[123I]Iomazenil SPECT Detects a Reversible Lesion of the Left Medial Temporal Lobe in a Case of Global Autobiographical Amnesia.

Global autobiographical amnesia is a rare disorder that is characterized by a sudden loss of autobiographical memories covering many years of an individual's life. Generally, routine neuroimaging studies such as CT and MRI yield negative findings in individuals with global autobiographical amnesia. However, in recent case reports, functional analyses such as SPECT and fMRI have revealed changes in activity in various areas of the brain when compared with controls. Studies using iomazenil (IMZ) SPECT with individuals with global autobiographical amnesia have not been reported. We report the case of a 62-year-old Japanese woman with global autobiographical amnesia who had disappeared for ∼4 weeks. [123I]-IMZ SPECT showed reduced IMZ uptake in her left medial temporal lobe and no significant reduction on N-isopropyl-[123I] p-iodoamphetamine (IMP) SPECT in the identical region. Because IMZ binds to the central benzodiazepine receptor, this dissociation between IMZ and IMP SPECT was thought to reflect the breakdown of inhibitory neurotransmission in the left medial temporal lobe. Moreover, when the woman recovered most of her memory 32 months after fugue onset, the IMZ SPECT-positive lesion had decreased in size. Because the woman had long suffered verbal abuse from her former husband's sister and brother, which can also cause global autobiographical amnesia, it is difficult to conclude whether the IMZ SPECT-positive lesion in the left medial temporal lobe was the cause or the result of her global autobiographical amnesia. Although only one case, these observations suggest that IMZ SPECT may be useful in uncovering the mechanisms underlying global autobiographical amnesia.

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy.

BACKGROUND: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. METHODS: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2'-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. RESULTS: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. CONCLUSION: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

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.

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.

[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.

Abnormal distribution of GABAA receptors in brain of duchenne muscular dystrophy patients.

INTRODUCTION: In this study we sought to: (1) determine the distribution of GABAA receptors (GABAA -Rs) in the brain of Duchenne muscular dystrophy (DMD) patients; and (2) ascertain if the distribution pattern correlates with cognitive dysfunction. METHODS: Fourteen DMD patients [young adult (n = 7, 18-25 years old) and older adult (n = 7, 30-37 years old) groups] and 16 age-matched normal volunteers participated. GABAA -R distribution was assessed using 123 I-IMZ-SPECT. Neuropsychological assessments were performed using 3 different test batteries, the WAIS-III, WMS-R, and Wisconsin Card Sorting Test (WCST). RESULTS: All DMD patients showed significant decline in 123 I-IMZ uptake in the prefrontal cortex (P < 0.05). Although no differences were detected in the WAIS-III and WMS-R, the WCST scores of DMD patients (2.8 ± 1.9) were significantly lower (P < 0.01) than those of normal volunteers (5.4 ± 0.7). Both abnormalities were more pronounced in older adult patients. CONCLUSION: The findings demonstrate that DMD is accompanied by a reduction in the prefrontal cortex distribution of GABAA -Rs. Muscle Nerve 55: 591-595, 2017.

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.

Unique Distribution of Benzodiazepine Receptors in the Brain during the First Two Years of Life.

BACKGROUND: 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) is a tool for evaluating epileptic foci and brain damage. To apply the method to children, information regarding the age-specific expression of benzodiazepine receptors (BDZ-Rs) is required. Unfortunately, there is no information currently available for children <2 years of age. METHODS: We used IMZ SPECT once in infants aged 3-8 months and again at 2 years of age in order to describe the maturational changes in BDZ-R distribution. RESULTS: No neurological deficits were found in any of the infants at the first examination. The BDZ-Rs were more dominantly distributed in the occipital lobe than in the frontal lobe before the age of 2 years. The frontal-occipital gradients of the distribution were obvious in children <8 months of age. Magnetic resonance imaging showed a spreading of myelination toward the frontal lobes simultaneously with BDZ-R expression. CONCLUSION: Information regarding the alteration in the BDZ-R distribution pattern is useful when assessing infantile epilepsy and brain injury. The age-related pattern of BDZ-R distribution could correspond with myelination, cerebral blood flow, metabolism and behavioral development.

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.

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.

Cortical damage following traumatic brain injury evaluated by iomazenil SPECT and in vivo microdialysis.

