Cases Of Subacute Sclerosing Panencephalitis Research Articles

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.

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.

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.

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.

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.

Identical tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy

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.

The EEG Features of Four Cases of Subacute Sclerosing Panencephalitis in North China: SSPE EEG Features.

Objective. To analyze the EEG features of four subacute sclerosing panencephalitis cases in North China. Methods. We retrospectively analyzed the EEG features in four patients with subacute sclerosing panencephalitis and 12 patients in control group from North China. Results. The periodic long-interval diffuse discharges were found in all of the four cases with subacute sclerosing panencephalitis. The morphology and component of periodic complexes were varied in different patients and different wakefulness states. Some EEG parameter settings help to identify periodic long-interval diffuse discharges including the slowed sweep speed, decreased sensitivity and reduced number of montages. In each patient with subacute sclerosing panencephalitis, the periodic long-interval diffuse discharges associated with two types of brief episodes (1:1) during awake period were found and none of the patients in the control group had this EEG pattern. The score system based on the periodic discharges and brief episodes also shows that all the patients with SSPE reached score 5 while none of the patients in the control group has a score greater than 3, which suggests that this EEG pattern may have diagnostic value. Conclusions. In subacute sclerosing panencephalitis, the morphology and component of periodic long-interval diffuse discharges were varied in different patients and different wakefulness states. Specific EEG parameter settings help to identify periodic long-interval diffuse discharges. Periodic long-interval diffuse discharges associated with two types of brief episodes (1:1) during awake period may strongly suggest the diagnosis of subacute sclerosing panencephalitis.

A Re-emergence of Subacute Sclerosing Panencephalitis in the United Kingdom.

New pediatric and adult subacute sclerosing panencephalitis cases between 1996 and 2020 were reported based on an established UK registry with no evidence of under-ascertainment using a separate pediatric surveillance system. After 15 years with no pediatric UK-acquired cases, 3 cases arose from 2017 after increased measles. Modeling suggested this was in line with measles notifications, underreporting of laboratory-confirmed measles or increased subacute sclerosing panencephalitis risk.

Subacute Sclerosing Panencephalitis: Restricted Diffusion and Clinical Evolution.

Subacute sclerosing panencephalitis (SSPE) is a rare entity characterized by a protracted course and progressive neurological deterioration. We present patterns of diffusion restriction in eight cases of SSPE, a seldom described imaging attribute. A retrospective analysis was performed on the clinical and neuroimaging data obtained from records of patients with proven SSPE. Patients whose magnetic resonance imaging (MRI) showed evidence of diffusion restriction were included in the analysis. MRI was performed on 3 T and 1.5-T clinical MR systems. Imaging characteristics were reviewed and tabulated by two neuroradiologists. Eight SSPE patients (seven men, one woman; age range: 5-15 years; mean age: 11 years) diagnosed and managed at our institute were included in the analysis. Restricted diffusion was evident in the basal ganglia (n = 3), corpus callosum (n = 2), white matter (n = 2) and in bilateral middle cerebellar peduncles (MCP) (n = 2). One patient had diffusion restriction in the genu of the corpus callosum and bilateral frontal cortical white matter. None of the diffusion-restricted lesions showed contrast enhancement or susceptibility. Six cases fulfilled the diagnostic criteria for fulminant SSPE (fSSPE). The extent of neuroparenchymal involvement was greater in this subset of patients. Restricted diffusion in SSPE, hitherto infrequently described, can indeed occur in both grey and white matter structures and in both supratentorial and infratentorial compartments. Parenchymal diffusion restriction in SSPE possibly reflects an early time point in the clinical evolution. A greater extent of parenchymal diffusion restriction may portend a rapid downhill course, possibly qualifying for fSSPE.

Subacute sclerosing panencephalitis (SSPE) without electroencephalographic evidence throughout the illness: An unusual finding, challenging the diagnosis

SSPE is a chronic progressive encephalitis due to persistent measles viral infection. Clinical features, neuroimaging, EEG, CSF and serum measles antibody levels assist in the diagnosis. We report a case of SSPE confirmed by CSF measles antibodies and MRI abnormalities but without myoclonus or characteristic EEG changes.

Resurgence of Subacute Sclerosing Panencephalitis: Case Series and Global Epidemiological Trends

AbstractResurgence of subacute sclerosing panencephalitis (SSPE)—case series and global epidemiological trends. We noted a recent increase in cases of SSPE admitted in our institute, even though they had received measles vaccination. We did a detailed study of our cases and compared with global epidemiological trends of SSPE in preimmunization and era of developed immunity. Out of total 23 cases of SSPE, 12 presented in the year 2017 alone, reflecting a steep rise in incidence. Sixteen patients had received measles vaccine and never had prior measles infection. Mean age of onset was 8.2 years and average time of progression to advanced stage of disease was 65 days. Global data showed similar trends, that is, earlier age of onset with a faster rate of progression in the postvaccination era as compared with prevaccine era. Possible mechanisms to account for this trend include an early wild measles infection in the critical age of 6 to 9 months, before vaccination. There is a changing epidemiological trend of SSPE in terms of lower age of onset and faster rate of progression, also reflected in global data. There is a need for multicenter studies to verify the findings and explore possible measures like lowering the age of measles vaccination to halt this alarming trend.

