Acute presentation of craniopharyngioma in children and adults in a Danish national cohort.

We aimed to study the occurrence of acute-onset symptoms at initial presentation in a national Danish cohort of patients with childhood- or adult-onset craniopharyngioma, and to investigate potential risk factors for acute presentation. Medical records of 189 consecutive patients (39 children, 150 adults) presenting with craniopharyngioma during the period 1985-2004 were reviewed, and data regarding initial symptoms, neuroimaging results, vision and pituitary function were systematically collected. Acute symptoms preceding hospital admission were noted. Subgroup analyses were based on age, gender and calendar year period. Potential risk factors for acute presentation were analysed through uni- and multivariate analyses. Acute symptoms were reported in 24 (13%) patients. Acute visual symptoms, headache, nausea or vomiting were most frequently reported, and acute symptoms were more frequent among children (28%) than among adults (9%) (P < 0.01). There were no differences according to sex or calendar year period. Hydrocephalus was present in half of childhood cases and one-fifth of adult patients (P < 0.001). Intra-tumour haemorrhage was seen in two cases. Acute symptoms were more frequent among patients with tumours occupying the third ventricle (P < 0.01), radiologic signs of calcification (P < 0.05) or hydrocephalus (P < 0.01). In multivariate analysis, however, only childhood onset (P < 0.05) and calcification (P < 0.05) were independent risk factors for acute presentation. Craniopharyngioma presented with acute symptoms in 13% of patients. Childhood onset and radiologic signs of calcification were independent risk factors for acute presentation. Intra-tumour haemorrhage was rare.

Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults.

We studied the incidence of craniopharyngioma in Denmark during the period 1985-2004 and estimated worldwide incidence rates (IR) of craniopharyngioma based on a literature review. Craniopharyngioma patients diagnosed during the period 1985-2004 were identified from the Danish National Patient Registry, the Danish Cancer Registry and regional registries. Medical records were reviewed. Danish population data were obtained from Statistics Denmark. European and World population data were obtained from EU and WHO homepages. Prior studies providing data on craniopharyngioma IRs were identified via PubMed and, if appropriate, were included in a weighted analysis estimating overall and children's IRs of craniopharyngioma. IRs are given as new cases per million per year. We identified 189 patients with new verified (162) or probable craniopharyngioma. The overall WHO World-standardised incidence rate was 1.86 (1.60-2.14) for all ages and 2.14 (1.53-2.92) for children (age <15 years). Peak incidence rates were observed in age groups 5-9 and 40-44 years. Fifteen prior studies (including 1,232 craniopharyngioma cases) were identified. Seven and 11 studies, respectively, were eligible for weighted all-ages and childhood population IR analyses, yielding summary IRs of 1.34 (1.24-1.46) (all ages) and 1.44 (1.33-1.56) (children). We have provided a detailed survey of the incidence of craniopharyngioma in Denmark during a recent 20-year period. Overall IR of craniopharyngioma in Denmark was 1.86 (1.60-2.14) as compared to 2.14 (1.53-2.92) among children. Weighted estimates of craniopharyngioma world IRs were 1.34 (1.24-1.46) in all ages and 1.44 (1.33-1.56) among children.

Hypopituitarism and mortality in pituitary adenoma.

BACKGROUND AND OBJECTIVE: Previous studies on hypopituitarism and mortality have concluded that insufficient pituitary function is associated with decreased survival. For several reasons the results are difficult to compare - particularly because definitions and treatment of hypopituitarism have varied and various underlying disorders have been included. The purpose was to assess the relationship between mortality and pituitary function. PATIENTS AND DESIGN: One hundred and sixty consecutive patients (99 men and 61 women) with functionless, suprasellar pituitary adenoma. All were operated on transsphenoidally during the period 1985-1996. Additional radiotherapy was given to 29 patients. Mortality was calculated 12.4 years (median, range 8.1-19.9) after operation. Postoperative hormonal deficits were treated in most, though GH substitution was given only to a minority of patients. RESULTS: Postoperatively 30% of the patients had normal pituitary function (normal adrenocortical, thyroid and gonadal function), 26% were panhypopituitary and 36% had partial pituitary insufficiency. Forty-one patients had died (34.7 expected) yielding a standard mortality ratio (SMR) of 1.18 (95% confidence limits (CI) 0.87-1.60). SMR was significantly increased in women (1.97, CI 1.20-3.21) but not in men (0.83, CI 0.55-1.26). SMR in patients with normal pituitary function, panhypopituitarism and partial insufficiency were not different from that in the general population. SMR in hypopituitary women was substantially higher than in men with pituitary insufficiency. Treatment with growth hormone in GH-deficient patients did not influence survival. CONCLUSION: Pituitary surgery for nonfunctioning adenoma and subsequent pituitary insufficiency had no effect on mortality in men, but was associated with significantly increased mortality in women. Suboptimal hormonal substitution in women may play a role.

Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma.

BACKGROUND AND OBJECTIVE: There is agreement in the literature that pituitary apoplexy is a rare disorder. As our experience differs from this view, we analysed the incidence in patients operated on for a nonfunctioning pituitary adenoma. PATIENTS AND DESIGN: One hundred ninety-two consecutive patients with a suprasellar, clinically inactive adenoma operated on during the period 1985-1996 were retrospectively reviewed. A diagnosis of pituitary apoplexy was made from relevant neurological symptoms together with pertinent findings at operation. RESULTS: Pituitary apoplexy occurred in 41 patients (21%), in 23 patients within 12 days prior to the operation. The male/female ratio was 1.9. Median follow-up time was 13.7 years (range 8.9-19.9). During this period, 12 patients had died, yielding a standard mortality ratio of 1.09 (95% CI 0.62-1.92), similar to that in the patients who had not sustained pituitary apoplexy. Postoperatively, 24% of the patients had normal pituitary function, 38% were panhypopituitary and partial pituitary insufficiency was present in 38%. Subnormal GH secretion was present in virtually all patients tested. Two patients died within 60 days of surgery and in two no or incomplete data were available, although they most likely were panhypopituitary. CONCLUSION: Most of our findings add little to what is known about pituitary apoplexy. On one point, however, they are contrary to previously presented data. We found a much higher incidence of pituitary apoplexy despite rather rigorous criteria for the diagnosis. The outcome as regards survival and endocrine function was not different from that in patients with a nonfunctioning adenoma who did not suffer pituitary apoplexy.

[Treatment of carotid-cavernous fistulas via endovascular approaches]. / Behandling af karotiko-kavernøse fistler via endovaskulaere adgange.

INTRODUCTION: Carotid cavernous fistulas are abnormal communications between the arterial system and the cavernous sinus. The patients present with pulsating exophthalmos, chemosis, and ophthalmoplegia. MATERIAL AND METHODS: Since 1995, eleven patients have been treated for carotid cavernous fistulas at Odense University Hospital using different endovascular approaches. Five of them were treated from the internal carotid artery, four with detachable balloons and one with Guglielmi detachable coils. Five patients were treated by venous approaches. In three cases, the superior ophthalmic vein was used, and in two the inferior petrosal sinus. One patient could not be treated. RESULTS: Ten of the eleven patients were treated successfully. Two of the balloons deflated in a few weeks. In one of the patients the carotid artery was subsequently occluded without problems. The other was not treated again because of age (90 years) and partial relief of the symptoms. In the other eight patients, the symptoms disappeared or were relieved. There were no complications during the procedures. The best and most stable results were achieved by the venous approaches. CONCLUSION: Endovascular treatment, especially the venous approach, should be the first choice in treating carotid cavernous fistulas.

Incidence and late prognosis of cushing's syndrome: a population-based study.

The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.

Results of a neurosurgical two-wall orbital decompression in the treatment of severe thyroid associated ophthalmopathy.

