Eaneff et al. – Patient perspectives on neuromyelitis optica spectrum disorders: Data from the PatientsLikeMe online community

Mult Scler Relat Disord. 2017 Oct;17:116-122

by Eaneff S, Wang V, Hanger M, Levy M, Mealy MA, Brandt AU, Eek D, Ratchford JN, Nyberg F, Goodall J, Wicks P

BACKGROUND: Few studies have evaluated patient perspectives on neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD).
OBJECTIVE: Describe patient-reported clinical and treatment experience in NMOSD and compare disease characteristics of NMOSD with those of multiple sclerosis (MS).
METHODS: This retrospective, observational study included 522 members with NMO or NMOSD (hereafter collectively referred to as NMOSD) from PatientsLikeMe (PLM), an online patient community. Data describing member demographics, symptoms, and treatments were collected, analysed descriptively, and compared with data from PLM members with MS.
RESULTS: Fatigue, pain, and stiffness/spasticity were each rated as moderate to severe by more than half of NMOSD members, and 59% reported that their health limited the type of work or other activities they could perform all or most of the time. Overall, symptom severity and disability levels were comparable between NMOSD and MS members; however, NMOSD members were more likely than MS members to attribute disability to vision-related symptoms and were less likely to report moderate to severe cognitive and emotional symptoms, including brain fog, depressed or anxious mood, and emotional lability.
CONCLUSION: This analysis underscores the challenges of living with fatigue, pain, stiffness/spasticity, and visual difficulties, prevalent NMOSD symptoms among members of the PLM community.

Motognosis was selected for the BIH Digital Health program

We are happy to announce that the startup Motognosis, which originated from the Neurodiagnostics Labs, was selected for the BIH Digital Health program as part of the new BIH and Startupbootcamp collaboration.

Motognosis has already moved into the Startupbootcamp in Berlin Mitte and is now business coached over the next few months.

From the BIH’s press release:

Startupbootcamp, a global network of industry‐focused start‐up accelerators, runs 20 programs across five continents with a mentor and alumni network in over 30 countries. Startupbootcamp Digital Health Berlin is a leading program in Europe supporting innovative companies combining medical knowledge with smart technologies, with a special focus on behavioral change, big data and analytics, diagnostics and genomics.

“This partnership enables us to facilitate knowhow transfer between digital health start‐ups applying new technologies to advanced healthcare problems and the academic hospital Charité – Universitätsmedizin Berlin to benefit patients,” says Dr. Rolf Zettl, CFO and Member of the Executive Board of BIH. “We look forward to also explore collaboration opportunities for transformational digital health solutions with the other partners.” Partners include Philips, Sanofi in Germany, Vilua, Deutsche Apotheker‐ und Ärztebank and Munich Re.

The Startupbootcamp program provides 10 globally‐screened digital health start‐ups with hands‐on mentorship from over 100 industry experts, logistics support, office space in Berlin, and access to a global network of corporate partners and investors from across the healthcare industry. Two teams of Charité innovators are co‐located with the program as Entrepreneurs in Residence to benefit from knowhow transfer with start‐ups and mentors.

“This partnership creates common ground for BIH and SBC with the great potential to bring some truly innovative solutions to the heart of German healthcare,” says Lars Buch, Managing Director of Startupbootcamp Digital Health Berlin.

With this initiative, BIH further strengthens its commitment to supporting translational medicine in digital health, amongst other areas, to improve patients’ health and quality of life.

 

BIH Press Release

Motognosis Post on Facebook

Motognosis Website

 

Schematic Figure – Retina (Creative Commons License)

Do you need a free schematic figure of the retina for your work? We needed one, too. So we created one and publish it here under a Creative Commons License, so you can use for free in your own commercial and non-commercial works. The only thing we ask for is referencing this website, if you decide to use the figure. You are also allowed to alter it, under the condition that you keep the reference to our original version.

You can download a zipped eps vector file (ca. 3 MB) here: neurodial_retina_v1.eps

This figure is made vailable under the following Creative Commons License:
Creative Commons License
Schematic Figure – Retina by Neurodiagnostics Laboratory @ Charité – Universitätsmedizin Berlin, Germany is licensed under a Creative Commons Attribution 4.0 International License.

