Acute Neurological Dysfunction Research Articles

Neurological dysfunction and fatal encephalitis due to Halicephalobus gingivalis in two horses in Belgium

SummaryTwo horses kept on different farms at a geographical distance of 150 km were presented with acute neurological dysfunction. Ante‐mortem diagnostic tests including bloodwork, CT scan and cerebrospinal fluid analysis did not provide a diagnosis in either case. Due to rapid deterioration, both horses were euthanised shortly after admission. Postmortem histopathological examination revealed granulomatous meningoencephalitis with intralesional nematodes that were morphologically identified as Halicephalobus gingivalis. This is the first documentation of central nervous system infestation by H. gingivalis in horses residing in Belgium, emphasising the importance of considering aberrant parasitic migration in the differential diagnosis of acute neurological dysfunction.

Investigating the Risk Factors Associated With Acute Neurologic Dysfunction in Pediatric Hyperglycemic Emergencies on Transport.

This study aims to identify key characteristics of hyperglycemic emergencies in pediatric patients and those at risk for acute neurologic dysfunction during transport. We conducted a retrospective chart review of pediatric patients during interfacility transport by Ornge, Ontario's critical care transport service, from January 1, 2009, to December 31, 2019. Data were extracted from electronic patient care records and included demographic, clinical, and transport-specific variables. Two multiple logistic regression models were utilized to analyze associations between predictor variables and neurologic dysfunction (GCS, <14). Of the 399 patients included, 24% (n = 95) had a GCS score of <14. Patients with a GCS score of <14 were more acidotic compared with those with a GCS score of ≥14 (median pH, 6.9 [IQR, 6.8-7.1] vs median, pH 7.0 [IQR, 1.0-7.2]; P < 0.001). Higher median corrected sodium for glucose values were observed in patients with a GCS score of <14 compared to those with a GCS score of ≥14 (145.7 mmol/L [IQR, 140.6-149.9 mmol/L] vs 141.7 mmol/L [IQR, 138.3-146.4 mmol/L]; P < 0.001). Multiple logistic regression identified younger age (aOR, 0.91; 95% CI, 0.84-0.98; P = 0.01), severe acidosis (pH <7.10; aOR, 3.56; 95% CI, 1.33-11.62; P = 0.02), and higher creatinine (aOR, 1.01; 95% CI, 1.01-1.02; P < 0.001) as risk factors for acute neurologic dysfunction. Our findings reveal associations between acute neurologic dysfunction, younger age, severe acidosis, and elevated corrected sodium for glucose values in pediatric hyperglycemic emergencies during transport. Education and adherence to guidelines are recommended to improve outcomes in this population.

SCG2 mediates blood-brain barrier dysfunction and schizophrenia-like behaviors after traumatic brain injury.

Traumatic brain injury (TBI), which is characterized by acute neurological dysfunction, is also one of the most widely recognized environmental risk factors for various neurological and psychiatric disorders. However, the role of TBI in neurological perturbation and the mechanisms underlying these disorders remain unknown. We evaluated transcriptional changes in cells of the frontal cortex after TBI by exploiting single-cell RNA sequencing (scRNA-Seq). We adopted the gene expression omnibus and scRNA-Seq to identify the mediation by secretogranin II (SCG2) of TBI-induced schizophrenia. Astrocytes are a principal source of SCG2 in the frontal cortex after TBI. Our analysis indicated that SCG2-triggered disruption of the blood-brain barrier (BBB) via the CypA-MMP-9 signaling pathway. Furthermore, astrocytic SCG2 knockout in the frontal cortex reduced BBB damage, mitigated inflammation, and inhibited schizophrenia after TBI. In conclusion, we identified the SCG2-CypA-MMP-9 signaling pathway in reactive astrocytes as a key switch in the protection of the BBB and provided a novel therapeutic avenue for treating psychiatric disorders after TBI.