PURPOSE: Follow-up of patients with severe thyroid associated ophthalmopathy treated with a transcranial two-wall orbital decompression and reconstruction. METHODS: A two-wall transcranial orbital decompression was performed in 30 such patients (50 eyes). The patients were evaluated one month postoperatively, and long-term evaluation (median 14 months, range 2-54 months) was carried out. The main outcome measures were visual acuity, proptosis measured by Hertel ophthalmometry, soft tissue involvement, and restriction of eye motility. RESULT: Visual acuity improved rapidly in 28 of 32 affected eyes with normalization in 19 eyes (p<0.001). Worsening was not seen. Median proptosis was reduced by 4.0 mm, range 0-10.0 (p<0.001). Double vision was present in 24 patients before operation 14 of whom achieved binocular vision (p<0.001). Three patients had unchanged complaints and the double vision worsened in one patient. Seventeen of 20 patients on preoperative corticosteroid treatment discontinued this medication in relation to surgery. Complications included one case of perioperative minor stroke and two cases of facial nerve frontal branch palsy. CONCLUSION: The transcranial two-wall decompression is a simple, an efficient and a low-risk procedure for treatment of patients with severe thyroid associated ophthalmopathy.

In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas.

The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied. The basal LH, FSH and alpha-subunit levels were determined before and during 6 months' therapy with octreotide and cabergoline, and MR scans were used to evaluate tumour volume before and during this period of therapy. Octopus-perimetry was used to examine the visual fields. A reduction in tumour volume (mean +/- SEM (range); 30% +/- 4% (18-46%)) during 6 months of combination therapy with octreotide and cabergoline was recorded only in patients with in vivo secretory potential. Tumour volume was not reduced in four patients: in three of these patients it remained unchanged while in one patient it was observed to have increased (by 14%). Of the six patients with pretherapy secretory capacity, one displayed a very high basal level of alpha-subunit (74 microg/l) despite unmeasurable levels of LH and TSH, and an FSH-level of 1 IU/l. The other five patients presented paradoxical LH, FSH and/or alpha-subunit responses to TRH. A reduction in basal levels of LH, FSH and/or alpha-subunit was observed in all six patients, and the maximum reduction of at least one of the hormonal levels was 66% +/- 7% (50-98%). The basal levels of LH, FSH and alpha-subunit in the 10 patients were (mean +/- SEM (range)), 3.0 IU/l +/- 1.0 (0.0-7.4), 12.7 IU/l +/- 5.0 (0.0-39.0) and 9.0 IU/l +/- 7.0 (0.2-74.0). During six months of therapy with octreotide and cabergoline, the basal levels of LH, FSH and alpha-subunit were reduced by > or = 50% in seven patients - including the six patients with in vivo secretion prior to therapy. No new visual field defects were detected during therapy and no deterioration of existing visual field defects was recorded. The medical therapy was well tolerated. The in vivo basal and TRH-stimulated secretory capacity of LH, FSH and alpha-subunit predicted tumour reduction following intensive medical therapy in all of our patients with non-functioning pituitary adenomas.

Cerebral microdialysis monitoring: determination of normal and ischemic cerebral metabolisms in patients with aneurysmal subarachnoid hemorrhage.

OBJECT: The success of treatment for delayed cerebral ischemia is time dependent, and neuronal monitoring methods that can detect early subclinical levels of cerebral ischemia may improve overall treatment results. Cerebral microdialysis may represent such a method. The authors' goal was to characterize patterns of markers of energy metabolism (glucose, pyruvate, and lactate) and neuronal injury (glutamate and glycerol) in patients with subarachnoid hemorrhage (SAH), in whom ischemia was or was not suspected. METHODS: By using low-flow intracerebral microdialysis monitoring, central nervous system extracellular fluid concentrations of glucose, pyruvate, lactate, glutamate, and glycerol were determined in 46 patients suffering from poor-grade SAH. The results in two subgroups were analyzed: those patients with no clinical or radiological signs of cerebral ischemia (14 patients) and those who succumbed to brain death (five patients). Significantly lower levels of energy substrates and significantly higher levels of lactate and neuronal injury markers were observed in patients with severe and complete ischemia when compared with patients without symptoms of ischemia (glucose 0 compared with 2.12+/-0.15 mmol/L; pyruvate 0 compared with 151+/-11.5 micromol; lactate 6.57+/-1.07 compared with 3.06+/-0.32 mmol/L; glycerol 639+/-91 compared with 81.6+/-12.4 micromol; and glutamate 339+/-53.4 compared with 14+/-3.33 micromol). Immediately after catheter placement, glutamate concentrations declined over the first 4 to 6 hours to reach stable values. The remaining parameters exhibited stable values after 1 to 2 hours. CONCLUSIONS: The results confirm that intracerebral microdialysis monitoring of patients with SAH can be used to detect patterns of cerebral ischemia. The wide range from normal to severe ischemic values calls for additional studies to characterize further incomplete and possible subclinical levels of ischemia.

