Individualised patient profile: clinical utility of Flammer syndrome phenotype and general lessons for predictive, preventive and personalised medicine

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Abstract

This case report introduces a female patient, who since her teenager age evidently suffers from Flammer syndrome (FS) as the clearly defined sub-optimal health condition. Further, the patient has experienced collateral pathological conditions which primarily might be linked to the family (genetic) predisposition, but the development of which could be synergistically promoted by the FS-phenotype. The facts are thoroughly analysed and consequent hypotheses are presented, which are indicative for highly desirable predictive diagnostics and targeted preventive measures to be created based on the accurate interpretation of the individualised patient profile. The authors emphasise the great clinical relevance of the FS and field-related research.

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The primary vascular dysregulation syndrome: implications for eye diseases

Josef Flammer, Katarzyna Konieczka, Andreas J. Flammer (2013)

Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood–brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide recommendations on how to effectively promote the field in order to create innovative diagnostic tools to predict the pathology and develop more efficient treatment approaches tailored to the person.

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Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis.

Jonathan Borkum (2016)

Blau theorized that migraine triggers are exposures that in higher amounts would damage the brain. The recent discovery that the TRPA1 ion channel transduces oxidative stress and triggers neurogenic inflammation suggests that oxidative stress may be the common denominator underlying migraine triggers.

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Flammer syndrome

Katarzyna Konieczka, Robert Ritch, Carlo Enrico Traverso … (2014)

The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.

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Contributors

Olga Golubnitschaja: Olga.Golubnitschaja@ukbonn.de

Journal

Journal ID (nlm-ta): EPMA J

Journal ID (iso-abbrev): EPMA J

Title: The EPMA Journal

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1878-5077

ISSN (Electronic): 1878-5085

Publication date (Electronic): 22 February 2018

Publication date PMC-release: 22 February 2018

Publication date Collection: March 2018

Volume: 9

Issue: 1

Pages: 15-20

Affiliations

[1 ]ISNI 0000 0001 2240 3300, GRID grid.10388.32, Radiological Clinic, , Rheinische Friedrich-Wilhelms-Universität Bonn, ; Sigmund-Freud-Str 25, 53105 Bonn, Germany

[2 ]ISNI 0000 0001 2240 3300, GRID grid.10388.32, Breast Cancer Research Centre, , Rheinische Friedrich-Wilhelms-Universität Bonn, ; Bonn, Germany

[3 ]ISNI 0000 0001 2240 3300, GRID grid.10388.32, Centre for Integrated Oncology, Cologne-Bonn, , Rheinische Friedrich-Wilhelms-Universität Bonn, ; Bonn, Germany

[4 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, Department of Ophthalmology, , University of Basel, ; Basel, Switzerland

Article

Publisher ID: 127

DOI: 10.1007/s13167-018-0127-9

PMC ID: 5833886

PubMed ID: 29515684

SO-VID: c8b00eca-5cb9-4271-ac8e-0ece4fcc355c

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 23 January 2018

Date accepted : 26 January 2018

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ScienceOpen disciplines: Molecular medicine

Keywords: predictive preventive personalised medicine,flammer syndrome,diagnosis,cancer,pregnancy,risk assessment,multi-level diagnostics,recommendations

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ScienceOpen disciplines: Molecular medicine

Keywords: predictive preventive personalised medicine, flammer syndrome, diagnosis, cancer, pregnancy, risk assessment, multi-level diagnostics, recommendations

Individualised patient profile: clinical utility of Flammer syndrome phenotype and general lessons for predictive, preventive and personalised medicine

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Most cited references 22

The primary vascular dysregulation syndrome: implications for eye diseases

Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis.

Flammer syndrome

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