ABSTRACT
Background: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is an autoimmune disorder first described in 2007. It can cause severe neurologic and psychiatric symptoms, and patients often are misdiagnosed with a primary psychiatric disorder. Anti-NMDA-R encephalitis is an important differential diagnosis of psychosis, as the condition can be treated with the appropriate therapy. Case Report: A 42-year-old female with a history of hypothyroidism presented for evaluation of agitation and weakness. Six months prior to her presentation at our hospital, she had complained of headache, and neuroimaging showed a small right frontal hyperintensity on fluid-attenuated inversion recovery imaging. Workup was largely unremarkable, and she improved briefly with steroids at the outside institution. She then developed psychiatric symptoms and had 4 admissions to separate inpatient psychiatric facilities. She was tried on various antipsychotic medications and mood stabilizers with no improvement and lost 30 pounds in 3 months. When the patient was transferred to our facility, her neuroimaging was stable, and serum and cerebrospinal fluid were positive for antithyroid peroxidase and NMDA-R antibodies. She was treated with intravenous immunoglobulin (IVIG), high-dose steroids, and rituximab. Positron emission tomography scan revealed a parotid mass that was resected and determined to be a pleomorphic adenoma. The patient improved remarkably to her baseline and was able to return to full duties at work within 6 months. In the 2 years since her initial admission, she has had minor relapses that have responded well to rituximab and IVIG. Conclusion: This case demonstrates a typical presentation of anti-NMDA-R encephalitis, as well as the challenges that can delay diagnosis. Symptoms vary and are often psychiatric, making these patients difficult to diagnose clinically, and they therefore require thorough investigation. This case illustrates the necessity to be inquisitive and to challenge the diagnosis when a clinical picture is not congruent because an accurate diagnosis is imperative in guiding appropriate treatment.
ABSTRACT
Increased expression of vimentin intermediate filaments (VIFs) enhances directed cell migration, but the mechanism behind VIFs' effect on motility is not understood. VIFs interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here, we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of retinal pigment epithelial cells. By genome editing, we fluorescently labeled endogenous vimentin and α-tubulin, and we developed computational image analysis to delineate architecture and interactions of the two networks. Our results show that VIFs assemble an ultrastructural copy of the previously polarized microtubule network. Because the VIF network is long-lived compared to the microtubule network, VIFs template future microtubule growth along previous microtubule tracks, thus providing a feedback mechanism that maintains cell polarity. VIF knockdown prevents cells from polarizing and migrating properly during wound healing. We suggest that VIFs' templating function establishes a memory in microtubule organization that enhances persistence in cell polarization in general and migration in particular.
Subject(s)
Microtubules , Cell Movement , Cell Polarity , Cells, Cultured , Cytoskeleton , Intermediate Filaments , Microtubule-Associated Proteins , Tubulin , VimentinABSTRACT
OBJECT: No clear treatment guidelines for pediatric craniopharyngiomas exist. The authors developed a decision analytical model to evaluate outcomes of 4 surgical approaches for craniopharyngiomas in children, including attempted gross-total resection (GTR), planned subtotal removal plus radiotherapy, biopsy plus radiotherapy, and endoscopic resections of all kinds. METHODS: Pooled data, including the authors' own experience, were used to create evidence tables, from which incidence, relative risks, and summary outcomes in quality-adjusted life years (QALYs) were calculated for the 4 management strategies. RESULTS: Quality-adjusted life years at the 5-year follow-up were 2.3 ± 0.1 for attempted GTR, 2.9 ± 0.2 for planned subtotal removal plus radiotherapy, 3.9 ± 0.2 for biopsy plus radiotherapy, and 3.7 ± 0.2 for endoscopic resection (F = 17,150, p < 0.001). Similarly, QALYs at 10-year follow-up were 4.5 ± 0.2 for attempted GTR, 5.7 ± 0.5 for planned subtotal removal plus radiotherapy, and 7.8 ± 0.5 for biopsy plus radiotherapy (F = 6,173, p < 0.001). On post hoc pairwise comparisons, the differences between all pairs compared were also highly significant (p < 0.001). Since follow-up data at 10 years are lacking for endoscopic cases, this category was excluded from 10-year comparisons. CONCLUSIONS: Biopsy with subsequent radiotherapy is the preferred approach with respect to improved overall quality of life. While endoscopic approaches also show promise in preserving quality of life at five-year follow-up, there are not sufficient data to draw conclusions about this comparison at 10 years.