Metabolic Causes Research Articles

In-hospital new-onset seizures in patients admitted to the medical intensive care unit: An observational study and algorithmic approach.

Seizures are one of the most common neurological complications encountered in the intensive care unit (ICU). They can occur in the background of exacerbation of a known neurological disease or secondary to non-neurological conditions such as sepsis and metabolic disturbances. However, there is a paucity of literature on the incidence and pattern of new-onset seizures in ICUs. To study the incidence and patterns of new-onset seizures in patients admitted to the medical ICU. This was a prospective, multicenter, observational study performed in two tertiary care centers in Hyderabad, India over a period of 1 year. Patients upon ICU admission, who developed new-onset generalized tonic clonic seizures (GTCS), were enrolled. Those with a pre-existing seizure disorder, acute cerebrovascular accident, head injury, known structural brain lesions, or chronic liver disease were excluded as they have a higher likelihood of developing seizures. All enrolled patients were subjected to biochemical routines, radiological imaging of either computed tomography or magnetic resonance imaging, and other relevant laboratory tests as per clinical suspicion according to the protocol, and their data were recorded. Statistical analyses were conducted using descriptive statistics, χ 2 tests, and linear regression. A total of 61 of 2522 patients developed GTCS. Among all etiologies of seizures, metabolic causes were most frequent (35%) followed by infective causes (27%) and others (new-onset structural, drug withdrawal, drug-induced, toxicology-related, and miscellaneous factors). Logistic regression analysis showed that increased sodium and calcium levels were associated with a lower likelihood of developing seizures. This study identified the etiology of new-onset seizures developing in critically ill patients admitted to the ICU. These findings highlight the need for targeted monitoring of those at risk of developing seizures.

Gut-Brain Axis Microbiota in Stroke Pathogenesis

Stroke is the second cause of death globally and the third cause of global disability, causing substantial health and socioeconomic problems. Clinically, Stroke is defined as brain tissue injury caused by a lack of blood supply to a particular area, resulting in permanent nerve damage or death. Stroke is also frequently associated with metabolic causes, including insulin resistance, obesity, hypertension, and type 2 diabetes mellitus (T2DM), significantly influencing the composition and abundance of the gut microbiota. Therefore, identifying potential risk factors influencing stroke prognosis and underlying pathogenic mechanisms is essential for better management and treatment of Stroke. Several studies show the existence of two-way communication between the gut and the brain through the gut microbiota. Intimate two-way interactions between the gut and the brain occur via neural (central, autonomic, and enteric nervous systems), hormonal (endocrine system), and immunological (innate and acquired immune systems) pathways, commonly referred to as the gut-microbiota axis. Brain or gut-brain axis (Gut-Brain Axis/GBA). Gut microbiota and derived metabolites play an important role in brain function by regulating GBA signaling. Recent evidence also suggests that GBA is critical in regulating immune function post-stroke. Intestinal dysbiosis provides a chronic peripheral and central inflammatory response that accelerates stroke pathology. Gut microbial dysbiosis is a significant risk factor positively correlated with poor post-stroke outcomes. This literature review summarizes the pathogenesis of ischemic Stroke, the description of the gut microbiota, and preclinical and clinical evidence indicating the pathogenic influence of gut dysbiosis in cerebral ischemic Stroke. Keywords: Stroke, Gut-brain axis, dysbiosis

Epidemiology of chronic and acute pancreatitis in India (EPICAP-India): protocol for a multicentre study

IntroductionAcute and chronic pancreatitis (CP) are inflammatory conditions of the pancreas that cause local and systemic complications. The epidemiology of these conditions are not well-known in India.Methods and analysisWe describe...

