Successful treatment of respiratory failure in Hirayama disease.

Hirayama disease is a self-limiting cervical motor neuron disease, usually affecting the spinal cord at level C7-T1. We share an unusual case of Hirayama disease in a young man affecting roots C4-C6. He presented in coma due to diaphragm weakness and hypercapnic respiratory failure. Diagnosis was achieved via clinical presentation, neurophysiological examination, ultrasonography of the diaphragm and dynamic MR-imaging. Conservative treatment with a cervical collar resulted in remarkable improvement in respiratory and motor function.

High Prevalence of Weight Gain in Childhood Brain Tumor Survivors and Its Association With Hypothalamic-Pituitary Dysfunction.

PURPOSE: Childhood brain tumor survivors (CBTS) are at risk for developing obesity, which negatively influences cardiometabolic health. The prevalence of obesity in CBTS may have been overestimated in previous cohorts because of inclusion of children with craniopharyngioma. On the contrary, the degree of weight gain may have been underestimated because of exclusion of CBTS who experienced weight gain, but were neither overweight nor obese. Weight gain may be an indicator of underlying hypothalamic-pituitary (HP) dysfunction. We aimed to study prevalence of and risk factors for significant weight gain, overweight, or obesity, and its association with HP dysfunction in a national cohort of noncraniopharyngioma and nonpituitary CBTS. METHODS: Prevalence of and risk factors for significant weight gain (body mass index [BMI] change ≥ +2.0 standard deviation score [SDS]), overweight, or obesity at follow-up, and its association with HP dysfunction were studied in a nationwide cohort of CBTS, diagnosed in a 10-year period (2002-2012), excluding all craniopharyngioma and pituitary tumors. RESULTS: Of 661 CBTS, with a median age at follow-up of 7.3 years, 33.1% had significant weight gain, overweight, or obesity. Of the CBTS between 4 and 20 years of age, 28.7% were overweight or obese, compared with 13.2% of the general population between 4 and 20 years of age. BMI SDS at diagnosis, diagnosis of low-grade glioma, diabetes insipidus, and central precocious puberty were associated with weight gain, overweight, or obesity. The prevalence of HP dysfunction was higher in overweight and obese CTBS compared with normal-weight CBTS. CONCLUSION: Overweight, obesity, and significant weight gain are prevalent in CBTS. An increase in BMI during follow-up may be a reflection of HP dysfunction, necessitating more intense endocrine surveillance.

Coiling and clipping of middle cerebral artery aneurysms: a systematic review on clinical and imaging outcome.

BACKGROUND: There is an ongoing debate on the preferred treatment of middle cerebral artery (MCA) aneurysms. The purpose of this study was to assess the clinical and imaging outcomes comparing conventional coiling and clipping of unruptured and ruptured MCA aneurysms. METHODS: We searched the electronic databases PubMed, EMBASE, and Cochrane from January 1990 to May 2014. RESULTS: 51 studies were included in the analysis. Favorable outcome was reported in 97.0% and 77.1%, and in 97.2% and 72.8% of patients after coiling and clipping of unruptured and ruptured aneurysms, respectively. Death rates were 1.1% and 8.4% after coiling and 0.3% and 14.7% after clipping of unruptured and ruptured aneurysms, respectively. Initial adequate occlusion was obtained in 89.6% and 92.1% after coiling of unruptured and ruptured aneurysms, respectively. Only three studies on clipping reported on aneurysm occlusion during follow-up. CONCLUSIONS: Both coiling and clipping are procedures with low mortality and morbidity rates and, although it may seem that coiling is better for ruptured aneurysms and clipping for unruptured aneurysms, no firm conclusions can be drawn due to the variation in study design and lack of standardized reporting on MCA aneurysm treatments. Standardized observational studies from prospectively kept databases are needed to allow stronger conclusions to be drawn on what is the best treatment for MCA aneurysms. Comparable with aneurysms in other locations, a multidisciplinary approach is therefore recommended with selection of treatment modality based on the clinical condition of the patient and the morphological aspects of the aneurysm.

Cardiac dysfunction after aneurysmal subarachnoid hemorrhage: relationship with outcome.

OBJECTIVE: To assess whether cardiac abnormalities after aneurysmal subarachnoid hemorrhage (aSAH) are associated with delayed cerebral ischemia (DCI) and clinical outcome, independent from known clinical risk factors for these outcomes. METHODS: In a prospective, multicenter cohort study, we performed echocardiography and ECG and measured biochemical markers for myocardial damage in patients with aSAH. Outcomes were DCI, death, and poor clinical outcome (death or dependency for activities of daily living) at 3 months. With multivariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals. We used survival analysis to assess cumulative percentage of death in patients with and without echocardiographic wall motion abnormalities (WMAs). RESULTS: We included 301 patients with a mean age of 57 years; 70% were women. A wall motion score index ≥1.2 had an adjusted RR of 1.2 (0.9-1.6) for DCI, 1.9 (1.1-3.3) for death, and 1.8 (1.1-3.0) for poor outcome. Midventricular WMAs had adjusted RRs of 1.1 (0.8-1.4) for DCI, 2.3 (1.4-3.8) for death, and 2.2 (1.4-3.5) for poor outcome. For apical WMAs, adjusted RRs were 1.3 (1.1-1.7) for DCI, 1.5 (0.8-2.7) for death, and 1.4 (0.8-2.5) for poor outcome. Elevated troponin T levels, ST-segment changes, and low voltage on the admission ECGs had a univariable association with death but were not independent predictors for outcome. CONCLUSION: WMAs are independent risk factors for clinical outcome after aSAH. This relation is partly explained by a higher risk of DCI. Further study should aim at treatment strategies for these aSAH-related cardiac abnormalities to improve clinical outcome.

