Gary Stobbe

Differential SPECT Activation Patterns Associated with PASAT Performance May Indicate Frontocerebellar Functional Dissociation in Chronic Mild Traumatic Brain Injury

Patients with mild traumatic brain injury (TBI) often complain of cognitive fatigue during the chronic recovery phase. The Paced Auditory Serial Addition Test (PASAT) is a complex psychologic measure that may demonstrate subtle deficiencies in higher cognitive functions. The purpose of this study was to investigate the brain activation of regional cerebral blood flow (rCBF) with PASAT in patients with mild TBI to explore mechanisms for the cognitive fatigue. Methods: Two groups consisting of 15 patients with mild TBI and 15 healthy control subjects underwent 99mTc-ethylene cysteine dimer SPECT at rest and during PASAT on a separate day. Cortical rCBF was extracted using a 3-dimensional stereotactic surface projection and statistically analyzed to identify areas of activation, which were compared with PASAT performance scores. Results: Image analysis demonstrated a difference in the pattern of activation between patients with mild TBI and healthy control subjects. Healthy control subjects activated the superior temporal cortex (Brodmann area [BA] 22) bilaterally, the precentral gyrus (BA 9) on the left, and the precentral gyrus (BA 6) and cerebellum bilaterally. Patients with mild TBI demonstrated a larger area of supratentorial activation (BAs 9, 10, 13, and 46) but a smaller area of activation in the cerebellum, indicating frontocerebellar dissociation. Conclusion: Patients with mild TBI and cognitive fatigue demonstrated a different pattern of activation during PASAT. Frontocerebellar dissociation may explain cognitive impairment and cognitive fatigue in the chronic recovery phase of mild traumatic brain injury.

Natalizumab-related PML 2 weeks after negative anti-JCV antibody assay

Progressive multifocal leukoencephalopathy (PML) is a serious complication of natalizumab pharmacotherapy, caused by the JC virus (JCV), against which 60% of adults have detectable serum antibodies.1 The most common symptoms of PML are cognitive impairment, motor dysfunction, visual abnormalities, and speech deficit.2 Although the mortality rate of 23%3 in natalizumab-associated cases is lower compared to PML from other causes, most survivors have a poor functional outcome.4 As of March 3, 2015, Biogen had reported 541 cases of natalizumab-related PML. Of 278 cases with available data, only 2 were negative for anti-JCV antibody; these 2 patients had tests dating from 8 and 9 months prior to diagnosis.3

Diagnostic yield of array comparative genomic hybridization in adults with autism spectrum disorders

Purpose:Array comparative genomic hybridization is available for the evaluation of autism spectrum disorders. The diagnostic yield of testing is 5–18% in children with developmental disabilities, including autism spectrum disorders and multiple congenital anomalies. The yield of array comparative genomic hybridization in the adult autism spectrum disorder population is unknown.Methods:We performed a retrospective chart review for 40 consecutive patients referred for genetic evaluation of autism from July 2009 through April 2012. Four pediatric patients were excluded. Medical history and prior testing were reviewed. Clinical genetic evaluation and testing were offered to all patients.Results:The study population comprised 36 patients (age range 18–45, mean 25.3 years). An autism spectrum disorder diagnosis was confirmed in 34 of 36 patients by medical record review. One patient had had an abnormal karyotype; none had prior array comparative genomic hybridization testing. Of the 23 patients with autism who underwent array comparative genomic hybridization, 2 of 23 (8.7%) had pathogenic or presumed pathogenic abnormalities and 2 of 23 (8.7%) had likely pathogenic copy-number variants. An additional 5 of 23 (22%) of autism patients had variants of uncertain significance without subclassification.Conclusion:Including one patient newly diagnosed with fragile X syndrome, our data showed abnormal or likely pathogenic findings in 5 of 24 (21%) adult autism patients. Genetic reevaluation in adult autism patients is warranted.Genet Med 16 1 70–77.

Lifetime exposure to ultraviolet radiation and the risk of multiple sclerosis in the US radiologic technologists cohort study

Background: Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body. Objective: This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists. Methods: Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA’s Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose. Results: Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk. Conclusion: Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.

Impact of Multiple Sclerosis Project ECHO on Provider Confidence and Clinical Practice

Background Project ECHO (Extension for Community Healthcare Outcomes) represents a novel approach to addressing disparities in multiple sclerosis (MS) care. A primary mechanism of the program is the use of case consultations to rapidly transfer knowledge from content experts to community providers who care for individuals with MS. Methods MS Project ECHO was pilot tested as a weekly 60-minute videoconference delivered to 24 clinicians across 13 practice sites over 41 weeks. Participants completed a variety of measures related to their experience in the program and answered qualitative questions via exit interview. We report on the responses to exit interview questions related to the case consultation component of MS Project ECHO. Results Participant responses regarding case consultations generated four themes: 1) improved confidence among participants in the existing treatment decision, 2) direct change in the care of the patient provided by the participant, 3) changed practice habits for all of the participants patients with MS, and 4) increased perception that patients had confidence in the participant as an MS care provider. Conclusions Participant responses support MS Project ECHO as a program that may directly and indirectly affect the way providers deliver MS care in underserved areas. Further research is needed to examine the resulting effect on patient outcomes.

Project Extension for Community Healthcare Outcomes (ECHO) in Multiple Sclerosis

Background A pilot program using the Project Extension for Community Healthcare Outcomes (ECHO) model was conducted for multiple sclerosis (MS) clinicians in the Pacific Northwest. The pilot was a collaboration between the National Multiple Sclerosis Society and faculty at the University of Washington. The goal was to determine the feasibility of using this telehealth model to increase the capacity and capability of clinicians in rural areas to treat people with MS. Methods Thirteen practice sites with 24 clinicians were recruited to participate. Videoconferencing was used to conduct weekly sessions consisting of brief didactics followed by case consultations. Results Most participants completing the outcome survey (10 of 15) indicated that they were more confident in treating patients with MS. They were satisfied with the training, felt better able to care for their patients, and had made changes in their treatment based on the case consultations and didactic content. They valued the case studies and case-based didactics and learned from each other as well as from the team. Conclusions The pilot MS Project ECHO warrants further investigation regarding its potential effect on access to MS care delivery for underserved populations.

Accelerating international MS care through videoconference-based education and case consultation

Disparities exist in the international management of multiple sclerosis (MS). For example, when stratified by income, only high-income countries have a high rate of availability of all disease-modifying therapies (DMTs); as income decreases, the availability of DMTs declines rapidly, such that even upper-middle-income countries commonly only have access to first-line therapies but not the newer, potentially more potent agents, and low-income countries have no access to DMTs.1 As newer DMTs associated with greater risk of toxicity become more available, providers in those countries are playing catch-up to the international community in providing guideline-level MS care.2 This adds to the challenge already described by providers where advanced MS treatments are available: it is difficult to remain current on important domains related to DMT prescription, including selecting the correct DMT for a specific patients characteristics, safety data, and monitoring guidelines, resulting in a call for targeted continuing medical education.3 Taken together, it is in the interest of the international MS community to have providers with more experience using these DMTs spread the knowledge they have gleaned to providers in countries where these same treatments are emerging. Our videoconference-based education and case consultation program can efficiently meet this need.