Sural Nerve Research Articles

A Young Man With Hereditary Motor And Sensory Neuropathy: A Rare Genetic Association

Hereditary motor and sensory neuropathies with early onset are uncommon conditions that include Dejerine-Sottas neuropathy, which begins in infancy, and congenital hypomyelinating neuropathy, which manifests in the early postnatal period. However, these two historically defined disease entities are only small parts of the clinical spectrum. It is well recognized that very early onset hereditary neuropathies are frequently caused by de novo dominant mutations in PMP22, MPZ, and EGR2. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. A 20-year-old boy had complaints of weakness of both lower limbs for 1 year, followed by wasting and foot drop, which subsequently involved the upper limbs. Nerve conduction velocity and electromyography of both lower limbs revealed demyelinating sensory motor polyneuropathy. Histological examination of the sural nerve revealed a nerve trunk with perineural soft tissue, with the nerve bundles being irregular and separated by fibrous tissue bands. The later reveals small perivascular infiltration of chronic inflammatory cells, and no granuloma or AFB is seen. The genetic test of whole exome screening for heriditatory neuropathy showed pathogenic (PM2, PVS, PP5) with a gene impact of (NF2: c.363+1G>T), which is a rare entity in our case study to consider the diagnosis despite negative family history. We highlight this rare disease in young man with a high index of clinical suspicion for its diagnosis. Bangladesh J Medicine 2024; 35: 101-105

Frequent Sural Nerve Injury with Posterior Approach for Ankle Fracture Fixation

Introduction: The purpose of this study was to report the incidence of iatrogenic sural nerve injury in a large, consecutive sample of surgically managed ankle fractures and to identify factors associated with sural nerve injury and subsequent recovery. We hypothesize that a direct posterior approach may be associated with higher risk of iatrogenic sural nerve injury. Methods: A retrospective cohort study of 265 skeletally mature patients who sustained ankle fractures over a 2-year period was done. All were treated with open reduction and internal fixation of fractured malleoli. Patient, injury, and treatment features were documented. The presence (n = 26, 9.8%) of sural nerve injury and recovery of sural nerve function were noted. Results: All 26 sural nerve injuries were iatrogenic, occurring postoperatively after open reduction and internal fixation. Patients who sustained sural nerve injuries had more ankle fractures secondary to motor vehicle collisions (23.1% versus 9.2%), more associated trimalleolar fractures (69.2% versus 33.9%), and more Orthopaedic Trauma Association/AO 44B3 fractures (57.7% versus 25.1%), all P < 0.05. A posterior approach to the posterior malleolus through the prone position was used in 20.4% of patients. All 26 of the sural nerve injuries (100%) occurred when the patient was placed prone for a posterior approach, P < 0.001. Therefore, 26 of the 54 patients (48%) treated with a posterior approach sustained an iatrogenic sural nerve injury. 62% of patients had full recovery of sural nerve function with no residual numbness, and patients with nerve recovery had fewer associated fracture-dislocations (23.1% versus 100%, P = 0.003). Conclusions: A posterior approach for posterior malleolus fixation was associated with a 48% iatrogenic sural nerve injury rate, with 62% recovering full function within 6 months of injury. Morbidity of this approach should be considered, and surgeons should be cautious with nerve handling. Level of Evidence: Level III, Therapeutic.

Proximal Medial Gastrocnemius Recession for Recalcitrant Plantar Fasciitis.

