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Susac's syndrome, a rare, potentially severe or lethal neurological disease
Journal of the Neurological Sciences 297 (2010) 71–73
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Susac's syndrome, a rare, potentially severe or lethal neurological disease A. Saux a,⁎, G. Niango a, M. Charif a, R. Morales a, F. Mura b, A. Bonafe c, I. Mourand a a b c
Department of Neurology, Gui de Chauliac Hospital, Avenue Auguste Fliche, 34295, Montpellier, France Department of Ophthalmology, Gui de Chauliac Hospital, Montpellier, France Department of Neuroradiology, Gui de Chauliac Hospital, Montpellier, France
a r t i c l e
i n f o
Article history: Received 6 April 2010 Received in revised form 20 July 2010 Accepted 26 July 2010 Available online 17 August 2010 Keywords: Susac's syndrome Microangiopathy Encephalopathy Hearing loss Branch retinal artery occlusion Death
a b s t r a c t Susac's syndrome (SS) is a rare, immune-mediated endotheliopathy affecting the microvasculature of the brain, the inner ear and the retina. Clinical presentation is characterised by a triad: encephalopathy, hearing loss and branch retinal artery occlusion (BRAO). Given the rarity of this disease, its natural history still remains partially unknown, but lethal cases appear to be extremely rare since there has never been, to our knowledge, a report of SS leading to death. We report 2 cases of SS illustrating the multiplicity of neurological symptomatology and its unpredictable course. One case is particularly unusual due to its severe neurological evolution, leading to death despite treatments. This report presents clinical and paraclinical findings contributory to SS diagnosis and offers an innovative perspective on disease management. These cases represent the potential severity of this disease. Early, aggressive treatment strategies may be warranted for SS in order to avoid neurological deterioration and lethal evolution. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Susac's syndrome (SS) was first identified in the 1970s [1] in 2 patients presenting with microangiopathy of the brain, inner ear and retina. Since then, reports have been sparse, with around 100 cases published. Young women are predominantly affected. However, the ages range from 9 [2] to 69 years old [3]. Neurological manifestations are varied and nonspecific. Headache, sometimes with migrainous features, is frequent, as well as cognitive and psychiatric changes. Multifocal neurological signs are also common. The natural course of SS seems to follow 3 different patterns [4]: monocyclic, polycyclic or chronic. Cognitive and auditive sequelae are frequent despite treatments, but general prognosis is usually good [5]. SS-related fatality has never been published to our knowledge. We report two cases of SS admitted to our neurological department, which illustrate the potential severity of this disease.
2. Case report 2.1. Case 1 A 50 year old woman, with no medical history, had been experiencing recurrent episodes of vertigo for the last 9 months. She was hospitalized with the diagnosis of amnesic ictus and unilateral ⁎ Corresponding author. Tel.: +33 4 67 33 74 13; fax: +33 4 67 33 72 85. E-mail address: [email protected] (A. Saux). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2010.07.020
abrupt deafness 2 and 6 months prior to this admission, respectively. She subsequently developed progressive cognitive impairment and bilateral hearing loss. Neurological examination showed bilateral pyramidal signs and mild gait instability. The Mini Mental State (MMS) score was 20/30. Bilateral perception hearing loss of 60 dB was confirmed by audiogram. Cerebral MRI revealed diffuse small infra- and supratentorial white matter lesions (Fig. 3A), involving the corpus callosum (Fig. 3C), without gadolinium enhancement. Cerebrospinal fluid (CSF) analysis showed an elevated protein level (1.15 g/L), without pleiocytosis and 2 oligoclonal bands. Retinal angiography was initially normal. Factor VIII level and von Willebrand factor antigen were elevated (N250%; normal range 50–150%). The diagnosis of SS was suspected and methylprednisolone (1 g daily for 5 days) was administered, followed by high dose oral prednisone (1 mg/kg daily), resulting in cognitive improvement (MMS 29/30), although hearing loss remained. Retinal angiography revealed BRAO (Fig. 1A–B) and leakage of arteriolar walls, confirming the diagnosis of SS. After 3 months of treatment, the patient demonstrated cognitive and psychiatric (depression, compulsive behavior, paranoiac ideas, etc.) worsening. However, cerebral angiography was normal. Cerebral MRI showed an increase in number of white matter lesions, as well as a cerebellar micronodular gadolinium enhancement (Fig. 2B). Intravenous immunoglobulin (IVIG) (0.2 g/kg daily for 5 days) and low dose aspirin (75 mg daily) were administered. After 3 months of treatment, cognitive impairment remained and psychiatric disturbances worsened. Therefore, the patient was treated with
72
A. Saux et al. / Journal of the Neurological Sciences 297 (2010) 71–73
cyclophosphamide (700 mg/m2). A total of 6 monthly doses of IVIG and cyclophosphamide were administered in order to stabilize the patient's clinical state. A “maintenance” regimen of cyclophosphamide every 3 months with gradual corticosteroid tapering was implemented. Unfortunately, after 2½ months, the patient's clinical state worsened, with major gait instability, cognitive decline, and supplementary hearing loss. MRI showed dramatic increase in white matter hyperintensities with leptomeningeal and cerebellar enhancement (Fig. 2A). Cerebral and cerebellar atrophy (Fig. 2C) also worsened. Cyclophosphamide was administered without any clinical response. Given the severe neurological deterioration despite immunosuppressive treatments, Rituximab therapy was chosen, following the protocol used for dermatomyositis (375 mg/m² once weekly for 4 weeks). This treatment is ongoing and its effects are still being evaluated.
