Gait Abnormalities Research Articles

Change in Femoral Offset after Closed Reduction and Dynamic Hip Screw Osteosynthesis Via Lateral Approach in Patients with Medial Femoral Neck Fracture: A Retrospective Analysis.

Closed reduction and dynamic hip screw (DHS) osteosynthesis are preferred as joint-preserving therapy in case of medial femoral neck fractures (MFNFs). A change in the femoral offset (CFO) can cause gait abnormality, impingement, or greater trochanteric pain syndrome. It is unknown whether the femoral offset (FO) can be postoperatively fully restored. The aim of the study was to investigate the extent of a possible CFO in hip joints after DHS osteosynthesis in the case of an MFNF. In this retrospective study, 104 patients (mean age: 71.02 years, men: n = 50, women: n = 54) with MFNF who underwent closed reduction and DHS osteosynthesis were analyzed by postoperative x-rays to assess CFO between the operated (OS) and nonoperated joint side (NOS). The studies covered the time period 2010-2020. A statistical comparison was performed between the mean values of FO between OS and NOS, taking into account patient age, gender, and fracture severity. All operated hip joints showed a CFO. In 76.0% (79 of 104), the FO decreased (FOD), and in 24.0% (25 of 104), the FO increased (FOI). A critical CFO (>15% CFO) was detected in 52.9% (55 of 104). In hip joints with postoperative FOD, the mean FO between NOS (49.15 mm [±6.56]) and OS (39.32 mm [±7.87]) and in hip joints with postoperative FOI the mean FO between NOS (41.59 [±8.21]) and OS (47.27 [±6.68]) differed significantly (p < 0.001). Preoperative FO (rS: -0.41; p > 0.001) and caput-collum-diaphyseal angle (CCD; rS: 0.34; p > 0.001) correlated with postoperative CFO. FOD was found in hip joints with a preoperative FO >44 mm and CCD <134° vice versa FOI in hip joints with a preoperative FO <44 mm and CCD >134°. Closed reduction and DHS osteosynthesis in patients with MFNF result in a clustered significant CFO. The individual FO should be taken into account pre- and intraoperatively to avoid a postoperative extensive CFO.

Falls and fractures in men with prostate cancer taking second-generation androgen receptor antagonists: A retrospective chart review.

Second-generation androgen receptor antagonists, including enzalutamide, apalutamide, and darolutamide, are commonly used to treat metastatic and non-metastatic prostate cancer. Although these medications are typically well-tolerated, falls were reported in 4.2-15.6% of patients and fractures in 4.2-11.7% of patients enrolled in the phase III clinical trials evaluating these drugs in prostate cancer. However, post-marketing studies have reported a lower incidence than reported in clinical trials. The objective of this study is to determine the prevalence of falls and fractures in patients with prostate cancer receiving second-generation androgen receptor antagonists at UConn Health and identify potential risk factors associated with falls and fractures in these patients. A retrospective chart review involving patients with prostate cancer treated with darolutamide, enzalutamide, or apalutamide from March 1, 2022, to March 31, 2023, at UConn Health Carole & Ray Neag Comprehensive Cancer Center. Data recorded includes basic demographics, history of fall or fracture, presence of metastases, fall risk, history of osteoporosis, prescribed second-generation androgen receptor antagonist, and other comorbidities. Data was evaluated using descriptive statistics. Twenty-six men were included, all of whom were receiving enzalutamide. At baseline, 96.1% of patients had bone metastases, 15.4% had osteoporosis, 15.4% had osteopenia, and 34.6% had neuropathy. The incidence of falls was 19.2% and the incidence of fractures was 26.9%. The mean length of therapy at time of a fall was 19.44 months (range, 6-31 months). The mean length of therapy at time of a fracture was 19 months (range, 1-33 months). In patients experiencing fall, 100% had arthralgia, 60% had neuropathy, 40% had a gait problem, 40% had hypertension, and 80% of them were at risk of fall. In patients experiencing fracture, 28.6% had osteoporosis, 42.9% had osteopenia, 100% had bone metastases, and 57.1% were on denosumab at time of fracture. The prevalence of falls and fractures in patients receiving enzalutamide were higher in this retrospective chart review than reported in clinical trials and post-marketing studies. This could be due to the small patient population or the patient's comorbidities such as osteoporosis, bone metastases, or neuropathy. Fall/fracture risk with enzalutamide and other risk factors for fall and fracture should be considered when discussing treatment and developing a monitoring plan.

