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Case Number: DS-2003-07
http://w3.ouhsc.edu/pathology/aanp-oren/
Annual Diagnostic Slide Session
Established 1959
2003 Case 7

Contributor: Ana Sotrel, M.D., William Bellini, Ph.D., Atilano G. Lacson, M.D., Mario A. Reyes,
Nolan Altman, M.D., Jeannette Guarner, M.D., Glenn Morrison, M.D., and Michael Duchowny,
M.D., Miami Children’s Hospital and University of Miami, Miami, FL, Centers for Disease Control
and Prevention, Atlanta, GA, and All Children’s Hospital and University of South Florida, Tampa,
FL
Moderator: E. Tessa Hedley-Whyte, M.D. Manager and Editor: Leroy R Sharer, M.D.
Protocol:
Clinical History: The patient, RL, is an 11-year old girl, who was born and raised in
Tampa FL. She was in her usual state of health (with the possible exception of a recent
onset of subtle behavioral problems), when one night in March 2001, she developed
repetitive episodes of stiffness of all extremities lasting for about 10 seconds and
recurring 40 times during the first night. This evolved into generalized tonic-clonic
seizures that transiently responded to depakote; while on this antiepileptic medication,
one week later, she developed "head drops", 20-40 per day that necessitated an
increase in depakote dosage and addition of Dilantin. This combined drug treatment
worked for about one week, when head drops recurred at increasing frequency. Three
months later another medication (keppra) was added. The seizures eventually stopped,
but in mid July 2001, the patient became progressively more lethargic. She was
transferred from the local hospital to MCH for evaluation of "progressive
encephalopathy".
On admission, she was unresponsive, had a fever of 99.1 and supple neck; there was
horizontal nystagmus, 2+ deep tendon reflexes and bilaterally positive Babinski.
Bacterial and viral CSF cultures were negative; the CSF contained no cells, but there
was a minimal increase in protein and presence of oligoclonal bands.
Past medical history was unremarkable; the patient was vaccinated according to the
widely practiced schedule in USA.
Dual-echo FLAIR-MRI study demonstrated bilateral, diffusely hyperintense signal most
pronounced in the hemispheral white matter; there was no contrast enhancement. MR-
spectroscopy demonstrated reduction in N-acetylaspartate, normal choline and elevated
lactate & myoinositol.
A diagnostic right parietal brain biopsy was performed.
Histopathologically, there were minimal multifocal lymphocytic-plasmacellular
subarachnoidal infiltrates. Both cerebral cortex and subcortical white matter contained
This program is supported in part by the Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, and the Departments of Telemedicine, Radiologic Pathology, and Neuropathology & Ophthalmic Pathology at the Armed Forces Institute of Pathology (AFIP), Department of Defense, United States of America. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the Department of Defense, the University of Oklahoma Health Sciences Center or the American Association of Neuropathologists Inc. Case Number: DS-2003-07
http://w3.ouhsc.edu/pathology/aanp-oren/
perivascular lymphocytic infiltrates and rather pronounced ongoing neuronal, myelin and
axonal degeneration. Bacterial and viral brain tissue cultures were negative.
A treatment was initiated and the patient was discharged. She expired about one year
after the onset of her illness. Autopsy was not performed.
Material Submitted: H&E stained brain biopsy tissue sections.
Points for discussion: Diagnostic test?
This program is supported in part by the Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, and the Departments of Telemedicine, Radiologic Pathology, and Neuropathology & Ophthalmic Pathology at the Armed Forces Institute of Pathology (AFIP), Department of Defense, United States of America. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the Department of Defense, the University of Oklahoma Health Sciences Center or the American Association of Neuropathologists Inc. Case Number: DS-2003-07
http://w3.ouhsc.edu/pathology/aanp-oren/
Discussion:
Diagnosis: Subacute sclerosing panencephalitis (SSPE).
Comment from the presenter: SSPE is a rare, almost "forgotten," potentially
"resurging" CNS disorder of children and young adults. It is a slowly-evolving,
progressive, untreatable, viral/degenerative panencephalopathy with or without
retinopathy, caused by a persistent CNS-retinal infection with a defective, hypermutated,
SSPE-form of wild measles virus (WMV). SSPE usually starts ~9y after either a
clinically apparent or a subclinical form of systemic WMV infection. No vaccine strains of
measles virus have been documented as the cause, by genomic sequence analysis
(GSA) in SSPE patients, even though 50% of them have had a history of measles
vaccination. Their SSPE is most likely related to a presumed or known exposure to
WMV before vaccination took place, at <1y of age. From 1989-1991 there was
resurgence of measles in the USA, well documented in 55,622 children, most of whom
were either unvaccinated and less than 5 years of age, or pre-vaccinated at greater than
1 year of age. Most causative WMVs during this epidemic were shown to belong to a
single indigenous MV-genotype D3.
This patient was born in the USA in 1990 (during the period of the epidemic), and she was first vaccinated in 1991. The light and electron microscopic diagnosis of SSPE was confirmed by the CDC by the demonstration of CSF titers of MV-specific IgG (1:6,400), as well as by immunohistochemically demonstrable MV-antigen within the paraffin-embedded brain tissue, in glial and neuronal nuclei. MV RNA was detected in frozen brain tissue and was proven to be WMV-genotype D3 by GSA (as opposed to the MV-genotype A, which is contained in all currently used measles vaccines).
References:
1. Garg RK. Subacute sclerosing panencephalitis (review). Postgrad Med J 2002; 2. Griffin D, Bellini W: Measles virus. In: Field’s Virology, Field BN, et al., eds., Philadelphia-New York: Lippincott-Raven, 1996, pp. 1267-1312. 3. Mgone CS et al. Clinical presentation of subacute sclerosing panencephalitis in 4. Papua New Guinea. Tropical Medicine and International Health 2003; 8:219-227. 5. Orenstein WA, Strebel PM, Papania M, Sutter RW, Bellini WJ, and Cochi SL. Measles eradication: Is it in our future? Am J Pub Health 2000; 90:1521-1525. This program is supported in part by the Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, and the Departments of Telemedicine, Radiologic Pathology, and Neuropathology & Ophthalmic Pathology at the Armed Forces Institute of Pathology (AFIP), Department of Defense, United States of America. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the Department of Defense, the University of Oklahoma Health Sciences Center or the American Association of Neuropathologists Inc.

Source: http://neuropath.org/dss/DS-2003-07.pdf