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Subacute sclerosing panencephalitis (SSPE) is a progressive and catastrophic neurodegenerative disorder due to persistent infection with the aberrant measles virus in the brain. The exact etiology of SSPE is still unknown, and early diagnosis remains a challenge, especially with the atypical presentations. The pathogenesis of SSPE involves a complex interplay between viral factors and immunological response of the host. The presenting review demonstrates an extensive glimpse of the immuno‐genetics of SSPE, exploring the single‐nucleotide polymorphisms (SNPs), genetic risk factors and immune responses that influence susceptibility and disease progression. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: The mean age was 13.9 ± 6.7 years, 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 JS III stage patients, with diffuse cerebral atrophy being a significant 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 10 minutes correlated with normal neuroimaging, 10 patients died within the study period, 8 of whom had fulminant SSPE. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Children diagnosed with subacute sclerosing panencephalitis (SSPE) display a range of neuroimaging abnormalities during different stages of the disease, but their exact clinical significance remains unclear. Methods: In this retrospective cohort study, our objective was to examine magnetic resonance imaging (MRI) abnormalities in the brains of patients aged 18 years or younger with subacute sclerosing panencephalitis. We aimed to correlate these MRI abnormalities with clinical severity, sociodemographic variables, electroencephalographic (EEG) abnormalities, and cerebrospinal anti-measles antibody titers. Results: The study included 112 cases of subacute sclerosing panencephalitis (mean age at onset: 8.9 ± 2.6 years). MRI analysis at the time of presentation revealed the following abnormalities: subcortical white matter signal changes (n = 95), periventricular white matter signal changes (n = 76), splenium of corpus callosum involvement (n = 39), diffuse corpus callosum involvement (n = 27), cerebral atrophy (n = 35), basal ganglia involvement (n = 10), and brain stem involvement (n = 2). Notably, subcortical white matter involvement, periventricular white matter involvement, diffuse corpus callosum involvement, and basal ganglia involvement were more prevalent in patients with stage III and IV subacute sclerosing panencephalitis (P <.05 for all). Cerebral atrophy was also significantly more common in patients with stage III compared to those with stage IV subacute sclerosing panencephalitis (P <.0001). However, no substantial positive or negative associations were found between MRI findings and EEG abnormalities, other sociodemographic/clinical variables, and cerebrospinal fluid measles-specific antibody titers (P >.05). Conclusion: Early in the disease progression of subacute sclerosing panencephalitis, the temporoparietal and parietooccipital regions of the subcortical white matter are affected. Neuroimaging abnormalities exhibit a stronger association with Jabbour's clinical staging, but do not show significant associations with other clinical, sociodemographic, and EEG features. [ABSTRACT FROM AUTHOR]

This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal "counterparts" in a dual "One Health" and "Translational Medicine" perspective. Within this challenging context, special emphasis is placed upon Alzheimer's disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by "Subacute Sclerosing Panencephalitis" (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a "brain-only" form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human "analogues". [ABSTRACT FROM AUTHOR]

A 30-year-old male presented with sudden painless loss of vision in the right eye for the last two days. Slit-lamp examination of the right eye revealed a quiet anterior chamber and anterior vitreous. Fundus examination of the right eye revealed a large, focal retinitis lesion centered around the fovea, whereas examination of the left was unremarkable. He gave us a history of Measles at the age of 5 years but denied any history of systemic illness. Optical coherence tomography (OCT) revealed disruption of retinal architecture with ballooning of intact internal limiting membrane. His serology was negative for syphilis, human immunodeficiency virus and toxoplasmosis. Based on clinical suspicion, he was investigated by a neurologist. His electroencephalogram and Magnetic Resonance Imaging of brain were within normal limits, but high titres of anti-measles antibodies were found in serum and cerebrospinal fluid. The diagnosis of measles retinopathy should be considered in cases with focal necrotizing retinitis, even when classical findings of CNS involvement do not exist. [ABSTRACT FROM AUTHOR]

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;55:344–348.] [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by persistent measles virus infection. SSPE predominantly affects children and adolescents. The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases. Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks. Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid, these patients were diagnosed as SSPE. Antiepileptics were started for controlling myoclonus along with supportive treatment. Both patients were discharged on antiepileptics and supportive care. Whenever there are unusual clinical manifestations with unknown vaccination status, SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies. Our case study also highlights the importance of universal coverage of measles vaccination. To reduce the incidence of measles and associated deaths, it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program.

Nodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition.

We present a 20-year-old woman who was diagnosed with subacute sclerosing panencephalitis (SSPE) 20 months after presenting with unilateral retinitis. At presentation, the patient had two inferotemporal macular lesions in her left eye. Corresponding to these areas, optical coherence tomography (OCT) showed hyporeflective spaces with loss of nearly all of the retinal layers. OCT-angiography (OCTA) demonstrated some flow deficit areas with a reduction in the vessel density. Her serum measles antibody titre was high (IgG >5000.0 mIU/ml). Twenty months later the macular lesions had diminished in size, and there was some focal retinal thinning with interruption of the ellipsoid zone. OCTA showed that the flow deficit areas were diminished in size together with the relatively improved perfusion density. Neurological examination disclosed myoclonic jerks. Neuropsychological assessment demonstrated impaired executive function, attention, and narrowed lexical fluency. Measles IgG antibody was high in the cerebrospinal fluid (>230.0 U/ml). Brain magnetic resonance imaging demonstrated bilateral, non-specific, small foci of T2 hyperintensity in the frontoparietal subcortical white matter and centrum semiovale. The present case is the first where OCTA findings of SSPE-related retinal lesions have been described. [ABSTRACT FROM AUTHOR]

Measles is a vaccine-preventable illness. Nevertheless, in recent years, measles is still endemic and epidemic in both the developed world and the developing world. The public perception of measles in the past was that it was not a big deal. However, measles is associated with a number of complications which can be places in three categories which are: acute(diarrhea, otitis media, pneumonia, encephalitis, seizures, and death) and delayed-subacute sclerosing panencephalitis (SSPE) and post-measles immune amnesia. Contrary to the beliefs of the anti-vaccine lobby, measles is bad. In acute measles, the death rate is 1–3 per 1000 and the risk of encephalitis is 1 per 1000. Relatively recent investigations indicate that SSPE is considerably more common than previously believed. The worldwide contribution of post-measles immune amnesia to morbidity and mortality is likely to be huge. In exposure situations, two doses of measles vaccine will prevent 99% of cases. Presently in the United States, the first dose is given at 12 through 15 months of age. The second dose is most often administered at 4 through 6 years of age. In my opinion, the second dose of measles vaccine should be given 4–6 weeks after the first dose rather than at 4–6 years of age. Children who don't have antibody to measles should not travel to risk areas. [ABSTRACT FROM AUTHOR]

Rationale: Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by persistent measles virus infection. SSPE predominantly affects children and adolescents. The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases. Patient concerns: Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks. Diagnosis: Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid, these patients were diagnosed as SSPE. Interventions: Antiepileptics were started for controlling myoclonus along with supportive treatment. Outcomes: Both patients were discharged on antiepileptics and supportive care. Lessons: Whenever there are unusual clinical manifestations with unknown vaccination status, SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies. Our case study also highlights the importance of universal coverage of measles vaccination. To reduce the incidence of measles and associated deaths, it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late neurological complication of measles, caused by persistent measles virus (MeV) infection of the central nervous system. There are no drugs approved for the treatment of SSPE. Here, we followed the clinical progression of a 5-year-old SSPE patient after treatment with the nucleoside analog remdesivir, conducted a post-mortem evaluation of the patient's brain, and characterized the MeV detected in the brain. The quality of life of the patient transiently improved after the first two courses of remdesivir, but a third course had no further clinical effect, and the patient eventually succumbed to his condition. Post-mortem evaluation of the brain displayed histopathological changes including loss of neurons and demyelination paired with abundant presence of MeV RNA-positive cells throughout the brain. Next-generation sequencing of RNA isolated from the brain revealed a complete MeV genome with mutations that are typically detected in SSPE, characterized by a hypermutated M gene. Additional mutations were detected in the polymerase (L) gene, which were not associated with resistance to remdesivir. Functional characterization showed that mutations in the F gene led to a hyperfusogenic phenotype predominantly mediated by N465I. Additionally, recombinant wild-type-based MeV with the SSPE-F gene or the F gene with the N465I mutation was no longer lymphotropic but instead efficiently disseminated in neural cultures. Altogether, this case encourages further investigation of remdesivir as a potential treatment of SSPE and highlights the necessity to functionally understand SSPE-causing MeV. [ABSTRACT FROM AUTHOR]

