NEONATOLOGY ON THE WEB

Premature and Congenitally Diseased Infants

by Julius H. Hess, M.D.

Chapter XIII
Diseases of the Nervous System

Mental and Nervous Disturbances

The frequency of mental disturbances and other phenomena on the part of the central nervous system in premature infants has been variously estimated. Finkelstein states that mental disturbances and spastic phenomena are not more frequent in prematures than in full-term infants, but Ylppö strongly contests this statement. The attempt to express the frequency of permanent mental defects and other cerebral disturbances in percentages is only rarely possible before the end of the first year of life, with perhaps the exception of the typical Mongolian idiot. Demonstrable mental defects, either complete idiots or imbeciles, were found in 7.4 per cent of Ylppö's cases.

Mental defects in premature infants are frequently accompanied by other symptoms on the part of the central nervous system. The most common are the spastic paraplegias and diplegias. These are present in prematures with demonstrable mental defects in at least 75 per cent of all cases. However, mental development may be complete in the presence of spasticity of the extremities dependent upon cerebral irritation. In most instances this is secondary to intracranial hemorrhage. Paraplegia or diplegia was present in 3.1 per cent of all Ylppö's cases. These figures would certainly be much higher, had all the prematures remained alive, since most of the infants suffering from injury to the brain die very early. The cerebral affections occur the more frequently, the smaller the infant at birth.

In our experience mental disturbances and defects on the part of the central nervous system have been confined largely to those infants who survived from among the class of so-called weaklings. These are the infants who have suffered from intra-uterine disease or congenital malformations, traumata at birth, or postpartum dietetic errors and infection. Among the more mature that are normal for their fetal age the prognosis for a full mental development is good.

Treatment. -- In the postmortem examination of infants dying of cerebral hemorrhage, Rodda [1] found over 50 per cent followed non-instrumental deliveries and many followed normal and easy births. In these cases the blood was found slightly or not at all coagulated. Cerebral hemorrhage was by far the most frequent cause of death in the new born in his group of cases. In many cases at postmortem, no torn veins were found in the cerebrum or cerebellum to account for the hemorrhage, and multiple hemorrhages were found in portions of the body where it was inconceivable that they could be explained by trauma. Over 25 per cent of all infants dying of cerebral hemorrhage showed this picture of multiple hemorrhages. An analysis of cases reported in the literature deepened the conclusion that these hemorrhages were due to factors other than trauma. Further study led to the conclusion that there was a disturbance in the coagulation time of the blood in the new born. It was found that the average coagulation time in the new born was seven minutes. In icterus, melena, jaundice, syphilis and non-traumatic cerebral hemorrhage, the coagulation time of the blood was prolonged. In melena it might be delayed to ninety minutes. The subcutaneous injection of normal blood was effective in cases in which there was delayed or slow bleeding.

The further treatment in those cases with a diagnosis of intracranial hemorrhage is symptomatic and expectant. There is always the possibility that there may be spontaneous cure. The infant must be kept quiet and warm. For the motor hyperirritability and convulsions narcotics may be employed, before all chloral hydrate (0.12 to 0.5 gm per day per rectum), also bromides (0.25 to 1 gm. per day) or calcium lactate (1 to 2 gm.) or calcium bromide (0.3 to 0.5 gm. per mouth) per day.

Where the infants do not swallow well, feedings must be given per catheter or subcutaneous infusions must be used for emergency.

Lumbar puncture, although primarily a diagnostic measure, may have a beneficial therapeutic action. It is of diagnostic value when the hemorrhage is below the tentorium.

In the full term, cranial decompression when employed early has yielded favorable results, however little can be expected from such surgical interference in the premature.

Schulze's swingings and other violent measures for artificial respiration are distinctly contraindicated in the treatment of asphyxia in the premature.

For the paraplegias and diplegias, corrective measures should be undertaken early in order to prevent marked deformities. Massage and active and passive movements should be practised regularly beginning to advantage in the first year.

Muscle training in walking, climbing, and other activities should be instituted under the supervision of a trained assistant.

Orthopaedic appliances are frequently indicated.

Surgical procedures may be necessary later.

Another group is made up of premature infants with more or less serious mental defects in whom typical epilepsy gradually develops, often of the Jacksonian type. It is very difficult and often impossible to make a differential diagnosis between epilepsy and spasmophilia in the first attacks, and especially in those cases where the convulsions appear very early. Fortunately, as a general rule, the epileptic convulsions do not occur in the first year of life in prematures, while on the other hand electric hyperirritability and spasmophilic convulsions are quite frequent in this period of life. This makes the differential diagnosis somewhat easier.

