Lack of relationship between the HLA system and subacute sclerosing panencephalitis

Thirty-six HLA - A, B and C antigens were typed in 35 SSPE patients. No difference in the frequency of any of the antigens studied was noted between SSPE and age-, sex- and race-matched controls. Nor was there any difference when they were compared with the adult control group.     

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.     

Cell mediated immunity in patients with subacute sclerosing panencephalitis

Cell mediated immunity was assessed on the basis of total lymphocytes (TL), total T lymphocytes (TTL) counts, delayed skin test responses and in vitro leucocyte migration inhibition test (LIF) production in 25 patients with SSPE, classified according to the clinical stages of the disease. The patients in stage I of the disease did not show any defect in cellular immunity while the patients in stage II showed decreased TL and TTL counts, more negative skin test responses to PHA, SKSD and PPD, and unresponsiveness to SKSD of LIF production. When the patient group was evaluated as a whole, only the TL counts and the skin test responses against SKSD differed from those in the controls. These results suggest that the defects in cellular immunity demonstrated in the patients with SSPE may be due to SSPE or the measles virus itself rather than to a genetic factor predisposing patients to 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.     

Intraventricular interferon in a case of subacute sclerosing panencephalitis

a patient with subacute sclerosing panencephalitis (SSPE) was treated by direct administration of Interferon B into the cerebral ventricles. Immediately after the first dose intrathecal synthesis of IgG and the CNS antimeasles antibody titer fell significantly, only to rise again to the pretreatment levels 2 months after discontinuation of treatment. There was no improvement in the patient's clinical status.

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Sommario Viene descritto un caso di PESS trattato con Interferon B somministrato direttamente nei ventricoli cerebrali. Immediatamente dopo la prima somministrazione, l'indice della sintesi intratecale (CNS IgG SYN) e il livello liquorale degli anticorpi antimorbillo mostrarono un significativo decremento. Nel corso dei due mesi successivi i valori si riportarono ai livelli precedenti l'inizio della terapia. Un'azione antivirale solo iniziale e transitoria sembra essere stata innescata dalla terapia.

     

Morphometric study of the frontal cortex in subacute sclerosing panencephalitis

In biopsic material collected from the frontal cortex of 6 patients with subacute sclerosing panencephalitis (SSPE) and 5 patients with posterior fossa tumors, we estimated the neuronal and synaptic numerical densities as well as the mean volume of the neurons from layers II and III. The thickness of these layers was also determined. The evaluation of the layer's thickness suggested that there was no difference in the shrinkage in SSPE as compared to controls. No differences were found between the neuronal numerical densities and the neuronal soma sizes from SSPE and controls. Conversely the synaptic numerical density was reduced in SSPE. Given the maintenance of the neuronal numerical density in the frontal cortex of patients with SSPE, the presence of a decreased density of synapses must be regarded as a consequence of the dendritic and axonal degeneration that we previously described in this condition. It must then be borne in mind that SSPE's functional and behavioral changes might spring from alterations of the frontal cortex neuronal circuitry.     

Unilateral subacute sclerosing panencephalitis complexes with contralateral myoclonus

The characteristic EEG complexes seen in subacute sclerosing panencephalitis and the periodic myoclonus accompanying them are well known. That either of these can occur unilaterally is less well appreciated. However, the combination of unilateral SSPE complexes and contralateral myoclonus is most unusual. Attention is drawn to such a case in this paper.     

Atypical magnetic resonance imaging features in subacute sclerosing panencephalitis

Objectives:Subacute sclerosing panencephalitis (SSPE) is rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus. No cure for SSPE exists, but the condition can be managed by medication if treatment is started at an early stage.Conclusion:Early diagnosis and treatment is encouraging in SSPE, although it is not curable with current therapy. Clinico-radiological and electrophysiological correlation is very important in diagnosis of SSPE, more gravely in patients having atypical image findings as in our index case.     

Environmental risk factors for subacute sclerosing panencephalitis (SSPE)

In Israel, SSPE has been shown to be much more frequent among Sephardic Jews and Arabs than among Ashkenazic Jews. In the present study, we tried to explore environmental factors that may be of etiological importance and explain these differences in prevalence. The study is a case-control one, which includes 95 patients and 2 groups of controls, with 95 people in each. The general population controls were group-matched to the case group by sex, age, and ethnic origin. The family controls consisted of the sibling closest in age to each patient. A statistically significant positive correlation was found between risk of SSPE and early measles infection, large family, overcrowding in the home, older age of the mother, higher birth order, fewer years of schooling of the parents, fewer cultural activities, and rural place of birth. All these factors are interpreted as contributing to a higher risk of early measles infections, which thus may well be the main risk factor for SSPE.     

