A 50-year-old woman presented with an extremely uncommon case of solitary metastasis from follicu... more A 50-year-old woman presented with an extremely uncommon case of solitary metastasis from follicular carcinoma of the thyroid, which presented clinically as trigeminal neurinoma. Neuroimaging detected a tumor in the right petrous apex, which was removed surgically. Histological examination showed metastatic follicular carcinoma of the thyroid. However, no primary tumor was detected by various investigations. The tumor recurred twice, and was treated surgically both times. The patient finally agreed to adjuvant therapy for the suspected primary. Radiotherapy was performed followed by complete thyroidectomy. Examination of the gross specimen found the tumor nodule. Clinically significant metastasis can arise from histologically benign and silent follicular thyroid neoplasms.
Background and Objective: Meningiomas involving the foramen magnum (FM) region are rare and const... more Background and Objective: Meningiomas involving the foramen magnum (FM) region are rare and constitute 1% to 7% of intracranial meningiomas. Surgical excision is difficult in view of the complex anatomy and the proximity to critical neurovascular structures. Our aim was to analyze the clinical presentation and surgical outcome of patients operated for FM meningiomas. Materials and Methods: Thirty patients who underwent surgery for FM meningioma over a period of 21 years were studied retrospectively. Case records and imaging studies were reviewed for demographic data, presenting symptoms, tumor location, surgical approach, and postoperative complications. The outcome was assessed on the basis of the Glasgow Outcome Scale (GOS).
Symptomatic subdural hygroma due to foramen magnum decompression for Chiari malformation Type I i... more Symptomatic subdural hygroma due to foramen magnum decompression for Chiari malformation Type I is extremely rare. The authors present their experience with 2 patients harboring such lesions and discuss treatment issues. They conclude that the possibility of subdural hygromas should be considered in all patients presenting with increased intracranial tension following foramen magnum decompression for Chiari malformation Type I. Immediate neuroimaging and appropriate surgical intervention provides a good outcome.
BACKGROUND AND PURPOSE: Vestibular schwannomas (VS) may be difficult to differentiate from cerebe... more BACKGROUND AND PURPOSE: Vestibular schwannomas (VS) may be difficult to differentiate from cerebellopontine angle (CPA) meningiomas. Demonstration of microhemorrhages in VS on T2*weighted gradient-echo (GRE) sequences may have potential value to differentiate VS from CPA meningiomas. MATERIALS AND METHODS: In this prospective study of 20 patients, MR imaging was performed with T2*-weighted GRE in addition to all basic sequences. Histopathologic examination was performed after surgery. Intratumoral hemosiderin was confirmed by pigment staining. RESULTS: There were 15 patients in the VS group with 16 VS and 5 in the meningioma group with 5 posterior fossa meningiomas. Fourteen of the 16 VS and all 5 meningiomas were treated surgically and were confirmed on histopathologic examination. T2*-weighted GRE identified microhemorrhages on T2*-weighted sequence in 15 (93.75%) of the 16 VS. CT excluded calcification in all VS. T2-weighted turbo spin-echo (TSE) and fluid-attenuated inversion recovery (FLAIR) images recognized microhemorrhages in 2 cases. Pigment staining confirmed hemosiderin in all 14 surgically treated VS, and none of the meningiomas showed microhemorrhages on MR imaging. For the detection of microhemorrhages, T2*-weighted GRE showed a sensitivity of 93.8%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 83.3%. The sensitivity of T2 TSE and FLAIR for microhemorrhage was 12.5%. The Fisher exact test showed a statistically significant difference in the differentiation of VS from meningioma on the basis of detection of microhemorrhages (P Ͻ .01). CONCLUSION: Most VS demonstrate microhemorrhages on T2*-weighted GRE. This finding is useful to differentiate VS from CPA meningiomas. T2*-weighted GRE should be used as a basic sequence to evaluate CPA tumors. Identification of microhemorrhages may have the potential to assess the aggressive biologic behavior of VS.
