When It Rains It Pours...: Wernicke Encephalopathy with Sudden Blindness after Bariatric Surgery in a Patient with Congenital Deafness.

BACKGROUND: Malabsorption syndromes are known chronic complications of bariatric surgery. Therefore, it is recommended to take oral supplementation with multivitamins. Wernicke's encephalopathy represents an acute neuropsychiatric syndrome associated with alcoholism or severe malnutrition; sporadic cases of this potential complication related to bariatric surgery are described in the literature. We present a case of Wernicke's encephalopathy due to severe vitamin B1 deficiency after bariatric surgery. CASE REPORT: A 31-year-old woman with deaf-mutism from the age of 3 years old, operated 3 months before with a mini-gastric bypass for severe obesity, was transferred to our unit after accessing the emergency room. In the immediate medical history, there was the sudden and rapid decline in vision, leading to complete loss of vision, marked asthenia, and paresthesia in the four limbs. Considering the previous bariatric surgery, the diagnosis of non-alcoholic Wernicke's syndrome was suspected, for which IV therapy with Vitamin B1 was started at a dosage of 5 vials of 200 mg in 100 cc of saline solution (three times a day for the first 72 hours, subsequently 1 once/day). After 12 hours, there was an improvement in visual acuity, and the symptoms completely resolved within 48 hours. She was discharged with complete resolution of all symptoms after 1 month. CONCLUSION: Initial vision loss without confusion or encephalopathy is one atypical presentation of Wernicke syndrome. Clinical suspicion must be high in case of alcoholism or post-bariatric surgery. Early recognition of atypical symptoms, including vision loss, and timely administration of therapy improves the prognosis of this potentially reversible but time-dependent neurological emergency.

Cerebral hypometabolism in a pediatric patient with clinically resolved posterior reversible encephalopathy syndrome.

A 4-year-old boy with Nuclear factor-kappa B Essential Modulator deficiency syndrome presented with encephalopathy post haematopoietic stem cell transplantation. MRI demonstrated T2/FLAIR-hyperintensities in the posterior cerebral cortex concerning for posterior reversible encephalopathy syndrome. Clinical improvement was appreciated following withdrawal of the suspected offending pharmacological agent (Cyclosporine). An 18F-FDG PET/CT performed 2 months later to screen for post-transplant lymphoproliferative disease demonstrated markedly reduced FDG uptake in the posterior cerebral cortex, involving the parietal and occipital lobes. We describe, to the best of our knowledge, the first case of profound cerebral hypometabolism in a child with clinically resolved posterior reversible encephalopathy syndrome.

Heroin-induced leukoencephalopathy: Chasing the imaging findings.

We present a case of a 29-year-old male who was brought into the hospital due to unresponsiveness and found to have heroin inhalational leukoencephalopathy (HLE). HLE is one component of a broad spectrum of opioid encephalopathies that is associated with heroin inhalation and other opioids. There is considerable overlap of HLE with other toxic and hypoxic-ischemic encephalopathies; however, the specific territories of brain involvement help distinguish it from other cerebral insults. The goal of this study is to help elucidate the findings of HLE and compare these findings to other toxic and hypoxic-ischemic encephalopathies.

Navigating Diagnostic Challenges: A Case of Acquired Hepatocerebral Degeneration Presenting as Worsening Hepatic Encephalopathy in Chronic Liver Disease.

This case report details the complex diagnostic odyssey of a 60-year-old female grappling with chronic liver disease, initially diagnosed with hepatic encephalopathy (HE). Despite initial treatment with lactulose and rifaximin, her neurological symptoms worsened, leading to the identification of concurrent acquired hepatocerebral degeneration (AHD). This condition is characterised by cognitive decline, movement disorders and distinctive imaging abnormalities. The discussion highlights the challenges in distinguishing AHD from HE, underscoring the sophisticated diagnostic and management strategies required for such intricate cases in the realm of chronic liver disease. LEARNING POINTS: Recognizing coexisting conditions: emphasize the importance of identifying acquired hepatocerebral degeneration (AHD) alongside hepatic encephalopathy (HE) in patients with chronic liver disease. This recognition is crucial for comprehensive assessments and understanding the progression of neurological symptoms.Addressing management challenges: highlight the complexities of managing AHD due to limited therapeutic options and potentially irreversible outcomes. Discuss the challenges in decision-making, such as considering liver transplantation for patients with advanced neurological symptoms, and the need for exploring alternative therapeutic strategies.Conducting comprehensive evaluations: stress the significance of thorough evaluations in patients with chronic liver disease presenting with neurological symptoms. This comprehensive approach can help uncover underlying conditions like AHD, which may require different management strategies than those initially considered.

