Concomitant Use of Sulforaphane Enhances Antitumor Efficacy of Sunitinib in Renal Cell Carcinoma In Vitro.

Chronic treatment of renal cell carcinoma (RCC) with the tyrosine kinase inhibitor sunitinib (ST) inevitably induces resistance and tumor re-activation. This study investigated whether adding the natural compound sulforaphane (SFN) with its anti-cancer properties could improve ST efficacy in vitro. The RCC cell lines A498, Caki1, KTCTL26, and 786O were exposed to ST, SFN, or both (dual therapy, DT) before (short-term exposure) and during ST-resistance buildup (long-term 8-week exposure). Tumor growth, proliferation, and clone formation were evaluated, as was cell cycle progression and cell cycle regulating proteins. In nonresistant cells (short-term), DT induced a higher reduction in cell viability in three cell lines as compared to monotherapy with either ST or SFN. Long-term SFN or DT significantly reduced tumor growth and proliferation, whereas ST alone had no effect or even elevated proliferation in three cell lines. SFN or DT (but not ST alone) also blocked clonogenic growth. Both long-term SFN and DT enhanced the number of cells in the S- and/or G2/M-phase. Protein analysis in 786O cells revealed a down-regulation of cyclin dependent kinase (CDK) 1 and 2. CDK2 or Cyclin A knockdown caused reduced 786O growth activity. SFN therefore inhibits or delays resistance to chronic ST treatment.

Current Use of Intraoperative Neurophysiology in Neurosurgery: Supratentorial Part 1.

The general aim of the neurosurgical practice is to both anatomically and physiologically preserve functional neurological structures to ensure a higher quality of life. Intraoperative neuromonitorization (IONM) helps the neurosurgeon physiologically identify and assess the functional integrity of said neurological structures. The uses of IONM in neurosurgery practice are categorized into three areas; brain (supratentorial and infratentorial), brain stem, and spinal. For every anatomical region and surgical procedure, characteristic differences in electrophysiological methods exist for both recording and interpretation. In this first three-part paper, electrophysiological methods used in supratentorial surgeries for tumor, vascular, and epilepsy pathologies and their key points will be reviewed in detail. The second part uses infratentorial and brain stem surgeries; in the third part, uses in spinal surgery will be detailed.

Health-related Quality of Life Assessment in Patients with Malignant Gliomas.

BACKGROUND: High-grade gliomas have limited time of survival despite aggressive treatment. Patients experience a decline in their physical and mental capacities, affecting their quality of life (QoL), and require proper therapeutic strategies. OBJECTIVE: To assess the QoL of malignant glioma patients before and after the treatment in a longitudinal study of six months. METHODS AND MATERIAL: Forty-nine patients who were pathologically diagnosed with glioblastoma and anaplastic glioma according to WHO 2016 were included in this prospective study. The assessment of quality of life was done using the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QoL) questionnaire core-30 prior to surgery, 1 and 5 months after the operation. RESULTS: The decline in Karnofsky scores of the patients was statistically significant. Among the symptom scales, fatigue was more prominent after surgery while pain was noticeable during chemotherapy which was correlated with increased age. The mean overall QoL scores showed a clinically significant decline during the postoperative period. The functional scores demonstrated a significant decline in between all periods. Sex was significantly correlated with preoperative emotional and physical functioning. The patients with right-sided lesions had higher mean scores for social and cognitive functioning. CONCLUSIONS: Low KPS, older age, and female gender may affect cancer symptoms and physical and social activities in malignant glioma patients. Cognitive functions as well as social and occupational roles gradually decline during the first six months of treatments. Overall QoL of high-grade glioma patients deteriorates especially after radiotherapy and during the first months of chemotherapy.

Intraoperative Neuromonitoring in Surgery of Cauda Equina and Conus Medullaris Tumors.