Schematic Figure – Macular OCT with Intraretinal Layers (Creative Commons License)

Do you need a free schematic figure of a 3D macular OCT with labelled intraretinal layers for your work? We needed one, too. So we created one and publish it here under a Creative Commons License, so you can use for free in your own commercial and non-commercial works. The only thing we ask for is referencing this website, if you decide to use the figure. You are also allowed to alter it, under the condition that you keep the reference to our original version.

You can download a zipped eps vector file (ca. 2.5 MB) here: neurodial_oct_v1.eps

This figure is made vailable under the following Creative Commons License:
Creative Commons License
Schematic Figure – Macular OCT with Intraretinal Layers by Neurodiagnostics Laboratory @ Charité – Universitätsmedizin Berlin, Germany is licensed under a Creative Commons Attribution 4.0 International License.

Schematic Figure – The Afferent Visual System (Creative Commons License)

Do you need a free schematic figure of the afferent visual system for your work? We needed one, too. So we created one and publish it here under a Creative Commons License, so you can use for free in your own commercial and non-commercial works. The only thing we ask for is referencing this website, if you decide to use the figure. You are also allowed to alter it, under the condition that you keep the reference to our original version.

You can download a zipped eps vector file (ca. 8 MB) here: neurodial_avs_v1.eps

This figure is made vailable under the following Creative Commons License:
Creative Commons License
Schematic Figure – The Afferent Visual System by Neurodiagnostics Laboratory @ Charité – Universitätsmedizin Berlin, Germany is licensed under a Creative Commons Attribution 4.0 International License.

Yadav et al. – CuBe: parametric modeling of 3D foveal shape using cubic Bézier

Biomedical Optics Express, Vol. 8, Issue 9, pp. 4181-4199 (2017)

by Sunil Kumar Yadav, Seyedamirhosein Motamedi, Timm Oberwahrenbrock, Frederike Cosima Oertel, Konrad Polthier, Friedemann Paul, Ella Maria Kadas, and Alexander U. Brandt

Optical coherence tomography (OCT) allows three-dimensional (3D) imaging of the retina, and is commonly used for assessing pathological changes of fovea and macula in many diseases. Many neuroinflammatory conditions are known to cause modifications to the fovea shape. In this paper, we propose a method for parametric modeling of the foveal shape. Our method exploits invariant features of the macula from OCT data and applies a cubic Bézier polynomial along with a least square optimization to produce a best fit parametric model of the fovea. Additionally, we provide several parameters of the foveal shape based on the proposed 3D parametric modeling. Our quantitative and visual results show that the proposed model is not only able to reconstruct important features from the foveal shape, but also produces less error compared to the state-of-the-art methods. Finally, we apply the model in a comparison of healthy control eyes and eyes from patients with neuroinflammatory central nervous system disorders and optic neuritis, and show that several derived model parameters show significant differences between the two groups.

Rakhymzhan et al. – Synergistic Strategy for Multicolor Two-photon Microscopy: Application to the Analysis of Germinal Center Reactions In Vivo

Sci Rep. 2017 Aug 2;7(1):7101

by Rakhymzhan A, Leben R, Zimmermann H, Günther R, Mex P, Reismann D, Ulbricht C, Acs A, Brandt AU,  Lindquist RL, Winkler TH, Hauser AE, Niesner RA

(DIAL in cooperation with DRFZ AG Niesner)

Simultaneous detection of multiple cellular and molecular players in their native
environment, one of the keys to a full understanding of immune processes, remains
challenging for in vivo microscopy. Here, we present a synergistic strategy for
spectrally multiplexed in vivo imaging composed of (i) triple two-photon
excitation using spatiotemporal synchronization of two femtosecond lasers, (ii) a
broad set of fluorophores with emission ranging from blue to near infrared, (iii)
an effective spectral unmixing algorithm. Using our approach, we simultaneously
excite and detect seven fluorophores expressed in distinct cellular and tissue
compartments, plus second harmonics generation from collagen fibers in lymph
nodes. This enables us to visualize the dynamic interplay of all the central
cellular players during germinal center reactions. While current in vivo imaging
typically enables recording the dynamics of 4 tissue components at a time, our
strategy allows a more comprehensive analysis of cellular dynamics involving 8
single-labeled compartments. It enables to investigate the orchestration of
multiple cellular subsets determining tissue function, thus, opening the way for
a mechanistic understanding of complex pathophysiologic processes in vivo. In the
future, the design of transgenic mice combining a larger spectrum of fluorescent
proteins will reveal the full potential of our method.

