Cerebral glucose metabolism in the striate cortex positively correlates with fractional anisotropy values of the optic radiation in patients with glaucoma.

BACKGROUND: It has recently become clear that glaucoma is not only an ocular disease, but involves central visual pathways as well. The purpose of this study was to examine functional and structural alterations in the brains of glaucoma patients. DESIGN: Case-control study in a hospital. PARTICIPANTS: A total of 32 glaucoma patients and 19 healthy controls. METHODS: All participants underwent positron emission tomography with (18)F-fluorodeoxyglucose, diffusion-tensor magnetic resonance imaging, and the 30-2 program of the Humphrey Visual Field Analyzer. MAIN OUTCOME MEASURES: Fractional anisotropy values of the optic radiation were compared between the two groups by defining regions of interests. Cerebral glucose metabolism was compared using statistical parametric mapping software. The correlation coefficients were calculated between the average of the total deviation of hemivisual fields of both eyes, fractional anisotropy values of the contralateral optic radiation and glucose metabolism in the contralateral striate cortex. RESULTS: Fractional anisotropy values in the bilateral optic radiations were significantly lower in patients with glaucoma. A significant glucose hypometabolism in the bilateral striate cortex was also observed in the glaucoma group. Regression analyses for glaucoma patients demonstrated that the average of the total deviation of hemivisual fields significantly correlated with both fractional anisotropy value of the contralateral optic radiation and glucose metabolism in the contralateral striate cortex. Moreover, there were significant correlations between fractional anisotropy values of the optic radiation and ipsilateral striatal glucose metabolism. CONCLUSION: We observed structural alterations in the bilateral optic radiations and glucose hypometabolism in the bilateral striate cortex of glaucoma patients.

Positive correlation between the degree of visual field defect and optic radiation damage in glaucoma patients.

PURPOSE: We evaluated optic radiation (OR) damage in patients with glaucoma by using fractional anisotropy (FA) of diffusion-tensor magnetic resonance imaging. METHODS: We studied 29 patients with glaucoma and 19 healthy controls. Regions of interest were placed over the bilateral anterior and posterior ORs on the FA maps, and the FA value of each region was measured. RESULTS: FA values of the bilateral anterior and posterior ORs were significantly lower in patients with glaucoma (anterior right, P = 0.0002; anterior left, P = 0.00028; posterior right, P = 0.0004; and posterior left, P = 0.0001) than in the healthy controls. In glaucoma patients, significant correlations were observed between the FA values and the average of the total deviation of the contralateral hemifields of both eyes (left hemifield and anterior right OR, correlation coefficient [r] = 0.46 [P = 0.013]; right hemifield and anterior left OR, r = 0.43 [P = 0.021]; left hemifield and posterior right OR, r = 0.54 [P = 0.0027]; and right hemifield and posterior left OR, r = 0.46 [P = 0.012]). CONCLUSIONS: FA values of the entire OR were decreased in glaucoma patients and correlated with the degree of visual field defect.

Increased adenosine A1 receptor levels in hemianopia patients after cerebral injury: an application of PET using 11C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine.

PURPOSE: The aim of this study was to apply positron emission tomography (PET) with C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a radioligand for adenosine A1 receptor (A1R), to patients with hemianopia caused by brain injury to study neurorepair mechanisms in the brain. PATIENTS AND METHODS: Four patients with homonymous hemianopia and 15 healthy subjects were examined using PET to measure cerebral glucose metabolism, C-flumazenil (FMZ) binding to the central benzodiazepine receptor, and MPDX binding to A1R. Left and right regions of interest (ROIs) were selected, and semiquantitative data on the 3 kinds of PET examinations were obtained. The ROIs were referenced using the data for homologous regions in the contralateral hemisphere [ipsilateral/contralateral (I/C) ratio]. RESULTS: The I/C ratios for cerebral glucose metabolism and FMZ binding were low in the primary visual cortex (PVC) and visual association cortex in all the patients, whereas MPDX binding increased in the PVC in patients 1 and 2. Patients 1 and 2 experienced improvement in their visual field after 1 year. However, the other 2 patients showed no changes. We observed an increase in MPDX binding to A1R in the injured portion of the PVC in the patients who recovered. CONCLUSIONS: Evaluation of A1R by MPDX-PET may be useful for predicting prognosis and understanding the compensatory and reorganization processes in hemianopia caused by organic brain damage.

