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Radiol Case Rep
Radiol Case Rep
Radiology Case Reports
1930-0433
Elsevier

S1930-0433(24)00740-4
10.1016/j.radcr.2024.07.151
Case Report
Susac syndrome: A rare pediatric case
Benbrahim Fatima Zohra MD fzohrabenbrahim93@gmail.com
⁎
Belkouchi Lina MD
Allali Nazik PhD
El Haddad Siham PhD
Chat Latifa PhD
Department of Radiology, Children hospital of Rabat, Ibn Sina University Hospital, Mohammed V University, Rabat, Morocco
⁎ Corresponding author. fzohrabenbrahim93@gmail.com
24 8 2024
11 2024
24 8 2024
19 11 51915195
21 7 2024
24 7 2024
25 7 2024
© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Susac syndrome is a rare microangiopathy of unclear etiology, likely autoimmune, characterized by a characteristic clinical triad of encephalopathy, retinopathy, and hypoacusis. The majority of cases reported in the literature involve adult patients, with its occurrence in the pediatric population being extremely rare. Magnetic resonance imaging (MRI) is essential for diagnosis and patient monitoring, revealing nearly pathognomonic features, particularly valuable given the typically incomplete clinical triad and the consistent presence of encephalopathy, often as the initial symptom. We report the case of an 11-year-old child diagnosed with Susac syndrome, highlighting the importance of considering this diagnosis in cases of childhood encephalopathy and initiating treatment as early as possible to prevent irreversible sequelae.

Keywords

Susac syndrome
Child
Magnetic resonance imaging
Encephalopathy
Abbreviations

MRI magnetic resonance imaging

ORL oto-rhino-laryngology

MS multiple sclerosis

ADEM acute disseminated encephalomyelitis

SS Susac syndrome

IVIG intravenous immunoglobulins
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pmcIntroduction

Susac syndrome is a microangiopathy likely of dysimmune origin, affecting the precapillary arterioles of the brain, retina, and inner ear [1]. This rare entity was first described in 1979 by Susac et al. [2]. Susac syndrome is characterized by a clinical triad of encephalopathy, hearing loss, and branch retinal artery occlusions (BRAO) [3]. However, it is often underdiagnosed due to the inconsistent association of this triad and the presence of other multisystemic conditions with similar presentations [3,4]. Encephalopathy often constitutes the initial revealing manifestation, presenting with headaches, psychiatric disorders, or multifocal neurological symptoms [5]. In 2016, Kleffner et al. proposed diagnostic criteria for Susac syndrome, which include cerebral, retinal, and vestibulocochlear manifestations [6]. However, certain aspects of magnetic resonance imaging (MRI) are characteristic, particularly the involvement of the corpus callosum [7]. This syndrome is rare and even more uncommon in the pediatric population. We report a new case of Susac syndrome in an 11-year-old child to highlight the occurrence of this syndrome in children, and we emphasize the main symptoms, the currently established pathophysiology, as well as the imaging keys for making an accurate diagnosis and ruling out differential diagnoses.

Case presentation

An 11-year-old male child, with a history of decreased visual acuity in the right eye, presents to the emergency department with severe headaches and confusion evolving subacutely over the past 3 weeks. Neurological examination revealed temporal-spatial disorientation. Motor and sensory evaluations were normal.

Given the patient's neurological status, a brain MRI (Fig. 1) was promptly performed, showing multiple nodular signal abnormalities primarily involving the central part of the corpus callosum and the subcortical white matter above the tentorium. These abnormalities appeared hypointense on T1-weighted images, hyperintense on T2-weighted and FLAIR sequences, restricted diffusion, with no contrast enhancement at gadolinium injection and with no abnormalities at angiographic sequences (Fig. 2). These MRI findings strongly indicated Susac syndrome. The spinal MRI was normal. Fluorescein angiography of the retina revealed bilateral occlusion of retinal artery branches. Electroencephalography (EEG) showed diffuse slowing of brain electrical activity. Laboratory tests were unremarkable except for elevated protein levels in the cerebrospinal fluid (170 mg/dL). Systemic vasculitis biomarkers and oligoclonal bands in the cerebrospinal fluid were negative. Bilateral sensorineural hearing loss was confirmed by audiometry tests. The patient was diagnosed with Susac syndrome and received treatment with intravenous immunoglobulins (IVIG) and steroids for 7 days. There was partial resolution of clinical symptoms at the first month follow-up and complete resolution at 3 months without any new symptoms appearing.Fig. 1 Brain MRI in sagittal T1 (A), sagittal FLAIR (B), axial diffusion (C), and axial T1 with gadolinium injection (D): showing small lesions in the corpus callosum (red arrow) with hypointensity on T1 (A), hyperintensity on FLAIR (B), restriction on diffusion (C), with no contrast enhancement at gadolinium injection (D).

