Subacute sclerosing panencephalitis mortality, United States, 1979-2016: Vaccine-induced declines in SSPE deaths.

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease caused by measles virus. We estimate SSPE age-specific mortality in the United States, 1979-2016. The general decline in SSPE mortality reflects that of measles. Shifts, over time, in SSPE mortality by age echo changes in the age distribution of measles in the 1970s and in the 1989-91 outbreak. The current epidemiological situation is that autochthonous SSPE will disappear in the United States, assuming measles vaccination rates remain high.

Prognosis and demographic characteristics of SSPE patients in Istanbul, Turkey.

AIM: SSPE is a rare progressive, invariably fatal long-term complication of measles infection. In this study, we assessed the demographic and prognostic characteristics of 64 consecutive SSPE patients diagnosed at a tertiary center. METHODS: The study had a retrospective design; data were obtained from patient records. RESULTS: The study includes 64 patients diagnosed with SSPE. There was history of consanguineous marriage in 27 (42.2%) patients. The average patient lifespan was 3.8years (45days-12years). The average patient age at diagnosis was 12.3 (range, 5-17)years. A statistically significant correlation was found between the age at diagnosis and lifespan (p=0.002). A statistically significant correlation was found between the incubation period and patient lifespan (p<0.001). No significant correlation was found between duration in the intensive care unit and lifespan (p=0.122). Routine physical therapy had no significant impact on the average lifespan (p=0.619). No significant difference was found between the vaccination dose and lifespan (p=0.651). CONCLUSIONS: High frequency of parental consanguinity in SSPE patients need to be evaluated as there might a genetic influence. Physical therapy and supportive treatments seems to have no affect on lifespan in SSPE patients. The age at diagnosis and incubation period might have an affect on prognosis and lifespan.

Mutant fusion proteins with enhanced fusion activity promote measles virus spread in human neuronal cells and brains of suckling hamsters.

Subacute sclerosing panencephalitis (SSPE) is a fatal degenerative disease caused by persistent measles virus (MV) infection in the central nervous system (CNS). From the genetic study of MV isolates obtained from SSPE patients, it is thought that defects of the matrix (M) protein play a crucial role in MV pathogenicity in the CNS. In this study, we report several notable mutations in the extracellular domain of the MV fusion (F) protein, including those found in multiple SSPE strains. The F proteins with these mutations induced syncytium formation in cells lacking SLAM and nectin 4 (receptors used by wild-type MV), including human neuronal cell lines, when expressed together with the attachment protein hemagglutinin. Moreover, recombinant viruses with these mutations exhibited neurovirulence in suckling hamsters, unlike the parental wild-type MV, and the mortality correlated with their fusion activity. In contrast, the recombinant MV lacking the M protein did not induce syncytia in cells lacking SLAM and nectin 4, although it formed larger syncytia in cells with either of the receptors. Since human neuronal cells are mainly SLAM and nectin 4 negative, fusion-enhancing mutations in the extracellular domain of the F protein may greatly contribute to MV spread via cell-to-cell fusion in the CNS, regardless of defects of the M protein.

Long term survival in subacute sclerosing panencephalitis: an enigma.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) usually has a progressive stereotypic downhill course and results in premature death. Long-term stabilization or remission is exceptional. OBJECTIVE: To analyze the profile of patients with a relatively 'benign' course who survive beyond 3 years. DESIGN: Descriptive analysis of 19 (16 male, 3 females)/307 (6.2%) patients with benign course who were evaluated at NIMHANS between January 1995 and December 2004. Their diagnosis was based on characteristic myoclonic jerks, elevated antibody titers against measles virus in CSF and periodic complexes in EEG. RESULTS: The mean age at onset of symptoms was 11.7+/-3.9 years and mean duration of follow-up from first symptom was 5.9+/-3.1 years (3-13.8 years). Their initial symptoms were seizures (7), myoclonus (6), visual disturbances (4), behavioral changes (1) and cognitive impairment (1). These patients had varied clinical course: stabilization in different stages for 6 months to 5 years (13), remissions for 6 months to 9 years and reversal of staging with functional recovery from being bed bound to ambulant (8). Their diagnosis was often delayed. Small sample size did not permit to analyze the influence of possible disease modifying agents used in 10 patients (isoprenosine-3, amantidine-4, oral steroids-4, methylprednisolone-1, intravenous immunoglobulin-1). CONCLUSIONS: Our observations suggest that SSPE may have a highly variable clinical course and warrants cautious approach for counseling at initial evaluation and while interpreting beneficial effect of disease modifying agent(s). There is a need to explore prognostic marker(s).