Functional and neuroreceptor imaging of the brain in bicuculline-induced dystonic rats.

Dystonia is an involuntary movement disorder dominated by sustained muscle contractions that frequently cause twisting, repetitive movements, and postural changes. The purpose of this study was to determine the mechanism causing dystonia. We therefore employed a rat model of dystonia, which was induced by injecting (-)-bicuculine methiodide (BM), a gamma-aminobutyric acid A (GABA(A)) receptor antagonist, stereotaxically into the ventrolateral thalamic nuclei. Cerebral glucose metabolism reflecting cerebral activities and densities of central benzodiazepine and adenosine A(1) receptors that play an inhibitory role in neural excitation were evaluated in the brain by ex vivo autoradiography using appropriate (14)C/(18)F- or (11)C-labeled tracers. The dystonic signs were accompanied by increased glucose metabolism in the thalamus, substantia nigra, globus pallidus, and striatum. However, central benzodiazepine receptor density was not altered, and adenosine A(1) receptor density was reduced in the hippocampus. These results indicate the activation of a basal ganglia-thalamo-cortical motor circuit, which consists of the thalamus, substantia nigra, globus pallidus, and striatum. In this context, the activation of the above circuit has been reported in human dystonia patients. The decreased adenosine A(1) receptor density in the hippocampus might be related to a transient hippocampal dysfunction due to an acute type of dystonia. In conclusion, we have succeeded in generating a rat model of dystonia, and observed the activation of the basal ganglia-thalamo-cortical motor circuit that is related to dystonia.

A case of multiple sclerosis with homonymous hemianopia examined by positron emission tomography.

BACKGROUND: To demonstrate the efficacy of positron emission tomography (PET) for examining multiple sclerosis (MS) patients with hemianopia. CASE: A 20-year-old man visited us with a complaint of left homonymous hemianopia and headache. OBSERVATIONS: The patient's visual acuity was 1.2 (n.c.) OD and 0.9 (1.0) OS. Magnetic resonance imaging (MRI) showed a mass in the temporoparietal lobe. A pathological diagnosis of MS was made by brain biopsy. Low glucose metabolism in the lesion and visual cortex was observed by PET with (18)F-fluorodeoxy glucose. PET with (11)C-flumazenyl revealed a reduction of (11)C-uptake in the demyelinated optic radiation, and only a slight reduction of (11)C-uptake in the primary visual cortex. The results of (11)C-flumazenyl PET suggested a slight reduction of neuronal density. In 2 years, the visual field recovered to the normal state. CONCLUSION: PET can be a useful tool for estimating the visual outcome of patients with hemianopia in MS.

Microdissection and gene rearrangement analysis of paraffin-embedded specimens of orbital malignant lymphoma.

PURPOSE: To determine whether a definite diagnosis of malignant lymphoma can be made from paraffin-embedded archived orbital specimens by gene rearrangement analysis using microdissection and polymerase chain reaction (PCR). METHODS: Specimens from four patients with histopathologically diagnosed orbital malignant lymphoma were examined. The malignant cells were microdissected off the paraffin-embedded specimens. DNA was extracted from the cells, and the immunoglobulin heavy chain ( IgH) gene was amplified by PCR. Gene rearrangements were detected by using primers for the third framework (FR3A), the second framework (FR2A), and the complementary determining region 3 (CDR3). Translocation of the B-cell lymphoma/leukemia-2 ( bcl-2) gene was also examined. RESULTS: Malignant cells were present on the slides of the paraffin-embedded specimens of three of four cases. The specimens from these three cases showed IgH rearrangements for FR3A, FR2A, and CDR3. A bcl-2-associated translocation was also detected in one case. CONCLUSIONS: Gene rearrangement analysis is applicable to paraffin-embedded archived orbital specimens to confirm a diagnosis of malignant lymphoma. The advantage of this method is that only a small specimen is needed because the detection sensitivity is high.

