Cretinism, neurological

Fetal problems, including abortion, stillbirths, congenital anomalies, neurological cretinism. Goiter, hypothyroidism, impaired mental function, increased susceptibility to radiation. 

Fetus abortion, stillbirth, congenital anomalies, increased perinatal mortality, increased infant mortality, neurological cretinism (mental deficiency, deaf mutism, spastic deplegia, squint), hypothyroid cretinism (mental deficiency), psychomotor defects. 

DeLong (1989) also reports a unique patient with all the features of neurological cretinism occurring in a nonendemic area, who was treated for congenital hypothyroidism... 

The major features of the IDD effects on brain function arise from fetal damage (neurological cretinism) or hypothyroidism at various stages of life - fetus, neonate, juvenile and adult (Table 62.3). 

Table 64.1 Clinical features in neurological cretinism and in untreated congenital hypothyroidism Table 64.2 Conditions in which CNS damage has been associated with thyroid hormone deficiencies early in development and their prevention ...

Clinical features Neurological cretinism Congenital hypothyroidism ... 

To understand the brain damage observed in neurological cretinism it is important to keep in mind the main findings related to the presence and protective role of maternal... 

With respect to experimental studies in rats born from mothers with severe iodine deficiency, several neurological abnormalities have been demonstrated. The progeny has susceptibihty to audiogenic seizures, associated with irreversible hearing defects, similar to those found in neurological cretinism. Several areas of the brain, such as the cerebral cortex, hippocampus and cerebellum, present morphological abnormalities (Martinez-Galan et al, 1997). 

Neurological cretinism is caused by severe iodine deficiency during pregnancy and is characterized by severe mental retardation and neurological and motor abnormalities it can be corrected by the administration of iodine before conception. The clinical features of cretinism and CH are different. 

The neurological abnormalities observed in neurological cretinism seem to be caused by maternal hypothyroxinemia during the first period of brain development, early in pregnancy. In iodine deficiency the maternal plasma T4 is low, even if plasma T3 and TSH are normal. 

Figure 71.4 Neurological cretinism. Three-year-old boy from a severely selenium-deficient area of Tibet with neurological cretinism. He is severely mentally impaired, deaf-mute and suffered from spastic diplegia, but without clinical signs of Kashin-Beck disease.

The importance of the transfer of thyroid hormones from the mother to the fetus during the second half of pregnancy in humans has received increasing attention (Burrow et ai, 1994). Recently, it has become evident that maternal hypothyroxinemia results not only in the birth of children with neurological cretinism, but also in decreased mental and psychomotor development of the rest of the population without cretinism (Beichrodt and Born, 1994). 

There was controversy about the relationship between iodine deficiency and neurological cretinism. The apparent disappearance of cretinism in southern Europe without any iodized salt program suggested that it was not related to iodine deficiency. In 1964, there was an opportunity to investigate this question in New Guinea, because of the availabihty of a new method for the correction of iodine deficiency that is, injections of iodized oil (lipidol) were made available. 

Neurological cretinism has a characteristic standing posture characterized by flexion of the neck and flexed hips and knees with abductor tightness (Hollowell and Hannon, 1997). In this situation, the trunk tilts forward, the feet are flat and everted, and the gait is broad-based and knock-kneed. The arms are often held in a curious posture with shoulders abducted and the elbows and wrists flexed. Most individuals have characteristic gait disturbances ranging from an abnormal posture and rhythm to an inability to walk. 

All this activity has stemmed from a new perception of the effects of iodine deficiency. The concept of the Iodine Deficiency Disorders refers to a broad spectrum of conditions which affect the fetus, the neonate, the child and the adult. Particularly important are the fetal effects, including miscarriage, stillbirth, as well as neurological cretinism which is of special interest to this symposium, as it is the reference point for studies on iodine and the brain. This condition, well known in the ancient and mediaeval worlds, was described in Diderot s Encyclopedie in 1754 when a cretin was defined as an "imbecile with a goitre down to the waist". 

This is further indicated by evidence of the relation of maternal thyroxine levels to the risk of cretinism and the psychomotor defect from studies in Papua New Guinea (26). The subsequent lack of fetal thyroid hormones due to the inadequate supply of iodine in iodine deficiency would exacerbate the effects of maternal thyroid insufficiency and the combination of effects, which were represented experimentally in the sheep by maternal thyroidectomy before conception (21) combined with fetal thyroidectomy at 98 days (12), might be expected to produce the multiple defects of neurological cretinism. 

What is needed now is a comparison of brain pathology in neurological cretinism and cerebral palsy and in myxedematous cretinism and sporadic congenital hypothyroidism there is also a need for study of the brain in endemic mental retardation. 

Swiss authors (2, 17) reported that neurological cretins have hyperplastic, colloid, multinodular goiters similar to those seen in non cretin individuals in the same area. They showed that myxedematous endemic cretins have thyroid atrophy and sclerosis. As a consequence of their thyroid failure, myxedematous cretins also have hyperplastic pituitary glands. 

The fact that there are some similarities between neurological cretinism and cerebral palsy (18) raises the question of whether congenital infections or perinatal anoxia play a role in the etiology of cretinism. 

The data suggesting the direct role of elemental iodine on brain development is the observation that correction of iodine deficiency in mothers prevents the emergence of neurological cretinism only if correction takes place before or during early gestation, thus before the onset of fetal thyroid function (83). What we would like to know in greater detail is which parameter is corrected in the human fetus when maternal iodine deficiency is corrected before the onset of fetal thyroid function Is it the fetal deficiency in iodine, in thyroid hormones or in both ... 

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