Summary
The pathologic findings are described in a mentally-retarded 28-year old man with progressive spasticity and ataxia since childhood. They consisted in the widespread presence, throughout the brain and visceral organs, of eosinophilic intranuclear inclusions, with the association of larger, more intensely staining globular bodies. The corpora striata, internal capsule, pallida and thalami were the most severely affected. The globular bodies seemed to be derived from the enlargement of the intranuclear inclusions: both gave the tinctorial and histochemical reactions for protein. There was no evidence of inflammation.
Electron microscopy showed that the intranuclear inclusions and the globular bodies were composed of homogeneous finely granular material. In one such mass, in the internal capsule, virus-like particles, both randomly distributed and arranged in crystalline arrays, were seen. The particles resembled those of the herpesvirus group.
The possibility is discussed that these alterations may present the residuum of an old generalized herpesvirus infection which could have been incurred in early life, at birth, or in utero. The hypothesis of a primary immunologic deficiency, or of a viral infection having occurred before the acquisition of immunologic competence, is advanced in order to account for the unique morphologic features. The alternative suggestion of a primary metabolic disorder affecting nuclear protein is briefly considered.
Zusammenfassung
Es werden die pathologischen Befunde bei einem 28 jährigen, schwachsinnigen Patienten beschrieben, der seit früher Kindheit progressive Spastizität und Ataxie zeigte. In Gehirn und allen anderen Organen wurden weitverbreitet eosinophile, intranucleäre Einschlußkörperchen, zugleich mit größeren, intensiver gefärbten, globulären Ablagerungen, gefunden. Corpus striatum, innere Kapsel, Pallidum und Thalamus waren besonders schwer betroffen. Die globulären Ablagerungen hatten sich wahrscheinlich aus vergrößerten, intranucleären Einschlußkörperchen entwickelt. Färberisch und histochemisch gaben beide Strukturen eine positive Reaktion für Protein. Entzündliche Reaktionen waren nicht vorhanden.
Die Elektronmikroskopie zeigte, daß die intranucleären Einschlußkörperchen und die globulären Ablagerungen aus homogenem, feinkörnigem Material bestanden. Im Innern einer solchen Ablagerung in der inneren Kapsel wurden virusähnliche Partikel gesehen, die entweder unregelmäßig verteilt oder kristallartig angeordnet waren. Die Partikel sahen denen der Herpesvirusgruppe ähnlich.
Es wird die Möglichkeit diskutiert, ob diese Veränderungen den Endzustand einer alten, generalisierten Herpesvirusinfektion darstellen, die entweder in früher Kindheit, zur Zeit der Geburt oder im Uterus stattgefunden hatte. Um den einzigartigen morphologischen Befund zu erklären, wird die Hypothese aufgestellt, daß entweder eine primäre immunologische Unzulänglichkeit vorlag oder daß eine Virusinfektion stattfand, bevor eine immunologische Kompetenz erworben war. Es wird kurz auf die zweite Möglichkeit hingewiesen, daß der Prozeß eine primäre, das Kernprotein beeinflussende Stoffwechselkrankheit darstellen könnte.
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Supported in part by U.S.P.H.S. Training Grant No. 1T1 NB 5500-01 of the National Institute of Neurological Diseases and Blindness, Bethesda, Md.
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Lindenberg, R., Rubinstein, L.J., Herman, M.M. et al. A light and electron microscopy study of an unusual widespread nuclear inclusion body disease. Acta Neuropathol 10, 54–73 (1968). https://doi.org/10.1007/BF00690510
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DOI: https://doi.org/10.1007/BF00690510