Journal of Neurology, Neurosurgery & Psychiatry, 2008
Background: We propose a set of criteria for diagnosis of intracranial infectious aneurysm (IA). ... more Background: We propose a set of criteria for diagnosis of intracranial infectious aneurysm (IA). The proposed diagnostic criteria contain a mandatory criterion (demonstration of intracranial aneurysm by neuroimaging) and twelve supportive criteria drawn from three domains. Domain A encompasses infection, such as infective endocarditis, meningitis, cavernous sinus thrombophlebitis, or orbital cellulitis. Domain B encompasses angiographic features of the aneurysm, such as multiplicity, distal location, fusiform shape, change in size or appearance of new aneurysm at follow-up angiogram. Domain C encompasses other features, such as age < 45 years, recent history of fever, lumbar puncture or cerebral hemorrhage. Each criterion is given one point and the sum under each domain (A sum , B sum and C sum) and total score are calculated. Methods: We evaluated these criteria in 25 patients with confirmed IA and another 111 consecutive patients with non-infectious aneurysm. The sensitivity, specificity and receiver operator characteristic (ROC) curves were calculated for these cohorts. Results: The highest ROC was for total score (.997). A total score = 3 had high sensitivity (96%) and specificity (100%), as well as a positive predictive value of 100%, and negative predictive value of 99.4%. A total score = 2 had high sensitivity (100%) but low specificity (87.4%). Other combinations had lower ROC areas, sensitivities and specificities. Conclusion: Diagnosis of IA would be clinically compelling if three or more of the proposed supportive criteria are satisfied or clinically probable if two proposed supportive criteria are satisfied besides the mandatory criteria.
Acid catalyzed reactions of three proton pump inhibitors (PPIs), namely omeprazole, lansoprazole ... more Acid catalyzed reactions of three proton pump inhibitors (PPIs), namely omeprazole, lansoprazole and pantoprazole, have been investigated and monitored by direct current polarography at dropping mercury electrode (D.M.E) in phosphate buffer (0.1 M) of pH 3-7.5. This gives well defined current-time profiles of individual electroactive degradation products along with their starting materials. The investigation shows that the order of stability of three PPIs can be written as: pantoprazole > omeprazole > lansoprazole. The rate of degradation of PPIs decreases with decreasing the basicity of the corresponding benzimidazole nitrogen of PPIs, as predicted by the effect of individual substituents on each of the benzimidazole rings. At pH 7.5 all three PPIs are almost stable and the observed half wave potentials (E 1/2) are-1.07 V for omeprazole,-1.25 V for lansoprazole and-1.32 V for pantoprazole. On decreasing the pH from 7.5 to 3.0 the anodic shift in E 1/2 values were observed along with degradation of the PPIs and simultaneous appearance of degradation products. The present study may provide an insight for designing more potent new proton pump inhibitors.
Background Structural lesions in/near the sensorimotor cortex may cause distortion/obscuration of... more Background Structural lesions in/near the sensorimotor cortex may cause distortion/obscuration of the anatomic landmarks. Purpose To compare the localization of the sensorimotor cortex using anatomical landmarks and fMRI in the clinical setting in patients with structural lesions in/near the central sulcus. Material and Methods We analyzed the anatomic and fMRI data of 68 consecutive patients (42 tumors, 15 gliotic lesions, 11 focal cortical dysplasias [FCD]) who underwent MRI to assess the relationship of these lesions to the sensorimotor cortex. Anatomical data was analyzed on conventional two- and three-dimensional sequences. BOLD fMRI was performed with block design hand/leg or lip movement paradigm and general linear model was used for detecting the activated cortex. fMRI was considered as a valid method for identifying the sensorimotor cortex based on previously reported literature. Results The sensorimotor cortex could not be identified with anatomical landmarks in 9/68 (13.2...
