Journal of Pediatric Ophthalmology and Strabismus

Subacute Sclerosing Panencephalitis: Clinicopathological Study of the Eyes

E Meyer, MD; M Majlin, MD; S Zonis, MD

Abstract

Subacute sclerosing panencephalitis (SSPE) was described by Dawson first in 19331 and again in 19342 as a leukoencephalitis with inclusion bodies. I ? the past decade a mixovirus probably of the measles type was detected and the term of the subacute sclerosing panencephalitis was widely accepted.3'4 Although of viral etiology, this disease is included among the cerebral degenerative disorders because of its chronic course and absence of clinical hallmarks of an infection.

The incidence varies from one to four per million in different geographic areas; it seems, however, to be more frequent in Israel.5 Clinical manifestations appear between ages two and 21 years with peak incidence between eight and 1 4 years. Boys are affected more than girls in a ratio of 3:1 . The duration of the disease is ranging between 26 weeks to 1 0 years with an average of nine months.

It usually begins with subtle changes in personality or unexplained deterioration of school performance followed weeks or months later by myoclonic seizures and focal neurologic signs. This may include paresis, language difficulties, blindness, dyspraxias, memory impairment, and eventually progressive obtundation, stupor and coma. Characteristic EEG changes evolve during the second stage of the disease and show paroxysmal spiking at regular intervals with depressed activity between spikes.

Laboratory findings include marked elevation of gama globulin in cerebral spinal fluid (CSF) most notably of IgG fraction as well as elevated measles antibody titer in CSF and serum.

Pathologically, both gray and white matter of the brain showdiffusegliosiswith glial nodules and subacute perivascular infiltrates of inflammatory cells. There is nerve cell necrosis and varying degrees of demyelination. Occasionally, intracytoplasmic eosinophilic inclusion bodies are present within the neurons. Inclusion bodies in the retina of patients with SSPE have been confirmed by light and electron microscope studies. Of 20 children with SSPE, fifteen were found to have some ophthalmoscopic abnormalities.6 The most frequent ophthalmoscopical findings in this series were pigmentary macular changes or redorange color changes in the macular area and temporal pallor of the disc or edema. Very few changes have been described in the anterior segment of the eye as we had the opportunity to see in this case.

CASE REPORT

An 1 1 -year-old boy was admitted to the children's department of Rambam Medical Center on 10/8/75 with the suspicion of a psychotic condition, after having had personality changes, emotional lability, and declining school performance for one year. On admission, the general physical, neurologic, and eye examination were within normal limits except for his mental status which presented loss of awareness and inability to execute an order.

Family history, gestation, birth, and development were unremarkable. No clear history of measles in the past was obtained. Several days after admission a right exotropia was noticed. Fundus examination of the right eye revealed a fresh macular lesion redorange in color in the form of a half-moon. At the border of this lesion several grayish exudates in a rainbow form pointed towards the optic disc (Fig. 1 ).

SUMMARY

This paper described the clinicopathological findings in a patient who died of subacute sclerosing panencephalitis. During his sevenmonth hospitalization, we had the opportunity to study the evolution of the disease and especially the variability of the ocular findings. The patient was presenting with a right exotropia and later developed chorioretinal changes in the fundus. The pathological examinations of both eyes revealed undescribed details, mostly in the anterior segments of the eyes, namely lacy vacuolization of the pigment epithelium of the iris, vacuolization of the nonpigmentary ciliary epithelium, and proliferation of the ciliary pigment epithelium.

ACKNOWLEDGMENT

We are greatly indebted to Professor B.…

Subacute sclerosing panencephalitis (SSPE) was described by Dawson first in 19331 and again in 19342 as a leukoencephalitis with inclusion bodies. I ? the past decade a mixovirus probably of the measles type was detected and the term of the subacute sclerosing panencephalitis was widely accepted.3'4 Although of viral etiology, this disease is included among the cerebral degenerative disorders because of its chronic course and absence of clinical hallmarks of an infection.

