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.

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.

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.

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.

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.

Antidromic sensory nerve conduction study of the digital branches of the medial plantar nerve: a novel method to detect early diabetic sensory axonal polyneuropathy.

INTRODUCTION: Distal sensory neuropathy is the most common form of diabetic neuropathy. We developed a novel antidromic technique for assessment of distal nerve function for early diagnosis of diabetic neuropathy. METHODS: Diabetic and control groups underwent standard and more distal sensory nerve conduction studies (NCS); sensory nerve action potentials (SNAPs) of the proper digital branches of the medial plantar nerve were recorded with our method after stimulation at the sole and recording from digits I and II. RESULTS: Comparison between controls and diabetics showed a statistically significant difference in mean SNAP amplitudes for all nerves tested. A higher percentage of abnormal SNAPs was obtained with our technique than with either conventional or more distal NCS in all patients. CONCLUSIONS: As compared with clinical evaluation and other NCS, our antidromic stimulation was the most sensitive method to detect abnormal sensory nerve conduction in symptomatic and asymptomatic diabetic patients.

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.

Circadian variation in the effect of intravenous thrombolysis after non-lacunar stroke.

The onset of non-lacunar stroke symptoms has a circadian variation, with a higher risk in the early morning hours and lower risk during the nighttime period, but this circadian distribution has not been clearly established on the effect of intravenous (IV) thrombolysis. The aim of the present study was to assess whether the time interval based on time of Alteplase IV infusion may influence the effect of treatment in patients with non-lacunar stroke. We conducted an analysis on prospectively collected data of 476 non-lacunar stroke patients treated with IV thrombolysis. To identify a possible circadian variation in the effect of Alteplase IV infusion, we used the following outcome measures: major neurological improvement (NIH stroke scale [NIHSS] score decrease of ≤8 points from baseline or NIHSS score of 0 at 24 h), and hemorrhagic transformation according to European Cooperative Acute Stroke Study trial definition within 24 h. Multivariate analysis showed that ORs for major neurological improvement were lower in patients who started IV thrombolysis in the 6 AM-noon interval (OR 0.35, 95% CI 0.16-0.74, p = 0.006) and noon-6 PM interval (OR 0.40, 95% CI 0.20-0.81, p = 0.010), whereas ORs for hemorrhagic transformation were lower in patients who started IV thrombolysis in the noon-6 PM interval (OR 0.29, 95% CI 0.12-0.67, p = 0.004) and in the 6 PM-midnight interval (OR 0.26, 95% CI 0.11-0.62, p = 0.002), compared with midnight-6 AM interval. The effect of Alteplase IV infusion could show a circadian variation in patients with non-lacunar stroke. After comparison with the midnight-6 AM interval, thrombolysis could be more safe from noon to midnight, and less effective from 6 AM to 6 PM.

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke.

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95% CI 1.61-21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.

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.

Chronic fusiform aneurysm evolving into giant aneurysm in the basilar artery.

Fusiform basilar aneurysm is a rare condition with elevated mortality within a few days if untreated. On the basis of clinical course, the fusiform aneurysm can be distinguished in an acute type, such as dissecting aneurysm, which usually causes subarachnoid hemorrhage or cerebral ischemia and in a chronic type with a relatively slow growth, which may evolve into a giant aneurysm leading to serious complications. We report a case of an 80-year-old man with a surgically untreated fusiform aneurysm that evolved into a giant aneurysm of the basilar artery within 4 years. The patient presented recurrent ischemic events involving the posterior circulation without aneurysmal rupture or bleeding.

Oculo-pyramidal crossed syndrome heralded by seizure: a case report.

Ischemic oculo-pyramidal crossed syndrome, i.e. amaurosis fugax contralateral to hemiparesis, is caused by an embolus from internal carotid artery occluding the retinal or the ophthalmic artery as well as the middle cerebral artery. We report on a patient with an oculopyramidal crossed syndrome due to internal carotid artery dissection and clinically manifesting with amaurosis fugax and seizure. Ischemic lesions can present with symptomatic seizures and, conversely, seizures may precede ischemic strokes, thus being a warning sign of a cerebrovascular event.

Muscular pain in Parkinson's disease and nociceptive processing assessed with CO2 laser-evoked potentials.

Muscular pain is the most frequent kind of nondystonic pain associated with Parkinson's disease (PD). It might be related not only to peripheral factors but also to an abnormal nociceptive input processing in the central nervous system. To test this hypothesis, we recorded CO(2) laser-evoked potentials (LEPs) in response to shoulder stimulation (skin over deltoid muscle) in 11 hemiparkinsonian PD patients complaining of muscular pain in the shoulder (ipsilateral to motor symptoms) and compared the results with those obtained in 12 pain-free PD patients with hemiparkinson and in 11 normal subjects. N2/P2 LEP, which is thought to originate from the cingulate cortex and insula, was significantly lower in amplitude in both groups of PD patients than in controls, regardless of the clinically affected body side. In both groups of PD patients, no significant correlation was observed between the severity of motor symptoms and N2/P2 amplitude abnormalities. In PD patients with muscular pain, the N2/P2 amplitude obtained following stimulation of the painful shoulder was significantly reduced compared with that obtained in response to nonpainful shoulder stimulation and compared with the values obtained in pain-free PD patients. No significant correlation was observed between the intensity of muscular pain and N2/P2 amplitude abnormalities in this group of PD patients. These results suggest abnormal nociceptive input processing in PD, which appears to be independent of clinical expression of parkinsonian motor signs. These alterations are more evident in the presence of muscular pain.