Heart rate variability and autonomic dysfunction in SSPE.

Autonomic nervous system involvement in subacute sclerosing panencephalitis was studied in 29 patients by analysis of heart rate variability and compared with a control group which consisted of 20 age- and sex-matched healthy subjects. Holter recordings for 24 hours were obtained, and all recordings were analyzed using time-domain parameters. The patients with subacute sclerosing panencephalitis were found to have significantly lower values of standard deviation of all normal sinus intervals and triangular index when compared with the control group. Of 23 patients who had regular follow-up, 15 died in a period ranging from 1 to 13 months. Twelve of these patients had heart rate variability parameters lower than normal, but no significant difference was observed between the heart rate variability values of patients who survived or died. Also, there was no association between brain magnetic resonance imaging findings and heart rate variability indices. It is concluded that patients with subacute sclerosing panencephalitis have autonomic dysfunction; and this was thought to be mainly due to central involvement.

[Bilateral retinitis: early manifestation of subacute sclerosing panencephalitis. A case report]. / Rétinite bilatérale révélatrice d'une panencéphalite sclérosante subaiguë

Subacute sclerosing panencephalitis (SSPE) is a progressive encephalitis caused by persistent measles infection. The disease is almost always fatal and mainly affects children and young adults. Ophthalmological signs are frequently observed and can be the presenting manifestations. We report the case of a 22-year-old young man who presented with bilateral posterior retinal necrosis confirmed by fluorescein angiography and normal laboratory tests. The appearance of peripheral retinal tears and stereotyped myoclonic movements were signs of the evolving condition. Diagnosis of SSPE was confirmed by brain MRI, EEG, and cerebrospinal fluid examination. The patient's neurological condition deteriorated rapidly and he died 2 months following the onset of ophthalmological manifestations.

Evidence that the hypermutated M protein of a subacute sclerosing panencephalitis measles virus actively contributes to the chronic progressive CNS disease.

Subacute sclerosing panencephalitis (SSPE) is a progressive degenerative disease of the brain uniformly leading to death. Although caused by measles virus (MV), the virus recovered from patients with SSPE differs from wild-type MV; biologically SSPE virus is defective and its genome displays a variety of mutations among which biased replacements of many uridine by cytidine resides primarily in the matrix (M) gene. To address the question of whether the SSPE MVs with M mutations are passive in that they are not infectious, cannot spread within the CNS, and basically represent an end-stage result of a progressive infection or alternatively SSPE viruses are infectious, and their mutations enable them to persist and thereby cause a prolonged neurodegenerative disease, we utilized reverse genetics to generate an infectious virus in which the M gene of MV was replaced with the M gene of Biken strain SSPE MV and inoculated the recombinant virus into transgenic mice bearing the MV receptor. Our results indicate that despite biased hypermutations in the M gene, the virus is infectious in vivo and produces a protracted progressive infection with death occurring as long as 30 to 50 days after that caused by MV. In primary neuron cultures, the mutated M protein is not essential for MV replication, prevents colocalization of the viral N with membrane glycoproteins, and is associated with accumulation of nucleocapsids in cells' cytoplasm and nucleus.

[Epileptic seizures and epilepsy in subacute sclerosing panencephalitis (report of 30 cases]. / Crises épileptiques et épilepsie dans le cadre d'une panencéphalite sclérosante subaiguë (à propos de 30 cas).