AIM: To demonstrate the value of special intraoperative neuromonitoring techniques for cauda equina and conus medullaris tumors (CECMT) by describing standard methods used at our center. MATERIAL AND METHODS: Neurophysiological records were retrospectively reviewed for 16 patients (eight females and eight males; age range: 27â€"60 years) who underwent surgery for CECMT at our department between 2016 and 2018. RESULTS: Motor and/or sensorial deficits were preoperatively identified in 10 patients; no patients had bladder or sexual dysfunction. Motor evoked potential (MEP) loss occurred in seven patients with full or partial recovery. No changes were seen in pudendal somatosensory evoked potential (SEP) or bulbocavernosus reflex (BCR), and morphological deterioration and amplitude loss of tibial SEPs were present in four patients. Postoperatively, no new neurological deficits and/or bladder and sexual dysfunction were present. CONCLUSION: Pudendal SEP and BCR are useful tests for monitoring CECMT surgeries. BCR is an easily obtainable modality for preserving sacral functions and recommended as a primary monitoring modality in conjunction with traditional neurophysiological techniques during CECMT surgery.

The Impact of Affective State on Quality of Life in Focal Epilepsy in Turkey.

CONTEXT: Seizures and accompanying situations including social, medical, and psychiatric problems threaten the quality of life (QOL) in patients with epilepsy. The World Health Organization defines health is a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity. AIMS: This study examines the prevalence of both depression and anxiety symptoms and also impact of the affective state on QOL in patients with focal epilepsy in Turkey. SETTINGS AND DESIGN: One hundred and five patients with focal epilepsy over 18 years old were included in this study. The patients were classified into four groups according to the presence of AS and seizure control. SUBJECTS AND METHODS: Patients' affective symptoms (AS) and QOL were examined using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and QOL in Epilepsy Inventory-31 (QOLIE-31). STATISTICAL ANALYSIS USED: We used descriptive statistics, Chi-square test, independent samples t-test, one-way analysis of variance, Mann-Whitney U-test, Kruskal-Wallis H-test, and also Pearson's and Spearman's correlation test for correlations. RESULTS: There were positive correlations between total QOLIE-31 score and epilepsy surgery, employment, and seizure freedom, whereas negative correlations were found with antiepileptic drug use, anxiety, and depression. Statistically significant differences were found in QOLIE-31 totals and subscores between Groups 3 and 4 (P < 0.05). CONCLUSIONS: The presence of AS has a negative impact on QOL in patients with focal epilepsy. Physicians should be aware that psychiatric comorbidities in epilepsy have a severe impact and epilepsy treatment requires comprehensive management.

Multimodal Intraoperative Neurophysiological Monitoring in Neurosurgical Oncology.

AIM: Neurosurgical oncology that is performed for lesions located in critical areas like the sensorimotor area has additional risk because it may cause serious neurological deficiencies. Some intraoperative neuromonitoring (IONM) modalities can effectively help the surgeons to maximize resections of this kind of lesions with or without an acceptable neurological deficiency. Our aim was to share our IONM experiences with patients who underwent intracranial lesion surgery in critical areas between September 2013 and January 2015. MATERIAL AND METHODS: This retrospective study was performed on 31 patients who underwent brain surgery for the resection of lesions located in eloquent areas. Demographic characteristics, lesion localizations, lesion pathologies, surgery, IONM recordings, and pre- and postoperative neurological examinations were reviewed. RESULTS: Five of the 31 patients had lesions in the cerebellopontine angle and 26 patients had lesions close to critical locations. Transcranial motor evoked potentials and somatosensory evoked potentials were performed in 27, electroencephalography in 31, auditory evoked potentials in 8, visual evoked potentials in 2, triggered electromyography in 8, and central sulcus determination and brain mapping in 17 patients. Motor evoked potential changes occurred in 2 patients intraoperatively. One had right hemiparesia lasting 3 days while the other had monoparesia which improved within 2 months. Permanent neurological deficit was not observed. CONCLUSION: Intraoperative neuromonitoring helps the surgeons to maximize resection of lesions in or close to eloquent areas of the brain. Using only one modality is not sufficient, whereas a combination of modalities is required to obtain a better outcome.

