Since Pasteur’s proposal of the germ theory in the 1860s, our knowledge of how micro–organisms produce disease has progressed rapidly. We have learned to control most infectious diseases, and by doing so have increased the quality of life enormously. We have now entered into a new era of virological research, that of the chronic or persisting infection. Technical advancements now make it possible to examine the virus–host relationship in greater detail.
Slow virus infections were first described by Siggurdson (1954), who set forth a number of criteria some of which are subjected to different interpretations today. In usage, the term usually refers to a fatal illness with insidious onset resulting from a slowly progressive virus infection. This case study aims to review SSPE (Sub–acute Sclerosing Pan Encephalitis), one of the three slow virus diseases of the central nervous system, with respect to its diagnosis, pathogenesis, epidemiology and possible means of detection and control.
SSPE (Subacute Sclerosing Pan Encephalitis)
SSPE, knows as Sub–acute Sclerosing Pan Encephalitis is a slow virus infection of the brain of relatively recent recognition.
In 1933, Dawson described an “Inclusion body encephalitis” characterized by involuntary movements and progressive mental retardation. Van Bogaert (1945) reported a clinically similar disease that he called “Sub–acute luko encephalitis.” It is clear that both authors were describing the same disease, now called Sub–acute Sclerosing Pan Encephalitis (SSPE).
This disease generally attacks children, preceded by an attack of measles, often unusually early in life, or occasionally, by previous immunization against measles. The onset of the condition is usually heralded by personality changes followed by development of involuntary movements. The electro encephalogram (EEG) exhibits characteristic bursts of high voltage activity. In most cases, the disease progresses relentlessly to death.
Slow Virus Diseases
The agents that cause slow virus diseases not only have a long latent period but also, when they produce the disease, it evolves at a much slower pace than normal infection, and does not clinically resemble an infection at all.
Since 1968, when the concept was first formulated, advances in our understanding of these diseases have made it appropriate to divide them into two groups.
- True Slow Virus Infections
Have a recognizable or known viral cause, such as Sub–acute Sclerosing Pan Encephalitis (SSPE), Progressive Multifocal Luko Encephalophathy. (PML) and Progressive Rubella Panencephalitis.
- The Unconventional Agent (Spongiform) Encephalopathies
(Kuru and Creutz Feldt Jakob Disease) have a histological appearance and are caused by agents not yet identified, which have some resemblance to conventional viruses but clearly lack many of their characteristics.
The disease progresses through three stages. Initially, there are behavioral changes and intellectual deterioration, Myoclonus occurs late in the first stage. In the second phase, there is further intellectual impairment along with extra pyramidal disturbances, rigidity and cortical blindness. In the final stages, intellectual impairment is profound and there is hypothalamic dysfunction and decerebrate posturing. Although the clinical course is not stereotyped, variations of the common sequence are not unusual. The earliest behavioral changes include an insidious decrease in school performance, forgetfulness, disobedience and outbursts of temper, sleeplessness, distractibility and hallucinations may occur. As the disease progresses, disturbances in writing, reading and vasomotor performance and constructional impairment become evident. Dressing disturbances, ataxia, apraxia, agnosia and Balints Syndrome may also be seen.
The myoclonic jerks initially involve the head and subsequently spread to the trunk and limbs. There is a sudden flexion movement followed by a one to two second relaxation periods. Initially, they are infrequent, but as the disease advances, the myoclonus occurs every five to 15 seconds. With further progression, extra pyramidal disorders occur. There is an expressionless face, paucity of spontaneous movement and appearance of dystonic movements. Decelerate rigidity becomes manifest in the final phase of the illness. Chorioretinitis, cortical blindness and abnormal eye movements may occur in some patients. Terminally death results from aspiration pneumonia or irreversible autonomic abnormalities.
Pathogenesis of Subacute Sclerosing Pan Encephalitis
Natural infection with measles can take several courses, however the pathogenesis of SSPE remains unclear. Almost all patients with SSPE fail to make an antibody response to the measles virus, M (matrix) protein despite an adequate antibody response to other viral proteins.
Absence of M protein could theoretically result from transcriptional or translational errors or the production of an unstable protein, although none of these abnormalities have been documented consistently in SSPE. It has been hypothesized that lack of M protein results in intracellular accumulation of incomplete measles virions in brain cells. The host immune response is unable to clear the intracellular infection and the persisting accumulation leads to neuronal dysfunction.
Diagnosis of Subacute Sclerosing Pan Encephalitis
Diagnosis of SSPE is based on clinical signs, EEG readings and elevated measles antibody in serum and the cerebrospinal fluid. These studies are inconclusive but the diagnosis can be confirmed by brain biopsy and demonstration of measles nucleocapsids by electron microscopy.
The long lag period between the occurrence of measles and onset of SSPE makes it difficult to be diagnosed at an earlier stage. Many therapeutic approaches have been attempted in SSPE but none have been consistently successful.
SSPE occurs in children 4 to 18 years of age with a peak incidence between 7 to 10 years. Most patients have a history of exposure to measles virus, many within the first two years of life which is followed after an interval of 6 to 8 years by the development of a progressive virological disorder. 85% of the cases are of those between 5 to 15 years at the time of diagnosis. The disease is twice as common in boys and seems to be seen more in children from rural backgrounds, the ratio of occurrence being 1:1,00,000.