Edaravone combined with hyperbaric oxygen therapy in delayed encephalopathy after acute carbon monoxide poisoning: A meta-analysis.

BACKGROUND: The use of both edaravone (EDA) and hyperbaric oxygen therapy (HBOT) is increasingly prevalent in the treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). This meta-analysis aims to evaluate the efficacy of using EDA and HBOT in combination with HBOT alone in the treatment of DEACMP. METHODS: We searched and included all randomized controlled trials (RCTs) published before November 6, 2023, from 12 Chinese and English databases and clinical trial centers in China and the United States. The main outcome indicator was the total effective rate. The secondary outcome indicators included the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Hasegawa Dementia Scale (HDS), Fugl-Meyer Assessment (FMA), Superoxide Dismutase (SOD), and Malondialdehyde (MDA). Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (95 % CI). RESULTS: Thirty studies involving a combined total of 2075 participants were ultimately incorporated. It was observed that the combination of EDA with HBOT for the treatment of DEACMP demonstrated an improvement in the total effective rate (RR: 1.25; 95 % CI: 1.20-1.31; P < 0.01), MMSE (WMD: 3.67; 95 % CI: 2.59-4.76; P < 0.01), MoCA (WMD: 4.38; 95 % CI: 4.00-4.76; P < 0.01), BI (WMD: 10.94; 95 % CI: 5.23-16.66; P < 0.01), HDS (WMD: 6.80; 95 % CI: 4.05-9.55; P < 0.01), FMA (WMD: 8.91; 95 % CI: 7.22-10.60; P < 0.01), SOD (WMD: 18.45; 95 % CI: 16.93-19.98; P < 0.01); and a reduction in NIHSS (WMD: -4.12; 95 % CI: -4.93 to -3.30; P < 0.01) and MDA (WMD: -3.05; 95 % CI: -3.43 to -2.68; P < 0.01). CONCLUSION: Low-quality evidence suggests that for DEACMP, compared to using HBOT alone, the combined use of EDA and HBOT may be associated with better cognition and activity of daily living. In the future, conducting more meticulously designed multicenter and large-sample RCTs to substantiate our conclusions is essential.

The de novo missense mutation F224S in GABRB2, identified in epileptic encephalopathy and developmental delay, impairs GABAAR function.

Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABAAR) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the ß2 subunit of GABAAR. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABAAR channel function, we conducted transient expression experiments using GABAAR subunits in HEK293T cells. The GABAARs containing mutant ß2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABAAR containing the ß2 (F224S) subunit was significantly smaller compared to the wild type GABAAR. We propose that GABRB2 variant F224S is pathogenic and GABAARs containing this ß2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy.

Clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome.

Predominant limbic degeneration has been associated with various underlying aetiologies and an older age, predominant impairment of episodic memory and slow clinical progression. However, the neurological syndrome associated with predominant limbic degeneration is not defined. This endeavour is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying aetiology, disease course and therapeutic needs. We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome that is highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities. The criteria incorporate core, standard and advanced features, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degeneration and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate and low). We operationalized this set of criteria using clinical, imaging and biomarker data to validate its associations with clinical and pathologic outcomes. We screened autopsied patients from Mayo Clinic and Alzheimer's Disease Neuroimaging Initiative cohorts and applied the criteria to those with an antemortem predominant amnestic syndrome (Mayo, n = 165; Alzheimer's Disease Neuroimaging Initiative, n = 53) and who had Alzheimer's disease neuropathological change, limbic-predominant age-related TDP-43 encephalopathy or both pathologies at autopsy. These neuropathology-defined groups accounted for 35, 37 and 4% of cases in the Mayo cohort, respectively, and 30, 22 and 9% of cases in the Alzheimer's Disease Neuroimaging Initiative cohort, respectively. The criteria effectively categorized these cases, with Alzheimer's disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods and patients with both pathologies having intermediate likelihoods. A logistic regression using the criteria features as predictors of TDP-43 achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample predictions in an external cohort achieved a balanced accuracy of 73.3%. Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods. Stratifying patients with both Alzheimer's disease neuropathological change and limbic-predominant age-related TDP-43 encephalopathy from the Mayo cohort according to their likelihoods revealed that those with higher likelihoods had more temporo-limbic degeneration and a slower rate of decline and those with lower likelihoods had more lateral temporo-parietal degeneration and a faster rate of decline. The implementation of criteria for a limbic-predominant amnestic neurodegenerative syndrome has implications to disambiguate the different aetiologies of progressive amnestic presentations in older age and guide diagnosis, prognosis, treatment and clinical trials.

