Jean-François Hirsch

Intellectual outcome in children with malignant tumors of the posterior fossa: influence of the field of irradiation and quality of surgery

The purpose of this study was to determine the respective parts played by cerebral hemisphere irradiation, posterior fossa irradiation, and surgery in the poor late functional results often observed in children treated for medulloblastoma. To do this we compared the intellectual outcome in a series of 59 children operated on for medulloblastoma, who had received whole-brain irradiation, to that observed in a series of 37 children operated on for ependymoma of the posterior fossa, who had received radiotherapy only on the posterior fossa. Only patients who had survived for more than 2 years without recurrence were included. At the assessment 1 year after treatment, intellectual outcome was somewhat better in the ependymoma group, but the difference was not statistically significant. At the long-term follow-ups at 5 and 10 years the results remained stable in the children treated for ependymoma, around 60% having an IQ above 90, whereas the intellectual level of the children treated for medulloblastoma was seen to have deteriorated progressively: 20% had an IQ above 90 5 years after treatment and only 10% at the 10-year followup. This progressive degradation is most likely due to the irradiation of the cerebral hemispheres, as this prophylactic irradiation constituted the only difference between the two groups. Moreover, irradiation to the posterior fossa did not seem to affect intellectual functions, since in the group of children with ependymomas the proportion of IQs above 90 was high and remained stable over the years. Surgery was certainly responsible for some poor results. The percentage of IQs above 90 observed 1–2 years after treatment was between 70 and 80 when no postoperative complications occurred, and only between 20–40% in the presence of postoperative complications. Postoperative aggravation was in most cases related to a brain-stem lesion. These results encourage the reduction, when possible, of irradiation to the cerebral hemispheres and underline the importance of the quality of surgery.

Medulloblastoma in childhood: progressive intellectual deterioration.

A series of 120 medulloblastomas in children operated on between 1967 and 1987 at the Hôpital des Enfants-Malades has been reviewed in order to check whether the conclusions of our study published 10 years ago have remained valid and, in particular, to verify whether the quality of life of these patients, which had been found to be poor at the time, had improved or worsened over the years. The postoperative mortality for the whole series was 6.5% there have been no deaths in the 35 patients operated on after 1980. The overall survival rate for the 120 children was 60% at 5 years and 53% at 10 years; for the patients who completed radiotherapy, the survival rates was 73% at 5 years and 64% at 10 years. Survival rates were surprisingly better in patients treated when under 6 years of age than in older children. They were also better in girls than in boys, and in desmoplastic compared with other medulloblastomas; however, the differences were not significant. When comparing the groups after total or subtotal resection of tumors, survival rates were not significantly different, but were lower in the small group of partial resections. Cell differentiation did not influence the prognosis. Psychological sequelae were significant and worsened over the years. Five years after treatment 58% of the children showed an IQ above 80; 5 years later this group included only 15% of the patients. These psychological sequelae were related to age at the time of radiotherapy: the younger the child, the lower the final IQ. Five years after treatment, 40% of the children had a normal academic level; 5 years later this group was reduced to 11%. Ten years after treatment, 36% of the patients were unempolyed and 64% worked in a protected environment. No patient had normal employment. These disastrous results concerning the quality of life of these medulloblastoma patients justify new trials with reduced doses of irradiation over the hemispheres, at least in low-risk groups.

A New Approach in the Treatment of Hydrocephalus

To date, most patients suffering from hydrocephalus have been treated by insertion of differential-pressure valves that have fairly constant resistance. Since intracranial pressure (ICP) is a variable parameter (depending on such factors as patients position and rapid eye movement sleep) and since cerebrospinal fluid (CSF) secretion is almost constant, it may be assumed that some shunt complications are related to too much or too little CSF drainage. The authors suggest a new approach to treating hydrocephalus, the aim of which is to provide CSF drainage at or below the CSF secretion rate within a physiological ICP range. This concept has led the authors to develop a three-stage valve system. The first stage consists of a medium-pressure low-resistance valve that operates as a conventional differential-pressure valve until the flow through the shunt reaches a mean value of 20 ml/hr. A second stage consists of a variable-resistance flow regulator that maintains flow between 20 and 30 ml/hr at differential pressures of 80 to 350 mm H2O. The third stage is a safety device that operates at differential pressures above 350 mm H2O (inducing a rapid increase in CSF flow rate) and therefore prevents hyper-elevated ICP. An in vitro study is described that demonstrates the capability of this system to maintain flow rates close to CSF production under a range of pressures similar to those observed under various human physiological and postural conditions. Promising clinical results in 19 patients shunted with this valve are summarized.

Intracranial Ependymomas in Childhood Survival and Functional Results of 47 Cases

A pediatric series of 47 intracranial ependymomas (15 supra- and 32 infratentorial) is presented. All children were operated upon between 1969 and 1979. Among these children, 35 completed the treatment with radiotherapy. The irradiation was usually limited to the intracranial content but in 7 patients, it was extended to the spinal axis as well. Malignant ependymomas represented 69% of the whole series (86% of the supratentorial and 53% of the infratentorial ependymomas). The operative mortality rate was 17%. The 5-year survival rate was 39% in the whole series and 51% when excluding postoperative mortality. Recurrences developed in 41% of cases and metastases in 20%. The study of this series and of the literature points out that: (1) metastases from supratentorial ependymomas are not frequent, almost always supratentorial and secondary to a malignant ependymoma, and (2) metastases from infratentorial ependymomas are almost always intraspinal and occur in one third of these tumors. The rate of seeding is especially high in the case of malignant infratentorial ependymomas (50%) but is also 15% in the case of benign tumors. These data lead the authors to propose a craniospinal irradiation in the case of infratentorial ependymomas whether benign or malignant, an irradiation of only the brain in the case of malignant supratentorial ependymoma, an irradiation of only the tumoral bed when ependymomas are benign and supratentorial.

Prenatal hydrocephalus: outcome and prognosis

The clinical records of 108 infants presenting with hydrocephalus at birth and operated on from 1971 to 1981 were reviewed in order to evaluate the functional results. Premature newborns and spina bifida patients were excluded. Communicated hydrocephalus (39 cases) and aqueductal stenosis (32 cases, excluding 6 X-linked hydrocephalus and 4 toxoplasmoses) were the two main types of hydrocephalus in this series. Eighty-four percent of the infants were operated on before the age of 3 months. The mean follow-up time was 7 years (range 1 to 14 years). The survival rate, calculated by the life table method, was 62% at 10 years. The functional results were evaluated according to intellectual performance, academic level, and psychological status. Of the 75 surviving children, 28% have an I.Q. over 80 and 50% an I.Q. under 60. The mean I.Q. is 54 (range 0 to 130). Of the 52 children who have now reached school age, only 29% have reached a normal academic level. The psychological status is normal or borderline in 46% of the patients. The importance of head enlargement at birth, ventricular size, and the age at the time of surgery are not related to late functional results. The results were best when there were no associated malformations, no shunt infection, when hydrocephalus was due to aqueductal stenosis (excluding X-linked hydrocephalus and toxoplasmosis), or when the first developmental quotient measured at 6 months was over 80.

Pericerebral Collections after Shunting

Nineteen pericerebral collections (18 subdural and 1 epidural) occurred in a series of 682 consecutive initial shunt insertions for hydrocephalus in children, performed between 1976 and 1984. No collections were observed in 358 reoperations performed in the same patients during the same period. The incidence rate of this complication is nearly four times higher after 2 years of age than in younger children (6.5% versus 1.7%). The rate is also higher, regardless of age, in noncommunicating than in communicating hydrocephalus. Pericerebral collections are observed with high- as well as low-closing pressure valves. Pericerebral collections after shunting were diagnosed in 80% of the cases less than 2 months after surgery. They were asymptomatic in nearly 60% of the cases but could become symptomatic later when they were not treated. At the onset at least, these pericerebral collections are compensated by the outflow of an equal quantity of intraventricular CSF so that ICP is only moderately elevated. Postshunt pericerebral collections may be the consequence of CSF loss at the time of surgery. In most cases, however, they are due to a CSF overdrainage by the valve. This overdrainage, together with the reversal of CSF flow in the highly resistant CSF pathways of hydrocephalus, establishes a pressure lower in the ventricles than in the subarachnoid space and tends to open up the subdural space. The treatment of postshunt subdural collections is the insertion of a simple tubing without valve between the subdural space and the peritoneum, the ventriculoperitoneal shunt being left in place. With this treatment, more than 80% of the collections disappeared or were improved. No complications or secondary aggravation were observed in any of these patients.

Are the metabolic characteristics of congenital intraspinal lipoma cells identical to, or different from normal adipocytes? *

Congenital intraspinal lipomas are frequently responsible for progressive neurological deficits caused by distortion or compression of the nervous system. Since fat metabolism in these lesions has not been previously studied, the aim of this study was to determine whether intraspinal lipoma cells behave like lipomas or like normal adipocytes. In 11 patients, intraspinal lipoma cells were compared with normal adipocytes isolated from adjacent subcutaneous adipose tissue for the following parameters: lipoprotein lipase (LPL), lipogenesis from U14C glucose, ß-receptor number, adenylate cyclase activity, cyclic AMP production, and lipolysis in response to ß- and α2-adrenergic agonists. No significant difference between these two cell populations was found, suggesting that intraspinal lipomas are not lipomatous tumors, but hamartomatous lesions capable of growth and regression along with the changes in the rest of the fatty pool. This emphasizes the danger of an abnormal weight gain, as well as the possible usefulness of an hypocaloric diet in patients who worsen in spite of previous surgery.

Consensus: long-term outcome in hydrocephalus

Developments in the treatment of hydrocephalus and its outcome are traced from the time of Hippocrates up to the present day. various factors that have been suspected of influencing the outcome are discussed and their relative importance for long-term outcome is reviewed.

Cerebrospinal fluid flow dynamics in children with external ventricular drains.

Fifty-five children had 64 external ventricular drains (EVDs) placed predominantly (95%) for cerebrospinal fluid (CSF) shunt infections. In 9 children, a computer monitoring system measured the CSF output each second continuously for up to 24 hours. The monitoring was repeated daily for up to 9 days. The state of arousal of the patients was recorded simultaneously. In all children, daily EVD outputs were related to age, sex, weight, method of establishing the EVD, height of the drip chamber, time since insertion, and type of infecting organism. Computer monitoring revealed wide fluctuations in flow rate, with peak rates frequently greater than 20 ml/h and periods of flow arrest. These changes were usually associated with increased arousal, but also occurred with sleep. The mean EVD flow rate for all children was 6.3 ml/h. EVD output increased with age and weight. EVD output decreased with Gram-negative or multiple-organism infections and with elevation of the drip chamber. Resolution of the infection, sex of the patient, and method of establishing the EVD had no effect on output. These results predict that CSF production increases with brain growth in humans: that CSF production is depressed by Gram-negative and multiple-organism infections: that implanted CSF shunts with standard valves flow at equivalent rates to an EVD in the supine position; and that the CSF drainage requirements in this group are approximately equal to their EVD outputs.

Lumbosacral lipomas with spina bifida

The pathological and metabolic characteristics, as well as the anatomical and functional evolution of lumbosacral lipomas, were studied in a series of 73 patients operated on between 1970 and 1983. The pathological study showed that they are mainly composed of adipocytes, but that they also possess fibrous tissue, vessels, and nerve fibers. Innervated muscle fibers, contracting under proper nerve stimulation, were found in several cases. Lipogenesis and lipolysis are the same in lumbosacral lipomas and in normal fat tissue. However, these lipomas can grow with the rest of the fatty pool. Moreover, spontaneous progressive worsening of the clinical status has been observed in 36% of the cases. Surgery is efficient and not harmful to the patient. Postoperative mortality was nil. Early postoperative worsening occurred in 2.7% of the cases. The 6% rate of late postsurgical deteriorations should be compared to the 36% to 56% rate found when patients are not operated on. Three different mechanisms are responsible for clinical worsening: compression or stretching of the cord, and cord injury on the posterior upper limit of the spinal defect. In each case, one mechanism is prevalent. Three different types of lumbosacral lipomas can thus be individualized. The surgical implications of these data are discussed. The necessity for early and systematic surgical treatment is pointed out.