Francesco Latini | Uppsala University (original) (raw)

Papers by Francesco Latini

Brain sciences, Feb 26, 2024

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Neuro-Oncology

BACKGROUND Diffuse Low-grade gliomas (DLGG) show extensive infiltration through white matter (WM)... more BACKGROUND Diffuse Low-grade gliomas (DLGG) show extensive infiltration through white matter (WM) tracts. Diffusion tensor tractography with along-tract analysis (ATA) has been used to non-invasively assess the microstructural integrity of WM pathways. The possibility to detect the extension and direction of WM infiltration using local DTI-based parameters in DLGG has been investigated with different techniques but displayed inconsistent results. The aim of this study was to use ATA analysis to compare DTI parameters in white matter pathways invaded/spared by DLGGs. MATERIAL AND METHODS Fourteen patients with a diagnosis of DLGG were included. DLGGs were manually segmented based on 3D-FLAIR images spatially normalised to MNI space. DTI was acquired for all the subjects using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data was reconstructed within MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM path...

WFNOS 2022 Abstract Book, 2022

Neurosurgical Review, Oct 17, 2014

Recent anatomical and DTI data demonstrated new aspects in the subcortical occipito-temporal conn... more Recent anatomical and DTI data demonstrated new aspects in the subcortical occipito-temporal connections. Although a direct (inferior longitudinal fasciculus, ILF) pathway has been previously described, its fine description is still matter of debate. Moreover, a fast and direct subcortical connection between the limbic system and the occipital lobe has been previously recognized in many functional studies but it still remains poorly documented by anatomical images. We provided for the first time an extensive and detailed anatomical description of the ILF subcortical segmentation. We dissected four human hemispheres with modified Klingler's technique, from the basal to the lateral occipito-temporal surface in the two steps, tracking the ILF fibers until their cortical termination. Pictures of this direct temporo-occipital pathway are discussed in the light of recent literature regarding anatomy and functions of occipito-temporal areas. The dissection confirmed the classical originating branches of ILF and allowed a fine description of two main subcomponent of this bundle, both characterized by separate hierarchical distribution: a dorsal ILF and a ventral ILF. Moreover, a direct pathway between lingual cortex and amygdala, not previously demonstrated, is here described with anatomical images. Even if preliminary in results, this is the first fine description of ILF's subcomponents. The complex but clearly segregated organization of the fibers of this bundle (dILF and vILF) supports different level of functions mediated by visual recognition. Moreover, the newly described direct pathway from lingual to amygdala (Li-Am), seems involved in the limbic modulation of visual processing, so it may support physiological conditions the crucial role of this connection in human social cognition. In pathological conditions, on the other hand, this may be one of the hyperactivated pathways in temporooccipital epileptic and nonepileptic syndromes.

Neuro-oncology, Nov 1, 2022

Glioblastoma is a devastating disease with an overall median survival of 8 months from diagnosis.... more Glioblastoma is a devastating disease with an overall median survival of 8 months from diagnosis. The majority of patients die of a tumor relapse in close proximity of the resected primary tumor. Glioblastoma is intensely researched but most studies have been performed on tissues and cultures derived from the bulk tumor while it is the remaining edge cells that cause lethality. Investigations of edge cells are rare and few experimental models exist. Here we have established and analyzed a series of matched cell cultures derived from the tumor bulk and outer edge of six IDH wildtype glioblastoma patients with the purpose to understand glioblastoma edge cell biology. Tumor samples were resected guided by 5-ALA fluorescence using neuro-navigation and stringent procedures to not contaminate edge samples with bulk tumor cells. First bulk tumor samples were resected from 5-ALA fluorescent tissue. After removal of all fluorescent areas and careful irrigation of the cavity the edge sample was resected 1-2 cm outside of the fluorescent border in a non-eloquent area. Following dissociation the samples were used in sphere assays and for explantation. There was a significant difference in self-renewal across all patients between matched bulk and edge cultures, in line with results from sphere assays on acute cells, suggesting maintenance of glioblastoma cell properties in established cultures. Invasion analysis showed a reverse significant difference between matched bulk and edge cultures strengthening a general functional distinction between tumor bulk and edge cells across patients. To investigate the molecular basis of our findings we performed whole exome sequencing (WES) and combined single cell RNA- and ATAC-sequencing (10X Multiome). Analyses are ongoing but WES data does not support genetic causes for their differences while the 10X Multiome data indicate that epigenetic regulation may underlie the different properties of bulk and edge glioblastoma cells.

