The First Pituitary Proteome Landscape From Matched Anterior and Posterior Lobes for a Better Understanding of the Pituitary Gland.

To date, very few mass spectrometry (MS)-based proteomics studies are available on the anterior and posterior lobes of the pituitary. In the past, MS-based investigations have focused exclusively on the whole pituitary gland or anterior pituitary lobe. In this study, for the first time, we performed a deep MS-based analysis of five anterior and five posterior matched lobes to build the first lobe-specific pituitary proteome map, which documented 4090 proteins with isoforms, mostly mapped into chromosomes 1, 2, and 11. About 1446 differentially expressed significant proteins were identified, which were studied for lobe specificity, biological pathway enrichment, protein-protein interaction, regions specific to comparison of human brain and other neuroendocrine glands from Human Protein Atlas to identify pituitary-enriched proteins. Hormones specific to each lobe were also identified and validated with parallel reaction monitoring-based target verification. The study identified and validated hormones, growth hormone and thyroid-stimulating hormone subunit beta, exclusively to the anterior lobe whereas oxytocin-neurophysin 1 and arginine vasopressin to the posterior lobe. The study also identified proteins POU1F1 (pituitary-specific positive transcription factor 1), POMC (pro-opiomelanocortin), PCOLCE2 (procollagen C-endopeptidase enhancer 2), and NPTX2 (neuronal pentraxin-2) as pituitary-enriched proteins and was validated for their lobe specificity using parallel reaction monitoring. In addition, three uPE1 proteins, namely THEM6 (mesenchymal stem cell protein DSCD75), FSD1L (coiled-coil domain-containing protein 10), and METTL26 (methyltransferase-like 26), were identified using the NeXtProt database, and depicted tumor markers S100 proteins having high expression in the posterior lobe. In summary, the study documents the first matched anterior and posterior pituitary proteome map acting as a reference control for a better understanding of functional and nonfunctional pituitary adenomas and extrapolating the aim of the Human Proteome Project towards the investigation of the proteome of life.

Clinical analysis of surgical outcome of 89 patients having large cerebral arteriovenous malformations.

OBJECTIVE: The article analyzes the clinical features, morphological characteristics, surgical subtleties and long-term outcome of surgery in 89 cases of 'large' sized AVMs. MATERIALS AND METHODS: During the period 2004 to 2022, 89 cases of 'large' arteriovenous malformations were operated in the neurosurgery departments of the authors. Large AVMs were defined as those that were more than 4 cm on either lateral or antero-posterior view of digital subtraction angiogram. The factors that determined the extent of surgical difficulties included site and eloquence of the area, number of feeding vascular territories and draining veins, degree and rate of flow, presence of flow-related aneurysms, and the physical nature of the arteriovenous malformation. RESULTS: There were 59 males and 30 females and the average age was 32 years. Headache, giddiness and convulsions were the common presenting complaints. Six patients were unconscious after surgery. Of these, five patients died in the immediate post-operative period and one patient gradually recovered. Additionally, seven patients developed unilateral limb weakness that included hemiplegia (4 patients) and hemiparesis (3 patients) following surgery. Clinical follow-up ranged from 6 months to 18 years (average 43 months). All surviving patients are leading normal and essentially symptom free life and have recovered from their symptoms of headache, convulsions and giddiness. CONCLUSIONS: Large AVMs are amenable to 'curative' surgery with 'acceptable' results. The surgery can be challenging and appropriate case selection that is based on the surgeons experience is vital and decisive.

Downregulation of ARID1B, a tumor suppressor in the WNT subgroup medulloblastoma, activates multiple oncogenic signaling pathways.

Medulloblastoma, a common pediatric malignant brain tumor, consists of four distinct molecular subgroups WNT, SHH, Group 3 and Group 4. Exome sequencing of 11 WNT subgroup medulloblastomas from an Indian cohort identified mutations in several chromatin modifier genes, including genes of the mammalian SWI/SNF complex. The genome of WNT subgroup tumors is known to be stable except for monosomy 6. Two tumors, having monosomy 6, carried a loss of function mutation in the ARID1B gene located on chromosome 6. ARID1B expression is also lower in the WNT subgroup tumors compared to other subgroups and normal cerebellar tissues that could result in haploinsufficiency. The short hairpin RNA-mediated knockdown of ARID1B expression resulted in a significant increase in the malignant potential of medulloblastoma cells. Transcriptome sequencing identified upregulation of several genes encoding cell adhesion proteins, matrix metalloproteases indicating the epithelial-mesenchymal transition. The ARID1B knockdown also upregulated ERK1/ERK2 and PI3K/AKT signaling with a decrease in the expression of several negative regulators of these pathways. The expression of negative regulators of the WNT signaling like TLE1, MDFI, GPX3, ALX4, DLC1, MEST decreased upon ARID1B knockdown resulting in the activation of the canonical WNT signaling pathway. Synthetic lethality has been reported between SWI/SNF complex mutations and EZH2 inhibition, suggesting EZH2 inhibition as a possible therapeutic modality for WNT subgroup medulloblastomas. Thus, the identification of ARID1B as a tumor suppressor and its downregulation resulting in the activation of multiple signaling pathways opens up opportunities for novel therapeutic modalities for the treatment of WNT subgroup medulloblastoma.

