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Learn more: PMC Disclaimer | PMC Copyright Notice Ann Clin Transl Neurol . 2026 Jan 9;13(4):845–849. doi: 10.1002/acn3.70297 Search in PMC Search in PubMed View in NLM Catalog Add to search Adult‐Onset Subacute Sclerosing Panencephalitis Presenting With Subacute Cognitive Deficits Dennis Yeow Dennis Yeow 1 Neurodegenerative Service, Prince of Wales Hospital and Neuroscience Research Australia, Sydney, New South Wales, Australia 2 Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia 3 Department of Neurology, Royal North Shore Hospital, Sydney, New South Wales, Australia Find articles by Dennis Yeow 1, 2, 3, ✉ , Nicola McKern Nicola McKern 3 Department of Neurology, Royal North Shore Hospital, Sydney, New South Wales, Australia 4 School of Psychological Sciences, Macquarie University, Sydney, New South Wales, Australia Find articles by Nicola McKern 3, 4 , Vincent Oxenham Vincent Oxenham 3 Department of Neurology, Royal North Shore Hospital, Sydney, New South Wales, Australia 4 School of Psychological Sciences, Macquarie University, Sydney, New South Wales, Australia Find articles by Vincent Oxenham 3, 4 , Kate Ahmad Kate Ahmad 3 Department of Neurology, Royal North Shore Hospital, Sydney, New South Wales, Australia Find articles by Kate Ahmad 3 , Omar Ahmad Omar Ahmad 5 Department of Neurology, Sydney Adventist Hospital, Sydney, New South Wales, Australia 6 Department of Neurology, Hornsby Ku‐Ring‐Gai Hospital, Sydney, New South Wales, Australia Find articles by Omar Ahmad 5, 6 Author information Article notes Copyright and License information 1 Neurodegenerative Service, Prince of Wales Hospital and Neuroscience Research Australia, Sydney, New South Wales, Australia 2 Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia 3 Department of Neurology, Royal North Shore Hospital, Sydney, New South Wales, Australia 4 School of Psychological Sciences, Macquarie University, Sydney, New South Wales, Australia 5 Department of Neurology, Sydney Adventist Hospital, Sydney, New South Wales, Australia 6 Department of Neurology, Hornsby Ku‐Ring‐Gai Hospital, Sydney, New South Wales, Australia * Correspondence: Dennis Yeow ( [email protected] ) ✉ Corresponding author. Revised 2025 Nov 13; Received 2025 Aug 18; Accepted 2025 Nov 27; Collection date 2026 Apr. © 2026 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMC Copyright notice PMCID: PMC13071100 PMID: 41510914 ABSTRACT We describe the case of a 41‐year‐old man diagnosed with adult‐onset subacute sclerosing panencephalitis (SSPE). The patient presented with subacute progressive cognitive deficits and a neuropsychological profile indicating predominant frontoparietal dysfunction. MRI showed only mild parietal‐predominant cerebral atrophy. The patient later developed periodic myoclonic jerks with time‐locked periodic slow wave complexes on electroencephalography. Evidence of intrathecal synthesis of anti‐measles IgG was identified in the cerebrospinal fluid. The patient satisfied modified Dyken diagnostic criteria and was diagnosed with SSPE. A frontoparietal pattern of deficits on neuropsychological assessment may be an early clue to the diagnosis of adult‐onset SSPE. Keywords: adult‐onset, cognitive deficit, myoclonus, SSPE 1. Introduction Subacute sclerosing panencephalitis (SSPE) is a progressive, fatal disorder caused by persistence and subsequent reactivation of mutant measles virus in the CNS. SSPE typically presents 4–12 years after measles infection in infancy, usually resulting in onset of symptoms in childhood or adolescence [ 1 , 2 , 3 ]. Cases of adult‐onset SSPE are relatively uncommon and may present diagnostic challenges due to their rarity and atypical presentation [ 2 , 4 ]. The global resurgence in measles infection incidence in recent years, at least partly related to increased rates of vaccine hesitancy, has already led to a documented increase in incidence of childhood‐onset SSPE [ 5 , 6 ]. This may be followed by increased incidence of adult‐onset SSPE in the years to come. Here, we describe a case of adult‐onset SSPE presenting initially with subacute progressive cognitive deficits before subsequent development of more typical clinical and EEG findings prompted diagnostic testing for SSPE. 2. Case Presentation A 41‐year‐old man without significant medical history experienced subacute progressive cognitive changes and somnolence over eight months. His wife noted he was making unexpected driving errors, including mistakes judging the speed at which he should be taking turns, turning into wrong lanes, and accidentally mounting the curb. The patient had limited insight into his symptoms, although he did report difficulty concentrating at work and uncharacteristic errors when performing mental arithmetic. Seven months after the onset of cognitive symptoms, involuntary jerks of the limbs, imbalance, slow movements, and mild dysarthria developed, prompting referral to our neurology clinic. There was no history of weight loss, fevers, or night sweats. The patient was born in India to non‐consanguineous parents and moved to Australia five years