Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Comparison of MRI findings of hypothalamic-optic chiasmatic gliomas and craniopharyngiomas.

BACKGROUND: Differential diagnosis of hypothalamic-optic chiasmatic gliomas (HOCGs) and craniopharyngiomas on magnetic resonance imaging (MRI) can be quite challenging. PURPOSE: To compare the MRI features of HOCGs and cranipharyngiomas. MATERIAL AND METHODS: Patients diagnosed with HOCG or craniopharyngioma in histopathological evaluation between 2012 and 2022 and who underwent preoperative contrast-enhanced brain MRI were included. Various MRI features were retrospectively evaluated for each lesion: T2-weighted imaging and fluid attenuation inversion recovery hyperintensity, calcification, cystic change, T1-weighted (T1W) imaging hyperintensity of the cystic component, hemorrhage, involvement of sellar, suprasellar or other adjacent structures, lobulated appearance, presence of hydrocephalus, and contrast enhancement pattern. Apparent diffusion coefficient (ADC) values were also evaluated and compared. RESULTS: Among 38 patients included, 13 (34%) had HOCG and 25 (66%) had craniopharyngioma. Craniopharyngiomas had a significantly higher rate of cystic changes, calcification, and T1W imaging hyperintensity of the cystic component than HOCGs (P <0.05). Of HOCGs, 92% had chiasm involvement, 23% had optic nerve involvement, and 31% had brain stem involvement. On the other hand, chiasm involvement was observed in 8% of craniopharyngiomas, but none had optic nerve and/or brain stem involvement (P <0.05). While 62% (8/13) of HOCGs had diffuse homogeneous enhancement, 80% (20/25) of craniopharyngiomas had a diffuse heterogeneous enhancement pattern. Mean ADC values were significantly higher in craniopharyngiomas compared to HOCGs (2.1 vs. 1.6 ×10-3mm2/s, P <0.05). CONCLUSION: Although some neuroimaging findings may overlap, features such as presence of cyst and calcification, brain stem and optic pathway involvement, different enhancement patterns, and ADC values may be helpful in the differential diagnosis of HOCGs and craniopharyngiomas.

The Effect of the Ganglionic Segment Inflammatory Response to Postoperative Enterocolitis in Hirschsprung Disease.

INTRODUCTION: We examined the relationship between proinflammatory cytokines that occur in the inflammatory reaction in the intestine in Hirschsprung disease (HD) and Hirschsprung-associated enterocolitis (HAEC). METHODS: Thirty cases (M:27, F:3) operated on due to HD. The cases were divided into three groups: group 1 with pre and post operative EC, group 2 with post-operative, and group 3 with pre-operative EC. The intestinal segments were evaluated by immunohistochemistry for interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). RESULTS: IL-1ß staining was significantly higher in the ganglionic zone of groups with enterocolitis compared to the control group (p = 0.012). TNF-α staining in the transitional zone of Group 3 and IL-1ß staining in the ganglionic zone of Group 1 was significantly higher than the control group (p = 0.030, p = 0.020). CONCLUSION: In our study, older age at diagnosis and more than 20% IL-1ß staining in the ganglionic segment were found to be risk factors for HAEC. It is noteworthy that the increase in IL-1ß can be associated with HAEC.

Ewing Sarcoma Displaying Extensive Well Differentiated Neuroblastomatous Differentiation: A Case Report.

INTRODUCTION: A tumor with EWSR1/FLI fusion displaying extensive well differentiated neuroblastomatous differentiation is presented. CASE REPORT: A nine-year-old female patient had a thoracic vertebra 8 paraspinal mass. The lesion was resected incompletely. Histopathologically, a small round cell tumor with gangliomatous differentiation was seen. This was initially diagnosed as an intermixed ganglioneuroblastoma. In the completion surgery biopsy material, the small round cell component was more prominent. Immunohistochemistry for both samples showed membrane positivity for CD99 and nuclear positivity for NKX2.2 in the small round cell component of the tumor. Molecular analysis revealed EWSR1/FLI fusion. The diagnosis then considered a "Ewing Sarcoma Displaying Extensive Well Differentiated Neuroblastomatous Differentiation". CONCLUSION: Tumors with the EWSR1/FLI fusion may show neuroblastomatous differentiation. We chose to treat this as an Ewing Sarcoma (ES). Recognition of this phenomenon in ES cases may prevent a possible misinterpretation and a failure in oncologic treatment.