[(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT) has been reported to be a useful marker of neuronal integrity. We evaluated cortical damage following traumatic brain injury (TBI) with IMZ SPECT at the acute stage. After conventional therapy for a cranial trauma, an IMZ SPECT re-evaluation was performed at the chronic stage. A reduction in IMZ uptake in the location of cerebral contusions was observed during the TBI acute phase; however, images of IMZ SPECT obtained during the chronic phase showed that areas with decreased IMZ distribution were remarkably reduced compared with those obtained during the acute phase. As a result of in vivo microdialysis study, the extracellular levels of glutamate in the cortex, where decreased IMZ distribution was shown during the acute phase, were increased during the 168-h monitoring period. During the chronic phase, IMZ uptake in the region with the microdialysis probes was recovered. The results suggest that this reduction in IMZ uptake might not be a sign of irreversible tissue damage in TBI.

Cortical neuron loss in post-traumatic higher brain dysfunction using (123)I-iomazenil SPECT.

In patients with higher brain dysfunction (HBD) after mild traumatic brain injury (MTBI), diagnostic imaging of cortical neuron loss in the frontal lobes was studied using SPECT with (123)I-iomazenil (IMZ), as a radioligand for central benzodiazepine receptor (BZR). Statistical imaging analysis using three-dimensional stereotactic surface projections (3D-SSP) for (123)I-IMZ SPECT was performed in 17 patients. In all patients with HBD defined by neuropsychological tests, cortical neuron loss was indicated in the bilateral medial frontal lobes in 14 patients (83 %). A comparison between the group of 17 patients and the normal database demonstrated common areas of cortical neuron loss in the bilateral medial frontal lobes involving the medial frontal gyrus (MFG) and the anterior cingulate gyrus (ACG). In an assessment of cortical neuron loss in the frontal medial cortex using the stereotactic extraction estimation (SEE) method (level 3), significant cortical neuron loss was observed within bilateral MFG in 9 patients and unilateral MFG in 4, and bilateral ACG in 12 and unilateral ACG in 3. Fourteen patients showed significant cortical neuron loss in bilateral MFG or ACG. In patients with MTBI, HBD seemed to correlate with selective cortical neuron loss within the bilateral MFG or ACG where the responsible lesion could be. 3D-SSP and SEE level 3 analysis for (123)I-IMZ SPECT could be valuable for diagnostic imaging of HBD after MTBI.

Evaluation of cerebral function using iomazenil SPECT for patients with traumatic brain injury.

Traumatic brain injuries demonstrate various symptoms, including the disturbance of higher brain function, which is not visualized as a morphological lesion on magnetic resonance (MR) imaging. We examined the use of iomazenil single photon emission computed tomography (SPECT) for patients with traumatic brain injury and evaluated its diagnostic value. The study population included patients who were admitted to our hospital for traumatic brain injuries. All patients survived and were discharged from our hospital. MR imaging and iomazenil SPECT were examined during the acute and/or chronic phases. MR images were acquired using a 1.5-T clinical instrument. The T1- and T2-weighted and fluid-attenuated inversion recovery (FLAIR) axial images were evaluated. SPECT images were acquired using a multi-detector SPECT machine 3 h after the intravenous injection of 740 MBq of iomazenil. Axial, statistically analyzed images and stereotactic extraction estimation images were reconstructed and evaluated statistically based on the Z-score for each cerebral cortex. Iomazenil SPECT showed various lesions that were not demonstrated by MR imaging. Some clinical symptoms correlated with the iomazenil SPECT findings. Iomazenil SPECT is thus considered to be valuable for evaluating both brain lesions and the brain function after traumatic brain injury.

[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.

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.

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.

SPECT imaging of GABA(A)/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment.

PURPOSE: The involvement of neocortical and limbic GABA(A)/benzodiazepine (BZD) receptors in Alzheimer's disease (AD) is controversial and mainly reported in advanced stages. The status of these receptors in the very early stages of AD is unclear and has not been explored in vivo. Our aims were to investigate in vivo the integrity of cerebral cortical GABA(A)/BZD receptors in subjects with amnestic mild cognitive impairment (MCI) and to compare possible receptor changes to those in cerebral perfusion. METHODS: [(123)I]Iomazenil and [(99m)Tc]HMPAO SPECT images were acquired in 16 patients with amnestic MCI and in 14 normal elderly control subjects (only [(123)I]iomazenil imaging in 5, only [(99m)Tc]HMPAO imaging in 4, and both [(123)I]iomazenil and [(99m)Tc]HMPAO imaging in 5). Region of interest (ROI) analysis and voxel-based analysis were performed with cerebellar normalization. RESULTS: Neither ROI analysis nor voxel-based analysis showed significant [(123)I]iomazenil binding changes in MCI patients compared to control subjects, either as a whole group or when considering only those patients with MCI that converted to AD within 2 years of clinical follow-up. In contrast, the ROI analysis revealed significant hypoperfusion of the precuneus and posterior cingulate cortex in the whole group of MCI patients and in MCI converters as compared to control subjects. Voxel-based analysis showed similar results. CONCLUSION: These results indicate that in the very early stages of AD, neocortical and limbic neurons/synapses expressing GABA(A)/BZD receptors are essentially preserved. They suggest that in MCI patients functional changes precede neuronal/synaptic loss in neocortical posterior regions and that [(99m)Tc]HMPAO rCBF imaging is more sensitive than [(123)I]iomazenil GABA(A)/BZD receptor imaging in detecting prodromal AD.

