Parkinson's disease and levodopa-induced dyskinesias: a quantitative analysis through 99mTc-TRODAT-1 SPECT imaging of the brain.

Objective: To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD), with and without LID. Materials and Methods: We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson's Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum. Results: The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without. Conclusion: Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.

Objetivo: Comparar a densidade do transportador de dopamina (DAT) com outros fatores de risco para discinesia induzida pela L-DOPA em pacientes com doença de Parkinson, com e sem discinesias. Materiais e Métodos: Sessenta e sete sujeitos, 23 voluntários saudáveis e 44 pacientes pareados por idade com diferentes graus de gravidade da doença de Parkinson idiopática (29 homens; idade média ± desvio-padrão (DP), 59 ± 7 anos; duração média ± DP dos sintomas, 10 ± 6 anos; H&Y: média ± DP, 2,16 ± 0,65; UPDRS III: média ± DP, 29,74 ± 17,79). Todos os sujeitos realizaram SPECT cerebral com 99mTc-TRODAT-1. Além disso, foram calculadas as taxas de captação específica ou potenciais de ligação no estriado. Resultados: A densidade de DAT do estriado ipsilateral ou contralateral foi menor no grupo doença de Parkinson. As variáveis duração da doença, dosagem de L-DOPA, doses por dia, tempo de duração do efeito da L-DOPA, H&Y e UPDRS III explicaram a ocorrência de discinesia. Adicionalmente, pacientes com discinesia exibiram menor densidade de DAT no estriado ipsilateral ou contralateral e no núcleo caudado do que os pacientes sem discinesia. Conclusão: O presente estudo sugere que a denervação dopaminérgica pré-sináptica na doença de Parkinson está associada ao desenvolvimento de discinesia induzida pela L-DOPA.

Pharmacodynamic effect of gabapentin on central nervous system in patients with chronic low back pain: a [99mTc]Tc-ECD SPECT study.

BACKGROUND: Gabapentin is an effective therapeutic alternative for chronic low back pain, indicated in several guidelines for treating neuropathic pain as first-line medication. This study aimed to describe the pharmacodynamics of gabapentin in the central nervous system of patients with chronic low back pain (CLBP) by using single-photon emission CT (SPECT) with [99mTc]Tc-ECD. METHODS: We selected 13 patients with CLBP due to lumbar disc herniation. They underwent SPECT before and after using gabapentin, compared with a SPECT database of healthy volunteers. A second analysis compared regional cerebral blood flow (rCBF) changes between responders and non-responders to gabapentin and the healthy controls. RESULTS: The mean age of patients was 41 years, and the mean pain intensity was 5.92 points, measured by the Numeric Rating Scale. After using gabapentin, SPECT showed an increase of rCBF in the bilateral anterior cingulate gyrus and a decrease of rCBF in periaqueductal gray matter. Non-responder patients with gabapentin showed a post-treatment decrease of rCBF in the paracentral lobule of the brain. CONCLUSIONS: A lack of improvement in some patients with gabapentin may be associated with an activated affective circuit of pain, evidenced by the increase of rCBF of the anterior cingulate cortex. A maladaptive brain state in chronic pain can explain the decrease of rCBF in the default mode network structures. Gabapentin acts directly or indirectly on neurons of periaqueductal gray substance by increasing the pain threshold and decreasing the rCBF of this structure.

Reference Values for Dopamine Transporter Imaging With 99m Tc-TRODAT-1 in Healthy Subjects and Parkinson's Disease Patients.

