Problems with interhemispheric transfer of information in complete or partial agenesis of the corpus callosum.

OBJECTIVE: We assessed the presence of poor interhemispheric communication in agenesis of the corpus callosum (ACC) and hydrocephalus. METHODS: With specially designed tests, nine children with ACC were investigated and compared with 11 controls to see the degree of impairment present. Two subjects with a stretched corpus callosum due to hydrocephalus also were tested. A subject with the corpus callosum divided was tested for comparison. RESULTS: Significant differences were found in tests of coordination and stereognosis both with ACC patients and the callosotomy subject. No impairments were found in the hydrocephalics. CONCLUSIONS: When compared with controls, ACC patients perform poorly in several tests. The callosotomy patient also showed evidence of impairment similar to that of the ACC patients.

Fate of small diameter cervical veins grafted into the common carotid arteries of growing rabbits.

Autogenous cervical veins were grafted into the common carotid arteries of rabbits during their active growing period. A patency rate of 58.8% was achieved but the thin-walled vein grafts underwent massive dilatation. This dilatation is likely to severely limit the usefulness of these veins as a source of bridging grafts in clinical practice, particularly for use within the intracranial cavity.

Long-term effects of heparin on veins grafted into the common carotid arteries of rats--a scanning electron microscopic study.

Jump grafts made from veins with diameters of about 1 mm have very poor patency rates. Dissection and anastomosis damage the endothelia of the arteries and veins and expose collagen in the subendothelial layers of these vessels. Within 1 hr of the introduction of blood flow through the grafts, deposits of fibrin and platelets led to blockage of the grafts. In 9 rats, heparin was given intravenously about 0.5 hr before completion of the grafting procedure; heparin was also used to wash out the veins for grafting. In 11 rats, heparin was used only to wash out the veins for grafting. At periods 1-11 weeks later, the grafts were reexamined. All were patent except 1 from the first group, examined at 7 weeks, and 1 from the second group, examined at 10 weeks. Scanning electron microscopy showed that complete healing of the venous endothelium took several weeks. Heparin was equally effective in keeping the grafts patent when given intravenously and used locally or when only used locally. This study indicates, therefore, that long-term patency in small diameter vein grafts can be achieved merely by washing out the veins for grafting with a solution of heparin.

Effect of early revascularization on the ischaemic rat brain.

Rat brains made regionally ischaemic by manipulation of the large vessels in the neck were revascularized up to 4 hours later. Mortality rates, patterns of ink staining and the water content of the brains were studied. Scanning and transmission electron microscopy was carried out. The results showed that whilst revascularization did not reperfuse areas of the brain that had been subjected to very low levels of perfusion, it did reperfuse other areas with higher perfusion and, in so doing, prevented the extension of the ischaemic process into them.

CT observations on the natural history of asymptomatic cerebral infarction following transient ischaemic attacks.

Two hundred and sixty-one neurologically asymptomatic patients were examined by computed tomography (CT) following a variable number of transient ischaemic attacks (TIAs) experienced over different time intervals. Cerebral infarcts were discovered in 101 patients. Dominant hemisphere infarcts were usually small, of recent origin and most often associated with less than 5 TIAs and a short history; whereas non-dominant hemisphere infarcts were found twice as frequently and were larger and older and correlated with repeated TIAs over many months. All infarcts, independent of size, were confined to a single vascular territory, suggesting haemodynamic rather than embolic causes. By comparing the age and size of the infarcts with the number of TIAs and their chronicity, the hypothesis emerged, suggesting that infarcts may occur early on and progressively enlarge with repeated attacks.

Some scanning electron microscopic studies of the surface of coronal sections cut from the rat brain.

The cut surfaces of coronal sections of the rat cerebral hemispheres have been examined with the scanning electron microscope. Under low magnification the structures of the brain are easily identified. Using the focusing power of the microscope and the ability to tilt the specimen in its column, under higher magnification the neurones, glial cells, cell processes, bundles of myelinated axons and the cerebral blood vessels can be examined in great detail. This method of study should prove of value in the future for the investigation of brains which have been subjected to experimental procedures and those affected by disease.

Pre-natal ventriculomegaly and hydrocephalus.