The evolution of sphenoid sinus meningoencephalocoeles and cerebrospinal fluid (CSF) rhinorrhoea ... more The evolution of sphenoid sinus meningoencephalocoeles and cerebrospinal fluid (CSF) rhinorrhoea is poorly understood. We present a case demonstrating the gradual evolution of encephalocoeles from both the lateral walls of a previously normal sphenoid sinus in a patient with dural arteriovenous fistula (DAVF), the CSF leak which developed following staged embolisation of the DAVF was managed by an endoscopic endonasal transpterygoid approach. Our findings suggest that over a period of time, chronic elevation of intracranial pressure (ICP) results in gradual erosion of the lateral wall of the sphenoid with development of meningoencephalocoeles and CSF leaks.
Background The aim is to study the clinical, radiological and pathological features of childhood ... more Background The aim is to study the clinical, radiological and pathological features of childhood and adolescent meningiomas and analyse outcome prognosticators. Method A retrospective analysis of the case records of patients less than 20 years of age operated for a meningioma in our institute since 1982 was performed. The variables analysed included age, sex, presentation, associated neurofibromatosis (NF), imaging characteristics, extent of resection and histopathology. Results The study group included 20 males and 18 females with a mean age of 15.53 years. Eleven children (28.9%) had evidence of NF of whom three had NF2 with bilateral vestibular schwannomas. The common presenting symptoms were seizures (76.3%), raised intracranial tension (71%), and focal neurological deficits (39.4%). The location of the operated tumours were as follows: ten skull base (24.4%), ten falx/parasagittal (24.4%), eight spinal (19.5%), five convexity (12.2%), three posterior fossa (7.3%), three intraventricular (7.3%) and two optic nerve sheath (4.9%). Two children (4.9%) had cystic meningiomas. Grade I excision was achieved only in twenty tumours (48.8%). On histopathology, thirty (73.2%) were grade I, nine (21.9%) were grade II and two (4.9%) were grade III meningiomas. Seven tumours recurred of which six were located at the skull base. During the mean follow up period of 4.74 years, the majority, 32 (84.2%) had a good outcome and five (13.2%) had a poor outcome. One child (2.6%) expired due to post-operative sepsis. Conclusion Childhood meningiomas are uncommon but not rare lesions with a marginal male predominance. Absence of large series with long follow up precludes any definite conclusions on the clinical course and outcome. Uniform observations made in different series including ours, include a higher incidence of the skull base location and tumours with atypical histopathology. Favourable prognostic factors include younger age (<than 10 years), superficial location, total excision and absence of neurofibromatosis. Location and extent of excision appear to be more important than histopathology grade in predicting outcome.
Posterior inferior cerebellar artery (PICA) aneurysms are uncommon. The natural history and manag... more Posterior inferior cerebellar artery (PICA) aneurysms are uncommon. The natural history and management of these aneurysms remains poorly understood. Surgical treatment of PICA aneurysms is challenging in view of their close neurovascular relationship. Data relating to clinical presentation, radiological findings, operative approaches and outcomes were analyzed in 27 consecutive patients surgically treated for PICA aneurysms in a single hospital between January 1991 and December 2010. Headache was the most common presentation (100%) followed by gait ataxia (14.8%) and lower cranial nerve dysfunction (7.4%). SAH was seen in 20 patients, intraventricular hemorrhage in 22 patients, and 3 had evidence of intracerebellar hematoma. Eighteen aneurysms were located proximally and 9 were located distally. The 25 saccular and 2 fusi-saccular aneurysms were secured by direct clipping (24 cases) or aneurysmorrhaphy (3 cases) using a far-lateral suboccipital (without condylar resection) or midline/ paramedian suboccipital approach. Overall outcome at the time of hospital discharge was excellent or good in 88.9% of the patients. PICA aneurysms, by virtue of their rarity and strategic location pose a unique technical challenge. Depending on the PICA segment affected, variations in the surgical corridor and clipping strategy were major contributors to good outcomes.