Subacute Sclerosing Panencephalitis (SSPE) is becoming less frequent in Morocco since the generalization of measles vaccination in 1982. The aim of this study was first to analyze the semiological and elecrophysiological profiles of epilepsy in SSPE in both 'disease-revealing' seizures and sequellar ones, and second, to study the evolution of epilepsy and its possible prognostic value in SSPE. Among the neurological manifestations of SSPE, epilepsy is not as rare as frequently reported in the literature. In this longitudinal series concerning 70 cases of SSPE, 30 developed epilepsy. In two-thirds of our patients the epileptic seizures started in the first year of evolution; they revealed the SSPE in 23% of the cases and were sequellar in the rest. Seizures revealing the SSPE were widely dominated by partial seizures, secondarily generalized or not (86%), suggesting a focalized encephalitic process. Conversely, sequellar seizures were in most cases generalized tonic-clonic (43%), and therefore compatible with an already spread process. The EEG contributed both to the diagnosis of SSPE and to that of the epilepsy, showing epileptic abnormalities in ten patients. The outcome of epileptic seizures was very favorable under antiepileptic drugs, while that of SSPE remained severe and not modified by epilepsy. The authors underline the relative frequency of epilepsy in SSPE, the interest of the distinction between revealing and sequellar seizures, the good prognosis of epilepsy under adequate therapy, and the absence of prognostic value of epilepsy in SSPE.

[The evaluation of the use of antineoplaston AS2-1 treatment in subacute sclerosing panencephalitis]. / Ocena zastosowania Antyneoplastonu AS2-1 w podostrym stwardniajacym zapaleniu mózgu.

A follow-up study was carried out of 16 SSPE patients two years after completion of 6-month treatment with Antineoplaston. The study was based on an inquiry sent to the families of the patients and on control examinations at the clinic. In the period of follow-up 6 patients died, all had the downhill type of disease course and their mean survival was 18 months. Out of the remaining 10 patients 4 are in stationary condition and the remaining ones had minimal worsening. A more detailed clinical analysis showed that half the patients were in contact with and general orientation in the environment, but impairment of motor functions made difficult in most cases self-care and self-dependent functioning. All patients had evident changes in brain MRI. The survival time of the patients has been as yet from 2.5 to 5.5 years (mean 3.9 years). The results of the treatment with Antineoplaston AS2-1 + isoprinosine are comparable with those observed during isoprinosine alone treatment but significantly worse than those after administration of Propionibacterium granulosum with isoprinosine. This suggests that Antineoplaston AS2-1 fails to modify importantly the natural course of SSPE.

Isolation of a measles virus variant: protection of newborn mice from measles encephalitis by 24 h prior intracerebral inoculation with the variant.

A small plaque mutant with reduced neurovirulence in newborn mice was obtained from Edmonston strain measles virus after propagation for 5 months in NIH3T3 cells. It retained the antigenicity of the parental virus and tended to induce higher neutralizing antibody titers in the adult BALB/c mice. The intracerebral (but not intraperitoneal) inoculation of the live mutant virus one day before prevented the newborn BALB/c mice from encephalitis caused by the intracerebral challenge with the parental strain at a dose of 10-20 LD50. The intracerebral inoculation with the mutant virus whose replication capacity was inactivated by UV-irradiation was ineffective. The protection was not attributed to interferons nor to viral interference. The mechanism remains unknown.

Subacute sclerosing panencephalitis (SSPE): early diagnosis, prognostic factors and natural history.

We studied the value of long video-split electroencephalographic monitoring (VSEEG) in detecting myoclonus in nearly SSPE and evaluated the natural history and outcome-affecting factors. The 32 newly diagnosed patients had VSEEG to detect myoclonus and its correlations with EEG periodic complexes. Disease progression was monitored by a special "outcome score'; the chi-square test and multi-variable statistics analysed the outcome score in relation to different variables, such as age at onset, sex, duration of symptoms at presentation, CSF measles antibody titre, type and interval between periodic complexes (EEG discharges). Myoclonus or atonia occurred in all patients and was time-related to the EEG periodic complexes; in 32% of patients, myoclonus or atonia were not clinically evident. The EEG periodic complexes were of 3 types: Type I (16 patients) periodic giant delta waves; Type II (10 patients) periodic giant delta waves intermixed with rapid spikes or fast activity; and Type III (6 patients), long spike-wave discharges interrupted by giant delta waves. Outcome score was associated with symptoms duration (P < 0.01) and EEG periodic complexes (P < 0.05). Symptom duration was inversely related to final outcome (multi-variable analysis). Long VSEEG monitoring greatly improves early diagnosis and detection of subtle atonia or segmental myoclonus. Prognostic factors were the type of EEG periodic complexes and duration of symptoms at presentation.

