Alex M. Landolt

Gamma knife radiosurgery for prolactinomas

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Results of Transsphenoidal Extirpation of Craniopharyngiomas and Rathke's Cysts

Fourteen patients undergoing transsphenoidal extirpation of craniopharyngiomas or Rathkes cysts underwent endocrinological evaluation before and after surgery. One patient died during the procedure because of uncontrollable arterial bleeding. The other patients were followed for up to 16 years (average, 8.5 years). One patient had recurrence of tumor 12 years after surgery. Another patient, the only one operated on because of a recurrent craniopharyngioma after previous radiation therapy, died 2 years after the transsphenoidal operation. No patient recovered pituitary functions that had been lost before surgery. One patient, who had an isolated growth hormone deficiency, and another, who had panhypopituitarism with sustained antidiuretic hormone secretion, had no change postoperatively from their preoperative endocrine status. The other 11 patients lost pituitary function and required pharmacological replacement of one to four pituitary hormones.

Histology and ultrastructure of an oncocytic adenoma of the human pituitary

A male patient was operated upon at the age of 33 and again at 46 years because of a recurrent pituitary tumor. He received a course of radiation therapy after the first operation. He showed only minimal endocrinologic deficit on both occasions. The initial symptom was visual difficulty. The light microscopy examination of the tumor suggested an oncocytoma in both instances. This diagnosis was established by electron microscopy by the demonstration of an abnormal accumulation of altered mitochondria in the tumor cells with concomitant reduction of other cell organelles, features characteristic for oncocytic cells. Secretory granules were extremely rare. This appears to be the first case of pituitary oncocytic adenoma with ultra‐structural proof of the nature of the tumor.

Surgical treatment of pituitary prolactinomas: postoperative prolactin and fertility in seventy patients

The surgical results obtained in 70 patients with pituitary prolactinomas indicate that the success of surgery depends on the preoperative prolactin level and the diameter of the adenoma, and that the former is the more influential factor. Assessment of both of these parameters affords a good prediction of the endocrine result. The cure rates for different patient groups ranged from 4% to 90%. Postoperative results in women (57% with normal prolactin levels) were better than those in men (17% with normal prolactin levels). Of 19 women who desired pregnancy, 11 (58%) achieved successful pregnancies; 1 woman became pregnant twice. In addition, one woman had an extrauterine pregnancy and one suffered a spontaneous abortion. Five required additional bromocriptine therapy. The data were evaluated analytically.

Cholinergische Synapsen im Oberschlundganglion der Waldameise (Formica lugubris Zett.)

SummaryThe corpora pedunculata of the wood ant (Formica lugubris Zett.) consist of two sharply defined layers: The perikaryon layer and the subjacent neuropil. Synaptic endings are found exclusively in the neuropil. The synapses consist of a central, presynaptic end knob of 1.2–2.5 μ diameter and a relatively large number of surrounding postsynaptic processes of 0.3–1.1μ diameter. These junctions are analogous to axodendritic synapses of the vertebrates. The presynaptic process contains mitochondria and a multitude of light vesicles (300–600 Å diameter). Larger vesicles 700–1000 Å with a dark center are seen more rarely. The synaptic cleft has a diameter of approximately 130 Å and varies somewhat with different fixation methods. With glutaraldehyde-osmium fixation, this relatively wide gap is maintained only in circumscribed areas of the junction, while in adjacent areas it tends to contract and an “external compound membrane” is formed. The postsynaptic region is characterized by the presence of a subsynaptic network which is revealed only by suitable fixation methods. This and the persistent synaptic cleft are the main structural differentiations found in junctional areas thus far.Cholinesterase is located with the aid of thiolacetic acid (Barnett) and Eserin control studies. The enzyme is found in the cytoplasm immediately adjacent to the pre- and postsynaptic membranes. In two thirds of our observations the reaction is far more concentrated postsynaptically than presynaptically. In one third, the distribution is reversed. Only an insignificant amount of cholinesterase is present within the synaptic cleft. There is no evidence that cholinesterase is evenly distributed along the entire junctional region. In contrast, only small circumscribed areas show a positive reaction and these coincide with the extent of the synaptic cleft and the subsynaptic network. Such areas seem to correspond to the “active junctional areas”.