9-Demethoxy-medicarpin: A potential bone health supplement for the management of protein deficiency-induced bone loss in growing rats.

Human skeleton requires an adequate supply of many different nutritional factors for optimal growth and development. The role of nutrition in bone growth has piqued interest in recent years, especially in relation to maximizing peak bone mass and reducing the risk of osteoporosis. Protein deficiency-induced bone loss was induced in female growing rats. All experimental rodent diets were prepared as per recommendations for growing animals. 9-Demethoxy-medicarpin (DMM) treatment was given to growing Sprague Dawley (SD) rats at 1 mg and 10 mg dose orally for 30 days. Bones were collected for bone mineral density (BMD). Bone marrow cells were isolated from femur for calcium nodule formation. Serum samples were collected for biochemical parameters. We found that DMM treatment speeds up the recovery of musculoskeletal weakness by replenishing nutrients in proven rodent model. DMM supplementation for four weeks showed significantly increased vertebral, femur and tibial BMD compared with the untreated PD group. Albumin levels were significantly enhanced in treatment groups, in which 10 mg dose imparted a better effect. We conclude that DMM treatment led to increased BMD and biochemical parameters in protein deficient condition in growing rats and has potential as a bone growth supplement.

Evolving Concepts of Craniovertebral and Spinal Instability.

Weakness of the muscles of the nape of the neck and back of the spine and its related instability is the nodal point of pathogenesis of a number of clinical and pathological events at the craniovertebral junction and the spine. Whilst acute instability results in sudden and relatively severe symptoms, chronic or long-standing instability is associated with a range of musculoskeletal and structural spinal alterations. Telescoping of the spinal segments results in "vertical" spinal instability in the subaxial spine and central or axial atlantoaxial instability (CAAD) at the craniovertebral junction. Instability in such cases might not be observed on dynamic radiological imaging. Chiari formation, basilar invagination, syringomyelia, and Klippel-Feil alteration are some of the secondary alterations as a result of chronic atlantoaxial instability. Radiculopathy/myelopathy related to spinal degeneration or ossification of posterior longitudinal ligament appears to have their origin from vertical spinal instability. All the secondary alterations in the craniovertebral junction and subaxial spine that are traditionally considered pathological and to have compressive and deforming role are essentially protective in nature, are indicative of instability, and are potentially reversible following atlantoaxial stabilization. Stabilization of unstable spinal segments is the basis of surgical treatment.

Management of the Vertebral Artery in Craniovertebral Junction Stabilization Surgery.

The vertebral artery (VA) has an intimate relationship with the bones of the craniovertebral junction. An exact understanding of the VA anatomy in general and in the specific surgical case in particular is absolutely necessary in order to avoid intraoperative vascular injury. The course of the VA on the inferior aspect of the superior facet of the C2 vertebra makes it susceptible to damage during transarticular and interarticular fixation with the screw insertion in the adjacent lateral mass. The consequences of the intraoperative VA injury will depend on the patency of other arteries supplying the brain. In case of this complication, quick decision-making is essential to avoid excessive blood loss and to preserve adequate cerebral blood flow.

Central Atlantoaxial Dislocation: Presenting Symptoms, Diagnostic Parameters, and Surgical Treatment from Reports on 15 Surgically Treated Patients.

