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.     

Subacute sclerosing panencephalitis in Bulgaria (1978-2002)

The epidemiology of subacute sclerosing panencephalitis (SSPE) has changed substantially since the introduction of measles vaccine. We studied the incidence of SSPE in Bulgaria based on cases admitted to the Child Neurology Clinic, University Hospital of Neurology and Psychiatry, Sofia, for a 25-year period (1978-2002). The SSPE incidence prior to and during the period of routine measles immunization was analyzed. SSPE was diagnosed in 40 children (29 males and 11 females, mean age 8.5 years), 28 from 1978 to 1984 (average 4 patients/year), and 12 from 1995 to 2002 (average 1.7 patients/year). Thirty-eight cases (95%) were non-immunized and had early measles infection. Age at onset of SSPE ranged from 8 to 11 years (52.5%) with a mean latent period of 7 years following measles infection. The increase in SSPE incidence (1995-2002) following a 10-year disease-free period (1985-1994) appears to be related to early measles infection (mean age 11 months) during the measles epidemic of 1991-1992. During the period 1995-2002, children had earlier measles infection (average 11 months) and earlier onset of SSPE (mean age 8.4 years) than in the period 1978-1984 (mean age at measles infection 18 months, and of SSPE onset 11.2 years). The SSPE incidence in Bulgaria during the 25-year period from 1978 to 2002 confirms the importance of early measles infection as a risk factor for SSPE, and the role of routine measles immunization in SSPE prevention.     

Elevated ratio of late measles among subacute sclerosing panencephalitis patients in Karachi, Pakistan.

Subacute sclerosing panencephalitis (SSPE) in Western countries and Japan is found more often in early- than in late-measles sufferers. Recent SSPE findings in Karachi, however, present a different picture. Age at measles contraction was obtained and analyzed for 44 SSPE patients identified in Karachi between 1983 and 1988. The ratios of early- (< 2 years of age) and late- (> or = 2 years of age) measles sufferers among 36 of these patients who had experienced only one attack of measles were 0.33 and 0.67, respectively. This is in striking contrast to the predominance of early measles in the SSPE histories reported in Japan and an number of Western countries.     

Subacute sclerosing panencephalitis surveillance study in Istanbul

The exact incidence rate of subacute sclerosing panencephalitis (SSPE) in Turkey (and in Istanbul) is not known. We have conducted an active surveillance study to determine the epidemiological characteristics and the incidence rate of SSPE in Istanbul between the dates July 1, 2002 and July 1, 2004. We found that the incidence of SSPE in Istanbul is 2 per million. By logistic regression analysis, risk factors in SSPE development are determined as being at younger ages (OR: 1.199, 95%CI=1.047-1.372, P=0.009), living in crowded households (OR: 1.430, 95%CI=1.039-1.968, P=0.028), low education level of the mother (OR: 0.123, 95%CI=0.034-0.447, P=0.001), low household income (OR: 0.413, 95%CI=0.234-0.728, P=0.002), infant's being born out of Marmara region (Istanbul is in Marmara region of Turkey) (OR: 0.358, 95%CI: 0.172-0.746, P=0.006), infant's not being vaccinated against measles (OR: 0.495, 95%CI: 0.312-0.786), infant's having had measles before (OR: 0.235, 95%CI: 0.135-0.411). As a result, it is found in this study that SSPE is mostly related to having measles infection, and measles vaccination is found to be highly protective against SSPE. This is the first epidemiological study in SSPE from Turkey that conveys the incidence rate in Istanbul.     

Subacute sclerosing panencephalitis in Italy

An epidemiological inquiry in Italy led to the collection of 207 cases of subacute sclerosing panencephalitis (SSPE) with onset during the decade 1972-1981, with a mean incidence rate of 0.37 cases per year per million total population (CYMTP) and 1.24 cases per year per million young population aged 0-19 years (CYMYP). A striking difference was found among the 20 Italian regions, with a minimum of no cases in three regions, and a maximum incidence of 2.46 CYMTP (6.67 CYMYP) in Sardinia. The male/female ratio was 1.8/1. The mean age at SSPE onset was 10.6 (+/- 4.0) years in Italy, and was significantly lower in Sardinia (8.8 +/- 2.8). The mean age of measles was 2.8 +/- 1.7 years (in 106 cases), significantly lower than the mean age of measles in the general population. Moreover, the age of measles was significantly lower in males than in females, and this could represent a factor contributing to the higher SSPE incidence in males. The interval between measles and SSPE onset was significantly lower in Sardinia (mean 5.6 +/- 2.5 years). In Italy, as in other Mediterranean countries, SSPE incidence is higher than expected and unevenly distributed, suggesting that environmental factors play a role.     

