Flammer syndrome is a recently described clinical entity comprising a complex of clinical features caused mainly by dysregulation of the blood supply which has previously been called vascular dysregulation. It can manifest itself in many symptoms such as cold hands and feet and is often associated with low blood pressure. In certain cases it is associated with or predisposes for the development of diseases such as a normal tension glaucoma.Flammer syndrome is named after the Swiss ophthalmologist Josef Flammer.
Hypotension is low blood pressure, especially in the arteries of the left sided systemic circulation. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. A systolic blood pressure of less than 90 millimeters of mercury or diastolic of less than 60 mm Hg is generally considered to be hypotension. However, in practice, blood pressure is considered too low only if noticeable symptoms are present.
Normal tension glaucoma (NTG) is an eye disease, a neuropathy of the optic nerve, that shows all the characteristics of "traditional" glaucoma except one: the elevated intraocular pressure (IOP) - the classic hallmark of glaucoma - is missing. Normal tension glaucoma is in many cases closely associated with general issues of blood circulation and of organ perfusion like arterial hypotension, metabolic syndrome, and Flammer syndrome.
Josef Flammer is a Swiss ophthalmologist and long-time director of the Eye Clinic at Basel University Hospital. Flammer is a glaucoma specialist who developed a new pathogenetic concept of glaucomatous damage according to which unstable blood supply leads to oxidative stress, which in turn plays a major role in apoptosis of cells in optic nerve and retina in glaucoma patients.
Most of the symptoms of Flammer syndrome result from an impaired regulation of the blood supply. How these symptoms affect the patient depends on which organ's or body part's blood supply is inhibited. Typical symptoms of Flammer syndrome are cold hands or feet, a low blood pressure, occasional white and red patches on the face or neck, and migraine-like pain or a feeling of pressure behind the upper eyelid. In addition, there are symptoms not directly resulting from dysregulations of the blood supply such as a prolonged time needed to fall asleep,a reduced feeling of thirst, high sensitivity not only to cold but also to odors, vibrations, psychological stress or certain medications (e.g., calcium antagonists, beta blockers) etc. Pain and muscle spasms are common. People with Flammer syndrome are usually very precise, highly motivated and successful in their professional life.
Scientific studies have shown that in many patients with glaucoma the cause of the disease are perfusion issues of the optic nerve and retina while intraocular pressure is normal. Many patients with normal tension glaucoma have a basic constitution, which corresponds to the Flammer syndrome. Some of its features were formerly summarized under the term "primary vascular dysregulation syndrome".
Glaucoma is a group of eye diseases which result in damage to the optic nerve and vision loss. The most common type is open-angle glaucoma with less common types including closed-angle glaucoma and normal-tension glaucoma. Open-angle glaucoma develops slowly over time and there is no pain. Peripheral vision may begin to decrease followed by central vision resulting in blindness if not treated. Closed-angle glaucoma can present gradually or suddenly. The sudden presentation may involve severe eye pain, blurred vision, mid-dilated pupil, redness of the eye, and nausea. Vision loss from glaucoma, once it has occurred, is permanent.
The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which translates that image into electrical neural impulses to the brain to create visual perception, the retina serving a function analogous to that of the film or image sensor in a camera.
Signs of Flammer syndrome may include:
A migraine is a primary headache disorder characterized by recurrent headaches that are moderate to severe. Typically, the headaches affect one half of the head, are pulsating in nature, and last from two to 72 hours. Associated symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity. Up to one-third of people have an aura: typically a short period of visual disturbance that signals that the headache will soon occur. Occasionally, an aura can occur with little or no headache following it.
Tinnitus is the hearing of sound when no external sound is present. While often described as a ringing, it may also sound like a clicking, hiss or roaring. Rarely, unclear voices or music are heard. The sound may be soft or loud, low pitched or high pitched and appear to be coming from one ear or both. Most of the time, it comes on gradually. In some people, the sound causes depression or anxiety and can interfere with concentration.
People with Flammer syndrome typically respond excessively to mental or physical stimuli such as stress or exposure to cold. The disease is more prevalent in the following groups of people: in women compared to men, in people with lower blood pressure, in Asians compared with Caucasians, it is more frequent among academics than among blue collar-workers. People with Flammer syndrome are usually highly motivated in their professional life, they sleep poorlyand they have a decreased sensation of thirst.
The diagnosis of Flammer's syndrome is primarily based on the patient's history with its typical features as well as the findings of nail fold capillaroscopy. This test shows an excessive constriction (narrowing) in the smallest blood vessels (capillaries) of the fingers in response to being exposed to cold as a stimulus. Patients with vasospastic symptoms as they are characteristic for Flammer syndrome have shown a unique gene expression when their lymphocytes underwent gene expression profiling.
