Danielle D. DeSouza

Use of Diffusion Tensor Imaging to Examine Subacute White Matter Injury Progression in Moderate to Severe Traumatic Brain Injury

OBJECTIVE To demonstrate subacute progression of white matter (WM) injury (4.5mo-2.5y postinjury) in patients with traumatic brain injury using diffusion-tensor imaging. DESIGN Prospective, repeated-measures, within-subjects design. SETTING Inpatient neurorehabilitation program and teaching hospital MRI department. PARTICIPANTS Brain-injured adults (N=13) with a mean Glasgow Coma Scale score of 7.67+/-4.16. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Fractional anisotropy (FA) values were measured at 4.5 and 29 months postinjury in right and left frontal and temporal deep WM tracts and the anterior and posterior corpus callosum. RESULTS FA significantly decreased in frontal and temporal tracts: right frontal (.38+/-.06 to .30+/-.06; P<.005), left frontal (.37+/-.06 to .32+/-.06; P<.05), right temporal (.28+/-.05 to .22+/-.018; P<.005), and left temporal (.28+/-.05 to .24+/-.02; P<.05). No significant changes were in the corpus callosum. CONCLUSIONS Preliminary results demonstrate progression of WM damage as evidenced by interval changes in diffusion anisotropy. Future research should examine the relationship between decreased FA and long-term clinical outcome.

Abnormal trigeminal nerve microstructure and brain white matter in idiopathic trigeminal neuralgia.

Summary Trigeminal neuralgia patients have microstructural abnormalities in their trigeminal nerves and brain white matter connecting regions involved in pain perception, attention, and motor functions. ABSTRACT Idiopathic trigeminal neuralgia (TN) is classically associated with neurovascular compression (NVC) of the trigeminal nerve at the root entry zone (REZ), but NVC‐induced structural alterations are not always apparent on conventional imaging. Previous studies report lower fractional anisotropy (FA) in the affected trigeminal nerves of TN patients using diffusion tensor imaging (DTI). However, it is not known if TN patients have trigeminal nerve abnormalities of mean, radial, or axial diffusivity (MD, RD, AD – metrics linked to neuroinflammation and edema) or brain white matter (WM) abnormalities. DTI scans in 18 right‐sided TN patients and 18 healthy controls were retrospectively analyzed to extract FA, RD, AD, and MD from the trigeminal nerve REZ, and Tract‐Based Spatial Statistics (TBSS) was used to assess brain WM. In patients, the affected trigeminal nerve had lower FA, and higher RD, AD, and MD was found bilaterally compared to controls. Group TBSS (P < 0.05, corrected) showed patients had lower FA and increased RD, MD, and AD in brain WM connecting areas involved in the sensory and cognitive‐affective dimensions of pain, attention, and motor functions, including the corpus callosum, cingulum, posterior corona radiata, and superior longitudinal fasciculus. These data indicate that TN patients have abnormal tissue microstructure in their affected trigeminal nerves, and as a possible consequence, WM microstructural alterations in the brain. These findings suggest that trigeminal nerve structural abnormalities occur in TN, even if not apparent on gross imaging. Furthermore, MD and RD findings suggest that neuroinflammation and edema may contribute to TN pathophysiology.

Sensorimotor and Pain Modulation Brain Abnormalities in Trigeminal Neuralgia: A Paroxysmal, Sensory-Triggered Neuropathic Pain

Objective Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity. Methods Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants. Results TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia (putamen, caudate, nucleus accumbens) compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration. Conclusions TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks.

Reversal of insular and microstructural nerve abnormalities following effective surgical treatment for trigeminal neuralgia

Abstract Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder commonly associated with neurovascular compression at the trigeminal nerve root entry zone (REZ). Neurosurgical interventions can relieve TN pain, but the mechanisms underlying these effects are unknown. We determined whether the abnormalities we previously reported at the REZ of TN patients using diffusion tensor imaging (DTI) and brain gray matter (GM) analyses resolve after effective neurosurgical treatment. Twenty-five patients who underwent either microvascular decompression surgery or Gamma Knife radiosurgery for right-sided TN had magnetic resonance imaging scans before and after treatment and were compared with age-matched controls. Cortical thickness and voxel-based morphometry examined specific brain GM we previously reported as abnormal in TN. White matter metrics of fractional anisotropy (FA), mean, radial, and axial diffusivities (MD, RD, and AD, respectively) were extracted bilaterally from each trigeminal REZ. Before treatment, patients had widespread GM abnormalities including thinner ventral anterior insula (vAI) cortex, and REZ microstructural abnormalities (lower FA, and higher MD, RD, and AD) compared with controls. We considered a 75% reduction in pain as effective treatment. The right vAI was the only GM region that normalized toward the level of healthy controls after effective treatment. At the REZ, effective treatment reversed FA, MD, RD, and AD abnormalities and was correlated with pain relief after treatment. These results demonstrate that treatment can effectively resolve pain by normalizing REZ abnormalities, which may influence vAI abnormalities. Future studies should consider DTI as an adjunct to assess the patient outcome and subtle microstructural changes after treatment.

