Subacute Sclerosing Panencephalitis Research Articles

A Rare Case of Subacute Sclerosing Panencephalitis Presenting as Generalized Seizure (P9-4.002)

A Rare Case of Subacute Sclerosing Panencephalitis Presenting as Generalized Seizure (P9-4.002)

Sensory Trick in Cervical Dystonia with Subacute Sclerosing Panencephalitis.

Sensory Trick in Cervical Dystonia with Subacute Sclerosing Panencephalitis.

Cardiac Rhythm Aberrations in Subacute Sclerosing Panencephalitis: Insights From Heart Rate Variability Analysis.

Subacute sclerosing panencephalitis (SSPE) is a fatal neurological disorder resulting from persistent measles virus infection within the brain. Although neurological manifestations have been well-documented, the impact of SSPE on cardiac autonomic function, assessed through heart rate variability (HRV), remains understudied. In this prospective single-center study conducted from January 2022 to March 2023 in Southern India, 30 consecutive SSPE patients and age- and sex-matched controls underwent electrocardiogram recordings for HRV analysis. Various HRV parameters were assessed, including time-domain metrics (SD of normal-to-normal intervals, root mean square of successive differences between normal heartbeats, percentage of successive normal interbeat intervals greater than 50 msec), SD1 and SD2 for Poincaré plot analysis, and frequency-domain metrics (low frequency %, high frequency %, low frequency:high frequency ratio). In the study, SSPE patients exhibited markedly reduced HRV. Specifically, SD of normal-to-normal intervals (P = 0.003), percentage of successive normal interbeat intervals greater than 50 msec (P = 0.03), and SD2 (P = 0.0016) were significantly lower compared with controls. Frequency-domain analysis did not reveal significant distinctions. Correlation analysis demonstrated a negative relationship between percentage of successive normal interbeat intervals greater than 50 msec and SSPE severity (r = -0.37, P = 0.042). Heart rate variability did not significantly differ between SSPE stages or with clinical variables. The interbeat interval range showed a narrower distribution in SSPE subjects. Our study highlights the clinical relevance of HRV analysis in SSPE and autonomic dysfunction throughout the disease course underscoring its importance in SSPE. This investigation provides valuable insights into cardiac autonomic dysfunction probably because of affliction of the central autonomic networks caused by the disease process and may be a contributing factor to mortality in SSPE.

Clinical features, pathogenesis, pathology, neuroimaging, clinical course and outcome of measles inclusion-body encephalitis: a systematic review of published case reports and case series.

Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities.

TDP-43 pathology in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and neurodegenerative mechanisms appear to play significant roles in the pathogenesis. TAR DNA-binding protein 43 (TDP-43) inclusions are a common co-pathology in several neurodegenerative disorders with diverse pathogenesis. In the present study, we examined brains of 16 autopsied SSPE patients for the presence of TDP-43 pathology and possible associations with tau pathology. Immunohistochemical staining identified TDP-43 inclusions in 31% of SSPE cases. TDP-43 pathology was widely distributed in the brains, most severely in the atrophied cerebral cortex (temporal and parietal), and most frequently as tangle- and thread-like neuronal cytoplasmic inclusions. It was associated with longer disease duration (>4 years) and tau pathology (all TDP-43-positive cases had tau-positive neurofibrillary tangles). This study demonstrates for the first time an association between TDP-43 pathology and SSPE. The co-occurrence of TDP-43 and tau aggregates and correlation with the disease duration suggest that both pathological proteins are involved in the neurodegenerative process induced by viral inflammation.

Neuroimaging Abnormalities in Patients with Subacute Sclerosing Panencephalitis : Prospective Follow-up Study.

This study aimed to assess the neuroimaging abnormalities and their progression in patients with Subacute sclerosing panencephalitis (SSPE) and identify clinical predictors of these imaging findings. This prospective observational study evaluated clinical and neuroimaging features in patients with SSPE. Patients were categorized using Dyken's criteria, Jabbour's staging system, and the definition of fulminant SSPE. They underwent comprehensive clinical assessments, cerebrospinal fluid examination, Electroencephalogram (EEG), and Magnetic Resonance Imaging (MRI) scans. Treatment involved intrathecal interferon‑α and antiepileptic medications. Functional disability was assessed using the modified Barthel index. Follow-ups were performed at 6 months, including reassessment of Modified Barthel Index (MBI) and Jabbour's staging and EEG and MRI scans. The mean age was 13.9 ± 6.7years, with males comprising 81.5% (44/54) of the cohort. Fulminant SSPE was noted in 33% (18/54) of cases. Disease duration before presentation varied significantly between fulminant and non-fulminant forms (p = 0.001). Neuroimaging abnormalities were more prevalent in JSIII stage patients, with diffuse cerebral atrophy being asignificant finding (p = 0.011). Basal ganglia involvement correlated with movement disorders. The 6‑month follow-up showed increased cerebral atrophy (p = 0.004). Increasing disease duration was an independent predictor of cerebral atrophy. An Intercomplex interval (ICI) of more than 10minutes correlated with normal neuroimaging, 10 patients died within the study period, 8 of whom had fulminant SSPE. Parieto-occipital White matter hyperintensity (WMH) is the most prevalent and sensitive neuroimaging finding for the diagnosis of SSPE. Despite interferon treatment, cerebral atrophy progressed in both aggressive and fulminant SSPE. Increasing disease duration is an independent predictor of cerebral atrophy.