Background: Intracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting ... more Background: Intracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting in subarachnoid hemorrhage (SAH).There is no precise biochemical or phenotype marker for diagnosis of aneurysm. Environmental risk factors that associate with IA can result in modifying the effect of inherited genetic factors and thereby increase the susceptibility to SAH. In addition subsequent to aneurismal rupture, the nature and quantum of inflammatory response might be critical for repair. Therefore, genetic liability to inflammatory response caused by polymorphisms in cytokine genes might be the common denominator for gene and environment in the development of aneurysm and complications associated with rupture. Methods: Functionally relevant polymorphisms in the pro-and anti-inflammatory cytokine genes IL-1 complex (IL1A, IL1B, and IL1RN), TNFA, IFNG, IL3, IL6, IL12B, IL1RN, TGFB1, IL4, and IL10] were screened in radiologically confirmed 220 IA patients and 250 controls from genetically stratified Malayalam-speaking Dravidian ethnic population of south India. Subgroup analyses with genetic and environmental variables were also carried out. Results: Pro-inflammatory cytokines TNFA rs361525, IFNG rs2069718, and anti-inflammatory cytokine IL10 rs1800871 and rs1800872 were found to be significantly associated with IA, independent of epidemiological factors. TGFB1 rs1800469 polymorphism was observed to be associated with IA through co-modifying factors such as hypertension and gender. Functional prediction of all the associated SNPs of TNFA, IL10, and TGFB1 indicates their potential role in transcriptional regulation. Meta-analysis further reiterates that IL1 gene cluster and IL6 were not associated with IA. Conclusions: The study suggests that chronic exposure to inflammatory response mediated by genetic variants in pro-inflammatory cytokines TNFA and IFNG could be a primary event, while stochastic regulation of IL10 and TGFB1 response mediated by comorbid factors such as hypertension may augment the pathogenesis of IA through vascular matrix degradation. The implication and interaction of these genetic variants under a specific environmental background will help us identify the resultant phenotypic variation in the pathogenesis of intracranial aneurysm. Identifying genetic risk factors for inflammation might also help in understanding and addressing the posttraumatic complications following the aneurismal rupture.
A 50-year-old woman presented with an extremely uncommon case of solitary metastasis from follicu... more A 50-year-old woman presented with an extremely uncommon case of solitary metastasis from follicular carcinoma of the thyroid, which presented clinically as trigeminal neurinoma. Neuroimaging detected a tumor in the right petrous apex, which was removed surgically. Histological examination showed metastatic follicular carcinoma of the thyroid. However, no primary tumor was detected by various investigations. The tumor recurred twice, and was treated surgically both times. The patient finally agreed to adjuvant therapy for the suspected primary. Radiotherapy was performed followed by complete thyroidectomy. Examination of the gross specimen found the tumor nodule. Clinically significant metastasis can arise from histologically benign and silent follicular thyroid neoplasms.
Background and Objective: Meningiomas involving the foramen magnum (FM) region are rare and const... more Background and Objective: Meningiomas involving the foramen magnum (FM) region are rare and constitute 1% to 7% of intracranial meningiomas. Surgical excision is difficult in view of the complex anatomy and the proximity to critical neurovascular structures. Our aim was to analyze the clinical presentation and surgical outcome of patients operated for FM meningiomas. Materials and Methods: Thirty patients who underwent surgery for FM meningioma over a period of 21 years were studied retrospectively. Case records and imaging studies were reviewed for demographic data, presenting symptoms, tumor location, surgical approach, and postoperative complications. The outcome was assessed on the basis of the Glasgow Outcome Scale (GOS).
Symptomatic subdural hygroma due to foramen magnum decompression for Chiari malformation Type I i... more Symptomatic subdural hygroma due to foramen magnum decompression for Chiari malformation Type I is extremely rare. The authors present their experience with 2 patients harboring such lesions and discuss treatment issues. They conclude that the possibility of subdural hygromas should be considered in all patients presenting with increased intracranial tension following foramen magnum decompression for Chiari malformation Type I. Immediate neuroimaging and appropriate surgical intervention provides a good outcome.