The incidence varies from one to four per million in different geographic areas; it seems, however, to be more frequent in Israel.5 Clinical manifestations appear between ages two and 21 years with peak incidence between eight and 1 4 years. Boys are affected more than girls in a ratio of 3:1 . The duration of the disease is ranging between 26 weeks to 1 0 years with an average of nine months.

It usually begins with subtle changes in personality or unexplained deterioration of school performance followed weeks or months later by myoclonic seizures and focal neurologic signs. This may include paresis, language difficulties, blindness, dyspraxias, memory impairment, and eventually progressive obtundation, stupor and coma. Characteristic EEG changes evolve during the second stage of the disease and show paroxysmal spiking at regular intervals with depressed activity between spikes.

Laboratory findings include marked elevation of gama globulin in cerebral spinal fluid (CSF) most notably of IgG fraction as well as elevated measles antibody titer in CSF and serum.

Pathologically, both gray and white matter of the brain showdiffusegliosiswith glial nodules and subacute perivascular infiltrates of inflammatory cells. There is nerve cell necrosis and varying degrees of demyelination. Occasionally, intracytoplasmic eosinophilic inclusion bodies are present within the neurons. Inclusion bodies in the retina of patients with SSPE have been confirmed by light and electron microscope studies. Of 20 children with SSPE, fifteen were found to have some ophthalmoscopic abnormalities.6 The most frequent ophthalmoscopical findings in this series were pigmentary macular changes or redorange color changes in the macular area and temporal pallor of the disc or edema. Very few changes have been described in the anterior segment of the eye as we had the opportunity to see in this case.

CASE REPORT

An 1 1 -year-old boy was admitted to the children's department of Rambam Medical Center on 10/8/75 with the suspicion of a psychotic condition, after having had personality changes, emotional lability, and declining school performance for one year. On admission, the general physical, neurologic, and eye examination were within normal limits except for his mental status which presented loss of awareness and inability to execute an order.

Family history, gestation, birth, and development were unremarkable. No clear history of measles in the past was obtained. Several days after admission a right exotropia was noticed. Fundus examination of the right eye revealed a fresh macular lesion redorange in color in the form of a half-moon. At the border of this lesion several grayish exudates in a rainbow form pointed towards the optic disc (Fig. 1 ).

Fig. 1. Fundus examination of the right eye revealed a fresh macular lesion in the form of a half-moon red orange in color, with several grayish exudates at the border.

Fig. 1. Fundus examination of the right eye revealed a fresh macular lesion in the form of a half-moon red orange in color, with several grayish exudates at the border.

The optic disc itself was unremarkable. The left eye was normal. The lesion in the macular area of the right eye simulated a choroidal rupture or toxoplasmosis but there was no history of trauma and the Sabin-Feldman test was negative. Pertinent investigations at this time included a cerebrospinal fluid which was under normal pressure with a protein content 25 mg/1 00 ml and a negative Pandy. The IgG fraction in the CSF was markedly elevated (29.0%). The neutralizing measles virus antibody titer was 1:12. The serum titer was 1:512. An EEG revealed repetitive paroxysmal generalized bursts of sharp waves and intervals of slow wave activity (Fig. 2). Skull and chest roentgenograms were normal.

One month following admission, myoclonic seizures appeared with bilateral Babinsky reflexes, inappropriate stumbling, falling, language difficulties, and disorientation. The serum neutralizing measles virus antibody titer rose to 1 : 1 024 and in CSF to 1/256. A pendular nystagmus appeared at this stage. Fine granular pigmentation appeared at the edges of the macular lesion in the right eye.

Over the next months the patient became lethargic and sunk into a stage of semicoma responding only to painful stimuli. Six months' after admission fundus examination revealed pallor of both optic discs being more pronounced in the right eye. Over the two weeks prior to death he assumed a decebrate posture with preterminal hyperthermia. He died of cardiopulmonary arrest seven months following admission.

Fig. 2. EEG revealing repetitive paroxysmal generalized bursts of sharp waves and intervals of slow wave activity.

