Marcello Naccarato

Possible Anandamide and Palmitoylethanolamide involvement in human stroke

BackgroundEndocannabinoids (eCBs) are ubiquitous lipid mediators that act on specific (CB1, CB2) and non-specific (TRPV1, PPAR) receptors. Despite many experimental animal studies proved eCB involvement in the pathogenesis of stroke, such evidence is still lacking in human patients. Our aim was to determine eCB peripheral levels in acute stroke patients and evaluate their relationship with clinical disability and stroke volume.MethodsA cohort of ten patients with a first acute (within six hours since symptoms onset) ischemic stroke and a group of eight age- and sex-matched normal subjects were included. Groups were also matched for metabolic profile. All subjects underwent a blood sample collection for anandamide (AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) measurement; blood sampling was repeated in patients on admission (T0), at 6 (T1) and 18 hours (T2) thereafter. Patients neurological impairment was assessed using NIHSS and Fugl-Meyer Scale arm subitem (FMSa); stroke volume was determined on 48 h follow-up brain CT scans. Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.Results1)T0 AEA levels were significantly higher in stroke patients compared to controls. 2)A significant inverse correlation between T0 AEA levels and FMSa score was found. Moreover a positive correlation between T0 AEA levels and stroke volume were found in stroke patients. T0 PEA levels in stroke patients were not significantly different from the control group, but showed a significant correlation with the NIHSS scores. T0 2-AG levels were lower in stroke patients compared to controls, but such difference did not reach the significance threshold.ConclusionsThis is the first demonstration of elevated peripheral AEA levels in acute stroke patients. In agreement with previous murine studies, we found a significant relationship between AEA or PEA levels and neurological involvement, such that the greater the neurological impairment, the higher were these levels.

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue

PurposeThis study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue.Materials and methodsWe enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05).ResultsCompared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex.ConclusionsPatients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.RiassuntoObiettivoScopo del nostro lavoro è stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.Materiali e metodiSono stati arruolati 24 pazienti destrimani con SM recidivante-remittente (12 senza e 12 con fatica) e 15 volontari sani. L’indagine in risonanza magnetica (RM) (1,5 T) è stata eseguita in tutti i soggetti mediante sequenze convenzionali ed echo-planar imaging (EPI) per lo studio funzionale. Il compito motorio consisteva nel finger tapping sequenziale con la mano dominante. Sono state ottenute mappe statistiche di attivazione motoria. Il confronto fra i gruppi è stato condotto mediante analisi della varianza (ANOVA) (p<0,05).RisultatiRispetto ai controlli, nel gruppo di pazienti senza fatica è stato osservato un incremento dell’attivazione a livello delle aree sensitivo-motorie primarie, motoria supplementare di destra e premotoria di sinistra. è stata inoltre rilevata una maggiore attivazione a livello del cervelletto, controlateralmente al movimento, e a livello del lobulo parietale superiore bilateralmente. Dal confronto tra i due gruppi di pazienti, nei pazienti con fatica è emersa, a destra, una maggior attivazione a livello dell’area premotoria, del putamen e della corteccia prefrontale dorsolaterale.ConclusioniIn pazienti affetti da SM, l’insorgenza del sintomo fatica è accompagnato da una maggior attivazione del circuito motorio-attentivo omolaterale al movimento.Obiettivo Scopo del nostro lavoro e stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.

