Benign paroxysmal torticollis of infancy: An underdiagnosed condition

Benign paroxysmal torticollis is probably an under‐diagnosed condition of infancy. It is a self‐limiting disorder characterised by periods of unusual, sustained posture of the head and neck, during which the head tilts to one side. Episodes are often accompanied by marked autonomic features, irritability, ataxia, apathy and drowsiness. They last several hours to a few days and are often recurring every few weeks. They subside within the pre‐school years; however, during later childhood, there is a tendency to develop migraine. Three cases of benign paroxysmal torticollis are presented and are compared with cases in the literature. A telephone survey has been conducted to determine what is the general awareness of paediatricians of this condition in Cyprus. Eighty‐two paediatricians were randomly selected out of 235 paediatricians. All of them agreed to participate. Our cases revealed that benign paroxysmal torticollis may coexist with other problems during infancy. The telephone survey showed that only two out of eighty‐two (2.4%) of the paediatricians are aware of the condition, and none of them was confident regarding the management. Our telephone survey clearly shows that Cypriot paediatricians are not familiar with benign paroxysmal torticollis in infancy which is a benign, self‐limiting disorder. It is essential to recognise the condition and to reassure parents of its benign course and not to be misdiagnosed for other disorders, such as epileptic seizures. We have shown again that benign paroxysmal torticollis in infancy may coexist with motor delay and hearing problems.     

Multiparametric MRI for early identification of therapeutic response in recurrent glioblastoma treated with immune checkpoint inhibitors

BackgroundPhysiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM.MethodsInclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), K^trans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria.ResultsOut of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, K^trans, Vp, and Ve were not indicative of treatment response within 6 months.ConclusionsIn patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment.Key Points• In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response.• Interval change in rADC can be used as an imaging biomarker to determine PFS6.• Interval change in MR perfusion and permeability measures do not suggest ICI treatment response.     

Stereotactic radiosurgery for CNS nongerminomatous germ cell tumors. Report of four cases

In this study, we evaluated the results in four patients with nongerminomatous germ cell tumors (NGGCT) of the pineal region. All underwent radiosurgery in conjunction with surgical resection, fractionated radiotherapy or chemotherapy. Four male patients with pineal region NGGCT were treated with radiosurgery. The mean age was 16.5 years. Three patients had histological confirmation by stereotactic biopsy or craniotomy prior to radiosurgery. One patient was diagnosed by serum and CSF tumor markers. The mean tumor volume was 10.5 cm(3). Radiosurgery was performed with mean maximum and marginal doses of 28 and 14 Gy, respectively. At last follow-up, three patients were alive and one was dead. The mean follow-up after diagnosis and after radiosurgery was 34 and 25 months, respectively. At last follow-up, two tumors had regressed, one was unchanged and one had progressed. No patient had complications after radiosurgery. Radiosurgery can play an important adjuvant role for NGGCT patients who also undergo multimodal management. In the case of prepubertal patients, radiosurgery may play an important role by reducing the radiation dose to the surrounding normal brain.     

Stereotactic radiosurgery for motor cortex region arteriovenous malformations

OBJECTIVE: The optimal management of arteriovenous malformations (AVMs) in critical brain locations remains controversial. To reduce the risk of an AVM hemorrhage and to enhance the possibility of preserving neurological function, stereotactic radiosurgery was performed in 33 patients with newly diagnosed or residual AVMs located within the motor cortex. The role of embolization also was examined. METHODS: During a 9-year study period, 33 patients with AVMs located primarily in the motor cortex region were treated with stereotactic radiosurgery. These patients were followed up radiographically for a minimum of 36 months, or less if obliteration was documented before 36 months had elapsed. Of the 33 patients, 9 underwent embolization and 1 underwent microsurgery before radiosurgery. Nine patients required a second radiosurgery. The mean AVM target volume was 4.35 cc, and the average radiation dose to the AVM margin was 20 Gy. The median follow-up was 36 months (range, 10-91 mo), and angiographic follow-up of eligible patients was performed 24 or 36 months after radiosurgery. RESULTS: Results were stratified by radiosurgical target volumes: less than 3 cc (Group 1), 3 to 10 cc (Group 2), and greater than 10 cc (Group 3). Overall (including second radiosurgery), 13 (87%) of 15 patients in Group 1 had complete obliteration confirmed by angiography. Nine (64%) of 14 patients in Group 2 exhibited nidus obliteration, and one (25%) of four patients in Group 3 demonstrated obliteration on a magnetic resonance imaging scan. Eight patients (24%) underwent second-stage radiosurgery after angiography revealed a persistent AVM nidus; three patients demonstrated complete obliteration on follow-up angiography. The obliteration rate was higher (87%) for AVMs with less than 3 cc target volume and lower (56%) for those with target volumes larger than 3 cc. One patient experienced worsening neurological function after radiosurgery, and one died from delayed AVM hemorrhage during the latency period. No patient bled after angiographically confirmed AVM obliteration. CONCLUSION: Stereotactic radiosurgery is a successful and safe management option for patients with motor cortex AVMs. The obliteration of AVMs and the attendant low morbidity rates indicate a primary role for radiosurgery in these patients. Staged radiosurgery may be necessary to increase obliteration rates for larger AVMs or for those that are not obliterated after the first procedure.     

