Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients.

Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. In vitro, the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization (p < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.

Assessing the upper motor neuron in amyotrophic lateral sclerosis using the triple stimulation technique: A multicenter prospective study.

OBJECTIVE: To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. METHODS: Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. RESULTS: TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. CONCLUSIONS: TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. SIGNIFICANCE: This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies.

INTRODUCTION: Guidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting. MATERIAL AND METHODS: Clinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure. RESULTS: Among 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups. CONCLUSION: When used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.

Headache Related Alterations of Visual Processing in Migraine Patients.

Migraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 interictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analyzed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days. Compared to healthy controls, interictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days. Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. PERSPECTIVE: This study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signaling that differ with the presence of headache.

Correlation between deep brain stimulation effects on freezing of gait and audio-spinal reflex.

OBJECTIVE: A network of cortical, subcortical and brainstem structures might be involved in freezing of gait (FOG). Subthalamic nucleus (STN) deep brain stimulation (DBS) could modulate this network. The audio-spinal reflex (ASR), reduced in PD, but increased by treatment, can be used to further investigate that locomotor network. The aim of this study is to find whether a correlation exists between ASR and FOG in PD patients under DBS. METHODS: In 14 PD patients with STN DBS and previous FOG, ASR was recorded, with DBS switched on and off. We also assessed FOG Questionnaire (FOGQ) and Unified Parkinson's Disease Rating Scale (UPDRS) Part III. RESULTS: Switching "on" DBS increased ASR amplitude (+ 33.2% with DBS ON, p = 0.048). We also found a significant inverse correlation between FOGQ and modulation of ASR by DBS (r = -0.59, r2 = 0.35, p < 0.05). CONCLUSIONS: This study shows that the incremental effect of DBS on ASR is greater in PD patients with less severe FOG. SIGNIFICANCE: This study shows a link between electrophysiological and clinical data about gait control. It might contribute to better understand why some DBS patients report heavy FOG and others do not. ASR might be used to evaluate or maybe predict the effect of stimulation parameters changes on FOG.

Evidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials.

BACKGROUND: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers. METHODS: Twenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups. RESULTS: The mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann's areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers. CONCLUSION: This study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology. This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata.

Brain Correlates of Single Trial Visual Evoked Potentials in Migraine: More Than Meets the Eye.

Background: Using conventional visual evoked potentials (VEPs), migraine patients were found to be hyperresponsive to visual stimulus. Considering that a significant portion of neuronal activity is lost for analysis in the averaging process of conventional VEPs, in this study we investigated visual evoked responses of migraine patients and healthy volunteers using a different approach: single trial analysis. This method permits to preserve all stimulus-induced neuronal activations, whether they are synchronized or not. In addition, we used MRI voxel-based morphometry to search for cortical regions where gray matter volume correlated with single trial (st) VEP amplitude. Finally, using resting-state functional MRI, we explored the connectivity between these regions. Results: stVEP amplitude was greater in episodic migraine patients than in healthy volunteers. Moreover, in migraine patients it correlated positively with gray matter volume of several brain areas likely involved in visual processing, mostly belonging to the ventral attention network. Finally, resting state functional connectivity corroborated the existence of functional interactions between these areas and helped delineating their directions. Conclusions: st-VEPs appear to be a reliable measure of cerebral responsiveness to visual stimuli. Mean st-VEP amplitude is higher in episodic migraine patients compared to controls. Visual hyper-responsiveness in migraine involves several functionally-interconnected brain regions, suggesting that it is the result of a complex multi-regional process coupled to stimulus driven attention systems rather than a localized alteration.

Motor cortex excitability changes in mild Alzheimer's disease are reversed by donepezil.

BACKGROUND: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). METHODS: We used transcranial magnetic stimulation to measure the active cortical motor threshold (ACMT) in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could have a direct effect on the excitability of the motor cortex. RESULTS: An increase of the ACMT was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the threshold did not differ significantly from normal subjects. CONCLUSIONS: The results suggest an early functional impairment of cholinergic neurotransmission in AD, which is associated to early changes in the excitability of the motor system.

An Investigation of the Late Excitatory Potentials in the Hand following Transcranial Magnetic Stimulation in Early Alzheimer's Disease.

BACKGROUND: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). PATIENTS AND METHODS: We measured the silent period (SP) induced by transcranial magnetic stimulation in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could modify it. RESULTS: An increase in the duration of the SP was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the duration did not differ significantly from that of normal subjects. The results of our study show a fragmentation and an enlargement of the SP in the presence of multiple late excitatory potentials (LEPs) in early untreated AD patients. These LEPs were also modulated by donepezil. CONCLUSIONS: The results suggest an early functional impairment of cholinergic neurotransmission in AD. The disturbance in acetylcholine output in early AD leads to a decrease in excitability of the motor system.

Treatments for progressing Parkinson's disease: a clinical case scenario study.