Machine learning as a clinical decision support tool for patients with acromegaly.

OBJECTIVE: To develop machine learning (ML) models that predict postoperative remission, remission at last visit, and resistance to somatostatin receptor ligands (SRL) in patients with acromegaly and to determine the clinical features associated with the prognosis. METHODS: We studied outcomes using the area under the receiver operating characteristics (AUROC) values, which were reported as the performance metric. To determine the importance of each feature and easy interpretation, Shapley Additive explanations (SHAP) values, which help explain the outputs of ML models, are used. RESULTS: One-hundred fifty-two patients with acromegaly were included in the final analysis. The mean AUROC values resulting from 100 independent replications were 0.728 for postoperative 3 months remission status classification, 0.879 for remission at last visit classification, and 0.753 for SRL resistance status classification. Extreme gradient boosting model demonstrated that preoperative growth hormone (GH) level, age at operation, and preoperative tumor size were the most important predictors for early remission; resistance to SRL and preoperative tumor size represented the most important predictors of remission at last visit, and postoperative 3-month insulin-like growth factor 1 (IGF1) and GH levels (random and nadir) together with the sparsely granulated somatotroph adenoma subtype served as the most important predictors of SRL resistance. CONCLUSIONS: ML models may serve as valuable tools in the prediction of remission and SRL resistance.

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging­derived texture features.

PURPOSE: Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas. METHODS: The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy. RESULTS: A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types. CONCLUSIONS: Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.

The Use of Three-Dimensional Printed Technology for Mandibular Reconstruction in a Rare Case of Giant Odontogenic Myxofibroma.

ABSTRACT: Odontogenic myxofibroma is a benign odontogenic tumor of mesenchymal tissue that generally originates from the mandible. It is an extremely rare tumor accounting for approximately 2% of all odontogenic tumors. In this report, the authors presented a giant right mandibular mass that extends to the angle of the mandible and displacing the tongue laterally caused significant malocclusion, pain, and impaired oral intake. The tumoral involvement of the mandibula required a partial mandibulectomy with the resection of right mandibular ramus, body, and bilateral parasymphysis. Right mandibular condyle was preserved. The mandibular defect was reconstructed with a fibula free flap. Three-dimensional printed maxillofacial bone model of the patient was used as contour modeling and guide. Histopathologic examination confirmed the diagnosis as odontogenic myxofibroma.The purpose of the report is to present a very rare case of odontogenic myxofibroma and its general characteristics, radiological features, differential diagnosis, surgical management, and the use of three-dimensional printing technology in the field of mandibular reconstruction.

Prenatal Diagnosis of 5p Deletion Syndrome with Brain Abnormalities by Ultrasonography and Fetal Magnetic Resonance Imaging: A Case Report.

Introduction: 5p deletion syndrome commonly known as cri du chat syndrome is a well-described syndrome in neonates with catlike cry, craniofacial dysmorphic features, abnormal dermatoglyphics, microcephaly and severe psychomotor and developmental delay.Case report: We report a case of 5p deletion syndrome diagnosed prenatally in association with mild ventriculomegaly, cerebellar hypoplasia, pontine hypoplasia, increased subarachnoid space and high suspicion of cortical hypoplasia with ultrasound, magnetic resonance imaging, and postmortem examination.Conclusion: Best to our knowledge, this is the first case that pontine hypoplasia and increased subarachnoid space have been demonstrated prenatally and confirmed by postnatal autopsy.

Chondrosarcoma in the body of the C2 vertebral axis.

Chondrosarcoma, a malignant bone tumor, is rarely encountered in the cervical spine. This article describes a patient whose neck pain and dysphagia were caused by an expansive, destructive lesion with calcification that was located in the body of the axis (C2 vertebra), the first time a chondrosarcoma has been reported in this location.

Predicting response to somatostatin analogues in acromegaly: machine learning-based high-dimensional quantitative texture analysis on T2-weighted MRI.