AIM: This chapter reviews the clinical entity of central or axial atlantoaxial instability (CAAD). MATERIAL AND METHODS: From January 2018 to November 2020, 15 patients were identified as having CAAD, wherein there was no atlantoaxial instability when analyzed by conventional radiological parameters and wherein there was no evidence of neural or dural compression due to the odontoid process. The patients were identified as having atlantoaxial instability on the basis of the alignment of facets on lateral profile imaging and a range of telltale clinical and radiological indicators. The clinical statuses of the patients were recorded both before and after surgical treatment by using the specially designed Goel symptom severity index and visual analog scale (VAS) scores. All patients were treated via atlantoaxial fixation. RESULTS: There were six men and nine women ranging in age from 18 to 45 years (average: 37 years). The presenting clinical symptoms were relatively subtle and long-standing. Apart from symptoms that are generally related to neural compromise at the craniovertebral junction, a range of nonspecific cranial and spinal symptoms were prominent. The follow-up time after surgery ranged from 6 to 34 months. All patients showed early postoperative and sustained clinical recovery. CONCLUSIONS: The correct diagnosis and appropriate surgical treatment of CAAD can provide an opportunity for quick and lasting clinical recovery.

Central or axial atlantoaxial dislocation and craniovertebral junction alterations: a review of 393 patients treated over 12 years.

OBJECTIVE: The authors reviewed their scientific publications and updated their clinical material obtained over the last 12 years for cases of central or axial atlantoaxial dislocation (CAAD) identified in the presence of craniovertebral musculoskeletal and/or neural alteration(s). The management implications of diagnosing and treating CAAD are highlighted. METHODS: During a 12-year period, CAAD was diagnosed in 393 patients with craniovertebral junction-related musculoskeletal and neural alterations who underwent atlantoaxial fixation. No bone decompression was done. All CAAD-related craniovertebral junction structural changes were identified to have a naturally protective role. Hence, in this paper the term "craniovertebral alterations" is used for "craniovertebral junction anomalies" and the term "Chiari formation" is used instead of the commonly used term "Chiari malformation." RESULTS: The major radiological diagnosis was determined either singly or in cohort with one or more of other so-called pathological entities that included Chiari formation (367 cases), syringomyelia with Chiari (306 cases), idiopathic syringomyelia (12 cases), type B basilar invagination (147 cases), bifid arch of the atlas (9 cases), assimilation of the atlas (119 cases), C2-3 fusion (65 cases), Klippel-Feil alteration (4 cases), and dorsal kyphoscoliosis (15 cases). The follow-up period ranged from 6 to 155 months. Clinical improvement was observed in all patients. CONCLUSIONS: Understanding and treating CAAD may have significant implications in the surgical treatment of a number of clinical entities. The gratifying clinical outcomes obtained in patients after atlantoaxial fixation, without any type of decompression involving bone or soft-tissue resection, consolidate the concept that atlantoaxial instability has a defining role in the pathogenesis.

Pathogenesis, management strategies, and outcome of non-communicating extradural spinal arachnoid cyst (NEAC): a systematic review.

OBJECTIVE: Non-communicating extradural spinal arachnoid cysts (NEACs) are extremely rare aetiology of symptomatic spinal cord compression. The aim of this study was to address their pathogenesis, optimum management strategy and outcome through systematic review of existing published studies. MATERIALS AND METHOD: We have found 13 eligible publications by searching through PubMed, ScienceDirect, and Google Scholar databases, published from inception to December 2020. We have analysed the data of 21 patients extracted from those 13 publications by IBM SPSS version 23. RESULTS: According to our analysis congenital predisposition, trauma, and previous surgery history are the aetiology of NEAC. Clinical presentation of cyst depends upon the location and extent of compression or involvement of the neurovascular structures. Paraparesis with variable degree of sensory disturbance was seen among patients. Based on neuroimaging findings, NEACs are most commonly found at dorsal and dorsolumbar region. Magnetic resonance imaging (MRI) is the diagnostic modalities of choice and CT myelography can demonstrate the communication with the subarachnoid space. Recurrence rate of cyst after surgery is very low as only one out of twenty patients showed recurrence. If dural defect is not accurately addressed, the recurrence rate increased significantly. CONCLUSIONS: Our study has highlighted aetiology, treatment strategies, and neurological outcome of NEAC. These findings may help neurosurgeons to manage this rare surgical entity for favourable outcome.

Maintenance of increased bone mass after PTH withdrawal by sequential medicarpin treatment via augmentation of cAMP-PKA pathway.