To have Flammer syndrome does not necessarily mean that this individual is sick. On the contrary: most of those affected are and remain healthy. Certain diseases such as arteriosclerosis and its consequences are probably even rarer. Best known is the higher risk of normal tension glaucoma, a disease with an impaired regulation of blood flow in a large number of patients.If glaucomatous damage occurs despite normal eye pressure or if glaucomatous damage is progressive despite normalized intraocular pressure, frequently a Flammer syndrome is the cause. In these eyes, an elevated pressure in the retinal veins has been observed. Glaucoma patients with Flammer syndrome show some specific clinical signs like an increased frequency of the following: optic disc haemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization and fluctuating diffuse visual field defects. The association of normal tension glaucoma with the syndrome has recently been confirmed by a group of Chinese researchers. In a 2016 review on the risk factors for normal tension glaucoma by ophthalmologists from Asia (where this form of glaucoma is much more prevalent than in Europe or North America), Flammer syndrome has been attributed to increase the likelihood of ganglion cell damage in these patients with disc hemorrhages as a characteristic clinical sign. Migraine attacks, a common feature of Flammer syndrome, have been described as a risk factor for glaucoma progression, in open-angle glaucoma as well as in normal tension glaucoma. Flammer syndrome may also predispose to other eye diseases such as vascular occlusion (especially retinal vein occlusion) in relatively young people or central serous retinopathy. Muscle spasms and tension are common among individuals with Flammer syndrome. Tinnitus and sometimes even acute hearing loss can occur. There is currently insufficient data available on cases where Flammer syndrome is suspected like in the sudden, unexpected deaths of young athletes. People suffering from retinitis pigmentosa seem to have Flammer syndrome quite frequently, possible associations with the vascular factor endothelin-1 are under investigation.
Flammer syndrome requires no therapy as long as a person does not suffer from the symptoms or pathological sequelae occur. The treatment is based on three pillars: a) lifestyle interventions, b) diet and c) medication. A healthy lifestyle should include regular sleep, weight stabilization (in the sense of not being underweight), avoiding periods of fasting and avoidance of known trigger factors such as cold. Regular physical exercise is good, extreme sports might be detrimental. Nutrition should contain lots of antioxidants. Among these are green tea, black filter coffee, red wine, blue berries and fruits etc. Omega-3 fatty acids, especially in the form of fish, improve the regulation of blood flow. If blood pressure is very low, the salt intake should be increased. Drugs that can lead to vasoconstriction should be avoided. If blood pressure is too low, sleeping pills should be taken cautiously. Magnesium and calcium antagonists may help against the vascular dysregulation. With lifestyle interventions attacks - particularly pronounced symptoms such as massive cold extremities, tinnitus or migraine-like episodes - can be avoided or these can at least be reduced. Stabilizing weight (i.e. not being underweight) and the avoidance of periods of fasting are important.
Medical treatment is necessary when normal tension glaucoma is present. In these cases, in addition to the ophthalmologic treatment of glaucoma, the patient's usually low blood pressure should be addressed. With dietary measures such as salt intake and sometimes with low-dose steroids a drop in blood pressure - especially during sleep - can often be prevented. These nightly "dips" of blood pressure in normal tension glaucoma patients with Flammer syndrome can damage the sensory cells of the retina significantly.
For over 100 years vasospasms are known, particularly in the vessels supplying the retina of the eye with blood. These vasospasms are temporary narrowings of arteries or arterioles, which result in an insufficient supply of blood of the corresponding organs or parts of organs. Such spasms can occur at various locations in the human body; in this case medical terminology calls it "vasospastic syndrome". Over the years, it has been established that these spasms are usually part of a general dysregulation of blood vessels. These dysregulations can occur in spasms as well as in excessive or insufficient dilation of arteries, veins, and capillaries. The blood vessels of individuals suffering from vasospastic syndrome respond to stimuli insufficiently. If an identifiable disease does not cause this, it is called a primary vascular dysregulation (PVD); in case of an underlying disease it is called secondary PVD. PVD is almost always associated with other vascular and non-vascular symptoms and signs. [ citation needed ]This entire complex (PVD and accompanying symptoms) is today called Flammer syndrome.
Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically included under the umbrella term retinopathy but is often discussed as a separate entity. Retinopathy, or retinal vascular disease, can be broadly categorized into proliferative and non-proliferative types. Frequently, retinopathy is an ocular manifestation of systemic disease as seen in diabetes or hypertension. Diabetes is the most common cause of retinopathy in the U.S. as of 2008. Diabetic retinopathy is the leading cause of blindness in working-aged people. It accounts for about 5% of blindness worldwide and is designated a priority eye disease by the World Health Organization.
