Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration.

Nogo receptor 1 (NgR1) mediates the inhibitory effects of several myelin-associated inhibitors (MAIs) on axonal regeneration in the central nervous system. A truncated soluble NgR1 (sNgR) has been reported to act as a decoy receptor to block the actions of MAIs. In this study, we fused the sNgR to nerve growth factor (NGF) and used NGF as a carrier to deliver sNgR to the intercellular space to neutralize MAIs. NGF in NGF-sNgR remained biologically active and induced sprouting of calcitonin gene related peptide containing axons when expressed in the spinal cord using a lentiviral vector (LV). Secreted NGF-sNgR promoted neurite outgrowth of dissociated dorsal root ganglion neurons on myelin protein substrate. In a rat dorsal column transection model, regenerating sensory axons were found to grow into the lesion cavity in animals injected with LV/NGF-sNgR, while in animals injected with LV/GFP or LV/NGF-GFP few sensory axons entered the lesion cavity. The results indicate that NGF-sNgR fusion protein can reduce the inhibition of MAIs and facilitate sensory axon regeneration. The fusion constructs may be modified to target other molecules to promote axonal regeneration and the concept may also be adapted to develop gene therapy strategies to treat other disorders.

The Simultaneous Occurrence of Acute ST-Elevation Myocardial Infarction, Acute Ischemic Stroke, and Pulmonary Embolism.

Acute ST-elevation myocardial infarction (STEMI), acute ischemic stroke (AIS), and acute pulmonary embolism (PE) are life-threatening conditions, each posing a high risk of morbidity and mortality. When all three of these acute conditions occur simultaneously, the overall prognosis for the patient becomes considerably worse. We report a case of a 70-year-old woman who presented to the emergency department (ED) with a triad of acute STEMI, AIS, and PE as a consequence of atherosclerotic heart disease, atrial fibrillation, and a prolonged transatlantic flight. The diagnoses were promptly confirmed through emergent coronary and cerebral angiography, along with a computerized tomography pulmonary angiogram (CTPA). The patient underwent a combination of medical therapy and endovascular thrombectomy. However, she later developed a subarachnoid hemorrhage and eventually progressed to brain death.

Hemodynamics in acute stroke: Cerebral and cardiac complications.

Hemodynamics is the study of blood flow, where parameters have been defined to quantify blood flow and the relationship with systemic circulatory changes. Understanding these perfusion parameters, the relationship between different blood flow variables and the implications for ischemic injury are outlined in the ensuing discussion. This chapter focuses on the hemodynamic changes that occur in ischemic stroke, and their contribution to ischemic stroke pathophysiology. We discuss the interaction between cardiovascular response and hemodynamic changes in stroke. Studying hemodynamic changes has a key role in stroke prevention, therapeutic implications and prognostic importance in acute ischemic stroke: preexisting hemodynamic and autoregulatory impairments predict the occurrence of stroke. Hemodynamic failure predisposes to the formation of thromboemboli and accelerates infarction due to impairing compensatory mechanisms. In ischemic stroke involving occlusion of a large vessel, persistent collateral circulation leads to preservation of ischemic penumbra and therefore justifying endovascular thrombectomy. Following thrombectomy, impaired autoregulation may lead to reperfusion injury and hemorrhage.

Middle Meningeal Artery Embolization in Chronic Subdural Hematoma: Implications of Pathophysiology in Trial Design.

Background: Chronic subdural hematoma (cSDH) is a debilitating condition with a high rate of recurrence after surgical evacuation. Summary: This review is focused on middle meningeal artery (MMA) embolization to treat cSDH. We discuss the underlying pathophysiology of chronic subdural hematoma and how cessation of arterial flow may resolve a venous hemorrhage. We also present the current evidence for MMA embolization and the roadmap for future trials. Conclusion: Frequent multimodal imaging and cSDH sampling would enable us to understand mechanisms of MMA embolization in cSDH treatment and therefore improve our ability to offer MMA embolization to the eligible population.

