Cefepime-induced encephalopathy in an older patient with polypharmacy and renal insufficiency: a case report.

The world population is rapidly aging. Societal aging poses many challenges for individuals, families, nations, and the global healthcare system. Therefore, geriatric care is a crucial issue that demands our attention. In this case report, we describe a woman in her early 70s with multiple comorbidities, polypharmacy, and renal insufficiency who developed cefepime-induced encephalopathy with moderate to severe cerebral dysfunction during treatment of a urinary tract infection. The patient's consciousness level gradually improved, and no further seizures were observed following the discontinuation of cefepime for several days. This case report underscores the fact that polypharmacy and medication safety are significant concerns that are often overlooked when caring for older patients. The report also highlights the increased susceptibility of older individuals to antibiotic-associated adverse reactions during the management of infectious diseases. Therefore, optimization of antibiotic therapy for older patients is a critical issue that requires thorough investigation and consideration in geriatric care.

Corticosteroid-induced hyperammonaemic encephalopathy in a woman with late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is a rare, X linked disorder that can manifest in late adulthood in heterozygous females as severe hyperammonaemia following environmental stressors. We present a case of hyperammonaemic encephalopathy that was triggered by glucocorticoid administration in an adult woman with heterozygous OTCD with clinical response to haemodialysis, ammonia scavengers and a high-calorie, low-protein diet.

Metronidazole-Induced Encephalopathy With Probable Crohn Encephalitis: A Case Report.

OBJECTIVES: Metronidazole central nervous system toxicity is a rare finding in patients receiving the medication. We report a peculiar case of metronidazole central nervous system toxicity in which both the underlying condition (Crohn disease) and the drugs used to treat it are potential causes of encephalopathy. METHODS: A 26-year-old female with 6-year history of Crohn's disease for 6 years presented acute-onset encephalopathy. We provide bibliographic evidence to support metronidazole toxicity and potential Crohn disease-associated neurologic involvement. RESULTS: The patient presented dystonia, cerebellar ataxia, and altered mental status. Magnetic resonance imaging of the brain revealed typical findings of metronidazole toxicity and white matter involvement of the centrum semiovale. Immunoelectrophoresis and immunofixation of serum and cerebrospinal fluid proteins were consistent with a systemic inflammatory process. We concluded on an association between drug toxicity and probable Crohn-associated neurologic involvement. Metronidazole was stopped and the patient was placed on vitamin therapy and diazepam to control dystonia. She deteriorated and was transferred to the intensive care unit where she expired. CONCLUSIONS: Acute behavioral changes in a young patient constitute an emergency and differential diagnoses should include infective, inflammatory, metabolic, and toxic causes. Metronidazole is a potential toxic etiology.

Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

GNB1 Encephalopathy: Clinical Case Report and Literature Review.

GNB1 encephalopathy is a rare genetic disease caused by pathogenic variants in the G Protein Subunit Beta 1 (GNB1) gene, with only around 68 cases documented worldwide. Although most cases had been caused by de novo germline mutations, in this case, the pathogenic variant was inherited from patient's mother, indicating an autosomal dominant inheritance pattern. The patient presented at 25 years of age with mild developmental delay and cognitive impairment, prominent generalized dystonia, and horizontal nystagmus which are all characterizing symptoms of GNB1 encephalopathy. Electroencephalography (EEG) showed no epileptiform patterns, and magnetic resonance imaging (MRI) revealed hypointensities in globus pallidus and dentate nucleus areas. The main theory for GNB1 encephalopathy pathogenesis is neuronal hyperexcitability caused by impaired ion channel regulation. Due to low specificity of symptoms, diagnosis relies on genetic testing. As there are no standardized GNB1 encephalopathy treatment guidelines, evaluation of different treatment options is based on anecdotal cases. Reviewing different treatment options, deep brain stimulation and intrathecal baclofen pump, as well as some other medications still in preclinical trials, seem to be the most promising.

Molecular Dynamic Simulations to Determine Individualized Therapy: Tetrabenazine for the GNAO1 Encephalopathy E246K Variant.

INTRODUCTION: GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. METHODS: Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. RESULTS AND DISCUSSION: We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease.

Disease spectrum and strategy of acupuncture and moxibustion in treatment of encephalopathy. / è„‘ç— é’ˆç¸æ²»ç–—çš„ç— è°±ä¸Žç­–ç•¥æ€è€ƒ.