Parameter Estimation and Identifiability in Kinetic Flux Profiling Models of Metabolism

Metabolic fluxes are the rates of life-sustaining chemical reactions within a cell and metabolites are the components. Determining the changes in these fluxes is crucial to understanding diseases with metabolic causes and consequences. Kinetic flux profiling (KFP) is a method for estimating flux that utilizes data from isotope tracing experiments. In these experiments, the isotope-labeled nutrient is metabolized through a pathway and integrated into the downstream metabolite pools. Measurements of proportion labeled for each metabolite in the pathway are taken at multiple time points and used to fit an ordinary differential equations model with fluxes as parameters. We begin by generalizing the process of converting diagrams of metabolic pathways into mathematical models composed of differential equations and algebraic constraints. The scaled differential equations for proportions of unlabeled metabolite contain parameters related to the metabolic fluxes in the pathway. We investigate flux parameter identifiability given data collected only at the steady state of the differential equation. Next, we give criteria for valid parameter estimations in the case of a large separation of timescales with fast–slow analysis. Bayesian parameter estimation on simulated data from KFP experiments containing both irreversible and reversible reactions illustrates the accuracy and reliability of flux estimations. These analyses provide constraints that serve as guidelines for the design of KFP experiments to estimate metabolic fluxes.

Correlation analysis of taste phenotype and Gynostemma pentaphyllum saponins using computer virtual screening and UPLC-(HR)MS/MS metabolomics

Gynostemma pentaphyllum, a popular tea ingredient, can be categorized into bitter, sweet, and tasteless varieties based on flavor. However, the metabolic causes of these disparities remain unclear. In this paper, sensory evaluation, untargeted metabolomic analysis using UPLC-QTOF-MS/MS, molecular docking and e-tongue testing were conducted to reveal and verify the structural characteristics and mechanisms underlying these different flavor substances. Component analysis indicated sweet saponins were characterized by glucose chains and protopanaxadiol-type aglycones featuring diagnostic ions m/z 459/475/491 in MS2− spectra; whereas bitter saponins typically featured at least one terminal rhamnose and the higher unsaturated sapogenins with diagnostic ions m/z 473/489/521. Virtual screening on T2R14 and e-tongue testing consistently validated gypenosides with more terminal rhamnoses or higher unsaturated aglycone tended to be more bitter. Docking analysis revealed PHE 172, TYR 159 and ALA 77 were the key amino residue sites in bitterness conduction via hydrophobic and hydrogen bonding interactions.

The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.

The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF's development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications.

Recent advances associated with cardiometabolic remodeling in diabetes-induced heart failure.

Diabetes mellitus (DM) is characterized by chronic hyperglycemia, and despite intensive glycemic control, the risk of heart failure in patients with diabetes remains high. Diabetes-induced heart failure (DHF) presents a unique metabolic challenge, driven by significant alterations in cardiac substrate metabolism, including increased reliance on fatty acid oxidation, reduced glucose utilization, and impaired mitochondrial function. These metabolic alterations lead to oxidative stress, lipotoxicity, and energy deficits, contributing to the progression of heart failure. Emerging research has identified novel mechanisms involved in the metabolic remodeling of diabetic hearts, such as autophagy dysregulation, epigenetic modifications, polyamine regulation, and branched-chain amino acid (BCAA) metabolism. These processes exacerbate mitochondrial dysfunction and metabolic inflexibility, further impairing cardiac function. Therapeutic interventions targeting these pathways-such as enhancing glucose oxidation, modulating fatty acid metabolism, and optimizing ketone body utilization-show promise in restoring metabolic homeostasis and improving cardiac outcomes. This review explores the key molecular mechanisms driving metabolic remodeling in diabetic hearts, highlights advanced methodologies, and presents the latest therapeutic strategies for mitigating the progression of DHF. Understanding these emerging pathways offers new opportunities to develop targeted therapies that address the root metabolic causes of heart failure in diabetes.