Immunohistochemical identification of T-lymphocytes in the central nervous system of patients with multiple sclerosis and subacute sclerosing panencephalitis

T-lymphocytes were identified in frozen brain sections derived from patients with chronic inflammatory disorders of the CNS by using a specific heteroantiserum and the unlabelled antibody enzyme method. Clusters of T-cells were found in post-mortem material of cases with multiple sclerosis (MS) and subacute sclerosing penencephalitis (SSPE). The results suggest that T-lymphocytes are involved in the pathogenesis of both MS and SSPE.     

The distribution of Alzheimer's neurofibrillary tangles and gliosis in chronic subacute sclerosing panencephalitis

Summary In two cases of clinically verified chronic subacute sclerosing panencephalitis (case 1, male, 15 years with a 9-year history; case 2, male, 20 years with a 9-year history) numerous Alzheimer's tangles (AT) were identified throughout the cerebral cortex (containing paired helical filament on electron microsopical examination). The brains were severel atrophic with hydrocephalus ex vacuo, occasional scattered microglial nodules, scant perivascular inflammatory infiltrates and demyelination. Only in case 1 were a few atypical intranuclear inclusion bodies noted. In the six-layered neocortex, a distinct distribution pattern of AT was observed; these lesions were mainly seen in laminae II, III and V (laminar distribution). The glial fibrillary acidic protein stain displayed extensive laminar gliosis mainly of the layers I, IIa, IV and VI; layers III and V, largely occupied by the AT, remained conspicuously spared from gliosis (especially the lamina III). Gliosis was prevalent in the white matter which was atrophic and shrunk. In the hippocampus, the AT involved many pyramidal neurons and, in this layer gliosis was lighter than in the surrounding white matter. In case 2, AT were present in the nucleus of Meynert, hypothalamus and in rapha centralis of the upper brain stem. Overall, the distribution of AT resembled that seen in Alzheimer's disease and aging; however, the senile plaques, vascular amyloidosis and granulovacuolar change were totally absent in both cases.     

The treatment of subacute sclerosing panencephalitis with interferon: a case report

Summary A child with subacute sclerosing panencephalitis (SSPE) received intraventricular alpha interferon (IFN) as experimental treatment. The course was monitored by colleagues in pediatric neurology, neuro-opthalmology and clinical psychology, also by monthly EEGS and brain CT scans. Two courses of IFN were administered. During the first course, improvement occurred nearly to the premorbid level of function. About 1 month after this trial was stopped, a severe recrudescence rapidly produced a thalamic state. A second trial of IFN resulted in less improvement. When the brain CT showed severe degeneration, the second trial was stopped. Intraventricular administration of alpha IFN was well tolerated in both courses of therapy. Alpha IFN has promise in the treatment of SSPE but the optimal dosage and duration of treatment are undetermined.     

Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients from a tertiary care centre

Clinical and laboratory characteristics of 39 patients with adult onset subacute sclerosing panencephalitis (SSPE) are described and compared to those of juvenile onset patients regarding preceding measles, age at onset, gender, interval between onset and diagnosis, clinical profile, and course during follow up. Diagnosis was based on clinical and electroencephalographic findings and raised anti-measles antibody titres in cerebrospinal fluid. Mean age at SSPE symptom onset was 20.9+/-4.9 years and mean interval from onset to diagnosis was 6.3+/-9.6 months. Referral diagnosis was accurate in only 12 patients. Presenting symptoms included myoclonus, behavioural changes, seizures, and cognitive, visual, and extrapyramidal disturbance. All patients received symptomatic therapy; 19 also received disease modifying agents. Five of seven pregnant women had successful deliveries. The follow-up period varied widely (maximum 60 months, median 9 months). The profile of adult onset SSPE did not differ from the rest of the cohort, except for a longer interval between measles infection and symptom onset (p<0.0001). SSPE in adults poses diagnostic challenges for clinicians. A high index of suspicion and appropriate investigations are necessary for early diagnosis and counselling.     

Indication of peripheral nerve hyperexcitability in adult-onset subacute sclerosing panencephalitis (SSPE)

Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune-resistant measles virus. Diagnostic hallmarks include widespread cortical dysfunction on EEG, myoclonus, white matter abnormalities on neuroradiological examination and the presence of IgG anti-measles antibodies in the cerebrospinal fluid. We present the first case of SSPE with signs of peripheral nerve hyperexcitability, observed as extra discharges following the compound motor action potential at motor nerve stimulation. In addition we demonstrate the importance of SSPE in the differential diagnosis of adult patients with psychiatric and neurological symptoms.     

