Junction Pathology Research Articles

Paraspinal Sarcopenia and Lower Hounsfield Units are Independent Predictors of Increased Risk for Proximal Junctional Complications Following Thoracolumbar Fusions Terminating in the Upper Thoracic Spine.

Retrospective cohort study. The impact of paraspinal sarcopenia following fusions that extend to the upper thoracic spine remain unknown. The purpose of the present study was to assess the impact of sarcopenia on the development of PJK and PJF following spine fusion surgery from the upper thoracic spine to the pelvis. We performed a retrospective review of patients who underwent spine fusion surgery that extended caudally to the pelvis and terminated cranially between T1-6. The cohort was divided into 2 groups: (1) patients without PJK or PJF and (2) patients with PJK and/or PJF. Univariate and multivariate analyses were performed to determine risk factors for the development of proximal junctional complications. We identified 81 patients for inclusion in this study. Mean HU at the UIV was 186.1 ± 47.5 in the cohort of patients without PJK or PJF, which was substantially higher than values recorded in the PJK/PJF subgroup (142.4 ± 40.2) (P < 0.001). Severe multifidus sarcopenia was identified at a higher rate in the subgroup of patients who developed proximal junction pathology (66.7%) than in the subgroup of patients who developed neither PJK nor PJF (7.4%; P < 0.001). Multivariate analysis demonstrated both low HU at the UIV and moderate-severe multifidus sarcopenia to be risk factors for the development of PJK and PJF. Severe paraspinal sarcopenia and diminished bone density at the UIV impart an increased risk of developing PJK and PJF in following thoracolumbar fusions from the upper thoracic spine to the pelvis.

Minimally invasive ureteral reimplantation: trends in regions of the Russian Federation and The Republic of Belarus. Multi-center study

Introduction. Until recently, open ureteral reimplantation was considered the gold standard for the surgical treatment of ureterovesical junction (UVJ) pathologies. The introduction of minimally invasive ureteral reimplantation (MIUR) for the treatment of vesicoureteral reflux (VUR) and primary obstructive megaureter (POM) in children started in the 1990s. However, studies describing national trends in the use of minimally invasive and open approaches in the surgical treatment of UVJ pathology in children are limited.Objective. To describe changes in the use of MIUR and open ureteral reimplantation (OUR) between 2007 and 2022 in some regions of the Russian Federation and the Republic of Belarus and compare the results and complication rates of the two surgical approaches. Materials &amp; methods. The study includes 1273 patients (1793 ureters), operated on for UVJ pathology in the period from 2007 to 2022. MIR was performed in 1356 (75.6%) ureters (913 for VUR and 443 for POM). The studied parameters included an annual amount of reimplantation, the age of patients, the frequency of intra- and postoperative complications, as well as the medium-term results of operations.Results. The use of MIUR techniques has increased significantly over time, and in 2022, seventy-five percent of surgeries were performed using MIUR. Analysis of the rate of adoption of MIUR by clinics showed that those that began using it first experienced a significant increase in frequency of use after 4 to 6 years, while those that started later took 2 to 3 years to achieve a significant positive trend. There were 5 (0.4%) intraoperative complications in the MIUR group. All these complications were classified as grade I according to the Satava grading system. There was no significant difference between MIUR and OUR in terms of postoperative complication rates (6.6% vs. 7.6%, p = 0.8). The efficiency of reimplantation was 96.6% in the MIUR group compared to 95.9% in the OUR group for POM and 96.2% in the MIR group compared to 94.6% in the OUR for VUR.Conclusion. In the regions of Russia involved in the study, there has been a trend towards completely replacing open surgery with minimally invasive techniques. Regarding complication rates and efficacy, MIUR is not significantly different from OUR.

A Three-Step Submandibular Retropharyngeal Approach to the Craniovertebral Junction: Is Less Always More?

