Molecular Subgrouping Based on Immunohistochemistry in Medulloblastoma: a Single-Center Experience.

AIM: Medulloblastomas (MBs) are the most commonly observed malignant brain tumors affecting children; they can be classified into molecular subgroups based on the 2016 and 2021 WHO classifications, as WNT-activated, SHH-activated and TP53-wild type, SHH-activated and TP53-mutant, and non-WNT/non-SHH. However, the molecular methods to determine these subgroups are not easily accessible for routine testing as they are expensive. Here, we investigated the efficacy of immunohistochemical methods to determine molecular subgroups and prognostic predictions of MB. MATERIAL AND METHODS: ß-catenin, GAB1, YAP1, filamin A and p53 were immunohistochemically stained, and MYC and MYCN fluorescent in situ hybridization (FISH) procedures were applied to 218 cases in our series. RESULTS: Based on the histomorphological characteristics of the cases, 67.9% were deemed classic MB; 15.6% as desmoplastic/nodular medulloblastoma (DNMB); 12.8% as large cell/anaplastic (LC/A) MB; 3.7% as medulloblastoma with extensive nodularity (MBEN). Molecular characteristics revealed that 50.5% had non-WNT/non-SHH; 33.9% had SHH-activated and TP53-wildtype; 8.7% had WNT-activated; 6.9% had SHH-activated and TP53-mutant. According to the survival curves, LC/A MBs or non-WNT/non-SHH tumors showed the worst prognosis, whereas DNMBs and WNT-activated tumors showed the best prognosis. Classic MBs or SHH-activated tumors showed a moderate course. MYCN amplification was found to act as an independent poor prognostic factor in the study. CONCLUSION: The distribution of histological subtypes and molecular subgroups, amplification rates, and prognostic data obtained through immunohistochemical methods in our study were consistent with those reported in the literature. It was therefore hypothesized that the determination of molecular subgroups by immunohistochemical methods can be useful in daily diagnostic practice, especially in centers with limited access to molecular techniques.

Ictal Coprolalia: Three Cases with Nondominat Frontal Lobe Involvement and Review of the Literature.

Objective: Coprolalia is defined as the involuntary use of obscene, socially unacceptable, and derogatory words. Ictal coprolalia is a rare presentation of epilepsy. This study aimed to determine the localizing and lateralizing value and frequency of ictal coprolalia in epilepsy patients. Methods: Medical files, discharge summaries, and electroencephalography (EEG) reports of 2238 patients were reviewed retrospectively. We identified patients who suffered from ictal coprolalia. Electroencephalography reports, neuroimaging [brain magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), single-photon emission computerized tomography (SPECT)] records, F-18 FDG fused on MRI images, and ictal SPECT fused on MRI images were evaluated. Also, original and review articles were identified through a systematic search of Pubmed, Scopus, and Clarivate Analytics. Results: Ictal coprolalia was detected in 3 male (0.15%) patients. In all patients, ictal semiology was extratemporal-frontal type, and potential/proven epileptic focus was non-dominant hemisphere frontal lobe. Topectomy was done in one of the patients, including the suspected dysplastic area plus the area where the electroencephalographic ictal and interictal changes occur, on the left frontal lobe, and the patient had an Engel's classification class IIA. The data depending on the published cases showed that ictal coprolalia was dominant in the male gender and the responsible epileptic area tended to be located in the non-dominant hemisphere frontotemporal region. Conclusion: The rate of ictal coprolalia in the Turkish population is lower compared to other series. Our results are consistent with previous studies in which reported that male preponderance for ictal coprolalia and involvement of non-dominant frontal lobe.

Extracellular-Vesicle-Based Cancer Panels Diagnose Glioblastomas with High Sensitivity and Specificity.

