Spontaneous bleeding in COVID-19: A retrospective experience of an Italian COVID-19 hospital.

Background: Haemorrhages in coronavirus disease 2019 (COVID-19) patients require proper knowledge and management. Objectives: To highlight the characteristics of haemorrhages in patients with COVID-19 infection. Method: A retrospective study examined CT scans performed over a 13-month period in patients hospitalised with COVID-19 infection to determine those who developed spontaneous bleeding. The authors also investigated correlations between the bleeding events and the patients' characteristics. Results: Haemorrhages occurred in 2.22% (31/1396) of patients hospitalised with COVID-19 infection (7.88%, 19/241 in the intensive care unit). Bleeding, major in most cases, occurred in anticoagulated patients, especially males with multiple comorbidities, aged between 60 and 79 years and mainly appeared in a single anatomical region (especially retroperitoneal), with the most voluminous in the chest wall. The complication was diagnosed on average 16.7 days after admission and occurred predominantly in critically ill patients undergoing invasive ventilation and pronation-supination cycles. In just under half of the cases, the haematomas were active, and in these cases, mainly with a single contrast blush and with earlier onset after the start of anticoagulation than in non-active bleeding. Major bleeding was also earlier in the presence of multiple morbidity. The vast majority of patients were treated conservatively and survived. Conclusion: At COVID-19 hospital centres, it is advisable that there is knowledge of such a complication for which CT imaging is essential for diagnosis and proper management. Although some authors have expressed doubts about anticoagulant treatment in patients with COVID-19, the bleeding complication in this study did not significantly affect the outcome. Contribution: Spontaneous haemorrhage did not significantly affect the outcome in this series.

Morphological study of upper airways and long-term follow-up of obstructive sleep apnea syndrome in acromegalic patients.

Pathogenesis and long-term outcome of obstructive sleep apnea syndrome (OSAS) in acromegalic patients are still under debate. The aim of the study was to assess the prevalence and long-term follow-up of a series of acromegalic patients with OSAS and to investigate site, degree, and possible causes of upper airway obstruction by morphological study. Cross-sectional and longitudinal study was conducted in 58 acromegalic patients (33 active, 25 controlled) with polysomnography in all subjects, repeated in 25 patients with OSAS, and echocardiography. Morphological study including fiberoptic nasopharyngoscopy with the Müller maneuver (FNMM), magnetic resonance imaging (MRI), with 3-dimensional (3D) elaboration was also performed. The prevalence of OSAS was 58.6 % in the whole series: 63.6 % in the active group and 52 % in the controlled one. Left ventricular hypertrophy was more prevalent in patients with OSAS. OSAS improved in 62.5 % of active patients after achieving hormonal control, whereas it persisted or got worse in 66.6 % of the controlled ones. The uvula and tongue base were the main site of obstruction assessed by FNMM. Uvula diameters obtained by MRI study correlated with the severity of upper airway collapse assessed by FNMM and tongue measure with apnea-hypopnea index (p = 0.044). A greater narrowing and a smaller total volume of upper airways were confirmed by 3D-MRI in patients with more severe OSAS. Uvula and tongue hypertrophy plays a relevant role in the pathogenesis and severity of OSAS. Intensive treatment of acromegaly needs to be promptly adopted in order to reverse it.

The use of dynamic susceptibility contrast (DSC) MRI to automatically classify patients with first episode psychosis.

Hemodynamic changes in the brain have been reported in major psychosis in respect to healthy controls, and could unveil the basis of structural brain modifications happening in patients. The study of first episode psychosis is of particular interest because the confounding role of chronicity and medication can be excluded. The aim of this work is to automatically discriminate first episode psychosis patients and normal controls on the basis of brain perfusion employing a support vector machine (SVM) classifier. 35 normal controls and 35 first episode psychosis underwent dynamic susceptibility contrast magnetic resonance imaging, and cerebral blood flow and volume, along with mean transit time were obtained. We investigated their behavior in the whole brain and in selected regions of interest, in particular the left and right frontal, parietal, temporal and occipital lobes, insula, caudate and cerebellum. The distribution of values of perfusion indexes were used as features in a support vector machine classifier. Mean values of blood flow and volume were slightly lower in patients, and the difference reached statistical significance in the right caudate, left and right frontal lobes, and in left cerebellum. Linear SVM reached an accuracy of 83% in the classification of patients and normal controls, with the highest accuracy associated with the right frontal lobe and left parietal lobe. In conclusion, we found evidence that brain perfusion could be used as a potential marker to classify patients with psychosis, who show reduced blood flow and volume in respect to normal controls.

