Role of intraoperative ultrasound and MRI to aid grade of resection of pediatric low-grade gliomas: accumulated experience from 4 centers.

PURPOSE: Pediatric low-grade gliomas (pLGG) are the most common brain tumors in children and achieving complete resection (CR) in pLGG is the most important prognostic factor. There are multiple intraoperative tools to optimize the extent of resection (EOR). This article investigates and discusses the role of intraoperative ultrasound (iUS) and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of pLGG. METHODS: The tumor registries at Tuebingen, Rome and Pretoria were searched for pLGG with the use of iUS and data on EOR. The tumor registries at Liverpool and Tuebingen were searched for pLGG with the use of iMRI where preoperative CR was the surgical intent. Different iUS and iMRI machines were used in the 4 centers. RESULTS: We included 111 operations which used iUS and 182 operations using iMRI. Both modalities facilitated intended CR in hemispheric supra- and infratentorial location in almost all cases. In more deep-seated tumor location like supratentorial midline tumors, iMRI has advantages over iUS to visualize residual tumor. Functional limitations limiting CR arising from eloquent involved or neighboring brain tissue apply to both modalities in the same way. In the long-term follow-up, both iUS and iMRI show that achieving a complete resection on intraoperative imaging significantly lowers recurrence of disease (chi-square test, p < 0.01). CONCLUSION: iUS and iMRI have specific pros and cons, but both have been proven to improve achieving CR in pLGG. Due to advances in image quality, cost- and time-efficiency, and efforts to improve the user interface, iUS has emerged as the most accessible surgical adjunct to date to aid and guide tumor resection. Since the EOR has the most important effect on long-term outcome and disease control of pLGG in most locations, we strongly recommend taking all possible efforts to use iUS in any surgery, independent of intended resection extent and iMRI if locally available.

Developing a porcine model of severe traumatic brain injury induced by high amplitude rotational acceleration.

Introduction: It is unclear which pathophysiological processes initiate and drive dynamic cerebrovascular autoregulation (CA) impairment as seen in traumatic brain injury (TBI). This is not solely attributable to raised intracranial pressure (ICP), but also results from local tissue damage. Research question: In order to investigate CA disturbing processes, a porcine model is needed that mimics severe TBI as seen in humans. This model requires high amplitude rotational acceleration. Material and methods: A customized device was built to produce a rotational impulse with high amplitude and short pulse duration. Following preparatory tests on cadaver piglets, six piglets of six weeks old were sedated, ventilated and subjected to rotational impulses of different magnitudes. The impulse was immediately followed by installment of invasive monitoring of ICP, PbO2, Laser Doppler Flowmetry and arterial blood pressure. TBI was further characterized by magnetic resonance brain imaging. Results: The current setup enabled to reach sagittal head rotational maximal acceleration magnitudes up to 30 krad/s2. Half of the animals had an increase in ICP, measured shortly after the impulse. It has proved impossible so far to produce a sustained rise in ICP as seen in human severe TBI. MRI showed no anatomical abnormalities which would confirm severe TBI. Discussion and conclusion: The challenge to build a porcine model in which severe TBI with ICP raise and MRI changes as seen in humans can be reliably reproduced is still ongoing. It might be that higher peak rotational accelerations are needed.

Adjustable shunts and proton therapy: a magnetic combination.

OBJECTIVE: Due to evidence for proton beam therapy (PBT) in pediatric central nervous system (CNS) tumors, compact proton therapy systems became commercially available to allow better integration in a hospital setting. However, these systems have a non-zero magnetic field at the level of the patient. Often, these patients have a cerebrospinal fluid shunt, and most of them are adjustable through a magnet. Whether the induced magnetic fields could interfere with adjustable shunts is unknown. METHODS: In the first five CNS tumor patients with adjustable shunts who underwent PBT, the shunt setting was controlled before, during, and after treatment with PBT. Additionally, we used an ex vivo adjustable shunt to check if the settings could be altered by the magnetic field. RESULTS: We did not observe unintentional changes in shunt settings in vivo during treatment. In ex vivo testing, the shunt settings were altered directly cranial to the exit window of PBT due to the magnetic field. CONCLUSION: Although we did not observe any shunt setting alteration during PBT in this small cohort, caution is warranted. Given the lack of high-volume data, there should be a low threshold for checking the shunt setting at the end of PBT therapy or in a symptomatic patient.

Beyond intracranial pressure: monitoring cerebral perfusion and autoregulation in severe traumatic brain injury.