RM-f durante un compito motorio in pazienti con sclerosi multipla e fatica

PurposeThis study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue.Materials and methodsWe enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05).ResultsCompared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex.ConclusionsPatients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.RiassuntoObiettivoScopo del nostro lavoro è stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.Materiali e metodiSono stati arruolati 24 pazienti destrimani con SM recidivante-remittente (12 senza e 12 con fatica) e 15 volontari sani. L’indagine in risonanza magnetica (RM) (1,5 T) è stata eseguita in tutti i soggetti mediante sequenze convenzionali ed echo-planar imaging (EPI) per lo studio funzionale. Il compito motorio consisteva nel finger tapping sequenziale con la mano dominante. Sono state ottenute mappe statistiche di attivazione motoria. Il confronto fra i gruppi è stato condotto mediante analisi della varianza (ANOVA) (p<0,05).RisultatiRispetto ai controlli, nel gruppo di pazienti senza fatica è stato osservato un incremento dell’attivazione a livello delle aree sensitivo-motorie primarie, motoria supplementare di destra e premotoria di sinistra. è stata inoltre rilevata una maggiore attivazione a livello del cervelletto, controlateralmente al movimento, e a livello del lobulo parietale superiore bilateralmente. Dal confronto tra i due gruppi di pazienti, nei pazienti con fatica è emersa, a destra, una maggior attivazione a livello dell’area premotoria, del putamen e della corteccia prefrontale dorsolaterale.ConclusioniIn pazienti affetti da SM, l’insorgenza del sintomo fatica è accompagnato da una maggior attivazione del circuito motorio-attentivo omolaterale al movimento.Obiettivo Scopo del nostro lavoro e stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.

Expression of the Endocannabinoid Receptor 1 in Human Stroke: An Autoptic Study

OBJECTIVE Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved. Our aim was to evaluate the cerebral expression of CB1R in the ischemic brain areas of 9 patients who died due to acute cerebral infarction in the middle cerebral artery territory. METHODS The cerebral autoptic tissue was collected within 48 hours since death. Ischemic and contralateral normal-appearing areas were identified. After tissue preprocessing, 4-µm-thick cerebral sections were incubated with the primary CB1R antibodies (Cayman Chemical Company, Ann Arbor, MI). Thereafter, all cerebral sections were hematoxylin treated. In each section, the total cell number and CB1R-positive cells were counted and the CB1R-positive cell count ratio was calculated. For statistical analysis, Students t-test was used. RESULTS In normal tissue, CB1R-positive neurons were the majority; a few non-neuronal cells expressed CB1R. In the ischemic areas, a few neurons were detectable. A significant increase in total CB1R staining was found in the ischemic regions compared to contralateral areas. CONCLUSIONS We found an increase in CB1R expression in the ischemic region (neuronal and non-neuronal cell staining), suggesting the inflammatory reaction to the ischemic insult. Whether such response might mediate neuroprotective actions or excitotoxicity-related detrimental effects is still unclear.

Wake-up stroke and CT perfusion: effectiveness and safety of reperfusion therapy

ObjectiveIschemic stroke is a neuroemergency condition highly treatable with thrombolysis and thrombectomy. Recently, observational studies have brought insights into clinical and imaging characteristics of wake-up stroke, which interested up to 25% of ischemic stroke patients. In clinical practice, wake-up strokes are usually not considered for reperfusion therapy. The aim of this study was to investigate the use CT perfusion imaging in patients with wake-up stroke and to assess the effect of neuroimaging information provided by CT perfusion maps on the efficacy and safety of thrombolysis and thrombectomy.Patients and methodWe studied 22 wake-up stroke (WUS) patients (13F/9M mean age) who underwent reperfusion therapy after the eligibility assessed by the CT perfusion imaging (< 50% core-to-penumbra ratio and negative CT perfusion).ResultsMean National Institutes of Health Stroke Scale (NIHSS) was 8.1 ± 4.9 at admission while 3.3 ± 5.1 at discharge, significantly different from admission (p < 0.001). As many as ten patients had mRS lower than 3 at discharge. Intracranial hemorrhage occurred in five patients and caused symptoms worsening only in two patients (decrease of NIHSS score of 4 points) of which one patient died.ConclusionThe main finding of this study is that wake-up stroke with adequate selection by CT perfusion may benefit reperfusion treatment.

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech

BACKGROUND Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. MATERIALS AND METHODS Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. RESULTS The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). CONCLUSIONS Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement.