Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Regulating Mitophagy via mTOR-ULK1/FUNDC1 Axis in Rats

Objective: Electroacupuncture (EA) pretreatment has been shown to alleviate cerebral ischemia-reperfusion (I/R) injury; however, the underlying mechanism remains unclear. To investigate the involvement of mTOR signaling in the protective role of EA in I/R-induced brain damage and mitochondrial injury. Methods: Sprague-Dawley male rats were pretreated with vehicle, EA (at Baihui and Shuigou acupoints), or rapamycin + EA for 30 min daily for 5 consecutive days, followed by the middle cerebral artery occlusion to induce I/R injury. The neurological functions of the rats were assessed using the Longa neurological deficit scores. The rats were sacrificed immediately after neurological function assessment. The brains were obtained for the measurements of cerebral infarct area. The mitochondrial structural alterations were observed under transmission electron microscopy. The mitochondrial membrane potential changes were detected by JC-1 staining. The alterations in autophagy-related protein expression were examined using Western blot analysis. Results: Compared with untreated I/R rats, EA-pretreated rats exhibited significantly decreased neurological deficit scores and cerebral infarct volumes. EA pretreatment also reversed I/R-induced mitochondrial structural abnormalities and loss of mitochondrial membrane potential. Furthermore, EA pretreatment downregulated the protein expression of LC3-II, p-ULK1, and FUNDC1 while upregulating the protein expression of p-mTORC1 and LC3-I. Rapamycin effectively blocked the above-mentioned effects of EA. Conclusion: EA pretreatment at Baihui and Shuigou alleviates cerebral I/R injury and mitochondrial impairment in rats through activating the mTORC1 signaling. The suppression of autophagy-related p-ULK1/FUNDC1 pathway is involved in the neuroprotective effects of EA.     

A Single Immediate Use of the Cathodal Transcranial Direct Current Stimulation Induces Neuroprotection of Hippocampal Region Against Global Cerebral Ischemia

ObjectivesGlobal cerebral ischemia (CI) causes severe neuronal injury, mainly in the hippocampal CA1 region. This study aimed to investigate an immediate using transcranial direct current stimulation (tDCS) in reducing neuronal injury induced by CI.Materials and methodsThe 32 Wistar male rats were randomly divided into four groups (n=8 per group). In the ischemia group (I), CI was induced via the 4-vessel occlusion model. In the sham group (Sh), rats did not receive any intervention. In the ischemia+cathodal group (I+c/tDCS), the cathodal current was applied during CI. In the ischemia+anodal group (I+a/tDCS), the anodal current was applied. The current intensity of 400 μA was applied for 15-min during the ischemia. Hippocampal tissue was used to assess levels of NMDAR, IL-1β, TNF-α, MDA, SOD, NOS, and apoptosis markers. Histological assessment and TUNEL staining were performed in CA1 hippocampal region.ResultsThe c/tDCS significantly decreased the levels of IL-1β and TNF-α than the I and a/tDCS groups. The c/tDCS significantly reduced MDA and NOS levels, while increasing the level of SOD than the I and a/tDCS. The c/tDCS caused a significant decrease in NMDAR level than the a/tDCS. Using c/tDCS significantly reduced the Bax and Caspase-3 expressions, while increasing the Bcl-2 expression than the I group. In the c/tDCS group, DNA fragmentation and neuronal death were significantly lower than the I and a/tDCS groups.ConclusionUsing cathodal a direct current could attenuate primary pathophysiological pathways induced by CI, and it eventually reduced neurons death and apoptosis in the CA1 hippocampal region.     

