By Colm Gorey, Frontiers Science Communications Manager

Image: Shutterstock.com

In an ever-changing field of research such as neurology, it can be difficult to keep up with the latest breakthroughs. Now at Frontiers, we highlight just three of the latest research articles to shed more light on how the mind works.

The human brain is an organ that has fascinated our species for centuries, with vast amounts of research so far yielding a wealth of discoveries. However, so much of how the brain works remains a mystery waiting to be solved.

In 2022, Frontiers published one of the biggest neurological research breakthroughs of the year with the discovery that life may indeed flash before our eyes as we die. However, this was just one paper of thousands published by Frontiers this year that helped set the groundwork for new neurological discoveries, ranging from multiple sclerosis to deep brain stimulation.

Five such articles are essential reading to anyone looking to learn more about neurology were published as part of the research topic ‘Horizons in Neurology’.

The Neuroimmunology of Multiple Sclerosis: Fictions and Facts

There have been tremendous advances in the neuroimmunology of multiple sclerosis (MS) over the past five decades, which have led to improved diagnosis and therapy in the clinic. However, further advances must take into account an understanding of some of the complex issues in the field, particularly an appreciation of ‘facts’ and ‘fiction’.

Not surprisingly given the incredible complexity of both the nervous and immune systems, our understanding of the basic biology of the disease is very incomplete. This lack of understanding has led to many controversies in the field. 

Writing in Frontiers in Neurology, Dr Andrew R Pachner of Dartmouth–Hitchcock Medical Center listed a number of claims which are fiction, including that viral models of MS are irrelevant because MS is not a disease, and that MS is an autoimmune disease.

Link: https://www.frontiersin.org/articles/10.3389/fneur.2021.796378/full

Uncovering Essential Tremor Genetics: The Promise of Long-Read Sequencing

Genetic factors are known to contribute to various neurodegenerative diseases, and the development of next-generation sequencing (NGS) technologies during the last 15 years has accelerated the discovery of novel familial movement disorders and disease-causing variants.

However, despite the increase in genes and variants discovered in this group of disorders, routine NGS techniques have intrinsic limitations, mainly due to their ability to only sequence short-read length fragments.

In March this year, researchers in the US and Argentina published a paper to Frontiers in Neurology describing the genetics behind the neurological disorder called ‘essential tremor’. The use of Long-read sequencing (LRS) technologies has helped overcome the limitations of NGS, and their review of LRS in neurodegenerative disorders showed that 10 of the 22 (45%) genetic etiologies ascertained by LRS include tremor in their phenotypic spectrum.

This suggested that future clinical applications of LRS for tremor disorders may uncover genetic subtypes of familial ET that have eluded NGS, particularly those with associated leukoencephalopathy or family history of epilepsy.

Link: https://www.frontiersin.org/articles/10.3389/fneur.2022.821189/full

Therapeutic Advances in Multiple Sclerosis

Over the last three decades, there has been a rapid expansion of treatment options for MS as well as increasing efficacy of newer agents against relapses. Despite advances in our understanding of the biology of MS pathogenesis, there remains a scarcity of effective treatment for progressive disease. While newer DMTs have higher efficacy in reducing relapse rate and MRI disease activity, they also may carry higher side effect profiles due to increased levels of immunosuppression. 

In a review published to Frontiers in Neurology, researchers in the University of California San Diego and University of Florida said that part of the difficulty in the management of MS is the heterogenous nature of the disease, which is influenced by environmental and genetic factors as well as the naturally adaptive and evolving nature of the immune system that changes with time and age.

And while there is promising increased activity in the field for the development of neuroprotective and remyelinating therapies, further studies are needed to identify early risk factors for an increased inflammatory state, early neurodegeneration, or a combination of both.

Link: https://www.frontiersin.org/articles/10.3389/fneur.2022.824926/full

Past, Present, and Future of Deep Brain Stimulation: Hardware, Software, Imaging, Physiology and Novel Approaches

Deep brain stimulation (DBS) has evolved substantially over the past several decades. The technology first appeared in mainstream practice in the 1980's for the treatment of Parkinson's disease. Since then, innovative updates to DBS technology have led to an overwhelming expansion in its use and its applications. Technical advances include more lead contacts and an increased number of algorithms and stimulation patterns as well as an emergence of increasing treatment indications. 

Researchers in Frontiers in Neurology published a review earlier this year discussed the history of DBS, what exists today and what technology is in the pipeline.

They said that Improvements in lead design has allowed segmented contacts to be used for directional stimulation, and improvements in IPG design have led to smaller, longer-lasting, batteries that are MRI compatible.

Advances in software have enabled a variety of programming strategies to be employed to help improve efficacy while minimizing stimulation-induced side effects and also by maximizing battery life. Looking toward the future, brain sensing will help clinicians and researchers understand the physiologic aspects of DBS and potentially act as another programming strategy.

Link: https://www.frontiersin.org/articles/10.3389/fneur.2022.825178/full

Gut-Derived Sterile Inflammation and Parkinson's Disease

The etiology of Parkinson's disease is unknown, but evidence is increasing that there is a prominent inflammatory component to the illness. Epidemiological, genetic, and preclinical evidence support a role for gut-derived sterile inflammation, according to Dr Kathleen M Shannon of the University of Wisconsin, writing in Frontiers in Neurology.

Pro-inflammatory bacteria are over-represented in the gut microbiota of those with Parkinson’s and there is evidence for decreased gut barrier function and leak of bacterial antigen across the gut epithelium with sub-mucosal inflammation and systemic exposure to the bacterial endotoxin lipopolysaccharide.

Preclinical evidence supports these clinical findings and suggests that systemic inflammation can affect the CNS through vagal pathways or the systemic circulation. As part of her research, Shannon reviewed recent preclinical and clinical evidence to support this mechanism and suggested possible treatments directed at the gut-brain axis.

Link: https://www.frontiersin.org/articles/10.3389/fneur.2022.831090/full

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