Addressing the path-length-dependency confound in white matter tract segmentation

We derive the Iterative Confidence Enhancement of Tractography (ICE-T) framework to address the problem of path-length dependency (PLD), the streamline dispersivity confound inherent to probabilistic tractography methods. We show that PLD can arise as a non-linear effect, compounded by tissue complexity, and therefore cannot be handled using linear correction methods. ICE-T is an easy-to-implement framework that acts as a wrapper around most probabilistic streamline tractography methods, iteratively growing the tractography seed regions. Tract networks segmented with ICE-T can subsequently be delineated with a global threshold, even from a single-voxel seed. We investigated ICE-T performance using ex vivo pig-brain datasets where true positives were known via in vivo tracers, and applied the derived ICE-T parameters to a human in vivo dataset. We examined the parameter space of ICE-T: the number of streamlines emitted per voxel, and a threshold applied at each iteration. As few as 20 streamlines per seed-voxel, and a robust range of ICE-T thresholds, were shown to sufficiently segment the desired tract network. Outside this range, the tract network either approximated the complete white-matter compartment (too low threshold) or failed to propagate through complex regions (too high threshold). The parameters were shown to be generalizable across seed regions. With ICE-T, the degree of both near-seed flare due to false positives, and of distal false negatives, are decreased when compared with thresholded probabilistic tractography without ICE-T. Since ICE-T only addresses PLD, the degree of remaining false-positives and false-negatives will consequently be mainly attributable to the particular tractography method employed. Given the benefits offered by ICE-T, we would suggest that future studies consider this or a similar approach when using tractography to provide tract segmentations for tract based analysis, or for brain network analysis

Multimodal neuroimaging in patients with disorders of consciousness showing "functional hemispherectomy".

Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information on the structural location and extent of brain lesions (e.g., morphometric MRI and diffusion tensor imaging (DTI-MRI) assessing structural connectivity) but also their functional impact (e.g., metabolic FDG-PET, hemodynamic fMRI, and EEG measurements obtained in "resting state" conditions). We here illustrate the role of multimodal imaging in severe brain injury, presenting a patient in unresponsive wakefulness syndrome (UWS; i.e., vegetative state, VS) and in a "fluctuating" minimally conscious state (MCS). In both cases, resting state FDG-PET, fMRI, and EEG showed a functionally preserved right hemisphere, while DTI showed underlying differences in structural connectivity highlighting the complementarities of these neuroimaging methods in the study of disorders of consciousness.Peer reviewe

When light hurts: Comparative Morphometry of Human Brainstem in Traumatic Photalgia

Traumatic brain injury is an increasingly common affliction, although many of its serious repercussions are still underappreciated. A frequent consequence is the development of light-induced pain, or ‘photalgia’, which can often lead to prolonged debilitation. The mechanism underlying the sensitivity to light, however, remains unresolved. Since tissue oedema (swelling) is a common feature of traumatic brain injury, we propose that the brainstem oedema, in particular, might sensitize the brainstem trigeminal complex to signals from ocular mechanisms activated in bright light. To assess this hypothesis, we ran high-resolution Magnetic Resonance Imaging of the brainstems of concussion groups with mild and severe photalgia, without photalgia, and healthy controls. The 3D configuration of the brainstem was determined by Tensor-Based Morphometry (TBM) for each participant. The TBM revealed significant deviations in the brainstem morphology of all concussion groups, with a characteristic signature for each group. In particular, concussion without photalgia showed bilateral expansion at the pontine/medulla junction, whereas concussion with photalgia showed mid-pontine shrinkage, consistent with degeneration of nuclei of the trigeminal complex. These results support the hypothesis that brainstem shrinkage/degeneration represents a morphological substrate of the photalgic sensitization of the trigeminal pathway

Fast Acute Sedation at Intensive Care vs. High-Dose IV Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus:A Randomized, Multicenter Trial

