Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10-20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of 123I-iomazenil single-photon emission computerized tomography (IMZ-SPECT) for its diagnosis. CASE: A 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies. CONCLUSION: An anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.

Recovery of Cortical Neurotransmitter Receptor Function and Its Impact on Cognitive Improvement after Indirect Revascularization Surgery Alone for Adult Patients with Ischemic Moyamoya Disease: 123I-Iomazenil Single-Photon Emission Computed Tomography Study.

OBJECTIVE: Brain 123I-iomazenil single-photon emission computed tomography (SPECT) can assess the distribution of the binding potential of central benzodiazepine receptors in the cerebral cortex. This binding potential may reflect neuronal function in viable tissues. The present prospective study using brain 123I-iomazenil SPECT aimed to determine whether improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in neurotransmitter receptor function in the affected cerebral hemisphere among adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion. METHODS: Twenty-two patients who underwent indirect revascularization surgery alone also underwent brain SPECT scanning at 180 minutes after 123I-iomazenil administration and neuropsychological testing before and at 6 months after surgery. The affected-to-contralateral cerebral hemispheric asymmetry of tracer uptake before and after surgery was then calculated. RESULTS: The asymmetry of tracer uptake was significantly increased after surgery (P < 0.0001). A significant difference between the preoperative and postoperative asymmetry of tracer uptake was seen in patients with improved cognition compared with those with unchanged cognition (P = 0.0001). The area under the receiver operating characteristic curve was 0.99 for the difference between the preoperative and postoperative asymmetry of tracer uptake to assess the ability to discriminate patients with improved cognition from those with unchanged cognition. CONCLUSIONS: Improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in the binding potential of central benzodiazepine receptors in the affected cerebral hemisphere in adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion.

Long-Term Outcomes of Cerebral Blood Flow and Neurotransmitter Receptor Function on Iodine-123-Iomazenil Single-Photon Emission Computed Tomography and Cognitive Assessments After Parent Artery Occlusion Combined with Cerebral Revascularization for Internal Carotid Artery Aneurysms.

OBJECTIVE: Many studies of external-internal carotid artery (EC-IC) bypass as cerebral revascularization for unclippable internal carotid artery (ICA) aneurysms have reported surgical outcomes, including bypass patency and aneurysm resolution. However, no previous studies have assessed the long-term outcomes of cerebral blood flow (CBF), brain neural density, and cognition. The purpose of the present study was to evaluate the long-term outcomes of CBF and neurotransmitter receptor function using early and late images of iodine-123 (123I)-iomazenil (IMZ) single-photon emission computed tomography (SPECT) and the cognitive function of patients who had undergone EC-IC bypass for symptomatic aneurysms in the cavernous portion of the ICA. METHODS: We performed a prospective observational study of 11 patients who had undergone superficial temporal artery-middle cerebral artery bypass or bypass using a saphenous vein graft for symptomatic aneurysms in the cavernous portion of the ICA. One patient experienced extensive infarction and, therefore, did not undergo postoperative testing. 123I-IMZ SPECT was performed with scanning at 23 minutes (early) and 180 minutes (late) after tracer administration before and after surgery. The preoperative and follow-up neuropsychological test scores from 6 patients were also analyzed. RESULTS: None of 10 patients who had undergone EC-IC bypass showed reductions in CBF and brain neural density. In addition, the neuropsychological test scores had not changed significantly from preoperatively to postoperatively. CONCLUSION: Using early and late 123I-IMZ SPECT, the present study has demonstrated that patients undergoing uncomplicated cerebral revascularization for unclippable ICA aneurysms will not experience reductions in CBF or neurotransmitter receptor function, and their cognitive function was not impaired.

Improvement in gait function after carotid endarterectomy is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex: a 123I-iomazenil SPECT study.

