Abstract
Thirty-four MRI studies of 26 patients with subacute sclerosing panencephalitis are reported. Lesions of high signal intensity on T2-weighted images are the most common finding; they frequently involve the periventricular or subcortical white matter. Lesions tend to start in the cortex-subcortical white matter and progress with periventricular white matter involvement and diffuse cerebral atrophy. Pial and parenchymal contrast enhancement, local mass effect of parenchymal lesions, and involvement of the splenic portion of the corpus callosum are not infrequent. Basal ganglia and brainstem lesions were rare in this series. Although cortical and subcortical lesions have some correlation with clinical findings, the extent and location of the periventricular white matter lesions and cerebral atrophy did not reflect the neurologic status in many patients.
NEUROLOGY 1996;47: 1278-1283
Subacute sclerosing panencephalitis (SSPE) usually presents with mental deterioration and myoclonic jerks. The diagnosis is based on clinical findings, EEG, and the titer of measles antibodies in the CSF. Imaging procedures are not required for the diagnosis, but help in the differential diagnosis. There are few reports on MRI findings in SSPE. [1,2] We evaluated the MRI results of our series of SSPE patients to define the range of abnormalities in this disorder.
Patients and methods.
Thirty-four MRIs of 26 patients (aged 3 to 25 years; 21 male, 5 female) were examined. The diagnosis of SSPE was made according to previously established criteria. [3] The system of Risk and Haddad [4] was used for clinical staging. Briefly, the stages are defined as follows: stage 1 - psychointellectual symptoms; IIA - stereotyped attacks, but patient walks independently; IIB - patient falls from attacks, walks with support; IIC - patient is bedridden by the attacks; IIIA - no purposeful but some spontaneous movements, some responses to other than noxious stimuli; IIIB - vegetative responses to noxious stimuli; and IIIC - deep coma and death.
The course of the disease was classified as described earlier according to the increase in the neurologic disability index (NDI) per month [3]: rapidly progressive (RP) - more than 30% increase; progressive (P) - 10 to 30%; moderately progressive (MP) - 5 to 10%; slowly progressive (SP) - 0.5 to 5%; and stable (S) course - no significant change in NDI for 6 months.
Cranial MRIs were obtained in several different centers with different equipment (0.5-T Gyroscan, Phillips, 0.5-T GEMax, 1-T Picker Systems). MRI examinations included T1-weighted sagittal and axial and T2-weighted axial spinecho images. Additional T1- and T2-weighted coronal and T2-weighted sagittal images were obtained when necessary. In 14 of the patients, T1-weighted axial and coronal images were repeated following the administration of gadolinium-DTPA (Gd-DTPA) (0.1 mmol/kg). A neuroradiologist (I.S.) unaware of the patients' neurologic status evaluated the MRI findings with respect to cerebral and cerebellar atrophy and focal abnormalities in the brainstem, thalamus, basal ganglia, corpus callosum, periventricular white matter (PVWM), subcortical white matter (SCWM), and cortex. Signal characteristics, mass effect, associated edema, and, if present, contrast enhancement (CE) were noted for each focal lesion. Follow-up MRI examinations were available in seven patients.
Results.
Normal MRI.
Three patients with disease of 3 to 4 months' duration and clinical stages I-II had normal imaging results. Subsequent MRI, obtained in one of them, was abnormal (see below).
Abnormal MRI.
Two types of MRI abnormalities were observed: focal areas of increased signal intensity on T2-weighted images (hypo- or isointense on T1-weighted images) and atrophy. Signal abnormalities were observed in various locations: cerebral cortex, SCWM, PVWM, corpus callosum, basal ganglia, thalamus, and brainstem. Atrophy involved the brain diffusely, and, in some cases, the cerebellum. MRI findings with respect to the duration, course, and stage of the disease are summarized in Table 1 and in Figure 1.
Table 1. Lesions with increased signal intensity on T2-weighted MRI
Figure 1. MRI abnormalities according to clinical stages.
Cortex and SCWM lesions.
One patient had an isolated cortical (hippocampal) lesion on his initial MRI. More often (13 images), cortical lesions were accompanied by white matter involvement - SCWM (n = 5) or SCWM and PVWM (n = 8) Table 1. The gray-white matter differentiation at the cerebral cortex and SCWM interface had disappeared in six patients. The parietal and temporal lobes were most commonly affected. In one particular patient, focal regions of increased T1-signal intensity were noted in the cortex and SCWM Figure 2, A and C.
