CENTRAL RETINAL ARTERY OCCLUSION AND SUSAC SYNDROME: A CASE REPORT Tom Buelens, MD,* Laurent Herode, MD,* Isabelle Nubourgh, MD,† Laure Caspers, MD, PhD,* François Willermain, MD, PhD,* Laurence Postelmans, MD*

Background: Susac syndrome is a rare disease attributed to microangiopathy involving the arterioles of the brain, retina, and cochlea. Understanding the pathogenesis is incomplete, but an immune-mediated process remains the leading hypothesis. Methods: Report of a single case of a previously healthy 22-year-old female patient showing the complete clinical triad. Results: Diagnosis of Susac syndrome in this patient was first questioned due to the atypical initial ophthalmologic presentation with central retinal artery occlusion. Multiple relapses occurred in the fellow eye during follow-up, showing the typical branch retinal artery occlusions, allowing definite diagnosis. Conclusion: Susac syndrome should be considered in the differential diagnosis when facing (young) patients with central retinal artery occlusion, especially in the presence of unexplained encephalopathy and/or sensorineural hearing loss. RETINAL CASES & BRIEF REPORTS 8:187–192, 2014

accompanied or preceded by the areas of arterial wall hyperfluorescence on fluorescein angiography. Another typical feature is the presence of yellow-white retinal arterial wall plaques called Gass plaques.3,4 We report a single case of a 22-year-old female patient suffering from Susac syndrome complicated by central retinal artery occlusion.

From the Departments of *Ophthalmology, CHU Saint-Pierre and Brugmann, and †General Internal Medicine, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium.

T

he eponym “Susac syndrome” was suggested by Dr. William Hoyt in 19861 in reference to the description by John O. Susac in 1979 of 2 women who presented a clinical triad of encephalopathy, retinal arteriolar branch occlusions, and sensorineural hearing loss. Other terms for this disease entity have been suggested, such as “RED-M” (retinopathy, encephalopathy, deafness-associated microangiopathy), “retinocochleocerebral vasculopathy,” and “SICRET” (small infarctions of cochlear, retinal, and encephalic tissue). Today, approximately 200 cases have been reported in case reports or small case series.2 At the ocular level, the characteristic finding in patients with Susac syndrome is the branch retinal artery occlusion that may be

Case Report A 22-year-old female patient presented at ophthalmology department with a sudden painless loss of vision in her left eye, first noticed upon waking the morning of her presentation. She also presented neurologic symptoms resembling transient ischemic attacks that had developed 5 days earlier: a muscular weakness of the left side of the face and an episode of dysarthria lasting several minutes but resolving spontaneously. In addition, the patient described occipital headaches associated with “spots” in front of the eyes, for which she previously consulted emergency department. A positive family history for type 2 diabetes, dyslipidemia, and anemia was found (father, mother, and sister of the patient, respectively); there was no personal history of substance abuse. On initial examination, she was normotensive, afebrile, and showed no signs of meningism; further neurologic examination was normal except for an afferent pupillary defect of the left eye. Best-corrected visual acuity was 20/20 in her right eye and light perception in her left eye. Intraocular pressure was 12 mmHg in the

None of the authors have any financial/conflicting interests to disclose. Reprint requests: Tom Buelens, MD, Department of Ophthalmology,CHU Saint-Pierre and Brugmann, Université Libre de Bruxelles, 322 rue Haute, 1000 Brussels, Belgium; e-mail: tom. [email protected]

187

188

RETINAL CASES & BRIEF REPORTS´  2014  VOLUME 8  NUMBER 3

left eye and 13 mmHg in the right eye. Slit-lamp examination of the anterior segment revealed no signs of intraocular inflammation in both eyes. Fundoscopic examination of the left eye showed central retinal artery occlusion with cherry-red spot and retinal ischemic whitening except for the area around the optic disk. At the superotemporal arcade, multiple Gass plaques were found appearing as a string of pearls (Figure 1A). Fluorescein angiography of the right eye was normal (Figure 2A), whereas the left eye showed a delay in arterial filling and large areas of nonperfusion (Figure 1B). Macular optical coherence tomography of the left eye showed hyperreflectivity and edema of the internal layers, whereas optical coherence tomography of the right eye was normal (Figure 1C). Laboratory tests at admission showed normal blood count, normal renal function and ionogram, normal liver tests, normal C-reactive protein, normal glycosylated hemoglobin, and normal hemostasis. Erythrocyte sedimentation rate was elevated (32 mm/ hour) and a small dyslipidemia was noted. Cardiovascular workup (including electrocardiography, transthoracic echocardiography, and Doppler ultrasound of the carotid and vertebral arteries) was within normal limits. A head computed tomography scan at this time demonstrated no abnormalities. The patient was admitted to the intensive care coronary unit of the hospital for hemodynamic surveillance. Diffusion-weighted images of the first magnetic resonance imaging imaging study of the head the next day showed multiple punctiform lesions of the periventricular white matter resembling ischemia (Figure 3A). A lumbar puncture was performed the same day and analysis of the cerebrospinal fluid revealed hyperproteinorachy (0.845 g/L), pleocytosis (15 leukocytes per microliter), normal glucose and lactate levels, and an absence of oligoclonal bands. Aerobic and anaerobic bacteria and mycobacteria cultures were negative and no HSV1, HSV2, VZV, or CMV DNA was detected. Before the definite diagnosis of Susac syndrome was made, therapy with IV acyclovir and antibiotics (ceftriaxone and ampi-

