Antibody Therapies in Autoimmune Encephalitis

Autoimmune encephalitis (AE) comprises a heterogeneous group of disorders in which the host immune system targets self-antigens expressed in the central nervous system. The most conspicuous example is an anti-N-methyl-d-aspartate receptor encephalitis linked to a complex neuropsychiatric syndrome. Current treatment of AE is based on immunotherapy and has been established according to clinical experience and along the concept of a B cell-mediated pathology induced by highly specific antibodies to neuronal surface antigens. In general, immunotherapy for AE follows an escalating approach. When first-line therapy with steroids, immunoglobulins, and/or plasma exchange fails, one converts to second-line immunotherapy. Alkylating agents could be the first choice in this stage. However, due to their side effect profile, most clinicians give preference to monoclonal antibodies (mAbs) directed at B cells such as rituximab. Newer mAbs might be added as a third-line therapy in the future, or be given even earlier if shown effective. In this chapter, we will discuss mAbs targeting B cells (rituximab, ocrelizumab, inebulizumab, daratumumab), IL-6 (tocilizumab, satralizumab), the neonatal Fc receptor (FCRn) (efgartigimod, rozanolixizumab), and the complement cascade (eculizumab). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01178-4

Positioning and clock synchronization through entanglement

A method is proposed to employ entangled and squeezed light for determining the position of a party and for synchronizing distant clocks. An accuracy gain over analogous protocols that employ classical resources is demonstrated and a quantum-cryptographic positioning application is given, which allows only trusted parties to learn the position of whatever must be localized. The presence of a lossy channel and imperfect photodetection is considered. The advantages in using partially entangled states is discussed.Comment: Revised version. 9 pages, 6 figure

Diagnostic criteria for primary autoimmune cerebellar ataxia—guidelines from an international task force on immune-mediated cerebellar ataxias

Aside from well-characterized immune-mediated ataxias with a clear trigger and/or association with specific neuronal antibodies, a large number of idiopathic ataxias are suspected to be immune mediated but remain undiagnosed due to lack of diagnostic biomarkers. Primary autoimmune cerebellar ataxia (PACA) is the term used to describe this later group. An International Task Force comprising experts in the field of immune ataxias was commissioned by the Society for Research on the Cerebellum and Ataxias (SRCA) in order to devise diagnostic criteria aiming to improve the diagnosis of PACA. The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. The aim is to enable clinicians to consider PACA when encountering a patient with progressive ataxia and no other diagnosis given that such consideration might have important therapeutic implications

Macroscopic superpositions of Bose-Einstein condensates

We consider two dilute gas Bose-Einstein condensates with opposite velocities from which a monochromatic light field detuned far from the resonance of the optical transition is coherently scattered. In the thermodynamic limit, when the relative fluctuations of the atom number difference between the two condensates vanish, the relative phase between the Bose-Einstein condensates may be established in a superposition state by detections of spontaneously scattered photons, even though the condensates have initially well-defined atom numbers. For a finite system, stochastic simulations show that the measurements of the scattered photons lead to a randomly drifting relative phase and drive the condensates into entangled superpositions of number states. This is because according to Bose-Einstein statistics the scattering to an already occupied state is enhanced.Comment: 18 pages, RevTex, 5 postscript figures, 1 MacBinary eps-figur

Autoimmune-associated seizure disorders

With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders

Label-free peptide profiling of Orbitrap™ full mass spectra

Background. We developed a new version of the open source software package Peptrix that can yet compare large numbers of Orbitrap™ LC-MS data. The peptide profiling results for Peptrix on MS1 spectra were compared with those obtained from a small selection of open source and commercial software packages: msInspect, Sieve™ and Progenesis™. The properties compared in these packages were speed, total number of detected masses, redundancy of masses, reproducibility in numbers and CV of intensity, overlap of masses, and differences in peptide peak intensities. Reproducibility measurements were taken for the different MS1 software applications by measuring in triplicate a complex peptide mixture of immunoglobulin on the Orbitrap™ mass spectrometer. Values of peptide masses detected from the high intensity peaks of the MS1 spectra by peptide profiling were verified with values of the MS2 fragmented and sequenced masses that resulted in protein identifications with a significant score. Findings. Peptrix finds about the same number of peptide features as the other packages, but peptide masses are in some cases approximately 5 to 10 times less redundant present in the peptide profile matrix. The Peptrix profile matrix displays the largest overlap when comparing the number of masses in a pair between two software applications. The overlap of peptide masses between software packages of low intensity peaks in the spectra is remarkably low with about 50% of the detected masses in the individual packages. Peptrix does not differ from the other packages in detecting 96% of the masses that relate to highly abundant sequenced proteins. MS1 peak intensities vary between the applications in a non linear way as they are not processed using the same method. Conclusions. Peptrix is capable of peptide profiling using Orbitrap™ files and finding differential expressed peptides in body fluid and tissue samples. The number of peptide masses detected in Orbitrap™ files can be increased by using more MS1 peptide profiling applications, including Peptrix, since it appears from the comparison of Peptrix with the other applications that all software packages have likely a high false negative rate of low intensity peptide peaks (missing peptides)