This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal “counterparts” in a dual “One Health” and “Translational Medicine” perspective. Within this challenging context, special emphasis is placed upon Alzheimer’s disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by “Subacute Sclerosing Panencephalitis” (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a “brain-only” form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human “analogues”.

To report the fundus photographs and spectral domain optical coherence tomography (SD-OCT) findings of a patient with subacute sclerosing panencephalitis (SSPE) presenting merely with ocular symptoms. A 20-year-old patient presented with sudden loss of vision in the left eye (LE). Fundus photograph showed a yellow lesion in the macula and SD-OCT showed increased reflectivity of the inner retinal layers. Disorganization of the necrotizing retinal layers in the LE gradually progressed to the atrophic retina. Then, visual complaints began in the right eye (RE) accompanied by neurological symptoms. SD-OCT revealed the inner and outer plexiform layers edema and interruption of the ellipsoid zone in RE. Fundus photographs showed macular atrophy for both eyes on the day patient died. This case report demonstrates the SD-OCT findings of SSPE retinitis with close follow-up from the acute retinitis to the total atrophic macula. These unique findings may be considered as characteristical for the diagnosis. [ABSTRACT FROM AUTHOR]

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.

Abstract Subacute sclerosing panencephalitis (SSPE) occurs in some individuals after measles infection, following a symptom-free period of several years. It resembles chronic traumatic encephalopathy (CTE), which happens after repetitive head impacts or exposure to blast waves, following a symptom-free period. As in CTE, the neurofibrillary changes of SSPE are concentrated in superficial cortical layers. Here we used electron cryo-microscopy (cryo-EM) of tau filaments from two cases of SSPE to show that the tau folds of SSPE and CTE are identical. Two types of filaments were each made of two identical protofilaments with an extra density in the β-helix region. Like in CTE, the vast majority of tau filaments were Type I, with a minority of Type II filaments. These findings suggest that the CTE tau fold can be caused by different environmental insults, which may be linked by inflammatory changes.