Ultrasonic imaging of the human fetal brain has allowed ventriculomegaly and hydrocephalus to be categorized. In this study 40 fetuses with ventriculomegaly and 21 with an Arnold-Chiari malformation and a myelomeningocele had ventriculomegaly that resolved, stabilised or progressed in utero. Within the progressive group were those with hydrocephalus, hydrocephalus being defined as expansion of the cerebral ventricular atria together with disproportionate increase in the head circumference. The prognosis for fetuses with resolving and stable ventriculomegaly was good, reflecting the fact that the ventricular dilatation in these cases was probably caused by delayed parenchymal and cerebrospinal fluid pathway development. Whereas the prognosis for progressive ventriculomegaly was generally poor, suggesting that the causes were likely to have been chromosomal, genetic, an infective agent or a catastrophic event which had an adverse effect on parenchymal development. The causes of hydrocephalus also adversely affected brain development but additional damage was caused by raised intracranial pressure.

The fine structure of the axonal torpedo in Purkinje cells of the human cerebellum.

Axonal torpedoes on Purkinje cells of the cerebellum have been observed at electron microscopic level in the case of a 5-year-old boy suffering from juvenile astrocytoma present in the roof of the fourth ventricle and cerebellar hemisphere. The axon torpedo is characterised by a central accumulation of disoriented neurofilaments, which displace the mitrochondria and endoplasmic reticular elements to the periphery. The mitochondria are small and densely staining with longitudinally arranged cristae and are intimately associated with the smooth endoplasmic reticulum that occurs as stacked complexes. Multivesicular and lamellar bodies, typical of degenerating axons, are not consistently seen and this indicates that axon torpedoes are more likely to represent a regenerating state within the nerve fibre than a degenerative condition.

Comparison of healing of lesions in the calvarium of foetal lambs and young sheep.

This study compares the healing of lesions made in the occipital region of the calvarium of 5 foetal and 4 post-natal lambs. The foetuses, operated on between the 83rd and 91st day of gestation, had a bone flap elevated and the post-natal lambs, aged about 6 weeks, had a craniectomy and replacement of the bone pieces. The foetuses were delivered spontaneously at full-term. All the animals had computed tomographic (CT) scans and, after sacrifice, naked eye examination of the bony lesions. These showed that there was poor ossification of the lesions made in the foetuses compared to those made in the post-natal lambs. These findings need to be taken into account when intra-uterine correction of cranio-facial deformities are being contemplated.

The case for and against intrauterine surgery for myelomeningoceles.

The case for and against intrauterine surgery on a myelomeningocele depends on how and in what order the malformations in the spinal cord and brain are thought to develop. If the brain defects arise in the embryonic period and undergo no further change and if the spinal cord is so deformed that it is functionless from the start, then operative intervention before birth will have no significant effect on the ultimate neurological defect. If, on the other hand, the brain lesions evolve during gestation and the deformed spinal cord has some useful function that can be lost by contact with the amniotic fluid or is susceptible to mechanical damage, then intrauterine surgery may have a beneficial role. Long-term follow-up of children who have already undergone intrauterine surgery should answer whether this novel form of treatment imparts significant benefit to justify the risks it imposes on the mother and fetus.

The influence of systemic aspirin on rat small diameter vein grafts: a scanning electron microscopic study.

Small diameter vein grafts have been shown previously to have a poor patency rate unmedicated rats. Oral aspirin administered to male and female rats for one week pre-operatively reduced the number of platelets laid down on the luminal surface of their grafts, and resulted in a greater number of grafts remaining patent up to one hour after the blood flow through them had been established. The patency rate of grafts examined one to 17 weeks after operation was significantly better in female rats than in males given aspirin pre- and post-operatively. The different effect of aspirin in preventing thrombosis of the vein grafts of the two sexes makes its clinical usefulness for this purpose suspect.

Effect of excision of occipital lobe tissue on about the 70th day of gestation on the growth and development of the sheep's brain.

A unilateral occipital excision was performed on 14 fetal lambs at about the 70th day of gestation, and the brains were examined postnatally for gross morphological and histologic changes. Three operated brains revealed a posterior shift of the principal transverse sulcus in the ipsilateral hemisphere. This sulcus is remote from the area of excision, which was usually represented by a cystic cavity. Histologic examination showed that the dorsal lateral geniculate body was reduced in size in all but three of the operated brains. In two brains with the changed gyral pattern there was also a reduction in the size of the white fiber tracts of the frontal lobe. No evidence of neural regeneration was found in any of the brains. The implications of these findings from the point of view of possible neurosurgical intervention in the fetus are considered.