Spontaneous hepatocellular and gastric tumours in African clawed frogs (Xenopus laevis).

Three seven-year-old African clawed frogs (Xenopus laevis) from an animal research facility showed weight loss, coelomic distention and an abnormal swimming gait were euthanised on welfare grounds. A complete necropsy of each animal showed a focal, firm, dark brown to green mass with multifocal haemorrhages in the left liver lobe in two animals and a transmural, firm, beige, multilobulated gastric mass in another animal. Additionally, one of the frogs with the hepatic mass had haemocoeloma. Histologically, the hepatic masses were diagnosed as hepatocellular adenomas and the gastric mass as a gastric carcinoma with trans-coelomic metastases. The three tumours were immunophenotyped using the following antibodies: cytokeratin AE1/AE3, vimentin, E-cadherin, P53 and Ki67 and, additionally, for the hepatic tumours only, synaptophysin, Prox-1, S100 and Sox-9. Masson's trichrome, Periodic acid Schiff and Gram stains was also performed in selected cases. One of the hepatocellular adenomas was weakly positively labelled with E-cadherin whereas the other showed variable positivity for Sox-9 only. Vimentin labelled the stroma and sinusoidal endothelia. Interestingly in the liver, the cytokeratin AE1/AE3 labelling was restricted to the biliary epithelium and sinusoidal endothelia. The gastric carcinoma labelled positively with cytokeratin AE1/AE3 only. This report aims to guide laboratory animal veterinarians to accurately diagnose multi-organ masses in amphibians. To the authors' knowledge, this is the first comprehensive morphological study on a case series of hepatocellular and gastric neoplasia in X. laevis.

Phenotypic Variability in Camurati–Engelmann Disease: A Case Report of a Family with the c.653G&gt;A Pathogenic Variant in the TGFB1 Gene

Camurati–Engelmann Disease (CED), or Progressive Diaphyseal Dysplasia, is a rare autosomal dominant disorder caused by heterozygous mutations in the TGFB1 Gene, essential for bone regeneration. This study examines the genotype–phenotype relationship in a family diagnosed with CED, specifically focusing on a missense variant (c.653G&gt;A, p.Arg218Cys). The family comprised a mother and her two children, all of whom were found to carry the same disease-causing variant. The second child exhibited severe symptoms by age six, including progressive weakness and joint pain, leading to wheelchair dependency. The mother displayed milder symptoms with preserved independence. The firstborn son, initially asymptomatic, developed gait abnormalities and pain during adolescence. Clinical evaluations revealed characteristic hyperostosis of long bones, with significant variability in symptom onset and severity among family members, potentially indicative of genetic anticipation. This case underscores the importance of genetic testing and interdisciplinary management in CED, as traditional treatments, including corticosteroids and NSAIDs, often yield limited efficacy and notable side effects. Our findings contribute to the understanding of CED’s pathophysiology and highlight the necessity for tailored therapeutic approaches. The identification of the common TGFB1 variant in this family reinforces the critical role of TGFB1 in bone metabolism and suggests avenues for further research into targeted therapies. Such reports enhance awareness and provide valuable insights for healthcare professionals managing rare genetic disorders.

Clinical diagnosis and management of spinocerebellar Ataxia in a resource-constrained setting: a case report from Eastern Nepal

Introduction: Spinocerebellar ataxias (SCA) are a diverse group of neurodegenerative disorders with autosomal dominant inheritance, primarily affecting the cerebellum and its connections. Diagnosis typically involves genetic testing, but in resource-limited settings, clinical and neuroimaging assessments become critical. This case report highlights the role of non-genetic methods in diagnosing SCA and outlines management strategies in such settings. Case Presentation: A 41-year-old male presented with a two-year history of progressive gait imbalance, headache, and abnormal speech. He had a family history of similar symptoms in two siblings, but no significant past medical history. Clinical examination revealed scanning speech, dysmetria, and a broad-based gait. Clinical and neuroimaging findings, including cerebellar atrophy, led to a diagnosis of SCA in the absence of genetic testing. Patient management with speech, occupational, and physical therapies, showed gradual improvement. Discussion: SCA, characterized by cerebellar atrophy and a range of clinical symptoms, is typically diagnosed through genetic testing, but clinical and imaging assessments are crucial when genetic resources are limited. This case illustrates that a comprehensive clinical evaluation, including neuroimaging, can support the diagnosis of SCA even without genetic testing. Strategic management emphasizing symptomatic relief and functional improvement through a multidisciplinary approach, including regular follow-up and personalized therapy, are crucial, as evidenced by the timely improvement observed in our case. Conclusion: In resource-limited settings, a comprehensive clinical and neuroimaging assessment is essential for diagnosing Spinocerebellar Ataxia when genetic testing is not feasible. Effective management through multidisciplinary therapies can improve patient outcomes, underscoring the need for innovative strategies to enhance diagnostic and treatment capabilities in such environments.

