Computed tomography of the brain in subacute sclerosing panencephalitis

Twenty-four computed tomographic scans of 12 patients with confirmed subacute sclerosing panencephalitis were studied using standardized techniques of radiological assessment. Abnormalities encountered were of four types--(1) lateral ventricular dilatation, (2) cerebral cortical atrophy and sylvian fissure widening, (3) low parenchymal attenuation, and (4) brainstem atrophy and cerebellar atrophy--and of varying degrees. The abnormalities correlated best with the stage and duration of disease, but not necessarily well with the patient's mental state. The fewest radiological abnormalities were encountered in the acute or early stages, whereas more signs of parenchymal disturbances in the form of low attenuations emerged during intermediate periods. Chronic periods were accompanied by atrophic changes in the form of cortical atrophy, ventricular dilatation, and brainstem cerebellar atrophy.     

Atypical subacute sclerosing panencephalitis

Summary An unusual case of panencephalitis in a 4-year-old Japanese boy, with onset at three months after measles infection and rapid progression to a comatose state in approximately one month, is described. A rapid rise in serum measles antibody titre after the onset of the symptoms, and the appearance of various abnormal antibodies in the serum, were noted. Pathologically, the brain showed sclerosing polio- and leucoencephalitis with diffuse gliosis and sporadic intranuclear inclusions. The process is suggested to be intermediate or transitional between acute measles encephalitis and SSPE.     

Mononucleosis-associated subacute sclerosing panencephalitis

Summary A thirteen-year-old girl died of subacute sclerosing panencephalitis (SSPE) which occurred as part of a complex encephalitic illness related to acute infectious mononucleosis. The cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) fluorescent antibody (FA) titer was 1:64. Electron microscopic examination revealed 17 nanometer (nm) diameter paramyxovirus-like nucleocapsids in brain sections and 90nm diameter herpes virus-like enveloped particles in negatively stained brain tissue extracts. Indirect FA staining of cerebral cortex sections demonstrated both measles and EBV antigenic material. EBV antigenic material has not previously been demonstrated in brain tissue. The proportion of B lymphocytes among the patient's peripheral blood lymphocytes was significantly increased as compared to normal controls, while the T lymphocyte percentage was normal. It is suggested that defects in cellular immunity associated with infectious mononucleosis may have been responsible for activation of latent measles-like virus. This is the tenth reported case in which two viruses have been associated with SSPE. This is the third instance in the authors' experience in whichacute EBV infection has occurred coincident with the development of SSPE.and the Eunice ShriverSupported in part by NINDS Special Fellowship NSO 1674 (F.H.H.), NIH grants NSO 9675 (J.R.L.) and HDO 4147 (K.E.A.) and training grant NSO 5393 (E.P.R.).Presented in part at the 50th Annual Meeting of the American Association of Neuropathologists, Boston, Mass., June 1974.     

Computed tomography in subacute sclerosing panencephalitis: report of 15 cases

Computerized tomographic (CT) study of the brain was performed in 15 cases of subacute sclerosing panencephalitis (SSPE). Most patients in Stage II (6/8) had cerebral edema and diffuse white matter low attenuation, and patients in Stages III and IV (5/7) had atrophy of cerebral cortex, brainstem and cerebellum. Low density areas in deep grey matter nuclei (5 cases), large focal areas of white matter hypodensity (3/15) and evidence of brainstem atrophy without cerebral atrophy (2/15) were features not hitherto described. One patient in Stage III had normal scan. Correlation of scan findings was better with the stage of the disease than with the duration of SSPE.     

Intrathecal interferon in subacute sclerosing panencephalitis

Three patients at Stage II of subacute sclerosing panencephalitis (SSPE) were treated with semipurified alpha-interferon (IFN) using different combinations of intrathecal and intravenous routes: 1 x 10(6) IU of alpha-IFN were given every other day up to a total of 15 x 10(6) IU. Transient improvement of neurological symptoms and electroencephalogram were noted in all 3, while cognitive function slightly improved in 2 of them. Clinical benefits gradually disappeared 2 to 6 months after cessation of IFN. Intrathecal antibody production did not change substantially, but CSF Leu 3a/Leu 2a ratio appeared to increase. No significant side effects were observed, except for a mild meningeal inflammatory reaction after each intrathecal administration of IFN.     

