Morphological and neurochemical study of Pelizaeus-Merzbacher disease.

Of the various types of demyelinating disorder, Pelizaeus-Merzbacher disease (Pelizaeus, 1885; Merzbacher, 1910) is probably the rarest and least understood form. For while its genetic, clinical, and patho-anatomical features have been fairly well delineated, the underlying biochemical disturbance thus far has been only incompletely analysed. Consequently the pathogenesis of the disorder has remained unclear and controversial. Three main hypotheses have been advanced as to the manner in which the changes are produced, viz., through destruction or removal of myelin, similar to that in multiple sclerosis (Spielmeyer, 1923); through faulty or incomplete formation of myelin that undergoes progressive degeneration and thus is considered to be a form of leucodystrophy The purpose of this investigation is to report the patho-anatomical findings in a case of Pelizaeus-Merzbacher disease, and through a detailed chemical analysis of the fixed brain tissue, contribute to the chemical pathology of the disease. CASE REPORT HISTORY R.F., a 13-year-old white boy, had a normal birth with the exception of bilateral congenital cataracts. His birth weight was 6 lb. 2 oz. and his height was 20 inches. Up to the age of 6 months his development proceeded normally and by that time he more than doubled his birth weight, weighing 14 lb. 12 oz. But from the age of 6 months on he showed signs of increasing physical and mental retardation. His body weight and height remained virtually stationary so that by the age of 31 years his weight was only 17 lb. and height 29 inches. There was a marked degree of microcephaly. He displayed no signs of intelligence or interest in his surroundings, had no sense of balance, did not learn to walk or talk, and gradually developed marked contractures of the lower extremities (further details of his clinical course were lacking). He suffered frequently from upper respiratory infections and ultimately expired of bronchopneumonia. The family history showed that an older brother suffered from the same condition and died at the age of 22 years (there is, however, no record of a necropsy having been performed). A sister, age 15, is living and is apparently normal. POST-MORTEM FINDINGS The general necropsy findings were bilateral bronchopneumonia and pulmonary oedema; hypoplasia of the thyroid and pituitary glands; undescended atrophic testes, and general underdevelop-ment of the skeleto-muscular system. The brain weighed 500 g., being reduced by more than 50% of normal size (Fig. 1). The cerebral hemispheres were symmetrical and their …