Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method.

Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.

Multimodal neurometabolic investigation of the effects of zolpidem on leukoencephalopathy-related apathy.

BACKGROUND AND PURPOSE: The symptomatic effect of zolpidem on apathy has been reported in neurological disorders such as strokes and post-anoxic brain injuries, but not in white-matter disease of the brain. METHODS: A 38-year-old patient presenting with severe apathy related to a genetic leukoencephalopathy but showing marked improvement of apathy after taking 10 mg of zolpidem was studied. To understand what may mediate such a clinical effect, a multimodal neurometabolic approach using 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) and a dedicated magnetic resonance spectroscopy (MRS) sequence for gamma aminobutyric acid (GABA) and glutamine + glutamate metabolism was undertaken. RESULTS: Pre-zolpidem FDG-PET showed hypometabolism in the orbitofrontal cortex, dorsolateral cortex and basal ganglia compared to healthy controls. Post-zolpidem, FDG-PET displayed increased metabolism in the orbitofrontal cortex together with improvement in the emotional and auto-activation domains of apathy. There was no improvement in the cognitive domain of apathy, and no change in metabolism in the dorsolateral frontal cortex. Post-zolpidem, MRS showed increased GABA and glutamine + glutamate levels in the frontal cortex and pallidum. CONCLUSION: Our multimodal neurometabolic study suggests that the effects of zolpidem on apathy are related to increased metabolism in the orbitofrontal cortex and basal ganglia secondary to GABA modulation. Zolpidem may improve apathy in other white-matter disorders.

Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.

INTRODUCTION: The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition. STATE OF KNOWLEDGE: According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias. CONCLUSION AND PERSPECTIVE: The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder.

Utility of 123I-FP-CIT SPECT for dementia diagnoses and therapeutic strategies in elderly patients.

OBJECTIVES: Evaluation of the influence of single photon emission computed tomography (SPECT) of the dopamine transporter (123I-FP-CIT) on diagnosis and treatment strategies in elderly patients with mild dementia. DESIGN: Retrospective study. SETTING: Geriatrics memory clinic. PARTICIPANTS: Consecutive ambulatory patients who had 123I-FP-CIT SPECT for a suspicion of DLB. MEASUREMENTS: Clinical diagnoses before SPECT were compared with imaging results. RESULTS: 46 patients were included. Pre imaging clinical hypotheses were probable DLB in 14, possible DLB in 21 and alternate diagnoses in 11. Rates of abnormal imaging in these groups were respectively 71%, 43% and 18%. Overall, diagnoses were revised in 37% of the cases. Four patients with probable DLB had normal imaging. Their number of core criteria did not differ from the remainder (2.75 ± 0.5 vs. 2.1 ± 0.6), but hallucinations in 2 patients were not well formed and detailed as usual in DLB. Among 38 patients free of antipsychotics, rates of abnormal scans were 36% in patients with questionable parkinsonism, 57% in definite parkinsonism, 67% in patients with no parkinsonism. Among 9 patients on Levodopa, 6 had normal scans and Levodopa was stopped. CONCLUSION: We show a significant impact of 123I-FP-CIT SPECT on diagnoses, even in cases of definite parkinsonism or probable DLB. In the latter, scarcity of hallucinations, especially if there are not well formed and detailed, should prompt 123I-FP-CIT SPECT.

Neural correlates of the mini-SEA (Social cognition and Emotional Assessment) in behavioral variant frontotemporal dementia.

Although Frontotemporal Dementia (FTD) is the second most common form of dementia after Alzheimer's disease, its diagnosis remains particularly challenging today. This is particularly true for the behavioral variant (bvFTD), the most common phenotype of FTD, which is characterised by dramatic changes in personal and social conduct. Novel clinical cognitive tests have been recently proposed to diagnose and assess these patients. Among them, the mini-SEA (Social cognition & Emotional Assessment) has shown promising results. This quick clinical tool evaluates emotion recognition and theory of mind deficits, both recognized as hallmark features of bvFTD. In this study, we investigated the neural correlates of the mini-SEA in twenty bvFTD patients, using single photon emission computed tomography (SPECT) and focusing on the mPFC. Results showed that detection of faux pas during a theory of mind evaluation was related to rostral mPFC perfusion (BA 10) while recognition of emotion involved more dorsal regions within the mPFC (BA 9). As significant and early dysfunction of the mPFC has been extensively described in bvFTD, this study supports the use of the mini-SEA in evaluation and diagnosis purposes in bvFTD.

[Markers of prodromal Alzheimer's disease]. / Les marqueurs de la maladie d'Alzheimer prodromale.

The diagnosis of Alzheimer's disease has long been considered a diagnosis of probability, as the definitive diagnosis can only be established by histopathological examination. However, the development of in-vivo biomarkers, considered a reflection of physiopathological processes, has changed our view of the disease. New criteria have recently been proposed that integrate such biomarkers as found in the cerebrospinal fluid (CSF) using new diagnostic tools such as magnetic resonance imaging (MRI), brain scintigraphy, FDG-positron emission tomography (PET) and PET amyloid ligand uptake studies. The value of these new criteria for the diagnosis of prodromal Alzheimer's disease and the prospect of disease-modifying drugs are also discussed.