Pioglitazone ameliorates sepsis-associated encephalopathy through SIRT1 signaling pathway

Sepsis is a severe immune response to an infection. It is associated with multiple organ dysfunction syndrome (MODs) along with systemic and neuronal inflammatory response. This study focused on the acute neurologic dysfunction associated with sepsis by exploring the role of PPARγ/SIRT1 pathway against sepsis. We studied the role of this axis in ameliorating sepsis-associated encephalopathy (SAE) and its linked neurobehavioral disorders by using pioglitazone (PIO). This PPARγ agonist showed neuroprotective actions in neuroinflammatory disorders. Sepsis was induced in mice by LPS (10 mg/kg). Survival rate and MODs were assessed. Furthermore, behavioral deficits, cerebral oxidative, inflammatory, and apoptotic markers, and the cerebral expression level of SIRT1 were determined. In this study, we observed that PIO attenuated sepsis-induced cerebral injury. PIO significantly enhanced survival rate, attenuated MODs, and systemic inflammatory response in septic mice. PIO also promoted cerebral SIRT1 expression and reduced cerebral activation of microglia, oxidative stress, HMGB, iNOS, NLRP3 and caspase-3 along with an obvious improvement in behavioral deficits and cerebral pathological damage induced by LPS. Most of the neuroprotective effects of PIO were abolished by EX-527, a SIRT1 inhibitor. These results highlight that the neuroprotective effect of PIO in SAE is mainly SIRT1-dependent.

Emergent Management of Central Nervous System Demyelinating Disorders.

This article reviews the various conditions that can present with acute and severe central nervous system demyelination, the broad differential diagnosis of these conditions, the most appropriate diagnostic workup, and the acute treatment regimens to be administered to help achieve the best possible patient outcomes. The discovery of anti-aquaporin 4 (AQP4) antibodies and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in the past two decades has revolutionized our understanding of acute demyelinating disorders, their evaluation, and their management. Demyelinating disorders comprise a large category of neurologic disorders seen by practicing neurologists. In the majority of cases, patients with these conditions do not require care in an intensive care unit. However, certain disorders may cause severe demyelination that necessitates intensive care unit admission because of numerous simultaneous multifocal lesions, tumefactive lesions, or lesions in certain brain locations that lead to acute severe neurologic dysfunction. Intensive care may be necessary for the management and prevention of complications for patients who have severely altered mental status, rapidly progressive neurologic worsening, elevated intracranial pressure, severe cerebral edema, status epilepticus, or respiratory failure.

Clinico-radiologic Spectrum and Outcome of Pediatric Acquired Demyelinating Disorders of Central Nervous System: A Retrospective Indian Tertiary Care Hospital Cohort.

Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied. Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS (n = 27), ADEM (n = 16), NMOSD (n = 13), MS (n = 1), and MOGAD (n = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p = 0.004), spinal cord (p = 0.01), and cerebellar lesions (p = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% (n = 64) had good recovery, 8.6% (n = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed. The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.

Study the carotid Doppler and computed tomography of head in ischemic stroke patients

Background: A stroke is an episode of acute neurological dysfunction from either ischemic infarction or a collection of blood within the brain or ventricular system with resultant focal injury of the central nervous system. The estimated global incidence of stroke is 2–3/1000 person-years, with older patients and patients with carotid artery stenosis or atrial fibrillation having the highest risk. Hence, carotid studies may help with early prevention and management in patients. Aims and Objectives: We aimed to study the prevalence of carotid artery stenosis in acute ischemic stroke and the association of risk factors. Materials and Methods: This was a descriptive study conducted in the department of internal medicine over a period of 6 months. It was carried out in 125 ischemic stroke patients’ inpatient departments. The ischemic stroke was established with history, examination, and computed tomography (CT) with carotid color Doppler study for percentage of stenosis. Results: The 47 (37.6%) stroke patients had carotid stenosis &lt;50% and 78 (62.4%) had &gt;50%; out of them, 32% (40) had (≥50–69%) stenosis, 24% (30) exhibited 70–99%, and 6.4% (8) reported total occlusion. In the CT brain, lacunar infarcts were found in 42 (33.6%), normal and middle cerebral artery infarcts in 27 (21.6%), anterior cerebral artery infarcts in 17 (13.6%), and posterior cerebral artery infarcts in 12 (9.6%). In clinical profiles, 75 (60%) patients presented with right-sided hemiparesis, 50 (40%) with left-sided hemiparesis, 62 (49.6%) with loss of consciousness, 28 (22.4%) with dizziness, and 31 (24.8%) with motor aphasia. Conventional risk factors include hypertension in 68 (54.4%), diabetes in 39 (31.2%), dyslipidemia in 58 (46.4%), heart disease in 65 (52%), and smoking in 51 (40.8%). In the present study, the majority of patients found carotid stenosis &gt;50%, lacunar infarcts were the most common CT findings, and right hemiparesis was common paresis. Hypertension was the most common risk factor among others, and all were significant (P&lt;0.05) for the stroke. Conclusion: There is a high prevalence of carotid stenosis, with &gt;50% in ischemic stroke patients with hypertension being the most common risk factor.