Recalcitrant plantar fasciitis (RPF) is characterized by its unresponsiveness to conservative treatments, and its surgical management remains controversial. Although there is some evidence to suggest that gastrocnemius recession can be an effective treatment for RPF, no large series of patients with mid- to long-term follow-up has been published. The objective of this study was to compare physical performance, as measured by the Foot and Ankle Ability Measure activities of daily living score (FAAM-ADL), and pain levels before and 1 year after undergoing proximal medial gastrocnemius recession (PMGR) as a treatment for RPF. Additionally, we aimed to assess this cohort of patients in the mid- to long-term follow-up. This retrospective cohort study included 167 patients who underwent PMGR to address RPF between 2009 and 2021. Patients were examined with the FAAM ADL, visual analog scale (VAS) and satisfaction scores at baseline, 1 year, and at the end of follow-up. Other variables recorded were weight, duration of symptoms until surgery, time between surgery to substantial clinical improvement, calf power and Silfverskiold test, and postoperative complications. We observed that before surgery patients had an FAAM-ADL score of 22.5 (SD 11.1) and a VAS score of 8.6 (SD 9.3). One year after surgery, patients had an FAAM-ADL score of 89 (SD 17) and VAS of 1.33 (SD 2) (P < .01). We also observed that the FAAM-ADL score in the long-term follow-up (>12.5 years) group had a median of 86.4 (SD 22.6), the VAS score was 1.90 (SD 2.84), and the patient satisfaction score had a median of 1 (interquartile range 0-1). Regarding complications, we observed 1 lateral gastrocnemius recession and 1 sural nerve neuritis. Our study provides substantial evidence supporting the use of PMGR as an effective treatment for RPF. The long-term follow-up and large sample size of our series contribute to the existing literature on this topic. Level IV, case series.

[Postoperative effect analysis of different surgical techniques used in facial nerve reconstruction].

Objective:To investigate the factors and efficacy of different surgical techniques used in facial nerve（FN） reconstruction. Methods:A retrospective analysis was conducted on 24 patients who underwent facial nerve reconstruction surgery in our department from January 2016 to January 2021. The duration of total facial nerve paralysis was less than 18 months. The study included 5 surgical techniques, including 6 cases of FN anastomosis（Group A）, 5 cases of FN grafting（sural nerve or great auricular nerve）（Group B）, 5 cases of side-to-end facial-hypoglossal nerve anastomosis（Group C）, 4 cases of side-to-end FN grafting（sural nerve or great auricular nerve） hypoglossal nerve anastomosis（Group D）, and 4 cases of dual nerve reanimation（Group E）. The postoperative follow-up period was ≥1 year. Results:The HB-Ⅲ level of FN function at 1 year after surgery was 83.3%（5/6） in group A, 60.0%（3/5） in group B, 40.0%（2/5） in group C, 25.0%（1/4） in group D, and 50.0%（2/4） in group E. In patients without multiple FN repair, the incidence of synkinesis was 15.0%（3/20）, while no cases of synkinesis were observed in patients with dual nerve reanimation. The patients who underwent hypoglossal-facial side-to-end anastomosis showed no hypoglossal nerve dysfunction. Conclusion:Different FN repair techniques result in varying postoperative FN function recovery, as personalized repair should be managed. Among the various techniques, FN end-to-end anastomosis after FN transposition is recommended as to reduce the number of anastomotic stoma, while hypoglossal-facial side-to-end anastomosis is advocated as to prevent postoperative hypoglossal nerve dysfunction. Additionally, dual nerve repair can effectively improve smile symmetry and reduce synkinesis, which enhances patients' quality.

Anti-Myelin-associated Glycoprotein Neuropathy

Anti-myelin-associated glycoprotein (MAG) neuropathy, which occurs secondary to immunoglobulin (Ig)M paraproteinemia such as monoclonal gammopathy of undetermined significance, is characterized by slow progression, sensory or sensorimotor disturbances, and ataxia. The estimated prevalence of this neuropathy in Japan is 0.28 per 100,000 population with male preponderance. This neuropathy is diagnosed based on the detection of M protein and anti-MAG antibodies in patients' serum. Nerve conduction studies show prolonged distal latency, and histopathological evaluation of sural nerve biopsies shows widely spaced myelin on electron microscopy. Usually, immunotherapy, including administration of intravenous Ig and corticosteroids, is ineffective, and rituximab is beneficial in approximately 50% of patients. Novel therapies, such as administration of Bruton's tyrosine kinase inhibitors are expected to benefit patients with the MYD88L265P mutation.

Glycemic variability is associated with sural nerve conduction velocity in outpatients with type2diabetes: Usefulness of a new point-of-care device for nerve conduction studies.