Background: Gliomas are neuroepithelial tumours classified by cell type and grade. In adults, low... more Background: Gliomas are neuroepithelial tumours classified by cell type and grade. In adults, low-grade gliomas are comprised mainly of astrocytomas and oligodendrogliomas grade II. The aim was to non-invasively characterise suspected low-grade gliomas through use of 11C-methionine-PET and physiological MRI in order to facilitate treatment decisions.Materials and methods: Patients with suspected low-grade glioma were prospectively and consecutively included after referral to the Neurosurgical Department, Uppsala University Hospital, between February 2010 and February 2014. All patients underwent morphological MRI, perfusion MRI, diffusion MRI and 11C-methionine PET. The institutional review board approved the study, and written informed consent was obtained prior to participation from each patient.Results: 11C-methionine PET hot spot regions corresponded spatially with regions of maximum relative cerebral blood volume in dynamic susceptibility contrast (DSC) perfusion MRI. The skewness of the transfer constantin dynamic contrast-enhanced (DCE) perfusion MRI, and the standard deviation of relative cerebral blood flow in DSC perfusion MRI could most efficiently discriminate between glioma grades II and III. In diffusion MRI, tumour fractional anisotropy differed between suspected low-grade gliomas of different neuropathological types. Quantitative diffusion tensor tractography was applicable for the evaluation of tract segment infiltration.Conclusion: PET and physiological MRI are able to characterise low-grade gliomas and are promising tools for guiding therapy and clinical decisions before neuropathological diagnosis has been obtained.

Childs Nervous System, Dec 10, 2021

Stroke caused by dissection of arteries of the vertebrobasilar system in children is still poorly... more Stroke caused by dissection of arteries of the vertebrobasilar system in children is still poorly investigated in terms of etiology, means of treatment, course of disease, and prognosis. The aim of this report was to describe the unusual course of a spontaneous dissection of the basilar artery (BA) in a child treated with endovascular techniques and to point out that the plasticity of the brain stem can fully compensate for structural damage caused by stroke. We report the case of a 15-year-old boy who suffered a wake-up stroke with BA occlusion caused by spontaneous dissection. A blood clot was aspirated from the false lumen and the true lumen reopened , but the patient deteriorated a few hours later, and repeated angiography revealed that the intimal flap was detached, occluding the BA again. The lumen of BA was then reconstructed by a stent. Despite a large pons infarction, the patient was completely recovered 11 months after the onset. The case was analyzed with angiograms and magnetic resonance imaging, macroscopic and microscopic pathological analysis, computed tomographic angiography, magnetic resonance-based angiography, and diffusion tensor imaging. This case illustrates that applied endovascular techniques and intensive care measures can alter the course of potentially fatal brain stem infarction. Our multimodal analysis gives new insight into the anatomical basis for the plasticity mechanism of the brain stem.

Frontiers in Human Neuroscience, Feb 22, 2018

Background: Neurovascular coupling is associated with white matter (WM) structural integrity, and... more Background: Neurovascular coupling is associated with white matter (WM) structural integrity, and it is regulated by specific subtypes of dopaminergic receptors. An altered activity of such receptors, highly expressed in reward-related regions, has been reported in carriers of obesity-risk alleles of the fat mass and obesity associated (FTO) gene. Among the reward-related regions, the thalamus and the nucleus accumbens are particularly vulnerable to blood pressure dysregulation due to their peculiar anatomovascular characteristics, and have been consistently reported to be altered in earlystage obesity. We have thus hypothesized that a disruption in thalamus and nucleus accumbens WM microstructure, possibly on neurovascular basis, could potentially be a predisposing factor underlying the enhanced risk for obesity in the risk-allele carriers. Methods: We have tested WM integrity in 21 male participants genotyped on the FTO risk single nucleotide polymorphisms (SNP) rs9939609, through a deterministic tractography analysis. Only homozygous participants (9 AA, 12 TT) were included. 11 tracts were selected and categorized as following according to our hypothesis: "risk tracts", "obesity-associated tracts", and a control tract (forcpes major). We investigated whether an association existed between genotype, body mass index (BMI) and WM microstructural integrity in the "risk-tracts" (anterior thalamic radiation and accumbofrontal fasciculus) compared to other tracts. Moreover, we explored whether WM diffusivity could be related to specific personality traits in terms of punishment and reward sensitivity, as measure by the BIS/BAS questionnaire. Results: An effect of the genotype and an interaction effect of genotype and BMI were detected on the fractional anisotropy (FA) of the "risk tracts". Correlations between WM diffusivity parameters and measures of punishment and reward sensitivity were also detected in many WM tracts of both networks.

