A New Hypothesis for SIDS and Cerebral Palsy

In a large proportion of SIDS cases, there are autopsy findings indicating that suffocation or collapse of lungs due to surfactant deficiency did not play a role in those deaths. The lungs were well-inflated and retained their shape upon removal from the body.

A small proportion of SIDS cases had a cardiac rhythm abnormality such as a prolonged Q-T interval, but "most babies with SIDS do not have a history of anything more than a minor illness in the days before death."

Other autopsy findings, such as pulmonary edema and congestion, are dismissed as common features found in infant deaths from many different causes, and not specific to SIDS.

However, certain "tissue markers of hypoxia" frequently found in SIDS -- brainstem gliosis and delayed myelination in the central nervous system, continued blood formation in the liver and persistence of fetal hemoglobin, and increased hypoxanthine in the vitreous humor of the eye -- have been "of great interest because they provide a potential link between prenatal factors such as maternal smoking and SIDS" (PJ Berry. Pathological findings in SIDS. J Clin Pathol 1992 Nov;45(Suppl):11-16).

"The sudden infant death syndrome (SIDS) is usually defined as the sudden, unexpected death of an apparently healthy infant for whom a routine autopsy fails to identify the cause of death. This definition reflects the unexpected nature of the deaths, but not the chronic abnormalities that are present in several organs of more than half of the victims. These abnormalities point to chronic damage in brainstem structures that regulate breathing, sucking, and several autonomic nervous system functions. There is a large overlap between the antenatal risk factors for long-term neurologic abnormalities in children. This supports the possibility that SIDS has its roots in antenatal brain damage or maldevelopment." And he concludes that "After taking other identified risk factors into account, maternal cigarette smoking into account, maternal cigarette smoking during pregnancy accounted for 16% of the SIDS deaths in the CPS" (RL Naeye. Disorders of the placenta, fetus and neonate, diagnosis and clinical significance. New York: CV Mosby Co., 1992).

They blame the abnormal prolifration of astroglial fibers found in the brain stems of many SIDS victims on repeated bouts of hypoxia, supposedly attributable to maternal or passive smoking, occurring over a long period of time. However, astrocytes proliferate rapidly in response to injury form any cause, forming the brain's scar tissue.

They are not curious about a viral etiology. But there are in fact viruses that have been known for decades to infect the relevant central nervous system and other tissues, whose potential role in SIDS and other congenital conditions such as cerebral palsy has evidently never yet been speculated, let alone investigated. The health has been too busy trying to accumulate and stretch circumstantial evidence in order to blame smoking.

The JC polyoma virus was first identified as the cause of progressive multifocal leukoencephalopathy, a demyelinating brain disorder mainly afflicting patients with AIDS, but occasionally also persons with no known immune deficiency.

The BK polyoma virus was isolated from kidney transplant patients receiving immunosuppressive drugs, in whom it is a major cause of graft dysfunction and loss.

Both were discovered nearly 30 years ago in 1971, and are ubiquitous in nearly all populations throughout the world. Both infections usually occur during childhood, with BKV infection occurring at a younger age than JCV. Around 50% of children have antibodies to BKV by age 3, and against JCV by age 6, with infection occurring sooner the lower the socioeconomic class.

The primary infections are usually mild and seldom clinically important. However, BKV can cause upper respiratory disease or urinary tract disease, such as tonsilitis or cystitis, and JCV can cause chronic meningoencephalitis.

After primary infection, the viruses do not disappear from the body. Both BKV and JCV latently infect the kidney epithelium, lymphoid tissue, and brain. Reactivation can occur under conditions of immunosuppression, such as AIDS, immunosuppressive drug therapy, and in other hereditary and acquired immunodeficiency syndromes.

Reactivation also occurs very frequently during pregnancy, in from 10 to 37% of women. The few infections which may occur in utero or in very early infancy, when the immune system and CNS are still immature, may have a far different prognosis from the mild infections which occur at later ages. "JCV infects oligodendrocytes [the brain cells responsible for myelin formation], replicates within an infected cell, and then lyses and destroys the oligodendrocyte and consequently the myelin sheath. JCV exhibits very limited tissue specificity in that the virus can replicate most efficiently in primary human foetal glial cells, but it is well established that the virus remains latent in the kidney and, more recently, several studies support its ability to replicate in B cells."

"Early studies on JCV T-antigen transgenic mice by Small et al. demonstrated that JCV T-antigen induced dysmyelination of the CNS by interfering with normal myelin sheath production and compaction. Further studies in our laboratory on these mice have suggested that the JCV T-antigen protein, independent of the entire virus, can affect myelin sheath formation by altering the expression of myelin basic protein (MBP), a major component of CNS myelin, at the gene level" (J Gordon et al. In: Simian Virus 40 (SV40): A possible human polyomavirus. Brown F, Lewis AM, eds. Dev Biol Stand. Basel, Karger, 1998;94:93-101).

There was one early study which should have provoked more serious research: BK virus. II. Serologic studies in children with congenital disease and patients with malignant tumors and immunodeficiencies. HJ Rziha et al. Med Microbiol Immunol (Berl) 1978 Jul 4;165(2):83-92. "Compared to age-matched control groups, higher percentages and significantly elevated geomatric mean titers of HI antibodies were found in all patient groups tested. Of children under six months of age with congenital diseases such as dysplasia, cerebral defects, and hyperbilirubinemia and hepatosplenomegaly, 4.2% (17/402) had BK virus specific IgM antibodies. No positive sera were found in 68 control sera."

Only a handful of other studies have been done to investigate possible infection in utero, the largest involving several hundred ordinary pregnancies. Antibodies were sought in cord blood to determine whether reactivated polyomaviruses in the mother could cross the placenta. No other outcomes were investigated, and the numbers were so small that, with SIDS or CP occurring only in a few per thousand pregnancies, there would have been few if any cases anyhow. And until recently, that was the extent of the research establishment's interest in the subject.

