Sensitivity and specificity of the action observation network to kinematics, target object, and gesture meaning.

Hierarchical models have been proposed to explain how the brain encodes actions, whereby different areas represent different features, such as gesture kinematics, target object, action goal, and meaning. The visual processing of action-related information is distributed over a well-known network of brain regions spanning separate anatomical areas, attuned to specific stimulus properties, and referred to as action observation network (AON). To determine the brain organization of these features, we measured representational geometries during the observation of a large set of transitive and intransitive gestures in two independent functional magnetic resonance imaging experiments. We provided evidence for a partial dissociation between kinematics, object characteristics, and action meaning in the occipito-parietal, ventro-temporal, and lateral occipito-temporal cortex, respectively. Importantly, most of the AON showed low specificity to all the explored features, and representational spaces sharing similar information content were spread across the cortex without being anatomically adjacent. Overall, our results support the notion that the AON relies on overlapping and distributed coding and may act as a unique representational space instead of mapping features in a modular and segregated manner.

The place of Free Will: the freedom of the prisoner.

Debates about the concept of Free Will date back to ancient times. About 40 years ago, Benjamin Libet designed an experiment showing that the conscious intention to move is preceded by a specific pattern of brain activation. His finding suggested that unconscious processes determine our decisions. Libet-style experiments have continued to dominate the debate about Free Will, pushing some authors to argue that the existence of Free Will is a mere illusion. We believe that this dispute is because we often measure Free Will using arbitrary human decisions rather than deliberate actions. After reviewing the definition of Free Will and the related literature, we conclude that the scientific evidence does not disprove the existence of Free Will. However, our will encounters several constraints and limitations that should be considered when evaluating our deeds' personal responsibility.

"When You're Smiling": How Posed Facial Expressions Affect Visual Recognition of Emotions.

Facial imitation occurs automatically during the perception of an emotional facial expression, and preventing it may interfere with the accuracy of emotion recognition. In the present fMRI study, we evaluated the effect of posing a facial expression on the recognition of ambiguous facial expressions. Since facial activity is affected by various factors, such as empathic aptitudes, the Interpersonal Reactivity Index (IRI) questionnaire was administered and scores were correlated with brain activity. Twenty-six healthy female subjects took part in the experiment. The volunteers were asked to pose a facial expression (happy, disgusted, neutral), then to watch an ambiguous emotional face, finally to indicate whether the emotion perceived was happiness or disgust. As stimuli, blends of happy and disgusted faces were used. Behavioral results showed that posing an emotional face increased the percentage of congruence with the perceived emotion. When participants posed a facial expression and perceived a non-congruent emotion, a neural network comprising bilateral anterior insula was activated. Brain activity was also correlated with empathic traits, particularly with empathic concern, fantasy and personal distress. Our findings support the idea that facial mimicry plays a crucial role in identifying emotions, and that empathic emotional abilities can modulate the brain circuits involved in this process.

Uncover the Offensive Side of Disparagement Humor: An fMRI Study.

Disparagement humor is a kind of humor that denigrates, belittles an individual or a social group. In the aim to unveil the offensive side of these kinds of jokes, we have run an event-related fMRI study asking 30 healthy volunteers to judge the level of fun of a series of verbal stimuli that ended with a sentence that was socially inappropriate but funny (disparagement joke -DJ), socially inappropriate but not funny (SI) or neutral (N). Behavioral results showed disparagement jokes are perceived as funny and at the same time offensive. However, the level of offense in DJ is lower than that registered in SI stimuli. Functional data showed that DJ activated the insula, the SMA, the precuneus, the ACC, the dorsal striatum (the caudate nucleus), and the thalamus. These activations suggest that in DJ a feeling of mirth (and/or a desire to laugh) derived from the joke (e.g., SMA and precuneus) and the perception of the jokes' social inappropriateness (e.g., ACC and insula) coexist. Furthermore, DJ and SI share a common network related to mentalizing and to the processing of negative feelings, namely the medial prefrontal cortex, the putamen and the right thalamus.

Safety and Outcomes of Thrombectomy in Ischemic Stroke With vs Without IV Thrombolysis.

