Subacute Sclerosing Panencephalitis Research Articles

ATYPICAL MANIFESTATIONS OF SUBACUTE SCLEROSING PANENCEPHALITIS: CASE SERIES

Subacute Sclerosing Panencephalitis (SSPE) is a rare, progressive degenerative disease of the brain caused by reactivation of aberrant measles virus. Classical symptoms of SSPE are described as behavioral changes, declining scholastic performance, myoclonic jerks etc. However, at times it presents with varied atypical manifestations, which makes diagnosis difcult. Hereby we report two patients with unusual manifestations of SSPE. In rst case, 14-year-old boy presented with recurrent falls of 9 months duration. Initially, it was 1-2 times per week, progressing over 9 months to frequency of 40-50 falls per day. In second case, 21-year-old gentleman presented with behavioral changes and memory disturbance of 1-year duration. However, his family members noticed worsening of symptoms 1 month before presentation as he started developing involuntary jerky movements involving the right upper and lower limb. In both of them electroencephalogram (EEG) was showing long interval periodic discharges and cerebrospinal uid was showing elevated titers of anti-measles antibody overall suggesting SSPE. Hence it needs much attention for atypical presentations and also considering SSPE in differential diagnosis of unsolved atypical neurological presentations.

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.

Myoclonic-Atonic Epilepsy Masquerading as Subacute Sclerosing Panencephalitis: A Clinical Conundrum

Myoclonic-Atonic Epilepsy Masquerading as Subacute Sclerosing Panencephalitis: A Clinical Conundrum

Preliminary seroprevalence study of neurotropic virus antibodies in Nodding syndrome.

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.

Adult onset subacute sclerosing panencephalitis presenting with acute ischemic stroke

Subacute sclerosing panencephalitis (SSPE) is a progressive, invariably fatal inflammatory disease of the brain, owing to persistent measles virus infection. It generally presents in childhood or adolescence, and usual presentation is with progressive cognitive decline and myoclonic jerks. An adult male, with an uneventful past medical history, presented with a rapidly progressive dementia and generalised myoclonus. During the course of his admission, he developed right sided spastic hemiparesis with evidence of subcortical infarct on brain imaging with focal narrowing of left middle cerebral artery. Subsequently diagnosed as SSPE, he was managed conservatively, without improvement. Intrathecal interferon could not be given owing to lack of consent from the patient’s relatives. Histopathological confirmation could not be done for the same reason. A medium to small vessel intracranial vasculitis, secondary to measles virus infiltration was a proposed explanation of the vascular event. Persistence of measles virus in the brain may be a potential risk factor for intracranial vasculitis and strokes.

Teaching Video NeuroImage: Slow Axial Myoclonus in Subacute Sclerosing Panencephalitis.

Slow periodic myoclonus (up to 1 second in duration) is a distinctive phenomenology described in fulminant subacute sclerosing panencephalitis (SSPE).1 We describe slow axial myoclonus in 2 children having SSPE (Videos 1 and 2). The slow myoclonus causes sudden alteration in tone of axial musculature, causing head drop or backward and sideways tilting of the trunk (axial tilt sign). The involvement of sensorimotor integration mechanism and basal ganglia ictal activity have been proposed as possible mechanisms for the periodic dystonic myoclonus.2 Basal ganglia involvement may also be responsible for associated dystonia. Fulminant Wilson disease and nonrhythmic, repetitive axial myoclonic jerks of propriospinal origin are important differential diagnoses.3,4

A Comprehensive Investigation of the Current Subacute Sclerosing Panencephalitis (SSPE) Treatment Options to Improve Patient Quality of Life.

Subacute sclerosing panencephalitis (SSPE) is a progressive, disabling, and deadly neurological disorder related to measles (rubeola) infection occurring primarily in children. The slow but persistent viral infection occurs in children or young adults and affects their central nervous system (CNS). There have been plenty of reports on SSPE throughout the world, but it is considered a rare disease in developed countries. This research focuses on comparing the current treatments available to prolong the life of patients for over three years after the onset of SSPE. The goal was to identify possible patterns or trends among the treatments in order to find the best possible method to lengthen a patient's life. The results indicated that interferon alpha, inosine pranobex, and ribavirin display the most effective treatment plan and indicate the most potential in discovering a more effective therapeutic for SSPE.

Diagnostic reference value of antibody levels measured using enzyme immunoassay for subacute sclerosing panencephalitis.

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.

Subacute Sclerosing Panencephalitis in Indian Children Under 5 Years during the COVID Pandemic

Background: Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disorder of children and young adults. In the setting of the COVID-19 pandemic, we have observed increasing admissions of SSPE and a change in the clinical profile, mainly younger age of presentation, i.e., children under the age of 5 years. Clinical Description: We presented the clinical and investigational characteristics of 20 children who were diagnosed as SSPE during the period March 2020–March 2021 in our hospital, based on the Dyken criteria. The mean age was observed to be 3 years 9 months and male-to-female ratio of 1:1. Most children presented with developmental regression and myoclonic jerks. The clinical details and investigations were presented and a few atypical cases were discussed. Management: All the patients were treated symptomatically: anticonvulsant drugs, nutritional rehabilitation and supported feeding, occupational therapy, and palliative therapy. A trial of isoprinosine was started in all the patients, but was discontinued by most due to the expense. There were no mortalities. Conclusion: The change in profile of SSPE to an earlier onset in the setting of the pandemic should make the clinician keep a high index of suspicion of this disorder in children under the age of five years who present with unexplained developmental regression or acute encephalopathy, before the onset of typical myoclonus.

