Hourglass-like constrictions on MRI are common in electromyography-confirmed cases of neuralgic amyotrophy (Parsonage-Turner syndrome): A tertiary referral center experience.

INTRODUCTION/AIMS: Hourglass-like constrictions (HGCs) of involved nerves in neuralgic amyotrophy (NA) (Parsonage-Turner syndrome) have been increasingly recognized with magnetic resonance neurography (MRN). This study sought to determine the sensitivity of HGCs, detected by MRN, among electromyography (EMG)-confirmed NA cases. METHODS: This study retrospectively reviewed records of patients with the clinical diagnosis of NA, and with EMG confirmation, who underwent 3-Tesla MRN within 90 days of EMG at a single tertiary referral center between 2011 and 2021. "Severe NA" positive cases were defined by a clinical diagnosis and specific EMG criteria: fibrillation potentials or positive sharp waves, along with motor unit recruitment (MUR) grades of "discrete" or "none." On MRN, one or more HGCs, defined as focally decreased nerve caliber or diffusely beaded appearance, was considered "imaging-positive." Post hoc inter-rater reliability for HGCs was measured by comparing the original MRN report against subsequent blinded interpretation by a second radiologist. RESULTS: A total of 123 NA patients with 3-Tesla MRN performed within 90 days of EMG were identified. HGCs were observed in 90.2% of all NA patients. In "severe NA" cases, based on the above EMG criteria, HGC detection resulted in a sensitivity of 91.9%. Nerve-by-nerve analysis (183 nerve-muscle pairs, nerves assessed by MRN, muscles assessed by EMG) showed a sensitivity of 91.0%. The second radiologist largely agreed with the original HGC evaluation, (94.3% by subjects, 91.8% by nerves), with no significant difference between evaluations (subjects: χ2 = 2.27, P = .132, nerves: χ2 = 0.98, P = .323). DISCUSSION: MRN detection of HGCs is common in NA.

Parsonage-Turner syndrome following monkeypox infection and vaccination.

Beginning in May 2022, monkeypox infection and vaccination rates dramatically increased due to a worldwide outbreak. This case highlights magnetic resonance (MR) neurography findings in an individual who developed Parsonage-Turner syndrome (PTS) 5 days after monkeypox symptom onset and 12 days after receiving the JYNNEOS vaccination. MR neurography of the patient's left suprascapular nerve demonstrated intrinsic hourglass-like constrictions, a characteristic finding of peripheral nerves involved in PTS. Other viral infections and vaccinations are well-documented triggers of PTS, an underrecognized peripheral neuropathy that is thought to be immune-mediated and results in severe upper extremity pain and weakness. The close temporal relationship between monkeypox infection and vaccination, and PTS onset, in this case, suggests a causal relationship and marks the first known report of peripheral neuropathy associated with monkeypox.

Leveraging Systematic Functional Analysis to Benchmark an In Silico Framework Distinguishes Driver from Passenger MEK Mutants in Cancer.

Despite significant advances in cancer precision medicine, a significant hurdle to its broader adoption remains the multitude of variants of unknown significance identified by clinical tumor sequencing and the lack of biologically validated methods to distinguish between functional and benign variants. Here we used functional data on MAP2K1 and MAP2K2 mutations generated in real-time within a co-clinical trial framework to benchmark the predictive value of a three-part in silico methodology. Our computational approach to variant classification incorporated hotspot analysis, three-dimensional molecular dynamics simulation, and sequence paralogy. In silico prediction accurately distinguished functional from benign MAP2K1 and MAP2K2 mutants, yet drug sensitivity varied widely among activating mutant alleles. These results suggest that multifaceted in silico modeling can inform patient accrual to MEK/ERK inhibitor clinical trials, but computational methods need to be paired with laboratory- and clinic-based efforts designed to unravel variabilities in drug response. SIGNIFICANCE: Leveraging prospective functional characterization of MEK1/2 mutants, it was found that hotspot analysis, molecular dynamics simulation, and sequence paralogy are complementary tools that can robustly prioritize variants for biologic, therapeutic, and clinical validation.See related commentary by Whitehead and Sebolt-Leopold, p. 4042.