Spatial and Temporal EEG-fMRI Changes During Preictal and Postictal Phases in a Patient With Posttraumatic Epilepsy.

The combined use of electroencephalography (EEG) and functional magnetic resonance imaging (EEG-fMRI) in epilepsy allows the noninvasive hemodynamic characterization of epileptic discharge-related neuronal activations. The aim of this study was to investigate pathophysiologic mechanisms underlying epileptic activity by exploring the spatial and temporal distribution of fMRI signal modifications during seizure in a single patient with posttraumatic epilepsy. EEG and fMRI data were acquired during two scanning sessions: a spontaneous critical episode was observed during the first, and interictal events were recorded during the second. The EEG-fMRI data were analyzed using the general linear model (GLM). Blood oxygenation level-dependent (BOLD) localization derived from the preictal and artifact-free postictal phase was concordant with the BOLD localization of the interictal epileptiform discharges identified in the second session, pointing to a left perilesional mesiofrontal area. Of note, BOLD signal modifications were already visible several seconds before seizure onset. In brief, BOLD activations from the preictal, postictal, and interictal epileptiform discharge analysis appear to be concordant with the clinically driven localization hypothesis, whereas a widespread network of activations is detected during the ictal phase in a partial seizure.

Paroxysmal dysarthria-ataxia in remitting-relapsing Bickerstaff's-like encephalitis.

Paroxysmal dysarthria-ataxia is a rare neurological condition due to ephaptic transmission, generally appearing in multiple sclerosis patients characterized by stereotyped attacks of slurred speech usually accompanied by ataxia, appearing many times a day. Here we describe a patient with an unusual remitting-relapsing form of Bickerstaff's-like brainstem encephalitis who manifested PDA after a relapse with the involvement of a peculiar region below the red nuclei and benefited from lamotrigine.

EEG-fMRI evaluation of patients with mesial temporal lobe sclerosis.

This preliminary study sought more information on blood oxygen level dependent (BOLD) activation, especially contralateral temporal/extratemporal spread, during continuous EEG-fMRI recordings in four patients with mesial temporal sclerosis (MTS). In two patients, EEG showed unilateral focal activity during the EEG-fMRI session concordant with the interictal focus previously identified with standard and video-poly EEG. In the other two patients EEG demonstrated a contralateral diffusion of the irritative focus. In the third patient (with the most drug-resistant form and also extratemporal clinical signs), there was an extratemporal diffusion over frontal regions, ipsilateral to the irritative focus. fMRI analysis confirmed a single activation in the mesial temporal region in two patients whose EEG showed unilateral focal activity, while it demonstrated a bilateral activation in the mesial temporal regions in the other two patients. In the third patient, fMRI demonstrated an activation in the supplementary motxor area. This study confirms the most significant activation with a high firing rate of the irritative focus, but also suggests the importance of using new techniques (such as EEG-fMRI to examine cerebral blood flow) to identify the controlateral limbic activation, and any other extratemporal activations, possible causes of drug resistance in MTS that may require a more precise pre-surgical evaluation with invasive techniques.

Reproducibility of EEG-fMRI results in a patient with fixation-off sensitivity.

Blood oxygenation level-dependent (BOLD) activation associated with interictal epileptiform discharges in a patient with fixation-off sensitivity (FOS) was studied using a combined electroencephalography-functional magnetic resonance imaging (EEG-fMRI) technique. An automatic approach for combined EEG-fMRI analysis and a subject-specific hemodynamic response function was used to improve general linear model analysis of the fMRI data. The EEG showed the typical features of FOS, with continuous epileptiform discharges during elimination of central vision by eye opening and closing and fixation; modification of this pattern was clearly visible and recognizable. During all 3 recording sessions EEG-fMRI activations indicated a BOLD signal decrease related to epileptiform activity in the parietal areas. This study can further our understanding of this EEG phenomenon and can provide some insight into the reliability of the EEG-fMRI technique in localizing the irritative zone.

Hyaluronic acid: in vitro and in vivo analysis, biochemical properties and histological and morphological evaluation of injected filler.

