Severe Neurological Deficits Research Articles

Longitudinal study of coping strategies in first-time stroke patients: association with cognitive dysfunction, stroke site and depression

BACKGROUND. Inadequate coping strategies are associated with affective disorders and poor quality of life in stroke survivors. Although coping strategies are determined by several non-modifiable factors they have been shown to change over time.
 AIM. Longitudinal assessment of coping strategies and associated factors in patients with first-ever stroke.
 MATERIAL AND METHODS. This study was a part of prospective observational study of a cohort of patients with first-ever stroke. Patients underwent standard psychiatric, neurological and cognitive assessment and CT. Patients without aphasia, severe fatigue, eye problems fulfilled the coping strategies indicator (Amirkhan J.H., 1990): 87 patients in the first week after stroke, 45 patients in the second week, 20 patients in 3 months, 21 patients in 6 months, 33 patients in 1 year after stroke. Non-parametric statistics were used.
 RESULTS. Different coping strategies were not determined by age, gender and severity of neurological deficit; there were some correlations with educational level, work status, cognitive dysfunction, stroke volume and lesion location. There were differences in the use of coping strategies in the groups with different depression manifestations: in the group with depression manifestations in the early recovery period and later, coping strategies did not differ from the control group in the acute stroke period, but since the manifestation of depression the amount of avoidance strategies increased. In the group with pre-stroke depression, a significant increase in avoidance strategies was observed in the first week after the stroke.
 CONCLUSIONS. The longitudinal study of coping strategies revealed that the use of coping strategies is a dynamic process determined by several modifiable and non-modifiable factors in combination. Coping strategies were not predictors of depression; on the contrary, depression seems to influence the choice of coping strategies.

THE SEVERITY OF NEUROLOGICAL DEFICIT IN PATIENTS WITH ISCHEMIC STROKE ON THE NIHSS SCALE DEPENDING ON THE STATUS OF COVID-19

This article discusses the severity of neurological deficit in patients with ischemic stroke on the NIHSS scale depending on the status of COVID-19. Based on the current situation, the need for a full-fledged dynamic study of the state of cerebral hemodynamics in terms of the relationship of these indicators with the results of neuro-immunological examinations and neuroimaging data, as well as determining the effect of cerebral blood flow reserves, as a parameter of functional plasticity of cerebral hemodynamics in patients with stroke against the background of COVID-19 is undeniable and unequivocally relevant from the point of view of practical neurology.

USP18 overexpression protects against spinal cord ischemia/reperfusion injury via regulating autophagy

BackgroundSpinal cord ischemia–reperfusion injury (SCII) is usually caused by spinal surgery, often leading to severe neurological deficits. The ubiquitin-specific protease 18 (USP18) plays a significant role in neurological diseases. ObjectiveThe present study was designed to assess the effects and mechanisms of USP18 on SCII. MethodsBy inducing transient aortic occlusion and subsequent reperfusion, a rat model of SCII was successfully established. The Basso-Beattie-Bresnahan scores, the inclined plane test, and hematoxylin and eosin (HE) were used to measure locomotor activity and histological changes in the injured spinal cords. Moreover, the SCII cell model was established using PC12 cells under oxygen-glucose deprivation and reoxygenation (OGD/R). Proinflammatory factors (TNF-α, IL-6, and INF-α) were examined using an ELISA kit. Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. Western blot was used to detect the expression levels of proteins related to apoptosis and autophagy. ResultsUSP18 expression was decreasedin vivo and in vitro SCII models. The upregulation of USP18 ameliorated hind limbs' motor function, inhibiting inflammation and apoptosis after SCII in rats. USP18 overexpression in vitro may protect PC12 cells from OGD/R-induced damage by modulating inflammatory responses and apoptosis. Moreover, Overexpression of USP18 enhanced autophagy to inhibit cell apoptosis induced by SCII in vivo and in vitro. ConclusionsIn summary, USP18 overexpression protects against SCII via regulating autophagy.

