Down syndrome, also known as Trisomy 21, is a genetic disorder associated with mild-to-moderate intellectual disability, delays in growth, and characteristic facial features. A wide range of ocular complications are seen in children with Down syndrome, including strabismus, nystagmus, refractive errors, congenital cataracts, the presence of keratoconus, and decreased visual acuity. Early ophthalmic examination is needed for early diagnosis and treatment in patients. This narrative review examines ocular manifestations in children with Down syndrome and the importance of prompt ophthalmic interventions for treatment.
Down Syndrome , Intellectual Disability , Nystagmus, Pathologic , Refractive Errors , Strabismus , Child , Humans , Down Syndrome/complications , Refractive Errors/complications , Strabismus/complications , Strabismus/diagnosis , Nystagmus, Pathologic/complications , Nystagmus, Pathologic/diagnosis , Nystagmus, Pathologic/genetics , Intellectual Disability/complications
CSF1R-related leukoencephalopathy is an autosomal dominant neurologic disorder causing microglial dysfunction with a wide range of neurologic complications, including motor dysfunction, dementia, and seizures. This case report highlights an unusual presentation of CSF1R-related leukoencephalopathy with radiographic spinal cord involvement initially diagnosed as multiple sclerosis. This case highlights the importance of considering adult-onset neurogenetic disorders in the setting of white matter disease. Genetic testing provides a confirmatory diagnosis for an expanding number of adult-onset leukoencephalopathies and informs therapeutic decision-making.
Leukoencephalopathies , Multiple Sclerosis , Adult , Humans , Multiple Sclerosis/diagnosis , Multiple Sclerosis/diagnostic imaging , Magnetic Resonance Imaging , Mutation , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/genetics , Receptor Protein-Tyrosine Kinases , Spinal Cord/pathology
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM TME, most notably multiple distinct neutrophil states, including an IL8-expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. In addition, we observed significant relationships between intracranial T-cell phenotypes and the distribution of T-cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data identify unique features of the MBM TME that may represent potential targets to improve clinical outcomes for patients with MBM.
Brain Neoplasms , Melanoma , Humans , Immune Checkpoint Inhibitors , Tumor Microenvironment
Importance: Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions. Objective: To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis. Design, Setting, and Participants: This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection. Results: In total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients. Conclusions and Relevance: This diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.
Circulating Tumor DNA/cerebrospinal fluid , Diagnostic Tests, Routine , Meningeal Neoplasms/cerebrospinal fluid , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/genetics , Neoplasms/complications , Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasms, Second Primary/cerebrospinal fluid , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/genetics , Predictive Value of Tests
Wilhelm Uhthoff, known for his contributions to both neurology and neuro-ophthalmology, was a German ophthalmologist who specialized in neurologic disorders. The eponym "Uhthoff's phenomenon" was first used to describe the reversible, transient blurring of vision in patients with multiple sclerosis during exercise. Subsequently, it was discovered that this neurologic sign not only was triggered by physical exertion but also by other homeostatic disruptions such as hot baths, menstruation, and high external temperatures. Here, we take a look at the life and career of Wilhelm Uhthoff and discuss the basis behind this phenomenon.
Multiple Sclerosis , Neurology , Exercise , Female , Hot Temperature , Humans , Vision Disorders
Chyluria, described as passage of milky white urine, has been recognized as a urological manifestation of the lymphatic system due to abnormal connection between the blocked and dilated lymphatics and the renal pelvicaliceal systems. We report the case of a 36-year-old female from an endemic area of filariasis in India who presented with chyluria. In addition to medical therapy, intermittent sclerotherapy of renal pelvis with 0.2% povidone iodine was carried out with a dose schedule different from the ones in practice earlier. The idea of intermittent sclerotherapy was to create pyelolymphatic and pyelosinus reflux so as to sclerose the communicating channel between the lymphatic and urinary systems. This method proved to be curative for the patient and she was relieved from her 8-year-old problem and subsequently remained asymptomatic.
