|Ahead of print publication
Brain fog and vessel clogs
Aditya Maitray, Anju Kuriakose, Anand Rajendran, Karthik Srinivasan, Maanasi Mahalingam
Department of Vitreo Retina Services, Aravind Eye Hospital, Chennai, Tamil Nadu, India
|Date of Submission||23-Aug-2022|
|Date of Acceptance||28-Nov-2022|
|Date of Web Publication||20-Jan-2023|
Department of Vitreo Retina Services, Aravind Eye Hospital, Chennai - 600 077, Tamil Nadu
Source of Support: None, Conflict of Interest: None
We present a unique case of a 36-year-old female presenting with features suggestive of bilateral combined vascular occlusion, hearing loss, and encephalopathy. Multimodal imaging was done for both eyes fundus evaluation including wide-field color fundus photography, optical coherence tomography, and fundus fluorescein angiography. After extensive ocular and systemic investigations, she was diagnosed to have Susac syndrome (SS). She was referred to a neurologist and otologist for systemic evaluation and underwent laser photocoagulation in both eyes, followed by pars plana vitrectomy in her left eye. Combined bilateral retinal vascular occlusion in association with SS is very rare.
Keywords: Bilateral CRAO, Combined vascular occlusion, Susac syndrome
| Introduction|| |
Susac syndrome (SS) was first described by J. O. Susac in 1979 as a rare autoimmune disease characterized by a triad of encephalopathy, sensorineural hearing loss, and branch retinal artery occlusions (BRAOs). It predominantly affects young women in their third or fourth decade and is often misdiagnosed.
| Methods|| |
This is a retrospective case report of a unique case of SS. Informed consent was obtained from the patient to use her data.
| Case Report|| |
A 36-year-old female presented to us with a diminution of vision in both eyes for the last6 weeks. She gave a history of admission at a local general hospital 2 months back with complaints of altered sensorium and breathlessness. She had no known systemic comorbidities. The limited records available with her showed that, after an initial evaluation, she was treated as a suspect case of infectious encephalitis, and was administered a course of empirical intravenous antibiotics (vancomycin and ceftazidime) and antivirals (acyclovir). She also received a blood transfusion for reduced hemoglobin (6.9 mg/dl). During her 3-week hospital stay, she developed bilateral hearing loss and a diminution of vision.
She presented 6 weeks after discharge to our tertiary care eye center for further worsening of vision in both eyes.
She had a significant hearing impairment and was not fully oriented to time and place. Her best corrected visual acuity (BCVA) was 1/60 in the right eye (OD) and 6/36 in the left eye (OS). Anterior segment examination was unremarkable in both eyes. Fundus examination of OD [Figure 1]a showed a pale optic disc, markedly sclerosed appearing vessels (both arteries and veins) devoid of blood column, and deep retinal hemorrhages in all quadrants. There were multiple small yellow refractile plaques along the arterioles and yellow crystalline deposits/plaques at the posterior pole. Similarly, the OS [Figure 1]b showed hemorrhage over the optic disc, and widespread deep retinal hemorrhages, with both arteries and veins appearing as fibrotic cords free of blood column in all quadrants except the inferonasal quadrant. Fundus fluorescein angiography (FFA) [Figure 1]c OD showed near total retinal nonperfusion with dye arrest at about ½–1 disc diameters from the disc which remained so till the late phases [Figure 1]d. FFA OS similarly showed striking retinal nonperfusion just beyond the optic disc sparing partly only the vessels of the inferonasal quadrant (INQ) [Figure 1]e. In the mid-venous phase, segmental staining of the arterial wall was also noted [Figure 1]f. Spectral-domain optical coherence tomography through the macula showed marked the thinning and fused appearance of inner retinal layers in both eyes (OU) with partial sparing of nasal aspect macula in OS. Hyperreflective foci were also seen corresponding to crystalline exudate deposits at the macula [Figure 1]a and [Figure 1]b.
