High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study.

OBJECTIVES: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. METHOD: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. RESULTS: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). CONCLUSION: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19.

DeltaScan for the Assessment of Acute Encephalopathy and Delirium in ICU and non-ICU Patients, a Prospective Cross-Sectional Multicenter Validation Study.

OBJECTIVES: To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). DESIGN: Prospective cross-sectional study. SETTING: Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. PARTICIPANTS: 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. MEASUREMENTS: DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. METHODS: Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. RESULTS: DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. CONCLUSIONS: DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes.

Advancing specificity in delirium: The delirium subtyping initiative.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

Time course of serum cytokine level changes within 72 h after onset in children with acute encephalopathy and febrile seizures.

BACKGROUND: Cytokine levels have been measured in acute encephalopathy (AE) to determine its pathology or as a diagnostic biomarker to distinguish it from febrile seizures (FS); however, the dynamics of cytokine level changes have not yet been fully captured in these two neurological manifestations. Thus, we aimed to explore the time course of serum cytokine level changes within 72 h after onset in AE and FS. METHODS: We retrospectively measured cytokine level in residual serum samples at multiple timepoints in seven children whose final diagnoses were AE or FS. RESULTS: The levels of 13 cytokines appeared to increase immediately after onset and peaked within 12-24 h after onset: interleukin (IL)-1ß, IL-4 IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, fibroblast growth factor, granulocyte colony-stimulating factor, interferon gamma, interferon-inducible protein-10, and macrophage chemoattractant protein-1. There were no dynamic changes in the levels of three cytokines (IL-1 receptor agonist, macrophage inflammatory protein-1α, and platelet-derived growth factor-bb) 72 h after onset. Levels of some cytokines decreased to around control levels within 48 h after onset: IL-1ß, IL-4, IL-5, IL-17, fibroblast growth factor, and interferon gamma. The levels of most cytokines appeared to be higher in AE, especially in hemorrhagic shock encephalopathy syndrome, than in FS. CONCLUSIONS: Cytokine levels in both AE and FS change dynamically, such as the levels of several cytokines increased within a few hours after onset and decreased at 12-24 h after onset. Therefore, it will be desirable to make clinical decisions regarding the administration of anti-inflammatory therapy in 24 h after onset in AE.

Modifiable risk factors for post-operative delirium in older adults undergoing major non-cardiac elective surgery: a multi-centre, trainee delivered observational cohort feasibility study and trainee survey.

BACKGROUND: Post-operative delirium (POD) is an acute brain failure which may occur following major surgery, with serious implications for participants and caregivers. Evidence regarding optimal anaesthetic management for older participants at higher risk of POD is conflicting. We conducted a feasibility study of our protocol in 5 centres to guide sample size estimation and inform future recruitment strategies for a larger cohort study. METHODS: Participants aged over 65 and scheduled for major surgery were recruited. They were assessed pre-operatively for delirium, cognitive impairment, depression, comorbidity, activity levels and alcohol use. Details of management during surgery, all medications and complications were recorded by a trainee-led research team. Participants were assessed for delirium in the immediate recovery period and then on post-operative days 1-4 using the 4 question attention test (4AT) with complications assessed at day 4 using the post-operative morbidity survey (POMS). Primary outcomes were the incident rates of POD. Secondary outcomes were number of eligible patients, recruitment rates and retention rates throughout the study, time required for data collection, preoperative risk factors assessment and daily postoperative delirium assessments. Also to assess the added value of employing the regional trainee research network (INCARNNET) to deliver the study. Specifically, what proportion of patient consent, data collection and post-operative testing is performed by anaesthesia trainees from this group, especially the success of weekend delirium assessment by trainees? A survey was completed at the end of the study by the trainees involved regarding their involvement in the study. RESULTS: Ninety-five participants were recruited, of whom 93 completed the study. Overall, POD occurred in 9 patients. Of these, three were detected in recovery and six on post-op days 1-4. Median length of stay was 6 days. Recruitment rates were high in all but one site. 59 (62%) participants were consented by trainees and 189 (63%) of post op delirium assessments were performed by trainees. A total of six patients declined the study (in a follow up survey of trainees). Pre-existing cognitive impairment, depression and problem drinking were detected in 4(4.3%), 3(3.2%) and 5(5.37%) participants, respectively. Co-morbidity was common with 55(59%) in class three or four of the geriatric index of morbidity. Overall, from a total of 641 data points, levels of missing data were as follows, site A = 9.3%, B = 13.5%, C = 15.4%, D = 10.9%, E = 11.1% (data could not be completed retrospectively). CONCLUSIONS: A multi-centre observational cohort study of delirium carried out by UK trainee anaesthetists is feasible. Patients are content to undergo day of surgery consent and multiple short questionnaires pre-operatively. Proposed data, especially pharmacological, should be carefully considered for their relevance to modifiable mechanisms that can lead to POD. Future research to enable prognostic modelling of POD should involve large scale cohort studies of enriched populations to capture a higher POD incidence. POD remains a common complication in older persons undergoing major surgery in the UK and studies of interventions are urgently needed. TRIAL REGISTRATION: All methods were carried out in accordance with relevant guidelines and regulations. The study was retrospectively registered with ISRCTN94663125 on 07/02/2018.

