Defining role of atlantoaxial and subaxial spinal instability in the pathogenesis of cervical spinal degeneration: Experience with "only-fixation" without any decompression as treatment in 374 cases over 10 years.

Aim: The authors analyze their published work and update their experience with 374 cases of cervical radiculopathy and/or myelopathy related to spinal degeneration that includes ossification of the posterior longitudinal ligament (OPLL). The role of atlantoaxial and subaxial spinal instability as the nodal point of pathogenesis and focused target of surgical treatment is analyzed. Materials and Methods: During the period from June 2012 to November 2022, 374 patients presented with acute or chronic symptoms related to radiculopathy and/or myelopathy that were attributed to degenerative cervical spondylotic changes or due to OPLL. There were 339 males and 35 females, and their ages ranged from 39 to 77 years (average 62 years). All patients were treated for subaxial spinal stabilization by Camille's transarticular technique with the aim of arthrodesis of the treated segments. Atlantoaxial stabilization was done in 128 cases by adopting direct atlantoaxial fixation in 55 cases or a modified technique of indirect atlantoaxial fixation in 73 patients. Decompression by laminectomy, laminoplasty, corpectomy, discoidectomy, osteophyte resection, or manipulation of OPLL was not done in any case. Standard monitoring parameters, video recordings, and patient self-assessment scores formed the basis of clinical evaluation. Results: During the follow-up period that ranged from 3 to 125 months (average: 59 months), all patients had clinical improvement. Of 130 patients who had clinical evidences of severe myelopathy and were either wheelchair or bed bound, 116 patients walked aided (23 patients), or unaided (93 patients) at the last follow-up. One patient in the series was operated on 24 months after the first surgery by anterior cervical route for "adjacent segment" disc herniation. No other patient in the entire series needed any kind of repeat or additional surgery for persistent, recurrent, increased, or additional related symptoms. None of the screws at any level backed out or broke. There were no implant-related infections. Spontaneous regression of the size of osteophytes was observed in 259 patients where a postoperative imaging was possible after at least 12 months of surgery. Conclusions: Our successful experience with only spinal fixation without any kind of "decompression" identifies the defining role of "instability" in the pathogenesis of spinal degeneration and its related symptoms. OPLL appears to be a secondary manifestation of chronic or longstanding spinal instability.

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.

Basilar invagination associated with brainstem tumor opposite the odontoid process.

An 8-year-old girl presented with the symptom of nasal regurgitation and hoarseness of voice. Investigations revealed severe basilar invagination and a large intra-axial pons-medulla brainstem tumor adjoining the tip of the odontoid process. The child underwent lateral mass plate and screw atlantoaxial fixation and attempted craniovertebral junction realignment. Biopsy of the brainstem tumor was done during the same surgical procedure. Histology of the brainstem tumor revealed it to be a pilocytic astrocytoma. Simultaneous presence of brainstem tumor and basilar invagination is a rare clinical association and a complex therapeutic challenge. The possible cause of genesis of brainstem tumor in an unusual location is speculated.

Unilateral facet fixation as a salvage procedure: Report of two cases with cervical primary bone tumors with extensive bone destruction.

We describe cases of two patients with primary cervical bone tumors that resulted in extensive destruction of bones of the region. In the first patient, the tumor and its growth resulted in the destruction of C3-C5 vertebral bodies and the unilateral destruction of facets and pedicles. In the second case, there was focal destruction of the body and odontoid process and unilateral pedicle and facet of C2. Tumor resection and spinal stabilization were the aims of the surgery. In both cases, unilateral fixation of facets was done. In the first patient, multi-segmental transarticular fixation by Camille's technique was done, and in the second patient, unilateral lateral mass plate and screw fixation was done by the Goel technique. Solid bone fusion of spinal segments was observed at more than a 2-year follow-up in both cases. Based on this experience, it appears that unilateral facetal fixation can provide firm stability and can be used when other more frequently and popularly used techniques are either not available or possible.

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.

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.

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.

"Only fixation" in cases with failed decompression for lumbar canal stenosis - Analysis of outcome in 14 cases.