Fig. 2. EEG revealing repetitive paroxysmal generalized bursts of sharp waves and intervals of slow wave activity.

Fig. 3. Gross view of the right eye showing patchy iris atrophy near the pupillary border.

Fig. 3. Gross view of the right eye showing patchy iris atrophy near the pupillary border.

The clinical diagnosis prior to autopsy was SSPE. At autopsy the immediate cause of death was attributed to bilateral bronchopneumonia. Other abnormalities were confined to the central nervous system and eyes.

Gross examination of the brain revealed that the consistency of the temporo-occipital lobes and the left parietal lobe were softer than normal. The subcortical areas were firmer than usual. On the coronary sections of the brain there was meningial and periventricular congestion. The ventricular spaces were enlarged. Microscopically there was widespread fibrillary gliosis of the white matter of the cortex. Varying degrees of focal necrosis of the brain was found. In the areas of necrosis there were many Scavenger cells. In the meninges there were small lymphocitic infiltrates around blood vessels. Similar changes were found in the brain stem. On multiple sections no inclusion bodies were found.

Gross pathological examination of the eyes revealed that the right eye measured 26x24x26 mm with 1 1 mm of optic nerve attached to the globe. Near the pupillary border, patchy iris atrophy could be seen Fig. 3). Patches of depigmentation were present also in the corona ciliaris and pars plana. There was swelling and pallor of the nerve head. The macular area revealed folding of the retina and was yellowish in color (Fig. 4). The remainder of the eye was normal. Gross pathological findings of the anterior part of the left eye were identical to those of the right eye except for pigment on the anterior surface of the lens. The optic disc was whitish in color (Fig. 5). There was a chorioretinal scar near the ora serata on the nasal side (Fig. 6).

Microscopically the findings of the anterior part of both eyes were identical. They revealed lacy vacuolization of the pigment epithelium of the iris (Fig. 7). Vacuolization ofthenonpigmentary ciliary epitheilum and proliferation of the ciiiary pigment epithelium were more marked in the pars plana (Figs. 8,9). Inthe macular area of the right eye there were many swollen ganglion cells (Fig. 10). The retina showed atrophy of nerve fiber layer (Fig. 11). There were granular changes in the pigment epithelium mostly in the macular area (Fig. 12). The optic nerve was atrophic with proliferation of glial cells(Fig. 1 3). In the left eye the changes were similar to those of the right but for the changes in the macular area where no swollen ganglion cells were seen.

Fig. 4. Gross view of the right eye showing swelling and pallor of the nerve head.

Fig. 4. Gross view of the right eye showing swelling and pallor of the nerve head.

Fig. 5. Gross view of the left eye showing disc with indistinct borders.

Fig. 5. Gross view of the left eye showing disc with indistinct borders.

Fig. 6. Gross view of the left eye showing a chorio retinal scar near the ora serrata on the nasal side

Fig. 6. Gross view of the left eye showing a chorio retinal scar near the ora serrata on the nasal side

Fig. 7. Lacy vacuolization of the pigment epithelium of the iris. (Paraffin section, H and E stain original magnification ? 380)

Fig. 7. Lacy vacuolization of the pigment epithelium of the iris. (Paraffin section, H and E stain original magnification ? 380)

Fig. 8. Vacuolization of the nonpigmentari ciliary epithelium of the pars plana. (Paraffin section. H and E stain original magnification x380)

Fig. 8. Vacuolization of the nonpigmentari ciliary epithelium of the pars plana. (Paraffin section. H and E stain original magnification x380)

Fig. 9. Proliferation of the ciliary pigment epithelium of the pars plans. Paraffin section, ? and E stain original magnification x380)

Fig. 9. Proliferation of the ciliary pigment epithelium of the pars plans. Paraffin section, ? and E stain original magnification x380)

Fig. JO. Right eye: swollen ganglion cells in the macular area. (Paraffin section, ? and E stain original magnification x380}

Fig. JO. Right eye: swollen ganglion cells in the macular area. (Paraffin section, ? and E stain original magnification x380}