Brain computer tomography in critically ill patients--a prospective cohort study.

BACKGROUND: Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients. METHODS: In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An "expected abnormality" was any finding that had been predicted by the physician requesting the brain CT. A brain CT was "diagnostically positive", if the abnormality found was new or if an already known abnormality was increased. It was "diagnostically negative" if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as "treatment as planned", "treatment changed, not as planned", "treatment unchanged". RESULTS: Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), p 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned. CONCLUSIONS: The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.

PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation.

Poly ADP-ribose polymerase (PARP) is a protein involved in single strand break repair. Recently, PARP inhibitors have shown considerable promise in the treatment of several cancers, both in monotherapy and in combination with cytotoxic agents. Synthetic lethal action of PARP inhibitors has been observed in tumors with mutations in double strand break repair pathways. In addition, PARP inhibition potentially enhances sensitivity of tumor cells to DNA damaging agents, including radiotherapy. Aim of this study is to determine the radiosensitizing properties of the PARP inhibitor Olaparib in childhood medulloblastoma, ependymoma and high grade glioma (HGG). Increased PARP1 expression was observed in medulloblastoma, ependymoma and HGG, as compared to non-neoplastic brain tissue. Pediatric high grade glioma, medulloblastoma and ependymoma gene expression profiling revealed that high PARP1 expression is associated with poor prognosis. Cell growth inhibition assays with Olaparib resulted in differential sensitivity, with IC50 values ranging from 1.4 to 8.4 µM, irrespective of tumor type and PARP1 protein expression. Sensitization to radiation was observed in medulloblastoma, ependymoma and HGG cell lines with subcytotoxic concentrations of Olaparib, which coincided with persistence of double strand breaks. Combining PARP inhibitors with radiotherapy in clinical studies in childhood high grade brain tumors may improve therapeutic outcome.

Homing properties of adipose-derived stem cells to intracerebral glioma and the effects of adenovirus infection.

The inevitable clinical recurrence of high grade gliomas after standard treatment is due to the highly diffuse infiltrating parts of these tumors, which remain after surgery and respond poorly to radiation and chemotherapy. It has been proposed to employ the homing capacity of neural stem cells (NSCs) to different types of intracerebral pathology for selective targeting of glioma cells, and delivery of transgenic expressed therapeutics. This approach has been successful in a number of preclinical experimental studies, however, a major drawback for clinical translation has been the limitation of harvesting and ex vivo expansion of NSCs in patients. Here we demonstrate that adipose derived stem cells (ASCs), which are easily harvested in relatively large quantities in humans, display the same tropism for gliomas as NSCs in vitro and in vivo. Both ipsilateral as well as contralateral injection of these cells in brains of glioma-bearing mice, led to extensive homing to the tumor by the ASCs. The potential of loading these cellular vehicles with transgenes was assessed using adenoviral vectors. ASCs could be infected with adenoviral vectors, albeit at very high MOI. Insertion of the arg-gly-asp (RGD) motif into the adenovirus fiber knob, thereby redirecting primary attachment of the virus to integrins, resulted in a striking 7000-fold increase in infection efficiency. However, in vivo migration of adenovirus-infected ASCs was not observed, most likely due to an inflammatory response to these cells which was not observed with control non-infected ASCs. These results indicate that ASCs are an interesting candidate for further development for cell-based therapy of gliomas, however adenoviruses are not appropriate vectors for delivery of transgenes in this context.

Treatment-related changes in functional connectivity in brain tumor patients: a magnetoencephalography study.

Widespread disturbances in resting state functional connectivity between remote brain areas have been demonstrated in patients with brain tumors. Functional connectivity has been associated with neurocognitive deficits in these patients. Thus far, it is unknown how (surgical) treatment affects functional connectivity. Functional connectivity before and after tumor resection was compared in primary brain tumor patients. Data from 15 newly diagnosed brain tumor patients were analyzed. Patients underwent tumor resection, and both preoperative (up to five months prior to surgery) and postoperative (up to ten months following surgery) resting state magnetoencephalography (MEG) recordings. Seven of the patients (47%) underwent radiotherapy after neurosurgery. Functional connectivity was assessed by the phase lag index (PLI), a measure of the correlation between MEG sensors that is not sensitive to volume conduction. PLIs were averaged to one short-distance and two long-distance (interhemispheric and intrahemispheric) scores in seven frequency bands. We found that functional connectivity changed in a complex manner after tumor resection, depending on frequency band and functional connectivity type. Post-hoc analyses yielded a significant decrease of interhemispheric PLI in the theta band after tumor resection. This result proved to be robust and was not influenced by radiotherapy or a variety of tumor- and patient-related factors.