Measles to Misfortune: A Case Report on Subacute Sclerosing Panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of children or young adults caused by measles infection. An abnormal immune response to the virus is said to cause brain inflammation, which may last for years. Mortality rate of the disease is around 95%. In this case report, we present the case of a 15-year-old unimmunized boy from rural Assam who presented with progressive sudden jerky movements of his limbs for 2 months, along with difficulty in doing his daily activities and forgetfulness. Although he was initially admitted with a provisional diagnosis of seizure disorder and treated with tab sodium valproate and tab clobazam, his mother, revealed a history of measles infection at 7 years of age. His Electroencephalogram (EEG) reports and CSF IgG measles antibody findings were suggestive of SSPE. He was immediately started on Tab Isoprinosine at adequate doses, but he later succumbed to his illness within 3 months of the onset of symptoms. Immunization of children with the measles vaccine plays a significant role in averting this deadly condition.

Multimodal Imaging for Subacute Sclerosing Panencephalitis: Including Anterior Segment.

Subacute sclerosing panencephalitis (SSPE) is an irreversible and progressive neurological disorder. A 20-year-old woman with SSPE presented with a decline in visual acuity. Anterior segment was evaluated with slit lamp and in vivo confocal microscopy, revealing the presence of dendritiform keratic precipitates and +2 cells in the anterior chamber. In fundus examination, white-yellowish lesions involving the macula and periphery were observed, which gradually progressed into atrophy over time. Optical coherence tomography (OCT) imaging showed progression to atrophy of moth-eaten shaped cavities including all retinal layers due to necrotizing retinitis. OCT angiography (OCTA) further revealed reduced vessel densities and flow void areas. Notably, to the best of our knowledge, this is the first case documenting anterior segment findings in SSPE in detail. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Brain tropism acquisition: The spatial dynamics and evolution of a measles virus collective infectious unit that drove lethal subacute sclerosing panencephalitis.

It is increasingly appreciated that pathogens can spread as infectious units constituted by multiple, genetically diverse genomes, also called collective infectious units or genome collectives. However, genetic characterization of the spatial dynamics of collective infectious units in animal hosts is demanding, and it is rarely feasible in humans. Measles virus (MeV), whose spread in lymphatic tissues and airway epithelia relies on collective infectious units, can, in rare cases, cause subacute sclerosing panencephalitis (SSPE), a lethal human brain disease. In different SSPE cases, MeV acquisition of brain tropism has been attributed to mutations affecting either the fusion or the matrix protein, or both, but the overarching mechanism driving brain adaptation is not understood. Here we analyzed MeV RNA from several spatially distinct brain regions of an individual who succumbed to SSPE. Surprisingly, we identified two major MeV genome subpopulations present at variable frequencies in all 15 brain specimens examined. Both genome types accumulated mutations like those shown to favor receptor-independent cell-cell spread in other SSPE cases. Most infected cells carried both genome types, suggesting the possibility of genetic complementation. We cannot definitively chart the history of the spread of this virus in the brain, but several observations suggest that mutant genomes generated in the frontal cortex moved outwards as a collective and diversified. During diversification, mutations affecting the cytoplasmic tails of both viral envelope proteins emerged and fluctuated in frequency across genetic backgrounds, suggesting convergent and potentially frequency-dependent evolution for modulation of fusogenicity. We propose that a collective infectious unit drove MeV pathogenesis in this brain. Re-examination of published data suggests that similar processes may have occurred in other SSPE cases. Our studies provide a primer for analyses of the evolution of collective infectious units of other pathogens that cause lethal disease in humans.

Assessing Implicit and Explicit Polarizable Solvation Models for Nuclear-Electronic Orbital Systems: Quantum Proton Polarization and Solvation Energetics.

Accurate simulations of many chemical processes require the inclusion of both nuclear quantum effects and a solvent environment. The nuclear-electronic orbital (NEO) approach, which treats electrons and select nuclei quantum mechanically on the same level, combined with a polarizable continuum model (PCM) for the solvent environment, addresses this challenge in a computationally practical manner. In this work, the NEO-PCM approach is extended beyond the IEF-PCM (integral equation formalism PCM) and C-PCM (conductor PCM) approaches to the SS(V)PE (surface and simulation of volume polarization for electrostatics) and ddCOSMO (domain decomposed conductor-like screening model) approaches. IEF-PCM, SS(V)PE, C-PCM, and ddCOSMO all exhibit similar solvation energies as well as comparable nuclear polarization within the NEO framework. The calculations show that the nuclear density does not leak out of the molecular cavity because it is much more localized than the electronic density. Finally, the polarization of quantized protons is analyzed in both continuum solvent and explicit solvent environments described by the polarizable MB-pol model, illustrating the impact of specific hydrogen-bonding interactions captured only by explicit solvation. These calculations highlight the relationship among solvation formalism, nuclear polarization, and energetics.

Jaw Opening Myoclonus in Subacute Sclerosing Panencephalitis: A New Phenotypic Observation.

Jaw Opening Myoclonus in Subacute Sclerosing Panencephalitis: A New Phenotypic Observation.

Subacute sclerosing panencephalitis: current threat

   The relevance of this problem is associated with a predicted increased incidence of subacute sclerosing panencephalitis, a steadily progressive and difficult to diagnose fatal brain disease. Subacute sclerosing panencephalitis develops after measles and it does not correlate with clinical type of an acute measles infection: it affects both persons with manifest measles and ones who have had an asymptomatic or abortive disease. WHO estimates the incidence of subacute sclerosing panencephalitis as 4–11 per 100,000 measles cases. The latency period from measles to the onset of subacute sclerosing panencephalitis is between 2.5 and 34 years. As a result of measles outbreaks in 2011–2014 and 2017–2019 an increase in the number of subacute sclerosing panencephalitis cases in Russia is expected soon. Diagnostic difficulties are caused by multiplicity of subacute sclerosing panencephalitis clinical manifestation and the absence of MRI changes in early stages. Thereby, it is important to exclude SSPE in patients with neurological symptoms. Screening tests for subacute sclerosing panencephalitis should be conducted in children with acute cognitive impairment, myoclonus, or a new onset of epileptic syndrome. The specific cure for subacute sclerosing panencephalitis has not been developed yet. Most treatments aim at reducing symptoms. Up to date, the only way to conquer this disease is routine measles vaccination.

Subacute sclerosing panencephalitis (SSPE): Late onset of measles complication - Case of IVIG treatment failure

Subacute sclerosing panencephalitis (SSPE) is characterized by gradual deterioration of cognitive motor and cognitive functions. SSPE more often occurs in individuals who had a history of measles viral infection. We present a case of 8 year old male child who was presented with generalized progressive weakness, recurrent falls to one side, multiple episodes of seizure, urinary incontinence. On liaison it was understood that he had a history of measles at the age of 3 years. Examination showed elevated serum measles antibody titer, electro-encephalogram (EEG) analysis revealed stereotyped polymorphic discharge seen periodically, suggestive of SSPE. He was treated with IVIG and other symptomatic treatment. However he had recurrent episodes of vomiting after IVIG administration, Ribavirin administration caused multiple oral lesions. Upon discharge he was given Syr. Valproate, Oral Steroid (Prednisolone) tapering therapy, THP 2 mg BD, PPI and Laxatives. Parents were advised to maintain RT feed of 150 mL, once in 3 hours. After 1 week, he succumbed to his illness at his residence.

Seizures as Presenting Feature of Subacute Sclerosing Panencephalitis: a Systematic Review of Case Reports and Case Series

Seizures as Presenting Feature of Subacute Sclerosing Panencephalitis: a Systematic Review of Case Reports and Case Series

Atypical early presentation of subacute sclerosing panencephalitis in children: A case series

Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease of children and young adults that may occur as an uncommon complication 7–10 years after a measles infection. In measles – endemic countries like India, the incidence of this fatal disease is high and more number of new cases are detected in recent times. In this case series, we have presented three cases of SSPE between the 4 and 5 years age group, presented with abnormal movement and neuroregression and diagnosed by characteristic clinical features, raised anti-measles antibody titer in CSF, and typical Electroencephalography findings. All of them had a history of measles infection before the vaccination and very short latency period between measles infection and the development of SSPE. They were discharged in stable condition after the treatment with oral Isoprinosine and intrathecal Interferon alfa 2b. Early age of presentation, short latency period, and apparently good response to treatment for the time being prompted us to present these cases.