An acute variant of subacute sclerosing panencephalitis: an autopsy case report

An acute variant of subacute sclerosing panencephalitis (SSPE) was described in a 5-year-old boy who showed rapid progression of coma within 14 days of right hemiplegia. He had measles at 3 years of age. The diagnosis of SSPE was based on the following findings: high anti-measles antibody titer in the serum and in the spinal fluid, periodic complex of EEG, and typical pathological changes of the brain. Treatment with transfer factor failed to improve the worsening clinical course. It is suggested that SSPE should be considered in the differential diagnosis of acute fulminating encephalitides or intracranial vascular lesions.     

Myelin basic protein antibodies in the serum and CSF of multiple sclerosis and subacute sclerosing panencephalitis patients

A solid-phase radioimmunoassay was developed for the detection of myelin basic protein antibodies of immunoglobulin G (IgG) class. Purified basic protein of myelin (MBP) was adsorbed onto polystyrene beads, followed by incubation in dilutions of serum or cerebrospinal fluid (CSF). ¹²⁵I-labelled anti-human IgG was used to quantify antibodies bound to the solid-phase. The assay was optimized in tests with rabbit antibodies to MBP and with ¹²⁵I-labelled anti-rabbit IgG.
Serum and CSF specimens from 41 multiple sclerosis (MS), 16 subacute sclerosing panencephalitis (SSPE) and 58 control patients were tested for MBP antibodies. No statistically significant differences were found between MS and control patient groups, but the subgroup of acute MS patients had slightly elevated ( P 0.02) antibody levels in their CSF specimens. The SSPE patients had markedly elevated levels ( P 0.001) of antibodies to MBP in their CSF specimens.     

Expression of the interferon-alpha/beta-inducible MxA protein in brain lesions of subacute sclerosing panencephalitis

The type-I interferon (IFN) inducible human MxA protein exhibits antiviral activity against a variety of RNA viruses including the measles virus (MV). In this study, we investigated the association between the expression of MV antigens and MxA in subacute sclerosing panencephalitis (SSPE) brains. We analyzed the MxA expression in and around lesions in brains of three SSPE patients and compared it with normal brains. Double staining with antibodies against MxA and the MV nucleocapsid revealed that MxA was highly expressed in a belt surrounding MV-antigen-positive lesions in SSPE brains. In normal appearing regions distant from a lesion in SSPE brains and in normal brains, MxA was not detected. Furthermore, MxA was often less or not expressed in the center of lesions expressing high amounts of MV antigens. Such a pattern of MxA expression in SSPE brains clearly indicates that newly infected cells release type I IFN and will become demarcated by a protecting barrier of MxA expressing cells. Double staining with antibodies against MxA and glial fibrillary acidic protein (GFAP) showed that the MxA protein was expressed mainly in the cytoplasm of astrocytes. MxA expression did not correlate with the presence of cellular infiltrates of inflammatory cells, although some lymphoid cells were also positive for MxA. Since MxA inhibits the replication of MV, these findings suggest that the IFN-induced MxA protein plays an important role in slowing down the viral spread in SSPE brains and by doing so may contribute to the persistence of the MV-infection.     

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.     

Signaling lymphocyte activating molecule (SLAM) expression in subacute sclerosing panencephalitis

Signaling lymphocyte activating molecule (SLAM) is a receptor for measles virus which also has immunomodulatory activity. We analyzed SLAM expression in mononuclear cells (MNC) of patients with SSPE (n=7) and control subjects (n=7) from the same population. Native 10% PAGE analysis in cell and brain tissue extracts followed by Western blotting using monoclonal anti-human SLAM showed four types of bands. Differences in the type and amount of SLAM expression were observed between SSPE and control cases. Lymphocytes of SSPE patients showed two types of SLAM bands in comparison to only one in control lymphocytes. Stimulation of cells with lipopolysaccharide (80 u/ml) and concanavalin A (1 microg/ml) in vitro led to the appearance of a second isoform in both groups. Brain homogenates of SSPE patients (n=2) displayed all four types of SLAM isoforms at significantly higher levels than those of control brains (n=2). Our results show native PAGE enables the detection of all SLAM isotypes. The expression of SLAM is increased in lymphocytes, monocytes, and brain tissues of SSPE patients.