Inhibition of DNA repair by a herpes simplex virus vector enhances the radiosensitivity of human glioblastoma cells

Expression of the herpes simplex virus (HSV) protein, ICP0, from the viral genome, rendered two radioresistant human glioblastoma multiforme cell lines more sensitive to the effects of ionizing radiation. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and clonogenic survival assays, U87-MG and T98 cell survival was more greatly decreased as a function of ionizing radiation dose when ICP0 was preexpressed in cells compared with when ICP0 was not expressed. Consistent with previous results, we found that the catalytic subunit of DNA-dependent protein kinase was degraded as a function of ICP0 in both cell types. This most likely resulted in the inhibition of DNA repair as inferred by the persistence of gammaH2AX foci or DNA double-strand breaks. Enhanced apoptosis was also found to occur following irradiation of U87-MG cells preinfected with the ICP0-producing HSV-1 mutant, d106. Our results suggest that expression of ICP0 in human glioblastoma multiforme cells inhibits the repair of DNA double-strand breaks after ionizing radiation treatment, decreasing the survival of these cells in part by induction of apoptosis.     

5-ALA and FDA approval for glioma surgery

Journal of Neuro-Oncology - Telomere length-associated SNPs have been associated with incidence and survival rates for malignant brain tumors such as glioma. Here, we study the influence of...     

Non-routine discharge disposition is associated with post-discharge complications and 30-day readmissions following craniotomy for brain tumor resection

Several studies have reported an association between high-volume brain tumor centers and greater rates of routine discharge disposition in the context of better outcomes. However, the relationship between in-hospital complications, discharge destination, and postoperative adverse events (AEs) remains unexplored. The purpose of this study was thus to use a large, prospectively collected database to examine the association between discharge destination, post-discharge complications, readmissions, and reoperations among patients undergoing craniotomy for brain tumor. The 2011–2014 National Surgical Quality Improvement (NSQIP) database was employed to identify all adult patients who underwent a craniotomy for brain tumor resection. Demographics, comorbidities, and perioperative variables were collected for each patient. Univariate statistics with subsequent binary logistic regression analyses were used to explore the relationship between these perioperative factors and postoperative events, including major post-discharge complications, minor post-discharge AEs, readmissions, and return to the operating room (ROR). Significant variables such as demographics, comorbidities, operative time, body mass index, ASA classification and pre-discharge complications were controlled for in each model. Of the 14,854 patients identified, 11,409 (77.9%) were discharged home. After controlling for comorbidities and in-hospital AEs, discharge to skilled rehabilitation was an independent predictor of major post-discharge complications (OR 1.74, 95% CI 1.31–2.30, p?<?0.001), minor post-discharge events (OR 1.60, 95% CI 1.07–2.41, p?=?0.024), and ROR (OR 1.68, 95% CI 1.27–2.22, p?<?0.001). Discharge to a care facility was predictive of major complications (OR 1.51, 95% CI 1.04–2.19, p?=?0.030) and ROR (OR 2.02, 95% CI 1.46–2.80, p?<?0.001). These factors may be considered in discharge planning and further outcomes studies for patients undergoing resection.     

BRCA2 germline mutations in Cypriot patients with familial breast/ovarian cancer

Germline mutations in the BRCA2 gene have been shown to be associated with familial female and male breast cancer. Mutations occur throughout the entire coding region of the gene, and there is considerable ethnic and geographical diversity in the deleterious mutations detected in different populations. No data exist on the role of the BRCA2 gene in the Cypriot population. In this study we present the results of characterizing mutations in the BRCA2 gene, in 26 Cypriot families with multiple cases of breast/ovarian cancer. The entire coding region, including splice sites, of BRCA2 were sequenced using cycle sequencing. In total 29 BRCA2 variants were detected which include 3 truncating mutations, 8 missense mutations, 6 polymorphisms and 12 intronic variants. The 3 truncating mutations are frameshift mutation 8984delG (exon 22), and two nonsense mutations, namely C1913X (exon 11) which is a novel mutation, and K3326X (exon 27). It is of interest that frameshift mutation 8984delG was the most frequent, since it was detected in 5 patients from three different families. Among the 6 polymorphisms detected, polymorphism T77T is novel and similarly 4 of the 12 intronic variants were also novel, namely IVS1+8G>A, IVS1-96insA, IVS4+36A>G and IVS11-51G>T. These results show that deleterious BRCA2 mutations, occur at the same frequency, about 20%, in Cypriot families, as that recorded in other European populations. We conclude that the BRCA2 gene plays a significant role in the familial breast cancer phenotype in the Cypriot population.