A 4-year-old with pica, progressive incoordination, and decreased responsiveness

This article reports a typical case of subacute sclerosing panencephalitis (SSPE). The patient contracted measles as an infant during the 1989 to 1991 United States measles epidemic. At 4 1/2 years of age, he developed behavioral changes and quickly progressed through the typical clinical stages of SSPE. His EEG was characteristic. Serum and CSF measles immunoglobulin G were markedly elevated. He remains alive but is vegetative. To our knowledge, this is the first case of SSPE stemming from the 1989 to 1991 measles epidemic. Because infants--the group at highest risk to develop SSPE--were most severely affected by this measles outbreak, other cases of SSPE stemming from this epidemic may occur.     

Subacute sclerosing panencephalitis in a child with human immunodeficiency virus (HIV) infection on antiretroviral therapy

Subacute Sclerosing Panencephalitis (SSPE) in HIV-infected children is a scarcely reported entity with previous reports describing fulminant course. The impact of highly active antiretroviral therapy (HAART) in altering its course remains unknown. We describe a child with HIV infection, who developed measles at 5 months of age and later developed SSPE at 14 years of age, remaining stable at 7 month follow-up, while on HAART for WHO (World Health Organisation) stage IV disease. The dynamics of HIV-related immunosuppression has an impact on the clinical course of SSPE. Contrary to reported cases of fulminant progression, a classic presentation with slow progression can be expected in children on HAART. We reemphasize the recommendation of “early measles vaccination” to prevent measles infection and subsequent SSPE in these children with an increasingly good life expectancy in the era of HAART.     

Epidemiology of subacute sclerosing panencephalitis in Okinawa, Japan (1977-2005)

The epidemiology of subacute sclerosing panencephalitis (SSPE) has changed since the introduction of measles immunization in 1970's. We studied the incidence of SSPE in Okinawa. There were 22 cases (16 males and 6 females) of SSPE from 1977 to 2005 in Okinawa. The incidence was 0.63 per million population per year from 1977 to 1986, 0 from 1987 to 1993, 1.17 from 1994 to 1999 and 0.75 from 2000 to 2005. Twenty-one SSPE patients had a history of non-immunized measles and 19 of them (90%) had measles infection under 2 years of age. There were measles epidemic every 2-5 years in Okinawa. Ten of 21 cases contracted measles in 1990-1991. The percentage of patients with measles infection under 2 years of age during measles epidemics ranged from 46% to 56%. Early measles infection (under 2 years of age) is a risk factor for SSPE. Routine measles immunization to prevent measles infection is very important for the prevention of SSPE.     

Subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a subacute encephalopathy of childhood and young adolescence. Infrequently, SSPE can occur in adults and pregnant women. It is caused by an aberrant measles virus, known as the SSPE virus. SSPE virus differs from wild-type measles viruses in the form of several mutations affecting the viral genome. The matrix gene is most commonly affected by these mutations. The characteristic clinical manifestations of SSPE include behavioral changes, cognitive decline, myoclonic jerks, seizures, abnormalities in vision, bilateral pyramidal signs and coma. Ocular changes may occur in up to 50 % of patients. The most characteristic ophthalmological lesion is necrotizing retinitis. Cortical blindness can be the early feature of SSPE. The diagnosis of SSPE is often difficult in the early stages. In a typical case diagnosis is based on clinical, electroencephalographic, and cerebrospinal fluid findings. At present, there is no effective treatment to completely cure SSPE. Oral isoprinosine and intrathecal or intraventricular alpha-interferon may prolong survival to some extent. Immunization against measles is currently the most effective strategy against SSPE. Electronic Supplementary Material  The online version of this article DOI contains supplementary material, which is available to authorized users.     

早期生活-阿尔茨海默病发病的危险因素

目的 研究早期生活因素与阿尔茨海默病（AD）的关系。方法 在社区基础上行病例对照研究（病例组和对照组各11例）。研究这些病例25岁以前的居住地、教育、出生时母亲年龄、父亲年龄、同胞个数及家中排行。结果 兄弟姐妹人数每增加一个,发病的危险性增加2％（OR=1.02）;同胞数7个以上者患AD的危险性是7个以下的4.19倍（OR=4.19）;出生时母亲年龄在35岁以上的患病危险性高（OR=1.25）;出生排行中,排行每增加一个,患病危险性增加26％（OR=1.26）。早期生活在农村的低文化者患病危险性（OR=2.14,95％CI=1.05-4.87）高于其他环境的患者。结论 早期生活因素和环境因素与阿尔茨海默病发生的危险性有关,低文化本身可能是这些因素的一个伴随标记。     