PURPOSE: The aim of this study was to evaluate different quantitative indexes of striatum dopamine transporter density in healthy subjects and patients with PD. PATIENTS AND METHODS: Sixty-seven patients, 23 healthy (8 male; 59 ± 11 years old) and 44 age-matched patients (29 male; 59 ± 7 years old), with various degrees of severity of idiopathic PD (duration of symptoms, 10 ± 6 years; Hoehn and Yahr Scale, 2.16 ± 0.65; UPDRS-3, 29.74 ± 17.79). All patients performed 99m Tc-TRODAT-1 SPECT. Binding potential indexes (BPIs) of striatum and subregions, asymmetry index (AI), and putamen/caudate ratio (P/C) were calculated. RESULTS: Binding potential index was lower in the PD than in healthy subjects. A BPI cutoff for striatum and putamen ranging from 0.73 to 0.78 showed 95% to 100% sensitivity and 84% to 88% specificity. For the caudate nucleus, a BPI threshold of 0.8 to 0.88 revealed 100% sensitivity and 77% to 84% specificity. The BPI's respective areas under the curve ranged from 0.92 to 0.98. For AI and P/C, the area under the curve was less than 0.70. Binding potential index intraclass correlation coefficient was close to 1.0 in the intraobserver evaluation and 0.76 to 0.87 in the interobserver assessment. Intraclass correlation coefficient for AI and P/C was inferior to 0.75 in the intraobserver and interobserver evaluations. CONCLUSIONS: Different semiquantitative indices differentiated PD and healthy subjects and may help the differential diagnosis of other entities involving the dopaminergic system. Asymmetry index and P/C performances were lower than BPI, including their intraobserver and interobserver reliability, and therefore should be used with caution.

Sleeve Gastrectomy with Pyloroplasty in Wistar Rats: Assessment of Gastric Emptying, Intestinal Transit, and Possible Duodenogastric Alkaline Reflux.

BACKGROUND: Studies indicate sleeve gastrectomy (SG) as a factor of aggravation or even emergence of symptoms of gastroesophageal reflux disease. Accelerated gastric emptying is described as a mitigating factor. SG may be potentiated by adding a pyloroplasty, although with the potential risk of resulting in duodenogastric alkaline reflux. The objective was to standardize sleeve gastrectomy with pyloroplasty in rats, analyze the complementation in terms of mortality and weight evolution, and conduct assessments on gastric emptying, intestinal transit, and genesis of possible duodenogastric reflux. METHODS: Ninety-three male Wistar rats were divided into a pilot study (standardization of the surgical technique and the scintigraphic study), and the main study. They were then subdivided into the SHAM group, the sleeve gastrectomy (SG) group, and the sleeve gastrectomy with pyloroplasty (SGP) group. After 3 months, the animals were submitted to two scintigraphic experiments and histological analysis of gastric biopsies. RESULTS: The surgical groups (SG and SGP) lost initially more weight than the SHAM group, and the gastric emptying and intestinal transit in the first were more accelerated. However, no difference was found between the SG and SGP groups. Scintigraphic and histological analyses did not reveal statistical differences among the SG and SGP groups regarding gastroesophageal and duodenogastric refluxes. CONCLUSIONS: Pyloroplasty did not affect weight reduction or increase duodenogastric reflux, after three postoperative months in this animal model of sleeve gastrectomy.

Assessment of different regions of interest-based methods for [99mTc]Tc DAT-SPECT quantification using an anthropomorphic striatal phantom.

BACKGROUND AND AIMS: Molecular imaging of the dopamine transporters (DAT) provides valuable information about neurodegenerative diseases, such as Parkinson's. This study assessed the accuracy and precision of DAT-SPECT quantification methods. METHODS: Twenty-three DAT-SPECT images of a striatal phantom were acquired. The specific (caudate and putamen) and the non-specific (background activity) chambers were filled with [99mTc]Tc. Different specific-to-non-specific activity ratios (10, 9, 8, 7, 6, 5, 4, 3 and 2 to 1) and the specific binding ratio (SBR) were calculated. Five methods using ROIs were assessed: (a) Manual ROIs on SPECT images; (b) TwoBox and (c) ThreeBox methods and Volume of Interest (VOI) using structural images; (d) MRI and (e) CT. Accuracy was evaluated by the concordance correlation coefficient (CCC) and precision by Pearson's coefficient and linear regression. RESULTS: The SBR quantified in the specific and striatal chambers resulted in a CCC increase with a decrease in the nominal values. For lower SBR, MRI and CT showed higher CCCs when caudate ([Formula: see text] = 0.89 e [Formula: see text] = 0.84) and putamen ([Formula: see text] = 0.86 e [Formula: see text] = 0.82) were evaluated. For striatal assessments, the TwoBox method was the most accurate ([Formula: see text] = 0.95). High Pearson's coefficients were found in the correlations between all methods. CONCLUSIONS: All five methods showed high precision even when applied to images with different activities. MRI and CT were the most accurate for assessing the caudate or putamen. To assess the striatal chamber and in the absence of structural information, the TwoBox method is advisable.