A rare presentation of fulminant subacute sclerosing panencephalitis with acute disseminated encephalomyelitis and meningoencephalitis

Subacute sclerosing panencephalitis (SSPE) is a rare form of chronic progressive neurodegenerative disorder, caused by persistent central nervous system (CNS) infection by hypermutated strains of Measles virus. It primarily affects children and early adolescent age group. Since there is widespread involvement of CNS, the primary symptoms may start with behavior and personality changes with intellectual involvement followed with myoclonic jerks, convulsion, and hemi or quadriparesis. In later stage, the patient may experience dementia, stupor, coma, or death. However, initial presentation can be variable and atypical, making the diagnosis very challenging in clinical practice. Herein, we report a case of fulminant SSPE in a 13-year-old adolescent male who presented with the features of acute disseminated encephalomyelitis (ADEM) and meningoencephalitis. The patient presented in altered sensorium with the history of poor communications, jerky movement of limbs, and fever for 10–14 days. Preliminary investigations were suggestive of meningoencephalitis and ADEM. After initial course of treatment, the patient did not improve, deteriorated further, and succumbed to his illness, a day before we received the conclusive reports for SSPE. As we experienced from our case report, SSPE can create a lot of diagnostic dilemma to the clinicians in such a fulminant presentation, mainly due to limitation of resources, time, and lack of proper vaccination records. The lack of definitive treatment for SSPE once again proved the proverb that “prevention will always be better than cure.”

Case of Subacute Sclerosing Pan-Encephalitis (SSPE) presenting as catatonic schizophrenia

A 15-year-old boy presented with insidious onset psychotic symptoms of 6 months duration characterised by excitement, smiling and muttering to self, catatonic posturing, negativism, periods of mutism, irritability, episodes of aggression and poor self care which were gradually progressive in nature. For the last 2 months preceding his presentation to the clinic he developed myoclonic jerks predominantly involving the trunks and upper limbs and apraxia. There was marked decline in scholastic performance over a relatively shorter period of time. On examination, there was generalised cognitive impairment, subcortical myoclonus occurring every 2-3 minutes, paratonia and echolalia. Non contrast Magnetic Resonance Imaging (MRI) Brain study was unremarkable. Electroencephalogram (EEG) showed slow background and periodic generalised slow waves. His cerebrospinal fluid (CSF) and serum antimeasles antibody as measured by EIA was positive in high titres (15586 U/ml and 8457 U/ml respectively) [Image 1]. A diagnosis of SSPE stage 2 was kept. This case highlights that SSPE can present with symptoms suggestive of catatonic schizophrenia even in initial stages.

Expanding the Spectrum of EEG Periodic Discharges in Subacute Sclerosing Panencephalitis: A Case Report

Abstract Background Atypical electroencephalogram (EEG) abnormalities emerge in patients with subacute sclerosing panencephalitis (SSPE), especially in cases with an atypical clinical presentation that can lead to diagnostic difficulties. Case Report In this article, we presented a case of SSPE with an atypical onset with epileptic seizures and Parkinson's features. The neurological examination during the initial evaluation of the patient showed extrapyramidal syndrome, hyperreflexia, intention tremor, and dysmetria. Cranial magnetic resonance imaging was normal. Video EEGs were performed in wakefulness and sleep. In wakefulness, multiple brief seizures (1–1.5 seconds were recorded, consisting of gradual bending of the body forward and to the right that lacked the sudden characteristic of myoclonia. During those episodes, we recorded generalized epileptiform activity of 4 or 5 sharp waves, with higher amplitude in the anterior regions, in some of the paroxysms superimposed on a slow wave or followed by a high amplitude slow wave. The paroxysms appeared periodically every 15 to 30 seconds. However, 2 months later, the EEG showed typical periodic generalized activity of biphasic/triphasic slow waves (Radermecker complexes), accompanied by myoclonias. Conclusion We reported a peculiar EEG pattern in a patient with SSPE that consists of periodic generalized activity of sharp waves. Atypical EEG patterns can appear when the disease progresses, but initially too, before typical periodic complexes and can complicate the diagnostic process.

Subacute Sclerosing Panencephalitis (SSPE) in Toddlers and Young Children: A Case Series

SSPE is a neurodegenerative disorder caused by persistent defective or mutant measles virus. The disease has a gradual progressive course leading to death within 1-3 yrs or even early. SSPE is a disease of childhood and early adolescence. The classic age at presentation is 8-11 years and usually occurs after a latent period of average 6 years. Here we report 3 cases of SSPE in toddlers. Diagnosis was made on the basis of clinical presentation, EEG pattern and elevated CSF anti measles antibody titer as described in Dykan criteria for diagnosis of SSPE. Clinical presentation was very early with a relatively shorter latency and fatal progression. Two patients had past history of measles and all patients were immunized against measles. One patient died within 4 months of disease expression and 2 patients went into vegetative state within 3 months of disease onset.
 Bangladesh J Child Health 2020; VOL 44 (2) :114-117