OBJECTIVE: To test the hypothesis that IV thrombolysis (IVT) treatment before endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the Safe Implementation of Treatment in Stroke-International Stroke Thrombectomy Register (SITS-ISTR). METHODS: We identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014 to 2019. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery, and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS-Monitoring Study. We performed propensity score-matched (PSM) and multivariable logistic regression analyses. RESULTS: Of 6,350 patients from 42 centers, 3,944 (62.1%) received IVT. IVT + EVT-treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure, and prestroke disability. PSM analysis showed that IVT + EVT-treated patients had a higher rate of functional independence than patients treated with EVT alone (46.4% vs 40.3%, p < 0.001) and a lower rate of death at 3 months (20.3% vs 23.3%, p = 0.035). SICH rates (3.5% vs 3.0%, p = 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM. CONCLUSION: Pretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS-ISTR. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding, and possible residual confounding by indication. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IVT before EVT increases the probability of functional independence at 3 months compared to EVT alone.

The Effect of Dopaminergic Replacement Therapy on Creative Thinking and Insight Problem-Solving in Parkinson's Disease Patients.

Parkinson's disease (PD) patients receiving dopaminergic treatment may experience bursts of creativity. Although this phenomenon is sometimes recognized among patients and their clinicians, the association between dopamine replacement therapy (DRT) in PD patients and creativity remains underexplored. It is unclear, for instance, whether DRT affects creativity through convergent or divergent thinking, idea generation, or a general lack of inhibition. It is also unclear whether DRT only augments pre-existing creative attributes or generates creativity de novo. Here, we tested a group of PD patients when "on" and "off" dopaminergic treatment on a series of tests of creative problem-solving (Alternative Uses Task, Compound Remote Associates, Rebus Puzzles), and related their performance to a group of matched healthy controls as well as to their pre-PD creative skills and measures of inhibition/impulsivity. Results did not provide strong evidence that DRT improved creative thinking in PD patients. Rather, PD patients "on" medication showed less flexibility in divergent thinking, generated fewer ideas via insight, and showed worse performance in convergent thinking overall (by making more errors) than healthy controls. Pre-PD creative skills predicted enhanced flexibility and fluency in divergent thinking when PD patients were "on" medication. However, results on convergent thinking were mixed. Finally, PD patients who exhibited deficits in a measure of inhibitory control showed weaker convergent thinking while "on" medication, supporting previous evidence on the importance of inhibitory control in creative problem-solving. Altogether, results do not support the hypothesis that DRT promotes creative thinking in PD. We speculate that bursts of artistic production in PD are perhaps conflated with creativity due to lay conceptions of creativity (i.e., an art-bias).

Novel pathogenic TGFBR1 and SMAD3 variants identified after cerebrovascular events in adult patients with Loeys-dietz syndrome.

INTRODUCTION: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder due to heterozygous pathogenic variants in transforming growth factor beta (TGFß) signaling-related genes. LDS types 1-6 are distinguished depending on the involved gene. LDS is characterized by multiple arterial aneurysms and dissections in addition to variable neurological and systemic manifestations. Patient 1: a 68-year-old man was admitted due to an aphasic transient ischemic attack (TIA). Brain CT-scan and CT angiography revealed a chronic and asymptomatic right vertebral artery dissection. Stroke diagnostic panel was unremarkable. His history showed mild stroke familiarity. At age of 49, he was treated for dissecting-aneurysm of the ascending aorta and started anticoagulation therapy. Seven years later, he underwent surgery for dissecting aneurysm involving aortic arch, descending-thoracic aorta, left subclavian artery, and both iliac arteries. Patient 2: a 47-year-old man presented a left hemiparesis due to right middle cerebral artery (MCA) and anterior cerebral artery (ACA) occlusion caused by right internal carotid artery (ICA) dissection after sport activity. Despite i.v. thrombolysis and mechanical thrombectomy, he developed malignant cerebral infarction and underwent decompressive hemicraniectomy. Digital subtraction angiography showed bilateral carotid and vertebral kinking, aneurysmatic dilatation on both common iliac arteries and proximal ectasia of the descending aorta. His father and his uncle died because of an ischemic stroke and a cerebral aneurysm rupture with a subarachnoid hemorrhage (SAH), respectively. DISCUSSION: in both cases, considering the family history and the multiple dissections and aneurysms, LDS molecular analysis was performed. In patient 1, the novel NM_005902.3 (SMAD3): c.840T > G; p.(Asn280Lys) likely pathogenic variant was identified, thus leading to a diagnosis of LDS type 3. In patient 2, the novel NM_004612.2 (TGFBR1): c.1225T > G; p.(Trp409Gly) likely pathogenic variant was found, allowing for a diagnosis of LDS type 1. CONCLUSION: LDS is characterized by genetic and clinical variability. Our report suggests that this genetically-determined connective tissue disorder is probably underestimated, as it might firstly show up with cerebrovascular events, although mild systemic manifestations. These findings could lead to identify people at risk of severe vascular complications (i.e., through genetic consult on asymptomatic relatives), in order to perform adequate vascular assessments and follow-up to prevent complications such as stroke.