2.2. Case 2
Fig. 1. Retinal angiography showing BRAO (A, B) and leakage of arteriolar walls (C).
A 62 year old woman, with a history of high blood pressure, was admitted for moderate headache, sudden ataxia and visual blur upon waking. Neurological examination showed a slight decrease in muscular force of her left lower limb, bilateral Babinski sign and major gait instability. Visual examination revealed a right lateral homonymous hemianopsia. Cerebral MRI revealed multifocal supra- and infratentorial white matter lesions (Fig. 3B), involving the corpus callosum, without gadolinium enhancement. CSF analysis showed an elevated protein level (1.99 g/L) without pleiocytosis or oligoclonal bands. Factor VIII level and von Willebrand factor antigen were elevated (184% and 222%, respectively; normal range 50–150%). In a few days, the patient developed compartmental (aggressivity) and cognitive changes, left spastic hemiparesia, bilateral tinnitus and hearing loss. Bilateral perception hearing loss was confirmed by audiogram. Retinal angiography showed bilateral distal BRAO (Fig. 1C), confirming the diagnosis of SS. Cerebral angiography was normal. Cerebral MRI showed worsening of the diffuse white matter lesions. T1-weighted images with gadolinium revealed infra- and supratentorial gadolinium enhancement with a miliary appearance of the cerebellum. Methylprednisone (1 g daily for 5 days) was administered, followed by IVIG (0.2 g/kg daily for 5 days). Given the rapid and drastic clinical decline, the patient was treated with cyclophosphamide bolus (700 mg/m2). Despite this therapy, the patient developed severe encephalopathy and her general state prevented the use of immunosuppressive drugs. The patient was in a bed ridden state with mutism upon her death 12 weeks after onset of symptoms. Autopsy was not performed.
Fig. 2. Initial brain MRI (axial flair and sagital T2) showing infra- and supratentorial white matter lesions involving the corpus callosum (A, B, C).
A. Saux et al. / Journal of the Neurological Sciences 297 (2010) 71–73
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Fig. 3. Control brain MRI (axial T1 with gadolinium and axial Flair) showing cerebellar gadolinium enhancement (A, B) and cerebral atrophy (C).