Adenosine A1 and benzodiazepine receptors and glucose metabolism in the visual structures of rats monocularly deprived by enucleation or eyelid suture at a sensitive period.

PURPOSE: To determine the changes in the adenosine A(1) and benzodiazepine receptor density and in glucose metabolism in the visual centers of the rat brain following monocular enucleation or eyelid suture on postnatal day 10 (PN10). METHODS: Following monocular enucleation or eyelid suture on PN10 rats, the alterations in adenosine A(1) and benzodiazepine receptor density, and in glucose metabolism were evaluated in the superior colliculus (SC), the dorsal lateral geniculate body (DLG), and the visual cortex (VC) by ex vivo autoradiography with [11C]MPDX, [11C]flumazenil and [14C]2-deoxyglucose, respectively. RESULTS: Enucleation reduced the [11C]MPDX binding in the SC and DLG, and enhanced the [11C]flumazenil binding in the SC. Eyelid suture reduced the [11C]flumazenil binding in the VC at day 20. [14C]2-deoxyglucose uptake was not decreased by enucleation in any region except in the SC and DLG at day 1, but was decreased by eyelid suture in the SC at days 20 and 55 and in the VC at day 55. CONCLUSIONS: The decrease in the presynaptic adenosine A(1) receptors in the SC following enucleation is coupled with an upregulation of postsynaptic benzodiazepine receptors. These neural reactions are completely different from those following eyelid suture. The development of neural architecture for visual functions is not completed at PN10 in rats.

Neuroimaging analysis of a case with left homonymous hemianopia and left hemispatial neglect.

PURPOSE: To correlate the neuro-ophthalmological observations with the magnetic resonance images (MRI) and positron emission tomographic (PET) findings in a case with left homonymous hemianopia and left hemispatial neglect. CASE: A 57-year-old woman underwent surgery for a ruptured anterior communicating artery aneurysm. After she recovered consciousness, it was found that she had left homonymous hemianopia and left hemispatial neglect. Although the hemispatial neglect slowly improved, the homonymous hemianopia persisted. MRI and measurements of cerebral glucose metabolism by 2-fluoro-2-deoxy-D-glucose(FDG)-PET were performed 1 year later. RESULTS: MRI revealed infarctions on the medial surface of the frontal lobe, on the right medial surface of the occipital lobe, and global atrophy of the right cortical hemisphere. FDG-PET disclosed severe glucose hypometabolism in the entire right hemisphere. Glucose metabolism in the right occipital cortex was 61.1% of that in the homologous region on the left side, 62.8% in the right anterior cingulate gyrus, and 93.8% in the temporal-parietal-occipital junction. CONCLUSIONS: The low glucose metabolism in the right visual cortex explains the persistent left hemianopia, and that in the right anterior cingulate gyrus and the right temporal-parietal-occipital junction may be responsible for the left hemispatial neglect. The relatively mild damage in the right temporal-parietal-occipital junction explained the recovery of the neglect symptom. Measurements of regional cerebral glucose metabolism by PET are useful for determining the cause of cerebral visual dysfunction and its prognosis after a cerebral lesion.

Mapping adenosine A(1) receptors in the cat brain by positron emission tomography with [(11)C]MPDX.

We evaluated the potential of [(11)C]MPDX as a radioligand for mapping adenosine A(1) receptors in comparison with previously proposed [(11)C]KF15372 in cat brain by PET. Two tracers showed the same brain distribution. Brain uptake of [(11)C]MPDX (Ki = 4.2 nM) was much higher and washed out faster than that of [(11)C]KF15372 (Ki = 3.0 nM), and was blocked by carrier-loading or displaced with an A(1) antagonist. The regional A(1) receptor distribution evaluated with kinetic analysis is consistent with that previously measured in vitro. [(11)C]MPDX PET has a potential for mapping adenosine A(1) receptors in brain.