Acta neurochirurgica, Jul 2, 2020

Background The postoperative course after surgery for primary brain tumours can be difficult to p... more Background The postoperative course after surgery for primary brain tumours can be difficult to predict. We examined the time course of postoperative neurological deficits and analysed possible predisposing factors. Method Hundred adults with a radiological suspicion of low-or high-grade glioma were prospectively included and the postoperative course analysed. Possible predictors of postoperative neurological deterioration were evaluated. Results New postoperative neurologic deficits occurred in 37% of the patients, and in 4%, there were worsening of a preoperative deficit. In 78%, the deficits occurred directly after surgery. The probable cause of deterioration was EEG-verified seizures in 7, ischemic lesion in 5 and both in 1, resection of eloquent tissue in 6, resection close to eloquent tissue including SMA in 11 and postoperative haematoma in 1 patient. Seizures were the main cause of delayed neurological deterioration. Two-thirds of patients with postoperative deterioration showed complete regression of the deficits, and in 6% of all patients, there was a slight disturbance of the function after 3 months. Remaining deficits were found in 6% and only in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of postoperative neurological deterioration and preoperative neurological deficits of remaining deficits. Conclusions Postoperative neurological deficits occurred in 41% and remained in 6% of patients. Remaining deficits were found in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of neurological deterioration and preoperative neurological deficits of remaining deficits.

Frontiers in Neuroscience, Dec 8, 2022

Upsala Journal of Medical Sciences, May 10, 2022

Background: Neurological and psychiatric manifestations related to severe acute respiratory syndr... more Background: Neurological and psychiatric manifestations related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are widely recognised. Standard magnetic resonance imaging (MRI) investigations are normal in 40-80% of symptomatic patients, eventually delaying appropriate treatment when MRI is unrevealing any structural changes. The aim of this study is to investigate white matter abnormalities during an early stage of post-COVID-19 (coronavirus disease 2019) encephalitis while conventional MRI was normal. Methods: A patient with post-COVID-19 autoimmune encephalitis was investigated by serial MRIs and diffusion tensor imaging (DTI). Ten healthy control individuals (HC) were utilised as a control group for the DTI analysis. Major projection, commissural and association white matter pathways were reconstructed, and multiple diffusion parameters were analysed and then compared to the HC average using a z-test for serial examinations. Results: Eleven days after the onset of neurological symptoms, DTI revealed early white matter changes, compared with HC, when standard MRI was normal. On day 68, DTI showed multiple white matter lesions compared with HC, visible at this time also by the MRI images, indicating inflammatory changes in different association and projection white matter pathways. Conclusion: We confirm a limitation in the sensitivity of conventional MRI at the acute setting of post-COVID-19 autoimmune encephalitis. A complementary DTI investigation could be a valuable diagnostic tool in early therapeutic decisions concerning COVID-19-related neurological symptoms.