Fig 1:

Fig. 2 Angiographic MRI sequence showing no abnormalities.

Fig 2:

Discussion

Susac syndrome, also known by the acronym SICRET which stands for Small Infarcts of Cochlear, Retinal, and Encephalic Tissues [8], is a rare and often misunderstood condition. It is a microangiopathy of undetermined origin, likely of dysimmune nature, affecting the brain, retina, and inner ear. First described by Susac et al. in 1979, approximately 500 cases have been reported up to 2021, primarily in case reports and small case series [9]. This syndrome predominantly affects young women (sex ratio : 3 females to 1 male) between the ages of 20 and 40 years, and it rarely occurs in the pediatric population, accounting for only 1% of all cases reported [[10], [11], [12], [13], [14]]. Reported pediatric cases range in age from 10 to 16 years, with only 1 case reported at the age of 2.5 years [15].

The pathophysiology of Susac syndrome, long debated, is now increasingly clear. The main mechanism of this neuroinflammatory condition is an oligoclonal expansion of terminally differentiated activated CD8+ cells (CTLs). The resulting endotheliopathy causes vascular leakage and small infarcts, primarily in the corpus callosum, inner ear, retina, and cerebellum. This mechanism paves the way for new therapeutic perspectives [16]. Anatomical cortical microlesions, too small to be detected by MRI, explain the impressive clinical symptoms of diffuse encephalopathy, contrasting with the absence of radio-clinical correlation. Cerebral and retinal capillary leak phenomena are considered a probable cause of the enhancement observed after gadolinium injection at the beginning of the acute ^phase and their reversibility.

In children, clinical manifestations generally do not differ from those described in adults and typically correspond to the characteristic triad of encephalopathy, retinal arterial branch occlusions, and hypoacusis. Diagnosis is often challenging, as simultaneous presence of all 3 clinical manifestations is rare. The clinical triad is often incomplete, and even if 2 elements are sufficient for diagnosis, their simultaneous appearance can vary from weeks to 2 years, contributing to diagnostic difficulty [17].

Given that neurological involvement is consistent in the initial assessment and the triad is often incomplete, it is essential to systematically request ophthalmological examination to detect subclinical involvement, as well as ORL evaluation, and to repeat diagnostic tests over time [18]. The characteristic aspects of the retina and brain definitively allow recognition of incomplete Susac syndrome.