3. Discussion SS is a rare cause of cognitive impairment and multifocal neurological symptoms. As illustrated by our cases, the disease presents with neurological and otological symptoms and retinal involvement is generally asymptomatic. When the complete clinical triad is present, SS is relatively easy to diagnose. However, the 3 organs are not necessarily involved from the beginning, as these cases demonstrate. The absence of a clear clinical triad may cause diagnostic difficulties, especially with multiple sclerosis (MS) or acute demyelinating encephalomyelitis (ADEM). Since hearing loss is rarely seen in MS or ADEM, the diagnosis of SS may be indicated in the presence of hearing loss and associated symptoms. Audiometry usually shows bilateral perception hearing loss, predominantly on lower tones [6]. Retinal involvement is generally asymptomatic but it can sometimes cause vision loss, photopsia, and scotoma. Fundoscopic examination may result in normal findings. Therefore, systematic fluorescein angiography should be performed and should be repeated if initially normal, since BRAO can appear secondarily [6] as in case 1. Cerebral MRI and CSF analyses are helpful tools in diagnosing SS. MRI can identify multiple infra- and supratentorial white matter lesions, which are typically small (3–7 mm) and “snow-ball” like [7]. In SS with neurological manifestations, the corpus callosum is always involved, typically in its central fibers. This differs from MS in which peripheral fibers are more likely involved. Parenchymal enhancement can be present in SS and sometimes has a miliary appearance, especially in the cerebellum [7] as in our cases. Deep gray matter lesions and leptomeningeal enhancement associated with SS have also been reported [7]. In severe cases, cerebral and cerebellar atrophy can develop, as was observed in case 1. CSF analysis usually reveals a high protein level (over 1 g/L; which is unusual in either MS or ADEM) and discrete pleiocytosis [5]. Oligoclonal bands, as found in case 1, are unusual in SS [5,8] but do not challenge the diagnosis. The natural history of SS is still unclear but the disease seems to follow 3 different patterns [4]: monocyclic (remission within 1–2 years without recurrence), polycyclic (recurrences over a period of N2 years alternating with periods of remission) or chronic (prolonged, continuous course for more than 2 years). Case 1 appears to fit the criteria for the chronic pattern evolution and illustrates the importance of clinical fluctuations throughout disease duration. Recent data on long term follow-up [5] indicates a favorable general prognosis, even though cognitive sequelae are frequent. Hearing loss does not improve despite treatment. To our knowledge, case 2 is the first case of SS with severe neurological evolution leading to death. Unfortunately, autopsy was not performed. No clinical trial is available with regard to treatment management for SS. Therapeutic recommendations [4] have been proposed based on
anecdotical reports and physiopathological similarities with dermatomyositis. Corticosteroids are the first step of treatment and immunomodulating (IVIG) or immunosuppressive (cyclophosphamide, mycophenolate mofetil) drugs may be indicated, depending on severity and organs involved. Recently, Rituximab has also been considered [9]. Case 1 is a good example of the difficulties involved in managing longterm treatment given the high degree of fluctuations associated with this disease. Questions such as when to start therapy tapering or when to escalate treatment, still remain unresolved. The dramatic evolution of case 2 demonstrates that starting treatment in an urgent and aggressive manner before neurological deterioration contraindicates administrating such therapies warrants consideration. However, none of these treatments are validated and caution should be used given the absence of definitive diagnostic data and the uncertainty concerning the natural history of the disease. Overall, these cases may help physicians recognize the potential gravity of SS and offer appropriate management solutions.
4. Conclusion Susac's syndrome is a rare cause of multifocal neurological symptomatology. Inner ear or retinal involvement may indicate SS. Retinal angiography may provide valuable diagnostic evidence of SS. Cerebral MRI and CSF analyses are also useful diagnostic tools. SS can be a life-threatening neurological disease, as demonstrated by the lethal outcome of case 2. Neurological involvement should prompt clinicians to implement an early and aggressive treatment.
References [1] Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 1979;29:313–6. [2] Eluvathingal Muttikal TJ, Vattoth S, Keluth Chavan VN. Susac syndrome in a young child. Pediatr Radiol Jul 2007;37(7):710–3. [3] Roeser MM, Driscoll CL, Shallop JK, Gifford RH, Kasperbauer JL, Gluth MB. Susac syndrome — a report of cochlear implantation and review of otologic manifestations in 23 patients. Otol Neurotol 2009 Jan;30(1):34–40. [4] Rennebohm RM, Susac JO. Treatment of Susac's syndrome. J Neurol Sci 2007 Jun 15;257(1–2):215–20. [5] Aubart-Cohen F, Klein I, Alexandra JF, Bodaghi B, Doan S, Fardeau C, et al. Long-term outcome in Susac syndrome. Medicine (Baltimore) 2007 Mar;86(2):93–102. [6] Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac's syndrome: 1975–2005 microangiopathy/autoimmune endotheliopathy. J Neurol Sci 2007 Jun 15;257(1–2): 215–20. [7] Susac JO, Murtagh FR, Egan RA, Berger JR, Bakshi R, Lincoff N, et al. MRI findings in Susac's syndrome. Neurology 2003 Dec 23;61(12):1783–7. [8] Papo T, Biousse V, Lehoang P, Fardeau C, N'Guyen N, Huong DL, et al. Susac syndrome. Medicine (Baltimore) 1998;77:3–11. [9] Rennebohm RM, Egan RA, Susac JO. Treatment of Susac's syndrome. Curr Treat Options Neurol 2008 Jan;10(1):67–74.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Susac's syndrome, a rare, potentially severe or lethal neurological disease A. Saux a,⁎, G. Niango a, M. Charif a, R. Morales a, F. Mura b, A. Bonafe c, I. Mourand a a b c
