Neuroimaging of Epilepsy: EEG-fMRI in the Presurgical Evaluation of Focal Epilepsy

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Primary Cardiac High-grade Myxofibrosarcoma Presenting with Multiple Brain Metastases: A Case Report

Herein we describe the case of a young patient who presented with a recent history of epilepsy due to multiple brain lesions; he did not complain about any cardiopulmonary impairments. The patient died as a consequence of hemorrhagic progression of brain metastatic disease. Regardless of a thorough investigation, the heart tumor remained occult. Primary cardiac tumors are very rare entities. Most of these are benign, but approximately 25% are malignant, and the majority of these are sarcomas. Myxofibrosarcoma and osteosarcoma are exceptionally rare. To date, we find only small series of cardiac myxofibrosarcoma, and to our knowledge, this one exceptionally presented with multiple brain metastatic lesions without cardiopulmonary symptoms

How long is the recovery of global aphasia? Twenty-five years of follow-up in a patient with left hemisphere stroke

Background. Current knowledge regarding the time course of aphasia recovery is based on observations limited to the first years after stroke. Objective. The authors studied long-term outcome (25 years) of language in a patient with global aphasia. Methods. A 37-year-old man with global aphasia from a large ischemic lesion in the left middle cerebral artery territory was tested 9 times between 3 weeks and 25 years poststroke by means of the Milan Language Examination, Token Test, Raven Test, and apraxia tests. Results. Three main periods of recovery were identified. The first year after stroke was characterized by recovery of verbal comprehension and word repetition. From 1 to 3 years, naming and reading improved. From 3 to 25 years, progressive improvement of previously emerged functions was found, as well as the appearance of spontaneous speech. Conclusions. This unique long-term follow-up shows that the time span for recovery of language functions in global aphasia after stroke may be much longer than previously documented

Effect of balance training on postural instability in patients with idiopathic Parkinson’s disease

Background. Postural instability (PI) is a disabling sign of Parkinson’s disease (PD) not easily amenable to treatment with medication. Objective. To evaluate the effects of balance training on PI in patients with PD. Methods. A total of 64 patients with PI were randomly assigned to the experimental group (n = 33) for balance training or to the control group (n = 31) for general physical exercises. Each patient received 21 treatment sessions of 50 minutes each. Patients were evaluated by a blinded rater before and after treatment as well as 1 month posttreatment using the Berg Balance Scale (BBS), ActivitiesSpecific Balance Confidence Scale (ABC), postural transfer test, self-destabilization of the center of foot pressure test, number of falls, Unified Parkinson’s Disease Rating Scale (UPDRS), modified Hoehn and Yahr (H&Y) Staging Scale, and Geriatric Depression Scale (GDS). Results. At the end of treatment, the experimental group showed significant improvements in all outcome measures, except for the UPDRS and the H&Y scale. Improvement was maintained at the 1-month follow-up in all outcome measures except for the GDS. No significant changes in performance were observed in the control group. Conclusions. A program of balance training can improve PI in patients with PD

Neuroplastic changes related to pain occur at multiple levels of the human somatosensory system: A somatosensory-evoked potentials study in patients with cervical radicular pain

Studies suggest that pain may play a major role in determining cortical rearrangements in the adult human somatosensory system. Most studies, however, have been performed under conditions whereby pain coexists with massive deafferentation (e.g., amputations). Moreover, no information is available on whether spinal and brainstem changes contribute to pain-related reorganizational processes in humans. Here we assess the relationships between pain and plasticity by recording somatosensoryevoked potentials (SEPs) in patients who complained of pain to the right thumb after a right cervical monoradiculopathy caused by compression of the sixth cervical root, but did not present with clinical or neurophysiological signs of deafferentation. Subcortical and cortical potentials evoked by stimulation of digital nerves of the right thumb and middle finger were compared with those obtained after stimulation of the left thumb and middle finger and with those obtained in a control group tested in comparable conditions. Amplitudes of spinal N13, brainstem P14, parietal N20 and P27, and frontal N30 potentials after stimulation of the painful right thumb were greater than those of the nonpainful left thumb and showed a positive correlation with magnitude of pain. This right-left asymmetry was absent after stimulation of the patients' middle fingers and in control subjects. Results suggest that chronic cervical radicular pain is associated with changes in neural activity at multiple levels of the somatosensory system. The absence of correlation between the amplitude of spinal, brainstem, and cortical components of SEPs suggests that enhancement of cortical activity is not a simple amplification of subcortical enhancement

Deep learning-based algorithm for postoperative glioblastoma MRI segmentation: a promising new tool for tumor burden assessment

