-
Communications Medicine Jun 2024Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence...
BACKGROUND
Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence has not been well-characterized in most Arab countries where rates of consanguinity are high. Understanding SMA disease epidemiology has important implications for screening, prevention, and treatment in those populations.
METHODS
We perform SMA diagnostic testing in a clinical multi-national patient cohort (N = 171) referred for hypotonia and/or muscle weakness. In addition, we carry out genetic newborn screening for SMA on 1502 healthy Emirati newborns to estimate the carrier frequency and incidence of the disease in the United Arab Emirates.
RESULTS
Patients referred for SMA genetic testing are mostly Arabs (82%) representing 18 countries. The overall diagnostic yield is 33.9%, which is higher (>50%) for certain nationalities. Most patients (71%) has two SMN2 copies and earlier disease onset. For the first time, we estimate SMA carrier frequency (1.3%) and incidence of the disease (1 in 7122 live births) in the United Arab Emirates. Using birth and marriage rates in two Arab populations (United Arab Emirates and Saudi Arabia), as well as disease incidence in both countries, we show that, besides preventing new cases, premarital genetic screening could potentially result in around $8 to $324 million annual cost savings, respectively, relative to postnatal treatment.
CONCLUSIONS
The SMA carrier frequency and incidence we document suggests high potential benefit for universal implementation of premarital genomic screening for a wide range of recessive disorders in Arab populations.
PubMed: 38879606
DOI: 10.1038/s43856-024-00548-1 -
Arthritis Research & Therapy Jun 2024Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at...
Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons.
BACKGROUND
Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis.
METHODS
We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells.
RESULTS
Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1β and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia-astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells.
CONCLUSIONS
Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain.
Topics: Animals; Azetidines; Sulfonamides; Pyrazoles; STAT3 Transcription Factor; Purines; Arthritis, Experimental; Ganglia, Spinal; Neuralgia; Janus Kinases; Signal Transduction; Mice; Interleukin-6; Male; Neurons; Mice, Inbred DBA; Inflammation; Janus Kinase Inhibitors
PubMed: 38879555
DOI: 10.1186/s13075-024-03354-1 -
Journal of the Korean Society of... May 2024Recent studies have demonstrated the usefulness of diffusion-weighted MR neurography (DW MRN) for assessing nerve roots. This study aimed to evaluate the utility of DW...
PURPOSE
Recent studies have demonstrated the usefulness of diffusion-weighted MR neurography (DW MRN) for assessing nerve roots. This study aimed to evaluate the utility of DW MRN with a unidirectional motion-probing gradient (MPG) for the lumbar nerve roots at 1.5T MR.
MATERIALS AND METHODS
Sixty-four lumbar spine MRI scans with DW MRN using anteroposterior unidirectional MPG were retrospectively analyzed. Any changes in the 512 lumbar spinal nerve roots from L3 to S1 were evaluated using T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CE T1WI), and DW MRN, with agreement and correlation analysis.
RESULTS
T2WI revealed compression of 78 nerve roots, and CE T1WI revealed 52 instances of nerve root enhancement. Sixty-seven nerve roots showed swelling and hyperintensity on DW MRN. A total of 42 nerve roots showed changes in the CE T1WI and DW MRN sequences. Moderate to substantial agreement and moderate positive correlation were observed between DW MRN and CE T1WI, as well as DW MRN and T2WI (κ = 0.59-0.65, ρ = 0.600-0.653).
CONCLUSION
DW MRN with unidirectional anteroposterior MPG can help evaluate neuritis-related changes in spinal nerve roots and could serve as a sequence capable of complementing or substituting gadolinium CE imaging.
PubMed: 38873379
DOI: 10.3348/jksr.2023.0052 -
Frontiers in Neurology 2024To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury...
OBJECTIVE
To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).
METHODS
Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.
STUDY SELECTION
Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.
DATA EXTRACTION
Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.
DATA SYNTHESIS
Twenty-nine studies were included; 11 were animal models of stroke, TBI, and SCI, and eight involved humans with stroke. While there was heterogeneity in methods of delivering VNS with respect to rehabilitation therapy in animal studies and human non-invasive studies, a similar methodology was used in all human-invasive VNS studies. In animal studies, pairing VNS with rehabilitation therapy consistently improved motor outcomes compared to controls. Except for one study, all human invasive and non-invasive studies with controls demonstrated a trend toward improvement in motor outcomes compared to sham controls post-intervention. However, compared to non-invasive, invasive VNS, studies reported severe adverse events such as vocal cord palsy, dysphagia, surgical site infection, and hoarseness of voice, which were found to be related to surgery.
CONCLUSION
Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans. Hence, VNS human studies are needed in these populations (referring to SCI and TBI?) or just SCI. There are risks related to device implantation to deliver invasive VNS compared to non-invasive VNS. Future human comparison studies are required to study and quantify the efficacy vs. risks of paired VNS delivered via different methods with rehabilitation, which would allow patients to make an informed decision.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330653.
