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Clinical Rheumatology Jan 2024Neuromyelitis optica (NMO), also known as Devic's disease, is a rare inflammatory demyelinating disorder causing myelitis and optic neuritis. While there have been...
OBJECTIVE
Neuromyelitis optica (NMO), also known as Devic's disease, is a rare inflammatory demyelinating disorder causing myelitis and optic neuritis. While there have been reports of systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (SS) occurring with NMO, a formal association is not established. We aimed to investigate the occurrence of NMO in SLE and SS patients and study the clinical characteristics and outcomes of NMO and SLE/SS hospitalizations utilizing the national inpatient sample (NIS) database.
METHODS
The NIS database from 2016 to 2019 was used to extract data. Adult hospitalizations with the principal or secondary diagnosis of NMO were included. We classified NMO patients with and without concomitant diagnosis of SLE or Sjogren's syndrome. We evaluated and compared the clinical characteristics and outcomes of NMO hospitalizations with and without SLE or Sjogren's syndrome. STATA17 was used for data analysis. We also calculated the odds ratio of NMO in SLE and Sjogren's syndrome.
RESULTS
There were a total of 16,360 adult hospitalizations with the principal or secondary discharge diagnosis of NMO. Among all NMO hospitalizations, 1425 (8.71%) had the primary or secondary diagnosis of SLE or SS. The odds of NMO in SLE and Sjogren's syndrome were noted to be 12.29 and 5.56, respectively. NMO with SLE/SS group had higher proportion of females (89.82% vs 79%, P value < 0.001), African Americans (56.63% vs 38.28, P value < 0.001), and Asians (5.73% vs 3.25, P value 0.04). The Charlson comorbidity index was higher for NMO-SLE/SS overlap (2.44 vs 1.28, P value < 0.001). There was no significant difference in overall mortality rates of both groups (2.11% vs 1.2%, P value 0.197). There were significantly higher reported seizures (14.73% vs 6.05, P value < 0.001) and paraplegia (21.75% vs 13.93%, P value < 0.001) in NMO-SLE/SS patients. These patients also had a longer length of stay in comparison to the reference group (7 vs 5 days, P value < 0.001) as well as higher total charges.
CONCLUSIONS
NMO patients had a 12-fold higher risk of SLE and 5-fold higher risk of Sjogren's disease when compared to general population. Patients with overlap of NMO and SLE or Sjogren's were predominantly women and were more likely to be African-American. Co-existence of these autoimmune disorders was associated with poor prognosis in terms of higher morbidity for patients and increased health care burden. Key Points • NMO is a rare autoimmune disease seen predominantly in women in the middle age group with low overall mortality. • SLE and Sjogren's have increased odds of NMO in comparison to general population. • NMO patients have high rates of several complications such as paraplegia, quadriplegia, seizures, blindness, sepsis, and respiratory failure with even higher rates of seizures and paraplegia in those with concomitant SLE or Sjogren's.
Topics: Adult; Middle Aged; Humans; Female; Male; Sjogren's Syndrome; Neuromyelitis Optica; Lupus Erythematosus, Systemic; Autoimmune Diseases; Seizures; Paraplegia
PubMed: 37980305
DOI: 10.1007/s10067-023-06809-z -
Neuroscience Research Dec 2023Kinesin motor proteins play crucial roles in anterograde transport of cargo vesicles in neurons, moving them along axons from the cell body towards the synaptic region.... (Review)
Review
Kinesin motor proteins play crucial roles in anterograde transport of cargo vesicles in neurons, moving them along axons from the cell body towards the synaptic region. Not only the transport force and velocity of single motor protein, but also the number of kinesin molecules involved in transporting a specific cargo, is pivotal for synapse formation. This collective transport by multiple kinesins ensures stable and efficient cargo transport in neurons. Abnormal increases or decreases in the number of engaged kinesin molecules per cargo could potentially act as biomarkers for neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), spastic paraplegia, polydactyly syndrome, and virus transport disorders. We review here a model constructed using physical measurements to quantify the number of kinesin molecules associated with their cargo, which could shed light on the molecular mechanisms of neurodegenerative diseases related to axonal transport.