Early detection of patients in the pre demented stage of Alzheimer's disease: the Pre-Al Study.

OBJECTIVES: The aim of the Pre-Al study is to evaluate and compare the predictive value of different tools for an early identification of Alzheimer's disease. DESIGN AND PARTICIPANTS: Patients coming for consultation to memory clinics without dementia were included if they had an objective memory or attention trouble assessed by a MMSE score > 25 (with at least one missing item at the words recall) and / or an Isaac set test score < 28. All were examined by a neuropsychological battery (Free and Cued Selective Reminding Test, digit ordering test, WAIS-R digit symbol, Trail making test, Benton visual retention test, verbal fluency, confrontation naming and Baddeley's double task test). A subpopulation received an MRI and SPECT assessment. RESULTS AND DISCUSSION: 251 patients were included (mean age: 72.0 years; mean education duration: 10.9 years). Validation of the predictive tests will be based on the comparison of these tests in patients developing dementia and others, after a follow-up of at least 3 years. This paper presents methodology of the study and the population description.

[Ictal single photon computed tomography and SISCOM: methods and utility]. / Tomographie d'émission monophotonique ictale et Siscom: technique et utilité

Ictal single photon emission computed tomography (SPECT) reflects epileptic activity through hyperperfusion associated with ictal discharge. It provides valuable spatial information on ictal activity, but its temporal resolution is limited. Therefore, information provided by SPECT is not restricted to the epileptogenic zone, but demonstrates a larger epileptogenic network, related to the spatiotemporal dynamics of ictal processes. This review includes a description of the technique, followed by a description of the different parameters likely to influence the ictal perfusion images. SPECT gives contributes original diagnostic data to the decision-making process which will complete, the other evaluation parameters.

["Boxer's dementia" without motor signs]. / "Démence pugilistique" sans signes moteurs.

BACKGROUND: The neurological complications related to boxing include dementia. Boxer's dementia is generally associated with severe motor impairment. CASE REPORT: A former professional boxer presented dementia with no motor signs. The diagnostic discussion was based on clinical observations, and neuropsychological and supplementary explorations, and eliminated all other etiological hypotheses. DISCUSSION: This case draws attention to the possibility of cognitive disorders without motor impairment in the neurological complications of boxing.

Proportional anatomical stereotactic atlas for visual interpretation of brain SPET perfusion images.

A semi-automatic method was developed to determine the anterior (AC) and posterior (PC) commissures on brain single-photon emission tomographic (SPET) perfusion images, and then to draw the proportional anatomical Talairach's grid on each axial SPET image. First, the AC-PC line was defined on SPET images from the linear regression of four internal landmarks (frontal pole of the brain, inferior limit of the anterior corpus callosum, sub-thalamic point and occipital pole). Second, the SPET position of AC and PC points on the AC-PC line was automatically determined from measurements made on hard copies of magnetic resonance (MR) images of the patients. Finally, a proportional Talairach's grid was automatically drawn on each axial SPET image. To assess the accuracy of localization of AC and PC points, co-registered technetium-99m hexamethylpropylene amine oxime SPET and MR images from 11 subjects were used. The mean displacements between estimated points on SPET and true points on MRI (Deltax=sagittal, Deltay=frontal and Deltaz=axial displacement) were calculated. The mean displacements (in mm) were Deltax=-1.4+/-1.8, Deltay=-1.7+/-3.3 and Deltaz=-1. 1+/-2.5 for AC, and Deltax=-1.8+/-1.8, Deltay=0.3+/-3.2 and Deltaz=-1.3+/-2.7 for PC. These displacements represented an error of less than 5 mm at the anterior or posterior pole of the brain or at the vertex. Intra- and inter-observer comparisons did not reveal significant differences in mean displacements. Thus, this semi-automatic method results in reproducible and accurate stereotactic localization of SPET perfusion abnormalities. This method can be used routinely for repeat follow-up studies in the same subject as well as in different individuals without requiring SPET-MRI co-registration.

Inter-ictal brain SPET in frontal epilepsy: correlations with stereo-electroencephalography.

