Alangar S. Hegde

Posterior fossa morphometry in symptomatic pediatric and adult Chiari I malformation.

The linear dimensions and volume of the posterior fossa, and the length of the supra-occiput and the clivus in children with Chiari I malformations (CMI) were studied. A statistical relationship between patient demographics, radiological features, posterior fossa and occipital bone morphometry in the study and control groups was investigated. The results of 21 pediatric patients was compared to those of a matched control group. The posterior fossa volume (PFV) of an adult CMI group was also studied. Linear measurements were used to calculate the length of the occipital bone, spherical PFV and intracranial volume (ICV) using pre-operative MRI and CT scans. A PFV to ICV ratio was obtained to standardize the comparison. The volumetric measurement in the pediatric study group was also compared to the adult CMI group. The antero-posterior dimension, width, and volume of the posterior fossa and the PFV to ICV ratio in pediatric CMI patients was significantly lower than in the control group (p<0.05). There was no statistical difference in the length of the clivus and the supra-occiput between the two pediatric groups. The difference in the PFV to ICV ratio between pediatric and adult CMI patients was not statistically significant. Thus, the authors provide a simple, yet accurate, and reproducible method of comparison of posterior fossa volume in patients with CMI in different age groups, based on linear measurements. There is no significant difference between the length of the occipital bone at the base of the skull in pediatric CMI patients and the normal pediatric population. Development of the clivus due to late fusion of the sphenoid and occipital synchondroses in the second decade could result in manifestation of the disease in adulthood in CMI patients who were asymptomatic as children.

Diagnostic and clinical implications of pituicytoma

Pituicytoma is a rare, indolent, benign tumor of the sellar and suprasellar region arising from pituicytes of the neurohypophysis. It is most often diagnosed pre-operatively as a pituitary adenoma. We report two patients with pituicytoma operated on at our Institute over 8 years. Imaging of one patient showed a parasellar and medial temporal extension, which has not been reported to our knowledge. The radiological features that help distinguish this low-grade tumor from other sellar and parasellar tumors are discussed along with its distinct histological findings. The authors also review the literature on its clinical presentation, diagnosis, surgical management and outcome.

IDH1 Mutations in Diffusely Infiltrating Astrocytomas Grade Specificity, Association With Protein Expression, and Clinical Relevance

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 [83.3%] secondary, and 1/42 [2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < . 001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

Morphometric analysis of foramen magnum dimensions and intracranial volume in pediatric Chiari I malformation

PurposeForamen magnum dimensions and intracranial volume in Chiari I malformations in children were studied, and the statistical relationship between patient demographics, radiological features and foramen magnum morphometry was investigated.MethodsLinear measurements were used to calculate the intracranial volume using preoperative magnetic resonance images and computed tomogram images. The area of the foramen magnum was obtained independently using computer imaging software and a regression formula. The result of 21 pediatric patients was compared with a matched control group.ResultsThe area of the foramen magnum was within the range of the expected value deduced using a formula based on the intracranial volume. There was no statistical difference in the area and linear dimensions of the foramen magnum in the study and control groups. Six patients (28%) had a foramen magnum in close proximity to a spherical shape.ConclusionThe authors provide a simple, accurate and reproducible method of estimating foramen magnum area in the pediatric Chiari I group. The irregular shape of the foramen magnum is accentuated by developmental bony and soft tissue anomalies at the cranio-vertebral junction in Chiari malformation. Consequently, an individualized cross-sectional assessment of the foramen magnum in relation to the hindbrain tissue in the same plane is required to study the initiation and propagation of the Chiari I symptomatology.