Neurodegenerative mechanisms in subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated measles virus, showing inflammation, neuronal loss, and demyelination. We neuropathologically examined six autopsy cases of subacute sclerosing panencephalitis, using in situ nick end-labeling and immunohistochemistry. Both the neurons and glial cells in the cerebral cortex showed immunoreactive nuclei in the nick end-labeling in two cases with disease duration within 2 years, whereas they were confined to the glial cells in the demyelinated cerebral white matter in three cases with disease duration ranging from 2 to 10 years. The nuclei and cytoplasm were immunoreactive for 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine, markers of oxidative damage to DNA and ribonucleic acid, respectively, in the cerebral cortex in three cases with disease duration within 9 years. In contrast, 4-hydroxy-2-nonenal-modified proteins, products of lipid peroxidation, were deposited in the demyelinated white matters in four cases with disease duration longer than 9 years. In three cases with long survival, the expression of glial glutamate transporters was reduced in the cerebral cortex. It is speculated in subacute sclerosing panencephalitis that apoptosis and oxidative stress to DNA can contribute to the early neuronal damage, whereas lipid peroxidation and disturbed glutamate transport may be related to the subsequent neurodegeneration.     

Brainstem involvement in subacute sclerosing panencephalitis

The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.     

Radionuclide imaging in subacute sclerosing panencephalitis

Three patients with subacute sclerosing panencephalitis (SSPE)--two with acute disease and one with an exacerbation--had abnormal radionuclide brain scans during periods of rapid neurologic deterioration. In two of the three patients radionuclide brain scan showed lesions of both cortex and deeper structures, indicating the panencephalic nature of the disease. There was no contrast enhancement on computerized tomography (CT) in the areas of radiopharmaceutical accumulation in the two patients studied. We feel that delayed radionuclide scanning is more sensitive in detecting acute SSPE than routine contrast-enhanced CT, because more time is allowed for tracer accumulation in lesions and for background activity to decrease.     

Isoprinosine in subacute sclerosing panencephalitis.

An open therapeutic trial of isoprinosine was conducted in 15 patients with subacute sclerosing panencephalitis (SSPE). Long-term remissions occurred in 5 (33 percent), with documented improvement sustained for 2 or more years. Another patient was in remission 9 months after starting treatment, and three patients had transient remissions or stabilization. The disease was unaltered in five patients who had rapidly progressive SSPE when treatment started. These results compare with an average remission rate of about 5 percent in several series of untreated cases of SSPE or in cases treated with other antiviral agents. Patients in remission continued to have elevated cerebrospinal fluid (CSF) IgG and measles antibody titers, with one exception. Isoprinosine was tolerated for several years without side effects, except for mild hyperuricemia.     

Intrathecal interferon in subacute sclerosing panencephalitis

Five patients with clinically advanced subacute sclerosing panencephalitis (SSPE) were given human leukocyte interferon (IFN) by the lumbar route, 1 million IU every other day for a total of 30 days. Intrathecal IFN produced a meningeal inflammatory reaction in all patients and was associated with transient hemiparesis in 1. It persisted in the cerebrospinal fluid at measurable levels for 48 hours after a single injection. Although improvement was temporally related to intrathecal IFN in 1 patient, it is not clear whether this was induced by IFN or a spontaneous remission. A randomized controlled trial would be necessary to evaluate IFN critically as a therapy for SSPE.     

Humoral immunological reactivity in subacute sclerosing panencephalitis

In a group of 37 children with SSPE serum protein and cerebrospinal fluid electrophoresis was done (in 34 and 25 cases respectively) determining immunoglobulins in the serum and cerebrospinal fluid in all 37 cases. The obtained results demonstrated a lack of correlation between the changes observed in the serum and cerebrospinal fluid. The most frequent change in the serum was a rise in alpha 2 globulin level (85%) and reduced IgA level (58%), while in the cerebrospinal fluid a rise in gamma globulins (92% of cases) and IgG (100%) was observed most frequently. A comparison of these results with past history of measles, with the clinical course of SSPE and with the survival time of the children showed no correlations. Measles antibodies were determined in the serum and cerebrospinal fluid in 37 children, and the determinations, were repeated several times in the serum of all children and in the cerebrospinal fluid of 9 children. Measles antibodies were found in the serum in all children and in the cerebrospinal fluid in 21 children (57%). The highest titres of antibodies above 1:32 in the cerebrospinal fluid were demonstrated in children with measles at the age up to 2 years. The prognosis was worst in children with acute onset of the disease preceded frequently by cranial injury or infection, with a high serum antibody level and absence of antibody in the cerebrospinal fluid.     