On the other hand, however, in connection with febrile diseases of later life, convulsions occur very frequently in premature infants. Only the further course of the disease will show whether the convulsions are of epileptic or spasmophilic nature.

Hydrocephalus; Megacephalus

True congenital hydrocephalus is usually of the internal type with enlarged ventricles. The external form is very rare. Megacephalus must be differentiated from hydrocephalus, the two often being confused in the premature, as previously mentioned in the discussion of Pathology and Rachitis. Internal hydrocephalus results from a transudation or exudation. Obstruction to the outflow may be the cause as in the case of intracranial hemorrhage or cerebellar cysts. However, most of the cases are probably due to an intra-uterine serous meningitis or meningoencephalitis of unknown origin. Syphilis is frequently the cause of congenital hydrocephalus.

The inflammatory process bringing about hydrocephalus may be at end by the time of completion of pregnancy, but usually persists thereafter. Most of the infants show enlargement of the head soon after birth or the enlargement becomes apparent at a later period. When the process begins early, intra-uterine, it may bring about a marked retardation in brain development. The head need not necessarily be enlarged; indeed the head may be small as in a microcephalic. The brain in these cases is really a large cyst. Often the skull is enlarged at birth, and it may hinder labor to such an extent that perforation or puncture of the head becomes necessary.

When the head has the classic hydrocephalic configuration the diagnosis is, of course, easy. In many instances there are also the following symptoms at birth: Hypertonus and spasms of the muscles, increased reflexes, convulsions, psychic disturbances and apathy.

Where the characteristic head is not seen and only slight enlargement of the fontanelle areas is noted, the diagnosis is difficult. Intracranial hemorrhage and meningitis must be ruled out. Lumbar or ventricular puncture is of great assistance.

The prognosis is usually difficult to make early. The only early therapeutic measure is lumbar or ventricular puncture with drawing off of cerebrospinal fluid. Late surgical interference may be indicated.

The term megacephalus is applied to conditions in which the head develops out of proportion to the other body measurements and length. It is characterized by an abnormally large head, with a relatively larger brain. This condition is a characteristic finding in a high percentage of infants prematurely born and is seen in inverse proportion to the fetal age and birth weight. Rosenstern [2], in a series of sixty-one prematures observed over a period of at least three months, noted megacephalus in forty-four. He concluded that the lower the birth weight of the premature the more likely is megacephalus to develop.

Birth weight	No. cases	Present				Absent
		Severe	Moderate	Mild	Total
to 1000 gm.	1	0	1	0	1	0
1001 to 1500 gm.	12	5	6	1	12	0
1501 to 2000 gm.	21	3	14	1	18	3
2001 to 2500 gm.	27	1	9	3	13	14
Total	61				44	17

It usually occurs before the age at which rachitic changes are noted in the long bones and chest. However, as rickets occurs much earlier in premature infants than in full-term infants, I do not believe that we are at present in a position to dissociate these two conditions. There is therefore great probability that the same etiological factors underlying the development of megacephalus in the first months may be the cause of rachitic manifestations in the bones or other organs at later periods.

Age in months	Cases
1	9
2	11
3	11
4	0
5	4
6	0
7	1
8	1
9-11	0
12	1

It is most frequently seen during the second and third months of life and reaches its maximum between the sixth and eighth months. It then gradually becomes less manifest. There is usually an increased spinal fluid pressure in which it resembles hydrocephalus. The brain, on section, is found to be abnormally large but in true cases there is a complete absence of hydrocephalus.

Associated with the large skull and wide-open fontanelles and sutures, exophthalmos is frequently seen. The latter probably results from the lack of skull capacity, the eyes being protruded, with prominent cornea and, not infrequently, dilated pupils. Further characteristics of the head are a broad face and mouth, nose and eyes which appear closely set together: the nose is stumpy and small and rises but little above the face; the tongue is often large and protruded.

Encephalitis

The subject of encephalitis of the premature and full-term new born is still very much in the dark. The etiology is obscure and a clinical picture for the encephalitic processes has not yet been described.