We report an interesting case of visual loss and visual hallucinations in a 37-year-old man. He presented with decreased vision in both eyes and visual hallucinations for the last one and a half months. He also had multiple focal to bilateral tonic-clonic seizures. On examination, there was no perception of light rays in both eyes. Fundus examination revealed disc oedema with peripapillary small haemorrhages in both eyes. Initially, the discs were hyperaemic, which turned pale in the subsequent examination at 1 month. Magnetic resonance imaging (MRI) of the brain revealed T2 hyperintensities in periventricular white matter and right fronto-parietal-occipital gray matter. His electroencephalogram showed intermittent slowing. His cerebrospinal fluid (CSF) examination showed five cells (all lymphocytes), protein 50 mg/dl, sugar 76 mg/dl (corresponding blood sugar 90 mg/dl). His CSF specimen was positive for anti-measles IgG antibodies. In conclusion, acute vision loss can rarely be the presenting symptom and, therefore, SSPE should also be considered in differential diagnoses of acute vision loss in measles-endemic regions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An unvaccinated young boy developed rapidly progressive bilateral necrotizing retinitis that healed with foveal atrophy. He had history of poor academic performance and generalized tonic-clonic seizures. Based on clinical presentation, systemic findings, and laboratory investigations, diagnosis of subacute sclerosing panencephalitis-associated retinopathy was made. Purpose: To describe clinical and imaging findings in a young boy presenting with bilateral rapidly progressive necrotizing macular retinitis. Methods: A 12-year-old Asian Indian boy developed bilateral progressive macular retinitis. He had generalized tonic-clonic seizures for the past 3 months and gave a history of poor scholastic performance with dementia of recent onset. Multimodal imaging comprising and detailed systemic and laboratory work-up was performed. Results: Both eyes showed rapidly progressive full-thickness retinitis lesions observed as disruption of retinal architecture in both eyes. Left eye optical coherence tomography shows full-thickness retinal involvement with sparing of the internal limiting membrane. Electroencephalogram and magnetic resonance imaging (brain) were suggestive of subacute sclerosing panencephalitis and the diagnosis was confirmed by elevated cerebrospinal fluid and serum IgG measles. The patient did not survive despite treatment with systemic interferon therapy. Conclusion: It is important to look for the measles virus as a probable cause of necrotizing retinitis and neurologic symptoms in immunocompetent unvaccinated young patients. Early referral to a neurologist may assist in the early diagnosis of subacute sclerosing panencephalitis and targeted therapy. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) occurs in some individuals after measles infection, following a symptom-free period of several years. It resembles chronic traumatic encephalopathy (CTE), which happens after repetitive head impacts or exposure to blast waves, following a symptom-free period. As in CTE, the neurofibrillary changes of SSPE are concentrated in superficial cortical layers. Here we used electron cryo-microscopy (cryo-EM) of tau filaments from two cases of SSPE to show that the tau folds of SSPE and CTE are identical. Two types of filaments were each made of two identical protofilaments with an extra density in the β-helix region. Like in CTE, the vast majority of tau filaments were Type I, with a minority of Type II filaments. These findings suggest that the CTE tau fold can be caused by different environmental insults, which may be linked by inflammatory changes. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a chronic slow progressive neurodegenerative disease that is often associated with measles complications. The disease is characterized by seizures, behavioral changes, motor deficit and eventually death. In this case report we discuss the case of an 8-year-old male who developed SSPE and was presented to our hospital with a history of generalized tonic colonic convulsion followed by gait abnormality, episodes, abnormal behaviors, and cognitive regression. On clinical exploration, the child had a history of measles at 8 months of age and meningitis at 18 months. The electroencephalogram (EEG) investigation showed high amplitude spikes, with focal seizure and slowing, while the magnetic resonance imaging reveal signals synonymous with high fluidattenuated inversion recovery (FLAIR), both of which are consistent with probable SSPE. The case was managed symptomatically; until his parents decided to take him back home, after which his condition deteriorated, and he sadly died. To the best of our knowledge, this is the first recorded case of SSPE in Mogadishu, Somalia. Hence, the need to further investigation to better understand the incidence of the disease in the population and propose better ways of managing the condition. [ABSTRACT FROM AUTHOR]

Purpose: To report ocular findings in a case of atypical fulminant SSPE Case report: A 20-year-old male who came with macular necrotising retinitis in both his eyes in absence of any neurological feature. Within a week the patient developed dystonic posturing and seizures. CSF examination revealed raised measles antibody titres and EEG was suggestive of SSPE. The patient succumbed to the disease within 35 days of presentation. Conclusion: SSPE can rarely have a rapidly progressive downhill course without typical neurological features and ophthalmic features which appear to be more consistent may help in clinching the diagnosis in these cases. [ABSTRACT FROM AUTHOR]

