Subacute sclerosing panencephalitis in an infant: Diagnostic role of viral genome analysis

Abstract

Subacute sclerosing panencephalitis (SSPE) is related to "defective" measles virus or vaccination, though an association with parainfluenza viruses has been reported. SSPE is characterized by a slow, erratic course and elevated cerebrospinal fluid measles titers. An immunocompetent, vaccinated infant, with onset of symptoms in parainfiuenza virus season and a catastrophic course is described. Cerebrospinal fluid titers were negative, but postmortem brain had typical SSPE lesions. Patient brain-derived RNA, subjected to reverse transcription followed by polymerase chain reaction yielded polymerase chain reaction products with measles virus but not parainfluenza virus genes. The sequenced fragment revealed multiple mutations, typical for SSPE. SSPE can thus present in infants, with short latency and no cerebrospinal fluid antibodies. Viral genomic analysis may be diagnostic, permitting early therapy.The incidence of subacute sclerosing panencephalitis (SSPE), a fatal neurodegenerative disease most commonly associated with prior measles infection [1,2], has significantly decreased in the United States [3]. Since the introduction of measles vaccines, age of onset and vaccine-associated cases have increased [3]. Cases associated with parainfluenza virus (PIV), relatively common in eastern Europe and the Middle East [4][5][6], have recently been reported in this country [7]. New therapies, e.g., interferon, hold hope for affected individuals, making timely diagnosis important [8,9]. We report an infant who presented in PIV season with no cerebrospinal fluid (CSF) measles antibodies and document the diagnostic utility of molecular analysis of the virus.Copyright © 1994 by the American Neurological Association. All rights reserved. RNA Preparation. Reverse Transcription-Polymerase Chain Reaction and SequencingFrozen brain tissue specimens were ground in liquid nitrogen, and total cellular RNA was extracted. RNA samples from measles virus (MV), or PIV type 1-, 2-, or 3-infected Vero cells, were used as positive controls. Reverse transcription-polymerase chain reaction (RT-PCR) was performed as described [10], using published primers specific for measles matrix and fusion protein [11] genes. Three pairs of measles nucleocapsid protein genespecific nested primers, as follows, were developed: MN7/MN8 (5 -CAATCTGGCCTTACCTTCGCAT-3 / 5 -CTCCTTACCATCTCTTGCCCTA-3 ); MV1/ MV2(5 -GCTAAGAAGGTGGATAAA-3 / 5 -TATGCTGGATCAAAGTAAG-3 ), and MV3/MV4 (5 -TTGGAGAGAAAATGGTTGGA-3 / 5 -CAGAGCAGAGGGTATGAT-3 ). Also developed was a primer pair, as follows, recognizing conserved PIV-1, 2, and 3 nucleocapsid gene: PIN1/PIN2 (5 -AATGCTGATGTCAAGTATGT-3 / 5 -ATCCTGTCTGAATGCTTCTAA-3 )-A 410-bp fragment of the matrix gene PCR product derived from two brain specimens was sequenced along with a wild-type isolate. Other ProceduresMagnetic resonance (MR) images (5 mm) were obtained on a 0.5-T magnet. CSF MV IgG and IgM antibody titers were performed by MRL (Cypress, CA); aliquots were cultured for viruses, including PIV. Brain specimens were stain...

Subacute Sclerosing Panencephalitis: More Cases of This Fatal Disease Are Prevented by Measles Immunization than Was Previously Recognized

“…The patients had a history of measles or rash during that period and lived in California, Pennsylvania, or New York-states that were known to have large numbers of measles cases. In addition, 1 of the case reports (that of Baram et al [34]) included measles virus sequence data, but the virus genotype had not been identified. We analyzed the published sequence and identified the genotype as D3 (data not shown).…”

Adult‐onset subacute sclerosing panencephalitis: Case reports and review of the literature

“…SSPE is relatively rare in the Western world, while the incidence is still high in areas of the world where natural measles infection is common, such as the Middle East and India (8). The incidence in the United States has decreased dramatically since 1960 with the advent of measles vaccine (introduced in 1963) (2), from 0.61 case per million persons under the age of 20 years to 0.06 case in 1980 (3) with only 4-5 new cases being registered each year for the entire country (2,9,10).…”

Severe Infantile Measles Encephalitis Occurred Three Months after Neonatal Measles

“…The latent period between the ini- tial contact with the virus and the onset of the neurological signs is recognized several years later, usually more than six years later. Only a few cases with neonatal measles and development of rapid progressive SSPE in infancy, were reported previously [1,2]. Compared to these cases with atypical SSPE, this case showed many similarities including an extremely short latency period, fulminant subacute neurological symptoms, prolonged elevation of serum IgG antibodies against measles virus, and a striking destructive brain lesion.…”