This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.

UNASSIGNED: Hypoxia can cause central nervous system dysfunction and injury. Hypoxia is a particular risk during rebreather diving. Given its subtle symptom profile and its catastrophic consequences there is a need for reliable hypoxia monitoring. Electroencephalography (EEG) is being investigated as a real time monitor for multiple diving problems related to inspired gas, including hypoxia.
UNASSIGNED: A systematic literature search identified articles investigating the relationship between EEG changes and acute cerebral hypoxia in healthy adults. Quality of clinical evidence was assessed using the Newcastle-Ottawa scale.
UNASSIGNED: Eighty-one studies were included for analysis. Only one study investigated divers. Twelve studies described quantitative EEG spectral power differences. Moderate hypoxia tended to result in increased alpha activity. With severe hypoxia, alpha activity decreased whilst delta and theta activities increased. However, since studies that utilised cognitive testing during the hypoxic exposure more frequently reported opposite results it appears cognitive processing might mask hypoxic EEG changes. Other analysis techniques (evoked potentials and electrical equivalents of dipole signals), demonstrated sustained regulation of autonomic responses despite worsening hypoxia. Other studies utilised quantitative EEG analysis techniques, (Bispectral index [BISTM], approximate entropy and Lempel-Ziv complexity). No change was reported in BISTM value, whilst an increase in approximate entropy and Lempel-Ziv complexity occurred with worsening hypoxia.
UNASSIGNED: Electroencephalographic frequency patterns change in response to acute cerebral hypoxia. There is paucity of literature on the relationship between quantitative EEG analysis techniques and cerebral hypoxia. Because of the conflicting results in EEG power frequency analysis, future research needs to quantitatively define a hypoxia-EEG response curve, and how it is altered by concurrent cognitive task loading.

Diffuse cortical diffusion changes on magnetic resonance imaging (MRI) are characteristically ascribed to global cerebral anoxia, typically after cardiac arrest. Far from being pathognomonic, however, this neuroimaging finding is relatively nonspecific, and can manifest in a myriad of disease states including hypoxia, metabolic derangements, infections, seizure, toxic exposures, and neuroinflammation. While these various conditions can all produce a neuroimaging pattern of widespread cortical diffusion restriction, many of these underlying causes do have subtly unique imaging features that are appreciable on MRI and can be of clinical and diagnostic utility. Specific populations of neurons are variably sensitive to certain types of injury, whether due to differences in perfusion, receptor type density, or the unique tropisms of infectious organisms. In this narrative review, we discuss a number of distinct etiologies of diffuse cortical diffusion restriction on MRI, the unique pathophysiologies responsible for tissue injury, and the resulting neuroimaging characteristics that can be of assistance in differentiating them. As widespread cortical injury from any cause often presents with altered mental status or coma, the differential diagnosis can be enhanced with rapid acquisition of MRI when clinical history or detailed physical examination is limited. In such settings, the distinct imaging features discussed in this article are of interest to both the clinician and the radiologist.

Monitoring of brain tissue oxygenation (PbtO2) is an important component of multimodal monitoring in traumatic brain injury. Over recent years, use of PbtO2 monitoring has also increased in patients with poor-grade subarachnoid hemorrhage (SAH), particularly in those with delayed cerebral ischemia. The aim of this scoping review was to summarize the current state of the art regarding the use of this invasive neuromonitoring tool in patients with SAH. Our results showed that PbtO2 monitoring is a safe and reliable method to assess regional cerebral tissue oxygenation and that PbtO2 represents the oxygen available in the brain interstitial space for aerobic energy production (i.e., the product of cerebral blood flow and the arterio-venous oxygen tension difference). The PbtO2 probe should be placed in the area at risk of ischemia (i.e., in the vascular territory in which cerebral vasospasm is expected to occur). The most widely used PbtO2 threshold to define brain tissue hypoxia and initiate specific treatment is between 15 and 20 mm Hg. PbtO2 values can help identify the need for or the effects of various therapies, such as hyperventilation, hyperoxia, induced hypothermia, induced hypertension, red blood cell transfusion, osmotic therapy, and decompressive craniectomy. Finally, a low PbtO2 value is associated with a worse prognosis, and an increase of the PbtO2 value in response to treatment is a marker of good outcome.

Traumatic brain injury (TBI) is a major public health burden, causing death and disability worldwide. Intracranial hypertension and brain hypoxia are the main mechanisms of secondary brain injury. As such, management strategies guided by intracranial pressure (ICP) and brain oxygen (PbtO2) monitoring could improve the prognosis of these patients. Our objective was to summarize the current evidence regarding the impact of PbtO2-guided therapy on the outcome of patients with TBI. We performed a systematic search of PubMed, Scopus, and the Cochrane library databases, following the protocol registered in PROSPERO. Only studies comparing PbtO2/ICP-guided therapy with ICP-guided therapy were selected. Primary outcome was neurological outcome at 3 and 6 months assessed by using the Glasgow Outcome Scale; secondary outcomes included hospital and long-term mortality, burden of intracranial hypertension, and brain tissue hypoxia. Out of 6254 retrieved studies, 15 studies (n = 37,245 patients, of who 2184 received PbtO2-guided therapy) were included in the final analysis. When compared with ICP-guided therapy, the use of combined PbO2/ICP-guided therapy was associated with a higher probability of favorable neurological outcome (odds ratio 2.21 [95% confidence interval 1.72-2.84]) and of hospital survival (odds ratio 1.15 [95% confidence interval 1.04-1.28]). The heterogeneity (I2) of the studies in each analysis was below 40%. However, the quality of evidence was overall low to moderate. In this meta-analysis, PbtO2-guided therapy was associated with reduced mortality and more favorable neurological outcome in patients with TBI. The low-quality evidence underlines the need for the results from ongoing phase III randomized trials.