Homozygous 10q23/PTEN deletion and its impact on outcome in glioblastoma: A prospective translational study on a uniformly treated cohort of adult patients

Tumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n = 73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situ hybridization (FISH). Statistical methods were employed to evaluate the degree of association between 10q23/PTEN deletion status and patient age. Survival analysis was performed using Kaplan‐Meier log‐rank test and multivariable Cox models to assess the prognostic value of 10q23/PTEN deletion. Interestingly, 10q23/PTEN homozygous deletion was frequent in patients >45 years of age (P = 0.034) and the median age of patients harboring PTEN homozygous deletions was significantly higher than those with the retained status (P = 0.019). 10q23/PTEN homozygous deletion was associated with shorter survival in the entire cohort as well in patients >45 years (P < 0.05), indicating that loss of 10q23/PTEN showed clinical importance in elderly patients. Our study highlights the independent prognostic/predictive value of 10q23/PTEN deletion status as identified by FISH, particularly in glioblastoma patients aged >45 years.

Rosette forming glioneuronal tumor pineal gland and tectum: An intraoperative diagnosis on smear Preparation

We present an extremely rare case of newly described entity called rosette forming glioneuronal tumor (RGNT), involving the pineal gland, tectum, and the adjacent thalamus in a 22‐year‐old male. Interestingly, the ventricular system was not involved in this case. The tumor was diagnosed intraoperatively on smear preparation on cytomorphology. If sampled adequately, it is fairly easy to diagnose RGNT on smear preparation as it has a very distinctive cytomorphology of being composed of two population of cell. One of the components is pilocytic astrocytoma and the other is composed of small cells with scant cytoplasm, vesicular nuclei, arranged around neuropil‐like material forming “neurocytic rosettes.” To the best of our knowledge, this is the first case of RGNT in this rare location being diagnosed intraoperatively on smear preparation. Diagn. Cytopathol. 2010;38:590–593. 2009 Wiley‐Liss, Inc.

Coexisting intracranial tumors with pituitary adenomas: Genetic association or coincidence?

The co-occurrence of two or more brain tumors with different histological features is rare. The authors report three rare cases of intracranial tumors associated with pituitary adenomas. Two of the pituitary tumors were functioning adenomas: a prolactinoma and a thyrotropin secreting adenoma. Two of the associated intracranial neoplasms were gliomas and one was a meningioma. Radiological and clinical examination for syndromal association was negative in all cases. We briefly discuss the presentation and treatment options of these cases and review the 19 previous publications in the literature of pituitary tumors occurring in association with other neoplasms and explore the possible links underlying these co-occurring neoplasms. Our three cases represent 0.86% of all pituitary tumors operated at our institute over a 9-year period.

PI3 kinase pathway regulated miRNome in glioblastoma: identification of miR-326 as a tumour suppressor miRNA

BackgroundGlioblastomas (GBM) continue to remain one of the most dreaded tumours that are highly infiltrative in nature and easily preclude comprehensive surgical resection. GBMs pose an intricate etiology as they are being associated with a plethora of genetic and epigenetic lesions. Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated pathways and genes have been comprehensively studied, its impact on the miRNome is yet to be explored. The objective of this study was to elucidate the PI3 kinase pathway regulated miRNAs in GBM.MethodsmiRNA expression profiling was conducted to monitor the differentially regulated miRNAs upon PI3 kinase pathway abrogation. qRT-PCR was used to measure the abundance of miR-326 and its host gene encoded transcript. Proliferation assay, colony suppression assay and wound healing assay were carried out in pre-miR transfected cells to investigate its role in malignant transformation. Potential targets of miR-326 were identified by transcriptome analysis of miR-326 overexpressing cells by whole RNA sequencing and selected targets were validated. Several publically available data sets were used for various investigations described above.ResultsWe identified several miRNA that were regulated by PI3 kinase pathway. miR-326, a GBM downregulated miRNA, was validated as one of the miRNAs whose expression was alleviated upon abrogation of the PI3 kinase pathway. Overexpression of miR-326 resulted in reduced proliferation, colony suppression and hindered the migration capacity of glioma cells. Arrestin, Beta 1 (ARRB1), the host gene of miR-326, was also downregulated in GBM and interestingly, the expression of ARRB1 was also alleviated upon inhibition of the PI3 kinase pathway, indicating similar regulation pattern. More importantly, miR-326 exhibited a significant positive correlation with ARRB1 in terms of its expression. Transcriptome analysis upon miR-326 overexpression coupled with integrative bioinformatics approach identified several putative targets of miR-326. Selected targets were validated and interestingly found to be upregulated in GBM.ConclusionsTaken together, our study uncovered the PI3 kinase regulated miRNome in GBM. miR-326, a PI3 kinase pathway inhibited miRNA, was demonstrated as a tumour suppressor miRNA in GBM.

