The Historical Case for a Strong and Diverse Neurology Clerkship Leadership Team.

The role of the clerkship director has evolved significantly over the past century and now requires a diverse range of skills to meet the rigorous standards set by national accrediting bodies such as the Liaison Committee on Medical Education. We conducted a historical exploration, spanning the past 43 years, of the educational practices in the Neurology Department at Johns Hopkins University School of Medicine. We learned that no entity is responsible for documenting the history of the clerkship.

Clinical Reasoning: A 63-Year-Old Man With Progressive Multicranial Neuropathy and Leptomeningeal Enhancement.

A 63-year-old man, with a history of melanoma and basal cell carcinoma, presented with progressive right-sided facial numbness, vertical diplopia, and headache. Brain MRI revealed leptomeningeal enhancement of multiple cranial nerves and an enhancing mass-like lesion along the anterolateral surface of the pons and midbrain. Subsequent brain biopsy demonstrated the final diagnosis.

Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1).

Consensus recommendation published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation to enable appropriate intervention for affected patients. To this end, we assembled a multi-institutional expert pathology working group as part of a "Symposium on Atypical Neurofibroma: State of the Science".

Cutaneous Neurofibromas and Quality of Life in Adults With Neurofibromatosis Type 1.

Importance: There is a burgeoning interest in therapeutic development for cutaneous neurofibromas (cNFs), a major cause of morbidity in persons with neurofibromatosis type 1 (NF1). To determine meaningful clinical trial outcomes, deeper understanding is needed regarding how cNFs are associated with quality of life (QoL). However, this understanding has been hampered by challenges in recruiting participants with this rare genetic disease.

Existing and Developing Preclinical Models for Neurofibromatosis Type 1-Related Cutaneous Neurofibromas.

Neurofibromatosis type 1 (NF1) is caused by a nonfunctional copy of the NF1 tumor suppressor gene that predisposes patients to the development of cutaneous neurofibromas (cNFs), the skin tumor that is the hallmark of this condition. Innumerable benign cNFs, each appearing by an independent somatic inactivation of the remaining functional NF1 allele, form in nearly all patients with NF1. One of the limitations in developing a treatment for cNFs is an incomplete understanding of the underlying pathophysiology and limitations in experimental modeling.

Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography.

Cutaneous Neurofibroma Heterogeneity: Factors that Influence Tumor Burden in Neurofibromatosis Type 1.

Neurofibromatosis type 1 is one of the most common genetic disorders of the nervous system and predisposes patients to develop benign and malignant tumors. Cutaneous neurofibromas (cNFs) are NF1-associated benign tumors that affect nearly 100% of patients with NF1. cNFs dramatically reduce patients' QOL owing to their unaesthetic appearance, physical discomfort, and corresponding psychological burden.

Target Product Profile for Cutaneous Neurofibromas: Clinical Trials to Prevent, Arrest, or Regress Cutaneous Neurofibromas.

Cutaneous neurofibromas (cNFs) are benign tumors of the skin that affect >95% of adults with neurofibromatosis type 1. Despite their benign histology, cNFs can significantly impact QOL due to disfigurement, pain, and pruritus. There are no approved therapies for cNFs.

RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.

Cutaneous neurofibromas (cNFs) are the most common tumor in people with the rasopathy neurofibromatosis type 1. They number in hundreds or even thousands throughout the body, and currently, there are no effective interventions to prevent or treat these skin tumors. To facilitate the identification of novel and effective therapies, essential studies including a more refined understanding of cNF biology and the role of RAS signaling and downstream effector pathways responsible for cNF initiation, growth, and maintenance are needed.

Curriculum Innovation: Teaching Neuroethics Through a Case-Based Undergraduate Medical Education Workshop: Implementation and Evaluation.

Background And Problem Statement: Medical students on their clinical neurology clerkship often encounter ethically challenging situations, yet formal neuroethics training is limited. This study sought to evaluate a case-based small-group workshop that was implemented to introduce students to important neuroethics concepts and resources.

Objectives: (1) To define decision-making capacity and describe how it is assessed in neurologic illness; (2) to define the legal category of brain death and its evolution over time; (3) to describe the legal process for surrogate decision making in the state of Maryland; (4) to identify barriers to goals-of-care conversations; and (5) to reflect on how personal beliefs of patients and physicians influence delivery of care and medical decision making.

cNF-Skindex in Adults Living with Neurofibromatosis 1: Severity Strata in France and Validation in United States Adults.

Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient's burden.

Whole body MRI with DWI in people with NF1 and Schwannomatosis: Are qualitative and quantitative imaging features of peripheral lesions comparable to localized MRI?