Glioblastoma is one of the most devastating neoplasms of the central nervous system. This study focused on the development of serum extracellular vesicle (EV)-based glioblastoma tumor marker panels that can be used in a clinic to diagnose glioblastomas and to monitor tumor burden, progression, and regression in response to treatment. RNA sequencing studies were performed using RNA isolated from serum EVs from both patients (n = 85) and control donors (n = 31). RNA sequencing results for preoperative glioblastoma EVs compared to control EVs revealed 569 differentially expressed genes (DEGs, 2XFC, FDR < 0.05). By using these DEGs, we developed serum-EV-based biomarker panels for the following glioblastomas: wild-type IDH1 (96% sensitivity/80% specificity), MGMT promoter methylation (91% sensitivity/73% specificity), p53 gene mutation (100% sensitivity/89% specificity), and TERT promoter mutation (89% sensitivity/100% specificity). This is the first study showing that serum-EV-based biomarker panels can be used to diagnose glioblastomas with a high sensitivity and specificity.

Rhombencephalitis and longitudinal extensive myelitis associated with dinutuximab use in high-risk neuroblastoma.

BACKGROUND: Dinutuximab is a monoclonal antibody that targets the GD2 antigen used in the treatment of high-risk neuroblastoma. Dinutuximab-associated rhombencephalitis and myelitis is a rare, steroid-responsive, serious, but reversible pathology. To date, three transverse myelitis cases and one rhombencephalitis case due to dinutuximab have already been reported. Moreover, a recently published article identified five inflammatory CNS demyelination cases (four myelitis and one rhombencephalitis). We present a 5-year-old patient with rhombencephalitis and myelitis following dinutuximab-beta treatment. CASE: A 5-year-old patient with a left-sided retroperitoneal mass infiltrating the left kidney and multiple lytic bone lesions was diagnosed with neuroblastoma with a percutaneous biopsy from the abdominal mass. Surgery was performed after a prominent treatment response was detected on the abdominal CT. Radiotherapy was applied to the abdomen. While she was still undergoing maintenance treatment with 13-cis retinoic acid, a metaiodobenzylguanidine (MIBG) scan detected new bone lesions, and brain MRG identified pachymeningeal involvement. A new chemotherapy regimen was started and decreased MIBG uptake was seen in all previous bone lesions. However, newly developed eighth rib metastasis was seen in the following MIBG scan. Autologous stem cell transplantation was done. Soon after, dinutuximab-beta, together with temozolomide and irinotecan, was initiated. Following the third cycle hypotension, somnolence, paraparesis, and unilateral fixed dilated pupil were developed. Afterward, hemiballismus-like irregular limb movements were observed. Work-up studies were unremarkable, except for hypodensity in the brain stem on the brain CT. MRI revealed T2 hyperintensity of the brainstem and spinal cord extending from the cervicomedullary junction to the T7 level. Moreover, incomplete contrast enhancement and facilitated diffusion were observed. Imaging findings suggested demyelination. Steroids and intravenous immune globulin (IVIG) treatment were initiated. Both imaging abnormalities and clinical symptoms resolved partially at one month and disappeared at six months. CONCLUSIONS: Awareness of the radiological findings of dinutuximab toxicity will lead to prompt diagnosis and treatment.

Imaging Cancer in Neuroradiology.

Neuroimaging plays a pivotal role in the diagnosis, management, and prognostication of brain tumors. Recently, the World Health Organization published the fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS5), which places greater emphasis on tumor genetics and molecular markers to complement the existing histological and immunohistochemical approaches. Recent advances in computational power allowed modern neuro-oncological imaging to move from a strictly morphology-based discipline to advanced neuroimaging techniques with quantifiable tissue characteristics such as tumor cellularity, microstructural organization, hemodynamic, functional, and metabolic features, providing more precise tumor diagnosis and management. The aim of this review is to highlight the key imaging features of the recently published CNS5, outlining the current imaging standards and summarizing the latest advances in neuro-oncological imaging techniques and their role in complementing traditional brain tumor imaging and management.

SMART syndrome: a case report.