An infantile traumatic brain injury with a bright tree appearance detected before the late seizure.

INDRODUCTION: Infantile traumatic brain injury (TBI) rarely follows a biphasic clinical course and exhibits a bright tree appearance (BTA) on magnetic resonance imaging (MRI). This is termed infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD). TBIRD has clinical features similar to those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). It remains to be clarified which patients with infantile TBI will develop TBIRD and the prevention and treatment of TBIRD. CASE AND REVIEW: We report a case of TBIRD that exhibited BTA 1 day before the late seizure and review 12 cases of TBIRD. All patients developed a subdural hematoma (SDH), were younger than 2 years, and presented with a biphasic phase within 3-6 days. The median interval between BTA and TBI was 5 days. Of the 5 cases examined with MRI before the biphasic phase, only our case was detected with BTA 4 days after TBI. CONCLUSION: Predicting the biphasic clinical course may be possible by examining MRI after TBI in patients under 2 years of age who develop SDH with unconsciousness, seizure, or hemiplegia, and these patients should be strictly followed up for 1 week.

Efficacy of cEEG and hepatic function to diagnose early acute encephalopathy.

BACKGROUND: Early treatment may improve the prognosis of acute encephalopathy (AE). However, methods for early diagnosis have not yet been established. In this paper, we examined methods for the early diagnosis of AE. METHODS: We extracted data on patients with febrile status epilepticus from the electronic medical records in our department between March 2016 and April 2021. Among these, 79 patients who underwent continuous electroencephalography (cEEG) were included in this study. Patients who exhibited psychomotor retardation or abnormal brain magnetic resonance imaging findings were assigned to Group E (n = 20), and the remaining patients were the control group (Group C, n = 59). The following tests were compared retrospectively between these two groups on admission: cEEG, serum hepatic function tests, and blood coagulation tests. RESULTS: The percentage of patients who exhibited high-amplitude slow waves or flat waves on cEEG at the time of admission was statistically significantly higher in Group E than in Group C (p < 0.01). Moreover, the percentage of patients whose high-amplitude slow waves or flat brain waves on admission disappeared within 6 h after an initial episode of convulsion was statistically significantly lower in Group E than in Group C (p < 0.01). Furthermore, all the items in the coagulation and the hepatic function tests were statistically significantly different in Group E from those in Group C (p < 0.05). CONCLUSION: These results showed that cEEG together with hepatic function and coagulation tests may be useful for the differential diagnosis of AE.

Chemical elucidation of acute encephalopathy by ingestion of angel-wing mushroom (Pleurocybella porrigens) - involvement of three constituents in onset.

The mushroom, Pleurocybella porrigens, is widely consumed in Japan; however, in autumn 2004, acute encephalopathy due to ingestion of the mushroom in a large group of patients was reported in Japan. We have continued working on the mushroom to clarify the mechanisms underlying the acute encephalopathy that occurred due to its consumption. The data collected to date have shown that three compounds, pleurocybelline (PC), a Pleurocybella porrigens lectin (PPL), and pleurocybellaziridine (PA), in the mushroom are potentially responsible for the onset of the disease; PC that exhibit lethal activity in mice and PPL formed a complex, and the complex of the two components exhibited proteolytic activity and disrupted the blood-brain barrier. Although PA was not isolated directly from the mushroom, the existence of this compound in the mushroom was predicted. The compound was chemically synthesized and its endogeneity in the mushroom was demonstrated. Furthermore, PA exhibited toxicity to oligodendrocytes.