Osteoporosis is a metabolic bone disorder associated with impaired bone microarchitecture leading to fragility fractures. Long-term usage of parathyroid hormone (PTH) enhances bone resorption and leads to osteosarcoma in rats which limits its exposure to maximum 2 years in human. Notably, the anabolic effects of PTH do not endure in the absence of sustained administration. Studies in our lab identified osteogenic and antiresorptive activity in medicarpin, a phytoestrogen belonging to the pterocarpan class. Considering dual-acting property of medicarpin and limitations of PTH therapy, we envisaged that medicarpin sequential treatment after PTH withdrawal could serve as promising therapeutic approach for osteoporosis treatment. As PTH exerts its bone anabolic effect by increasing osteoblast survival, our study aims to determine whether medicarpin amplifies this effect of PTH. Our results show that PTH withdrawal led to reduced bone mineral density and bone parameters, while sequential treatment of medicarpin after PTH withdrawal significantly enhanced these parameters. Remarkably, these effects were more pronounced than 8-week PTH treatment. Sequential therapy also significantly increased P1NP levels and decreased CTX levels and TRAP positive cells compared to PTH 8W group where CTX levels were quite high due to bone resorptive action of PTH. Protein expression studies revealed that medicarpin along with PTH betters the antiapoptotic potential compared to PTH alone, through augmentation of cyclic adenosine monophosphate-PKA-CREB pathway. These results proclaim that medicarpin sequential treatment prevented the reduction in bone accrual and strength accompanying PTH withdrawal and also aided in antiapoptotic role of PTH. The study points toward the potential use of medicarpin as a replacement therapeutic option postdiscontinuation of PTH.

Metabolomics Profiling of Pituitary Adenomas by Raman Spectroscopy, Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy, and Mass Spectrometry of Serum Samples.

To date, no studies are available in which pituitary adenomas (PAs) have been studied using techniques like confocal Raman spectroscopy, attenuated total reflection-Fourier transform infrared (FT-IR), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the same serum samples. To understand the metabolomics fingerprint, Raman spectra of 16 acromegaly, 19 Cushing's, and 33 nonfunctional PA (NFPA) and ATR-FTIR spectral acquisition of 16 acromegaly, 18 Cushing's, and 22 NFPA patient's serum samples were acquired. Next, Principal component-based linear discriminant analysis (PC-LDA) models were developed, Raman spectral analysis classified acromegaly with an accuracy of 79.17%, sensitivity of 75%, and specificity of 81.25%, Cushing's with an accuracy of 66.67%, sensitivity of 100%, and specificity of 52.63%, and NFPA with an accuracy of 73.17%, sensitivity of 75%, and specificity of 72.73%. ATR-FTIR spectral analysis classified acromegaly with an accuracy of 95.83%, sensitivity of 100%, and specificity of 93.75%, Cushing's with an accuracy of 65.38%, sensitivity of 87.5%, and specificity of 55.56%, and NFPA with an accuracy of 70%, sensitivity of 87.5%, and specificity of 43.75%. In either of the cases, healthy individual cohorts were clearly segregated from the disease cohort, which identified differential regulated regions of nucleic acids, lipids, amides, phosphates, and polysaccharide/C-C residue α helix regions. Furthermore, LC-MS/MS-based analysis of sera samples resulted in the identification of various sphingosine, lipids, acylcarnitines, amino acids, ethanolamine, choline, and their derivatives that differentially regulated in each tumor cohort. We believe cues obtained from the study may be used to generate the metabolite-based test to diagnose PAs from serum in addition to conventional techniques and also to understand disease biology for better disease management, point of care, and improving quality of life in PA patients.

Nitazoxanide potentiates linezolid against linezolid-resistant Staphylococcus aureus in vitro and in vivo.

BACKGROUND: Antimicrobial resistance is a growing menace, claiming millions of lives all over the world. In this context, drug repurposing is one approach gaining interest as a suitable alternative to conventional drug discovery and development. METHODS: Whole-cell assays were used to screen FDA-approved drugs to identify novel antimicrobial agents active against bacterial pathogens. Following identification of nitazoxanide, its various characteristics, such as antimicrobial activity against MDR isolates, time-kill kinetics, ability to synergize with approved drugs, antibiofilm activity and ability to generate resistance in Staphylococcus aureus, were determined, followed by determination of its in vivo potential against MDR S. aureus. RESULTS: Nitazoxanide demonstrated a potent in vitro antistaphylococcal profile, including equipotent activity against clinical drug-resistant S. aureus and Enterococcus spp. Nitazoxanide exhibited concentration-dependent killing, significantly eradicated preformed S. aureus biofilm and S. aureus did not generate resistance to it. Nitazoxanide strongly synergized with linezolid both in vitro and in vivo against linezolid-susceptible and -resistant S. aureus, displaying superior activity to untreated control and drug-alone treatment groups. CONCLUSIONS: Nitazoxanide can be utilized in combination with linezolid against infections caused by linezolid-resistant S. aureus as it exhibits strong synergism in vitro and in vivo.

