W.P. Vandertop

Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury

AbstractnObjective. Therapeutic hypothermia may improve outcome in patients with severe head injury, but clinical studies have produced conflicting results. We hypothesised that the severe side effects of artificial cooling might have masked the positive effects in earlier studies, and we treated a large group of patients with severe head injury with hypothermia using a strict protocol to prevent the occurrence of cooling-induced side effects.nDesign. Prospective clinical trial.nSetting. University teaching hospital.nPatients. Hundred thirty-six consecutive patients admitted to our hospital with severe head injury (Glasgow Coma Scale (GCS) ≤8).nMeasurements and results. Patients included are the 136 patients with a GCS of 8 or less on admission in whom intracranial pressure (ICP) remained above 20xa0mmHg in spite of therapy according to a step-up protocol. Those who responded to the last step of our protocol (barbiturate coma) constituted the control group (n=72). Those who did not respond to barbiturate coma (n=64) were treated with moderate hypothermia (32–34°C). Average APACHE II scores were higher (28.9±14.4 vs 25.2±12.1, p<0.01) and average GCS at admission slightly lower (5.37±1.8 vs 5.9±2.1, p<0.05) in the hypothermia group, indicating greater severity of illness and more severe neurological injury. Predicted mortality was 86% for the hypothermia group versus 80% in controls (p<0.01). Actual mortality rates were significantly lower: 62% versus 72%; the difference in mortality between hypothermic patients and controls was significant (p<0.05). The number of patients with good neurological outcome was also higher in the hypothermia group: 15.7% versus 9.7% for hypothermic patients versus controls, respectively (p<0.02). These differences were explained almost entirely by the subgroup of patients with GCS of 5 or 6 at admission (mortality 52% vs 76%, p<0.01; good neurological outcome 29% vs 8%, p<0.01).nConclusions. Artificial cooling can significantly improve survival and neurological outcome in patients with severe head injury when used in a protocol with great attention to the prevention of side effects. Because there is likely to have been bias against the hypothermia group in this study, the positive effects of hypothermia might even have been underestimated. In addition, our results confirm the value of therapeutic hypothermia in treating refractory intracranial hypertension.

Diffuse intrinsic pontine gliomas: A systematic update on clinical trials and biology

Patients with diffuse intrinsic pontine gliomas (DIPG) have a poor prognosis. Although DIPG constitute only 10-15% of all pediatric brain tumors, they are the main cause of death in this group. Despite 26 clinical trials in newly diagnosed DIPG in the past 5years (including several targeted agents), there is no clear improvement in prognosis. However, knowledge on DIPG biology is increasing, mainly due to the (re)introduction of biopsies and autopsies, the possibility of gene expression profiling, and the development of in vivo models. Translation of this knowledge into clinical trials in combination with improved drug distribution methods may eventually lead to more effective treatment of this devastating disease.

Repeated surgery for glioblastoma multiforme: only in combination with other salvage therapy.

BACKGROUNDnThe purpose of the study was to evaluate the effects, frequency, and complications of repeated surgical resection for GBM relapse.nnnMETHODSnA group of 32 patients with tumor recurrence, derived from a total of 126 consecutive patients with prior GBM, treated between 1999 and 2005 in the VU University Medical Center, Amsterdam, Netherlands, were retrospectively studied. Survival, functional status, morbidity, and mortality after starting salvage therapy for recurrent GBM were studied. Survival was analyzed using Kaplan-Meier survival curves, and log-rank statistics were used for group comparison.nnnRESULTSnOf the 32 patients with recurrent primary GBM, 20 received repeated surgery as salvage therapy. In 11 (55%) cases, repeated surgery was followed by CT or SRS. Nine (45%) patients receiving only repeated surgery showed significantly lower survival rates compared with the aforementioned 11 cases. The remaining 12 patients received only salvage CT or SRS and showed a significantly prolonged survival compared with the 9 cases receiving repeated surgery only. Surgical morbidity was 15%, and surgical mortality, 5%.nnnCONCLUSIONnDespite inherent selection bias, this retrospective analysis suggests that repeated surgery for GBM relapse should only be considered in patients with severe symptoms and if additional salvage treatment can be administered postoperatively.

