Pravin Salunke

Molecular markers of glioma: an update on recent progress and perspectives

BackgroundSignificant progress has been made in the molecular diagnostic subtyping of brain tumors especially gliomas. Designing effective tailored therapy remains the cornerstone for delving into the molecular heterogeneity and classification of gliomas. More homogenous tumor populations may lead to more uniform tumor responses in particular molecular constellation. Recent decade has seen a surge of molecular markers of glioma which hold a promise and potential of being strong prognostic, predictive, and diagnostic markers. They are also extremely critical for the stratification of current clinical trails.MethodReview of the pertinent literature regarding the molecular markers of glioma was performed. Methods of detection of these markers and their clinical relevance are also discussed.Results and conclusionsThis review provides an update on progress and perspectives of these newest set of biomarkers which can also supplement and refine histological classification and serves as important prognostic and predictive markers; particularly relevant in this aspect are O6-methylguanine-DNA methyltransferase promoter methylation, IDH1 mutations, and codeletion of 1p/19q. BRAF fusion/mutations and EGFR amplification provide important clues diagnostically.

Congenital atlantoaxial dislocation: a dynamic process and role of facets in irreducibility

OBJECT Patient age at presentation with congenital atlantoaxial dislocation (CAAD) is variable. In addition, the factors determining irreducibility or reducibility in these patients remain unclear. The facets appear to contribute to the stability of the joint, albeit to an unknown extent. The objective of this paper was to study the characteristics of C1-2 facets in these patients and their bearing on the clinicoradiological presentation and management. METHODS Twenty-four patients with CAAD were studied. Fifteen patients had irreducible CAAD (IrAAD); 3 of these patients experienced incomplete reduction after traction, and 9 had reducible CAAD (RAAD). The images (CT scans of the craniovertebral junction in a neutral position) obtained in the parasagittal, axial, and coronal planes were studied with respect to the C1-2 facets and were compared with 32 control scans. The inferior sagittal and coronal C-1 facet angles were measured. The lordosis of the cervical spine (cervical spine angle calculated on radiographs of the cervical spine, neutral view) in these patients was compared with normal. The management of these patients is described. RESULTS The inferior sagittal C-1 facet angle and at least one coronal angle in patients with IrAAD were significantly acute compared with those in patients with RAAD and the control population. A significant correlation was found between age and the acuteness of the inferior sagittal C-1 facet angle (that is, the more acute the angle, the earlier the presentation). The lordosis of the cervical spine was exaggerated in patients with IrAAD. Three patients with IrAAD who had smaller acute angles experienced a partial reduction after traction and a complete reduction after intraoperative distraction of the facets, thereby avoiding a transoral procedure. An inferior sagittal C-1 facet angle of more than 150° in the sagittal plane predicted reducibility. Drilling a wedge off the facet in the sagittal plane to make the inferior sagittal C-1 facet angle 150° can reduce the C1-2 joint intraoperatively by posterior approach alone. CONCLUSIONS The acuteness of the inferior C-1 sagittal facet angles possibly determines the age at presentation and reducibility. The coronal angles determine the telescoping of C-2 within C-1. Patients with IrAAD can be treated using a posterior approach alone with the exception of those with extremely acute angles or a retroflexed dens. The exaggerated lordosis of the cervical spine in these patients is a compensatory phenomenon.

Operative nuances to safeguard anomalous vertebral artery without compromising the surgery for congenital atlantoaxial dislocation: untying a tough knot between vessel and bone