Using motion capture technology to assess gait patterns in runners and investigate injury risks: A short review

Motion capture technology has become integral in studying gait patterns among runners to understand their implications for injury risks. This review synthesizes current literature to examine methodologies and findings related to using motion capture technology for gait analysis in runners. A systematic search was conducted across major academic databases to identify relevant studies published in peer-reviewed journals and conference proceedings. Inclusion criteria focused on studies utilizing motion capture technology to assess biomechanical factors associated with running-related injuries.The review highlights key biomechanical parameters analyzed through motion capture, including joint angles, forces, and muscle activations during running. Studies consistently report on the relationship between gait abnormalities and various injuries such as stress fractures, patellofemoral pain syndrome, and Achilles tendonitis. Practical implications for injury prevention strategies are discussed including personalized gait assessments, targeted interventions such as gait retraining, and advancements in footwear design aimed at optimizing running mechanics and reducing injury risks. Motion capture technology offers a robust platform for advancing our understanding of gait mechanics in runners and their impact on injury prevention. Future research directions should focus on standardizing methodologies, integrating multi-modal data, and applying findings to enhance clinical practice and athletic performance.

Kinematic Changes throughout Childhood in Youth with Cerebral Palsy: Influence of Age and Orthopaedic Surgery.

Abnormal gait kinematics are common in youth with cerebral palsy (CP), but prior studies have not analyzed their longitudinal change throughout childhood. This study examines how age and orthopaedic surgery influence gait kinematics throughout childhood in those with ambulatory CP. In this institutional review board-approved prospective cohort study, children with spastic CP (GMFCS I-III) were recruited at age 17-40 months. Instrumented gait analysis was performed at 3-year intervals from age 4 to 21 years, collecting longitudinal kinematic data in bare feet at a self-selected speed. The change in Gait Profile Score (ΔGPS) between each pair of gait analyses (intervals) was analyzed by age distribution (<10, 10-15, ≥15 years) and by presence/absence of orthopaedic surgery. The study included 31 children (GMFCS: I [13], II [14], III [4]). A baseline instrumented gait analysis was performed at age 5.8 ± 1.6 years with subsequent analysis at 2.5 ± 1.3-year intervals. Examining ΔGPS from baseline to final outcome, 87% of limbs were improved/unchanged; 298 intervals of ΔGPS were analyzed and classified as nonsurgical or surgical. Analysis revealed greater GPS improvement in intervals with surgery versus intervals without (p = 0.0004). Surgical intervals had significantly greater GPS improvement in the <10- vs. >15-year-old groups, p = 0.0063. Improvement in gait kinematics in children with CP is significantly influenced by age and timing of orthopaedic surgical intervention for gait correction, and was most pronounced for children <10 years old. Although surgery was associated with improved outcomes in all age groups, these improvements were significantly less for children >10 years old. These results reinforce the importance of considering the timing of orthopaedic surgery.

Targeting the Sirtuin–1/PPAR–Gamma Axis, RAGE/HMGB1/NF-κB Signaling, and the Mitochondrial Functions by Canagliflozin Augments the Protective Effects of Levodopa/Carbidopa in Rotenone-Induced Parkinson’s Disease

Background and Objectives: Parkinson’s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD.

