Int Ophthalmol DOI 10.1007/s10792-014-9914-z
CASE REPORT
Optic neuritis and rapidly progressive necrotizing retinitis as the initial signs of subacute sclerosing panencephalitis: a case report with clinical and histopathologic findings Merih Oray • Samuray Tuncer • Nur Kir Murat Karacorlu • Ilknur Tugal-Tutkun
•
Received: 21 December 2013 / Accepted: 28 January 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract We report a case of subacute sclerosing panencephalitis (SSPE) presenting first with optic neuritis and rapidly progressive necrotizing retinitis at the posterior pole. We reviewed the clinical, laboratory, photographic, angiographic, and histopathologic records of a patient with SSPE. A 15-year-old girl was referred after rapid loss of vision due to optic neuritis and macular necrosis in the right eye. She had a history of cardiac valve surgery, but had no systemic symptoms and extensive work-up was unrewarding. Contralateral involvement with rapidly progressive optic neuritis and macular necrotizing retinitis prompted retinochoroidal biopsy of the right eye, which revealed necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration with intact choroid and outer retina without any findings of inclusion bodies, microorganisms, or atypical cells. The diagnosis was based on histopathologic findings consistent with SSPE, and detection of elevated measles antibody titers in cerebrospinal fluid and serum. It was further confirmed by development of typical electroencephalography pattern at 6 months and neurological symptoms at 4-year follow-up. Clinicians need to be M. Oray S. Tuncer N. Kir I. Tugal-Tutkun (&) Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul Tip Fakultesi, Goz Hastaliklari A.D., 34390 Capa, Istanbul, Turkey e-mail: [email protected]; [email protected] M. Karacorlu Istanbul Retina Institute, Istanbul, Turkey
aware that optic neuritis and necrotizing retinitis at the posterior pole may be the presenting features of SSPE. Keywords Subacute sclerosing panencephalitis Optic neuritis Necrotizing retinitis
Introduction Subacute sclerosing panencephalitis (SSPE) is a rare, progressive neurodegenerative disorder due to reactivation of a latent measles infection affecting both gray and white matter of the central nervous system [1–3]. Ocular and visual manifestations of SSPE include papilledema, optic neuritis, optic atrophy, chorioretinitis, macular edema, retinitis, retinal hemorrhage, serous retinal detachment, cortical blindness, nystagmus, and supranuclear gaze palsies [1, 4]. We report the clinical features of an unusual case of SSPE with sudden-onset rapidly progressive ocular involvement preceding neurological signs and symptoms.
Case report A 15-year-old girl was referred with a history of acute painless vision loss in the right eye within 1 week. There was a history of a ventricular septal defect, patent ductus arteriosus, and coarctation of the aorta;
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Int Ophthalmol
Fig. 1 Color fundus photograph of the right eye at the initial visit shows a swollen optic disc with partial pallor, retinal edema, and serous macular detachment (a). Fluorescein angiographic frame at 2 min shows optic disc hyperfluorescence and hypofluorescence corresponding to the area of retinal involvement (b). Indocyanine green angiographic frame at
14 min shows a marked staining of the overlying retinal arterial and leakage of small venous branches (c). Fluorescein (d) and indocyanine green angiography (e) of the left eye show focal staining of the optic disc. OCT of the right eye reveals disruption of retinal layers and serous detachment (f)
she had undergone cardiac valve surgery three times. She had a pacemaker and was receiving anticoagulant therapy. At initial presentation, the visual acuity was no light perception in the right eye and 20/20 in the left eye. Slit-lamp examination was unremarkable. A right afferent pupillary defect was detected. Intraocular pressure was 14 mmHg in both eyes. There were no
cells in the anterior chamber or vitreous. The right eye had a swollen optic disc with partial pallor, retinal necrosis at the posterior pole, and serous macular detachment (Fig. 1). The left eye was entirely normal. Fluorescein angiography (FA) and indocyanine green angiography revealed optic disc hyperfluorescence, hypofluorescence corresponding to the retinal necrosis, and staining and leakage of the overlying retinal