Fig. 1. Initial presentation in the left eye with fundus photograph showing central retinal artery occlusion with segmentation of the blood column at the superotemporal branch (arrows), cherry-red spot, and retinal ischemic whitening except for the area around the optic disk (A), fluorescein angiography showing a delay in arterial filling and large areas of nonperfusion (B), and macular optical coherence tomography showing hyperreflectivity of the neuroretinal layers (C).

cillin) was started together with methylprednisolone (1 g/day IV pulses for 3 consecutive days, followed by oral administration of 64 mg/day) and subcutaneous injections of a low–molecular weight heparin. Laboratory investigations for viral (HIV, CMV, HSV, Varicella, Hepatitis B) and bacteriologic serology (syphilis, Borrelia, Bartonella henselae, QuantiFERON assay for tuberculosis) and autoimmune disease (ANA, ANCA) all turned out to be negative. An extensive research for thrombophilic disorders (Inherited: antithrombin III, activated protein C (free) protein S, plasminogen, activated protein C resistance, factor II G20210A mutation; Acquired: lupus anticoagulant, anticardiolipin antibodies, CD55 and CD59 levels for paroxysmal nocturnal hemoglobinuria (PNH); and/or Mixed: fibrinogen, homocystein, MTHFR) was normal. After considering all these findings, together with the normal physical examination, Susac syndrome was high on the list of differential diagnoses, and after a review of literature, it was decided to add IV immunoglobulines and oral cyclosporine to the treatment. To complete the workup, an audiogram was performed that showed mild sensorineural hearing loss of the left ear. A repeat magnetic resonance imaging imaging study with additional sagittal T2-weighted and fluid-attenuated inversion recovery sequences was performed 2 weeks later and demonstrated the presence of multiple periventricular hyperintense lesions in the white matter with involvement of the corpus callosum, highly compatible with Susac syndrome (Figure 3, B–D). Acyclovir and antibiotic therapy were interrupted, and the patient was discharged from the hospital with corticotherapy tapering 16 days after admission. Unfortunately, 1 month later, the patient presented a relapse with fluorescein angiography demonstrating retinal arteriolar branch occlusions and staining of the arterial wall of the temporal inferior branch of the right eye (Figure 2B), whereas reperfusion was incomplete in the left eye and fundoscopic and optical coherence tomography examination demonstrated atrophy of the optic disk and atrophy of the internal

CRAO AND SUSAC SYNDROME: A CASE REPORT

189

Fig. 2. Normal fluorescein angiogram of the right eye at initial presentation (A) and relapses with occlusions (arrows) and staining of the arterial wall (arrow heads) of the temporal inferior branch after 6 weeks (B), and new areas of arterial wall hyperfluorescence another 6 weeks (C) and 8 weeks (D) later (arrowheads).

retinal layers, respectively (Figure 4, A–C). Intravenous immunoglobulines and IV methylprednisolone (1 g/day for 3 consecutive days) were administered, followed by oral administration of methylprednisolone, together with cyclosporine and azathioprine. Considering the clinical course, the definite diagnosis of Susac syndrome was made. Despite very slow tapering of the oral administration of methylprednisolone, new vessel staining was visualized in the right eye 6 weeks later (Figure 2C), and the patient reported that headaches

had reappeared. At this time, IV cyclophosphamide was added to the treatment regime. Another relapse at the right eye was observed only 2 weeks later (14 weeks after initial presentation) (Figure 2D), the patient was readmitted to the hospital to receive IV methylprednisolone and IV immunoglobulines; treatment with infliximab was administered 1 week later (instead of repeated treatment with IV cyclophosphamide). Aspirin was added to the treatment to reduce procoagulopathic states. Monthly treatments with IV methylprednisolone, infliximab, and IV immunoglobulines were installed.

190

RETINAL CASES & BRIEF REPORTS´  2014  VOLUME 8  NUMBER 3

Fig. 3. Magnetic resonance imaging of the brain with axial diffusion-weighted images showing a hyperintense lesion (arrow) at the periventricular white matter at the anterior horn of the left lateral ventricle anterior to the head of the caudate nucleus (A); Sagittal T2 images showing the typical snowball lesions at the genu (B) and the splenium (C) of the corpus callosum (arrows); And axial T2 fluid-attenuated inversion recovery images (D) showing another hyperintense lesion (arrow) at the periventricular white matter lateral to the left caudate nucleus.