Triage of Acute Ischemic Stroke in Confirmed COVID-19: Large Vessel Occlusion Associated With Coronavirus Infection.

The outbreak of COVID-19 has posed a significant challenge to global healthcare. Acute stroke care requires rapid bedside attendance, imaging, and intervention. However, for acute stroke patients who have a diagnosis of or are under investigation for COVID-19, the concern for nosocomial transmission moderates operational procedures for acute stroke care. We present our experience with an in-hospital stroke code called on a COVID-19-positive patient with a left middle cerebral artery syndrome and the challenges faced for timely examination, imaging, and decision to intervene. The outlook for the ongoing COVID-19 pandemic necessitates the development of protocols to sustain timely and effective acute stroke care while mitigating healthcare-associated transmission.

Third time's a charm: diagnosis of herpes simplex encephalitis after two negative polymerase chain reaction results.

INTRODUCTION: Polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) is a sensitive and specific method in diagnosing herpes simplex virus (HSV) encephalitis. However there are increasing reports of false negative HSV PCR. CASE DESCRIPTION: We present a patient in the 9th decade of life with abnormal behavior and focal seizures with MRI showing a right temporal T2 hyperintense non-enhancing lesion with electrographic evidence of right lateralized periodic discharges. CSF analysis and PCR for HSV-1 and 2 yielded negative results twice, and therefore acyclovir was discontinued. Patient initially improved following correction of hyponatremia. Patient however deteriorated and imaging revealed a new right parietal lesion. Third CSF sample showed lymphocytic pleocytosis with positive HSV-1 PCR. Patient improved following antiviral treatment. DISCUSSION: Acyclovir treatment should continue in high clinical suspicion scenarios despite negative HSV PCR. We further discuss causes of PCR false negatives and challenges it poses for patient care.

Decision-Making Visual Aids for Late, Imaging-Guided Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Speedy decision-making is important for optimal outcomes from endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Figural decision aids facilitate rapid review of treatment benefits and harms, but have not yet been developed for late-presenting patients selected for EVT based on multimodal computed tomography or magnetic resonance imaging. METHODS: For combined pooled study-level randomized trial (DAWN and DEFUSE 3) data, as well as each trial singly, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of EVT for patients with AIS and large vessel occlusion using automated (algorithmic) and expert-guided joint outcome table specification. RESULTS: Among imaging-selected patients 6 to 24 hours from last known well, for the full 7-category modified Rankin Scale (mRS), EVT had number needed to treat to benefit 1.9 (interquartile range [IQR], 1.9 to 2.1) and number needed to harm 40.0 (IQR, 29.2 to 58.3). Visual displays of treatment effects among 100 patients showed that, with EVT: 52 patients have better disability outcome, including 32 more achieving functional independence (mRS 0 to 2); three patients have worse disability outcome, including one more experiencing severe disability or death (mRS 5 to 6), mediated by symptomatic intracranial hemorrhage and infarct in new territory. Similar features were present in person-icon figures based on a 6-level mRS (levels 5 and 6 combined) rather than 7-level mRS, and based on the DAWN trial alone and DEFUSE 3 trial alone. CONCLUSIONS: Personograph visual decision aids are now available to rapidly educate patients, family, and healthcare providers regarding benefits and risks of EVT for late-presenting, imaging-selected AIS patients.

Extravasation control with preserved vessel patency after wire perforation during neurothrombectomy: Case report and literature review.

Parallel to a more widespread application of endovascular neurothrombectomy in acute ischemic stroke, it is critical to understand the nature and management of associated complications, including wire perforation of the middle cerebral artery (MCA). Sacrifice of the perforated vessel may be necessary to avoid fatal intra-cranial hemorrhage. Here we describe a case of right MCA distribution ischemia complicated by a right MCA perforation. Using super selective injection of contrast through a microcatheter, the point of extravasation was located and sealed with liquid embolic agent (Onyx) while preserving patency of the MCA. By avoiding vessel sacrifice, blood perfusion to distal areas was preserved and therefore the patient was discharged with minimal neurological impairment. Causes of perforation and technical aspects to control extravasation are further discussed.