Simple numerical chromosome aberrations characterize pituitary adenomas.

Although pituitary adenomas are among the most frequent intracranial neoplasms, only very few have been cytogenetically analyzed. We have short-term cultured and karyotyped 28 consecutive pituitary adenomas (16 clinically nonfunctioning adenomas and 12 clinically functioning adenomas), finding a normal karyotype in 22, whereas 6 had clonal chromosome aberrations (5 nonfunctioning pituitary adenomas and 1 prolactinoma). The abnormal karyotypes were relatively simple. Most anomalies were numerical, with a structural rearrangement, t(6;19), being found in only one tumor. The most common aberrations were trisomy 7 (3 adenomas), trisomy 9 (2 adenomas), trisomy 12 (2 adenomas), trisomy 20 (2 adenomas), and loss and gain in 2 separate clones of one X chromosome (2 adenomas).

Extensive and symptomatic cranial pneumatization: caused by frequent performance of Valsalva's manoeuvre?

Pneumocranium and spontaneous pneumocephalus are very rare disorders. We report a case in which the patient had suffered for some time from neck pain and neurological symptoms which originated from an extensively pneumatized cranium. The symptoms and the abnormal bone pneumatization disappeared after normalization of a high middle-ear pressure. The history and the findings suggest that the pathological pneumatization was caused by the patient's habit of frequently performing Valsalva's manoeuvre, in combination with the Eustachian tube functioning as a valve.

Aneurysm on a persisting primitive trigeminal artery occluded with guglielmi detachable coils.

SUMMARY: A persisting primitive trigeminal artery (PPTA) is present in 0.2 - 0.6% of all cerebral angiographies. 27 cases of PPTA aneurysms have been reported. We present a case with sixth cranial nerve palsy due to a non ruptured aneurysm on a persisting primitive trigeminal artery. The aneurysm was successfully occluded with Guglielmi Detachable Coils with preservation of the parent artery. The cranial nerve palsy resolved and recovery was uneventful.

Effect of glucocorticoids on ICP in patients with a cerebral tumour.

Preoperative treatment with glucocorticoids in patients with an intracranial tumour has been neurosurgical practice for more than 30 years. Recently, however, a less beneficial effect in patients with a meningeoma is reported. This study included 4 patients with a glioma, 4 with a metastasis and 5 with a meningeoma. All patients had a substantial amount of oedema. The effect of methylprednisolone was monitored during 5 days by clinical examination and epidural pressure measurement. ICP reduction was found in 4 of 13 patients. All observations of decreasing pressure were in patients with a malignant tumour and an initial ICP > 15 mmHg. All 4 patients improved clinically. Another 4 patients with a benign meningioma had a significant increase of ICP and none of them experienced clinical improvement. Clinical deterioration was not observed in any patient despite increasing ICP in some cases. In summary, a beneficial effect of GC was demonstrated only in patients with a malignant tumour and augmented pre-treatment ICP.

[Endovascular occlusion of intracranial aneurysms using the "Guglielmi Detachable Coil"]. / Endovaskulaer lukning af intrakraniale sakkulate aneurismer med "Guglielmi Detachable Coil".

Thirty-seven patients with 42 sacculate intracranial aneurysms of delicate location were treated, or attempted treated, with Guglielmi Detachable Coils (GDC) from July 1994 through December 1995. Intended aneurysm occlusion was not achieved in five patients (five aneurysms) due to unfavourable anatomy. In two additional cases the procedure was interrupted because of complications. In 31 patients (35 aneurysms) the aneurysms were successfully occluded. So far 16 patients (19 aneurysms) have undergone angiography six months postoperatively, and four of five partly recanalized aneurysms were reoccluded. Two patients died following a major complication, and five patients recovered following a minor complication to the procedure. A total of 39 procedures were uncomplicated, and the patients recovered uneventfully. In conclusion, endovascular occlusion with GDC of intracranial aneurysms of delicate location is a promising innovative procedure.