PubMed: 38872818
DOI: 10.3389/fneur.2024.1390217 -
BMC Musculoskeletal Disorders Jun 2024Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital... (Review)
Review
BACKGROUND
Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review.
METHODS
The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases.
RESULTS
In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases.
CONCLUSION
Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.
Topics: Humans; Male; Female; Middle Aged; Adult; Ulnar Nerve Compression Syndromes; Ulnar Nerve; Electromyography; Crush Syndrome; Wrist; Neural Conduction; Elbow; Treatment Outcome; Aged
PubMed: 38872094
DOI: 10.1186/s12891-024-07574-z -
National Science Review Jun 2024Dural defects and subsequent complications, including cerebrospinal fluid (CSF) leakage, are common in both spine surgery and neurosurgery, and existing clinical...
Dural defects and subsequent complications, including cerebrospinal fluid (CSF) leakage, are common in both spine surgery and neurosurgery, and existing clinical treatments are still unsatisfactory. In this study, a tissue-adhesive and low-swelling hydrogel sealant comprising gelatin and -phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) is developed via the OPA/amine condensation reaction. The hydrogel shows an adhesive strength of 79.9 ± 12.0 kPa on porcine casing and a burst pressure of 208.0 ± 38.0 cmHO. The hydrogel exhibits a low swelling ratio at physiological conditions, avoiding nerve compression in the limited spinal and intracranial spaces. In rat and rabbit models of lumbar and cerebral dural defects, the 4aPEG-OPA/gelatin hydrogel achieves excellent performance in dural defect sealing and preventing CSF leakage. Moreover, local inflammation, epidural fibrosis and postoperative adhesion in the defect areas are markedly reduced. Thus, these findings establish the strong potential of the hydrogel sealant for the effective watertight closure of dural defects.
PubMed: 38867893
DOI: 10.1093/nsr/nwae160 -
Scientific Reports Jun 2024Whilst pharmacological therapies remain the cornerstone of pain management in chronic pain, factors including the current opioid epidemic have led to non-pharmacological... (Meta-Analysis)
Meta-Analysis
Whilst pharmacological therapies remain the cornerstone of pain management in chronic pain, factors including the current opioid epidemic have led to non-pharmacological techniques becoming a more attractive proposition. We explored the prevalence of medical device use and their treatment efficacy in non-cancer pain management. A systematic methodology was developed, peer reviewed and published in PROSPERO (CRD42021235384). Key words of medical device, pain management devices, chronic pain, lower back pain, back pain, leg pain and chronic pelvic pain using Science direct, PubMed, Web of Science, PROSPERO, MEDLINE, EMBASE, PorQuest and ClinicalTrials.gov. All clinical trials, epidemiology and mixed methods studies that reported the use of medical devices for non-cancer chronic pain management published between the 1st of January 1990 and the 30th of April 2022 were included. 13 studies were included in systematic review, of these 6 were used in the meta-analysis. Our meta-analysis for pain reduction showed that transcutaneous electrical nerve stimulation combined with instrument-assisted soft tissue mobilization treatment and pulsed electromagnetic therapy produced significant treatment on chronic lower back pain patients. Pooled evidence revealed the use of medical device related interventions resulted in 0.7 degree of pain reduction under a 0-10 scale. Significant improvement in disability scores, with a 7.44 degree reduction in disability level compared to a placebo using a 50 score range was also seen. Our analysis has shown that the optimal use of medical devices in a sustainable manner requires further research, needing larger cohort studies, greater gender parity, in a more diverse range of geographical locations.
Topics: Humans; Chronic Pain; Pain Management; Bayes Theorem; Low Back Pain; Transcutaneous Electric Nerve Stimulation; Equipment and Supplies; Treatment Outcome
PubMed: 38866854
DOI: 10.1038/s41598-024-63499-6 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jun 2024This study compares the efficacy and safety of lateral approach surgery with and without radial nerve dissection in treating humeral diaphyseal fractures. It assesses...
BACKGROUND
This study compares the efficacy and safety of lateral approach surgery with and without radial nerve dissection in treating humeral diaphyseal fractures. It assesses clinical, radiological, and complication outcomes, providing a description of the surgical methods and perioperative benefits.
METHODS
We retrospectively analyzed data from 71 patients admitted between May 2015 and December 2022 who underwent lateral approach surgery for humeral diaphyseal fractures. Group 1, consisting of 34 patients without radial nerve dissection, and Group 2, comprising 37 patients with radial nerve dissection, were compared. Parameters such as age, gender, fracture side (right/left), fracture type, follow-up time, surgical duration, blood loss, radiological and clinical evaluations (including Shoulder-Elbow range of motion [ROM] and Quick Disabilities of the Arm, Shoulder, and Hand score [Q-DASH]), and complications were examined. Surgical techniques and outcomes were documented.