Neurobiological substrates of chronic low back pain (CLBP): a brain [99mTc]Tc-ECD SPECT study.

BACKGROUND: Recent neuroimaging studies have demonstrated pathological mechanisms related to cerebral neuroplasticity in chronic low back pain (CLBP). Few studies have compared cerebral changes between patients with and without pain in the absence of an experimentally induced stimulus. We investigated the neurobiological substrates associated with chronic low back pain using [99mTc]Tc-ECD brain SPECT and correlated rCBF findings with the numeric rating scale (NRS) of pain and douleur neuropathique en 4 questions (DN4). Ten healthy control volunteers and fourteen patients with neuropathic CLBP due to lumbar disc herniation underwent cerebral SPECT scans. A quantitative comparison of rCBF findings between patients and controls was made using the Statistical Parametric Mapping (SPM), revealing clusters of voxels with a significant increase or decrease in rCBF. The intensity of CLBP was assessed by NRS and by DN4. RESULTS: The results demonstrated an rCBF increase in clusters A (occipital and posterior cingulate cortex) and B (right frontal) and a decrease in cluster C (superior parietal lobe and middle cingulate cortex). NRS scores were inversely and moderately correlated with the intensity of rCBF increase in cluster B, but not to rCBF changes in clusters A and C. DN4 scores did not correlate with rCBF changes in all three clusters. CONCLUSIONS: This study will be important for future therapeutic studies that aim to validate the association of rCBF findings with the pharmacokinetic and pharmacodynamic profiles of therapeutic challenges in pain.

Temporal and spatial changes in cerebral blood flow in neuropsychiatric systemic lupus erythematosus: a subtraction brain spect study.

This study was addressed to evaluate the temporal and spatial changes in regional cerebral blood flow (rCBF) of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Our objective was to correlate the subtracted SPECT coregistered to MRI features (SISCOM) with demographic, clinical and laboratory findings to shed light upon the pathophysiological evolution of the NPSLE. Twenty-six NPSLE patients with MRI and pre- and post-treatment brain SPECT with [99mTc]Tc-ECD. SISCOM features were categorized as improvement, worsening, activation and/or deactivation of rCBF findings. Patients mean age of 43.19 years and 65.38% white were evaluated. The patients mean age at onset of SLE was 26.05 and 42.29 for NPSLE. The mean time between the onset of SLE and first NPSLE symptoms was 05.57 years. The disease has already been initiated as NPSLE in 4 patients. The SLEDAI average score was 31.69 and the SLICC/ACR-DI score was 06.96. The patients underwent an average of 09.23 cyclophosphamide. The SISCOM findings showed functional and pathological states on different brain regions. The rCBF changes were not associated with index scores. There was, however, a trend towards an association between lower SLEDAI scores with improvement and higher SLEDAI with worsening in SISCOM, Also a trend of association between lower SLICC score with improvement, and higher SLICC with worsening. The female gender was predictive of activation and worsening, separately, and deactivation and worsening in a set. Non-white patients were predictive of worsening. The seizure was predictive of deactivation separately, and deactivation and worsening in a set. Finally, normal C3 was a predictor of improvement. The present study showed dynamic brain changes in NPSLE patients. SISCOM technique showed improved rCBF in some brain areas, and worsening, activation and deactivation in others. There were associations between rCBF changes and gender, skin colour and complement C3 and association trends with SLEDAI and SLICC scores.

Regional cerebral blood flow at rest in obesity.

