Short-term outcomes of the use of intraventricular ribavirin in Filipino patients with subacute sclerosing panencephalitis

@#<p style="text-align: justify;"><strong>Background.</strong> 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.</p><p style="text-align: justify;"><strong>Objective.</strong> 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.</p><p style="text-align: justify;"><strong>Methods.</strong> 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.</p><p style="text-align: justify;"><strong>Results.</strong> 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.</p><p style="text-align: justify;"><strong>Conclusion.</strong> 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.</p>

A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years / 소아과

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.

Measles may be a Risk Factor for Malignant Brain Tumors

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.

Subacute sclerosing panencephalitis resembling Rasmussen's encephalitis on magnetic resonance imaging

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.

Fulminant Subacute Sclerosing Panencephalitis Presenting with Acute Ataxia and Hemiparesis in a 15-Year-Old Boy

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.

Measles Viral Infection in PD-1 Gene Knockout Mice / 소아감염

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.

Basal ganglia lesions in subacute sclerosing panencephalitis / Lesões nos gângliios da base em panencefalite esclerosante subaguda

The parieto-occipital region of the brain is the most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. We describe apatient with SSPE confirmed by neuropathology based on brain magnetic resonance imaging showing extensive basal ganglia involvement and no significant involvement of other cortical structures. Though rarely described in SSPE, clinicians should be aware of this involvement. SSPE should be kept in mind when changes in basal ganglia signal are seen on brain magnetic resonance imaging with or without involvement of other regions of the human brain to avoid erroneous etiological diagnosis of other pathologies causing rapidly progressive dementia.

A região parietooccipital é mais frequente e gravemente acometida na panencefalite esclerosante subaguda(PEESA). Os gânglios da base, cerebelo e corpo caloso são menos envolvidos. Descrevemos um paciente com PEESA confirmada por neuropatologia com imagens de ressonância magnética (RNM) evidenciando acometimento extenso dosgânglios da base sem envolvimento de outras estruturas corticais. Embora raramente descritas nesta doença, deve-se ficar atento para tal acometimento e PEESA deve ser lembrada quando alterações de sinal nos gânglios da base são vistas naRNM com ou sem acometimento de outras regiões do cérebro a fim de evitar outros diagnósticos etiológicos errôneos de patologias que cursam com demência rapidamente progressiva.

Acute bilateral vision loss as the presenting feature of subacute sclerosing panencephalitis.

A 12-yr-old boy with an atypical presentation of subacute sclerosing panencephalitis (SSPE) is described. Bilateral macular chorioretinitis preceded the neurological symptoms by 3 weeks. Both visual and neurological features had an acute onset. Clinicians need to be aware that macular chorioretinitis in a child may be the heralding feature of SSPE.

Usefulness of Bacteriological Tests and sspE PCR for Identification of Bacillus cereus Group

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.

Atypical subacute sclerosing panencephalitis: case report

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disorder of the central nervous system with both poor prognosis and high mortality. The disease has been related to a persistent and aberrant measles virus infection and no effective treatment has been available. We report a case of SSPE with atypical features including seizures at onset and a fulminant course in a 8 years-old boy who had been previously immunized against measles.

Panencefalite esclerosante subaguda (PES) é uma doença inflamatória e progressiva do sistema nervoso central com prognóstico reservado e alta mortalidade. A doença tem sido relacionada com a infecção persistente e anormal pelo vírus do sarampo e não há tratamento específico disponível. Relatamos um caso de PES com características atípicas representadas por início do quadro com crises convulsivas e apresentação fulminante em menino de 8 anos previamente imunizado contra o vírus do sarampo.

Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis.

Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis of childhood and young adolescence due to persistent measles virus infection of the central nervous system. In majority of cases onset occurs from 5-15 years of age. In a nonimmunized population the average onset is 8 years. Children with SSPE had experienced natural infection with the rubeola virus at an early age, half before age 2 years. SSPE generally occurs 5-10 years after measles infection. In the early stages of the disease behavioral and personality changes is followed by myoclonic jerks and convulsions. In late stages dementia, stupor and coma develops. Diagnosis is achieved by typical clinical findings, measles antibody titer increase in cerebrospinal fluid (CSF) and serum, high amplitude, slow, sharp waves in EEG. Prognosis is poor and death ensues in about 3 yr after the diagnosis. Here it is presented a 7-years-old boy with involuntary movements in both hands, drop attacks while walking, ataxia and stupor. Due to suggestive radiological and clinical findings and a history of recent mumps infection he was thought to have acute disseminated encephalomyelitis initially and given treatment. But due to clinical deterioration and detection of anti measles IgG in serum and CSF, SSPE diagnosis was confirmed. With this SSPE case presenting initially as ADEM, the authors tried to emphasize that presentation of SSPE may clinically and radiologically be diverse and a thorough differential diagnosis is mandatory for a definite diagnosis.

Panencefalitis esclerosante subaguda: experiencia en la consulta de neuropediatría del Hospital J.M. de Los Ríos / Subacute sclerosing panencephalitis: experience in the ambulatory clinic of the Hospital J.M. de Los Rios

