Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors.

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.

Lack of association of lysyl oxidase (LOX) gene polymorphisms with intracranial aneurysm in a south Indian population.

Intracranial aneurysm (IA) accounts for 85 % of haemorrhagic stroke and is mainly caused due to weakening of arterial wall. Lysyl oxidase (LOX) is a cuproenzyme involved in cross linking structural proteins collagen and elastin, thus providing structural stability to artery. Using a case-control study design, we tested the hypothesis whether the variants in LOX gene flanking the two LD block, can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. SNPs were genotyped by fluorescence-based competitive allele-specific PCR (KASPar) chemistry. We selected 200 radiologically confirmed aneurysmal cases and 235 ethnically and age and gender matched controls from the Dravidian Malayalam speaking population of South India. We observed marked interethnic differences in the genotype distribution of LOX variants when compared to Japanese and African populations. However, there was no significant association with any of the LOX variants with IA. This study also could not observe any significant role of LOX polymorphisms in influencing IA either directly or indirectly through its confounding factors such as hypertension and gender in South Indian population.

Versatility Of Square Flaps In Post-Burn Contractures Involving Upper Limb.

Post-burn contractures are a common problem and functionally limiting for upper limbs. Many different techniques have been described in the literature for their treatment. Z-plasty and release with SSG cover are the commonest procedures done for post-burn contractures. In this study we assess the use of the square flap technique in post-burn contractures of upper limb. Eleven patients with a total number of twelve upper limb contractures (mild to moderate) involving axilla, elbow and finger underwent release by standard square flap technique. All cases were followed up for at least 6 months and analyzed for range of motion and aesthetic outcome. Patient and surgeon satisfaction was recorded. All operated cases achieved a satisfactory range of movement post-operatively without any recurrence. The number of patients who were satisfied with the surgery were 7 out of 11, and 4 patients were somewhat satisfied with the results obtained. In contrast, the surgeons were satisfied in all cases. Square flap is shown to be an easy and reliable flap for mild to moderate contractures of the anterior or posterior axillary folds, elbow contractures and finger contractures with low recurrence rate.

Les rétractions séquellaires de brûlure sont fréquentes et engendrent des limitations fonctionnelles au membre supérieur. Beaucoup de techniques différentes ont été décrites dans la littérature pour leur traitement : plastie en Z, libération et couverture par greffe de peau, sont les techniques les plus couramment utilisées. Dans cette étude, nous évaluons l'usage du double lambeau rhomboïde ou lambeau carré de Hyakusoku dans les rétractions séquellaires de brûlure du membre supérieur. 11 patients représentant 12 rétractions au membre supérieur (minimes à modérées) intéressant la région axillaire, le coude, et les doigts ont bénéficié d'une libération de la rétraction par la technique du double lambeau rhomboïde ou lambeau carré de Hyakusoku. Tous les patients ont été suivis pendant au moins six mois post-opératoire. L'analyse porte à la fois sur les mobilités et le résultat esthétique. La satisfaction du patient et du chirurgien a été notée. Toutes les interventions ont permis une nette amélioration de la fonction, sans récidive. 7 patients sur 11 ont été satisfaits par le résultat du geste chirurgical et quatre patients ont été assez satisfaits. En revanche, les chirurgiens ont noté les résultats comme satisfaisants dans tous les cas. Le double lambeau rhomboïde ou lambeau carré de Hyakusoku semble donc être un lambeau simple et fiable dans le traitement des rétractions minimes à modérées des piliers axillaires antérieur ou postérieur, du coude ou des doigts avec un très faible taux de récidive.

Risk factors for aneurysmal subarachnoid hemorrhage in an Indian population.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) has a mortality rate as high as 50%. The prevalence of intracranial aneurysms from various parts of India varies from 0.75 to 10.3%, with higher numbers of cases being diagnosed due to the increasing age of the population and improvements in imaging techniques. However, little is known about the attributable risk factors of aSAH in the Indian population. METHODS: Using a case-control study we estimated the risk of factors such as hypertension, cigarette smoking, alcohol consumption, diabetes mellitus and family history of aSAH in a South Indian population. The population-attributable risk (PAR) of smoking, hypertension and alcohol use was estimated for the South Indian as well as for the general Indian population. RESULTS: Our results showed that cigarette smoking (OR, 3.59; p < 0.001) and a history of hypertension (OR, 2.98; p < 0.001) were significant risk factors associated with aSAH. When patients were classified by gender, it was observed that being a smoker and having hypertension increased the risk for aSAH by nearly fourfold in men. Among women, hypertension and older age were significant risk factors. The PAR estimates indicated that smoking (OR, 3.59; 95% CI, 2.13-6.06) and hypertension (OR, 2.98; 95% CI, 1.73-5.12) are significant risk factors. CONCLUSIONS: Hypertension and smoking may be causal risk factors which might also modify the effect of genetic factors that could increase susceptibility to aSAH in the Indian population. Since these risk factors are amenable to effective modification, our findings will be useful for a gender-specific management of aSAH.