Case report: Encephalitis with Guillain-Barré Syndrome secondary to extensively multi-drug resistant Salmonella infection

Abstract Background This case report presents a highly unusual and challenging medical case involving a 16-month-old previously healthy boy who developed encephalitis followed by Guillain-Barré Syndrome (GBS) as complications of multi-drug resistant Salmonella infection, despite an initial misdiagnosis of gastroenteritis and outpatient treatment with Cefixime. Methods The patient initially experienced an increase in stool frequency, accompanied by low-grade fevers, which was initially attributed to gastroenteritis. Outpatient treatment with oral Cefixime was started, but the child’s symptoms worsened, ultimately leading to high-grade fevers and an increase in vomiting and loose stools. In light of his clinical deterioration, he was admitted to our hospital with signs of mild metabolic acidosis and elevated inflammatory markers. During his hospitalization, the patient’s condition worsened, with drowsiness, irritability, and a generalized tonic-clonic seizure, prompting concern for brain involvement. Consequently, he underwent lumbar puncture, and neuroimaging, and received high-dose intravenous steroids. Further medical investigations including lumbar puncture and brain Magnetic Resonance Imaging (MRI), which revealed normal cerebrospinal fluid (CSF) analysis and non-enhancing white matter changes in the occipital region, respectively. In addition, a collected blood culture confirmed the presence of extensively multi-drug resistant Salmonella typhi and prompted an adjustment of antibiotics to intravenous Meropenem. Due to autonomic dysfunction, the patient was transferred to the Pediatric Intensive Care Unit (PICU) for close monitoring and specialized care. While in the PICU, he developed flaccid limb weakness and axial hypotonia. A repeat lumbar puncture was normal, but nerve conduction studies showed features of axonal polyneuropathy diagnosis, consistent with the diagnosis of GBS. To treat the encephalopathy and polyneuropathy, high-dose dexamethasone and Intravenous Immunoglobulin (IVIG) treatments were initiated, without necessitating respiratory or inotropic support. After receiving these treatments, the patient’s autonomic instability and motor strength improved, prompting his transfer back to the general pediatrics wards. He was treated with a 21-day course of IV Meropenem. Upon discharge, his motor power had returned to normal, and he displayed progress in movement transitions, including the ability to stand and walk independently, albeit with mild gait abnormalities. Results The co-occurrence of encephalitis and Guillain-Barré Syndrome due to Typhoid fever is exceedingly rare. The patient’s origin, with recent travel to Pakistan where extensively drug-resistant Salmonella typhi prevails, necessitates heightened awareness among healthcare providers. Initial misdiagnosis and inadequate antibiotics treatment may have contributed to encephalitis and polyneuropathy. High-dose dexamethasone and IVIG were pivotal in the patient’s treatment. While Typhoid fever-related neurological complications are infrequent, high-dose dexamethasone offers promise in reducing mortality and mitigating typhoid-induced encephalopathy. Importantly, IVIG is not conventionally employed in Salmonella encephalopalitis but was used due to polyneuropathy and its role in GBS management. Conclusion This exceptional pediatric case serves as a striking example of the possibility simultaneous encephalitis and Guillain-Barré Syndrome as rare complications of Typhoid fever. This case report underscores the importance of early diagnosis, prompt management with appropriate antibiotics and caution of possible neurological complications. Furthermore, it calls for further research into the role of high-dose glucocorticoids and IVIG in the management of extensively multi-drug resistant Salmonella infection and its neurological complications.

Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/β-endorphin Signaling in the Spinal Cord of Rats.

The underlying pathogenesis of chronic inflammatory pain is greatly complex, but the relevant therapies are still unavailable. Development of effective candidates for chronic inflammatory pain is highly urgent. We previously identified that trifluoro-icaritin (ICTF) exhibited a significant therapeutic activity against complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, however, the precise mechanisms remain elusive. Here, the paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis were used to determine the pain-related behaviors. The expression and co-localization of pain-related signaling molecules were detected by Western blot and immunofluorescence staining. Our results demonstrated that ICTF (3.0mg/kg, i.p.) effectively attenuated mechanical allodynia, thermal hyperalgesia and improved motor dysfunction induced by CFA, and the molecular docking displayed that CB2 receptor may be the therapeutic target of ICTF. Furthermore, ICTF not only up-regulated the levels of CB2 receptor, IL-10, β-endorphin and CD206, but also reduced the expression of P2Y12 receptor, NLRP3, ASC, Caspase-1, IL-1β, CD11b, and iNOS in the spinal cord of CFA rats. Additionally, the immunofluorescence staining from the spinal cord showed that ICTF significantly increased the co-expression between the microglial marker Iba-1 and CB2 receptor, IL-10, β-endorphin, respectively, but markedly decreased the co-localization between Iba-1 and P2Y12 receptor. Conversely, intrathecal administration of CB2 receptor antagonist AM630 dramatically reversed the inhibitory effects of ICTF on CFA-induced chronic inflammatory pain, leading to a promotion of pain hypersensitivity, abnormal gait parameters, microglial activation, and up-regulation of P2Y12 receptor and NLRP3 inflammasome, as well as the inhibition of CB2 receptor and IL-10/β-endorphin cascade. Taken together, these findings highlighted that ICTF alleviated CFA-induced neuroinflammation by enhancing CB2 receptor-mediated IL-10/β-endorphin signaling and suppressing microglial activation in the spinal cord, and uncovered that CB2 receptor may be exploited as a novel and promising target for ICTF treatment of chronic inflammatory pain.