Hangman's fracture: a clinical review based on surgical treatment of 15 cases.

This is a retrospective analysis of cases with hangman's fracture. The subject of 'hangman's fracture' has been elaborately evaluated in the literature. The authors propose an alternative format of surgical treatment that is based on modification of existing classification schemes. During the period 2015 to March 2020, 15 patients having hangman's fracture were identified and were surgically treated. The clinical condition was classified on the basis of American Spinal Injury Association scale (ASIA scale) and VAS parameters. The patients were classified into 4 groups depending on the presence (or absence) of atlantoaxial and/or C2-3 instability. Surgical decisions were guided by the proposed classification. Clinical evaluation and dynamic CT scan were done at follow-up visits. During the average follow-up of 26 months, all patients are essentially asymptomatic. There was marginal restriction of extent of neck movements in all cases. There was solid bone fusion in all cases. The proposed novel classification scheme based on the presence of atlantoaxial and C2-3 instability assisted in directing the treatment strategy of hangman's fracture.

Zonisamide in Parkinson's disease: a current update.

Parkinson's disease (PD) is a progressive neurodegenerative disease due to the depletion of the neurotransmitter dopamine in basal ganglia. There is a scarcity of available therapies for motor and non-motor symptoms of PD. Zonisamide (ZNS) may be one such potential candidate to alleviate PD symptoms. It was serendipitously found to be useful for PD in a patient with both epilepsy and PD. Since then, there have been many clinical trials, case series, observational studies, and case reports published supporting the efficacy of ZNS in PD. This review focuses on the efficacy and usefulness of ZNS in various motor and non-motor symptoms of PD. A predefined inclusion and exclusion criteria were used for the search protocol and databases searched were PubMed, Cochrane Library, Ovid, and clinicaltrials.gov. Most of the randomized clinical trials used UPDRS III as the primary efficacy point and showed positive results favouring ZNS. This review shows that there is evidence of the efficacy of ZNS in motor symptoms as an adjunctive therapy to levodopa, but for non-motor symptoms, the evidence is lacking and needs further investigation.

Cabergoline may act as a radioprotective agent in Cushing's disease.

CONTEXT: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect. OBJECTIVE: To determine long-term outcome of CRT and its predictors in CD patients. DESIGN, SETTING AND PATIENTS: This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. RESULTS: The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016). CONCLUSION: Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD.

First Dual Responsive "Turn-On" and "Ratiometric" AIEgen Probe for Selective Detection of Hydrazine Both in Solution and the Vapour Phase.

A new dual responsive "turn-on" and "ratiometric" aggregation-induced emission luminogen (AIEgen) 3-formyl-5-(piperidin-1-yl)biphenyl-4-carbonitrile 6 a (FPBC 6 a) for selective detection of hydrazine in solution as well as in vapour phase is described. At a low concentration of 2.5 µm, the probe FPBC 6 a is non-fluorescent (turn-off) but remarkably lights up (turn-on with blue emission) in the presence of hydrazine solution (0.25-25 µm). Interestingly, at higher concentrations, the nanoaggregates of FPBC 6 a (>25 µm, 99 % HEPES in DMSO) displayed ratiometric response in the presence of hydrazine with a remarkable hypsochromic shift from the green (500-550 nm) to blue regions (440-480 nm). Furthermore, a real application of FPBC 6 a was successfully demonstrated through the detection and visualization of hydrazine in live cervical cancer cells as well as using portable test strips.

Synthesis of Solution-Processable Donor-Acceptor Pyranone Dyads for White Organic Light-Emitting Devices.

A series of donor-acceptor pyranones (3a-m, 4a-h) were synthesized using α-oxo-ketene- S, S-acetal as the synthon for their application as emissive materials for energy-saving organic light-emitting devices (OLEDs). Among them, five pyranones 3f, 3g, 3h, 3m, and 4e exhibited highly bright fluorescence in the solid state and weak or no emission in the solution state. Photophysical analysis of these dyes revealed that only 3f and 3m showed aggregation-induced emission behavior in a THF/water mixture (0-99%) with varying water fractions ( fw) leading to bright fluorescence covering the entire visible region, while other derivatives 3g, 3h, and 4e did not show any fluorescence signal. The computational studies of the compounds revealed that the longer wavelength absorption originates from HOMO to LUMO electronic excitation. These dyes exhibited good thermal stability with 5% weight loss temperature in the range of 218-347 °C. The potential application of the donor-acceptor pyranone dyads was demonstrated by fabrication of solution-processed OLEDs. Remarkably, OLED devices prepared using highly emissive compounds 6-(anthracen-9-yl)-4-(methylthio)-2-oxo-2 H-pyran-3-carbonitrile (3m) and 6-(4-methoxyphenyl)-4-(methylthio)-2-oxo-2 H-pyran-3-carbonitrile (3f) displayed pure white emission with CIE coordinates of (0.29, 0.31) and (0.32, 0.32), respectively. Additionally, the resultant devices exhibited external quantum efficiencies of 1.9 and 1.2% at 100 cd m-2, respectively.