Role of endothelial nitric oxide synthase gene polymorphisms in predicting aneurysmal subarachnoid hemorrhage in South Indian patients.

Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been implicated as predisposing genetic factors that can predict aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from different populations. Using a case-control study design, we tested the hypothesis whether variants in eNOS gene can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We enrolled 122 patients, along with 224 ethnically matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic differences in the genotype distribution of eNOS variants when comparing the South Indian population with the reported frequencies from Caucasian and Japanese populations. Genotype distributions in control and patient populations were found to be in Hardy-Weinberg equilibrium. In patients, the allele, genotype and estimated haplotype frequencies did not differ significantly from the controls. Multiple logistic regression indicated hypertension and smoking as risk factors for the disease, however the risk alleles did not have any interaction with these risk factors. Although the eNOS polymorphisms were not found to be a likely risk factor for aSAH, the role of factors such as ethnicity, gender, smoking and hypertension should be evaluated cautiously to understand the genotype to phenotype conversion.

Anomalous origin of the callosomarginal artery from the A1 segment with an associated saccular aneurysm.

Although anatomic variations are well known in the A1 segment of the anterior cerebral artery (ACA), anomalous origin of a cortical artery from the A1 segment is extremely rare. The only reported cortical branch to arise from the A1 segment is the fronto-orbital artery. We report a case of anomalous origin of the callosomarginal artery (CMA) in association with a saccular aneurysm from the A1 segment of the left ACA in a 35-year-old man who presented with intracerebral hemorrhage. To our knowledge, this is the first report of anomalous origin of the CMA from the A1 segment.

Medial trigonal arteriovenous malformations.

A retrospective analysis of 48 patients of medial paratrigonal arteriovenous malformations (AVMs) which constituted 18% of the total 258. AVMs surgically managed in our institute for 16 years was carried out to study their clinical presentation, radiological features, operative approaches and functional outcome. While hemorrhage was the initial presenting symptom in 35, it was longstanding headache in 10, focal seizures in two and progressive weakness in one. However, 41 of these presented with bleed at the time of admission to our hospital and in 15 there was history of multiple bleeds. Twelve and eleven patients had field cut and hemiparesis respectively. Arterial supply to the malformation was quite uniform with posterior (43 patients) and anterior cerebral (25 patients) being the most frequent source. Venous drainage was predominantly into the galenic system (70%). Preoperative embolization was carried out in six patients. While the AVM was excised through a parasagittal interhemispheric approach in 34 patients, the nidus was approached through a direct transcortical (superior parietal lobule) approach in fourteen patients. There was only one operative mortality. Twelve patients whose preoperative fields were normal developed field cut postoperatively. An improvement of the preoperative field deficit was noted only in one patient. While eight of the ten patients with preoperative weakness improved and remained independent the remaining two were moderately disabled. Only two of the 10 patients who developed postoperative weakness remained severely disabled. Our operative results suggest that these AVMs which are prone to recurrent bleeds can be resected with acceptable morbidity. Hemianopia resulting from bleed or surgery is unlikely to improve.

Carotid artery injury during transsphenoidal resection of pituitary tumor: anesthesia perspective.

The authors describe two patients who suffered carotid artery injury during transsphenoidal resection of a pituitary tumor. Anesthesiologists were involved in resuscitation after initial hemorrhage, in securing the airway, in initiating cerebral protection strategies, and in transporting these patients. Anesthesia was provided for resection of the tumors, removal of packs from the pituitary fossae, and diagnostic and therapeutic radiologic procedures. In each case hemostasis was achieved by packing the sella turcica, sphenoid sinus, and nostrils. Both patients were electively ventilated. In one patient, a pseudoaneurysm of the carotid artery was detected by angiography in the operating room. It was treated by trapping the internal carotid artery. The other patient developed a carotid-cavernous fistula, which was treated by balloon embolization. Both patients were discharged after dealing with these complications.

Primary osteogenic sarcoma involving sella-sphenoid sinus--case report.

A 38-year-old male presented with an extremely rare primary osteogenic sarcoma, unassociated with Paget's disease or late effects of radiation, involving the sella and sphenoid sinus region. Complete excision of the tumor was achieved through an extended frontobasal approach. Postoperatively, six cycles of combination chemotherapy (adriamycin, ifosphamide, and cisplatin) followed by a total of 55 Gy local radiotherapy in 33 fractions was given. Primary osteogenic sarcoma should be considered in the differential diagnosis of the central skull base tumors. Osteogenic sarcoma, in general, has a bad prognosis, and should be managed aggressively with multimodality treatment including gross total surgical resection, combination chemotherapy, and radiotherapy.

Solitary metastasis from occult follicular carcinoma of the thyroid mimicking trigeminal neurinoma--case report.

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.

