Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension.

BACKGROUND: Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy (HE). It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt (TIPS) is related to postoperative HE. AIM: To investigate the relationship between spleen volume and the occurrence of HE. METHODS: This study included 135 patients with liver cirrhosis who underwent TIPS, and liver and spleen volumes were elevated upon computed tomography imaging. The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes. Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE (OHE). Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk. RESULTS: The results showed that 37 (27.2%) of 135 patients experienced OHE during a 1-year follow-up period. Compared with preoperative spleen volume (901.30 ± 471.90 cm3), there was a significant decrease in spleen volume after TIPS (697.60 ± 281.0 cm3) in OHE patients. As the severity of OHE increased, the spleen volume significantly decreased (P < 0.05). Compared with patients with a spleen volume ≥ 782.4 cm3, those with a spleen volume < 782.4 cm3 had a higher incidence of HE (P < 0.05). Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE (hazard ratio = 0.494, P < 0.05). Restricted cubic spline model showed that with an increasing spleen volume, OHE risk showed an initial increase and then decrease (P < 0.05). CONCLUSION: Spleen volume is related to the occurrence of OHE after TIPS. Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

Epileptic foci and networks in children with epilepsy after acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) develops along with status epilepticus and widespread subcortical white matter edema. We aimed to evaluate the epileptic foci and networks in two patients with epilepsy after AESD using simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI). METHODS: Statistically significant blood oxygen level-dependent (BOLD) responses related to interictal epileptiform discharges (IEDs) were analyzed using an event-related design of hemodynamic response functions with multiple peaks. RESULTS: Patient 1 developed focal seizures at age 10 years, one year after AESD onset. Positive BOLD changes were observed in the bilateral frontotemporal lobes, left parietal lobe, and left insula. BOLD changes were also observed in the subcortical structures. Patient 2 developed epileptic spasms at age two years, one month after AESD onset. Following total corpus callosotomy (CC) at age three years, the epileptic spasms resolved, and neurodevelopmental improvement was observed. Before CC, positive BOLD changes were observed bilaterally in the frontotemporal lobes. BOLD changes were also observed in the subcortical structures. After CC, the positive BOLD changes were localized in the temporal lobe ipsilateral to the IEDs, and the negative BOLD changes were mainly in the cortex and subcortical structures of the hemisphere ipsilateral to IEDs. CONCLUSION: EEG-fMRI revealed multiple epileptic foci and extensive epileptic networks, including subcortical structures in two cases with post-AESD epilepsy. CC may be effective in disconnecting the bilaterally synchronous epileptic networks of epileptic spasms after AESD, and pre-and post-operative changes in EEG-fMRI may reflect improvements in epileptic symptoms.

Atypical posterior reversible encephalopathy syndrome: A lentiform fork sign following transplantation.

Key Clinical Message: Posterior Reversible Encephalopathy Syndrome, typically characterized by parieto-occipital vasogenic edema, can present atypically, as a bilateral symmetrical vasogenic edema in the basal ganglia, featuring the called "lentiform fork sign." Prompt recognition of such variations is crucial for accurate diagnosis and tailored management, highlighting the complexity of this syndrome's manifestations. Abstract: Posterior Reversible Encephalopathy Syndrome (PRES) manifests as transient neurological symptoms and cerebral edema, commonly associated with immunosuppressive drugs (ISDs) in transplant recipients. ISDs can lead to endothelial dysfunction and compromise the blood-brain barrier. Typically, PRES exhibits identifiable MRI patterns, often demonstrating vasogenic edema in the bilateral parieto-occipital white matter. Identifying unique presentations, such as the recently observed "lentiform fork sign," commonly seen in uremic encephalopathy, emphasizes this syndrome's broad spectrum manifestations. A 19-year-old male, who underwent bilateral lung and liver transplantation, experienced a bilateral tonic-clonic seizure of unknown onset 47 days post-surgery. MRI findings revealed an unconventional PRES pattern, featuring the "lentiform fork sign" as bilateral symmetrical vasogenic edema in the basal ganglia, surrounded by a hyperintense rim outlining the lentiform nucleus bilaterally. Subsequent management, including ISD modification and magnesium supplementation, resulted in clinical and neuroimaging resolution. An almost complete clinical and radiological resolution was achieved after 14 days. The occurrence of PRES in transplant recipients highlights the intricate interplay among ISDs, physiological factors, and cerebrovascular dynamics, potentially involving direct neurovascular endothelial toxicity and disruption of the blood-brain barrier. Neuroimaging plays a pivotal role in diagnosis. The distinctive "lentiform fork sign" was observed in this patient despite the absence of typical metabolic disturbances. Management strategies usually involve reducing hypertension, discontinuing ISDs, correcting electrolyte imbalances, and initiating antiseizure drugs if necessary. Identifying the presence of the "lentiform fork sign" alongside typical PRES edema in a patient lacking renal failure emphasizes that this manifestation is not solely indicative of uremic encephalopathy. Instead, it might represent the final common pathway resulting from alterations in the blood-brain barrier integrity within the deep white matter. Understanding such atypical imaging manifestations could significantly aid earlier and more precise diagnosis, influencing appropriate management decisions.

