Justin M. Honce

Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities.

Natalizumab (Tysabri) is a monoclonal antibody (α4 integrin antagonist) approved for treatment of multiple sclerosis, both for patients who fail therapy with other disease modifying agents and for patients with aggressive disease. Natalizumab is highly effective, resulting in significant decreases in rates of both relapse and disability accumulation, as well as marked decrease in MRI evidence of disease activity. As such, utilization of natalizumab is increasing, and the presentation of its associated complications is increasing accordingly. This review focuses on the clinical and neuroimaging features of the major complications associated with natalizumab therapy, focusing on the rare but devastating progressive multifocal leukoencephalopathy (PML). Associated entities including PML associated immune reconstitution inflammatory syndrome (PML-IRIS) and the emerging phenomenon of rebound of MS disease activity after natalizumab discontinuation are also discussed. Early recognition of neuroimaging features associated with these processes is critical in order to facilitate prompt diagnosis, treatment, and/or modification of therapies to improve patient outcomes.

Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations

It is abundantly clear that there is extensive gray matter pathology occurring in multiple sclerosis. While attention to gray matter pathology was initially limited to studies of autopsy specimens and biopsies, the development of new MRI techniques has allowed assessment of gray matter pathology in vivo. Current MRI techniques allow the direct visualization of gray matter demyelinating lesions, the quantification of diffuse damage to normal appearing gray matter, and the direct measurement of gray matter atrophy. Gray matter demyelination (both focal and diffuse) and gray matter atrophy are found in the very earliest stages of multiple sclerosis and are progressive over time. Accumulation of gray matter damage has substantial impact on the lives of multiple sclerosis patients; a growing body of the literature demonstrates correlations between gray matter pathology and various measures of both clinical disability and cognitive impairment. The effect of disease modifying therapies on the rate accumulation of gray matter pathology in MS has been investigated. This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage.

Neuroimaging of Concussion

In this review, we discuss the literature regarding both concussion and mild traumatic brain injury. We focus on the role for neuroimaging in the concussed patient and describe the recommended practices related to imaging in concussion. This discussion first focuses on the exclusion of severe injuries and is followed by a discussion of the potential utility of various advanced imaging techniques in research and clinical practice.

Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence

PURPOSE To investigate whether sex modulates the effects of stimulant dependence on gray matter volume (GMV) in patients who have achieved long-term abstinence and to characterize how sex modulates GMV according to specific behavioral measures, such as dependence symptom count, behavioral approach, and impulsivity. MATERIALS AND METHODS Colorado Multiple Institutional Review Board approval and informed consent were obtained. In this prospective parallel group study, 127 age- and sex-matched participants (68 control subjects [28 women, 40 men] and 59 patients with stimulant dependence [28 women, 31 men]) underwent T1-weighted spoiled gradient-echo inversion recovery magnetic resonance imaging of the brain at 3 T. Images were segmented by using voxel-based morphometric software. After adjustment for age, education, and head size, the effects of group according to sex on GMV and main effects were analyzed throughout the whole brain by using an analysis of covariance family-wise cluster corrected for multiple comparisons, with a threshold P value of less than .05. Dependence symptom count and behavioral measurements were correlated with GMV in the whole brain and in five a priori regions of interest. RESULTS The effects of group according to sex on GMV were significant in numerous regions (P < .001). Compared with female control subjects, women with stimulant dependence had significantly lower GMV in widespread brain regions (P < .001). There were no significant differences in GMV between male control subjects and men with stimulant dependence (P = .625). Dependence symptom count negatively correlated with GMV in the nucleus accumbens in women (left: r = -0.364, P = .047; right: r = -0.407, P = .031) but not in men (left: r = -0.063, P = .737; right: r = -0.174, P = .349). Behavioral approach (P = .002) and impulsivity (P = .013) correlated negatively with frontal and temporal GMV changes in women with stimulant dependence but not in the other groups. CONCLUSION Vast changes in GMV were observed in women with stimulant dependence after prolonged abstinence, but were not observed in men. Sexual dimorphism in drug-related neuroanatomic changes and brain-behavior relationships may be mechanisms underlying the difference in clinical profiles of addiction between women and men.

Cannabis use in people with Parkinson's disease and Multiple Sclerosis: A web-based investigation.

OBJECTIVES Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinsons disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users. METHODS An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016. The survey collected demographic and cannabis use information, and used standardized questionnaires to assess neurological function, fatigue, balance, and physical activity participation. Analysis of variance and chi-square tests were used for the analysis. RESULTS The survey was viewed 801 times, and 595 participants were in the final data set. Seventy-six percent and 24% of the respondents reported PD and MS respectively. Current users reported high efficacy of cannabis, 6.4 (SD 1.8) on a scale from 0 to 7 and 59% reported reducing prescription medication since beginning cannabis use. Current cannabis users were younger and less likely to be classified as obese (P < 0.035). Cannabis users reported lower levels of disability, specifically in domains of mood, memory, and fatigue (P<0.040). CONCLUSIONS Cannabis may have positive impacts on mood, memory, fatigue, and obesity status in people with PD and MS. Further studies using clinically and longitudinally assessed measurements of these domains are needed to establish if these associations are causal and determine the long-term benefits and consequences of cannabis use in people with PD and MS.