Figure 2. Patient 5. (A) T1-weighted left parasagittal image showing the hyperintensity in the posterior parietal and occipital cortex (also seen on panel C), which may represent subacute blood products, i.e., methemoglobin. The cortical and subcortical white matter differentiation has disappeared with decreased signal intensity in this region. (B through D) T2-weighted (B) and pre- (C) and postcontrast (D) T1-weighted axial images through the same level depicting the multiple, asymmetric lesions involving the cortex and the subcortical white matter, hyperintense on T (2-) and hypointense on T1-weighted images. Note the hyperintensity on the surface of some (right parietal and left occipital) cortical lesions on T1-weighted images (C), possibly representing hemorrhagic foci (small thin white arrows). Pial (small white arrows) and parenchymal (large white arrow) contrast enhancement are observed (D).
Asymmetric involvement was observed in eight MRIs. The clinical symptoms and signs, especially motor and visual, correlated with the MRI site of involvement in 10 of 13 patients.
PVWM lesions.
Twenty-five MRIs showed PVWM involvement. As stated above, cortex or SCWM, or both, accompanied the PVWM in most cases Figure 3, A through C. The parietal PVWM was the most commonly affected site. Asymmetric involvement was frequent (8 of 25). Among the 11 patients with isolated PVWM lesions, neurologic signs correlated with the MRI lesions in only three. The duration of the disease was significantly longer in patients with isolated PVWM lesions. The course of disease did not show any particularity in cortex, SCWM, or PVWM lesions (see Table 1).
Figure 3. Patient 6. (A) Initial MRI 1 month after the onset of symptoms. T2-weighted axial image demonstrating equivocal hyperintense areas in the parietal periventricular region bilaterally (white triangles) and normal sized lateral ventricles. (B, C) MRI 6 months after onset. Double spin-echo (B) proton density (left) and T (2-weighted) (right) as well as T1-weighted (C) axial images at the same level with panel A showing diffuse, symmetric involvement of the periventricular and subcortical white matter in the frontal and parietal regions bilaterally. Signal intensity increased on proton density and T2-weighted images and decreased on T1. Note the diffuse involvement of the corpus callosum (panel B, black arrow-heads). The ventricles and cortical sulci are enlarged, indicating cerebral atrophy. (D) T2-weighted sagittal image. Hyperintense area in the pons anteriorly (white arrows).
Corpus callosum.
The following two types of involvement were observed: (1) Increased signal intensity in T2-weighted images (n = 6). The splenium was always involved, either alone (n = 5) Figure 4A or as part of diffuse changes (n = 1) Figure 3B. All six patients had parietal SCWM involvement as well. The duration of disease in these patients was 5.5 +/- 3.3 months, median 4.5 months; the course and stage were variable. (2) Atrophy (n = 7). All had associated PVWM involvement. Duration of disease was significantly longer in this group: mean 40 +/- 26.2 months, median 36 months (p < 0.01). Their stages varied, but their course was S or SP.
Figure 4. Patient 15. (A) T2-weighted sagittal image demonstrating focal hyperintense lesion in the splenium of the corpus callosum (white arrow). (B, C) T2-weighted (B) and postcontrast T1-weighted (C) axial image at the same level showing bilateral parietal lesions, more apparent on the right side with mild mass effect on the trigone of the right lateral ventricle. The right-sided lesion involves the cortex and subcortical white matter, extending to the periventricular region. There is pial contrast enhancement. Note the involvement of the splenium of the corpus callosum (white arrows).
Mass effect.
Edema and mass effect were observed in five patients with cortical, subcortical, or basal ganglia lesions Figure 4, B and C. Four had SP disease of 2 to 7 months' duration; one had a 12-month history of intellectual deterioration, but had entered an RP stage in the preceding 2 weeks.
Contrast enhancement.
Of 14 MRI studies in which Gd-DTPA was given, 2 had pial, 1 parenchymal, and 2 both pial and parenchymal CE Figure 2D and Figure 4C. The stages of patients varied between IB and IIIB; duration varied from 2 to 12 months. Their clinical course was not distinctive.
Cerebral with or without cerebellar atrophy.
Cerebral with or without cerebellar atrophy was found in 12 MRIs of patients with disease duration of 5 months to 8 years. Patients with short disease (<8 months) were at an advanced stage - IIIB. On the other hand, atrophy could be observed in patients with long disease (years) but little disability (stage I or II). Patients with atrophy always had PVWM or PVWM and SCWM involvement. Clinical courses were variable.
Other lesions.
Brainstem lesions were observed in two patients. Both were in stage IIIB, with marked cerebral and cerebellar atrophy as well as associated lesions in the PVWM and SCWM Figure 3D. Thalamus was involved in two patients, and basal ganglia in one. Duration of disease in this group was 5 to 7 months.
Serial MRIs.