OBJECTIVE: To investigate the value of machine learning (ML)-based high-dimensional quantitative texture analysis (qTA) on T2-weighted magnetic resonance imaging (MRI) in predicting response to somatostatin analogues (SA) in acromegaly patients with growth hormone (GH)-secreting pituitary macroadenoma, and to compare the qTA with quantitative and qualitative T2-weighted relative signal intensity (rSI) and immunohistochemical evaluation. METHODS: Forty-seven patients (24 responsive; 23 resistant patients to SA) were eligible for this retrospective study. Coronal T2-weighted images were used for qTA and rSI evaluation. The immunohistochemical evaluation was based on the granulation pattern of the adenomas. Dimension reduction was carried out by reproducibility analysis and wrapper-based algorithm. ML classifiers were k-nearest neighbours (k-NN) and C4.5 algorithm. The reference standard was the biochemical response status. Predictive performance of qTA was compared with those of the quantitative and qualitative rSI and immunohistochemical evaluation. RESULTS: Five hundred thirty-five out of 828 texture features had excellent reproducibility. For the qTA, k-NN correctly classified 85.1% of the macroadenomas regarding response to SAs with an area under the receiver operating characteristic curve (AUC-ROC) of 0.847. The accuracy and AUC-ROC ranges of the other methods were 57.4-70.2% and 0.575-0.704, respectively. Differences in predictive performance between qTA-based classification and the other methods were significant (p < 0.05). CONCLUSIONS: The ML-based qTA of T2-weighted MRI is a potential non-invasive tool in predicting response to SAs in patients with acromegaly and GH-secreting pituitary macroadenoma. The method performed better than the qualitative and quantitative rSI and immunohistochemical evaluation. KEY POINTS: • Machine learning-based texture analysis of T2-weighted MRI can correctly classify response to somatostatin analogues in more than four fifths of the patients. • Machine learning-based texture analysis performs better than qualitative and quantitative evaluation of relative T2 signal intensity and immunohistochemical evaluation. • About one third of the texture features may not be excellently reproducible, indicating that a reliability analysis is necessary before model development.

Preoperative evaluation of tumour consistency in pituitary macroadenomas: a machine learning-based histogram analysis on conventional T2-weighted MRI.

PURPOSE: To evaluate the potential value of machine learning (ML)-based histogram analysis (or first-order texture analysis) on T2-weighted magnetic resonance imaging (MRI) for predicting consistency of pituitary macroadenomas (PMA) and to compare it with that of signal intensity ratio (SIR) evaluation. METHODS: Fifty-five patients with 13 hard and 42 soft PMAs were included in this retrospective study. Histogram features were extracted from coronal T2-weighted original, filtered and transformed MRI images by manual segmentation. To achieve balanced classes (38 hard vs 42 soft), multiple samples were obtained from different slices of the PMAs with hard consistency. Dimension reduction was done with reproducibility analysis, collinearity analysis and feature selection. ML classifier was artificial neural network (ANN). Reference standard for the classifications was based on surgical and histopathological findings. Predictive performance of histogram analysis was compared with that of SIR evaluation. The main metric for comparisons was the area under the receiver operating characteristic curve (AUC). RESULTS: Only 137 of 162 features had excellent reproducibility. Collinearity analysis yielded 20 features. Feature selection algorithm provided six texture features. For histogram analysis, the ANN correctly classified 72.5% of the PMAs regarding consistency with an AUC value of 0.710. For SIR evaluation, accuracy and AUC values were 74.5% and 0.551, respectively. Considering AUC values, ML-based histogram analysis performed better than SIR evaluation (z = 2.312, p = 0.021). CONCLUSION: ML-based T2-weighted MRI histogram analysis might be a useful technique in predicting the consistency of PMAs, with a better predictive performance than that of SIR evaluation.

The investigation of hyaluronic acid and hyaluronidase-1 levels as tumour marker in larynx cancer.

