Effect of ribavirin on subacute sclerosing panencephalitis virus infections in hamsters

The antiviral activity of ribavirin was studied in hamsters infected with subacute sclerosing panencephalitis (SSPE) virus. Ribavirn did not improve the survival of infected hamsters when administered intraperitoneally at the maximal nonlethal dose of 50 mg/kg/day for 10 days. However, when administered intracranially, ribavirin improved the survival of infected hamsters in a dose-dependent manner. The 50% effective dose was calculated to be 1.4 mg/kg/day, and the selectivity index, based on the ratio of the 50% lethally toxic dose (31 mg/kg/day) to the 50% effective dose, was 22. When begun 12 h, but not 36 h, postinfection, ribavirin at a dose of 10 mg/kg/day completely prevented mortality and inhibited the replication of SSPE virus in brains of infected hamsters. Intrathecal or intraventricular administration of ribavirin should be explored for potential use in the treatment of patients with SSPE.     

Long-term follow-up of patients with subacute sclerosing panencephalitis treated with intraventricular alpha-interferon

We treated 22 patients with subacute sclerosing panencephalitis (SSPE) with intraventricular alpha-interferon (alpha-IFN) and oral inosiplex between 1986 and 1991. The follow-up for 56 to 108 months demonstrates a higher survival rate in these patients compared with those who did not receive alpha-IFN. However, eight of 11 patients whose condition improved after alpha-IFN treatment and five of five patients whose condition stabilized after alpha-IFN experienced neurologic deterioration 6 to 90 months after treatment; three of 11 and four of five died. The use of inosiplex did not influence the prognosis. Re-administration of the same regimen was not effective in one patient. Treatment-induced remissions in SSPE can be temporary, analogous to spontaneous remissions. Longer treatment with higher doses, or combinations of drugs, may be required.     

Characteristic clinical features in a case of fulminant subacute sclerosing panencephalitis

A 12-year-old girl with fulminant subacute sclerosing panencephalitis (SSPE) without myoclonic jerk and periodic EEG complexes is reported. She presented with blurred vision, fell into a coma after 2 weeks and died within 4 months. Magnetic resonance image (MRI) disclosed high intensity lesions in the lateral geniculate bodies, when the patient initially complained of blurred vision. Reviewing the cases of fulminant SSPE in the literature, more than half of the patients showed blurred vision or visual agnosia as an initial symptom. Most of those patients were female and rapidly deteriorated to a comatose state within 2 weeks. Based on the MRI study of the present patient, we speculate that the initial visual impairment in such patients can be attributed to the involvement of the lateral geniculate body.     

Study of human foamy virus proviral integration in chronically infected murine cells

BACKGROUND: An altered nocturnal sleep pattern and a dysfunction of the hypothalamic-pituitary-adrenocortical system are neurobiological abnormalities typical for depression. A persistence of these neurobiological alterations during remission has been shown to be associated with an increased risk for a relapse. However, it remains unclear whether these persisting abnormalities are trait markers indicative of an increased vulnerability for affective disorders or only represent 'biological scars' acquired during past episodes. Thus, respective examinations need to be performed in the premorbid state in order to answer this open question. METHODS: In the present article we have summarized the various results of the index investigation of a prospectively designed study in which we investigated 54 healthy first-degree relatives (high-risk probands; HRPs) of patients with an affective disorder using polysomnography, the combined dexamethasone corticotropine-releasing hormone (DEX-CRH) test and psychometric measurements. RESULTS: In the cross-sectional part of this study the HRPs, as a group, exhibited a 'depression-like' sleep EEG profile and DEX-CRH test result, while their psychometric profile was characterized by elevated scores on the measures 'Rigidity' and 'Autonomic lability'. On an individual level, 35% of the HRPs were identified as conspicuous in at least two of the three areas under investigation. CONCLUSIONS: The question of whether these abnormalities do indeed reflect trait markers indicative of an increased vulnerability for depression will be answered by the longitudinal part of the study that allows for the retrospective identification of the premorbid status of those HRPs who develop an affective disorder during the follow-up period.     

Quantitation of intrathecal measles virus IgG antibody synthesis rate: subacute sclerosing panencephalitis and multiple sclerosis

A method for quantitating specific anti-viral antibodies in serum and cerebrospinal fluid (CSF) is established using enzyme-linked immunosorbent assay (ELISA). Quantitated antibody levels are used to determine intrathecal specific IgG synthesis rate for the particular antibody. Measles virus was used as a model for validating this quantitative technique: a mutated form of measles virus is a cause of subacute sclerosing panencephalitis (SSPE) and there is a possibility that measles virus is related to the cause of multiple sclerosis (MS). Matched serum and CSF samples were assayed. Concentration of anti-measles IgG was determined and intrathecal measles-specific IgG synthesis rate was calculated. For the SSPE samples, measles-specific IgG synthesis rate was elevated and comprised > 20% of the total intrathecal IgG synthesis rate; these results are consistent with the literature. The ELISA method can be performed routinely, providing a quick, simple, reproducible means of quantitating specific antibody concentrations, with sensitivity greater than 1 nanogram per milliliter. With this method, quantitation of IgG antibodies to any other viral antigen can be reliably and precisely determined.     

Adult-onset subacute sclerosing panencephalitis: case reports and review of the literature

Temperature was measured during drilling in bovine cortical bone specimens. A surgical drill fitted with a custom-designed speedometer and mounted on a drill press was used to drill holes at one speed, 49,000 rpm, and at forces in the range of 1.5 to 9.0 N. The resulting temperatures were recorded by thermocouples placed at various locations. The distribution of maximum local temperature rise (delta T) was best fitted by the function delta T = aR-b, where R is the distance from the center of the drilled hole and a and b are constants that were found by regression analysis. It was also found that the temperature increased with force, up to about 4.0 N, and then decreased at forces greater than that because of decreased drilling time. A separate series of tests revealed that temperatures were higher in the longitudinal direction than in the circumferential direction; this difference was attributed to the anisotropic thermal properties of bone.     