Long-Term Functional Outcomes Following Surgical Treatment of Spinal Schwannomas: A Population-Based Cohort Study

Spinal schwannomas are the second most common form of primary intradural spinal tumor. Despite being benign, they may cause spinal cord compression and subsequently acute or chronic neurological dysfunction. The primary treatment is surgical resection. The aim of this study was to identify pre- and postoperative predictors of favorable outcomes after surgical treatment for spinal schwannoma. All adult patients surgically treated for spinal schwannoma between 2006 and 2020 were eligible for inclusion. Medical records and imaging data were retrospectively reviewed. The primary outcome measures were neurological improvement according to the modified McCormick Scale (mMC) and changes in motor deficit, sensory deficit, gait disturbance, bladder dysfunction, and pain at long-term follow-up. In total, 180 patients with a median follow-up time of 4.4 years were included. Pain was the most common presenting symptom (87%). The median time between symptom presentation and surgery was 12 months, while the median time between diagnosis (first MRI) and surgery was 3 months. Gross total resection (GTR) was achieved in 150 (83%) patients and the nerve root could be preserved in 133 (74%) patients. A postoperative complication occurred in 10 patients (5.6%). There were significant postoperative improvements in terms of motor, sensory, gait, and bladder functions, as well as pain (p &lt; 0.001). Of these symptoms, bladder dysfunction was the one most often improved, with complete symptom resolution in all cases. However, no other predictors of improvement could be identified. There were three cases of recurrence after GTR and nine cases of regrowth after STR. Reoperation was performed in six (3.3%) cases. GTR was associated with a significant improvement in neurological status at long-term follow-up and increased the chance of progression-free survival.

Efficacy of Repetitive Transcranial Magnetic Stimulation (r-TMS) Therapy on Improving Motor Strength in Storke Patients at Dr. Moewardi Surakarta

Background: Stroke, an acute neurological dysfunction, poses a health challenge with potential fatality, emerging as a leading cause of long-term disability. This study explores the efficacy of repetitive Transcranial Magnetic Stimulation (r-TMS) with medical rehabilitation in enhancing stroke patients' motor strength, comparing it with standard therapy, focusing on the Medical Research Council score. Objective: Stroke is an acute manifestation resulting from neurological dysfunction, persisting for ≥24 hours or leading to death due to blood vessel disorders. The study aims to determine the effectiveness of r-TMS therapy in improving stroke patients' motor strength, comparing it with standard therapy based on the Medical Research Council score. Methods: A quasi-experimental study with a pre-post control group design involved 30 respondents selected through consecutive sampling in stroke units and outpatient clinics. Upper extremity muscle strength, measured with the Medical Research Council score, was analyzed using the Mann-Whitney U test, with a significance level set at p &lt; 0.05. Result: The post-test ranking value of the r-TMS group (20.56) exceeded that of the Non r-TMS group (10.46). The Mann-Whitney U test indicated a significant difference in the average ranking of the Medical Research Council scores between the two groups (p &lt; 0.05, 0.001), highlighting the efficacy of r-TMS therapy in enhancing motor strength. Conclusion: This study shows that stroke patients receiving standard therapy and transcranial magnetic stimulation exhibit improvements in extremity motor strength compared to those undergoing medical rehabilitation alone. The r-TMS group notably showed a significant increase in extremity motor strength.