OBJECTIVE: The purpose of this study was to investigate the hyaluronic acid (HA) and hyaluronidase-1 (HYAL-1) levels in laryngeal cancer patients. STUDY DESIGN: Prospective, controlled clinical trial. SETTING: University Medical Center. PARTICIPANTS: Fifty laryngeal squamous cell carcinoma patients and 50 volunteers who gave saliva samples investigated prospectively between 2016 and 2017. METHODS: Hyaluronidase-1 expression was measured by RT-PCR in normal and tumour tissue samples; hyaluronic acid values of saliva and tumour tissues were measured by ELISA method. RESULTS: HYAL-1 expression increased 2.5-fold in tumour tissues compared to normal tissues, and the difference was statistically significant (P < 0.001).Mean saliva HA levels were 103.93 ± 69.04 ng/mL and 177.29 ± 98.44 ng/mL in the patients and controls' saliva specimens, respectively. The difference was not statistically significant (P = 0.657). HA levels were higher in tumour tissue samples than saliva samples, but there was not statistically significant difference between saliva and tumour tissue HA levels. CONCLUSION: HYAL-1 expression in laryngeal squamous cell carcinomas is elevated compared to normal tissues of same patients. Targeting this gene and HA catabolism products may use treatment of larynx cancer in the future.

Frequency of ALK and GD2 Expression in Neuroblastoma.

Background: The aim of this study was to elucidate the significance of immunohistochemical staining patterns of ALK and GD2 in peripheral neuroblastic tumors with different stages and favorable/unfavorable features. Materials and methods: 32 neuroblastomas, 7 ganglioneuroblastomas, and 1 ganglioneuroma cases were immunohistochemically stained with ALK and GD2, and the expressions were graded and correlated with differentiation, size, and favorable/unfavorable histology. Results: There was no statistically significant correlation between ALK immunopositivity and tumor differentiation or stage. Although there was no statistically significant correlation between GD2 immunopositivity and stage, the intensity and prevalence of GD2 immunostaining were statistically significantly higher in the well differentiated group and in tumors which were smaller than 10 cm. Conclusion: GD2 immunostaining levels correlated with tumor differentiation and size. ALK immunostaining was not related to tumor differentiation or stage.

Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1-5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues.

OBJECTIVE: To determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1-5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs). METHODS: A total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors. RESULTS: Several variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p < 0.05 for all), and other SSTRs did not differ between the groups (p > 0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p < 0.05 for all). CONCLUSIONS: Lack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.

Dysembryoplastic neuroepithelial tumours: clinical, radiological, pathological features and outcome.

OBJECT: To analyse the clinical, imaging and histopathological data of patients who were diagnosed to have Dysembrioplastic Neuroepithelial Tumour (DNET) and underwent surgery between 1995-2015. MATERIALS AND METHODS: Age at seizure onset, age at surgery, gender, disease duration, seizure outcome of 44 patients were analysed together with Magnetic Resonance Imaging (MRI) of 21 patients. MRI types were classified as type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodularlike,heterogeneous), type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring). RESULTS: Histopathological classification revealed simple form in 19, complex in 14 and non-specific in 11 patients. Lobar distribution of the lesions was as follows: 21 Temporal (47.7%), 12 parietal (27.3%), 8 frontal (18.2%) and 3 occipital (6.8%). Type 1 MRI was observed in 10, type 2 was in 7, and type 3 in 4 patients on radiological evaluation. All cases with type 1 MRI corresponded to either simple or complex forms and all cases with type 3 MRI corresponded to nonspecific form. The histopathological distribution of cases with type 2 MRI was 4 as non-specific, 2 as simple, 1 as complex. There was no significant difference in the age of onset, age at operation and duration of epilepsy between the patients with different MRI subtypes. The majority of patients (N:36) had Engel I outcome (81,8%). In groups with Engel II and III outcome, duration of epilepsy was significantly higher (p:0,014) and simple form of DNET has significantly higher seizure freedom after surgery compared to complex and nonspecific forms of DNET (p:0,002). CONCLUSION: Patients with DNET constitute a group with favorable outcomes after epilepsy surgery especially with early referral to surgery. Longer duration of epilepsy was associated with worse seizure outcome for DNET patients. There was significant correlation between radiological and histopathological types of DNET especially in type 1 and 3.

Osteosarcoma of the Ethmoid Sinus.