Suppression of viral RNA polymerase activity is necessary for persistent infection during the transformation of measles virus into SSPE virus.

Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by measles virus (MV), which typically develops 7 to 10 years after acute measles. During the incubation period, MV establishes a persistent infection in the brain and accumulates mutations that generate neuropathogenic SSPE virus. The neuropathogenicity is closely associated with enhanced propagation mediated by cell-to-cell fusion in the brain, which is principally regulated by hyperfusogenic mutations of the viral F protein. The molecular mechanisms underlying establishment and maintenance of persistent infection are unclear because it is impractical to isolate viruses before the appearance of clinical signs. In this study, we found that the L and P proteins, components of viral RNA-dependent RNA polymerase (RdRp), of an SSPE virus Kobe-1 strain did not promote but rather attenuated viral neuropathogenicity. Viral RdRp activity corresponded to F protein expression; the suppression of RdRp activity in the Kobe-1 strain because of mutations in the L and P proteins led to restriction of the F protein level, thereby reducing cell-to-cell fusion mediated propagation in neuronal cells and decreasing neuropathogenicity. Therefore, the L and P proteins of Kobe-1 did not contribute to progression of SSPE. Three mutations in the L protein strongly suppressed RdRp activity. Recombinant MV harboring the three mutations limited viral spread in neuronal cells while preventing the release of infectious progeny particles; these changes could support persistent infection by enabling host immune escape and preventing host cell lysis. Therefore, the suppression of RdRp activity is necessary for the persistent infection of the parental MV on the way to transform into Kobe-1 SSPE virus. Because mutations in the genome of an SSPE virus reflect the process of SSPE development, mutation analysis will provide insight into the mechanisms underlying persistent infection.

Low glycemic index therapy in children with sub-acute sclerosing panencephalitis (SSPE): an experience from a measles-endemic country.

Sub-acute sclerosing panencephalitis (SSPE) is a chronic, progressive neurodegenerative disorder, commonly seen in measles-endemic countries leading to progressive neuronal loss and death. Currently, there is no proven cure for this devastating disease. We started a low glycemic index therapy (LGIT) in children with SSPE using the same principle as per its role in intractable epilepsy. Low glycemic index diet was started in children with a confirmed diagnosis of SSPE based on Dyken's criteria. All children were then classified into four stages according to disease progression. The response to diet was evaluated by improvement in their myoclonic jerks, motor activities, and changes in their stage of the disease. A total of 12 children were enrolled. The mean age was 6.65 years (range 3.3-10 years), with a male-to-female ratio of 2:1. Five children were at stage IV, five were at stage III, and two were at stage II at the start of the diet. Nine (75%) children showed improvement in their stage of illness. Of three children who were at stage IV at the initiation of the diet, one improved to stage II and two to stage III. Four children at stage III reverted to stage II. Two children initiated at stage II went into total remission. Seven (58.3%) children showed a >50% reduction in myoclonic jerks with three (25%) having a 100% reduction. Three (25%) children died due to pneumonia. LGIT may play an effective role in the management of SSPE and gives hope to families having children with this potentially life-threatening disease.

Pisa Syndrome in Subacute Sclerosing Panencephalitis: A Case Report and Review of the Literature.

Pisa Syndrome in Subacute Sclerosing Panencephalitis: A Case Report and Review of the Literature.

Bilateral retinitis as the initial presentation of subacute sclerosing panencephilitis

Subacute sclerosing panencephalitis (SSPE) is a ravaging disease of the central nervous system caused by persistent mutant measles virus. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. SSPE may have atypical clinical features at the onset. Herein, we report an atypical case of SSPE in an adolescent with bilateral retinitis as the initial presenting feature. The disease progressed with an appearance of cognitive worsening, myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of SSPE. The case warrants a high degree of suspicion on ophthalmologist’s part to clinch the definitive diagnosis of not so common deadly disease.

A Case of Subacute Sclerosing Panencephalitis: A Myriad of Masquerades on Neuroimaging

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease caused by persisting measles virus (MeV) in the central nervous tissue of the patients. About one in ten thousand children who contract the infection in early childhood develop SSPE. Fulminant SSPE is a rare disease with fatal consequences. Magnetic resonance imaging (MRI) can help in making a diagnosis, but all the possible changes encompassing all stages and their correlation with severity are yet to be described. We report a case of fulminant SSPE with unusual findings on MRI, which led to great difficulty and delay in making the correct diagnosis.