[Subacute sclerosing panencephalitis in Poland in the years 1990-1993. Stage V of epidemiologic studies]. / Podostre stwardniajace zapalenie mózgu (SSPE) w Polsce w latach 1990-1993. V etap badan epidemiologicznych.

The authors summarize the results of the fifth stage of epidemiological investigation on SSPE. The first stage covered the years 1971-1976, the next stages covered the periods: 1977-1983; 1984-1986; 1987-1989. In the period 1990-1993 data on 95 patients with SSPE were obtained. Morbidity rates continued to show a decreasing tendency (from 0.8 to 0.6 per 1,000,000 population) in the years 1990-1993, being lower the median morbidity (amounting to 0.98) in 1985-1989. Morbidity rates continued to shift towards older age groups: while the peak morbidity (25.7%) in the years 1990-1992 was noted in the 14-15 age range, in 1993 the peak (28.6%) was found in the age group of 16 to 19 years.

[Selective problems from catamnestic studies of SSPE patients (1980-1989)]. / Wybrane zagadnienia z badan katamnestycznych pacjentów z SSPE (1980-1989).

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.

Subacute sclerosing panencephalitis in Wales.

Twenty cases of subacute sclerosing panencephalitis (SSPE) occurring over an 18-year period in Wales are described and used as the basis for a comparison of measles infection, vaccination rates and the incidence of SSPE in England and Wales. Rates of measles infection were higher in Wales in all age groups, and fewer Welsh children were vaccinated, which maintained a high risk of SSPE per case of measles. Following vaccination, there was a more pronounced change in the age distribution of measles infection in Wales than in England, and it is proposed that one contribution to the high frequency of SSPE in the 1980s was the reservoir of measles in unvaccinated 2-4-year-olds, acting as a source of infection for children aged < 2 years, in whom the risk of SSPE following measles is known to be higher than in other groups.

Subacute sclerosing panencephalitis in Riyadh, Saudi Arabia.

The clinical features and outcome of disease in 14 cases of subacute sclerosing panencephalitis (SSPE) diagnosed at the King Khalid University Hospital, Riyadh during an 8-year period are similar to those described elsewhere. Therapy was associated with arrest of deterioration for 2.5 years in one patient, and with survival after diagnosis for 2-7 years in four others. Many of the cases had initial misdiagnoses because of the frequently bizarre modes of presentation. It is thought that many more cases of SSPE occur in Saudi Arabia and also in many other tropical countries than are currently recognized. The establishment of national SSPE registries is advocated to improve early identification and management of cases.

Neurological diseases in Karachi, Pakistan--elevated occurrence of subacute sclerosing panencephalitis.

Neurological diseases, especially subacute sclerosing panencephalitis (SSPE), were surveyed in Karachi, Pakistan disclosing following major results. (1) Indirectly estimated prevalence rates of selected neurological disease entities were comparable with the rates from western countries and Japan in heredodegenerative diseases, but grossly elevated in infectious diseases. (2) Estimated mortality statistics for the Karachi community revealed highly elevated rates for infectious, parasitic and perinatal causes of death. (3) SSPE represented about 10% of inflammatory afflictions of the cerebral parenchyma, its incidence rate being about 100% times more than that observed in developed countries. A case-control study preliminarily showed that infants who later contract SSPE have unhealthy mothers, are born small, and have various occurrences of ill health from birth to the onset of SSPE. (4) Age at the onset of measles was very young in the cases as well as in controls, unlike the average young age at onset of cases only in developed countries. Measles contracted at young age is a well known risk factor to SSPE. Whereas few children in developed countries acquire measles at such an early age, many Karachi children do. Elevated occurrence of SSPE is probably conditioned by such age patterns of measles infection, together with other risk factors more common in Karachi due to poorer health standards. A proper immunization programme is urgently needed to control measles and SSPE.