This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
Very-long-chain fatty acids (VLCFAs) play important roles in membrane structure and cellular signaling, and their contribution to human health is increasingly recognized. Fatty acid elongases catalyze the first and rate-limiting step in VLCFA synthesis. Heterozygous mutations in ELOVL4, the gene encoding one of the elongases, are known to cause macular degeneration in humans and retinal abnormalities in mice. However, biallelic ELOVL4 mutations have not been observed in humans, and murine models with homozygous mutations die within hours of birth as a result of a defective epidermal water barrier. Here, we report on two human individuals with recessive ELOVL4 mutations revealed by a combination of autozygome analysis and exome sequencing. These individuals exhibit clinical features of ichthyosis, seizures, mental retardation, and spasticity-a constellation that resembles Sjögren-Larsson syndrome (SLS) but presents a more severe neurologic phenotype. Our findings identify recessive mutations in ELOVL4 as the cause of a neuro-ichthyotic disease and emphasize the importance of VLCFA synthesis in brain and cutaneous development.
The biceps or the posterior deltoid can be transferred to improve elbow extension function for many individuals with C5 or C6 quadriplegia. Maximum strength after elbow reconstruction is variable; the patient's ability to voluntarily activate the transferred muscle to extend the elbow may contribute to the variability. We compared voluntary activation during maximum isometric elbow extension following biceps transfer (n = 5) and deltoid transfer (n = 6) in three functional postures. Voluntary activation was computed as the elbow extension moment generated during maximum voluntary effort divided by the moment generated with full activation, which was estimated via electrical stimulation. Voluntary activation was on average 96% after biceps transfer and not affected by posture. Individuals with deltoid transfer demonstrated deficits in voluntary activation, which differed by posture (80% in horizontal plane, 69% in overhead reach, and 70% in weight-relief), suggesting inadequate motor re-education after deltoid transfer. Overall, individuals with a biceps transfer better activated their transferred muscle than those with a deltoid transfer. This difference in neural control augmented the greater force-generating capacity of the biceps leading to increased elbow extension strength after biceps transfer (average 9.37 N-m across postures) relative to deltoid transfer (average 2.76 N-m across postures) in our study cohort.
The use of the supine training position to enhance aerobic training was evaluated in a 10-week upper-body exercise study. Fourteen subjects with quadriplegia (QD) were matched on initial peak power output (PO) values and then randomly assigned to either a supine (SUP, n = 7) or sitting (SIT, n = 7) training group. Peak VO2 and PO were measured pretraining and posttraining in both the supine and sitting positions. There were significant (p < .01) increases in peak VO2 (720 to 780 mL.min-1) and PO (29.3 to 33.3W) with training. Although the SIT group exhibited a small training effect size (0.1), while the SUP group exhibited a moderate effect size (0.6), the interaction between time and training group failed to reach significance (p = .07) because of a large injury level-related variation in VO2. The training effect achieved by the SUP group generalized to the sitting position, as their peak VO2 increased 80mL.min-1 in the sitting position. Endurance improved (p < .0001) in all subjects, with time to exhaustion increasing from 52min to 135min over the 10 weeks of training. The sum of 4 skinfolds decreased (p < .05) from 67.5 to 61.0mm. The lack of change in stroke volume at rest and at 50% of peak PO suggests that an inotropic adaptation of the heart, commonly observed in subjects without SCI, did not occur in this population. However, a 4.7bpm increase (p < .01) in resting heart rate (HR) and a near significant increase (p = .07) in peak HR from pretraining to posttraining suggests a training-induced chronotropic adaptation of the heart. Although improvements in aerobic capacity can be achieved by training in either supine or sitting positions, the training effect size was larger in the supine position. Improvements in SV were not observed in either training position; this may be because of low absolute workloads were used. Central cardiovascular adaptation may occur in subjects with QD but changes are reflected as chronotropic and not inotropic adaptations.
Cerebral palsy (CP) is a group of nonprogressive syndromes of posture and motor impairment associated with lesions of the immature brain. Spastic quadriplegia is the most severe form with a high incidence of scoliosis, back pain, respiratory compromise, pelvic obliquity, and poor sitting balance. Surgical stabilization of the spine is an effective technique for correcting deformity and restoring sitting posture. The decision to operate in this group of patients is challenging.
