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The Journal of Clinical Investigation Jul 2022Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited demyelinating peripheral neuropathy, is caused by PMP22 gene duplication. Overexpression of WT...
Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited demyelinating peripheral neuropathy, is caused by PMP22 gene duplication. Overexpression of WT PMP22 in Schwann cells destabilizes the myelin sheath, leading to demyelination and ultimately to secondary axonal loss and disability. No treatments currently exist that modify the disease course. The most direct route to CMT1A therapy will involve reducing PMP22 to normal levels. To accomplish this, we developed a gene therapy strategy to reduce PMP22 using artificial miRNAs targeting human PMP22 and mouse Pmp22 mRNAs. Our lead therapeutic miRNA, miR871, was packaged into an adeno-associated virus 9 (AAV9) vector and delivered by lumbar intrathecal injection into C61-het mice, a model of CMT1A. AAV9-miR871 efficiently transduced Schwann cells in C61-het peripheral nerves and reduced human and mouse PMP22 mRNA and protein levels. Treatment at early and late stages of the disease significantly improved multiple functional outcome measures and nerve conduction velocities. Furthermore, myelin pathology in lumbar roots and femoral motor nerves was ameliorated. The treated mice also showed reductions in circulating biomarkers of CMT1A. Taken together, our data demonstrate that AAV9-miR871-driven silencing of PMP22 rescues a CMT1A model and provides proof of principle for treating CMT1A using a translatable gene therapy approach.
Topics: Animals; Charcot-Marie-Tooth Disease; Genetic Therapy; Mice; Myelin Proteins; Myelin Sheath; RNA Interference; RNA, Messenger; Schwann Cells
PubMed: 35579942
DOI: 10.1172/JCI159814 -
The Cochrane Database of Systematic... Jul 2017People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various... (Review)
Review
BACKGROUND
People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various names for the condition include diabetic amyotrophy, diabetic lumbosacral radiculoplexus neuropathies, diabetic femoral neuropathy or Bruns-Garland syndrome. Some studies suggest that diabetic amyotrophy may be an immune-mediated inflammatory microvasculitis causing ischaemic damage of the nerves. Immunotherapies would therefore be expected to be beneficial. This is the second update of a review first published in 2009.
OBJECTIVES
To review the evidence from randomised trials for the efficacy of any form of immunotherapy in the treatment of diabetic amyotrophy.
SEARCH METHODS
On 5 September 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We also contacted authors of relevant publications and other experts to obtain additional references, unpublished trials, and ongoing trials.
SELECTION CRITERIA
We intended to include all randomised and quasi-randomised trials of any immunotherapy in participants with the condition fulfilling all the following: diabetes mellitus as defined by internationally recognised criteria; acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs; weakness that is not confined to one nerve or nerve root distribution; and exclusion of other causes of lumbosacral radiculopathies and plexopathy.
DATA COLLECTION AND ANALYSIS
Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria.
MAIN RESULTS
We found only one completed placebo-controlled trial (N = 75) using intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results have not been fully published and were not available for analysis. The risk of bias was unclear because there was too little information to make a judgement, but we considered the trial at high risk of selective reporting. The published abstract did not report adverse events. We found no additional trials when the searches were updated in September 2016.
AUTHORS' CONCLUSIONS
There is presently no evidence from randomised trials to support a positive or negative effect of any immunotherapy in the treatment in diabetic amyotrophy.
Topics: Diabetic Neuropathies; Humans; Immunotherapy; Injections, Intravenous; Methylprednisolone; Neuroprotective Agents
PubMed: 28746752
DOI: 10.1002/14651858.CD006521.pub4 -
Ugeskrift For Laeger Apr 2020This review summarises the treatment of meralgia paraesthetica. The condition is easy to recognise clinically, and in most cases the effect of conservative treatment is... (Review)
Review
This review summarises the treatment of meralgia paraesthetica. The condition is easy to recognise clinically, and in most cases the effect of conservative treatment is good. In case of persistent symptoms, further work-up is recommended including neurophysiological testing and ultrasound examination. If surgery is decided, we recommend nerve decompression primarily, since this procedure holds a success rate of 60-70%. In case of persistent symptoms, neurectomy should be performed. Ultrasound examination immediately before surgery can be helpful in localising the nerve and shortening procedural time.
