The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

BACKGROUND: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. OBJECTIVE: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. METHODS: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). RESULTS: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03). CONCLUSIONS: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.

Predictors of faculty narrative evaluation quality in medical school clerkships.

INTRODUCTION: Narrative approaches to assessment provide meaningful and valid representations of trainee performance. Yet, narratives are frequently perceived as vague, nonspecific and low quality. To date, there is little research examining factors associated with narrative evaluation quality, particularly in undergraduate medical education. The purpose of this study was to examine associations of faculty- and student-level characteristics with the quality of faculty member's narrative evaluations of clerkship students. METHODS: The authors reviewed faculty narrative evaluations of 50 students' clinical performance in their inpatient medicine and neurology clerkships, resulting in 165 and 87 unique evaluations in the respective clerkships. The authors evaluated narrative quality using the Narrative Evaluation Quality Instrument (NEQI). The authors used linear mixed effects modelling to predict total NEQI score. Explanatory covariates included the following: time to evaluation completion, number of weeks spent with student, faculty total weeks on service per year, total faculty years in clinical education, student gender, faculty gender, and an interaction term between student and faculty gender. RESULTS: Significantly higher narrative evaluation quality was associated with a shorter time to evaluation completion, with NEQI scores decreasing by approximately 0.3 points every 10 days following students' rotations (p = .004). Additionally, women faculty had statistically higher quality narrative evaluations with NEQI scores 1.92 points greater than men faculty (p = .012). All other covariates were not significant. CONCLUSIONS: The quality of faculty members' narrative evaluations of medical students was associated with time to evaluation completion and faculty gender but not faculty experience in clinical education, faculty weeks on service, or the amount of time spent with students. Findings advance understanding on ways to improve the quality of narrative evaluations which are imperative given assessment models that will increase the volume and reliance on narratives.

Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.

Hypomyelinating leukodystrophies are genetically heterogeneous disorders with overlapping clinical and neuroimaging features reflecting variable abnormalities in myelin formation. We report on the identification of biallelic inactivating mutations in NKX6-2, a gene encoding a transcription factor regulating multiple developmental processes with a main role in oligodendrocyte differentiation and regulation of myelin-specific gene expression, as the cause underlying a previously unrecognized severe variant of hypomyelinating leukodystrophy. Five affected subjects (three unrelated families) were documented to share biallelic inactivating mutations affecting the NKX6-2 homeobox domain. A trio-based whole exome sequencing analysis in the first family detected a homozygous frameshift change [c.606delinsTA; p.(Lys202Asnfs*?)]. In the second family, homozygosity mapping coupled to whole exome sequencing identified a homozygous nucleotide substitution (c.565G>T) introducing a premature stop codon (p.Glu189*). In the third family, whole exome sequencing established compound heterozygosity for a non-conservative missense change affecting a key residue participating in DNA binding (c.599G>A; p.Arg200Gln) and a nonsense substitution (c.589C>T; p.Gln197*), in both affected siblings. The clinical presentation was homogeneous, with four subjects having severe motor delays, nystagmus and absent head control, and one individual showing gross motor delay at the age of 6 months. All exhibited neuroimaging that was consistent with hypomyelination. These findings define a novel, severe form of leukodystrophy caused by impaired NKX6-2 function.

Numerical versus narrative: A comparison between methods to measure medical student performance during clinical clerkships.

BACKGROUND: Medical school evaluations typically rely on both language-based narrative descriptions and psychometrically converted numeric scores to convey performance to the grading committee. We evaluated inter-rater reliability and correlation of numeric versus narrative evaluations for students on their Neurology Clerkship. DESIGN/METHODS: 50 Neurology Clerkship in-training evaluation reports completed by their residents and faculty members at the University of Rochester School of Medicine were dissected into narrative and numeric components. 5 Clerkship grading committee members retrospectively gave new narrative scores (NNS) while blinded to original numeric scores (ONS). We calculated intra-class correlation coefficients (ICC) and their associated confidence intervals for the ONS and the NNS. In addition, we calculated the correlation between ONS and NNS. RESULTS: The ICC was greater for the NNS (ICC = .88 (95% CI = .70-.94)) than the ONS (ICC = .62 (95% CI = .40-.77)) Pearson correlation coefficient showed that the ONS and NNS were highly correlated (r = .81). CONCLUSIONS: Narrative evaluations converted by a small group of experienced graders are at least as reliable as numeric scoring by individual evaluators. We could allow evaluators to focus their efforts on creating richer narrative of greater value to trainees.

Enhancing neural transmission in multiple sclerosis (4-aminopyridine therapy).

Enhancing neural transmission by improving axonal conduction and synaptic neurotransmitter release is a novel strategy to improve symptoms in multiple sclerosis. Dalfampridine (4-aminopyridine extended-release) is a first-in-class medication that targets the damaged nervous system through blockage of voltage-gated potassium channels. Through a series of clinical trials, dalfampridine (dosed at 10 mg twice daily) has been found to improve walking speed by approximately 25 % on average in one third of individuals with multiple sclerosis regardless of disease stage. Furthermore, it significantly improves patients' perception of their ambulatory disability and may improve lower extremity strength. Given the mechanism of action, the most serious adverse effect is its pro-convulsant property, which occurs more frequently at high serum concentrations. The most common adverse events include increased falls, urinary tract infections, dizziness, insomnia, and headaches. Despite these potential side-effects, the vast majority of individuals who derive benefit continue on the treatment. The exact mechanism of action is uncertain, as is the reason for response variability. The medication serves as proof-of-concept that targeting axonal transmission can improve disability in multiple sclerosis.