Do Adults with Stroke have Altered Interhemispheric Inhibition? A Systematic Review with Meta-Analysis

ObjectiveInterhemispheric inhibition is an important cortical mechanism to support motor control. Altered interhemispheric inhibition has been the target of neuromodulation interventions. This systematic review investigated the evidence for altered interhemispheric inhibition in adults with unilateral neurological conditions: stroke, amyotrophic lateral sclerosis, cerebral palsy, complex regional pain syndrome, traumatic brain injury, and cerebral palsyMethodsWe pre-registered the protocol and followed PRISMA guidelines. Five databases were systematically searched to identify studies reporting interhemispheric inhibition measures in unilateral neurological conditions and healthy controls. Data were grouped according to the measure (ipsilateral silent period and dual-coil), stimulated hemisphere, and stage of the condition (subacute and chronic).Results1372 studies were identified, of which 14 were included (n = 226 adults with stroke and 161 age-matched controls). Ipsilateral silent period-duration was longer in people with stroke than in controls (stimulation of dominant hemisphere) regardless of stroke stage. Motor evoked potential was less suppressed in people with sub-acute stroke (stimulation of the unaffected hemisphere) than controls (stimulation of dominant hemisphere) and this reversed in chronic stroke.ConclusionDetection of altered interhemispheric inhibition appears to be dependent on the measure of interhemispheric inhibition and the stage of recovery.SignificanceRebalancing interhemispheric inhibition using neuromodulation is considered a promising line of treatment for stroke rehabilitation. Our results did not find compelling evidence to support consistent alterations in interhemispheric inhibition in adults with stroke.     

Dynamic Changes in Brain Iron Metabolism in Neonatal Rats after Hypoxia-Ischemia

ObjectivesThe pathogenesis of hypoxic-ischemic white matter injury (WMI) in premature infants is still unclear, and the imbalance of cerebral iron metabolism may play an important role. Our study set out to investigate the changes in iron distribution, iron content and malondialdehyde (MDA) in disparate brain regions (parietal cortex, corpus callosum, hippocampus) within 84 days after hypoxia-ischemia (HI) in neonatal rats and to clarify the role of iron metabolism in WMI.Materials and MethodsWe adopted a rat model of hypoxic-ischemic WMI. Alterations in iron metabolism were detected by iron staining and iron assay kits, and the degree of brain injury was determined by MDA assays.ResultsOur results showed that different degrees of brain iron deposition occurred within 28 days after HI, and iron staining was the most obvious 3 days after HI. The iron content increased remarkably at 1–7 d after HI in the mixed tissues, especially at 3 d after HI. While the iron content in the parietal cortex and corpus callosum elevated obviously 14 days after HI. And the change trend of MDA was almost consistent with that of the iron content.ConclusionsOur findings revealed that brain iron metabolism changed dynamically in 3-day-old neonatal rats suffering from HI, which may cause lipid peroxidation damage to brain tissues. This process may be one of the pathogeneses of hypoxic-ischemic WMI.     

Effect of S-Nitrosylation of RIP3 Induced by Cerebral Ischemia on its Downstream Signaling Pathway

ObjectivesOur preliminary experiments indicate that receptor-interacting protein 3 (RIP3) is S-nitrosylated and contributes to its autophosphorylation (activation) after 3 h of rat brain ischemia/reperfusion mediated by activation of the N-methyl-D-aspartate receptor (NMDAR)-dependent neuronal NO synthase (nNOS) and is involved in the process of neuronal injury. Here, we will to demonstrate whether S-nitrosylation of RIP3 facilitates the activation of the downstream signaling pathway and finally exacerbates ischemic neuron death.Materials and methodsAdult male Sprague-Dawley rat transient brain ischemia/reperfusion and cortical neurons oxygen and glucose deprivation (OGD)/reoxygenation models were performed. The hippocampal CA1 regions or cultured cells were homogenized and the cytosolic fraction were collected as tissue samples. Coimmunoprecipitation and western blot analysis were carried out for detecting phosphorylation of RIP1 and mixed lineage kinase-like domains (MLKL) and the Cleaved-Caspase8 (Cl-Caspase8). The activities of Glycogen phosphorylase (PYGL), Glutamate-ammonia ligase (GLUL) and Glutamate dehydrogenase (GLUD1) were detected with ultraviolet absorption method.ResultsThis study showed that active RIP3 could phosphorylate RIP1 and MLKL through its kinase activity, promote the conversion of Caspase8 to active Cl-Caspase8, enhance the activities of PYGL, GLUL and GLUD1, and finally aggravate neuronal injury in cerebral ischemia/reperfusion. The inhibition of RIP3 S-nitrosylation inhibited the phosphorylation of RIP1 and MLKL, inhibited the activities of Caspase8, PYGL, GLUL, and GLUD1, and alleviated neuronal damage in cerebral ischemia/reperfusion.ConclusionsS-nitrosylation of RIP3 increased RIP1 and MLKL phosphorylation levels, Cl-Caspase8 content and PYGL, GLUL and GLUD1 activities and aggravated neuronal damage during cerebral ischemia/reperfusion and regulating the S-nitrosylation of RIP3 and its downstream signaling pathway might be a therapeutic target for stroke.     