Common Causes of Neonatal Seizure among Neonates Admitted to Neonatal Care Unit at Al Ramadi Teaching Hospital for Maternity and Children

Neonatal seizures are the transient occurrence of signs and symptoms due to an abnormal excessive or synchronous neuronal activity in the neural cells causing paroxysmal electro clinical changes. Neonates are at high risk for seizures as compared to other age groups. The aim of this study was to identify the common causes that lead to neonatal seizure during the period from first of October 2020 to the end of July 2021using history, physical examination, and investigations in Al Ramadi teaching hospital for maternity and children. The total number of neonates diagnosed as neonatal seizure during the period of study in Al Ramadi teaching hospital for maternity and childhood was 64 cases. Total number of admissions to neonatal care unit was 4102 so the prevalence in neonatal care unit was 15.6 per 1000 live births. 30 (47.1 %) cases were diagnosed as perinatal asphyxia, 18 (28 %) cases were diagnosed as metabolic, 6 (9.4 %) cases were diagnosed as infections, seizures, 4 (6.3%) cases were diagnosed as intracranial hemorrhage, 3(4.6%) cases were diagnosed as CNS malformation, while 3 cases (4.6 %) were Unknown etiology. 38 (59.3%) of studied neonatal seizures were male, while 26 (40.7%) were female. Male to female ratio was (1.4:1). 37 (57.8%) were term babies (≥37 gestational age), while 27 (42.2%) were preterm babies (<37 gestational age). 41 (64%) of studied neonatal seizure cases were born by normal vaginal delivery, while 23 (36%) of cases were born by caesarian section delivery. The most common cause of neonatal seizure was perinatal asphyxia followed by metabolic causes then infection, intracranial hemorrhage, CNS malformations and unknown causes. Male are more common than female. In term neonates more common than preterm and in normal vaginal delivery more than cesarean section.

Melatonin receptor 1A variants as genetic cause of idiopathic osteoporosis.

Idiopathic osteoporosis (IOP) is a rare form of early-onset osteoporosis diagnosed in patients with no known metabolic or hormonal cause of bone loss and unknown pathogenesis. Patients with IOP commonly report both childhood fractures and family history of osteoporosis, raising the possibility of genetic etiologies of IOP. Whole-exome sequencing analyses of different IOP cohorts identified multiple variants in melatonin receptor 1A (MTNR1A) with a potential pathogenic outcome. A rare MTNR1A variant (rs374152717) was found in members of an Ashkenazi Jewish family with IOP, and an MTNR1A variant (rs28383653) was found in a nonrelated female IOP cohort (4%). Both variants occur at a substantially higher frequency in Ashkenazi Jewish individuals than in the general population. We investigated consequences of the heterozygous (rs374152717) variant [MTNR1Ac.184+1G>T (MTNR1Ac.184+1G>T)] on bone physiology. A mouse model of the human rs374152717 variant reproduced the low bone mass (BM) phenotype of young-adult patients with IOP. Low BM occurred because of induction of senescence in mutant osteoblasts followed by compromised differentiation and function. In human cells, introduction of rs374152717 led to translation of a nonfunctional protein and subsequent dysregulation of melatonin signaling. These studies provide evidence that MTNR1A mutations entail a genetic etiology of IOP and establish the rs374152717 variant as a loss-of-function allele that impairs bone turnover by inducing senescence in osteoblasts. The higher prevalence of the MTNR1A variants identified in IOP cohorts versus the general population indicates a greater risk of IOP in those carrying these variants, especially Ashkenazi Jewish individuals bearing the rs374152717 variant.

Using widely targeted metabolomics profiling to explore differences in constituents of three Bletilla species