Background: Subacute sclerosing panencephalitis is a progressive neurodegenerative disease that is a late complication of measles infection. However, to date, the pathogenesis of subacute sclerosing panencephalitis is still not explained; both viral and host factors seem to be associated. The present study aimed to investigate the relationship between NOD1 and NOD2 gene variants and subacute sclerosing panencephalitis. Methods: The gene variants of NOD1 (rs2075820 and rs2075818) and NOD2 (R334Q and R334W) were explored in 64 subacute sclerosing panencephalitis patients and 70 controls using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of the AA genotype and A allele of rs2075820 (NOD1 ; c.796G>A) polymorphism were lower in patients compared with controls (P =.022 and.014, respectively). The presence of the A allele of rs2075820 may be considered as a protective factor for subacute sclerosing panencephalitis. There was a significant difference between the groups in rs2075818 (NOD1 G/C) polymorphism, and the CC genotype increased the risk of subacute sclerosing panencephalitis by 3.471-fold. The carriers of the C allele of rs2075818 (G/C) had a 1.855-fold susceptibility to subacute sclerosing panencephalitis (P =.018). The GC genotype might be associated with subacute sclerosing panencephalitis susceptibility in the patients compared with patients without having that haplotype (P =.03). Conclusions: Thus, we identified an association between subacute sclerosing panencephalitis and the rs2075820 (NOD1 G/A) and rs2075818 (NOD1 G/C) polymorphisms. These findings implicate a possible effect of this genetic polymorphism in susceptibility to subacute sclerosing panencephalitis, which needs to be confirmed in bigger populations. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune‐dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective of this case‐control study was to analyse the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case–control study conducted at a tertiary‐care referral‐facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age‐and‐sex‐matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (±6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B‐cells, T cells, helper T‐cells, and cytotoxic T‐cells were significantly higher in cases. IgG, IgM, and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0–2 and 86.7% had a score of 3–6; at 6 months 10% had a mRS score 0–2 (favorable outcome) while 90% had a mRS score 3–6 (poor outcome). Higher IgE levels were found to correlate significantly with favorable outcome. Immune‐dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine‐efficacy. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a rare disease seen more frequently in children although cases of adult onset have also been described. There are very few cases of SSPE in pregnancy and most have been diagnosed on autopsy. It is a debilitating condition usually resulting in death within 1–3 years. Due to its etiology and presenting features which occur 6–8 years after measles infection, SSPE often gets misdiagnosed or remains undiagnosed. We describe a case of SSPE in pregnancy who presented with psychiatric manifestations 7 days postpartum, and was treated as a case of postpartum psychosis. Her presenting neurological symptoms of confusion, ocular symptoms, and rigidity were masked by the behavioral component due to which the diagnosis of SSPE was a distant thought.

The measles vaccine represents a monumental achievement in modern medicine, effectively curtailing childhood mortality and morbidity on a global scale. However, recent trends in measles vaccine uptake present a concerning scenario, with declining rates posing a threat to the progress achieved in eradicating this highly contagious disease. Here, Judith Harford, paediatric nurse practitioner, Adam Practice, Poole, Dorset delves into the pivotal role of the measles vaccine in safeguarding child health, exploring the reasons underlying vaccine hesitancy, including the controversial Lancet article, and discusses the additional impact of the Covid-19 pandemic on vaccine adoption. Drawing on global data from the World Health Organization (WHO) and Global Alliance for Vaccine and Immunisation (GAVI), this piece also assesses the consequences of dwindling measles, mumps, rubella (MMR) vaccine coverage on community well-being and offers strategies to combat vaccine hesitancy. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder because of the persistence of mutated measles virus in the central nervous system. Till date, no curative therapy has been established for SSPE. Multiple drugs have been tried to modify the disease process but have shown mild to moderate benefit at best. It is also challenging to attribute the relative success of some strategies described in single case reports because of the known phenomenon of spontaneous improvement in 5% of patients with SSPE. Critical gaps in understanding the pathophysiological processes involved exist. Current therapies such as interferon alfa require invasive strategies for administration by the intraventricular or intrathecal route, with varying dosage regimens. Oral therapies such as isoprinosine and ribavirin are expensive and not readily available in resource-constrained settings. Most of the evidence so far favors the use of combinational regimens. In this viewpoint, we critically summarize the current evidence on disease-modifying strategies in the context of our region. [ABSTRACT FROM AUTHOR]

Different movement disorders are reported in association with infectious diseases. In addition, myoclonus can be associated with different types of viral and bacterial infections. We screened three electronic databases for cases of myoclonus as a feature of different infections and collected cases and series describing myoclonus associated with infections. Data regarding study design, sample size, neurological assessment, and diagnostic workup including brain imaging and cerebrospinal fluid analysis were extracted from the identified studies. In this narrative review, we review different infections associated with myoclonus and discuss their salient features. The infections presenting with myoclonus include predominantly subacute sclerosing panencephalitis due to measles. In addition, we describe other viral infections that are reported to associated with myoclonus. Recently, coronavirus disease 2019 infections have been reported to be increasingly associated with myoclonus. The hypothesized mechanisms of infection-related myoclonus are vasculopathy, autoimmune reactions, and inflammation. Although myoclonus is considered to be a result of heredodegenerative, metabolic, or autoimmune disorders, infections may present with myoclonus, especially in tropical and developing countries. In this review, we describe the infections that are associated with myoclonus.