Diffusivity signatures characterize trigeminal neuralgia associated with multiple sclerosis

Background: Trigeminal neuralgia secondary to multiple sclerosis (MS-TN) is a facial neuropathic pain syndrome similar to classic trigeminal neuralgia (TN). While TN is caused by neurovascular compression of the fifth cranial nerve (CN V), how MS-related demyelination correlates with pain in MS-TN is not understood. Objectives: We aim to examine diffusivities along CN V in MS-TN, TN, and controls in order to reveal differential neuroimaging correlates across groups. Methods: 3T MR diffusion weighted, T1, T2 and FLAIR sequences were acquired for MS-TN, TN, and controls. Multi-tensor tractography was used to delineate CN V across cisternal, root entry zone (REZ), pontine and peri-lesional segments. Diffusion metrics including fractional anisotropy (FA), and radial (RD), axial (AD), and mean diffusivities (MD) were measured from each segment. Results: CN V segments showed distinctive diffusivity patterns. The TN group showed higher FA in the cisternal segment ipsilateral to the side of pain, and lower FA in the ipsilateral REZ segment. The MS-TN group showed lower FA in the ipsilateral peri-lesional segments, suggesting differential microstructural changes along CN V in these conditions. Conclusions: The study demonstrates objective differences in CN V microstrucuture in TN and MS-TN using non-invasive neuroimaging. This represents a significant improvement in the methods currently available to study pain in MS.

Structural Magnetic Resonance Imaging Can Identify Trigeminal System Abnormalities in Classical Trigeminal Neuralgia.

Classical trigeminal neuralgia (TN) is a chronic pain disorder that has been described as one of the most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ) by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC) for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN.

Diffusion imaging in trigeminal neuralgia reveals abnormal trigeminal nerve and brain white matter.

(eg, anxiety and depression) to changes in WM microstructure. This WM remodeling may be merged with input from the sensory component of pain. Distinguishing between the effects of these 2 pain components on WM microstructure changes is not easy. The TBSS used in the paper by DeSouza et al. is based on an analysis of whole-brain WM voxel diffusion tensor imaging metrics, and likely reflects both sensory and mood components of pain. Future studies using TBSS need to investigate the effects of pain-related mood alterations in patients with TN. In order to determine the precise nature of WM changes associated with TN, the influence of mood factors should be carefully assessed and considered.

Making Sense of Gray Matter Abnormalities in Chronic Orofacial Pain—Synthesizing Divergent Findings

Several studies have investigated various chronic pain populations for structural brain abnormalities in gray matter (GM). Most studies report decreases in GM volume and/or thickness in regions related to antinociceptive, cognitive, and/or limbic functions ([May, 2011][1]). Conversely, some of these

Comparison of Diffusion-Weighted MRI Reconstruction Methods for Visualization of Cranial Nerves in Posterior Fossa Surgery

Diffusion-weighted imaging (DWI)-based tractography has gained increasing popularity as a method for detailed visualization of white matter (WM) tracts. Different imaging techniques, and more novel, advanced imaging methods provide significant WM structural detail. While there has been greater focus on improving tract visualization for larger WM pathways, the relative value of each method for cranial nerve reconstruction and how this methodology can assist surgical decision-making is still understudied. Images from 10 patients with posterior fossa tumors (4 male, mean age: 63.5), affecting either the trigeminal nerve (CN V) or the facial/vestibular complex (CN VII/VIII), were employed. Three distinct reconstruction methods [two tensor-based methods: single diffusion tensor tractography (SDT) (3D Slicer), eXtended streamline tractography (XST), and one fiber orientation distribution (FOD)-based method: streamline tractography using constrained spherical deconvolution (CSD)-derived estimates (MRtrix3)], were compared to determine which of these was best suited for use in a neurosurgical setting in terms of processing speed, anatomical accuracy, and accurate depiction of the relationship between the tumor and affected CN. Computation of the tensor map was faster when compared to the implementation of CSD to provide estimates of FOD. Both XST and CSD-based reconstruction methods tended to give more detailed representations of the projections of CN V and CN VII/VIII compared to SDT. These reconstruction methods were able to more accurately delineate the course of CN V and CN VII/VIII, differentiate CN V from the cerebellar peduncle, and delineate compression of CN VII/VIII in situations where SDT could not. However, CSD-based reconstruction methods tended to generate more invalid streamlines. XST offers the best combination of anatomical accuracy and speed of reconstruction of cranial nerves within this patient population. Given the possible anatomical limitations of single tensor models, supplementation with more advanced tensor-based reconstruction methods might be beneficial.

Imaging in CDH

Our understanding of brain abnormalities in headache syndromes has greatly improved with the use of advanced neuroimaging methods. Neuroimaging allows for the noninvasive examination of brain structure and function using modalities such as magnetic resonance imaging (MRI). Measures of brain structure include those that can assess gray matter volume or thickness and white matter microstructure, whereas measures of brain function include those that assess brain activity and connectivity in patients compared to controls. While most studies in the headache literature have examined episodic headache disorders, there has been a recent push toward understanding neuroimaging-based brain abnormalities associated with chronic daily headache (CDH) to gain insight into its underlying pathophysiology. This chapter focuses on studies that have primarily used MRI methods to assess structural and functional brain abnormalities in CDH. These findings are discussed in the context of clinical symptoms and other chronic pain disorders. We conclude with a discussion on future directions for neuroimaging research in CDH.