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.     

Oligoclonal measles virus-specific IgG antibodies isolated from cerebrospinal fluids, brain extracts, and sera from patients with subacute sclerosing panencephalitis and multiple sclerosis

Measles virus-specific antibodies were isolated from sera, cerebrospinal fluids (CSF), and brain extracts of patients with subacute sclerosing panencephalitis (SSPE) and multiple sclerosis (MS) by absorption with measles antigens and subsequent acid elution of the antigen-antibody precipitates. Electrophoretically homogeneous measles antibodies were isolated from CSF or brain extracts in five patients with SSPE and in five out of seven patients with MS. Homogeneous IgG antibodies were also demonstrated in the sera from all SSPE patients and from three of the MS patients. The antibodies isolated from various control sera and from pooled CSF were electrophoretically heterogeneous. The results support the concept of a local synthesis in the nervous system of oligoclonal IgG antibodies to measles virus in all patients with SSPE and in some patients with MS. In SSPE, most or all oligoclonal IgG proteins of the CSF or brain carry measles antibody activities. In MS, only part of the oligoclonal IgG appears to be associated with measles antibody activity.     

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.     

Defective bud formation in human cells chronically infected with subacute sclerosing panencephalitis virus

Human prostate cells chronically infected with the Mantooth strain of subacute sclerosing panencephalitis (SSPE) virus multiply normally, fuse only occasionally to form giant cells, and yet have twisted intracytoplasmic nucleocapsids. These cells are able to support replication of vesicular stomatitis virus, although they release only small amounts of SSPE virus. To determine why carrier cells do not produce virus, they were examined with techniques for surface replication, freeze-fracturing, and immunoperoxidase labeling with SSPE antibody. The surface of carrier cells, like that of productive cells, is characterized by ridges crowned with viral antigens and devoid of the intramembrane particles revealed by freeze-fracture techniques. Since surface ridges form where nucleocapsids attach to the membrane, the shape and length of ridges are indicative of the shape and length of the underlying nucleocapsid. Whereas ridges on productive cells are serpentine in shape, those on carrier cells are typically straight or hairpin shaped, and the hairpin ridges are twice as long as serpentine ridges on productive cells. Furthermore, the spacing between ridges on carrier cells is never as small as that in productive infections, so that continuous sheets of viral membrane are never formed. The majority of carrier cells lack the round viral buds observed in productive cells but have, instead, many elongated processes attached to the cell surface. Each of these processes contains one or two hairpin ridges overlying hairpin-shaped nucleocapsids. These "hairpin buds" are restricted to a single region of the carrier cell surface, whereas viral buds are distributed over the entire surface of productive cells. Thus, there are several structural defects in carrier cells that depend on the specific interaction of a certain viral strain with a certain cell type. These defects prevent the deployment of viral antigen in some regions of the cell surface, the formation of nucleocapsids of normal length, the coiling of attached nucleocapsids, and the consolidation of sheets of viral membrane into spherical buds with the nucleocapsids coiled inside. These defects may account for the failure of carrier cells to shed infectious virus.     

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.     

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.     

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.     

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.     

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.     

IgG1 subclass restriction of oligoclonal IgG from cerebrospinal fluids and brain extracts in patients with multiple sclerosis and subacute encephalitides

Glucose metabolism in the healthy heart is stimulated by dichloroacetate (DCA). The possibility has been examined in dogs that DCA, by increasing glucose utilization, might limit the severity of acute myocardial ischaemic injury. Intravenous administration of DCA reduced the degree of epicardial ST-segment elevation induced by subsequent coronary occlusion, both under basal conditions and during isoprenaline infusion. A similar result was obtained when DCA was given during an established coronary occlusion. This effect could not be explained by changes in mean aortic blood pressure, heart rate, or regional myocardial blood flow as measured by radioactive microspheres. Measurements in arterial and coronary sinus blood demonstrated an increase in the extraction of glucose and a decrease in that of FFA by the heart. Glucose extraction also tended to be increased in the ischaemic zone, as shown by the differences in the concentrations of these substrates between arterial blood and blood obtained from the local vein draining that zone. Lactate release by the ischaemic zone was markedly reduced.     

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.     

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.     

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.     

Cerebrospinal fluid IgG profiles and multiple sclerosis in Japan

Since the introduction of acid-citrate-dextrose (ACD) in 1947 to anticoagulate and preserve whole blood for transfusion, various improved formulas, such as citrate-phosphate-dextrose-adenine (CPDA-1), have been successfully introduced, extending the current acceptable blood storage time to 35 days. Additional nutrient-anticoagulant solutions, including CPDA-2, CPDA-3, AS-1, and AS-5, among others, have more recently been studied with comparable results. In this study, lipid peroxidation (LP) was compared, as determined by the measurement of plasma malondialdehyde (MDA) by liquid chromatography, in stored blood preserved with various nutrient solutions with blood treated with CPDA-1. Although minor but inconsistent differences were noted with most of these solutions compared with CPDA-1, AS-1 gave consistently lower MDA levels (P < 0.01). Further improvements in red cell storage and viability may require approaches other than nutrient formula variations, such as the addition of metal chelating agents or other selected antioxidants to the nutrient-anticoagulant solutions, donor supplementation with vitamin free radical scavengers, or other as yet undetermined conditions.     

The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis

Sexual assault on children and adolescents has become a common topic of study, but there has been little research into the specific characteristics of the population of male victims. A national survey representative of school-age adolescents in France enabled us to study 465 adolescents reporting sexual assault (121 boys, 344 girls; mean age 15.4, SD 2.5 years). Girls were shown to be more frequently affected by certain medicopsychological symptoms: nightmares, multiple somatic complaints and some items concerning mood disorders. On the other hand, behavioural symptoms were much more frequently expressed in boys, in particular: repeated suicide attempts, running away, fits of violence and substance use. Boys presenting these symptoms should be questioned as a matter of routine concerning a history of sexual assault.     

Clinical picture and dynamics of psychopathologic disorders in subacute leuko-and panencephalitis

The report contains the results of clinico-dynamic studies of mental disorders in patients with Schilder's leukoencephalitis and subacute sclerosing panencephalitis after van-Bogart. The authors come to the conclusion that only parallel comparisons of the psychopathological symptomatology with focal neurological signs and a simultaneous study of the EEG and other paraclinical indices may facilitate the differential diagnosis of encephalitis.