Appropriate /Measles Vaccination Is Key for Prevention of Subacute Sclerosing Panencephalitis

Given the current focus on COVID-19, serious vaccine-preventable infections may resurface if provider and parental education on pediatric immunizations is not prioritized. In this volume of The Journal, Cataldi et al present the results of a national survey that aimed to determine the current knowledge, experience and clinical practice of primary pediatricians regarding the diagnosis and prevention of measles. The major knowledge gaps identified included pretravel vaccination for a preschooler, presentation of subacute sclerosing panencephalitis (SSPE), and isolation practices. SSPE is a fatal long-term complication of measles infection that causes progressive degeneration of the central nervous system. Despite its low prevalence due to widespread measles vaccination, the risk for resurgence of this devastating complication is a threat in the setting of declining immunization rates and lack of proper pre-travel inoculation. The risk for SSPE can be as high as one in 609 cases of measles when primary infection occurs before the first year of life. Young infants and partially immunized children may have milder presentations of measles that go unnoticed, but that still leaves them vulnerable to developing SSPE and other complications. Therefore, pediatricians need to ensure that every child that travels internationally should have one dose of MMR vaccine if over 6 months age, and two if older than 12 months. Article page 213

A CASE REPORT OF PAEDIATRIC SUBACUTE SCLEROSING PANENCEPHALITIS

Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset.We report a 10 year old boy presented with convulsions and visual disturbances. The disease progressed with behavioural and cognitive disturbances and periodic high amplitude generalised complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis.

Cortical activation and motor body representations in a patient with subacute sclerosing panencephalitis

The current neuroimaging study investigated the sensorimotor maps during hand, feet and lips movements at one year after diagnosis of of subacute sclerosing panencephalitis (SSPE) in a 17 years-old patient. A lesion prediction algorithm showed that the posterior thalamic radiations, the splenium of the corpus callosum, the posterior and superior corona radiate, and the cingolum, showed a high lesion probability.Comparing the fMRI activations of the left and right hemisphere, we found that the representation of the left hand movement was more inferior/anterior and less represented than the representation of the right one; and the representation of the right foot movement was more superior, less represented than the representation of the left one and poorly activated at the predefined statistical threshold. The fMRI results are in line with the clinical report, describing an asymmetrical distribution of the periodic stereotyped myoclonic jerks, which mainly occurred for the left arm/hand and for the right leg/foot.This is the first fMRI study investigating the representation of the body parts in patients with SSPE. Results show that in SSPE the hyper-stimulation of the motor system (dedicated to the arm/hand and leg/foot more involved by the occurrence of the jerks) is accompanied by an under-activation of the corresponding motor representations in coincidence with voluntary movements.

Measles subacute sclerosing panencephalitis (SSPE): A still present and still mysterious fatal disease. History, Diagnosis and Assumptions

Subacute sclerosing panencephalitis, a late complication of measles, is still present during epidemics of this disease due to insufficient vaccination. After a historical review, the importance of the diagnostic criteria and the pathophysiology of SSEP are discussed. Numerous studies on the parameters of innate immunity and interferon responses tend to show a decrease in the activity of cellular immunity. Several hypotheses are formulated based on the publications of the different forms of the disease: Congenital, perinatal, forms with short incubation similar to acute inclusion encephalitis (AIE), rapidly evolving forms, forms of the immunocompromised, or even adults. Familial forms have been identified, suggesting a genetic cause. Based on the duration of the latency period, two groups have been individualized, prompting a retrospective and prospective analysis of the exomes of these patients. The knowledge of the genes involved should be useful for the understanding of the pathophysiology of SSPE and other late neurological RNA virus infections.

Upregulation of viral RNA polymerase activity promotes adaptation of SSPE virus to neuronal cells

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurodegenerative disease caused by measles virus variants (SSPE viruses) that results in eventual death. Amino acid substitution(s) in the viral fusion (F) protein are key for viral propagation in the brain in a cell-to-cell manner, a specific trait of SSPE viruses, leading to neuropathogenicity. In this study, we passaged an SSPE virus in cultured human neuronal cells and isolated an adapted virus that propagated more efficiently in neuronal cells and exhibited increased cell-to-cell fusion. Contrary to our expectation, the virus harbored mutations in the large protein, a viral RNA-dependent RNA polymerase, and in the phosphoprotein, its co-factor, rather than in the F protein. Our results imply that upregulated RNA polymerase activity, which increases F protein expression and cell-to-cell fusion, could be a viral factor that provides a growth advantage and contributes to the adaptation of SSPE viruses to neuronal cells.

