Subacute sclerosing panencephalitis: a rare cause of acute cortical visual impairment in an adult

Abstract

Adult onset subacute sclerosing panencephalitis (SSPE) after the third decade of life is rare and the manifestations can mimic disorders such as dysmyelinating and metabolic disorders. This case report presents a patient with acute binocular visual impairment in his fifth decade as the first manifestation of SSPE. This is preventable with immunisation against measles. A prior history of measles infection may not be forthcoming in adult onset SSPE. This should be kept in mind as a differential diagnosis when a patient from endemic area presents with acute visual loss even in the absence of classic features. Periodic generalised discharges on the EEG without myoclonus may be seen in this condition rarely as in this case.

Keywords

Encephalitis Asia viral infection diagnosis

Introduction

Subacute sclerosing panencephalitis (SSPE) is a degenerative disorder of the central nervous system (CNS) and occurs due to persistent CNS infection with the SSPE virus, which is a mutated measles virus. The global prevalence of SSPE has reduced to 1 per 100,000 cases of measles after the introduction of live attenuated vaccination against measles, which is secondarily useful to prevent SSPE.^1,2 In Sri Lanka, this vaccine was introduced to the expanded programme of immunisation (EPI) in August 1984, initially as a single dose. However, after a measles outbreak in 1999–2000, this was extended to a double-dose vaccine. Despite this, in 2013, Sri Lanka experienced a large outbreak of measles, with approximately 4000 new cases.

SSPE is well described in childhood and adolescence.² However, its presentation in adult life, especially after the third decade, is very rare. Adult-onset SSPE may present atypically with common visual symptoms owing to involvement of the visual cortex, optic nerve or retina, and can occur at onset without other cardinal features. We report a case of SSPE presenting with acute binocular visual impairment in a patient in his fifth decade.

Case report

A 40-year-old healthy man presented with hyper-acute onset of binocular visual impairment (‘within a fraction of a second’) without other features of posterior circulation involvement. No preceding history of fever, headache, constitutional symptoms or substance abuse was noted. Three months later he developed psychosis with delusional jealousy. Examination revealed a reduction in visual acuity bilaterally (6/60) with normal fundi and pupillary reflexes. Confrontation method and perimetry for visual fields were difficult to perform as the patient was uncooperative. The remaining neurological examination was unremarkable and the systemic examination was normal.

Magnetic resonance imaging (MRI) of the brain showed bilateral asymmetrical occipitoparietal T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities without diffusion restriction or contrast enhancement (Figure 1a), which showed an interval progression with extension to the frontal regions over three months (Figure 1b). MR angiogram and venogram were normal. We were unable to perform visual evoke potentials. The full cerebrospinal fluid (CSF) report, urine toxicology, metabolic and vasculitic screen, and transthoracic echo were non-contributory. Electroencephalogram (EEG) showed quasiperiodic generalised delta activity occurring at intervals of approximately 8–10 s (Figure 1c). The serum and CSF were positive for measles IgG antibodies by Enzyme-Linked Immunosorbent Assay (ELISA; EuroImmun, Germany) in high titres (serum = 1:3600, CSF ratio = 1:5000, CSF/serum ratio = 1.3:1). Titres were derived using the third international standard serum National Institute for Biological Standards and Control (NIBSC) 97/648. Based on the clinical presentation, EEG and CSF measles antibodies, SSPE was diagnosed and our patient started on oral ribavirin; however, there was neither clinical nor radiological improvement three months after diagnosis.

Figure 1.

(a) 3-T MRI showing T2 FLAIR hyperintensities in occipital lobes bilaterally. (b) 3-T MRI three months later, showing T2 FLAIR hyperintensities spreading to both frontal lobes. (c) EEG showing generalised periodic delta activity (one large square equals 1 s). EEG, electroencephalogram; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.

Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor in Chief of this journal.

Discussion

In our case, visual symptoms and developing psychosis occurred late; together with the MRI findings, the differential diagnoses considered included progressive multifocal leucoencephalopathy, adult onset leucodystrophies and the Heidenhain variant of Creutzfeldt–Jakob disease. The diagnosis of SSPE was made based on Dyken’s criteria, which include two possible major and four minor criteria (Figure 2), of which the major criteria plus one minor criterion are required for diagnosis.³ Raised titres of anti-measles antibodies in CSF and serum also support the diagnosis of SSPE (raised anti-measles antibody titres of >1:4 in CSF and >1:256 in serum is significant). The normal ratio of CSF:serum titre is in the range of 1:200–1:500 and in SSPE this is in the range of 1:4–1:128 (<200);² in our patient, it was 1.3:1.

Figure 2.

Dyken’s criteria to diagnose SSPE which include two major and four minor criteria.³ SSPE, subacute sclerosing panencephalitis.

Personality change and ophthalmic manifestations are common in adult-onset disease compared to childhood-onset SSPE. There are very few adult SSPE case series reported in the literature, the largest being 39 and 13 patients, respectively.^4,5 They reported two and six patients with visual symptoms at onset, respectively. The latter reported three as having cortical blindness, while in the former study it was unclear if the visual symptoms were due to cortical blindness. Another series of 13 cases of adult SSPE showed eight patients had visual symptoms.⁶

Visual abnormalities reported in SSPE include chorioretinitis, the commonest manifestation, followed by macular pigmentation, optic neuritis, papilledema, optic atrophy, nystagmus, cranial nerve palsies with ophthalmoplegia and hemianopia. Acute cortical blindness as the first clinical presentation before onset of CNS symptoms is rare in SSPE.

The mean age of onset of symptoms in adult SSPE was 21 and 19.3 years in the abovementioned studies.^4,5 A high proportion of patients with adult-onset SSPE do not have a documented history of prior measles infection.

A classic EEG pattern, during the myoclonic phase of SSPE, is virtually diagnostic; it is characterised by bilaterally symmetrical, synchronous, high voltage (200–500 mv), polyphasic, stereotyped periodic complexes of delta waves (Rademaker complexes). These periodic complexes can be seen at fairly regular intervals of 4–10 s and have a 1:1 relationship with myoclonic jerks. However, periodic generalised discharges on the EEG without myoclonus are sparsely described in the literature which was seen in our patient. The commonest abnormality on MRI includes signal changes (hyperintensities on T2-weighted and FLAIR sequences) in bilateral occipital and parietal regions involving both grey and white matter.¹ Often these changes spread to involve other regions, as seen in the follow-up images of this patient.

Intrathecal or intraventricular alpha-interferon with oral isoprinosine may prolong survival of patients with SSPE to some extent but this was not available for our patient. A recombinant adenovirus expressing a small interfering RNA that could efficiently inhibit the SSPE virus replication has been recently discovered and has shown some promising results in experimental levels.⁷

Owing to limitation of the availability of data, the clinical course of adult-onset SSPE is not clearly described and perhaps could be highly variable. The authors believe that with disease modifying treatment, adult patients with SSPE may achieve a higher rate of spontaneous remission and favourable response.

Footnotes

Acknowledgements

This case was presented at a conference of the Association of Sri Lankan Neurologists as a poster.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

HMMTB Herath

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