The paper presents the summary of the spectrum of encephalopathy treated with acupuncture and moxibustion and the analysis on the existing questions in its clinical research, and proposes the potential strategies on treatment of encephalopathy with acupuncture and moxibustion. The spectrum of encephalopathy includes 23 diseases of central nervous system (superspinal center) and 33 kinds of mental and behavioral disorders. There are three problems in clinical research of acupuncture and moxibustion for encephalopathy, i.e. lack of high-quality clinical evidences, inadequate support from theoretic study of TCM and limited study on the rules of treatment. Hence, the author proposes five strategies on the treatment of encephalopathy with acupuncture and moxibustion, i.e. ① stimulating the peripheral nerve trunk associated with brain dysfunction, triggering the interaction between peripheral and central nerves and emphasizing the autonomic rehabilitation training to promote the reorganization of brain function; ② improving the cerebral circulation and metabolism by stimulating the trigeminal nerve and sphenopalatine ganglion; ③ stimulating the sites with high-dense distribution of peripheral nerve endings and the large projection area in the somatosensory region of the brain to induce strong brain responses, which may adjust the abnormal operation of the default mode network in the resting state; ④ stimulating the vagus nerve to improve the mood, suppressing the abnormal firing of brain neurons and stimulating the sites with the stellate ganglion distributed to modulate the hypothalamic function; ⑤ delivering the therapeutic regimens in association with the specific conditions and symptoms, and the classification of the physical signs on the base of the treatment of encephalopathy.

Propofol and Dexmedetomidine Ameliorate Endotoxemia-Associated Encephalopathy via Inhibiting Ferroptosis.

Background: Sepsis is recognized as a multiorgan and systemic damage caused by dysregulated host response to infection. Its acute systemic inflammatory response highly resembles that of lipopolysaccharide (LPS)-induced endotoxemia. Propofol and dexmedetomidine are two commonly used sedatives for mechanical ventilation in critically ill patients and have been reported to alleviate cognitive impairment in many diseases. In this study, we aimed to explore and compare the effects of propofol and dexmedetomidine on the encephalopathy induced by endotoxemia and to investigate whether ferroptosis is involved, finally providing experimental evidence for multi-drug combination in septic sedation. Methods: A total of 218 C57BL/6J male mice (20-25 g, 6-8 weeks) were used. Morris water maze (MWM) tests were performed to evaluate whether propofol and dexmedetomidine attenuated LPS-induced cognitive deficits. Brain injury was evaluated using Nissl and Fluoro-Jade C (FJC) staining. Neuroinflammation was assessed by dihydroethidium (DHE) and DCFH-DA staining and by measuring the levels of three cytokines. The number of Iba1+ and GFAP+ cells was used to detect the activation of microglia and astrocytes. To explore the involvement of ferroptosis, the levels of ptgs2 and chac1; the content of iron, malondialdehyde (MDA), and glutathione (GSH); and the expression of ferroptosis-related proteins were investigated. Conclusion: The single use of propofol and dexmedetomidine mitigated LPS-induced cognitive impairment, while the combination showed poor performance. In alleviating endotoxemic neural loss and degeneration, the united sedative group exhibited the most potent capability. Both propofol and dexmedetomidine inhibited neuroinflammation, while propofol's effect was slightly weaker. All sedative groups reduced the neural apoptosis, inhibited the activation of microglia and astrocytes, and relieved neurologic ferroptosis. The combined group was most prominent in combating genetic and biochemical alterations of ferroptosis. Fpn1 may be at the core of endotoxemia-related ferroptosis activation.

pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain.

Strict homeostatic control of pH in both intra- and extracellular compartments of the brain is fundamentally important, primarily due to the profound impact of free protons ([H+]) on neuronal activity and overall brain function. Astrocytes, crucial players in the homeostasis of various ions in the brain, actively regulate their intracellular [H+] (pHi) through multiple membrane transporters and carbonic anhydrases. The activation of astroglial pHi regulating mechanisms also leads to corresponding alterations in the acid-base status of the extracellular fluid. Notably, astrocyte pH regulators are modulated by various neuronal signals, suggesting their pivotal role in regulating brain acid-base balance in both health and disease. This review presents the mechanisms involved in pH regulation in astrocytes and discusses their potential impact on extracellular pH under physiological conditions and in brain disorders. Targeting astrocytic pH regulatory mechanisms represents a promising therapeutic approach for modulating brain acid-base balance in diseases, offering a potential critical contribution to neuroprotection.

Código encefalopatía hipóxico-isquémica: revisión sistematizada para entornos con recursos limitados / Hypoxic-ischaemic encephalopathy code: a systematic review for resource-limited settings

Se estima que el 96% de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI) nacen en entornos con recursos limitados (ERL) sin capacidad para ofrecer el estándar asistencial vigente desde hace cerca de 15 años en los países con altos recursos y que incluye hipotermia terapéutica, neuromonitorización continua electroencefalográfica y resonancia magnética, además de un control intensivo de las constantes vitales y del equilibrio homeostático. Esta situación no parece estar cambiando; sin embargo y aún con estas limitaciones, el conocimiento actualmente disponible permite mejorar la asistencia de los pacientes con EHI atendidos en ERL. El propósito de esta revisión sistematizada es ofrecer, bajo el término «código EHI», recomendaciones de prácticas asistenciales basadas en evidencia científica y factibles en ERL, que permitan optimizar la atención del RN con EHI y ayuden potencialmente a reducir los riesgos asociados a la comorbilidad y a mejorar los resultados neuroevolutivos. El contenido del código EHI se agrupó en nueve epígrafes: 1) prevención de la EHI, 2) reanimación, 3) primeras seis horas de vida, 4) identificación y graduación de la EHI, 5) manejo de las convulsiones, 6) otras intervenciones terapéuticas, 7) disfunción multiorgánica, 8) estudios complementarios, y 9) atención a la familia. (AU)