Aim: The rationale of "only fixation" of affected spinal segments without any form of bone or soft-tissue decompression in cases with failed decompressive laminectomy for lumbar canal stenosis is discussed on the basis of an experience with 14 cases. Materials and Methods: During the period between 2010 and 2022, 14 patients who symptomatically worsened or did not improve following a long-segment "wide" decompressive laminectomy for multisegmental lumbar canal stenosis were identified. All patients were treated by segmental spinal stabilization aimed at arthrodesis by facetal distraction by Goel's facetal spacers (6 cases) or Camille's transarticular facetal fixation (8 cases). No bone, soft tissue, or disc resection was done for spinal or neural canal "decompression." Oswestry Disability Index and Visual Analog Scale were used to clinically assess the patients before and after the surgery and at follow-up. In addition, video recordings of patient's self-assessment of clinical outcome were used to monitor the outcome. Results: During the average period of follow-up of 71 months (range 6 months to 16 years), all patients recovered in majority of their major symptoms, the recovery was observed in the immediate postoperative period. During the period of follow-up, none of the patients complained of recurrent symptoms or needed any additional surgery. There was firm stabilization and evidences of bone fusion of the treated spinal segments in all patients. There were no infections or implant failure. No patient worsened after treatment. Conclusions: Instability of the spinal segments is the primary issue in cases with lumbar canal stenosis and stabilization in the treatment.

Laminectomy with Rib Shears: A Technical Note.

Introduction: Laminectomy/laminoplasty either free or vascularized pedicle flap is currently performed with a variety of expensive instruments. Use of Tudor Edwards rib shears to perform above procedure is described. Materials and Methods: Tudor Edwards rib shear was used to cut lamina in 18 cases for a variety of spinal lesions. Depending upon the size of lesion, laminectomy/laminoplasty was required for 2 to 8 levels. Vascularized pedicle laminoplasty or free flap laminoplasty was done with Tudor Edwards rib shears. Ligamentum flavum and interspinous and supraspinous ligaments were preserved in cases of vascularized pedicled laminoplasty, which was carried out in 12 cases. Free flap laminoplasty was carried out in 6 cases. Results: In all our cases, laminectomy was successfully achieved with rib shears without any injury to the dura or its underlying structures. It was possible to perform vascularized pedicle laminoplasty or free flap laminoplasty in all cases. Laminectomy was easier to perform in the cervical region and dorsal region, while it was difficult in the lumbar region due to the wider, thick lamina and its angulation, especially in adults. Conclusion: Laminectomy/laminoplasty with Tudor Edwards rib shears is quick, safe, and easy. Beveled cut edges with minimal bony loss prevents sinking of laminoplasty, thereby facilitates lamina fixation. This is an alternative method of performing laminectomy/laminoplasty, especially for those not having accessibility to expensive equipment.

Vision Loss Following Vertebral Artery Injury during Surgery for Atlantoaxial Instability.

Background: A number of complications following surgery aimed at atlantoaxial fixation have been reported. However, there is no report in the literature describing visual loss following vertebral artery injury. Objective: Vision loss as a complication of vertebral artery injury during surgery for atlantoaxial fixation is reported. Material and Methods: This is a report of two patients who were operated for atlantoaxial instability by the Goel technique of atlantoaxial fixation. During surgery, there was an injury to the vertebral artery and the artery had to be sacrificed. Results: Both patients suffered severe visual loss following surgery. One patient had a partial visual recovery that started within few days of surgery while the other patient remained completely blind. Conclusions: Although rare, visual loss can be a complication of vertebral artery sacrifice during surgery for atlantoaxial stabilization.

Women in Neurosurgery - The Road Less Traveled.

Neurosurgery is one of the most challenging branches in medicine. Apart from rigorous training, it demands precision, perfection, and excellence. It calls for a kind of stubborn confidence in self and the will to go well beyond. It has always been a male-dominated speciality, and the path for women in neurosurgery was paved by a handful of female surgeons who took "the road less traveled." These pioneering few had to face a number of obstacles to attain their dreams, but their persistence prevailed and has set the route for future. This article highlights the progress of women in neurosurgery in India.

Antegrade Subperiosteal Temporalis Muscle Elevation and Posterior Retraction Technique Avoiding Muscle Incision for Pterional Craniotomy: A Technical Note.