Comparison of scanning electron and light microscopic appearances of sequential changes taking place in the ischemic cortex of the rat brain.

The right middle cerebral territory of rat brains was made ischemic (a) for periods varying from 30 minutes to 24 hours, and at the end of each of the times the animals were killed and their brains were fixed, or (b) for 30 minutes, and the animals were allowed to survive for between 1 week and 9 months before they were killed and their brains were fixed. The ischemic areas were examined by light and scanning electron microscopy and the findings of the two methods of examination were compared. Scanning electron microscopy allowed the tissues to be studied at a wider range of magnification than was possible with the light microscope. Scanning electron microscopy also provided a three-dimensional view of the structures so that their relationship to one another could be examined. However, because it is generally not possible to stain material for examination by scanning electron microscopy, it was sometimes difficult to identify positively the individual structures. Nevertheless, this study has shown that scanning electron microscopy provides a valuable new way of investigating the ischemic brain and is likely to prove useful in other studies in the future.

Ischemia and revascularization of the middle cerebral territory of the rat brain by manipulation of the blood vessels in the neck.

Ischemia of the middle cerebral territory in the rat brain has been produced by anastomosing the right common carotid artery to the right jugular vein, and occluding the left internal and common carotid arteries. Revascularization is performed by ligating the right common carotid artery distal to the arteriovenous anastomosis and removing the clips from the left carotid arteries. The majority of the rats made ischemic deteriorated progressively and died if revascularization was not carried out, but only 10% of them died if the operation was performed within one hour, although the rate rose to 90% if the operation was delayed for 4 hours.

Fate of 6 fetuses with ventriculo-megaly or potential ventriculo-megaly followed up post-natally.

Six fetuses were studied--3 with ventriculo-megaly and normal head circumferences, 2 with ventriculo-megaly and enlarged head circumferences, and 1 with a Dandy-Walker complex and normal lateral and third ventricles. Post-natally it was found that fetal ventriculo-megaly was not associated with raised intracranial pressure at least in the first few months of life unless the head size was enlarged. The baby with the Dandy-Walker complex developed ventriculo-megaly and raised intracranial pressure several months after birth following progressive enlargement of the posterior fossa extra-axial cyst.

A report of children with spinal dysraphism managed conservatively.

This investigation is a retrospective study of 12 patients with spinal dysraphism. There were 5 males and 7 females in the cohort. Their ages ranged from 4 to 13 years at the time of their last assessment. Initial presentation included one or more of the following--a blemish on the back in the midline (lump, hairy patch, sinus and/or angioma), abnormal neurological signs and symptoms in one or both legs, and in one case dribbling of urine. Investigations performed included plain X-rays of the spine, CT scans alone or in combination with a myelogram and MR scans. Findings included thickened filum terminale, low lying cord, lipoma, syringomyelia, diastematomyelia, spina bifida occulta and sacral agenesis. The children were followed up for between 2 and 10 years. During the period of observation, none developed new symptoms or signs, and there was no progression of existing neurological deficits. This preliminary report suggests that there is no justification for prophylactic surgery in this group of patients.

Hand function in subjects with spina bifida.

The aim of our study was to assess the influence of the Arnold-Chiari malformation, cervical cord dysraphism and hydrocephalus on hand function in subjects with meningomyelocele, but without many of the other confounding factors commonly found in this group e.g low IQ and cerebral palsy, which in themselves cause poor hand function. Three groups of subjects who attended main stream schools underwent a basic neurological examination of the upper limbs and a battery of hand function tests. Group 1 consisted of subjects with meningomyelocele and shunted hydrocephalus (n = 21), Group 2 subjects had isolated shunted hydrocephalus (n = 13) and Group 3 were normal controls (n = 18). The results show that subjects with meningomyelocele had weaker power in the small muscles of the hand as compared to the controls and those with isolated hydrocephalus (p = 0.01) and poorer fine motor control and co-ordination. The meningomyelocele group scored significantly poorer in all of the tests as compared to the control group using the dominant hand (overall, p = 0.0003), and all of the tests but one using the non-dominant hand (overall, p = 0.0005). Our study has demonstrated that children with meningomyelocele have poorer hand function than healthy controls, which is due to causes other than hydrocephalus, poor IQ or cerebral hemisphere pathology. Instead, cerebellar and cervical cord abnormalities appear to be exerting a significant deleterious influence on the function of the upper limbs.

Assessing the needs of the adult with spina bifida.

In recent years this society has heard of the plight of people with spina bifida who have graduated from childrens' to adult services, and of the lack of cohesive medical and counselling services offered to them. In the Manchester area, a joint clinic for adults has recently been set up, consisting of a Neurosurgeon, Nephrologist and Clinical Psychologist. Patients attending are those who attended the joint paediatric clinic who are now 16+ and new referrals from GPs and other consultants. 30 people of appropriate age to attend the clinic were identified, and these were contacted by mail to inquire about the sort of services they would like to receive and any problems they have or foresee for the future. 13 replies were received, 12 people indicating that a joint clinic would be of use to them. Results indicated that a total of 42 contacts with medical, paramedical and care services were lost, and 24 requests were received for contact to be resumed. Replies made it clear that guidance on work, education, social provision and sexual counselling were much in demand. Aids provided for mobility, and facilities for disabled people were not always appropriate for our respondents, who were quite vociferous about what they needed, but did not always know what was available. Conclusions to be drawn are that the joint clinic needs to include links with education, careers officers and counsellors, and that time needs to be made available to effectively meet the needs patients present. The clinic could act as a forum to collate experiences, and highlight the problems of the young disabled adult.

A study of prenatal ultrasound and postnatal magnetic imaging in the diagnosis of central nervous system abnormalities.

Accurate prenatal diagnosis of central nervous system (CNS) abnormalities is essential in counselling parents, as they are the most common developmental abnormalities causing considerable mortality. Currently, the standard in prenatal imaging is ultrasound scanning (USS). The introduction of fast acquisition magnetic resonance imaging (MRI) has lead to increased diagnostic confidence and information available for parents. Frequently USS initially identifies CNS abnormalities as ventriculomegaly alone. However, it is known that ventriculomegaly is commonly associated with other CNS pathology, which may adversely affect the prognosis. As MRI has superior soft tissue resolution and can be used at any time postnatally, it is expected to identify disorders of myelination that may result from prenatal ventriculomegaly. This study will evaluate the role of MRI as a postnatal imaging tool in patients that had a prenatal USS diagnosis of isolated ventriculomegaly. This was a retrospective review of patient notes and scan reports. The postnatal MRI study group consisted of 9 patients that had been diagnosed initially with prenatal isolated ventriculomegaly on USS, and followed up with postnatal MRI (cases of spina bifida and Dandy-Walker malformations were excluded). Findings from the scan reports were recorded and analysed. Both MRI and prenatal USS gave the same information in 55.6 % of the patients. In the remaining 44.4 %, MRI added to the information provided by the prenatal USS. An interesting finding was that MRI missed a small fluid-filled cyst and an arachnoid cyst in 2 cases. 55.6 % of patients went on to develop other CNS abnormalities prenatally, whereas 33.3 % showed prenatal regression of VM with no other pathology. 11.1 % showed postnatal persistence of isolated VM. As USS has the advantage of being cheap and easy to perform, it will remain as the primary imaging tool in obstetric care. MRI can provide significant additional information that can affect parent counselling, prenatal intervention, and postnatal management. Postnatally, MRI can give some idea of prognosis by evaluating myelination patterns, which is not possible with USS.

Pre-natal brain development of fetuses with a myelomeningocele.

Biometric measurements of 21 fetuses referred to the Fetal Management Unit at St. Mary's in Manchester with a diagnosis of myelomeningocele were analysed. Five fetuses had more than 3 sets of measurements carried out, the last of which were performed during the 3rd trimester. The majority of the head circumference measurements were on or below the 3rd percentile for normal head size whilst almost all of the cerebral ventricular atrial measurements were more than 10 mm, a figure generally accepted as being at the upper limit of normal, measurements above this indicate that ventriculomegaly is present. In normal fetuses the atrial measurement is constant at or below 10 mm throughout gestation, but in the fetuses with a myelomeningocele the atrial measurements got progressively larger as gestation proceeded. Because their head circumferences did not increase disproportionately quickly, there was no evidence that the fetuses were developing hydrocephalus in utero, rather the large atrial measurements were indicative of poor development of the cerebral hemispheres. These findings together with the Arnold-Chiari malformation and the abnormalities in the spinal cord indicate that the central nervous system in its entirety is abnormally developed in fetuses with a myelomeningocele.