Topics: Femoral Neuropathy; Humans; Neurosurgical Procedures; Paresthesia; Thigh
PubMed: 32286209
DOI: No ID Found -
The Bone & Joint Journal Jan 2017Nerve palsy is a well-described complication following total hip arthroplasty, but is highly distressing and disabling. A nerve palsy may cause difficulty with the... (Review)
Review
Nerve palsy is a well-described complication following total hip arthroplasty, but is highly distressing and disabling. A nerve palsy may cause difficulty with the post-operative rehabilitation, and overall mobility of the patient. Nerve palsy may result from compression and tension to the affected nerve(s) during the course of the operation via surgical manipulation and retractor placement, tension from limb lengthening or compression from post-operative hematoma. In the literature, hip dysplasia, lengthening of the leg, the use of an uncemented femoral component, and female gender are associated with a greater risk of nerve palsy. We examined our experience at a high-volume, tertiary care referral centre, and found an overall incidence of 0.3% out of 39 056 primary hip arthroplasties. Risk factors found to be associated with the incidence of nerve palsy at our institution included the presence of spinal stenosis or lumbar disc disease, age younger than 50, and smoking. If a nerve palsy is diagnosed, imaging is mandatory and surgical evacuation or compressive haematomas may be beneficial. As palsies are slow to recover, supportive care such as bracing, therapy, and reassurance are the mainstays of treatment. Cite this article: Bone Joint J 2017;99-B(1 Supple A):46-9.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Bone Lengthening; Disease Management; Female; Femoral Neuropathy; Humans; Incidence; Male; Middle Aged; Peripheral Nervous System Diseases; Prognosis; Risk Factors; Sciatic Neuropathy; Young Adult
PubMed: 28042118
DOI: 10.1302/0301-620X.99B1.BJJ-2016-0430.R1 -
Deutsches Arzteblatt International Sep 2023Pain and sensory disturbance in the distribution of the lateral femoral cutaneous nerve in the ventrolateral portion of the thigh is called meralgia paresthetica (MP).... (Review)
Review
BACKGROUND
Pain and sensory disturbance in the distribution of the lateral femoral cutaneous nerve in the ventrolateral portion of the thigh is called meralgia paresthetica (MP). The incidence of MP has risen along with the increasing prevalence of obesity and diabetes mellitus and was recently estimated at 32 new cases per 100 000 persons per year. In this review, we provide an overview of current standards and developments in the diagnosis and treatment of MP.
METHODS
This review is based on publications retrieved by a selective literature search, with special attention to meta-analyses, systematic reviews, randomized and controlled trials (RCTs), and prospective observational studies.
RESULTS
The diagnosis is mainly based on typical symptoms combined with a positive response to an infiltration procedure. In atypical cases, electrophysiological testing, neurosonography, and magnetic resonance imaging can be helpful in establishing the diagnosis. The literature search did not reveal any studies of high quality. Four prospective observational studies with small case numbers and partly inconsistent results are available. In a meta-analysis of 149 cases, pain relief was described after infiltration in 85% of cases and after surgery in 80%, with 1-38 months of follow-up. In another meta-analysis of 670 cases, there was pain relief after infiltration in 22% of cases, after surgical decompression in 63%, and after neurectomy in 85%. Hardly any data are available on more recent treatment options, such as radiofrequency therapy, spinal cord stimulation, or peripheral nerve stimulation.