BACKGROUND: The management of refractory status epilepticus (SE) remains an area of low evidence with varying management strategies. Treatment in the ICU is often postponed due to potential complications from sedation, and it is unknown if its efficacy is superior to additional treatment attempts with IV anti-seizure medications (ASMs). The Fast Acute Sedation at Intensive Care vs. High-Dose IV Anti-Seizure Medication for Treatment of Non-Convulsive Status Epilepticus (FAST) trial aims to compare the efficacy of rapid sedation in the ICU vs. add-on high-dose IV ASM alone for the treatment of refractory SE.METHODS/RESULTS: This prospective, randomized, multicenter trial will enroll adult patients with non-convulsive status epilepticus (NCSE) who either meet current EEG criteria or have unambiguous NCSE with minor motor phenomena ("subtle SE") but without ongoing tonic-clonic seizures that are refractory to benzodiazepines and treatment with at least one second-line ASM. Patients will be randomized to receive either rapid deep sedation for 20 hours with propofol and eventually low-dose midazolam or additional high-dose IV anticonvulsant therapy (levetiracetam, valproate, fosphenytoin, lacosamide, or topiramate) in the intermediate care unit. The primary endpoint is treatment failure, either defined as NCSE on EEG 24 hours after randomization or persistent NCSE after 3 hours despite therapy on continuous EEG or clinically. Secondary endpoints include assessment of new-onset neurologic deficits and modified Rankin Scale at discharge, economic analyses, length of hospital stay, in-hospital infections, and survival. Evaluations will be performed at baseline, discharge, and 3, 6, 12, and 24 months. The target sample size is 116 patients; we expect to have to randomize about 140 patients to reach the required number of patients.CONCLUSIONS: The FAST trial is the first randomized clinical trial to investigate refractory NCSE. Regardless of the outcome, the results of this trial protocol will provide new class 1 evidence for the treatment of NCSE and establish the standard of care for this patient population in the future.TRIAL REGISTRATION: EU CT: 2024-515507-18-00/clinicaltrials.gov: NCT05263674.</p

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. Methods fMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits. Results fMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus. Conclusions These results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.Published versio

Treatment of status epilepticus in children and adults

During the recent decades, the time limit that defines convulsive status epilepticus (CSE) has progressively shortened, to urge clinicians to treat early and aggressively. In addition to symptomatic antiseizure treatment, identification and treatment of the underlying cause is essential. This review investigates the current Danish national guidelines for the treatment of CSE in children and adults. While treatment of early and established CSE is now based on high-level evidence, currently limited evidence exists to guide treatment in refractory and superrefractory stages

Treatment of status epilepticus in children and adults

During the recent decades, the time limit that defines convulsive status epilepticus (CSE) has progressively shortened, to urge clinicians to treat early and aggressively. In addition to symptomatic antiseizure treatment, identification and treatment of the underlying cause is essential. This review investigates the current Danish national guidelines for the treatment of CSE in children and adults. While treatment of early and established CSE is now based on high-level evidence, currently limited evidence exists to guide treatment in refractory and superrefractory stages

Treatment of status epilepticus in children and adults

During the recent decades, the time limit that defines convulsive status epilepticus (CSE) has progressively shortened, to urge clinicians to treat early and aggressively. In addition to symptomatic antiseizure treatment, identification and treatment of the underlying cause is essential. This review investigates the current Danish national guidelines for the treatment of CSE in children and adults. While treatment of early and established CSE is now based on high-level evidence, currently limited evidence exists to guide treatment in refractory and superrefractory stages

Long-term white matter tract reorganization following prolonged febrile seizures

OBJECTIVE: Diffusion magnetic resonance imaging (MRI) studies have demonstrated acute white matter changes following prolonged febrile seizures (PFS), but their longer-term evolution is unknown. We investigated a population-based cohort to determine white matter diffusion properties 8 years after PFS. METHODS: We used diffusion tensor imaging (DTI) and applied Tract-Based Spatial Statistics for voxel-wise comparison of white matter microstructure between 26 children with PFS and 27 age-matched healthy controls. Age, gender, handedness, and hippocampal volumes were entered as covariates for voxel-wise analysis. RESULTS: Mean duration between the episode of PFS and follow-up was 8.2 years (range 6.7-9.6). All children were neurologically normal, and had normal conventional neuroimaging. On voxel-wise analysis, compared to controls, the PFS group had (1) increased fractional anisotropy in early maturing central white matter tracts, (2) increased mean and axial diffusivity in several peripheral white matter tracts and late-maturing central white matter tracts, and (3) increased radial diffusivity in peripheral white matter tracts. None of the tracts had reduced fractional anisotropy or diffusivity indices in the PFS group. SIGNIFICANCE: In this homogeneous, population-based sample, we found increased fractional anisotropy in early maturing central white matter tracts and increased mean and axial diffusivity with/without increased radial diffusivity in several late-maturing peripheral white matter tracts 8 years post-PFS. We propose disruption in white matter maturation secondary to seizure-induced axonal injury, with subsequent neuroplasticity and microstructural reorganization as a plausible explanation