Discussion Susac syndrome is a rare disease characterized by multisystemic microvascular endotheliopathy involving the precapillary arterioles of the brain, retina, and inner ear (cochlea and semicircular canals). The full clinical triad may not be apparent for years and only 20% of all patients present the complete triad at the onset of disease, while retinal involvement may be seen in only 46% of patients at initial presentation. The age range at diagnosis extends from 7 years to 72 years, but young women (20–40 years) are most vulnerable, with a female-to-male predilection of 3:1.3,5 Because the classical triad is commonly absent at symptom onset and/or encephalopathic patients may

Fig. 4. Presentation of the left eye 6 weeks after initial presentation with fundus photograph showing atrophy of the optic disk (A), fluorescein angiography showing incomplete reperfusion (B), and macular optical coherence tomography showing atrophy of the internal retinal layers (C).

not report visual or cochleovestibular symptoms, the diagnosis of Susac syndrome is often difficult. The exact pathogenic mechanism has yet to be definitively established, but an immune-mediated process remains the leading hypothesis. Hypercoagulable states, viral infection, and idiopathic vasospasm have also been suggested, but they remain unproven.1,3,5 In most patients, similar to our patient, headache is the first symptom, often occurring with scintillating scotoma and hence frequently misinterpreted as migraine. Although headaches are the most frequent complaint, other neurologic features may include psychiatric disorders (particularly paranoia), cognitive changes, memory loss, confusion, ataxia, vertigo, seizures, pyramidal signs, hyperreflexia, sensory and

CRAO AND SUSAC SYNDROME: A CASE REPORT

motor hemiparesis as well as the facial paresis and dysarthria presented in our patient.3,6 Typical multifocal, small hyperintense snowballlike white matter lesions at the corpus callosum were demonstrated by initial magnetic resonance imaging imaging, follow-up images 10 weeks later showed diminution of the size of these lesions but also the appearance of new gadolinium enhanced punctiform lesions at the level of the semioval centers. However, no pathognomonic central callosal holes were visualized,2,5 and no deep gray matter involvement or leptomeningeal enhancement was found (present in 70 and 33% of patients, respectively).1 The characteristic ophthalmologic feature is the presence of (bilateral) recurrent multiple branch retinal artery occlusions; and, in association with the absence of intraocular inflammation and the presence of a normal choroidal circulation, this finding highly suggests the diagnosis of Susac syndrome.3 Fluorescein angiography of the involved retina shows focal nonperfused retinal arterioles and areas of arterial wall hyperfluorescence, indicating active disease. Central retinal artery occlusion as the ophthalmic presentation of Susac syndrome has been described before, both as initial presentation7 and during follow-up (following typical branch retinal artery occlusion)8 but has not been widely reported in the literature. Another typical feature is the retinal arterial wall (or Gass) plaque; refractile or not refractile, yellow-white deposits, and unlike true emboli, usually located randomly between, rather than at, arteriolar bifurcations; they can form the so called “silver streaks” and they can be transient and disappear after their initial discovery.3–5 The occluded arterioles may result in the areas of retinal infarction, cotton-wool spots, and occasionally a cherry-red spot.5 In general, the extent of visual field loss varies depending on the arteriole(s) involved; occlusions affecting the periphery may not lead to clinical symptoms, while occlusions affecting the larger branches may result in visual field deficits, in addition, patients with extensive arteriolar involvement may develop consequent optic atrophy and constriction of the visual field.3 Depending on the availability of blood supply from surrounding arterioles, initial visual field defects may resolve and arterioarterial retinal collaterals may develop.9 Visual field testing in our patient was not performed ad admission, however, automated perimetry after the first relapse showed an infra-nasal field defect in her right eye that did resolve on follow-up, and almost complete loss of the visual field of the left eye. Audiometry in patients with Susac syndrome is likely to reveal unilateral or (usually) bilateral, often asymmetrical sensorineural hearing loss involving