Atlantoaxial Instability: Evolving Understanding.

The atlantoaxial joint is the most mobile joint in the body. The physical architecture of the joint is characterized by a uniformly round and approximately flat surface, which allows a wide range of unobstructed movements. The standing human posture and lifelong heartbeat like uninterrupted activity of the atlantoaxial joint, and its ability to facilitate saying both 'yes' and 'no' necessarily requires smooth and 'fluid' movements that are supported by strong yet supple ligaments. The magnificent architectural structure that is 'magically' designed and carved by nature to provide both stability and mobility and to allow a smooth and safe transit passage for the most critical neural and vascular structures can only be admired in awe and appreciated.

Role of Subaxial Spinal and Atlantoaxial Instability in Multisegmental Cervical Spondylotic Myelopathy.

AIM: In this paper the role of atlantoaxial and multilevel subaxial spinal instability as the primary nodal point of the pathogenesis of degenerative cervical spinal disease-related myelopathy, and the focus of surgical treatment for it, is evaluated. MATERIALS AND METHODS: The series analyses the treatment of 73 patients with single or multilevel degenerative cervical spinal disease by fixation of the involved spinal segment(s) alone, aimed at arthrodesis. No bone decompression or disc/osteophyte resection was done. In 23 patients, the atlantoaxial joint was included in the spinal fixation, as atlantoaxial instability was identified by facetal malalignment on imaging or by observations on direct bone manipulation during surgery. There were 70 males and 3 females. The ages of the patients ranged from 35 to 76 years (average 57 years). The transarticular screw method was deployed for subaxial spinal fixation and a lateral mass plate/rod and screw technique was used for atlantoaxial fixation. RESULTS: During the follow-up period, which ranged from 3 to 42 months (average 27 months), all patients improved in terms of their clinical symptoms. There were no surgery- or implant-related complications. CONCLUSION: Atlantoaxial joint instability is frequently associated with subaxial multilevel spinal instability in degenerative spinal disease. Fixation of the spinal segments provides a safe, effective and rational treatment for single or multilevel spinal degeneration.

Ossification of the Posterior Longitudinal Ligament: Analysis of the Role of Craniovertebral and Spinal Instability.

BACKGROUND: This paper reviews an experience of surgically treating ossification of the posterior longitudinal ligament (OPLL) with fixation of the involved spinal segments alone, without resorting to any bony or soft tissue decompression or attempts at direct resection of the OPLL. While in the early part of the experience, stabilization of only the involved subaxial cervical spinal segments was done, in the later part of the experience, atlantoaxial fixation was included in the multisegmental spinal fixation construct. This treatment is based on the understanding that spinal instability that includes atlantoaxial instability forms the nodal point of the pathogenesis and development of OPLL, and maturation of the presenting clinical symptoms. MATERIALS AND METHODS: Twenty-nine patients were treated in this series. There were 28 males and one female, and their ages ranged from 28 to 75 years (average 57 years). All patients presented with symptoms of neck pain, and progressive and disabling myelopathy-related quadriparesis. In the early part of the series (from 2012 to 2014), 14 patients underwent multilevel subaxial cervical spinal fixation by a transarticular technique of facetal fixation. After November 2014, atlantoaxial lateral mass fixation was included in the fixation construct in the subsequent 15 patients. Clinical assessments were done using a visual analogue scale (VAS), the Japanese Orthopaedic Association (JOA) scale and Goel's clinical grading scale. RESULTS: All patients' clinical symptoms improved in the immediate postoperative period, and the improvement was sustained and progressive in 28 patients. CONCLUSION: Atlantoaxial and subaxial spinal instability seems to be the nodal pathogenetic factor in OPLL. Only stabilization of spinal segments that includes the atlantoaxial joint can provide a safe, simple and rational form of treatment.