutic options when secondary prevention fails; however, its effects after recurrent stroke are largely unknown. The aim of the present review was to assess the risks and benefits of IV re-thrombolysis after recurrent stroke as compared with IV thrombolysis after index stroke. METHODS: We identified 8 patients who repeated IV thrombolysis after recurrent stroke from among the 615 consecutive stroke patients who received IV thrombolysis at our Stroke Unit and 22 cases of IV re-thrombolysed patients extracted for the literature review of case reports and case series. RESULTS: After excluding the 6 patients treated with endovascular procedures, we included in the analyses 21 patients for which we had data on pre-stroke functional status and baseline neurological severity for each stroke event and post-treatment functional status for each IV thrombolysis. We compared second (n=21) and third (n=3) IV thrombolytic treatments with first IV thrombolytic treatments (n=21). Also, we compared IV thrombolytic re-treatments ≤3 months from previous IV thrombolysis (n=10) with those >3 months (n=14). No significant differences in the rate of intracranial hemorrhage with neurological deterioration, mortality and restitution of the pre-existing functional status were observed in the comparative analyses. CONCLUSIONS: IV re-thrombolysis may be safe and effective when recurrent stroke occurs after a period of complete neurologic regression lasting at least 24h or minor disability (mRS score ≤2) lasting at least 3 months since the previous stroke.

The cerebellum and visual perceptual learning: evidence from a motion extrapolation task.

Visual perceptual learning is widely assumed to reflect plastic changes occurring along the cerebro-cortical visual pathways, including at the earliest stages of processing, though increasing evidence indicates that higher-level brain areas are also involved. Here we addressed the possibility that the cerebellum plays an important role in visual perceptual learning. Within the realm of motor control, the cerebellum supports learning of new skills and recalibration of motor commands when movement execution is consistently perturbed (adaptation). Growing evidence indicates that the cerebellum is also involved in cognition and mediates forms of cognitive learning. Therefore, the obvious question arises whether the cerebellum might play a similar role in learning and adaptation within the perceptual domain. We explored a possible deficit in visual perceptual learning (and adaptation) in patients with cerebellar damage using variants of a novel motion extrapolation, psychophysical paradigm. Compared to their age- and gender-matched controls, patients with focal damage to the posterior (but not the anterior) cerebellum showed strongly diminished learning, in terms of both rate and amount of improvement over time. Consistent with a double-dissociation pattern, patients with focal damage to the anterior cerebellum instead showed more severe clinical motor deficits, indicative of a distinct role of the anterior cerebellum in the motor domain. The collected evidence demonstrates that a pure form of slow-incremental visual perceptual learning is crucially dependent on the intact cerebellum, bearing the notion that the human cerebellum acts as a learning device for motor, cognitive and perceptual functions. We interpret the deficit in terms of an inability to fine-tune predictive models of the incoming flow of visual perceptual input over time. Moreover, our results suggest a strong dissociation between the role of different portions of the cerebellum in motor versus non-motor functions, with only the posterior lobe being responsible for learning in the perceptual domain.

Mild cognitive impairment in patients with moderate to severe chronic plaque psoriasis.

BACKGROUND: Psoriasis is frequently associated with cardiometabolic comorbidities and depression that are risk factors for cognitive impairment. OBJECTIVE: To investigate cognitive performance in psoriatic patients. METHOD: Cognitive performances were assessed by neuropsychological tests in 41 patients with psoriasis and 37 controls. Diagnostic criteria for mild cognitive impairment (MCI) were (1) subjective complaint of a memory deficit, confirmed by a relative or caregiver, (2) pathological performance on neuropsychological tests investigating cognitive domains, (3) normal performance of daily living activities and (4) no dementia. Neuroimaging was studied by high-field magnetic resonance imaging and cortical thickness analysis. RESULTS: MCI was found in 18 out of 41 (44%) patients with psoriasis compared to 4 out of 37 (11%) controls (p = 0.002). In particular, patients with psoriasis had lower scores in the delayed recall of the Rey Auditory Verbal Learning Test (p = 0.04), Backwards Digit Span Test (p = 0.002), Weigl's Sorting Test (p = 0.01) and Trail Making Test B (p = 0.008). In the 7 patients submitted to cortical thickness analysis, a reduction in brain thickness in parahippocampal, superior temporal and frontal gyri of the left hemisphere was observed. CONCLUSIONS: Patients with psoriasis may have a precocious impairment of long-term verbal memory, executive functions and attention.