Encephalitis interstitialis congenita was described by Virchow [3], with changes in the medullary substance of the cerebrum, as a diffuse infiltration with fatty infiltrative cells. Later, other observers declared that this was not pathological (Jastrowitz [4], Limbeck [5]). Brain defects (porencephaly) have been linked with congenital encephalitis. Septic encephalitis is either a metastatic condition or a meningo-encephalitis, the difference between the two being almost impossible to define. The medullary substance shows clumps of bacteria and leukocytes, and later there appears a suppurative inflammation on the brain substance. Not infrequently in prematures the meningo-encephalitis is a distinctly luetic process (see chapter on Syphilis in Prematures).

Meningitis

The meningitic processes are as little understood as the encephalitic. They may be acute or chronic. Serous meningitis which is not well understood is supposed to be intimately related to congenital hydrocephalus. Pachymeningitis hemorrhagica interna seems to be a luetic process entirely (see Syphilis of Prematures).

Purulent meningitis follows suppurative conditions in the middle ear, accessory nasal sinuses or is metastatic. Sometimes one sees typical meningeal symptoms as: Convulsions, rigidity of the neck, hypertonus, protruding fontanelles. However, meningitis may be present without any characteristic signs. The infants are flaccid, exhausted, and dried out. The diagnosis is verified by lumbar puncture. Fever is often absent or only present terminally.

The prognosis is absolutely poor. Death usually follows in twenty-four hours, but some linger eight to fourteen days. The inception of the process is difficult to fix because of the uncertainty of the symptoms.

Sinus thrombosis following middle-ear infections or phlebitis after navel infections sometimes are responsible for the meningitis.

Epidemic cerebrospinal meningitis is not an uncommon complication in premature infants during the first year. A spinal puncture should be made in every case showing marked evidence of cerebral irritation. In positive cases serum should first be administered intravenously through the longitudinal sinus, because of the tendency to generalization of the infection in this class of infants. Intraspinal administration of serum must always be made by the gravity method after withdrawal of as much fluid as is to be administered.

Finally we find among the prematures a number of idiots that have to be classified as "degenerative idiots." These are the infants that at birth already show stigmata of Mongolism or other malformations. These children are prematurely born with special frequency, and it follows therefore that a considerable number of children with Mongolian idiocy are prematures. After all, it is a known fact that children with various congenital malformations, be they congenital bone diseases, bone anomalies, congenital heart disease, malformations of the brain or spinal cord, etc., are born in an immature condition. This circumstance, as previously mentioned, is the reason that prematures have been very generally but erroneously regarded as congenitally inferior.

Spasmophilic Convulsions

With reference to spasmophilic convulsions we must not regard them as purely functional convulsions; on the contrary the readiness with which they occur and their frequency in premature infants speaks very strongly for organic lesions, probably most frequently among these being cerebral hemorrhage occurring during labor. Naturally certain extra-uterine noxae, as anemia and rachitis, are of importance as determining factors that make the spasmophilic disturbances manifest. Numerous roentgenological examinations of the long bones of premature infants have shown that the rachitic changes are not confined to the skull, but that the other bones are also early affected, as early as the second and third months of life.

Footnotes

[1] Am. Jour. Dis. Child., 1920, 19, 268.

[2] Rosenstern, J.: Ztschr. f. Kinderh., 1922, 22, 129.

[3] Virchow's Arch., 1867, 38, 129.

[4] Arch. f. Psych., 1870, vol. 2 and 1871, vol. 3.

[5] Prague Ztschr. f. Heilk., 1885, 7, 87.

	Fig. 162. Megacephalus. Baby P. H. at four months.
	Fig. 163. Baby P. H. at six months.
	Fig. 164. Weight and food curves and calor intake. Estimated fetal age, 32 weeks. One of triplets. Second died shortly after birth. Third born macerated. Born April 1, admitted April 1. Discharged, October 12; age one hundred and ninety-three days. Birth weight, 840 gm; lowest weight, 645 gm.; doubled birth weight in one hudred and fifty-three days; tripled lowest weight in one hundred and seventy-five days. (From service of Dr. L. E. Frankethal, Michael Reese Hospital.)
	Fig. 165. Hydrocephalus. First signs when infant was four weeks old.
	Fig. 166. Oxycephalus (Tower skull). Usually associated with other congenital defects and stigmata of degeneration. The skull is dome shape with bulging temporal regions. The deformity was present at birth. It is generally associated with exophthalmos, propotosis and frequently with other ocular abnormalities. Some children are mentally normal. Others subnormal.