Background: Accessing the craniovertebral junction poses unique challenges due to its anatomical complexity and proximity to critical structures, such as the cord-brainstem junction, great vessels of the neck, cranial nerves, oropharynx, and rhinopharynx. Among the approaches that have been developed over the years, the submandibular retropharyngeal approach offers good antero-lateral access without the need of transgressing mucosal layers. In its traditional form, however, this approach involves multiple sequential steps and requires intricate dissection, extensive retraction, and meticulous maneuvering, which can increase operative time and produce approach-related morbidity. Methods: With this paper, we propose a simplified technique for a submandibular retropharyngeal approach involving only three surgical steps. The advantages and limitations of this technique are illustrated through three surgical cases of neoplastic and degenerative craniovertebral junction pathologies. Results: In two out of the three cases, our technique allowed for a wide exposure of the lesions that could be resected totally or sub-totally with good outcome. In one case with involvement of the clivus and the occipital condyle, the exposure was inadequate; a biopsy was obtained, and the lesion was subsequently resected via and endoscopic transmucosal approach. Conclusions: Our technique represents a significant simplification of the traditional submandibular retropharyngeal approach; with appropriate indication, it permits a fast, safe, and adequate exposure of craniovertebral junction pathologies.

Upper end of the central canal of the human spinal cord: Quantitative anatomical study and 3D modeling

AbstractThe upper end of the central canal of the human spinal cord has been repeatedly implicated in the pathogenesis of various diseases, yet its precise normal position in the medulla oblongata and upper cervical spinal cord remains unclear. The purpose of this study is to describe the anatomy of the upper end of the central canal with quantitative measurements and a three‐dimensional (3D) model. Seven formalin‐embalmed human brainstems were included, and the central canal was identified in serial axial histological sections using epithelial membrane antigen antibody staining. Measurements included the distances between the central canal (CC) and the anterior medullary fissure (AMF) and the posterior medullary sulcus (PMS). The surface and perimeter of the CC and the spinal cord were calculated, and its anterior–posterior and maximum lateral lengths were measured for 3D modeling. The upper end of the CC was identified in six specimens, extending from the apertura canalis centralis (ACC) to its final position in the cervical cord. Positioned on the midline, it reaches its final location approximately 15 mm below the obex. No specimen showed canal dilatation, focal stenosis, or evidence of syringomyelia. At 21 mm under the ACC in the cervical cord, the median distance from the CC to the AMF was 3.14 (2.54–3.15) mm and from the CC to the PMS was 5.19 (4.52–5.43) mm, with a progressive shift from the posterior limit to the anterior third of the cervical spinal cord. The median area of the CC was consistently less than 0.1 mm2. The upper end of the CC originates at the ACC, in the posterior part of the MO, and reaches its normal position in the anterior third of the cervical spinal cord less than 2 cm below the obex. Establishing the normal position of the upper end of this canal is crucial for understanding its possible involvement in cranio‐cervical junction pathologies.

Foramen magnum stenosis in patients with mucopolysaccharidoses: diagnosis and surgical treatment. Review of literature

Cervico-medullary compression and atlantoaxial dislocation syndromes are the dominant clinical manifestations of mucopolysaccharidoses at the craniovertebral level. The review provides an analysis of international literary sources concerning modern aspects of diagnosis and neurosurgical correction of the foramen magnum stenosis in patients with different types of mucopolysaccharidoses. The existing surgical approaches to determining the indications and choosing the method of surgical treatment and some aspects of the use of enzyme replacement therapy and hematopoietic stem cell transplantation are presented. A variety of options for surgical correction of pathology at the craniovertebral level have been demonstrated in patients with different types of mucopolysaccharidosis, however the described recommendations can be considered from the point of view of traditions of the hospitals or personal experience of surgeons, but not as recognized standards of treatment this pathology. Further accumulation of individual observations or clinical series is required to conduct a comparative analysis of the effectiveness of various approaches on a sufficiently large and homogeneous material to determine standards for the diagnosis and treatment of craniovertebral junction pathology in patients with mucopolysaccharidoses.

Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model – the mdx mouse – is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function.

A novel classification and management scheme for craniocervical junction disorders with ventral neural element compression.