Neurological involvement is consistently present and often initiates the disease. It manifests in diverse ways, including headaches, behavioral changes such as agitation, aggression, disorientation, cognitive function impairments, memory disturbances, and psychiatric disorders. Multiple manifestations are often common. MRI is the imaging modality of choice for highlighting lesions in both white and gray matter. White matter lesions are particularly characteristic and are often misdiagnosed as multiple sclerosis. These lesions typically involve periventricular regions, the centrum semiovale, subcortical regions, and the corpus callosum. In Susac syndrome, corpus callosum involvement is pathognomonic and should prompt radiologists to consider the possibility of this syndrome. Typically, multiple microlacunar lesions affect the central part of the corpus callosum, sparing the periphery, and are well-defined (3-7 mm) but can become confluent as they enlarge (>7 mm), resembling snowballs. Unlike other vasculitides that cause larger lesions, Susac syndrome affects microvasculature and results in microinfarctions. Linear lesions of central fibers can extend from the callosal-septal surface to the upper margin of the corpus callosum, resembling wheel spokes. These lesions appear hyperintense on T2-weighted and FLAIR images. During the subacute or late phase, lesions appear hypointense on T1-weighted images as central callosal holes, which are pathognomonic for this syndrome when the clinical context is appropriate [19,20]. Unlike Susac syndrome, involvement of the callosal substance in multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) is located on the inferior surface of the corpus callosum at the callosal-septal interface. In addition to callosal involvement, deep gray matter and posterior fossa lesions can also be observed. Infratentorial lesions are less frequent than supratentorial lesions and primarily affect the cerebellum, followed by the brainstem and middle cerebellar peduncles. Restricted diffusion of microinfarcts can occur, which is an indicator in Susac syndrome, but it is noteworthy that aggressive demyelinating lesions can also show restricted diffusion [10,21]. Variable parenchymal enhancement may occur in Susac syndrome but should not be confused with the larger open-ring enhancement observed in demyelinating syndromes such as MS or ADEM. Leptomeningeal enhancement is a highly relevant differential criterion, appearing in 30% of cases on postgadolinium T1 sequences [22,23] and in 100% of cases on postgadolinium FLAIR sequences, emphasizing their importance [24]. Lumbar puncture may reveal elevated protein levels and mild lymphocytosis [25]. Cerebral angiography is often normal because the caliber of the predominantly affected cerebral arteries (less than 100 microns) is undetectable on this examination.

All investigations for infectious, metabolic, or systemic etiologies were negative, as was the case in our patient.

Among the diagnoses to consider in the face of inflammatory central nervous system involvement in children, ADEM remains rare (0.4 per 100,000 population per year) as does pediatric MS (2% to 4% of cases of the disease). It is important not to overlook the diagnosis of Susac syndrome in the presence of central inflammatory neuropathy in children.

Ocular involvement is reported in half of patients and is exceptionally initial, underscoring the importance of performing an ophthalmological examination in cases of unknown encephalopathy and repeating it if initially normal, as ocular involvement may develop later in the course of the disease. Fundoscopic examination reveals often bilateral and asymmetric branch retinal artery occlusions, possibly accompanied by Gass plaques and cotton wool spots [21]. These occlusions can be proximal, leading to significant visual field loss, scotomas, and decreased visual acuity depending on the affected vascular territory. When more distal, they are often asymptomatic and may present with photopsies.

Fluorescein angiography of the retina is the ophthalmic test that confirms branch retinal artery occlusions and capillary leakage consistent with vasculopathy. The absence of intraocular inflammation associated with retinal arteriolar occlusion and normal choroidal circulation is an ophthalmologic characteristic strongly suggestive of Susac syndrome.

Auditory involvement is variable and corresponds to an occlusive disease of the precapillary arterioles of the cochlea and semicircular canals [26]. It presents as bilateral and asymmetric sensorineural hearing loss in the mid and low frequencies, accompanied by vertigo [25]. It can be subclinical and should be assessed using audiometry. These manifestations can lead to sequelae such as hypoacusis, tinnitus, and recurrent vertigo. A study involving 9 patients with a follow-up of 6.4 years showed no improvement in auditory involvement either spontaneously or with treatment [25].

Diagnostic criteria have been proposed for Susac syndrome (SS). They include clinical and paraclinical elements for each organ of the triad. Based on symptoms and paraclinical results, the diagnosis of SS can be classified as certain, probable, or highly probable [6]. In the case of our patient, given the combination of encephalopathy, visual impairment dating back to childhood, and subclinical auditory involvement revealed by audiometry, the diagnosis of SS is considered certain.

Several differential diagnoses can be considered: in the presence of psychiatric symptoms, a psychiatric disorder may be suspected. Small T2 hyperintense foci may suggest diagnoses such as acute disseminated encephalomyelitis or multiple sclerosis. Retinal arterial occlusion could indicate inflammatory conditions (e.g., systemic lupus erythematosus, sarcoidosis) or embolic events (sepsis, atheromatous emboli). Other differential diagnoses include sickle cell disease, hematologic disorders, carotid dissection associated with Marfan syndrome, Takayasu's disease, and Kawasaki disease.