INTRODUCTION: Stroke-like migraine attacks after radiation therapy (SMART) syndrome, is a late complication of brain radiotherapy (1). Symptoms are commonly subacute in onset and involve migraine type of headache, seizures, focal neurologic deficits (2). Magnetic resonance imaging (MRI) findings are usually unilateral and posterior predominant cortical-subcortical hyperintensity, swelling and prominent gyriform (cortical and leptomeningeal) gadolinium enhancement in the areas of the brain that underwent irradiation with or without diffusion restriction (1). There is no standard treatment protocol for SMART syndrome. Antiepileptics and corticosteroids are commonly used drugs. CASE REPORT: A 65 years old woman was diagnosed with breast cancer with brain metastases and treated with more than 50 Gy brain radiotherapy. The patient presented with acute right-sided weakness and numbness, episodic myoclonic jerking of the right arm and leg, and gait instability five months later. MRI and magnetic resonance angiography of the brain with gadolinium revealed left parietooccipital cortical diffusion restriction and accompanying dilatation of the left posterior cerebral artery as new findings. Computed tomography (CT) perfusion revealed increased perfusion in the affected area. The patient was diagnosed with SMART syndrome. MANAGEMENT AND OUTCOME: The patient was treated with dexamethasone (16 mg/day) and anticonvulsant therapy. Myoclonic seizures had almost completely remitted. However, her cognitive impairment persisted, then the patient was arrested because of aspiration a month later. DISCUSSION: Besides confirming SMART syndrome, diagnostic investigations are also important to exclude other etiologies. Posterior reversible encephalopathy syndrome, post-ictal changes, meningoencephalitis, and cerebrovascular diseases are radiological differential diagnoses considered (3). Proper and early diagnosis of SMART syndrome is significant in preventing unnecessary aggressive approaches and appropriate treatment to avoid lesions of sequela.

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.

Lesional resective epilepsy surgery in childhood: Comparison of two decades and long-term seizure outcome from a single center.

OBJECTIVE: Epilepsy surgery has shown efficacy in children. We aimed to assess long-term seizure outcome in children who underwent epilepsy surgery and determine predictive factors for seizure freedom. METHODS: This is a retrospective study of 196 children who underwent epilepsy surgery between 1994 and 2015 and had a minimum postoperative follow-up of 5 years. RESULTS: The median age at the time of surgery was 9.5 (0.08-19.8) years; 110 (56.1%) had temporal, 62 (31.6%) had extratemporal resections, and 24 (12.2%) had hemispheric surgery. The duration of postsurgical follow-up was between 5 and 20 years (mean±SD: 7 ± 3.2). Overall, 129 of 196 (65.8%) patients had Engel class I outcome at final visit. Among patients who underwent temporal, extratemporal and hemispheric surgery; 84 of 110 (76.4%), 34 of 62 (54.8%), and 11 of 24 (45.8%) patients had complete seizure freedom, respectively (p: 0.016). Patients with tumors had the best outcome, with 83.1% seizure freedom. The number of preoperative antiseizure medications (OR 3.19, 95% CI 1.07-9.48), the absence of postoperative focal epileptiform discharges (OR 8.98, 95% CI 4.07-19.79) were independent predictors of seizure freedom. Across two decades, the age at surgery was decreased (p: 0.003), overall seizure freedom (61.8% vs 68%) did not differ. In the past decade, a higher proportion of malformations of cortical development was operated (14.7% vs 35.9%, p: 0.007). SIGNIFICANCE: Our findings showed favorable long-term seizure outcome in children who underwent epilepsy surgery. The results are encouraging for developing centers with limited resources to establish pediatric epilepsy programs.

Deep White Matter Lesions with Persistent Diffusion Restriction on MRI as a Diagnostic Clue: Neuroimaging of a Turkish Family with Hereditary Diffuse Leukoencephalopathy with Spheroids and Literature Review.