OBJECT Stabilization of the craniovertebral junction (CVJ) by using lateral masses requires extensive dissection. The vertebral artery (VA) is commonly anomalous in patients with congenital CVJ anomaly. Such a vessel is likely to be injured during dissection or screw placement. In this study the authors discuss the importance of preoperative evaluation and certain intraoperative steps that reduce the chances of injury to such vessels. METHODS A 3D CT angiogram was obtained in 15 consecutive patients undergoing surgery for congenital atlantoaxial dislocation. The course of the VA and its relationship to the C1-2 facets was studied in these patients. The anomalous VA was exposed intraoperatively, facet surfaces were drilled in all, and the screws were placed according to the disposition of the vessel. RESULTS A skeletal anomaly was found in all 10 patients who had an anomalous VA. Four types of variations were noted: 1) the first intersegmental artery in 5 patients (bilateral in 1); 2) fenestration of VA in 1 patient; 3) anomalous posterior inferior cerebellar artery crossing the C1-2 joint in 1 patient; and 4) medial loop of VA in 5 patients. The anomalous vessel was dissected and the facet surfaces were drilled in all. The C-1 lateral mass screw was placed under vision, taking care not to compromise the anomalous vessel, although occipital screws or sublaminar wires were used in the initial cases. A medial loop of the VA necessitated placement of transpedicular or C-2 lateral mass screws instead of pars interarticularis screws. The anomalous vessel was injured in none. CONCLUSIONS Preoperative 3D CT angiography is a highly useful method of imaging the artery in patients with CVJ anomaly. It helps in identifying the anomalous VA or its branch and its relationship to the C1-2 facets. The normal side should be surgically treated and distracted first because this helps in opening the abnormal side, aiding in dissection. In the posterior approach the C-2 nerve root is always encountered before the anomalous vessel. The defined vascular anatomy helps in choosing the type of screw. The vessel should be mobilized so as to aid the drilling of facets and the placement of screws and spacers under vision, avoiding its injury (direct or indirect) or compression. With these steps, C1-2 (short segment) rigid fusion can be achieved despite the presence of anomalous VA.

Technique for direct posterior reduction in irreducible atlantoaxial dislocation: Multi-planar realignment of C1-2

OBJECTIVE Apart from the commonly seen antero-posterior subluxation of C1 over C2, the dislocation may occur in vertical, lateral or rotational plane. Desired C1-2 realignment can be achieved by corrrecting its dislocation in all planes. We describe a technique for the same. MATERIAL AND METHODS The clinical and radiological features of 16 patients (4 – traumatic and 12 – congenital) with irreducible atlantoaxial dislocation (AAD) admitted in the last 1.5 years were studied. Specific attention was paid to vertical dislocation with lateral and rotational components, apart from anterior-posterior subluxation. They were operated through direct posterior approach. The technique using a long rod holder as lever and screw head (tulip) as fulcrum was employed to achieve C1-2 realignment in all planes. The postoperative clinical and radiological data was analyzed and compared with preoperative data. RESULTS Patients presented with progressive myelopathy and/or progressive worsening of neck pain. Vertical dislocation was seen in 11 patients with congenital AAD in addition to the antero-posterior subluxation seen in all. Three patients with traumatic AAD and 8 with congenital AAD had additional lateral dislocation or lateral tilt. Three patients with traumatic AAD and 7 with congenital AAD showed rotational component. Postoperatively, all patients showed clinical improvement. CONCLUSIONS The antero-posterior and vertical realignment could be achieved in all except one. Similarly, rotational and lateral components could be completely corrected in 8 out of 10 patients. The technique appears to realign the C1-2 in all planes and provides good anatomical restoration.

Intradural anterior petrosectomy for petroclival meningiomas: a new surgical technique and results in 5 patients: Technical note

Excision of petroclival meningiomas remains a surgical challenge. Extradural anterior petrosectomy is widely used as a skull base approach for these tumors; however, this approach has significant procedure-related morbidity. The authors describe an alternative technique of tailored intradural petrosectomy for removal of petroclival meningiomas. This technique was used successfully in 5 patients. Gross-total or near-total resection was possible in 2 patients, whereas a subtotal removal was achieved in 3 patients, without significant morbidity. The petrous drilling was tailored depending on the extent of tumor. Transsylvian intradural anterior petrosectomy is a safe approach for petroclival meningiomas. This approach avoids problems related to subtemporal retraction and rationalizes the degree of bone drilling.