Background: The current technique of pterional craniotomy involves temporalis muscle incision followed by retrograde elevation. Feasibility of antegrade temporalis muscle elevation without any direct incision over its bulk is evaluated. Objective: Incisionless "antegrade, subgaleal, subfascial, and subperiosteal elevation" of temporalis muscle preserves vascularity and muscle bulk. Posterior maneuvering of "bare" temporalis muscle bulk either above (out rolling) or under (in rolling) the scalp for pterional craniotomy is discussed. Material and Methods: Technique of antegrade, subfascial, subperiosteal elevation, and posterior rotation of temporalis muscle without incising in its bulk by "out rolling" or "in rolling" along the posterior aspect of the scalp incision was carried out in 15 cadavers and later in 50 surgical cases undergoing pterional craniotomy. Postoperatively, patients were evaluated for subgaleal collection and periorbital edema. Operated side cosmesis and temporalis muscle bulk was compared with nonoperated temporalis muscle at 6 months interval. Results: Antegrade subperiosteal dissection of temporalis muscle was possible in all cases. "In-rolling" or "out rolling" technique provided adequate surgical exposure during pterional craniotomy. Postoperative subgaleal collection and periorbital edema was prevented. Facial nerve paresis or temporalis muscle-related complications were avoided. Conclusion: Antegrade, subgaleal, subfascial, and subperiosteal dissection techniques of temporalis muscle elevation without any direct incision in its bulk enables neurovascular and muscle volume preservation. Posterior maneuvering of elevated temporalis muscle with "out rolling" or "in-rolling" technique is easy, quick, and provides adequate exposure during pterional craniotomy. Opening and closing of scalp layers without violating subgaleal space prevent postoperative subgaleal hematoma and periorbital edema.

Radiological Evaluation of Anatomical Extensions of Gliomas Based on White Fiber Tracts: Proposal of a Novel Classification.

Background: We speculate on the origin and extensions of gliomas based on our understanding of anatomy of the subcortical network, radiological evaluation and surgical experience. Objective: We recently classified the white fibers of the brain into four horizontal and one vertical group. The role of this classification in understanding the origin and spread of gliomas is analyzed. Materials and Methods: A series of 220 consecutive radiological images of patients with low and high grade gliomas were retrospectively evaluated. The classification discussed was applied to these images to study the location and direction of growth of the gliomas. Results: Our results identify that gliomas arise and spread along a named white fiber tract and displace the adjoining tracts. Gliomas that arose from arcuate fibres either remained limited to a gyrus or extended to the adjacent gyri along the course of the arcuate fibres. Gliomas arising from the LAF spread in the direction of the affected tract. Gliomas arising from the CF tended to involve both the hemispheres and extended across the midline. Conclusion: This radiological evaluation of gliomas correlated well with our proposed anatomical classification of white fibers. Gliomas probably originate in the fiber tract and grow along its extension. The adjoining fiber tracts form a reliable barrier to its spread. The surgical implication of the understanding is outlined in brief here and evaluated in details in part B of this study.

Evaluation of autoantibody signatures in pituitary adenoma patients using human proteome arrays.

PURPOSE: To identify the specific diagnostic biomarkers related to pituitary adenomas (PAs), we performed serological antibody profiles for three types of PAs, namely Acromegaly, Cushing's and Nonfunctional Pituitary Adenomas (NFPAs), using the human proteome (HuProt) microarray. This is the first study describing the serum autoantibody profile of PAs. EXPERIMENTAL DESIGN: We performed serological autoantibody profiling of four healthy controls, four Acromegaly, three Cushing's and three NFPAs patient samples to obtain their autoantibody profiles, which were used for studying expression, interaction and altered biological pathways. Further, significant autoantibodies of PAs were compared with data available for glioma, meningioma and AAgAtlas for their specificity. RESULTS: Autoantibody profile of PAs led to the identification of differentially expressed significant proteins such as AKNAD1 (AT-Hook Transcription Factor [AKNA] Domain Containing 1), NINJ1 (Nerve injury-induced protein 1), L3HYPDH (Trans-3-hydroxy-L-proline dehydratase), RHOG (Rho-related GTP-binding protein) and PTP4A1 (Protein Tyrosine Phosphatase Type IVA 1) in Acromegaly. Protein ABR (Active breakpoint cluster region-related protein), ST6GALNAC6 (ST6 N-acetylgalactosaminide alpha-2, 6-sialyltransferase 6), NOL3 (Nucleolar protein 3), ANXA8 (Annexin A8) and POLR2H (RNA polymerase II, I and III subunit H) showed an antigenic response in Cushing's patient's serum samples. Protein dipeptidyl peptidase 3 (DPP3) and reticulon-4 (RTN4) exhibited a very high antigenic response in NFPA patients. These proteins hold promise as potential autoantibody biomarkers in PAs.

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.