Shashank Sharad Kale

Effect of whole-body vibration on the low back. A study of tractor-driving farmers in north India.

STUDY DESIGN A retrospective cohort study of tractor-driving farmers (study group) and non-tractor-driving farmers (control group) matched for age, gender, generic/ethnic group, land-holding, and work routines. OBJECTIVES To determine, using magnetic resonance imaging and clinical investigations, the effect of whole-body vibrations on the back in tractor-driving farmers. SUMMARY OF BACKGROUND DATA Low back pain and pathologic changes in the lower backs of tractor drivers have been reported. However, no study with a control group matched for work-related risk factors has been reported. METHODS Fifty tractor-driving farmers were compared with 50 non-tractor-driving farmers matched for age, gender, ethnic group, land-holding, and work routine. Both groups were interviewed for details of work routine, assets held, family profile, and vibration exposure to assess the influence of these parameters on signs and symptoms of backache. Magnetic resonance imaging was done to assess the effect of exposure on whole-body vibration and degenerative changes in the back. Vibration measurements also were done on tractors to observe the actual severity of the vibrations. RESULTS Regular work-related backache was more common among tractor-driving farmers (40%) than among non-tractor-driving farmers (18%, P = 0.015). Anthropometric evaluation showed abdominal girth and weight to be significantly higher in tractor-driving farmers (P = 0.006 and 0.046, respectively), whereas while height and arm span were similar between the two groups. Clinical examination for evidence of disc or facet degeneration showed no difference between the two groups. Evaluation of magnetic resonance images of tractor-driving farmers and non-tractor-driving farmers by an orthopedic surgeon, radiologist, and neurosurgeon showed degenerative changes to be similar between the two groups (P > 0.050). CONCLUSIONS Tractor-driving farmers report backache more often than non-tractor-driving farmers, but no significant objective differences on clinical or magnetic resonance imaging evaluation were found between the two groups.

A global perspective on the outcomes of surgical decompression in patients with cervical spondylotic myelopathy: results from the prospective multicenter AOSpine international study on 479 patients.

Study Design. Prospective, multicenter international cohort. Objective. To evaluate outcomes of surgical decompression for cervical spondylotic myelopathy (CSM) at a global level. Summary of Background Data. CSM is a degenerative spine disease and the most common cause of spinal cord dysfunction worldwide. Surgery is increasingly recommended as the preferred treatment strategy for CSM to improve neurological and functional status and quality of life. The outcomes of surgical intervention for CSM have never been evaluated at an international level. Methods. Between October 2007 and January 2011, 479 symptomatic patients with image evidence of CSM were enrolled in the prospective, multicenter AOSpine CSM-International study from 16 global sites. Preoperative and postoperative clinical status, functional impairment, and quality of life were evaluated using the modified Japanese Orthopaedic Assessment Scale, Nurick Scale, Neck Disability Index, and Short-Form-36v2. Preoperative and 12- and 24-month postoperative outcomes were compared using mixed-model analysis of covariance for repeated measurements. Results. The study cohort consisted of 310 males and 169 females, with a mean age of 56.37 ± 11.91 years. There were significant differences in age, etiology, and surgical approaches between the regions. At 24 months postoperatively, the mean modified Japanese Orthopaedic Assessment Scale score improved from 12.50 (95% confidence interval [CI], 12.24–12.76) to 14.90 (95% CI, 14.64–15.16); the Neck Disability Index improved from 36.38 (95% CI, 34.33–38.43) to 23.20 (95% CI, 21.24–25.15); and the SF36v2 Physical Component Score and Mental Composite Score improved from 34.28 (95% CI, 33.46–35.10) to 40.76 (95% CI, 39.71–41.81) and 39.45 (95% CI, 38.25–40.64) to 46.24 (95% CI, 44.94–47.55), respectively. The rate of neurological complications was 3.13%. Conclusion. Surgical decompression for CSM is safe and results in improved functional status and quality of life in patients around the world, irrespective of differences in medical systems and sociocultural determinants of health. Level of Evidence: 3

Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing

BACKGROUND Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas. MATERIALS AND METHODS Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations. RESULTS Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells. CONCLUSIONS IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.

Bipartite atlas with os odontoideum: case report.