Craniocervical junction (CCJ) pathologies with ventral neural element compression are poorly understood, and appropriate management requires accurate understanding, description, and a more uniform nomenclature. The aim of this study was to evaluate patients to identify anatomical clusters and better classify CCJ disorders with ventral compression and guide treatment. A retrospective review of adult and pediatric patients with ventral CCJ compression from 2008 to 2022 at a single center was performed. The incidence of anatomical abnormalities and compressive etiologies was assessed. Surgical approach, radiographic data, and outcomes were recorded. Association rules analysis (ARA) was used to assess variable clustering. Among 51 patients, the main causes of compression were either purely bony (retroflexed dens [n = 18]; basilar invagination [BI; n = 13]) or soft tissue (degenerative pannus [n = 16]; inflammatory pannus [n = 2]). The primary cluster in ARA was a retroflexed dens, platybasia, and Chiari malformation (CM), and the secondary cluster was BI, C1-2 subluxation, and reducibility. These, along with degenerative pannus, formed the three major classes. In assessing the optimal treatment strategy, reducibility was evaluated. Of the BI cases, 12 of the 13 patients had anterolisthesis of C1 that was potentially reducible, compared with 2 of the 18 patients with a retroflexed dens (both with concomitant BI), and no pannus cases. The mean C1-2 facet angle was significantly higher in BI at 32.4°, compared with -2.3° in retroflexed dens and 8.1° in degenerative pannus (p < 0.05). Endonasal decompression with posterior fixation was performed in 48 (94.0%) of the 51 patients, whereas posterior reduction/fixation alone was performed in 3 patients (6.0%). Of 16 reducible cases, open posterior reduction alone was successful in 3 (60.0%) of 5 cases, with all successes containing isolated BI. Reduction was not attempted if vertebral anatomy was unfavorable (n = 9) or the C1 lateral mass was absent (n = 5). The mean follow-up was 28 months. Symptoms improved in 88.9% of patients and were stable in the remaining 11.1%. Tracheostomy and percutaneous G-tube placement occurred in 7.8% and 11.8% of patients, respectively. Reoperation for an endonasal CSF leak repair or posterior cervical wound revision both occurred in 3.9% of patients. In classifying, one cluster caused decreased posterior fossa volume due to an anatomical triad of retroflexed dens, platybasia, and CM. The second cluster caused pannus formation due to degenerative hypertrophy. For both, endonasal decompression with posterior fixation was ideal. The third group contained C1 anterolisthesis characterized by a steep C1-2 facet angle causing reducible BI. Posterior reduction/fixation is the first-line treatment when anatomically feasible or endonasal decompression with in situ posterior fixation when anatomical constraints exist.

Differentiated diagnostic and surgical algorithm for isolated and combined Chiari malformation Type I

Introduction: Arnold-Chiari malformation (ACM) type I is a craniovertebral junction pathology with ectopy of the cerebellar tonsils through the great occipital foramen with compression of the brain stem and upper cervical spinal cord. Until now, there have been more than 20 types of surgical interventions for the Arnold-Chiari malformation type. Objective: The main purpose of this research is the decompression of craniovertebral stem structures and occipital foramen, and the search for effective methods to repair cerebrospinal fluid (CSF) circulation. Methods: The complex examination and surgical treatment at the Neurosurgery Department No. 1 of the National Hospital of the Ministry of Health of the Kyrgyz Republic (Bishkek, Kyrgyzstan) passed 201 patients (aged 16-74) with symptomatic ACM I from 2008 to 2020.

Functional and radiological outcomes following craniovertebral junction surgery.

