Faculty Bibliography

OBJECTIVE:Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS. METHODS:In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs). RESULTS:In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs. INTERPRETATION/CONCLUSIONS:In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups.

Spinal neurosarcoidosis is a rare form of neurosarcoid which can be challenging to diagnose given its clinical or radiographic findings are often indistinguishable from other causes of spinal demyelinating disease. We present a series of three patients with spinal neurosarcoid, all of whom demonstrated concurrent longitudinally enhancing transverse myelitis as well as spinal nerve root enhancement. These findings may be suggestive of spinal neurosarcoid and may help clinicians make the diagnosis as well as reduce the need for invasive biopsy.

OBJECTIVE:Medical student knowledge about brain death determination is limited. We describe an educational initiative to improve medical student awareness about brain death and assess the impact of this initiative. SUBJECTS AND METHODS/METHODS:Beginning in July 2016, students at our medical school were required to attend a 90-min brain death didactic and simulation session during their neurology clerkship. Students completed a test immediately before and after participating in the initiative. RESULTS:Of the 145 students who participated in this educational initiative between July 2016 and June 2017, 124 (86%) consented to have their data used for research purposes as part of a medical education registry. Students correctly answered a median of 53% of questions (IQR 47-58%) on the pretest and 86% of questions (IQR 78-89%) on the posttest (p < .001). Comfort with both performing a brain death evaluation and talking to a family about brain death improved significantly after this initiative (18% of students were comfortable performing a brain death evaluation before the initiative and 86% were comfortable doing so after the initiative, p < .001; 18% were comfortable talking to a family about brain death before the initiative and 76% were comfortable doing so after the initiative, p < .001). CONCLUSIONS:Incorporation of simulation in undergraduate medical education is high-yield. At our medical school, knowledge about brain death and comfort performing a brain death exam or talking to a family about brain death was limited prior to development of this initiative, but awareness and comfort dealing with brain death improved significantly after this initiative.

Objectives: To investigate the immune response to vaccinations in patients with relapsing forms of MS treated with delayed-release dimethyl fumarate (DMF) vs nonpegylated interferon (IFN). Methods: In this open-label, multicenter study, patients received 3 vaccinations: (1) tetanus-diphtheria toxoid (Td) to test T-cell-dependent recall response, (2) pneumococcal vaccine polyvalent to test T-cell-independent humoral response, and (3) meningococcal (groups A, C, W-135, and Y) oligosaccharide CRM197 conjugate to test T-cell-dependent neoantigen response. Eligible patients were aged 18-55 years, diagnosed with relapsing-remitting MS (RRMS), and either treated for >/=6 months with an approved dose of DMF or for >/=3 months with an approved dose of nonpegylated IFN. Primary end point was the proportion of patients with >/=2-fold rise in antitetanus serum IgG levels from prevaccination to 4 weeks after vaccination. Results: Seventy-one patients (DMF treated, 38; IFN treated, 33) were enrolled. The mean age was 45.3 years (range 27-55); 86% were women. Responder rates (>/=2-fold rise) to Td vaccination were comparable between DMF- and IFN-treated groups (68% vs 73%). Responder rates (>/=2-fold rise) were also similar between DMF- and IFN-treated groups for diphtheria antitoxoid (58% vs 61%), pneumococcal serotype 3 (66% vs 79%), pneumococcal serotype 8 (95% vs 88%), and meningococcal serogroup C (53% vs 53%), all p > 0.05. In a post hoc analysis, no meaningful differences were observed between groups in the proportion of responders when stratified by age category or lymphocyte count. Conclusions: DMF-treated patients mount an immune response to recall, neoantigens, and T-cell-independent antigens, which was comparable with that of IFN-treated patients and provided adequate seroprotection. ClinicalTrialsgov identifier: NCT02097849. Classification of evidence: This study provides Class II evidence that patients with RRMS treated with DMF respond to vaccinations comparably with IFN-treated patients.

Background: Paroxysmal tonic spasms, also known as tonic seizures or paroxysmal dystonia, can be an atypical presenting or complicating feature of multiple sclerosis (MS). They entail sudden, stereotyped episodes of abnormal posture. They are often brief, occurring many times a day, either spontaneously or provoked by movement, touch, or other maneuvers. We describe five such patients, all of whom had a demyelinating lesion in the contralateral corticospinal tract in the posterior limb of the internal capsule. Objective: To present a case series of five patients with MS who experienced tonic spasms and their localisation. Methods: Chart review and literature search. Results: Five cases of tonic spasms in MS with correlating corticospinal tract lesions: Case 1: A 29-year-old female presented with cramping in her right arm and leg with abnormal posturing of the hand and foot with clenching and overlapping of digits. Case 2: A 30-year-old female with frequent episodes of right arm and leg dystonic movements with fanning of the fingers and toes. Case 3: A 39-year-old male with left facial twitching and spams of the left hand elicited by yawning. Case 4: A 29-year-old female with MS with involuntary clenching of the left hand. Case 5: A 34-year-old female with tingling of the right arm and leg followed by involuntary flexion of the right wrist and fingers. In all cases, a brain MRI showed a demyelinating lesion in the contralateral corticospinal tract in the posterior limb of the internal capsule, as well as other lesions consistent with MS. Conclusions: Tonic spasms in MS can be localised to the contralateral posterior limb of the internal capsule. While non-epileptic in origin, they often respond to anti-epileptic drugs. Prompt recognition of this phenomenon can expedite work up and facilitate treatment

BACKGROUND: Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS). OBJECTIVES: The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS). METHODS: Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores. RESULTS: PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R2 0.328, p = 0.00004; adjusted R2 0.187, p = 0.002 and adjusted R2 0.180, p = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R2 value 0.361, p = 0.00001) and LCVA 2.50% (adjusted R2 value 0.323, p = 0.00003). CONCLUSION: A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS.

Objective: To present clinical and radiographic descriptions of conditions that may feature corticospinal tract abnormalities observed on magnetic resonance imaging (MRI). Background: Corticospinal tract lesions have a broad differential diagnosis, including neurodegenerative diseases, toxic/metabolic derangements, malignancies, autoimmune diseases, infectious diseases, and neurogenetic conditions. Design/Methods: Review of clinical presentations and brain MRIs. Results: Conditions that have been associated with corticospinal tract hyperintensities on brain MRI include: amyotrophic lateral sclerosis, primary lateral sclerosis, heroin leukoencephalopathy, brainstem glioma, neuroBehcets, HIV infection, neuromyelitis optica, Krabbe A disease, adult polyglucosan body disorder, Xlinked Charcot-Marie-Tooth disease, Behr syndrome, Whipple disease, and sequela of liver transplantation. We present representative images and discuss clinical and radiographic features that distinguishing these conditions. Conclusions: Corticospinal tract lesions have a heterogenous etiology, with widely different treatments and prognoses. An understanding of these potential etiologies will assist neurologists confronted with this imaging finding