Background When measles vaccines were widely introduced in the 1970s, there were concerns that they might cause subacute sclerosing panencephalitis (SSPE): a very rare, late-onset, neurological complication of natural measles infection. Therefore, SSPE registries and routine measles immunization were established in many countries concurrently. We conducted a comprehensive review of the impact of measles immunization on the epidemiology of SSPE and examined epidemiological evidence on whether there was any vaccine-associated risk. Methods Published epidemiological data on SSPE, national SSPE incidence, measles incidence and vaccine coverage, reports of SSPE in pregnancy or shortly post partum were reviewed. Potential adverse relationships between measles vaccines and SSPE were examined using available data. Results Epidemiological data showed that successful measles immunization programmes protect against SSPE and, consistent with virological data, that measles vaccine virus does not cause SSPE. Measles vaccine does not: accelerate the course of SSPE; trigger SSPE or cause SSPE in those with an established benign persistent wild measles infection. Evidence points to wild virus causing SSPE in cases which have been immunized and have had no known natural measles infection. Perinatal measles infection may result in SSPE with a short onset latency and fulminant course. Such cases are very rare. SSPE during pregnancy appears to be fulminant. Infants born to mothers with SSPE have not been subsequently diagnosed with SSPE themselves. Conclusions Successful measles vaccination programmes directly and indirectly protect the population against SSPE and have the potential to eliminate SSPE through the elimination of measles. Epidemiological and virological data suggest that measles vaccine does not cause SSPE.

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Review of the effect of measles vaccination on the epidemiology of SSPE

Over the last decade, studies have implicated the cerebellum not only in motor functioning, but also in cognition and social cognition. Although some aspects of cognition have been explored in the five most common forms of Spinocerebellar Ataxia (SCA), social cognition in these patients has rarely been examined. The present study provides a preliminary characterisation of the severity of cognitive and social cognitive impairments in patients with SCA2, SCA1 and SCA7 using an identical battery to the one previously used in SCA3 and SCA6 patients for comparison. The cognitive profiles of SCA1 and SCA7 patients were comparable to that of SCA6 patients; SCA1 patients had relatively intact profiles, while SCA7 patients demonstrated only some selective deficits. In contrast, SCA2 patients showed the greatest impairments, similarly to SCA3 patients. On tests of social cognition, SCA2 and SCA7 patients were impaired on a task of emotion attribution, whereas one SCA1 patient had a Theory of Mind deficit, which has also been documented in SCA3 and SCA6. We provide preliminary evidence that the neuropsychological profiles of SCA patients correspond well with the severity of pathological and clinical features. Moreover, these patients may also have social cognition impairments. Overall, we suggest that there is a degree of heterogeneity in the types of cognitive and social cognitive impairments in SCA patients.

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A preliminary characterisation of cognition and social cognition in spinocerebellar ataxia types 2, 1, and 7.

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 × 2 × 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 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.

http://www.ajnr.org/content/ajnr/24/3/501.full.pdf

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

Subacute sclerosing panencephalitis (SSPE) is a progressive, slow virus infection of the brain, caused by the measles virus, attacking children and young adults. We investigated 15 patients with SSPE by MRI, with 5 normal and 10 pathological results. In the early period, lesions were in the grey matter and subcortical white matter. They were asymmetrical and had a predilection for the posterior parts of the hemispheres. Later, high-signal changes in deep white matter and severe cerebral atrophy were observed. Parenchymal lesions significantly correlated with the duration of disease. A significant relationship between MRI findings and clinical stage was observed in the 1st year of the disease.

MRI in subacute sclerosing panencephalitis

Background
Subacute Sclerosing Panencephalitis (SSPE) is so rare in developed countries with measles immunization programs that national active surveillance is now needed to capture sufficient number of cases for meaningful analysis of data. Through the Canadian Paediatric Surveillance Program (CPSP), the SSPE study was able to document a national incidence and determine the epidemiology of affected Canadian children.

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Subacute Sclerosing Panencephalitis: Results of the Canadian Paediatric Surveillance Program and review of the literature

In 25 patients with subacute sclerosing panencephalitis in various phases of the disease CT and NMR imaging of the brain were done at the same times and the findings were related to clinical symptomatology. NMR imaging, in contrast to CT imaging, demonstrated even very small brain changes in the initial stage. The inflammatory-demyelinizing process begins in SSPE as a rule in the white matter of the occipital lobes, and only later in appears in the vicinity of the anterior horns of the lateral ventricles. Spreading of subcortical changes in the occipital lobes and their later penetration into the parietal lobes causes the development of ideatory apraxia frequent in these cases, and involvement of the cortex of the occipital lobes leads to visual agnosia. The paresis of extremities in later stages not always are correlated with greater intensity of changes in the contralateral cerebral with greater intensity of changes in the contralateral cerebral hemisphere. Hydrocephalus developing after longer duration of the disease is an expression of postinflammatory brain atrophy and not of disturbances in cerebrospinal fluid absorption.

