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Neuroanatomical tract tracers are important for studying axoplasmic transport and the complex interconnections of the nervous system. Though traditional fluorescent tracers are widely used, they have several prominent drawbacks when imaging, including low resolutions and low tissue penetrations and inability to be supervised dynamically within a long peripheral nerve during the long term. Here, we explored the potential of ICG as a neural tracer for axoplasmic transport and for the first time demonstrated that ICG could be used to detect transport function within peripheral nerve by near-infrared region II (NIR-II) imaging. On basis of this finding, a novel bi-directional neural tracer biotinylated dextran amine-indocyanine green (BDA-ICG) was prepared and characterized with better long-term stability and higher nerve-to-background ratio than ICG in vivo, and successfully imaged the injured peripheral nerve from the healthy one within 24 h. Our results show that BDA-ICG are promising neural tracers and clinically available dyes with NIR-II emission tail characteristics as ICG.
ABSTRACT
OBJECTIVES: To investigate the immunopathogenic mechanisms of anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) by characterizing the changes of immune cells in both peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with NMDAR-E. METHODS: Cytology and flow cytometry were used to explore and compare different immunological parameters in PB and CSF of patients with NMDAR-E, viral encephalitis (VE) and healthy volunteers. Moreover, different models were established to assess the possibility of identifying NMDAR-E patients based on PB and CSF parameters. RESULTS: The neutrophil counts and monocyte-to-lymphocyte ratios (MLR) in PB are higher in NMDAR-E patients than in both VEs and controls (P < 0.001, respectively), while the percentages of CD3 + T, CD4 + T lymphocytes, and the leukocytes count in CSF were lower in NMDAR-Es than in VEs (P < 0.01, respectively). The higher percentages of CD8 + T cells in blood and CSF were both correlated with more severe NMDAR-E (P < 0.05, respectively). The poor neurological status group had significantly higher PB leukocytes but lower CSF leukocyte count (P < 0.05). Longitudinal observations in patients with NMDAR-E showed a decreasing trend of leukocyte count, neutrophils count, neutrophil-to-monocyte ratios (NMR), and neutrophil-to-lymphocyte ratios (NLR) with the gradual recovery of neurological function. CONCLUSIONS: The expression patterns of T lymphocyte subsets were different in patients with NMDAR-E and viral encephalitis. The changing trends of leukocyte and lymphocyte populations in peripheral blood and cerebrospinal fluid may provide clues for the diagnosis of different types of encephalitides, including NMDARE, and can be used as immunological markers to assess and predict the prognosis.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Encephalitis, Viral , Humans , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Prognosis , CD4-Positive T-Lymphocytes , Immunity, CellularABSTRACT
Neuro-COVID, a condition marked by persistent symptoms post-COVID-19 infection, notably affects various organs, with a particular focus on the central nervous system (CNS). Despite scant evidence of SARS-CoV-2 invasion in the CNS, the increasing incidence of Neuro-COVID cases indicates the onset of acute neurological symptoms early in infection. The Omicron variant, distinguished by heightened neurotropism, penetrates the CNS via the olfactory bulb. This direct invasion induces inflammation and neuronal damage, emphasizing the need for vigilance regarding potential neurological complications. Our multicenter study represents a groundbreaking revelation, documenting the definite presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of a significant proportion of Neuro-COVID patients. Furthermore, notable differences emerged between RNA-CSF-positive and negative patients, encompassing aspects such as blood-brain barrier integrity, extent of neuronal damage, and the activation status of inflammation. Despite inherent limitations, this research provides pivotal insights into the intricate interplay between SARS-CoV-2 and the CNS, underscoring the necessity for ongoing research to fully comprehend the virus's enduring effects on the CNS. The findings underscore the urgency of continuous investigation Neuro-COVID to unravel the complexities of this relationship, and pivotal in addressing the long-term consequences of COVID-19 on neurological health.
