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Journal of Acute Medicine Jun 2024Fenitrothion is one of the most globally used organophosphorus pesticides, which can cause neurological symptoms, including involuntary movements. However, due to the...
Fenitrothion is one of the most globally used organophosphorus pesticides, which can cause neurological symptoms, including involuntary movements. However, due to the limited number of case report, information on its treatment is also scarce. Here we presented a 74-year-old Japanese woman who was admitted to our hospital due to a persistent nausea and vomiting after ingesting 200 mL of 50% fenitrothion for a suicidal attempt. She received continuous intravenous infusion of atropine and 2-pyridine aldoxime methiodide under mechanical ventilation and continuous hemodiafiltration. However, she developed fasciculations of the face and right arm on day 11, which raised suspicions of delayed neuropathy associated with organophosphorus poisoning. To reduce the risk of respiratory depression, she received intravenous levetiracetam at a dosage of 1,000 mg/day. However, as her fasciculations persisted, the levetiracetam dosage was adjusted to 2,000 mg/day on day 14. On the following day, her fasciculations subsided. Neurologic symptoms of lipid-soluble organophosphorus poisoning, including fenitrothion, can sometimes delay following ingestion. Temporary administration of levetiracetam may prove effective in alleviating fasciculations.
PubMed: 38855047
DOI: 10.6705/j.jacme.202406_14(2).0004 -
Cureus May 2024Madras motor neuron disease (MMND) is a rare childhood or juvenile motor neuron disease. Herein, we present a unique case of MMND in an 18-year-old patient, which...
Madras motor neuron disease (MMND) is a rare childhood or juvenile motor neuron disease. Herein, we present a unique case of MMND in an 18-year-old patient, which challenges the conventional understanding of the disease's onset and progression. The patient, a previously healthy adolescent, presented with insidious onset and gradually progressive weakness of all four limbs, wasting, tongue fasciculation, and bilateral sensorineural hearing loss. Neurological examination revealed signs consistent with lower motor neuron involvement. Electromyography (EMG) and nerve conduction studies (NCS) supported the diagnosis of MMND. The patient's clinical course exhibited rapid deterioration, leading to significant functional impairment within a short timeframe. Treatment modalities, including supportive care and symptomatic management, were implemented; however, disease progression remained relentless. This case highlights the significance of considering MMND in the differential diagnosis of motor neuron diseases, even in young individuals. It highlights the importance of conducting more studies to comprehend the underlying mechanisms and consider potential therapeutic strategies for this uncommon ailment.
PubMed: 38854224
DOI: 10.7759/cureus.59812 -
Annals of Clinical and Translational... May 2024Compare efficacy of gene therapy alone (monotherapy) or in combination with an SMN2 augmentation agent (dual therapy) for treatment of children at risk for spinal...
OBJECTIVE
Compare efficacy of gene therapy alone (monotherapy) or in combination with an SMN2 augmentation agent (dual therapy) for treatment of children at risk for spinal muscular atrophy type 1.
METHODS
Eighteen newborns with biallelic SMN1 deletions and two SMN2 copies were treated preemptively with monotherapy (n = 11) or dual therapy (n = 7) and followed for a median of 3 years. Primary outcomes were independent sitting and walking. Biomarkers were serial muscle ultrasonography (efficacy) and sensory action potentials (safety).
RESULTS
Gene therapy was administered by 7-43 postnatal days; dual therapy with risdiplam (n = 6) or nusinersen (n = 1) was started by 15-39 days. Among 18 children enrolled, 17 sat, 15 walked, and 44% had motor delay (i.e., delay or failure to achieve prespecified milestones). Those on dual therapy sat but did not walk at an earlier age. 91% of muscle ultrasounds conducted within 60 postnatal days were normal but by 3-61 months, 94% showed echogenicity and/or fasciculation of at least one muscle group; these changes were indistinguishable between monotherapy and dual therapy cohorts. Five children with three SMN2 copies were treated with monotherapy in parallel: all sat and walked on time and had normal muscle sonograms at all time points. No child on dual therapy experienced treatment-associated adverse events. All 11 participants who completed sensory testing (including six on dual therapy) had intact sural sensory responses.
INTERPRETATION
Preemptive dual therapy is well tolerated and may provide modest benefit for children at risk for severe spinal muscular atrophy but does not prevent widespread degenerative changes.
PubMed: 38817128
DOI: 10.1002/acn3.52093 -
Gut Microbes 2024Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial species (, , ), and after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.