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Int Ophthalmol Fig. 2 Color fundus photograph and FA of the left eye on the 2nd day of follow-up shows diffuse hyperemia of the left optic disc (a) and diffuse disc staining on FA (b). Color fundus photographs show rapidly progressive area of retinal necrosis at the posterior pole on the 5th (c), 6th (d), 9th (e), and 15th (f) day of follow-up. Retinochoroidal biopsy specimen shows necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration (g). Color fundus photograph of the left eye at 2 years shows optic atrophy, diffuse retinal atrophy, and ghost vessels (h)
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vessels in the right eye and focal staining at the optic disc in the left eye (Fig. 1). Optical coherence tomography (OCT) demonstrated diffuse thickening of the retina with disruption of the inner retinal architecture, and serous detachment in the right eye (Fig. 1). She was hospitalized for work-up and treatment. Laboratory results consisted of a normal complete blood count and biochemistry. Cranial computed tomography and chest X-ray were within normal limits. Initial neurologic examination was unremarkable. Cerebrospinal fluid (CSF) examination showed normal glucose and protein levels with four lymphocytes, four polymorph-nuclear cells and 15 erythrocytes, and elevated immunoglobulin G titer (4.6 mg/dl; normal \3.5). Septic embolus due to infectious endocarditis was suspected initially; however, the diagnosis was ruled out by sterile blood cultures and absent valvular vegetations on trans-esophageal echocardiogram. Laboratory work-up regarding active infectious and autoimmune etiologies were unrewarding. Coagulation-screening tests and protein electrophoresis revealed no pathology. Two days later, the vision in the left eye started to deteriorate and rapidly declined to counting fingers. There was diffuse swelling and hyperemia of the left optic disc and marked disc hyperfluorescence on FA (Fig. 2). She was given intravenous methylprednisolone pulse therapy (750 mg daily for 2 days). Retinal necrosis at the macular area emerged on the third day and expanded rapidly leading to a vision of hand movement in the following 3 days (Fig. 2). She underwent diagnostic pars plana vitrectomy and retinochoroidal biopsy with silicone oil tamponade in the right eye. Vitreous polymerase chain reaction revealed negative DNA for cytomegalovirus, herpes simplex virus, and varicella zoster virus. Vitreous cytology revealed no pathology. Retinochoroidal biopsy specimen showed necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration with intact choroid and outer retina without any findings of inclusion bodies, microorganisms, or atypical cells (Fig. 2). These findings were suggestive of a neurotropic viral infection and SSPE was considered as the most probable association. She was referred again to the neurology department for electroencephalography (EEG). Reanalysis of CSF and serum for measles antibodies revealed 1 IU/ml (normal \0.15 IU/ml) and 1.94 IU/ml (normal \0.15 IU/ml),
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respectively; confirming our initial diagnosis of SSPE. EEG showed abnormal patterns which were not typical for SSPE. Three days after surgery in the right eye, the vision became no light perception in the left eye. The patient’s vaccination chart confirmed a single dose of measles, mumps and rubella vaccination in childhood. She was started on isoprinosine (100 mg/ kg/day) 1,000 mg t.i.d. and ribavirin 200 mg 3 9 2 therapy for the treatment of latent neurologic infection. Ribavirin was stopped after 1 month of treatment due to gastrointestinal disturbance and since there were no neurological manifestations, the neurologist also discontinued isoprinosine therapy at 6 weeks. Six months after her initial presentation EEG revealed typical pattern for SSPE despite the absence of any neurological symptoms. At the 2-year follow-up, fundoscopy revealed bilateral optic atrophy, diffuse retinal atrophy, pigmentary changes at the macula, and ghost vessels (Fig. 2). OCT showed complete retinal atrophy. An emotional lability and behavioral alteration developed 4 years later.