Mortality risk factors in children with influenza-associated encephalopathy admitted to the paediatric intensive care unit between 2009 and 2021.

AIM: The purpose of this study was to determine the risk factors for death in children with influenza-associated encephalopathy (IAE) in the paediatric intensive care unit (PICU). METHODS: Forty-six paediatric patients with IAE admitted to the PICU at shenzhen Children's Hospital between December 2009 and December 2021 were evaluated. Their clinical characteristics were retrospectively analysed. RESULTS: A total of 46 patients were diagnosed with influenza A virus infection and encephalopathy. The cases were concentrated in children <5 years of age (27/46, 58.7%). Twenty-nine patients (63.0%) survived and 17 patients (37.0%) died, of which 70.6% (12/17) of the patients died within 1 week of hospitalisation. Thirty-two patients (69.6%) developed neurological symptoms within 1-2 days of fever onset. Common symptoms included fever (45/46, 97.8%), loss of consciousness (39/46, 84.8%), seizures (31/46, 67.4%), cough (19/46, 41.3%), and vomiting (16/46, 34.8%). Multivariate logistic regression analysis indicated that vomiting (odds ratio [OR], 11.005), loss of consciousness (AVPU score: P; OR, 15.871), lymphopenia (OR, 8.964), alanine aminotransferase (>80 IU/L; OR, 32.060) and serum sodium concentration (>145 mmol/L or <135 mmol/L; OR, 16.264) were related to mortality. CONCLUSIONS: The mortality in this study population was 37.0%. Children with IAE who have corresponding clinical manifestations and abnormal examination results in PICU should be warned of the high mortality rate.

18F-FDG PET/CT in early phase of sporadic Creutzfeldt-Jacob disease: A case report.

Key Clinical Message: Creutzfeldt-Jakob disease is a neurodegenerative disorder caused by brain accumulation of a misfolded form of the cellular prion protein, whose diagnosis is challenging, particularly in early stages, due to the variability and nonspecificity of the clinical and radiological features. 18F-fluorodeoxyglucose positron-emitted tomography has the potential to be considered a crucial investigation in these patients, revealing metabolic abnormalities earlier than the conventional neuroimaging analysis. Abstract: A 59-year-old man, the military officer, was referred to our Units for the onset of neurological symptoms rapidly evolving within a month, characterized by akinetic mutism, constructional apraxia, and disorders of spatial orientation. Brain 18F-fluorodeoxyglucose (18F-FDG) positron-emitted tomography (PET)/CT depicted an asymmetric hypometabolism in the left fronto-temporo-parietal cortex, as well as in the left thalamus and the right cerebellar hemisphere, while the glucose metabolism appears to be preserved in the somatosensory cortex and the basal ganglia. Laboratory routine analyses, cerebrospinal fluid routine, infective tests, electroencephalography (EEG), and brain magnetic resonance (MR) were all unremarkable. A positive RT-QuIC result on cerebro-spinal fluid (CSF) was subsequently shown, without any pathogenic gene mutations and, therefore, the result was consistent with a diagnosis of sporadic Creutzfeld-Jacob disease. The clinical evolution was quickly unfavorable, and the patient died about 4 months after hospital admission. FDG PET/computed tomography (CT) has the potential to be considered a crucial investigation in these patients, documenting metabolic changes long time before other diagnostic investigations such as CSF, EEG, brain CT, and brain MR, thus suggesting a greater sensitivity of glucose metabolic evaluation in the early stage of the disease in question.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation.

In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from Streptomyces tsukubaensis, is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.

History of biological, mechanistic, and clinical understanding of concussion.

The history behind the biological, mechanistic, and clinical insights into concussion provides awareness of the current understanding and future areas for study. Although the initial description of concussion appeared in the 10th century, the potential long-term structural consequences were first defined by Harrison Martland, M.D., who performed a postmortem study of former boxers in 1928. He found evidence of perivascular microhemorrhage that he believed eventually evolved into a "replacement gliosis" underlying a clinical syndrome that he named "punch drunk," which was characterized by acute confusion with chronic cognitive and physical symptoms developing in those with prolonged exposure. Further research into the potential long-term consequences of repetitive concussions, particularly in athletics and the military, led to an understanding of chronic traumatic encephalopathy. To ameliorate possible long-term risks, research has been focused on preventative and therapeutic measures for concussion. In this review article, the authors present the history of concussion and the long-term sequelae of repeated head injury. Specifically, they consider how the understanding of concussion has evolved from antiquity into the modern era, and how this change in understanding of head injury has led to an appreciation of the fact that its long-term implications sometimes manifest as the clinical and histopathological entity of chronic traumatic encephalopathy.