Unusually Late Onset of Creutzfeldt-Jakob Disease Following COVID-19 Infection in India: A Case Report.

Numerous studies have demonstrated the rise in neurological and psychiatric issues linked to post-COVID-19 infections. The most prevalent symptoms include encephalopathy, seizures, depression, anxiety, and ischemic or hemorrhagic stroke. The occurrence of Creutzfeldt-Jakob disease (CJD) after COVID-19 was unusual, but recent studies have shown a connection between COVID-19 and prion disease. Most cases of CJD present within weeks or a few months after the onset of COVID-19. The late onset of Creutzfeldt-Jakob disease following the COVID-19 infection raises questions about the potential pathophysiological mechanisms underlying this association. Although the exact link remains elusive, this case adds to the growing body of evidence suggesting a possible relationship between COVID-19 and neurodegenerative diseases. Further research is warranted to elucidate the underlying mechanisms and optimize management strategies for post-COVID-19 neurological complications. We present to you an 83-year-old man with a history of COVID-19 infection who presents with memory impairment, mood instability, and declining cognitive function. Despite initial improvement, his condition rapidly deteriorated, ultimately leading to a diagnosis of probable Creutzfeldt-Jakob disease.

Dual Dialysis for Post-bilateral Orthotopic Lung Transplantation Hyperammonemia.

Hyperammonemia is a metabolic disorder characterized by supraphysiologic ammonia (NH3) concentrations in the blood. Although usually seen in adults with liver disease, hyperammonemia is a notable complication in 4.1% of lung transplants. It is associated with cerebral edema and neurological dysfunction and carries up to 75% mortality in critically ill patients. Opportunistic infections caused by Mycoplasma and Ureaplasma species have been implicated as the cause of this metabolic disturbance. Literature in neonates has shown that renal replacement therapy (RRT) is the best choice for treating patients with neurologic manifestations of hyperammonemia, in cases of NH3 clearance than continuous renal replacement therapy (CRRT). In contrast, continuous venovenous hemodialysis (CVVHD) is usually better tolerated for patients with hemodynamic instability for NH3 clearance. NH3 is a small molecule whose clearance mirrors urea in dialysis. Even though RRT can be a treatment modality for hyperammonemia in adults and neonates, there is very little literature on adults. We present a unique case demonstrating improvement in neurologic manifestations of hyperammonemia by using both IHD and CVVHD in an adult patient.

Retrospective study on neonatal seizures in a tertiary center of northern Italy after ILAE classification: Incidence, seizure type, EEG and etiology.