Spreading Depolarizations Contribute to the Acute Behavior Deficits Associated With a Mild Traumatic Brain Injury in Mice.

Concussions or mild traumatic brain injuries (mTBIs) are often described and diagnosed by the acute signs and symptoms of neurological dysfunction including weakness, dizziness, disorientation, headaches, and altered mental state. The cellular and physiological mechanisms of neurological dysfunction and acute symptoms are unclear. Spreading depolarizations (SDs) occur after severe TBIs and have recently been identified in closed-skull mouse models of mTBIs. SDs are massive waves of complete depolarization that result in suppression of cortical activity for multiple minutes. Despite the clear disruption of brain physiology after SDs, the role of SDs in the acute neurological dysfunction and acute behavioral deficits following mTBIs remains unclear. We used a closed-skull mouse model of mTBI and a series of behavioral tasks collectively scored as the neurological severity score (NSS) to assess acute behavior. Our results indicate that mTBIs are associated with significant behavioral deficits in the open field and NSS tasks relative to sham-condition animals. The behavioral deficits associated with the mTBI recovered within 3 h. We show here that the presence of mTBI-induced bilateral SDs were significantly associated with the acute behavioral deficits. To identify the role of SDs in the acute behavioral deficits, we used exogenous potassium and optogenetic approaches to induce SDs in the absence of the mTBI. Bilateral SDs alone were associated with similar behavioral deficits in the open field and NSS tasks. Collectively, these studies demonstrate that bilateral SDs are linked to the acute behavioral deficits associated with mTBIs.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. ClinicalTrials.gov Identifier: NCT05094154.

Early Postoperative Neurologic Events Are Associated With Worse Outcome and Fatal Midterm Survival After Adult Heart Transplantation.

Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P=0.009), longer mechanical ventilation (192 versus 48 hours; P<0.001), and higher need for blood transfusion, and need for hemodialysis after HTx was substantially higher (81% versus 55%; P=0.01). Resternotomy (36% versus 26%; P=0.05) and mechanical life support (extracorporeal life support) after HTx (46% versus 24%; P=0.02) were also significantly higher in patients with neurologic events. Covariable-adjusted multivariable Cox regression analysis revealed a significant independent association of neurologic events and increased 30-day (hazard ratio [HR], 2.5 [95% CI, 1.0-6.0]; P=0.049), 1-year (HR, 2.2 [95% CI, 1.1-4.3]; P=0.019), and overall (HR, 2.5 [95% CI, 1.5-4.2]; P<0.001) mortality after HTx and reduced Kaplan-Meier survival up to 5 years after HTx (P<0.001). Conclusions Neurologic events after HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after HTx.

Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes

Pituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs. To document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy. Twenty-six client-owned dogs with acute onset of neurological dysfunction. Retrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports. Common presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1-weighted hypo- to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7-641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41-1719 days). Dogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome.

Review of Noninvasive Neuromonitoring Modalities in Children II: EEG, qEEG.

Critically ill children with acute neurologic dysfunction are at risk for a variety of complications that can be detected by noninvasive bedside neuromonitoring. Continuous electroencephalography (cEEG) is the most widely available and utilized form of neuromonitoring in the pediatric intensive care unit. In this article, we review the role of cEEG and the emerging role of quantitative EEG (qEEG) in this patient population. cEEG has long been established as the gold standard for detecting seizures in critically ill children and assessing treatment response, and its role inbackground assessment and neuroprognostication after brain injury is also discussed. We explore the emerging utility of both cEEG and qEEG as biomarkers of degree of cerebral dysfunction after specific injuries and their ability to detect both neurologic deterioration and improvement.

Cold-stored Platelets for Bleeding Patients: Comment.

Cold-stored Platelets for Bleeding Patients: Comment.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

An Explainable Machine Learning Pipeline for Stroke Prediction on Imbalanced Data.