Practice Variations for Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: An International Survey.

OBJECTIVE: To evaluate variations in management of therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) among international clinical sites and to identify areas for harmonization. STUDY DESIGN: An electronic survey was sent to Children's Hospitals Neonatal Consortium site sponsors, Canadian Neonatal Network site investigators, members of the Newborn Brain Society, and American Academy of Pediatrics Neonatology chiefs. RESULTS: 105 sites responded, with most from high-income regions (n=95). Groupings were adapted from the United Nations regional groups: United States (US, n=52 sites); Canada (n=20); Western Europe and other states excluding Canada and US Group (WEOG, n=18); and non-WEOG (central and eastern Europe, Asia, Africa, Latin America, and Caribbean, n=15). Regional variations were seen in the eligibility criteria for TH, such as the minimum gestational age, grading of HIE severity, use of electroencephalography (EEG), and the frequency of providing TH for mild HIE. Active TH during transport varied among regions and was less likely in smaller volume sites. Amplitude-integrated (aEEG) and/or continuous EEG (cEEG) to determine eligibility for TH was used by most sites in WEOG and non-WEOG, but infrequently by the US and Canada Groups. For sedation during TH, morphine was most frequently used as first choice but there was relatively high (33%) use of dexmedetomidine in the US Group. Timing of brain MRI and neurodevelopmental follow-up (NDFU) were variable. NDFU occurred earlier and more frequently, although for a shorter duration, in the non-WEOG. CONCLUSIONS: We found significant variations in practices for TH for HIE across regions internationally. Future guidelines should incorporate resource availability in a global perspective.

MRI in LARS1 deficiency-Spectrum, patterns, and correlation with acute neurological deterioration.

Leucine aminoacyl tRNA-synthetase 1 (LARS1)-deficiency (infantile liver failure syndrome type 1 (ILFS1)) has a multisystemic phenotype including fever-associated acute liver failure (ALF), chronic neurologic abnormalities, and encephalopathic episodes. In order to better characterize encephalopathic episodes and MRI changes, 35 cranial MRIs from 13 individuals with LARS1 deficiency were systematically assessed and neurological phenotype was analyzed. All individuals had developmental delay and 10/13 had seizures. Encephalopathic episodes in 8/13 were typically associated with infections, presented with seizures and reduced consciousness, mostly accompanied by hepatic dysfunction, and recovery in 17/19 episodes. Encephalopathy without hepatic dysfunction occurred in one individual after liver transplantation. On MRI, 5/7 individuals with MRI during acute encephalopathy had deep gray matter and brainstem changes. Supratentorial cortex involvement (6/13) and cerebellar watershed injury (4/13) occurred with seizures and/or encephalopathy. Abnormal brainstem contour on sagittal images (8/13), atrophy (8/13), and myelination delay (8/13) were not clearly associated with encephalopathy. The pattern of deep gray matter and brainstem changes are apparently characteristic of encephalopathy in LARS1-deficiency, differing from patterns of hepatic encephalopathy or metabolic stroke in organic acidurias and mitochondrial diseases. While the pathomechanism remains unclear, fever and energy deficit during infections might be causative; thus, sufficient glucose and protein intake along with pro-active fever management is suggested. As severe episodes were observed during influenza infections, we strongly recommend seasonal vaccination.

A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

Wernicke's encephalopathy treated with high dose intravenous thiamine: a case report.

Wernicke's encephalopathy (WE) is a dangerous and potentially fatal neurological condition associated with thiamin deficiency. The standard treatment for WE is intravenous (IV) thiamin, but limited research describes optimal dosing. We present a case of a 40-year-old male with severe alcohol use disorder (AUD) and chronic malnourishment who developed WE. Upon administration of 100 mg IV thiamin, symptoms of WE persisted, but when the dose was increased to 500 mg, altered mental status and ophthalmoplegia resolved rapidly. IV thiamin is a reliable and low-risk treatment for WE, even when administered at high doses. High-dose IV thiamin (i.e., >/100 mg) can treat neurological symptoms and cognitive dysfunction in WE and should be considered for first-line treatment. Further study of WE diagnostic and treatment guidelines is warranted to maximize recovery potential.

Tralopyril poisoning due to respiratory exposure.