Cytokine expression in human anterior pituitary adenomas

OBJECTIVE There is increasing evidence for the role of cytokines in pituitary differentiated function and tumorigenesis, but the spectrum of cytokines found in the pituitary is unknown. Therefore profiles of cytokine expression were determined in different human anterior pituitary adenoma sub‐types.

Elektronenmikroskopische Untersuchungen an der Perikaryenschicht der Corpora pedunculata der Waldameise (Formica lugubris Zett.) Mit besonderer Bercksichtigung der Neuron-Glia-Beziehung

1. The supraoesophageal ganglion of a common wood ant species (Formica lugubrisZett.) is separated from the fat and glycogen containing extracerebral tissue by a sheath consisting of a cell-free neural lamella and a layer of perilemma cells. 2. The neurons of the corpora pedunculata form a superficial cortical layer consisting of small perikarya (5–15 μ in diameter), which are assembled in epithelial fashion. They give rise to only one single process (axon) and receive neither dendritic nor axonic synapses. The perikarya contain a relatively poorly differentiated endoplasmic reticulum, yet an abundance of ribosomes preponderantly not organized within a typical ergastoplasmic assembly. Two types of inclusion bodies have been found which seem to be common stock of insect neuronal cytoplasm. 3. The glial cells form a complex mesh of processes surrounding the neurons of the cortical layer. Relatively few cell bodies, outnumbered 10–50 times by the neurons, develop a stupendous surface matching the one of neuronal perikarya. The inner structure is characterized by an electron dense cytoplasm (denser than that of neurons), high content in ribosomes and glycogen granules, occasional gliosomes and a dense, lobated nucleus. The Golgi apparatus of glial cells is less well developed than that of neurons. 4. The neuroglial processes reach within the glycogen packed perilemma cell layer and extend from the dorsal to the ventral surface of the cortex. Its marked glycogen content suggests that the neuroglia forms a link in glycogen transport from the extracerebral storage tissue via perilemma cells to neurons. 5. The neuroglial processes separate the neurons from the tracheal system throughout. Furthermore, conglomerations of glial endings immediately contact the distal portions of the tracheolar system forming the “tracheolar end organs”. These observations suggest specific glial functions relative to gas exchange and energy metabolism of the neuron. 6. The plasma membranes of glial cells and neurons consist of “unit membranes” of 90 A diameter. The interstitial space is conspicuously narrow (30 A) and can be experimentally expanded by means of hypertonic solutions. No decrease in extracellular space was seen with use of hypotonie fixatives. The role of interstitial space and the interposed meshwork of glial cytoplasm for the mechanism of polarisation and depolarisation of the neuron plasmalemma is discussed in the light of current theory.Summary1.The supraoesophageal ganglion of a common wood ant species (Formica lugubrisZett.) is separated from the fat and glycogen containing extracerebral tissue by a sheath consisting of a cell-free neural lamella and a layer of perilemma cells.2.The neurons of the corpora pedunculata form a superficial cortical layer consisting of small perikarya (5–15 μ in diameter), which are assembled in epithelial fashion. They give rise to only one single process (axon) and receive neither dendritic nor axonic synapses. The perikarya contain a relatively poorly differentiated endoplasmic reticulum, yet an abundance of ribosomes preponderantly not organized within a typical ergastoplasmic assembly. Two types of inclusion bodies have been found which seem to be common stock of insect neuronal cytoplasm.3.The glial cells form a complex mesh of processes surrounding the neurons of the cortical layer. Relatively few cell bodies, outnumbered 10–50 times by the neurons, develop a stupendous surface matching the one of neuronal perikarya. The inner structure is characterized by an electron dense cytoplasm (denser than that of neurons), high content in ribosomes and glycogen granules, occasional gliosomes and a dense, lobated nucleus. The Golgi apparatus of glial cells is less well developed than that of neurons.4.The neuroglial processes reach within the glycogen packed perilemma cell layer and extend from the dorsal to the ventral surface of the cortex. Its marked glycogen content suggests that the neuroglia forms a link in glycogen transport from the extracerebral storage tissue via perilemma cells to neurons.5.The neuroglial processes separate the neurons from the tracheal system throughout. Furthermore, conglomerations of glial endings immediately contact the distal portions of the tracheolar system forming the “tracheolar end organs”. These observations suggest specific glial functions relative to gas exchange and energy metabolism of the neuron.6.The plasma membranes of glial cells and neurons consist of “unit membranes” of 90 Å diameter. The interstitial space is conspicuously narrow (30 Å) and can be experimentally expanded by means of hypertonic solutions. No decrease in extracellular space was seen with use of hypotonie fixatives. The role of interstitial space and the interposed meshwork of glial cytoplasm for the mechanism of polarisation and depolarisation of the neuron plasmalemma is discussed in the light of current theory.