Kuchling et al. – Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system.

EPMA J. 2017 Jul 25;8(3):279-294

by Kuchling J, Brandt AU, Paul F, Scheel M.

The afferent visual pathway represents the most frequently affected white matter pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt brain tissue damage and quantify pathological processes. DTI facilitates the reconstruction of major white matter fiber tracts allowing for the assessment of structure-function and damage-dysfunction relationships. In this review, we outline DTI studies investigating the afferent visual pathway in idiopathic optic neuritis (ON), NMOSD, and MS. Since MS damage patterns are believed to depend on multiple factors, i.e., ON (anterior visual pathway damage), inflammatory lesions (posterior visual pathway damage), and global diffuse inflammatory and neurodegenerative processes, comprehensive knowledge on different contributing factors using DTI in vivo may advance our understanding of MS disease pathology. Combination of DTI measures and visual outcome parameters yields the potential to improve routine clinical diagnostic procedures and may further the accuracy of individual prognosis with regard to visual function and personalized disease outcome. However, due to the inherent limitations of DTI acquisition and post-processing techniques and the so far heterogeneous and equivocal data of previous studies, evaluation of the true potential of DTI as a possible biomarker for afferent visual pathway dysfunction is still substantially limited. Further research efforts with larger longitudinal studies and standardized DTI acquisition and post-processing validation criteria are needed to overcome current DTI limitations. DTI evaluation at different levels of the visual pathway has the potential to provide markers for individual damage evaluation in the future. As an imaging biomarker, DTI may support individual outcome prediction during personalized treatment algorithms in MS and other neuroinflammatory diseases, hereby leveraging the concept of predictive, preventive, and personalized medicine in the field of clinical neuroimmunology.

Albrecht et al. Optical coherence tomography for the diagnosis and monitoring of idiopathic intracranial hypertension

J Neurol. 2017 Jul;264(7):1370-1380

by Albrecht P, Blasberg C, Ringelstein M, Müller AK, Finis D, Guthoff R, Kadas EM, Lagreze W, Aktas O, Hartung HP, Paul F, Brandt AU, Methner A

(in cooperation with Universitätsklinikum Düsseldorf AG Albrecht)

The objectives of the study were to investigate the value of optical coherence tomography in detecting papilledema in patients with idiopathic intracranial hypertension (IIH), a disease which is difficult to monitor and which can lead to permanent visual deficits; to analyze retinal changes over time. In this non-interventional case-control study, spectral-domain optical coherence tomography (SD-OCT) was used to analyze the retinal and optic nerve head (ONH) morphology of 21 patients with IIH and 27 age- and sex-matched healthy controls over time. We analyzed the ONH volume using a custom-made algorithm and employed semi-automated segmentation of macular volume scans to assess the macular retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer complex as well as the total macular volume. In IIH patients, the ONH volume was increased and correlated with cerebrospinal fluid (CSF) pressure. The ONH volume decreased after the initiation of treatment with acetazolamide. The macular RNFL volume decreased by 5% in 3.5 months, and a stepwise multivariate regression analysis identified CSF pressure as the main influence on macular RNFL volume at diagnosis. The only factor predicting macular RNFL volume loss over time was ONH volume. SD-OCT can non-invasively monitor changes in retinal and ONH morphology in patients with IIH. Increased ONH volume leads to retinal atrophy in the form of macular RNFL volume loss, presumably due to mechanic jamming of the optic nerve at the disc and subsequent axonal loss.

Schlemm et al. – Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients

Mult Scler. 2017 Jun;23(7):963-972

by Schlemm L, Chien C, Bellmann-Strobl J, Dörr J, Wuerfel J, Brandt AU, Paul F, Scheel M

BACKGROUND: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs).
OBJECTIVE: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration.
METHODS: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic).
RESULTS: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs -0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR ( p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration.
CONCLUSION: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd-BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity.