Subacute Brachial Plexopathy due to Intraneural Epithelioid Hemangioma: A Case Report.

Brachial plexopathy is a common consideration in the differential diagnosis of upper extremity sensory and motor deficits, and neoplasms signify one possible etiology of brachial plexopathy. Of the neoplastic brachial plexopathies, hemangiomas involving the brachial plexus are rare. Most reported cases describe extraneural brachial plexus hemangiomas that present as a palpable, tender neck mass associated with pain and sensory disturbance, with minimal motor deficits. Here we share the case of a 48 year-old man with intraneural epithelioid hemangioma of the brachial plexus who presented with prominent motor weakness and no palpable mass. The patient presented with subacute onset of left arm pain, numbness and progressive weakness. Neurologic exam revealed lower motor neuron signs and weakness spanning multiple nerve root and peripheral nerve distributions. Dedicated brachial plexus MRI showed two mass lesions involving the cords of the brachial plexus, with corresponding FDG-avidity on PET/CT. Biopsy revealed intraneural atypical epithelioid hemangioma. After nerve transfer surgery, he had moderate improvement in left arm strength. This case serves to: emphasize the importance of both clinical localization and dedicated brachial plexus imaging in the evaluation of brachial plexopathy; introduce to the literature a new clinical presentation of brachial plexus hemangiomas; encourage consideration of neoplastic brachial plexopathy even when faced with an illness script resembling Parsonage-Turner Syndrome, to avoid delays in diagnosis and treatment.

Artificial intelligence in neuro-oncology.

Artificial intelligence (AI) describes the application of computer algorithms to the solution of problems that have traditionally required human intelligence. Although formal work in AI has been slowly advancing for almost 70 years, developments in the last decade, and particularly in the last year, have led to an explosion of AI applications in multiple fields. Neuro-oncology has not escaped this trend. Given the expected integration of AI-based methods to neuro-oncology practice over the coming years, we set to provide an overview of existing technologies as they are applied to the neuropathology and neuroradiology of brain tumors. We highlight current benefits and limitations of these technologies and offer recommendations on how to appraise novel AI-tools as they undergo consideration for integration into clinical workflows.

Glioblastoma in Patients With Multiple Sclerosis.

Background: Although rare, the co-occurrence of multiple sclerosis (MS) and glioma poses unique challenges in terms of diagnosis and management for both neurologists and neuro-oncologists. Methods: Here we report on a single-center cohort of four patients with a diagnosis of multiple sclerosis who developed gliomas. Results: Our cohort reflects the epidemiology of glioma in terms of the relative frequency of IDH-wildtype and IDH-mutant cases. The patients in 3 out of the 4 cases presented did not develop their tumors in areas of pre-existing demyelinating lesions. Conclusions: We did not find evidence to support the hypothesis that chronic gliosis from demyelinating plaques may serve as a substrate for secondary induction of a glial neoplasm. In our Discussion, we provide recommendations for distinguishing neoplastic from demyelinating lesions, review the evidence for demyelination as a risk factor for gliomagenesis, and highlight important considerations for the concurrent management of glioma and MS.

Early-life trauma endophenotypes and brain circuit-gene expression relationships in functional neurological (conversion) disorder.

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network-trauma relationships in this population. In this neuroimaging-gene expression study, we used two graph theory approaches to elucidate ELM subtype effects on resting-state functional connectivity architecture in 30 patients with motor FND. Twenty-one individuals with comparable depression, anxiety, and ELM scores were used as psychiatric controls. Thereafter, we compared trauma endophenotypes in FND with regional differences in transcriptional gene expression as measured by the Allen Human Brain Atlas (AHBA). In FND patients only, we found that early-life physical abuse severity, and to a lesser extent physical neglect, correlated with corticolimbic weighted-degree functional connectivity. Connectivity profiles influenced by physical abuse occurred in limbic (amygdalar-hippocampal), paralimbic (cingulo-insular and ventromedial prefrontal), and cognitive control (ventrolateral prefrontal) areas, as well as in sensorimotor and visual cortices. These findings held adjusting for individual differences in depression/anxiety, PTSD, and motor phenotypes. In FND, physical abuse also correlated with amygdala and insula coupling to motor cortices. In exploratory analyses, physical abuse correlated connectivity maps overlapped with the AHBA spatial expression of three gene clusters: (i) neuronal morphogenesis and synaptic transmission genes in limbic/paralimbic areas; (ii) locomotory behavior and neuronal generation genes in left-lateralized structures; and (iii) nervous system development and cell motility genes in right-lateralized structures. These circuit-specific architectural profiles related to individual differences in childhood physical abuse burden advance our understanding of the pathophysiology of FND.