Purpose: To compare the qualitative and quantitative features of peripheral lesions on localized (L) and whole-body (WB) magnetic resonance imaging (MRI) in people with neurofibromatosis type 1 (NF1) and schwannomatosis.

Materials And Methods: This is a retrospective, HIPAA compliant study with twenty-seven patients (14 women, 13 men; mean age (years): 38 (3-67)) who underwent both L-MRI and WB-MRI without interval treatment. WB-MRI and L-MRI were comprised of T1-weighted, fat suppressed (FS) T2-weighted or short tau inversion recovery (STIR), diffusion-weighted imaging (DWI) using b-values of 50, 400, and 800 s/mm2, apparent diffusion coefficient (ADC) mapping and pre- and post-contrast FST1 sequences.

Clinical, histological, and molecular features of gliomas in adults with neurofibromatosis type 1.

Background: People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research.

Methods: Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified.

Quantitation of terameprocol in human plasma by liquid chromatography-tandem mass spectrometry.

The global transcription inhibitor terameprocol is being evaluated clinically as an oral formulation to treat high-grade glioma. A sensitive, reliable method was developed to quantitate terameprocol using LC-MS/MS to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile.

Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Adult Medulloblastoma Workshop.

Background: Medulloblastoma (MB) is a rare brain tumor occurring more frequently in children in whom research has been primarily focused. Treatment recommendations in adults are mainly based on retrospective data and pediatric experience; however, molecular features and treatment tolerance differ between the 2 age groups. In adults, prognostic tools are suboptimal, late recurrences are typical, and long-term sequelae remain understudied.

Quantifying the utility of a multidisciplinary neuro-oncology tumor board.

Objective: There has been limited research on the efficacy of multidisciplinary tumor boards (MDTBs) in improving the treatment of patients with tumors affecting the nervous system. The objective of the present study was to quantify the utility of MDTBs in providing alternative diagnostic interpretations and treatment plans for this patient population.

Methods: The authors performed a prospective study of patients in 4 hospitals whose cases were discussed at MDTBs between July and November 2019.

NCI-CONNECT: Comprehensive Oncology Network Evaluating Rare CNS Tumors-Histone Mutated Midline Glioma Workshop Proceedings.

Histone mutations occur in approximately 4% of different cancer types. In 2012, mutations were found in the gene encoding histone variant H3.3 ( gene) in pediatric diffuse intrinsic pontine gliomas and pediatric hemispheric gliomas.

A systematic review of tumor treating fields therapy for high-grade gliomas.

Introduction: Tumor treating fields (TTF) is a unique treatment modality that utilizes alternating electric fields to deliver therapy. Treatment effects have been assessed in patients with newly diagnosed and recurrent glioblastoma in clinical trials and retrospective studies. While the results of these studies led to FDA approval for both populations, a portion of the neuro-oncology and neurosurgery community remains skeptical of TTF.

Management of glioblastoma: a perspective from Mexico.

Access to healthcare in Mexico is available to its population via publicly and privately funded institutions. The public sector, administered by both the local and federal government under the jurisdiction of the Department of Health, provides healthcare to the majority of the country's population. Privately funded institutions vary in size and scope of practice, ranging from small clinics focused on family practice, to large tertiary hospitals with capacity for treating patients with complex conditions and performing clinical research.

Brain Metastases as a First Site of Recurrence in Patients Receiving Chemotherapy with Controlled Systemic Cancer: a Critical but Under-Recognized Clinical Scenario.

Purpose Of Review: As the treatment of many malignancies has improved, brain metastases (BM) have been observed as a site of the first recurrence in patients with controlled systemic cancers. This suggests that while the administered chemotherapy is effective against systemic cancer, drug concentrations in the central nervous system (CNS) are likely too low to be effective. These findings are in accord with data suggesting that more than 98% of FDA-approved drugs on the market today are unable to cross the blood-brain barrier (BBB).

Widely metastatic IDH1-mutant glioblastoma with oligodendroglial features and atypical molecular findings: a case report and review of current challenges in molecular diagnostics.

Background: Gliomas with 1p/19q-codeletion as well as mutation of isocitrate dehydrogenase (IDH) 1 are typically characterized as oligodendrogliomas with comparatively good response to treatment with radiation and chemotherapy.

Case Presentation: We present the case of a 28-year-old man with an IDH1 and TP53 mutant high grade glioma with abnormalities in chromosomes 1 and 19 suggestive of anaplastic oligodendroglioma that rapidly progressed to widespread metastatic disease. Biopsy of a liver lesion confirmed metastasis of the patient's known brain primary and chemotherapy with temozolomide was initiated.