CONCLUSION
The state of the evidence is limited in both quantity and quality, corresponding to evidence level 2a for surgical and non-surgical methods. Advances in imaging and neurophysiological testing have made the diagnosis easier to establish. When intervention is needed, good success rates have been achieved with surgery (decompression, neurectomy), and variable success rates with infiltration.
Topics: Humans; Decompression, Surgical; Femoral Neuropathy; Nerve Compression Syndromes; Observational Studies as Topic; Pain; Thigh
PubMed: 37534445
DOI: 10.3238/arztebl.m2023.0170 -
Neurosurgical Focus: Video Jan 2023Lateral femoral cutaneous neuropathy, also known as meralgia paresthetica, is a pathology commonly encountered by neurosurgeons. Symptoms include numbness, tingling, and...
Lateral femoral cutaneous neuropathy, also known as meralgia paresthetica, is a pathology commonly encountered by neurosurgeons. Symptoms include numbness, tingling, and burning pain over the anterolateral thigh due to impingement on the lateral femoral cutaneous nerve (LFCN). Surgical treatment has traditionally involved nerve release or neurectomy. LFCN transposition is a relatively new approach that can provide excellent symptomatic relief. In this video, the authors highlight key operative techniques to ensure easy identification, adequate decompression, and transposition of the nerve. Key steps include ultrasound-guided wire localization, superficial decompression, opening of the inguinal ligament, deep decompression, and medial transposition. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2289.
PubMed: 36628093
DOI: 10.3171/2022.10.FOCVID2289 -
Neurology India 2016
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World Journal of Hepatology May 2015Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis (primarily necrosis of the femoral head), but the... (Review)
Review
Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis (primarily necrosis of the femoral head), but the main alterations observed in the bones of alcoholic patients are osteoporosis and an increased risk of fractures. Decreased bone mass is a hallmark of osteoporosis, and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanol may affect both mechanisms. It is generally accepted that ethanol decreases bone synthesis, and most authors have reported decreased osteocalcin levels (a "marker" of bone synthesis), but some controversy exists regarding the effect of alcohol on bone breakdown, and, indeed, disparate results have been reported for telopeptide and other biochemical markers of bone resorption. In addition to the direct effect of ethanol, systemic alterations such as malnutrition, malabsorption, liver disease, increased levels of proinflammatory cytokines, alcoholic myopathy and neuropathy, low testosterone levels, and an increased risk of trauma, play contributory roles. The treatment of alcoholic bone disease should be aimed towards increasing bone formation and decreasing bone degradation. In this sense, vitamin D and calcium supplementation, together with biphosphonates are essential, but alcohol abstinence and nutritional improvement are equally important. In this review we study the pathogenesis of bone changes in alcoholic liver disease and discuss potential therapies.
PubMed: 26019741
DOI: 10.4254/wjh.v7.i9.1258 -
Cureus Sep 2022The posterior femoral cutaneous nerve (PFCN) is an extensive nerve with numerous collateral branches which provide cutaneous innervation to 2/3 of the posterior thigh,...
The posterior femoral cutaneous nerve (PFCN) is an extensive nerve with numerous collateral branches which provide cutaneous innervation to 2/3 of the posterior thigh, the infragluteal fold, as well as the lateral anal region, scrotum, and labia majora through its inferior cluneal and pudendal nerve branches. It has been noted in multiple studies that patients can experience persistent PFCN neuropathy after surgery for decompression of known collateral branches. In this study, we used 17 formaldehyde (7 male and 10 female) perfused cadavers obtained from Hershey Medical Center's donor program to study the branching patterns of the PFCN. As a result, we found that 41% of individuals have an unidentified proximal branch of PFCN that recurs over the inferolateral border of the gluteus maximus, suggesting other areas of potential compression or nerve entrapment that could lead to persistent PFCN neuropathy that's not improved after treatment for sciatic, pudendal, or inferior cluneal neuralgia. We hope these findings allow clinicians to modify current surgical techniques and improve patients' post-operative quality of life.
PubMed: 36299977
DOI: 10.7759/cureus.29447