But some intriguing evidence has come up in a recent study showing that levels of MxA protein and other markers of viral infection are increased in SIDS cases compared to controls: Transcriptional activation of CYP2C, MxA and Fas in sudden infant death syndrome. F Beurton, G Gueret, M Horisberger, G Cheron, T Cresteil. Int J Mol Med 1999 Jan;3(1):33-39.

And newer studies using PCR have demonstrated that BKV does cross the placenta. It was found in a high proportion of both the tissues of aborted fetuses and in the placentas of normal births. (Transplacental transmission of polyomavirus BK. V Pietropaolo et al. J Med Virol 1998 Dec;56(4):372-376.)

Also, reactivated polyomavirus infections cause systemic lupus erythematosus - see "Polyoma Viruses Cause Lupus."

Infants born to mothers with SLE may have neonatal lupus, caused by the passage of maternal antibodies to the fetus. These antibodies cause the characteristic skin rash, which is temporary, and fades by about six months of age when maternal antibodies disappear from the baby's circulation. But some are also born with a dangerous heartbeat defect, often requiring a pacemaker at birth, which is permanent. Most compellingly, reactivations of polyomavirus infection are most likely to occur late in the second trimester, which is exactly the time when congenital heart block is most likely to be detected.

Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. JP Buyon et al. J Am Coll Cardiol 1998 Jun;31(7):1658-1666.

Immune response to SS-A 52-kDa and 60-kDa proteins and to SS-B 50-kDa protein in mothers of infants with neonatal lupus erythematosus. N Yukiko. Br J Dermatol 2000 May;142(5):908-912.

Neonatal lupus syndrome: the heart as a target of the immune system. S Garcia, AC Campos-de-Carvalho. An Acad Bras Cienc 2000;72(1):83-89.

Short- and long-term outcome of children with congenital complete heart block diagnosed in utero or as a newborn. M Eronen et al. Pediatrics 2000 Jul;106(1 Pt 1):86-91.

The fact that maternal antibodies provoked by polyomavirus infection attack the heart adds to the evidence implicating primary polyomavirus infections in cases of sudden and unexpected deaths in older infants. And there are many other complications attributable to polyomavirus infection in these pregnancies as well, including preterm birth, intrauterine growth retardation, hypertension, preeclampsia, premature rupture of membranes, and low birthweight. Thrombocytopenia and hepatic disease occur as frequently as congenital heart block.

The clinical spectrum of anti-Ro-positive cutaneous neonatal lupus erythematosus. WL Weston et al. J Am Acad Dermatol 1999 May;40(5 Pt 1):675-681.

Obstetrical outcome of pregnancy in patients with systemic lupus erythematosus. A study of 60 cases. F Carmona et al. Eur J Obstet Gynecol Reprod Biol 1999 Apr;83(2):137-142.

Intrauteirne gowth retardation and/or polyoma infection impairs the development of the infant's kidneys:

The effect of intrauterine growth retardation on the development of renal nephrons. SA Hinchliffe et al. Br J Obstet Gynaecol 1992 Apr;99(4):296-301.

Renal developmental arrest in sudden infant death syndrome. SA Hinchliffe et al. Pediatr Pathol 1993 May-Jun;13(3):333-343.

Renal developmental delay expressed by reduced glomerular number and its association with growth retardation in victims of sudden infant death syndrome and in "Normal" infants. DJ Beech et al. Pediatr Dev Pathol 2000 Sep-Oct;3(5):450-454.

There is a report in the literature of likely congenital polyomavirus infection, in two brothers who suffered intrauterine growth retardation, intracranial calcifications, hepatitis, and platelet deficiency, and who developed systemic lupus erythematosus and a complement deficiency in their first year of life (Familial systemic lupus erythematosus and congenital infection-like syndrome. RC Dale, SP Tang, JZ Heckmatt, FM Tatnall. Neuropediatrics 2000 Jun;31(3):155-158). The reporting physicians exemplify the mentality of denial of the health establishment, taking pains to refer to it as an "infection-like syndrome," and describing the symptoms as "mimicking a congenital virus infection." And they recommend that "Complement levels and autoantibody profiles should be considered part of the investigation of a child with congenital infection-like syndrome, particularly when there are progressive dermatological complications." (But what about a workup for polyomavirus infection?!)

Our Tax Dollars at Work: A Field Trip to the National Institute of Neurological Disorders and Stroke, Neuroepidemiology Branch

At the laboratory of Karin B. Nelson, Senior Investigator: According to a Reuters news story of Sep. 30, 1999, this intrepid investigator has discovered that "Cerebral palsy may not be caused by physical trauma during birth, but by natural chemicals gone awry." Said Nelson: "It does seem that strong immune activity is playing an important role here," and, "We think now that there may be inflammation other than infection that may play a role here, such as autoimmune disease." And the Reuters correspondent explained that "Cytokines send out signals that cause immune cells to rush in and repair the damage or eat up the invader. But the swelling that this causes can be as bad as the original hurt, and, in the case of autoimmune diseases such as rheumatoid arthritis or lupus, perfectly healthy tissue is attacked." [Sic - except for that polyomavirus they didn't look for.]

Re Nelson: "...Moreover, blood from three children with cerebral palsy, but none from the control group, contained an anticoagulant associated with lupus. (Ignore the next rubbish: "This hints that the autoimmune disease, in which the body's immune cells attack its own tissue, might have been present in the mother or child." What about reactivated polyomavirus?) (Infections may underlie cerebral palsy. N Seppa. Science News Online 1998 Oct 17.)

See Also: Infections are implicated in SIDS

cast 04-07-01