OBJECTIVE: We aimed to evaluate epidemiology, seizure type, EEG, and etiology of neonatal seizures (NS) in a tertiary neonatal intensive care unit. METHODS: Data on infants with a neurophysiological confirmation of NS were collected between 2009 and 2022. Seizure types and epileptic syndromes were classified by the ILAE classification and EEG by the Italian Neonatal Seizure Collaborative Network (INNESCO) score. RESULTS: Out of 91,253 neonates, 145 presented with NS; 69.7 % were born at term and 30.3 % were preterm infants. The incidence of NS in neonates born at our center was 1.2 per 1,000 live newborns (96/80697 neonates) while in the entire neonatal population admitted to our center it was 1.6 per 1,000 live births, increasing with lower preterm age. Compared to previous studies, we found a lower proportion of hypoxic-ischemic encephalopathy (HIE) (23.4 %) and a higher rate of genetic contribution (26.2 %). The infection rate was higher in preterm (31.8 %) than in full term (9.9 %) infants. Electrographic seizures were associated with acute provoked seizures (35.9 %), preterm age (52.3 %), and HIE (52.9 %). Vascular etiology was associated with focal clonic seizures (56.8 %). Non-structural neonatal genetic epilepsy was associated with sequential seizures (68.2 %), particularly KCNQ2 and SCN2A epilepsy. Background EEG was abnormal in all HIE, infections (85.7 %) and metabolic NS (83.3 %). In genetic epilepsy, background EEG depended on the epileptic syndrome: normal in 80 % of self-limited neonatal epilepsy and abnormal in 77.8 % of developmental and epileptic encephalopathy. Electroclinical seizures were associated with focal onset, while electrographic seizures correlated with a multifocal onset. CONCLUSIONS: A low incidence of HIE and a high incidence of genetic etiology were observed in our cohort of NS. Seizure type and EEG features are fundamental to address etiology.

Efficacy of anti-seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1-related epilepsy: A systematic review.

OBJECTIVE: KCNT1-related epilepsies encompass three main phenotypes: (i) epilepsy of infancy with migrating focal seizures (EIMFS), (ii) autosomal dominant or sporadic sleep-related hypermotor epilepsy [(AD)SHE], and (iii) different types of developmental and epileptic encephalopathies (DEE). Many patients present with drug-resistant seizures and global developmental delays. In addition to conventional anti-seizure medications (ASM), multiple alternative therapies have been tested including the ketogenic diet (KD), cannabidiol (CBD-including Epidyolex © and other CBD derivatives) and quinidine (QUIN). We aimed to clarify the current state of the art concerning the benefits of those therapies administered to the three groups of patients. METHODS: We performed a literature review on PubMed and EMBase with the keyword "KCNT1" and selected articles reporting qualitative and/or quantitative information on responses to these treatments. A treatment was considered beneficial if it improved seizure frequency and/or intensity and/or quality of life. Patients were grouped by phenotype. RESULTS: A total of 43 studies including 197 patients were reviewed. For EIMFS patients (32 studies, 135 patients), KD resulted in benefit in 62.5% (25/40), all types of CBD resulted in benefit in 50% (6/12), and QUIN resulted in benefit in 44.6% (25/56). For (AD)SHE patients (10 studies, 32 patients), we found only one report of treatment with KD, with no benefit noted. QUIN was trialed in 8 patients with no reported benefit. For DEE patients (10 studies, 30 patients), KD resulted in benefit for 4/7, CBD for 1/2, and QUIN for 6/9. In all groups, conventional ASM are rarely reported as beneficial (in 5%-25% of patients). SIGNIFICANCE: Ketogenic diet, CBD, and QUIN treatments appear to be beneficial in a subset of patient with drug-resistant epilepsy. The KD and CBD are reasonable to trial in patients with KCNT1-related epilepsy. Further studies are needed to identify optimal treatment strategies and to establish predictive response factors. PLAIN LANGUAGE SUMMARY: We performed an extensive review of scientific articles providing information about the therapeutic management of epilepsy in patients with epilepsy linked to a mutation in the KCNT1 gene. Conventional anti-seizure treatments were rarely reported to be beneficial. The ketogenic diet (a medical diet with very high fat, adequate protein and very low carbohydrate intake) and cannabidiol appeared to be useful, but larger studies are needed to reach a conclusion.

Assessing the Incidence of Head Trauma in Australian Mixed Martial Arts: A Retrospective Analysis of Fight Outcomes.