Measles virus-specific immunoglobulin D antibody in cerebrospinal fluid and serum from patients with subacute sclerosing panencephalitis and multiple sclerosis

Quantitation of measles-specific immunoglobulin D (IgD) antibody was carried out in cerebrospinal fluid (CSF) and serum samples from 18 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS) and seven normal controls with high measles antibody titers in serum, using polyclonal and monoclonal antibodies specific for human IgD and enzyme-linked immunosorbent assay. Measles-specific IgD activity was significantly higher in CSF and serum from SSPE patients compared to that found in patients with MS or normal controls. The IgD antibody to measles virus was not due to high levels of measles-specific IgG since significant measles IgD activity was found after eluting IgG from SSPE serum. The increased level of measles-specific IgD found in SSPE sera is consistent with the levels observed in patients with acute and chronic viral infections.     

Early-life risk factors and the development of Alzheimer's disease

OBJECTIVE: To investigate the association of early-life factors with AD. BACKGROUND: The early-life environment and its effect on growth and maturation of children and adolescents are linked to many adult chronic diseases (heart disease, stroke, hypertension, and diabetes mellitus), and these effects are also linked to maternal reproduction. AD may have an early-life link. The areas of the brain that show the earliest signs of AD are the same areas of the brain that take the longest to mature during childhood and adolescence. A poor-quality childhood or adolescent environment could prevent the brain from reaching complete levels of maturation. Lower levels of brain maturation may put people at higher risk for AD. METHODS: In a community-based case-control study (393 cases, 377 controls), we investigated the association of early-life factors and AD. Early-life variables include mother's age at patient's birth, birth order, number of siblings, and area of residence before age 18 years. Patient education level and apolipoprotein E (APOE) genotypes were also included in the analysis. Results: Area of residence before age 18 years and number of siblings are associated with subsequent development of AD. For each additional child in the family the risk of AD increases by 8% (OR = 1.08, 95% CI = 1.01 to 1.15). More controls compared with cases grew up in the suburbs (OR = 0.45, 95% CI = 0.25 to 0.82). APOE epsilon 4 and the patient's education level did not confound or modify the associations. CONCLUSIONS: The early-life childhood and adolescent environment is associated with the risk of AD.     

Very preterm birth, birth trauma, and the risk of anorexia nervosa among girls.

BACKGROUND: Obstetrical complications, based on parental recall, have been reported to be associated with development of anorexia nervosa. We used prospectively collected data about pregnancy and perinatal factors to examine the subsequent development of anorexia nervosa. METHODS: This population-based, case-control study was nested in cohorts defined by all liveborn girls in Sweden from 1973 to 1984. From the Swedish Inpatient Register, 781 girls had been discharged from any hospital in Sweden with a main diagnosis of anorexia nervosa at the age of 10 to 21 years. For each case, 5 controls were randomly selected, individually matched by year and hospital of birth (n = 3905). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for potential risk factors. RESULTS: Increased risk of anorexia nervosa was found for girls with a cephalhematoma (OR, 2.4; 95% CI, 1.4-4.1) and for very preterm birth (< or = 32 completed gestational weeks) (OR, 3.2; 95% CI, 1.6-6.2). In very preterm births, girls who were small for gestational age faced higher risks (OR, 5.7; 95% CI, 1.1-28.7) than girls with higher birth weight for gestational age (OR, 2.7; 95% CI, 1.2-5.8). CONCLUSIONS: Our results show that perinatal factors, possibly reflecting brain damage, had independent associations with anorexia nervosa. These risk factors may uncover the mechanisms underlying the development of the disorder, even if only a fraction of cases of anorexia nervosa may be attributable to perinatal factors.     