Serial MRIs performed in seven patients showed that MRI lesions may improve or enlarge without necessarily correlating with clinical features. The initial MRIs were either normal or cortex with or without SCWM involvement was observed. PVWM became involved later, to be followed or accompanied by atrophy.
Discussion.
This series illustrates that, unlike CT, MRI is frequently abnormal in SSPE and allows a more accurate study of lesions in evolution. [5] Normal MRI was found only in three patients in the first 4 months of the disease.
The distribution of MRI abnormalities may vary among different series. The timing of the imaging during the course of the disease, the proportion of early and late cases, and the number of serially studied patients may account for certain discrepancies among reports on the relative frequency of MRI findings. In our series, PVWM lesions were most common. PVWM is involved relatively late in the disease, as shown in Table 1 and Figure 1 and Figure 5; lesions start in the cortex and SCWM and spread later to the PVWM. This is in partial agreement with the pathologic study of Ohya et al. [6] who reported on the cortical involvement early in the disease, followed by SCWM, brainstem, and spinal cord involvement. All areas of the brain can be affected, but the parietal lobes were involved more frequently in our series. In their CT and MRI study, Kulczycki et al. [7] observed that the inflammatory process starts in the occipital white matter and proceeds toward the frontal regions.
Figure 5. Serial MRI findings of seven patients. open triangle = 2 cases; open square = 5 cases; nabla =6 cases; fill circle = 7 cases; open circle = 8 cases; fill triangle = 9 cases; * = 10 cases.
Since PVWM involvement is a late feature, the frequency of stage I and II patients among the group with PVWM lesions may be questioned Figure 5. Disease in these patients is in a slower or arrested stage (SP or S), allowing them to have longer survival and to show late MRI findings.
Three patients treated with intraventricular interferon had disease duration of 36 to 72 months; their MRI showed PVWM changes and cerebral atrophy, findings usually associated with long disease. Atrophy was also observed in some patients with short disease and an advanced stage. This finding differs from previous CT reports in which atrophy occurred only late in the course of SSPE. [8] Apparently, atrophy is a result of postinflammatory tissue damage and may occur earlier in some patients with a faster course. On the other hand, two patients with disease duration of 3 and 6 years had no atrophy on MRI.
CE is not a well-known feature of SSPE [9]; however, we observed this finding in some cortical-SCWM lesions. CE was either pial or intraparenchymal. The disease was of 2 to 12 months' duration. Our patients with CE had varied types of clinical courses; therefore CE does not seem to be particular to certain clinical types or stages. This finding might be encountered more often with more widespread use of Gd-DTPA in MRI studies of patients with suspected degenerative disease.
Local mass effect was present in five of our patients. As with CE, the disease duration was 2 to 12 months, suggesting that edema is also a feature of early or active disease. Pederson and Wolff [10] reported brain edema on CT in two SSPE patients with disease duration of 2 and 6 months.
To our knowledge, there are no previous reports of focal hyperintense lesions of the corpus callosum with a predilection for the splenium. Though no histopathologic examination is available, we believe that the corpus callosum involvement is an extension of the posterior PVWM abnormality rather than primary involvement since there were no isolated corpus callosum lesions. Patients with atrophy of the corpus callosum had significantly longer disease, probably related to their SP or S courses.
The focal hyperintense areas in the T1-weighted images of patient 5 were interpreted as methemoglobin. Other possibilities are laminar necrosis associated with infarcts or mineralization. [11] This patient had a frontal brain biopsy that demonstrated areas of hemorrhage in the gray and white matter, and no laminar necrosis, supporting our interpretation of focal hemorrhages. Mineralization has not been observed in SSPE, and since this patient had a normal MRI 4 months ago, the lesions observed in the second MRI should be in acute stage, making dystrophic calcification unlikely.
As reported previously, parenchymal lesions had a weak correlation with clinical signs. [7] There was a correlation with neurologic examination findings, especially motor and visual symptoms, for cortical and subcortical lesions, but usually not with PVWM lesions. The degree of atrophy did not have direct clinical significance. There may have been better concordance between MRI and clinical findings if the age and the global deterioration of these patients did not limit the precision of the neurologic examination.
In conclusion, there were areas of increased signal intensity in the cerebral cortex, SCWM, and PVWM in SSPE patients. The latter was the most common finding in this series, but this may differ depending on the timing of the MRI studies. White matter involvement may extend to the corpus callosum, particularly the splenium. CE and mass effect were present in relatively early cases (in the first 12 months). In contrast, basal ganglia, thalamic nuclei, and brainstem involvement were infrequent.
Acknowledgment
We thank Maide Dagasan, MS, for her assistance in the preparation of the figures.
- Copyright 1996 by Advanstar Communications Inc.
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