Craniovertebral junction (CVJ) pathologies include atlantoaxial instability/deformities resulting in myelopathy, respiratory failure, and even death. Here, we describe the indications, preoperative planning, and intra-operative/postoperative complications following surgical management of CVJ anomalies. A prospective analysis of 34 patients with CVJ pathology was evaluated between 2015 and 2022. Their various etiologies included atlantoaxial instability, trauma, tuberculosis, Down's syndrome, Morquio syndrome, os odontoideum, and atlantoaxial abnormalities. Clinical outcomes were assessed using the American spinal injury association (ASIA) impairment scale score and Benzel's modified Japanese Orthopedic Association (mJOA) score. Surgical assessments included length of hospital stay, operative time, blood loss, and intraoperative postoperative complications. Radiological parameters included fusion (i.e., implant loosening/implant failure), preoperative/ postoperative atlanto-dens interval (ADI), clivus canal angle (CCA), and space available for cord (SAC). Five patients were managed conservatively, while 29 patients had surgery. Operations included occipitocervical fusion (14 patients), C1-2 fusion (10 patients), C1-2 transarticular screw fixation (four patients), and one patient underwent anterior corpectomy decompression/fusion. Seven patients had vertebral artery anomalies, and 13 patients had atlantoaxial abnormalities. At the final follow-up, atlantoaxial instability (i.e., mean preoperative ADI of 6.6 ± 2.3 mm) was restored to 4.2 ± 0.6 mm, significant cord compression (i.e., with mean SAC of 8.3 ± 2.9 mm) was relieved to 17.2 ± 1.6 mm, and the mean preoperative CCA (i.e., 130.2 ± 15.3) was improved to 143.3 ± 8.3°. There was also a statistically significant improvement in the ASIA scale and mJOA score. Surgical management of CVJ abnormalities requires expertise and meticulous planning to avoid devastating complications such as wound dehiscence and catastrophic vertebral artery injury.

Extremely Rare Pathologies of the Craniovertebral Junction Region: A Case Series and Review of the Literature

Background: The craniovertebral junction is a complex region, connecting the occiput, the atlas, the axis, and the containing vital neural and vascular structures. There is a great variability in diseases involving the craniovertebral junction, of different nature, each rare in frequency. Methods: We conducted a retrospective chart review of the patients diagnosed with extremely rare pathologies of the craniovertebral junction that we have operated in the last 5 years. Results: After excluding the relatively more frequent pathologies, we identified nine cases of rare craniovertebral junction pathologies. Six were operated using an endoscopic endonasal approach, two using a far lateral transcranial approach, and one underwent a C1 hemilaminectomy. Conclusions: Diagnosis and management of the rare pathologies of the craniovertebral junction are challenging. A multidisciplinary approach is recommended for the proper management of these patients.

Os odontoideum of C2 vertebra: Aspects of epidemiology, etiopathogenesis, clinical manifestations, and diagnosis. Literature review

We present a literature review devoted to the study of a craniovertebral malformation such as the os odontoideum of C2 vertebra. This is a rare anomaly that often results in atlantoaxial instability and, as a consequence, a wide range of clinical manifestations. The review is analytic and was conducted using medical literature databases and search resources, namely, PubMed (MEDLINE), Google Scholar, and eLibrary. The review focused on the definition of os odontoideum and its epidemiology, including the structure of craniovertebral junction pathologies. Features of the embryonic development of the craniovertebral junction, which are important in terms of the notion of the theories of the origin of os odontoideum, are described. The anatomical variants of the os odontoideum are presented, and a wide range of clinical manifestations of this pathological condition and approaches to its diagnosis are described.

Improving outcomes in adult spinal deformity surgery

Proximal junctional kyphosis and failure are important complications in reconstructive spine surgery. The impact of proximal junctional pathology on health status is variable, and junctional failure may involve compromise of neural and physical function, and may require revision surgery. The risk factors for proximal junctional kyphosis include multilevel fusion to the sacrum, malalignment of the spine, choice of upper instrumented vertebra, magnitude of realignment, bone and muscle quality, tension band integrity and characteristics of the unfused spine. The pathophysiology of proximal junctional pathology involve fracture and bony failure, ligamentous and soft tissue failure, and combined bone and soft tissue failure. Prevention of proximal junctional pathology is an important goal, and has a significant impact on improving the outcomes and durability of spinal reconstructive surgery. Prevention strategies are derived from an understanding of the underlying causes of junctional pathology. Preoperative planning to determine optimal post-operative alignment, and intraoperative strategies to achieve that alignment are important for prevention of junctional pathology. Preoperative preparation of the patient with optimization of bone quality, extensor muscle strength and body mass index may prevent junctional complications. Surgical strategies including anterior column load sharing and posterior augmentation of fixation are useful for prevention of junctional pathology. Cement augmentation at the upper instrumented vertebra, with possible inclusion of the next cephalad vertebra may be protective of bone failure. Ligamentoplasty and preservation of the tension band may be protective of soft tissue failure. Proximal junctional pathology remains an important complication in spinal reconstructive surgery. Understanding the factors associated with proximal junctional pathology including the mechanisms underlying junctional kyphosis, and awareness of the strategies for avoidance of junctional pathology will empower the surgeon to reduce the risk of post-operative junctional kyphosis and lead to improved outcomes in adult spinal deformity surgery.

