The precise delineation and excision of brain tumor extent allows to improve survival outcome and quality of life of surgically treated patients. In order to refine the resection of gliomas, we are ...developing a novel intraoperative probe specifically dedicated to the localization of residual tumor after the bulk has been excised. The probe, built around clear and plastic scintillating fibers, was designed to detect positrons emitted from radiolabeled brain tissue in order to discriminate more specifically neoplastic from normal tissues. The probe was also built to be directly coupled to the excision tool leading to simultaneous detection and removal of tumor. We report here performances of the first radio-isotopic configuration of the intraoperative probe which consists of a detection head composed of eight detection elements held around the excision tool in a closed packed annular arrangement. This head is coupled to an optic fiber bundle that exports the scintillating light to a multi-channel photomultiplier tube. The gamma ray background generated by the annihilation of beta + in tissues is eliminated by a real-time subtraction method. The detector exhibits a beta sensitivity of 139 cps/kBq and a gamma ray rejection efficiency of 99.5%. The ability of the probe to detect residual lesions was evaluated with a realistic brain phantom representing the surgical cavity and the boundaries of the tumor. We showed that lesions as small as 5 mm in diameter can be detected for tumor to normal tissue uptake ratios of fluorinated tracers greater than 3.5. This ratio is achieved with radiopharmaceuticals like 18 F-FET or 18 F-choline. These promising results suggest that the features of our system are compatible with in situ localization of residual radiolabeled tumors.
The authors report a rare case of most likely radiation-induced glioma (RIG) with epithelioid features and the presence of molecular features consistent with RIG. This occurred 70 years after ...craniofacial brachytherapy. Such a late development of radiation-induced glioblastoma (RIGBM) and the advanced age of presentation for an epithelioid glioblastoma are both unique in the literature. Despite not receiving the full course of adjuvant chemotherapy after surgery and radiotherapy, the patient displayed no signs of recurrence during a 5-year follow-up. RIGBM should be further studied to reveal potential unique clinical and molecular characteristics, as well as to better predict survival and treatment response.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Huntington’s disease is a hereditary disease in which degeneration of neurons in the striatum leads to motor and cognitive deficits. Foetal striatal allografts reverse these deficits in phenotypic ...models of Huntington’s disease developed in primates. A recent open‐label pilot study has shown some clinical improvement or stabilization in three out of five Huntington’s disease patients who received bilateral striatal grafts of foetal neurons. We show here that the clinical changes in these three patients were associated with a reduction of the striatal and cortical hypometabolism, demonstrating that grafts were able to restore the function of striato‐cortical loops. Conversely, in the two patients not improved by the grafts, striatal and cortical hypometabolism progressed over the 2‐year follow‐up. Finally, detailed anatomical–functional analysis of the grafted striata, enabled by the 3D fusion of MRI and metabolic images, revealed considerable heterogeneity in the anatomic and metabolic profiles of grafted tissue, both within and between Huntington’s disease patients. Our results demonstrate the usefulness of PET measurements of brain glucose metabolism in understanding the effects of foetal grafts in patients with Huntington’s disease.
Asymmetry of striatal dopaminergic deficits and motor symptoms is a typical characteristic of idiopathic Parkinson’s disease (PD). This study aims to characterise the trend of asymmetry in ...moderate-stage PD. We performed a 19-month longitudinal study in 27 patients with PET-CT imaging and appropriate clinical assessments.
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C-PE2I non-displaceable binding potential (BP
ND
) was calculated bilaterally for the striatum at baseline and follow-up to estimate the in vivo density of striatal dopamine transporters (DAT). Changes in striatal
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C-PE2I BP
ND
over time were more prominent in the ipsilateral as compared to contralateral side. Changes in MDS-UPDRS-III (motor component of the Movement Disorders Society Unified PD Rating Scale) were not different between the clinically most and least affected body sides. Our data support that the asymmetry in striatal dopaminergic degeneration becomes less prominent in moderate-stage PD. In contrast, during the above period, the asymmetry of motor symptoms was maintained between the clinically most and least affected body sides.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Biotherapies in neurosurgery : an example in Parkinson’s disease.
Parkinson disease (PD) is mainly characterized by a severe loss of substantia nigral neurons that provide dopaminergic innervation to ...the striatum. Although L-Dopa and dopaminergic agonists treatment provide a significant clinical benefit at the earliest stage of the disease, these drugs were soon recognized to lose some of their efficacy and generate their own adverse effects both motors and non-motors over time. One of the therapeutic challenges is to induce a more physological continuous and local release of dopamine in the striatum to avoid these adverse effects. Thus, dopamine replacement strategies using biotherapies seemed to be the next logical step, and studies were initiated over the last 30 years to explore the possibility of dopaminergic cell transplantation and gene therapy. In this review, we outline the history and the future of these therapeutic approaches to PD.
La maladie de Parkinson (MD) est principalement liée à une perte de neurones de la substance noire qui projettent des axones dopaminergiques vers le striatum. Bien que le traitement, par la L-Dopa et/ou les agonistes dopaminergiques, permette d’obtenir un effet bénéfique clinique au début de la MP, les traitements oraux perdent de leur efficacité avec le temps et entrainent des effets indésirables moteurs et non-moteurs. L’un des défis thérapeutiques actuels serait d’induire une sécrétion continue et locale de dopamine, plus physiologique, afin de prévenir l’apparition de ces effets indésirables. Des stratégies thérapeutiques utilisant les biothérapies constitueraient l’étape logique pour une administration locale et continue de dopamine. Des études ont été entreprises depuis plus de 30 ans maintenant sur les greffes neuronales de neurones produisant de la dopamine et sur des approches de thérapie génique. Dans cette revue, nous abordons l’historique et les perspectives de ces approches thérapeutiques dans la MP.
Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the ...clinical, neurophysiologic, and morphologic characteristics of FXTAS.
Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women.
A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04).
We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.
Delayed abnormal movements can be observed in patients with acute neurologic insult after a prolonged period of apparent neurologic stability. To reproduce such a secondary neurologic manifestation ...in primates, the present experiment investigated whether systemic administration of subacute 3‐nitropropionic acid (3NP), a mitochondrial toxin, could induce abnormal movements that were delayed and progressive over time. Four Cebus apella monkeys received systemic 3NP injections until acute neurologic signs manifested. The monkeys were regularly video‐recorded and rated for abnormal movements for up to 15 weeks after the cessation of 3NP treatment. Five to 6 weeks after the 3NP treatment, monkeys displayed a significant increase in dyskinesias compared with pretreatment conditions. Over time the chorea attenuated, whereas the dystonic movements increased in intensity and severity which was characterized by a delayed decrease of peak tangential velocity. The intensity of abnormal movements and extent of affected body regions observed in each monkey were consistent with the size of basal ganglia hypersignal as documented by T2 sequence on magnetic resonance imaging. Thus, more severe motor impairments were associated with large magnetic resonance image abnormalities. This novel primate model may be particularly useful for studying the structural changes underlying delayed and progressive manifestations of abnormal movements with the ultimate goal of facilitating the evaluation of novel therapeutic strategies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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