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Background: Flammer syndrome (FS) occurs from well-described signs and symptoms. The syndrome itself is not a disease, but it may be a directive marker for advancing therapeutic approaches by predictive and preventive measures as well as for personalization of treatments. The syndrome is related to many diseases, but FS has been rarely studied in multiple sclerosis (MS). The study aimed to determine whether FS signs and symptoms occur more often in people with MS than in healthy controls, and in order to personalize the treatment, we investigated the possible effect of current therapies on FS signs and symptoms. Methods: Two hundred twenty-two MS patients and 203 healthy controls answered the questionnaire consisting of 15 signs and symptoms of FS. Results: MS patients had significantly more complaints in 9 items of FS signs and symptoms (cold hands or/and feet, the reduced feeling of thirst, dizziness, drug side effects, other headaches (tension-type, medication overuse), weight loss, feeling cold, long sleep-onset time, and skin blotches) compared to healthy controls. Six items (low blood pressure, tinnitus, increased odor sensitivity, low pain threshold, and perfectionism) were similar between the two groups. The treatment agents currently used did not have any effect on the signs and symptoms of FS. Conclusion: This study showed that FS might be associated with MS. Injectable or oral agents are not related to the signs and symptoms of FS. Further studies are needed to validate this association. Relevance of the article for predictive, preventive, and personalized medicine: FS is common among MS patients. Being aware of this incidence that might impair the life quality of MS patients is useful to predict the comorbidity and develop preventive strategies and applying personalized treatment options and procedures. [ABSTRACT FROM AUTHOR]

Flammer syndrome (FS) is a prevalent and mostly benign condition. Subjects with FS seem to have a good life expectancy. Nevertheless, FS subjects are at increased risk for certain diseases, mainly when they are challenged by psychological stress or other stimuli such as coldness. FS is related to ocular diseases, such as normal-tension glaucoma, retinitis pigmentosa, central serous chorioretinopathy, optic nerve compartment syndrome, Leber's hereditary optic neuropathy, arterial or venous occlusions in the retina, and choroid and optic nerve head, despite the absence of classical vascular risk factors. FS is also related to some non-ocular diseases, such as multiple sclerosis, breast cancer, and altitude sickness. The role of FS in other diseases such as tinnitus, sudden hearing loss, Ménière's disease, anorexia nervosa, and thyroid dysfunction is currently under investigation. The exact relationship of FS to related diseases however still needs to be established. This may hopefully lead to more targeted diagnostics and personalized treatments. [ABSTRACT FROM AUTHOR]

This review describes the clinical and basic research that led to the description of Flammer syndrome. It is narrated from a personal perspective. This research was initiated by the observation of an increased long-term fluctuation of visual fields in a subgroup of glaucoma patients. As these patients had strikingly cold hands, peripheral blood flow was tested with a capillary microscopy, and vasospastic syndrome (VS) was diagnosed. Further studies on these patients revealed frequently weakened autoregulation of ocular blood flow and increased flow resistivity in retroocular vessels. Their retinal vessels were more rigid and irregular and responded less to flickering light. Holistic investigation demonstrated low blood pressure, silent myocardial ischaemia, altered beat-to-beat variation, altered gene expression in the lymphocytes, slightly increased plasma endothelin level and increased systemic oxidative stress. This combination of signs and symptoms was better described by the term primary vascular dysregulation (PVD) than by VS. Subsequent studies showed additional symptoms frequently related to PVD, such as low body mass index, cold extremities combined with slightly increased core temperature, prolonged sleep onset time, reduced feelings of thirst, increased sensitivity to smell and also for certain drugs and increased retinal venous pressure. To better characterise this entire syndrome, the term Flammer syndrome (FS) was introduced. Most subjects with FS were healthy. Nevertheless, FS seemed to increase the risk for certain eye diseases, particularly in younger patients. This included normal-tension glaucoma, anterior ischaemic optic neuropathy, retinal vein occlusions, Susac syndrome and central serous chorioretinopathy. Hereditary diseases, such as Leber's optic neuropathy or retinitis pigmentosa, were also associated with FS, and FS symptoms and sings occurred more frequent in patients with multiple sclerosis or with acute hearing loss. Further research should lead to a more concise definition of FS, a precise diagnosis and tools for recognizing people at risk for associated diseases. This may ultimately lead to more efficient and more personalised treatment. [ABSTRACT FROM AUTHOR]