Primary progressive aphasia and the FTD-MND spectrum disorders: clinical, pathological, and neuroimaging correlates.

Objective: Behavioral variant frontotemporal dementia (bvFTD), is commonly considered the cognitive presentation of the frontotemporal dementia-motor neuron disease (FTD-MND) spectrum disorder. We evaluated the prevalence of primary progressive aphasia in a series of pathologically confirmed cases of FTD-MND spectrum. Methods: Pathologically confirmed cases of frontotemporal lobar degeneration-motor neuron disease (FTLD-MND) were obtained from the UCSF brain bank. Cases were analyzed for presence of language impairment via retrospective chart review of research visits that include neurologic exam, in-depth cognitive testing and magnetic resonance imaging (MRI) imaging. Forty one cases were included. Thirty two were diagnosed with FTD-MND, while nine cases were diagnosed as MND-only from clinical evaluation. Results: Ten FTLD-MND cases (31%) presented with prominent or isolated language involvement consistent with a diagnosis of primary progressive aphasia (PPA), which we called progressive aphasia with motor neuron disease (PA-MND). Of these, three cases that mirrored the non-fluent variant of PPA (nfvPPA) were named nfvPA-MND. The imaging pattern of these nfvPA-MND showed atrophy strictly confined to the frontal and anterior temporal language cortical areas. Another group of seven cases that resembled patients with the semantic variant PPA (svPPA) were named svPA-MND. The group of svPPA-MND on imaging analysis showed selective atrophy of the temporal lobe and orbitofrontal cortex. Conclusions: Language impairment was a frequent phenotype of FTD-MND associated with focal atrophy patterns within the language networks. This data suggest patients with FTD-MND can present quite often with language phenotype of nfvPPA and svPPA, as opposed to exclusive bvFTD symptoms.

Mechanical knowledge does matter to tool use even when assessed with a non-production task: Evidence from left brain-damaged patients.

In the literature on apraxia of tool use, it is now accepted that using familiar tools requires semantic and mechanical knowledge. However, mechanical knowledge is nearly always assessed with production tasks, so one may assume that mechanical knowledge and familiar tool use are associated only because of their common motor mechanisms. This notion may be challenged by demonstrating that familiar tool use depends on an alternative tool selection task assessing mechanical knowledge, where alternative uses of tools are assumed according to their physical properties but where actual use of tools is not needed. We tested 21 left brain-damaged patients and 21 matched controls with familiar tool use tasks (pantomime and single tool use), semantic tasks and an alternative tool selection task. The alternative tool selection task accounted for a large amount of variance in the single tool use task and was the best predictor among all the semantic tasks. Concerning the pantomime of tool use task, group and individual results suggested that the integrity of the semantic system and preserved mechanical knowledge are neither necessary nor sufficient to produce pantomimes. These results corroborate the idea that mechanical knowledge is essential when we use tools, even when tasks assessing mechanical knowledge do not require the production of any motor action. Our results also confirm the value of pantomime of tool use, which can be considered as a complex activity involving several cognitive abilities (e.g., communicative skills) rather than the activation of gesture engrams.

Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment.