Systemic gene therapy corrects the neurological phenotype in a mouse model of NGLY1 deficiency.

The cytoplasmic peptide:N-glycanase (NGLY1) is ubiquitously expressed and functions as a de-N-glycosylating enzyme that degrades misfolded N-glycosylated proteins. NGLY1 deficiency due to biallelic loss-of-function NGLY1 variants is an ultrarare autosomal recessive deglycosylation disorder with multisystemic involvement; the neurological manifestations represent the main disease burden. Currently, there is no treatment for this disease. To develop a gene therapy, we first characterized a tamoxifen-inducible Ngly1-knockout (iNgly1) C57BL/6J mouse model, which exhibited symptoms recapitulating human disease, including elevation of the biomarker GlcNAc-Asn, motor deficits, kyphosis, Purkinje cell loss, and gait abnormalities. We packaged a codon-optimized human NGLY1 transgene cassette into 2 adeno-associated virus (AAV) capsids, AAV9 and AAV.PHPeB. Systemic administration of the AAV.PHPeB vector to symptomatic iNgly1 mice corrected multiple disease features at 8 weeks after treatment. Furthermore, another cohort of AAV.PHPeB-treated iNgly1 mice were monitored over a year and showed near-complete normalization of the neurological aspects of the disease phenotype, demonstrating the durability of gene therapy. Our data suggested that brain-directed NGLY1 gene replacement via systemic delivery is a promising therapeutic strategy for NGLY1 deficiency. Although the superior CNS tropism of AAV.PHPeB vector does not translate to primates, emerging AAV capsids with enhanced primate CNS tropism will enable future translational studies.

Pre- and Postnatal Vitamin A Deficiency Impairs Motor Skills without a Consistent Effect on Trace Mineral Status in Young Mice

Pregnant women and children are vulnerable to vitamin A deficiency (VAD), which is often compounded by concurrent deficiencies in other micronutrients, particularly iron and zinc, in developing countries. The study investigated the effects of early-life VAD on motor and cognitive development and trace mineral status in a mouse model. C57BL/6J dams were fed either a vitamin A-adequate (VR) or -deficient (VD) diet across two consecutive gestations and lactations. Offspring from both gestations (G1 and G2) continued the same diets until 6 or 9 weeks of age. Behavioral assays were conducted to evaluate motor coordination, grip strength, spatial cognition, and anxiety. Hepatic trace minerals were analyzed. A VD diet depleted hepatic retinoids and reduced plasma retinol across all ages and gestations. Retracted rear legs and abnormal gait were the most common clinical manifestations observed in VD offspring from both gestations at 9 weeks. Poor performance on the Rotarod test further confirmed their motor dysfunction. VAD didn’t affect hemoglobin levels and had no consistent effect on hepatic trace mineral concentrations. These findings highlight the critical role of vitamin A in motor development. There was no clear evidence that VAD alters the risk of iron deficiency anemia or trace minerals.

Surgical correction of pes varus deformity in dachshunds using three-dimensional-printed patient-specific guide system: nine tibiae in seven cases (2018-2022).