Single photon emission tomography (SPET) imaging holds promise for localization of the site of extratemporal seizures, but limited data currently exist; in particular, correlations with stereo-electroencephalography (S-EEG) have not been made. Ten patients aged 14-44 years (mean 25 years) with a proven frontal or central epilepsy by S-EEG and post-surgical follow-up were studied retrospectively: 7 patients had frontal cortectomy and one patient had a callosotomy for bifrontal epilepsy. All patients underwent clinical, inter-ictal and ictal video-EEG, computed tomography scan and/or magnetic resonance imaging, SPET and S-EEG examinations. SPET was performed inter-ictally, while on usual epileptic medications, using 99Tcm-HMPAO (n = 4) or 123I-IMP (n = 6) as the perfusion tracer. The SPET images were evaluated independently by two observers, blind to any data other than the diagnosis of frontral or central epilepsy. Localization of inter-ictal SPET hypoperfusion was compared with the epileptogenic (EZ), irritative (IZ) and lesional (LZ) zones, as defined by S-EEG. Six patients showed structural frontal abnormalities. One patient had normal SPET and one had a contralateral hypoperfusion. Therefore, concordance of sides was found in 8 of 10 patients (including one with bilateral SPET and S-EEG abnormalities). The hypoperfusion was equal to or larger than the EZ + IZ + LZ in 6 patients (5 had a frontal lesion). SPET hypoperfusion was smaller than the EZ in one patient, and different from the EZ, IZ and LZ in two patients. Although this was a retrospective study, it provides qualitative data regarding the significance of inter-ictal SPET abnormalities in frontal or central epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

[SPECT and depressive pseudo-dementia. A case report]. / SPECT et pseudo démence dépressive. A propos d'un cas.

The SPECT (Single Photon Emission Computed Tomography), a new advance in medical imagery, allows the measure of cerebral blood flow and could be of interest in studying mental disorders. We report here a case of pseudo-dementia for which a SPECT has been performed before and after treatment. Mrs V., a 49 years old female, has been suffering from a dementia-like syndrome for several months. She is divorced, has two children, lives with a boy-friend, and has been working in a factory for 25 years. The first psychiatric disorders began three years ago with a gradual apragmatism and muteness. A neuroleptic treatment gave no result. One year later, without any reason, Mrs V. recovered a normal way of life. Nevertheless, from time to time, she had some periods of subexcitation. Few months later, she relapsed in her previous state of apragmatism and muteness. During a new hospitalization, neuroleptic treatment is tried again without any success. Mrs V. is then referred to us for medical screening of a dementia syndrome. In the Unit, it is difficult to communicate with her; she looks sad or amimic and has motor stereotypies (like rubbing her feet continuously against the floor). She has polidypsia and glutonny. Neurologic examination is normal, as well as EEG, X Scan, Nuclear Magnetic Resonance. The Folstein Mini Mental State score is 9/30.(ABSTRACT TRUNCATED AT 250 WORDS)

(99mTc)-HM-PAO SPECT and cognitive impairment in Parkinson's disease: a comparison with dementia of the Alzheimer type.

Regional cerebral perfusion was evaluated by single photon emission tomography (SPECT) using (99mTc)-HM-PAO as a tracer, in thirty Parkinsonian patients with (n = 15) or without (n = 15) dementia, nineteen patients with dementia of the Alzheimer type (DAT) and thirteen control subjects. HM-PAO uptake was measured in the frontal, parietal, temporal and occipital cortex and tracer perfusion was expressed as cortical/cerebellar activity ratios. Regional HM-PAO ratios in nondemented Parkinsonian patients did not differ from controls, whereas in demented patients with Parkinson's disease (DPD) a significant reduction was found in the parietal, temporal and occipital cortex. Tracer uptake ratios were significantly reduced in all regions in the DAT group. Thus DPD and DAT shared a common pattern of marked posterior hypoperfusion, although the perfusion defect was greater and more extensive in the DAT patients.

A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia.

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n = 19), presumed Pick's disease (n = 5), idiopathic Parkinson's disease with dementia (DPD, n = 15) and progressive supranuclear palsy (PSP, n = 5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups.

Low thyrotropin (TSH) levels in goiter. Relationship with scintigraphic findings and other biological parameters.

Low TSH levels are frequently encountered in patients presenting with goiter. We assayed TSH in 599 goitrous patients who were referred to us for scintigraphy and ultrasonography. When TSH levels were low or when a hot nodule was discovered at scintigraphy, free T3, free T4 and sex hormone-binding globulin (SHBG) were also assayed. TSH levels were always low in overt hyperthyroidism with elevated free T3. TSH levels were also low in patients with normal free T3 and free T4 in circumstances leading to mild hyperthyroidism such as hot nodules that suppressed extranodular thyroid tissue uptake, toxic multinodular goiter, De Quervain thyroiditis and some patients on amiodarone treatment. Low TSH levels were also encountered in 29% of the clinically euthyroid patients presenting with a multinodular goiter with normal iodine uptake, no hot area and normal free T3 levels. In diffuse goiter, low TSH and normal free T3 levels were more frequently associated when iodine uptake was low, mainly due to subacute thyroiditis which can be clinically silent. Low TSH levels were rarely observed in patients with "simple" goiter or uninodular goiter without hot areas. SHBG, which was elevated in 94% of the Graves' disease patients tested, was normal in all but two patients with low TSH and normal free T3 levels. This assay appeared to be of little relevance in goiter. In addition to imaging techniques which are usually performed first, TSH should be systematically assayed in goiter, except in cases of solitary cold nodules. When low, the patient is at risk of developing overt hyperthyroidism. Conversely, when an isolated low TSH level is observed, scintigraphy should be performed.