Fig. 1 1 . Atrophy of the nerve fiber layer of the retina. (Paraffin section, ? and E stain original magnification x240)

Fig. 1 1 . Atrophy of the nerve fiber layer of the retina. (Paraffin section, ? and E stain original magnification x240)

Fig. 12. Granular changes in the pigment epithelium of the retina in the macular area. (Paraffin section, H and E stain original magnification x240)

Fig. 12. Granular changes in the pigment epithelium of the retina in the macular area. (Paraffin section, H and E stain original magnification x240)

DISCUSSION

The ophthalmologics! manifestations in our patient were generally consistent with those described in the literature. However, there were several outstanding features which seem to us to be worthwhile describing. An exotropia as a presenting symptom is unusual. Describing the ophthalmoscopic findings in 20 patients with SSPE, Green6 points out that there were no satellite lesions in the macular area such as demonstrated in the right eye of our case. Yet, the outstanding findings were the pathological changes in the anterior segment of both eyes, mainly, the lacy vacuolization of the iris pigment epithelium, vascuolization of the nonpigmentary ciliary epithelium and proliferation of the ciliary pigment epithelium. Lacy vacuolization of iris pigment epithelium is found in other intraocular viral diseases like Rubella.7 Viruses have a predilection for pigment epithelium and grow very well in tissue culture producing a cytopathic effect.

Whereas, we could find only one report on lacy vacuolization of the iris pigment epithelium in SSPE,8 no reference to pathological changes in the ciliary body was found. The pathological changes in the iris pigment epithelium similar to those seen in Rubella may be further evidence for viral etiology of this disease. Such pathological findings may also have clinical implications in as much as one could possible find foci of depigmentation by transilluminating the iris of these patients on slit-lamp examination.

Fig. 13. Atrophy of the optic nerve with proliferation of glial cells. (Paraffin section, H and E stain original magnification x380)

Fig. 13. Atrophy of the optic nerve with proliferation of glial cells. (Paraffin section, H and E stain original magnification x380)

SUMMARY

This paper described the clinicopathological findings in a patient who died of subacute sclerosing panencephalitis. During his sevenmonth hospitalization, we had the opportunity to study the evolution of the disease and especially the variability of the ocular findings. The patient was presenting with a right exotropia and later developed chorioretinal changes in the fundus. The pathological examinations of both eyes revealed undescribed details, mostly in the anterior segments of the eyes, namely lacy vacuolization of the pigment epithelium of the iris, vacuolization of the nonpigmentary ciliary epithelium, and proliferation of the ciliary pigment epithelium.

ACKNOWLEDGMENT

We are greatly indebted to Professor B. Gellei and Dr. H. Kerner for describing the pathological findings of the brain.

REFERENCES

1. Dawson JR Jr: Cellular inclusions in cerebral lesions of lethargic encephalitis. Amer J Path 9.7-15, 1933.

2. Dawson JR Jr: Cellular inclusions in cerebral lesions of epidemic encephalitis. Second Report. Arch Neurol Psychiat 31:685-700, 1934.

3. Zeman W, Kolar 0: Reflections on the etiology and pathogenesis of subacute sclerosing panencephalitis. Neurology 18:1-7, 1968.

4. Herndon RM, Rubinstein U: Light and electron microscopy observations on the development of viral particles in the inclusions of Dawson's encephalitis (subacute sclerosing panencephalitis). Neurology 18:8-20, 1968.

5. Lerman P: Letter to the editor. SSPE in Israel. Lancet 1:1289, 1974.

6. Green SH, Wirtschafter JO: Ophthalmoscopic findings in subacute sclerosing panencephalitis. Brit J Ophthal 57:780-787, 1973.

7. Meyer E, Zonis S, Zeltzer M: Clinical and pathological manifestations in a case of congenital Rubella syndrome. J Ped Ophthal 12:184-188, 1975.

8. Boniuk V: Rubeola (Measles, Morbili). Int Ophthal Clin 15(4):243-255, 1975.

10.3928/0191-3913-19780101-07

Sign up to receive

Journal E-contents