The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions. Here we review many emerging NMOSD biomarkers including markers of cellular damage, neutrophil-to-lymphocyte ratio, complement, and cytokines, with a focus on how each biomarker can potentially be used for initial diagnosis, relapse surveillance, disability prediction, and treatment monitoring.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Presently, three FDA-approved drugs are available to help slow functional decline for patients with ALS, but no cure yet exists. With an average life expectancy of only two to five years after diagnosis, there is a clear need for biomarkers to improve the care of patients with ALS and to expedite ALS treatment development. Here, we provide a review of the efforts made towards identifying diagnostic, prognostic, susceptibility/risk, and response fluid biomarkers with the intent to facilitate a more rapid and accurate ALS diagnosis, to better predict prognosis, to improve clinical trial design, and to inform interpretation of clinical trial results. Over the course of 20 + years, several promising fluid biomarker candidates for ALS have emerged. These will be discussed, as will the exciting new strategies being explored for ALS biomarker discovery and development.

The COVID-19 outbreak has emerged as one of the most profound medical events of the 21st century, leaving an indelible impact on a global scale. The widespread prevalence causing significant illness and death needs collaborative and inventive efforts to deal with this challenge. One of the particular subset of the general population that had endured a significant impact was the pregnant population. A key complication of pregnancy seen in patients with a COVID-19 infection was the increased risk of developing preeclampsia. The angiotensin-converting enzyme 2 (ACE2) receptor is an important part of the renin-angiotensin system, which has been implicated in the control of blood flow and also is a key receptor in the pathogenesis of the multitude of symptoms of COVID-19. This study aimed to evaluate the psychiatric, hematological, neurological, and social factors influenced by the COVID-19 virus and its subsequent effect on the development of preeclampsia. Increased rates of anxiety and depression were seen globally during the COVID-19 pandemic and due to the following physiological response of anxiety and depression, elevated blood pressure levels and development of preeclampsia were noted. Neurological factors such as the development of posterior reversible encephalopathy syndrome and its relationship between COVID-19 and preeclampsia were also strongly observed. The observation suggested biomarkers such as serum neurofilament light may be used as a screening tool to stratify the severity of preeclampsia. Hematological parameters observed were most notable for the presence of thrombocytopenia, which itself is a marker of the severity of preeclampsia. The numerous effects of COVID-19 on preeclampsia have proven to have a tremendous impact on the healthcare burden. Careful analysis and prevention strategies, if implemented, will contribute to reducing the morbidity and mortality of patients with preeclampsia and COVID-19 infections.

Neurodegenerative diseases are heterogeneous in their cause and clinical presentation making clinical assessment and disease monitoring challenging. Because of this, there is an urgent need for objective tools such as fluid biomarkers able to quantitate different aspects of the disease. In the last decade, technological improvements and awareness of the importance of biorepositories led to the discovery of an evolving number of fluid biomarkers covering the main characteristics of neurodegenerative diseases such as neurodegeneration, protein aggregates and inflammation. The ability to quantitate each aspect of the disease at a high definition enables a more precise stratification of the patients at inclusion in clinical trials, hence reducing the noise that may hamper the detection of therapeutical efficacy and allowing for smaller but likewise powered studies, which particularly improves the ability to start clinical trials for rare neurological diseases. Moreover, the use of fluid biomarkers has the potential to support a targeted therapeutical intervention, as it is now emerging for the treatment of amyloid-beta deposition in patients suffering from Alzheimer\'s disease. Here we review the knowledge that evolved from the measurement of fluid biomarker proteins in neurodegenerative conditions.

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders and can be caused by mutations in over 100 different genes. One of the causative genes is NEFL on chromosome 8 which encodes neurofilament light protein (NEFL), one of five proteins that co-assemble to form neurofilaments. At least 34 different CMT-causing mutations in NEFL have been reported which span the head, rod, and tail domains of the protein. The majority of these mutations are inherited dominantly, but some are inherited recessively. The resulting disease is classified variably in clinical reports based on electrodiagnostic studies as either axonal (type 2; CMT2E), demyelinating (type 1; CMT1F), or a form intermediate between the two (dominant intermediate; DI-CMTG). In this article, we first present a brief introduction to CMT and neurofilaments. We then collate and analyze the data from the clinical literature on the disease classification, age of onset and electrodiagnostic test results for the various mutations. We find that mutations in the head, rod, and tail domains can all cause disease with early onset and profound neurological impairment, with a trend toward greater severity for head domain mutations. We also find that the disease classification does not correlate with specific mutation or domain. In fact, different individuals with the same mutation can be classified as having axonal, demyelinating, or dominant intermediate forms of the disease. This suggests that the classification of the disease as CMT2E, CMT1F or DI-CMTG has more to do with variable disease presentation than to differences in the underlying disease mechanism, which is most likely primarily axonal in all cases.