Neuro-oncology, Sep 1, 2022

of subcortical structures is still unclear. Aim of this study was to evaluate the impact of neuro... more of subcortical structures is still unclear. Aim of this study was to evaluate the impact of neurosurgical removal of right gliomas on visuospatial selective attention performances. MATERIAL AND METHODS: The visuospatial selective attention domain was assessed pre-and postoperatively (1 month follow-up) in 73 patients operated for right hemisphere gliomas. Supportvector-regression lesion-symptom mapping and disconnectome analysis (Lesion Quantification Toolkit, HCP 1065 data) were used to evaluate the relationship between the resection cavities and the postoperative performance on a standardized selective attention test. To test and refine the atlas-based results, in a subset of 17 patients with preoperative diffusion tractography, the postoperative outcome was correlated with the percentage of disconnection for different white matter tracts. RESULTS: Results showed that resection of a cluster enclosing the SMA-complex and the surrounding white matter was significantly associated with a decline in visuospatial selective attention performances (p<.05). Disconnectome analysis at population level revealed that the deficit was significantly correlated with the resection of superior cortico-striatal fibres, superior thalamic radiations, corticopontine projections, callosal connections and fibres of the frontal aslant tract. Within all the cortico-subcortical terminations of these tracts, disconnection of streamlines of the SMA-complex was the most associated with selective attention deficits. Tractography in single patients confirmed the population level results and suggested that ventro-lateral resections in case of inferior frontal or insular tumours significantly disconnecting the frontal aslant tract but sparing superior projection fibres were not associated with any postoperative disturbances. CONCLUSION: Results show converging evidence to support a critical role for the SMA/preSMA and its projections in maintaining efficiency of attentive control. The present results reveal the importance of a fronto-medial descending connectivity in mediating the voluntary control of visuospatial selective attention. From a surgical standpoint, to avoid postoperative deficits, it seems crucial to preserve SMA projection pathways, while the disconnection of the frontal aslant tract is feasible without any postoperative decline. P01.15.A.

INTRODUCTION The origin of ecstatic seizures has previously been linked to the temporal lobe and/... more INTRODUCTION The origin of ecstatic seizures has previously been linked to the temporal lobe and/or the anteriordorsal insula. The aim of this study was to further investigate a possible anatomical ...

Epilepsy & behavior reports, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Current Neurology and Neuroscience Reports, Jul 21, 2018

Purpose of Review The purpose was to review the most recent literature on neuroimaging in the Kle... more Purpose of Review The purpose was to review the most recent literature on neuroimaging in the Kleine-Levin syndrome (KLS). We aimed to investigate if frontotemporal and thalamic dysfunction are key KLS signatures, and if recent research indicates other brain networks of interest that elucidate KLS symptomatology and aetiology. Recent Findings In a comprehensive literature search, we found 12 original articles published 2013-2018. Most studies report deviations related to cerebral perfusion, glucose metabolism, or blood-oxygen-level-dependent responses in frontotemporal areas and/or the thalamus. Studies also report dysfunction in the temporoparietal junction and the oculomotor network that also were related to clinical parameters. We discuss these findings based on recent research on thalamocortical networks and brain stem white matter tracts. Summary The hypothesis of frontotemporal and thalamic involvement in KLS was confirmed, and additional findings in the temporoparietal junction and the oculomotor system suggest a broader network involvement, which can be investigated by future high-resolution and multimodal imaging. Keywords Kleine-Levin syndrome (KLS). Functional magnetic resonance imaging (fMRI). Positron emission tomography (PET). Single photon emission computed tomography (SPECT). Magnetic resonance spectroscopy (MRS). Diffusion weighted imaging (DWI) This article is part of the Topical Collection on Sleep

Childs Nervous System, Jan 11, 2022

In this article the author name "Sylwia Libard" was incorrectly written as "Sylvia Libard". The o... more In this article the author name "Sylwia Libard" was incorrectly written as "Sylvia Libard". The original article has been corrected. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

European Journal of Neurology, May 28, 2021

Visual snow is a condition where patients see constant, innumerable flickering dots throughout th... more Visual snow is a condition where patients see constant, innumerable flickering dots throughout the whole visual field, similar to "TV static" [1,2]. Patients with visual snow syndrome (VSS) frequently have comorbid migraine, but visual snow appears to be a separate entity from persistent migraine aura [1-4]. Not only is the pathophysiology underlying visual snow unclear, also the localization is under debate [3,5]. Eye disease, thalamic dysfunctions, pure cortical phenomena, altered connection between visual networks and other large-scale networks have been proposed as possible causes of VSS [1,3]. Each mechanism could possibly coexist or be responsible for

Journal of Neuro-Oncology

Purpose Since the introduction of the molecular definition of oligodendrogliomas based on isocitr... more Purpose Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. Methods All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. Results 126 patients d...