Neuronal loss is an early component of subacute sclerosing panencephalitis.

OBJECTIVE: We performed diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) studies in a group of patients with subacute sclerosing panencephalitis (SSPE) in order to estimate the pathologic process underlying the phenotypic variability. METHODS: Patients with SSPE who had MRI including DTI and MRS examinations were evaluated according to their clinical status as determined by the SSPE Scoring System and their mental age as determined by tests appropriate for age and developmental level. Comparisons of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and metabolite ratios of frontal periventricular white matter, parieto-occipital periventricular white matter, and globus pallidus in both hemispheres were made between control and SSPE groups, and between SSPE subgroups. RESULTS: Control (n = 18) and SSPE (n = 39) groups differed in all DTI and MRS parameters except FA, choline (Cho), and Cho/creatine (Cr). SSPE cases had higher ADC and lower N-acetylaspartate (NAA), NAA/Cho, and NAA/Cr in all regions of interest, suggesting cell loss. Disease progression rate and neurologic deficit appeared to be associated with the degree of ADC elevation and NAA reduction: the group with severe global deterioration had the lowest NAA (230.75 ± 197.97 in forceps minor), and rapid progression was associated with acute reduction in NAA. CONCLUSIONS: The combination of MRS and diffusion MRI findings suggests neuronal loss can be a primary target in rapidly or subacutely progressing SSPE, and preservation or regeneration of axonal structure may be beneficial in chronic cases.

Correlation of quantitative diffusion tensor tractography with clinical grades of subacute sclerosing panencephalitis.

BACKGROUND AND PURPOSE: SSPE is a persistent infection of the central nervous system caused by the measles virus. The correlation between the clinical staging and conventional MR imaging is usually poor. The purpose of this study was to determine whether tract-specific DTI measures in the major white mater tracts correlate with clinical grades as defined by the Jabbour classification for SSPE. MATERIALS AND METHODS: Quantitative DTT was performed on 20 patients with SSPE (mean age, 9 years) and 14 age- and sex-matched controls. All patients were graded on the basis of the Jabbour classification into grade II (n=9), grade III (n=6), and grade IV (n=5) SSPE. The major white matter tracts quantified included the CC, SLF, ILF, CST, CNG, SCP, MCP, ICP, ATR, STR, and PTR. RESULTS: Although a successive decrease in mean FA values was observed in all the fiber tracts except for the SCP and ICP, moving from controls to grade IV, a significant inverse correlation between clinical grade and mean FA values was observed only in the splenium (r=-0.908, P<.001), CST (r=-0.663, P=.013), SLF (r=-0.533, P=.050), ILF (r=-0.776, P=.001), STR (r=-0.538, P=.047), and PTR (r=-0.686, P=.035) fibers. No significant correlation of mean MD values from these white matter tracts was observed with clinical grades of the disease. CONCLUSIONS: We conclude that the grade of encephalopathy correlates inversely with the tract-specific mean FA values. This information may be valuable in studying the disease progression with time and in assessing the therapeutic response in the future.

Proton magnetic resonance spectroscopy in three subacute sclerosing panencephalitis patients: correlation with clinical status.

INTRODUCTION: Subacute sclerosing panencephalitis is progressive, fatal encephalitis caused by a persistent defective measles virus in the central nervous system. The diagnosis is based upon characteristic clinical manifestations, the presence of characteristic periodic EEG discharges, and demonstration of elevated antibody titer against measles in the plasma and cerebrospinal fluid. There has been no correlation between the clinical status and the MRI findings. METHODS: We performed single voxel magnetic resonance spectroscopy (MRS) on white matter areas that appeared normal or abnormal on conventional MRI in three patients with different clinical stages. RESULTS: N-acetyl aspartate:creatine ratios were decreased and choline:creatine ratios were increased in white matter lesions in the late stages of the disease. A lactate peak was observed in a patient in the last stage of the disease. Increased myoinositol:creatine ratio was seen in white matter areas on conventional MRI and in the white matter lesions at early stage of the disease, before neuronal loss.

Early- and late-state subacute sclerosing panencephalitis: chemical shift imaging and single-voxel MR spectroscopy.

BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, inflammatory neurodegenerative disease. Our aim was to determine the metabolic abnormalities of brain in early- and late-stage SSPE by using MR spectroscopy and to assess areas of involvement in the early stages when MR imaging findings were normal. METHODS: Children with stage II (n = 3) or III (n = 3) SSPE and 10 healthy, age-matched children underwent MR imaging, multivoxel MR spectroscopy, and short-echo single-voxel MR spectroscopy (SVS). Areas of involvement in the brain were determined with chemical shift imaging. For SVS, 2 x 2 x 2-cm voxels were placed in the frontal subcortical white matter (FSWM) and parieto-occipital white matter (POWM). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (Ins)/Cr, and NAA/Cho ratios were calculated. RESULTS: Comparisons of NAA/Cr, Cho/Cr, Ins/Cr and NAA/Cho ratios between patients and control subjects showed significant differences in FSWM and POWM (P <.01). In patients with SSPE, NAA/Cr ratios in POWM were significantly less than those in FSWM (P <.01). NAA/Cr ratios in patients with stage II SSPE and those in the control group were not significantly different; this may reflect the absence of neuronal loss. Decreased NAA/Cr, increased Cho/Cr and Ins/Cr ratios, and increased lactate and lipid peaks were found in patients with stage III SSPE. CONCLUSION: MR spectroscopy showed findings suggestive of inflammation in stage II and findings of demyelination, gliosis, cellular necrosis, and anaerobic metabolism in stage III. MR spectroscopy could be a promising technique for early diagnosis and treatment planning in cases of SSPE.

