A case of intravascular large B cell lymphoma with brain involvement mimicking progressive multifocal leukoencephalopathy.

Intravascular large B-cell lymphoma (IVLBCL) is a very rare form of extranodal lymphoma, characterized by the proliferation of neoplastic B cells within the lumen of small vessels. Due to its high aggressivity, for years the prognosis had been really poor with only anectodical cases of remission after traditional chemotherapy. More recently, new therapeutic protocols allowed a significant increase in overall survival. It can virtually involve every organ, being skin and central nervous system the most affected. The clinical presentation is often unspecific and insidious; therefore, diagnosis can be challenging. Tissue biopsy, in particular random deep skin biopsy, is the gold standard for definitive diagnosis. We describe the case of a 58-year-old woman with a previous diagnosis of myelofibrosis, who presented with a rapidly progressive neurological deterioration and a brain MRI suggestive of Progressive Multifocal Leukoencephalopathy. Due to the absence of BK and JC viruses in cerebrospinal fluid and the presence of severe myalgias and subcutaneous nodules, a skin and muscle biopsy was performed, allowing diagnosis of IVLBCL. We describe the diagnostic pitfalls of this case, briefly reviewing existing literature about IVLBCL.

Role of magnetic resonance imaging following postoperative radiotherapy in clinical decision-making of patients with high-grade glioma.

OBJECTIVES: The present study aims to investigate the role of the first magnetic resonances (MRI) following radio-chemotherapy (RT-CT) in patients diagnosed with high-grade glioma. METHODS: We retrospectively recorded radiological evaluations following RT-CT, symptoms related to disease progression (avoiding any sign due to radiotherapy or chemotherapy) and the change of therapeutic strategy. RESULTS: In March 2021, at data analysis, the data of 149 patients diagnosed with high-grade glioma and treated between May 2013 and July 2020 were retrieved for the present analysis. Two out of 122 (1.6%), 5 out of 106 (4.7%) and 8 out of 92 (8.6%) asymptomatic patients received the diagnosis of disease recurrence at the time of the first, second and third MRI, respectively. Otherwise, 16 out of 27 (59.2%), 16 out of 24 (66.6%) and 13 out of 16 (82.2%) symptomatic patients changed their therapy after the first, second and third MRI, respectively. Among patients that experienced radiological signs of distant progression, 10 out of 14 were symptomatic and changed their therapy. CONCLUSIONS: MRIs performed by 6 months after the end of RT-CT lead to change treatment strategy mostly in symptomatic patients.

Impact of a posttraumatic cerebral infarction on outcome in patients with TBI: the Italian multicenter cohort INCEPT study.

BACKGROUND: Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors. METHODS: This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models. RESULTS: We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66-0.82; increased to AUC = 0.79, 95% CI 0.71-0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65-0.81 increased to AUC = 0.80, 95% C.I. 0.69-0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups. CONCLUSIONS: PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS. TRIAL REGISTRATION: The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.

Susceptibility-weighted imaging in parenchymal neurosyphilis: identification of a new MRI finding.

BACKGROUND: General paresis (GP) is a late form of parenchymal neurosyphilis causing dementia and neuropsychiatric disorders. The diagnosis is often difficult since the clinical signs are protean. So far, neuroimaging has played a minor role as radiological findings are not specific. METHODS: We studied three immunocompetent patients, admitted to hospital for cognitive impairment. The diagnosis of neurosyphilis was formulated on the basis of serological texts and cerebrospinal fluid analysis. The patients underwent a 3 T MR examination including susceptibility-weighted imaging (SWI) sequence before and after the initiation of penicillin therapy. RESULTS: In all patients, SWI revealed cortical hypointensity, mostly distributed in frontal and temporal lobes. In drug-naive patients, the hypointensity extended over the whole cortical thickness, from the cortical/subcortical junction to the pial surface. After starting the penicillin therapy, the cortical hypointensity partially reversed, involving only the deep cortical layers. CONCLUSIONS: The MRI pattern at SWI observed in patients with GP was not reported in other infectious or inflammatory disease of the central nervous system, thus we suggest it could be a peculiar radiological finding of the disease. On the basis of previous pathological data, we hypothesise that cortical SWI hypointensity could be expression of iron deposits within activated microglia.

MR imaging of the substantia nigra at 7 T enables diagnosis of Parkinson disease.