PURPOSE OF REVIEW: Severe traumatic brain injury (TBI) remains the most prevalent neurological condition worldwide. Observational and interventional studies provide evidence to recommend monitoring of intracranial pressure (ICP) in all severe TBI patients. Existing guidelines focus on treating elevated ICP and optimizing cerebral perfusion pressure (CPP), according to fixed universal thresholds. However, both ICP and CPP, their target thresholds, and their interaction, need to be interpreted in a broader picture of cerebral autoregulation, the natural capacity to adjust cerebrovascular resistance to preserve cerebral blood flow in response to external stimuli. RECENT FINDINGS: Cerebral autoregulation is often impaired in TBI patients, and monitoring cerebral autoregulation might be useful to develop personalized therapy rather than treatment of one size fits all thresholds and guidelines based on unidimensional static relationships. SUMMARY: Today, there is no gold standard available to estimate cerebral autoregulation. Cerebral autoregulation can be triggered by performing a mean arterial pressure (MAP) challenge, in which MAP is increased by 10% for 20 min. The response of ICP (increase or decrease) will estimate the status of cerebral autoregulation and can steer therapy mainly concerning optimizing patient-specific CPP. The role of cerebral metabolic changes and its relationship to cerebral autoregulation is still unclear and awaits further investigation.

NID1-related autosomal dominant Dandy-Walker malformation with occipital cephalocele in three generations.

The combination of Dandy-Walker malformation and occipital cephalocele is a rare autosomal dominant condition, known as ADDWOC, and caused by mutations in NID1 or LAMC1. We present a three-generation family with variable manifestations of Dandy-Walker malformation and occipital cephalocele. They all have normal psychomotor development and lack neurological manifestations. Mutation analysis revealed a likely pathogenic missense variant in NID1 (c.3336T > G, p.Asn1112Lys), affecting an amino acid residue crucial in the nidogen/laminin interaction.

Pocket Pain and Neuromodulation: Negligible or Neglected?

OBJECTIVES: Pain encountered at the site of the implantable pulse generator (IPG) after invasive neuromodulation is a well-known and important complication. The reported incidence of implant site pain is variable, ranging between 0.4 and 35%. Implant site pain has never been systematically studied and no treatment guidelines are available. MATERIAL AND METHODS: We performed an observational study (study registration number mp05728) on the incidence and the determining factors of implant site pain, the subjective rating of intensity by sending questionnaires (n = 554) to our cohort of neuromodulation patients with IPGs. The number of revision surgeries and explants due to implant site pain were also analyzed. RESULTS: Total response rate was 50% (n = 278). Pain patients suffered significantly (p < 0.05) more often from IPG site pain than other patients undergoing neuromodulation therapies. Up to 64% of patients undergoing spinal cord stimulation reported IPG site discomfort or pain. Severe pocket pain was found in up to 8% of patients. No association was found between other variables (age, BMI, duration of follow-up, gender, smoking, number of pocket surgeries) and implant site pain. CONCLUSION: Pocket pain represents an important problem after invasive neuromodulation and is more prevalent in pain patients. We believe further technological improvements with miniaturized IPGs will impact the incidence of pocket pain and could even obviate the need for an IPG pocket.

Neurosurgery in a patient at peak levels of rivaroxaban: taking into account all factors.

We present a patient who underwent urgent neurosurgery for acute onset paraplegia due to a spontaneous subdural spinal hematoma less than 5 hours after she had taken rivaroxaban. The Key Clinical Question was whether early high-risk surgery on a patient taking direct oral anticoagulants is feasible. Prothrombin complex concentrate (PCC) and tranexamic acid were administered and perioperative hemostasis was good. There is scant data on neurosurgical procedures performed within 12 hours after the intake of a direct oral anticoagulant. With the hemostatic support of high-dose PCC, early surgery after administration of rivaroxaban seems feasible in case of an emergency indication, but should only be considered when delaying surgery is esteemed hazardous to the patient. More experience is needed to allow balancing risks and benefits of urgent vs delayed intervention and on the optimal hemostatic support in the absence of a specific antidote.

Comment on "ApoE-directed therapeutics rapidly clear ß-amyloid and reverse deficits in AD mouse models".

Cramer et al. (Reports, 23 March 2012, p. 1503; published online 9 February 2012) tested bexarotene as a potential ß-amyloid-lowering drug for Alzheimer's disease (AD). We were not able to reproduce the described effects in several animal models. Drug formulation appears very critical. Our data call for extreme caution when considering this compound for use in AD patients.