|Figure 1: Imaging characteristics at presentation. (a) Wide field fundus photograph of right eye showing a pale optic disc, markedly sclerosed vessels (both arteries and veins) and deep retinal hemorrhages in all quadrants along with multiple small yellow refractile “Gass Plaques” along the arterioles (blue arrow) and crystalline deposits at posterior pole (yellow arrow). Inset-spectral domain optical coherence tomography through macula showed severe thinning and fused appearance of inner retinal layers. (b) Wide field fundus photograph of left eye showing widespread deep retinal hemorrhages, hemorrhage over optic disc and markedly sclerosed vessels appearing free of blood column in all quadrants except inferonasal quadrant (Inset-SD-OCT through macula showing severe thinning and fused appearance of inner retinal layers, partly sparing the nasal macula). (c) Fundus fluorescein angiography early phase showing striking retinal nonperfusion right eye with dye arrest just beyond optic disc. (d) Late phase FFA of right eye showing the persistent severe nonperfusion. (e) FFA left eye showing striking retinal nonperfusion with dye arrest just beyond optic disc, sparing partly only the vessels of inferonasal quadrant. (f) Fundus fluorescein angiography left eye showing segmental arterial wall hyperfluorescence in mid-venous phase (asterisks). SD-OCT = Spectral-domain optical coherence tomography, FFA = Fundus fluorescein angiography|
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The findings were suggestive of bilateral combined vascular occlusion in OU with INQ sparing in OS.
We considered differential diagnoses of systemic lupus erythematosus, syphilis, antiphospholipid antibody (APLA) syndrome, viral encephalitis, multiple sclerosis, and SS.
The patient was referred to a neurologist and a thorough systemic evaluation and work-up were planned. Magnetic resonance imaging (MRI) brain showed focal periventricular white matter lesions consistent with a demyelinating process. The erythrocyte sedimentation rate was mildly elevated, at 29 mm/h. Lumbar puncture showed elevated lymphocyte count. Serologic testing for VDRL, HIV, and vasculitis workup (APLA profile, antinuclear antibody, rheumatoid factor, and P-antineutrophil cytoplasmic antibody [p-ANCA] and c-ANCA) was negative. Serum angiotensin-converting enzyme levels were within normal limits, and a coagulation screen gave normal results. Pure-tone audiometry evaluation showed moderate and profound sensorineural hearing loss in right and left ears, respectively.
Hence, after excluding other potential etiologies, and considering the classical clinical and imaging characteristics, the patient was diagnosed to have SS.
She underwent pan-retinal photocoagulation (PRP) in both eyes, with the aim to prevent neovascular glaucoma, considering the severe retinal nonperfusion. Systemically, she was managed by a team of a general physician, a neurologist, and an otorhinolaryngologist. She was started on antiplatelet medication (clopidogrel 75 mg OD).
On subsequent follow-up after 2 weeks, she presented with a further drop in vision in OS to a BCVA of 5/60. OD vision remained poor at hand movements. Fundus examination revealed a stable picture in OD post-PRP [Figure 2]a, while OS showed a diffuse subhyaloid and vitreous hemorrhage over the posterior pole with a fibrovascular proliferative membrane over the disc [Figure 2]b. She was kept under observation for 4 weeks and subsequently underwent OS pars plana vitrectomy with silicone oil injection. Her vision in OS had improved to 6/24 BCVA 1-month postoperatively [Figure 2]c. She underwent OS silicone oil removal (SOR) 3 months later and her OS BCVA and fundus picture remained stable till her final visit 4 months post-SOR [Figure 2]d. Her hearing remained impaired, while her cognitive function had markedly improved. She remains on regular follow-ups with her treating neurologist.
|Figure 2: Fundus images at the follow-up. (a) Widefield fundus image of right eye at 1 month postpanretinal photocoagulation. (b) Fundus image of left eye showing diffuse subhyaloid and vitreous hemorrhage over the posterior pole with a fibrovascular proliferative membrane over disc and PRP marks in periphery. (c) Fundus image of left eye 2 weeks postpars plana vitrectomy with silicone oil injection. (d) Montage fundus image of left eye shows a stable picture 4 months postsilicone oil removal|
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| Discussion|| |
SS is a rare autoimmune microangiopathy of medium and small vessels, affecting young women in the third or fourth decade of life. It includes the clinical triad of encephalopathy, retinal arterial occlusion, and sensorineural hearing loss.