Tumor-Volume Changes after Radiosurgery for Vestibular Schwannoma: Implications for Follow-Up MR Imaging Protocol

BACKGROUND AND PURPOSE: The outcome of radiosurgery for vestibular schwannoma (VS) is assessed by posttreatment measurement of tumor size and could be influenced by the timing and quality of the assessment. This study evaluates the volumetric changes of VS after radiosurgery and proposes a radiologic follow-up program. MATERIALS AND METHODS: Of 142 patients with VS treated with radiosurgery, we selected patients who were followed at least 3 times during a minimum of 32 months with a T1-weighted gadolinium-enhanced high-resolution 3D MR imaging examination identical to the pretreatment MR imaging. Forty-five patients were identified with a mean follow-up of 50 months (range, 32–78 months). Pre- and posttreatment tumor volumes were calculated by using BrainSCAN software by manually contouring tumors on each MR imaging study. Volume changes of >13% were defined as events. RESULTS: At last follow-up MR imaging, volumes were smaller in 37 (82.2%) of the 45 patients. Eleven (29.7%) of these 37 tumors showed transient swelling preceding regression, with a median time to regression of 34 months (range, 20–55 months). Seven (15.6%) of the 45 tumors had volume progression compared with the tumor on pretreatment MR imaging studies. Of these 7 tumors, 3, however, had volume regression compared with the preceding MR imaging study, and in 4, volume progression was ongoing. One tumor remained the same. CONCLUSIONS: Tumor-volume measurements by standardized T1-weighted gadolinium-enhanced high-resolution 3D MR imaging follow-up protocols revealed good local control of VS after radiosurgery. The first-follow-up MR imaging at 2 years and the second at 5 years postradiosurgery differentiated transient progression from ongoing progression and may prevent unnecessary therapeutic interventions.

Implementation of a multi-institutional diffuse intrinsic pontine glioma autopsy protocol and characterization of a primary cell culture

V. Caretti, M. H. A. Jansen, D. G. van Vuurden, T. Lagerweij, M. Bugiani, I. Horsman, H. Wessels, P. van der Valk, J. Cloos, D. P. Noske, W. P. Vandertop, P. Wesseling, T. Wurdinger, E. Hulleman and G. J. L. Kaspers (2013) Neuropathology and Applied Neurobiology39, 426–436

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40xa0years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6–6.4 months) and the median overall survival is 11.0 months (95% CI 10.5–11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.

Recurrent brain abscess due to an unexpected foreign body

We report an exceptional case of a patient with chronic frontal sinusitis complicated by chronic osteomyelitis and a cutaneous fistula. A recurrent brain abscess developed and was only cured after a very unusual wooden retained foreign body was removed at surgery. The hazards of wood as a foreign body are discussed and it is stressed that the possibility of a retained foreign body, even unsuspected, must always be borne in mind.

Beneficial effect of an ACTH4 9 analogue on experimentally induced diabetic autonomic neuropathy in the eye of the rat under general anaesthesia

While peripheral polyneuropathy is a well-known complication in diabetes mellitus, and the subject of a great deal of study, the clinical importance of autonomic diabetic neuropathy is increasingly recognised. Using an animal model, where the pupil diameter of the eye serves as a parameter of autonomic function, we produced an age and weight curve of pupil diameter and studied the development of autonomic neuropathy in rats with streptozotocin-induced diabetes. We show that diabetic rats develop significantly (P < 0.009) smaller pupils compared with controls, most probably due to a defective sympathetic input, caused by sympathetic neuropathy. Treatment with the neurotrophic peptide Org 2766, a synthetic ACTH4-9 analogue, prevents the occurrence of this sympathetic neuropathy, as the pupil diameters in the ACTH4-9 analogue-treated group are significantly (P < 0.05) larger than the pupils of placebo-treated rats, and are comparable to the pupil diameters of the rats in the control group.

Experimentally-induced autonomic neuropathy : beneficial effect of a topical ACTH4-9 analogue on oculomotor nerve regeneration

Melanocortins, peptides related to corticotropin (ACTH) and melanocyte-stimulating hormone, are known to exert beneficial neurotrophic effects in peripheral sensorimotor neuropathies. This has been demonstrated after both systemic and local administration of the peptides. By photographing the rats pupil under standardized conditions, the authors have previously shown that systemic administration of a synthetic ACTH4-9 analogue can also be beneficial in autonomic neuropathies. The present study demonstrates that topical application of a synthetic ACTH4-9 analogue incorporated in a two-component fibrin glue enhances the speed of recovery of the parasympathetic nerve fibers in the oculomotor nerve after a crush lesion. This may have implications for future use in neurosurgery.

Imaging-documented repeated intratumoral hemorrhage in vestibular schwannoma: a case report.

Intratumoral hemorrhage in vestibular schwannomas is rare. Symptoms often have an acute onset and include headache, nausea, vomiting, vertigo, and depressed consciousness. Intratumoral hemorrhage is probably caused by vascular fragility associated with tumor characteristics and growth. With hemorrhage in VS being rare, repeated hemorrhage has only been reported twice, and on clinical grounds only. The present report details the case of acute neurological deterioration in a patient with repeated intratumoral hemorrhage inside a vestibular schwannoma with computed tomography and magnetic resonance imaging confirmation. To our knowledge, repeated hemorrhage in vestibular schwannoma with radiological confirmation has not been reported before.