Study Design. A case report of bipartite atlas associated with os odontoideum and review of the pertinent literature are presented. Objective. To illustrate an unusual association of bipartite atlas and os odontoideum and explain the embryological basis. Summary of Background Data. To the authors’ knowledge, only one case of bipartite atlas with os odontoideum had been reported previously. Most of the previously reported cases of bipartite atlas are asymptomatic. Methods. A 16-year-old boy presented with a 2-month history of weakness and numbness of all four limbs after sustaining a minor head trauma. Radiographs of cervical spine revealed aplasia of anterior arch of atlas, ventral displacement of C1 over C2 on flexion, which reduced on extension. CT scan showed anterior arch aplasia, posterior arch midline defect, and os odontoideum, which had a small projection on the anterior surface at the level of anterior arch. MRI demonstrated increased cord signal at C1–C2 levels on T2-weighted image. Transoral odontoidectomy and posterior fixation of occiput with C2–C3 spinous processes was performed. Results. The patient had significant improvement over next 3 months. Conclusions. We described a rare association of an anterior arch aplasia, posterior arch defect and os odontoideum. The natural history of patients with os odontoideum suggests that these people have a potentially precarious existence.

Molecular profile of oligodendrogliomas in young patients.

Several studies on molecular profiling of oligodendrogliomas (OGs) in adults have shown a distinctive genetic pattern characterized by combined deletions of chromosome arms 1p and 19q, O6-methylguanine-methyltransferase (MGMT) methylation, and isocitrate dehydrogenase 1 (IDH1) mutation, which have potential diagnostic, prognostic, and even therapeutic relevance. OGs in pediatric and young adult patients are rare and have been poorly characterized on a molecular and biological basis, and it remains uncertain whether markers with prognostic significance in adults also have predictive value in these patients. Fourteen cases of OGs in young patients (age, ≤ 25 years) who received a diagnosis over 7 years were selected (7 pediatric patients age ≤ 18 years and 7 young adults aged 19-25 years). The cases were evaluated for 1p/19q status, MGMT promoter methylation, p53 mutation, and IDH1 mutation. None of the pediatric cases showed 1p/19q deletion. In young adults, combined 1p/19q loss was observed in 57% and isolated 1p loss in 14% of cases. The majority of cases in both subgroups (71% in each) harbored MGMT gene promoter methylation. TP53 and IDH1 mutations were not seen in any of the cases in both the groups. To our knowledge, this is the first study to show that molecular profile of OGs in pediatric and young adult patients is distinct. Further large-scale studies are required to identify additional clinically relevant genetic alterations in this group of patients.

IDH1 mutations in gliomas: first series from a tertiary care centre in India with comprehensive review of literature.

OBJECT Mutations of the gene encoding isocitrate dehydrogenase (IDH) have been shown in a significant proportion of diffuse gliomas. These mutations are specific to gliomas and their utility for diagnosis and prognostication of these tumors is being proclaimed. The present study was conducted with the aim of assessing frequency of IDH1 mutations in gliomas, their correlation with other molecular alterations along with a comprehensive review of available literature. METHODS A total of 100 gliomas of various grades and subtypes from Indian patients were screened for assessing frequency of IDH1 mutations. The findings were correlated with TP53 mutations, 1p/19q deletion, EGFR amplification and PTEN deletion status. The detailed comprehensive review of literature was performed comparing all studies available till date. RESULTS IDH1 mutations in codon 132 were observed in 46% cases. The frequency was 68.8% in grade II, 85.7% in grade III and 12.8% in GBMs. R132H mutation was most frequent (84.8%). Overall frequency of these mutations was relatively higher in oligodendroglial tumours as compared to astrocytic phenotype (66.7% versus 38.4%; p=0.06). Primary GBMs showed IDH1 mutation in only 4.4% cases. In contrast, 66.7% of secondary GBMs harboured this alteration. Patients with IDH1 mutations were significantly younger as compared to those without mutation (p=0.001). There was a significant correlation between IDH1 mutation and TP53 mutation (p=0.004). Although IDH1 mutation showed a positive correlation with 1p/19q deletion, the association was not statistically significant (p=0.653). There was no correlation with EGFR amplification or PTEN deletion. CONCLUSION IDH1 mutations are present in large proportion of Indian patients with diffuse astrocytic and oligodendroglial neoplasms similar to the reported literature form west. The frequency is lower in primary GBMs and as compared to secondary GBMs. Association with younger age and positive correlation with TP53 mutation and 1p/19q loss is observed. More importantly it is emerging as an independent prognostic marker. Hence the greatest challenge now is establishing a reliable user friendly test for incorporating this novel genetic alteration to routine clinical practice.