Experimental Study of Neuroprotective Properties of Inhaled Argon-Oxygen Mixture in a Photoinduced Ischemic Stroke Model

Acute ischemic stroke is a serious problem for healthcare systems worldwide. Searching for the optimal neuroprotector is a contemporary challenge. Various studies have demonstrated neuroprotective properties of argon in ischemic brain damage models. However, the published data are inconsistent.The aim of the study was to evaluate the effect of 24-hour argon-oxygen mixture (Ar 70%/O₂ 30%) inhalation on the severity of neurological deficit and the extent of brain damage in rats after a photoinduced ischemic stroke. Material and methods. The experiments were carried out on male Wistar rats weighing 430–530 g (N=26). Focal ischemic stroke was modeled in the sensorimotor cortex of the rat brain using photochemically induced vascular thrombosis. The animals were randomly divided into 3 groups: sham procedure + N₂ 70%/O₂ 30% inhalation (SP, N=6); stroke + N₂ 70%/O₂ 30% inhalation (Stroke, N=10); Stroke + Ar 70%/O₂ 30% inhalation (Stroke+iAr, N=10). The limb placement test (LPT) was used for neurological assessment during 14 days. Additionally, on day 14 after the stroke, brain MRI with lesion size morphometry was performed. Summarized for days 3,7 and 14 LPT scores were lower in the Stroke and Stroke + iAr groups as compared to the SP group.Results. Statistically significant differences in LPT scores between SP, Stroke, and Stroke+iAr groups were revealed on day 3 post-stroke: (scores: 14 (13; 14), 6.5 (4; 8), and 5 (3; 8), respectively, P=0.027). However, there was no statistical difference between the Stroke and Stroke+iAr groups.Conclusion. 24-hour inhalation of argon-oxygen mixture (Ar 70%/O₂ 30%) after stroke does not reduce the extent of brain damage or the severity of neurological deficit.

Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke

Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke.Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.

Postoperative Complications and Neurological Deficits After Petroclival Region Meningioma Resection: A Case Series.

Surgical management of meningiomas involving the petroclival junction remains a challenge because of nearby critical neurovascular structures. To describe surgical approach selection, outcomes, and factors associated with postoperative complications and neurological deficits in a series of patients undergoing resection of petroclival region meningiomas. Retrospective review of patients undergoing symptomatic petroclival region meningioma resection was performed. Logistic regression was performed to identify variables associated with postoperative complications and new neurological deficits. Sixty-five patients underwent 54 one-stage and 11 two-stage resections with median follow-up of 51 months. Most tumors were World Health Organization grade 1 (90.8%), and the median volume was 23.9 cm 3 . Posterior petrosectomy and anterior petrosectomy were performed in 67.1% and 6.6% of operations, respectively. The gross or near total resection rate was 15.4%, and 8 patients (12.3%) progressed on follow-up. The surgical complication rate was 26.2% with no perioperative mortalities. Postoperatively, 45.8% of patients had new, persistent neurological deficits, with cranial nerves VII palsy being most common. On multivariate analysis, higher body mass index (odds ratio [OR]: 1.1, P = .04) was associated with risk of surgical complications. Longer operative time (OR: 1.4, P = .004) and staged procedures (OR: 4.9, P = .04) were associated with risk of new neurological deficit on follow-up, likely reflecting more challenging tumors. Comparing early vs later career surgeries performed by the senior author, rates of severe complications and neurological deficits decreased 23.1% and 22.3%, respectively. Petroclival region meningiomas remain surgically challenging, but improved outcomes are seen with surgeon experience. These data help inform patients on perioperative morbidity risk and provide a guide for surgical approach selection.

Predictors of In-Hospital Mortality Among Patients with COVID-19 Related Stroke

Introduction. COVID-19-related stroke is associated with a significantly higher mortality than COVID-19 or stroke alone. Mechanisms underlying the increased mortality of patients with stroke and COVID-19 should be thoroughly studied.
 Objective: to analyze predictors of hospital mortality associated with COVID-19-related stroke.
 Materials and methods. We retrospectively analyzed 1,386 cases of COVID-19-related stroke reported by an infectious diseases inpatient clinic in 2020. We studied clinical, laboratory, and instrumental parameters in patients with different outcomes. Logistic regression was used to identify independent predictors of mortality.
 Results. 539 (38.9%) patients died during their hospital stay, with 437 (38.0%) deaths from ischemic stroke and 102 (42.7%) deaths from hemorrhagic stroke (p = 0.0001). Independent predictors of mortality associated with COVID-19-related stroke included age, neurological deficit severity measured by NIHSS, COVID-19 severity, and laboratory parameters including white blood cell count, creatinine, glucose, and D-dimer blood levels.
 Discussion. The results of logistic regression analysis were able to explain only 41% of the variability in hospital deaths among patients with stroke associated with COVID-19.
 Conclusion. Hospital mortality in patients with COVID-19-related stroke is associated with severity of inflammatory response, impaired coagulation, age, neurological deficit severity, and somatic comorbidities.