BACKGROUND AND PURPOSE: Vestibular schwannomas (VS) may be difficult to differentiate from cerebe... more BACKGROUND AND PURPOSE: Vestibular schwannomas (VS) may be difficult to differentiate from cerebellopontine angle (CPA) meningiomas. Demonstration of microhemorrhages in VS on T2*weighted gradient-echo (GRE) sequences may have potential value to differentiate VS from CPA meningiomas. MATERIALS AND METHODS: In this prospective study of 20 patients, MR imaging was performed with T2*-weighted GRE in addition to all basic sequences. Histopathologic examination was performed after surgery. Intratumoral hemosiderin was confirmed by pigment staining. RESULTS: There were 15 patients in the VS group with 16 VS and 5 in the meningioma group with 5 posterior fossa meningiomas. Fourteen of the 16 VS and all 5 meningiomas were treated surgically and were confirmed on histopathologic examination. T2*-weighted GRE identified microhemorrhages on T2*-weighted sequence in 15 (93.75%) of the 16 VS. CT excluded calcification in all VS. T2-weighted turbo spin-echo (TSE) and fluid-attenuated inversion recovery (FLAIR) images recognized microhemorrhages in 2 cases. Pigment staining confirmed hemosiderin in all 14 surgically treated VS, and none of the meningiomas showed microhemorrhages on MR imaging. For the detection of microhemorrhages, T2*-weighted GRE showed a sensitivity of 93.8%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 83.3%. The sensitivity of T2 TSE and FLAIR for microhemorrhage was 12.5%. The Fisher exact test showed a statistically significant difference in the differentiation of VS from meningioma on the basis of detection of microhemorrhages (P Ͻ .01). CONCLUSION: Most VS demonstrate microhemorrhages on T2*-weighted GRE. This finding is useful to differentiate VS from CPA meningiomas. T2*-weighted GRE should be used as a basic sequence to evaluate CPA tumors. Identification of microhemorrhages may have the potential to assess the aggressive biologic behavior of VS.
Journal of Neurology, Neurosurgery & Psychiatry, 2008
Background: We propose a set of criteria for diagnosis of intracranial infectious aneurysm (IA). ... more Background: We propose a set of criteria for diagnosis of intracranial infectious aneurysm (IA). The proposed diagnostic criteria contain a mandatory criterion (demonstration of intracranial aneurysm by neuroimaging) and twelve supportive criteria drawn from three domains. Domain A encompasses infection, such as infective endocarditis, meningitis, cavernous sinus thrombophlebitis, or orbital cellulitis. Domain B encompasses angiographic features of the aneurysm, such as multiplicity, distal location, fusiform shape, change in size or appearance of new aneurysm at follow-up angiogram. Domain C encompasses other features, such as age < 45 years, recent history of fever, lumbar puncture or cerebral hemorrhage. Each criterion is given one point and the sum under each domain (A sum , B sum and C sum) and total score are calculated. Methods: We evaluated these criteria in 25 patients with confirmed IA and another 111 consecutive patients with non-infectious aneurysm. The sensitivity, specificity and receiver operator characteristic (ROC) curves were calculated for these cohorts. Results: The highest ROC was for total score (.997). A total score = 3 had high sensitivity (96%) and specificity (100%), as well as a positive predictive value of 100%, and negative predictive value of 99.4%. A total score = 2 had high sensitivity (100%) but low specificity (87.4%). Other combinations had lower ROC areas, sensitivities and specificities. Conclusion: Diagnosis of IA would be clinically compelling if three or more of the proposed supportive criteria are satisfied or clinically probable if two proposed supportive criteria are satisfied besides the mandatory criteria.
