Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Abstract:

Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood.

These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration.

Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.

Source: Cohen J, Mathew A, Dourvetakis KD, Sanchez-Guerrero E, Pangeni RP, Gurusamy N, Aenlle KK, Ravindran G, Twahir A, Isler D, Sosa-Garcia SR, Llizo A, Bested AC, Theoharides TC, Klimas NG, Kempuraj D. Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders. Cells. 2024 Mar 14;13(6):511. doi: 10.3390/cells13060511. PMID: 38534355; PMCID: PMC10969521. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10969521/ (Full text)

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease

Abstract:

Importance: While the understanding of inflammation in the pathogenesis of many neurological diseases is now accepted, this special commentary addresses the need to study chronic inflammation in the propagation of cognitive Fog, Asthenia, and Depression Related to Inflammation which we name Brain FADE syndrome. Patients with Brain FADE syndrome fall in the void between neurology and psychiatry because the depression, fatigue, and fog seen in these patients are not idiopathic, but instead due to organic, inflammation involved in neurological disease initiation.

Observations: A review of randomized clinical trials in stroke, multiple sclerosis, Parkinson’s disease, COVID, traumatic brain injury, and Alzheimer’s disease reveal a paucity of studies with any component of Brain FADE syndrome as a primary endpoint. Furthermore, despite the relatively well-accepted notion that inflammation is a critical driving factor in these disease pathologies, none have connected chronic inflammation to depression, fatigue, or fog despite over half of the patients suffering from them.

Conclusions and relevance: Brain FADE Syndrome is important and prevalent in the neurological diseases we examined. Classical “psychiatric medications” are insufficient to address Brain FADE Syndrome and a novel approach that utilizes sequential targeting of innate and adaptive immune responses should be studied.

Source: Khalid A. Hanafy, Tudor G. Jovin. Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease. Front. Immunol., 17 January 2024, Sec. Inflammation, Volume 15 – 2024 | https://doi.org/10.3389/fimmu.2024.1332776 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1332776/full (Full text)

Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients

Abstract:

BACKGROUND: We report 4 patients with young-onset monogenetic parkinsonism, each of whom was misdiagnosed with either a psychogenic movement disorder or chronic fatigue syndrome for 10 to 23 years after the onset of their first symptoms.

RESULTS: Once the diagnosis was eventually made, they all had a rapid and excellent response to levodopa, albeit with the early appearance of interdose dyskinesias in 3.

CONCLUSIONS: We discuss possible reasons for the missed diagnosis despite the relentless progression of their motor handicap. DAT scanning supported the revised clinical diagnosis of parkinsonism.

Copyright © 2011 Movement Disorder Society.

 

Source: Ling H, Braschinsky M, Taba P, Lüüs SM, Doherty K, Hotter A, Poewe W, Lees AJ. Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients. Mov Disord. 2011 Jun;26(7):1337-40. doi: 10.1002/mds.23563. Epub 2011 Mar 29. https://www.ncbi.nlm.nih.gov/pubmed/21449012

 

Adaptive tasks, coping and quality of life of chronically ill patients: the cases of Parkinson’s disease and chronic fatigue syndrome

Abstract:

This article is a report of a larger study on the relationship between adaptive tasks, coping and quality of life, taking Parkinson’s disease and chronic fatigue syndrome (CFS) as examples. The concept of adaptive tasks or disease-related stressors testing the adaptive capacities of chronically ill patients (N=134) was explored by applying the method of concept mapping.

Results show that patients both with Parkinson’s disease and with CFS generally refer to the same themes when asked for the adaptive tasks their disease brings about. However, the actual contents of these adaptive tasks differ as well as their impact on coping and quality of life. In the case of patients with Parkinson’s disease, objective disease characteristics appear to be more important in predicting quality of life than in the case of patients with CFS, whose evaluation of adaptive tasks is predictive of quality of life.

 

Source: De Ridder DT, Schreurs KM, Bensing JM. Adaptive tasks, coping and quality of life of chronically ill patients: the cases of Parkinson’s disease and chronic fatigue syndrome. J Health Psychol. 1998 Jan;3(1):87-101. Doi: 10.1177/135910539800300107. http://www.ncbi.nlm.nih.gov/pubmed/22021345