Changes in NMR and CT images in SSPE

The authors analysed the results of controlled treatment by three methods of patients in the 1st or 2nd phase of SSPE in a randomized group. The groups received: I. Propionibacterium granulosum KP-45 (interferon inducer) + isoprinosine, II--TFX (thymus extract) + isoprinosine, III--only isoprinosine. In all groups the treatment was continued during 6 months. The analysis of the clinical results of these methods failed to demonstrate a statistically significant superiority of any of these methods (among others, due to small number of cases) but an evident statistical tendency was revealed suggesting a better effectiveness of combined treatment (immunostimulator + isoprinosine) in relation to treatment with isoprinosine only. The final evaluation of the results requires further observations of these patients.

Comparison of the results of the treatment of patients with SSPE using various immunomodulating preparations

The analysis of disease courses and survival times of 132 cases of SSPE treated by various methods in the I Department of Neurology, Institute of Psychiatry and Neurology, in years 1980-1989 is reported. Follow-up data were obtained during control examinations of patients or from an inquiry answered by parents or doctors at the place of residence of the patients. In the treatment all patients were given immunomodulating drugs. About 25% of the patients were treated with isoprinosine, in the remaining groups other drugs active on the immune system were added: TFX, alpha interferon (intraventricularly through a Rickham chamber), beta interferon (through lumbar tap) or Propionibacterium granulosum strain K 14 vaccine as an inductor of endogenous interferon. The reference group comprised 22 patients who had not been systematically treated for various reasons. The statistical analysis of the clinical courses showed that early begun immunomodulatory treatment increases the number of cases with remissions in the group of patients with the subacute form of the disease. In primarily acute cases no effect of the treatment was noted. The best results were obtained using Propionibacterium granulosum vaccine and treating with interferons. The survival times were shortest in the group not treated systematically.

[Selective problems from catamnestic studies of SSPE patients (1980-1989)].

Spinocerebellar ataxia is a group of diseases with autosomal dominant inheritance heterogenous both clinically and genetically. So called dynamic mutations underlie most these nosological units. The clinical patterns of various SCA types have not yet been defined completely. The purpose of the present report was description of the typical symptoms and signs of type 1 SCA. Seventeen patients from 13 families (M-2, F-15) were studied clinically in detail. The diagnosis was confirmed by DNA analysis. The assessment included neurological status, cognitive functions, the results of EEG, EMG, SEP, VEP, BAER and MRI examinations. The pedigrees indicated autosomal dominant inheritance pattern. The mean age at onset was 35.5 +/- 6.8 years (range 23-45 years) and it suggested negative correlation with the number of CAG repetitions. Cerebellar syndrome limb and truncal, ataxia and dysarthria was present in all cases. Six patients had nystagmus, 3 had slow saccades, 2 had gaze limitation upward, and lateral and 6 had dysphagia. Signs of pyramidal system involvement were found in 10 cases, one had athetotic movements, one had orthostatic hypotension. Two patients had dementia features, 9 had some decline of intellectual functions, mainly with difficulties of memorization, learning and concentration. In 16 cases MRI demonstrated vermis atrophy and atrophy of cerebellar hemispheres, 14 had fourth ventricle dilatation, 8 had flattening of pons base, 8 had narrowing of cervical spinal cord, 8 had dilated CSF spaces over frontal lobes and in 6 cases lateral ventricles were dilated. Electrophysiological peripheral nervous system investigations showed in 16 cases long-standing damage to the motor and sensory peripheral neurons at the level of nerve trunks, more pronounced in sensory nerves. In 13 cases peripheral neuron damage was subclinical. SEP showed in all patients disturbed function of ascending sensory pathways at peripheral and spinocortical levels.

Clinical picture of spinocerebellar ataxia type I (SCA1)

The aim of this study is a clinical and electroencelographic analysis of those SSPE patients who suffered epileptic seizures in course of the disease. The material is based on an analysis of a computed database including 1180 case histories from multiple hospitalizations of 248 SSPE patients (141 males, 107 females) in years 1978-1995. The analysis was made using computer system EPI-INFO 6. The average age of SSPE onset was 12.3 +/- 4.5 (range 4-27.5). 74.2% of patients developed the disease before the age of 15. Epileptic seizures occurred in 43.5% (N = 108) of all SSPE patients in different stages of the disease. In 47 patients (M-21; F-26) they were observed among first SSPE symptoms, in 41 of those the seizures had the form of GTCS. Epileptic seizures were more frequent in patients with SSPE onset before the age of 15 (50.5%) than in patients with later onset (23.4%). More frequent occurrence of epileptic seizures and epileptiform changes in EEG in children under 15 can be associated with specificity of developmental age: immaturity of nervous and endocrine system and decreased convulsant threshold.

D Milewska

Papers

Changes in NMR and CT images in SSPE

Comparison of the results of the treatment of patients with SSPE using various immunomodulating preparations

[Selective problems from catamnestic studies of SSPE patients (1980-1989)].

Clinical picture of spinocerebellar ataxia type I (SCA1)

Epileptic seizures in relation to the age of SSPE onset