BACKGROUND: Post-thrombotic intracerebral hemorrhage (ICH) is experienced by 6-8% of stroke patients and is associated with multiple factors, including acquired coagulopathy induced by the thrombolytic drug. OBJECTIVES: The objective of this study was to assess the outcome of the intravenous (IV) administration of fibrinogen concentrate in a series of acute stroke patients who developed iatrogenic fibrinogen critical depletion after IV thrombolysis. MATERIAL AND METHODS: Of the 39 ischemic stroke patients treated with IV thrombolysis with a severe hypofibrinogenemia requiring infusion with IV fibrinogen concentrate, 30 patients were treated with 2 g of IV recombinant tissue plasminogen activator (rt-PA), followed by further doses until the fibrinogen level reached 200 mg/dL in hemorrhagic patients or 100 mg/dL in non-hemorrhagic patients, and 9 were treated with IV rt-PA followed by endovascular thrombectomy. RESULTS: Preand post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) scores were statistically different for the Cochran-Mantel-Haenszel test overall (p = 0.0002), at 24-hour evaluation (p = 0.0455) and at 7-day assessment (p = 0.0006). Within the first 7 days post-thrombolysis, the brain computed tomography (CT) scans showed that 20/39 (51.28%) patients had ICH. Of the whole sample, 25.6% of the ICH patients had symptomatic intracerebral hemorrhage (SICH), according to National Institute of Neurological Disorders and Stroke (NINDS) classification. After rt-PA treatment, the median pre-thrombolysis fibrinogenemia of 332 mg/dL significantly dropped to 133 mg/dL (p < 0.0001). After the fibrinogen concentrate infusion, the median level of fibrinogenemia rose to 160 mg/dL, which was significantly higher than the median postthrombolysis levels (p < 0.0001). Recanalization was observed in 25/28 patients (89.29%): complete in 18 and partial in 7 patients. After fibrinogen IV infusion, no thrombotic complications were seen in 37 out of 39 patients (94.77%); 2/39 (0.05%) patients experienced a pulmonary embolism, 1 of them a segmental one. CONCLUSIONS: This study showed the clinical safety of administering IV fibrinogen concentrate in order to increase plasma fibrinogen levels in a series of acute stroke patients with iatrogenic fibrinogen depletion after IV thrombolysis.

Eight Weddings and Six Funerals: An fMRI Study on Autobiographical Memories.

"Autobiographical memory" (AM) refers to remote memories from one's own life. Previous neuroimaging studies have highlighted that voluntary retrieval processes from AM involve different forms of memory and cognitive functions. Thus, a complex and widespread brain functional network has been found to support AM. The present functional magnetic resonance imaging (fMRI) study used a multivariate approach to determine whether neural activity within the AM circuit would recognize memories of real autobiographical events, and to evaluate individual differences in the recruitment of this network. Fourteen right-handed females took part in the study. During scanning, subjects were presented with sentences representing a detail of a highly emotional real event (positive or negative) and were asked to indicate whether the sentence described something that had or had not really happened to them. Group analysis showed a set of cortical areas able to discriminate the truthfulness of the recalled events: medial prefrontal cortex, posterior cingulate/retrosplenial cortex, precuneus, bilateral angular, superior frontal gyri, and early visual cortical areas. Single-subject results showed that the decoding occurred at different time points. No differences were found between recalling a positive or a negative event. Our results show that the entire AM network is engaged in monitoring the veracity of AMs. This process is not affected by the emotional valence of the experience but rather by individual differences in cognitive strategies used to retrieve AMs.

Neural Correlates of Anosognosia in Alzheimer's Disease and Mild Cognitive Impairment: A Multi-Method Assessment.