Isolated focal dystonia phenotypes are associated with distinct patterns of altered microstructure

Objective Isolated adult-onset focal dystonia is considered a network disorder with disturbances to the motor basal ganglia and cerebellar circuits playing a pathophysiological role, but why specific body regions become affected remains unknown. We aimed to use diffusion tensor imaging to determine if the two most common phenotypes of focal dystonia are associated with distinguishing microstructural changes affecting the motor network. Methods Fifteen blepharospasm patients, 20 cervical dystonia patients, and 30 age- and sex-matched healthy controls were recruited. Maps of fractional anisotropy and mean diffusivity were analyzed using a voxel-based approach and an automated region-of-interest technique to evaluate deep gray matter nuclei. Correlations between diffusion measures and dystonia severity were tested, and post hoc discriminant analyses were conducted. Results Voxel-based analyses revealed significantly reduced fractional anisotropy in the right cerebellum and increased mean diffusivity in the left caudate of cervical dystonia patients compared to controls, as well as lower fractional anisotropy in the right cerebellum in cervical dystonia patients relative to blepharospasm patients. In addition to reduced fractional anisotropy in the bilateral caudate nucleus of cervical dystonia patients relative to controls and blepharospasm patients, region-of-interest analyses revealed significantly reduced fractional anisotropy in the right globus pallidus internus and left red nucleus of blepharospasm patients compared to both controls and cervical dystonia patients. Diffusivity measures in the red nucleus of blepharospasm patients correlated with disease severity. In a three-group discriminant analysis, participants were correctly classified with only modest reliability (67–75%), but in a two-group discriminant analysis, patients could be distinguished from each other with high reliability (83–100%). Conclusions Different focal dystonia phenotypes are associated with distinct patterns of altered microstructure within constituent regions of basal ganglia and cerebellar circuits.

Association of MRI Measurements with Cognitive Outcomes After STN-DBS in Parkinson's Disease: Association of Quantitative Measures with Cognitive Outcomes of STN-DBS

Subthalamic nucleus deep brain stimulation (STN‐DBS) is an effective treatment for improving the motor symptoms of Parkinsons disease (PD). Overall, cognitive function remains stable after STN‐DBS in most patients. However, cognitive decline, specifically in the verbal fluency domain, is seen in a subset of STN‐DBS patients. Currently, predictors of cognitive decline in PD patients treated with STN‐DBS are not well known. Thus, identification of presurgical predictors might provide an important clinical tool for better risk‐to‐benefit assessment. This study explores whether whole brain white matter lesion (WML) volume, or hippocampal and forebrain volumes, measured quantitatively on MRI, are associated with cognitive changes following STN‐DBS in PD patients.

The impact of very short transition times on switching from Natalizumab to Fingolimod on imaging and clinical effectiveness outcomes in multiple sclerosis

BACKGROUND Due to the recurrence of disease activity in multiple sclerosis (MS) patients, a washout period of <3 months has been suggested for the transition from natalizumab (NTZ) to fingolimod (FTY). However, very short transition periods of <1 month may be more beneficial. METHODS Retrospective analysis of patients from the Rocky Mountain MS Center at the University of Colorado who were: a) on NTZ for ≥6 months prior to switching to FTY; b) had a transition period ≤ 6 months; and c) initiated FTY treatment prior to November 2013. Transition periods were grouped as follows: <1 month, 1-2 months, and 3-6 months. Outcomes assessed include clinical and MRI measures within one year of FTY initiation. RESULTS Thirty-seven, 56 and 24 patients had a transition period < 1 month, 1-2 months and 3-6 months, respectively. Baseline characteristics were well matched: mean age 45-49 years (p = 0.17), disease duration 11-13 years (p = 0.42), and ~70% women (p = 1.00). Following the switch (including transition period), clinical relapses were observed in 0% (<1 month), 12.5% (1-2 months), 37.5% (3-6 month) (p < 0.001) of patients. New gadolinium enhancing lesions occurred in 3.3% (<1 month), 13% (1-2 months), 21.4% (3-6 months) (p = 0.13) patients. New T2 lesions were observed in 11.1% (<1 month), 16.3% (1-2 months), 33.3% (3-6 months) (p = 0.28) of patients. There were no unexpected adverse events or PML observed. CONCLUSIONS Minimizing transition times from NTZ to FTY was beneficial and safe.

PRES: Review of Histological Features

Posterior reversible encephalopathy syndrome was described in 1996 as a clinical-neuroimaging entity characterized by parieto-occipital watershed-region edema without overt infarction. It has been linked to hypertension, eclampsia, immunosuppressive therapies, infections, and autoimmune disorders. The condition usually has an acute onset, presents with seizures, and ameliorates within days. There have been few neuropathological studies, but in some cases, tissue damage may be more permanent.

Multiple Sclerosis, Cannabis Use, and Clinical Disability: A Preliminary [18F]-Fluorodeoxyglucose Positron Emission Tomography Study

Abstract Introduction: Long-term consequences of medicinal cannabis use in people with multiple sclerosis (PwMS) are unknown. This study investigated whether PwMS using cannabis had lower resting brain glucose uptake (GU) and worse clinical test results compared with nonusers. Methods: Sixteen PwMS, eight users, underwent clinical testing followed by [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography imaging. Results: Users had lower cognitive function test scores, but performed similarly on the other clinical evaluations. Accounting for disease duration, resting brain GU was similar between the groups. Conclusions: Lower cognitive function was not associated with resting brain GU. Cognitive dysfunction may be a contraindication or consequence of cannabis use in PwMS.