A 59-year-old male presented to the emergency department complaining of severe posterior neck pain and progressive extremity weakness for 2 weeks. He was found to be quadriplegic with complete sensory and motor deficits at the C5 level and hypotensive. Diagnostic imaging revealed discitis/osteomyelitis at the C5-C6 and C6-C7 vertebral levels with multiple spinal epidural abscesses extending from C5-C7 with resulting severe spinal canal narrowing with cord compression. Imaging also showed a right vertebral artery occlusion, acute right posterior cerebral artery infarct, retropharyngeal abscess, and extensive paraspinal soft tissue myonecrosis. Vasopressors and broad-spectrum antibiotics were started. He was then transferred to a tertiary medical center where he underwent emergent cervical spine decompression surgery with laminectomy from C3-C7, paraspinal soft tissue debridement, and abscess incision and drainage. He suffered a complicated hospital course and despite aggressive treatment developed worsening infectious myelopathy and died in the hospital. This case involves the rare presentation of quadriplegia and acute cerebral infarction associated with necrotizing fasciitis and spinal epidural abscesses that originated from a retropharyngeal abscess. To date, there have been no cases documenting such a phenomenon, and epidural abscess has not been known to cause adjacent necrotizing fasciitis. Furthermore, vertebral artery thrombosis via mass effect from local infection leading to acute embolic stroke has never been reported. This report sheds light on rare sequela of a tracking retropharyngeal and epidural abscess. Prompt recognition, diagnosis, and treatment are vital to maintain infectious source control and preserve neurological function, although many develop persistent deficits.
A de novo 9q33.3-q34.11 microdeletion involving STXBP1 has been found in one of four individuals (group A) with early-onset West syndrome, severe hypomyelination, poor visual attention, and developmental delay. Although haploinsufficiency of STXBP1 was involved in early infantile epileptic encephalopathy in a previous different cohort study (group B), no mutations of STXBP1 were found in two of the remaining three subjects of group A (one was unavailable). We assumed that another gene within the deletion might contribute to the phenotype of group A. SPTAN1 encoding alpha-II spectrin, which is essential for proper myelination in zebrafish, turned out to be deleted. In two subjects, an in-frame 3 bp deletion and a 6 bp duplication in SPTAN1 were found at the initial nucleation site of the alpha/beta spectrin heterodimer. SPTAN1 was further screened in six unrelated individuals with WS and hypomyelination, but no mutations were found. Recombinant mutant (mut) and wild-type (WT) alpha-II spectrin could assemble heterodimers with beta-II spectrin, but alpha-II (mut)/beta-II spectrin heterodimers were thermolabile compared with the alpha-II (WT)/beta-II heterodimers. Transient expression in mouse cortical neurons revealed aggregation of alpha-II (mut)/beta-II and alpha-II (mut)/beta-III spectrin heterodimers, which was also observed in lymphoblastoid cells from two subjects with in-frame mutations. Clustering of ankyrinG and voltage-gated sodium channels at axon initial segment (AIS) was disturbed in relation to the aggregates, together with an elevated action potential threshold. These findings suggest that pathological aggregation of alpha/beta spectrin heterodimers and abnormal AIS integrity resulting from SPTAN1 mutations were involved in pathogenesis of infantile epilepsy.
Hereditary spastic paraplegia (HSP) comprises a heterogeneous group of neuropathies affecting upper motor neurons and causing progressive gait disorder. Mutations in the gene SPG3A/atlastin-1 (ATL1), encoding a dynamin superfamily member, which utilizes the energy from GTP hydrolysis for membrane tethering and fusion to promote the formation of a highly branched, smooth endoplasmic reticulum (ER), account for approximately 10% of all HSP cases. The continued discovery and characterization of novel disease mutations are crucial for our understanding of HSP pathogenesis and potential treatments. Here, we report a novel disease-causing, in-frame insertion in the ATL1 gene, leading to inclusion of an additional asparagine residue at position 417 (N417ins). This mutation correlates with complex, early-onset spastic quadriplegia affecting all four extremities, generalized dystonia, and a thinning of the corpus callosum. We show using limited proteolysis and FRET-based studies that this novel insertion affects a region in the protein central to intramolecular interactions and GTPase-driven conformational change, and that this insertion mutation is associated with an aberrant prehydrolysis state. While GTPase activity remains unaffected by the insertion, membrane tethering is increased, indicative of a gain-of-function disease mechanism uncommon for ATL1-associated pathologies. In conclusion, our results identify a novel insertion mutation with altered membrane tethering activity that is associated with spastic quadriplegia, potentially uncovering a broad spectrum of molecular mechanisms that may affect neuronal function.
A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder.
Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.
Asparagine synthetase deficiency (ASNSD) is a rare pediatric congenital disorder that clinically manifests into severe progressive microcephaly, global developmental delay, spastic quadriplegia, and refractory seizures. ASNSD is caused by inheritable autosomal recessive mutations in the asparagine synthetase (ASNS) gene.