Extensive meningeal enhancement in acute central nervous system Lyme: Case series and review of literature.

INTRODUCTION: Clinical presentation of the central nervous system Lyme disease is nonspecific and therefore brain imaging and disease-specific serological testing is generally pursued to assist with diagnosis. Brain imaging findings are, however, rare and often unspecific. CASE DESCRIPTION: In the current report, we are presenting a rare magnetic resonance imaging (MRI) finding of extensive meningeal enhancement in two patients with acute Lyme disease. DISCUSSION: We discussed clinical implications and reviewed the relevant literature.

Initial absence of N20 waveforms from median nerve somatosensory evoked potentials in a patient with cardiac arrest and good outcomes.

A 34-year-old male was brought to the hospital with a chest gunshot wound. Pulseless upon arrival, blood pressure was absent for 10 minutes. A thoracotomy resulted in return of spontaneous circulation. On hospital day 5, with brainstem reflexes present, he was unresponsive to call or pain, exhibited generalized hyperreflexia and bilateral Babinskys. Median nerve somatosensory evoked potentials (mSSEPs) and brainstem auditory evoked potentials were obtained. International Federation of Clinical Neurophysiology recommendations for mSSEPs and brainstem auditory evoked potentials were followed. Despite absence of the N20 responses from cortical mSSEPs no withdrawal from care was agreed upon. After awaking on day 7, mSSEPs were repeated and present. The patient survived and was discharged with minor deficits. Bilateral absence of N20 responses from mSSEPs performed beyond 48 hours after resuscitation from cardiac arrest is highly associated with bad neurological outcomes. However, variation due to hypothermia, noisy signals, medications, and brain hypo-perfusion must be taken into account.

Evoked potentials improve multimodal prognostication after cardiac arrest.

AIM: Predicting recovery in comatose post-cardiac arrest patients requires multiple modalities of prognostic assessment. In isolation, absent N20 cortical responses in somatosensory evoked potentials (SSEPs) are a specific predictor of poor outcome. It is unknown whether SSEP results, when assessed in the context of prior knowledge (demographic and clinical information), change the pretest predicted probability of recovery. METHODS: In a single center retrospective study, a cohort of 323 patients admitted to post-cardiac arrest service at a tertiary care center were classified into a group based on SSEP testing. We built adjusted logistic regression models including clinical examination findings on the day SSEPs were recorded to generate a pre-test outcome probability for awakening, withdrawal of life-sustaining therapy (WLST) and survival to discharge. We then added the upper extremity N20 cortical response results to the model to obtain updated outcome probabilities. ROC curve was used to determine the additive effect of using SSEPs to the model. Survival to discharge, awakening, and WLST due to neurological reasons were designated as primary, secondary and tertiary outcomes, respectively. RESULTS: Analyses showed that evoked potentials are ordered in sicker patients. Adding SSEP to the model increased the proportion of patients with less than 1% and 5% chance of survival, as well as the proportion of patients with over 95% chance of WLST. AUC for survival increased from 0.85 to 0.93 when SSEP was included (p = 0.006). CONCLUSION: Adding the N20 SSEP response results to prior knowledge changed the predicted probability of WLST and survival to discharge in comatose post-arrest patients.

Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: an interim report on safety considerations and possible outcomes.