OBJECTIVE: Carotid endarterectomy (CEA) often restores cerebral perfusion and neurotransmitter receptor function, which is seen on early and late images, respectively, on brain I-iomazenil single-photon emission computed tomography (SPECT). The reliability of gait-related parameters obtained using a triaxial accelerometer, a portable device for gait assessment, has been confirmed with test-retest measurements. The purpose of the present prospective cohort study was to determine whether improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex. METHODS: Gait testing using a triaxial accelerometer was performed preoperatively and 6 months postoperatively in 64 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%). I-iomazenil SPECT was also performed with scanning within 30 min (early images) and at 180 min (late images) after tracer administration before and after surgery. SPECT data were analyzed using a three-dimensional stereotactic surface projection, and motor (Brodmann 4) and premotor (Brodmann 6) cortexes in each hemisphere were combined and defined as the motor-related cortex. RESULTS: Based on preoperative and postoperative gait testing, seven patients (11%) showed postoperative improved gait. Logistic regression analysis revealed that postoperative increase in I-iomazenil uptake in the motor-related cortex ipsilateral to surgery on early [95% confidence interval (CI), 4.32-365.21; P = 0.0477) or late (95% CI, 9.45-1572.57; P = 0.0173) images was an independent predictor of postoperative improved gait. CONCLUSIONS: Improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex.

Detection of Transient Increase of Cerebral Blood Flow and Reversible Neuronal Dysfunction by Iodine-123-Iomazenil Single Photon Emission Computed Tomography After Cerebral Hyperperfusion Syndrome After Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Early and late images of single photon emission computed tomography (SPECT) using 123I-iomazenil (123I-IMZ) can demonstrate cerebral blood flow and cortical neuronal viability. Hyperperfusion syndrome is one of the serious complications after revascularization surgery for moyamoya disease; therefore, the real-time observation of the hemodynamics and neuronal viability is important for the treatment after the revascularization. Here we report, a case of moyamoya disease where 123I-IMZ SPECT had a significant efficacy to delineate the hemodynamics and transient neuronal dysfunction in hyperperfusion state after revascularization. CASE DESCRIPTION: A 47-year-old woman presented with motor aphasia 3 days after superficial temporal artery-middle cerebral artery anastomosis with indirect revascularization. Magnetic resonance imaging (MRI) on the same day showed no new ischemic changes but high intensities along the left frontal sulci observed on fluid-attenuated inversion recovery images, and 123I-IMZ SPECT demonstrated the increased uptake on the early images and the decreased uptake on the late images around the anastomosis site. The patient was completely recovered 1 month after surgery, and abnormal changes on MRI and 123I-IMZ SPECT returned to normal along with the symptom withdrawal. CONCLUSIONS: These findings indicate that 123I-IMZ SPECT could be the index for the treatment of revascularization for obstructive vascular diseases such as moyamoya disease.

Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children.

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.

[123I-Iomazenil Single-Photon Emission Computed Tomography Imaging in a Patient with Mild Traumatic Subdural Hematoma Accompanied by Delayed Transient Aphasia].

Early and late images of 123I-iomazenil(IMZ)single-photon emission computed tomography(SPECT)reflect distributions of cerebral blood flow and those of cortical benzodiazepine receptor binding potential, respectively. Crossed cerebellar diaschisis reflects left-to-right asymmetry of metabolism in the cerebral hemispheres. We present a case of a 67-year-old woman who developed transient aphasia 3 days after the onset of a mild acute subdural hematoma. Computed tomography scan and magnetic resonance imaging during aphasia did not show enlargement of the hematoma or any new lesions. Electroencephalography did not show any abnormalities. Early images of 123I-IMZ SPECT 3 days after the onset of aphasia revealed a decrease in radioactivity in the right cerebellar hemisphere relative to that in the left cerebellar hemisphere. Late images of the same 123I-IMZ SPECT displayed a decrease in radioactivity in the left cerebral hemisphere relative to that in the right cerebral hemisphere. Twenty-four days later, the aphasia disappeared and the left-to-right asymmetries of radioactivity in the cerebellar and cerebral hemispheres on the early and late 123I-IMZ SPECT images also resolved.

Double match of 18F-fluorodeoxyglucose-PET and iomazenil-SPECT improves outcomes of focus resection surgery.

BACKGROUND: When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. METHOD: Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. RESULTS: In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. CONCLUSION: Concordance between interictal 18FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

Histological Underpinnings of Grey Matter Changes in Fibromyalgia Investigated Using Multimodal Brain Imaging.

Chronic pain patients present with cortical gray matter alterations, observed with anatomical magnetic resonance (MR) imaging. Reduced regional gray matter volumes are often interpreted to reflect neurodegeneration, but studies investigating the cellular origin of gray matter changes are lacking. We used multimodal imaging to compare 26 postmenopausal women with fibromyalgia with 25 healthy controls (age range: 50-75 years) to test whether regional gray matter volume decreases in chronic pain are associated with compromised neuronal integrity. Regional gray matter decreases were largely explained by T1 relaxation times in gray matter, a surrogate measure of water content, and not to any substantial degree by GABAA receptor concentration, an indirect marker of neuronal integrity measured with [18F] flumazenil PET. In addition, the MR spectroscopy marker of neuronal viability, N-acetylaspartate, did not differ between patients and controls. These findings suggest that decreased gray matter volumes are not explained by compromised neuronal integrity. Alternatively, a decrease in neuronal matter could be compensated for by an upregulation of GABAA receptors. The relation between regional gray matter and T1 relaxation times suggests decreased tissue water content underlying regional gray matter decreases. In contrast, regional gray matter increases were explained by GABAA receptor concentration in addition to T1 relaxation times, indicating perhaps increased neuronal matter or GABAA receptor upregulation and inflammatory edema. By providing information on the histological origins of cerebral gray matter alterations in fibromyalgia, this study advances the understanding of the neurobiology of chronic widespread pain. SIGNIFICANCE STATEMENT: Regional gray matter alterations in chronic pain, as detected with voxel-based morphometry of anatomical magnetic resonance images, are commonly interpreted to reflect neurodegeneration, but this assumption has not been tested. We found decreased gray matter in fibromyalgia to be associated with T1 relaxation times, a surrogate marker of water content, but not with GABAA receptor concentration, a surrogate of neuronal integrity. In contrast, regional gray matter increases were partly explained by GABAA receptor concentration, indicating some form of neuronal plasticity. The study emphasizes that voxel-based morphometry is an exploratory measure, demonstrating the need to investigate the histological origin of gray matter alterations for every distinct clinical entity, and advances the understanding of the neurobiology of chronic (widespread) pain.

Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal.

Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups--that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking.

Cognitive dysfunction might be improved in association with recovered neuronal viability after intracranial meningioma resection.

Intracranial meningiomas are the most common types of neoplasms that cause mental disorders. Although higher brain function can be restored and even improved in some patients after tumor resection, the mechanisms remain unclear. We investigated changes in the brains of patients after resection of an intracranial meningioma using (123)I-Iomazenil (IMZ)-single photon emission computed tomography (SPECT). Ten patients underwent IMZ-SPECT within 4 weeks before and 3 months after intracranial meningioma resection. Changes in IMZ accumulation in brain parenchyma were assessed as ratios of counts in the lesion-to-contralateral hemisphere (L/C ratios). Mean Mini-Mental State Examination scores before and after resection of 19.9±11.4 vs. 26.5±3.8, respectively (p=0.03) indicated that the cognitive function of these patients was significantly improved after tumor resection. The average L/C ratios calculated from image counts of IMZ were 0.92±0.05 and 0.98±0.02 before and after surgery, respectively. The L/C ratio of IMZ accumulation was significantly decreased after tumor resection (p=0.0003). In contrast, regional cerebral blood flow calculated from (123)I-Iodoamphetamine-SPECT images did not significantly differ after tumor resection. The recovered binding potential of IMZ in brain parenchyma surrounding the tumor bulk after resection indicates that the viability of central benzodiazepine receptors was reversibly depressed and recoverable after release from compression by the tumor. The recovered neuronal viability revealed by IMZ-SPECT might be responsible for the improved cognitive function after intracranial meningioma resection.

CRH receptor antagonism reverses the effect of social subordination upon central GABAA receptor binding in estradiol-treated ovariectomized female rhesus monkeys.

Persistent exposure to environmental stressors causes dysregulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and alters GABAA receptor (GABAAR) levels throughout the brain. Social subordination in socially housed female rhesus results in distinctive stress-related physiological and behavioral phenotypes that are dependent on the ovarian hormone estradiol (E2). In the present study, we utilized ovariectomized adult female rhesus monkeys undergoing hormone replacement with E2 to test the hypothesis that the chronic psychosocial stress of subordination alters GABAAR binding potential (GABAAR BPND) in limbic regions implicated in emotional processing including the prefrontal cortex, temporal lobe (amygdala and hippocampus), and hypothalamus. Furthermore, we tested the hypothesis that peripheral administration of a corticotropin-releasing hormone (CRH) receptor antagonist (astressin B) would reverse the alterations in GABAAR binding within these regions in subordinate females. After subjects received astressin B or saline for three consecutive days, GABAAR BPND was determined by positron emission tomography (PET) using (18)F-flumazenil as a radioligand. T1-weighted structural magnetic resonance imaging scans were also acquired for PET scan co-registration, in order to perform a region of interest analysis using the pons as a reference region. Compared to socially dominant females, subordinate females exhibited increased GABAAR BPND in the prefrontal cortex but not in the temporal lobe or the hypothalamus. Administration of astressin B eliminated the status difference in GABAAR BPND in the prefrontal cortex, suggesting that the chronic stressor of social subordination modulates GABAergic tone via effects on CRH and the LHPA axis, at least in prefrontal regions.

123I-iomazenil single photon emission computed tomography visualizes recovery of neuronal integrity by bone marrow stromal cell therapy in rat infarct brain.

BACKGROUND AND PURPOSE: This study was aimed to assess whether (123)I-iomazenil (IMZ) single photon emission computed tomography can serially monitor the effects of bone marrow stromal cell (BMSC) transplantation on neuronal integrity in infarct brain of rats. METHODS: The BMSCs were harvested from green fluorescent protein-transgenic rats and were cultured. The rats were subjected to permanent middle cerebral artery occlusion. Their motor function was serially quantified throughout the experiments. The BMSCs or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 days after the insult. Using small-animal single photon emission computed tomography/computed tomography apparatus, the (123)I-IMZ uptake was serially measured at 6 and 35 days after the insult. Finally, fluorescence immunohistochemistry was performed to evaluate the distribution of engrafted cells and their phenotypes. RESULTS: The distribution of (123)I-IMZ was markedly decreased in the ipsilateral neocortex at 6 days postischemia. The vehicle-transplanted animals did not show a significant change at 35 days postischemia. However, BMSC transplantation significantly improved the distribution of (123)I-IMZ in the peri-infarct neocortex as well as motor function. The engrafted BMSCs were densely distributed around cerebral infarct, and some of them expressed neuronal nuclear antigen and γ-aminobutyric acid type-A receptor. CONCLUSIONS: The present findings strongly suggest that the BMSCs may enhance functional recovery by improving the neuronal integrity in the peri-infarct area, when directly transplanted into the infarct brain at clinically relevant timing. (123)I-IMZ single photon emission computed tomography may be a promising modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situation.

Statistical parametric mapping of interictal 123I-iomazenil SPECT in temporal lobe epilepsy surgery.

Brain single photon emission computed tomography (SPECT) for epilepsy is divided into two types (using three radionuclide tracers)-perfusion SPECT (123I-IMP or 99 mTc-ECD), identifying epileptogenic foci by detecting abnormality in regional cerebral blood flow, and 123I-iomazenil SPECT, identifying epileptogenic foci based on distribution of central benzodiazepine receptors. This study aimed to statistically evaluate and compare the SPECT effectiveness for the three tracers. Statistical parametric mapping (SPM) analysis was performed on 30 mesial temporal lobe epilepsy (mTLE) patients. The radionuclide and patient data were categorized as follows: abnormality in the medial temporal lobe on the operated hemisphere (AAA), in the entire temporal lobe on the operated hemisphere (AA), in the dominantly affected temporal lobe on the operated hemisphere (A), in bilateral temporal lobes (B), with no abnormalities in bilateral temporal lobes (C), and with abnormality in the temporal lobe on the nonoperated hemisphere (D). For analyses of (AAA), (AA), and (A), examining the hemisphere containing epileptogenic foci, IMP-SPECT was significantly superior to ECD-SPECT (P<0.05). For (AAA), indicating localization, IMZ-SPECT was significantly superior to the other two (P<0.05). IMP-SPECT was superior for lateralizing and IMZ-SPECT was useful for localizing epileptogenic foci in mTLE patients though the applicability of the results in extratemporal lobe epilepsy is unknown.

Sex-specific differences in GABA(A) -benzodiazepine receptor availability: relationship with sensitivity to pain and tobacco smoking craving.

Sex differences exist in tobacco smoking behaviors. Nicotine, the primary addictive ingredient in tobacco smoke, indirectly affects γ-amino butyric acid (GABA) function. Previous studies reported sex-by-smoking interactions in brain GABA levels. The goal of the present study was to evaluate if there is a sex-by-smoking interaction at the GABA(A)-benzodiazepine receptors (GABA(A)-BZRs), as well as relationships between GABA(A)-BZR availability and behavioral variables before and after 1 week of smoking cessation. Twenty-six women (8 non-smokers, age 36.0 ± 13.4 years; 19 smokers, age 34.6 ± 8.9 years) and 25 men (8 non-smokers, age 37.9 ± 13.8 years; 17 smokers, 34.1 ± 12.4 years) were imaged using [123I]iomazenil and single-photon emission computed tomography. Smokers were imaged at baseline 7 hours after the last cigarette. A significantly great number of men were able to abstain from smoking for 1 week (P = 0.003). There were no significant differences in nicotine dependence and cigarette craving, mood or pain sensitivity between male and female smokers. There was a significant effect of gender across all brain regions (frontal, parietal, anterior cingulate, temporal and occipital cortices, and cerebellum; P < 0.05), with all women (smokers and non-smokers combined) having a higher GABA(A)-BZR availability than all men. There was a negative correlation between GABA(A)-BZR availability and craving (P ≤ 0.02) and pain sensitivity (P = 0.04) in female smokers but not male smokers. This study provides further evidence of a sex-specific regulation of GABA(A)-BZR availability in humans and demonstrates the potential for GABA(A)-BZRs to mediate tobacco smoking craving and pain symptoms differentially in female and male smokers.

MR imaging-based correction for partial volume effect improves detectability of intractable epileptogenic foci on iodine 123 iomazenil brain SPECT images: an extended study with a larger sample size.

BACKGROUND AND PURPOSE: It has been suggested, on the basis of a previous pilot study conducted in a small number of patients, that MR imaging-based PVE correction in I-123 iomazenil brain SPECT improves the detectability of cortical epileptogenic foci. In the present study, we performed an investigation by using a larger sample size to establish the effectiveness of the PVE correction and to conduct a detailed evaluation based on the histologic classification of lesions. MATERIALS AND METHODS: Seventy-five patients (male/female, 37/38; age, 28 ± 12 years) with intractable epilepsy who had undergone surgical treatment were enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were performed before the operation in all patients. I-123 iomazenil SPECT images with and without MR imaging-based PVE correction were assessed visually and by semiquantitative analysis based on the AI(%) of the SPECT count in the resected lesions. RESULTS: The sensitivity, specificity, and accuracy of foci detection by visual assessment were significantly higher after PVE correction compared with the values obtained before the correction. The results of the semiquantitative analysis revealed that the asymmetry of the SPECT counts was significantly increased after the PVE correction in the surgically resected lesions in cases of mesial temporal sclerosis, tumor, and malformations of cortical development. CONCLUSIONS: The effectiveness of MR imaging-based PVE correction in I-123 iomazenil brain SPECT in improving the detection of cortical epileptogenic foci with abnormal histologic findings was established by our investigation conducted on a large sample size.

[Usefulness of 123I-iomazenil SPECT in pediatric patients with neurological disease].

This study examined the usefulness of 123I-iomazenil SPECT (IMZ-SPECT), a type of brain scintigram that focuses on the central benzodiazepine receptor in order to determine its distribution and the function of inhibitory neurons. IMZ-SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Interictal study by IMZ-SPECT is widely available at numerous institutions and its usefulness has been confirmed in patients with not only focal cortical dysplasia and hippocampal sclerosis, but also tuberous sclerosis and neuronal migration disorders, even when magnetic resonance image fails to demonstrate any abnormal findings. When interpreting scintigrams, the developmental dynamic change of the central benzodiazepine receptor in childhood and the duration of the benzodiazepine exposure period should be taken into consideration. It is expected that IMZ-SPECT will be used in various neurological disorders other than epilepsy in the future allow medical services to be provided based on findings in the inhibitory synaptic system obtained with IMZ-SPECT.

Combination of preoperative cerebral blood flow and 123I-iomazenil SPECT imaging predicts postoperative cognitive improvement in patients undergoing uncomplicated endarterectomy for unilateral carotid stenosis.

PURPOSE: The purpose of the present study was to determine whether preoperative cerebral blood flow (CBF) or cortical central benzodiazepine receptor binding potential as measured by brain perfusion or (123)I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) imaging, respectively, can predict cognitive improvement after uncomplicated carotid endarterectomy (CEA). METHODS: Neuropsychological testing was performed preoperatively and after 1 month postoperatively in 140 patients who underwent CEA for unilateral internal carotid artery (ICA) stenosis (≥ 70%). Brain perfusion SPECT using N-isopropyl-p-[(123)I]-iodoamphetamine and IMZ SPECT was also performed before surgery. SPECT data were analyzed using a 3-dimensional stereotaxic region-of-interest template. RESULTS: Fourteen patients (10%) showed improved cognitive function postoperatively. Logistic regression analysis demonstrated that, among the variables tested, low relative CBF in the cerebral hemisphere ipsilateral to surgery was significantly associated with postoperative cognitive improvement (95% confidence interval: 0.623-0.868; P = 0.0003). The combination of reduced relative CBF and moderately reduced relative uptake of IMZ identified development of postoperative cognitive improvement with 100.0% sensitivity, 84.9% specificity, a positive predictive value of 42.4%, and a negative predictive value of 100%. Further, in a subgroup of patients with reduced relative CBF and moderately reduced relative uptake of IMZ, the difference between these 2 values was significantly greater in patients with postoperative cognitive improvement than in those without (P < 0.0001). CONCLUSIONS: The combination of preoperative CBF and cortical central benzodiazepine receptor binding potential as determined by SPECT can predict cognitive improvement after CEA.

Decreased benzodiazepine receptor and increased GABA level in cortical tubers in tuberous sclerosis complex.

PURPOSE: To elucidate the functional characteristics of cortical tubers that might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton magnetic resonance spectroscopy ((1)H-MRS) and [123I] iomazenil (123I-IMZ) single photon emission computed tomography (SPECT) were performed. METHODS: (1)H-MRS using a clinical 3-tesla magnetic resonance imager was performed in four children with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was set on the right parietal lobe in control subjects. In patients with TSC, a single voxel was set on the epileptogenic tuber in the parietal or temporal lobe, and another voxel was set on the contralateral normal-appearing brain region. N-Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four patients with TSC. RESULTS: A significant decrease in the NAA concentration and significant increases in the mIns and GABA concentrations were detected in the cortical tubers of all 4 patients. No significant difference was observed in Glu concentrations. In all of the cortical tubers detected by magnetic resonance imaging, 123I-IMZ binding was significantly decreased. CONCLUSION: Epileptogenesis in TSC might be caused by decreased inhibition secondary to the decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase in the GABA concentration may compensate for decreased inhibition.

Neuroradiological and neurofunctional examinations for patients with 22q11.2 deletion.

Since the neuroradiological features of patients with 22q11.2 deletion syndrome are not well-understood, examinations using functional imaging were performed in this study. Brain magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (MRS) were performed using a clinical 3-Tesla MR imager in 4 patients with 22q11.2 deletion syndrome (2 boys and 2 girls; aged 2-6 years.) and 20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I-iomazenil (IMZ) single photon emission computed tomography (SPECT) was examined in 2 of the 4 patients. Among the 4 patients with 22q11.2 deletion syndrome, 2 patients showed polymicrogyria and 1 patient showed agyria. Those patients with brain malformations also showed abnormal brain artery patterns and decreased accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic discharges in their electroencephalograms (EEG), one patient with polymicrogyria had no seizure episodes. Decreases in γ-aminobutyric acid (GABA) corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG were shown in all patients except for the patient with agyria. Although consistent evidence was not seen in patients with 22q11.2 deletion syndrome in this study, brain malformations and disturbances of the GABAergic nervous system would be underlying mechanisms of the neurodevelopmental abnormalities in this syndrome.