PURPOSE: To evaluate the anatomy of the substantia nigra (SN) in healthy subjects by performing 7-T magnetic resonance (MR) imaging of the SN, and to prospectively define the accuracy of 7-T MR imaging in distinguishing Parkinson disease (PD) patients from healthy subjects on an individual basis. MATERIALS AND METHODS: The 7-T MR imaging protocol was approved by the Italian Ministry of Health and by the local competent ethics committee. SN anatomy was described ex vivo on a gross brain specimen by using highly resolved proton-density (spin-echo proton density) and gradient-recalled-echo (GRE) images, and in vivo in eight healthy subjects (mean age, 40.1 years) by using GRE three-dimensional multiecho susceptibility-weighted images. After training on appearance of SN in eight healthy subjects, the SN anatomy was evaluated twice by two blinded observers in 13 healthy subjects (mean age, 54.7 years) and in 17 PD patients (mean age, 56.9 years). Deviations from normal SN appearance were described and indicated as abnormal, and both diagnostic accuracy and intra- and interobserver agreement for diagnosis of PD with 7-T MR imaging were calculated. RESULTS: Three-dimensional multiecho susceptibility-weighted 7-T MR imaging reveals a three-layered organization of the SN allowing readers to distinguish pars compacta ventralis and dorsalis from pars reticulata. The abnormal architecture of the SN allowed a discrimination between PD patients and healthy subjects with sensitivity and specificity of 100% and 96.2% (range, 92.3%-100%), respectively. Intraobserver agreement (κ = 1) and interobserver agreement (κ = 0.932) were excellent. CONCLUSION: MR imaging at 7-T allows a precise characterization of the SN and visualization of its inner organization. Three-dimensional multiecho susceptibility-weighted images can be used to accurately differentiate healthy subjects from PD patients, which provides a novel diagnostic opportunity.

Abnormal response to photic stimulation in juvenile myoclonic epilepsy: an EEG-fMRI study.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a young-onset electroclinical syndrome, characterized by myoclonic, generalized tonic-clonic, and possibly typical absence seizures. Interictal electroencephalography (EEG) displays 3-6 Hz spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to explore the blood oxygen level-dependent (BOLD) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena seen in patients with photosensitive JME. METHODS: We studied 13 JME patients and 18 healthy controls using EEG-functional magnetic resonance imaging (fMRI) performed during low luminance intermittent photic stimulation (IPS). The BOLD response to IPS was investigated both in JME and control groups. In photosensitive JME subjects, we also performed a dynamic evaluation of BOLD signal changes evoked by the photoparoxysmal response (PPR) in a time frame ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward. RESULTS: The IPS evoked a positive BOLD response in striate and extrastriate visual areas, which was less in JME patients than in controls. Moreover, people with JME had a reduced positive BOLD response in the frontoparietal areas and putamen but a stronger negative BOLD response in the primary sensorimotor cortex (SM1) and in cortical regions belonging to the default mode network (DMN). In JME, the dynamic evaluation of BOLD signal changes related to PPR revealed an early positive response in the putamen and SM1, followed by BOLD signal decrements in the putamen, caudate nuclei, thalami, and SM1. SIGNIFICANCE: Our results confirm the hypothesis that people with JME might have an altered interaction between the motor circuit and other neuronal networks, with prominent involvement of basal ganglia circuitry. The PPR could be a final expression of pathogenic phenomena occurring in the striato-thalamocortical system, possibly a core feature of system epilepsy JME.

3-T magnetic resonance angiography in primary angiitis of the central nervous system.

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare disease characterized by an inflammatory process of intracranial vessels. Magnetic resonance angiography (MRA) (3 T) offers increased signal-to-noise ratio and background suppression, leading to better depiction of the intracranial vessels. The aim of our work was to compare the sensitivity of 3-T MRA to that of 1.5-T MRA in the diagnosis of PACNS. METHODS: Eight patients with PACNS and signs of angiitis at digital subtraction angiography (DSA) underwent MRA at 1.5 and 3 T. Magnetic resonance angiograms obtained with time-of-flight (TOF) technique were evaluated for the presence of stenosis with respect to DSA. RESULTS: In PACNS patients, DSA identified 827 intracranial stenoses. Sensitivity for vessel stenosis of 3-T TOF MRA was 47% and 14% for 1.5-T TOF. CONCLUSIONS: Time-of-flight MRA at 3 T improved the sensitivity of MRA in the noninvasive preliminary evaluation of patients with PACNS.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor-sensory tasks of different complexity, i.e. continuous hand tapping and writing of "8" figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age-matched healthy controls were recruited. Task execution was monitored and recorded using MR-compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the "8" by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory-motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo-activation during hand tapping. During writing of the "8" task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the "8" increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance.