Several experimental studies have introduced Schwann cell transplantation as a means of recovery in animal models of spinal cord injury (SCI). The reported promising results together with the availability of autologous sources for Schwann cells indicate Schwann cell transplantation as a possible treatment for SCI. To address the safety and feasibility concerns we report 1-year follow-up of four patients aged between 22 and 43 years who had stable chronic (28-80 months) spinal cord injury at mid-thoracic level and treated with autologous Schwann cell transplantation. Purified Schwann cells used for transplantation were acquired from autologous sural nerve and cultured without the use of any specific mitogenic or growth factors. The patients were evaluated by means of American Spinal Injury Association (ASIA) criteria, sphincter, sexual function and Magnetic Resonance Imaging assessments for 1 year after transplantation. None of the patients were found to have any adverse effects indicating transfer of infection, neurological deterioration or other related clinical problems. Of the four patients, only one patient with incomplete SCI showed motor and sensory improvement 1 year after transplantation with extensive and continuous rehabilitation. All the four patients experienced transient paresthesia or increased muscle spasm after transplantation. Magnetic Resonance (MR) images of the patients did not show any visible changes or pathological findings after 1 year. This preliminary report shows that autologous Schwann cell transplantation is generally safe for the selected number of SCI patients but it does not prove beneficial effects. Further safety and outcome studies are recommended.

Direct Aspiration Catheter Fracture and Retrieval during Neurothrombectomy.

BACKGROUND: Application of direct aspiration catheters has revolutionized acute stroke care and has led to significant improvement in clinical outcome with a good safety profile. Catheter fracture and retention is a rare but potentially devastating complication. CASE DESCRIPTION: Here we present two cases of acute stroke complicated by aspiration catheter fracture and retention. Successful catheter retrieval and revascularization was achieved in both cases. The stenosis or tortuosity of vascular anatomy appears to be the probable contributor to catheter breakage by anchoring the catheter with resultant fracture at the constraint point from catheter withdrawal tensile stress. CONCLUSION: This report describes application of snare devices in retrieving a broken catheter during thrombectomy in the anterior and posterior circulation, and therefore presents a technique that can be safely utilized to address catheter breakage complicating thrombectomy in different vascular anatomic locations.

Dual origin of the right vertebral artery from the right common carotid and aberrant right subclavian arteries.

This report describes a case of duplicated origin of the right vertebral artery incidentally found in a young patient. Computed tomographic angiography and digital subtraction angiography showed a dominant branch derived from the right common carotid artery and an accessory branch that derived from the right subclavian artery, which aberrantly originated from the far left aortic arch, and adjoined the dominant branch at the C5 level. We discuss angiographic findings, clinical implications and embryological basis for this rare anomaly.

Factor Structure and Psychometric Properties of the Farsi Versions of Empathy and Systemizing Quotient: Short Forms.

Objective: We aimed to examine the validity and reliability of the empathy quotient (EQ) and systemizing quotient (SQ) in a Farsi-speaking population. Method : This study explores the factor structure and psychometric properties of the Farsi translations of the 22-item version of EQ and the 25-item version of SQ among 542 young university students. Results: Applying a cross-validation approach, a 14-item two-factor model and a 15-item four-factor model for the Farsi translations of the short versions of EQ and SQ, respectively, were extracted from the exploratory dataset using exploratory factor analysis (EFA). Confirmatory factor analysis (CFA) on the validation dataset confirmed the factor structures identified by EFA. In addition, acceptable internal consistency and test-retest reliability were demonstrated for the Farsi translations of the 14-item two-factor EQ model and the 15-item four-factor SQ model. Conclusion: The results suggested further evidence in favor of the multi-factorial constructs of the EQ and SQ and validity and reliability of the scales.

Provocative Testing Prior to Anterior Cerebral Artery Fusiform Aneurysm Embolization.

We report 2 cases of parent artery occlusion (PAO) for anterior cerebral artery (ACA) fusiform aneurysm embolization after superselective provocative testing was performed to confirm distal territory viability. The first case involves a patient in the second decade of life who presented with subarachnoid hemorrhage and underwent PAO after a balloon test occlusion in the distal ACA revealed no neurophysiology changes. The second case involves another patient in the forth decade of life who presented with an enlarging pseudoaneurysm and underwent PAO after a sodium amobarbital infusion in the distal ACA revealed no clinical change. Both patients tolerated PAO without clinical compromise. PAO after provocative testing may be a safe and effective strategy in the management of fusiform aneurysm treatment. KEY MESSAGES: Provocative testing with superselective balloon test occlusion and sodium amobarbital infusion are both viable options for clinical and physiological interrogation of brain tissue prior to parent vessel occlusion. Neurophysiological monitoring may be a useful surrogate for clinical examination after provocative testing, particularly if patients were treated under general anesthesia.