Utility of Repetitive Nerve Stimulation in the Diagnosis of Myasthenia Gravis in the Inpatient Setting.

Sensitivity and specificity of Repetitive Nerve Stimulation (RNS) is typically reported from outpatient centers, and we hypothesized that these values might not apply to hospitalized patients with higher grades of weakness. RNS may be helpful in rapidly confirming diagnosis of myasthenia gravis (MG) in the inpatient setting, as results from confirmatory antibody testing are often delayed. We sought to characterize the sensitivity and specificity of RNS in the inpatient setting to assist in the early diagnosis of MG. We performed a retrospective analysis of all adult patients who had inpatient RNS at our center from 2016 to 2021. Inclusion criteria included RNS performed at least at one site and a neurological evaluation which prompted an electrodiagnostic study to evaluate for neuromuscular junction (NMJ) pathology. Descriptive statistics and Fisher exact analysis were performed. Of the 32 identified hospitalized patients, 6 had greater than 10% decrement on slow RNS, confirming NMJ dysfunction. Five were diagnosed with MG, and 1 with Lambert-Eaton myasthenic syndrome. Of the 26 patients with normal RNS, 25 ultimately had alternative causes of weakness. One was later diagnosed as seronegative MG based on clinical improvement with acetylcholinesterase inhibitors. In our inpatient population, the overall sensitivity and specificity of RNS were 83.3% and 96.2% respectively. There was a statistically significant association between a positive RNS and diagnosis of MG (P = .0002). RNS is a highly sensitive and specific test for the diagnosis of MG in an inpatient setting, and these results are likely more rapidly available compared to antibody testing.

Advances, Challenges, and Future Directions in the Management of Craniovertebral Junction Pathologies

In this third article in a 3-article series on the craniocervical junction, we define the terms "basilar impression," "cranial settling," "basilar invagination," and "platybasia," noting that these terms are often used interchangeably but represent distinct entities. We then provide examples that represent these pathologies and treatment paradigms. Finally, we discuss the challenges and future direction in the craniovertebral junction surgery space.

Nuance in Craniovertebral Junction Surgical Approach for Posterior C1-C2 Harms Stabilization: "Window Transposition" of the External Vertebral Venous Plexus for Bloodless C1 Lateral Mass Screw Insertion: Anatomical Aspects and Technical Notes.

Atlas and axis instrumentation may be necessary in cases of several craniocervical junction pathologies. According to the Harms technique, C1-C2 polyaxial screws are inserted respectively in the C1 lateral masses and in C2 pedicles. C1 lateral mass screw insertion requires the careful subperiosteal dissection of the posterior elements of C1, the identification of the screw entry point by the downward distraction of C2 nerve root, and the cautious sparing of the overlying posterior external vertebral venous plexus (peVVP), whose bleeding, obstructing the surgical field, is sometimes barely controlled by hemostatic agents and swabbing. The authors describe in detail the anatomical aspects of an alternative surgical technique developed for the microsurgical transposition of the C1-C2 interposed external vertebral venous plexus in the case of Harms C1-C2 screw stabilization. The longitudinal median incision of the atlantoaxial membrane, followed by bilateral subperiosteal dissection and microsurgical section respectively at the inferior borders of the C1 laminae and at the superior borders of the C2 laminae, allows, as a "window opening," the symmetrical mediolateral transposition of the peVVP. This procedure provides a faster and cleaner anatomical exposition of the posterior surface of the C1 lateral mass and the C2 isthmus, preventing troublesome intraoperative venous bleeding that hinders C1 lateral mass screw insertion.

Glial Gap Junction Pathology in the Spinal Cord of the 5xFAD Mouse Model of Early-Onset Alzheimer's Disease.