Association Between Dietary Copper Intake and Cognitive Decline: A Perspective Cohort Study in Chinese Elderly

ObjectiveThe association between dietary copper (Cu) intake and cognitive decline remains uncertain. We aim to investigate the longitudinal association of dietary Cu with cognitive decline in Chinese elderly.MethodsA total of 3,106 Chinese adults aged older than or equal to 55 years from China Health and Nutrition Survey (CHNS) were included. Dietary nutrients information was collected by 24-hours dietary recalls in combination with a food-weighted method. The 5-year change rates in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status–modified (TICS-m) was calculated as the last-survey score minus the baseline score, then divided by the follow-up time (unit, years) and multiplied by five.ResultsThe median follow-up duration was 5.9 years. There was a nonlinear association of dietary Cu intake with the 5-year change rates in global or composite cognitive scores, with the inflection point at approximately 1.3 mg/day of dietary Cu intake. Accordingly, for the composite cognitive score, compared to the first quantile (<1.28 mg/day), those with dietary Cu in quantiles 2–8 (≥1.28 mg/day) had a significantly slower cognitive decline rate (B, 0.30; 95% CI, 0.13, 0.47). Similar results were found for the global cognitive score. Moreover, the inverse association between dietary Cu and cognitive decline was stronger in those with lower dietary fat intake and lower levels of physical activity (All p-interactions <0.05).ConclusionThere was a nonlinear inverse association of dietary Cu intake with cognitive decline in the elderly, with an inflection point at approximately 1.3 mg/day of dietary Cu intake.     

Cerebral fat embolism syndrome at a single trauma center

ObjectivesBased on a 16-year case series, we sought lessons about diagnosis and treatment of cerebral fat embolism syndrome.Materials and methodsUsing discharge codes at a Level 1 Trauma Center, we performed a retrospective chart review of clinical characteristics, diagnostic studies, treatments, and outcome in cerebral fat embolism syndrome.ResultsThirty-nine (40%) of 97 patients with fat embolism syndrome were diagnosed with cerebral fat embolism syndrome, with 29 (74%) presenting with coma. All had abnormal brain magnetic resonance imaging, with scattered cytotoxic edema (starfield pattern) in 29 (74%). All but two of the 21 patients with dilated fundoscopy showed retinal embolism. Among 29 patients with transcranial Doppler, the presence of microembolic signals in 15 (52%) was associated with fever (p = 0.039), right-to-left intracardiac shunting (p = 0.046) and a trend towards initial coma. In 11 patients with serial transcranial Dopplers and treatment with high-intensity statin therapy, the frequency of microembolic signals tended to decrease after therapy was initiated. Of the 28 (72%) of the 39 patients discharged, 16 (57%) had mild to moderate disability at last follow up.ConclusionsThe recognition of cerebral fat embolism syndrome may be improved with routine inclusion of brain magnetic resonance imaging, dilated fundoscopy, and transcranial Doppler. We share our empiric management algorithm for cerebral fat embolism syndrome using these studies and with consideration of experimental therapies in select patients to prevent ongoing cerebral injury.     