Topics: Amyotrophic Lateral Sclerosis; Humans; Fecal Microbiota Transplantation; Respiratory Insufficiency; Male; Middle Aged; Aged; Female; Bacteroides; Gastrointestinal Microbiome; Faecalibacterium prausnitzii; Treatment Outcome; Respiration, Artificial; Feces
PubMed: 38778483
DOI: 10.1080/19490976.2024.2353396 -
Cureus Apr 2024We report an unusual patient who, at age 47 years, had presented with complaints of muscle fasciculations. After neurological examination and electromyogram testing, he...
We report an unusual patient who, at age 47 years, had presented with complaints of muscle fasciculations. After neurological examination and electromyogram testing, he was diagnosed with motor neuropathy. Over the next 10 years, in addition to fasciculations, he developed numbness in his feet without any other symptoms. His current neurological examination at age 57 years was normal, except for mildly decreased light touch in the anterior portion of both feet. The nerve conduction studies performed repeatedly showed sensorimotor polyneuropathy with demyelination features. Blood tests, including anti-ganglioside antibodies, were normal. Genetic testing revealed two rare variants in in the gene, c.3413 G>A p.(S1138N) and c.3269 C>G p.(A1090G). Protein modeling suggests that these are disease-producing mutations and likely the cause of the neuropathy of our patient. Our study expands the clinical and genetic spectrum of patients with Charcot-Marie-Tooth disease type 4C.
PubMed: 38707135
DOI: 10.7759/cureus.57550 -
Breast Cancer (Dove Medical Press) 2024Distant metastasis remains the leading cause of death among patients with breast cancer (BRCA). The process of cancer metastasis involves multiple mechanisms, including...
BACKGROUND
Distant metastasis remains the leading cause of death among patients with breast cancer (BRCA). The process of cancer metastasis involves multiple mechanisms, including compromised immune system. However, not all genes involved in immune function have been comprehensively identified.
METHODS
Firstly 1623 BRCA samples, including transcriptome sequencing and clinical information, were acquired from Gene Expression Omnibus (GSE102818, GSE45255, GSE86166) and The Cancer Genome Atlas-BRCA (TCGA-BRCA) dataset. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed using the GSE102818 dataset to identify the most relevant module to the metastasis of BRCA. Besides, ConsensusClusterPlus was applied to divide TCGA-BRCA patients into two subgroups (G1 and G2). In the meantime, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a metastasis-related immune genes (MRIGs)_score to predict the metastasis and progression of cancer. Importantly, the expression of vital genes was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC).
RESULTS
The expression pattern of 76 MRIGs screened by WGCNA divided TCGA-BRCA patients into two subgroups (G1 and G2), and the prognosis of G1 group was worse. Also, G1 exhibited a higher mRNA expression level based on stemness index score and Tumor Immune Dysfunction and Exclusion score. In addition, higher MRIGs_score represented the higher probability of progression in BRCA patients. It was worth mentioning that the patients in the G1 group had a high MRIGs_score than those in the G2 group. Importantly, the results of RT-qPCR and IHC demonstrated that fasciculation and elongation protein zeta 1 (FEZ1) and insulin-like growth factor 2 receptor (IGF2R) were risk factors, while interleukin (IL)-1 receptor antagonist (IL1RN) was a protective factor.
CONCLUSION
Our study revealed a prognostic model composed of eight immune related genes that could predict the metastasis and progression of BRCA. Higher score represented higher metastasis probability. Besides, the consistency of key genes in BRCA tissue and bioinformatics analysis results from mRNA and protein levels was verified.
PubMed: 38634039
DOI: 10.2147/BCTT.S448642 -
Scientific Reports Apr 2024One of the major consequences of the COVID-19 pandemic has been the significant incidence of persistent fatigue following resolution of an acute infection (i.e....
One of the major consequences of the COVID-19 pandemic has been the significant incidence of persistent fatigue following resolution of an acute infection (i.e. post-COVID fatigue). We have shown previously that, in comparison to healthy controls, those suffering from post-COVID fatigue exhibit changes in muscle physiology, cortical circuitry, and autonomic function. Whether these changes preceded infection, potentially predisposing people to developing post-COVID fatigue, or whether the changes were a consequence of infection was unclear. Here we present results of a 12-month longitudinal study of 18 participants from the same cohort of post-COVID fatigue sufferers to investigate these correlates of fatigue over time. We report improvements in self-perception of the impact of fatigue via questionnaires, as well as significant improvements in objective measures of peripheral muscle fatigue and autonomic function, bringing them closer to healthy controls. Additionally, we found reductions in muscle twitch tension rise times, becoming faster than controls, suggesting that the improvement in muscle fatigability might be due to a process of adaptation rather than simply a return to baseline function.