Defective cerebral gamma-aminobutyric acid-A receptor density in patients with systemic lupus erythematosus and central nervous system involvement. An observational study.

Gamma-aminobutyric acid-A (GABA-A) receptors play a crucial role in regulating neuronal excitability and cognitive functions. Single-photon emission computerized tomography (SPECT) analysis of GABA-A receptors binding by (123)I-labelled Iomazenil ((123)I-IMZ) has been applied in some neuropsychiatric disorders to investigate conditions where GABA-A receptor density can be detected in several pathophysiological conditions. In this study we investigate cerebral GABA-A receptor density in a small series of patients with systemic lupus erythematosus (SLE) and cognitive impairment characterized by recurrent, episodic memory loss. Nine female patients with SLE and cognitive alterations underwent to a clinical neuropsychiatric evaluation including digital video-EEG, brain MRI, (99m)Tc-ECD brain SPECT and (123)I-IMZ brain SPECT. All patients tested showed diffuse or focal GABA-A receptor density reduction. This is, to our knowledge, the first report on GABA-A receptor density abnormalities associated with cognitive defects in SLE patients. We hypothesize that in our series a decrease in GABA-A receptor density might be related to the neurological manifestations. Further studies are needed to clarify this aspect and the possible mechanisms. GABA-A receptor density impairment might be due to the SLE-related cerebral vasculopathy, or to neuronal-reacting auto-antibodies or drugs which could interfere with GABA-A receptors expression/binding. This study may support the concept that cognitive impairment in systemic lupus erythematosus could be the outcome of fine-tuned neurotransmission alterations.

Postcarotid endarterectomy improvement in cognition is associated with resolution of crossed cerebellar hypoperfusion and increase in 123I-iomazenil uptake in the cerebral cortex: a SPECT study.

BACKGROUND: The purpose of the present study was to investigate whether resolution of crossed cerebellar hypoperfusion (CCH) and increase in (123)I-iomazenil (IMZ) uptake in the ipsilateral cerebral cortex after carotid endarterectomy (CEA) are associated with postoperative improvement of cognitive function. METHODS: Neuropsychological testing was performed preoperatively and after 1 postoperative month in 79 patients undergoing CEA for ipsilateral internal carotid artery stenosis (>or=70%). Brain perfusion single photon emission computed tomography (SPECT) using N-isopropyl-p-(123)I-iodoamphetamine and (123)I-IMZ SPECT were also performed before and after surgery. Data were analyzed using a three-dimensional stereotaxic region of interest template. RESULTS: Seven patients (9%) showed improvement in postoperative cognitive function. All the 7 patients exhibited both postoperative increase in blood flow in the ipsilateral cerebral cortex and resolution of CCH. Five patients (6%) had a postoperative hemispheric increase in (123)I-IMZ uptake, and cognitive function improved in all of these 5 patients. Analysis by a receiver operating characteristic (ROC) curve was used to estimate the ability to discriminate between patients with and without postoperative cognitive improvement. The area under the ROC curve was significantly greater when analyzing the magnitude of postoperative resolution of CCH (0.991; 95% CI 0.984-1.001) or postoperative hemispheric increase in (123)I-IMZ uptake (0.981; 95% CI 0.972-0.999) when compared with the magnitude of postoperative increase in cerebral blood flow (0.929; 95% CI 0.886-0.971) (p < 0.05). CONCLUSIONS: Resolution of CCH and increase in (123)I-IMZ uptake in the ipsilateral cerebral cortex after CEA is associated with postoperative improvement in cognitive function. These results may indicate that cognitive impairment is related to a state of potentially reversible central benzodiazepine receptor downregulation in the cortex in response to transient ischemic attack or minor stroke.