Quantitative electroencephalography characteristics of tilt-induced neurally-mediated syncope among youth

ObjectiveTo characterize the quantitative electroencephalographic (QEEG) patterns associated with tilt-induced syncope in youth.MethodsSeveral QEEG parameters were analyzed. Data were calculated for peak or nadir changes with syncope for amplitude-EEG, fast Fourier transform (FFT) power in several frequency ranges, 8–13 Hz/1–4 Hz frequency ratio, and FFT edge.ResultsChanges in QEEG parameters were present among all patients with tilt-induced syncope (n = 76). These changes included increases in the low frequency FFT power (1–4 Hz range), decreases in the power ratio (8–13 Hz/1–4 Hz) and decreases in the FFT edge (95%, 1–18 Hz). All patients had suppression of EEG amplitudes that closely followed loss of consciousness. Asymmetry indices demonstrated cerebral hemisphere lateralization at multiple periods during the evolution of syncope, but the side of lateralization did not differ from 0.5 probability.ConclusionsQEEG parameters can be used to characterize EEG changes associated with tilt-induced, neurally-mediated syncope.SignificanceQEEG may serve as a useful tool for the study of syncope neurophysiology, and the modeling of changes with syncope may improve our understanding of other neurologic disorders caused by defects in cerebral perfusion.     

Semaphorin 6D regulate corralling,hematoma compaction and white matter injury in mice after intracerebral hemorrhage

ObjectivesThe Semaphorin 6D (SEMA6D) shows important roles in cell guidance and lipid metabolism, but the effects and mechanisms of SEMA6D on tissue repair, white matter injury and the recovery of neurological function after intracerebral hemorrhage have not been well studied.Materials and MethodsIn this study, the autologous whole blood injection model of intracerebral hemorrhage was established in C57 male mice. SEMA6D knockout CRISPR utilized in the study. Assessments included neurological score evaluation and immunofluorescence.ResultsSEMA6D increased and peaked at 7d after intracerebral hemorrhage, and mainly located in neurons, microglia and astrocytes. SEMA6D knockout CRISPR aggravated neurological function and showed signs of poorer corralling and hematoma resolution, with more compartments of well-established physical barrier and more extensive GFAP positive astrocytic border. Furthermore, SEMA6D can prevent the decrease of NF-H in the peri-hematoma region, while SEMA6D knockout aggravated WMI.ConclusionsOur study suggested that SEMA6D could influence the recovery of neurological function by regulating the corralling, hematoma compaction and WMI in mice after intracerebral hemorrhage.     

Cerebral foreign body granulomas after mechanical thrombectomy: Two case reports and a review of the literature

ObjectivesA foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case.Material and MethodsCase 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy.ResultsMRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy.ConclusionsThe cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.     

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population.Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE.ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors.ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.     

Associations of carotid artery flow parameters with MRI markers of cerebral small vessel disease and patterns of brain atrophy

ObjectivesA growing body of evidence links age related brain pathologies to systemic vascular processes. We aimed to study the prevalence and interrelations between magnetic resonance imaging (MRI) markers of cerebral small vessel disease and patterns of brain atrophy, and their association to carotid duplex ultrasound flow parameters.Materials and methodsWe investigated a population based randomised cohort of older adults (n=391) aged 70-87, part of the Swedish Good Aging in Skåne Study. Peak systolic and end diastolic velocities of the carotid arteries were measured by ultrasound, and resistivity- and pulsatility indexes were calculated. Subjects with increased peak systolic velocity indicating carotid stenosis were excluded from analysis. Nine MRI findings were rated by visual scales: white matter changes, pontine white matter changes, microbleeds, lacunar infarctions, medial temporal lobe atrophy, global cortical atrophy, parietal atrophy, precuneus atrophy and central atrophy.ResultsMRI pathologies were found in 80% of subjects. Mean end diastolic velocity in common carotid arteries was inversely associated with white matter hyperintensities (OR=0.92; p=0.004), parietal lobe atrophy (OR=0.94; p=0.039), global cortical atrophy (OR=0.90; p=0.013), precuneus atrophy (OR=0.94; p=0.022), “number of CSV pathologies” (β=-0.07; p<0.001) and “MRI-burden score” (β=-0.11; p<0.001), after adjustment for age and sex. The latter three were also associated with pulsatility and resistivity indexes.ConclusionsLow carotid end diastolic velocity, as well as increased carotid resistivity and pulsatility, were associated with signs of cerebral small vessel disease and patterns of brain atrophy, indicating a vascular component in the process of brain aging.     

