Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury

Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-CoV-2. Affected individuals typically present with rapid changes in consciousness, focal neurological deficits, and seizures. Neuroimaging reveals symmetric, bilateral deep gray matter lesions, often involving the thalami, with evidence of necrosis and/or hemorrhage. The clinical and radiologic picture must be distinguished from direct infection of the central nervous system by some viruses, and from metabolic and mitochondrial disorders. Outcomes following ANE are poor overall and worse in those with brainstem involvement. Specific management is often directed toward modulating immune responses given the potential role of systemic inflammation and cytokine storm in potentiating neurologic injury in ANE, though benefits of such approaches remain unclear. The finding that many patients have mutations in the nucleoporin gene RANBP2, which encodes a multifunctional protein that plays a key role in nucleocytoplasmic transport, may allow for the development of disease models that provide insights into pathogenic mechanisms and novel therapeutic approaches.

Sports-Related Neurologic Injuries: More Than Just Concussion

ObjectiveDescribe important patterns of neurologic injury in sports related trauma.BackgroundSports related neurologic trauma represents a unique, complex pattern of injury with potential significant impactful morbidity. An estimated 8.6 million sports injuries occur annually, 300,000 of which result in traumatic brain injury (TBI). The incidence of other nervous system injury is underreported.Design/MethodsRetrospective analysis of consecutive patients who presented to an emergency department between January 1, 2015 and January 1, 2020 with a sports related injury. Characterization of neurologic vs non-neurological bodily injury, sports activity, and demographic data were collected.ResultsOut of 15,525 patients with sports injuries, 390 sustained neurologic involvement of which 50% were between 1-18 years of age. Although TBI represented the majority (85%) of neurologic injury, 5.6% sustained spinal cord involvement and 5.1% had peripheral nerve injury. Spinal cord and peripheral nerve involvement were associated with prolonged hospitalization when compared to those with mild-moderate concussion X2 (1, N = 199) = 5.73, p = 0.0167.ConclusionsSpinal cord and peripheral nerve injury represent the minority of sports related neurologic involvement, however, may lead to significant prolonged hospitalization, morbidity and mortality.

Plasma markers of neurologic injury and systemic inflammation in individuals with self-reported neurologic post-acute sequelae of SARS-CoV-2 infection (PASC)

Background: The biologic mechanisms underlying neurologic post-acute-sequelae of SARS-CoV-2 infection (PASC) are incompletely understood. Methods: We measured markers of neuronal injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery following the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported central nervous system (CNS) PASC symptoms during the late recovery timepoint. We compared fold-changes in marker values between those with and without CNS PASC symptoms using linear mixed effects models and examined relationships between neurologic and immunologic markers using rank linear correlations. Results: Of 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p=0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p=0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison to those who did not report CNS PASC symptoms (p=0.041). Those who went on to report CNS PASC also exhibited elevations in IL-6 (48% higher during early recovery and 38% higher during late recovery), MCP-1 (19% higher during early recovery), and TNF-alpha (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune activation markers during early recovery; these correlations were attenuated during late recovery. Conclusions: Self-reported neurologic symptoms present >90 days following SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at early recovery timepoints, suggesting that early injury can result in long-term disease. The correlation of GFAP and NfL with markers of systemic immune activation suggests one possible mechanism that might contribute to these symptoms. Additional work is needed to better characterize these processes and to identify interventions to prevent or treat this condition.

Toxins and Environmental Neurologic Injury

Toxins and environmental exposures may result in central or peripheral nerve dysfunction. Toxins may be purposely ingested (eg, substance misuse), or exposure may be accidental (eg, occupational exposure or terrorism). Certain environmental exposures (eg, lightning or high altitude) may also result in neurologic injury. This chapter reviews neurologic clinical syndromes associated with toxins and the physical effects of certain environmental conditions.

Radiological changes, infections and neurological complications after reverse shoulder arthroplasty related to different design types and their rates: Part II

Early reported complication rates with the Grammont-type reverse shoulder arthroplasty (RSA) were very high, up to 24%. A ‘problem’ is defined as an intraoperative or postoperative event that is not likely to affect the patient’s final outcome, such as intraoperative cement extravasation and radiographic changes. A ‘complication’ is defined as an intraoperative or postoperative event that is likely to affect the patient’s final outcome, including infection, neurologic injury and intrathoracic central glenoid screw placement. Radiographic changes around the glenoid or humeral components of the RSA are very frequently observed and described in the literature. High complication rates related to the Grammont RSA design led to development of non-Grammont designs which led to a dramatic fall in the majority of complications. The percentage of radiological changes after RSA is not negligible and remains unsolved, despite a decrease in its occurrence in the last decade. However, such changes should be now considered as simple problems because they rarely have a negative influence on the patient’s final outcome, and their prevalence has dramatically decreased. With further changes in indications and designs for RSA, it is crucial to accurately track the rates and types of complications to justify its new designs and increased indications. Cite this article: EFORT Open Rev 2021;6:1109-1121. DOI: 10.1302/2058-5241.6.210040

Increased interhemispheric asymmetry of cerebral blood flow in comatose adult patients on extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is a mechanical circulatory support method that is associated with a high burden of neurologic injury, but neurologic examination and imaging of this population presents prohibitive medical and logistical challenges. Diffuse correlation spectroscopy (DCS) can measure relative cerebral blood flow (rBF) non-invasively at the bedside. In this study we observed interhemispheric differences in rBF in response to mean arterial pressure (MAP) changes in adult ECMO recipients. Thirteen patients were recruited (ages 21-78, 7 with cardiac arrest, 4 with acute heart failure, 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n=4) and non-comatose (GCS-M > 4; n=9) groups. Comatose patients had more interhemispheric rBF asymmetry (ASYM_rBF) vs. non-comatose patients over a range of MAP values, (29% [IQR 23-34%] vs. 11% [IQR 8-13%], p=0.009). ASYM_rBF in comatose patients resolved near a MAP range of 70-80 mm Hg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Associations between post-oxygenator pCO2 or pH vs. ASYM_rBF individually did not meet significance, though the linear model slopes were different between comatose and non-comatose subgroups. Here we have demonstrated asymmetric cerebral autoregulation in comatose ECMO patients.

Inebilizumab for treatment of neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by recurrent optic neuritis and transverse myelitis often resulting in severe disability. Anti-AQP4-immunoglobulin G (IgG) is a pathogenic product of CD19-positive plasma cells found in most, but not all, individuals with NMOSD and is associated with immune-mediated neurologic injury. Inebilizumab, an afucosylated humanized IgG1κ, anti-CD19 monoclonal antibody, may target pathogenic CD19-expressing B cells. In a Phase II/III trial, inebilizumab significantly reduced the proportion of participants experiencing an NMOSD attack and was well tolerated versus placebo. Fewer treated participants had worsening disability than those receiving placebo. Inebilizumab was approved in 2020 by the US FDA for treatment of anti-AQP4 antibody positive NMOSD.