Department of Neurology, Gui de Chauliac Hospital, Avenue Auguste Fliche, 34295, Montpellier, France Department of Ophthalmology, Gui de Chauliac Hospital, Montpellier, France Department of Neuroradiology, Gui de Chauliac Hospital, Montpellier, France
a r t i c l e
i n f o
Article history: Received 6 April 2010 Received in revised form 20 July 2010 Accepted 26 July 2010 Available online 17 August 2010 Keywords: Susac's syndrome Microangiopathy Encephalopathy Hearing loss Branch retinal artery occlusion Death
a b s t r a c t Susac's syndrome (SS) is a rare, immune-mediated endotheliopathy affecting the microvasculature of the brain, the inner ear and the retina. Clinical presentation is characterised by a triad: encephalopathy, hearing loss and branch retinal artery occlusion (BRAO). Given the rarity of this disease, its natural history still remains partially unknown, but lethal cases appear to be extremely rare since there has never been, to our knowledge, a report of SS leading to death. We report 2 cases of SS illustrating the multiplicity of neurological symptomatology and its unpredictable course. One case is particularly unusual due to its severe neurological evolution, leading to death despite treatments. This report presents clinical and paraclinical findings contributory to SS diagnosis and offers an innovative perspective on disease management. These cases represent the potential severity of this disease. Early, aggressive treatment strategies may be warranted for SS in order to avoid neurological deterioration and lethal evolution. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Susac's syndrome (SS) was first identified in the 1970s [1] in 2 patients presenting with microangiopathy of the brain, inner ear and retina. Since then, reports have been sparse, with around 100 cases published. Young women are predominantly affected. However, the ages range from 9 [2] to 69 years old [3]. Neurological manifestations are varied and nonspecific. Headache, sometimes with migrainous features, is frequent, as well as cognitive and psychiatric changes. Multifocal neurological signs are also common. The natural course of SS seems to follow 3 different patterns [4]: monocyclic, polycyclic or chronic. Cognitive and auditive sequelae are frequent despite treatments, but general prognosis is usually good [5]. SS-related fatality has never been published to our knowledge. We report two cases of SS admitted to our neurological department, which illustrate the potential severity of this disease.
2. Case report 2.1. Case 1 A 50 year old woman, with no medical history, had been experiencing recurrent episodes of vertigo for the last 9 months. She was hospitalized with the diagnosis of amnesic ictus and unilateral ⁎ Corresponding author. Tel.: +33 4 67 33 74 13; fax: +33 4 67 33 72 85. E-mail address: [email protected] (A. Saux). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2010.07.020
abrupt deafness 2 and 6 months prior to this admission, respectively. She subsequently developed progressive cognitive impairment and bilateral hearing loss. Neurological examination showed bilateral pyramidal signs and mild gait instability. The Mini Mental State (MMS) score was 20/30. Bilateral perception hearing loss of 60 dB was confirmed by audiogram. Cerebral MRI revealed diffuse small infra- and supratentorial white matter lesions (Fig. 3A), involving the corpus callosum (Fig. 3C), without gadolinium enhancement. Cerebrospinal fluid (CSF) analysis showed an elevated protein level (1.15 g/L), without pleiocytosis and 2 oligoclonal bands. Retinal angiography was initially normal. Factor VIII level and von Willebrand factor antigen were elevated (N250%; normal range 50–150%). The diagnosis of SS was suspected and methylprednisolone (1 g daily for 5 days) was administered, followed by high dose oral prednisone (1 mg/kg daily), resulting in cognitive improvement (MMS 29/30), although hearing loss remained. Retinal angiography revealed BRAO (Fig. 1A–B) and leakage of arteriolar walls, confirming the diagnosis of SS. After 3 months of treatment, the patient demonstrated cognitive and psychiatric (depression, compulsive behavior, paranoiac ideas, etc.) worsening. However, cerebral angiography was normal. Cerebral MRI showed an increase in number of white matter lesions, as well as a cerebellar micronodular gadolinium enhancement (Fig. 2B). Intravenous immunoglobulin (IVIG) (0.2 g/kg daily for 5 days) and low dose aspirin (75 mg daily) were administered. After 3 months of treatment, cognitive impairment remained and psychiatric disturbances worsened. Therefore, the patient was treated with
72
A. Saux et al. / Journal of the Neurological Sciences 297 (2010) 71–73
cyclophosphamide (700 mg/m2). A total of 6 monthly doses of IVIG and cyclophosphamide were administered in order to stabilize the patient's clinical state. A “maintenance” regimen of cyclophosphamide every 3 months with gradual corticosteroid tapering was implemented. Unfortunately, after 2½ months, the patient's clinical state worsened, with major gait instability, cognitive decline, and supplementary hearing loss. MRI showed dramatic increase in white matter hyperintensities with leptomeningeal and cerebellar enhancement (Fig. 2A). Cerebral and cerebellar atrophy (Fig. 2C) also worsened. Cyclophosphamide was administered without any clinical response. Given the severe neurological deterioration despite immunosuppressive treatments, Rituximab therapy was chosen, following the protocol used for dermatomyositis (375 mg/m² once weekly for 4 weeks). This treatment is ongoing and its effects are still being evaluated.
