Susac syndrome is a rare autoimmune disease with a triad of clinical syndromes: encephalopathy, hearing loss, retinal microangiopathy. Symptoms include impaired attention, memory, behavior, hearing impairment and variable visual disorders. The diagnosis is established by the results of cerebral MRI, fluorescent retinal angiography, audiometry. Intensive immunosuppressive treatment with a combination of glucocorticoid and cytostatic drugs with the addition of intravenous interferon and therapy with monoclonal antibodies to B lymphocytes is considered the most effective.
ICD 10
M31.8 Other specified necrotizing vasculopathies
General information
Susac syndrome (retino-cochleo-cerebral vasculopathy) is a rare pathology first described by American physician John Susak and two of his colleagues in 1979 on the example of two patients suffering from hearing loss in combination with encephalopathy and retinal angiopathy. All known cases of the disease were observed in persons aged 9 to 72 years. However, the most characteristic age of the debut falls on the period from 20 to 40 years. To date, more than 500 cases of Susac syndrome have been registered worldwide. Women get sick 2-3 times more often than men. There is evidence that the disease is more severe in men.
Causes
Susac syndrome is an autoimmune pathology, the exact causes of which have not yet been determined. There are no genetic or hereditary links in the occurrence of the disease. As for most autoimmune processes, among the etiological factors leading to dysfunction of the immune system, there are transferred viral infections, restructuring of the mother’s body during pregnancy, long-term therapy with hormonal pharmaceuticals. These triggers can provoke the production of autoantibodies, which causes the development of Susak vasculopathy.
Pathogenesis
The main pathogenetic mechanism of the disease is currently considered to be dysfunction of individual parts of the immune system, leading to the production of antibodies against their own endothelial cells lining the walls of small-caliber vessels (arterioles, capillaries) in the inner ear, brain and retina. Damage to the endothelium of the vessels of the microcirculatory bed with the development of microangiopathy entails their narrowing and occlusion with impaired microcirculation. The result is insufficient blood supply (ischemia) and oxygen starvation (hypoxia) of the surrounding tissues.
Changes in the brain are characterized by foci of microinfarcts that damage neurons, their processes and myelin sheath. In such places, the nerve tissue is replaced by glial tissue, the formation of small foci of gliosis occurs, which leads to encephalopathy. Retinal vascular endotheliopathy is accompanied by a decrease in vision.
Microcirculation disorder in the inner ear leads to hearing impairment. The issue of selective localization of vascular changes has not been fully investigated. The predisposition to a triad of symptoms in Susac syndrome may be due to the fact that microvascular occlusions in the brain, retina and cochlea cause more pronounced symptoms than in other places.
Symptoms
A characteristic triad of clinical manifestations of Susac syndrome includes disorders of the brain (encephalopathy), hearing loss, vision. However, in 80% of patients, pathology manifests as a mono-organ lesion. The onset of the disease is manifested by intense migraine headaches, localized in one or the other half of the head. Nausea and photophobia are possible at the height of pain. Headache is considered the most common prodromal symptom and may appear several months before the development of encephalopathy.
In some cases, the syndrome debuts with obvious signs of encephalopathy: mental disorders, cognitive changes, memory impairment. Mental disorders range from depressive states to aggressive behavior. Paranoid disorders are possible, characterized by the presence of an obsessive delusional idea and related changes in behavior: increased suspicion, irritability, resentment or hostility. Since the patient’s perception of reality is distorted, these changes can only be noticed by his relatives.
Cognitive disorder is manifested by absent-mindedness, difficulty concentrating, difficulties remembering current information, memory loss (amnesia). The progression of Susak’s vasculopathy is accompanied by the appearance of focal neurological symptoms: muscle weakness in the upper limb (monoparesis) and dysarthria. The patient cannot fully move his hand, hold objects in it. His speech becomes indistinct and incomprehensible to others. Confusion of consciousness is noted, dementia (dementia) develops. In some cases, seizures are observed.
Damage to the vessels of the inner ear is manifested by hearing loss (hearing loss), having a unilateral or asymmetric bilateral character. Perception of mainly low- and medium-frequency sound vibrations is difficult, poor speech intelligibility is common. Hearing loss is accompanied by ringing in the ear, combined with vestibular disorders: dizziness, discoordination, nystagmus (involuntary twitching of the eyeballs). The addition of symptoms of auditory and vestibular dysfunction exacerbates mental disorders.
The severity of visual dysfunction depends on the localization and prevalence of retinal vasculopathy. Patients note photopsias — periodic flashes or “shiny balls” in the field of vision. Typical are the loss of individual areas of the visual field (scotomas), described by patients as “spots” in which the surrounding is vaguely visible. Susac syndrome with extensive lesion of arterioles is accompanied by atrophy of the optic nerve and a significant narrowing of the visual fields. When microcirculatory disorders are localized exclusively in the peripheral parts of the retina, their clinical manifestations may be absent.
Complications
The progressive course of vasculopathy leads to pronounced pathological changes in the brain tissues with the development of severe mental symptoms and focal disorders in the form of paresis, making it difficult for the patient to self-care. Aggravation of microcirculatory disorders of the retina can lead to complete blindness. A complication of hearing loss is complete hearing loss. Rapid and early therapy in many cases can stop the progression, prevent the development of severe mental disorders, irreversible changes in the retina and hearing organ.