Faciobrachial dystonic seizure is a distinctive phenomenology that is considered pathognomonic of leucine-rich glioma-inactivated protein 1 (LGI1) antibody-associated autoimmune limbic encephalitis. However, similar phenomenology has been described with other neurological disorders as well. Here, we report the case of a 26-year-old man with subacute sclerosing panencephalitis who presented with multiple episodes of involuntary movements resembling faciobrachial dystonic seizure. Serum and cerebrospinal fluid autoimmune encephalitis panel, including leucine-rich glioma-inactivated protein 1 antibody, were negative. Classical periodic stereotypical slow wave discharges on the electroencephalogram and raised measles antibody titre in cerebrospinal fluid confirmed the diagnosis of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a rare disease seen more frequently in children although cases of adult onset have also been described. There are very few cases of SSPE in pregnancy and most have been diagnosed on autopsy. It is a debilitating condition usually resulting in death within 1–3 years. Due to its etiology and presenting features which occur 6–8 years after measles infection, SSPE often gets misdiagnosed or remains undiagnosed. We describe a case of SSPE in pregnancy who presented with psychiatric manifestations 7 days postpartum, and was treated as a case of postpartum psychosis. Her presenting neurological symptoms of confusion, ocular symptoms, and rigidity were masked by the behavioral component due to which the diagnosis of SSPE was a distant thought. [ABSTRACT FROM AUTHOR]

Background: Homozygous variants of the TREM2 and TYROBP genes have been shown to be causative for multiple bone cysts and neurodegeneration leading to progressive dementia (NHD, Nasu-Hakola disease).Objective: To determine if biallelic variants of these genes and/or oligogenic inheritance could be responsible for a wider spectrum of neurodegenerative conditions.Methods: We analyzed 52 genes associated with neurodegenerative disorders using targeted next generation sequencing in a selected group of 29 patients (n = 14 Alzheimer's disease, n = 8 frontotemporal dementia, n = 7 amyotrophic lateral sclerosis) carrying diverse already determined rare variants in exon 2 of TREM2. Molecular modeling was used to get an insight into the potential effects of the mutation.Results: We identified a novel mutation c.401_406delinsTCTAT; p.(Asp134Valfs*55) in exon 3 of TREM2 in an Alzheimer's disease patient also carrying the p.Arg62His TREM2 variant. Molecular modeling revealed that the identified mutation prevents anchoring of the TREM2 protein in the membrane, leaving the core of the Ig-like domain intact.Conclusion: Our results expand the spectrum of neurodegenerative diseases, where the carriers of biallelic mutations in TREM2 have been described for Alzheimer's disease, and highlight the impact of variant burden in other genes on phenotypic heterogeneity. [ABSTRACT FROM AUTHOR]

High measles‐specific antibody titers in the cerebrospinal fluid (CSF) have important diagnostic significance for subacute sclerosing panencephalitis (SSPE), a progressive neurological disorder caused by measles virus variants. However, the diagnostic reference value of antibody levels and the usefulness of the CSF/serum ratio measured using enzyme immunoassays (EIAs) for SSPE diagnosis remain unclear. To facilitate SSPE diagnosis using EIAs, measles immunoglobulin G (IgG) titers in the CSF and serum of patients with and without SSPE were measured and their CSF/serum antibody ratios evaluated. Serum and CSF antibody levels were compared among three patients with SSPE (59 paired samples), 37 non‐SSPE patients, and 2618 patients of unknown backgrounds. Of the 59 paired samples from three patients with SSPE, 56 paired samples (94.9%) showed CSF measles IgG levels ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, whereas non‐SSPE cases showed CSF measles IgG levels <0.1 IU/mL and a CSF/serum ratio <0.03. Of the 2618 CSF samples with unknown backgrounds, 951 showed measurable IgG levels with EIA, with a CSF/serum ratio peak of 0.005–0.02, with a 90th percentile of 0.05. Assuming the SSPE criteria as CSF measles IgG ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, only 20 samples (0.8%) with unknown backgrounds were categorized as having SSPE. Conversely, assuming the non‐SSPE criteria as CSF measles IgG <0.1 IU/mL and a CSF/serum ratio <0.03, 2403 samples (92%) with unknown backgrounds were categorized as not having SSPE. In conclusion, high CSF/serum ratios (≥0.05) and high measles CSF IgG levels (≥0.5 IU/mL) may be useful for diagnosing SSPE. [ABSTRACT FROM AUTHOR]