Reperfusion by endovascular thrombectomy and early cerebral edema in anterior circulation stroke: Results from the SITS-International Stroke Thrombectomy Registry.

A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. To investigate the association of reperfusion with development of early CED after stroke thrombectomy. From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored. In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37-0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction. In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy.

Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.

Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.

Comparing clinical outcomes of dogs suffering from degenerative lumbosacral stenosis upon surgical or nonsurgical treatment

PICO question In dogs suffering from degenerative lumbosacral stenosis (DLSS), is surgical treatment more effective than nonsurgical therapy in reducing lumbosacral pain and neurological dysfunction in the long-term? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Two papers were critically reviewed. They were prospective and retrospective studies. Strength of evidence Weak. Outcomes reported Besides the two studies, there are no other studies currently available that directly compare long-term clinical outcome of patients that have undergone nonsurgical and surgical treatment respectively. In the study comparing clinical outcome of nonsurgical treatment by epidural steroid injection (ESI) and surgical treatment of degenerative lumbosacral stenosis, dogs were classified into clinical severity groups ranging from mild to moderate to severe. Mild cases demonstrated degenerative lumbosacral stenosis (DLSS) compatible clinical signs such as lumbosacral pain, reluctance to climb stairs / jump / raise up, lameness and muscle atrophy but no neurological deficits. Moderate cases presented DLSS compatible clinical signs in combination with neurological deficits such as reduced flexor withdrawal, proprioceptive deficits and nerve root signature. Severe cases demonstrated DLSS compatible clinical signs with more severe neurological deficits such as tail paresis and absent perineal reflex. Clinical outcomes were considered complete if clinical signs had resolved at follow-up consultations, partial if there was substantial but incomplete improvement in clinical signs and failed if the dog did not improve or deteriorated further. Improvements in patient condition were measured in terms of clinical outcome grading which is in relation to the initial clinical severity group assigned to each dog. Improvement after single dose of ESI was seen in 27/32 dogs, with 17/22 (after accounting for four dogs whose owners have refused further treatment, five dogs lost to follow-up after re-check as well as one dog whose owners have opted for repeated ESI instillations) relapsing within 6 months. All 17 of these dogs that suffered a relapse after single ESI subsequently underwent surgical treatment and demonstrated improvement in clinical signs, with a complete response seen in eight dogs and a partial response seen in nine dogs. In the study comparing clinical outcome of conservative treatment of exercise restriction with phenylbutazone administration and surgical treatment of degenerative lumbosacral stenosis, outcomes were classified as good in dogs that regained preoperative activity levels; acceptable in dogs with persistent abnormality or requiring continued medication though otherwise active, and poor in all other cases. Out of 16 dogs treated surgically, 11 were treated by dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc, while the other five had additional unilateral facetectomy to decompress the seventh lumbar nerve. Out of the 11 dogs treated with dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc, 6/11 (54.5%) of dogs were deemed to have a good outcome, while 3/11 (27.3%) of dogs were deemed to have an acceptable outcome. Out of the five dogs treated with dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc with additional unilateral facetectomy, 3/5 (60%) of dogs were deemed to have an acceptable outcome. The outcome of conservative treatment was deemed good in 8/16 (50%) of dogs in the conservative treatment group. Conclusion There is evidence suggesting that both nonsurgical and surgical treatments can improve clinical outcomes and reduce lower back pain and neurological deficits. However, based on the current limited literature, it cannot be ascertained whether surgical treatments are more effective than nonsurgical treatments in improving long-term clinical outcomes and vice versa. In the study that tested the efficacy of epidural steroid injection, only a single dose of steroids was given in this study, making it a potential reason for the high rate of relapse following nonsurgical treatment. For surgical treatment of DLSS, the type of surgical procedure chosen would also depend on the part of the lumbosacral region which fails and leads to compression. In conclusion, randomised controlled trials that compare different forms of nonsurgical treatment with surgical treatment for dogs with DLSS caused by different underlying factors need to be conducted to properly address the PICO question. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Complete Remission in Paralytic Late Tick-Borne Neurological Disease Comprising Mixed Involvement of Borrelia, Babesia, Anaplasma, and Bartonella: Use of Long-Term Treatments with Antibiotics and Antiparasitics in a Series of 10 Cases.