La panencefalitis esclerosante subaguda (PEES), o enfermedad de Van Boager, es una encefalopatía lentamente progresiva, originada por la infección persistente por una forma mutante del virus del sarampión, que ocasiona una desmielinización inflamatoria multifocal del sistema nervioso central. Es conocido que infecciones antes de los 2 años de edad aumentan el riesgo de padecer PEES, no demostrándose hasta la actualidad casos secundarios a vacunación. Presentar una revisión de cinco casos clínicos, que consultaron el Hospital de Niños "J.M de Los Ríos", en el periodo comprendido entre los años 1990-2005, con diagnóstico de PEES; en quienes se analiza la forma de presentación, manifestaciones clínicas, hallazgos en los estudios serológicos, de imágenes y evolución. Todos los pacientes tuvieron antecedentes de infección por sarampión cuatro de ellos antes de los dos años de edad. La edad promedio de presentación fue de 7 años 3 meses, con una media para el período de latencia de 5,2 años. En relación a las manifestaciones clínicas iniciales, en todos hubo crisis epilépticas mioclónicas, en dos de ellos trastornos conductuales y en otros dos somnolencia. Los estudios electroencefalográficos mostraron un patrón periódico en todos los casos. Los t¡tulos de anticuerpos antisarampión positivos en suero y líquido cefalorraquídeo confirmaron el diagnóstico en cuatro casos. La evolución fue fatal en un caso y desfavorable en los otros, con compromiso en áreas motoras, sensoriales y cognitivas. El tratamiento hasta los momentos sigue siendo preventivo, erradicando el sarampión y manteniendo un plan de vacunación.

Subacute sclerosing panencephalitis (SSPE), or disease of Boager Goes, is a slowly progressive encephalopathy originated by the persistent infection of a mutant form of the measles virus, which causes an inflammatory multifocal demielinization of the central nervous system. It is known that infections before 2 years of age increase the risk of SSPE. Cases following vaccination have not been demonstrated. To present a review of five children with SSPE attended at the Children's Hospital ¨J.M de Los Ríos" between 1990 and 2005. The initial presentation, clinical manifestations, serologic and imaging findings as well as the clinical outcome were analysed. All patients had a precedent measles infection, four of them before two years of age. The average age of presentation was 7 years 3 months, with an average for the period of latency of 5.2 years. In relation to the clinical initial manifestations, myoclonic events were common to all patients, two of them presented with cognitive deterioration and two with drowsiness. The EEG studies demonstrated a periodic boss in all cases. Anti measles antibodies titers in serum and spinal liquid confirmed the diagnosis in four cases. The outcome was fatal in one case and unfavourable in the others, whom presented motor, sensory and cognitive deterioration. Treatment at the present time continues to lie in preventive measures, supporting the plan of vaccination and aiming to the eradication of measles.

Role of CSF serology in follow-up of subacute sclerosing panencephalitis patients on treatment.

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disease of the central nervous system with poor prognosis and high mortality. No effective treatment has a proven role; oral isoprinosine and intrathecal administration of alpha-interferon may prolong survival. We report an unusual case of adult onset SSPE patient on treatment with significant clinical improvement, even in the absence of conversion to seronegativity in either CSF or serum, on follow-up serological examination.

Changing trend of SSPE over a period of ten years.

Sub acute sclerosing pan-encephalitis (SSPE) is a slowly progressive inflammatory disorder of the central nervous system. A decline in frequency has been noticed in most of the developed countries, whereas it continues to be high in developing countries. Though a number of studies have been carried out, the exact trend of SSPE is still not clear. Hence the present study was carried out to analyze the trend of SSPE over the past ten years in and around Chandigarh. A total of 205 patients with clinical features suggestive of SSPE were enrolled for the study during Jan'92 to Dec. 2001. Measles specific antibodies were detected in blood and CSF by HAI method. 114 patients were found to be positive for measles specific HAI antibody with a male preponderance. The number of SSPE cases were found to be more during the period 1992-95 in comparison to the next 6 years (p < 0.05). The high incidence of SSPE in our country could be due to improper vaccine coverage, poor cold chain maintenance or circulation of atypical measles virus strain.

Diagnostic dilemmas in fulminant subacute sclerosing panencephalitis (SSPE).

This report describes an eleven-year-old boy with atypical features of subacute sclerosing panencephalitis (SSPE), a rare complication of measles. He had only visual symptoms for 2 months followed by rapid neurological worsening to a vegetative state in 10 days. A diagnosis of SSPE was made based on the history of measles, characteristic ocular findings, compatible magnetic resonance imaging and electroencephalographic changes, and elevated ratio of cerebrospinal fluid to serum anti-measles antibody titers.

Achados EEG no coma e status epilepticus: paraxismos periódicos / Electroencephalografic findings in coma and status epilepticus: periodic discharges

Este artigo de revisão aborda os aspectos EEG principais do coma, morte cerebral, status epilepticus (SE) e, também, de várias classificações atuais dos paroxismos periódicos (PP). São apresentados os padrões EEG do coma: alfa, lentificações difusas e paroxísticas, PP, susto-supressão, monorrítmicos (coma alfa/ teta, beta e de fusos), atividade epileptiforme e supressão generalizada. São mencionados os padrões EEG preditivos de gravidade no coma, principalmente os por encefalopatia isquêmica. São considerados os critérios para definição de inatividade eletrocerebral / silêncio elétrico cerebral. São também lembrados os padrões EEG do SE convulsivo generalizado e os critérios para o diagnóstico EEG do SE generalizado não convulsivo. Os PP não são doença-específicos, mas existem grupos que compartilham características comuns pelas descargas periódicas: difusas de intervalos longos ou curtos (síncronas ou assíncronas); unilaterais de intervalos longos ou curtos. As ondas dos paroxismos podem ser difásica, trifásica, polifásica ou polimorfa e apresentam valor diagnóstico de especial relevância na panðencefalite esclerosante subaguda e doença de CreutzfeldtðJacob que mais freqüentemente vêm acompanhadas de mioclonias. Os PP são relativamente menos comuns ou mesmo raros em outras situações que são mais prevalentes como encefalite necrotizante aguda, encefalopatias hepáticas, encefalopatias pósðanóxicas, comas tóxicos, abscessos cerebrais, acidentes vasculares isquêmicos e tumores cerebrais