Comprehensive drilling of the C1–2 facets to achieve direct posterior reduction in irreducible atlantoaxial dislocation

OBJECT The cause of irreducibility in irreducible atlantoaxial dislocation (AAD) appears to be the orientation of the C1-2 facets. The current management strategies for irreducible AAD are directed at removing the cause of irreducibility followed by fusion, rather than transoral decompression and posterior fusion. The technique described in this paper addresses C1-2 facet mobilization by facetectomies to aid intraoperative manipulation. METHODS Using this technique, reduction was achieved in 19 patients with congenital irreducible AAD treated between January 2011 and December 2013. The C1-2 joints were studied preoperatively, and particular attention was paid to the facet orientation. Intraoperatively, oblique C1-2 joints were opened widely, and extensive drilling of the facets was performed to make them close to flat and parallel to each other, converting an irreducible AAD to a reducible one. Anomalous vertebral arteries (VAs) were addressed appropriately. Further reduction was then achieved after vertical distraction and joint manipulation. RESULTS Adequate facet drilling was achieved in all but 2 patients, due to VA injury in 1 patient and an acute sagittal angle operated on 2 years previously in the other patient. Complete reduction could be achieved in 17 patients and partial in the remaining 2. All patients showed clinical improvement. Two patients showed partial redislocation due to graft subsidence. The fusion rates were excellent. CONCLUSIONS Comprehensive drilling of the C1-2 facets appears to be a logical and effective technique for achieving direct posterior reduction in irreducible AAD. The extensive drilling makes large surfaces raw, increasing fusion rates.

‘Atlas shrugged’: congenital lateral angular irreducible atlantoaxial dislocation: a case series of complex variant and its management

PurposeThe commonly described congenital atlanto-axial dislocation and Basilar-Invagination is antero-posterior or rotational or vertical plane. However, congenital dislocation in lateral plane has received scant attention. The purpose of this manuscript is to describe this unusual entity and discuss its management.Materials and methodsThe clinic-radiological feature of seven patients with congenital lateral angular AAD (CLAAAD) were studied and managed. The unilateral C1 facet had subluxed lateral to C2–3 complex. The C1 and C2 facets were drilled comprehensively and repositioned with distraction, placement of metallic spacers and facet manipulation after insertion of screws. The post operative outcome was studied.ResultsThe presentation is usually with neck tilt (progressive in 3) and/or progressive spastic quadriparesis. The mean C1–2 tilt was 25.2°. C1 was bifid in six patients. C1 lateral mass was assimilated with occipital condyle on dislocated side in and the other side was normal (6 patients). The dislocated C1–2 joint was abnormally oblique as compared to contralateral side. The relationship of occiput and C1 was normal. Correction of dislocation and lateral tilt was achieved in all patients with subsequent correction of neck tilt and deficits. One patient required reoperation.ConclusionsThe acute angulation of joint on one side and near normal on other side leads to differential vertical movement, further accentuated by splaying of bifid C1. The entity is seen in young patients and often present with neck tilt and spastic quadriparesis. Management requires reshaping the joints and facet manipulation. If the reshaping is inappropriate, the joint is likely to redislocate before fusion occurs.

Focusing on the delayed complications of fusing occipital squama to cervical spine for stabilization of congenital atlantoaxial dislocation and basilar invagination

OBJECTIVES Occipito-cervical(OC) fusion is often practiced for congenital atlanto-axial dislocation (CAAD) and basilar invagination (BI) with claims of good long term outcome. Little has been discussed about the delayed complications following fusing occipital squama to cervical spine (OC fusion). We have described and analyzed delayed complications with OC fusion in our patients that helps us understand the underlying dynamics and biomechanics. PATIENTS AND METHODS Twenty seven patients of CAAD and BI underwent OC fusion (between 2008 and 11) after transoral odontoidectomy or direct posterior reduction with OC distraction. OC fusion was achieved using either sublaminar wiring or with precurved rods and screws or contoured loop. One patient was referred after OC fusion with contoured loop and wires with additional C1 laminectomy. The outcome (>12months) and delayed complications in these patients were analyzed. RESULTS Five types of delayed complications were noticed in 6 of the 28 patients who underwent OC fusion. Five of 6 patients were adults. Vertical redislocation with posterior midline fusion (n=2), adjacent level angular listhesis (n=1) and swan neck deformity (n=1) was seen in cases of OC fusion with sublaminar wires alone. Progressive C1 dislocation was seen in the lone patient who was referred after OC fusion with loop and wires. Vertical and angular dislocation was seen in 1 patient of OC fusion with precurved rod and screws. CONCLUSION Progressive redislocation and adjacent level dislocation are delayed complications seen after OC2 fusion. These complications are more often seen in adults, especially with sublaminar wiring/semi rigid OC fixation.