BACKGROUND: Hereditary diffuse leukoencephalopathy with spheroids (HDLS), first described in 1984 is a rare disorder. Generally, it presents at adulthood with dementia, motor impairment, extrapyramidal abnormalities, and epilepsy. Definitive diagnosis is made by brain biopsy. Neuroimaging studies have revealed confluent white matter lesions predominantly in the frontal lobes, corpus callosum, and corticospinal tracts on conventional magnetic resonance imaging. Only a few reports showed diffusion restriction in the cerebral white matter; furthermore, rarer reports emphasized persistent foci of diffusion restriction as a diagnostic imaging marker. OBJECTIVE: Herein, we have aimed to illustrate the first biopsy-proven Turkish HDLS pedigree consisting of 18 persons in 3 generations which contained 4 affected individuals. MATERIALS AND METHODS: Four individuals in the pedigree of HDLS [two affected patients (patient III-1 and patient III-2) and two unaffected individuals (patient II-4 and patient III-5)] were investigated with conventional MRI and Diffusion-weighted imaging (DWI) using 1.5 Tesla (T) scanner. All four individuals were evaluated via neurological examinations and Mini-Mental State Examination. Brain biopsy study was performed on patient III-2. Finally, an extensive literature review involving pathology investigations and neuroimaging studies of HDLS patients was conducted. RESULTS: DWIs of two investigated patients showed deep white matter lesions with persistent diffusion restriction. Computed tomography imaging showed punctate mineralization in the lesions. Biopsy specimens of patient III-2 demonstrated axonal spheroids which were typical for HDLS. CONCLUSIONS: Via the presentation of our pedigree and literature review, we suggest HDSL as a first-line differential diagnosis in patients with undiagnosed adult-onset familial leukoencephalopathy, in particular, those with MRI lesions of frontal white matter and centrum semiovale associated with foci of diffusion restriction and mineralization. Finally, we think that the persistence of the diffusion restriction in deep white matter lesions should be kept in mind as a crucial neuroimaging sign for HDLS.

Prenatal diagnosis of central nervous system abnormalities: Neurosonography versus fetal magnetic resonance imaging.

OBJECTIVE: To share our experience in diagnosis of congenital central nervous system (CNS) abnormalities by fetal magnetic resonance imaging (MRI). STUDY DESIGN: This study consisted of 110 pregnancies. Neurosonography (NS) findings were compared with MRI results. Anomalies were categorized into 10 groups: 1) Corpus callosum (CC) and cavum septum pellucidum (CSP) anomalies, 2) Neural tube defects (NTD), 3) Posterior fossa anomalies (PFA), 4) Primary ventriculomegaly (PVM), 5) Microcephaly, 6) Macrocephaly, 7) Periventricular leukomalacia (PVL), 8) Craniosynostosis, 9) Intracranial hemorrhage (ICH) and 10) Lumbosacral teratoma. Demographic features, clinical characteristics and perinatal outcomes of the study subjects were evaluated. RESULTS: Gestational weeks for NS and for MRI were 25.5 and 26.5 weeks, respectively. Fourteen (12.7%) pregnancies were terminated. PVM (n = 36, 32.7%), CC and CSP anomalies (n = 29, 26.3%), PFA (n = 11, 10%) and NTD (n = 11, 10%) were the most common fetal MRI indications. There were no statistically significant differences between the accuracy of fetal NS and fetal MRI for CC and CSP anomalies, NTDs, PFA and PVM (p = 0.09, 0.43, 0.45 and 0.23, respectively). However, fetal MRI was more accurate for the detection of normal anatomic findings in cases with suspected microcephaly, macrocephaly and craniosynostosis in NS when pooled together (p = 0.007). Furthermore, MRI also seemed to be advantageous in CC & CSP anomalies though it was not validated by statistical measures. No statistically significant difference was found for diagnostic performance of NS and MRI according to gestational week (p = 0.27). CONCLUSION: Fetal MRI in addition to NS may improve diagnostic accuracy in pregnancies with congenital CNS abnormalities.

Clinical Characteristics, Management, and Treatment Outcomes of Primary Hypophysitis: A Monocentric Cohort.