Distinct limbic connectivity in left and right benign mesial temporal lobe epilepsy: Evidence from a resting state functional MRI study.

Background: Functional connectivity (FC) studies showed that pharmaco-resistant mesial temporal lobe epilepsy (MTLE) affects not only the limbic system, but also several extra-limbic regions, including areas belonging to resting state networks. Less is known about FC in subjects with benign MTLE (i.e., sensitive to antiseizure medication, bMTLE). Aim and methods: We evaluated FC of hippocampus and amygdala in subjects with bMTLE, distinguished based on the epileptic focus lateralization. We enrolled 19 patients (10 with left and 9 with right bMTLE) and 10 age-matched healthy subjects. Connectivity was investigated at rest by using a seed-based regression analyses approach with four regions of interest (left and right hippocampus, left and right amygdala). Patients were also tested with a neuropsychological battery and their scores were correlated with fMRI data. Results and conclusions: Our study documented an asymmetrical disruption of FC in bMTLE, in relation to the side of the focus. Right subjects only exhibited limited altered connections, while left subjects-who performed worse in verbal memory tests-showed a wide bilateral hypoconnectivity of hippocampus and amygdala with areas belonging to language and memory network. The strength of FC between left limbic areas and language and memory network correlated with better performances in verbal memory tests. Moreover, we observed an increased FC with areas of default mode network, more pronounced in left subjects, a possible attempt to compensate cognitive deficit but without effectiveness.We believe that these findings could help to better characterize bMTLE, in which a dysfunction of limbic connectivity is detectable despite well-controlled epilepsy.

Technical note: DTI measurements of fractional anisotropy and mean diffusivity at 1.5 T: comparison of two radiofrequency head coils with different functional designs and sensitivities.

PURPOSE: Diffusion tensor imaging (DTI) is highly sensitive to noise and improvement of radiofrequency coil technology represents a straightforward way for augmenting signal-to-noise ratio (SNR) performance in magnetic resonance imaging (MRI) scanners. The aim of this study was to characterize the dependence of DTI measurements of fractional anisotropy (FA) and mean diffusivity (MD) on the choice of head coil, comparing two head coils with different functional designs and sensitivities. METHODS: Fourteen healthy subjects underwent DTI acquisitions at 1.5 T. Every subject was scanned twice, using a standard quadrature birdcage head coil (coil-A) and an eight-channel array head coil (coil-B). FA and MD maps, estimated using both the linear least squares (LLS) and nonlinear least squares (NLLS) methods, were nonlinearly normalized into a standard space. Then, volumetric regions of interest encompassing typical white and gray matter structures [splenium of the corpus callosum (SCC), internal capsule (IC), cerebral peduncles (CP), middle cerebellar peduncles (MCP), globus pallidus (GP), thalamus (TH), caudate (CA), and putamen (PU)] were analyzed. Significant differences and trends of variation in DTI measurements were assessed by the Wilcoxon test for paired samples with and without Bonferroni correction for multiple comparisons, respectively. RESULTS: The overall SNR of coil-B was 30% higher than that of coil-A. When comparing DTI measurements (coil-B versus coil-A), mean FA values (SCC, IC, and TH), mean MD values (IC, CP, GP, and TH), FA standard deviation (CP, MCP, GP, and CA), and MD standard deviation (IC, CP, TH, and PU) resulted decreased (significant difference, p(cor) < 0.05, or trend of variation, P(uncor) < 0.05) in several gray and white matter regions of the human brain. With the exception of CP, the results in terms of revealed significant difference or trend of variation were independent of the method (LLS and NLLS) used for estimating the diffusion tensor. CONCLUSIONS: In various gray and white matter structures, the eight-channel array head coil yielded more precise and accurate measurements of DTI derived indices compared to the standard quadrature birdcage head coil.

Reproducibility of BOLD localization of interictal activity in patients with focal epilepsy: intrasession and intersession comparisons.