Validation of a New Clinico-Radiological Grading for Compound Head Injury: Implications on the Prognosis and the Need for Surgical Intervention

BACKGROUND Lack of risk stratification among patients with varying severities of compound head injury has resulted in too-inconsistent and conflicting results to support any management strategy over another. The purpose of this study was to validate a new clinico-radiological grading scheme with implications on outcome and the need for surgical debridement. METHODS Patients who sustained an external compound head injury with no serious systemic injury and no pre-established infection and who continued the entire treatment were studied prospectively for their proposed grade of compound injury in relation to infective complications, unfavorable Glasgow Outcome Scale (GOS), delayed seizures, mortality, and hospital stay for 3 months. Appropriate univariate and multivariate analyses were performed. RESULTS Among a total of 344 patients, 182 (53%) had no dural violation or midline shift (Grade 1), 56 (16%) had cerebrospinal fluid leak or pneumocephalus (Grade 2), 34 (10%) had exposed brain (Grade 3), 47 (14%) had midline shift (Grade 4), and 25 (7%) had both exposed brain and midline shift (Grade 5). Each successive grade of compound injury had significant incremental impact on all the outcome measures studied. Infective complications in Grades 1 to 5 were noted among 7%, 9%, 27%, 28%, and 36% of patients, respectively (P < 0.001). There was a significant difference in unfavorable GOS (23% vs. 56%, odds ratio [OR] 4.3, P < 0.001) and mortality (17% vs. 42%, OR 3.5, P < 0.001) between Grades 1-2 and Grades 3-5. Delayed seizures were noted in 4%, 4%, 9%, 13%, and 16% of patients in Grades 1-5 (P = 0.04). The median hospital stay was 1, 3, 6, 6, and 8 days, respectively (P < 0.001). All patients in Grades 4-5 (72) underwent surgery. Only 32 of 182 (18%) patients in Grade 1, 9 of 56 (16%) patients in Grade 2, and 23 of 34 (68%) patients in Grade 3 underwent surgical debridement, whereas the rest were managed conservatively. Patients who were managed conservatively had significantly lower infective complications (3% vs. 25%, OR 9.67, P < 0.001) in Grade 1, and (2% vs. 44%, OR 36.8, P = 0.002) in Grade 2, compared with those who underwent surgical debridement. In multivariate analysis, the proposed grade had significant independent association with infection (P < 0.001), unfavorable GOS (P = 0.01), delayed seizures (P = 0.001), and hospital stay (P < 0.001), and each successive grade had significant incremental impact on both infective complications and unfavourable GOS, independent of GCS and other prognostic factors. CONCLUSION The new grading scheme appears to be of practical clinical significance. It shows significant statistical associations with the rates of infection, unfavorable neurologic outcome, delayed seizures, mortality, and duration of hospital stay. The incremental impact of each successive grade on infective complications and unfavorable GOS was independent of GCS and other prognostic factors. Conservative management had significantly lower infection compared to surgical debridement, at least in patients with Grades 1 and 2.

Bilateral inverted vertebral arteries (V3 segment) in a case of congenital atlantoaxial dislocation: Distinct entity or a lateral variant of persistent first intersegmental artery?

Background: Anomalous vertebral arteries (VAs), commonly involving the persistent first intersegmental artery (FIA), are often seen with congenital atlantoaxial dislocations (AAD). Here we describe an unusual variant consisting of bilateral VAs with normal loops but passing below the C1 (inverted VA) arch, distinctly different from the FIA. Case Description: A 9-year-old boy presented with a spastic quadriparesis. Preoperative radiographic studies showed an irreducible AAD with an occipitalized CO-C1 and C2-3 fusion. Although both VAs exhibited proximal and distal loops like normal VA, the distal loops did not pass through the C1 transverse foramina and coursed inferior to the C1 arch instead. With this critical preoperative information, both VAs could be better safeguarded during dissection of the C1-2 facets. Conclusion: In the case presented, although the course of the inverted VAs is similar, the norm, they coursed inferior to both C1 arches. Careful evaluation of the preoperative radiological studies allowed for careful dissection of the inverted VA (horizontal loop) while opening the C1-2 joint for subsequent alignment (e.g. reduction) and bony fusion. This information also facilitates safer insertion of lateral mass screws (e.g. choosing the appropriate C1 screw length to gain adequate bony purchase without compromising anomalous VA).