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BACKGROUND: The identification of patients with seizures of unknown etiology who would benefit from neural antibody testing necessitates effective assessment tools. The study aimed to compare the performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and the "Obvious" Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist. We also intended to evaluate whether the performance of the tools varied by types of antibody. METHODS: Patients diagnosed with epilepsy, seizures, or status epilepticus of unknown etiology at West China Hospital from January 2019 to December 2021 were included. Paired serum/cerebrospinal fluid samples were analyzed for antineuronal and antiglial antibodies. The APE2 score and ONES checklist were applied, and their outcomes were compared to laboratory antibody test results. Possible false positive neuronal antibody results were excluded in sensitivity/specificity analysis reasonably. RESULTS: A total of 113 antibody-positive and 159 antibody-negative patients were enrolled in sensitivity/specificity analysis. The ONES checklist showed superior sensitivity than APE2 score (95.6 % vs.79.6 %, P < 0.001). Specificity was not statistically different (60.4 % vs. 57.9 %, P = 0.557). The negative predictive value (NPV) of ONES checklist was higher than that of APE2 score (94.8 % vs 80.7 %, P < 0.001). The positive predictive value of them was not statistically different (61.7 % vs 58.8 %, P = 0.557). APE2 score exhibited lower sensitivity for predicting LGI-Abs (52.9 % vs. 80.3 %, P = 0.022) compared to NMDAR-Abs. Similarly, ONES checklist showed lower sensitivity for LGI1-Abs than NMDAR-Abs (82.4 % vs. 100.0 %, P = 0.009). CONCLUSIONS: The ONES checklist demonstrates superior sensitivity for neural antibody positivity than APE2 score. Specificity of the two assessment tools was similar. ONES checklist performed better NPV than the APE2 score. Both assessment tools performed less well in predicting the presence of LGI1- Abs when compared to NMDAR-Abs.
Subject(s)
Brain Diseases , Epilepsy , Humans , Autoantibodies , Seizures , Epilepsy/complications , NeuronsABSTRACT
Temporal lobe epilepsy (TLE) is the most common form of epileptic syndrome. It has been established that due to its complex pathogenesis, a considerable proportion of TLE patients often progress to drug-resistant epilepsy. Ferroptosis has emerged as an important neuronal death mechanism in TLE, which is primarily influenced by lipid accumulation and oxidative stress. In previous studies of ferroptosis, more attention has been focused on the impact of changes in the levels of proteins related to the redox equilibrium and signaling pathways on epileptic seizures. However, it is worth noting that the oxidative-reduction changes in different organelles may have different pathophysiological significance in the process of ferroptosis-related diseases. Mitochondria, as a key organelle involved in ferroptosis, its structural damage and functional impairment can lead to energy metabolism disorders and disruption of the excitatory inhibitory balance, significantly increasing the susceptibility to epileptic seizures. Therefore, secondary mitochondrial dysfunction in the process of ferroptosis could play a crucial role in TLE pathogenesis. This review focuses on ferroptosis and mitochondria, discussing the pathogenic role of ferroptosis-related mitochondrial dysfunction in TLE, thus aiming to provide novel insights and potential implications of ferroptosis-related secondary mitochondrial dysfunction in epileptic seizures and to offer new insights for the precise exploration of ferroptosis-related therapeutic targets for TLE patients.
Subject(s)
Epilepsy, Temporal Lobe , Ferroptosis , Mitochondrial Diseases , Humans , Epilepsy, Temporal Lobe/metabolism , Epilepsy, Temporal Lobe/pathology , Seizures/complications , Seizures/metabolism , Seizures/pathology , Mitochondria/metabolism , Mitochondrial Diseases/complications , Mitochondrial Diseases/metabolism , Mitochondrial Diseases/pathologySubject(s)
Adenocarcinoma , Encephalitis , Male , Humans , Autoimmunity , Dopamine , Prostate , Adenocarcinoma/complicationsABSTRACT
BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.
Subject(s)
Brain Diseases , COVID-19 , Encephalitis , Humans , Cohort Studies , COVID-19/complications , COVID-19/epidemiology , China/epidemiology , SeizuresABSTRACT
Background: Idiopathic congenital nystagmus (ICN) is an inherited disorder characterized by uncontrollable binocular conjugating oscillation. X-linked idiopathic congenital nystagmus is one of the most prevalent types of ICN. Elucidation of the genetic mechanisms involved in ICN will enhance our understanding of its molecular etiology. Case presentation: We report a girl with uncontrollable binocular oscillation and anomalous head posture, then presented a novel heterozygous missense variant (c.686G>T) within the mutation-rich region of the FERM domain containing 7 (FRMD7) gene in her family member. The girl received occlusion therapy and surgical operation which balanced her binocular vision and corrected the anomalous head posture. Conclusions: This is the first report on a mutation (c.686G>T) caused the substitution of Arg (R) with Leu (L) at position 229 (p.R229L) of the FRMD7 protein in a patient with ICN.