Susac syndrome: the key triad in diagnosis

¹Department of Neurology, Military Hospital of Instruction of Tunis, Tunis, Tunisia

^&Corresponding author
Sirine Frikha, Department of Neurology, Military Hospital of Instruction of Tunis, Tunis, Tunisia

Introduction    

Susac syndrome (SuS) is a rare autoimmune encephalopathy characterized by microvascular involvement of the central nervous system, the retina, and the inner ear. First described in 1979 by the American neurologist John O. Susac in Pereira et al. [1], the condition presents with a typical clinical triad associating encephalopathy, retinal arteriole occlusions, and sensorineural hearing loss [2]. The disease predominantly affects young women, generally between 20 and 40 years of age, although cases have also been reported in men and children [3].

The pathophysiological mechanism is based on an autoimmune microangiopathy leading to inflammation, obstruction, and ischemia of the affected territories. This microvascular involvement explains the wide range of symptoms observed: neurological manifestations (cognitive impairment, confusion, headaches, gait disturbances); ophthalmological signs (reduced visual acuity, scotomas, blurred vision); and auditory symptoms (sudden hearing loss, tinnitus, vertigo) [4,5]. Because the clinical presentation may be incomplete or progressive, diagnosis is often difficult or delayed [5]. Furthermore, its rarity and clinical variability mean that it is frequently confused with other autoimmune or demyelinating disorders, including multiple sclerosis, systemic lupus erythematosus, or certain autoimmune encephalitis [6].

From a diagnostic standpoint, brain magnetic resonance imaging (MRI) plays a central role [3]. The typical lesions located in the corpus callosum, showing a “snowball” or “punched-out” appearance, are considered almost pathognomonic [7]. Retinal angiography reveals arteriole occlusions, while audiometric tests demonstrate sensorineural hearing loss, which is often irreversible if not treated promptly [1]. Treatment is based on early and aggressive immunosuppression aimed at limiting ischemic damage and halting disease progression. High-dose corticosteroids represent the first-line therapy, often combined with immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil, or rituximab. A multidisciplinary approach is essential to tailor treatment and monitor disease evolution [8].

Although the course of Susac syndrome may be monophasic or biphasic, it can sometimes become chronic or recurrent, leaving significant cognitive or sensory sequelae [4]. Early recognition of this condition is therefore crucial to prevent irreversible complications.

Methods     

This is a descriptive case-report study involving three patients followed for Susac syndrome in the Neurology Department of the Tunis Military Teaching Hospital between 2002 and 2025. The cases were selected according to established diagnostic criteria. All data were collected from medical records, complementary examinations, and patient interviews.

The variables studied included demographic, clinical, therapeutic, and outcome data. A descriptive and comparative analysis of the three cases was conducted.

Results     

Case 1: this case concerns a 50-year-old man with no significant medical history who presented with gait disturbances, diplopia, and acute-onset hearing loss. Neurological examination revealed cerebellar ataxia, coordination impairment, and bilateral hearing loss [9].

Brain and spinal MRI showed white-matter lesions in both supratentorial and infratentorial regions, along with contrast-enhancing cervical lesions after gadolinium injection. According to the 2017 McDonald criteria, a diagnosis of multiple sclerosis (MS) was initially considered. The patient received a 5-day course of intravenous corticosteroids, resulting in partial symptom improvement. However, due to the atypical clinical and radiological presentation, no long-term MS treatment was initiated.

One year later, the patient experienced worsening ataxia, hypoesthesia of the right lower limb, and urinary dysfunction. Another course of intravenous corticosteroids was administered. Biological tests (serologies, immunological workup, angiotensin-converting enzyme level, tumor markers) were all negative. Audiometry confirmed bilateral hearing loss. Retinal angiography revealed ischemic retinal vasculitis (Figure 1). A follow-up brain and spinal MRI showed typical corpus callosum “snowball” lesions, which are pathognomonic for Susac syndrome (SuS) (Figure 2).

Lumbar puncture results were normal. Given the typical clinical triad - central nervous system involvement, branch retinal artery occlusions (BRAO), and hearing loss - the diagnosis of Susac syndrome was established. The patient was treated with acetylsalicylic acid (100 mg/day) and oral corticosteroid therapy (1 mg/kg/day), with a gradual taper of 5 mg every two weeks.