Although various reports describe the course of Susac syndrome according to 3 main patterns: monocyclic with an active period of ≤ 2 years, polycyclic with alternating phases of remission over more than 2 years, and chronic continuous [27], the natural history of SS remains poorly understood. A case of recurrence after an 18-year remission has been reported. Remission often occurs spontaneously with or without sequelae. Sequelae can be severe, including cognitive impairment or deafness [28]. However, the prognosis is generally good without severe sequelae [25].

There is a lack of randomized controlled therapeutic trials; therefore, all recommendations stem from case series and expert opinions. Treatment strategies, including immunosuppression and immunomodulation, are based on the immune-mediated inflammatory endothelial etiology of the disease [29]. Early and aggressive therapy is necessary to prevent relapses due to the unpredictable course of the disease and potentially devastating neurological sequelae [30]. There is consensus that high-dose corticosteroids should be the first-line treatment, and early, aggressive, sustained immunosuppressive therapy can significantly improve outcomes. The most commonly used immunosuppressive agents include intravenous immunoglobulins (IVIG), plasma exchange, azathioprine, mycophenolate mofetil (MMF), methotrexate, cyclosporine A, and cyclophosphamide.

According to the recommended treatment guidelines reported by Rennebohm et al., maintenance therapy with gradual tapering is recommended even for mild to moderate cases like ours [30].

Anticoagulants or antiplatelet drugs such as acetylsalicylic acid or clopidogrel may be considered, especially in patients treated with IVIG. In a recently published study involving 7 patients, antiplatelet agents were used in all patients [31]. Their anti-inflammatory and antiplatelet properties could play a role. Long-term prospective studies are needed to confirm or refute this observation.

Conclusion

Susac syndrome is an immune-mediated disease that is exceptionally rare in children. It is characterized by a distinctive triad of encephalopathy, retinal artery occlusions, and hypoacusis, often presenting insidiously. This triad is frequently incomplete, highlighting the importance of radiological examinations and potentially MRI in diagnosis. Brain MRI is the imaging modality of choice in the presence of neurological manifestations, revealing pathognomonic lesions in the corpus callosum. Early diagnosis and treatment are essential to prevent severe neurological sequelae due to the unpredictable course of the disease.

Author contribution

All the authors contributed to study concept, data analysis and writing the paper.

Patient consent

Written informed consent for the publication of this case report was obtained from the patient.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Références