BACKGROUND: Mixed martial arts (MMA) is experiencing a surge in popularity in Australia. Previous research has suggested knockout (KO) and technical knockout (TKO) are frequent outcomes during competition, raising concern about the brain health of athletes. This study aims to describe fight outcomes in Australian MMA and to explore differences in fight-ending outcomes between male and female athletes, amateur and professional competition, and different weight classes. HYPOTHESIS: There is no difference in the incidence of KO/TKO between level of competition, sex, and weight class. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 3. METHODS: Retrospective analysis of 143 Australian MMA events from 2020 to 2023 was conducted using video replay to assess fight outcomes between sex and level of competition. Binary logistic regression analysis was used to determine relationships between weight class and KO/TKO fight outcomes. RESULTS: Male competition (34%) had a significantly greater number of KO/TKO secondary to head strikes fight outcomes compared with female competition (23%) (P = 0.01). The KO/TKO rate secondary to head strikes for amateur and professional male competition was 16.6 and 18.7 per 100 athlete-exposures (AEs), respectively. The amateur and professional female rate was 12.6 and 7.4 per 100 AEs, respectively. Amateur male light heavyweight and heavyweight, and professional male heavyweight were at greater odds of a KO or TKO compared with other weight classes in their equivalent level of competition. CONCLUSION: There is a sex and professional level disparity in the incidence of fight-ending head trauma in Australian MMA. The study findings highlight the urgent need for targeted safety protocols and medical oversight, particularly for men in heavier weight classes. CLINICAL RELEVANCE: This study highlights the need for enhanced safety protocols and medical oversight in Australian MMA, particularly for male athletes in heavier weight divisions.

Neonatal Encephalopathy is a Complex Phenotype Representing Reproductive and Pregnancy Exposome Effects on the Maternal-Placental-Fetal Triad.

Reproductive, pregnancy, and placental exposomes influence the fetal neural exposome through toxic stressor interplay, impairing the maternal-placental-fetal (MPF) triad. Neonatal encephalopathy represents different clinical presentations based on complex time-dependent etiopathogenetic mechanisms including hypoxia-ischemia that challenge diagnosis and prognosis. Reproductive, pregnancy, and placental exposomes impair the fetal neural exposome through toxic stressor interplay within the MPF triad. Long intervals often separate disease onset from phenotype. Interdisciplinary fetal-neonatal neurology training, practice, and research closes this knowledge gap. Maintaining reproductive health preserves MPF triad health with life-course benefits.

Causes and Terminology in Neonatal Encephalopathy: What is in a Name? Neonatal Encephalopathy, Hypoxic-ischemic Encephalopathy or Perinatal Asphyxia.

Neurologic depression in term/near-term neonates (neonatal encephalopathy, NE) is uncommon with modern obstetric care. Asphyxial birth, with or without co-factors, accounts for a minority of NE, while maldevelopment (congenital malformations, growth aberrations, genetic, metabolic and placental abnormalities) plays an enlarging role in identifying etiologic subgroups of NE. The terms NE and hypoxic-ischemic encephalopathy (HIE) have not been employed uniformly, hampering research and clinical care. The authors propose the term NE as an early working-diagnosis, to be supplemented by a diagnosis of NE due to HIE or to other factors, as a final diagnosis once workup is complete.

Advances in Electroencephalographic Biomarkers of Neonatal Hypoxic Ischemic Encephalopathy.

Electroencephalography (EEG) is a key objective biomarker of newborn brain function, delivering critical, cotside insights to aid the management of encephalopathy. Access to continuous EEG is limited, forcing reliance on subjective clinical assessments. In hypoxia ischaemia, the primary cause of encephalopathy, alterations in EEG patterns correlate with. injury severity and evolution. As HIE evolves, causing secondary neuronal death, EEG can track injury progression, informing neuroprotective strategies, seizure management and prognosis. Despite its value, challenges with interpretation and lack of on site expertise has limited its broader adoption. Technological advances, particularly in digital EEG and machine learning, are enhancing real-time analysis. This will allow EEG to expand its role in HIE diagnosis, management and outcome prediction.

Reverse Therapy: Impact of Hyperthermia and Rewarming on Newborn Outcomes.

Therapeutic hypothermia is now well established to improve neurodevelopmental outcomes after hypoxic-ischemic encephalopathy (HIE). Although the overall principles of treatment are now well established, many smaller questions are unclear. The potential impact of reversal of hypothermia therapy and the effect of high temperatures on recovery of the neurovascular unit after therapeutic hypothermia for HIE has received relatively little attention. This article will address the effects of hypoxia-ischemia and rewarming and increased temperatures on the neurovascular unit in preclinical and clinical models.

Long-Term Outcomes Following Hypoxic Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy and results in significant morbidity and mortality. Long-term outcomes of the condition encompass impairments across all developmental domains. While therapeutic hypothermia (TH) has improved outcomes for term and late preterm infants with moderate to severe HIE, trials are ongoing to investigate the use of TH for infants with mild or preterm HIE. There is no evidence that adjuvant therapies in combination with TH improve long-term outcomes. Numerous trials of various adjuvant therapies are underway in the quest to further improve outcomes for infants with HIE.