UNASSIGNED: Therapeutic hypothermia (TH) is regarded as the most efficacious therapy for neonatal hypoxic encephalopathy. However, limitations in previous systematic reviews and the publication of new data necessitate updating the evidence. We conducted this up-to-date systematic review to evaluate the effects of TH in neonatal encephalopathy on clinical outcomes.
UNASSIGNED: In this systematic review and meta-analysis, we searched Medline, Cochrane Library, Embase, LIVIVO, Web of Science, Scopus, CINAHL, major trial registries, and grey literature (from inception to October 31, 2021), for randomized controlled trials (RCT) comparing TH vs normothermia in neonatal encephalopathy. We included RCTs enrolling neonates (gestation ≥35 weeks) with perinatal asphyxia and encephalopathy, who received either TH (temperature ≤34°C) initiated within 6 hours of birth for ≥48 hours, vs no cooling. We excluded non-RCTs, those with delayed cooling, or cooling to >34°C. Two authors independently appraised risk-of-bias and extracted data on mortality and neurologic disability at four time points: neonatal (from randomization to discharge/death), infancy (18-24 months), childhood (5-10 years), and long-term (>10 years). Other outcomes included seizures, EEG abnormalities, and MRI findings. Summary data from published RCTs were pooled through fixed-effect meta-analysis.
UNASSIGNED: We identified 36 863 citations and included 39 publications representing 29 RCTs with 2926 participants. Thirteen studies each had low, moderate, and high risk-of-bias. The pooled risk ratios (95% confidence interval, CI) were as follows: neonatal mortality: 0.87 (95% CI = 0.75, 1.00), n = 2434, I2  = 38%; mortality at 18-24 months: 0.88 (95% CI = 0.78, 1.01), n = 2042, I2  = 51%; mortality at 5-10 years: 0.81 (95% CI = 0.62, 1.04), n = 515, I2  = 59%; disability at 18-24 months: 0.62 (95% CI = 0.52, 0.75), n = 1440, I2  = 26%; disability at 5-10 years: 0.68 (95% CI = 0.52, 0.90), n = 442, I2  = 3%; mortality or disability at 18-24 months: 0.78 (95% CI = 0.72, 0.86), n = 1914, I2  = 54%; cerebral palsy at 18-24 months: 0.63 (95% CI = 0.50, 0.78), n = 1136, I2  = 39%; and childhood cerebral palsy: 0.63 (95% CI = 0.46, 0.85), n = 449, I2  = 0%. Some outcomes showed significant differences by study-setting; the risk ratio (95% CI) for mortality at 18-24 months was 0.79 (95% CI = 0.66,0.93), n = 1212, I2  = 7% in high-income countries, 0.67 (95% CI = 0.41, 1.09), n = 276, I2  = 0% in upper-middle-income countries, and 1.18 (95% CI = 0.94, 1.47), n = 554, I2  = 75% in lower-middle-income countries. The corresponding pooled risk ratios for \'mortality or disability at 18-24 months\' were 0.77 (95% CI = 0.69, 0.86), n = 1089, I2  = 0%; 0.56 (95% CI = 0.41, 0.78), n = 276, I2  = 30%; and 0.92 (95% CI = 0.77, 1.09), n = 549, I2  = 86% respectively. Trials with low risk of bias showed risk ratio of 0.97 (95% CI = 0.80, 1.16, n = 1475, I2  = 62%) for neonatal mortality, whereas trials with higher risk of bias showed 0.71 (95% CI = 0.55, 0.91), n = 959, I2  = 0%. Likewise, risk ratio for mortality at 18-24 months was 0.96 (95% CI = 0.83, 1.13), n = 1336, I2  = 58% among low risk-of-bias trials, but 0.72 (95% CI = 0.56, 0.92), n = 706, I2  = 0%, among higher risk of bias trials.
UNASSIGNED: Therapeutic hypothermia for neonatal encephalopathy reduces neurologic disability and cerebral palsy, but its effect on neonatal, infantile and childhood mortality is uncertain. The setting where it is implemented affects the outcomes. Low(er) quality trials overestimated the potential benefit of TH.

