ro-16-0154 and Cognition-Disorders

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.

Topics: Aged; Aged, 80 and over; Brain; Brain Neoplasms; Cell Survival; Cerebrovascular Circulation; Cognition Disorders; Female; Flumazenil; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Meningioma; Mental Status Schedule; Middle Aged; Neurons; Radiopharmaceuticals; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

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.. 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.. 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).. 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.

Topics: Adult; Afferent Pathways; Aged; Carotid Artery, Internal; Carotid Stenosis; Cerebellum; Cerebral Cortex; Cognition Disorders; Dominance, Cerebral; Down-Regulation; Endarterectomy, Carotid; Female; Flumazenil; Humans; Iodine Radioisotopes; Ischemia; Male; Middle Aged; Neuropsychological Tests; Receptors, GABA-A; ROC Curve; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

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.. [(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.. 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.. 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.

Topics: Aged; Alzheimer Disease; Case-Control Studies; Cerebrovascular Circulation; Cognition Disorders; Female; Flumazenil; Humans; Male; Middle Aged; Receptors, GABA-A; Synapses; Tomography, Emission-Computed, Single-Photon

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.

Topics: Adult; Central Nervous System; Cerebral Cortex; Cerebrovascular Circulation; Cognition Disorders; Electroencephalography; Female; Flumazenil; Humans; Iodine Radioisotopes; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Middle Aged; Pregnancy; Radiopharmaceuticals; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Although cerebral hyperperfusion after carotid endarterectomy (CEA) often impairs cognitive function, MRI does not always demonstrate structural brain damage associated with postoperative cognitive impairment. The purpose of the present study was to determine whether postoperative cortical neural loss, which can be detected by (123)I-iomazenil single-photon emission CT, is associated with cerebral hyperperfusion after CEA and whether it correlates with postoperative cognitive impairment.. In 60 patients undergoing CEA for ipsilateral internal carotid artery stenosis (>70%), cerebral blood flow was measured using N-isopropyl-p-[(123)I]-iodoamphetamine single-photon emission CT before and immediately after CEA and on the third postoperative day. The distribution of benzodiazepine receptor binding potential in the cerebral cortex was assessed using (123)I-iomazenil single-photon emission CT before and 1 month after surgery and was analyzed using 3-dimensional stereotactic surface projection. Neuropsychological testing was also performed preoperatively and at the first postoperative month.. Post-CEA hyperperfusion and postoperative cognitive impairment were observed in 9 patients (15%) and 8 patients (13%), respectively. Post-CEA hyperperfusion was significantly associated with postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 2.765 to 148.804; P=0.0031). Post-CEA hyperperfusion (95% CIs, 1.183 to 229.447; P=0.0370) and postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 1.003 to 77.381; P=0.0496) were also significantly associated with postoperative cognitive impairment.. Cerebral hyperperfusion after CEA results in postoperative cortical neural loss that correlates with postoperative cognitive impairment.

Topics: Adult; Aged; Analysis of Variance; Carotid Stenosis; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition Disorders; Endarterectomy, Carotid; Female; Flumazenil; Humans; Iofetamine; Male; Middle Aged; Neurons; Neuropsychological Tests; Postoperative Complications; Radiopharmaceuticals; Stereotaxic Techniques; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed