Consensus Recommendations for the Management of Neurosarcoidosis: A Delphi Survey of Experts Across the United States.

Background And Objectives: Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies.

Methods: In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis.

Pathogenic Variants Resulting in Dural Based Fibroinflammatory Mass Lesions and H Syndrome Treated With Cobimetinib: A Case Report.

Objectives: Pathogenic variants are known to cause autosomal recessive disease with a spectrum of systemic involvement. We sought to expand on the spectrum of variants and describe potential treatment.

Methods: We describe a case of newly diagnosed -related disorder, also known as H syndrome or familial histiocytosis, associated with CNS inflammatory pseudotumor and spinal cord compression.

Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights.

Objective: To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.

Methods: In this case-control study, we validated 17 cytokines/chemokines (interleukin [IL]-1-beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and tumor necrosis factor [TNF]-alpha) in a multiplexed automated immunoassay system (ELLA; Bio-Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011-02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin-4 immunoglobulin G positivity, non-inflammatory disorders, and healthy individuals were used as controls.

Novel RAB39B loss-of-function mutation in patient with typical early-onset Parkinson's disease.

RAB39B mutations have been identified in X-linked developmental delays. Recently, RAB39B mutations were identified in males with early-onset parkinsonism and intellectual disability. A novel loss-of-function RAB39B mutation was found in a female patient with typical early-onset Parkinson's disease (EOPD).

Optic Neuropathy and Myelopathy in a Teenager With Biotinidase Deficiency.

A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6-T7 and descending through the lower extremities.

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression.

Importance: Progressive multifocal leukoencephalopathy can occur in the context of systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression and can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis. Earlier recognition of S-PML could lead to more effective treatment of the disease.

Objective: To describe characteristics of patients with S-PML.

Analysis of Clinical Features, Diagnostic Tests, and Biomarkers in Patients With Suspected Creutzfeldt-Jakob Disease, 2014-2021.

Importance: Detection of prion proteins in cerebrospinal fluid (CSF) using real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD), facilitating earlier and more complete recognition of affected patients. It is unclear how expanded recognition of affected patients may affect the diagnostic and prognostic relevance of clinical features and diagnostic tests historically associated with CJD.

Objective: To evaluate clinical features and diagnostic testing in patients presenting with CJD and determine the associations of these features with prognosis.

Interaction between Macrophages and Human Mesenchymal Stromal Cells Derived from Bone Marrow and Wharton's Jelly-A Comparative Study.

Despite intensive clinical research on the use of mesenchymal stromal cells (MSCs), further basic research in this field is still required. Herein, we compared human bone marrow MSCs (BM-MSCs, = 6) and Wharton's jelly MSCs (WJ-MSCs, = 6) in their ability to interact with human primary macrophages. Evaluation of secretory potential revealed that under pro-inflammatory stimulation, WJ-MSCs secreted significantly more IL-6 than BM-MSCs (2-fold).

Utility of MRI Enhancement Pattern in Myelopathies With Longitudinally Extensive T2 Lesions.

Objective: To determine whether MRI gadolinium enhancement patterns in myelopathies with longitudinally extensive T2 lesions can be reliably distinguished and assist in diagnosis.

Methods: We retrospectively identified 74 Mayo Clinic patients (January 1, 1996-December 31, 2019) fulfilling the following criteria: (1) clinical myelopathy; (2) MRI spine available; (3) longitudinally extensive T2 hyperintensity (≥3 vertebral segments); and (4) characteristic gadolinium enhancement pattern associated with a specific myelopathy etiology. Thirty-nine cases with alternative myelopathy etiologies, without previously described enhancement patterns, were included as controls.

Meningitis.

Purpose Of Review: This article reviews the diagnosis and treatment of infectious meningitis, including updates on newer molecular diagnostic techniques for microbiological diagnosis.