In-hospital cardiac arrest (IHCA) is a major adverse event with a high mortality rate if not treated appropriately. Extracorporeal cardiopulmonary resuscitation (ECPR), as adjunct to conventional cardiopulmonary resuscitation (CCPR), is a promising technique for IHCA treatment. Evidence pertaining to neurological outcomes after ECPR is still scarce.
We performed a comprehensive systematic search of all studies up to December 20, 2019. Our primary outcome was neurological outcome after ECPR at any moment after hospital discharge, defined by the Cerebral Performance Category (CPC) score. A score of 1 or 2 was defined as favourable outcome. Our secondary outcome was post-discharge mortality. A fixed-effects meta-analysis was performed.
Our search yielded 1215 results, of which 19 studies were included in this systematic review. The average survival rate was 30% (95% CI 28-33%, I2 = 0%, p = 0.24). In the surviving patients, the pooled percentage of favourable neurological outcome was 84% (95% CI 80-88%, I2 = 24%, p = 0.90).
ECPR as treatment for in-hospital cardiac arrest is associated with a large proportion of patients with good neurological outcome. The large proportion of favourable outcome could potentially be explained by the selection of patients for treatment using ECPR. Moreover, survival is higher than described in the conventional CPR literature. As indications for ECPR might extend to older or more fragile patient populations in the future, research should focus on increasing survival, while maintaining optimal neurological outcome.

BACKGROUND: Hypoxic ischemic brain injury (HIBI) occurs as a result of complete or partial disruption of cerebral oxygen supply. The physical and cognitive sequelae of adults following hypoxia varies widely.
OBJECTIVE: To systematically review studies exploring the neuropsychological outcomes following hypoxic brain insult in adults.
METHODS: Data was sourced using six databases (CINAHL, Cochrane, Embase, Medline, PsycInfo and Web of Science). Initial MESH terms identified 2,962 articles. After a three-stage independent review process, 18 articles, 9 case studies and 9 group studies were available for data synthesis from 1990-2012. Case study data was converted to standardised scores and compared to available test norms. Cohen\'s d was calculated to permit group data interpretation.
RESULTS: Intellectual decrement was observed in some studies although difficult to delineate given the lack of use of measures of premorbid ability. Cognitive sequelae varied albeit with predominant disturbance in verbal memory, learning ability and executive function observed across studies. Wechsler Memory Scale Revised (WMS-R) visual memory was comparable to normative data. Impaired Rey Osterrieth Complex Figure (ROCFT) performance was found among group studies. Across visuo-constructional and attention domains, performance varied, although no significant difference relative to reported means was observed.
CONCLUSIONS: Future studies should consider the use of standardised assessment protocols, which include measures of premorbid functioning and performance validity.

Child abuse was suspected in a case of out-of-hospital arrest with minor brain injuries. Confronted with continued disputes on pathophysiologic correlates even after autopsy, to assist the differentiation of potential causes of sudden cardiopulmonary arrest in children, we tried to identify the mechanism of cardiopulmonary arrest in brain injuries from different causes. Systematic review was carried out in two stages. First, major external causes of cardiopulmonary arrest among children and infants were identified from Pubmed and Google Scholar search, and then the exact sequence of cardiopulmonary arrest, and their pathophysiologic features were identified based on articles of animal models of brain injury. From the review, we have identified four major groups of external circumstances for rather sudden cardiopulmonary arrest from brain damage in children, after excluding congenital and other unrelated diseases; 1) impact brain apnea, 2) anoxic insults, 3) drug or other substance induced central nervous system depression, and 4) traumatic brain damage. Each group has different features in the course of cardiac and respiratory arrests. Based on this review of pathophysiologic features of cardio-respiratory responses from external causes, we have presented a suspected, but unlikely, child abuse case of respiratory arrest from brain injury. The social consequences of both unknowingly missing, and falsely incriminating the abuse can be grave, and the identification of the mechanisms of cardiopulmonary arrest from brain injury can be important for the differentiation of various potential causes.

BACKGROUND: Complex spinal deformities are a common issue in pediatric patients with an underlying neurologic diagnosis or syndrome. Management of neuromuscular scoliosis is an awesome responsibility, because these patients present with the most challenging pathologies of the deformed spine. Along with surgical correction of the underlying deformity, an intrathecal baclofen (ITB) pump is considered effective in managing the associated spasticity.
METHODS: We present the case of an 11-year-old female who sustained an episode of severe ischemic encephalopathy accompanied by hydrocephalus and severe spastic quadriplegia. An ITB pump was inserted to manage spasticity. Two years later, a very severe decompensated spinal curvature developed. In addition, malfunction of the pump was noted, and the decision was made to perform revision along with open hemilaminectomy at the L3-4 level. The inability of cerebrospinal fluid (CSF) to access the pump was verified intraoperatively, with the absence of CSF glow through the intrathecal space demonstrating blockage of CSF flow.
CONCLUSIONS: The association of cerebral palsy and relevant disorders with the relentless progression of scoliosis is analyzed, along with the possible offending mechanisms. The efficacy of an ITB pump in controlling intractable spasticity associated with neuromuscular scoliosis is reviewed, as well as its potential to accentuate the clinical progression of neuromuscular scoliosis. Although this is an extremely infrequent situation, we must always bear in mind the possibility that malfunction of an ITB pump could be related to obstruction of CSF flow, owing to the extreme severity of the curves established during the course of, most likely untreated, neuromuscular scoliosis.