Stimulus-induced focal motor seizure in a pediatric patient with carbamazepine overdose

IntroductionCarbamazepine (CBZ) is a common antiepileptic drug that may cause overdoses with seizures as a common neurological manifestation. In previous reports, patients with CBZ overdose exhibited stimulus-induced generalized clinical or electrical seizures. To date, no previous cases of focal motor seizures have been reported.Case reportWe report the case of an 11-year-old girl with spontaneous and stimulus-induced clustering of focal motor seizures following CBZ overdose. The patient had been treated with CBZ (150 mg daily) for focal epilepsy since the age of six years. At the age of 11, she forgot to take a morning dose, took ten CBZ pills (CBZ 1000 mg) as compensation, and presented with generalized seizures. The patient arrived at the hospital in a coma. She demonstrated clustering of focal-to-bilateral tonic-clonic seizures induced by pain stimulus or spontaneously, with focal epileptiform discharges observed on EEG. Her CBZ blood concentration measured 40.4 μg/mL and she was diagnosed with CBZ overdose. The patient showed improvement without any specific treatment, and was later discharged without neurological sequelae.ConclusionPrevious cases of CBZ overdose with stimulus-induced generalized seizures resulted in death or required intensive care. Stimulus-induced focal seizures may indicate a favorable prognosis for CBZ overdose.     

A novel nomogram for early prediction of death in severe neurological disease patients with electroencephalographic periodic discharges

ObjectiveTo investigate death-related factors in patients with electroencephalographic (EEG) periodic discharges (PDs) and to construct a model for death prediction.MethodsThis case-control study enrolled a total of 80 severe neurological disease patients with EEG PDs within 72 h of admission to the neuroscience intensive care unit (NICU). According to modified Rankin scale (mRS) scores half a year after discharge, patients were divided into a survival group (<6 points) and a death group (6 points). Their relevant clinical and biochemical indicators as well as EEG characteristics were retrospectively analyzed. Logistic regression analysis was used to identify the risk factors associated with the death of patients with EEG PDs. A death risk prediction model and an individualized nomogram prediction model were constructed, and the prediction performance and concordance of the models were evaluated.ResultsMultivariate logistic regression analysis showed that the involvement of both gray and white matter in imaging, disappearance of EEG reactivity, occurrence of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), and an interval time of 0.5–4 s were independent risk factors for death. A regression model was established according to the multivariate logistic regression analysis, and the area under the curve of this model was 0.9135. The accuracy of the model was 87.01%, the sensitivity was 87.17%, and the specificity was 89.17%. A nomogram model was constructed, and a concordance index of 0.914 was obtained after internal validation.ConclusionThe regression model based on risk factors has high accuracy in predicting the risk of death of patients with EEG PDs.SignificanceThis model can help clinicians in the early assessment of the prognosis of severe neurological disease patients with EEG PDs.     

Changes in the treatment of pediatric acute encephalopathy in Japan between 2015 and 2021: A national questionnaire-based survey