CDKN2A deletion in pediatric versus adult glioblastomas and predictive value of p16 immunohistochemistry

Cell cycle regulator genes are major target of mutation in many human malignancies including glioblastomas (GBMs). CDKN2A is one such tumor suppressor gene which encodes p16INK4a protein and serves as an inhibitor of cell cycle progression. Very few studies are available regarding the association of CDKN2A deletion with p16 protein expression in GBMs. There is limited data on the frequency of CDKN2A deletion in different age groups. The aim of the present study was to analyze the frequency of CDKN2A gene deletions in GBM and correlate CDKN2A deletional status with (i) age of the patient (ii) p16 protein expression and (iii) other genetic alterations, namely EGFR amplification and TP53 mutation. A combined retrospective and prospective study was conducted. Sixty seven cases were included. The patients were grouped into pediatric (≤18 years), young adults (19‐40 years) and older adults (>40 years). CDKN2A and EGFR status were assessed by Fluorescence in situ Hybridization.TP53 mutation was analyzed by PCR based method. p16 expression was assessed using immunohistochemistry. CDKN2A deletion was noted in 40.3% cases of GBM with majority being homozygous deletion (74%). It was commoner in primary GBMs (65.8%) and cases with EGFR amplification (50%). A variable frequency of CDKN2A was observed in older adults (42.3%), young adults (44%), and pediatric patients (31.25%). The difference however was not statistically significant. There was statistically significant association between CDKN2A deletion and p16 immunonegativity with a high negative predictive value of immunohistochemistry.

Spindle cell oncocytoma of the adenohypophysis: report of a rare case and review of literature.

Spindle cell oncocytoma of the adenohypophysis was first escribed by Roncaroli et al. in 2002, in their multi-institutional eries of 5 cases [1]. Since then ten reports of thirteen cases of this umor have been published in literature bringing the total number f reported cases to eighteen [2–11]. This new entity was included n the WHO classification of tumors of the Central Nervous System n 2007 [12]. In nearly all the cases presentation was akin to a non unctioning pituitary adenoma in an elderly patient, however the ehaviour of these tumors varied as seven of the eighteen published ases showed recurrence with or without morphological features of naplasia in the form of nuclear pleomorphism, frequent mitoses, igh Ki-67 index and/or foci of necrosis [2–8]. We report the nineeenth case of spindle cell oncocytoma (SCO) in a 68-year-old male atient and review the available English literature till date on this umor.

Does age affect surgical outcomes in patients with degenerative cervical myelopathy? Results from the prospective multicenter AOSpine International study on 479 patients

Background In general, older patients with degenerative cervical myelopathy (DCM) are felt to have lower recovery potential following surgery due to increased degenerative pathology, comorbidities, reduced physiological reserves and age-related changes to the spinal cord. This study aims to determine whether age truly is an independent predictor of surgical outcome and to provide evidence to guide practice and decision-making. Methods A total of 479 patients with DCM were prospectively enrolled in the CSM-International study at 16 centres. Our sample was divided into a younger group (<65 years) and an elderly (≥65 years) group. A mixed model analytic approach was used to evaluate differences in the modified Japanese Orthopaedic Association (mJOA), Nurick, Short Form-36 (SF-36) and Neck Disability Index (NDI) scores between groups. We first created an unadjusted model between age and surgical outcome and then developed two adjusted models that accounted for variations in (1) baseline characteristics and (2) both baseline and surgical factors. Results Of the 479 patients, 360 (75.16%) were <65 years and 119 (24.84%) were ≥65 years. Elderly patients had a worse preoperative health status (p<0.0001) and were functionally more severe (p<0.0001). The majority of younger patients (64.96%) underwent anterior surgery, whereas the preferred approach in the elderly group was posterior (58.62%, p<0.0001). Elderly patients had a greater number of decompressed levels than younger patients (p<0.0001). At 24 months after surgery, younger patients achieved a higher postoperative mJOA (p<0.0001) and a lower Nurick score (p<0.0001) than elderly patients. After adjustments for patient and surgical characteristics, these differences in postoperative outcome scores decreased but remained significant. Conclusions Older age is an independent predictor of functional status in patients with DCM. However, patients over 65 with DCM still achieve functionally significant improvement after surgical decompression.

Spectrum of pediatric brain tumors in India: a Multi-Institutional study

BACKGROUND Till date there is no published multi-institutional data regarding the epidemiological profile of pediatric brain tumors in India. AIM The present retrospective study analyses the histological spectrum of pediatric age group brain tumors in seven tertiary care hospitals in India. MATERIAL AND METHODS Data regarding frequencies of various primary brain tumors (diagnosed according to the World Health Organization (WHO) classification), in 3936 pediatric patients (<18 yrs of age), was collected from seven tertiary care hospitals in India. RESULTS The most common primary pediatric brain tumors were astrocytic tumors (34.7%), followed by medulloblastoma and supratentorial primitive neuro-ectodermal tumors (22.4%), craniopharyngiomas (10.2%) and ependymal tumors (9.8%). The most common astrocytic tumor was pilocytic astrocytoma. In comparison to adults, oligodendrogliomas and lymphomas were rare in children. CONCLUSIONS Our study is the first such report on the histological spectrum of brain tumors in children in India. Except for a slightly higher frequency of craniopharyngiomas, the histological profile of pediatric brain tumors in India is similar to that reported in the Western literature.