Discussion SSPE has been known as a slow virus infection [4]. Neurological and ocular progression may take years; however, bilateral ocular involvement in this patient had an incredibly rapid progression, which led to loss of light perception within a week. Although there have been reports on ocular involvement with visual loss preceding neurological symptoms by years [5–7], two large studies have shown that ocular involvement develops shortly after onset of neurological symptoms in the majority of cases [8, 9]. The diagnosis may be quite challenging and requires a high index of suspicion in the absence of characteristic neurological features. The diagnosis of SSPE is principally based on clinical presentation if neurological symptoms are present. Supportive diagnostic criteria include the presence of CSF anti-measles antibodies, and ancillary findings such as those obtained by EEG, brain tissue analysis, and magnetic resonance imaging [10]. SSPE patients who present first with ocular involvement can be misdiagnosed as hereditary retinal dystrophy, acute multifocal placoid pigment epitheliopathy, or toxoplasma retinitis [2, 11, 12]. The most characteristic ocular lesion in SSPE is a focal area of
Int Ophthalmol
necrotizing retinitis at the posterior pole without vitreal inflammation [13]. Demonstration of measles antibodies in CSF may help early diagnosis in such cases. We had not encountered this type of presentation before and considered SSPE only after neurosensory retinal destruction was found on biopsy specimen. Retinochoroidal biopsy would have been unnecessary if we had previously performed CSF analysis for measles antibodies.
Conclusion Optic neuritis and necrotizing retinitis may be the presenting features of SSPE. An increased awareness of this atypical presentation may allow early diagnosis and avoidance of unnecessary investigations. Acknowledgments The authors wish to thank Candan Gurses, MD for neurological evaluation of the patient, and Nesimi Buyukbabani, MD for the histopathological analysis of the retinochoroidal biopsy specimen.
References 1. Green SH, Wirtschafter JD (1973) Ophthalmoscopic findings in subacute sclerosing panencephalitis. Br J Ophthalmol 57:780–787 2. Sharma S, Chanana B, Gulati S, Venkatesh P, Singh S (2009) Acute bilateral vision loss as the presenting future of subacute sclerosing panencephalitis. Indian J Pediatr 76:952–953
3. Samba R, Bloem MW (2004) Measles blindness. Surv Ophthalmol 49:243–255 4. Garg RK (2002) Subacute sclerosing panencephalitis. Postgrad Med J 78:63–70 5. Zagami AS, Lethlean AK (1991) Chorioretinitis as a possible very early manifestation of subacute sclerosing panencephalitis. Aust N Z J Med 21:350–352 6. Caruso JM, Robbins-Tien D, Brown WD, Antony JH, Gascon GG (2000) Atypical chorioretinitis as an early presentation of subacute sclerosing panencephalitis. J Pediatr Ophthalmol Strabismus 37:119–122 7. Park DW, Boldt HC, Massicotte SJ, Akang EE, Roos KL, Bodnar A, Pless J, Ghetti B, Pascuzzi RM (1997) Subacute sclerosing panencephalitis manifesting as viral retinitis: clinical and histopathological findings. Am J Ophthalmol 123:533–542 8. Yuksel D, Sonmez PA, Yilmaz D, Senbil N, Gurer Y (2011) Ocular findings in subacute sclerosing panencephalitis. Ocul Immunol Inflamm 19:135–138 9. Cochreau-Massin I, Gaudric A, Reinert P, Lehoang P, Rousselie F, Coscas G (1992) Changes in the fundus in subacute sclerosing panencephalitis: apropos of 23 cases. J Fr Ophthalmol 15:255–261 10. Gutierrezi J, Issacsoni RS, Koppel BS (2010) Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol 52:901–907 11. Chawla A, Jain S (2012) Subacute sclerosing panencephalitis masquerading as toxoplasmosis chorioretinitis. Can J Ophthalmol 47:e1–e2 12. Floegel I, Haas A, El-Shabrawi Y (2003) Acute multifocal placoid pigment epitheliopathy-like lesion as an early presentation of subacute sclerosing panencephalitis. Am J Ophthalmol 135:103–105 13. Kloucek F, Otradovec J (1969) Histopathological form of central chorioretinal changes in subacute sclerosing leukoencephalitis. Ophthalmologica 157:442–450
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CASE REPORT
