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Copyright 2003, 2004, 2009, 2012
NORD is very grateful to John O. Susac, MD, deceased; Robert Rennebohm, MD, Pediatric Rheumatology and Immunology, Cleveland Clinic; and Robert A. Egan, MD, Director of Neuro-Ophthalmology, Oregon Neurology, for the preparation of this report.
Susac's syndrome is a rare disorder characterized by three main problems: impaired brain function (encephalopathy), partial or complete blockage (occlusion) of the arteries that supply blood to the retina (branch retinal artery occlusion, or BRAO), and inner ear disease (hearing loss, most notably).
Three main forms of Susac's syndrome have become apparent. In one form, encephalopathy is the main problem. In the second form, BRAO and hearing loss are the main problems, and there is little or no brain disease. In the third form, encephalopathy is the main problem in the beginning, but recurrent episodes of BRAO and hearing loss become the main problem after the encephalopathy goes away.
The encephalopathic form of Susac's syndrome often resolves spontaneously (often going away within 1 years), even without treatment (self-limited); the other forms tend to follow a more prolonged, more chronic course (3-10 years, or more).
Although considered rare, Susac's syndrome is being recognized more often worldwide and its true frequency in the general population is unknown. This is because the disorder may be misdiagnosed as multiple sclerosis.
Susac's syndrome is an autoimmune disease---specifically, an autoimmune endotheliopathy. "Autoimmune" means that a person’s own immune system is mistakenly attacking one's own healthy tissue. An "endotheliopathy" is any disorder that involves injury to the endothelium, which is the thin layer of cells that line the inner walls of blood vessels. In Susac's syndrome, the person's own immune system is mistakenly attacking the endothelial lining of the smallest blood vessels (the capillaries, venules and arterioles) in the brain, retina, and inner ear. When the endothelial cells become injured, they tend to swell, and this endothelial cell swelling plays a key role in the partial or complete occlusion (blockage) of the tiny vessels in the brain, retina and inner ear. This blockage results in decreased blood flow through the vessels and, therefore, decreased delivery of oxygen and nutrients to the brain, retina, and inner ear---causing these three organs to suffer.
The specific symptoms, severity, and outcome of Susac's syndrome vary from one person to another. The three main features (encephalopathy, branch retinal arterial occlusions, and hearing loss) are not always present at onset and all three do not necessarily develop in all cases.
In most cases, headaches (including migraine-like headaches) may precede the development of other symptoms of Susac's syndrome. A variety of additional neurological findings may develop including gait disturbances, slurred speech (dysarthria) and cognitive dysfunction including memory loss, confusion and, potentially, dementia. Many individuals develop psychiatric symptoms such as paranoia or personality or behavioral changes. The specific neurological symptoms that develop will vary from one person to another.
Branch retinal artery occlusion (BRAO) can cause the patient to notice a "dark spot" or "black area" in their field of vision; or, some patients describe a "curtain or shade being drawn" over a portion of their vision. The medical term for these symptoms is "scotoma." These symptoms are due to permanent injury to the retina, because of blocked blood flow. The retina is the thin layer of nerve cells that sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. Both eyes can be affected in individuals with Susac's syndrome. Permanent impairment of vision is the norm and the blind spot typically is very close to a patient's central vision. BRAOs may occur early in some individuals or much later in the course of the disease in others.
Many individuals with Susac's syndrome develop hearing loss due to damage to the small, snail-shaped organ of the inner ear known as the cochlea. The cochlea converts sound into nerve impulses to be sent to the brain. The damage to the cochlea is caused by the blockage of blood flow through the small vessels that supply blood to the cochlea. Hearing loss in Susac's syndrome may affect both ears (bilateral) and its severity can range from mild to severe. In some cases, hearing loss may occur before other symptoms of Susac's syndrome develop. Hearing loss is often accompanied by intense ringing of the ears (tinnitus). The vestibular apparatus, which is also located in the inner ear, can also be affected by the microvascular endotheliopathy of Susac's syndrome, resulting in vertigo (dizziness).