Paraspinal muscle morphometry in cervical spondylotic myelopathy and its implications in clinicoradiological outcomes following central corpectomy: clinical article.

OBJECT The objective of this study was to assess the cross-sectional areas (CSAs) of the superficial, deep flexor (DF), and deep extensor (DE) paraspinal muscles in patients with cervical spondylotic myelopathy (CSM), and to evaluate their correlations with functional status and sagittal spinal alignment changes following central corpectomy with fusion and plating. METHODS In this retrospective study of 67 patients who underwent central corpectomy with fusion and plating for CSM, the CSAs of the paraspinal muscles were calculated on the preoperative T2-weighted axial MR images and computed as ratios with respect to the corresponding vertebral body areas (VBAs) and as flexor/extensor CSA ratios. These ratios were then compared with those in the normative population and analyzed with respect to various clinicoradiological factors, including pain status, Nurick grade, and segmental angle change at follow-up (SACF). RESULTS The mean CSA values for all muscle groups and the DF/DE ratio were significantly lower in the study cohort compared with an age- and sex-matched normative study group (p < 0.001). Among various independent variables tested in a multivariate regression analysis, increasing age and female sex significantly predicted a lower total extensor CSA/VBA ratio (p < 0.001), while a longer duration of symptoms significantly predicted a greater total flexor/total extensor CSA ratio (p = 0.02). In patients undergoing single-level corpectomy, graft subsidence had a positive correlation with SACF in all patients (p < 0.05), irrespective of the preoperative segmental angle and curvature, while in patients undergoing 2-level corpectomy, graft subsidence demonstrated such a correlation only in the subgroup with lordotic curvatures (p = 0.02). Among the muscle area ratios, the DF/DE ratio demonstrated a negative correlation with SACF in the subgroup with preoperative straight or kyphotic segmental angles (p = 0.04 in the single corpectomy group, p = 0.01 in the 2-level corpectomy group). There was no correlation of any of the muscle ratios with change in Nurick grade. CONCLUSIONS Patients with CSM demonstrate significant atrophy in all the flexor and extensor paraspinal muscles, and also suffer a reduction in the protective effect of a strong DF/DE CSA ratio. Worsening of this ratio significantly correlates with greater segmental kyphotic change in some patients. A physiological mechanism based on DF dysfunction is discussed to elucidate these findings that have implications in preventive physiotherapy and rehabilitation of patients with CSM. Considering that the influence of a muscle ratio was significant only in patients with hypolordosis, a subgroup that is known to have facetal ligament laxity, it may also be postulated that ligamentous support supersedes the influence of paraspinal muscles on postoperative sagittal alignment in CSM.

Pseudotumor cerebri: as a cause for early deterioration after Chiari I malformation surgery

IntroductionChiari I malformation is associated with a small posterior fossa which cannot accommodate a growing hindbrain. Pseudotumor cerebri has been linked to developmental posterior fossa malformations.Case reportsThe authors present two cases of early-deterioration post-Chiari I malformation surgery in a young and an adult patient, which were linked to raised intracranial pressure and had a stormy post-operative period. The pathophysiology of pseudotumor cerebri in early post-operative complications of Chiari malformation surgery is addressed along with arguments favoring its association.DiscussionPotential clinical risk factors and red flags linking pseudotumor cerebri and Chiari malformation patients are discussed. The management of post-operative complications produced by the association is addressed.