Optic neuritis and rapidly progressive necrotizing retinitis as the initial signs of subacute sclerosing panencephalitis: a case report with clinical and histopathologic findings Merih Oray • Samuray Tuncer • Nur Kir Murat Karacorlu • Ilknur Tugal-Tutkun
•
Received: 21 December 2013 / Accepted: 28 January 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract We report a case of subacute sclerosing panencephalitis (SSPE) presenting first with optic neuritis and rapidly progressive necrotizing retinitis at the posterior pole. We reviewed the clinical, laboratory, photographic, angiographic, and histopathologic records of a patient with SSPE. A 15-year-old girl was referred after rapid loss of vision due to optic neuritis and macular necrosis in the right eye. She had a history of cardiac valve surgery, but had no systemic symptoms and extensive work-up was unrewarding. Contralateral involvement with rapidly progressive optic neuritis and macular necrotizing retinitis prompted retinochoroidal biopsy of the right eye, which revealed necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration with intact choroid and outer retina without any findings of inclusion bodies, microorganisms, or atypical cells. The diagnosis was based on histopathologic findings consistent with SSPE, and detection of elevated measles antibody titers in cerebrospinal fluid and serum. It was further confirmed by development of typical electroencephalography pattern at 6 months and neurological symptoms at 4-year follow-up. Clinicians need to be M. Oray S. Tuncer N. Kir I. Tugal-Tutkun (&) Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul Tip Fakultesi, Goz Hastaliklari A.D., 34390 Capa, Istanbul, Turkey e-mail: [email protected]; [email protected] M. Karacorlu Istanbul Retina Institute, Istanbul, Turkey
aware that optic neuritis and necrotizing retinitis at the posterior pole may be the presenting features of SSPE. Keywords Subacute sclerosing panencephalitis Optic neuritis Necrotizing retinitis
Introduction Subacute sclerosing panencephalitis (SSPE) is a rare, progressive neurodegenerative disorder due to reactivation of a latent measles infection affecting both gray and white matter of the central nervous system [1–3]. Ocular and visual manifestations of SSPE include papilledema, optic neuritis, optic atrophy, chorioretinitis, macular edema, retinitis, retinal hemorrhage, serous retinal detachment, cortical blindness, nystagmus, and supranuclear gaze palsies [1, 4]. We report the clinical features of an unusual case of SSPE with sudden-onset rapidly progressive ocular involvement preceding neurological signs and symptoms.
Case report A 15-year-old girl was referred with a history of acute painless vision loss in the right eye within 1 week. There was a history of a ventricular septal defect, patent ductus arteriosus, and coarctation of the aorta;
123
Int Ophthalmol
Fig. 1 Color fundus photograph of the right eye at the initial visit shows a swollen optic disc with partial pallor, retinal edema, and serous macular detachment (a). Fluorescein angiographic frame at 2 min shows optic disc hyperfluorescence and hypofluorescence corresponding to the area of retinal involvement (b). Indocyanine green angiographic frame at
14 min shows a marked staining of the overlying retinal arterial and leakage of small venous branches (c). Fluorescein (d) and indocyanine green angiography (e) of the left eye show focal staining of the optic disc. OCT of the right eye reveals disruption of retinal layers and serous detachment (f)
she had undergone cardiac valve surgery three times. She had a pacemaker and was receiving anticoagulant therapy. At initial presentation, the visual acuity was no light perception in the right eye and 20/20 in the left eye. Slit-lamp examination was unremarkable. A right afferent pupillary defect was detected. Intraocular pressure was 14 mmHg in both eyes. There were no
cells in the anterior chamber or vitreous. The right eye had a swollen optic disc with partial pallor, retinal necrosis at the posterior pole, and serous macular detachment (Fig. 1). The left eye was entirely normal. Fluorescein angiography (FA) and indocyanine green angiography revealed optic disc hyperfluorescence, hypofluorescence corresponding to the retinal necrosis, and staining and leakage of the overlying retinal