Different movement disorders are reported in association with infectious diseases. In addition, myoclonus can be associated with different types of viral and bacterial infections. We screened three electronic databases for cases of myoclonus as a feature of different infections and collected cases and series describing myoclonus associated with infections. Data regarding study design, sample size, neurological assessment, and diagnostic workup including brain imaging and cerebrospinal fluid analysis were extracted from the identified studies. In this narrative review, we review different infections associated with myoclonus and discuss their salient features. The infections presenting with myoclonus include predominantly subacute sclerosing panencephalitis due to measles. In addition, we describe other viral infections that are reported to associated with myoclonus. Recently, coronavirus disease 2019 infections have been reported to be increasingly associated with myoclonus. The hypothesized mechanisms of infection-related myoclonus are vasculopathy, autoimmune reactions, and inflammation. Although myoclonus is considered to be a result of heredodegenerative, metabolic, or autoimmune disorders, infections may present with myoclonus, especially in tropical and developing countries. In this review, we describe the infections that are associated with myoclonus. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

Subacute sclerosing panencephalitis (SSPE) is a late complication of measles virus infection that occurs in previously healthy children. This disease has no specific cure and is associated with a high degree of disability and mortality. In recent years, there has been an increase in its incidence in relation to a reduction in vaccination adherence, accentuated by the COVID-19 pandemic. In this article, we take stock of the current evidence on SSPE and report our personal clinical experience. We emphasise that, to date, the only effective protection strategy against this disease is vaccination against the measles virus. [ABSTRACT FROM AUTHOR]

Introduction  Subacute sclerosing panencephalitis (SSPE) is a devastating neurodegenerative disease occurring as a complication of measles infection that is still prevalent in low-resource countries. Clinical and electrographical variability in SSPE can lead to diagnostic delays. Methods  Children diagnosed with SSPE in a tertiary care pediatric hospital in India in a period of 8 years were included in the study. The diagnosis was established on the basis of Dyken's criteria. The demographic data, clinical presentations, investigations, treatment approaches, and outcomes were reviewed and recorded. Results  Thirty-four patients were included in the analysis. Average age at symptom onset was 7 years, 5 months. Majority of the children were not vaccinated for measles. Most patients (80%) presented with stage 2 of illness. Nearly 25% presented with atypical clinical features. Myoclonus was the most predominant feature seen after diagnosis. Electroencephalography (EEG) was the most useful investigation for suspecting the diagnosis. All patients showed deterioration in neurological status with time and 20% died during follow-up. Conclusion  Atypical presentations of SSPE must be recognized in areas with high incidence to institute timely treatment and establish prognosis. EEG findings were found to be the most important indicator for diagnosis. Measles eradication will pave the way for elimination of this dreaded disease. [ABSTRACT FROM AUTHOR]

Atypical presentations of subacute sclerosing panencephalitis include hemiparesis, acute disseminated encephalomyelitis, cerebellar ataxia, visual disturbances, symptoms suggestive of the intracranial spaceoccupying lesion, and extrapyramidal movement disorders. Parkinsonism as the presenting feature of subacute sclerosing panencephalitis is a rare occurrence. Here we report a child who presented with bradykinesia and rigidity, underwent extensive investigations, finally turned out to be subacute sclerosis panencephalitis. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE), an insidiously progressive slow viral infection of the central nervous system caused by the mutated measles virus, is invariably fatal. Various medications have been tried unsuccessfully till date with rare remissions. A case of 21-year woman with adult-onset SSPE who improved after treatment is reported. She had seizures, psychosis, and extrapyramidal symptoms and was on multiple anti-seizure medications without response. She was given a trial of levamisole with gradual escalation and achieved complete clinical remission by 21 months. This case demonstrates the curative potential of levamisole in adult-onset SSPE. A review of previous treatments attempted in cases who underwent remission of SSPE is also presented. [ABSTRACT FROM AUTHOR]

Purpose of the review: Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, and frequently fatal neurodegenerative disorder caused by measles virus. The risk of SSPE remains significant globally, with fluctuating incidence noted in in tandem with measles vaccine uptake. This review aims to explore the current global status of SSPE, its treatment, and preventive measures. Recent findings: An increase in measles cases have been reported in various parts of the world for different reasons related to the regional context of the outbreak. With reduction in measles vaccine doses since the onset of the COVID-19 pandemic, the future risk of SSPE can only accelerate. In recent years, subsequent cases of SSPE have been reported in the period following documented measles outbreaks in different settings. Concomitantly, there have been efforts to evaluate the efficacy of immunomodulatory, antiviral, and anti-seizure therapies that could ameliorate the devastating effects of this disease. This review elucidates on these approaches and their limitations, reasons for poor vaccine coverage in low- and middle-income countries, as well as the possible solutions to the prevention of measles and eventual avoidance of SSPE. Summary: Prevention of measles virus infection with the resultant sequelae would be the most effective strategy for the management of SSPE. This approach would be particularly important in low resource setting that currently bears the double burden of widespread communicable diseases and malnutrition. [ABSTRACT FROM AUTHOR]

Measles virus (MeV), an enveloped RNA virus in the family Paramyxoviridae, usually causes acute febrile illness with skin rash but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). MeV bears two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. The H protein possesses a head domain that initially mediates receptor binding and a stalk domain that subsequently transmits the fusion-triggering signal to the F protein. We recently showed that cell adhesion molecule 1 (CADM1; also known as IGSF4A, Necl2, and SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, and SynCAM2) are host factors enabling cell-cell membrane fusion mediated by hyperfusogenic F proteins of neuropathogenic MeVs as well as MeV spread between neurons lacking the known receptors. CADM1 and CADM2 interact in cis with the H protein on the same cell membrane, triggering hyperfusogenic F protein-mediated membrane fusion. Multiple isoforms of CADM1 and CADM2 containing various lengths of their stalk regions are generated by alternative splicing. Here, we show that only short-stalk isoforms of CADM1 and CADM2 predominantly expressed in the brain induce hyperfusogenic F protein-mediated membrane fusion. While the known receptors interact in trans with the H protein through its head domain, these isoforms can interact in cis even with the H protein lacking the head domain and trigger membrane fusion, presumably through its stalk domain. Thus, our results unveil a new mechanism of viral fusion triggering by host factors. [ABSTRACT FROM AUTHOR]

Background: Subacute sclerosing panencephalitis (SSPE) is a chronic, progressive disease caused by a persistent infection of the measles virus. Despite extensive efforts, the exact neurodegeneration mechanism in SSPE remains unknown. MicroRNAs (miRNAs) have emerged as an essential part of cellular antiviral defense mechanisms and can be modulated by antiviral cytokines Such as interferon-beta (IFN-β). Aims and Objectives: In this study, we aimed to elucidate the role of antiviral miRNAs in the pathogenesis of SSPE and analyze the interaction between host antiviral miRNAs and virus genes. Materials and Methods: Thirty-seven patients who were followed with SSPE and age-matched healthy children were included in the study. Peripheral blood mononuclear cell levels of miR-196b, miR-296, miR-431, and miR-448 were analyzed using quantitative polymerase chain reaction. Target predictions and pathway constructions of deregulated miRNAs were assessed. Results: Here, we showed that IFN-β-modulated miR-196b, miR-296, and miR-431 were significantly upregulated in patients with SSPE compared with healthy controls. Besides, sequence complementarity analysis showed that miR-296 and miR-196b predicted binding regions in measles virus genomic RNA. Conclusion: Our findings suggest that antiviral miRNAs are upregulated in patients with SSPE, which could be a part of the host antiviral defense mechanism.