The encephalopathic form of Susac's syndrome is typically self-limited (i.e., goes away on its own, even without treatment). It usually runs a course of several months, during which time individuals experience fluctuating levels of symptoms (relapsing-remitting). Although the encephalopathic form eventually goes away on its own, treatment is necessary to prevent or minimize damage that can occur while the disease is active. Relapse of encephalopathy after a long period of remission is rare, but has been reported. The forms of Susac's syndrome in which BRAO and hearing loss are (or become) the main problems, usually follow a longer-lasting course (3-10 years, or longer).
Susac's syndrome is an autoimmune endotheliopathy, a disorder in which the body's immune system mistakenly attacks the inside lining (endothelium) of the walls of the very tiny blood vessels that supply blood to the brain, retina, and inner ear. The exact, underlying reason why this occurs is unknown. Why the microvasculature in the brain, retina, and inner ear are primarily affected is also unclear. The skin may also be involved.
Susac's syndrome primarily affects young women between the ages of 20-40, but has occurred in individuals ranging in age from 9 to 72. Women are affected three times more often than men. Although considered a rare disorder, Susac's syndrome is being recognized more often worldwide and may be more common than originally thought. However, because the disorder often goes unrecognized or misdiagnosed, determining the true frequency of Susac's syndrome in the general population is difficult.
So far, Susac's syndrome has not been noted to occur more frequently in any particular ethnic group. It also has not been known to occur in more than one member of any family, even when the extended family is taken into account.
Susac's syndrome was first reported in the medical literature in 1979 by Dr. John Susac. It has also been referred to as "retinopathy, encephalopathy, deafness associated microangiopathy (RED-M)" or "small infarctions of cochlear, retinal and encephalic tissue (SICRET)." When the characteristic ocular finding (BRAO) has occurred in the absence of encephalopathy and inner ear disease, it has been referred to as "idiopathic recurrent branch retinal arterial occlusion."
The encephalopathic form of Susac's syndrome is frequently misdiagnosed as multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). When Susac's syndrome presents primarily with hearing loss, tinnitus, and vertigo, it is frequently misdiagnosed as Meniere's disease.
Multiple sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the covering (myelin sheath) over the nerves. It is a demyelinating disease. The course of this disease is variable; it may advance, relapse, remit, or stabilize. The demyelinating plaques or patches scattered throughout the central nervous system interfere with the ability of the nerves to communicate (neurotransmission) and can cause a wide range of neurological symptoms including impairment of speech, numbness or tingling sensation in the limbs and difficulty walking. Dysfunction of the bladder and bowel may also be present. (For more information on this disorder, choose "multiple sclerosis" as your search term in the Rare Disease Database.)
Acute disseminated encephalomyelitis (ADEM) is a central nervous system disorder characterized by inflammation of the brain and spinal cord caused by damage to the fatty sheath (myelin) surrounding the nerves. This can occur spontaneously, but usually follows a viral infection or inoculation such as a bacterial or viral vaccine. The symptoms of ADEM usually develop rapidly and may include fever, headaches, vomiting, and fatigue. In severe cases, seizures or coma may develop. Vision loss can also occur due to inflammation of the optic nerve.
Meniere's disease is a rare disorder that affects the inner ear. Meniere's disease is characterized by periodic episodes of vertigo or dizziness; fluctuating, progressive, low-frequency hearing loss; ringing in the ears (tinnitus); and a sensation of fullness or pressure in the ear. The disorder usually affects only one ear. As with Susac's syndrome, hearing loss in Meniere's disease is caused by damage to the cochlea. The exact cause of Meniere's disease is unknown. (For more information on this disorder, choose "Meniere" as your search term in the Rare Disease Database.)
A diagnosis of Susac's syndrome is suspected based upon the identification of characteristic findings, a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests including magnetic resonance imaging (MRI) and fluorescein angiography.