Short-term Outcomes of the Use of Intraventricular Ribavirin in Filipino Patients with Subacute Sclerosing Panencephalitis

Background. Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus mutant. Though various treatment modalities have been tried, there is no effective treatment to completely cure SSPE and new therapeutic strategies are needed.&#x0D; Objective. This is a prospective uncontrolled observational open label trial to describe the short-term outcomes and safety of intraventricular ribavirin in combination with oral isoprinosine in Filipino SSPE patients.&#x0D; Methods. Sixteen (16) unrelated SSPE patients between ages 3-26 years and in various clinical stages were included in this study. Demographic data were described. Intraventricular instillation of ribavirin (1-3 mg/kg/dose) through an Ommaya reservoir was given for a duration of 3-6 months in 13 patients. The duration of follow-up was 48 weeks. The clinical outcome was assessed before, during, and after treatment using the Neurological Disability Index (NDI), Brief Assessment Examination (BAE), and clinical staging using the Jabbour Classification. Adverse side effects from intraventricular ribavirin were enumerated.&#x0D; Results. Six of 13 (46.15%) patients mostly in Stage III illness had clinical improvement showing decreasing NDI and BAE scores during treatment and the clinical improvement was maintained or improved further during the 48-week follow-up period. Clinical improvement manifested as improved mental alertness, decrease in spasticity and reduction of seizures. The clinical staging of those who improved remained stable during and after treatment was discontinued. Five (38.46%) patients in Stage II disease worsened and progressed to Stage III despite ribavirin therapy including 1 (7.6%) patient who died after the treatment phase due to pneumonia and brainstem failure. The clinical course of two (15.38%) patients remained unchanged. Minor adverse side effects of ribavirin included transient fever, rash, oral sores, seizure episodes, drowsiness, bladder retention and mild increase in transaminases. Ommaya reservoir infection was a serious adverse event in 5 (31.25%) patients.&#x0D; Conclusion. There is still no definitive cure for SSPE. Although ribavirin may help alleviate some of the symptoms of SSPE and prolong life, it may not reverse or halt the progression of the disease. Long term follow-up of these patients and continuous use of intraventricular ribavirin will better clarify its role in modifying the fatal course of SSPE. The role of ribavirin in Stage I patients and a controlled clinical trial in Stage II SSPE needs further studies.

Pediatric Research Challenge, Alignment with the National Research Agenda

Pediatric Research Challenge, Alignment with the National Research Agenda

Subacute Sclerosing Panencephalitis in Children: The Archetype of Non-Vaccination

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.

Spectrum of Movement Disorders Among Children With Subacute Sclerosing Panencephalitis: A Cross-Sectional Study.

Background: Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised by myoclonus, seizures, and neuropsychiatric issues. Movement disorders apart from myoclonus are reportedly uncommon. We aimed to describe frequency and proportion of movement disorders among children with subacute sclerosing panencephalitis, hypothesizing that these occur more frequently than previously reported. Methods: In this cross-sectional study, we enrolled children with subacute sclerosing panencephalitis between 1 month and 18 years of age who fulfilled the diagnosis of subacute sclerosing panencephalitis as per modified Dyken criteria, and examined them for movement disorders. We also assessed their clinical profile and disease severity via Jabbour staging and modified Rankin Scale score. We compared demographic, clinical, and laboratory features of children with and without movement disorders. Results: We enrolled 50 children (36 males; 72%) (age range 1.5-14 years). Of these, 28 (56%) had movement disorders. Among movement disorders, the most frequent was myoclonus (92%), followed by ataxia (9; 18%), chorea-athetosis (7; 14%), dystonia (6; 12%), tremor (4; 8%), repetitive behavior (4; 8%), and parkinsonism (3; 6%). Movement disorders were the presenting feature of subacute sclerosing panencephalitis among 7 children. There were no significant differences in clinical or laboratory features among children with and without movement disorders. Conclusions: Movement disorders were frequent in subacute sclerosing panencephalitis. Hyperkinetic disorders were dominant. Dystonia and chorea-athetosis occurred more commonly among nonmyoclonus movement disorders. Movement disorders may manifest even in earlier stages of subacute sclerosing panencephalitis and may be the heralding feature. Recognition of these features is important to plan management and reduce morbidity.

The immunogenetics of subacute sclerosing panencephalitis: A comprehensive review

Background: Subacute sclerosing panencephalitis (SSPE) is a rare devastating complication of measles virus (MV) involving the central nervous system (CNS). SSPE occurs 4–11/100,000 cases of the measles. Main Body: A poor cellular immune response seems to predispose individuals to the development of SSPE. The presence of mutations that may lead to MV persistence has also been demonstrated in samples obtained from SSPE patients. However, no study to date has definitively revealed the pathogenesis of SSPE caused by persistent infection in the CNS of MV. Conclusion: In this review, we provide a brief overview of SSPE from both an immunological and genetic perspective. We will try to focus on the mechanisms underlying the pathogenesis of SSPE that results in MV persistence. Clarifying the pathogenesis of SSPE will enable both the expansion of therapeutic options and the prediction of disease prognosis.