The Inverse Lhermitte Phenomenon Suggests Nitrous Oxide-Induced Myelopathy: Case Report and Review of the Literature

Nitrous oxide-induced myelopathy is a relatively well-known clinical entity. Less well-known, however, is the rare inverse Lhermitte phenomenon, where neck flexion elicits an ascending, rather than descending, electric shock-like sensation. This is a characteristic symptom and sign that may occur in nitrous oxide toxicity. In this article, we present the case of a patient who was admitted to our hospital with suspected Guillain-Barré syndrome due to her ascending numbness and unsteady gait. We describe her examination and laboratory features leading to the correct diagnosis, along with a historical review of the various subtypes of the Lhermitte phenomenon and the pathophysiology of nitrous oxide-induced myelopathy

Migraine with prolonged aphasic aura associated with a CACNA1A mutation: A case report and narrative review

ObjectiveTo demonstrate that a known CACNA1A variant is associated with a phenotype of prolonged aphasic aura without hemiparesis.BackgroundThe usual differential diagnosis of prolonged aphasia without hemiparesis includes vascular disease, seizure, metabolic derangements, and migraine. Genetic mutations in the CACNA1A gene can lead to a myriad of phenotypes, including familial hemiplegic migraine (FHM) type 1, an autosomal dominant disorder characterized by an aura of unilateral, sometimes prolonged weakness. Though aphasia is a common feature of migraine aura, with or without hemiparesis, aphasia without hemiparesis has not been reported with CACNA1A mutations.MethodsWe report the case of a 51-year-old male who presented with a history of recurrent episodes of aphasia without hemiparesis lasting days to weeks. His headache was left sided and was heralded by what his family described as "confusion." On examination, he had global aphasia without other focal findings. Family history revealed several relatives with a history of severe headaches with neurologic deficits including aphasia and/or weakness. Imaging revealed T2 hyperintensities in the left parietal/temporal/occipital regions on MRI scan with corresponding hyperperfusion on SPECT. Genetic testing revealed a missense mutation in the CACNA1A gene.ConclusionsThis case expands the phenotypic spectrum of the CACNA1A mutation and FHM to include prolonged aphasic aura without hemiparesis. Our patient's SPECT imaging demonstrated hyperperfusion in areas correlating with aura symptoms which can occur in prolonged aura

Transient Worsening of Optic Neuropathy as a Sequela of the Jarisch-Herxheimer Reaction in the Treatment of Lyme Disease.

A 58-year-old woman developed neurologic and neuroophthalmologic manifestations of Lyme disease, including a radiculomyelitis, cranial neuritis and mild right optic neuropathy. Upon treatment with intravenous ceftriaxone a Jarisch-Herxheimer reaction occurred with encephalopathy, mild fever, worsening radiculomyelitis, and deterioration of her visual acuity. Intravenous methylprednisolone was given, and the visual acuity recovered over 72 hours. This case suggests that transient worsening of optic neuropathy can develop as a sequela of the Jarisch-Herxheimer reaction in the treatment of Lyme disease

Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections

Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence

<div><p>Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the <i>de novo</i> development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in <i>Mycobacterium tuberculosis</i> infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.</p></div

Letters to the editor

SCOPUS: le.jinfo:eu-repo/semantics/publishe

iregDC extrinsic MyD88 signaling, but not direct LCMV infection or IFNβ signaling is required for iregDC differentiation.

<p><b>A.</b> WT mice were CD8 depleted and then infected with LCMV-Cl13-GFP. Flow plots show GFP expression (i.e., LCMV infection) in splenic iregDC and stimDC (gated on CD39 and CD95) on day 9 after infection. In parallel, naïve splenic DC (N), and iregDC and stimDC were FACSorted based on GFP expression on day 9 after infection. The level of GFP+ stimDC was too small to obtain adequate numbers for RNA isolation. Bar graphs show relative expression of IL-10 RNA, LCMV-GP RNA and the MFI of PDL1 protein expression from the sorted populations. To obtain sufficient cell numbers for the RNA analyses, infected and uninfected iregDC and stimDC were sorted from a pool of 8 mice. Data show one of two experiments. <b>B.</b> Flow plots show the percent and bar graphs the number of iregDC and stimDC in the indicated mouse strain from CD11b+ DCs at day 9 after LCMV-Cl13 infection. <b>C.</b> Bar graphs indicate plasma IL-10 concentration and PDL1 expression in WT, IFNαR-/-, and MyD88-/- mice at day 9 after LCMV-Cl13 infection. <b>D.</b> Naïve WT and MyD88-/- monocytes were transferred into WT mice and analyzed on day 9 after LCMV-Cl13 infection as described in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005356#ppat.1005356.g004" target="_blank">Fig 4E</a>. <b>E.</b> Mixed chimera mice were generated using bone marrow from WT and MyD88-/- bone marrow. Flow plots depict WT and MyD88-/- lineage splenic CD11b+ DCs at day 9 after LCMV-Cl13 of WT. Histogram shows PDL1 expression on iregDCs from WT (white) and MyD88-/- (grey) lineage cells. Bar graphs indicate PDL1 expression and the number of iregDC and stimDC from each lineage in the chimera mice. Data are representative of 2 or more independent experiments each consisting of 3–5 mice per group. *, p<0.05.</p