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia, continuous electroencephalographic monitoring and magnetic resonance imaging in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term «HIE Code», evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: 1) prevention of HIE, 2) resuscitation, 3) first 6hours post birth, 4) identification and grading of encephalopathy, 5) seizure management, 6) other therapeutic interventions, 7) multiple organ dysfunction, 8) diagnostic tests and 9) family care. (AU)

Uraemic brainstem encephalopathy mimicking ocular myasthenia: a case report.

BACKGROUND: Uraemia causes a generalised encephalopathy as its most common neurological complication. Isolated brainstem uraemic encephalopathy is rare. We report a case of fatigable ptosis and complex ophthalmoplegia in brainstem uraemic encephalopathy. CASE PRESENTATION: A 22-year-old Sri Lankan man with end stage renal failure presented with acute onset diplopia and drooping of eyelids progressively worsening over one week. The patient had not complied with the prescribed renal replacement therapy which was planned to be initiated 5 months previously. On examination, his Glasgow coma scale score was 15/15, He had a fatigable asymmetrical bilateral ptosis. The ice-pack test was negative. There was a complex ophthalmoplegia with bilateral abduction failure and elevation failure of the right eye. The diplopia did not worsen with prolonged stare. The rest of the neurological examination was normal. Serum creatinine on admission was 21.81 mg/dl. The repetitive nerve stimulation did not show a decremental pattern. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse midbrain and pontine oedema with T2 weighted/FLAIR hyperintensities. The patient was haemodialyzed on alternate days and his neurological deficits completely resolved by the end of the second week of dialysis. The follow up brain MRI done two weeks later demonstrated marked improvement of the brainstem oedema with residual T2 weighted/FLAIR hyperintensities in the midbrain. CONCLUSIONS: Uraemia may rarely cause an isolated brainstem encephalopathy mimicking ocular myasthenia, which resolves with correction of the uraemia.

Development and Validation of a High-Performance Liquid Chromatography Method to Quantify Marker Compounds in Lysimachia vulgaris var. davurica and Its Effects in Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS), a common gastrointestinal disorder worldwide, is characterized by chronic abdominal pain, bloating, and disordered defecation. IBS is associated with several factors, including visceral hypersensitivity, gut motility, and gut-brain interaction disorders. Because currently available pharmacological treatments cannot adequately improve symptoms and may cause adverse effects, the use of herbal therapies for managing IBS is increasing. Lysimachia vulgaris var. davurica (LV) is a medicinal plant used in traditional medicine to treat diarrhea. However, information on whether LV can effectively improve diarrhea-predominant IBS (IBS-D) remains limited. In this study, using an experimental mouse model of IBS-D, we elucidated the effects of the LV extract. The methanol extract of LV decreased fecal pellet output in the restraint stress- or 5-hydroxytryptamine (5-HT)-induced IBS mouse model and inhibited 5-HT-mediated [Ca2+]i increase in a dose-dependent manner. Furthermore, we developed and validated a high-performance liquid chromatography method using two marker compounds, namely, chlorogenic acid and rutin, for quality control analysis. Our study results suggest the feasibility of the methanol extract of LV for developing therapeutic agents to treat IBS-D by acting as a 5-HT3 receptor antagonist.

Genomics of Brain Disorders 4.0.

Several historic, scientific events have occurred in the decade 2013-2023, in particular the COVID-19 pandemic. This massive pathogenic threat, which has affected the world's population, has had a devastating effect on scientific production worldwide. [...].

Biomarkers of Brain Dysfunction in Perinatal Iron Deficiency.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with a risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcomes in perinatal iron deficiency.

[A case of COVID-associated encephalopathy in a patient with multiple sclerosis]. / Klinicheskii sluchai COVID-assotsiirovannoi entsefalopatii u patsienta s rasseyannym sklerozom.

A case of acute encephalopathy manifested with impaired consciousness, hemichorrhea, speech and cognitive impairment in a female patient with COVID-19 and multiple sclerosis is presented. In the literature, there are isolated reports of such a combination of diseases, and therefore difficulties arise in carrying out differential diagnosis and prescribing therapy. Given the limited knowledge about the long-term consequences of COVID-19, systematic analysis of such cases and follow-up of such patients is necessary.