This study aimed to demonstrate that severe neurological motor deficits in the context of late tick-borne disease with mixed microorganism involvement are eligible for long-term combined antibiotic/antiparasitic treatments. The inclusion criteria were: 1. neurological limb paralysis with a disability score >4 according to the EDSS Kurtzke disability scale; 2. serological tests pointing to an involvement of the main tick-borne microorganisms Borrelia burgdorferi s.l., Babesia, Anaplasma, and Bartonella; 3. a general disease for more than 6 months with fatigue, pain and subjective cognitive deficit. The patients were administered long-term treatments with repeated cycles (at least three) of 35-day IV ceftriaxone and repeated oral regimens of azithromycin-doxycycline and azithromycin-doxycycline-rifampicin. For Babesia, repeated courses of atovaquone-azithromycin were administered. Ten patients had intractable or severe motor deficits before treatment in the context of Borrelia (two cases) Borrelia-Babesia (four cases), Borrelia-Babesia-Anaplasma (two cases), Borrelia-Babesia-Anaplasma-Bartonella (one case) and Babesia-Anaplasma (one case). For several months, five had been in wheelchairs, and four had been walking with sticks. Seven patients out of 10 (70%) showed complete remission after a mean active treatment duration of 20.1 + 6.6 months, with a mean number of 4 ceftriaxone cycles. Three patients showed an initial remission but suffered secondary antibiotic/antiparasitic-resistant motor recurrences. Among the nine patients with Borrelia serologic positivity, treatments obtained complete remission in seven cases (77%). The findings of this ten-case series suggest the usefulness of long-term antibiotic/antiparasitic treatments in patients with severe late tick-borne neurological deficits with highly significant elements of tick-borne involvement.

High-Flow Nasal Oxygen Therapy for Management of Postoperative Pneumocephalus

AbstractPostoperative pneumocephalus (PNC) is very common in craniotomy surgeries. It can be asymptomatic or if present in more volumes can cause symptoms such as lethargy, headache, confusion, or even severe neurological deficit. Treatment of pneumocephalus with supplemental oxygen via facemask is a common neurosurgical practice. There is not much evidence of use of high-flow nasal oxygen therapy (HFNOT) for the management of PNC. Here we report a case of an 8-year-old boy with postoperative symptomatic pneumocephalus, which resolved with the application of supplemental oxygen via a high-flow nasal cannula with 30 L/min flow and FiO2 of 0.7 over 72 hours. High-flow nasal oxygen therapy can be an effective modality of treatment for postoperative PNC with added advantages of patient comfort and maintenance of warmth and moisture of the respiratory tract.

External Validation of the Nelson Equation for Kidney Function Decline in Patients with Acute Ischemic Stroke or Transient Ischemic Attack.

There is a close brain-kidney interaction following ischemic cerebrovascular disease. The new-onset kidney injury after stroke leads to severe neurological deficits and poor functional outcomes. We aimed to validate the Nelson equation for predicting the new-onset and long-term kidney function decline in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). A total of 3169 patients were enrolled in the Third China National Stroke Registry, whose baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2. The outcome of interest was the incident eGFR< 60 mL/min/1.73 m2 at 3 months. The prediction equation of participants with or without diabetes was validated respectively. The receiver operating characteristic curve (AUC) evaluated prediction performance. The Delong test compared the Nelson equation performance with the O'Seaghdha equation and the Chien equation. Continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were determined to evaluate the incremental effect. During the 3-mo follow-up period, among 1151 patients with diabetes, there were 31 cases (2.7%) of reduced eGFR. Meanwhile, among 2018 non-diabetic patients, there were 23 cases (1.1%) of reduced eGFR. The Nelson equation showed good discrimination and was well-calibrated in patients with diabetes (AUC 0.82, Hosmer-Lemeshow test p = 0.67) or without diabetes (AUC 0.82, Hosmer-Lemeshow test p = 0.09). The performance of the Nelson equation was superior to other equation, as increased continuous NRI (diabetic, 0.64; non-diabetic, 1.13) and IDI (diabetic, 0.10; non-diabetic, 0.13) to the Chien equation. The Nelson equation reliably predicted the risks of the new-onset and long-term kidney function decline in patients with AIS or TIA, which could help clinicians screen high-risk patients and improve clinical care.