Stroke is an acute neurological dysfunction attributed to a focal injury of the central nervous system due to reduced blood flow to the brain. Nowadays, stroke is a global threat associated with premature death and huge economic consequences. Hence, there is an urgency to model the effect of several risk factors on stroke occurrence, and artificial intelligence (AI) seems to be the appropriate tool. In the present study, we aimed to (i) develop reliable machine learning (ML) prediction models for stroke disease; (ii) cope with a typical severe class imbalance problem, which is posed due to the stroke patients’ class being significantly smaller than the healthy class; and (iii) interpret the model output for understanding the decision-making mechanism. The effectiveness of the proposed ML approach was investigated in a comparative analysis with six well-known classifiers with respect to metrics that are related to both generalization capability and prediction accuracy. The best overall false-negative rate was achieved by the Multi-Layer Perceptron (MLP) classifier (18.60%). Shapley Additive Explanations (SHAP) were employed to investigate the impact of the risk factors on the prediction output. The proposed AI method could lead to the creation of advanced and effective risk stratification strategies for each stroke patient, which would allow for timely diagnosis and the right treatments.

Pearls & Oy-sters: Tumefactive Demyelinating Lesions With MOG Antibodies Preceding Late Infantile Metachromatic Leukodystrophy.

The development of acute neurologic dysfunction associated with tumefactive demyelinating lesions and mild diffuse involvement of the corpus callosum has been described in children as a sentinel event that may allow diagnosis of juvenile metachromatic leukodystrophy (MLD) at an early and potentially treatable stage. We report a child who developed this clinico-radiologic pattern associated with myelin oligodendrocyte glycoprotein antibodies several months before the onset of progressive symptoms of late infantile MLD.

Acute Neurologic Dysfunction in Critically Ill Children: The PODIUM Consensus Conference

Acute neurologic dysfunction is common in critically ill children and contributes to outcomes and end of life decision-making. To develop consensus criteria for neurologic dysfunction in critically ill children by evaluating the evidence supporting such criteria and their association with outcomes. Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, by using a combination of medical subject heading terms and text words to define concepts of neurologic dysfunction, pediatric critical illness, and outcomes of interest. Studies were included if the researchers evaluated critically ill children with neurologic injury, evaluated the performance characteristics of assessment and scoring tools to screen for neurologic dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies with an adult population or premature infants (≤36 weeks' gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and studies not published in English with an inability to determine eligibility criteria were excluded. Data were abstracted from each study meeting inclusion criteria into a standard data extraction form by task force members. The systematic review supported the following criteria for neurologic dysfunction as any 1 of the following: (1) Glasgow Coma Scale score ≤8; (2) Glasgow Coma Scale motor score ≤4; (3) Cornell Assessment of Pediatric Delirium score ≥9; or (4) electroencephalography revealing attenuation, suppression, or electrographic seizures. We present consensus criteria for neurologic dysfunction in critically ill children.

Tacrolimus-associated posterior reversible encephalopathy syndrome after kidney transplantation

Calcineurin inhibitors are essential immunosuppressive agents for kidney transplant patients. Posterior reversible leukoencephalopathy syndrome is a rare complication of treatment with calcineurin inhibitors. Herein, we report three cases of tacrolimus-associated posterior reversible leukoencephalopathy syndrome after kidney transplantation and their unique clinical courses. Patients in Cases 1 and 2 presented with headache and visual field disturbance on the fourth day after transplantation. Both patients were successfully treated with antihypertensive therapy and a change in medications from tacrolimus to cyclosporine and everolimus. Case 3 was a kidney transplant patient at 12 years post-transplant who developed fever and conjugate eye deviation to the right. The patient was initially treated with antihypertensive medication and a reduction in tacrolimus dose, but she experienced prolonged disturbance of consciousness, which eventually improved. These cases highlight the importance of considering the possibility of posterior reversible leukoencephalopathy syndrome in kidney transplant recipients taking calcineurin inhibitors who present with acute neurological dysfunction. They also demonstrate the need to perform appropriate imaging to confirm the diagnosis and initiate treatment, even if a significant amount of time has passed since transplantation. The introduction of an mTOR inhibitor may be practical when changing or discontinuing calcineurin inhibitors.