1 Kleffner I Duning T Lohmann H Deppe M Basel T Promesberger J A brief review of Susac syndrome J Neurol Sci Nov 15 1–2 2012 35 40
2 Susac JO Hardman JM Selhorst JB Microangiopathy of the brain and retina Neurology 29 1979 313 316 10.1212/wnl.29.3.313 571975
3 García-Carrasco M Mendoza-Pinto C Cervera R Diagnosis and classification of Susac syndrome Autoimmun Rev 13 2014 347 350 24424186
4 Sauma J Rivera D Wu A Donate-Lopez J Gallego-Pinazo R Chilov M Susac’s syndrome : an update J. Ophthalmol. 104 2020 1190 1195 10.1136/bjophthalmol-2019-315597
5 Rennebohm RM Egan RA Susac JO Treatment of Susac's syndrome Curr Treat Options Neurol 10 1 2008 67 74 18325301
6 Kleffner I Dörr J Ringelstein M Gross CC Böckenfeld Y Schwindt W Diagnostic criteria for Susac syndrome J. Neurol. Neurosurg. Psychiatry. 87 12 2016 1287 1295 28103199
7 Triplett JD Qiu J O’Brien B Gopinath S Trewin B Spring PJ Diagnosis, differential diagnosis and misdiagnosis of Susac syndrome Eur J Neurol 29 6 2022 1771 1781 35262238
8 Schwitter J Agosti R Ott P Kalman A Waespe W Small infarctions of cochlear, retinal, and encephalic tissue in young women Stroke 23 1992 903 907 1595113
9 David C Sacré K Henri-Feugeas MC Klein I Doan S Cohen FA Susac syndrome : a scoping review Autoimmun Rev 21 2022 103097 10.1016/j.autrev.2022.103097 35413469
10 Eluvathingal Muttikkal TJ Vattoth S Keluth Chavan VN Susac syndrome in a young child Pediatr Radiol 37 2007 710 713 17476496
11 Saliba B Pelosse M Momtchilova L Susac syndrome and ocular manifestation in a 14-year-old girl J Fr Ophthalmology 30 10 2007 1017 1022
12 Hahn JS Lannin WC Sarwal MM Microangiopathy of brain, retina, and inner ear (Susac's syndrome) in an adolescent female presenting as acute disseminated encephalomyelitis Pediatrics 114 2004 276 281 15231946
13 Rennebohm RM Lubow M Rusin J Martin L Grzybowski DM Susac JO Aggressive immunosuppressive treatment of Susac’s syndrome in an adolescent: using treatment of dermatomyositis as a model Pediatr. Rheumatol. Online J. 6 2008 3 10.1186/1546-0096-6-3 18230188
14 Yalçınkay BÇ Çetin ÖE Kılıç H Demirci O Çokyaman T Uygunoğlu U A rare presentation of Susac syndrome: report of three pediatric cases Multiple Scleros Related Disord 53 2021 10307410 10.1016/j.msard.2021.103074
15 Prakash G Jain S Gupta M Nathi T Susac’s syndrome: first from India and youngest in the world Indian J Ophthalmol 61 2013 772 773 10.4103/0301-4738.118446 24088634
16 Gross CC Meyer C Bhatia U Yshii L Kleffner I Bauer J CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome Nat Commun 10 1 2019 5779 31852955
17 Pawate S Agarwal A Moses H Sriram S The spectrum of Susac's syndrome 1Neurol Sci 30 2009 59 64
18 Zengin Karahan S Boz C Saip S Kale N Demirkaya S Celik Y Susac syndrome: clinical characteristics, diagnostic findings and treatment in 19 cases Mult Scler Relat Disord 33 2019 94 99 10.1016/j.msard.2019.05.018 31176296
19 Demir MK Case 142: Susac syndrome Radiology 250 2 2009 598 602 19188329
20 Allmendinger AM Spektor V Destian S CT and MR imaging of Susac syndrome in a young male presenting with acute disorientation Clin Imaging 34 2 2010 138 142 20189079
21 Susac JO Egan RA Rennebohm RM Lubow M Susac's syndrome: 1975-2005 microangiopathy /auto-immune endotheliopathy J Neurol Sci 257 2007 270 272 17331544
22 Susac JO Murtagh FR Egan RA Berger JR Bakshi R Lincoff N MRI findings in Susac’s syndrome Neurology 61 12 2003 1783 1787 14694047
23 Saenz R Quan AW Magalhaes A Kish K. MRI of Susac’s syndrome Am J Roentgenol 184 5 2005 1688 1690 15855140
24 Bellanger G Biotti D Adam G Leptomeningeal enhancement on post-contrast FLAIR images for early diagnosis of Susac syndrome Mult Scler 28 2 2022 189 197 33988466
25 Aubart-Cohen F Klein I Alexandra JF Bodaghi B Doan S Fardeau C Long-term outcome in Susac syndrome Medicine (Baltimore) 86 2 2007 93 102 17435589
26 Rennebohm R Susac O Egan RA Daroff RB Susac's Syndrome — Update J Neurol Sci 299 2010 86 91 10.1016/j.jns.2010.08.032 20855088
27 El Chehab H Le Corre A Ract-Madoux G Le Moigne F Drouet A Guilloton L Syndrome de SUSAC. Modes d’entrée et évolutions variables: à propos de deux cas J Franç Ophtalmol 33 8 2010 575.e1 575.e7
28 Susac JO Susac's syndrome Am J Neurolradiol 25 2004 351 352
29 Dörr J Krautwald S Wildemann B Jarius S Ringelstein M Duning T Characteristics of Susac syndrome: a review of all reported cases Nat. Publ. Gr. 9 2013 307 316 10.1038/nrneurol.2013.82
30 Rennebohm RM Asdaghi N Srivastava S Gertner E Guidelines for treatment of Susac syndrome: an update Int. J. Stroke 15 2020 484 494 10.1177/1747493017751737 29319463
31 Wilf-Yarkoni A Elkayam O Aizenstein O Oron Y Furer V Zur D Increased incidence of Susac syndrome: a case series study BMC Neurol 20 2020 332 10.1186/s12883-020-01892-0 32878610