Bletilla striata has been used in traditional Chinese medicine for thousands of years to treat a variety of health diseases. Currently, metabolic causes of differences in medicinal values are unknown, due to the lack of a large-scale and comprehensive investigation of metabolites in Bletilla species. In order to gain a better understanding of the major chemical constituents responsible for the medicinal value, this study aimed to explore the metabolomic differences among three Bletilla species (Bletilla striata: Bs, Bletilla ochracea: Bo and Bletilla formosana: Bf). There were 258 different metabolites between ‘Bo’ and ‘Bf’, the contents of 109 metabolites had higher abundance, while 149 metabolites showed less accumulation. There were 165 different metabolites between the ‘Bs’ and ‘Bf’, content of 72 metabolites was increased and content of 93 metabolites was decreased. There were 239 different metabolites between the ‘Bs’ and ‘Bo’, content of 145 metabolites was increased and content of 94 metabolites was decreased. In the Bo_vs_Bf, Bs_vs_Bf and Bs_vs_Bo groups, the major differential categories were flavonoids, phenolic acids, organic acids and alkaloids. Moreover, the differential metabolites were clustered into clear and distinct profiles via K-means analysis. In addition, the major differential categories were flavonoids, phenolic acids, organic acids and alkaloids. The ‘Flavonoid biosynthesis’ (ko00941) and ‘Phenylalanine metabolism’ (ko00360) pathways were significantly enriched in Bo_vs_Bf, Bs_vs_Bf and Bs_vs_Bo comparisons. These results clarify the metabolomics in different Bletilla species, as well as providing basis for the phamaceutical value of novel species of Bletilla.

Study of etiology, clinical profile, and outcome of altered sensorium patients admitted in a tertiary care hospital

Background: Altered sensorium is one of the most common presentations in patients coming to the emergency room. It includes decreased level of consciousness, attention disorder, arousal disorder, and cognitive disorder. The causes of altered sensorium can be varied, some of which are cerebrovascular diseases, alcoholism, cerebral trauma, hypoglycemia, epilepsy, drug intoxication, and neuroinfection. 4–10% of the patients presenting to the emergency department may have altered mental status. The outcome is dependent on early identification and effective treatment using investigations and imaging technologies, and it might range from full recovery to permanent damage to death. Aims and Objectives: (1) To study clinical profile and etiology in altered sensorium patients. (2) To assess outcomes in altered sensorium patients. Materials and Methods: In this prospective cross-sectional study, clinical examination and investigations are done and data are collected using pro forma for patients fulfilling the inclusion criteria. In this study, all altered sensorium patients were evaluated by detailed history, clinical examination, Glasgow Coma Scale (GCS), laboratory investigations, computed tomography brain, and other investigations. All patients were followed up till discharge or death of the patient in the hospital. Results: There were 270 patients who presented with encephalopathy, 184 (68%) were males. The majority of these patients 60 (22.2%) were in the age group of 51–60 years old. The most common cause is neurological in 109 (40.3%) patients, metabolic in 64 (24%) patients, and sepsis in 50 (19%) patients. Ischemic stroke 83 (76%) is the most common neurological cause. Hepatic encephalopathy was the most common cause of metabolic encephalopathy present in 21 (32%) patients. Pneumonia was the most common infection. There were 114 (42.2%) deaths. Septic encephalopathy is the most common cause of mortality. Early presentation to the hospital, higher GCS, and conscious level at presentation were good prognostic markers of outcome in patients, while septic encephalopathy was found to have the worst prognosis. Conclusion: The common etiologies of encephalopathy are neurological followed by metabolic and sepsis. Early presentation to the emergency room within 6 h of symptom onset, higher GCS, neurological and metabolic causes are associated with a good prognosis. The mortality rate was 42.2%. Septic encephalopathy is the most common cause of death with pneumonia being the most common source of infection.

Seeking a Treatable Cause of Out-of-Hospital Cardiac Arrest during and after Resuscitation

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Eales’ disease with secondary coats’-like reaction: a case report