Gap junctions (GJs) are specialized transmembrane channels assembled by two hemi-channels of six connexin (Cx) proteins that facilitate neuroglial crosstalk in the central nervous system (CNS). Previous studies confirmed the crucial role of glial GJs in neurodegenerative disorders with dementia or motor dysfunction including Alzheimer's disease (AD). The aim of this study was to examine the alterations in astrocyte and related oligodendrocyte GJs in association with Aβ plaques in the spinal cord of the 5xFAD mouse model of AD. Our analysis revealed abundant Aβ plaque deposition, activated microglia, and astrogliosis in 12-month-old (12M) 5xFAD mice, with significant impairment of motor performance starting from 3-months (3M) of age. Additionally, 12M 5xFAD mice displayed increased immunoreactivity of astroglial Cx43 and Cx30 surrounding Aβ plaques and higher protein levels, indicating upregulated astrocyte-to-astrocyte GJ connectivity. In addition, they demonstrated increased numbers of mature CC1-positive and precursor oligodendrocytes (OPCs) with higher immunoreactivity of Cx47-positive GJs in individual cells. Moreover, total Cx47 protein levels were significantly elevated in 12M 5xFAD, reflecting increased oligodendrocyte-to-oligodendrocyte Cx47-Cx47 GJ connectivity. In contrast, we observed a marked reduction in Cx32 protein levels in 12M 5xFAD spinal cords compared with controls, while qRT-PCR analysis revealed a significant upregulation in Cx32 mRNA levels. Finally, myelin deficits were found focally in the areas occupied by Aβ plaques, whereas axons themselves remained preserved. Overall, our data provide novel insights into the altered glial GJ expression in the spinal cord of the 5xFAD model of AD and the implicated role of GJ pathology in neurodegeneration. Further investigation to understand the functional consequences of these extensive alterations in oligodendrocyte-astrocyte (O/A) GJ connectivity is warranted.

Robotic ureteral reimplantation and uretero-ureterostomy treating the ureterovesical junction pathologies in children: technical considerations and preliminary results.

Robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR) and robotic ureteroureterostomy (RUU) are two mini-invasive surgical techniques that have begun to be performed in pediatric urology in recent years. RALUR has been employed especially for VUR treatment, while RUU is considered principally in case of complex doubled ureteral systems. Our aim is to discuss the safety and feasibility of these approaches in children, focusing on technical considerations and supporting their use in different anomalies and pathologies of the ureterovesical junction. We retrospectively collected data about 58 patients who underwent 44 dismembered RALUR (D-RALUR), 28 non-dismembered RALUR (ND-RALUR) and 5 RUU between May 2020 and December 2021. Indications for surgery were primary or secondary vesicoureteral reflux, megaureter, secondary UVJ obstructions, complicated doubled ureteral systems. Mean age was 3.5years (range 0.6-12.9) and mean weight 17.1 (range 7.2-80). No intraoperative complications occurred nor conversion to open approach were reported. Major postoperative complications were reported in 11.7% of cases with a higher incidence for ND-RALUR. Mean hospital stay was 2.14days (range 1-8). Success rate at the short-term follow-up was 91.9% for D-RALUR, 96.3% for ND-RALUR and 100% for RUU. RALUR and RUU are two feasible and safe procedures to perform in children. RALUR represents the most required and adequate technique in the treatment of UVJ pathologies, however, in selected cases RUU could represent an effective alternative that has to be considered.

C1-C2 coronal and sagittal joint angle based treatment algorithm for the need of transoral odointectomy in complex craniovertebral junction anomalies with Clinico-Radiological outcome analysis