P93: Neuro-Rehabilitation in a Pediatric Stroke Patient Supported on a CentriMag Right Ventricular Assist Device: A Case Report

Introduction: With strokes being one of the most common and morbid ventricular assist device (VAD) complications, the need for physical rehabilitation dramatically increases when a patient on a VAD suffers neurological injury. Patients with severe neurological deficits require intense rehabilitation that includes base of support challenges, utilization of dynamic surfaces, and positions in prone, kneeling, or quadruped for neuro-motor re-education. Neuro-rehabilitation can be challenged by short cannulas, an external motor, a large interface, and a confining intensive care unit admission at our institution when a patient is supported on a CentriMag device. Case Description: The patient is a 10-year-old male diagnosed with Ebstein’s anomaly, on a CentriMag RVAD as a bridge to cardiac transplant who sustained a massive right middle cerebral artery stroke requiring hemicraniectomy. The patient presented with dense left hemiparesis and multi-system impairments such as vision, vestibular, and proprioception deficits which required intensive neuro-rehabilitation treatment. Given the challenges of being on the Centrimag device, therapy treatments required a multi-disciplinary team and strategies such as removing the CentriMag motor from the bracket to minimize cannula tension and risk of dislodgement to allow greater degree of movements without causing disruption to flow and cannula stability. The patient completed 101 sessions progressing from dependent for all mobility to ambulating 20 ft with a hemi-walker prior to his transplant. Treatment interventions included usage of dynamic surfaces, tilt table, and partial weight bearing gait trainers. Discussion: While ICU mobility progression from bed mobility to ambulation have been reported, intense neuro-rehabilitation requiring high frequency and complex mobility is not readily described. This case suggests that implementing progressive mobility and intensive neurological rehabilitation can be safe and feasible with a trained multidisciplinary team for pediatric patients on a CentriMag.

Clinical manifestations and neuron-specific enolase cerebrospinal fluid concentration in HIV/AIDS patients with cerebral toxoplasmosis

Background. Cerebral toxoplasmosis (CT) is one of the most common cause of focal neurological defi cit in HIV/ AIDS group of patients. Timely diagnosis of CT and antiparasitic therapy contribute to decrease of lethal outcomes and disability. Aim. To study neurological manifestations, cognitive functions and neuron-specifi c enolase (NSE) concentration in cerebrospinal fluid (CSF), in HIV/AIDS patients with CT. Material and methods. The 35 patients (10 females and 25 males) from 28 to 50 years old with confirmed diagnosis of HIV/AIDS-associated CT were included in the investigation group. Neurological status, cognitive function and laboratory CSF changings had been studied in prospective investigation before and during the treatment with control points in the 1st and 10th days of the observation. Results. The method of neurological manifestation of CT evaluation had been developed and implemented in practice. The association between neurological defi cit severity (movement and sensory disorders), cognitive decline and increasing CSF concentration of NSE in HIV/AIDS-associated CT was determined that demonstrates the activity of encephalitic process. Conclusion. Dynamic evaluation of NSE concentration in CSF with clinical assessment of neurological manifestation in patients with HIV/AIDS-associated CT may be used for confirmation of specific antiparasitic treatment effectiveness and for increasing clinical criteria significance.

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy

PurposeMendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)–associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. MethodsThis study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. ResultsAll 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. ConclusionBiallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.

Bioinformatic identification of hub genes Myd88 and Ccl3 and TWS-119 as a potential agent for the treatment of massive cerebral infarction.