Acid catalyzed reactions of three proton pump inhibitors (PPIs), namely omeprazole, lansoprazole ... more Acid catalyzed reactions of three proton pump inhibitors (PPIs), namely omeprazole, lansoprazole and pantoprazole, have been investigated and monitored by direct current polarography at dropping mercury electrode (D.M.E) in phosphate buffer (0.1 M) of pH 3-7.5. This gives well defined current-time profiles of individual electroactive degradation products along with their starting materials. The investigation shows that the order of stability of three PPIs can be written as: pantoprazole > omeprazole > lansoprazole. The rate of degradation of PPIs decreases with decreasing the basicity of the corresponding benzimidazole nitrogen of PPIs, as predicted by the effect of individual substituents on each of the benzimidazole rings. At pH 7.5 all three PPIs are almost stable and the observed half wave potentials (E 1/2) are-1.07 V for omeprazole,-1.25 V for lansoprazole and-1.32 V for pantoprazole. On decreasing the pH from 7.5 to 3.0 the anodic shift in E 1/2 values were observed along with degradation of the PPIs and simultaneous appearance of degradation products. The present study may provide an insight for designing more potent new proton pump inhibitors.
Background Structural lesions in/near the sensorimotor cortex may cause distortion/obscuration of... more Background Structural lesions in/near the sensorimotor cortex may cause distortion/obscuration of the anatomic landmarks. Purpose To compare the localization of the sensorimotor cortex using anatomical landmarks and fMRI in the clinical setting in patients with structural lesions in/near the central sulcus. Material and Methods We analyzed the anatomic and fMRI data of 68 consecutive patients (42 tumors, 15 gliotic lesions, 11 focal cortical dysplasias [FCD]) who underwent MRI to assess the relationship of these lesions to the sensorimotor cortex. Anatomical data was analyzed on conventional two- and three-dimensional sequences. BOLD fMRI was performed with block design hand/leg or lip movement paradigm and general linear model was used for detecting the activated cortex. fMRI was considered as a valid method for identifying the sensorimotor cortex based on previously reported literature. Results The sensorimotor cortex could not be identified with anatomical landmarks in 9/68 (13.2...
The evolution of sphenoid sinus meningoencephalocoeles and cerebrospinal fluid (CSF) rhinorrhoea ... more The evolution of sphenoid sinus meningoencephalocoeles and cerebrospinal fluid (CSF) rhinorrhoea is poorly understood. We present a case demonstrating the gradual evolution of encephalocoeles from both the lateral walls of a previously normal sphenoid sinus in a patient with dural arteriovenous fistula (DAVF), the CSF leak which developed following staged embolisation of the DAVF was managed by an endoscopic endonasal transpterygoid approach. Our findings suggest that over a period of time, chronic elevation of intracranial pressure (ICP) results in gradual erosion of the lateral wall of the sphenoid with development of meningoencephalocoeles and CSF leaks.
Background The aim is to study the clinical, radiological and pathological features of childhood ... more Background The aim is to study the clinical, radiological and pathological features of childhood and adolescent meningiomas and analyse outcome prognosticators. Method A retrospective analysis of the case records of patients less than 20 years of age operated for a meningioma in our institute since 1982 was performed. The variables analysed included age, sex, presentation, associated neurofibromatosis (NF), imaging characteristics, extent of resection and histopathology. Results The study group included 20 males and 18 females with a mean age of 15.53 years. Eleven children (28.9%) had evidence of NF of whom three had NF2 with bilateral vestibular schwannomas. The common presenting symptoms were seizures (76.3%), raised intracranial tension (71%), and focal neurological deficits (39.4%). The location of the operated tumours were as follows: ten skull base (24.4%), ten falx/parasagittal (24.4%), eight spinal (19.5%), five convexity (12.2%), three posterior fossa (7.3%), three intraventricular (7.3%) and two optic nerve sheath (4.9%). Two children (4.9%) had cystic meningiomas. Grade I excision was achieved only in twenty tumours (48.8%). On histopathology, thirty (73.2%) were grade I, nine (21.9%) were grade II and two (4.9%) were grade III meningiomas. Seven tumours recurred of which six were located at the skull base. During the mean follow up period of 4.74 years, the majority, 32 (84.2%) had a good outcome and five (13.2%) had a poor outcome. One child (2.6%) expired due to post-operative sepsis. Conclusion Childhood meningiomas are uncommon but not rare lesions with a marginal male predominance. Absence of large series with long follow up precludes any definite conclusions on the clinical course and outcome. Uniform observations made in different series including ours, include a higher incidence of the skull base location and tumours with atypical histopathology. Favourable prognostic factors include younger age (<than 10 years), superficial location, total excision and absence of neurofibromatosis. Location and extent of excision appear to be more important than histopathology grade in predicting outcome.