Recent Findings: New polymerase chain reaction (PCR)-based molecular diagnostic techniques have improved the timeliness of microbiological diagnosis in meningitis, but clinicians must be aware of the limitations of such tests. Next-generation sequencing can now be applied to CSF, allowing for diagnosis of infections not identifiable by conventional means.

Superficial siderosis associated with an iatrogenic posterior fossa dural leak identified on CT cisternography.

Superficial siderosis refers to hemosiderin deposition along the pial surface of the brain and spinal cord. It results from chronic and repetitive low-grade bleeding into the subarachnoid space. Dural tears are a common cause of superficial siderosis.

A multi-center case series of sarcoid optic neuropathy.

Objective: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes.

Methods: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers.

Treatment of Viral Encephalitis.

Viral encephalitis is difficult to treat. Herpes simplex encephalitis has been successfully treated with acyclovir, but is still a cause for significant morbidity even with that treatment. A rare form of autoimmune encephalitis related to NMDA receptor antibody after infection by herpes simplex can be treated with corticosteroid therapy.

Retrospective Review of Clinical Utility of Shotgun Metagenomic Sequencing Testing of Cerebrospinal Fluid from a U.S. Tertiary Care Medical Center.

Shotgun metagenomic sequencing can detect nucleic acids from bacteria, fungi, viruses, and/or parasites in clinical specimens; however, little data exist to guide its optimal application to clinical practice. We retrospectively reviewed results of shotgun metagenomic sequencing testing requested on cerebrospinal fluid samples submitted to an outside reference laboratory from December 2017 through December 2019. Of the 53 samples from Mayo Clinic patients, 47 were requested by neurologists, with infectious diseases consultation in 23 cases.

TNF-α and IL-1β sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment.

During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1β, and IFN-γ, IL-1β further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ.

Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events.

Importance: Tumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood.

Objective: To evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events.

Rheumatoid Meningitis: Clinical Characteristics, Diagnostic Evaluation, and Treatment.

Background And Purpose: Due to the potential for high mortality and neurologic complications of rheumatoid meningitis (RM), awaiting biopsy confirmation may delay vital treatment intervention. Our aim was to describe the clinical presentations of RM in our population and determine whether meningeal biopsy impacted diagnosis, treatment, and outcomes.

Methods: A retrospective chart review was completed for patients at Mayo Clinic with a diagnosis of RM within the last 28 years.

End of life: Expert care and support, not physician-hastened death.

In legal physician-hastened death, a physician prescribes medication with the primary intent of causing the death of a willing terminally ill patient. This practice differs radically from palliative sedation, intended to relieve a patient's suffering rather than cause a patient's death. In this position paper, we argue that the practice of physician-hastened death is contrary to the interests of patients, their families, and the sound ethical practice of medicine.

Building a neuroinfectious disease consensus curriculum.

Objective: To delineate a comprehensive curriculum for fellowship training in neuroinfectious diseases, we conducted a modified Delphi approach to reach consensus among 11 experts in the field.

Methods: The authors invited a diverse range of experts from the American Academy of Neurology Neuro-Infectious Diseases (AAN Neuro-ID) Section to participate in a consensus process using a modified Delphi technique.

Results: A comprehensive list of topics was generated with 101 initial items.

The Influence of Cell Source and Donor Age on the Tenogenic Potential and Chemokine Secretion of Human Mesenchymal Stromal Cells.

Background: Cellular therapy is proposed for tendinopathy treatment. Bone marrow- (BM-MSC) and adipose tissue- (ASC) derived mesenchymal stromal cells are candidate populations for such a therapy. The first aim of the study was to compare human BM-MSCs and ASCs for their basal expression of factors associated with tenogenesis as well as chemotaxis.

Characteristics of Spontaneous Spinal Cord Infarction and Proposed Diagnostic Criteria.

Importance: Spinal cord infarction (SCI) is often disabling, and the diagnosis can be challenging without an inciting event (eg, aortic surgery). Patients with a spontaneous SCI are often misdiagnosed as having transverse myelitis. Diagnostic criteria for SCI are lacking, hindering clinical care and research.