Objective: Clinical and surgical decisions for glioblastoma patients depend on a tumor imaging-based evaluation. Artificial Intelligence (AI) can be applied to magnetic resonance imaging (MRI) assessment to support clinical practice, surgery planning and prognostic predictions. In a real-world context, the current obstacles for AI are low-quality imaging and postoperative reliability. The aim of this study is to train an automatic algorithm for glioblastoma segmentation on a clinical MRI dataset and to obtain reliable results both pre- and post-operatively. Methods: The dataset used for this study comprises 237 (71 preoperative and 166 postoperative) MRIs from 71 patients affected by a histologically confirmed Grade IV Glioma. The implemented U-Net architecture was trained by transfer learning to perform the segmentation task on postoperative MRIs. The training was carried out first on BraTS2021 dataset for preoperative segmentation. Performance is evaluated using DICE score (DS) and Hausdorff 95% (H95). Results: In preoperative scenario, overall DS is 91.09 (± 0.60) and H95 is 8.35 (± 1.12), considering tumor core, enhancing tumor and whole tumor (ET and edema). In postoperative context, overall DS is 72.31 (± 2.88) and H95 is 23.43 (± 7.24), considering resection cavity (RC), gross tumor volume (GTV) and whole tumor (WT). Remarkably, the RC segmentation obtained a mean DS of 63.52 (± 8.90) in postoperative MRIs. Conclusions: The performances achieved by the algorithm are consistent with previous literature for both pre-operative and post-operative glioblastoma's MRI evaluation. Through the proposed algorithm, it is possible to reduce the impact of low-quality images and missing sequences

Time-frequency analysis of short-lasting modulation of EEG induced by TMS during wake, sleep deprivation and sleep

The occurrence of dynamic changes in spontaneous electroencephalogram (EEG) rhythms in the awake state or sleep is highly variable. These rhythms can be externally modulated during transcranial magnetic stimulation (TMS) with a perturbation method to trigger oscillatory brain activity. EEG-TMS co-registration was performed during standard wake, during wake after sleep deprivation and in sleep in six healthy subjects. Dynamic changes in the regional neural oscillatory activity of the cortical areas were characterized using time-frequency analysis based on the wavelet method, and the modulation of induced oscillations were related to different vigilance states. A reciprocal synchronizing/desynchronizing effect on slow and fast oscillatory activity was observed in response to focal TMS after sleep deprivation and sleep. We observed a sleep-related slight desynchronization of alpha mainly over the frontal areas, and a widespread increase in theta synchronization. These findings could be interpreted as proof of the interference external brain stimulation can exert on the cortex, and how this could be modulated by the vigilance state. Potential clinical applications may include evaluation of hyperexcitable states such as epilepsy or disturbed states of consciousness such as minimal consciousness

Chloride intracellular channel 1 activity is not required for glioblastoma development but its inhibition dictates glioma stem cell responsivity to novel biguanide derivatives

Background: Chloride intracellular channel-1 (CLIC1) activity controls glioblastoma proliferation. Metformin exerts antitumor effects in glioblastoma stem cells (GSCs) inhibiting CLIC1 activity, but its low potency hampers its translation in clinical settings. Methods: We synthesized a small library of novel biguanide-based compounds that were tested as antiproliferative agents for GSCs derived from human glioblastomas, in vitro using 2D and 3D cultures and in vivo in the zebrafish model. Compounds were compared to metformin for both potency and efficacy in the inhibition of GSC proliferation in vitro (MTT, Trypan blue exclusion assays, and EdU labeling) and in vivo (zebrafish model), migration (Boyden chamber assay), invasiveness (Matrigel invasion assay), self-renewal (spherogenesis assay), and CLIC1 activity (electrophysiology recordings), as well as for the absence of off-target toxicity (effects on normal stem cells and toxicity for zebrafish and chick embryos). Results: We identified Q48 and Q54 as two novel CLIC1 blockers, characterized by higher antiproliferative potency than metformin in vitro, in both GSC 2D cultures and 3D spheroids. Q48 and Q54 also impaired GSC self-renewal, migration and invasion, and displayed low systemic in vivo toxicity. Q54 reduced in vivo proliferation of GSCs xenotransplanted in zebrafish hindbrain. Target specificity was confirmed by recombinant CLIC1 binding experiments using microscale thermophoresis approach. Finally, we characterized GSCs from GBMs spontaneously expressing low CLIC1 protein, demonstrating their ability to grow in vivo and to retain stem-like phenotype and functional features in vitro. In these GSCs, Q48 and Q54 displayed reduced potency and efficacy as antiproliferative agents as compared to high CLIC1-expressing tumors. However, in 3D cultures, metformin and Q48 (but not Q54) inhibited proliferation, which was dependent on the inhibition dihydrofolate reductase activity. Conclusions: These data highlight that, while CLIC1 is dispensable for the development of a subset of glioblastomas, it acts as a booster of proliferation in the majority of these tumors and its functional expression is required for biguanide antitumor class-effects. In particular, the biguanide-based derivatives Q48 and Q54, represent the leads to develop novel compounds endowed with better pharmacological profiles than metformin, to act as CLIC1-blockers for the treatment of CLIC1-expressing glioblastomas, in a precision medicine approach