[Nonfunctioning pituitary macroadenomas: diagnosis, treatment and follow-up]. / Niet-functionerende macroadenomen van de hypofyse: diagnostiek, behandeling en follow-up.

*Nonfunctioning pituitary adenomas are benign tumours characterised by the absence of hormone overproduction. *Clinical symptoms are caused by the mass effects of the tumour. The main symptoms are pituitary insufficiency, visual field defects, vision impairment and headache. *Treatment is unnecessary for tumours less than 1 cm, and an expectative approach can be used for some patients with larger tumours but no visual field defects. *Transsphenoidal surgery is indicated for patients with visual field defects. *Because nonfunctioning adenomas can recur, lifelong follow-up after treatment is necessary. *Poor quality of life has been reported in treated patients with nonfunctioning pituitary adenomas, which may be due to the intrinsic imperfections of hormonal replacement therapy.

Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma.

CONTEXT: Increased mortality in patients with pituitary tumors after surgical treatment has been reported. However, it is unknown to what extent excess mortality is caused by pituitary tumors and their treatment in general and to what extent by previous exposure to hormonal overproduction. OBJECTIVE: The aim of the study was to compare mortality between patients treated for Cushing's disease and nonfunctioning pituitary macroadenomas (NFMAs). DESIGN: This was a follow-up study. PATIENTS: We included 248 consecutive patients with pituitary adenomas treated by transsphenoidal surgery in our hospital for NFMAs (n = 174) and ACTH-producing adenomas (n = 74). The mean duration of follow-up after surgery was 10.1 +/- 7.2 yr for the whole cohort. OUTCOME MEASURES: The standardized mortality ratio (SMR) was calculated for the whole cohort and also for the two diseases separately. Cox regression analysis was used to compare mortality in patients with Cushing's disease with NFMA patients. RESULTS: Patients with Cushing's disease (39.1 +/- 16.1 yr) were significantly younger at time of operation than NFMA patients (55.3 +/- 13.4 yr). The SMR for the whole cohort was 1.41 [95% confidence interval (CI), 1.05-1.86]. The SMR in NFMA patients was 1.24 (95% CI, 0.85-1.74) vs. 2.39 (95% CI, 1.22-3.9) in patients with Cushing's disease. In patients with Cushing's disease, compared with NFMAs, the age-adjusted mortality was significantly increased: hazard ratio 2.35 (95% CI, 1.13-4.09, P = 0.008). CONCLUSIONS: Mortality in patients previously treated for Cushing's disease is increased, compared with patients treated for NFMAs. This implies that previous, transient overexposure to cortisol is associated with increased mortality.

Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma.

OBJECTIVE: Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas (NFMA). In this study we evaluated the long-term effects of a treatment strategy in which postoperative radiotherapy was not routinely applied to patients with NFMA. DESIGN: This was a retrospective follow-up study. PATIENTS: We included 109 consecutive patients (age 56 +/- 13 yr) operated for NFMA between 1992 and 2004. RESULTS: Radiological imaging revealed a macroadenoma in all patients, with suprasellar extension in 96% and parasellar/infrasellar extension in 36% of cases. Visual field defects were present in 87% of the patients and improved in 84% of these patients after surgery. Only six patients received postoperative radiotherapy. Ten patients died during the follow-up period. Ninety-seven patients could be assessed for tumor regrowth or tumor recurrence after a mean follow-up period of 6.0 +/- 3.7 yr. In nine patients there was evidence for tumor regrowth, and in one patient tumor recurrence was observed. The mean time to tumor growth/recurrence after initial therapy was 6.9 (range 3-12) yr. Follow-up duration was found to be an independent predictor for tumor regrowth. CONCLUSION: Transsphenoidal surgery without postoperative radiotherapy is an effective and safe treatment strategy for NFMA, without evidence for tumor regrowth in 90% of all patients, at least for the duration of follow-up presented in this study. Additional studies are required to exclude higher regrowth and recurrence rates during prolongation of the duration of follow-up.

The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age.