OBJECTIVE: A 'case scenario' study on clinical decisions in progressing Parkinson's disease (PD) was developed to complement scientific evidence with the collective judgment of a panel of experts. METHODS: The opinions of 9 experts in movement disorders on the appropriateness of 9 common pharmacological treatments for 33 hypothetical patient profiles were compared to those of 14 general neurologists. Before rating the case scenarios, all participants received a document integrating European and US guidelines for the treatment of patients with advanced PD. Case scenarios showing disagreement or with inconsistencies in appropriateness ratings were discussed at a feedback meeting. A tool for interactive discussion on the clinical case scenarios included was developed based on the outcome of the study. RESULTS: Current guidelines are often insufficient to adequately guide the management of patients with progressing PD. The case scenario study did not reveal major differences in opinions between experts in movement disorders and general neurologists about the appropriateness of certain drug choices for specific case scenarios. However in about 1 out of 5 treatment decisions where experts stated appropriateness or inappropriateness, the general neurologists panel had no or dispersed opinions. CONCLUSIONS: This study reveals more uncertainty about treatment of advanced PD in general neurologists compared with experts in movement disorders and underlines the need for additional support for guiding treatment decisions in clinical practice.

Transcranial magnetic stimulation in disorders of consciousness.

We have reviewed the literature on transcranial magnetic stimulation studies in patients with brain death, coma, vegetative, minimally conscious, and locked-in states. Transcranial magnetic stimulation permits non-invasive study of brain excitability and may extend our understanding of the underlying mechanisms of these disorders. However, use of this technique in severe brain damage remains methodologically ill-defined and must be further validated prior to clinical application in these challenging patients.

Early boost and slow consolidation in motor skill learning.

Motorskill learning is a dynamic process that continues covertly after training has ended and eventually leads to delayed increments in performance. Current theories suggest that this off-line improvement takes time and appears only after several hours. Here we show an early transient and short-lived boost in performance, emerging as early as 5-30 min after training but no longer observed 4 h later. This early boost is predictive of the performance achieved 48 h later, suggesting its functional relevance for memory processes.

Motor cortex excitability in Alzheimer's disease and in subcortical ischemic vascular dementia.

Twenty Alzheimer's disease (AD) patients, 20 subcortical ischemic vascular dementia (SIVD) patients and 20 neurologically and cognitively normal subjects underwent transcranial magnetic stimulation to study motor cortex excitability changes. Motor threshold (MT), amplitude of motor evoked potentials, silent period and the H/M ratio (amplitude of maximal Hoffman reflex vs. that of maximal motor response) were considered. MT was lower in SIVD patients when compared with AD patients (P = 0.003) and the control group (P < 0.001) and lower in AD patients when compared with the control group (P < 0.001). The increment of motor cortex excitability in AD and SIVD did not lead us to distinguish clearly the two types of dementia. It is likely that the electrophysiological similarity between AD and SIVD could represent another common mechanism shared from these forms of dementia.

Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance.

Migraine is a disorder in which central nervous sytem dysfunction might play a pivotal role. Electroneurophysiology seems thus particularly suited to study its pathophysiology. We have extensively reviewed evoked potential and transcranial magnetic stimulation studies performed in migraineurs in order to identify their pathophysiologic significance. Publications available to us were completed by a Medline search. Retrieved and personal data were compared with respect to methodology and interpreted according to present knowledge on cortical information processing. Results are in part contradictory which appears to be method-, patient- and disease- related. Nonetheless, both evoked potential and transcranial magnetic stimulation studies demonstrate that the cerebral cortex, and possibly subcortical structures, are dysfunctioning interictally in both migraine with and without aura. These electrophysiologic abnormalities tend to normalise just before and during an attack and some of them seem to have a clear familial and predisposing character. Besides the studies of magnetophosphenes which have yielded contrasting results, chiefly because the method is not sufficiently reliable, most recent electrophysiologic investigations of cortical activities in migraine favour deficient habituation and decreased preactivation cortical excitability as the predominant interictal dysfunctions. We propose that the former is a consequence of the latter and that it could favour both interictal cognitive disturbances as well as a cerebral metabolic disequilibrium that may play a role in migraine pathogenesis. To summarize, electrophysiologic studies demonstrate in migraine between attacks a cortical, and possibly subcortical, dysfunction of which the hallmark is deficient habituation.

Single motor axon conduction velocities of human upper and lower limb motor units. A study with transcranial electrical stimulation.

OBJECTIVES: To calculate conduction velocities (CV) of single motor axons innervating hand, forearm and leg muscles, weak anodal electrical transcranial stimuli were used and single motor unit potentials were recorded in 17 normal subjects. METHODS: The central motor conduction time and neuromuscular transmission delay were subtracted from the latency of unit response to cortical stimulation and single motor axon CV were calculated. RESULTS: In extensor indicis proprius (EIP) units, CV ranged from 30.3 to 76.1m/s (mean: 51.3 +/- 7.1m/s, 139 units). In first dorsal interosseous (FDI), they ranged from 45.1 to 66.2m/s (mean: 54.6 +/- 2.6m/s, 88 units). In tibialis anterior (TA), velocities ranged from 27.8 to 55.9m/s (mean: 41.3 +/- 7.5m/s, 123 units). In FDI units, velocities were compared with those obtained with the F-wave method (range: 50.3-64.5m/s, mean: 58.1 +/- 2.0m/s). CONCLUSIONS: Compared with previously published values, the present method gives better access to slow-conducting units, first recruited by transcranial stimulation and voluntary effort. The spectrum of individual CV was much broader for EIP and TA than for FDI. A linear decline of maximal CV with age was observed, while minimal CV were not affected, suggesting that aging causes a selective loss of the fastest-conducting units.