BackgroundEales’ disease is an idiopathic, inflammatory condition characterized by peripheral retinal phlebitis, distal non-perfusion, and neovascularization. Coats’ disease, on the other hand, is an idiopathic, retinal vasculopathy characterized by telangiectasia and yellowish exudation. Both diseases commonly affect males. Here, we report an atypical case of unilateral Eales’ disease with co-existing, secondary Coats’-like reaction in a 25-year-old male exhibiting unilateral retinal telangiectasia accompanied by subtle macular edema, extensive peripheral vascular sheathing, and distal non-perfusion in the absence of clinically visible exudation.MethodsCase report.ResultsA 25-year-old male presented with painless blurring of vision in the right eye for two months. Best-corrected Snellen visual acuity was 3/60 in the affected eye, with relative afferent pupillary defect observed, and 6/9 contralaterally. Anterior segment examination was unremarkable. Right eye fundoscopy showed aneurysmal telangiectasia at the macula, 360 degrees perivascular sheathing and telangiectasia of peripheral retinal vessels. There was no exudation, neovascularization, tractional membranes, vitritis, retinitis, and choroiditis. Left eye fundus was unremarkable. Optical coherence tomography of the macula revealed disorganization and thinning of the inner retinal layers with minimal intraretinal fluid. Fundus fluorescein angiography showed leakage from the aneurysms but not from the sheathed vessels, and an enlarged foveolar avascular zone. A well-defined zone of non-perfusion and retinal vascular telangiectasia with shunts was observed. Blood investigations ruled out metabolic, infectious, haematological, and autoimmune causes. Carotid Doppler showed no stenosis, and CT angiography of the brain did not show any vascular abnormalities. In view that no cause was identified, a diagnosis of Eales’ disease with secondary Coats’-like reaction was made. Treatment consisted of FFA-guided laser photocoagulation to the areas of non-perfusion. Intavitreal anti-vascular endothelial growth factor injection was not done in view of poor visual prognosis. The condition and visual acuity remained stable during 18 months of follow-up.ConclusionThis report highlights an atypical case of Eales’ disease with co-existing, secondary Coats’-like reaction.

Secondary parkinsonism associated with focal brain lesions.

Focal imaging abnormalities in patients with parkinsonism suggest secondary etiology and require a distinctive clinical approach to diagnosis and treatment. We review different entities presenting as secondary parkinsonism associated with structural brain lesions, with emphasis on the clinical course and neuroimaging findings. Secondary parkinsonism may be due to vascular causes, hydrocephalus, space-occupying lesions, metabolic causes (including acquired hepatocerebral degeneration, diabetic uremic encephalopathy, basal ganglia calcifications, osmotic demyelination syndrome), hypoxic-ischaemic brain injury, intoxications (including methanol, carbon monoxide, cyanide, carbon disulfide, manganese poisoning and illicit drugs), infections and immune causes. The onset can vary from acute to chronic. Both uni-and bilateral presentations are possible. Rigidity, bradykinesia and gait abnormalities are more common than rest tremor. Coexisting other movement disorders and additional associated neurological signs may point to the underlying diagnosis. Neuroimaging studies are an essential part in the diagnostic work-up of secondary parkinsonism and may point directly to the underlying etiology. We focus primarily on magnetic resonance imaging to illustrate how structural imaging combined with neurological assessment can lead to diagnosis. It is crucial that typical imaging abnormalities are recognized within the relevant clinical context. Many forms of secondary parkinsonism are reversible with elimination of the specific cause, while some may benefit from symptomatic treatment. This heterogeneous group of acquired disorders has also helped shape our knowledge of Parkinson's disease and basal ganglia pathophysiology, while more recent findings in the field garner support for the network perspective on brain function and neurological disorders.

Next-generation sequencing in pediatric-onset epilepsies: Analysis with target panels and personalized therapeutic approach.

The objective of this study is to report the results of the genetic analysis in a large and well-characterized population with pediatric-onset epilepsies and to identify those who could benefit from precision medicine treatments. In this retrospective observational study, we consecutively recruited patients with pediatric-onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in-depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next-generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy. We detected likely pathogenic or pathogenic variants (classes IV and V) in 24% of the 562 patients who underwent genetic investigations. By the evaluation of patients' data, we observed that some features (onset of epilepsy before one year old, presence of neurological deficits, psychomotor delay/cognitive disability, and malformative aspects at brain MRI) were significantly associated with class IV or V variants. Moreover, statistical analysis showed that the diagnostic yield resulted higher for patients affected by Progressive Myoclonic Epilepsy (PME) and with early onset developmental and epileptic encephalopathies (DEE), compared with focal epilepsies, genetic generalized epilepsies, DEE with onset at/after 1 y.o., and unclassified epileptic syndromes. According to the results of the genetic screening, up to 33% of patients carrying class IV or V variants resulted potentially eligible for precision medicine treatments. The large-scale application of NGS multigene panels of analysis is a useful tool for the molecular diagnosis of patients with pediatric-onset epilepsies, allowing the identification of those who could benefit from a personalized therapeutic approach. The analysis of patients with pediatric-onset epilepsy using advanced technologies for the screening of all the implicated genes allows the identification of the cause of diseases in an ever-increasing number of cases. Understanding the pathogenic mechanisms could, in some cases, guide the selection and optimization of appropriate treatment approaches for patients.