123
Int Ophthalmol Fig. 2 Color fundus photograph and FA of the left eye on the 2nd day of follow-up shows diffuse hyperemia of the left optic disc (a) and diffuse disc staining on FA (b). Color fundus photographs show rapidly progressive area of retinal necrosis at the posterior pole on the 5th (c), 6th (d), 9th (e), and 15th (f) day of follow-up. Retinochoroidal biopsy specimen shows necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration (g). Color fundus photograph of the left eye at 2 years shows optic atrophy, diffuse retinal atrophy, and ghost vessels (h)
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vessels in the right eye and focal staining at the optic disc in the left eye (Fig. 1). Optical coherence tomography (OCT) demonstrated diffuse thickening of the retina with disruption of the inner retinal architecture, and serous detachment in the right eye (Fig. 1). She was hospitalized for work-up and treatment. Laboratory results consisted of a normal complete blood count and biochemistry. Cranial computed tomography and chest X-ray were within normal limits. Initial neurologic examination was unremarkable. Cerebrospinal fluid (CSF) examination showed normal glucose and protein levels with four lymphocytes, four polymorph-nuclear cells and 15 erythrocytes, and elevated immunoglobulin G titer (4.6 mg/dl; normal \3.5). Septic embolus due to infectious endocarditis was suspected initially; however, the diagnosis was ruled out by sterile blood cultures and absent valvular vegetations on trans-esophageal echocardiogram. Laboratory work-up regarding active infectious and autoimmune etiologies were unrewarding. Coagulation-screening tests and protein electrophoresis revealed no pathology. Two days later, the vision in the left eye started to deteriorate and rapidly declined to counting fingers. There was diffuse swelling and hyperemia of the left optic disc and marked disc hyperfluorescence on FA (Fig. 2). She was given intravenous methylprednisolone pulse therapy (750 mg daily for 2 days). Retinal necrosis at the macular area emerged on the third day and expanded rapidly leading to a vision of hand movement in the following 3 days (Fig. 2). She underwent diagnostic pars plana vitrectomy and retinochoroidal biopsy with silicone oil tamponade in the right eye. Vitreous polymerase chain reaction revealed negative DNA for cytomegalovirus, herpes simplex virus, and varicella zoster virus. Vitreous cytology revealed no pathology. Retinochoroidal biopsy specimen showed necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration with intact choroid and outer retina without any findings of inclusion bodies, microorganisms, or atypical cells (Fig. 2). These findings were suggestive of a neurotropic viral infection and SSPE was considered as the most probable association. She was referred again to the neurology department for electroencephalography (EEG). Reanalysis of CSF and serum for measles antibodies revealed 1 IU/ml (normal \0.15 IU/ml) and 1.94 IU/ml (normal \0.15 IU/ml),
123
respectively; confirming our initial diagnosis of SSPE. EEG showed abnormal patterns which were not typical for SSPE. Three days after surgery in the right eye, the vision became no light perception in the left eye. The patient’s vaccination chart confirmed a single dose of measles, mumps and rubella vaccination in childhood. She was started on isoprinosine (100 mg/ kg/day) 1,000 mg t.i.d. and ribavirin 200 mg 3 9 2 therapy for the treatment of latent neurologic infection. Ribavirin was stopped after 1 month of treatment due to gastrointestinal disturbance and since there were no neurological manifestations, the neurologist also discontinued isoprinosine therapy at 6 weeks. Six months after her initial presentation EEG revealed typical pattern for SSPE despite the absence of any neurological symptoms. At the 2-year follow-up, fundoscopy revealed bilateral optic atrophy, diffuse retinal atrophy, pigmentary changes at the macula, and ghost vessels (Fig. 2). OCT showed complete retinal atrophy. An emotional lability and behavioral alteration developed 4 years later.