Subacute sclerosing pan encephalitis in a tertiary care centre in North India

Background: Subacute sclerosing pan encephalitis (SSPE) is caused by persistent, aberrant measles virus infection presenting as rapid neurocognitive decline, associated with myoclonus. Diagnosis is by distinctive clinical presentation, characteristic EEG changes and measles serology. Methods and materials: Retrospective study from a tertiary care hospital SGPGI, Lucknow – a total of non-replicate 89 paired CSF and blood samples from patients presenting to OPD with clinical features suggestive of SSPE (i.e. dementia, myoclonic jerks and/or ataxia in a previously healthy individual) were analyzed from 2015 to 2018. Total IgG and measles-specific IgG levels for CSF and value of relative CSF/serum quotient ≥ 1.5 was accepted indicative for intrathecal measles antibody synthesis. History of previous attack of measles, immunization status, EEG pattern were recorded. Results: Presenting symptoms included myoclonus, behavioural changes, seizures, and cognitive, visual, and extrapyramidal disturbance. A total of 52.08% (47/89) patients had a high cerebrospinal fluid: serum anti-measles antibody ratio showing male preponderance. Age at onset of SSPE ranged from 6 years to 34 years, showing an increase in mean age at onset of SSPE. A sizable percentage of the patients were ≥18 years old and considered to have adult onset SSPE. A definitive history of measles could be elicited in 20% cases. Previous complete immunization history was present in about 40% and partial could be elicited in 35%. Characteristic EEG findings were present in about 80%. All patients received symptomatic therapy; 20% also received disease modifying agents with poor compliance. Demographic details showed more frequent clustering in some neighboring districts of UP. Conclusion: WHO and Indian association of Pediatrics recommends two doses of vaccine. High SSPE cases could be attributed either to referral bias, decrease in the potency of the vaccine at the receiving end/inefficient cold chain system, improper vaccine coverage, poor quality of vaccine and possible circulation of atypical measles virus strain cannot be ruled out.

Utility of enzyme immunoassays for diagnosis of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disorder caused by the measles virus (MV) and is identified by positive MV-specific antibody titers, detected mainly by hemagglutination inhibition (HI) tests in the cerebrospinal fluid (CSF). However, an alternative method, the enzyme immunoassay (EIA), has increasingly become a preferred method for detecting MV antibodies. To establish the index for SSPE diagnosis using EIA, we investigated the correlation between HI and EIA titers of MV antibodies in SSPE patients. Data on MV antibody titers and measurement methods at the time of diagnosis in 89 Japanese SSPE cases diagnosed between 1979 and 2006 were obtained by a survey. We also assessed the serum and CSF MV antibody titers in three patients with SSPE and serum MV antibody titers in 38 healthy adults using immunoglobulin G (IgG)-EIA and HI. In all cases diagnosed as SSPE, IgG-EIA titers in the CSF were ≥0.49IU/mL. There was a positive correlation between serum antibody values in the controls measured by IgG-EIA and HI. In patients with SSPE, both serum and CSF antibody values, measured by IgG-EIA, and HI, were positively correlated, and a positive correlation was found between the serum and CSF MV antibody titers as measured by IgG-EIA. The serum/CSF MV antibody titer ratios determined by IgG-EIA were <20 in most SSPE patients. Immunoglobulin G-EIA may be a suitable alternative method for SSPE diagnosis; however, its potential utility and the cut-off point of ≥0.49IU/mL should be tested with additional patient cohorts.

High risk of subacute sclerosing panencephalitis following measles outbreaks in Georgia

ObjectiveTo describe cases and estimate subacute sclerosing panencephalitis (SSPE) risk following large-sale measles outbreaks in Georgia. A rare, fatal late complication of measles, SSPE is often overlooked in assessments focused on the acute illness. Georgia had 8377 and 11,495 reported measles cases during the 2004–2005 and 2013–2015 outbreaks, respectively, but SSPE burden has not been assessed. MethodsSSPE cases diagnosed during 2008–2017 were identified from hospitalization registries in major neurological departments likely to admit SSPE patients. Information on reported measles cases and deaths was obtained from the national measles surveillance system and published reports. The risk of SSPE (number of measles cases per one SSPE case) was calculated for cases associated with the 2004–2005 outbreak. Crude estimates were adjusted to account for potential under-reporting of measles, using 50%, 25% and 10% estimates of completeness of reporting. ResultsSixteen SSPE cases diagnosed during 2008–2017 were identified. Eleven (92%) of 12 SSPE cases with a known history of measles had infection at ≤2 years and one (8%) at 3 years of age. Crude estimate of SSPE risk for the 2004–2005 outbreak was 1:1396. Adjusted estimates were 1:2792, 1:1:5584 and 1:13 960, assuming 50%, 25% and 10% completeness of reporting measles cases, respectively. ConclusionsThe review demonstrated substantial risk of SSPE in Georgia, supporting recent data suggesting that risk of SSPE following measles infection is higher than previously thought. To prevent SSPE in Georgia, very high timely immunization coverage for measles should be achieved among children, and immunity gap among adults should be closed.