Overview of Neuro-Ophthalmic Findings in Leukodystrophies.

Background: Leukodystrophies are a group of rare genetic diseases that primarily affect the white matter of the central nervous system. The broad spectrum of metabolic and pathological causes leads to manifestations at any age, most often in childhood and adolescence, and a variety of symptoms. Leukodystrophies are usually progressive, resulting in severe disabilities and premature death. Progressive visual impairment is a common symptom. Currently, no overview of the manifold neuro-ophthalmologic manifestations and visual impact of leukodystrophies exists. Methods: Data from 217 patients in the Hamburg leukodystrophy cohort were analyzed retrospectively for neuro-ophthalmologic manifestations, age of disease onset, and magnetic resonance imaging, visual evoked potential, and optical coherence tomography findings and were compared with data from the literature. Results: In total, 68% of the patients suffered from neuro-ophthalmologic symptoms, such as optic atrophy, visual neglect, strabismus, and nystagmus. Depending on the type of leukodystrophy, neuro-ophthalmologic symptoms occurred early or late during the course of the disease. Magnetic resonance imaging scans revealed pathologic alterations in the visual tract that were temporally correlated with symptoms. Conclusions: The first optical coherence tomography findings in Krabbe disease and metachromatic leukodystrophy allow retinal assessments. Comprehensive literature research supports the results of this first overview of neuro-ophthalmologic findings in leukodystrophies.

Altered Mental Status in the Solid-Organ Transplant Recipient.

Patients undergoing solid-organ transplantation (SOT) face a tumultuous journey. Prior to transplant, their medical course is characterized by organ dysfunction, diminished quality of life, and reliance on organ support, all of which are endured in hopes of reaching the haven of organ transplantation. Peritransplant altered mental status may indicate neurologic insults acquired during transplant and may have long-lasting consequences. Even years after transplant, these patients are at heightened risk for neurologic dysfunction from a myriad of metabolic, toxic, and infectious causes. This review provides a comprehensive examination of causes, diagnostic approaches, neuroimaging findings, and management strategies for altered mental status in SOT recipients. Given their complexity and the numerous etiologies for neurologic dysfunction, liver transplant patients are a chief focus in this review; however, we also review lesser-known contributors to neurological injury across various transplant types. From hepatic encephalopathy to cerebral edema, seizures, and infections, this review highlights the importance of recognizing and managing pre- and posttransplant neurological complications to optimize patient outcomes.

L2-hydroxyglutaric aciduria presenting with learning disability and cerebellar signs: A case report

L-2-hydroxyglutaric aciduria (L2HGA) is a rare, autosomal recessive neurometabolic disorder due to variants in the L2HGDH gene, which encodes L-2-hydroxyglutarate dehydrogenase (L2HGDH), an enzyme involved in tricarboxylic acid cycle. Deficiency of L2HGDH causes leukoencephalopathy predominantly affecting the cerebellum. This case presents L2HGA in a 12-year-old Sri Lankan boy born to third-degree consanguineous parents, who also showed learning disability and bilateral cerebellar signs. Magnetic resonance imaging (MRI) of the brain revealed T2/FLAIR hyperintensities in bilateral symmetrical subcortical white matter involving the cerebellum. A diagnosis of 2-hydroxyglutaric aciduria was made after a massive peak of 2-hydroxyglutaric acid (2HG) was observed in the analysis of urine organic acids (UOA) using gas chromatography/mass spectrometry. Genetic variant analysis revealed two heterozygous pathogenic variants in the L2HGDH gene, confirming the genetic diagnosis of autosomal recessive L2HGA. Parental genetic testing confirmed the trans phase of the variants in the index patient and their carrier status of a pathogenic L2HGDH variant. Despite typical clinical features and classical MRI findings, initial clues toward the diagnosis are mainly derived from the UOA analysis. In conclusion, this case underscores the paramount importance of analyzing the UOA profile in the process of identifying rare metabolic causes, such as L2HGA, that contribute to learning disability with neurological involvement in children.

