The Clinical and Treatment Characteristics of Neuromyelitis Optica. Summary of the Doctoral Thesis

Abstract

The doctoral theses “The clinical and treatment characteristics of neuromyelitis optica” has been dedicated to cover a topic about a condition called neuromyelitis optica (NMO) or Devic’s disease, which is a disease that is not fully understood yet. NMO is a relapsing inflammatory demyelinating disease of the central nervous system, and clinically it affects predominantly the optic nerves and spinal cord. Despite significant work, which has been previously made to diagnose NMO, it is still often not recognised, or accidentally diagnosed as multiple sclerosis. In fact, many clinical, laboratory or radiological characteristics are common in both NMO and multiple sclerosis. Devic’s disease, if not treated promptly or accidentally treated as multiple sclerosis, is a very disabling disease with a high mortality rate (Palace, Leite et al. 2010, Barnett, Prineas et al. 2012, Jacob, Hutchinson et al. 2012, Kleiter, Hellwig et al. 2012, Min, Kim et al. 2012, Izaki, Narukawa et al. 2013, Jurynczyk, Zaleski et al. 2013, Lee, Laemmer et al. 2014, Dubey, Kieseier et al. 2015). Treatment of the disease is based on anecdotal case reports. Due to severity and high disability of the disease, randomised placebo controlled treatment trials are unethical (Jacob, McKeon et al. 2013, Mealy, Wingerchuk et al. 2014). Many characteristics of NMO have probably not been identified and studied yet. Criteria to select the best treatment for patients with different phenotypes are also unknown. The purpose of this work was to analyse and characterise clinical features, efficacy of treatment of NMO/NMO spectrum, as well as to analyse the data entered into the Latvian MS register, for the purpose to improve diagnostic accuracy, treatment efficacy, and the outcomes of patients with NMO/NMOS. As a result of this work, several previously ignored NMO features have been described which may lead to earlier identification of the disease and therefore an earlier initiation of treatment. This is the first report describing NMO seasonality in western populations. The results, in contrast to MS, indicated higher NMO relapse activity during October and November but lower in June and July (Koziol and Feng 2004, Fonseca, Costa et al. 2009, Handel, Disanto et al. 2011, Damasceno, Von Glehn et al. 2012). For the first time it has been established that gradual NMO onset over 4 or more weeks represents around one fifth of the cases. The study also confirmed that secondary progressive disease occurs in 4% of the patients (Wingerchuk, Pittock et al. 2007). This is the first report describing the frequency and characteristics of neuropathic pruritus (NP) in patients with NMO/NMOS. Results showed that NP and also tonic spasms are common representing features of NMO/NMOS and can be the first sign of upcoming relapse. This study also looked at clinical phenotype of patients tested positive for MOG-IgG. In contrast to the previous reports (Kitley, Woodhall et al. 2012, Kitley, Waters et al. 2014), it was found that MOG-IgG are present in the sera of both, monophasic and relapsing NMO patients. Results confirmed that azathioprine is an effective immunosupresant in up to 89% (relapse free 61%) of patients (Mandler, Ahmed et al. 1998, Bichuetti, Lobato de Oliveira et al. 2010, Costanzi, Matiello et al. 2011), but also showed that its efficacy is significantly reduced in patients with more active and frequently relapsing disease (relapse free 44%). Despite its good efficacy, side effects were the most common reason for discontinuation of azathioprine. These are the first case series-describing efficacy of intravenous immunoglobulins in treatment of NMO relapse. IVIG were effective if used early in almost half of the patients. The analysis of Latvian MS register showed that the quality and quantity of data entered into the register is not sufficient for retrospective identification of suspected NMO/NMOS cases. As the result of work, recommendations to improve the quality of Latvian MS register, early recognition and treatment of NMO were made.