OBJECTIVES: Imaging studies have shown brain abnormalities associated with eating behavior (taste perception, food intake, and food reward), neural connectivity, and cognition related to obesity. The aim of this study was to investigate whether obese individuals have changes in regional cerebral blood flow (rCBF) during fasting and rest using single-photon emission computed tomography (SPECT), and whether these differences are associated with body fat and serum levels of leptin, insulin, and glucose. METHODS: For this purpose, rCBF assessed by ([99]mTc)-ECD-SPECT was compared between 10 obese women (30 ± 5 y of age, body fat: 38 ± 3 kg) and 10 lean women (30 ± 6 y of age, body fat: 17 ± 5 kg) using statistical parametric mapping. Pearson's coefficient and linear regression were used to search for associations among variables. RESULTS: The obese women showed antagonic rCBF in the left frontoparietal region and greater rCBF in areas related to the default mode network and the salience network (P = 0.0001). Positive linear correlations of rCBF, body fat, and the serum levels of glucose and insulin were found, but no associations were detected using linear regression. CONCLUSION: Obese women showed rCBF differences in areas related to the frontoparietal neural circuit, the default mode network, and the salience network, suggesting loss of cognitive control and a higher perception of physiologic processes, such as hunger. Hyperactivation in these areas might jeopardize the recognition of changes in energy homeostasis.

The Reperfusion of Ischemic Vasculitis in a Patient with Neuropsychiatric Lupus: A Serial Single-Photon Emission Computed Tomography Study.

We report a 44-year-old female patient diagnosed with neuropsychiatric systemic lupus erythematosus and probable ischemia secondary to vasculitis in the speech motor region (Broca's area). After corticosteroid treatment, the patient recovered the speech, presented clinical improvement, and SISCOM showed reperfusion of the ischemic area (luxury perfusion).

18F-FDG PET/CT/MRI Fusion Images Showing Cranial and Peripheral Nerve Involvement in Neurolymphomatosis.

We report a 56-year-old female patient with non-Hodgkin's diffuse large B cell lymphoma (NHL) who, on magnetic resonance imaging (MRI) with a T1 weighted and gadolinium-enhanced imaging, was found to have thickening and infiltration in 75% of peripheral nerves of the patient and enlargements of cranial nerves, possibly related to lymphomatous infiltration. Subsequent positron emission tomography/computed tomography (PET/CT) using 18F-labeled 2-deoxy-2-fluoro-d-glucose (18F-FDG) showed widespread active involvement of the cervical plexus, bilateral peripheral nerves, right femoral nerve, the parasellar region of the skull, and marked hypermetabolism in the left trigeminal ganglia. This case re-emphasizes that while CT and MRI provide anatomical details, 18F-FDG PET/CT images better delineate the metabolic activity of neurolymphomatosis (NL) in the peripheral and central nervous system.

Systematic review of the efficacy in seizure control and safety of neuronavigation in epilepsy surgery: The need for well-designed prospective studies.

PURPOSE: To evaluate the efficacy of surgery with neuronavigation compared to conventional neurosurgical treatment of epilepsy in terms of safety and seizure outcomes and to assess the quality of the evidence base of neuronavigation in this clinical context. METHOD: Systematic review using the electronic databases of Cochrane, CRD, PubMed, Embase, SciELO and LILACS in Portuguese, English and Spanish. The [MeSH] terms included "epilepsy" and "neuronavigation". ELIGIBILITY CRITERIA: Studies assessing surgery with neuronavigation for the surgical treatment of epilepsy or brain injuries associated with epileptic seizures. RESULTS: We identified 28 original articles. All articles yielded scientific evidence of low quality. Outcome data presented in the articles identified was heterogeneous and did not amount to compelling evidence that epilepsy surgery with neuronavigation produces higher rates of seizure control, a reduced need for reoperations, or lower rates of complications or postoperative neurological deficits. CONCLUSION: We were unable to find any publications providing convincing evidence that neuronavigation improves outcomes of epilepsy surgery. Whilst this does not mean that neuronavigation cannot improve neurosurgical outcomes in this clinical setting, well-designed research studies evaluating the role of neuronavigation are urgently needed.