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.

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.

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.

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.

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.

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.
Central Nervous System ; Consensus ; Follow-Up Studies ; Humans ; Immunity, Cellular ; Interferon-alpha ; Measles ; Measles virus ; Subacute Sclerosing Panencephalitis ; Survivors

BACKGROUND: A possible risk factor for brain tumor might be measles, since late neurologic sequelae are part of measles pathology. Subacute sclerosing panencephalitis, a devastating neurologic illness, is prone to develop years after measles infection. METHODS: Because measles damage to the brain might increase the risk of brain tumor, we examined the relationship of measles incidence in 1960 and brain tumor incidence in 50 US States and the District of Columbia, 2004-2007. Data on number of cases of measles by state in 1960 are from the Morbidity and Mortality Weekly Report. In 1960 measles was a childhood illness. We calculated measles incidence by obtaining the population of each state from the 1960 US Census and then age adjusting our results to the cumulative percent of the state population under age 21, since this would have been the measles-infected group. Data on the percentage white population by state are from the US Census (www.census.gov). Age-adjusted incidence (to the 2000 US standard population) of brain tumors is from the Central Brain Tumor Registry of the United States 2011 report. RESULTS: There was a significant correlation between 1960 measles incidence and incidence of malignant brain tumors in persons 20 and older in 2004-2007 (r=0.321, p=0.026). Because glioblastoma is more frequent in whites and males, multivariate linear regression was performed with tumor incidence as the dependent variable, measles incidence, percent white population, and sex ratio by state as independent variables. Measles incidence was significantly correlated with malignant brain tumor incidence (beta=0.361, p<0.001) and independent of the effect of race (beta=0.734, p<0.001) and sex ratio m/f (beta=-0.478, p<0.001). There was no correlation of measles incidence with brain tumor incidence in persons younger than 20. CONCLUSION: Inflammation is a critical component of tumor development. The inflammation of measles-induced subacute sclerosing panencephalitis, even subclinical cases, could well promote tumor formation, since many tumors arise from sites of infection, chronic irritation and inflammation.
Brain Neoplasms* ; Brain* ; Censuses ; Continental Population Groups ; Glioblastoma ; Glioma ; Humans ; Incidence ; Inflammation ; Linear Models ; Male ; Measles* ; Meningioma ; Mortality ; Pathology ; Risk Factors* ; Sex Ratio ; Subacute Sclerosing Panencephalitis ; United States

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressing but invariably fatal disease that is related to a prior measles virus infection and most commonly affects paediatric patients. Magnetic resonance (MR) imaging is the modality of choice for determining such changes in white matter. SSPE typically demonstrates bilateral but asymmetric periventricular and subcortical white matter involvement. We herein report a rare case of unilateral white matter involvement in a 13-year-old boy with SSPE that closely simulated Rasmussen's encephalitis. To the best of our knowledge, this is the first report of an atypical presentation on MR imaging in which SSPE was a rare cause of unilateral brain parenchymal involvement in a patient with intractable seizures.
Adolescent ; Brain ; pathology ; Diagnosis, Differential ; Encephalitis ; diagnosis ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Subacute Sclerosing Panencephalitis ; diagnosis ; pathology

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a delayed and fatal manifestation of measles infection. Fulminant SSPE is a rare presentation in which the disease progresses to death over a period of 6 months. The clinical features are atypical and can be misleading. CASE REPORT: We report herein a teenage boy who presented with acute-onset gait ataxia followed by right hemiparesis that evolved over 1 month, with left-hemispheric, delta-range slowing on the electroencephalogram (EEG). Magnetic resonance imaging disclosed multiple white-matter hyperintensities, suggesting a diagnosis of acute disseminated encephalomyelitis. He received intravenous steroids, and within 4 days of hospital admission he developed unilateral slow myoclonic jerks. Repeat EEG revealed Rademecker complexes, pathognomonic of SSPE, and an elevated titer of IgG antimeasles antibodies was detected in his cerebrospinal fluid. The disease progressed rapidly and the patient succumbed within 15 days of hospitalization. The diagnosis of SSPE was confirmed by autopsy. CONCLUSIONS: This case illustrates the difficulty of recognizing fulminant SSPE when it manifests with asymmetric clinical and EEG abnormalities.
Adolescent* ; Antibodies ; Ataxia* ; Autopsy ; Cerebrospinal Fluid ; Diagnosis ; Electroencephalography ; Encephalomyelitis, Acute Disseminated ; Gait Ataxia ; Hospitalization ; Humans ; Immunoglobulin G ; Magnetic Resonance Imaging ; Male ; Measles ; Myoclonus ; Paresis* ; Steroids ; Subacute Sclerosing Panencephalitis*

PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a neurodegerative disease due to persistent measles virus infection. We investigated the role of programmed death-1 (PD-1) molecule which is related with chronic viral infection in developing SSPE in mouse. METHODS: We adopt the PD-1-/-, PD-1-/+, and wild type BALB/c 3 week old mice to make an animal model of SSPE by injecting measles virus (SSPE strain) intraventricularly. Three months after infusion of virus, the mice were sacrificed and examined if the typical pathologic lesions had been progressed. The sera were collected from each group of mice and the serum level of IL-21 was measured with ELISA kit. RESULTS: The necrotic lesions on white matter and gliosis were found in focal areas in wild type BALB/c. The extent of lesion was smaller in heterotype BALB/c. Scanty lesions were found in PD-1-/- mice. The sera level of IL-21 was not elevated in all three groups. CONCLUSION: Our data suggest that the PD-1 molecule may play a role in persistent viral infection.
Animals ; Enzyme-Linked Immunosorbent Assay ; Gene Knockout Techniques* ; Gliosis ; Measles virus ; Measles* ; Mice* ; Models, Animal ; Subacute Sclerosing Panencephalitis ; Viruses

Humans ; Subacute Sclerosing Panencephalitis

INTRODUCTION: Subacute sclerosing panencephalitis (SSPE) affects primarily children and adolescents with age of onset from 5 to 15 years. Only 12.7% of cases present with symptoms after the age of 18 years. We present a case of Subacute Sclerosing Panencephalitis Jabbour Stage 11 in a 26-year old male with progressive decline in mental function and myoclonic jerks.

CLINICAL PRESENTATION: This is a case of a 26 year-old male with a one year history of decreasing cognitive function and a seven week history of progressive myoclonic jerks resulting in difficulty ambulating, frequent falls and loss of balance with decreasing verbal output. There was a history of measles infection and meningitis at 8 months.

DIAGNOSTIC WORK-UP: The EEG was abnormal showing generalized complexes of sharps, sharp-slow wave and slow delta waves that appeared with pseudo-periodicity and time-locked with the appearance of myoclonic jerks that involved mainly the trunk. There was generalized slowing of the background activity. The findings support the clinical impression of Subacute Sclerosing Panencephalitis. CSF and Serum Measles lgG antibodies showed positive results with values of 5.55 and 11.06, respectively (cutoff at 0.70 for both serum and CSF lgGAb).

TREATMENT AND FOLLOW-UP: The patient was given Valproic Acid titrated to 25 mg/kg/day, and lsoprinosine at 100 mg/kg/day. The patient's family was appraised of the patient's condition and prognosis. Regular OPD follow-up was encouraged.

The Bacillus cereus group includes B. anthracis, B. cereus, B. thuringiensis, B. mycoides, B. weihenstephanensis, B. pseudomycoides. The members of B. cereus group shares strong degree of DNA sequence similarity. Even though the biochemical test and bacteriological test have been used to identify the B. cereus group, an accurate identification system of the B. cereus group is required. We have developed a highly specific PCR-based assay for the B. cereus group chromosome using a sequence motif found within a spore structural gene (sspE). Using the assay, we were able to discriminate B. anthracis from the other members of B. cereus group. We also tried to find a new system for the B. cereus group identification. Five bacteriological tests (hemolysis, motility, penicillin susceptibility, rhizoid growth, toxic crystal formation), API system (API 50CHB & API 20E), MLST and sspE PCR were performed on 28 strains of the B. cereus group. The dendrogram generated from API system and bacteriological tests revealed that B. cereus and B. thuringiensis are grouped into the same cluster. In combination of sspE PCR and bacteriological tests, the dendrogram showed that 4 strains of B. cereus clustered within the same group. B. thuringiensis formed the subgroup in the same cluster. All strains of B. mycoides were encompassed together. Another cluster only included B. anthracis. The best system was determined to be sspE PCR and bacteriological tests. It is concluded that sspE PCR and bacteriological tests could be used for rapid discrimination and identification of B. anthracis and provided an effective means of differentiation between the B. cereus group.
Bacillus ; Bacillus cereus ; Base Sequence ; Discrimination (Psychology) ; Penicillins ; Polymerase Chain Reaction ; Social Identification ; Spores ; Subacute Sclerosing Panencephalitis

INTRODUCTION: Subacute sclerosing panencephalitis (SSPE) affects primarily children and adolescents with age of onset from 5 to 15 years. Only 12.7% of cases present with symptoms after the age of 18 years. We present a case of Subacute Sclerosing Panencephalitis Jabbour Stage 11 in a 26-year old male with progressive decline in mental function and myoclonic jerks.

CLINICAL PRESENTATION: This is a case of a 26 year-old male with a one year history of decreasing cognitive function and a seven week history of progressive myoclonic jerks resulting in difficulty ambulating, frequent falls and loss of balance with decreasing verbal output. There was a history of measles infection and meningitis at 8 months.

DIAGNOSTIC WORK-UP: The EEG was abnormal showing generalized complexes of sharps, sharp-slow wave and slow delta waves that appeared with pseudo-periodicity and time-locked with the appearance of myoclonic jerks that involved mainly the trunk. There was generalized slowing of the background activity. The findings support the clinical impression of Subacute Sclerosing Panencephalitis. CSF and Serum Measles lgG antibodies showed positive results with values of 5.55 and 11.06, respectively (cutoff at 0.70 for both serum and CSF lgGAb).

TREATMENT AND FOLLOW-UP: The patient was given Valproic Acid titrated to 25 mg/kg/day, and lsoprinosine at 100 mg/kg/day. The patient's family was appraised of the patient's condition and prognosis. Regular OPD follow-up was encouraged.