Intrathecal liposomal cytarabine in combination with temozolomide in low-grade oligoastrocytoma with leptomeningeal dissemination.

Leptomeningeal dissemination of low-grade gliomas is an uncommon event. A 43-year old male presented with dizziness, gait ataxia, and diplopia. A nonenhancing lesion in the right cerebellar peduncle was identified, subtotally resected, and diagnosed as a grade II astrocytoma. After one year a nodular spread in the brain and leptomeninges was diagnosed, so the patient started chemotherapy with temozolomide and liposomal cytarabine. Complete remission was achieved after 12 months of treatment and the patient is still free from the disease after a follow-up of 24 months. We suggest that this combination may be a valuable treatment option.

Dide-Botcazo syndrome due to bilateral occlusion of posterior cerebral artery.

Dide-Botcazo syndrome is a rare clinical syndrome characterized by a combination of cortical blindness with anosognosia for blindness, amnesia and topographical disorientation, secondary to bilateral occipital cortex lesions also involving the infero-medial temporal lobe structure. We report a case of a man who acutely presented confusion and cortical blindness. The cerebral angiography demonstrated bilateral occlusion of posterior cerebral artery (PCA). Sequential intravenous (i.v.) and intra-arterial (i.a.) thrombolysis were ineffective and the patient developed a complete Dide-Botcazo syndrome.

Blue rubber bleb nevus syndrome with late onset of central nervous system symptomatic involvement.

Blue rubber bleb nevus syndrome is a rare vascular disorder characterized by cavernous angiomas of skin and other organs including the gastrointestinal tract. The central nervous system involvement is seldom reported, and neurological symptoms at onset in adulthood are extremely rare. Here, we describe a case of 82-year-old patient presenting multiple skin haemangiomas for some years, who was admitted for a brain hemorrhage. The MRI demonstrated the presence of multiple cavernous angiomas within the cerebral tissue.

Late-onset choreoathetotic syndrome following heart surgery.

Choreoathetotic syndromes are frequently observed in children after congenital cardiopathy surgery. To report the case of an adult patient who developed a choreoathetotic syndrome after cardiac operation, probably related to a transitory hypometabolism of basal ganglia. A 52-year-old patient underwent heart surgery under circulatory arrest and deep hypothermia, for type III dissecting thoracic aorta aneurysm. Two weeks later she developed an acute choreic syndrome. The positron emission tomography using fluorodeoxyglucose (FDGC-PET) showed a bilateral hypometabolism of basal ganglia. After haloperidol administration, choreic syndrome improved and 6 months later FDGC-PET was normal. Choreoathetosis has been described as a rare complication after heart surgery. The authors suggest that this movement disorder may be related to hypothermia that can induce a reversible basal ganglia metabolic damage.

Association study between P53 and P73 gene polymorphisms and the sporadic late-onset form of Alzheimer's disease.

An important pathological aspect of Alzheimer's disease (AD) is the apoptosis of neuronal and glial cells. Two members of the same protein family that regulates many genes involved in apoptosis are P53 and the heterologue P73. One single nucleotide polymorphism (SNP) in the gene encoding P53 (Arg72Pro, RS1042522), one dinucleotide polymorphism (G4C14-to-A4T14, RS 2273953, RS1801173) in the gene encoding P73, and two further SNPs in the same gene (-386 G/A, RS3765728; exon 5 T/C, RS1801174) were studied to determine whether DNA variations could influence the occurrence of the disease in a sample of Italian subjects with the sporadic late-onset form of AD. We observed that carrying the Pro/Pro genotype of P53 Arg72Pro was a risk factor with respect to the Pro/Arg + Arg/Arg genotypes [Odds Ratio (OR) = 2.02; 95% Confidence Interval (CI) 1.02-4.00; p = 0.047]. Furthermore, carrying the G/G genotype of the P73 -386 G/A was a risk factor with respect to the G/A + A/A genotypes (OR = 4.27; 95% CI 1.00-18.65; p = 0.047). A significant result was also obtained for P73 G4C14-to-A4T14. Among the patients, the homozygotes for the AT allele of this SNP had developed AD symptoms 5 years earlier than other genotypes (ANOVA p = 0.017). Though the results of particular polymorphisms analyses were not highly significant after correction for multiple comparisons, present data suggest that variation at the two genes may have a role in AD occurrence.