Clinico-pathological study of cerebral aneurysms.

AIMS AND OBJECTIVES: A clinico-pathological study of cerebral aneurysms was undertaken to understand the histopathogical nature of the lesions and to ascertain possible etiological risk factors. MATERIAL AND METHODS: Of the 255 cases of cerebral aneurysms operated upon at our Institute during the two-year period between Jan 1999 to Dec 2000, a detailed study was conducted on 57 cases where the aneurysm sac could be excised and subjected to histopathological examination. Aneurysm sacs were fixed in 10% buffered formaldehyde and processed through graded alcohol. Paraffin-embedded sections were examined, using hematoxylin and eosin, Verhoeff van Gieson's and toluidine blue staining techniques. Histopathological observations were analyzed and correlated with clinical features. RESULTS: The ages of the patients ranged from 17-65 years and there were 33 males and 24 females. Twenty-six patients were chronic smokers and 19 patients had hypertension. There were 54 saccular and 3 fusiform aneurysms, predominantly involving the anterior circulation (52 cases) than posterior circulation (5 cases). In 35 cases, histopathological studies demonstrated mucoid deposits between hyperplastic cellular elements in the true and false aneurysm wall and/or parent artery or vasavasora. The changes were associated with dystrophic changes in the internal elastic lamina. CONCLUSION: Besides significant risk factors like smoking and hypertension, such mucoid vasculopathic changes may have predisposed vessels to structural weakness and aneurysm formation in our patients.

Dissecting intracranial vertebral artery aneurysms.

Dissecting aneurysms of the intracranial arteries are exceedingly rare vascular lesions that can produce acute cerebral or brain stem infarction in young healthy adults. They carry a high mortality rate. Two cases of dissecting vertebral artery aneurysms that presented with bleed, were successfully operated by trapping and excision of the dissecting segment. Both dissecting aneurysms were located distal to PICA origin. Both the patients developed post operative lower cranial nerve paresis and one developed lateral medullary syndrome, which improved subsequently. Dissecting aneurysms presenting with bleed should be surgically managed by trapping and excising the involved segment sparing the PICA origin or by interventional radiological techniques. Revascularisation procedures should be considered in addition to trapping of the main vertebral segment if PICA is involved in the trapped segment. The diagnostic and therapeutic difficulties associated with dissecting vertebral artery aneurysms and the controversies regarding their management have been reviewed.

Liponeurocytoma of the cerebellum--a case report.

We report the characteristic neuropathological features of a rare case of cerebellar liponeurocytoma in a 62-year-old female. The tumor has a low proliferative potential and carries a favorable prognosis.

Germinoma of the basal ganglia: a case report and review of literature.

Germs cell tumors of extrapineal region are extremely uncommon. The clinicopathological features of germinoma in the basal ganglia, in a 21 year old male are presented in this report. Post-operative radiotherapy is advocated, in view of the good radiosensitivity of these tumors.

Cerebellar hemisphere, an uncommon location for pleomorphic xanthoastrocytoma and lipidized glioblastoma multiformis.

Lipidized glioblastoma multiformis (LGB) and pleomorphic xanthoastrocytoma (PXA) are often supratentorial in location and occur in the second to fourth decade. This report presents two young patients, one having LGB and the other having PXA in the cerebellum. Histological differentiation between LGB and PXA is discussed.

Infrasellar craniopharyngioma mimicking a clival chordoma: a case report.

An unusual case of entirely infrasellar craniopharyngioma mimicking a clival chordoma is described. Only 22 cases of craniopharyngioma with nasopharyngeal extension have been reported in the literature. Of the reported cases, most were primarily intracranial with secondary downward extension; only two were thought to originate from an infrasellar location. The present case is another example of an entirely infrasellar craniopharyngioma, with extensive clival destruction, mimicking a clival chordoma. Relevant literature on the subject is reviewed.

False aneurysm of cavernous carotid artery and carotid cavernous fistula: complications following transsphenoidal surgery.

We present two cases of carotid injury during transsphenoidal surgery for pituitary adenoma. While in one of the cases it resulted in the formation of a false aneurysm of cavernous carotid artery, in the other patient, a carotid cavernous fistula (CCF) formed. The false aneurysm was managed by surgical trapping and the patient had an uneventful recovery. The CCF was initially managed with balloon embolization. The balloon got deflated and resulted in a false aneurysm with persistent CCF. This was occluded with Guglielmi Detachable Coils (GDC). The management options are discussed and relevant literature is reviewed. We emphasize the importance of an early cerebral angiography to know the status of the injured carotid artery and formation of false aneurysm / fistula.

Intracranial aneurysmal bone cyst manifesting as a cerebellar mass.

A 17-year-old boy presented with symptoms of raised intracranial pressure for a month. Investigations revealed a large extra-cerebellar mass. The lesion was radically resected. It arose from the petrous bone. Histology revealed that the lesion was an aneurysmal bone cyst [ABC].