Kjell Bergström

A parallel study of the roentgen anatomy of the sella turcica and the histopathology of the pituitary gland in 205 autopsy specimens

SummaryTo further elucidate to what extent minor sellar roentgenological changes imply the presence of a microadenoma or other histopathological findings in the pituitary gland, an autopsy series of 205 cases was investigated. Plain sellar films and multidirectional tomograms in frontal and lateral projections were obtained and the pituitary gland was histopathologically examined after being serial sectioned. Sloping of the sellar floor amounting to 2–14° was found in 39 cases and minor cortical changes and configuration variations (locally thinner cortical layer, erosion and bulging) were seen in 23 cases. Histopathology revealed a solitary tumour in the anterior lobe in three cases and focal nodular hyperplasia in a fourth case. The diameter of these nonencapsulated ‘adenomas’ varied between 3 and 5 mm. Small cysts were a fairly common finding and fibrous tissue was present in about every second gland. No correlation was found between the roent-genological changes of the sella and histopathological findings in the gland. It was concluded that the type of roentgenological sellar findings described should be considered as normal variations without pathological significance when diagnosing a pituitary microadenoma.

Cerebral computed tomography in methanol intoxication.

In lout of six patients with methanol intoxication, computed tomog taphy (CT) showed nectotic changes in the atea of the putamma Hemorrhages were also seen in some cases I here. Was a clear relationship between the seventy of the clinical symptoms and the CT findings. indicating the potential of CT for prognosis a possible therapy guidance.

Magnetic resonance imaging of the brain in Wilson's disease

SummaryFifteen patients with Wilsons disease were examined, using spin-echo (SE) and gradient-echo (GE) sequences with 0.5 T and 1.5 T magnetic resonance (MR) imagers. They fell into three groups: groups 1 and 2 were examined retrospectively after 3–18 years of treatment, while group 3 was examined prospectively from the start of treatment, after recommencement of treatment, or inadequate treatment. MRI was sensitive to changes in the basal ganglia at sites typical of Wilsons disease and was useful for documenting the effects of treatment. It was found necessary to estimate the relaxation times T1 and T2, to better assess improvement or transient worsening of the disease in the prospective group. Residual cavitation and gliosis could be distinguished in the retrospective group using a subtraction technique.

Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone.

Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.

Correlative craniospinal anatomy studies by computed tomography and cryomicrotomy

To produce accurate correlating anatomical reference material, fresh frozen craniospinal cadaver specimens were examined in a computed tomography (CT) scanner and sectioned through on a large-format cryomicrotome in the identical plane. Macrophotography of the surface of the specimen during the course of trimming rendered undistorted sectional-anatomical images showing in great detail the morphological structures of the corresponding CT scan.

Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study.

Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-[11C]methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells.

Malignant Prolactinoma with Multiple Intracranial Metastases Studied with Positron Emission Tomography

A rare case of a patient with multiple intracranial metastases from a prolactin-secreting pituitary neoplasm is described. At the age of 14 years, the patient had been operated on for a sellar tumor; he presented 12 years later with severe headache, at which time computed tomographic and magnetic resonance imaging scans revealed multiple intracranial metastases. Histopathology examination showed pituitary neoplastic cells with positive immunostaining for prolactin. The patient was investigated with positron emission tomography (PET) and dopamine D2-receptor binding, and the amino acid metabolism of the tumor was characterized in vivo. High dopamine D2-receptor binding and high amino acid metabolism were found in the tumor. The patient was subsequently treated with bromocriptine injections that resulted in a decrease in serum prolactin levels, decreased dopamine D2-receptor binding, reduced amino acid metabolism, and a reduction in tumor volume. This case demonstrates a beneficial effect of bromocriptine treatment in a patient with prolactinoma with multiple intracranial metastases. It also illustrates the great potential of PET in the in vivo characterization of the D2-binding and the high sensitivity of 11C-labeled L-methionine in the follow-up of treatment in patients with pituitary adenomas.

Cerebrospinal fluid ferritin in patients with cerebral infarction or bleeding

By the use of a radioimmunoassay, ferritin was detected in the cerebrospinal fluid (CSF) of apparently healthy individuals at a mean concentration of 5.1 arb U/l, i.e. a level about 5 % of the mean normal serum‐ferritin concentration. Fourteen patients with acute cerebrovascular stroke or transient ischemic attacks (one case) were followed by serial determinations of CSF‐ferritin during 2 weeks or more from onset of symptoms. After cerebral stroke all patients exhibited an increase of CSF‐ferritin with peak levels between 4 and 6 days from admission. Those three patients in whom computed tomography showed cerebral bleeding had the highest peak CSF‐ferritin concentrations (mean value 249 ± 65 (SEM) arb U/l). The mean peak CSF‐ferritin was 28 ± 11 arb U/l in the patients who had cerebral infarction without signs of bleeding. In seven patients CSF‐ferritin returned to the control range after 2 weeks. The extent of the rise of ferritin in CSF could not be explained by damaged blood‐CSF barrier. We suggest that the increment of ferritin in CSF of patients with cerebrovascular lesions may reflect an inflammatory response within the brain possibly mediated by macrophages.

Amino Acid Distribution and Metabolism in Pituitary Adenomas Using Positron Emission Tomography with D-[11C]Methionine and L-[11C]Methionine

Four patients with hormonally inactive pituitary adenomas were examined with positron emission tomography (PET) after injection, during different examinations, of L-[methyl-11C]methionine and D-[methyl-11C]methionine, respectively. After the rapid distribution phase, the enantiomer L-[11C]methionine, which is metabolically active, showed a considerable continuous irreversible trapping attributed to amino acid metabolism. The stereoisomer D-[11C]methionine, which does not participate in protein synthesis, showed a rapid distribution within the whole adenoma tissue, with a distribution space on the order of 100%. A minimal irreversible trapping was observed which could be explained by technical factors. It is concluded that PET using the two enantiomers allows a separation of passive distribution and metabolism, and that L-[11C]methionine can be used for in vivo quantitative studies of amino acid metabolism of pituitary adenomas.

Distribution of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in experimental animals studied by postiron emission tomography and whole body autoradiography

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a selective potent neurotoxin which has induced a syndrome similar to parkinsonism both in man and in monkeys. At autopsy degeneration of pigmented nerve cells in the pars compacta of the substantia nigra has been confirmed. The regional distribution of intravenously administered 1-(11C-methyl)-4-phenyl-1,2,3,6-tetrahydropyridine (11C-MPTP) in the brain of Rhesus monkeys was studied by positron emission tomography and the whole body distribution in mice was documented by autoradiography and by impulse counting of selected tissues. A very rapid and high uptake of 11C-MPTP derived radioactivity was seen in areas corresponding to striatum and midbrain, including the substantia nigra area. No elimination from these regions was seen during the study period of 2 h. The uptake was in the order of 7-8 times the homogenous distribution of the radioactivity in the monkey. The uptake was generally high also in other regions of the brain, but there some elimination could be distinguished. Pretreatment of the monkey with spiperone, a selective dopamine receptor antagonist, did not alter uptake nor the kinetics of the 11C-MPTP derived radioactivity. Thus 11C-MPTP does not have a high affinity for postsynaptic dopamine receptors. A remarkably high uptake of 11C-MPTP derived radioactivity was seen in the eye of the monkey. The selective uptake of radioactivity in the eye was also confirmed in pigmented but not in albino mice. The melanin affinity of MPTP may cause high intracellular concentrations of the compound or its metabolites in the melanin containing nerve cells in substantia nigra, which may explain the serious vulnerability of these neurons to MPTP.