Primary hypophysitis (PH) is a rare autoimmune inflammatory disease of the pituitary gland. The aim of the study was to evaluate clinical characteristics, disease management, and outcomes of cases with PH. Medical records of PH patients admitted to Hacettepe University Hospital between 1999 and 2017 were analyzed retrospectively. Paraffin-embedded pathology blocks were obtained for both re-examination and IgG4 immunostaining. Twenty PH patients (15 females, 5 males) were evaluated. Mean age at diagnosis was 41.5±13.4 years. Some form of hormonal disorder was present in 63.2% of cases, hypogonadism (66.6%) being the most common. Panhypopituitarism was present in 36.8%. All patients had pituitary gland enlargement on magnetic resonance imaging; stalk thickening and loss of neurohypophyseal bright spot were present in 17.6 and 23.5%, respectively. Lymphocytic hypophysitis was the most common histopathological subtype (50%). Among pathology specimens available for IgG and IgG4 immunostaining (n=10), none fulfilled the criteria for IgG4-related hypophysitis. Four patients were given glucocorticoid treatment in diverse protocols; as initial therapy in 3. Sixteen cases underwent surgery, 7 of whom due to neuro-ophthalmologic involvement. Only 1 patient was observed without any intervention. Reduction of pituitary enlargement was seen in all surgical and glucocorticoid treated cases. None of the surgical patients showed hormonal improvement while one case in glucocorticoid group improved. PH should be considered in the differential diagnosis of sellar masses causing hormonal deficiencies. MRI findings are usually helpful, but not yet sufficient for definitive diagnosis of PH. Treatment usually improves symptoms and reduces sellar masses while hormonal recovery is less common.

Validated imaging biomarkers as decision-making tools in clinical trials and routine practice: current status and recommendations from the EIBALL* subcommittee of the European Society of Radiology (ESR).

Observer-driven pattern recognition is the standard for interpretation of medical images. To achieve global parity in interpretation, semi-quantitative scoring systems have been developed based on observer assessments; these are widely used in scoring coronary artery disease, the arthritides and neurological conditions and for indicating the likelihood of malignancy. However, in an era of machine learning and artificial intelligence, it is increasingly desirable that we extract quantitative biomarkers from medical images that inform on disease detection, characterisation, monitoring and assessment of response to treatment. Quantitation has the potential to provide objective decision-support tools in the management pathway of patients. Despite this, the quantitative potential of imaging remains under-exploited because of variability of the measurement, lack of harmonised systems for data acquisition and analysis, and crucially, a paucity of evidence on how such quantitation potentially affects clinical decision-making and patient outcome. This article reviews the current evidence for the use of semi-quantitative and quantitative biomarkers in clinical settings at various stages of the disease pathway including diagnosis, staging and prognosis, as well as predicting and detecting treatment response. It critically appraises current practice and sets out recommendations for using imaging objectively to drive patient management decisions.

The Anatomy of the Sigmoid-Transverse Junction According to the Tentorial Angle.

Dural sinuses have critical importance during intracranial approaches. Detailed anatomical knowledge of the dural sinuses is crucial for surgeons to reduce unexpected venous bleeding. The aim of this study was to investigate anatomical relation of sigmoid sinus and tentorium cerebelli according to clinically palpable landmarks and cranial morphometry. The authors evaluated 222 individuals' (94 women, 128 men) 3-dimensional computed tomography angiograms, retrospectively. The authors also studied on 12 mid-sagittal cut dried hemiskulls and 8 formalin fixed cadaver heads hemisected midsagitally. All measurements were completed using Osirix-Lite version 9 software. Craniometrical values were measured to define cranium morphology. Furthermore, level of the sigmoid sinus according to asterion and tentorial angle were evaluated in detail. Our results demonstrated that there were significant differences between parameters and genders, except vertical angle of the tentorium cerebelli. Distance between asterion and sigmoid sinus was statistically different between right and left sides in favor of the left side. This also varied depending on the position of the sigmoid sinus, as well. Only transverse angle between the upper point of external acoustic meatus and asterion demonstrated a significant correlation with age. This study evaluated the detailed 3D anatomy of sigmoid sinus and tentorium cerebelli related with the cranium morphology. Determining to sigmoid sinus anatomy according to clinically palpable landmarks has advantages for setting surgical protocols and reducing to unexpected injuries while surgery to these structures.

A case of Woodhouse-Sakati syndrome with pituitary iron deposition, cardiac and intestinal anomalies, with a novel mutation in DCAF17.