BACKGROUND: No human model has emerged as an accepted standard to evaluate tissue filler longevity. OBJECTIVES: To validate a human model adequate to compare soft tissue filler degradation and tissue reaction. MATERIALS AND METHODS: We evaluated in 18 patients the persistence of hyaluronic acid (HA) filler injected into labial tissue analyzing hyaluronidase (HYAL) activity by means of in vitro and in vivo tests, MRI and histological and ultra-structural examination at 3 and 6 months postop. RESULTS: MRI examination revealed the presence of HA filler in a clear hyperintense area. Histology demonstrated fibroblast activation. The amount and the degradation rate of HYAL and HA did not show a linear correlation. CONCLUSION: MRI demonstrated the presence of HA in lip tissue even after 6 months. Biopsies at 3 months revealed tissue maturation and at 6 months confirmed the ability of HA to reorganize and integrate the extracellular matrix. The absence of linear correlation between HYAL and HA revealed that the result clinically is probably dependent on systemic factors which can determine HYAL activity and therefore HA longevity.

Brain modifications after acute alcohol consumption analyzed by resting state fMRI.

Resting-state functional magnetic resonance imaging (fMRI) is a recent breakthrough in neuroimaging research able to describe "in vivo" the spontaneous baseline neuronal activity characterized by blood oxygen level dependent (BOLD) signal fluctuations at slow frequency (0.01-0.1Hz) that, in the absence of any task, forms spatially distributed functional connectivity networks, called resting state networks (RSNs). The aim of this study was to investigate, in the young and healthy population, the changing of the RSNs after acute ingestion of an alcohol dose able to determine a blood concentration (0.5g/L) that barely exceeds the legal limits for driving in the majority of European Countries. Fifteen healthy volunteers underwent two fMRI sessions using a 1.5T MR scanner before and after alcohol oral consumption. The main sequence acquired was EPI 2D BOLD, one per each session. To prevent the excessive alcohol consumption the subjects underwent the estimation of blood rate by breath test and after the stabilization of blood alcohol level (BAL) at 0.5g/L the subjects underwent the second fMRI session. Functional data elaboration was carried out using the probabilistic independent component analysis (PICA). Spatial maps so obtained were further organized, with MELODIC multisession temporal concatenation FSL option, in a cluster representing the group of pre-alcohol sessions and the group of post-alcohol sessions, followed by the dual regression approach in order to evaluate the increase or decrease in terms of connectivity in the RSNs between the two sessions at group level. The results we obtained reveal that acute consumption of alcohol reduces in a significant way the BOLD signal fluctuations in the resting brain selectively in the sub-callosal cortex (SCC), in left temporal fusiform cortex (TFC) and left inferior temporal gyrus (ITG), which are cognitive regions known to be part of the reward brain network and the ventral visual system.

White matter microstructure alterations in bipolar disorder.

Genetic, neuropathological and magnetic resonance imaging findings support the presence of diffuse white matter cytoarchitectural disruption in bipolar disorder. In this study, diffusion-weighted imaging (DWI) was applied to study cortical white matter microstructure organisation in 24 patients with DSM-IV bipolar disorder and 35 matched normal controls. DWI images were obtained using a 1.5 Tesla scanner and apparent diffusion coefficient (ADC) values were determined over regions of interest placed, bilaterally, in the frontal, temporal, parietal, and occipital white matter. Significantly increased ADC values were found in bipolar patients with respect to normal controls in the right temporal lobe, left parietal lobe and bilateral occipital lobes. ADC values did not associate significantly with age or with clinical variables (p>0.05). Diffuse cortical white matter alterations on DWI in bipolar disorder denote widespread disruption of white matter integrity and may be due to altered myelination and/or axonal integrity.

A multimodal imaging approach to the evaluation of post-traumatic epilepsy.

OBJECT: Electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration and high-density EEG (hdEEG) can be combined to map noninvasively abnormal brain activation elicited by epileptic processes. By combining noninvasive imaging techniques in a multimodal approach, we sought to investigate pathophysiological mechanisms underlying epileptic activity in seven patients with severe traumatic brain injury. MATERIALS AND METHODS: Standard EEG and fMRI data were acquired during a single scanning session. The EEG-fMRI data were analyzed using the general linear model and independent component analysis. Source localization of interictal epileptiform discharges (IEDs) was performed using 256-channel hdEEG. Blood oxygenation level dependent (BOLD) localizations were then compared to EEG source reconstruction. RESULTS: On hdEEG, focal source localization was detected in all seven patients; in six out of seven it was concordant with the expected epileptic activity as defined by EEG data and clinical evaluation; and in four out of seven in whom IEDs were recorded, BOLD signal changes were observed. These activities were partially concordant with the source localization. CONCLUSION: Multimodal integration of EEG-fMRI and hdEEG combining two different methods to localize the same epileptic foci appears to be a promising tool to noninvasively map abnormal brain activation in patients with post-traumatic brain injury.