Osteosarcoma (OS) is a malignant bone tumor and it is very rare in head and neck region. If it arises in this area, most common localizations of this tumor are mandible and maxilla and ethmoid sinus is very rare site for this malignancy. A 43-year-old female admitted to our clinic with the complaint of pain in the right half of the face and headache persisting for 2 months. According to the clinical symptoms and imaging studies, sinonasal ossifying fibroma was suspected. For this reason, patient was operated endoscopically and histopathological examination revealed that osteoid matrix producing atypical osteoblastic cells so these findings identified osteoblastic variant OS. This article is about a very rare case of OS of ethmoid sinus. The differential diagnosis, general characteristics, and classification of this tumor, radiological features, and surgical techniques are also presented.

Antenatal Diagnosis of Fetal Retinoid Syndrome at 20 Weeks of Gestation: A Case Report.

INTRODUCTION: Isotretinoin, a synthetic derivative of vitamin A, is one of the most potent human teratogens, and is mainly utilized for the treatment of severe recalcitrant nodular acne. Retinoic acid embryopathy is well defined in the literature. CASE REPORT: The mother was referred for a fetal posterior fossa abnormality, first detected at 20 weeks of gestation. The mother used isotretinoin until 18 weeks gestation. Ultrasound examination revealed hypertelorism, cerebellar hypoplasia, vermian agenesis, truncus arteriosus, anotia, thymic aplasia, corpus callosum hypoplasia. An intrauterine diagnosis of fetal retinoid syndrome was confirmed by fetopsy after termination of pregnancy. CONCLUSION: The typical findings of fetal retinoid syndrome can be visualized with ultrasound in early second trimester.

Clinicopathological Features of Three Rare EWSR1::NFATC2 Sarcomas of Bone and Soft Tissues.

Certain undifferentiated round cell sarcomas displaying EWSR1::NFATC2 fusion have recently been reported, mostly in the bones. This report presents clinicopathological features of 3 additional EWSR1::NFATC2 fusion sarcomas of bone and soft tissues. We present 2 soft tissue and 1 bone tumors: A 62-year-old man with pain and a slowly growing, 8-cm-sized soft tissue mass in the anterolateral compartment of his right calf, along with multiple pulmonary metastatic lesions; a 63-year-old man with a 5-cm sized axillary mass of 4 months duration and a cystic renal mass; and a 53-year-old man with a complaint of leg pain was found to have a 2-cm diameter, intramedullary, lytic mass in the diaphysis of his left femur. Microscopic examination of the tumors in all patients revealed round to epithelioid cells arranged in cords and trabeculae in a myxohyaline stroma. Immunohistochemically, the tumor cells were positive for MIC2/CD99 (3/3), EMA (3/3), NKX3.1 (3/3), NKX2.2 (2/2), CD10 (2/2), and aggrecan (1/1), while negative for S100P and GFAP. Various keratins were also negative except focal AE1/AE3 positivity in the third tumor. By fluorescence in-situ hybridization, 2 tumors (#1 and #3) revealed EWSR1 gene rearrangement and amplification. Furthermore, 2 tumors (#1 and #2) displayed EWSR1ex8::NFATC2ex3 fusion with next-generation sequencing (NGS). The first patient was offered chemotherapy. However, he died of pulmonary metastasis. This report highlights the value of combining histopathological features and immunostains such as NXK3.1, NKX2.2, CD10, and aggrecan, along with EWSR1 testing for triaging these tumors for rare gene fusions by NGS that has prognostic implications.

Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury.

This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO) levels and neuroprotection, in rats with experimentally induced traumatic brain injury (TBI). Forty Wistar albino rats were categorized into four groups: sham operated (S), trauma (T), trauma + vehicle (T + V) and trauma + simvastatin (T + S). The T, T + V and T + S groups were subjected to TBI. The T + V group was administered vehicle [ethanol:saline (1/2)] and the T + S group was administered 1 mg/kg of simvastatin 3 h after the injury insult. Blood and brain tissue specimens were obtained 24 h after the trauma to measure VEGFs and NO levels and perform histopathological examinations. The histopathological injury scores of brain tissues were significantly higher in the T group, and simvastatin significantly prevented brain injury in the T + S group. In the T group, significant increases of VEGF levels in serum and brain tissues were noted, which were prevented with simvastatin treatment in the T + S group. The markedly high levels of NO in brain tissues of the T group were decreased by simvastatin treatment in the T + S group. It can be concluded that, as evidenced by histopathological findings, simvastatin treatment improves neuropathology in acute stages of TBI.