Angina, also known as angina pectoris, is chest pain or pressure, usually due to not enough blood flow to the heart muscle.
Headache is the symptom of pain anywhere in the region of the head or neck. It occurs in migraines, tension-type headaches, and cluster headaches. Frequent headaches can affect relationships and employment. There is also an increased risk of depression in those with severe headaches.
Alice in Wonderland Syndrome (AiWS), also known as Todd's syndrome or dysmetropsia, is a disorienting neuropsychological condition that affects perception. People may experience distortions in visual perception such as micropsia, macropsia, pelopsia, or teleopsia. Size distortion may occur in other sensory modalities as well.
Retinopathy of prematurity (ROP), also called retrolental fibroplasia (RLF) and Terry syndrome, is a disease of the eye affecting prematurely born babies generally having received intensive neonatal care, in which oxygen therapy is used on them due to the premature development of their lungs. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve spontaneously, but it may lead to blindness in serious cases. As such, all preterm babies are at risk for ROP, and very low birth-weight is an additional risk factor. Both oxygen toxicity and relative hypoxia can contribute to the development of ROP.
Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which spasm of arteries cause episodes of reduced blood flow. Typically, the fingers, and less commonly the toes, are involved. Rarely, the nose, ears, or lips are affected. The episodes result in the affected part turning white and then blue. Often, numbness or pain occurs. As blood flow returns, the area turns red and burns. The episodes typically last minutes, but can last several hours.
Cardiac syndrome X is a historic term for microvascular angina, angina with signs associated with decreased blood flow to heart tissue but with normal coronary arteries.
Amaurosis fugax is a painless temporary loss of vision in one or both eyes.
Sheehan's syndrome, also known as postpartum pituitary gland necrosis, is hypopituitarism, caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.
Variant angina, often termed Prinzmetal's angina, Prinzmetal angina, and less commonly vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina that unlike classical angina, which is triggered by exertion or exercise, commonly occurs in individuals at rest or even asleep. It is caused by vasospasm, a narrowing of the coronary arteries due to contraction of the smooth muscle tissue in the vessel walls. This contrasts with classical angina which is due to the permanent occlusion of these vessels by atherosclerosis.
Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells, or neurons, leads to characteristic features of optic neuropathy. The main symptom is loss of vision, with colors appearing subtly washed out in the affected eye. On medical examination, the optic nerve head can be visualised by an ophthalmoscope. A pale disc is characteristic of long-standing optic neuropathy. In many cases, only one eye is affected and patients may not be aware of the loss of color vision until the doctor asks them to cover the healthy eye.
The central retinal vein is the venous equivalent of the central retinal artery and, like that blood vessel, it can suffer from occlusion, similar to that seen in ocular ischemic syndrome. Since the central retinal artery and vein are the sole source of blood supply and drainage for the retina, such occlusion can lead to severe damage to the retina and blindness, due to ischemia and edema (swelling).
Retinal migraine is a retinal disease often accompanied by migraine headache and typically affects only one eye. It is caused by ischaemia or vascular spasm in or behind the affected eye.
Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare genetic disorder, which affects multiple organs. Its hallmarks are widespread progressive calcifications, cysts and abnormalities of the white matter of the brain, usually occurring together with abnormalities of the blood vessels of the retina. Additional features include poor prenatal growth, preterm birth, anemia, osteopenia and bone fractures, and gastrointestinal bleeding. It is caused by compound heterozygous mutations in the conserved telomere maintenance component 1 (CTC1) gene, but its exact pathophysiology is still not well understood.
The eye is made up of the sclera, the iris, and the pupil, a black hole located at the center of the eye with the main function of allowing light to pass to the retina. Due to certain muscle spasms in the eye, the pupil can resemble a tadpole, which consists of a circular body, no arms or legs, and a tail.
Kounis syndrome is defined as acute coronary syndrome caused by an allergic reaction or a strong immune reaction to a drug or other substance. It is a rare syndrome with authentic cases reported in 130 males and 45 females, as reviewed in 2017; however, the disorder is suspected of being commonly overlooked and therefore much more prevalent. Mast cell activation and release of inflammatory cytokines as well as other inflammatory agents from the reaction leads to spasm of the arteries leading to the heart muscle or a plaque breaking free and blocking one or more of those arteries.
Tonic tensor tympani syndrome is a disease of the tensor tympani muscle, described by Klochoff et al in 1971. It involves a decrease in the contraction threshold of the tensor tympani. This hypercontraction leads to chronic ear pain, in particular in the case of hyperacusis and acoustic shock.