Diagnostics
The debut of the Susac syndrome as one of the characteristic triad of signs significantly complicates its early diagnosis. The detection of focal symptoms (nystagmus, paresis, dysarthria) and cognitive changes helps the neurologist to suspect the organic nature of the existing mental disorders and diagnose encephalopathy. ENT specialists and ophthalmologists are involved in the examination of the patient along with a neurologist. The following studies are of key importance in the diagnosis:
- Analysis of cerebrospinal fluid. The material for analysis is obtained by spinal puncture. The studied material reveals a moderately elevated protein content and lymphocytic pleocytosis — an increased cell content mainly due to lymphocytes.
- MRI of the brain. Multiple small focal lesions are observed in the corpus callosum, inner capsule, periventricular white matter, trunk, cerebral and cerebellar pedicels, basal ganglia and thalamus. The pathognomonic sign for Susac syndrome is the typical form of lesions in the form of a “pearl necklace” or “snowflakes”, detected on a T2-weighted image. In a study with contrast enhancement, a more intense coloration of fresh foci is noted.
- Perimetry. It is possible to detect narrowing of the visual fields, loss of various quadrants, the presence of central and paracentral cattle.
- Ophthalmoscopy. Fundus examination may show occlusion of branches of the central retinal artery. When occlusions are limited to small peripheral arterioles, the fundus looks normal.
- Fluorescence angiography. It is the best method for detecting occlusions of retinal arterioles. Multiple occlusions and foci of fluorescein “leakage” are pathognomonic criteria for Susak’s vasculopathy, diagnosed even in patients who do not have clinically pronounced ophthalmic symptoms. The macular region remains intact in most cases.
- Optical coherence tomography. It is used as a diagnostic tool for analyzing the morphological integrity of retinal structures. Allows you to differentiate Susac syndrome with a typical spotty thinning of the nerve fiber layer from multiple sclerosis, in which the thinning is diffuse.
- Tonal audiometry. Fixes sensorineural hearing loss in the range of low and medium frequencies. Additionally, the study of acoustic evoked potentials is recommended.
Differential diagnosis
The syndrome is differentiated from demyelinating diseases (multiple sclerosis, multiple encephalomyelitis) based on the data of cerebral MRI and retinal angiography. Encephalopathy requires differentiation from infectious encephalitis. When hearing loss is combined with vestibular dysfunction, it is necessary to exclude Meniere’s disease.
Multiple organ disorders are also characteristic of systemic vasculitis, such as Kogan’s syndrome, Wegener’s granulomatosis. Unlike Susak’s vasculopathy, Kogan’s syndrome is accompanied by interstitial keratitis. In Wegener’s granulomatosis, hearing loss is combined with damage to the respiratory tract and kidneys, which is atypical for Susac syndrome.
Treatment
Patients are recommended a low-salt diet with a high content of B vitamins, vitamin C and K. Etiopathogenetic pharmacotherapy is based on intensive immunosuppression aimed at reducing the production of autoantibodies that damage the vascular endothelium. In practical neurology, complex therapy of the syndrome is carried out by individual selection of several medications. The attending physician makes an appointment in accordance with the clinical picture, prescription and severity of the disease, corrects it based on the dynamics of symptoms. The main groups of drugs used are:
- Glucocorticoids. They have immunosuppressive properties, have an anti-inflammatory effect. The ability of glucocorticosteroids to support metabolic processes in the body against the background of a chronic disease is important.
- Cytostatics. They are characterized by a pronounced inhibitory effect on the immune system. Despite the pronounced side effects, they are a necessary component of the therapy of Susaka vasculopathy of any severity.
- Intravenous immunoglobulins (IVIG). They act as nonspecific correctors of immunity. The immunomodulatory effect is associated with a decrease in the production of own (autoimmune) immunoglobulins and immune complexes. IVIG makes it possible to provide antimicrobial immunity in immunodeficient patients through substitution therapy.
- Genetically engineered biological preparations (GEBP). Monoclonal antibodies to the antigens of mature B lymphocytes responsible for the production of autoantibodies are used. After binding to the B-lymphocyte, EIBP initiates its lysis, which leads to a decrease in the number of antiendothelial autoantibodies formed. Hematopoietic cells and healthy plasma cells remain intact.
- Antithrombotic drugs. They are prescribed to patients with an increased risk of thrombosis.
In severe cases, plasmapheresis is used to purify the blood from the immune complexes circulating in it. It is possible to conduct sessions of hyperbaric oxygenation to compensate for hypoxic processes caused by vascular damage.
Prognosis and prevention
Susac syndrome has a monocyclic, polycyclic or chronic continuous course. With early initiation of therapy, a good prognosis is possible. Timely diagnosis and early administration of immunosuppressive therapy lead to almost complete recovery, despite significant encephalopathy when the patient is treated. However, the diagnosis is usually delayed, which leads to the development of complications. Approximately 50% of patients retain cognitive impairment. Since the etiological factors of autoimmune pathology have not been determined, real methods of prevention have not yet been developed.