Diversity among editorial boards and in the peer review process maximizes the likelihood that the dissemination of reported results is both relevant and respectful to readers and end users. Past studies have examined diversity among editorial board members and reviewers for factors such as gender, geographic location, and race, but limited research has explored the representation of people with disabilities. Here, we sought to understand the landscape of inclusivity of people with lived experience of spinal cord injury specifically in journals publishing papers (2012-2022) on their quality of life.
Spinal cord injury (SCI) is one of the most devastating diseases that challenges neurology and medicine, leading to paraplegia or quadriplegia worldwide. Neuroprotection conferred by histone deacetylase (HDAC) inhibitors against various insults and deficits in the central nervous system has been reported previously. Herein, we set out to ascertain whether HDAC3 inhibition exerts neuroprotective effects against SCI.
Very long-chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in ELOVL4 are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt-like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single-nucleotide variants.
Introduction. The acquired muscle paralysis associated with modern critical care can be of neurogenic or myogenic origin, yet the distinction between these origins is hampered by the precision of current diagnostic methods. This has resulted in the pooling of all acquired muscle paralyses, independent of their origin, into the term Intensive Care Unit Acquired Muscle Weakness (ICUAW). This is unfortunate since the acquired neuropathy (critical illness polyneuropathy, CIP) has a slower recovery than the myopathy (critical illness myopathy, CIM); therapies need to target underlying mechanisms and every patient deserves as accurate a diagnosis as possible. This study aims at evaluating different diagnostic methods in the diagnosis of CIP and CIM in critically ill, immobilized and mechanically ventilated intensive care unit (ICU) patients. Methods. ICU patients with acquired quadriplegia in response to critical care were included in the study. A total of 142 patients were examined with routine electrophysiological methods, together with biochemical analyses of myosin:actin (M:A) ratios of muscle biopsies. In addition, comparisons of evoked electromyographic (EMG) responses in direct vs. indirect muscle stimulation and histopathological analyses of muscle biopsies were performed in a subset of the patients. Results. ICU patients with quadriplegia were stratified into five groups based on the hallmark of CIM, i.e., preferential myosin loss (myosin:actin ratio, M:A) and classified as severe (M:A < 0.5; n = 12), moderate (0.5 ≤ M:A < 1; n = 40), mildly moderate (1 ≤ M:A < 1.5; n = 49), mild (1.5 ≤ M:A < 1.7; n = 24) and normal (1.7 ≤ M:A; n = 19). Identical M:A ratios were obtained in the small (4-15 mg) muscle samples, using a disposable semiautomatic microbiopsy needle instrument, and the larger (>80 mg) samples, obtained with a conchotome instrument. Compound muscle action potential (CMAP) duration was increased and amplitude decreased in patients with preferential myosin loss, but deviations from this relationship were observed in numerous patients, resulting in only weak correlations between CMAP properties and M:A. Advanced electrophysiological methods measuring refractoriness and comparing CMAP amplitude after indirect nerve vs. direct muscle stimulation are time consuming and did not increase precision compared with conventional electrophysiological measurements in the diagnosis of CIM. Low CMAP amplitude upon indirect vs. direct stimulation strongly suggest a neurogenic lesion, i.e., CIP, but this was rarely observed among the patients in this study. Histopathological diagnosis of CIM/CIP based on enzyme histochemical mATPase stainings were hampered by poor quantitative precision of myosin loss and the impact of pathological findings unrelated to acute quadriplegia. Conclusion. Conventional electrophysiological methods are valuable in identifying the peripheral origin of quadriplegia in ICU patients, but do not reliably separate between neurogenic vs. myogenic origins of paralysis. The hallmark of CIM, preferential myosin loss, can be reliably evaluated in the small samples obtained with the microbiopsy instrument. The major advantage of this method is that it is less invasive than conventional muscle biopsies, reducing the risk of bleeding in ICU patients, who are frequently receiving anticoagulant treatment, and it can be repeated multiple times during follow up for monitoring purposes.
Epidural electrical epinal cord stimulation (ESCS) is an established therapeutic option in various chronic pain conditions. In the last decade, proof-of-concept studies have demonstrated that ESCS in combination with task-oriented rehabilitative interventions can partially restore motor function and neurological recovery after spinal cord injury (SCI). In addition to the ESCS applications for improvement of upper and lower extremity function, ESCS has been investigated for treatment of autonomic dysfunction after SCI such as orthostatic hypotension. The aim of this overview is to present the background of ESCS, emerging concepts and its readiness to become a routine therapy in SCI beyond treatment of chronic pain conditions.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: