Measurement of Cerebral Glucose Metabolism in the Visual Cortex Predicts the Prognosis of Hemianopia.

BACKGROUND AND OBJECTIVE: Homonymous hemianopia caused by cerebrovascular disease may improve over time. This study investigated whether functional neuroimaging can predict the prognosis of hemianopia due to cerebral infarction. METHODS: We studied 19 patients (10 men and 9 women) with homonymous hemianopia and compared them with 34 healthy subjects (20 men and 14 women). Cerebral glucose metabolism was measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), 1 to 6 months after the onset. Bilateral regions of interest (ROIs) were selected from the posterior and, anterior striate cortices, extrastriate cortex, and thalamus. Furthermore, semi-quantitative data on cerebral glucose metabolism were obtained for ROIs and compared with the data obtained for homologous regions in the contralateral hemisphere by calculating the ipsilateral/contralateral (I/C) ratio. RESULTS: The I/C ratio for the cerebral glucose metabolism in the posterior striate cortex was high (>0.750) in 8 patients, and the central visual field of these patients improved or showed macular sparing. The I/C ratio for cerebral glucose metabolism in the anterior striate cortex was high (>0.830) in 7 patients, and the peripheral visual field of these patients improved. However, no improvement was observed in 9 patients with a low I/C ratio for cerebral glucose metabolism in both the posterior and anterior striate cortices. CONCLUSION: Measurement of cerebral glucose metabolism in the striate cortex is useful for estimating visual field prognosis. Furthermore, FDG-PET is useful in predicting the prognosis of hemianopia.

Relationship between Diabetic Nephropathy and Development of Diabetic Macular Edema in Addition to Diabetic Retinopathy.

This study aimed to examine the relationship between diabetic retinopathy (DR) and systemic factors. We evaluated 261 patients (143 men, 118 women, aged 70.1 ± 10.1 years) with type 2 diabetes. All participants underwent a fundus examination, fundus photography using spectral domain optical coherence tomography (SD-OCT), and blood tests. For glycated hemoglobin (HbA1c) levels, the average and highest values in the past were used. We observed DR in 127 (70 men and 57 women) of 261 patients. Logistic regression analyses revealed a significant correlation between DR development and the duration of diabetes (OR = 2.40; 95% CI: 1.50), average HbA1c level (OR = 5.57; 95% CI: 1.27, 24.4), highest HbA1c level (OR = 2.46; 95% CI: 1.12, 5.38), and grade of diabetic nephropathy (DN) (OR = 6.23; 95% CI: 2.70, 14.4). Regression analyses revealed a significant correlation between the severity of DR and duration of diabetes (t = -6.66; 95% CI: 0.21, 0.39), average HbA1c level (t = 2.59; 95% CI: 0.14, 1.02), and severity of DN (t = 6.10; 95% CI: 0.49, 0.97). Logistic regression analyses revealed a significant correlation between diabetic macular edema (DME) development and DN grade (OR = 2.22; 95% CI: 1.33, 3.69). DN grade correlates with the development of DR and DME, and decreased renal function predicts the onset of DR.

Cardiac Hypertrophy May Be a Risk Factor for the Development and Severity of Glaucoma.

The purpose of this study was to examine the relationship between glaucoma and cardiac abnormalities. We evaluated 581 patients with open-angle glaucoma (285 men and 296 women) and 595 individuals without glaucoma (273 men and 322 women). All of the participants underwent visual field testing using a Humphrey Visual Field Analyzer (30-2 program), an electrocardiogram (ECG), and blood pressure measurement. We examined the ECG abnormalities and other factors (age, intraocular pressure (IOP) and systemic hypertension) involved in the development and severity of glaucoma. Logistic regression analyses revealed significant correlations of glaucoma with IOP (OR = 1.43; 95% CI: 1.36−1.51; p < 0.00001), atrial fibrillation (OR = 2.02; 95% CI: 1.01−4.04; p = 0.04), left ventricular hypertrophy (LVH) (OR = 2.21; 95% CI: 1.15−4.25; p = 0.02), and bradycardia (OR = 2.19; 95% CI: 1.25−4.70; p = 0.02). Regression analyses revealed significant correlations of the mean deviation of the visual field with age (t = −6.22; 95% CI: −0.15, −0.08; p < 0.00001), IOP (t = −6.47; 95% CI: −0.42, −0.23; p < 0.00001), and LVH (t = −2.15; 95% CI: −3.36, −0.29; p = 0.02). Atrial fibrillation, LVH and bradycardia may decrease the cerebral blood flow, and may also affect the ocular blood flow. Cardiac abnormalities may be associated with the development and severity of glaucoma.

Visual Acuity in Glaucomatous Eyes Correlates Better with Visual Field Parameters than with OCT Parameters.

The visual acuity is very important for glaucoma patients in their lives. The purpose of this study was to examine about the correlation of visual acuity and visual field (VF) parameters or optical coherence tomography (OCT) parameters in patients with glaucoma. We evaluated 210 eyes of 210 patients (110 men and 100 women; mean age, 69.6 ± 9.6 years) with open-angle glaucoma and 68 eyes of healthy controls. In glaucomatous eyes including healthy eyes, correlation between visual acuity and each of the VF parameters or each of the OCT parameters was estimated using regression analyses. The average visual acuity of control group was - 0.08, and that of glaucoma group was - 0.06 (early stage), - 0.03 (moderate stage), and 0.08 (severe stage), respectively. Regression analyses including healthy eyes and glaucomatous eyes revealed significant correlations between visual acuity and mean deviation (MD) of 30-2 Humphrey VF (rs = - 0.44), MD of 10-2 VF (rs = - 0.45), total deviation in central 10-2 VF (rs = - 0.42), ganglion cell complex thickness (macula, rs = - 0.33; superior, rs = - 0.33; inferior, rs = - 0.35; and global, rs = - 0.34), and circumpapillary retinal nerve fiber layer (rs = - 0.38). The visual acuity of glaucomatous eyes correlated with VF parameters and OCT parameters. The visual acuity decreased as glaucoma progressed.

Optic perineuritis with anti-myelin oligodendrocyte glycoprotein antibody.

A 25-year-old male presented with blurred peripheral vision and movement pain in his right eye. Fundus examination revealed unilateral disc swelling in his right eye with normal intracranial pressure. MRI showed remarkably high intensity in the optic nerve sheath and slightly high intensity in the optic nerve, indicating optic perineuritis (OPN). Anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive in both serum and cerebrospinal fluid. The patient responded promptly to corticosteroid treatment. OPN can be associated with the presence of anti-MOG antibody.

Glucose hypometabolism in the visual cortex proportional to disease severity in patients with essential blepharospasm.

Essential blepharospasm (EB) causes difficulty in eyelid opening because of involuntary movements of the orbicularis oculi muscle. Patients with EB have functional visual loss due to sustained eyelid closure. We examined cerebral glucose metabolism in 39 patients with EB (12 men and 27 women; mean age, 52.1 years) by using positron emission tomography with 18F-fluorodeoxyglucose. Forty-eight eye open healthy subjects and 48 eye close healthy subjects served as controls. We analyzed and compared the data between the patients and controls by using both statistical parametric mapping (SPM) and regions of interest (ROIs). We defined ROIs on both sides of the posterior striate cortex, anterior striate cortex, extrastriate cortex, and thalamus. In SPM analysis, glucose hypometabolism were observed in both sides of the extrastriate cortex compared to eye open controls but not to eye close controls. We also observed a significant negative correlation between the Jankovic Rating Scale (JRS) sum score and relative glucose metabolism level in the striate cortex of these patients. ROI analysis, a significant correlation was observed between the JRS sum score and glucose metabolism level in the posterior (right: r = -0.53, P = .0005; left: r = -0.65, P = .00001) and anterior (right: r = -0.33, P = .04; left: r = -0.37, P = .02) striate cortices of patients with EB. We surmise that the interruption of visual input cause glucose hypometabolism in the visual cortex of patients with EB.

Cerebral Functional Response during Eyelid Opening/Closing with Bell's Phenomenon and Volitional Vertical Eye Movements in Humans.

Bell's phenomenon is a physiological phenomenon wherein the eye ball involuntarily rolls upward during eyelid closing. Although this phenomenon occurs in healthy individuals, the neural mechanism related to Bell's phenomenon has not yet been identified. We aimed to investigate the brain regions relevant to Bell's phenomenon and volitional eye movement using [15O] H2O and positron emission tomography (PET). We measured regional cerebral blood flow (rCBF) in 8 normal subjects under 3 conditions: at rest with eyes closed, during opening and closing of the eyelids in response to sound stimuli (lid opening/closing), and during vertical movement of the eyes with lids closed in response to sound stimuli (volitional eye movement). The supplementary motor area (SMA) proper, right superior temporal gyrus, right insular cortex and left angular gyrus were activated during lid opening/closing. The right frontal eye field (FEF), pre-SMA, left primary motor area, right angular gyrus, and SMA proper were activated during volitional eye movement. The SMA proper was active during both tasks, while the FEF and pre-SMA were active during volitional eye movement, but not during eyelid opening/closing. A comparison of activation during volitional eye movements and lid opening/closing tasks revealed a relative increase in rCBF in the FEF. There were no areas that are activated in relation to Bell's phenomenon. In conclusion, activation in the FEF mainly occurs during volitional eye movement. Since Bell's phenomenon is a reflexive eye movement, the FEF is scarcely concerned in Bell's phenomenon.

Improvement of Glucose Metabolism in the Visual Cortex Accompanies Visual Field Recovery in a Patient with Hemianopia.

Damage to the visual cortex or the geniculostriatal pathways could cause homonymous visual field (VF) defects at the contralateral side of the lesion. In clinical practice, it is known that the VF defects are gradually recovered over months on the cases. We report a case with recovered homonymous hemianopia following an infarction in the visual cortex by positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-flumazenil (FMZ). A 58-year-old man experienced defect of left VF, and magnetic resonance imaging (MRI) revealed a localized infarction in the right occipital lobe. Goldmann VF perimetry revealed left homonymous hemianopia, but central VF was intact. Three months after the onset of infarction, we measured cerebral glucose metabolism with FDG and FMZ binding using PET. FMZ binding reflects the density of surviving neurons. Moreover, eight months after the onset, FDG-PET scan was performed. Goldmann VF perimetry was also performed at the same times of PET examinations. Decrease of cerebral glucose metabolism in the right anterior striate cortex was observed at three months after onset, while FMZ binding in the same area did not decrease in the patient. At eight months after onset, we observed recovery of VF and improvement of cerebral glucose metabolism in the anterior striate cortex. We presented change of cerebral glucose metabolism using PET accompanying improvement of VF. Evaluation of cerebral glucose metabolism and FMZ binding in the striate cortex is useful for estimating the prognosis of hemianopia caused by organic brain damage.

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.

Alteration of the optic radiations using diffusion-tensor MRI in patients with retinitis pigmentosa.

PURPOSE: To evaluate alteration of the optic radiation (OR) in patients with retinitis pigmentosa (RP) using fractional anisotropy (FA) measured by diffusion tensor MRI. METHODS: We performed MRI and evaluated alteration of the ORs in 17 patients with RP and 27 healthy controls. Regions of interest were placed over the bilateral anterior and posterior areas of the ORs, and we measured the FA value of each region. Visual field (VF) tests were examined in all subjects, and we corrected the residual VF area according to the projection area to the striate cortex. Differences between the FA values of patients and healthy controls were tested. We performed regression analyses between the sum of the corrected VF areas and FA values in the anterior or posterior contralateral ORs in patients with RP. Moreover, we performed regression analyses between the average of FA values of ORs and the average of both eyes of visual acuity in patients with RP. RESULTS: FA values of the bilateral anterior and posterior ORs were lower in patients with RP (anterior right, p=0.012; posterior right, p=0.0004; anterior left, p=0.0008; and posterior left, p=0.0004) compared with those of healthy controls. In patients with RP, significant correlations were observed between average FA values of anterior ORs and average visual acuity (correlation coefficient (r)=-0.54; p=0.025). CONCLUSIONS: In patients with RP, alterations may occur not only in the retina but also in the brain.

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.

Glucose hypermetabolism in the thalamus of patients with hemifacial spasm.

The purpose of this study was investigate functional alteration in the brains of patients with hemifacial spasm using positron emission tomography (PET). We studied cerebral glucose metabolism using PET with (18) F-fluorodeoxyglucose in 13 patients with right lateral hemifacial spasm and 13 with left lateral hemifacial spasm. All patients underwent 2 PET scans before treatment (active state) and after treatment (suppressive state) with the botulinum neurotoxin type A. At the time of the PET scans, the severity of the spasm was rated according to the Jankovic Disability Rating Scale. We also used magnetic resonance imaging to evaluate the grade of neurovascular compression in each patient using scores of 1 to 3 (1 = mild, 3 = severe). Fifty-two normal volunteers were examined as controls. Compared with controls, patients with right and left hemifacial spasm showed bilateral cerebral glucose hypermetabolism in the thalamus in both the active and suppressive states. However, thalamic glucose metabolism after the suppressive state was significantly reduced compared with that in the active state using region of interest analysis. There was a positive correlation between the severity of the spasm in the active state and the score of neurovascular compression (rs = 0.65) that was estimated using Spearman order correlation coefficient. We observed bilateral cerebral glucose hypermetabolism in the thalamus of patients with hemifacial spasm. The thalamic glucose hypermetabolism may be attributed to multiple sources, including afferent input from the skin and muscle spindle, antidromic conduction of the facial nerve, and secondary alteration in the central nervous system.

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism.

A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Wakakura classification. Sixteen women (mean age 42.4 ± 11.7 years) were examined as normal controls. The thalamic glucose metabolism in our patient was significantly increased on days 149, 212, and 688. The severity of the blepharospasm was positively correlated with the thalamic glucose metabolism, suggesting that the severity of blepharospasms reflects thalamic activity.

Gray matter density increase in the primary sensorimotor cortex in long-term essential blepharospasm.

In this study, we investigated gray matter density in essential blepharospasm (EB) patients, focusing on the duration of disease and severity of symptoms. We studied 32 patients (10 males and 22 females; age, 55.0 ± 6.5years) with EB and 48 controls (15 males and 33 females; age, 54.4 ± 10.3years) by using 3D T1-weighted magnetic resonance imaging and voxel-based morphometry. We defined an activity index (AI) that reflects the severity and duration of EB symptoms in each patient. The difference between the 2 groups was examined by statistical parametric mapping software (SPM8). After controlling for age, gray matter density increased in the bilateral primary sensorimotor cortex (S1M1) and cingulate gyrus. The gray matter density in the bilateral S1M1 was found to have a significant positive correlation with the duration of disease and a more robust correlation with AI. The correlation coefficients, after correcting for age, in the S1M1 and left cingulate gyrus were as follows: with duration, right S1M1, 0.72 (P<0.00001); left S1M1, 0.72 (P<0.00001); and left cingulate gyrus, 0.33 (not significant); and with AI, right S1M1, 0.81 (P<10(-7)); left S1M1, 0.74 (P<0.00001); and left cingulate gyrus, 0.43 (P<0.05). The increase in gray matter density in the S1M1 and cingulate gyrus might be a secondary effect caused by long-term hyperactivity in these areas instead of a predisposing factor.

The pre-supplementary and primary motor areas generate rhythm for voluntary eye opening and closing movements.

Blinking and opening/closing of the eyelid are considered to be different movements with independent control mechanisms. Apraxia of lid opening (ALO) is a clinical syndrome in which patients experience difficulty in opening their eyes voluntarily. Our previous study with fluorodeoxyglucose and positron emission tomography (PET) has suggested that functional impairments in the supplementary motor area (SMA) and the anterior cingulate gyrus may be involved in the pathophysiology of ALO. The aim of this study was to explore the physiological mechanisms for voluntary eyelid opening/closing and the difference between self-initiated and triggered movements, using [(15)O]H(2)O and PET. We measured the regional cerebral blood flow in 8 healthy subjects under 3 conditions: [A] at rest with eyes closed, [B] with self-paced lid opening/closing, and [C] with triggered lid opening/closing. All tasks were done with a blindfold to exclude the influence of visual input. The SMA proper and the angular gyrus were activated during self-paced and triggered lid opening/closing movements; however, the pre-SMA and the primary motor area (M1) were activated only during self-paced movements. The anterior cingulate gyrus and the cerebellum were activated during self-paced condition over triggered condition. The roles of SMA, M1 and cerebellum were assumed in eyelid opening/closing movements: the preparation and processing of movements in SMA, execution of movements in M1, and rhythmic generation in pre-SMA, M1 and cerebellum. We suggest that the activation in pre-SMA, anterior cingulate gyrus, and cerebellum may be responsible for the self-initiated eyelid opening/closing movements.

Photophobia in essential blepharospasm--a positron emission tomographic study.

To localize regional alterations in cerebral glucose metabolism in essential blepharospasm (EB) patients with photophobia. We have studied 22 EB patients by performing positron emission tomography and [(18)F]-fluorodeoxyglucose analysis. The patients were classified into two subgroups, namely, EB with photophobia (P group) and EB without photophobia (NP group), and compared with a healthy control group (n = 44). There were no significant differences between the two patient groups with respect to the severity of motor symptoms or the duration for which the condition persisted. The FDG-PET images were analyzed using the statistical parametric mapping software. As compared to the control group, the P group exhibited significant hypermetabolism in the thalamus (P = 0.002), while the NP group exhibited significant hypometabolism in the dorsal midbrain, especially, in the superior colliculus (P = 0.005). The P group exhibited significant hypermetabolism in the thalamus and the dorsal midbrain as compared to the NP group (P < 0.001). These findings suggest that photophobia in EB patients may be associated with abnormal hyperactivity in the thalamus. Either hyperactivity of the thalamus or hypoactivity of the superior colliculus, or both may be associated with excessive blinking in these patients.

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.