The clinical course was favorable neurologically, with marked improvement in ataxia and partial recovery of hearing and urinary function. Ophthalmologic and angiographic follow-up showed partial improvement of the retinal vasculitis, while follow-up brain MRI demonstrated reduced lesion enhancement. After one year of follow-up, no neurological relapse was observed. The patient is currently in stable remission, without complications.

Case 2: this case concerns a 62-year-old woman with a history of asthma who had experienced, for twelve years, an annual relapsing course (approximately one relapse per year) characterized by neurological, visual, and auditory manifestations. Neurological examination showed right-sided hemiparesis associated with right-sided hypoesthesia, as sequelae of previous relapses. Ophthalmologic examination revealed bilateral peripapillary hyperfluorescence without peripheral ischemia or branch retinal artery occlusion; the optic discs appeared normal.

Brain MRI demonstrated bilateral demyelinating lesions of the subcortical frontal and parietal white matter, periventricular regions, and corpus callosum, without contrast enhancement, suggesting non-active inflammatory involvement. On ophthalmologic evaluation, fluorescein angiography showed vascular wall staining in the nasal region of the right macula, indicating inflammatory retinal involvement. Audiometry revealed right-sided sensorineural hearing loss, consistent with cochlear involvement.

Biological testing (hematologic, thyroid, and immunologic workup) was entirely normal, with no antithyroid antibodies or specific autoantibodies detected. Taken together, these clinical and radiological findings were consistent with a chronically relapsing form of Susac syndrome involving typical retinal, cochlear, and encephalic manifestations. Therapeutically, the patient was treated with corticosteroids combined with antiplatelet therapy, leading to clear clinical improvement.

Case 3: this case concerns a 36-year-old woman with a history of anemia and vitamin D deficiency under substitution therapy, who was admitted for an encephalopathic syndrome characterized by memory impairment, behavioral changes, headaches, binocular diplopia, and gait ataxia. She also reported bilateral hearing loss and visual field loss, with a similar episode occurring three months earlier. Clinical examination revealed apathy, a pyramidal syndrome, and bilateral kinetic cerebellar syndrome.

Lumbar puncture showed 4 white cells/mm³, 48 red blood cells/mm³, and elevated protein levels at 1.54 g/L, with no oligoclonal bands detected in the cerebrospinal fluid (CSF). Brain MRI revealed supra- and infratentorial white-matter lesions without gadolinium enhancement, along with more than six typical corpus callosum lesions (Figure 3).

Audiometry revealed bilateral conductive hearing loss, more pronounced on the left side. Ophthalmologic examination, complemented by fluorescein angiography, demonstrated occlusive retinal vasculitis with neovascularization. The left eye showed a central retinal artery occlusion (Figure 4).

The overall clinical and radiological picture, combining encephalopathy, cochlear involvement, and occlusive retinal vasculitis, was highly suggestive of Susac syndrome. Therapeutically, the patient was treated with intravenous corticosteroid boluses, followed by an oral taper. Due to corticosteroid-related adverse effects, treatment was switched to mycophenolate mofetil (MMF), leading to progressive clinical improvement.

Discussion     

Susac syndrome (SuS) is a rare autoimmune microangiopathy affecting the central nervous system, retina, and cochlea. Although the exact mechanism remains incompletely understood, it is likely an autoimmune endotheliopathy leading to occlusion of precapillary microvessels. Autoantibodies directed against endothelial cells have been described, suggesting a mechanism similar to that observed in certain systemic vasculitides [5].

Our three cases illustrate the clinical diversity and variable course of SuS. While the classical triad (encephalopathy, BRAO, hearing loss) is highly suggestive, it is complete in only 15-30% of cases at the time of diagnosis [10]. In our series, the diagnostic delay ranged from several months to several years, highlighting the frequent diagnostic challenge of the disease, often mistaken for multiple sclerosis (MS) or autoimmune encephalomyelitis. Indeed, the multifocal distribution of white-matter lesions and their demyelinating appearance can be misleading [6]. However, some features help distinguish SuS: corpus callosum lesions, with their central, rounded, and well-defined appearance, are almost pathognomonic.