Although several studies have shown the association between continuous glucose monitoring (CGM)-derived glycemic variability (GV) and diabetic peripheral neuropathy, no studies have focused on outpatients or used NC-stat®/DPNCheck™, a new point-of-care device for nerve conduction study (NCS). We investigated the association between CGM-derived GV and NCS using DPNCheck™ in outpatients with type 2 diabetes, and further analyzed the difference in results between patients with and without well-controlled HbA1c levels. All outpatients with type 2 diabetes using the CGM device (FreeStyle Libre Pro®) between 2017 and 2022 were investigated. Sural nerve conduction was evaluated by sensory nerve action potential (SNAP) amplitude and sensory conduction velocity (SCV) using DPNCheck™. Associations of CGM-derived GV metrics with SNAP amplitude and SCV were investigated. In total, 304 outpatients with type 2 diabetes were included. In a linear regression model, most CGM-derived GV metrics except for the mean amplitude of glucose excursion and low blood glucose index were significantly associated with SCV, but not with SNAP amplitude. The significant associations of most CGM-derived GV metrics with SCV remained after adjustment for possible confounding factors, but not after adjustment for glycated hemoglobin (HbA1c). Most CGM-derived GV metrics were significantly associated with SCV after adjustment for HbA1c in patients with a HbA1c ≤ 6.9%, but not in those with a HbA1c ≥ 7.0%. In outpatients with type 2 diabetes, multiple CGM-derived GV metrics were significantly associated with SCV obtained by DPNCheck™. GVmay have independent impacts on peripheral nerve function, particularly in patients with well-controlled HbA1c levels.

High serum levels of CCL11/Eotaxin-1 are associated with diabetic sensorimotor polyneuropathy and peripheral nerve function but not with cardiac autonomic neuropathy in people with type 2 diabetes

ABSTRACT Aims To investigate whether higher serum CCL11/Eotaxin-1, a biomarker for aging and neurodegenerative and neuroinflammatory disorders, is associated with diabetic sensorimotor polyneuropathy (DSPN), peripheral nerve dysfunction, and cardiac autonomic neuropathy in people with type 2 diabetes. Methods This cross-sectional study included 106 patients with type 2 diabetes and 40 healthy controls, matched for the age and sex distribution of the diabetes group as a whole. The CC chemokines CCL11/Eotaxin-1 and CCL22/MDC were measured in fasting serum samples. DSPN and peripheral nerve function were assessed by neurological examination and nerve conduction studies, and cardiac autonomic function, by heart rate variability (HRV) and corrected QT (QTc) time. The cardio-ankle vascular index (CAVI) was measured as a marker for arterial stiffness Results Serum CCL11/Eotaxin-1 levels were significantly higher in diabetic patients than in healthy controls (183 ± 63.5 vs. 113.1 ± 38.5 pg/ml, p < 0.001), but serum CCL22/MDC levels were not significantly different between the two groups. In the diabetes group, the serum CCL11/Eotaxin-1 level was positively correlated with ulnar and sural nerve conduction velocities (p = 0.0009, p = 0.0208, respectively) and sensory nerve action potential (p = 0.0083), and CAVI (p = 0.0005), but not with HRV indices or QTc time, and serum CCL22/MDC was not significantly correlated with any indices of nerve conduction. In a model adjusted for age and duration of diabetes, serum CCL11/Eotaxin-1 was still associated with ulnar nerve conduction velocity (p = 0.02124). Serum CCL11/Eotaxin-1, but not CCL22/MDC, was significantly higher in patients with than in those without DSPN (208.2 ± 71.6 vs. 159.1 ± 45.1 pg/ml, respectively; p < 0.0001). Conclusions Serum CCL11/Eotaxin-1 is elevated in patients with DSPN and is associated with peripheral nerve dysfunction, in particular sensory nerve conduction velocity, suggesting that serum CCL11/Eotaxin 1 May be a potential biomarker for DSPN. Clinical Trial Registration University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000040631).

Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.

Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP- donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Contemporary prevalence of diabetic neuropathies in individuals with type 1 and type 2 diabetes in a Danish tertiary outpatient clinic

BackgroundPopulation-based prevalence estimates of distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN) are scares. Here we present neuropathy estimates and describe their overlap in a large cohort of people with type 1 and type 2 diabetes. MethodsIn a large population of outpatient participants, DPN was assessed using vibration perception threshold, sural nerve function, touch, pain and thermal sensation. Definite DPN was defined by the Toronto Consensus Criteria. Painful DPN was defined by Douleur Neuropathique 4 Questions. DAN measures were: cardiovascular reflex tests, electrochemical skin conductance, and gastroparesis cardinal symptom index. ResultsWe included 822 individuals with type 1 (mean age (±SD) 54 ± 16 years, median [IQR] diabetes duration 26 [15–40] years) and 899 with type 2 diabetes (mean age 67 ± 11 years, median diabetes duration 16 [11−22] years).Definite DPN was prevalent in 54 % and 68 %, and painful DPN was in 5 % and 15 % of type 1 and type 2 participants, respectively. The prevalence of DAN varied between 6 and 39 % for type 1 and 9–49 % for type 2 diabetes. DPN without other neuropathy was present in 45 % with T1D and 50 % with T2D. ConclusionThe prevalence of DPN and DAN was high. DPN and DAN co-existed in only 50 % of cases.

Peripheral Nerve Stimulation in Postoperative Analgesia: A Narrative Review.

Recent research has shown the effectiveness of peripheral nerve stimulators (PNS) in managing chronic pain conditions. Ongoing studies aim to explore its potential application in treating acute postoperative pain states. The purpose of this systematic review is to assess the role of PNS in providing relief for postoperative pain. Clinical studies investigating the use of peripheral nerve stimulators (PNS) for analgesia following various surgeries, such as total knee arthroplasty, anterior cruciate ligament repair, ankle arthroplasty, rotator cuff repair, hallux valgus correction, and extremity amputation, have shown promising results. Lead placement locations include the brachial plexus, sciatic, femoral, tibial, genicular, perineal, sural, radial, median, and ulnar nerves. These studies consistently report clinically significant reductions in pain scores, and some even indicate a decrease in opioid consumption following PNS for postoperative pain. PNS involves the subcutaneous placement of electrode leads to target peripheral nerve(s) followed by delivery of an electric current via an external pulse generator. While the precise mechanism is not fully understood, the theory posits that PNS modulates electrical stimulation, hindering the signaling of nociceptive pain. PNS presents itself as an alternative to opioid therapy, holding promise to address the opioid epidemic by offering a nonpharmacologic approach for both acute and chronic pain states.

The Hexokinase 1 5'-UTR Mutation in Charcot-Marie-Tooth 4G Disease Alters Hexokinase 1 Binding to Voltage-Dependent Anion Channel-1 and Leads to Dysfunctional Mitochondrial Calcium Buffering.

Demyelinating Charcot-Marie-Tooth 4G (CMT4G) results from a recessive mutation in the 5'UTR region of the Hexokinase 1 (HK1) gene. HK participates in mitochondrial calcium homeostasis by binding to the Voltage-Dependent Anion Channel (VDAC), through its N-terminal porin-binding domain. Our hypothesis is that CMT4G mutation results in a broken interaction between mutant HK1 and VDAC, disturbing mitochondrial calcium homeostasis. We studied a cohort of 25 CMT4G patients recruited in the French gypsy population. The disease was characterized by a childhood onset, an intermediate demyelinating pattern, and a significant phenotype leading to becoming wheelchair-bound by the fifth decade of life. Co-IP and PLA studies indicated a strong decreased interaction between VDAC and HK1 in the patients' PBMCs and sural nerve. We observed that either wild-type HK1 expression or a peptide comprising the 15 aa of the N-terminal wild-type HK1 administration decreased mitochondrial calcium release in HEK293 cells. However, mutated CMT4G HK1 or the 15 aa of the mutated HK1 was unable to block mitochondrial calcium release. Taken together, these data show that the CMT4G-induced modification of the HK1 N-terminus disrupts HK1-VDAC interaction. This alters mitochondrial calcium buffering that has been shown to be critical for myelin sheath maintenance.

Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice.

Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer from peripheral neuropathy. Nerve fiber loss in DN occurs due to myelin defects and is characterized by symptoms of impaired nerve function. Schwann cells (SCs) are the main support cells of the peripheral nervous system and play important roles in several pathways contributing to the pathogenesis and development of DN. We previously reported that human tonsil-derived mesenchymal stem cells differentiated into SCs (TMSC-SCs), named neuronal regeneration-promoting cells (NRPCs), which cells promoted nerve regeneration in animal models with peripheral nerve injury or hereditary peripheral neuropathy. In this study, NRPCs were injected into the thigh muscles of BKS-db/db mice, a commonly used type 2 diabetes model, and monitored for 26weeks. Von Frey test, sensory nerve conduction study, and staining of sural nerve, hind foot pad, dorsal root ganglia (DRG) were performed after NRPCs treatment. Von Frey test results showed that the NRPC treatment group (NRPC group) showed faster responses to less force than the vehicle group. Additionally, remyelination of sural nerve fibers also increased in the NRPC group. After NRPCs treatment, an improvement in response to external stimuli and pain sensation was expected through increased expression of PGP9.5 in the sole and TRPV1 in the DRG. The NRPCs treatment may alleviate DN through the remyelination and the recovery of sensory neurons, could provide a better life for patients suffering from complications of this disease.

Corneal Neurotization for Neurotrophic Keratopathy: A Multicentre Experience.

Corneal neurotization is an emerging technique that offers potential for visual rehabilitation in neurotrophic keratopathy. This study reports on a multicenter experience and outcomes for both direct and indirect methods of corneal neurotization. Retrospective case series. Sixteen patients with neurotrophic keratopathy who underwent corneal neurotization across 5 centers in Australia and Israel were identified for inclusion. Corneal neurotization was performed via direct neurotization from the ipsilateral or contralateral supraorbital/supratrochlear nerve or by the use of an interpositional sural nerve graft. Change in corneal sensitivity (measured in millimeters by the Cochet-Bonnet aesthesiometer), visual acuity, and corneal health. Over a mean follow-up period of 31.3 months (range: 3 months-8 years), mean corneal sensitivity improved from 3.6 mm (range: 0-25 mm) to 25.3 mm (range: 0-57 mm). Visual acuity improved on average from 20/380 to 20/260. Twelve of 16 patients (75.0%) improved in at least 2 out of the 3 main outcome measures. Nine patients (56.3%) showed an improvement in visual acuity; 13 (81.3%) showed an improvement in average corneal sensitivity; and 11 (68.8%) showed an improvement in corneal health. There were no intraoperative or postoperative complications. Corneal neurotization is an emerging surgical treatment option for the management of neurotrophic keratopathy. With appropriate case selection, outcomes are favorable and complication rates are low, for a condition that is otherwise challenging to manage. Patients with severe neurotrophic keratopathy should be considered for this surgical treatment option.

Analgesic effect of a cholinergic agonist (carbachol) in a sural nerve ligation-induced hypersensitivity mouse model

ABSTRACT Objectives Neuropathic pain is characterized by long-lasting, intractable pain. Sciatic nerve ligation is often used as an animal model of neuropathic pain, and the spared nerve injury (SNI) model, in which the common peroneal nerve (CPN) and tibial nerve (TN) are ligated, is widely used. In the present study, we evaluated the analgesic effect of a cholinergic agonist, carbachol, on a neuropathic pain model prepared by sural nerve (SN) ligation in mice. Methods The SN was tightly ligated as a branch of the sciatic nerve. Mechanical and thermal allodynia, and hyperalgesia were assessed using von Frey filaments and heat from a hot plate. The analgesic effects of intracerebroventricularly-administered morphine and carbachol were compared. Results SN ligation resulted in a significant decrease in pain threshold for mechanical stimulation 1 day after ligation. In response to thermal stimulation, allodynia was observed at 50°C and hyperalgesia at 53 and 56°C 3 days after ligation. Content of thiobarbituric acid reactive substances (TBARS) in the spinal cord increased significantly at 6 and 12 h after ligation. Acetylcholine content of the spinal cord also increased at 5 and 7 days after ligation. Intracerebroventricular administration of carbachol at 7 days after ligation produced a marked analgesic effect against mechanical and thermal stimuli, which was stronger and longer-lasting than morphine at all experimental time points. Conclusion These findings suggest that cholinergic nerves are involved in allodynia and hyperalgesia of the SN ligation neuropathic pain model.