Communicating with Parents About Therapeutic Hypothermia and Hypoxic Ischemic Encephalopathy: Integrating a Palliative Care Approach into Practice.

Parents of newborns with hypoxic ischemic encephalopathy (HIE) can face communication challenges in the neonatal intensive care unit. Both specialty palliative care and primary palliative care trained clinicians can assist parents as they navigate traumatic experiences and uncertain prognoses. Using evidence-based frameworks, the authors provide samples of how to communicate with parents and promote parent well-being across the care trajectory. The authors demonstrate how to involve parents in a shared decision-making process and give special consideration to the complexities of hospital discharge and the transition home. Sustained investment to guide the development of effective communication skills is crucial to support families of infants with HIE.

A New Horizon for Understanding the Comparative Effectiveness for Cooling Prospectively Infants with Mild Encephalopathy.

The authors summarize the methodology for a new pragmatic comparative effectiveness research investigation, Cooling Prospectively Infants with Mild Encephalopathy (COOLPRIME), which uses sites' existing mild hypoxic-ischemic encephalopathy (HIE) treatment preference (hypothermia or normothermia) to assess hypothermia effectiveness and safety. COOLPRIME's primary aim is to determine the safety and effectiveness of hypothermia compared to normothermia in mild HIE. Engagement of Families and Community Affected by Hypoxic-Ischemic Encephalopathy strongly favored Effectiveness over Efficacy Trials leading to COOL PRIME design.

Key Inflammatory Biomarkers in Perinatal Asphyxia: A Comprehensive Review.

This article summarizes the current evidence regarding inflammatory biomarkers (placental and postnatal) and provides a comprehensive understanding of their roles: (1) diagnostic accuracy to predict the severity of hypoxic-ischemia encephalopathy (HIE), (2) value in assessing treatment responses, and (3) prediction of both short- and long-term neurodevelopmental outcomes. In the early critical stages of perinatal asphyxia, inflammatory biomarkers may guide clinical decision-making. Additional research is required to increase our understanding of the optimal utility of biomarkers to predict the severity, evolution, and developmental outcomes after exposure to HIE.

Pipeline to Neonatal Clinical Transformation: The Importance of Preclinical Data.

Historically, neonatal neuroscience boasted a robust and successful preclinical pipeline for therapeutic interventions, in particular for the treatment of hypoxic-ischemic encephalopathy (HIE). However, since the successful translation of therapeutic hypothermia (TH), several high-profile failures of promising adjunctive therapies, in addition to the lack of benefit of TH in lower resource settings, have brought to light critical issues in that same pipeline. Using recent data from clinical trials of erythropoietin as an example, the authors highlight several key challenges facing preclinical neonatal neuroscience for HIE therapeutic development and propose key areas where model development and collaboration across the field in general can ensure ongoing success in treatment development for HIE worldwide.

Moving the Needle in Low-Resource Settings: Is Hypothermia a Friend or a Foe?

Hypoxic-ischemic encephalopathy in low resource settings is associated with low occurrence of perinatal sentinel events, growth restriction, short birth depression, early seizure onset, white matter injury, and non-acute hypoxia on whole genome expression profile suggesting that intra-partum hypoxia might be occurring from a normal or augmented labor process in an already compromised fetus. Induced hypothermia increases mortality and does not reduce brain injury. Strict adherence to the updated National Neonatology forum guidelines is essential to prevent harm from induced hypothermia in low resource settings.

Ethical and Legal Perspectives on the Treatment of Hypoxic Ischemic Encephalopathy in the Newborn.

Hypoxic ischemic encephalopathy (HIE) in neonates can cause severe, life-long functional impairments or death. Treatment of these neonates can involve ethically challenging questions about if, when, and how it may be appropriate to limit life-sustaining medical therapy. Further, parents whose infants suffer severe neurologic damage may seek recourse in the form of a medical malpractice lawsuit. This study uses several hypothetical cases to highlight important ethical and legal considerations in the care of infants with HIE.

COVID-19 related acute necrotizing encephalopathy and acute myocarditis in an adult female: a novel case report of brain injury and myocarditis.

BACKGROUND: Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection. CASE PRESENTATION: A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment. CONCLUSIONS: This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.