Etiology, Characteristics, and Outcomes of Neonatal Liver Failure: Lessons Learned Over the Last 3 Decades

To evaluate trends in etiology and outcomes of neonatal liver failure (NLF) over 30years retrospectively at a single institution. Inclusion criteria for this retrospective cohort study were babies presenting at a chronological age of ≤28days between 1991 and 2020 with prothrombin time≥20seconds and biochemical liver injury. Demographics, etiology, laboratory investigations, need for extrahepatic organ support, acute kidney injury, and intervention with liver transplant (LT) were recorded. Survival outcomes were measured as discharge from the hospital alive with native liver or LT. The study period was stratified into 3 10-year blocks. Trends were analyzed for hospital admissions, etiology, and survival outcomes. One hundred twenty-six babies met the NLF criteria. Admissions to the hospital increased from 21 in 1991-2000 to 65 in 2011-2020. An increasing trend in infectious and metabolic causes, while a decreasing trend in indeterminate etiology, was noted. Survival with native liver improved from 23.8% in 1991-2000 to 55.4% in 2011-20 (P=.021), and mortality reduced from 52.4% to 35.4% during the same periods (P=.213). Twenty-three (18.2%) neonates received LT. Post-LT survival outcomes were 100% for gestational alloimmune liver disease, 66.6% in the indeterminate group, and 25% for herpes simplex virus. Specific etiologies (gestational alloimmune liver disease, OR=0.07 [0-0.77, P=.048]), presence of acute kidney injury (OR=6.22 [1.45, 29.38, P=.015]) and need for inotropes (OR=6.22 [1.45, 29.38, P=.028]) influenced mortality in multivariable logistic regression analysis. In the last 30years, advances in diagnosis, treatment, and increasing experience with LT have improved survival in NLF.

A Study of Neurological Involvement in Dengue and Chikungunya Infection.

Chikungunya virus (CHIKV) and dengue fever have been reported for recent epidemics worldwide, with varied clinical involvement. Chikungunya was first reported to affect the nervous system in the 1960s. The clinical profile of dengue with multi-organ involvement is varied with reported involvement of the central nervous system in some. The aim of this study was to study the frequency and pattern of neurological involvement in patients admitted with dengue and chikungunya in a tertiary care hospital. Patients admitted with confirmed chikungunya and dengue were evaluated clinically and investigations were enrolled in the study. Patients with preexisting neurological issues, obvious metabolic, vascular, or septic causes for neurological involvement were excluded from the study. A total of 309 patients with chikungunya were included in the study. Out of these, 11 (3.56%) patients were found to have neurological involvement. The most common presentations were altered sensorium (100%) followed by headache (81.81%). The relative risk of mortality in patients with neurological involvement due to chikungunya was 7.96. A total of 443 patients with dengue fever were enrolled in the study. Out of these, 5 (1.10%) patients were found to have neurological involvement. The most common presentations were altered sensorium and headache (100%), followed by vomiting (80%). The relative risk of mortality in patients with neurological involvement due to dengue was 5.15. The recent epidemic of chikungunya and dengue virus infections was associated with various neurological complications. Neurological involvement of chikungunya and dengue was identified to be a bad prognostic factor with significantly higher mortality. This is a single center study, involving only the patients admitted to the hospital. Furthermore, being an observational study, follow-up could not be done to look for neurological sequelae.