A complete neurological and ophthalmological examination is essential to making the diagnosis of Susac's syndrome. The neurological examination may detect the encephalopathy which can present as confusion. The eye examination should also include visual field testing to determine how any BRAOs have affected the patient's vision. Patients often continue to have 20/20 vision even after BRAOs since the BRAO does not typically reduce visual acuity. Pupils should be dilated and the back of the eye examined carefully. BRAOs should be looked for as well as Gass plaques. Gass plaques appear as small yellow dots in the retinal vessels specifically the arterioles. These Gass plaques are sites of inflammation in the endothelium and do not have to be associated at the location of the BRAO.
An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. In individuals with Susac's syndrome, an MRI typically shows characteristic changes in the brain, especially the corpus callosum, which is the structure that connects the right and left halves of the brain. The most characteristic MRI abnormality is presence of lesions ("snowballs," "spokes," or "holes") in the central portion of the corpus callosum. These lesions are best seen on sagittal T2 FLAIR images of the corpus callosum.
A fluorescein angiogram (FA) is necessary for individuals suspected of having Susac's syndrome. Fluorescein angiography is an eye test that uses a special dye and a camera to evaluate blood flow (circulation) in the retina. In Susac's syndrome FA abnormalities include: evidence of partial or complete branch retinal artery occlusion (BRAO); vessel wall hyperfluorescence (increased intensity of dye staining the walls of vessels); "leakage" of dye; and chronic changes out in the periphery (capillary dropout, neovascularization, microaneurysms), with potential for vitreous hemorrhage.
Individuals with Susac's syndrome should also receive a hearing exam to detect any hearing loss. All patients with suspected Susac's syndrome should undergo an audiogram
When a patient with Susac's syndrome first presents to a physician, only one or two of the three components of the triad may be present. This adds to the difficulty in making the diagnosis and contributes to the probable underreporting of the disorder.
Although Susac's syndrome can be self-limited, early, aggressive and sustained treatment is needed to avoid or minimize potential irreversible neurological damage or hearing or vision loss. The two current mainstays of therapy are medications that suppress the activity of the immune system (immunosuppressive agents)---corticosteroid (e.g. prednisone) and intravenous immunoglobulins (IVIG). Additional drugs may also be necessary. Additional drugs that have been used to treat individuals with Susac's syndrome include mycophenylate mofetil (Cellcept), azathioprine (Imuran), methotrexate, cyclophosphamide, rituximab, and anti-TNF therapies.
For individuals with significant hearing loss, a hearing aid may be indicated. For those with profound hearing loss, a specific type of hearing aid called a cochlear implant may be beneficial.
To date, no clinical trials have been developed for the treatment of Susac's syndrome. If and when a clinical trial is developed for Susac's syndrome, information on such a trial will be posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Contacts for additional information about Susac's syndrome:
Robert Rennebohm, MD
Pediatric Rheumatology and Immunology
Robert A. Egan, MD
St. Helena Hospital
St. Helena, CA
Novel: Patient Rare Disease Registry
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Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac's Syndrome---Update. J Neurol Sci. 2010; 299(1-2): 86-91.
Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac's syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy. J Neurol Sci. 2007;257:270-272.
Rennebohm RM, Susac JO. Treatment of Susac's syndrome. J Neurol Sci. 2007;257:273-277.
Susac JO. Susac's syndrome. AJNR Am J Neuroradiol. 2004;25:351-352.
Susac JO, Murtagh FR, Egan RA, et al. MRI findings in Susac's syndrome. Neurology. 2003;61:1783-1787.
Egan RA, Nguyen TH, Gass JDM, Rizzo JF, Tivnan J, Susac JO. Retinal Artery Wall Plaques in Susac Syndrome. American Journal of Ophthalmolog. 2003;135:483-6.
Fialho D, Holmes P, Riordan-Eva P, Silber E. A blinding headache falling on deaf ears (Susac's syndrome). Pract Neurol. 2002;2:358-361.
Susac JO. Susac's syndrome: the triad of microangiopathy of the brain and retina with hearing loss in young women. Neurology. 1994;44:591-593.
Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology. 1979. 29:313-316.
Susac syndrome. Orphanet. http://www.orpha.net//consor/cgi-bin/OC_Exp.php?lng=EN&Expert=838. Last Updated January 2003. Accessed August 30, 2012.
Report last updated: 2012/09/05 00:00:00 GMT+0