PURPOSE: To determine if in patients with single brain metastasis the addition of neurosurgery to radiotherapy leads to lengthening of survival or to better quality of life. METHODS AND MATERIALS: From 1985 to 1990, 66 patients with single brain metastasis from a solid tumor were entered in a randomized trial of neurosurgery plus radiotherapy vs. radiotherapy alone. Patients were stratified for lung cancer vs. other sites of cancer and for progressive vs. stable systemic cancer. Radiotherapy was given to the whole brain by a novel scheme of two fractions of 2 Gy per day for a total dose of 40 Gy in 2 weeks, to obtain a relatively high total dose and short overall time, with minimal risk of late damage to normal tissue in long-term survivors. RESULTS: In the whole group of 63 evaluable patients, both with lung cancer as with other tumors, the combined treatment led to a better duration of survival (median 10 vs. 6 months; p = 0.04). The largest difference between both treatment arms was observed in patients with inactive extracranial disease (median 12 vs. 7 months; p = 0.02). Patients with active extracranial disease had an equal median survival of only 5 months, irrespective of given treatment. Age proved to be a strong and independent prognostic factor: patients older than 60 years had a hazard ratio of dying of 2.74 (p = 0.003) compared with younger patients. Following treatment, most patients remained functionally independent until a few weeks before death. In the majority of patients the cause of death was systemic tumor progression. CONCLUSION: Patients with single brain metastasis and with controlled or absent extracranial tumor activity should be treated with surgery and radiotherapy, especially when they are younger than 60 years. For patients with progressive extracranial disease, radiotherapy alone seems to be sufficient. The accelerated radiotherapy scheme of 40 Gy in 2 weeks to the whole brain is tolerated well and should also be considered for patients in a good performance status with surgically unaccessible single metastasis or even with multiple brain metastases.

Hemostatic agents: brain tissue reaction and effectiveness. A comparative animal study using collagen fleece and oxidized cellulose.

In a series of 26 young rabbits, three cortical lesions were made in each hemisphere. Two of these holes were filled with collagen fleece (CF) and oxidized cellulose (OC), respectively, while the third was left empty as a control. The bleeding time was measured. Hemostasis with CF was statistically significantly faster than with OC, which in turn was statistically significantly faster than with no hemostatic agent. The animals were killed successively on Days 7, 14, 28, 42, and 241 after operation. Histopathological investigation showed that CF did not induce more tissue reaction that the control lesion and that CF was resorbed faster than OC. The removal of OC occurred from the borders of the material, moving gradually inward. With CF, there was an immediate ingrowth of reactive cells throughout the material. In contrast to OC, CF did not induce the formation of polynucleated giant cells. From these results, it can be concluded that CF is a fast, safe, and absorbable topical hemostatic agent suitable for use in neurosurgical procedures.

Interphase cytogenetics: a new tool for the study of genetic changes in brain tumors.

Interphase cytogenetics is the application of nonradioactive in situ hybridization with chromosome-specific DNA probes to interphase nuclei. In this study, interphase cytogenetics was used to investigate 66 primary brain tumors (33 gliomas, 30 meningiomas, and three medulloblastomas) for numerical chromosomal aberrations of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. Of the 33 gliomas (17 astrocytomas grades II, III, and IV, five oligoastrocytomas, seven oligodendrogliomas, and four ependymal tumors), 22 were near diploid, while the remaining 11 showed a significant triploid or tetraploid component. The predominant specific aberrations in gliomas were an over-representation of chromosome 7 (13 cases) and an under-representation of chromosome 10 (16 cases). These changes were observed in grade III and grade IV astrocytomas, as well as in oligodendrogliomas. Other frequent numerical changes were a gain of chromosome 17 (six cases) and a loss of chromosome 18 (seven cases). This loss of chromosome 18 seemed relatively specific for gliomas with an oligodendroglial component (six cases). Only two of 33 gliomas displayed no genetic abnormality with the probes used. Seven patients with astrocytomas died of their brain tumor during the clinical follow-up period. Their astrocytomas did not show a different chromosomal constitution compared to the other gliomas. For the meningiomas, the probe panel was extended with a probe specific for chromosome 22. Loss of chromosome 22 was obvious in 21 of the 30 meningiomas, and was the sole abnormality in 11 meningiomas; in the other 10, this loss was associated with other chromosomal changes. Five of these tumors with additional aberrations were recurrent or atypical meningiomas. It is suggested that interphase cytogenetics can contribute to a better understanding of the biological behavior of these tumors and possibly result in better insights into prognosis and strategies for therapy.

Arachnoid cysts of the middle cranial fossa. Surgical management for headache.

To answer the question whether headache in association with a middle cranial fossa arachnoid cyst without other signs warrants surgery, an analysis of five cases is performed. Three of 5 patients became free of symptoms, compared with 15 of 19 (79%) patients that have been collected in the literature. Both failures were treated with a low pressure cysto-peritoneal shunt without fenestration. They complained of headache resembling postural headache after lumbar puncture. Surgical treatment in the form of a craniotomy with fenestration can be advised, but is major neurosurgery. Alternatively, the merit of a cysto-ventriculo-peritoneal shunt should be considered in this group of patients.

