Brief Communication

Blindness, Dancing Extremities, and Corpus Callosum and Brain Stem Involvement: An Unusual Presentation of Fulminant Subacute Sclerosing Panencephalitis

Journal of Child Neurology 2015, Vol. 30(1) 87-90 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813520498 jcn.sagepub.com

Pratibha Singhi, MD1, Arushi Gahlot Saini, MD1, Naveen Sankhyan, MD, DM1, Pankaj Gupta, MS2, and Sameer Vyas, MD3

Abstract A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. Keywords subacute sclerosing panencephalitis, chorioretinitis, splenium, acute vision loss, pons Received September 14, 2013. Received revised November 06, 2013. Accepted for publication December 09, 2013.

Subacute sclerosing panencephalitis is a progressive, slow viral infection of the nervous system due to persistent brain infection by an aberrant wild measles virus.1 The characteristic clinical manifestations are progressive cognitive decline and behavioral abnormalities followed by myoclonic jerks, seizures, and motor problems.1 Involuntary movements are an uncommon initial presentation.2 Ocular manifestations occur in 10% to 50% of patients of subacute sclerosing panencephalitis and could precede neurologic features in 10% to 20% of patients by a few weeks to months.3,4 These include chorioretinitis, retinal pigmentary changes, increased retinal vessel tortuosity, papilledema, papillitis and disc pallor, cortical blindness, nystagmus, ptosis, and gaze palsies.1 Radiologically, the most commonly involved areas in subacute sclerosing panencephalitis are periventricular and subcortical white matter in the parieto-occipital lobes. Involvement of the basal ganglia, cerebellum, brain stem, and corpus callosum at presentation is unusual and occurs in later stages of the disease.5 We describe here an unusual case of fulminant subacute sclerosing panencephalitis presenting with acute vision loss, choreo-athetoid movements and hyperintensities in the ventral pons and splenium of corpus callosum at presentation. Our case highlights the importance of considering the diagnosis of

subacute sclerosing panencephalitis in cases with unusual presentations such as vision loss due to unexplained chorioretinitis in the absence of neurologic manifestations at the outset or brain stem lesions.

Case Report A 4-year-old girl, born of nonconsanguineous marriage and immunized for age, was brought with complaints of painless loss of vision, neuroregression, loss of speech and audition, and abnormal, intermittent, involuntary, twisting movements of the 1

Pediatric Neurology and Neurodevelopment unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India 2 Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 3 Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India Corresponding Author: Pratibha Singhi, MD, Chief Pediatric Neurology and Neurodevelopment Unit, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Email: [email protected]

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Journal of Child Neurology 30(1) showed generalized, periodic, high-amplitude sharp and slowwave complexes of 350 to 500 microvolts recurring every 2 to 3 seconds on a slow, minimally variable delta background, and a total lack of sleep markers. Cerebrospinal fluid examination showed nil cells, protein 32 mg/dL, glucose 60 mg/dL (blood glucose 110 mg/dL), and negative Gram stain and culture. Measles IgG antibody titers were 1:512 in the cerebrospinal fluid and serum. Brain magnetic resonance imaging showed T2 and fluidattenuated inversion recovery hyperintensities in the midbrain, ventral pons, and splenium of the corpus callosum (Figure 2AD). Physical and nutritional rehabilitative measures were initiated and the child was started on oral isoprinosine. Parents were explained regarding the nature of the disease and the prognosis. Measles vaccine was advised to all the siblings. At 2 months’ follow-up, the child continued to be in the same neurologic state with no further worsening.

Discussion

Figure 1. Fundus photograph of the right eye showing macular scar with atrophy of retinal pigment epithelium with temporal disc pallor.