Impaired human leukocyte antigen-restricted measles virus-specific cytotoxic T-cell response in subacute sclerosing panencephalitis

The capacity of peripheral blood lymphocytes to proliferate in response to measles virus and to generate measles virus-specific cytotoxic T lymphocytes (CTL) was examined in 4 patients with subacute sclerosing panencephalitis (SSPE). The lymphoproliferative response to measles virus was obtainable in the 4 SSPE patients. In contrast, the CTL response to measles virus was reduced in 3 of the 4 SSPE patients. This defect appeared to be in the generation of the measles virus-specific CTLs, since measles virus-infected target cells from the patients could be lysed by human leukocyte antigen-matched peripheral blood lymphocytes from healthy individuals. The SSPE patients with reduced measles virus CTL response had a normal ability to generate mumps virus, influenza virus, or alloantigen-specific CTLs. The lysis of measles virus-infected targets that was observed with these SSPE patients could be reduced by depleting the effectors of natural killer cells or by performing cold target blocking with K562 cells, indicating that the lysis of the measles virus-infected targets was probably mediated by natural killer cells. These results demonstrate a reduction in the cell-mediated immune response to measles virus as measured by the generation of measles virus-specific CTLs in 3 of the 4 SSPE patients studied. This defect could relate to the persistence of measles virus in these patients.     

Subacute sclerosing panencephalitis in only one member of a monozygotic twin pair. Clinical, laboratory, electroencephalographic, and immunological study of both twins

Male monozygotic twins, one of whom developed subacute sclerosing panencephalitis (SSPE) are reported in detail. Both patients had measles at the age of 4 years and 6 months. The diagnosis of SSPE was based on clinical, electroencephalographic and laboratory findings. Titration of antibodies against measles was carried out in both cases. The healthy twin, who had been admitted with a clinical picture initially similar to that displayed by his brother, showed clinical manifestations mimicking those of the affected sib, but these vanished 4 days after his admission and were attributed to transient conversion hysteria.The genetic factors involved and the biological response of the antibodies against measles are discussed.     

SSPE-epidemiology and measles vaccination: our cases

We are discussing the results of an epidemiologic prospective study of 194 children with SSPE. We analyzed, registered and treated these SSPE patients in the period from 1952 to 1983 at the Department for Child Neurology and Psychiatry in Belgrade. There were 140 boys and 54 girls with SSPE. The male to female ratio was 2.6:1. The average age of onset was 8.3 years for boys and 7.2 years for girls, the overall average being 7.7 years. The average duration of illness was 10 months for boys and 8 months for girls; the overall average duration of SSPE was 9 months. The average age for measles infection was 2.4 years. The interval between measles infection and clinical manifestation of SSPE was 5.5 years. The patients came from different parts of Yugoslavia. Most of them were from SR Serbia (95 patients or 49%), AP Vojvodina (39 patients or 20%), SR Bosnia and Herzegovina (22 patients or 11%), AP Kosovo (14 patients or 7.2%), SR Macedonia (14 patients or 7.2%), SR Croatia (6 patients or 3%), and SR Montenegro (4 patients or 2.5%). Mass measles vaccination started in SR Serbia in 1972. In the period 1952-1983 there was an average of six registered patients with SSPE per year. In the same period, there were four peaks of illness: 20 patients in 1957, 15 patients in 1958, 12 patients in 1961, and 9 patients in 1977. The average number of SSPE per year in the period 1952-1972 was 7.2 patients before mass vaccination. The average number of SSPE per year in the period 1973-1983 was 3.3 patients after mass vaccination.     

The effects of measles virus and various strains of SSPE virus on organotypic cultures of nervous tissue

Summary The neurotropic effects, virologic behaviors and morphologic appearances of 4 strains of subacute sclerosing panencephalitis (SSPE) virus have been examined in organotypic cultures of hamster cerebellar tissue and have been compared with the Edmonston strain of measles virus in the same system. While measles virus caused extensive damage to nervous tissue, the SSPE strains, in general, exerted a less deleterious effect. All of the SSPE viruses replicated in this tissue. The SSPE strains showed morphologic variation ranging from normal measles-type virions to apparently nucleocapsid deficient forms. It is speculated that some of these differences between measles and SSPE virus may account for the differences in the in vivo conditions with which they are associated.     

Subacute sclerosing panencephalitis in only one of identical twins. A seven-year follow-up

We report a seven-year follow-up of identical twins, in one of whom subacute sclerosing panencephalitis (SSPE) developed. Primary measles infection occurred simultaneous in both twins at age 4. The affected twin sustained a grade 1 closed head injury within six months of her primary measles infection. At age 13, SSPE was diagnosed following the onset of personality change and myoclonic seizures. Measles antibody level was elevated in the serum and CSF. After remaining in stage 2 for five years, rapid mental and neurological deterioration occurred. Measles antibody level remained elevated, and oligoclonal IgG was present in both serum and CSF. Results of neurological examination as well as virological and immunological tests were normal in the unaffected twin. Besides the occurrence of head injury, factors known to be associated with SSPE were not obviously different in the twins. We have been unable to determine a difference that would easily explain the occurrence of SSPE in only one of two identical twins.