prior to presentation. His childhood vaccination record was not available. Although neither the patient nor his wife recalled him previously having a measles infection, subsequently further history obtained from the patient's mother revealed that the patient had measles at age 3, approximately 37 years prior to onset of his current symptoms. On examination, the patient was alert and oriented but bradyphrenic. There were frequent square wave jerks in primary gaze and saccades were hypermetric. Periodic myoclonus with a slow relaxation phase was present involving bilateral shoulder abductors and lower limb leg flexors (Video S1 ). There was mild upper limb bradykinesia with decrement but no rigidity or tremor. Gait was wide‐based and the patient was unable to perform tandem gait. There were no upper motor neuron or frontal release signs. Expressive and receptive language was intact as were basic reading, writing, and verbal repetition. There was acalculia but no left–right disorientation, finger agnosia, or agraphia. Visual fields were intact to confrontation. Formal neuropsychological assessment was conducted (Table S1 ). Educational and occupational history suggested that premorbid cognitive functioning was within the average range. The patient displayed good orientation, and object naming, basic visuoconstructional skills (e.g., copying a cross), sequencing, learning and memory of new verbal information, semantic fluency, and verbal abstract reasoning were low average to average for his age. Impairments were noted in auditory attention span, working memory, information processing speed, basic mathematical skills, learning and memorisation of new visual information, higher‐level visuospatial and visuoconstructional skills (Figure 1 ), and most aspects of executive functioning (higher‐level divided attention, multitasking, self‐monitoring, mental flexibility, problem‐solving, planning and organisation, switching, inhibitory control, and basic concept formation). This pattern suggested predominant frontoparietal dysfunction. FIGURE 1. Open in a new tab Rey‐Osterrieth complex figure task (A). The patient's copy of this image (B) demonstrates difficulties in integrating the overall gestalt with local elements when processing complex visual information, leading to mild visuospatial distortion and inaccuracies in angles, relative lengths, size, and positions of objects within the overall structure. When asked to draw the image from memory after a 3‐min (C) and 30‐min (D) interval, there were multiple errors of accuracy, orientation, and omission indicating impaired learning and memorisation of novel visual information. Brain MRI performed near the onset of cognitive symptoms revealed mild global atrophy, most prominent in the parietal lobes, and several small, non‐enhancing, subcortical T2/fluid‐attenuated inversion recovery (FLAIR) hypertense lesions (Figure 2A,B ). Fluorodeoxyglucose PET of the brain did not reveal any abnormal hypometabolism (Figure 2C ). EEG at the time of neurology review demonstrated generalised, periodic, high‐amplitude (up to 170 μV) slow waves occurring every 4–5 s throughout the recording time‐locked to the myoclonic jerks (Radermecker complexes; Figure 2D ). FIGURE 2. Open in a new tab Brain MRI near onset of symptoms with T1 (A) and T2 fluid‐attenuated inversion recovery (FLAIR) (B) sequences showing mild generalised atrophy most prominent biparietally and only a few foci of non‐specific T2 FLAIR hyperintensity in the subcortical white matter. Fluorodeoxyglucose PET of the brain (C) showing normal fluorodeoxyglucose avidity. Longitudinal bipolar montage electroencephalogram (D) showing a normal background with high amplitude, generalised, periodic, slow‐wave discharges (Radermecker complexes) that were time‐locked to the patient's myoclonic jerks. CSF examination revealed normal glucose, no cells, and negative bacterial culture, cryptococcal antigen, and PCR for measles RNA, Mycobacterium tuberculosis , and JC virus. Other negative CSF findings included anti‐neuronal, anti‐GAD65, anti‐NMDA‐R, anti‐LGI‐1, anti‐CASPR2, anti‐GABA‐B, anti‐DPPX, and anti‐IgLON5 antibodies, as well as 14‐3‐3 protein and prion protein real‐time quaking‐induced conversion. CSF protein and albumin were normal (0.47 and 0.21 g/L, respectively) but CSF IgG was elevated at 0.2 g/L (normal range 0.01–0.07 g/L) yielding an elevated CSF IgG/albumin ratio of 0.95 (normal range 0.05–0.25). Multiple CSF‐restricted oligoclonal bands were present. Anti‐measles IgG but not IgM was found in both CSF and serum using an enzyme immunoassay (Euroimmun, Lübeck, Germany), whereas IgG against varicella zoster was only present in serum but not CSF. Based on the history of cognitive impairment and periodic myoclonus, typical EEG findings and CSF suggestive of intrathecal synthesis of anti‐measles IgG, the patient was diagnosed with SSPE using modified Dyken criteria [ 1 ] and a trial of isoprinosine was initiated. The patient slowly progressed to a mute, tetraparetic state and passed away 3 years after symptom onset. 