Neuroimaging is often supportive with majority of children having normal neuroimaging findings in the early stages of SSPE. Other neuroimaging findings in children with SSPE include parieto-occipital white matter involvement, involvement of corpus callosum (CC), discrete asymmetrical patchy involvement like acute disseminated encephalomyelitis (ADEM) [1]. We report a leukodystrophy-like presentation in a boy with early-onset (at 22 months of age) cognitive decline, generalized dystonia and myoclonus that posed a diagnostic challenge.

A 24-month-old boy born to nonconsanguineous parents, with insignificant perinatal period and normal developmental milestones until the age of 22 months, presented with dystonic posturing of limbs followed by daily episodes of myoclonic jerks of 2 months duration. He had generalized twisting postures of whole body which subsided during sleep and increased on emotional triggers. In addition, he had sudden electric shock like jerks involving the trunk and limbs whole through the day that persisted during sleep. Over this duration, he had gradual regression of all attained milestones, and he was non-ambulatory at the time of presentation. He did not have any history of exanthematous febrile illness in the past and was immunized for measles at 10 months of age. Examination revealed a minimally conscious state with intermittent awareness of surroundings. There was no cranial nerve involvement. Motor examination revealed central hypotonia, bipyramidal signs (brisk deep tendon reflexes, spasticity) and appendicular dystonia. Fundus evaluation ruled out pigmentary retinal changes and hearing evaluation was normal.

Considering the subacute presentation of progressive dystonia, cognitive decline, and myoclonus, neuroimaging was planned with possibility of grey-matter predominant degenerative brain disorder. Brain magnetic resonance imaging (MRI) showed nearly symmetrical T2 and fluid-attenuated inversion recovery (FLAIR) hyperintense signals in the deep periventricular and subcortical white matter of both superior frontoparietal lobes, with corresponding hypo-iso intense T1-weighted findings, indicative of leukodystrophy (Fig. 1A–F), like that of metachromatic leukodystrophy (MLD) or mitochondrial disorders. No diffusion restriction or abnormal contrast enhancement was observed (Fig. 1G and H). Perfusion imaging (Fig. 1I–K) revealed hyperperfusion in the left cerebral cortical and subcortical regions and right temporal and posterior parietal cortices. Magnetic resonance spectroscopy (MRS) showed elevated choline and reduced N-acetylaspartate (NAA) in affected white matter (Fig. 1L). However, EEG revealed periodic discharges of large-amplitude slow-wave complexes with gross disorganization of the background raising a strong possibility of SSPE (Fig. 2). Cerebrospinal fluid (CSF) examination was unremarkable for cytology and biochemistry, however tested positive for antimeasles antibody in ratio of 1:625, thus confirming the diagnosis of SSPE. In view of this finding, genetic testing which was planned at the end of radiological differential was deferred.

Seizures were partly controlled by sodium valproate, levetiracetam and clonazepam. He was started on oral Isoprinosine with no meaningful improvement. The cognitive decline, myoclonus and generalized dystonia continued to progress to vegetative state till the last follow-up.

The present case adds leukodystrophy-like presentation to other white matter changes reported in children with SSPE. Early-onset SSPE does not follow the typical four stages of Jabbour staging classification and is known to have rapid progressive course to a vegetative state within 3 months. The earliest reported case had onset at 4 months of age [2]. The latency has been reported as short as 2 months. Genetic polymorphisms involving cell-mediated immunity have been linked to this early fulminant course following a measles infection [3]. Our child had symptom onset at 22 months of age with a fulminant progression to vegetative state within 3 months of onset. He was diagnosed based on the Dyken’s criteria (based on clinical, EEG, and positive antibody titer in the CSF). A definite history of measles infection was not documented in our patient. However, measles infection may often be subclinical or go unrecognized, particularly in early childhood. In addition, infection during early infancy, either prior to vaccination or before adequate immune maturation may pass unnoticed. Furthermore, parental recall of febrile exanthematous illnesses is often unreliable, and even when reported, it can be difficult to distinguish measles from other conditions [4]. Similarly, SSPE in vaccinated children is not uncommon. It can be related to inadequate immune response after vaccine or acquiring early subclinical infection even before the vaccination.

Majority of children in the first stages of SSPE will have normal neuroimaging. Keerthiraj et al. [5] published data of 54 patients with SSPE of which the most common findings were parieto-occipital white matter hyperintensity (86.84 % in Jabbour staging III) and diffuse cerebral atrophy. However, it is not uncommon to find ADEM-like asymmetric patchy white matter signal changes and involvement of basal ganglia in children with SSPE. Contrast enhancement, diffusion restriction and edema are uncommon radiological findings [6,7]. Diffuse symmetrical white matter involvement in clinical context of generalized dystonia, myoclonus and cognitive decline prompted us to think of even mitochondrial disorders. Children tend to get misdiagnosed as genetic leukodystrophies due to the atypical findings that deviates the diagnostic workflow from the most important CSF study causing further delay in diagnosis as in our case.

In our case, MRI demonstrated near-symmetric T2/FLAIR hyperintensities involving the periventricular and deep white matter, with minimal subcortical involvement and sparing of the CC, without diffusion restriction or postcontrast enhancement. This pattern may mimic MLD due to its symmetric periventricular distribution; however, MLD typically shows early CC involvement and a tigroid pattern. Other leukodystrophies were considered less likely: Canavan disease typically shows diffuse involvement extending into subcortical U-fibers with elevated NAA on MRS; L-2-hydroxyglutaric aciduria involves the basal ganglia (putamen) and dentate nuclei with reduced NAA; Krabbe disease can show similar periventricular or parieto-occipital white matter involvement but often, additionally involves the thalami and hilum of the dentate nucleus. Alexander disease shows frontal predominance with enhancement, and X-linked adrenoleukodystrophy demonstrates posterior predominance with splenial involvement and U-fiber sparing [8-10].

Thus, a nonspecific leukodystrophy pattern, along with the clinical and electrophysiological findings (pseudoperiodic discharges), supports SSPE despite overlapping imaging features. Irrespective of the initial findings, they progress to diffuse cortical atrophy in later stages. Integrated structural (magnetization-prepared 2 rapid gradient echoes) and perfusion (3-dimensional arterial spin labeling) imaging assessment suggested that functional involvement need not necessarily overlap with the extent of structural damage and may precede or extend beyond the extent of structural involvement. Further studies are needed to explore such fusion analysis in SSPE.

Our case further adds leukodystrophy-like presentation of SSPE to the existing wide clinical and radiological heterogenicity of presentation in endemic region. We learned that SSPE must be considered as one of the differentials in subacute onset of neurological illness with leukodystrophy-like radiological picture.