To describe the use of a three-dimensional-printed patient-specific guide system for the treatment of distal tibial varus deformity in Dachshunds and retrospectively report the clinical and radiographic outcome. Pes varus deformity in nine limbs of seven dachshunds was treated with corrective osteotomy using a three-dimensional-printed patient-specific guide system. Data from computed tomography were processed to obtain virtual 3D-models of the tibias, which were used for computer-aided design-based surgical planning, three-dimensional-printed patient-specific guide system design and evaluation of planned versus achieved tibial correction. Clinical outcomes were evaluated by lameness score and post-operative owner-reported questionnaire at a minimum of 15 months. The gait abnormality resolved in all limbs. The osteotomy healed uneventfully in eight tibiae. Implant failure occurred in one tibia but was successfully revised. There was good correlation between planned and achieved deformity correction, with mean translational error <1 mm in all planes, and mean angulation correction error <2° in all planes. A 3D-printed patient-specific osteotomy and reduction guide system facilitates the accurate correction of tibial pes varus deformity with very good clinical outcomes. Opening osteotomy, stabilised with orthogonal locking plates and without the application of bone graft led to satisfactory bone healing in all cases.

7238 A rare cause of primary ovarian failure in an adolescent due to a genetic mutation in mitochondrial poly-A-polymerase (mTPAP) mRNA

Abstract Disclosure: J. Epstein: None. S. Veera: None. J. Pappas: None. B.C. Shah: None. Primary ovarian insufficiency (POI) is a dysfunction or loss of ovarian follicles with associated amenorrhea. While most causes are idiopathic, approximately 15% of POI cases are due to single gene or chromosomal abnormalities, such as X chromosome abnormalities. Many of these nuclear genes encode for proteins that function within the mitochondria. Mitochondrial disorders affect tissues with high energy demand, such as the neurological, skeletal, cardiac, and endocrine systems. Furthermore, mature ovaries have a relatively higher concentration of mitochondria, which play a role in cellular respiration along with steroidogenesis. Mutations that disrupt these pathways can therefore lead to ovarian dysfunction. We present a case of a 17-year-old female with concern for primary amenorrhea. She underwent pubarche at age 12 years and thelarche at 14 years, with slowed progression. Height Z score was -1.61 and weight Z score was -0.41. Lab work at presentation was significant for LH 18.6 IU/L (N 2.4-12.6 IU/L), FSH 43.9 IU/L (N 1.1-9.6 IU/L), low estradiol &amp;lt;2.5 pg/mL (N 30-100 pg/mL), low total testosterone 8.3 ng/dL (N 15-31 ng/dL), unremarkable HbA1C, cortisol, thyroid levels, and a 46 XX karyotype. Pelvic ultrasound showed small ovarian volumes with a 1.9 cc right ovary, 1.5 cc left ovary consistent with lack of hormonal stimulation, and uterus length of 4.9 cm (N &amp;gt; 4 cm) consistent with early hormonal stimulation. She was started on transdermal estrogen replacement. Past medical history included stable pericardial effusion, episodes of supraventricular tachycardia, pre-cataracts, speech delays, mild learning disabilities, spastic diplegia, progressive gait abnormalities, ligamentous laxity, and recurrent patellar dislocations requiring multiple orthopedic limb surgeries. Family history was significant for parental consanguinity as first cousins. As the etiology of the POI remained unknown, genetic testing was completed. Whole exome sequencing (WES) revealed a homozygous pathogenic variant in the MTPAP gene: p.(Leu495Arg) (CTG&amp;gt;CGG): c.1484 T&amp;gt;G in exon 9 on chromosome 10p11.23. MTPAP, also known as SPAX4, TENT6, or PAPD1, is a nuclear-encoded polymerase involved in synthesizing the 3’ poly(A) tail of mitochondrial transcripts as well as in mRNA degradation. She was diagnosed with autosomal recessive MTPAP-related neurodevelopmental and movement disorder. Monogenic disorders affecting mitochondrial function are rare causes of POI. A high index of suspicion should be raised when a constellation of neurological, musculoskeletal, and cardiac problems co-exist. WES can be a very useful tool for uncovering rare genetic disorders. Further studies are needed to clarify details of organ specific mitochondrial dysfunction and possible therapeutics in individuals affected with MTPAP-related neurodevelopmental and movement disorders. Presentation: 6/1/2024

B-301 Deciphering Neuropathy features in the Context of Nitrous Oxide abuse: An Integrated Analysis of Electrophysiology and Metabolism