Retinal changes in subacute sclerosing panencephalitis]

In a 12-year-old boy with histologically confirmed subacute sclerosing panencephalitis changes resembling chorioretinitis were found in the peripheral part of the left retina. Fluorescein angiography demonstrated signs of atrophy of pigmented epithelium. On the basis of pertinent literature the authors suggest that in this disease retinal involvement may precede neurological manifestations. It would be interesting to try whether therapy applied in this early stage would be effective.     

Serial diffusion-weighted imaging in subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis may be associated with clinical features of frontal lobe dysfunction. We previously reported that frontal lobe volume falls significantly as clinical stage progresses, using three-dimensional magnetic resonance imaging-based brain volumetry. The hypothesis that frontal volume increases correlate with clinical improvement, however, was not tested in our previous study. Therefore, we reevaluated our patient with subacute sclerosing panencephalitis, to determine whether apparent diffusion coefficient maps can characterize the clinical course of subacute sclerosing panencephalitis. We studied an 8-year-old boy with subacute sclerosing panencephalitis, using serial diffusion-weighted imaging magnetic resonance imaging, and measured the regional apparent diffusion coefficient. The regional apparent diffusion coefficient of the frontal lobe decreased significantly with clinical progression, whereas it increased to within normal range during clinical improvements. The apparent diffusion coefficient of the other regions did not change. These results suggest that the clinical signs of patients with subacute sclerosing panencephalitis are attributable to frontal lobe dysfunction, and that apparent diffusion coefficient measurements may be useful in predicting the clinical course of subacute sclerosing panencephalitis.     

Cerebrospinal fluid pressures in subacute sclerosing panencephalitis

Increased intracranial pressure can rarely be the initial symptom in subacute sclerosing panencephalitis (SSPE). We examined cerebrospinal fluid (CSF) pressures and their correlation with clinical features in 58 patients with SSPE. CSF pressure varied between 50 and 500 mmH2O, mean 210.9+/-103.7 mmH2O. Twenty-five (42%) patients had pressures above 200 mmH2O and 15/58 (25%), above 250 mmH2O. There was no correlation between CSF pressure and neurological disability, spasticity, or clinical stage. Frequent myoclonia and shorter interval between measles and onset of SSPE were associated with CSF pressure >200 mmH2O (p=0.035). The causes of high pressure in certain SSPE patients is unknown but may include the effect of myoclonic jerks or inflammatory reaction. Because these patients may be unable to express symptoms, increased intracranial pressure should be considered in the presence of irritability or frequent myoclonia.     

Long survival in subacute sclerosing panencephalitis.

A case is reported of a boy who at the age of 14 years developed subacute sclerosing panencephalitis. He deteriorated over a period of 9 months, improved greatly and remained stable for 7 years before relapse. The final deterioration to death extended over 6 years. During the whole period he was examined regularly and the electroencephalogram recorded at 3 to 6 monthly intervals. The brain was examined histologically after death. Electroencephalographic and pathological features are described.     

The electroencephalogram in subacute sclerosing panencephalitis.

Electroencephalogram studies of 31 patients with proved subacute sclerosing panencephalitis (SSPE) revealed periodic high-amplitude complexes in all except one. The periodic complexes consisted of two to four high-amplitude delta waves, were usually bisynchronous and symmetrical, and repeated once in five to seven seconds. When both the clinical myoclonic jerks and the periodic EEG complexes were present, a one to one relationship existed between the two phenomena. Besides periodic complexes, several atypical EEG findings were also noted that included frontal rhythmic delta activity in intervals between periodic complexes, electrodecremental periods following EEG complexes, paroxysm of bisynchronous spike wave activity, random spikes over frontal regions, and focal abnormalities, such as spike and slow wave foci. In spite of variability of EEG findings, there is usually no difficulty in making the diagnosis of SSPE if both the EEG and clinical findings are considered.