Susac syndrome is a rare neurological disorder characterized by inflammation and occlusion of the smallest blood vessels (microangiopathy) in three distinct anatomical regions: the brain, the retina, and the inner ear. The resulting disruption of blood flow can lead to a variety of symptoms that affect cognitive function, vision, and hearing. Because of its multi-system involvement and rarity, Susac syndrome often presents a diagnostic challenge to clinicians.
Understanding Susac Syndrome
The disorder is named after Dr. John Susac, who first described the condition in 1979. Susac syndrome is considered an orphan disease due to its extreme rarity, with only a few hundred cases reported worldwide. Estimates suggest the annual incidence may be as low as 0.024 to 0.13 cases per 100,000 people.
Susac syndrome predominantly affects young adults, with the average age of onset around 32 years. Young women are significantly more susceptible than men, exhibiting a female-to-male ratio of approximately 3:1. The condition is defined as a form of immune-mediated endotheliopathy, a disease process involving the innermost lining of blood vessels.
The Underlying Cause: Autoimmune Microangiopathy
Susac syndrome is believed to be an autoimmune process where the body’s own immune system mistakenly attacks the endothelial cells that line the interior walls of small blood vessels (microvasculature) within the brain, retina, and inner ear. This attack is thought to be mediated by an inflammatory response, possibly involving cytotoxic CD8+ T cells, which leads to damage of the endothelial lining.
The inflammation causes the endothelial cells to swell and proliferate, narrowing the vessel lumen and leading to partial or complete occlusion of blood flow. This blockage results in micro-infarcts, or small areas of tissue death due to lack of oxygen and nutrients, which is known as ischemia. The resulting ischemic damage in the specific organs generates the characteristic clinical manifestations. The exact trigger for this autoimmune response remains unclear.
The Characteristic Symptoms
The clinical presentation of Susac syndrome is defined by the classic triad: encephalopathy, branch retinal artery occlusions (BRAO), and sensorineural hearing loss. Only a small percentage of patients (13% to 30%) present with all three components simultaneously at the time of initial diagnosis. The symptoms may appear sequentially over weeks or months, making early diagnosis challenging.
Encephalopathy, or brain dysfunction, is a frequent initial symptom and can manifest as a broad spectrum of neurological issues. Patients may experience cognitive impairment, such as memory loss, confusion, and difficulty concentrating, along with behavioral changes, psychosis, or paranoia. A severe headache, which can be migrainous or oppressive in nature, is also a common neurological complaint, affecting up to 80% of patients.
The second component involves the eyes, specifically BRAO, which are blockages in the small arteries of the retina. These occlusions lead to visual disturbances, including partial or temporary loss of vision, blind spots called scotomata, or blurred vision. Because the occlusions are often located in the peripheral parts of the retina, a patient may be asymptomatic, requiring a specialized eye examination to detect the damage.
Sensorineural hearing loss is typically sudden in onset and commonly affects both ears, though one side may be more involved. This hearing loss characteristically involves the low-to-mid frequency ranges and is often accompanied by bothersome ringing in the ears, known as tinnitus, or occasionally vertigo. Unlike the brain and eye symptoms, the hearing loss is frequently irreversible, sometimes necessitating hearing aids or cochlear implants.
Diagnosis and Medical Imaging
Diagnosing Susac syndrome relies on a combination of clinical evaluation and specific diagnostic tests to confirm the presence of at least two of the three components of the triad. Specialized tests are crucial because the full triad is rarely present at onset and some symptoms, like retinal occlusions, can be clinically silent. Primary diagnostic tools involve brain imaging, retinal imaging, and hearing assessment.
Magnetic Resonance Imaging (MRI) of the brain is a foundational test that often reveals characteristic findings in patients with Susac syndrome. The most specific findings are small, rounded areas of damage, known as T2 hyperintensities, which frequently affect the central part of the corpus callosum. These lesions can resemble small “snowballs” in the acute phase, and as they resolve, they can leave behind pathognomonic central callosal “holes.”
Ophthalmological assessment requires fluorescein angiography (FA) to visualize the blood flow within the retina. This procedure involves injecting a fluorescent dye into the bloodstream to highlight the retinal vessels, allowing for the detection of BRAO. FA can also reveal arterial wall hyperfluorescence, or leakage, which is a sign of active inflammation and microvascular damage characteristic of the syndrome.
The integrity of the inner ear function is assessed using audiometry, a test that measures a person’s ability to hear different sounds, pitches, and intensities. In Susac syndrome, audiometry confirms the pattern of sensorineural hearing loss, typically demonstrating a loss in the low and mid-frequencies. This combination of specific findings across the three organ systems allows clinicians to differentiate Susac syndrome from other conditions.
Managing the Syndrome
The management of Susac syndrome focuses on reducing the acute inflammation and suppressing the autoimmune response to prevent further microvascular damage and tissue death. Early, aggressive, and sustained treatment minimizes the risk of long-term disability, such as permanent hearing loss or cognitive deficits. Due to the severity and multi-system nature of the disease, a multidisciplinary approach involving neurologists, ophthalmologists, and audiologists is necessary.
High-dose corticosteroids, such as intravenous methylprednisolone, are the mainstay of initial acute treatment to rapidly suppress the inflammatory process. Following this initial phase, long-term immunosuppressive therapy is typically initiated to sustain disease control and prevent relapses. Commonly used long-term agents include immunosuppressants like mycophenolate mofetil, azathioprine, and cyclophosphamide, which modulate the immune system’s activity.
In cases of severe or resistant disease, other immunomodulatory treatments, such as intravenous immunoglobulin (IVIG) or the biologic agent rituximab, may be employed. Treatment is often tailored to the individual patient, considering the severity of their symptoms and their response to therapy. The goal is to achieve rapid and complete disease suppression to protect the affected organs from irreversible ischemic damage.