Brain MRI is the main diagnostic tool for SuS, highlighting these “snowball” lesions of the corpus callosum, which correspond to microvascular infarctions affecting commissural fibers. Other typical central demyelinating abnormalities may be observed, such as hyperintensities in supratentorial and infratentorial white matter, involvement of the brainstem, basal ganglia, or cerebellar cortex [11]. Ophthalmologic manifestations observed in our patients - ischemic retinal vasculitis, central retinal artery occlusion, and neovascularization - are characteristic of SuS. Fluorescein angiography is essential for detecting small-caliber retinal arteriole occlusions (BRAO) and peripapillary leakage, often asymptomatic. The latter, observed in our second patient, is considered an early and specific lesion of the disease [12-14].

Hearing involvement, present in all three patients, most often manifests as asymmetric bilateral sensorineural hearing loss affecting predominantly low frequencies, reflecting apical cochlear involvement. However, mixed or conductive forms, as in our third case, have also been reported. Audiometry and auditory evoked potentials are useful tools for functional follow-up [15]. Lumbar puncture, performed in two cases, showed moderate protein elevation without major albumin and cytologic dissociation. This profile is found in approximately 50% of SuS patients. Oligoclonal bands, often positive in MS, are generally absent in SuS, which constitutes an important differential criterion [16].

Therapeutically, SuS management relies on early, aggressive, and prolonged immunosuppression to prevent irreversible neurological, visual, and auditory sequelae. Intravenous corticosteroids (methylprednisolone boluses) followed by oral taper remain the first-line treatment. The use of immunosuppressive agents is often necessary in case of inadequate response, such as azathioprine, mycophenolate mofetil (MMF), cyclophosphamide, or targeted biologics (rituximab, infliximab) in refractory cases. Plasmapheresis or intravenous immunoglobulins (IVIG) have also shown benefit in severe or rapidly progressive forms [5,8,17,18].

The overall prognosis of SuS is favorable when treatment is initiated early. The disease course may be monophasic, relapsing, or chronic continuous, the latter being the most disabling. Auditory and cognitive sequelae remain frequent, particularly in cases of delayed diagnosis [19].

Limitations: our study has several limitations. First, it is based on a small case series from a single center, which limits the generalizability of the findings. Second, the rarity of Susac syndrome limits the sample size and precludes statistical analysis or comparison between different therapeutic approaches. Finally, larger multicenter studies are needed to validate our observations and better define optimal management strategies.

Conclusion     

Susac syndrome remains a rare and often underrecognized entity, with diagnosis relying on recognition of the clinical triad - encephalopathic, retinal, and cochlear involvement - supported by characteristic corpus callosum findings on MRI. Our cases highlight that incomplete or atypical forms are frequent, underscoring the need for heightened diagnostic vigilance in any unexplained encephalopathy associated with visual or auditory disturbances. Early and appropriate immunosuppressive management usually allows durable stabilization and limits functional sequelae. Multidisciplinary follow-up remains essential to optimize long-term prognosis.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Sirine Frikha: conceptualization, methodology, investigation, literature review, and writing original draft; Hajer Derbali: conceptualization, methodology, supervision, writing review & editing; Amel AlHaj Mabrouk and Ferdaous Ben Chihi: visualization and literature review; Mariem Messalmani and Jamel Zaouali: supervision and validation; Ines Bedoui: resources and supervision; Malek Mansour: resources and validation. All the authors read and approved the final version of this manuscript.

Figures     

Figure 1: fluorescein angiography showing ischemic occlusion of small vessels, consistent with retinal vasculitis: A) right fundus; B) left fundus; C) fluorescein angiography of the right eye; and D) left eye

Figure 2: brain magnetic resonance imaging (MRI) showing characteristic “snowball” lesions in the corpus callosum on sagittal T2-weighted imaging

Figure 3: (A,B) brain magnetic resonance imaging (MRI) showing characteristic lesions of the corpus callosum on the T2 FLAIR sequence

Figure 4: (A,B,C,D) retinal angiography of patient 3

References