Patients with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) may present anosognosia for their cognitive deficits. Three different methods have been usually used to measure anosognosia in patients with AD and MCI, but no studies have established if they share similar neuroanatomical correlates. The purpose of this study was to investigate if anosognosia scores obtained with the three most commonly used methods to assess anosognosia relate to focal atrophy in AD and MCI patients, in order to improve understanding of the neural basis of anosognosia in dementia. Anosognosia was evaluated in 27 patients (15 MCI and 12 AD) through clinical rating (Clinical Insight Rating Scale, CIRS), patient-informant discrepancy (Anosognosia Questionnaire Dementia, AQ-D), and performance discrepancy on different cognitive domains (self-appraisal discrepancies, SADs). Voxel-based morphometry correlational analyses were performed on magnetic resonance imaging (MRI) data with each anosognosia score. Increasing anosognosia on any anosognosia measurement (CIRS, AQ-D, SADs) was associated with increasing gray matter atrophy in the medial temporal lobe including the right hippocampus. Our results support a unitary mechanism of anosognosia in AD and MCI, in which medial temporal lobes play a key role, irrespectively of the assessment method used. This is in accordance with models suggesting that anosognosia in AD is primarily caused by a decline in mnemonic processes.

Antibody profile may predict outcome in ocular myasthenia gravis.

An unsolved issue remains whether there are clinical and immunological features to predict in a single patient the risk of conversion from ocular Myasthenia Gravis (OMG) to generalized disease (GMG) as 50-60% of patients may progress within 1-2 years since onset. Anti-acetylcholine receptor antibodies (AChR Abs) are found in up to 50% of OMG patients; muscle-specific tyrosine kinase antibodies (MuSK-Abs) are present in about 70% of the whole seronegative (SN), who usually develop a severe disease with bulbar involvement. We surveyed a cohort of 175 OMG patients with purely ocular symptoms and we compare the outcome of patients with antibodies to AChR or to MuSK with those seronegative for both Abs (DSN). All patients had purely ocular signs for at least 24 months. Gender, age at onset, time to generalization or to worsening in quantitative ocular QMG scores, electrophysiological results were analyzed. Males were 58.9%, females 41.1%. Patients with late onset of symptoms after 50 years (LOMG) were 78.3%. We assayed anti-MuSK-Abs in 4.7%, anti-AChR Abs in 38.5%; 57.3% were defined DSN. Thirty-seven patients (21.1%) progressed to GMG during the observational time: 23 were females, 62% of the whole group of the generalized subjects, 75% of MuSK-positive OMG converted to GMG versus the 26.2% of AChR positive and 13.7% of DSN. Statistical analysis showed that gender and presence of antibodies either to AChR or to MuSK were independent predictors of worse outcome; the DSN subjects had lower risk of conversion to GMG.

Modulation of neural circuits underlying temporal production by facial expressions of pain.

According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.

Factors affecting outcome in ocular myasthenia gravis.

AIM OF THE STUDY: 50%-60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables. MATERIALS AND METHODS: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients. RESULTS: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL. CONCLUSIONS: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment.

BACKGROUND: Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. METHODS: We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer's dementia. RESULTS: Twenty-one out of the 56 subjects developed Alzheimer's dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer's dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0-9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer's dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer's dementia at the beginning of the follow-up. CONCLUSIONS: These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer's dementia.

Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study.

BACKGROUND: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms. METHODS: A total of 624 stroke patients on antiplatelet therapy were included. Two different groups were identified: "non-naive patients", and "naive patients". Platelet function was measured with multiple electrode aggregometry, and genotyping assays were used to determine CYP2C19 polymorphisms. RESULTS: Aspirin (ASA) responsiveness was significantly more frequent in naive patients compared with non-naive patients (94.9% versus 82.6%, P < .0010). A better responsiveness to ASA compared with Clopidogrel or combination therapy was found in the entire population (P < .0010), in non-naive patients (P < .0253), and in naive patients (P < .0010). Multivariate analysis revealed a strong effect of Clopidogrel as a possible "risk factor" for unresponsiveness (odds ratio 3.652, P < .0001). No difference between etiological subgroups and no correlations between responsiveness and CYP2C19 polymorphisms were found. CONCLUSION: In our opinion, platelet function testing could be potentially useful in monitoring the biological effect of antiplatelet agents. A substantial proportion of patients with stroke on ASA were "resistant", and the treatment with Clopidogrel was accompanied by even higher rates of unresponsiveness. Longitudinal studies are needed to assess whether aggregometry might supply individualized prognostic information and whether it can be considered a valid tool for future prevention strategies.

Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome.

Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years.