Discussion SSPE has been known as a slow virus infection [4]. Neurological and ocular progression may take years; however, bilateral ocular involvement in this patient had an incredibly rapid progression, which led to loss of light perception within a week. Although there have been reports on ocular involvement with visual loss preceding neurological symptoms by years [5–7], two large studies have shown that ocular involvement develops shortly after onset of neurological symptoms in the majority of cases [8, 9]. The diagnosis may be quite challenging and requires a high index of suspicion in the absence of characteristic neurological features. The diagnosis of SSPE is principally based on clinical presentation if neurological symptoms are present. Supportive diagnostic criteria include the presence of CSF anti-measles antibodies, and ancillary findings such as those obtained by EEG, brain tissue analysis, and magnetic resonance imaging [10]. SSPE patients who present first with ocular involvement can be misdiagnosed as hereditary retinal dystrophy, acute multifocal placoid pigment epitheliopathy, or toxoplasma retinitis [2, 11, 12]. The most characteristic ocular lesion in SSPE is a focal area of
Int Ophthalmol
necrotizing retinitis at the posterior pole without vitreal inflammation [13]. Demonstration of measles antibodies in CSF may help early diagnosis in such cases. We had not encountered this type of presentation before and considered SSPE only after neurosensory retinal destruction was found on biopsy specimen. Retinochoroidal biopsy would have been unnecessary if we had previously performed CSF analysis for measles antibodies.
Conclusion Optic neuritis and necrotizing retinitis may be the presenting features of SSPE. An increased awareness of this atypical presentation may allow early diagnosis and avoidance of unnecessary investigations. Acknowledgments The authors wish to thank Candan Gurses, MD for neurological evaluation of the patient, and Nesimi Buyukbabani, MD for the histopathological analysis of the retinochoroidal biopsy specimen.
References 1. Green SH, Wirtschafter JD (1973) Ophthalmoscopic findings in subacute sclerosing panencephalitis. Br J Ophthalmol 57:780–787 2. Sharma S, Chanana B, Gulati S, Venkatesh P, Singh S (2009) Acute bilateral vision loss as the presenting future of subacute sclerosing panencephalitis. Indian J Pediatr 76:952–953
3. Samba R, Bloem MW (2004) Measles blindness. Surv Ophthalmol 49:243–255 4. Garg RK (2002) Subacute sclerosing panencephalitis. Postgrad Med J 78:63–70 5. Zagami AS, Lethlean AK (1991) Chorioretinitis as a possible very early manifestation of subacute sclerosing panencephalitis. Aust N Z J Med 21:350–352 6. Caruso JM, Robbins-Tien D, Brown WD, Antony JH, Gascon GG (2000) Atypical chorioretinitis as an early presentation of subacute sclerosing panencephalitis. J Pediatr Ophthalmol Strabismus 37:119–122 7. Park DW, Boldt HC, Massicotte SJ, Akang EE, Roos KL, Bodnar A, Pless J, Ghetti B, Pascuzzi RM (1997) Subacute sclerosing panencephalitis manifesting as viral retinitis: clinical and histopathological findings. Am J Ophthalmol 123:533–542 8. Yuksel D, Sonmez PA, Yilmaz D, Senbil N, Gurer Y (2011) Ocular findings in subacute sclerosing panencephalitis. Ocul Immunol Inflamm 19:135–138 9. Cochreau-Massin I, Gaudric A, Reinert P, Lehoang P, Rousselie F, Coscas G (1992) Changes in the fundus in subacute sclerosing panencephalitis: apropos of 23 cases. J Fr Ophthalmol 15:255–261 10. Gutierrezi J, Issacsoni RS, Koppel BS (2010) Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol 52:901–907 11. Chawla A, Jain S (2012) Subacute sclerosing panencephalitis masquerading as toxoplasmosis chorioretinitis. Can J Ophthalmol 47:e1–e2 12. Floegel I, Haas A, El-Shabrawi Y (2003) Acute multifocal placoid pigment epitheliopathy-like lesion as an early presentation of subacute sclerosing panencephalitis. Am J Ophthalmol 135:103–105 13. Kloucek F, Otradovec J (1969) Histopathological form of central chorioretinal changes in subacute sclerosing leukoencephalitis. Ophthalmologica 157:442–450
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