3. Discussion Adult‐onset SSPE, although uncommon, is well described in the literature with case series showing an average age of onset of 20–25 years [ 2 , 7 ]. More recently, onset in later adulthood has been recognised, with case reports documenting onset as late as the seventh decade, some 50+ years after primary measles infection [ 7 , 8 ]. Determinants of the length of this latent period are poorly characterised but may relate to interactions between host immune factors (e.g., age and immune status at time of primary measles infection, pregnancy, etc.) and viral factors (e.g., measles genotype, measles RNA mutations resulting in altered virulence, etc.) [ 9 ]. The rarity of adult‐onset SSPE, particularly in countries with high rates of measles vaccination, may result in delayed diagnosis of this disorder [ 10 ]. Additionally, in our case, the initial non‐specific presentation with subacute cognitive and non‐specific brain MRI findings also contributed to delayed referral for neurology review. However, by the time of neurologic review, despite the initial missing history of prior measles infection and lack of classic radiologic features (i.e., confluent subcortical T2/FLAIR hyperintense lesions predominantly in the parieto‐occipital lobes [ 11 ]), the development of slow periodic myoclonus with timed‐locked Radermecker complexes on EEG raised suspicion for SSPE and prompted confirmatory diagnostic testing on CSF. Lack of history of prior measles infection is more common in adult‐onset SSPE than typical childhood‐onset SSPE, although it is unclear if this finding reflects a genuine association between subclinical measles infection and adult‐onset of SSPE or if it is artefactual, related to the cognitive impairment of SSPE affecting recall of distant childhood infections and/or adult age meaning that collateral history from parents is more often unavailable [ 2 , 4 ]. Given that cognitive changes were the predominant initial manifestation in our case, predating the onset of the characteristic periodic myoclonus by more than 6 months, we sought to thoroughly characterise the nature of the cognitive deficits through detailed neuropsychological assessment. The neuropsychological profile of our patient demonstrated predominant frontoparietal deficits, correlating with the radiologic finding of mild cerebral atrophy that was most prominent in the parietal regions and also with the known predilection of SSPE for parieto‐occipital regions early in the course of disease [ 11 ]. Existing literature concerning the neuropsychological profile of adult‐onset SSPE is sparse. This likely reflects both the rarity of adult‐onset SSPE and also the variability in cognitive phenotypes that are seen, ranging from a slowly progressive dementing illness over years to more rapidly progressive dementia or even acute encephalopathy [ 12 ]. Nevertheless, our findings generally agree with previous reports of neuropsychological testing in adult‐onset SSPE presenting with cognitive symptoms which also report prominent visuoperceptual deficits and impairments in attention and verbal fluency [ 13 , 14 , 15 ]. Our report adds to the literature regarding the neuropsychological profile of adult‐onset SSPE, highlighting frontoparietal deficits as a potential diagnostic clue. Increased awareness of this pattern of cognitive deficits as a potential presenting manifestation of adult‐onset SSPE may help to increase suspicion for and prompt earlier diagnosis of this disorder, particularly when history of measles infection and more typical clinical and radiological features may be absent. Earlier diagnosis may provide the opportunity to intervene with antiviral and/or immunomodulatory agents (e.g., isoprinosine and/or interferon) which may slow disease progression [ 16 , 17 ]. Author Contributions Study conceptualisation and design: D.Y., V.O., O.A. Data acquisition: D.Y., N.M., V.O., K.A., O.A. Drafting of manuscript and preparation of figures: D.Y. Review and editing of manuscript: all authors. Funding The authors have nothing to report. Conflicts of Interest The authors declare no conflicts of interest. Supporting information Table S1: Neuropsychological assessment of patient with adult‐onset subacute sclerosing panencephalitis. ACN3-13-845-s002.docx (23.5KB, docx) Video S1: Periodic myoclonus with a slow relaxation phase is present predominantly involving bilateral shoulder abductors and lower limb hip flexors. Download video file (47.4MB, mp4) Acknowledgements The authors thank the patient's family who provided written consent for publication of this case report. D.Y. is supported by a PhD scholarship from Muscular Dystrophy NSW. 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[ DOI ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Table S1: Neuropsychological assessment of patient with adult‐onset subacute sclerosing panencephalitis. ACN3-13-845-s002.docx (23.5KB, docx) Video S1: Periodic myoclonus with a slow relaxation phase is present predominantly involving bilateral shoulder abductors and lower limb hip flexors. Download video file (47.4MB, mp4) Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. 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