Journal of Pediatric Neurology, Vol. 2, No. 3, July-Sept, 2004, pp. 121-124

EDITORIAL

Some aspects about the clinical and pathogenetic characteristics of the presumed persistent measles infections: SSPE and MINE

Paul Richard Dyken 

Institute for Research in Childhood Neurodegenerative Diseases, Mobile, Alabama, U.S.A.
Correspondence: Paul Richard Dyken, M.D., MLA, BS. Director of the USA/World SSPE
Registry since 1980 Offices located in Institute for Research in Childhood Neurodegenerative Diseases 283 Wingfield Drive Mobile, Alabama, 36607, U.S.A. Tel: 1 251-478-6424, fax: 1 251-476-8277. E-mail: pdyken@aol.com

Received: June 4, 2004. Accepted: June 5, 2004.

Code Number: pn04025

It is well known that Subacute Sclerosing PanEncephalitis (SSPE) is due to an aborted form of the wild measles virus which results from a faulty immune reaction of the human body (1). The pathogenesis of this particular slow virus disease begins when an immunologically incompetent individual is attacked by the virus and is thereby unable to launch a full immune response, allowing parts of the aborted virus to harbor in the central nervous system. As is typical of all slow virus diseases, the aborted virus remains quiescent for a number of months to years only to break out to produce the neurological and ophthalmic symptoms of SSPE. The major components of the disease results from the progressive deterioration of the host’s nervous system, first starting with sometimes subtle and nonspecific higher cortical symptoms such as abnormal behavior, learning disabilities, single epileptic seizures and visual disturbances which formulate in months into a characteristic clinical period called stage I. Then the near diagnostic period of repetitive massive myoclonic jerks, beginning mental failure, motor disability in its early stages and immobility are seen which constitutes what has been called stage II. This stage is also progressive and in a few months the involuntary movements disappear and the dementia worsens. Stage III is a nonambulatory state of clinical affairs with ultimately complete motor failure, loss of the previously seen involuntarymovements and severe dementia. Stage IV represents a severe “vegetative” stage which plateaus to severe neurological disability of at least 90% or death. This typical clinical progression is closely correlated with a rostral-caudal neural destruction. Most of what is thought to be clinically typical about this disease, is a manifestation of the neuropathological and clinical happenings which occur in stage II. This stage represents the classical subacute progressive clinical picture of what I call the subacute progressive form (SPF) of SSPE. There are other more atypical forms of the disease. The classical or SPF form and presentation represents only about 75% of the cases of SSPE which has been reported to the USA/World SSPE Registry since 1989.

In the 1960s, in the heyday of SSPE and natural measles in the USA, about 60 cases of SSPE were reported per year whereas there were over 500,000 cases of natural measles infections reported, giving a ratio of 1 case of SSPE to 10,000 cases of measles exanthema. After the first national immunization program against measles was initiated in this country in the early 1960s, measles began to drop in frequency. There is usually a 7 to 10 year latent or interval period in the development of SSPE after the first contact with the wild measles virus. After correcting for the interval period, SSPE was also shown to drop in frequency (2). Because of these phenomena, other countries began to develop national immunization programs, and they soon found, in most instances, that mass immunization produced similar dramatic results.

In the USA, it is generally believed that SSPE is a figment disease of antiquity. It is true that only 80 cases of SSPE has been reported to the Registry by USA physicians in the last 15 years. Yet, because of the disease’s well worked out mechanisms of etiology, pathogenesis and near elimination, understanding is of great importance, to USA pediatric neurologists and other health care workers. This understanding is even of greater importance to the health care workers in developing and developed nations outside of the USA where the incidence of this disease is at present greater than in the USA. It is particularly important because, in spite of a declining incidence due to effective national measles immunization programs, these mechanisms of disease may be an explanation for entirely new or unrecognized disorders with similar pathogenesis and etiology. In other words, other diseases of similar nature, such as the progressive childhood neurodegenerative diseases, specifically and generally, may also be caused by similar mechanisms. It goes without saying that the childhood neurodegenerative diseases of unknown or uncertain cause represent a large portion of any practice of pediatric neurology in both the “developed” and the “developing” nations of the world.