Effects of non-pharmacologic prevention on delirium in critically ill patients: A network meta-analysis.

BACKGROUND: Delirium is a common complication among patients in the intensive care unit (ICU). It is important to prevent the occurrence of delirium in critically ill patients. AIM: This review aimed to evaluate the efficacy of non-pharmacological interventions and determine what combination of these is effective in preventing delirium among Intensive Care Unit patients. STUDY DESIGN: A systematic review and meta-analysis. This review follows the guidelines of the Preferred Reporting Items for Systematic reviews and Meta Analysis statements for Network Meta-Analysis (PRISMA-NMA). Data sources included the Cumulative Index to Nursing & Allied Health Literature., MEDLINE, and Cochrane library databases. The integrated data were investigated with odds ratio (OR) and 95% confidence interval (95% CI), using the random-effects Mantel-Haenszel model. Data were considered significant when p < 0.05. Furthermore, to reveal what combination of care is effective, we performed a network meta-analysis estimated OR, 95% CI. RESULTS: We identified three randomized controlled trials and eight controlled before-after trials (11 in total, with 2549 participants). The pooled data from 11 trials of multicomponent intervention had a significant effect on delirium prevention (OR 0.58, 95% CI 0.44-0.76, p < 0.001). As a result of network meta-analysis, two bundles were effective compared to the control group in reducing the incidence of delirium: a) the combination of sleep promotion (SP), cognitive stimulation (CS), early mobilization (EM), pain control (PC), and assessment (AS) (OR 0.47, 95% CI 0.35-0.64, p < 0.002), and b) the combination of SP and CS (OR 0.46, 95% CI 0.28-0.75, p < 0.001). CONCLUSION: This study revealed that non-pharmacological interventions, particularly multicomponent interventions, helped to prevent delirium in critically ill patients. In the network meta-analysis, the most effective care combination for reducing incidence of delirium was found to be multicomponent intervention, which comprises SP-CS-EM-PC-AS, and SP-CS. RELEVANCE TO CLINICAL PRACTICE: These findings reveal an efficient combination of multicomponent interventions for preventing delirium, which may be a very important prerequisite in planning care programs in the future.

SARS-COVID-19 TRIGGERED WERNICKE'S ENCEPHALOPATHY (CLINICAL CASE).

Patient P., born in 1956, was found by relatives in a state of confused consciousness, an act of involuntary urination and defecation, numbness and weakening of the strength of both lower limbs were recorded. He was taken by ambulance to the reception room of the Regional Clinical Center of Neurosurgery and Neurology. The following concomitant diseases are known from the life anamnesis: Atrial fibrillation, gout, hypertension and type II non-insulin-dependent diabetes mellitus. Objective status: general condition of medium severity, tophuses of small joints of hands and feet, knee and elbow joints. Pronounced deformity of hands and feet due to gouty lesions. Heart tones are weakened. Breath sounds are weakened. The abdomen is soft, not painful on palpation. Glasgow coma scale 14-15 points. Consciousness is confused, disoriented in time, space and own person. To clarify the diagnosis, clinical and laboratory and instrumental diagnostic methods were used. Neurological complications, in particular, acute encephalopathy, on the background of coronavirus infection, may develop in patients with the presence of such risk factors as advanced age, cardiovascular diseases, hypertension, diabetes, gout. Most of the neurological complications in COVID-19 are probably not related to the direct penetration of the virus into the CNS, but are a trigger for the development of the pathology. Neuroimaging in such cases does not reveal pathological changes or reflects non-specific disorders.

MicroRNA expression profiling of cerebrospinal fluid/serum exosomes in children with human herpesvirus 6-associated encephalitis/encephalopathy by high-throughput sequencing.

Primary human herpesvirus 6 (HHV-6) infection is sometimes accompanied by acute encephalopathy with reduced subcortical diffusion (AED) in immunocompetent children. We investigated exosomal microRNA (miRNA) expression profiles in cerebrospinal fluid (CSF) and sera of patients with HHV-6-associated AED (n = 5) and febrile seizure (FS) (n = 5) using high-throughput sequencing. A total of 176 and 663 miRNAs were identified in CSF and serum exosomes, respectively. Comparative analysis determined that some miRNAs (miR-381-3p, miR-155) were exclusively expressed in the CSF exosomes of AED but not of FS patients, suggesting their potential application as novel diagnostic biomarkers for AED.

Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

Delirium and COVID-19: a narrative review of emerging evidence.

Delirium is a common condition affecting hospital inpatients, including those having surgery and on the intensive care unit. Delirium is also common in patients with COVID-19 in hospital settings, and the occurrence is higher than expected for similar infections. The short-term outcomes of those with COVID-19 delirium are similar to that of classical delirium and include increased length of stay and increased mortality. Management of delirium in COVID-19 in the context of a global pandemic is limited by the severity of the syndrome and compounded by the environmental constraints. Practical management includes effective screening, early identification and appropriate treatment aimed at minimising complications and timely escalation decisions. The pandemic has played out on the national stage and the effect of delirium on patients, relatives and healthcare workers remains unknown but evidence from the previous SARS outbreak suggests there may be long-lasting psychological damage.

The Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19.

BACKGROUND: Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline. SUMMARY: The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia. KEY MESSAGES: The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies.

De novo homozygous variant of the SCN1A gene in a patient with severe Dravet syndrome complicated by acute encephalopathy.

Variants in the SCN1A gene have been identified in epilepsy patients with widely variable phenotypes and they are generally heterozygous. Here, we report a homozygous missense variant, NM_001165963.4: c.4319C>T (p.Ala1440Val), in the SCN1A gene which seemed to occur de novo together with a gene conversion event. It's highly possible that this variant, although located in a critical functional domain of protein Nav1.1, depending on the nature of the amino acid substitution, may not cause the complete loss of protein function. And the accumulated effect by having this variant on both alleles results in a Dravet syndrome phenotype which is more severe than average. This first report of a de novo homozygous variant in the SCN1A gene, therefore, provides a clear illustration of a complex genotype-phenotype relationship.

Towards the development of a human in vitro model of the blood-brain barrier for virus-associated acute encephalopathy: assessment of the time- and concentration-dependent effects of TNF-α on paracellular tightness.

The pathogenesis of virus-associated acute encephalopathy (VAE) involves brain edema caused by disruption of the blood-brain barrier (BBB). We aimed to develop an in vitro VAE model using an in vitro BBB model, to evaluate the dynamics of vascular dysfunction caused by tumor necrosis factor (TNF)-α. A co-culture model, consisting of Transwell®-grown human brain microvascular endothelial cells and pericytes, was treated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using cellZscope®. A permeability assay, using fluorescein isothiocyanate-conjugated sodium or dextran, was performed. Changes in claudin-5 localization and expression after TNF-α treatment were observed using immunofluorescence staining and western blot analysis. The TER decreased and permeability increased after TNF-α treatment; recovery time was dependent on TNF-α concentration. Claudin-5 was delocalized after TNF-α treatment and recovered in a TNF-α concentration-dependent manner. The expression of claudin-5 decreased 24 h after the TNF-α treatment and completely recovered 48 h after TNF-α treatment. Claudin-5 delocalization was likely associated with vascular hyperpermeability. To conclude, we evaluated vascular endothelial cell permeability and injury in VAE using an in vitro BBB model treated with TNF-α. This system can be useful for developing novel therapeutic strategies for VAE and designing treatments that target vascular permeability.

Rescue from Stx2-Producing E. coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice.

Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae. Current treatments, including immunoglobulin G (IgG) immunoadsorption, plasma exchange, steroid pulse therapy, and the monoclonal antibody eculizumab, have limited effects against the severe neurologic sequelae. Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative non-tumorigenic stem cells that naturally reside in the body and are currently under clinical trials for regenerative medicine. When administered intravenously, Musecells accumulate to the damaged tissue, where they exert anti-inflammatory, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, and replace damaged cells by differentiating into tissue-constituent cells. Here, severely immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice orally inoculated with 9 × 109 colony-forming units of STEC O111 and treated 48 h later with intravenous injection of 5 × 104 Muse cells exhibited 100% survival and no severe after-effects of infection. Suppression of granulocyte-colony-stimulating factor (G-CSF) by RNAi abolished the beneficial effects of Muse cells, leading to a 40% death and significant body weight loss, suggesting the involvement of G-CSF in the beneficial effects of Muse cells in STEC-infected mice. Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection.