Distribution of growth hormone and prolactin in secretory granules of the normal and neoplastic human adenohypophysis.

SummaryGrowth hormone [GH] and prolactin [PRL] can be demonstrated simultaneously in electron micrographs by means of the double immunocytochemical labeling technique using colloidal gold particles of two different sizes. This method was used to study biopsy specimens obtained from 15 patients suffering from acromegaly, 11 patients suffering from prolactinomas, and eight biopsy specimens obtained during adenomectomy from the normal, paraadenomatous pituitary tissue. Four granule populations with different immunoreactions were found: (1) granules containing GH only, (2) granules containing PRL only, (3) mixed granules containing GH and PRL, and (4) granules displaying no immunoreactivity. The existence of mixed granules indicated that the two hormones are synthesized by the same cell and in communicating compartments of the cells; i.e., the roughsurfaced endoplasmic reticulum. The number of GH-containing granules (pure GH granules and mixed GH-PRL granules) was greater than that of PRL-containing granules (pure PRL granules and mixed PRL-GH granules) in adenomas causing acromegaly and in the normal pituitary tissue, whereas the opposite was true for prolactinomas. The number of PRL-containing granules was larger in biopsy specimens from patients who had acromegaly and hyperprolactinemia than in patients with acromegaly and normal serum PRL levels.

Alpha-subunit-producing pituitary adenomas

Immunohistological techniques demonstrate the alpha-subunit of glycoprotein hormones in the majority of endocrine-inactive, undifferentiated pituitary adenomas and pituitary oncocytomas. In about one-fifth of endocrine-active adenomas, the alpha-subunit is produced in combination with either adrenocorticotropic hormone or prolactin, and it is found in combination with growth hormone in about half of those adenomas causing acromegaly. Pure alpha-subunit-producing, endocrine-inactive adenomas characteristically have small secretory granules that are destroyed by direct osmium fixation, but are well preserved after prefixation with glutaraldehyde. As only a few atypical prolactinomas show similar secretory granules, and as they display a positive reaction for the alpha-subunit only exceptionally, this ultrastructural feature can serve as a guide to differentiate such adenomas.

Cerebrospinal fluid rhinorrhea: a complication of therapy for invasive prolactinomas.

The majority of invasive prolactinomas can be predicted with a high probability if the preoperative prolactin level is above 2000 ng/ml. As these tumors cannot be extirpated radically, adjunctive radiation therapy is used to improve the results of treatment. On the basis of reports that bromocriptine induces tumor shrinkage and has an antimitotic effect, we combined adjunctive irradiation with bromocriptine therapy in 14 patients who had particularly extensive invasion. Two of these patients developed cerebrospinal fluid rhinorrhea 3 and 5 months, respectively, after the completion of radiation therapy. In both patients, the fistula was localized in the sellar region and was closed successfully. Rapid tumor shrinkage caused by irradiation combined with bromocriptine therapy may be a factor causing this complication; postoperative rhinorrhea is otherwise extremely rare in our surgical series. We also observed a third patient who did not have an operation, but who developed rhinorrhea after a course of irradiation and bromocriptine treatment. The periods of rhinorrhea coincided with periods of bromocriptine treatment.