Topics: Humans; Follow-Up Studies; Longitudinal Studies; COVID-19; Pandemics; Fasciculation
PubMed: 38632415
DOI: 10.1038/s41598-024-59232-y -
Frontiers in Cellular Neuroscience 2024During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct...
During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct partners at the right time and place. Many axon guidance cues have been identified and they play pleiotropic roles in not only axon guidance but also axon fasciculation, axon pruning, and synaptogenesis as well as cell migration, angiogenesis, and bone formation. In search of receptors for Sema3E in axon guidance, we unexpectedly found that Plexin B3 is highly expressed in retinal ganglion cells of zebrafish embryos when retinal axons are crossing the midline to form the chiasm. Plexin B3 has been characterized to be related to neurodevelopmental disorders. However, the investigation of its pathological mechanisms is hampered by the lack of appropriate animal model. We provide evidence that Plexin B3 is critical for axon guidance . Plexin B3 might function as a receptor for Sema3E while Neuropilin1 could be a co-receptor. The intracellular domain of Plexin B3 is required for Semaphorin signaling transduction. Our data suggest that zebrafish could be an ideal animal model for investigating the role and mechanisms of Sema3E and Plexin B3 .
PubMed: 38628398
DOI: 10.3389/fncel.2024.1292969 -
Journal of Clinical and Experimental... Mar 2024Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare lesion of a traumatic-reactive nature of the oral mucosa that can clinically mimic an oral...
Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare lesion of a traumatic-reactive nature of the oral mucosa that can clinically mimic an oral carcinoma. A 59-year-old male patient presented painful ulceration with indurated margins on the base of the tongue, extending to the floor of the mouth. The use of ill-fitting denture hurting the mucosa of the region was reported by the patient. The evolution time was 45 days. The presumptive diagnoses were oral squamous cell carcinoma and chronic ulcer. An incisional biopsy revealed an ulceration associated with an eosinophil-rich inflammatory infiltrate and a bed of proliferating histiocyte-like cells in either diffuse or fasciculate arrangement. There was diffuse immunopositivity for CD3, but focal for CD68 and α-SMA, and negativity for CD30. The final diagnosis was TUGSE. The use of the ill-fitting dental prosthesis was suspended and the lesion had complete spontaneous remission three weeks later. TUGSE is an uncommon traumatic self-limiting lesion that must be included in the differential diagnosis of ulcerative lesions resembling oral cancer. The correlation of clinical and histopathological findings is pivotal for a proper diagnosis, avoiding unnecessary aggressive surgical approaches. Oral ulcer, eosinophilia, immunohistochemical, differential diagnosis.
PubMed: 38600925
DOI: 10.4317/jced.61322 -
BioRxiv : the Preprint Server For... Mar 2024Specific and highly diverse connectivity between functionally specialized regions of the nervous system is controlled at multiple scales, from anatomically organized...
Specific and highly diverse connectivity between functionally specialized regions of the nervous system is controlled at multiple scales, from anatomically organized connectivity following macroscopic axon tracts to individual axon target-finding and synapse formation. Identifying mechanisms that enable entire subpopulations of related neurons to project their axons with regional specificity within stereotyped tracts to form appropriate long-range connectivity is key to understanding brain development, organization, and function. Here, we investigate how axons of the cerebral cortex form precise connections between the two cortical hemispheres via the corpus callosum. We identify topographic principles of the developing trans-hemispheric callosal tract that emerge through intrinsic guidance executed by growing axons in the corpus callosum within the first postnatal week in mice. Using micro-transplantation of regionally distinct neurons, subtype-specific growth cone purification, subcellular proteomics, and in utero gene manipulation, we investigate guidance mechanisms of transhemispheric axons. We find that adhesion molecule levels instruct tract topography and target field guidance. We propose a model in which transcallosal axons in the developing brain perform a "handshake" that is guided through co-fasciculation with symmetric contralateral axons, resulting in the stereotyped homotopic connectivity between the brain's hemispheres.
PubMed: 38585721
DOI: 10.1101/2024.03.28.587108