Woodhouse-Sakati syndrome is a rare genetic syndrome caused by homozygous mutations of the DCAF17 gene. Several endocrine organs may be affected in the course of the disease. We present a new case with pituitary iron deposition, cardiac and intestinal anomalies, with a novel mutation in DCAF17 gene. An 18-year-old female was admitted because of delayed puberty and amenorrhea. Hormonal evaluation revealed combined hyper-hypogonadotropic hypogonadism. GH and IGF-1 levels were low without short stature. ACTH levels were high and cortisol levels were supranormal with the lack of clinical findings of cortisol excess or deficiency. Pituitary MRI indicated paramagnetic substance deposition in gland. On follow-ups, non-autoimmune, insulinopenic diabetes mellitus and secondary hypothyroidism emerged. Woodhouse-Sakati syndrome was diagnosed on the basis of consistent clinical context and subsequently a novel mutation in DCAF17 was detected.

Deficiency of adenosine deaminase 2; special focus on central nervous system imaging.

PURPOSE: To increase the knowledge of central nervous system (CNS) imaging features in deficiency of adenosine deaminase 2 (DADA2) by examining magnetic resonance imaging (MRI) studies of a relatively large number of patients. METHODS: We retrospectively examined neuroimages of 12 patients (7 male, 5 female) diagnosed with DADA2. The mean age of the patients at the time of initial brain MRI was 16.7±10.2 years. Seven patients (58.3%) fulfilled the classification criteria of polyarteritis nodosa. Brain MRI studies were assessed with respect to findings of ischemia, intracranial hemorrhages, focal parenchymal signal abnormalities, cerebral/cerebellar volume loss, and abnormal contrast enhancement. Angiographic studies of 7 patients were evaluated for the signs of vasculitis. RESULTS: The most frequent finding was acute and/or chronic lacunar ischemic lesions in the brainstem and/or deep gray matter (n=9, 75%). Six patients (50%) revealed MRI findings compatible with recurrent ischemic attacks. Small nodular contrast enhancement (n=2, 16.6%), acute putaminal hemorrhage (n=1, 8.3%) and findings compatible with posterior reversible encephalopathy syndrome (n=1, 8.3%) were also detected. Slight-to-moderate diffuse cerebral and/or cerebellar volume loss (n=7, 58.3%), decreased T1 signal of the bone marrow (n=6, 50%) and optic atrophy (n=1, 8.3%) were the other findings on brain MRI. The only abnormal angiographic finding was reduced caliber of the right distal posterior cerebral artery in MRA of a patient (14.6%). CONCLUSION: DADA2 should be included in the differential diagnosis of young patients presenting with ischemic and/or hemorrhagic lesions located in the brainstem and deep gray matter, especially if they have a family history or additional systemic abnormalities.

Ewing sarcoma in an infant and review of the literature.

Bedük Esen ÇS, Gültekin M, Aydin GB, Akyüz C, Karli Oguz K, Orhan D, Cengiz M, Gürkaynak M, Yildiz F. Ewing sarcoma in an infant and review of the literature. Turk J Pediatr 2019; 61: 760-764. Ewing sarcoma (ES) is a rare tumor in infants and prognosis is controversial. There are no standard recommendations for treatment in such very young patients. Generally, radiotherapy (RT) is not a part of treatment in infants due to the risk of severe late side effects. In this case report, we report a 7-month-old boy with diagnosis of left mastoid bone ES with lung metastases at diagnosis, showing a rapidly fatal outcome despite aggressive systemic chemotherapy and RT without surgery.

A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles.

New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500µM freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment.

The Added Value of Diffusion Magnetic Resonance Imaging in the Diagnosis and Posttreatment Evaluation of Skull Base Chordomas.