Objective Craniovertebral junction (CVJ) pathology by virtue of its complexity is a surgical challenge in the realm of neurosurgery. We analyzed the need for transoral odointectomy in view of their C1-C2 joint coronal and sagittal angle of 58 patients with complex CVJ anomalies treated surgically. The clinical and radiological outcome of the patients was assessed and a treatment algorithm is proposed. Methods A total of 58 cases were included in the Prospective study over the period of 2 years. Patients were evaluated clinically, investigated, and operated with reduction and rigid internal fixation with screws and rod. The clinical outcome was measured by Modified Japanese orthopedic association score(mJOA) and radiologically by conventional craniometrics indices. Paired ‘t’ test used for statistical analysis. Results Mean age of patients: 30 years, with mean, follow up: 20.5 months. 46(80%) patients were operated by posterior and 12(20%) by combined approach (anterior transoral with posterior). Occipitocervial fixation was done in 15(25.8%) cases and C1-C2 fixation in 43(74.2%) cases. As compared to patients with low coronal angle, the patient with coronal angle >65° needed anterior decompression (87.5%) and all (100%) had Occipitocervical fixation. Clinical outcome analysis showed significant improvement in mean mJOA score (preop 11.9 Vs postop 14.6) after surgery. All craniometrics indices were significantly improved after surgery. The overall complication rate was 10% with a mortality of 1.7%. 6 months follow up completed in all patients with a 100% fusion rate. Conclusion Occipitocervical fixation and anterior decompression is required in increased C1-C2 joint CA (>65°) for bony realignment and adequate decompression. Measurement of C1-C2 joint coronal and sagittal angle in complex CVJ anomalies will easily anticipate the surgeon regarding the need for anterior decompression inform of transoral odointectomy.

Suppression of the necroptotic cell death pathways improves survival in Smn 2B/- mice.

Spinal muscular atrophy (SMA) is a monogenic neuromuscular disease caused by low levels of the Survival Motor Neuron (SMN) protein. Motor neuron degeneration is the central hallmark of the disease. However, the SMN protein is ubiquitously expressed and depletion of the protein in peripheral tissues results in intrinsic disease manifestations, including muscle defects, independent of neurodegeneration. The approved SMN-restoring therapies have led to remarkable clinical improvements in SMA patients. Yet, the presence of a significant number of non-responders stresses the need for complementary therapeutic strategies targeting processes which do not rely solely on restoring SMN. Dysregulated cell death pathways are candidates for SMN-independent pathomechanisms in SMA. Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 have been widely recognized as critical therapeutic targets of necroptosis, an important form of programmed cell death. In addition, Caspase-1 plays a fundamental role in inflammation and cell death. In this study, we evaluate the role of necroptosis, particularly RIPK3 and Caspase-1, in the Smn2B/− mouse model of SMA. We have generated a triple mutant (TKO), the Smn2B/−; Ripk3−/−; Casp1−/− mouse. TKO mice displayed a robust increase in survival and improved motor function compared to Smn2B/− mice. While there was no protection against motor neuron loss or neuromuscular junction pathology, larger muscle fibers were observed in TKO mice compared to Smn2B/− mice. Our study shows that necroptosis modulates survival, motor behavior and muscle fiber size independent of SMN levels and independent of neurodegeneration. Thus, small-molecule inhibitors of necroptosis as a combinatorial approach together with SMN-restoring drugs could be a future strategy for the treatment of SMA.

Neuromuscular junction pathology is correlated with differential motor unit vulnerability in spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is an X-linked, neuromuscular neurodegenerative disease for which there is no cure. The disease is characterized by a selective decrease in fast-muscle power (e.g., tongue pressure, grip strength) accompanied by a selective loss of fast-twitch muscle fibers. However, the relationship between neuromuscular junction (NMJ) pathology and fast-twitch motor unit vulnerability has yet to be explored. In this study, we used a cross-model comparison of two mouse models of SBMA to evaluate neuromuscular junction pathology, glycolytic-to-oxidative fiber-type switching, and cytoskeletal alterations in pre- and postsynaptic termini of tibialis anterior (TA), gastrocnemius, and soleus hindlimb muscles. We observed significantly increased NMJ and myofiber pathology in fast-twitch, glycolytic motor units of the TA and gastrocnemius compared to slow-twitch, oxidative motor units of the soleus, as seen by decreased pre- and post-synaptic membrane area, decreased pre- and post-synaptic membrane colocalization, increased acetylcholine receptor compactness, a decrease in endplate area and complexity, and deficits in neurofilament heavy chain. Our data also show evidence for metabolic dysregulation and myofiber atrophy that correlate with severity of NMJ pathology. We propose a model in which the dynamic communicative relationship between the motor neuron and muscle, along with the developmental subtype of the muscle, promotes motor unit subtype specific vulnerability, metabolic alterations, and NMJ pathology.