BackgroundAlthough acute encephalopathy (AE) is the most serious disorder associated with a viral infection in childhood and often causes death or neurological sequelae, standard treatments have not been established. In 2016, the Japanese Society of Child Neurology published the “Guidelines for the Diagnosis and Treatment of Acute Encephalopathy in Childhood 2016” (AE GL 2016). We conducted a questionnaire survey to evaluate the status of the treatment of pediatric AE in 2021 and the changes in treatment before and after the publication of the AE GL 2016.MethodsIn October 2021, questionnaires were mailed via the web to members of two mailing lists who were involved in the practice of pediatric neurological disorders.ResultsMost Japanese physicians (98 %) engaged in the treatment of pediatric AE used the AE GL 2016 as a clinical reference. From 2015 to 2021, the number of institutions that implemented targeted temperature management (TTM), vitamin administration, and continuous electroencephalographic monitoring increased significantly. Regarding the targeted temperature for TTM, the proportion of patients who were treated with normothermia (36.0–37.0 °C) increased from 2015 (55 %) to 2021 (79 %). The use of corticosteroids in patients with AE caused by a cytokine storm, which is recommended in the AE GL 2016, had already been implemented in most institutions by 2015.ConclusionThe AE GL 2016 could be used to disseminate the knowledge accumulated to date. Evidence of the efficacy and proper indication criteria for the treatment of AE is insufficient and must be further accumulated.     

The impact of the approval of prothrombin complex concentrates for vitamin K antagonist-related intracerebral hemorrhage: A retrospective study

ObjectivesThis study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage.Materials and MethodsWe retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physician's discretion (previous dose group). After approval, we adopted the manufacturer's recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio <1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0–3 at discharge, and in-hospital mortality.ResultsThirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio <1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p<0.001 and 100% vs. 68%, p = 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups.ConclusionAfter prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage; however, there was no apparent difference in clinical outcomes.     

Median somatosensory evoked potential as a predictor of clinical outcome after urgent surgical extracranial internal carotid artery recanalization

ObjectiveChanges in the N20/P25 amplitude of somatosensory evoked potentials (SEP) of the median nerve have been found to correlate with those in cortical regional cerebral blood flow (rCBF). Our study presents the use of median nerve SEP amplitude in predicting the clinical outcome of urgent surgical internal carotid artery (ICA) recanalization.MethodsA total of 27 patients suffering an acute ischemic stroke (AIS) with extracranial ICA occlusion within 24 h were prospectively recruited. The primary preoperative endpoints included the SEP amplitude absolute value (SEP-amp) and the SEP amplitude side-to-side ratio (SEP-ratio).Clinical outcome at 3 months postoperatively was assessed using the modified Rankin scale (mRS-3M).ResultsThe positive predictive values (PPVs) for SEP-amp and SEP-ratio were 95.5% and 100%, respectively, with the negative predictive values (NPVs) being 60.0% and 100%, respectively. The SEP-ratio correlated fully with mRS-3M.ConclusionThe median SEP side-to-side N20/P25 amplitude ratio seems to be a very strong positive and negative predictor of the clinical outcome of urgent recanalization of an extracranial ICA occlusion.SignificanceThe results suggest that cortical evoked activity may help in selection patient for surgical recanalization and predict clinical recovery after an acute ischemic stroke.     

Clinical failure of natalizumab in multiple sclerosis: Specific causes and strategy

BackgroundNatalizumab is a very effective treatment of multiple sclerosis (MS). Failure is rare and should lead to consider some specific etiologies. The purpose of our study was to describe causes of subacute neurological events under natalizumab.MethodsObservational single-center retrospective study in the MS expert center of Lyon, France. Inclusion criteria: any patient with definite MS who received at least three infusions of natalizumab between April 2007 and February 2017. Clinical data were extracted from the Lyon EDMUS/OFSEP database. Events of interest: occurrence of a subacute neurological deficit, characterized by new clinical symptoms. We excluded pseudo-relapses and progression.FindingsA subacute neurological deficit occurred in 35 cases, for 607 patients treated with natalizumab. Ten patients presented natalizumab antibodies, nine had progressive multifocal leukoencephalopathy (PML), five presented an isolated subacute neurological deficit and two had AQP4 antibodies. No myelin oligodendrocyte glycoprotein (MOG) antibodies were found.InterpretationThe occurrence of an acute or subacute neurological deficit with natalizumab is rarely a MS relapse and should lead systematically to explore some important alternate etiologies, eliminating PML first.