INTRODUCTION: Tralopyril is a metabolite of the pesticide chlorfenapyr. Direct toxicity by tralopyril has not been described. We report two cases of tralopyril poisoning via inhalation. CASE PRESENTATIONS: Two workers developed heat intolerance, diaphoresis, and weight loss after occupational inhalational exposure to tralopyril. Patient 1: The exposure was due to the absence of respiratory protection. Magnetic resonance imaging showed abnormal signals in the bilateral periventricular white matter, corpus callosum, basal ganglia, brainstem, and spinal cord. The patient's blood tralopyril concentrations on days 1, 3, 5, 8, and 11 post-admission were 1.09 mg/L, 1.04 mg/L, 1.01 mg/L, 0.71 mg/L, and 0.313 mg/L, respectively. Haemoperfusion (HA330), haemoperfusion (HA380), and haemodiafiltration were performed on days 1-3, 5-8, and 9-10, respectively. Patient 2: The patient's symptoms followed inappropriate use of respiratory protection. His blood tralopyril concentrations on days 1, 4, 5, and 6 were 0.592 mg/L, 0.482 mg/L, 0.370 mg/L, and 0.228 mg/L, respectively. DISCUSSION: The patients presented with features typical of chlorfenapyr poisoning, which suggests that tralopyril is the main toxic metabolite of chlorfenapyr. CONCLUSION: Tralopyril can be absorbed by inhalation, leading to delayed clinical symptoms and organ damage, including toxic encephalopathy and spinal cord damage.

Nutritional management for acute liver failure.

Acute liver failure (ALF) induces increased energy expenditure and disrupts the metabolism of essential nutrients. Hepatic encephalopathy is a complication of ALF with a poor prognosis and mainly involves the metabolic disturbance of amino acids in its pathogenesis. In this review, we discuss the nutritional management for ALF in consideration of the pathophysiology of ALF with respect to the impairment of hepatocyte function. It is known that enteral nutrition is recommended for patients with ALF, while parenteral nutrition is recommended for patients who cannot tolerate enteral nutrition. As ALF leads to a hypermetabolic state, the energy intake is recommended to cover 1.3 times the resting energy expenditure. Because of the high risk of hypoglycemia associated with disturbances in glucose metabolism, substantial glucose intake is recommended. Along with the deterioration of glucose metabolism, protein metabolism is also disrupted. As patients with ALF have increased systemic protein catabolism together with decreased protein synthesis, appropriate amounts of amino acids or protein under monitoring serum ammonia levels are recommended. In conclusion, nutritional management based on the understanding of nutritional pathophysiology is a pivotal therapeutic approach for patients with ALF. The approach should be individualized in the acute phase, the recovery phase, and the pretransplant phase.

Renal and cardiac biopsy findings in an adolescent patient with the 3243A>G mitochondrial DNA mutation: Favorable renal prognosis post renal transplantation from the mother.

We investigated the pathogenesis of a perihilar variant of focal segmental glomerulosclerosis detected by kidney biopsy in a 16-year-old male. The disease was refractory to steroid therapy, and at the second kidney biopsy, abnormal mitochondrial proliferation was newly observed in the podocytes. The patient also developed late-onset hearing loss and had a family history of diabetes, and genetic testing confirmed the mitochondrial DNA mutation 3243A>G (48%). Eight months after hemodialysis was started, encephalopathy occurred presumably due to rapid dehydration. After changing dialysis into continuous ambulatory peritoneal dialysis, encephalopathy was resolved, but the patient developed myocardial hypertrophy, probably because of the myocardial overreaction to congestion. A myocardial biopsy showed mitochondrial proliferation in the myocardium. After renal transplantation from his mother with a heteroplasmy of 4%, the cardiomyopathy improved, and the renal function has remained stable for 4 years. We speculated that the abnormal mitochondrial morphology in the kidney and heart may be characteristic of mitochondrial genetic disease, and renal transplantation from the mother with a low heteroplasmy was considered desirable for mitochondrial nephropathy with poor prognosis.

Complete Match of Streptococcus salivarius from Oral Saliva and Stool in a Patient with Hepatic Encephalopathy.

We herein report a 67-year-old Japanese woman with liver cirrhosis caused by primary biliary cholangitis. The patient was admitted to the hospital with loss of consciousness. Hepatic encephalopathy (HE) was diagnosed after diagnostic imaging and symptom assessments. Molecular biology tests were performed on oral saliva and stool samples. The test results indicated sequence similarity between urease-positive S. salivarius in both oral saliva and stool, as revealed by the signals in the overlapping peaks. This bacterium can potentially increase ammonia production in the gut, leading to HE in patients with liver cirrhosis.

Metformin improves cognitive dysfunction through SIRT1/NLRP3 pathway-mediated neuroinflammation in db/db mice.

Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1ß, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment.