The neurological and neuroradiological manifestations of pediatric achondroplasia are analyzed on the basis of 10 cases. In addition to the classical symptomatology of an enlarging head, with or without increased intracranial pressure, several patients presented symptoms related to a small foramen magnum. Respiratory problems and quadriparesis were also observed in these patients. Six patients who were treated by foramen magnum decompression showed remarkable improvement. Neuroradiological evaluation revealed a significant number of patients with dilated cortical sulci and basal cisterns, and mild dilatation of the ventricles on computerized tomography (CT) and/or ventriculography. Two patients showed signs of obstruction at the fourth ventricle outlets. Some exhibited anomalous dilatation of cerebral veins and dural sinuses, narrowing of the sinuses at the jugular foramen, and enlarged emissary veins. Ventriculoperitoneal or ventriculoatrial shunts were placed in three patients. In the other children with a large head and dilated ventricles, head growth curves paralleled the normal slope, and there was no significant clinical evidence of increased intracranial pressure or enlarging ventricles on follow-up CT scan.

The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquinolinesulfonamide) and HA 1077(1-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 X 10(-6) M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10(-5) M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10(-5) M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a "two-hemorrhage" canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% +/- 2% (mean +/- standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA 1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA 1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.

As part of an ongoing series, 100 patients with Cushing's disease underwent transsphenoidal operations. Pituitary adenomas were confirmed in 93 patients, and initial remission was achieved in 86 (92%) of them. Hypercortisolemia was not corrected in 7 patients, and in 4 this was due to invasive adenomas. These patients were subjected to irradiation, medical treatment, or both after operation. Only 7 of the 100 patients had no pituitary adenoma found at operation, and they obtained no clinical remission even after partial or subtotal hypophysectomy. Follow-up review, with an emphasis on endocrinological studies, was performed on these patients for a mean period of 38 months. Seventy-eight patients were in long term remission after operation and had restoration of noncorticotropic hormone secretion as well as pituitary-adrenal function. Recurrence was noted in 8 patients after 19 to 82 months in remission. In all of these patients, pituitary adenomas were verified by reoperation and no case of corticotrophic cell hyperplasia was noted. We conclude that late recurrence of Cushing's disease may occur after adenoma removal and is due to the regrowth of adenoma cells left behind in the peritumoral tissue at the first operation. In view of the overall remission rate, transsphenoidal adenomectomy is considered a highly effective treatment for Cushing's disease.

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Clinical characteristics of six cases of germinoma involving a unilateral basal ganglion and thalamus are summarized. The incidence was estimated as 10% of all intracranial germinomas. The average age at the onset was 10.5 years. The sex incidence showed a male dominance. The clinical course was slowly progressive, and the average duration between onset and diagnosis was 2 years 5 months. Common symptoms and signs were hemiparesis in all cases, fever of unknown origin and eye symptoms in most, mental deterioration and psychiatric signs in three, and convulsions, pubertas praecox, and diabetes insipidus in two. Signs of increased intracranial pressure were found in only two cases in the later state of the disease. Early diagnosis is difficult because of nonspecific symptomatology and slow progression. Carotid angiography and pneumoencephalography showed abnormal findings compatible with basal ganglia and thalamic tumors, but not specific to germinoma. Ipsilateral cortical atrophy and ventricular dilatation might be significant findings. Radioisotope scanning was useful. Computerized tomography scans were the best method of detecting the location and nature of this tumor, and repeat scans showed response to radiation therapy.

The anterior pituitary function in 25 patients with Cushing's disease was assessed before and after transsphenoidal adenomectomy. Pituitary adenoma was detected and removed in 24 cases, resulting in clinical remission in 22. Postoperative hypoadrenocorticism was observed in all of the cases with remission, necessitating substitution of glucocorticoid. One case had a recurrence after a year in remission. Plasma ACTH and cortisol rapidly decreased after surgery and remained at subnormal levels. However, diurnal rhythmicity of ACTH and cortisol appeared in 5 of 9 cases within 6 months after surgery and exhibited normal suppressibility in response to low dose dexamethasone. The impaired ACTH response to hypoglycemia was restored after surgery. The GH response to hypoglycemia and the TSH response to TRH were improved by correction of hypercorticism and became evident over time. These results suggest that preoperative impairment of anterior pituitary hormone secretion is secondary to hyperadrenocorticism and that ACTH hypersecretion by a primary pituitary adenoma is the primary etiology in Cushing's disease. We conclude that transphenoidal pituitary exploration should be considered as a first choice of treatment of Cushing's disease because of its high clinical remission rate in association with normalization of other endocrine functions.

Therapeutic results in 17 cases of alpha-fetoprotein (AFP)-secreting tumors of the central nervous system are reported. Twelve of the patients were male and five female. The patients' ages ranged from 5 years to 25 years (mean 13.6 years). The tumors originated in the pineal region in 10 cases, in the suprasellar region in four cases, and in both regions in one case; of the other two tumors, one originated in the basal ganglia and one in the sacrococcygeal region. Extraneural metastases or subarachnoid dissemination occurred in seven cases. Increased AFP titer in the serum or cerebrospinal fluid was verified in 13 cases. The patients were divided into two groups: those treated before (Group A) and those treated after (Group B) the introduction in 1980 of cisplatin as a chemotherapeutic agent. All seven Group A patients died, even after extensive therapy consisting of surgery, radiotherapy, and chemotherapy (ACNU or adriamycin) in some of the cases. The mean survival time following diagnosis for Group A was 23.7 months. Six of the 10 Group B patients died an average of 25.8 months after diagnosis; however, the other four were still alive and well an average of 25.3 months after diagnosis. The tumors responded well to chemotherapy consisting of cisplatin either alone or combined with bleomycin and vinblastine. The initial response rate to treatment in Group B was 100% and five cases had a complete remission, verified by computerized tomography or the serum AFP level. Once the tumor recurred, the response to cisplatin was markedly decreased. It is suggested that an effective therapy must still be sought for recurrent tumors.

The levels of two calcium-binding proteins, S-100 protein and calmodulin, were measured serially in the cerebrospinal fluid (CSF) of patients after subarachnoid hemorrhage (SAH) and aneurysm surgery. These two proteins have a similar molecular structure and are highly concentrated in the central nervous system (CNS). The levels of S-100 protein found in the earliest postoperative CSF samples correlated with the preoperative SAH grades. High S-100 protein levels in the CSF were found in patients with poor SAH grades. Moreover, the prognosis of the patients correlated with the S-100 protein levels in the CSF samples taken during the immediate postoperative period and with the daily changes of the S-100 protein levels. Severe diffuse cerebral vasospasm was followed by a sharp S-100 protein increase. These results suggest that S-100 protein levels in the CSF provide a useful index of organic damage in the CNS, and furthermore that S-100 protein levels and their changes may have prognostic value for patients after SAH. On the other hand, there was a lack of correlation between the calmodulin levels and the preoperative grade or outcome. It would be inappropriate, however, to speculate from the results of this study that these calcium-binding proteins in the CSF play any causative role in pathological processes such as cerebral vasospasm or brain ischemia after SAH, since changes in the levels of these proteins followed the onset of clinical signs of deterioration.