RESULTS
Both groups exhibited comparable distributions in age, gender, fracture types, and follow-up times (p>0.05). Group 1 demonstrated significantly lower surgical duration and blood loss compared to Group 2 (p<0.05 for both). Clinical assessment revealed satisfactory shoulder and elbow ROM within functional limits for all patients, with no instances of infection. Q-DASH scores were similar between groups. Postoperative radial nerve palsy occurred in one patient in Group 1 and three patients in Group 2, with all cases resolving uneventfully during outpatient follow-ups. Radiological assessment confirmed uneventful union in all patients.
CONCLUSION
Lateral approach surgery without radial nerve dissection for humeral diaphyseal fractures offers comparable effectiveness and safety to conventional surgery, with potential perioperative advantages such as reduced operation time and blood loss.
Topics: Humans; Male; Female; Humeral Fractures; Retrospective Studies; Adult; Radial Nerve; Middle Aged; Fracture Fixation, Internal; Range of Motion, Articular; Treatment Outcome; Diaphyses; Young Adult
PubMed: 38863290
DOI: 10.14744/tjtes.2024.49500 -
Frontiers in Neurology 2024To observe changes in the cauda equina nerve on lumbar MRI in patients with central lumbar spinal stenosis (LSS).
BACKGROUND
To observe changes in the cauda equina nerve on lumbar MRI in patients with central lumbar spinal stenosis (LSS).
METHODS
878 patients diagnosed with LSS by clinical and MRI were divided into the redundant group (204 patients) and the nonredundant group (674 patients) according to the presence or absence of redundant nerve roots (RNRs). The anteroposterior diameter of the spinal canal (APDS) and the presence of multiple level stenosis, disc herniation, thickening of ligamentum flavum (LF) and increased epidural fat were assessed on MRI. Univariate and multivariate logistic regression analyses were performed to explore the predictors of LSS combined with RNRs.
RESULTS
Patients with LSS combined with RNRs had thicker epidural fat, smaller APDS and more combined multifaceted stenosis. Female patients and older LSS patients were more likely to develop RNRs; there was no difference between two groups in terms of disc herniation ( > 0. 05). Age, APDS, multiple level stenosis, and increased epidural fat were significantly correlated with the formation of LSS combined with RNRs ( < 0.05).
CONCLUSION
A smaller APDS and the presence of multiple level stenosis, thickening of LF, and increased epidural fat may be manifestations of anatomical differences in patients with LSS combined with RNRs. Age, APDS, multiple level stenosis, and increased epidural fat play important roles. The lumbar spine was measured and its anatomy was observed using multiple methods, and cauda equina changes were assessed to identify the best anatomical predictors and provide new therapeutic strategies for the management of LSS combined with RNRs.
PubMed: 38859971
DOI: 10.3389/fneur.2024.1385770 -
Neurology Perspectives 2024Myeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous,...
INTRODUCTION
Myeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous, even for the most consummate clinicians, because symptomatology can mimic either spinal cord or peripheral nerve disease. Besides, examination findings suggest a predominantly myelopathic or neuropathic picture. This article reports a rendezvous of rare cases of clinically diagnosed myeloneuropathy with different etiological backgrounds and therapeutic responses.
METHODS
Eleven cases of non-compressive myeloneuropathy were admitted to the Department of General Medicine of Burdwan Medical College and Hospital, Burdwan, West Bengal, India, between May 2018 and May 2022.
RESULTS
We report the cases of 11 patients (6 men and 5 women) who presented with myeloneuropathy of different etiologies (vitamin B12, copper, and vitamin E deficiencies, organophosphate poisoning, chronic alcohol abuse, illicit substances abuse, anti-thyroid peroxidase/anti-thyroglobulin antibody-related neurologic disorder responsive to steroids, Sjögren syndrome, chikungunya infection, paraneoplastic, and hereditary).
CONCLUSION
Meticulous historical analysis, careful clinical examination, and apposite utilization and interpretation of biochemical, electrophysiological, and neuroimaging findings are sine-qua-non for an accurate and consistent approach to evaluating a suspected case of myeloneuropathy, facilitating early treatment and recovery. Differential identification of these disorders needs an in-depth perception of the mode of onset of symptoms, the course of progression of the disease, the pattern of myelopathic/neuropathic findings, and recognition of other neurological or systemic manifestations. For untroubled understanding, etiologies of myeloneuropathies should be subdivided into a few broad categories, e.g., metabolic (nutritional), toxic (toxin-induced), infectious, inflammatory (immune-mediated), paraneoplastic, and hereditary disorders.
PubMed: 38859960
DOI: 10.1016/j.neurop.2023.100138