Functional (Psychogenic) Neurological Disorders: Assessment and Acute Management in the Emergency Department.

Functional neurological disorders (FND) are complex and prevalent neuropsychiatric conditions. Importantly, some patients with FND develop acute onset symptoms requiring emergency department (ED) evaluations. Historically, FND was a "rule-out" diagnosis, making assessment and management in the ED difficult. While the rapid triage of potential neurological emergencies remains the initial task, advancements have altered the approach to FND. FND is now a "rule-in" diagnosis based on validated neurological examination signs and semiological features. In this perspective article, we review signs and semiological features that can help guide the initial assessment of FND in the acute setting. Thereafter, we outline potential approaches to introduce a suspected diagnosis of FND to patients in the ED, while emphasizing the need for a comprehensive neurological evaluation. Physical and occupational therapy may be useful adjunct assessments in some individuals. Notably, clinicians in the ED setting are important members of the interdisciplinary approach to FND.

Longitudinal growth curves for children with classical osteogenesis imperfecta (types III and IV) caused by structural pathogenic variants in type I collagen.

PURPOSE: Growth deficiency is a cardinal feature of osteogenesis imperfecta (OI) types III and IV, caused by pathogenic variants in type I collagen. OI-specific longitudinal growth charts are needed for patient care. METHODS: We compiled longitudinal length, weight, head circumference, and body mass index (BMI) data from 100 children with types III and IV OI and known type I collagen pathogenic variants. Effects of gender, OI type, and pathogenic variant were examined using multilevel modeling. OI-specific centile curves were constructed using generalized additive model for location, scale, and shape (GAMLSS). RESULTS: OI type and gender, but not the specific mutated collagen gene, significantly affect stature, but only OI type affects weight. Head circumference was not significantly different by gender, type, or mutated gene. In both genders, length curves for types III and IV OI overlap and the type IV 95th centile curve overlaps the lower US Centers for Disease Control and Prevention (CDC) curves for the general population. A pubertal growth spurt is generally absent or blunted in types III/IV OI. The body mass index 50th and 95th centile curves are distinctly shifted above respective US CDC curves in both genders. CONCLUSIONS: OI type is a stronger contributing factor than gender for OI growth, while curves do not differ for COL1A1 versus COL1A2 pathogenic variants. Types III and IV OI-specific growth curves are presented.

CDKN2B Loss Promotes Progression from Benign Melanocytic Nevus to Melanoma.

UNLABELLED: Deletion of the entire CDKN2B-CDKN2A gene cluster is among the most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss of CDKN2A-encoded p16 and p14ARF tumor suppressors. The degree to which the associated CDKN2B-encoded p15 loss contributes to human tumorigenesis is unclear. Here, we show that CDKN2B is highly upregulated in benign melanocytic nevi, contributes to maintaining nevus melanocytes in a growth-arrested premalignant state, and is commonly lost in melanoma. Using primary melanocytes isolated directly from freshly excised human nevi naturally expressing the common BRAF(V600E)-activating mutation, nevi progressing to melanoma, and normal melanocytes engineered to inducibly express BRAF(V600E), we show that BRAF activation results in reversible, TGFß-dependent, p15 induction that halts proliferation. Furthermore, we engineer human skin grafts containing nevus-derived melanocytes to establish a new, architecturally faithful, in vivo melanoma model, and demonstrate that p15 loss promotes the transition from benign nevus to melanoma. SIGNIFICANCE: Although BRAF(V600E) mutations cause melanocytes to initially proliferate into benign moles, mechanisms responsible for their eventual growth arrest are unknown. Using melanocytes from human moles, we show that BRAF activation leads to a CDKN2B induction that is critical for restraining BRAF oncogenic effects, and when lost, contributes to melanoma.