Posterior inferior cerebellar artery (PICA) aneurysms are uncommon. The natural history and manag... more Posterior inferior cerebellar artery (PICA) aneurysms are uncommon. The natural history and management of these aneurysms remains poorly understood. Surgical treatment of PICA aneurysms is challenging in view of their close neurovascular relationship. Data relating to clinical presentation, radiological findings, operative approaches and outcomes were analyzed in 27 consecutive patients surgically treated for PICA aneurysms in a single hospital between January 1991 and December 2010. Headache was the most common presentation (100%) followed by gait ataxia (14.8%) and lower cranial nerve dysfunction (7.4%). SAH was seen in 20 patients, intraventricular hemorrhage in 22 patients, and 3 had evidence of intracerebellar hematoma. Eighteen aneurysms were located proximally and 9 were located distally. The 25 saccular and 2 fusi-saccular aneurysms were secured by direct clipping (24 cases) or aneurysmorrhaphy (3 cases) using a far-lateral suboccipital (without condylar resection) or midline/ paramedian suboccipital approach. Overall outcome at the time of hospital discharge was excellent or good in 88.9% of the patients. PICA aneurysms, by virtue of their rarity and strategic location pose a unique technical challenge. Depending on the PICA segment affected, variations in the surgical corridor and clipping strategy were major contributors to good outcomes.
Background: Intracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting ... more Background: Intracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting in subarachnoid hemorrhage (SAH).There is no precise biochemical or phenotype marker for diagnosis of aneurysm. Environmental risk factors that associate with IA can result in modifying the effect of inherited genetic factors and thereby increase the susceptibility to SAH. In addition subsequent to aneurismal rupture, the nature and quantum of inflammatory response might be critical for repair. Therefore, genetic liability to inflammatory response caused by polymorphisms in cytokine genes might be the common denominator for gene and environment in the development of aneurysm and complications associated with rupture. Methods: Functionally relevant polymorphisms in the pro-and anti-inflammatory cytokine genes IL-1 complex (IL1A, IL1B, and IL1RN), TNFA, IFNG, IL3, IL6, IL12B, IL1RN, TGFB1, IL4, and IL10] were screened in radiologically confirmed 220 IA patients and 250 controls from genetically stratified Malayalam-speaking Dravidian ethnic population of south India. Subgroup analyses with genetic and environmental variables were also carried out. Results: Pro-inflammatory cytokines TNFA rs361525, IFNG rs2069718, and anti-inflammatory cytokine IL10 rs1800871 and rs1800872 were found to be significantly associated with IA, independent of epidemiological factors. TGFB1 rs1800469 polymorphism was observed to be associated with IA through co-modifying factors such as hypertension and gender. Functional prediction of all the associated SNPs of TNFA, IL10, and TGFB1 indicates their potential role in transcriptional regulation. Meta-analysis further reiterates that IL1 gene cluster and IL6 were not associated with IA. Conclusions: The study suggests that chronic exposure to inflammatory response mediated by genetic variants in pro-inflammatory cytokines TNFA and IFNG could be a primary event, while stochastic regulation of IL10 and TGFB1 response mediated by comorbid factors such as hypertension may augment the pathogenesis of IA through vascular matrix degradation. The implication and interaction of these genetic variants under a specific environmental background will help us identify the resultant phenotypic variation in the pathogenesis of intracranial aneurysm. Identifying genetic risk factors for inflammation might also help in understanding and addressing the posttraumatic complications following the aneurismal rupture.
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Papers by Suresh Nair