Dokument: Future diagnostic and therapeutic perspectives in rare neuroinflammatory, neurovascular and neurodegenerative diseases Habilitationsschrift
| Titel: | Future diagnostic and therapeutic perspectives in rare neuroinflammatory, neurovascular and neurodegenerative diseases Habilitationsschrift | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=45848 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210427-094437-2 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Habilitation | |||||||
| Medientyp: | Text | |||||||
| Autor: | PD Dr. med. Ringelstein, Marius [Autor] | |||||||
| Dateien: |
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| Stichwörter: | Optical coherence tomography, Neuromyelitis optica, Susac Syndrome, Amyotrophic lateral sclerosis | |||||||
| Beschreibung: | Neuro-axonal degeneration is the key feature in the pathogenesis of primarily neurodegenerative disorders but also occurs as a secondary phenomenon in inflammatory and vascular CNS diseases. As a result of CNS degeneration, being not reversible but possibly preventable in most of the diseases, the patient´s disease
burden and disability tend to increase, and the economic costs are tremendous. Thus, non-invasive, easy-applicable and cost-effective diagnostic tools such as OCT are highly appreciated to quantify and to follow-up axonal and neuronal cell loss for as early as possible diagnosis and in the light of therapeutic decisions. This is particularly true in “rare diseases” with their tendency to be underdiagnosed or even neglected. This thesis highlights the diagnostic value of SD-OCT in primary neuroinflammatory (MS), neurodegenerative (ALS) and neurovascular (SuS) diseases in comparison to healthy controls or important differential diagnoses. Moreover, we evaluated the impact of diagnostic spinal cord biopsies and VEPs in NMOSD patients and analyzed the longterm efficacy and safety of Tocilizumab in these patients to answer the initially raised questions: 1. Our first OCT study in MS patients demonstrated a significant reduction of the RNFL and the TMV compared to HCs in patients both with and without previous ON [Brandt et al. 2011]. Our 2012 SD-OCT study confirmed these previous findings, but also carved out distinct OCT patterns in RRMS, SPMS and PPMS subtypes [Oberwahrenbrock et al. 2012; above publication No. 1]. In the same year we published one of the first studies that analyzed the deeper retinal layers in highresolution SD-OCT scans [Albrecht et al. 2012c; above publication No. 2]. Besides a reduction of the RNFL and GCIPL complex in all MS subtypes, highlighting axonal and neuronal degeneration, we also found a thinning of the INL, exclusively in PPMS patients, suggesting a primary retinal pathology in contrast to a retrograde trans-synaptic degeneration after ON. Finally, we detected by SD-OCT a primary neuronal cell loss in eyes of patients with CIS, justifying treatment interventions already in this earliest stage of MS [Oberwahrenbrock et al. 2013; above publication No. 3]. As opposed to neuro-inflammatory MS, we investigated patients with ALS, a classical primary neurodegenerative motor neuron disease [Ringelstein et al. 2014b; above publication No. 4]. Here, SD-OCT for the first time revealed subtle reductions of the macular thickness and the RNFL as well as a marked thinning of the INL, highlighting the neuro-ophthalmologic involvement in ALS and giving further insights into the pathophysiology of the disease. Finally, with SD-OCT we characterized the retinal pathology in patients with SuS, a rare micro-vascular disease of the retina, brain, and inner ear and an important differential diagnosis of MS [Ringelstein et al. 2015a; above publication No. 8]. Distinct OCT patterns of scattered, scar-like intraretinal damage in SuS eyes suggest a retinal, in contrast to a choroidal vascular pathomechanism and clearly differentiate SuS from MS patients. Depending on the disease stage, SD-OCT and fluorescein angiography provide important complementary diagnostic information to accelerate the correct diagnosis and prompt early treatment. 2. Diagnostic spinal cord biopsies in NMOSD patients resulted in serious postoperative complications and did not even lead to the correct diagnosis in the majority of cases. AQP4-Ab testing is mandatory in patients with inconclusive LESCL prior to spinal biopsy, which should be restricted to otherwise inconclusive cases (Ringelstein et al. 2014d; above publication No. 6). Considering VEP latency prolongations and amplitude reductions, we were not able to define a distinct NMO pattern, as suggested by others, but found prolonged latencies in eyes without prior ON, indicating a subclinical affection [Ringelstein et al. 2014c; above publication No. 5]. 3. Long-term IL-6 receptor blockade with tocilizumab, significantly reduces the ARR, EDSS, AQP4-Ab titers and pain levels without relevant adverse effects in highly active NMOSD patients, when administered following a strict therapeutic regimen [Ringelstein et al. 2015b; above publication No. 7]. Taken together, SD-OCT reliably detects neuro-axonal loss in primary neuroinflammatory, neurodegenerative and neurovascular diseases and facilitates the early diagnosis in several i.a. “orphan diseases”. As OCT is a non-invasive, safe, and highly precise diagnostic tool, we expect an increasing impact of OCT on the future differential diagnostic workup in various neurological disorders. In this context, we are currently preparing a first approach of diagnostic criteria for SuS, where SD-OCT should play an important role for the detection of retinal involvement of the disease. Tocilizumab revealed an excellent efficacy/safety balance and can be considered a promising future therapy in highly disease active NMOSD patients, particularly in rituximab non-responders. Diagnostic spinal cord biopsies in NMOSD patients should be avoided or at least restricted to specific AQP4-Ab seronegative cases with no other diagnostic options. Longitudinal VEP studies in NMOSD are currently ongoing to further investigate subclinical disease processes and differential diagnostic issues. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 27.04.2021 | |||||||
| Dateien geändert am: | 27.04.2021 |