Topics: Humans; Kinesins; Axonal Transport; Axons; Dyneins; Amyotrophic Lateral Sclerosis
PubMed: 37734449
DOI: 10.1016/j.neures.2023.09.004 -
Neurology Oct 2023
Topics: Humans; Pneumorrhachis; Anesthesia, Spinal; Paraplegia; Anesthesia, Epidural
PubMed: 37596044
DOI: 10.1212/WNL.0000000000207824 -
Molecular Psychiatry Apr 2024The ionotropic glutamate delta receptor GluD1, encoded by the GRID1 gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but...
The ionotropic glutamate delta receptor GluD1, encoded by the GRID1 gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but instead cerebellin and D-serine, which allow the formation of trans-synaptic bridges, and trigger transmembrane signaling. Despite wide expression in the nervous system, pathogenic GRID1 variants have not been characterized in humans so far. We report homozygous missense GRID1 variants in five individuals from two unrelated consanguineous families presenting with intellectual disability and spastic paraplegia, without (p.Thr752Met) or with (p.Arg161His) diagnosis of glaucoma, a threefold phenotypic association whose genetic bases had not been elucidated previously. Molecular modeling and electrophysiological recordings indicated that Arg161His and Thr752Met mutations alter the hinge between GluD1 cerebellin and D-serine binding domains and the function of this latter domain, respectively. Expression, trafficking, physical interaction with metabotropic glutamate receptor mGlu1, and cerebellin binding of GluD1 mutants were not conspicuously altered. Conversely, upon expression in neurons of dissociated or organotypic slice cultures, we found that both GluD1 mutants hampered metabotropic glutamate receptor mGlu1/5 signaling via Ca and the ERK pathway and impaired dendrite morphology and excitatory synapse density. These results show that the clinical phenotypes are distinct entities segregating in the families as an autosomal recessive trait, and caused by pathophysiological effects of GluD1 mutants involving metabotropic glutamate receptor signaling and neuronal connectivity. Our findings unravel the importance of GluD1 receptor signaling in sensory, cognitive and motor functions of the human nervous system.
Topics: Humans; Intellectual Disability; Male; Synapses; Female; Receptors, Metabotropic Glutamate; Signal Transduction; Homozygote; Receptors, Glutamate; Receptor, Metabotropic Glutamate 5; Pedigree; Adult; Paraplegia; Animals; Child; Neurons; Adolescent; HEK293 Cells; Mutation
PubMed: 38418578
DOI: 10.1038/s41380-024-02469-w -
MicroPublication Biology 2024Pharyngeal pumping and its reduction following mechanical insult are well-studied behaviors. Here, we assessed new applications of pharyngeal pumping assays in the...
Pharyngeal pumping and its reduction following mechanical insult are well-studied behaviors. Here, we assessed new applications of pharyngeal pumping assays in the study of neurodegenerative disease and psychiatric illness. We examined five genes implicated in two forms of neurodegeneration, Hereditary Spastic Paraplegia (HSPs) and Alzheimer's Disease (AD), for both baseline pharyngeal pumping and the depressive response after touch stimulus. All five mutants showed reduced baseline pumping rate, suggesting a potential utility of this assay to study neurodegenerative disease on a broad scale. However, regarding the induced pumping response, which has been linked to schizophrenia, only specific genes, the HSP-related Atlastin and the AD-related tau, showed defects. Together, we highlight two pharyngeal pumping behaviors as genetically distinct, potentially informative settings for understanding the functions of genes linked to neurodegeneration.
PubMed: 38550607
DOI: 10.17912/micropub.biology.000897 -
Einstein (Sao Paulo, Brazil) 2023Post-thoracotomy paraplegia after non-aortic surgery is an extremely uncommon complication. A 56-year-old woman presented with a 1-year history of progressive shortness...
Post-thoracotomy paraplegia after non-aortic surgery is an extremely uncommon complication. A 56-year-old woman presented with a 1-year history of progressive shortness of breath. Computed tomography revealed a locally advanced posterior mediastinal mass involving the ribs and the left neural foramina. Tumor excision with a left pneumonectomy was performed. Post-resection, bleeding was noted in the vicinity of the T4-T5 vertebral body, and the bleeding point was packed with oxidized cellulose gauze (Surgicel®). Postoperatively, the patient complained of bilateral leg numbness extending up to the T5 level, with bilateral paraplegia. An urgent laminectomy was performed, and we noted that the spinal cord was compressed by two masses of Surgicel® with blood clots measuring 1.5 × 1.5cm at T4 and T5 levels. The paraplegia did not improve despite the removal of the mass, sufficient decompression, and aggressive postoperative physiotherapy. Surgeons operating in fields close to the intervertebral foramen should be aware of the possible threat to the adjacent spinal canal as helpful hemostatic agents can become a preventable threat.
Topics: Female; Humans; Middle Aged; Cellulose, Oxidized; Thoracotomy; Spinal Cord Compression; Paraplegia; Laminectomy
PubMed: 37436267
DOI: 10.31744/einstein_journal/2023RC0078 -
Autophagy Jan 2024atl atlastin; ALR autophagic lysosome reformation; ER endoplasmic reticulum; GFP green fluorescent protein; HSP hereditary spastic paraplegia; Lamp1 lysosomal associated...
atl atlastin; ALR autophagic lysosome reformation; ER endoplasmic reticulum; GFP green fluorescent protein; HSP hereditary spastic paraplegia; Lamp1 lysosomal associated membrane protein 1 PolyUB polyubiquitin; RFP red fluorescent protein; spin spinster; mTor mechanistic Target of rapamycin; VCP valosin containing protein.
Topics: Animals; Autophagy; Drosophila; Lysosomes; Muscles; TOR Serine-Threonine Kinases
PubMed: 37649246
DOI: 10.1080/15548627.2023.2249794 -
Veterinary Radiology & Ultrasound : the... May 2024A 3-year-old Pygmy Wether was presented for chronic hindlimb paralysis. A neurological exam revealed nonambulatory paraplegia with absent deep pain nociception, lack of...
A 3-year-old Pygmy Wether was presented for chronic hindlimb paralysis. A neurological exam revealed nonambulatory paraplegia with absent deep pain nociception, lack of hindlimb withdrawal reflexes, and paraspinal pain on palpation with T3 to L3 neurolocalization. MRI of the lumbar spine revealed an extensive, dorsal to dorsolateral, severely compressive, heterogeneously contrast-enhancing extradural lesion of the lumbar spine with intervertebral foraminal extension into the surrounding paraspinal musculature. Vertebral bone marrow involvement was also noted in the L5 and L6 vertebrae. A diagnosis of lymphoma was obtained after cytological sampling. This is the first case report describing specific MRI findings (signal characteristics, enhancement pattern, and perilesional changes) in a goat with paraspinal lymphoma.
Topics: Animals; Goats; Goat Diseases; Lymphoma; Magnetic Resonance Imaging; Spinal Neoplasms; Lumbar Vertebrae; Female
PubMed: 38349192
DOI: 10.1111/vru.13339 -
Frontiers in Neuroscience 2023is the most common form of autosomal recessive hereditary spastic paraplegia (HSP). There is a lack of HSP- human neuronal models to understand the disease mechanism...
is the most common form of autosomal recessive hereditary spastic paraplegia (HSP). There is a lack of HSP- human neuronal models to understand the disease mechanism and identify new drug treatments. We generated a human neuronal model of HSP- using induced pluripotent stem (iPS) cell technology. We first generated iPS cells from three HSP- patients carrying different disease-causing variants and three healthy controls. The iPS cells were differentiated to form neural progenitor cells (NPCs) and then from NPCs to mature cortical neurons. Mitochondrial and neuronal defects were measured using a high throughout imaging and analysis-based assay in live cells. Our results show that compared to control NPCs, patient NPCs had aberrant mitochondrial morphology with increased mitochondrial size and reduced membrane potential. Patient NPCs develop to form mature cortical neurons with amplified mitochondrial morphology and functional defects along with defects in neuron morphology - reduced neurite complexity and length, reduced synaptic gene, protein expression and activity, reduced viability and increased axonal degeneration. Treatment of patient neurons with Bz-423, a mitochondria permeability pore regulator, restored the mitochondrial and neurite morphological defects and mitochondrial membrane potential back to control neuron levels and rescued the low viability and increased degeneration in patient neurons. This study establishes a direct link between mitochondrial and neuronal defects in HSP- patient neurons. We present a strategy for testing mitochondrial targeting drugs to rescue neuronal defects in HSP- patient neurons.
PubMed: 37766787
DOI: 10.3389/fnins.2023.1231584 -
Anales de Pediatria Jun 2024
PubMed: 38853057
DOI: 10.1016/j.anpede.2024.06.004