[1] 14w Neurofibrillary Changes in the Cerebral Cortex of a Patient with Subacute Sclerosing Panencephalitis (SSPE)

[1] 118w Biopsy fragments from the frontal cortex of one patient with SSPE were studied with ultrastructural methods. Special attention was given to the presence of neurofibrillary tangles observed in all cortical layers. These tangles were composed either of filaments with a diameter of 10-12nm or of paired helical filaments 22-24 nm at their widest and periodically reduced to 10 nm about every 80 nm. These tangles were observed in all cortical layers, while those formed by single filaments were only visualized in layer 3. The simultaneous appearance of both types of tangles in the same patient suggests that they may be chemically related, which is in keeping with recent chemical data concerning the nature of the neurofilament protein subunit.

[1] 47w Perivascular inflammatory signs and nuclear bodies of the five morphological types previously described by Bouteille et al. (1967) were observed in neurons and glial cells. A moderate glial reaction was present with glial filaments, 10 nm in diameter, forming tangles or rods in some processes (Fig. 1).

[2] 47w Neurofibrillary tangles although observed within neuron cell bodies were more frequently recognized in their dendrites. They were seen in all cortical layers, but their density was higher in the third, which is in keeping with the observations of Ishino and Otsuki (1976) made in progressive supranuclear palsy.

[3] 168w Neuronal tangles were composed either of filaments measuring 10-12 nm in diameter (Fig. 2) or of pairs of helical filaments measuring 22-24nm in diameter, alternating with constricted areas measuring 10 nm at about every 80 nm (Fig. 3). These neurofibrillary tangles were observed throughout all cortical layers, while those composed of single filaments were only observed in the third cortical layer, often in close proximity of tangles formed by paired helical filaments (Fig. 4). 0001-6322/79/0048/0157/$1.00 Fig. 1. Straight 10-nm astrocytic filaments forming a rodlike structure, observed in the third cortical layer, x 28,800. Inset. Greater magnification of the same filaments shown above (arrows). x 57,600 Fig. 2. A tangle of single, straight 10 to 12-nm filaments, observed in a dendrite from the third cortical layer, x 28,800. The arrow points to the area shown in the inset at a greater magnification, x 57,600 Fig. 3. Paired helical filaments, 20 nm apart, with constrictions (arrows) each 80 nm, observed in a dendrite from the fifth cortical layer, x 115,200

[1] 640w Neurofibrillary tangles are prominent features of senil and pre-senil dementia (Kidd, 1963;Terry, 1963). Nevertheless, their presence has also been described in experimental and other neuropathological situations. In the former, the aluminium encephalopathy (Terry and Pena, 1965) and the changes observed after the administration of mitotic spindle inhibitors to nervous tissue (Shelanski and Wisniewiski, 1969) must be stressed. In neuropathology their presence has been reported in postencephalitic parkinsonism (Hallervorden, 1933), in the complex "amyotrophic lateral sclerosis-parkinsonism dementia" (Hirano et al., 1961), mongolism (Hirano, 1970), tuberous sclerosis (Hirano, 1970) lead encephalopathy (Nikowitz and Mandybur, 1975), and in progressive supranuclear palsy (Tellez-Nagel and Wisniewiski, 1973), among other situations (Wisniewiski and Soifer, 1979). Light microscopy reports on neurofibrillary tangles in SSPE were made by Malamud et al. (1950) and Corselis (1951), and ultrastructural descriptions of neurofibrillary tangles have recently been made by Mandibur et al. (1977). It must be stressed, however, that most of these cases had a protracted clinical course, ranging from 5 -9 years, and presented no evidence of active in- f l a m m a t i o n , which do n o t fit in with this case in which there was a s u b a c u t e course a n d in which the inf l a m m a t o r y signs were striking. M o s t of the n e u r o f i b r i l l a r y tangles described are c o m p o s e d of pairs of twisted filaments each a b o u t 22 n m at their widest, a n d periodically reduced to 10 n m a b o u t every 8 0 n m (Wisniewiski et al., 1976). In the a b o v e -m e n t i o n e d e x p e r i m e n t a l conditions, however, a n d in progressive s u p r a n u c l e a r palsy, the tangles are c o m p o s e d of straight 1 0 -n m filaments w i t h o u t periodic c o n s t r i c t i o n s (Tellez-Nagel a n d Wisniewski, 1973). The s i m u l t a n e o u s presence of straight a n d paired helical f i l a m e n t o u s tangles in this patient, in a way, similar to the report m a d e by S h i b a y a m a a n d K i t o h ( 1978) in the cortex of a p a t i e n t with senil d e m e n t i a , m a k e s it t e m p t i n g to a d v a n c e the hypothesis that a close chemical r e l a t i o n s h i p m i g h t exist between b o t h types of filaments. This hypothesis is in keeping with the d a t a recently presented by Iqbal et al. (1978) w h o suggest that the paired helical f i l a m e n t p r o t e i n s u b u n i t is closely related chemically to the n o r m a l n e u r o f i l a m e n t p r o t e i n s u b u n i t . Obviously, m a n y studies r e m a i n to be done to prove or disprove this.

[1] 76w Tissue fragments of cerebral cortex and underlying white matter were removed under general anaesthesia from the non-dominant second frontal gyrus of a 15-year-old boy whose clinical history, neurological and psychiatric examination and electroencephalographic recording were compatible with SSPE. Moreover, measles antibody titer was 1/64 in CSF and 1/256 in serum. Electrophoresis of lumbar CSF proteins revealed an oligoclonal gamma globulinic pattern. The previous diagnosis was confirmed by the histological examination of part of the biopsy fragments.

[2] 64w For electron microscopy, fragments were cut into thin slices perpendicular to the pial surface and fixed in 4 % unbuffered OsO 4. Details of this method have been described in a previous publication (Paula-Barbosa and Gray, 1974). Slices were dehydrated in ascending alchools and embedded in Epon. Semi-thick sections were stained with paraphenylenediamine and ultra-thin sections were doublestained with uranyl acetate and lead citrate.

[1] 50w The earliest clinical symptoms of SSPE are personality changes, irritability, abnormal behaviour, failing memory, and lethargy. Although the dendritic alterations recently observed in the neuropil of these patients (Paula-Barbosa et al., 1979) can be related to these symptoms (Marin-Padilla, 1972;Purpura, 1974;Huttenlocher, 1974;Scheibel and Tomiyasu, 1978), their true pathogenesis remains unknown.

[2] 82w On the other hand, although the function of neurofilaments is not clearly understood (Iqbal et al., 1977(Iqbal et al., , 1978) ) they must play a part in the complex mechanisms of axonal transport (Iqbal et al., 1977), and therefore their quantitative and qualitative changes might be related to the neuronal dysfunction which is known to occur in some organic dementias. The purpose of this study is to report on neurofibrillary changes found in the cortical neuropil of one patient with SSPE.

[3] 10w Offprint requests to: M. M. Paula-Barbosa, M.D. (address see above)