Multimodal Intraoperative Neurophysiological Monitoring in Spinal Cord Surgery.

AIM: Intraoperative neurophysiological monitoring (IONM) monitors the functional integrity of critical neural structures by electrophysiological methods during surgery. Multimodality combines different neurophysiological methods to maximize diagnostic efficacy and provide a safety margin to improve the outcomes of spinal surgery. Our aim was to share our intraoperative monitoring experiences with patients who underwent surgery because of spinal cord pathologies between September 2013 and January 2015. MATERIAL AND METHODS: We had twenty-six cases. Location of the lesions, surgery, neurological findings, and electrophysiological findings intraoperatively and postoperatively were documented. RESULTS: The combination of motor evoked potential (MEP), somatosensorial evoked potential (SSEP), free-run and trigger electromyography (EMG) were performed according to lesion localization. MEPs plus SSEPs were run in 23 patients and MEPs with triggered EMG were performed in 4 patients. In only one patient, optimal recording could not be elicited because of technical problems. MEP and SSEP changes were recorded in 12 and 3 patients respectively. Postoperative neurological deficits were observed in 2 patients. Deficits were transient in one case and permanent in the other. While baseline MEP responses were either absent or low amplitude ( < 50 microvolt) in 7 patients, following resection they were either visible or increased in amplitude. Surgery was ended in one patient with C7-T2 intramedullary tumour after the right distal MEP response disappeared. CONCLUSION: Multimodal IONM is an important method to monitor the neural structures under risk in spine surgery and to keep the surgery within safety limits, especially for intramedullary spinal cord lesion surgery.

Ictal kissing: Electroclinical features of an unusual ictal phenomenon.

PURPOSE: The study aimed to describe the electroclinical features of ictal kissing, an unusual behavior that may occur during focal seizures. METHOD: Twenty-five patients collected from four epilepsy centers and previously published reports were reviewed for their demographic, clinical, and electrophysiological features. RESULTS: Sixteen of 25 patients were female. The mean age was 32.9 years (9.9-51 years) and the average age at seizure onset was 14.5 years. All seizures were localized to the temporal lobe (TL) and lateralized to right side in 17 patients, left side in 2 patients, and unclear in 6 patients. A total of 55 ictal video electroencephalograms (EEGs) were analyzed. There were other symptoms such as speaking, spitting, hugging, and oral and upper-extremity automatisms along with different types of ictal kissing behavior during the seizures. The median duration of all seizures was 106.7±73.73s. Kissing occurred at a median time of 71s (1-95s) after the onset of seizure, and ictal epileptiform discharges usually involved TL during kissing episode. CONCLUSION: Ictal kissing is mainly associated with right TL and female gender, although association with left TL may also occurs, possibly related to the circuits involving temporo-insular structures.

Ictal kissing behavior: neurological and psychodynamic overview.

This study is based on the psychodynamic and neurological analysis of three Turkish patients who displayed ictal kissing automatism during their seizures. To unveil the probable underlying causes of their kissing behaviors, all patients underwent psychiatric interviews after being evaluated by ictal video-EEG recordings. The group consisted of two females (ages 35 and 29) and one male (age 26). In addition to prominent oral automatisms, each patient also displayed behaviors of kissing or blowing kisses to individuals at close proximity. Seizures were related to the right temporal lobe in two patients and the left temporal lobe in one patient. Magnetic resonance imaging showed mesial temporal sclerosis in two of the patients (one left, one right) and was normal in one. According to the DSM-IV-TR criteria, each of the three patients also suffered from major depression, while the psychodynamic interviews revealed traumatic childhood histories and intense unfulfilled affective needs.

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia.

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.