The fate of neurons after traumatic spinal cord injury in rats: A systematic review.

OBJECTIVES: To reach an evidence-based knowledge in the context of the temporal-spatial pattern of neuronal death and find appropriate time of intervention in order to preserve spared neurons and promote regeneration after traumatic spinal cord injury (TSCI). MATERIALS AND METHODS: The study design was based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review. PubMed and EMBASE were searched (24 October, 2015) with no temporal or linguistic restrictions. Hand-search was performed in the bibliographies of relevant articles. Non-interventional animal studies evaluating time-dependent neuronal death following acute mechanical trauma to the spinal cord were included. We separately evaluated the fate of various populations of neurons including propriospinal neurons, ventral motor neurons, Clarke's column neurons, and supraspinal neurons. RESULTS: We found 11,557 non-duplicated studies. Screening through the titles and abstracts led to 549 articles, 49 of which met the inclusion criteria. Both necrotic and apoptotic neuronal deaths occur after TSCI, though necrosis is the prominent mechanism. There are differences in the responses of intrinsic neurons of the spinal cord to the TSCI. Also, the extent of neuronal death in the supraspinal neurons depends on the anatomical location of their axons. CONCLUSION: In order to develop new therapies, selection of the injury model and time of intervention has a crucial role in the efficacy of therapy. In addition, examining the safety and efficacy of an intervention by reliable methods not confounded by the injury-related changes would promote translation of therapies to the clinical application.

Subacute histopathological features in a case of varicella zoster virus myelitis and post-herpetic neuralgia.

INTRODUCTION: Post-herpetic neuralgia is a crippling complication of varicella zoster virus (VZV) reactivation, also known as zoster disease. In rare cases, VZV spreads to the spinal cord and causes myelitis. There is a paucity of data on spinal cord histopathology in the subacute phase of post-herpetic neuralgia and VZV myelitis. CASE DESCRIPTION: In this report, we present a case of post-herpetic neuralgia in a patient who died 5 weeks after initiation of symptoms. Autopsy limited to the spinal cord revealed severe tissue vacuolization associated with macrophage and lymphocytic infiltration that was most intense in the right posterior horn, corresponding to an area of magnetic resonance imaging (MRI) T2-weighted hyperintensity. There was some extension of the inflammatory response to the ipsilateral posterior column, dorsolateral column, precentral gray matter, and contralateral lateral column. No significant axonal or myelin loss was observed. Nerve roots and meninges were free of significant inflammation. DISCUSSION: Our findings provide histopathological insight into early subacute changes in post-herpetic neuralgia and suggest the involvement of the cord and subsequent macrophage and lymphocyte inflammatory response may lead to pain fiber irritation and the clinical pain syndrome of post-herpetic neuralgia.

Effect of Social Stimuli on Postural Responses in Individuals with Autism Spectrum Disorder.

This study was aimed to investigate the effects of social versus non-social stimuli on postural responses in 21 boys with autism spectrum disorder (ASD) (mean age of 11.6 ± 1.5) compared with 30 typically developing (TD) boys (mean age of 11.7 ± 1.8). Postural control of children was examined while they were standing on a force plate and viewing images of an object, male face, or female face in sequence. Each image was shown in two trials and each trial lasted for 20 s. Results indicated a significant interaction between group and task (p < 0.05), meaning that children with ASD but not TD children showed an increased postural sway during face tasks than during object task. Furthermore children with higher autism severity compared to those with lower severity showed an increased change in response to social stimuli (p < 0.01). It seems that the postural control of children with ASD was more affected by the social stimuli than TD children.

Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.