The elution of IgG from subacute sclerosing panencephalitis and multiple sclerosis brains

IDU (5-iodo-2'-deoxyuridine), BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] and placebo ointments were studied for their effects on experimental herpes simplex (type 1) keratoconjuncitivitis in rabbits. When treatment was begun 65 h after virus inoculation, both BVDU and IDU prevented development of keratitis. Both BVDU and IDU were also effective in suppressing the severity of conjunctivitis, and in this respect, BVDU proved significantly better than IDU. When treatment was started 110 h after virus inoculation, BVDU proved significantly better than IDU in promoting healing of established keratitis.     

Assessment of early treatment results with antineoplaston AS2-1 in subacute sclerosing panencephalitis]

A tentative treatment with Antineoplaston AS2-1 was carried out in a group of 16 patients with subacute sclerosing panencephalitis (SSPE). Most patients were in phase II of SSPE (after Jabbour) with mean disease duration 6.4 months. Their age ranged from 13 to 28 years. They were given for 6 months 15 capsules of Antineoplaston AS2-1 and 6 tablets of isoprinosine daily. Despite that treatment progression was observed of the disturbances of higher nervous functions, less so of motor functions. The treatment had no effect on MRI results, EEG and antimeasles antibodies levels. No adverse effects were observed.     

Case report and molecular analysis of subacute sclerosing panencephalitis in a South African Child

This is the first case of subacute sclerosing panencephalitis from South Africa in which the molecular characteristics of the causative measles virus were examined. The virus found is classified as genotype D3, which has not previously been found in Africa and was last circulating in the United States before 1992.     

Ocular manifestation of subacute sclerosing panencephalitis (SSPE) (author's transl)

A case history of a patient with subacute sclerosing panencephalitis (SSPE) is presented with emphasis on the initial ocular manifestation of the disease. Acute necrotising retinitis was found clinically and proved histologically. Clinical and histological findings are compared with reports in the literature.     

Encephalitis in ferrets caused by a nonproductive strain of measles virus (D.R.) isolated from patient with subacute sclerosing panencephalitis

A nonproductive, syncytiogenic strain (D.R.) of measles virus, isolated from a patient with subacute sclerosing panencephalitis (SSPE), was inoculated intracerebrally into ferrets in an attempt to induce subacute encephalitis. Inoculation of freeze-thawed syncytia before immunization was the least effective procedure, and inoculation of live syncytia after immunization with measles virus vaccine was the most effective procedure, for induction of subacute or persistent subclinical encephalitis in the animals. After the latter procedure three of five ferrets developed subacute or subclinical encephalitis, whereas ferrets inoculated with live syncytia without prior immunization consistently contracted acute fatal encephalitis in one to two weeks. The subacute encephalitis in ferrets was characterized by high titers of antibody to measles virus in serum. At the time of sacrifice 1.25, 4.5, or 8.0 months after inoculation, brains of the ferrets showed histologic lesions similar to those characteristic of SSPE, and nonproductive syncytiogenic measles virus was recovered from the brains of two of the animals. All three ferrets had greatly increased concentrations of gamma-globulin in their brains and high levels of neutralizing and hemagglutination-inhibiting antibodies to measles virus. Only one of these animals developed clinical signs 1.25 months after inoculation.     

Measles virus infection of cells in perivascular infiltrates in the brain in subacute sclerosing panencephalitis: confirmation by non-radioactive in situ hybridization, immunocytochemistry and electron microscopy

As part of continuing multidisciplinary studies on the neuropathogenesis of subacute sclerosing panencephalitis (SSPE), in situ hybridisation, immunocytochemistry and electron microscopy were used to detect measles virus nucleic acid, protein and nucleocapsids in brain perivascular infiltrates of three cases. Perivascular cuffing cells which contained measles virus nucleic acid and antigens were found in all cases. Infected cuffs occurred predominantly in areas of general parenchymal cell infection and in many of these a high proportion of the infiltrating cells were infected. Other cuffs in these areas were either uninfected or contained only a few infected cells. Occasional infected cells were also seen in cuffs in non-infected areas. In contrast, no specific immunocytochemical reactions or in situ hybridisation for measles virus was observed in brain tissue from a patient with herpes encephalitis. By electron microscopy viral nucleocapsid, consistent with measles virus, was found within the cytoplasm of plasma cells in the inflammatory cuffs in SSPE brain tissue. Possible explanations for our results are that infiltrates become infected on arrival in the CNS or alternatively, that the infected infiltrates reflect a generalised infection of the reticuloendothelial system. The frequent presence of uninfected cuffs favours the former explanation.     

Polygraphic recordings in subacute sclerosing panencephalitis. A study of the pathophysiology of the periodic EEG complexes

Polygraphic whole night recordings were performed in 10 patients with SSPE. In most cases sleep states could not be classified according to the usual criteria, but two different states with differing EEG patterns were always seen. A significant correlation was obtained between EEG complexes and phase of the respiratory cycle in 8 out of 9 patients, irrespective of the sleep state. Slowing of heart rate for one R-R interval was observed to occur during the onset of the complex in 7 patients in both sleep states, and in 2 patients only in one state. Periodic occurrence of complexes was stable throughout the night. This stability seems to be maintained by a mechanism regulating the duration of an interval according to the duration of the preceding one. It is suggested that diffuse involvement of subcortical structures rather than a localized change is responsible for the generation of the EEG complexes in SSPE.