The relationship of SSPE to persistent measles infection is well established, but the second syndrome discussed in this paper is not. The syndrome (3) that I call MINE (Measles Induced Neuroautistic Encephalopathy) is properly categorized as a childhood neurodegenerative disease but with uncertain etiology. In the last few years, this syndrome has been shown to be related to the live measles vaccination, if not proven to be caused by it. The syndrome was first recognized in the late 1990s by Wakefield et al. (4), a gastroenterologist in Britain. What was initially described was a syndrome consisting of chronic recurrent enterocolitic symptoms starting in young children. These patients also seemed to have chronic neurological symptoms which were considered to be autistic in nature. Wakefield et al. (4) considered the syndrome to be related to the immunization of infants with live-attenuated measles vaccine. Over the following years, approximately 2000 children with variants of this autistic-colitic syndrome were reported. Because of my interests in SSPE, I was able to carefully evaluate 12 of these patients, sharing the patient’s clinical information and full laboratory data with the Solicitor firm (5) which handled the rather large class action suit resulting from these reports.

Altogether, the key features of this syndrome were not always associated with both enterocolitis and pervasive developmental disorder. In the review of 12 patients, two major varieties of the syndrome were identified, one with pure neuroautistic features (n=4) and the second with additional chronic recurrent enterocolitis (n=8). In addition to at least two of the four classic symptoms of autism (i.e. defects of intellect, behavior, social adjustment and language development), the children who were evaluated had other neurological symptoms such as epileptic seizures, micrencephaly, dysgenetic features and rarely progressive mental retardation which would more rightly be considered to be frank  dementia. Both of these variations, that is, the pure neuroautistic and the neuroautistic/enterocolitic patients seemed to be induced by the live-attenuated measles virus vaccination, after a latency period of several months. In each patient, regardless of type, measles virus genes were found in the tissues studied, such as blood, gut and spinal fluid. In those with enough antigen identified, the genes were found to arise from the vaccine-related live-attenuated measles virus and not from the usual wild measles virus which is associated with measles exanthema. The two viruses have the same antigenic make-up. The proteins are the same but one of them is wildly alive and the other is alive but attenuated.    

These are the constellation of features which make up the MINE syndrome

An opinion can be given that MINE develops in the same fashion as does SSPE. Although the syndromes are different the etiology and the pathogenesis are similar. For both syndromes, two factors are required: an immature or defective immune system which is unable to inactivate the attacking measles virus whether it is the wild or the live-attenuated form. In the situation of SSPE the full antigenic wild virus is only partially inactivated, allowing the remaining, aborted form to escape and harbor within the large neurons of the cerebral cortex where they are sheltered and persist, to grow. Then, in years, the persistent virus breaks out, devastatingly inflames and destroys in a rostral-caudal fashion other neurons, endothelial cells, glial elements and cellular processes. It is presumed that in SSPE, susceptible patients have had contact with the wild measles virus before immunization if they are ever immunized. Yet, this is the reason the incidence of both measles exanthema and SSPE are dropping with the institution of effective national immunization programs. All data that has been accumulated suggests that measles immunization does not cause SSPE, but the opposite occurs. In the situation of MINE, the child has not been exposed to the wild measles virus yet but instead is immunized with a much less virulent but antigenically comparable live-attenuated measles virus. Most individuals become immune to the wild measles virus when the live-attenuated one is given them, but a relatively small portion of them react in a different fashion. This small portion is judged to be 1 in 10,000; based on the fact that in Britain about 20,000,000 children have been immunized in the last 20 years and about 2,000 have developed the MINE syndrome. Those who develop MINE do not completely neutralize the live-attenuated virus and an aborted form of the virus ensues. The aborted form escapes and harbors in the nervous system in particularly susceptible areas such as the hippocampus, limbic system and older portions of the cerebral cortex where the blood-brain barrier is less protective, especially in the temporal-limbic areas where dysfunction may be important in the formation of the clinical features of the various autistic syndromes. Opposed to the lengthy period of quiescence seen in SSPE when the “escape” of the aborted, partially damaged wild measles virus acts upon the larger neurons residing in neocortical areas, the interval period in MINE is only a matter of months. It would appear that “break-out” is not as devastating as in SSPE and the clinical symptoms after the short interval may be more due to chronic sapping of the selected host cell’s metabolic activity. Although this pathogenesis explains the neuroautistic symptoms of MINE, it does not explain the often associated enterocolonic symptomatology. Since vaccine-related measles genes are found in the enterocolon literally years after the immunization of an affected individual, it is probable, as opposed to the situation in SSPE, that some of the aborted live-attenuated virus harbors in gut as well, which periodically breaks out rather than harbor for long periods of time as occurs in SSPE.

There are many questions which are still unanswered about SSPE and MINE. Yet, there is still enough known to identify the syndromes as real ones. Certainly the recognition of the MINE syndrome represent at least one explanation for the increased incidence of the infantile pervasive disorders in the so-called developed nations of the world, but also the increase in learning disabilities, behavioral problems, seizure disorders and neurodegenerative diseases seen in the practices of most pediatric neurologists of the world.