Microvascular decompression for trigeminal neuralgia: a critical reappraisal.

The results of posterior fossa explorations for trigeminal neuralgia over the period 1980-1990 in 58 patients and in 59 procedures were studied retrospectively. In 51 procedures vascular compression was treated by microvascular decompression (MVD). In the absence of such a compression, partial sensory rhizotomy (PSR) was performed in 5 cases and only adhesiolysis of thickened arachnoidea in 2 cases. In one additional case the procedure was terminated prematurely due to the development of cerebellar edema. Two months postoperatively a good or fair result was obtained in 80% of the procedures. At long-term follow-up (mean 77.3 months, range 8-146 months), a good or fair result was maintained in 71%. There was no significant difference in outcome between the MVD group and the other procedures, or between the three groups formed according to the type of vascular compression. However, in the group of 10 patients with a history of a procedure affecting the trigeminal ganglion or nerve root the result was worse. In the group of 41 MVD patients rendered free of pain at 2 months postoperatively, 8 patients perceived a recurrence. The annual recurrence rate was calculated to be 2.6%. There was no mortality in this series but the morbidity rate was 22% including 1.7% persistent neurological deficit. Compared to the literature results of percutaneous controlled differential thermocoagulation (PCDT), the recurrence and failure rates in the present series appear to be more or less the same. As neither of the two is an unequivocally more effective treatment, we are of the opinion that the less invasive procedure should be preferred.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme histochemistry of the spinal cord after experimental transection (Th 9) in the cat.

Subpial complete resection of a 10 mm segment of the spinal cord at Th 9 was performed in 9 adult cats. Topographic enzyme histochemical investigations of the terminal clubs were performed after different survival times after transection in 7 cats and three days after a subsequent one-week-delayed autologous sciatic grafting procedure in the remaining two cats. For acid phosphatase (ACP), the count of active terminal clubs was high (200 per m2) from 12 hours until day 3 after transection. Then the count of active terminal clubs decreased to a low level (20 per m2) and remained the same until day 14. Removal of necrotic tissue and subsequent grafting with autologous sciatic nerve did not change these findings. For succinate dehydrogenase (SDH), the numbers of terminal clubs showed the same pattern at a lower level. The SDH defined terminal clubs were smaller than the ACP ones. The length of the SDH positive area decreased after 7 days while the ACP positive area remained the same until day 14. The SDH active terminal clubs are overgrown by the ACP positive terminal clubs, after the 7th day. Considering that SDH is linked to constructive activity in mitochondria and ACP to destructive activity in lysosomes, this phenomenon might be responsible for the termination of the capacity of the spinal cord tissue to regenerate.

Immunocytochemical localization of neurofilaments in the fibre systems of the developing rat spinal cord white matter.

The appearance and localization of the protein subunits of neurofilaments in the ascending and descending fibre systems of the developing rat spinal cord white matter were studied. The monoclonal antibody NF-90 (specific for the phosphorylated NF-L, NF-M and NF-H subunits) was used as neurofilament marker in fresh cryostat and Bouin fixed paraffin sections. The results were compared with Nissl and Bodian stained sections. Within the white matter, phosphorylated neurofilament proteins were expressed with regional variations. At embryonal day 12 (E12), the first positive fibres were found in the lateral funiculus. During further development, the peripheral region of the lateral funiculus showed an intense neurofilament staining, due to the presence of a higher number of fibres. From postnatal day 12 (P12) on, an increased amount of neurofilaments was found in the region close to the periphery, probably due to the presence of large calibre fibres. The dorsolateral part of the lateral funiculus filled in with fibres after birth, which indicated the extended development of the rubrospinal tract. At E13, positive fibres were present in the ventral commissure and the ventral funiculus. At E14, an increased amount of neurofilaments was detected in the periphery of the ventral funiculus. At maturity, an intense staining in the subsurface region could be found, due to the presence of large calibre fibres of the fasciculus longitudinalis medialis. At E13, the first neurofilament positive fibres were present in the dorsal funiculus. At this day, a concentration of fibres was found in the dorsal part of the dorsal root bifurcation zone and three days later, more fibres were detected in the medial part of the dorsal funiculus. At E18, a higher number of fibres was present in the dorsal region of the fasciculus gracilis. The mature fasciculus cuneatus showed an intense neurofilament staining, which was mainly present in large calibre fibres. The ventral part of the dorsal funiculus filled in with neurofilament positive fibres after birth. This indicated the relative late arrival of the corticospinal tract.