191

mainly the low and mid frequencies; vertigo and tinnitus may be accompanying features, while prominent jerk nystagmus may indicate infarction of the membranous labyrinth.5 Unfortunately, an audiogram of our patient was only obtained after a week of highdose corticotherapy, making it difficult to interpret the mild sensorineural hearing loss of the left ear that was documented, however, repeated audiogram after 3 more days of therapy showed improvement, suggesting that the hearing loss, before treatment was started, might have been more severe. Although diagnosis is based on clinical features, additional tests are often useful in excluding other potential etiologies because, despite extensive laboratory investigation, no consistent evidence of connective tissue disorder, procoagulant state, or infectious disease has been encountered in Susac syndrome.1,5 However, increases in cerebrospinal fluid protein (range, 100– 3,000 mg/dL; 84.5 mg/dL in our patient) and mild pleocytosis, usually lymphocytic (5–30 cells per cubic millimeter; 15 cells per cubic millimeter in our patient) that may be found during encephalopathy1,5 are considered suggestive of Susac syndrome. The presence of oligoclonal bands and elevated immunoglobulin G index or synthesis rate is rare (and absent in our case) but may be misinterpreted as being due to multiple sclerosis.1,5 Multiple sclerosis, acute disseminated encephalomyelitis (ADEM), immunologic processes (such as vasculitis, lupus erythematosus, Behcet disease, sarcoidosis, dermatomyositis, Sjögren syndrome, cryoglobulinemia, and/or cerebral angiitis), and infectious diseases (such as syphilis, Lyme disease, toxoplasma, tuberculosis, and/or viral infections) are the most common misdiagnoses. Malignant tumors (such as lymphoma), Creutzfeldt– Jakob disease, psychosis, schizophrenia, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), or mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) have also been considered.3,4 Menière disease and Cogan syndrome are important differential diagnoses in the otologic field,4 while retinal arterial occlusions in young patients are usually due to migraine, coagulation abnormalities, cardiac disease, trauma, drug abuse, or connective tissue disease. To date, optimal treatment of Susac syndrome is unknown since there have been no controlled studies or clinical trials. Although spontaneous recovery of symptoms and long-term remissions have been described,1 classical immunosuppression is the mainstay of Susac syndrome.5 Given the immunopathogenic similarities between Susac syndrome and dermatomyositis, specific (preliminary) treatment recommendations based on steroids, and depending on the clinical course, additional IV immunoglobulines,

192

RETINAL CASES & BRIEF REPORTS´  2014  VOLUME 8  NUMBER 3

cyclophosphamide, mycophenolate mofetil, azathioprine, and/or methotrexate were made.3,10 In case of threatening disease that does not adequately respond to conventional therapies, plasmapheresis could be considered. More recently, rituximab and infliximab have been proposed as treatment options.10 In our patient, multiple relapses occurred despite treatment with methylprednisolone in conjunction with azathioprine and cyclosporine and later also cyclophosphamide, whereas the introduction of infliximab was associated with excellent outcome. Conclusion We have reported a new case of a young female patient who showed the clinical triad of Susac syndrome. However, this patient initially presented with atypical findings at the ocular level. To the best of our knowledge, this is only the second case where a patient with Susac syndrome is reported with central retinal artery occlusion as the first ocular sign. Because this finding has not been widely reported in patients with Susac syndrome, we want to remind ophthalmologists to consider this disease entity when facing (young) patients presenting with central retinal artery occlusion, especially in the presence of other features of the clinical triad (encephalopathy and/or sensorineural hearing loss).

Key words: central retinal artery occlusion, encephalopathy, microvascular endotheliopathy, Susac syndrome. References 1. Susac JO. Susac’s syndrome. AJNR Am J Neuroradiol 2004;25:351–352. 2. Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac’s syndrome—update. J Neurol Sci 2010;299:86–91. 3. García-Carrasco M, Jiménez-Hernández C, JiménezHernández M, et al. Susac’s syndrome: an update. Autoimmun Rev 2011;10:548–552. 4. Kleffner I, Duning T, Lohmann H, et al. A brief review of Susac syndrome. J Neurol Sci 2012;322:35–40. 5. Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac’s syndrome: 1975–2005 microangiopathy/autoimmune endotheliopathy. J Neurol Sci 2007;257:270–272. 6. Mala L, Bazard MC, Berrod JP, et al. Small retinal, cochlear, and cerebral infarctions in the young patient, “SICRET” syndrome or Susac syndrome [in French]. J Fr Ophtalmol 1998;21:375–380. 7. Adatia FA, Sheidow TG. Central retinal artery occlusion as the initial ophthalmic presentation of Susac’s syndrome. Can J Ophthalmol 2004;39:288–291. 8. Murata Y, Inada K, Negi A. Susac syndrome. Am J Ophthalmol 2000;129:682–684. 9. Postelmans L, Willermain F, Guillaume MP, et al. Retinal arterio-arterial collaterals in SUSAC syndrome. Retina 2008;28:1171–1173. 10. Rennebohm RM, Susac JO. Treatment of Susac’s syndrome. J Neurol Sci 2007;257:215–220.

Central retinal artery occlusion and Susac syndrome: a case report.

Susac syndrome is a rare disease attributed to microangiopathy involving the arterioles of the brain, retina, and cochlea. Understanding the pathogene...
551KB Sizes 0 Downloads 36 Views