The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Neurologic complications of polytrauma.

Neurologic complications in polytrauma can be classified by etiology and clinical manifestations: neurovascular, delirium, and spinal or neuromuscular problems. Neurovascular complications include ischemic strokes, intracranial hemorrhage, or the development of traumatic arteriovenous fistulae. Delirium and encephalopathy have a reported incidence of 67-92% in mechanically ventilated polytrauma patients. Causes include sedation, analgesia/pain, medications, sleep deprivation, postoperative state, toxic ingestions, withdrawal syndromes, organ system dysfunction, electrolyte/metabolic abnormalities, and infections. Rapid identification and treatment of the underlying cause are imperative. Benzodiazepines increase the risk of delirium, and alternative agents are preferred sedatives. Pharmacologic treatment of agitated delirium can be achieved with antipsychotics. Nonconvulsive seizures and status epilepticus are not uncommon in surgical/trauma intensive care unit (ICU) patients, require electroencephalography for diagnosis, and need timely management. Spinal cord ischemia is a known complication in patients with traumatic aortic dissections or blunt aortic injury requiring surgery. Thoracic endovascular aortic repair has reduced the paralysis rate. Neuromuscular complications include nerve and plexus injuries, and ICU-acquired weakness. In polytrauma, the neurologic examination is often confounded by pain, sedation, mechanical ventilation, and distracting injuries. Regular sedation pauses for examination and maintaining a high index of suspicion for neurologic complications are warranted, particularly because early diagnosis and management can improve outcomes.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Cranial migration of a lumboperitoneal shunt catheter.

We describe a patient with pseudotumor cerebri for which a lumboperitoneal (LP) shunt was placed. After a pseudomeningocele was noted at the lumbar incision site, an LP shunt revision was done, at which time migration of the catheter into the thecal sac was noted. Three months later, radiologic studies revealed cranial migration of the LP shunt into the posterior fossa. We believe no similar complication has been reported.

Evaluation of 1H magnetic resonance spectroscopic imaging as a diagnostic tool for the lateralization of epileptogenic seizure foci.

The purpose of this study was to assess whether a visual examination of 1H spectroscopic images could correctly lateralize patients with intractable temporal lobe epilepsy. 20 patients with intractable temporal lobe epilepsy and 10 volunteers were included in this study. Spectroscopic images were analysed using a protocol based on visual inspection. Images of the metabolites N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate were obtained from a transverse plane oriented along the sylvian fissure. Images from each individual were evaluated independently by six reviewers. Results of the lateralization procedure obtained from the visual examinations were compared with those obtained from quantitative analysis of the spectra and with those obtained by magnetic resonance imaging (MRI), positron emission tomography (PET), neuropsychological examinations, and electroencephalographic (EEG) recordings. NAA images were found to be the most effective, amongst metabolite images, in lateralizing the epileptogenic lobe. Using the site selected for resection as the definition of the correct lateralization, 70% of the patients who underwent temporal lobectomy were correctly lateralized by the majority of the examiners using the visual inspection protocol. Based on the results of this study it is concluded that visual examination of 1H spectroscopic images is potentially valid in lateralizing patients with intractable temporal lobe seizures. Confidence in the visual interpretation increased as the difference in NAA signal intensity between the temporal lobes increased. The threshold above which the majority of the examiners correctly lateralized the patients was approximately 15% in NAA signal loss in the ipsilateral lobe.

Visual loss and a suprasellar mass complicated by pregnancy.

A 43-year-old woman who was 12 weeks pregnant presented with a one-month history of visual loss in the right eye. Neuroimaging studies revealed multiple intracranial aneurysms, one of which compressed the right optic nerve. Her pregnancy raised many issues concerning her management. Evidence of aneurysm enlargement and the increased risk of aneurysm rupture as gestation progressed led to early, successful surgical intervention.