Intrathecal baclofen for dystonia of complex regional pain syndrome.

Dystonia in complex regional pain syndrome (CRPS) responds poorly to treatment. Intrathecal baclofen (ITB) may improve this type of dystonia, but information on its efficacy and safety is limited. A single-blind, placebo-run-in, dose-escalation study was carried out in 42 CRPS patients to evaluate whether dystonia responds to ITB. Thirty-six of the 38 patients, who met the responder criteria received a pump for continuous ITB administration, and were followed up for 12 months to assess long-term efficacy and safety (open-label study). Primary outcome measures were global dystonia severity (both studies) and dystonia-related functional limitations (open-label study). The dose-escalation study showed a dose-effect of baclofen on dystonia severity in 31 patients in doses up to 450 microg/day. One patient did not respond to treatment in the dose-escalation study and three patients dropped out. Thirty-six patients entered the open-label study. Intention-to-treat analysis revealed a substantial improvement in patient and assessor-rated dystonia scores, pain, disability and quality-of-life (Qol) at 12 months. The response in the dose-escalation study did not predict the response to ITB in the open-label study. Eighty-nine adverse events occurred in 26 patients and were related to baclofen (n=19), pump/catheter system defects (n=52), or could not be specified (n=18). The pump was explanted in six patients during the follow-up phase. Dystonia, pain, disability and Qol all improved on ITB and remained efficacious over a period of one year. However, ITB is associated with a high complication rate in this patient group, and methods to improve patient selection and catheter-pump integrity are warranted.

Aneurysmal bleeding. A plea for early surgery in good-risk patients.

From 1985 onwards we have aimed at operating on good-risk patients, i.e., those graded I-III on the WFNS SAH Scale, within 3 days after the aneurysmal bleed. We report on a series of 100 consecutive operations for saccular aneurysm, covering a period of 5 1/2 years. Early operations (in the above sense) were done in 57 good-risk but otherwise unselected patients. After a one year follow-up, 47 of them (82%) were found to have made a good recovery (Glasgow Outcome Score I). The outcome of (mostly early) surgery in 15 selected poor-risk patients (WFNS SAH Scale IV and V) was much less favourable. Late surgery (4 or more days after SAH) was performed in 28 good-risk patients, most of whom had been admitted several days or weeks after the bleeding. Almost all of these patients had a good outcome. It is argued that the known management results of delayed surgery, which during the deliberately chosen interval exposes the patient to the risk of rebleeding and vasospasm, have by now been surpassed by those of early surgery. However excellent the surgical results of delayed operations may be, early operation should become the treatment of choice in good-risk patients.

Arterial compression of the fifth cranial nerve causing trigeminal neuralgia: angiographic findings.

A common cause of trigeminal neuralgia (TN) is compression of the root of the fifth cranial nerve by a tortuous basilar artery or one of its branches. Microvascular decompression surgery has proved valuable in relieving the symptoms of these patients with nerve compression. We performed vertebral angiography on 22 patients with TN. The angiographic appearances were compared with the findings obtained from an anatomic study in which the positions of 20 trigeminal nerves in the skull were determined radiographically in 12 cadavers. By using this information, we were able to predict the presence of arterial-nerve compression in 20 of the 22 patients, and these positions were later confirmed at surgery. We describe the angiographic findings in patients with TN as well as the findings in a control group of 159 individuals with no history of TN. From these preliminary results, angiography appears to be valuable in the preoperative evaluation of patients with TN.

Magnetic resonance imaging in occult spinal dysraphism.

The value of magnetic resonance imaging (MRI), compared to myelography and computerized tomography, is illustrated in six patients with occult spinal dysraphism. MRI proved to be the diagnostic tool of choice.

Results of a feasibility trial to achieve total immobilization of patients in a neurosurgical intensive care unit with etomidate.

In the intensive care unit of Leiden University Neurosurgical Department 52 critically ill patients were given continuous infusions of etomidate to achieve 'total immobilization'. This can be defined as a state whereby there is complete elimination of all psychic, sensory and motor unrest. Etomidate administration varied from 2 hours to 25 days and dosages began at 20 micrograms/kg/minute and were increased to 110 micrograms/kg/minute according to need and indications for varying periods of time. Attempts were made to control unrest, convulsive seizure activity and raised intracranial pressure. Acceptance of artificial ventilation was achieved in most cases without muscle relaxants or morphinomimetic supplementation. Despite the long durations of administration and high doses no toxic or other detrimental side-effects were noted. Etomidate appears to show the potential of being a very valuable addition to the neurosurgical intensive care armamentarium.