Massive cerebral infarction (MCI) causes severe neurological deficits, coma and can even result in death. Here, we identified hub genes and pathways after MCI by analyzing microarray data from a murine model of ischemic stroke and identified potential therapeutic agents for the treatment of MCI. Microarray expression profiling was performed using the GSE28731 and GSE32529 datasets from the Gene Expression Omnibus (GEO) database. Data from a sham group (n = 6 mice) and a middle cerebral artery occlusion (MCAO) group (n = 7 mice) were extracted to identify common differentially expressed genes (DEGs). After identifying gene interactions, we generated a protein-protein interaction (PPI) network with Cytoscape software. Then, the MCODE plug-in in Cytoscape was used to determine key sub-modules according to MCODE scores. Enrichment analyses were then conducted on DEGs in the key sub-modules to evaluate their biological functions. Furthermore, hub genes were identified by generating the intersections of several algorithms in the cytohubba plug-in; these genes were then verified in other datasets. Finally, we used Connectivity MAP (CMap) to identify potential agents for MCI therapy. A total of 215 common DEGs were identified and a PPI network was generated with 154 nodes and 947 edges. The most significant key sub-module had 24 nodes and 221 edges. Gene ontology (GO) analysis showed that the DEGs in this sub-module showed enrichment in inflammatory response, extracellular space and cytokine activity in terms of biological process, cellular component and molecular function, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that TNF signaling was the most enriched pathway. Myd88 and Ccl3 were identified as hub genes and TWS-119 was identified as the most potential therapeutic agent by CMap. Bioinformatic analysis identified two hub genes (Myd88 and Ccl3) for ischemic injury. Further analysis identified TWS-119 as the best potential candidate for MCI therapy and that this target may be associated with TLR/MyD88 signaling.

SIRT2 plays complex roles in neuroinflammation neuroimmunology-associated disorders.

Neuroinflammation and neuroimmunology-associated disorders, including ischemic stroke and neurodegenerative disease, commonly cause severe neurologic function deficits, including bradypragia, hemiplegia, aphasia, and cognitive impairment, and the pathological mechanism is not completely clear. SIRT2, an NAD+-dependent deacetylase predominantly localized in the cytoplasm, was proven to play an important and paradoxical role in regulating ischemic stroke and neurodegenerative disease. This review summarizes the comprehensive mechanism of the crucial pathological functions of SIRT2 in apoptosis, necroptosis, autophagy, neuroinflammation, and immune response. Elaborating on the mechanism by which SIRT2 participates in neuroinflammation and neuroimmunology-associated disorders is beneficial to discover novel effective drugs for diseases, varying from vascular disorders to neurodegenerative diseases.

Gut microbiome plays a vital role in post-stroke injury repair by mediating neuroinflammation

Cerebral stroke is a common neurological disease and often causes severe neurological deficits. With high morbidity, mortality, and disability rates, stroke threatens patients' life quality and brings a heavy economic burden on society. Ischemic cerebral lesions incur pathological changes as well as spontaneous nerve repair following stroke. Strategies such as drug therapy, physical therapy, and surgical treatment, can ameliorate blood and oxygen supply in the brain, hamper the inflammatory responses and maintain the structural and functional integrity of the brain. The gut microbiome, referred to as the "second genome" of the human body, participates in the regulation of multiple physiological functions including metabolism, digestion, inflammation, and immunity. The gut microbiome is not only inextricably associated with dangerous factors pertaining to stroke, including high blood pressure, diabetes, obesity, and atherosclerosis, but also influences stroke occurrence and prognosis. AMPK functions as a hub of metabolic control and is responsible for the regulation of metabolic events under physiological and pathological conditions. The AMPK mediators have been found to exert dual roles in regulating gut microbiota and neuroinflammation/neuronal apoptosis in stroke. In this study, we reviewed the role of the gut microbiome in cerebral stroke and the underlying mechanism of the AMPK signaling pathway in stroke. AMPK mediators in nerve repair and the regulation of intestinal microbial balance were also summarized.

Therapeutic Efficacy and Migration of Mesenchymal Stem Cells after Intracerebral Transplantation in Rats with Experimental Ischemic Stroke.

We studied therapeutic efficacy and migration characteristics of mesenchymal stem cells isolated from the human placenta after their intracerebral (stereotactic) administration to rats with the experimental ischemic stroke. It was shown that cell therapy significantly improved animal survival rate and reduced the severity of neurological deficit. New data on the migration pathways of transplanted cells in the brain were obtained.