Increased positive selection pressure in persistent (SSPE) versus acute measles virus infections.

We compared the extent of positive selection acting on acute and persistent strains of measles virus (MV). Far stronger positive selection was found in the fusion (F) and haemagglutinin (H) genes from subacute sclerosing panencephalitis (SSPE) compared to acute MV cases. Most of the positively selected sites identified in these surface glycoprotein genes from SSPE cases correspond to structural, functional or antigenic areas, and could not be explained by the effects of cell passaging. The correlations between selected sites and functional studies of MV are discussed in detail with reference to the maintenance of persistent infection. No positive selection was found in the matrix (M) gene from acute cases of MV and the effects of including hypermutated SSPE M gene sequences in phylogenetic inference were also explored. Finally, using H gene data, we estimated the rate of molecular evolution for SSPE strains as 3.4 x 10(-4) substitutions/site/year, which is similar to previous estimates obtained for acute strains.

Subacute sclerosing panencephalitis: clinical and magnetic resonance imaging evaluation of 36 patients.

We studied 36 patients (24 males, 12 females), all of whom had definite subacute sclerosing panencephalitis with typical periodic complexes in their electroencephalograms and increased titers of measles antibody in serum and cerebrospinal fluid. Their clinical and laboratory findings on admission were reviewed retrospectively. The age at onset of symptoms varied from 4 to 23 years. The average age at onset of disease was 13.1 +/- 4.18 years. The mean of the duration from the infection to the onset of subacute sclerosing panencephalitis was 9 years. Unusual symptoms, especially in the early periods of disease, included hemiparesis (7 patients), headache (3), generalized tonic-clonic seizures (6), absence seizure (1), nausea (3), and vomiting (3). Twenty-six cranial magnetic resonance imaging (MRI) and 12 computed tomography examinations were performed. Nine patients had normal MRI. In the early stages, lesions usually involved parieto-occipital corticosubcortical regions asymmetrically. In time, symmetric periventricular white-matter changes became more prominent. In addition to the common clinical findings in cases of subacute sclerosing panencephalitis reported in the literature, there were some different clinical features of the disease. Eventually, we concluded that there seems to be no correlation between the clinical stages and either the duration from the onset of subacute sclerosing panencephalitis or the MRI findings.

Correlation between clinical stages and EEG findings of subacute sclerosing panencephalitis.

In this retrospective study 67 patients with SSPE seen between the years 1980 and 1998 were reviewed. Using the criteria of SSPE diagnosis (clinical signs, characteristic EEG patterns, high titres of measles antibodies in the serum and CSF), the patients were divided into two groups. Group A fulfilled all criteria, however, due to the inability of measuring measles antibody before 1987, it was not possible to observe the third criterion in Group B. Among 67 patients, groups A and B consisted of 51 boys and 16 girls ranging in age between 1 to 23 years, mean age 13.1. The male/female ratio was 3.1. The periodic EEG complexes (PCs) were usually bilateral, synchronous and symmetrical. PC amplitude asymmetry was seen in 12 patients and 2 patients had no PC synchronization between the hemispheres. Six patients had more than one form of PC. Delta activity in anterior hemispheres after PC was seen in 40 patients, mostly in stage 2A. Thirty-two patients had focal epileptiform abnormalities in multiple locations at every stage but most frequently in frontal, central and temporal regions. One patient had PC over both hemispheres and periodic lateralized epileptiform discharges (PLEDs) over the right hemisphere. The EEG findings described and observed in our study do not seem to be specific to SSPE but these findings were not atypical or unusual.

Fast-wave periodic complexes in a mentally retarded child who later developed subacute sclerosing panencephalitis: a modification of a classic EEG by preexisting brain damage?

The EEG of a 12-year-old girl with stage II subacute sclerosing panencephalitis (SSPE), who had also suffered from a non-progressive mental retardation of unknown aetiology since early childhood, revealed periodic generalised stereotyped fast wave bursts synchronous with myoclonic jerks. The background activity was nearly normal. The diagnosis of SSPE was established by raised serum and measles antibody titres, raised CSF IgG, and brain biopsy. This rare type of periodic complex has only once been described in the literature, again in a mentally retarded child who had developed SSPE. We suggest a mechanism of origin of this type of periodic complex drawn from observations in these two cases, and discuss its significance.

Measles virus in the brain.

Measles virus can give three different forms of infections in the central nervous system. These are acute postinfectious encephalitis, acute progressive infectious encephalitis, and subacute sclerosing panencephalitis (SSPE). The postinfectious acute disease is interpreted to reflect an autoimmune reaction. The acute progressive form of brain disease, also referred to as inclusion body encephalitis, reflects a direct attack by the virus under conditions of yielding cellmediated immunity. The late progressive form of encephalitis (SSPE) has been extensively analyzed. Recent molecular genetic studies have unravelled a range of mechanisms by which a defective expression of either the matrix, the fusion, or the hemagglutinin proteins may lead to viral persistence in brain cells under conditions not allowing identification by immune surveillance mechanisms. Many aspects of virus-cell interactions have been examined by use of explant cultures of neuronal cells of human and animal origin. Some of the findings are reviewed. Experimental animals, in particular rodents, have been used to establish systems in which phenomena, pivotal to the evolution of acute as well as persistent measles virus infections in the brain, can be studied. A wide range of potentially important mechanisms has been highlighted and is discussed. More recently, mice with genetic defects in immune functions were used to evaluate consequences as to initiation and dissemination of virus infection in the brain.