The exact pathogenesis of SS is not clearly understood, but an immune-mediated process remains to be the leading hypothesis.
In an extensive systematic review by Dörr et al., it was noted that at first presentation, only 13% of patients had the characteristic clinical triad of SS, but the complete triad was documented in 85% of cases during the course of the disease. Headache (80%) was noted to be the most common presenting feature; other neurologic features may include cognitive changes, memory loss, confusion, and ataxia.
In neuroimaging, both white and gray matter lesions and leptomeningeal involvement can be seen in SS. White matter lesions are nonspecific and can resemble multiple sclerosis. Corpus callosum involvement—in particular, evidence of “snowball lesions” on MRI is considered to be a characteristic sign of SS (78%). Although lack of callosal involvement is not sufficient to exclude a diagnosis. MRI in our patient showed focal periventricular white matter lesions consistent with a demyelinating process [Figure 3].
|Figure 3: MRI brain of the patient showing sub-cortical hyperintensity in the white matter of right temporal lobe in T1 weighted image (red asterisk). MRI = Magnetic resonance imaging|
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Otological manifestations include hearing loss of low-to-medium frequencies, noted in 68% of cases. SS can present with vertigo and nystagmus too.
Retinal manifestations include BRAOs which can present with symptoms such as scotoma, blurred vision, and field defects depending on the area of involvement. During the disease course, BRAO becomes bilateral in more than 90% of cases.
There are two prior reports of central retinal artery occlusion in SS, but concomitant retinal venous occlusion is not a typical feature.
A yellow refractile plaque deposit in the arterial wall, known as Gass plaque (GP), is considered pathognomonic in SS and can be seen in 45% of patients. It is proposed to be an atheromatous plaque derived from serum lipids and can disappear with time. It is typically located away from the site of obstruction, as opposed to Hollenhorst plaques, which are usually seen at the arterial bifurcation. Arterial wall hyperfluorescence on FFA, showing typical segmental staining away from the site of obstruction, can be seen in up to 96% of cases and is also considered a pathognomonic feature. In addition, retinal veins in the corresponding location of occluded arteries can also show late-phase leakage/staining, which is proposed to be due to secondary damage resulting from inflammation of the arterial vessels.
Up to 40% of patients can be visually asymptomatic at presentation, but FFA features can be detected in 85%–99% of patients., FFA should be considered in all cases of suspect SS even in the absence of visual symptoms as it can provide important diagnostic clues.,
Our patient had presented to us with the classical triad of symptoms and had other features consistent with the diagnosis of SS, including GPs and AWH [Figure 1].
A SS ophthalmology care pathway has been proposed by Bristol Eye Hospital. In the presence of central nervous system involvement, neurologists take the lead in management since these patients may need more aggressive treatment with co-management with otologists and ophthalmologists. In the active phase, corticosteroids form the mainstay of the therapy (in the form of three consecutive daily doses of IV methylprednisolone 1000 mg, followed by an oral tapering dose). Other second-line options include immunosuppressants such as mycophenolate mofetil, cyclophosphamide, and/or intravenous immunoglobulins and rituximab.
Early recognition and treatment may sometimes reverse some of the encephalopathic and visual disturbance, but hearing loss often remains permanent.
Our case presented to us, 2 months after the onset of initial symptoms, after receiving some empirical therapy at a local hospital. At that stage, the evaluating neurologist and physician did not consider the condition to be active and cautioned against systemic corticosteroids/immunosuppressive therapy, especially considering the ongoing COVID-19 pandemic peak in our region at the time. However, the patient was kept on a close follow-up initially to monitor disease activity and plan systemic therapy in case a flare-up of disease activity was noted. The combined occlusion/venous involvement in our case could also have been contributed to by severe anemia noted at the initial presentation for which she had received a blood transfusion.
| Conclusion|| |
We report a rare case of SS presenting with bilateral combined retinal vascular occlusion. Characteristic FFA features help in confirming the diagnosis and should be performed in all patients with suspected SS.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
The authors declare that there are no conflicts of interests of this paper.
| References|| |
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[Figure 1], [Figure 2], [Figure 3]