extremities for the past 2 months. She was apparently well 2 months back when she developed intermittent, low-grade fever with cold and a maculopapular rash. It started from the face toward the trunk and gradually faded after 4 to 5 days. There was no history of itching or rash coming in crops. This was followed by acute-onset diminution of vision followed by complete blindness over the next 2 days. Two weeks later, she developed rapidly progressive neuroregression in the form of loss of ability to understand or communicate and loss of speech and hearing. Simultaneously, parents also noticed the abnormal, intermittent, involuntary, movements of the extremities. There was no history of exanthematous illness with normal premorbid psychomotor development. On examination, she had normal anthropometric and vital parameters. She was conscious with spontaneous eye opening and preserved sleep-wake cycling. However, there was no awareness of self or environment. She was unable to respond meaningfully to any visual, auditory, tactile, or noxious stimuli. There was no meaningful speech. Fundus showed bilateral atrophic retina with epiretinal membrane on the right side and bilateral temporal disc pallor (Figure 1). Pupillary reactions were normal and symmetric in both eyes. There were no cranial nerve palsies. Muscle bulk was normal with diffuse spasticity, spontaneous symmetric antigravity movements were present in all limbs, muscle stretch reflexes were brisk and bilateral Babinski reflex was present. The limbs had intermittent, rhythmic, involuntary choreo-athetoid movements, which increased with agitation and disappeared in sleep. There were no signs of meningeal irritation or cerebellar involvement. Laboratory investigations showed normal hematologic and biochemical parameters. HIV was nonreactive. Toxoplasma and cytomegalovirus serology was negative. Sleep electroencephalogram

Our case highlights that subacute sclerosing panencephalitis, should be considered in all children with acute vision loss and neuroregression. Though the disease occurs insidiously 2 to 10 years after the primary measles infection and is usually considered in children above 5 years of age, the disease has been described in toddlers, and approximately 10% of patients have a fulminant course with indistinct stages of the disease as in our case.6 The characteristic pattern of evolution of disease symptoms and myoclonic jerks might not be evident in such cases and patients could rapidly become demented and spastic with involuntary movements. The other 2 neurologic disorders due to measles are measles encephalomyelitis, a postinfectious demyelinating disorder of immunocompetent hosts, and subacute measles virus encephalopathy (also known as subacute measles encephalitis or measles inclusion-body encephalitis), a rare disorder of immunocompromised hosts, and are easily distinguishable by their distinct presentations. It has been suggested that acute fulminant subacute sclerosing panencephalitis should always be included in the differential diagnosis of acute unexplained encephalopathic diseases.1 The most characteristic neuro-ophthalmic lesion in subacute sclerosing panencephalitis is necrotizing retinitis, which usually manifests as a focal retinitis in the region of macula and is due to viral invasion of the nuclear layers of the retina.7 Ocular involvement is usually seen shortly after neurologic symptoms appear and is more likely to be associated with the duration of neurologic symptoms.3 Hence, it can be difficult to diagnose subacute sclerosing panencephalitis in the absence of neurologic symptoms as in our case and can be misdiagnosed as hereditary dystrophy or toxoplasmosis. Subacute sclerosing panencephalitis should be considered in patients with vision loss due to unexplained retinal vasculitis, maculopathy, or chorioretinitis.1 The precedence of ocular symptoms over neurologic symptoms is probably because the measles virus acquires virulent neurotropism in the retina before invading the central nervous system in some cases.1

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Figure 2. Axial (A-C) and sagittal (D) T2-weighted magnetic resonance images (MRIs) showing hyperintense lesion involving the pons and ponto-medullary junctions (black arrows), predominantly the ventral part. Hyperintensities are also seen in the splenium of the corpus callosum (white arrows in C and D).

Vaccinated children developing subacute sclerosing panencephalitis constituted around 28% of the total cases of subacute sclerosing panencephalitis in a study from India with a rapid clinical worsening as compared to the nonvaccinated group.4 This has been attributed to various factors such as poor nutritional status of children in developing countries resulting in poor vaccine uptake, a different circulating strain in the environment, subclinical measles infection prior to measles vaccination, or due to faulty storage (cold chain) of the vaccine, acting singly or in combination.4 We believe that 1 or more of these factors could have played a role in our patient resulting in subacute sclerosing panencephalitis despite measles immunization. Our patient showed peculiar, discontiguous radiologic findings in the form of signal changes in the ventral pons and splenium of the corpus callosum in the absence of other white-matter changes in the brain. Subacute sclerosing panencephalitis progresses in the occipito-frontal and cephalo-caudal directions.8 The parieto-occipital region of the brain is most severely affected,