OBJECT: Simultaneous EEG-fMRI recordings allow the identification of haemodynamic changes induced by neuronal activity during ictal or interictal epileptiform events (IEDs). We evaluated the reproducibility of continuous EEG-fMRI (cEEG-fMRI) in patients with focal epilepsy. MATERIALS AND METHODS: We studied 15 patients with focal epilepsy (8 cryptogenic and 7 symptomatic) and frequent interictal abnormalities. Each patient underwent two cEEG-fMRI acquisitions (runs) in the same day (session) and 8 patients repeated the examination after one month. cEEG-fMRI reproducibility was defined by the existence of partially overlapping clusters between activation maps obtained from different runs. RESULTS: We detected IEDs in 40 out of 46 EEG-fMRI runs and a related significant BOLD-response in all 40 runs. A prevalent positive BOLD response was detected in 12 patients and a prevalent negative response in 3 subjects. Statistical maps included a mean of 10 significant clusters. Nearly 30% of clusters were reproducible in both intrasession and intersession comparisons, with a mean overlap of 30%. Reproducibility did not differ between positive and negative BOLD-responses. DISCUSSION: Among the reproducible clusters, those with the highest percentage of overlap were concordant with the EEG electric field in all patients and they were localized in the same lobe as the brain lesion in patients with symptomatic epilepsy. We hypothesize that reproducible clusters could be more consistently related to the irritative zone than non-reproducible ones. CONCLUSION: The evaluation of cluster reproducibility could improve our knowledge of IED-related BOLD response. Moreover, it could enhance the reliability of cEEG-fMRI to identify the irritative zone in focal epileptic patients.

Parkinson's disease and pathological gambling: results from a functional MRI study.

Seven patients with a diagnosis of Parkinson's disease (PD) and pathological gambling (PG) and 7 PD patients without PG were investigated by functional MRI and a block-design experiment with gambling-related visual cues alternating with neutral stimuli and rest periods. Compared with PD/non-PG, in PD/PG patients, several areas of increased cue-related blood oxygen level dependent (BOLD)-response were observed including bilateral anterior cingulate cortex, medial and superior frontal gyri, and precuneus, right inferior parietal lobule, and ventral striatum. The over activation of cingulate cortex and ventral striatum in PD/PG patients after the craving task is similar to that reported in addicted patients, whereas the activation of the parietal structures is probably related to the attentional network.

Evaluation of corticospinal tract impairment in the brain of patients with amyotrophic lateral sclerosis by using diffusion tensor imaging acquisition schemes with different numbers of diffusion-weighting directions.

Amyotrophic lateral sclerosis is characterized by degeneration of upper and lower motor neurons. Diffusion tensor imaging (DTI) indexes obtained along the corticospinal tracts distinguish ALS patients and control subjects. Diffusion tensor imaging can be estimated from at least 6 diffusion-weighted images; however an acquisition scheme with a higher number of diffusion directions allows a more robust estimation of DTI indexes. The aim of the study was to establish if a higher number of diffusion encoding gradients increases the diagnostic accuracy of DTI in ALS. We studied 18 patients and 16 control subjects acquiring 2 DTI data sets with 6 and 31 gradient orientations. The mean diffusivity and fractional anisotropy values were measured along the corticospinal tract. Mean diffusivity in ALS was significantly increased (P = 0.026) with respect to control subjects in acquisition scheme with 31 but not (P = 0.214) with 6 diffusion-weighting directions. Fractional anisotropy was significantly lower in patients both with 6 (P = 0.0036) and with 31 (P = 0.0004) diffusion-weighting directions (0.538 vs 0.588 and 0.530 vs 0.594). Fractional anisotropy receiver operating characteristic curve analysis showed a higher diagnostic accuracy by using 31 diffusion-weighting direction (85.76%) with respect to 6 directions (79.86%). Diffusion tensor imaging confirms its potentials in diagnosing ALS with a good accuracy; the acquisition scheme with a higher diffusion-weighting directions seems to better discriminate between ALS patients and control subjects.

Cerebello-thalamo-cortical network is intrinsically altered in essential tremor: evidence from a resting state functional MRI study.

Cerebello-thalamo-cortical network is suggested to be involved in the pathophysiology of Essential Tremor (ET). 23 patients with ET and 23 matched HC underwent a 3T-MRI with acquisition of a resting state sequence. Connectivity was investigated using a seed-based regression analyses approach. In ET patients were observed: Reduced connectivity between left primary motor cortex (M1) seed and right premotor cortex and cerebellum and bilateral premotor, parietal areas, supplementary motor area (SMA); Increased connectivity between left somatosensory cortex (S1) seed and parietal areas, M1, premotor cortex, SMA; reduced connectivity of this seed with cerebellum. Increased connectivity of SMA seed with premotor cortex and decreased with parietal and precentral areas; Increased connectivity between left thalamus seed and cerebellum; Reduced connectivity between right cerebellum seeds and other cerebellar areas, precentral and premotor areas. ET showed altered connectivity within the cortical sensory-motor network and between cerebral cortex and cerebellum. The increased connectivity between cerebellum and thalamus is consistent with their crucial role in tremor generation. These findings support the dynamical entrainment of multiple central oscillators throughout the cerebello-thalamo-cortical network in ET. This evidence is strengthened by the finding that this network is altered also when the core symptom is absent.