All-inside endoscopic semiautomatic running locked stitch technique shows favourable outcomes for acute Achilles tendon ruptures.

The safety and reliability of endoscopic Achilles tendon rupture repair are still concerning aspects. This study's aim is to evaluate an all-inside endoscopic semiautomatic running locked stitch (Endo-SARLS) technique. Forty cases with acute Achilles tendon rupture were treated with the all-inside Endo-SARLS technique between 2020 and 2021. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semiautomatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon subspace and then fixed into calcaneal insertion with a knotless anchor. Magnetic resonance imaging (MRI), surgical timeand complications were assessed. Achilles Tendon Total Rupture Score (ATRS), Achilles Tendon Resting Angle (ATRA)and Heel Rise Height Scale (HRHS) were utilised to evaluate final outcomes. The average follow-up time was 25.4 ± 0.4 (range: 24-32) months. Appropriate tendon regeneration was observed on MRI after 12 months. At the final follow-up, the median value of ATRS score was 95 (interquartile range: 94, 98). Furthermore, there is no significant difference between the injured and contralateral side in the average ATRA (18.2 ± 1.8 vs. 18.3 ± 1.9°, ns) and median value of HRHS [14.5 (13.3, 15.5) vs. 14.8 (13.5, 15.6) cm, ns]. No infection and nerve injuries were encountered. Thirty-ninepatients reported that they resumed casual sports activity after 6 months. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. An all-inside Endo-SARLS technique showed promising clinical results for acute Achilles tendon ruptures. This procedure reduces the risk of sural nerve injuries while establishing a reliable connection between the tendon stumps. Level IV.

Alcohol-related peripheral neuropathy: Clinico-neurophysiological characteristics and diagnostic utility of the neuropathy symptoms score and the neuropathy impairment score

Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available.

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Abstract Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient's Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 1012 (×2), and then consecutive infusions of 7.5 × 1012 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco's phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

Minimally-invasive lag screw fixation technique for posterior malleolus fractures: A cadaveric study

Anatomical reduction and lag screw fixation of posterior malleolar (PM) ankle fractures typically involves an open posterolateral approach. The aim of this anatomical study was to assess whether a minimally-invasive, percutaneous posterior-to-anterior lag screw fixation technique is safe to perform. Eighteen cadaveric ankle specimens were used. A transverse incision was made at the lateral border of the Tendo Achilles (TA). Windows were made lateral to and through the substance of the TA and simulated reduction and placement of a single lag screw. Specimens were then fully dissected to ascertain proximity and damage to anatomical structures. Lag screw fixation was placed appropriately in all ankles. No injury to neurovascular structures, ankle joint or syndesmotic ligaments were observed. The mean distance from the soft tissue window to sural nerve was 10.0 mm (range 5–16), and 9.5 mm to short saphenous vein (4–14). Whilst the muscle belly of flexor hallucis longus (FHL) was pierced in six specimens, no injuries to the FHL tendon were observed. The mean distance from screw to syndesmosis was 9.3 mm (range 3–15) and 12.7 mm to the ankle joint (7–17). This study demonstrates that posterior percutaneous lag screw fixation is both safe and accurate. Further work is required to evaluate the precision of reduction and the biomechanical stability of this fixation technique. This novel minimally-invasive technique may be beneficial in avoiding the wound complications associated with open posterolateral ankle approaches and also offer a functional advantage due to minimal soft tissue disruption.