Objectives To determine the use of diffusion-weighted imaging (DWI) in the pre- and posttreatment evaluation of skull base chordomas. Design Retrospective study. Setting Tertiary care university hospital. Participants In total, 17 patients with histopathological diagnosis of chordoma who had magnetic resonance (MR) imaging and DWI were evaluated. Of them, 13 patients had posttreatment MR imaging including DWI. Main Outcome Measures Three apparent diffusion coefficient (ADC) values were obtained from tumor, and an ADC value was measured from pons for the purpose of normalization. ADC values of the subtypes of chordomas (typical and chondroid chordomas) were compared. Results Ten (59%) masses had increased signal on trace DWI at pretreatment evaluation. The mean ADC entire tumor /ADC pons was calculated as 1.55 ± 0.44. The mean ADC entire tumor values of typical and chondroid chordomas were 1.26 ± 0.29 × 10 -3 mm 2 /s and 0.99 ± 0.46 × 10 -3 mm 2 /s, respectively. There was no statistically significant difference between ADC values of the subtypes ( p > 0.05). For posttreatment evaluation, DWI enabled detection of residual tumor in the majority (85%) of cases. Conclusions DWI is useful in diagnosis and posttreatment evaluation of skull base chordomas. However, ADC values in our series did not distinguish the subtypes of chordomas.

Effects of curcumin-loaded PLGA nanoparticles on the RG2 rat glioma model.

BACKGROUND: Curcumin, the active ingredient of turmeric, has a remarkable antitumor activity against various cancers, including glioblastoma. However, it has poor absorption and low bioavailability; thus, to cross the blood-brain barrier and reach tumor tissue, it needs to be transferred to tumor site by special drug delivery systems, such as nanoparticles. OBJECTIVE: We aimed to evaluate the antitumor activity of curcumin on glioblastoma tissue in the rat glioma-2 (RG2) tumor model when it is loaded on poly(lactic-co-glycolic acid)-1,2-distearoyl-glycerol-3-phospho-ethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt (PLGA-DSPE-PEG) hybrid nanoparticles. METHODS: Glioblastoma was induced in 42 adult female Wistar rats (250-300g) by RG2 tumor model. The curcumin-loaded nanoparticles were injected by intravenous (n=6) or intratumoral route (n=6). There were five control groups, each containing six rats. First control group was not applied any treatment. The remaining four control groups were given empty nanoparticles or curcumin alone by intravenous or intratumoral route, respectively. The change in tumor volume was assessed by magnetic resonance imaging and histopathology before and 5days after drug injections. RESULTS: Tumor size decreased significantly after 5days of intratumoral injection of curcumin-loaded nanoparticle (from 66.6±44.6 to 34.9±21.7mm3, p=0.028), whereas it significantly increased in nontreated control group (from 33.9±21.3 to 123.7±41.1mm3, p=0.036) and did not significantly change in other groups (p>0.05 for all). CONCLUSION: In this in vivo experimental model, intratumoral administration of curcumin-loaded PLGA-DSPE-PEG hybrid nanoparticles was effective against glioblastoma. Curcumine-loaded nanoparticles may have potential application in chemotherapy of glioblastoma.

Childhood hereditary ataxias: experience from a tertiary referral university hospital in Turkey.

Hereditary ataxias are a group of genetic disorders that are progressive and heterogeneous. The purpose of this study was to develop a practical and time-efficient approach to diagnosing childhood hereditary ataxias by analyzing characteristics and final diagnosis at a tertiary referral clinic for pediatric neurology. 196 patients admitted to the pediatric neurology department were included. The medical records were examined for demographic features, neurological, laboratory, electrophysiological, cranial imaging, and pathological findings, and for genetic studies. Patients were divided into two groups based on whether a final diagnosis was made. The undiagnosed and diagnosed groups consisted of 157 (81.1%) and 39 (19.9%) patients, respectively. The two groups differed in terms of levels of history of consanguineous marriage and mental and motor development before diagnosis, absence of deep tendon reflexes, and the presence of polyneuropathic changes detected by electromyelography (EMG), abnormal visual evoked potentials (VEPs), electroretinography (ERG), and muscle biopsy. To the best of our knowledge, this is the first study involving a large spectrum of diseases related to autosomal recessive ataxias in childhood in Turkey. One out of five patients with hereditary childhood ataxias can be diagnosed with clinical and laboratory and electrodiagnostic examination, especially with the help of imaging facilities, while genetic analysis is not possible for every child. Cranial magnetic resonance imaging followed by EMG provides the most important clues for the diagnosis of hereditary childhood ataxias.