Functional magnetic resonance imaging in episodic cluster headache.

We have investigated the cerebral activation centre in four patients with episodic cluster headache (CH) with functional magnetic resonance imaging (f-MRI). The patients underwent MRI scans for anatomical and functional data acquisition in the asymptomatic state, during a headache attack and after subcutaneous administration of sumatriptan. Anatomical images were acquired by means of 3D-MPRAGE sequences and f-MRI images were obtained by means of echo-planar imaging. Data was analysed using the BrainVoyager QX version 1.7.81 software package. In all patients, the data showed significant hypothalamic activation of the hypothalamus ipsilateral to the pain side, attributable to a headache attack. Overall, we have demonstrated the anatomical location of central nervous system activation by means the first f-MRI study in CH patients. f-MRI offers a good balance of spatial and temporal resolution, and this method of study appears appropriate for investigating the pathogenetic aspects of primary headaches. Positron emission tomography and f-MRI may be regarded as little or no importance in a clinical context, they do, however, offer great potential for the exploration of headache physiopathology and the effects of pharmacological treatment.

"Hit the missing stimulus". A simultaneous EEG-fMRI study to localize the generators of endogenous ERPs in an omitted target paradigm.

Event-Related Potentials (ERPs) occurring independently from any stimulus are purely endogenous (emitted potentials) and their neural generators can be unequivocally linked with cognitive processes. In the present study, the subjects performed two similar visual counting tasks: a standard two-stimulus oddball, and an omitted-target oddball task, characterized by the physical absence of the target stimulus. Our investigation aimed at localizing the neural sources of the scalp-recorded endogenous/emitted ERPs. To optimize the source localization, the high temporal resolution of electrophysiology was combined with the fine spatial information provided by the simultaneous recording of functional magnetic resonance (fMRI). Both tasks identified two endogenous ERP components in the 300 to 520 ms interval. An earlier component, pP2, showed a bilateral generator in the anterior Insula. A later P3 component (P3b) was generated bilaterally in the temporal-parietal junction, the premotor and motor area and the anterior intraparietal sulcus (this latter one only in the standard oddball). Anticipatory slow waves (beginning 900 to 500 ms pre-stimulus), also of endogenous nature, were produced by the inferior and middle frontal gyrus and the supplementary and cingulate motor areas. Our protocol disentangled pre- from post-stimulus fMRI activations and provided original clues to the psychophysiological interpretation of emitted/endogenous ERPs.

Independent component model of the default-mode brain function: combining individual-level and population-level analyses in resting-state fMRI.

Resting-state functional magnetic resonance imaging (RS-fMRI) is a technique used to investigate the spontaneous correlations of blood-oxygen-level-dependent signals across different regions of the brain. Using functional connectivity tools, it is possible to investigate a specific RS-fMRI network, referred to as "default-mode" (DM) network, that involves cortical regions deactivated in fMRI experiments with cognitive tasks. Previous works have reported a significant effect of aging on DM regions activity. Independent component analysis (ICA) is often used for generating spatially distributed DM functional connectivity patterns from RS-fMRI data without the need for a reference region. This aspect and the relatively easy setup of an RS-fMRI experiment even in clinical trials have boosted the combined use of RS-fMRI and ICA-based DM analysis for noninvasive research of brain disorders. In this work, we considered different strategies for combining ICA results from individual-level and population-level analyses and used them to evaluate and predict the effect of aging on the DM component. Using RS-fMRI data from 20 normal subjects and a previously developed group-level ICA methodology, we generated group DM maps and showed that the overall ICA-DM connectivity is negatively correlated with age. A negative correlation of the ICA voxel weights with age existed in all DM regions at a variable degree. As an alternative approach, we generated a distributed DM spatial template and evaluated the correlation of each individual DM component fit to this template with age. Using a "leave-one-out" procedure, we discuss the importance of removing the bias from the DM template-generation process.