Outcomes of Percutaneous Zadek Osteotomy for Insertional Achilles Tendinopathy with Two-Year Minimum Follow-Up: A Retrospective Study

Introduction/Purpose: Insertional Achilles tendinopathy (IAT) is a common source of posterior heel pain treated by orthopaedic foot and ankle surgeons. Traditional surgical treatment consists of an open Achilles tendon debridement with re-attachment as well as excision of the posterosuperior calcaneal prominence with or without a gastrocnemius recession. However, frequent complications include wound healing issue, scar pain, weakness and sural nerve injury. Accordingly, the percutaneous ZO is gaining popularity in the field as an alternative to an open midline splitting approach. Limited literature exists describing outcomes of the percutaneous ZO using a larger sample size. The purpose of this study was to analyze patient reported outcomes and complications after percutaneous ZO with a minimum two-year follow-up period. Methods: One hundred and eight cases treated with percutaneous ZO were retrospectively reviewed across October 2017-July 2021 and outcomes data was available for 104 cases with a minimum two-year follow-up. Patient sex, age, and pertinent comorbidities were recorded. Postoperative complications and patient satisfaction following intervention were evaluated. Foot Function Index score (FFI) was utilized to measure patients’ pain and functional outcomes. Visual Analyzing Scale score (VAS) was also utilized to evaluate pain. These measurements were taken at preoperative and final follow-up. Statistical comparisons were performed using two-tailed, paired t-test with p&lt; 0.05. Results: Mean follow-up time was 41.2±13.1 months (range 24-65 months). The mean FFI score improved from 56.1±5.9 (range 47-88) preoperatively to 11.0±5.1 (range 7-59) postoperatively (p &lt; 0.001). Average VAS score improved in patients receiving percutaneous ZO from 7.6±1.3 (range 5-10) to 0.4±0.9 (range 0-7) postoperatively (p &lt; 0.001). The overall complication rate was 3.8% (N =4). Of 104 cases, 98.1% of patients were satisfied with their procedure (102/104). Conclusion: The percutaneous ZO is a safe and highly effective intervention for treatment of IAT. At a minimum of two-years follow-up, this intervention is associated with minimal complications, improved functional outcomes, reduced pain, and high patient satisfaction. Table 1 Functional and subjective pain preoperative and postoperative scores as evaluated by functional foot index (FFI) and visual analogue scale (VAS), respectively

Encephalitis-like episodes with cortical edema and enhancement in patients with neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) exhibited significant clinical heterogeneities. However, the clinical features, radiographic changes, and prognosis of patients with encephalitis-like NIID have yet to be systematically elucidated. Clinical data including medical history, physical examination, and laboratory examinations were collected and analyzed. Skin and sural nerve biopsies were conducted on the patient. Repeat-primed PCR (RP-PCR) and fluorescence amplicon length PCR (AL-PCR) were used to detect the expansion of CGG repeat. We also reviewed the clinical and genetic data of NIID patients with cortical enhancement. A 54-year-old woman presented with encephalitis-like NIID, characterized by severe headache and agitative psychiatric symptoms. The brain MRI showed cortical swelling in the temporo-occipital lobes and significant enhancement of the cortical surface and dura, but without hyperintensities along the corticomedullary junction on diffusion-weighted image (DWI). A biopsy of the sural nerve revealed a demyelinating pathological change. The intranuclear inclusions were detected in nerve and skin tissues using the p62 antibody and electron microscopy. RP-PCR and AL-PCR unveiled the pathogenic expansion of CGG repeats in the NOTCH2NLC gene. A review of the literature indicated that nine out of the 16 patients with cortical lesions and linear enhancement exhibited encephalitis-like NIID. This study indicated that patients with encephalitis-like NIID typically exhibited headache and excitatory psychiatric symptoms, often accompanied by cortical edema and enhancement of posterior lobes, and responded well to glucocorticoid treatment. Furthermore, some patients may not exhibit hyperintensities along the corticomedullary junction on DWI, potentially leading to misdiagnosis.