2.2. Case 2
Fig. 1. Retinal angiography showing BRAO (A, B) and leakage of arteriolar walls (C).
A 62 year old woman, with a history of high blood pressure, was admitted for moderate headache, sudden ataxia and visual blur upon waking. Neurological examination showed a slight decrease in muscular force of her left lower limb, bilateral Babinski sign and major gait instability. Visual examination revealed a right lateral homonymous hemianopsia. Cerebral MRI revealed multifocal supra- and infratentorial white matter lesions (Fig. 3B), involving the corpus callosum, without gadolinium enhancement. CSF analysis showed an elevated protein level (1.99 g/L) without pleiocytosis or oligoclonal bands. Factor VIII level and von Willebrand factor antigen were elevated (184% and 222%, respectively; normal range 50–150%). In a few days, the patient developed compartmental (aggressivity) and cognitive changes, left spastic hemiparesia, bilateral tinnitus and hearing loss. Bilateral perception hearing loss was confirmed by audiogram. Retinal angiography showed bilateral distal BRAO (Fig. 1C), confirming the diagnosis of SS. Cerebral angiography was normal. Cerebral MRI showed worsening of the diffuse white matter lesions. T1-weighted images with gadolinium revealed infra- and supratentorial gadolinium enhancement with a miliary appearance of the cerebellum. Methylprednisone (1 g daily for 5 days) was administered, followed by IVIG (0.2 g/kg daily for 5 days). Given the rapid and drastic clinical decline, the patient was treated with cyclophosphamide bolus (700 mg/m2). Despite this therapy, the patient developed severe encephalopathy and her general state prevented the use of immunosuppressive drugs. The patient was in a bed ridden state with mutism upon her death 12 weeks after onset of symptoms. Autopsy was not performed.
Fig. 2. Initial brain MRI (axial flair and sagital T2) showing infra- and supratentorial white matter lesions involving the corpus callosum (A, B, C).
A. Saux et al. / Journal of the Neurological Sciences 297 (2010) 71–73
73
Fig. 3. Control brain MRI (axial T1 with gadolinium and axial Flair) showing cerebellar gadolinium enhancement (A, B) and cerebral atrophy (C).