subsequently; pathologic involvement spreads to the anterior portions of cerebral hemispheres, subcortical structures, brainstem, and spinal cord.5 Focal hyperintense lesions of the corpus callosum along with involvement of other brain areas is thought to be an extension of the posterior periventricular white matter abnormality.9,10 Early and dominant lesions of the pons in the absence of cortical involvement have been rarely described in children.11,12 The pattern of ventral pontine involvement is peculiar, with sparing of the dorsal pontine tegmentum and some of the transverse pontine fibers.13 Anatomically, the ventral pons contains longitudinal bundles of corticopontine, corticonuclear, and corticospinal fibers, which are relatively disease resistant, whereas the dorsal tegmentum is the region with direct continuation of the medulla oblongata, which is lesion free. Hence, these areas are spared. On the contrary, the disease has a tendency to involve nuclei pontis and its axonal extensions forming the transverse bundles.14 Hence, subacute sclerosing panencephalitis should be considered in the differential diagnosis of focal

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brainstem lesions observed on magnetic resonance imaging (MRI) in appropriate clinical settings.

Conclusion Subacute sclerosing panencephalitis is common in endemic countries and can have unusual clinical and radiologic presentations, including younger age at diagnosis. It should be considered in children with vision loss due to unexplained retinal vasculitis, maculopathy, or chorioretinitis and/or focal brain stem lesions with or without accompanying neurologic manifestations. Author Contributions PS was the clinician in charge who conceived and designed the study. AGS wrote the first draft of the manuscript and was responsible for patient management and literature search. PG was responsible for ophthalmologic data, and SV for radiologic data. PS, NS, PG, and SV critically reviewed the manuscript for important intellectual content and approved the final version to be published.

Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval This being a retrospective case study, it does not require ethical approval at our institute (PGIMER, Chandigarh). An informed written consent was however obtained from the parents of the patient.

References 1. Garg RK. Subacute sclerosing panencephalitis. J Neurol. 2008; 255:1861-1871.

2. Salmon JF, Pan EL, Murray AD. Visual loss with dancing extremities and mental disturbances. Surv Ophthalmol. 1991;35: 299-306. 3. Cochereau-Massin I, Gaudric A, Reinert P, et al. Changes in the fundus in subacute sclerosing panencephalitis. Apropos of 23 cases [in French]. J Fr Ophtalmol. 1992;15:255-261. 4. Khadilkar SV, Patil SG, Kulkarni KS. A study of SSPE: early clinical features. J Pediatr Neurol. 2004;2:73-77. 5. Anlar B. Subacute sclerosing panencephalitis: diagnosis and drug treatment options. CNS Drugs. 1997;7:111-120. 6. Risk WS, Haddad FS. The variable natural history of subacute sclerosing panencephalitis: a study of 118 cases from the Middle East. Arch Neurol. 1979;36:610-614. 7. Park DW, Boldt HC, Massicotte SJ, et al. Subacute sclerosing panencephalitis manifesting as viral retinitis: clinical and histopathologic findings. Am J Ophthalmol. 1997;123:533-542. 8. Oya T, Martinez AJ, Jabbour JT, et al. Subacute sclerosing panencephalitis. Correlation of clinical, neurophysiologic and neuropathologic findings. Neurology. 1974;24:211-218. 9. Alkan A, Sharifov R, Guler S, et al. Involvement of the corpus callosum splenium in a case with SSPE: magnetic resonance spectroscopy findings. Arch Med Sci. 2013;9:386-387. 10. Anlar B, Saatci I, Kose G, Yalaz K. MRI findings in subacute sclerosing panencephalitis. Neurology. 1996;47:1278-1283. 11. Yilmaz C, Caksen H, Yilmaz N, et al. Two cases of subacute sclerosing panencephalitis associated with brainstem involvement. J Trop Pediatr. 2007;53:280-283. 12. Sharma P, Singh D, Singh MK, et al. Brainstem involvement in subacute sclerosing panencephalitis. Neurol India. 2011;59: 273-275. 13. Senol U, Haspolat S, Cevikol C, Saatci I. Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern. Neuroradiology. 2000;42:913-916. 14. Sener RN. Subacute sclerosing panencephalitis with pontine involvement. J Comput Assist Tomogr. 2004;28:101-102.

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Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athe...
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