Prognostic Factors for Pediatric Acute Encephalopathy Associated with Severe Brain Edema.

BACKGROUND AND OBJECTIVE: Acute encephalopathy is a life-threatening brain dysfunction in children, often associated with a preceding infection and diffuse noninflammatory brain edema. At present, the role of decompressive craniectomy (DC) over the swollen area of the brain is unclear. The risk factors for predicting clinical deterioration also need clarification. METHODS: A retrospective study of pediatric patients admitted between 2015 and 2019 with acute cerebral encephalopathy was carried out. Patients were classified according to: (1) the preceding pathogens, (2) the syndromic classification, and (3) the extent of brain edema. The syndromic classification is a relatively new classification of acute encephalopathy proposed in 2016 and divides patients into 3 groups: those with systemic inflammatory reactions or "cytokine storms" (group 1), those with status epilepticus but no cytokine storm (group 2), and others (group 3). Glasgow Outcome Scale (GOS) scores of 1-3 were defined as unfavorable, while a GOS score of 4 or 5 was defined as a favorable outcome in this study. DC was performed for select patients with life-threatening signs of brainstem compression. RESULTS: Nineteen patients (mean age: 23.3 months) were included in the study, 8 (42.1%) of whom had an unfavorable outcome. There was no significant correlation between the types of pathogens and outcome. Unfavorable outcomes were observed in significantly more patients in group 1 (87.5%) than group 2 (14.3%) and group 3 (0%). There was a significant association between diffuse brain edema and unfavorable outcomes (72.7%). Neurosurgical DC was performed in 2 patients to alleviate life-threatening brainstem compression: one with a cytokine storm and diffuse bilateral brain edema, and the other with prolonged status epilepticus causing diffuse right-sided brain edema. The GOS score was 3 and 4, respectively. CONCLUSION: The risk factors for clinical deterioration in pediatric acute encephalopathy were evaluated based on a variety of classifications, including the new syndromic classification. Laboratory features of cytokine storms and radiological evidence of diffuse brain edema were associated with unfavorable outcomes. The role of surgical decompression is still controversial and should be assessed on a case-by-case basis.

Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion Associated with Dengue Infection in a Child.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a clinico-radiological syndrome in children secondary to viral or bacterial infections. The causes include viral (influenza, human herpes virus-6, adenovirus, rota) as well as bacterial infections. However, AESD with dengue infection has not been reported earlier. Here, we present an infant with dengue infection and AESD which recovered completely following treatment with intravenous human immunoglobulin therapy. A 9-month-old girl presented with seizures following fever and loose stools. Seizures recurred after 2 days of seizure-free interval. Cerebrospinal fluid analysis was not contributory. Dengue infection was confirmed by lab tests. Magnetic resonance imaging brain after the second seizure revealed diffusion restriction involving the bilateral frontal and parietal white matter, both hemispheres with a typical central perisylvian sparing lesion suggestive of AESD. This case report expands the reported spectrum of neurological manifestations of dengue infection.

Methadone-induced encephalopathy: a case series and literature review.

BACKGROUND: Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological deficits of methadone-poisoned patients admitted to a referral poisoning hospital using brain magnetic resonance (MR) and diffusion weighted (DW) imaging. METHODS: In this retrospective study, brain MRIs of the patients admitted to our referral center due to methadone intoxication were reviewed. Methadone intoxication was confirmed based on history, congruent clinical presentation, and confirmatory urine analysis. Each patient had an MRI with Echo planar T1, T2, FLAIR, and DWI and apparent deficient coefficient (ADC) sequences without contrast media. Abnormalities were recorded and categorized based on their anatomic location and sequence. RESULTS: Ten patients with abnormal MRI findings were identified. Eight had acute- and two had delayed-onset encephalopathy. Imaging findings included bilateral confluent or patchy T2 and FLAIR high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion restriction in DWI. Internal capsule involvement was identified in two patients while abnormality in globus pallidus and head of caudate nuclei were reported in another. Bilateral cerebral symmetrical confluent white matter signal abnormality with sparing of subcortical U-fibers on T2 and FLAIR sequences were observed in both patients with delayed-onset encephalopathy. CONCLUSIONS: Acute- and delayed-onset encephalopathies are two rare adverse events detected in methadone-intoxicated patients. Brain MRI findings can be helpful in detection of methadone-induced encephalopathy.