3. Discussion SS is a rare cause of cognitive impairment and multifocal neurological symptoms. As illustrated by our cases, the disease presents with neurological and otological symptoms and retinal involvement is generally asymptomatic. When the complete clinical triad is present, SS is relatively easy to diagnose. However, the 3 organs are not necessarily involved from the beginning, as these cases demonstrate. The absence of a clear clinical triad may cause diagnostic difficulties, especially with multiple sclerosis (MS) or acute demyelinating encephalomyelitis (ADEM). Since hearing loss is rarely seen in MS or ADEM, the diagnosis of SS may be indicated in the presence of hearing loss and associated symptoms. Audiometry usually shows bilateral perception hearing loss, predominantly on lower tones [6]. Retinal involvement is generally asymptomatic but it can sometimes cause vision loss, photopsia, and scotoma. Fundoscopic examination may result in normal findings. Therefore, systematic fluorescein angiography should be performed and should be repeated if initially normal, since BRAO can appear secondarily [6] as in case 1. Cerebral MRI and CSF analyses are helpful tools in diagnosing SS. MRI can identify multiple infra- and supratentorial white matter lesions, which are typically small (3–7 mm) and “snow-ball” like [7]. In SS with neurological manifestations, the corpus callosum is always involved, typically in its central fibers. This differs from MS in which peripheral fibers are more likely involved. Parenchymal enhancement can be present in SS and sometimes has a miliary appearance, especially in the cerebellum [7] as in our cases. Deep gray matter lesions and leptomeningeal enhancement associated with SS have also been reported [7]. In severe cases, cerebral and cerebellar atrophy can develop, as was observed in case 1. CSF analysis usually reveals a high protein level (over 1 g/L; which is unusual in either MS or ADEM) and discrete pleiocytosis [5]. Oligoclonal bands, as found in case 1, are unusual in SS [5,8] but do not challenge the diagnosis. The natural history of SS is still unclear but the disease seems to follow 3 different patterns [4]: monocyclic (remission within 1–2 years without recurrence), polycyclic (recurrences over a period of N2 years alternating with periods of remission) or chronic (prolonged, continuous course for more than 2 years). Case 1 appears to fit the criteria for the chronic pattern evolution and illustrates the importance of clinical fluctuations throughout disease duration. Recent data on long term follow-up [5] indicates a favorable general prognosis, even though cognitive sequelae are frequent. Hearing loss does not improve despite treatment. To our knowledge, case 2 is the first case of SS with severe neurological evolution leading to death. Unfortunately, autopsy was not performed. No clinical trial is available with regard to treatment management for SS. Therapeutic recommendations [4] have been proposed based on
anecdotical reports and physiopathological similarities with dermatomyositis. Corticosteroids are the first step of treatment and immunomodulating (IVIG) or immunosuppressive (cyclophosphamide, mycophenolate mofetil) drugs may be indicated, depending on severity and organs involved. Recently, Rituximab has also been considered [9]. Case 1 is a good example of the difficulties involved in managing longterm treatment given the high degree of fluctuations associated with this disease. Questions such as when to start therapy tapering or when to escalate treatment, still remain unresolved. The dramatic evolution of case 2 demonstrates that starting treatment in an urgent and aggressive manner before neurological deterioration contraindicates administrating such therapies warrants consideration. However, none of these treatments are validated and caution should be used given the absence of definitive diagnostic data and the uncertainty concerning the natural history of the disease. Overall, these cases may help physicians recognize the potential gravity of SS and offer appropriate management solutions.
4. Conclusion Susac's syndrome is a rare cause of multifocal neurological symptomatology. Inner ear or retinal involvement may indicate SS. Retinal angiography may provide valuable diagnostic evidence of SS. Cerebral MRI and CSF analyses are also useful diagnostic tools. SS can be a life-threatening neurological disease, as demonstrated by the lethal outcome of case 2. Neurological involvement should prompt clinicians to implement an early and aggressive treatment.
References [1] Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 1979;29:313–6. [2] Eluvathingal Muttikal TJ, Vattoth S, Keluth Chavan VN. Susac syndrome in a young child. Pediatr Radiol Jul 2007;37(7):710–3. [3] Roeser MM, Driscoll CL, Shallop JK, Gifford RH, Kasperbauer JL, Gluth MB. Susac syndrome — a report of cochlear implantation and review of otologic manifestations in 23 patients. Otol Neurotol 2009 Jan;30(1):34–40. [4] Rennebohm RM, Susac JO. Treatment of Susac's syndrome. J Neurol Sci 2007 Jun 15;257(1–2):215–20. [5] Aubart-Cohen F, Klein I, Alexandra JF, Bodaghi B, Doan S, Fardeau C, et al. Long-term outcome in Susac syndrome. Medicine (Baltimore) 2007 Mar;86(2):93–102. [6] Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac's syndrome: 1975–2005 microangiopathy/autoimmune endotheliopathy. J Neurol Sci 2007 Jun 15;257(1–2): 215–20. [7] Susac JO, Murtagh FR, Egan RA, Berger JR, Bakshi R, Lincoff N, et al. MRI findings in Susac's syndrome. Neurology 2003 Dec 23;61(12):1783–7. [8] Papo T, Biousse V, Lehoang P, Fardeau C, N'Guyen N, Huong DL, et al. Susac syndrome. Medicine (Baltimore) 1998;77:3–11. [9] Rennebohm RM, Egan RA, Susac JO. Treatment of Susac's syndrome. Curr Treat Options Neurol 2008 Jan;10(1):67–74.