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

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. Keywords: Blepharospasm, Cervical dystonia, Diffusion tensor imaging, Basal ganglia, Cerebellu

Understanding Patient Experiences, Opinions, and Actions Taken After Viewing Their Own Radiology Images Online: Web-Based Survey

BackgroundThe ability for patients to directly view their radiology images through secure electronic portals is rare in the American health care system. We previously surveyed patients within our health system and found that a large majority wanted to view their own radiology images online, and we have since implemented this new feature. ObjectiveWe aim to understand patient experiences, opinions, and actions taken after viewing their own radiology images online. MethodsWe emailed a web-based survey to patients who recently viewed their radiology images via our electronic patient portal. ResultsWe sent 1825 surveys to patients and received 299 responses (response rate 16.4%). Patients reported a favorable experience (258/299, 86.3% agree) viewing their radiology images online. Patients found value in reading their radiology reports (288/299, 96.3% agree) and viewing their images (267/299, 89.3% agree). Overall, patients felt that accessing and viewing their radiology images online increased their understanding of their medical condition (258/299, 82.9%), made them feel more in control and reassured (237/299, 79.2% and 220/299, 73.6%, respectively), and increased levels of trust (214/299, 71.6%). Only 6.4% (19/299) of the patients indicated concerns with finding errors, 6.4% (19/299) felt that viewing their images online made them worry more, and 7% (21/299) felt confused when viewing their images online. Of patients who viewed their images online, 45.2% (135/299) took no action with their images, 32.8% (98/299) saved a copy for their records, 25.4% (76/299) shared them with their doctor, and 14.7% (44/299) shared them with another doctor for a second opinion. A total of 9 patients (3%) shared their radiology images on Facebook, Instagram, or both, primarily to inform family and friends. Approximately 10.4% (31/299) of the patients had questions about their radiology images after viewing them online, with the majority (20/31, 65%) seeking out a doctor, and far fewer (5/31, 16%) choosing to ask a family member about their images. Finally, respondents viewed their images online using 1 or more devices, including computers, smartphones, tablets, or a combination of these devices. Approximately 26.7% (103/385) of the responses noted technical difficulties, with the highest incidence rate occurring with smartphones. ConclusionsWe report the first known survey results from patients who viewed their own radiology images through a web-based portal. Patients reported high levels of satisfaction and increased levels of trust, autonomy, reassurance, and medical understanding. Only a small minority of patients expressed anxiety or confusion. We suggest that patient access to radiology images, such as patient access to radiology reports, is highly desired by patients and is operationally practical. Other health care institutions should consider offering patients access to their radiology images online in the pursuit of information transparency

Microstructural changes within the basal ganglia differ between Parkinson disease subtypes

Diffusion tensor imaging (DTI) of the substantia nigra has shown promise in detecting and quantifying neurodegeneration in Parkinson disease (PD). It remains unknown, however, whether differences in microstructural changes within the basal ganglia underlie PD motor subtypes. We investigated microstructural changes within the basal ganglia of mild to moderately affected PD patients using DTI and sought to determine if microstructural changes differ between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes. Fractional anisotropy, mean diffusivity, radial and axial diffusivity were obtained from bilateral caudate, putamen, globus pallidus and substantia nigra of twenty-one PD patients (12 TD and 9 PIGD) and 20 age-matched healthy controls. T-tests and ANOVA methods were used to compare PD patients, subtypes, and controls, and Spearman correlations tested for relationships between DTI and clinical measures. We found our cohort of PD patients had reduced fractional anisotropy within the substantia nigra and increased mean and radial diffusivity within the substantia nigra and globus pallidus compared to controls, and that changes within those structures were largely driven by the PIGD subtype. Across all PD patients fractional anisotropy within the substantia nigra correlated with disease stage, while in PIGD patients increased diffusivity within the globus pallidus correlated with disease stage and motor severity. We conclude that PIGD patients have more severely affected microstructural changes within the substantia nigra compared to TD, and that microstructural changes within the globus pallidus may be particularly relevant for the manifestation of the PIGD subtype

Data from: Rituximab vs placebo induction prior to glatiramer acetate monotherapy in multiple sclerosis

Objective: To examine whether rituximab induction followed by glatiramer acetate (GA) monotherapy is more effective than GA alone for the treatment of relapsing MS with active disease. Methods: This was a single center, double-blind, placebo-controlled study(NCT01569451). Fifty-five participants were randomly assigned (1:1ratio) to either rituximab (R-GA) or placebo induction (P-GA), followed by all participants initiating GA therapy. Participants were followed up to 3-years. The primary endpoint was the number of participants with no evidence of disease activity (NEDA) (those without relapse, new MRI lesions and sustained change in disability. Results: Twenty-eight and 27 participants received rituximab and placebo induction, respectively, with one participant in each arm withdrawing prior to 6-month MRI. There were no significant differences in baseline characteristics. At end of study, 44.44% of R-GA participants demonstrated NEDA, vs 19.23% of P-GA participants (p = 0.049). A smaller proportion of R-GA participants failed treatment (37.04%R-GA vs 69.23%P-GA, p=0.019), and time to treatment failure was longer (23.32 monthsR-GA vs 11.29 monthsP-GA, p=0.027). Fewer participants in the R-GA arm had new lesions (25.93%R-GA vs 61.54%P-GA, p=0.009), and there were fewer new T2 lesions (0.48R-GA vs 1.96P-GA vs, p=0.027). Probability of demonstrating NEDA in the R-GA arm returned to baseline within the study period. There were no differences in adverse events. Conclusions: Induction therapy with rituximab followed by GA may provide superior efficacy in the short term to GA alone in relapsing MS, but this benefit appears to wane within the study period. Larger studies are needed to assess sustainability of results

Table e1 - Exploratory Patient Reported Outcomes Differences Between Study Groups

Table showing the differences in Patient Reported Outcome instruments from baseline to end of study with comparisons between the study groups

Table e2 - Infusion Reactions

Table detailing the various infusion reactions experienced in the two study groups (Rituximab vs Placebo infusion)