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1.
Brain Sci ; 14(2)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38391716

ABSTRACT

The surgical treatment of paediatric thalamic gliomas has been burdened with high morbidity, and these lesions were often considered inoperable. With new approaches and intraoperative technologies, we can remove tumours once deemed inoperable. In our single centre, we have operated on 11 paediatric patients over the course of 8 years. We have performed eight GTR resections and three intended subtotal resections. The postoperative neurological deficit ranged from mild to very severe for motor weakness and none to severe for aphasia after surgery, with all of the patients improving at 3-month follow-up. Radicality in the surgical approach to thalamic gliomas in children has shown significant benefits when compared to more conservative approaches. For children with LGGs, extensive surgical resection is associated with improved prognosis and longer progression-free survival. However, it does not yield the same proportional benefit for HGGs due to its aggressive nature and worse outlook.

2.
Eur J Med Chem ; 266: 116130, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38218127

ABSTRACT

Tacrine (THA), a long withdrawn drug, is still a popular scaffold used in medicinal chemistry, mainly for its good reactivity and multi-targeted effect. However, THA-associated hepatotoxicity is still an issue and must be considered in drug discovery based on the THA scaffold. Following our previously identified hit compound 7-phenoxytacrine (7-PhO-THA), we systematically explored the chemical space with 30 novel derivatives, with a focus on low hepatotoxicity, anticholinesterase action, and antagonism at the GluN1/GluN2B subtype of the NMDA receptor. Applying the down-selection process based on in vitro and in vivo pharmacokinetic data, two candidates, I-52 and II-52, selective GluN1/GluN2B inhibitors thanks to the interaction with the ifenprodil-binding site, have entered in vivo pharmacodynamic studies. Finally, compound I-52, showing only minor affinity to AChE, was identified as a lead candidate with favorable behavioral and neuroprotective effects using open-field and prepulse inhibition tests, along with scopolamine-based behavioral and NMDA-induced hippocampal lesion models. Our data show that compound I-52 exhibits low toxicity often associated with NMDA receptor ligands, and low hepatotoxicity, often related to THA-based compounds.


Subject(s)
Alzheimer Disease , Chemical and Drug Induced Liver Injury , Neuroprotective Agents , Piperidines , Humans , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Receptors, N-Methyl-D-Aspartate , Tacrine/chemistry , Cholinesterase Inhibitors/chemistry , Binding Sites , Cholinesterases , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy
3.
Children (Basel) ; 10(4)2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37189972

ABSTRACT

Our study evaluates the sensitivity of papilledema as a sign of high intracranial pressure in children. Patients younger than 18 years old, diagnosed with increased ICP, and who had received dilated fundus examination between 2019 and 2021 were retrospectively reviewed. Factors including the patient's age, sex, aetiology, duration of signs or symptoms, intracranial pressure (ICP), and presence of papilledema were evaluated. We included 39 patients in this study, whose mean age was 6.7 years. The 31 patients without papilledema had a mean age of 5.7 years, and 8 patients (20%) with papilledema had a mean age of 10.4 (p < 0.037). The mean duration of signs or symptoms was nine weeks in patients without papilledema and seven weeks in those with papilledema (p = 0.410). The leading causes of increased ICP with papilledema were supratentorial tumor (12.5%), infratentorial tumor (33.3%), and hydrocephalus (20%) (p = 0.479). Papilledema was statistically significantly more common in older patients. We found no statistical significance between sex, diagnosis, and symptoms. The relatively low incidence of papilledema (20%) in our study shows that papilledema's absence does not ensure the absence of increased ICP, especially in younger patients.

4.
Diagnostics (Basel) ; 12(12)2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36553139

ABSTRACT

Deep brain stimulation (DBS) is a beneficial procedure for treating idiopathic Parkinson's disease (PD), essential tremor, and dystonia. The authors describe their set of imaging modalities used for a frameless and fiducial-less method of DBS. CT and MRI scans are obtained preoperatively, and STN parcellation is done based on diffusion tractography. During the surgery, an intraoperative cone-beam computed tomography scan is obtained and merged with the preoperatively-acquired images to place electrodes using a frameless and fiducial-less system. Accuracy is evaluated prospectively. The described sequence of imaging methods shows excellent accuracy compared to the frame-based techniques.

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