Abstract Background Nitrous oxide (N2O), used medically for its analgesic and anxiolytic properties, has emerged as a common recreational substance, leading to a rise in chronic toxicity cases. N2O abuse induces peripheral neurological damage with a spectrum of clinical presentations, ranging from mild sensory disturbances to severe motor deficits. Neurological complications from N2O include axonal and demyelinating neuropathies, leading to diagnostic and prognostic challenges. The pathophysiology of N2O toxicity is linked to functional inactivation of vitamin B12, resulting in biochemical and electrophysiological alterations. This study aims to enhance understanding of N2O pathophysiology by examining metabolic changes in consumers with axonal and demyelinating patterns. Methods This study included 35 patients with recent N2O abuse (last declarative consumption within the past week) who were treated at Lille University Hospital between March 2020 and April 2023 and underwent electromyography. The collected clinical features encompassed sensory symptoms, motor weakness, gait abnormalities and deep tendon reflexes. Patients were classified based on clinical phenotypes, distinguishing between length-dependent and non-length dependent, sensory or sensory-motor involvement and their peripheral neuropathy disability (PND) score (ranging from I to IV). Neurophysiological data analysis followed the criteria of Hadden et al. to identify patients with demyelinating criteria, while those lacking demyelinating criteria were categorized as “axonal” in the neuropathy group. Simultaneously, biochemical evaluations of serum vitamin B12 and B9 by CLIA methods (Roche), along with plasma homocysteine by LC/MS/MS and CLIA methods (Snibe), methylmalonic acid (MMA), and methionine by LC/MS/MS, were systematically performed for all patients. Results 40% of the selected patients exhibited demyelination criteria. The demyelinated group showed a significantly higher disability PND score compared to the axonal group (3.0 and 2.2, respectively; p-value = 0.028). Elevated levels of homocysteine and methylmalonic acid were found in all patients. Interestingly, plasma concentrations of homocysteine were significantly higher in the group of patient with axonal outcomes compared to the demyelinating group (90 µM and 114 µM; p-value = 0.04), suggesting an involvement of homocysteine in the type of lesion related to N2O abuse. Conclusions This study highlights the diverse electrophysiological manifestations of N2O-induced neuropathy and highlight the potential role of metabolic parameters as biomarkers to understand the pathophysiology. Indeed, lower hyperhomocysteinemia levels were observed in demyelinating patterns, highlighting a potentially biochemical difference between the groups: plasma homocysteine could also be used as a marker of neurological severity. The homocysteine assay used in these conditions must enable the patient to be managed rapidly: it would therefore be preferable to use rapid methods such as immunoanalysis. On the other hand, plasma methylmalonic acid did not differ between groups, which also suggests that other mechanisms have yet to be identified in the pathophysiology of N2O abuse.

ID: 338075 Improvement in Gait Abnormality following Minimally Invasive, Posterior Approach Sacroiliac Joint Fusion

ID: 338075 Improvement in Gait Abnormality following Minimally Invasive, Posterior Approach Sacroiliac Joint Fusion

Diverse phenotype of Ménière’s disease associated with family history, thyroid disorder, migraine and associated disorders

ObjectiveTo better understand the clinical phenotype of Ménière’s disease (MD), we examined family history, thyroid disorder, migraine, and associated disorders in complaints of people living with MD. MethodWe designed the study as a retrospective and examined data gathered from 912 participants with MD. Their data were originally collected by the Finnish Ménière Federation (FMF). The survey data included individual case histories for environmental factors, comorbidities, disease-specific complaints, impact-related questions, cognitive complaints, health-related quality of life (HRQoL), and sense of coherence (SOC). ResultsWe observed significant differences between those with and without sporadic occurrence, family history, thyroid disorder, and migraine-associated complaints. Family history explained 20% of variability in patient complaints. Patients with a family history of MD whose disease started at younger age experienced balance problems, more severe vertigo spells, more severe vestibular drop attacks (VDA), and less nausea, although they had good SOC. Thyroid disorder explained 14% of variability in patient complaints. MD patients with a thyroid disorder comorbidity suffered more often from constant dizziness, balance problems, greater impact of hearing problems, cognitive complaints, and poor HRQoL. Migraine explained 12% of variability in patients’ complaints and was associated with poor SOC and cognitive balance problems. MD patients with both thyroid disorder and migraine used antidepressants more often than other groups. Logistic regression analysis showed comorbidities of ischemic brain disorder (among 7.1%), kidney insufficiency (among 1.2%), and diabetes (among 7.3%) had statistically significant but restricted association with balance and gait problems, VDA, and reduced HRQoL. ConclusionsFamily history of MD and thyroid disorder or migraine comorbidities in MD influence the complaint pattern and partially explain complex symptom profiles, including symptoms of cognitive problems. Confounders play a minimal role in complaint profile and impact of MD whereas comorbidities influence the complaint structure and partly explain the complex symptom profile in MD.

Unveiling hidden challenges: impaired foot posture due to skin involvement in systemic sclerosis

Systemic sclerosis [SSc] is a chronic autoimmune disease characterized by fibrosis, vasculopathy, and immune dysregulation, primarily affecting the skin and various internal organs. Musculoskeletal manifestations, particularly foot involvement, are common but often underrecognized. Foot problems, including pain, Raynaud's phenomenon, digital ulcers, and deformities such as hallux valgus, are reported in SSc patients and can significantly impair mobility and quality of life. Skin thickening, especially around the ankles and toes, may disrupt foot alignment and posture, potentially leading to gait abnormalities. Current literature on the relationship between skin involvement, foot posture, and gait characteristics in SSc is limited, highlighting the need for comprehensive studies to explore these associations. The current hypothesis posits that skin involvement in SSc may significantly influence foot posture, leading to subsequent alterations in gait dynamics.

Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway.

Neurodegenerative disorders like Huntington's disease (HD) are a major threat to human health, with severe gait abnormalities and pathological changes (oxidative stress, neuroinflammation, and apoptosis) playing important roles in their development. The effects of artemisinin (ART) alone and in combination with the ERK antagonist PD98059 against 3-nitropropionic acid (3-NPA)-induced cell death and oxidative stress in SH-SY5Y cells were determined using the MTT and DCFH-DA assays, as well as RT-qPCR assays. In vivo, possible neuroprotective effects of ART (10, 20, and 40mg/kg i.p.) against the neurotoxicity generated by 21-day 3-NPA (10mg/kg i.p.) treatment was evaluated in rats by assessing behavioral parameters on days 1, 14, and 21. Further, various biochemical, inflammatory, apoptotic markers, histopathological changes, and protein expression were assessed using brain striatal samples. ART significantly mitigated the neurotoxic effect of 3-NPA in SH-SY5Y cells by regulating the mRNA expression of ERK, Bax, Bcl2, and cytochrome C. However, ART's neuroprotective activity was reduced in the presence of PD98059. Also, ART treatment for 21days substantially alleviated the behavioral impairments associated with 3-NPA toxicity. It reduced the oxidative stress induced by 3-NPA, as evidenced by the lower levels of MDA, nitrite, and improved catalase, SOD activity, and GSH levels. ART treatment restored 3-NPA-induced histopathological alterations in the striatal area. ART effectively suppressed neuroinflammatory (IL-6) and apoptotic markers (caspase 3 and 9), increasing BDNF levels and restoring the p-ERK1/2, Nrf2, and HO-1 expression. ART could exert its neuroprotective effect via antioxidant, anti-inflammatory, and antiapoptotic properties with a possible involvement of the ERK/BDNF/Nrf2/HO-1 pathway.

A Portable Passive Ankle-Foot Orthosis for Walking Propulsion and Drop-Foot Prevention

Abstract Individuals with a drop-foot generally have issues of foot-slap and toe-drag, and ankle-foot orthoses (AFOs) have been developed for them to address the drop-foot gait. However, the currently available active AFOs usually have heavier mass, larger volume, and additional power sources, and almost all of the passive AFOs can achieve dorsiflexion assistance at the cost of making plantarflexion more difficult, which increases the wearer's metabolic cost of walking. This paper illustrates the development and validation of a passive AFO for walking propulsion and drop-foot prevention of individuals with a drop-foot gait. The AFO is primarily composed of a propulsion module, a drop-foot prevention module, and a support module. The propulsion module can detect the wearer's gait stages, and it can control the energy storage and release of an energy storage spring-A by switching the state of a clutch-A mechanism. The drop-foot prevention module is designed to correct the abnormal gait of individuals with a drop-foot gait during the swing phase. Experiments are conducted to evaluate the performance of the developed AFO. The experimental results demonstrate that during a gait cycle, reductions of 7.74%, 6.72%, and 16.36% of the average muscle activities of the gastrocnemius, soleus, and tibialis anterior are observed, respectively. The significance of this study is the development of a portable passive AFO that has the potential to provide plantarflexion assistance and dorsiflexion assistance for the wearers during the late stance phase and swing phase, respectively.