Clinical Outcome Assessments in Encephalitis

Background and ObjectivesMost patients with encephalitis experience persisting neurocognitive and neuropsychiatric sequelae in the years following this acute illness. Reported outcomes are often based on generic clinical outcome assessments that rarely capture the patient perspective. This may result in an underestimation of disease-specific sequelae. Disease-specific clinical outcome assessments can improve clinical relevance of reported outcomes and increase the power of research and trials. There are no patient-reported outcome measures (PROMs) developed or validated specifically for patients with encephalitis. The primary objective of this systematic literature review was to identify PROMs that have been developed for or validated in patients with encephalitis. MethodsWe performed a systematic review of the literature published from inception until May 2023 in 3 large international databases (MEDLINE, EMBASE and Cochrane libraries). Eligible studies should have developed or validated a PROM in patients with encephalitis or encephalopathy. Methodologic quality was evaluated using the Consensus-based Standards for the selection of health status Measurement Instruments study design checklist for PROMs. ResultsWe identified no disease-specific PROMs developed or validated for patients with encephalitis. We identified one study on the development and validation of a disease-specific PROM for hepatic encephalopathy, although this disease course is substantially different to that of patients with encephalitis. The methodologic quality of the included study was generally rated as "doubtful." We identified 30 PROMs that have been applied in 46 studies on encephalitis or encephalopathy, although not validated in these populations. The most commonly applied PROMs for measuring Health-Related Quality of Life were the Medical Outcomes Study Short Form-36 and the Sickness Impact Profile. Emotional well-being was often assessed with the Beck Depression Inventory (BDI-II). Sporadically, PROMs were applied to address other aspects of outcome including daily functioning and sleep quality. DiscussionThis systematic review confirms a critical gap in clinical outcome assessments in patients with encephalitis, failing to identify a validated measuring tool for detecting neurocognitive, functional, and health status. It is therefore essential to develop and/or validate disease-specific PROMs for the population with encephalitis to capture relevant information for patient management and clinical trials about the effects of disease that are at risk of being overlooked.</p

Spatial coherence and density correlations of trapped Bose gases

We study first and second order coherence of trapped dilute Bose gases using appropriate correlation functions. Special attention is given to the discussion of second order or density correlations. Except for a small region around the surface of a Bose-Einstein condensate the correlations can be accurately described as those of a locally homogeneous gas with a spatially varying chemical potential. The degrees of first and second order coherence are therefore functions of temperature, chemical potential, and position. The second order correlation function is governed both by the tendency of bosonic atoms to cluster and by a strong repulsion at small distances due to atomic interactions. In present experiments both effects are of comparable magnitude. Below the critical temperature the range of the bosonic correlation is affected by the presence of collective quasi-particle excitations. The results of some recent experiments on second and third order coherence are discussed. It is shown that the relation between the measured quantities and the correlation functions is much weaker than previously assumed.Comment: RevTeX, 25 pages with 7 Postscript figure

Multiple plasmon resonances in naturally-occurring multiwall nanotubes: infrared spectra of chrysotile asbestos

Chrysotile asbestos is formed by densely packed bundles of multiwall hollow nanotubes. Each wall in the nanotubes is a cylindrically wrapped layer of $Mg_3 Si_2 O_5 (OH)_4$. We show by experiment and theory that the infrared spectrum of chrysotile presents multiple plasmon resonances in the Si-O stretching bands. These collective charge excitations are universal features of the nanotubes that are obtained by cylindrically wrapping an anisotropic material. The multiple plasmons can be observed if the width of the resonances is sufficiently small as in chrysotile.Comment: 4 pages, 5 figures. Revtex4 compuscript. Misprint in Eq.(6) correcte

Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome

ObjectiveTo study survival and to characterize long-term functional impairments and health-related quality of life (HRQOL) of patients with Lambert-Eaton myasthenic syndrome (LEMS).MethodsIn this observational study, survival of patients with LEMS, separately for nontumor (NT) and small cell lung cancer (SCLC), was compared to that of the Dutch general population and patients with SCLC. Disease course in patients with LEMS was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed.ResultsWe included 150 patients with LEMS. Survival was similar to that of the general population in 65 patients with NT-LEMS. Tumor survival was significantly longer in 81 patients with SCLC-LEMS compared to patients with non-LEMS SCLC (overall median survival 17 vs 7.0 months, p <0.0001). At diagnosis, 39 (62%) of 63 patients with complete follow-up data were independent for activities of daily living, improving to 85% at the 1-year follow-up. The physical HRQOL composite score (55.9) was significantly lower than in the general population (76.3, p <0.0001) and comparable to that of patients with myasthenia gravis (60.5). The mental HRQOL composite score was 71.8 in patients with LEMS, comparable to that of the general population (77.9, p = 0.19) and patients with myasthenia gravis (70.3).ConclusionsThis study shows that patients with NT-LEMS have normal survival. Patients with SCLC-LEMS have an improved tumor survival, even after correction for tumor stage. A majority of patients with LEMS report a stable disease course and remain or become independent for self-care after treatment