Is neuregulin 1 involved in determining cerebral volumes in schizophrenia? Preliminary results showing a decrease in superior temporal gyrus volume.

BACKGROUND/AIMS: Reduced left superior temporal gyrus (STG) volume is one of the most replicated imaging findings in schizophrenia. However, it remains unclear whether genes play any role in our understanding of such structural alteration. It has been proposed that Neuregulin 1 (NRG1) might be a promising gene involved in schizophrenia, because of its role in neurodevelopment and neuroplasticity. In this study, the association between NRG1 and STG anatomy in patients with schizophrenia was explored for the first time. METHODS: We investigated a 1-year treated prevalence cohort of patients with schizophrenia in contact with the South Verona Community-Based Mental Health Service. A blood sample was collected for DNA extraction and brain structure was assessed with an MRI scan. A total of 27 subjects with schizophrenia underwent both assessments and were included in the study. RESULTS: We investigated the association between the polymorphism SNP8NRG222662 (rs4623364) of NRG1 and volume of the STG. We found that patients homozygous for the C allele had reduced left STG gray and white matter volumes in comparison to those homozygous for the G allele (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: This exploratory study suggests that NRG1 may be involved in determining STG size in schizophrenia, and may play a role in the neurogenetic basis of the language disturbances seen in this disorder. However, due to our small sample size, the results should be regarded as preliminary and replicated in a larger sample.

Thalamic-insular dysconnectivity in schizophrenia: evidence from structural equation modeling.

Structural and functional studies have shown that schizophrenia is often associated with frontolimbic abnormalities in the prefrontal and mediotemporal regions. It is still unclear, however, if such dysfunctional interaction extends as well to relay regions such as the thalamus and the anterior insula. Here, we measured gray matter volumes of five right-hemisphere regions in 68 patients with schizophrenia and 77 matched healthy subjects. The regions were amygdala, thalamus, and entorhinal cortex (identified as anomalous by prior studies on the same population) and dorsolateral prefrontal cortex and anterior insula (isolated by voxel-based morphometry analysis). We used structural equation modeling and found altered path coefficients connecting the thalamus to the anterior insula, the amygdala to the DLPFC, and the entorhinal cortex to the DLPFC. In particular, patients exhibited a stronger thalamus-insular connection than healthy controls. Instead, controls showed positive entorhinal-DLPFC and negative amygdalar-DLPFC connections, both of which were absent in the clinical population. Our data provide evidence that schizophrenia is characterized by an impaired right-hemisphere network, in which intrahemispheric communication involving relay structures may play a major role in sustaining the pathophysiology of the disease.

Infliximab-related seizures: a first case study.

Seizures following infliximab treatment are very rare and, to date, there is no detailed description of EEG abnormalities with cerebral radiological findings reported in cases with infliximab-related seizures. We describe a patient who acutely developed seizures temporally related to infliximab treatment, which disappeared after drug withdrawal. MRI showed encephalopathy involving mainly cortical regions and EEGs showed focal paroxysmal activity which completely disappeared a few days after infliximab withdrawal. No other plausible cause of the seizures was identified. The clear temporal association between seizure onset and infliximab treatment as well as the clinical improvement and disappearance of focal epileptiform activity after drug withdrawal indicated an evident correlation between seizures and infliximab therapy. The coexistence of pathological findings on MRI suggested that seizures were secondary to the encephalopathy. Further studies are required to evaluate whether infliximab per se has an epileptogenic effect or whether the seizures are caused by encephalopathy involving cortico-subcortical regions.

Cerebellar and lobar blood flow in schizophrenia: a perfusion weighted imaging study.

It is still not clear whether brain hemodynamics plays a role in the functional and structural alterations in schizophrenia, since prior imaging studies showed conflicting findings. In this study we non-invasively explored cerebral and cerebellar lobe perfusion in the largest population of participants with schizophrenia thus far studied with perfusion-weighted imaging (PWI). Forty-seven participants affected by schizophrenia and 29 normal controls were recruited. PWI images were acquired following the intravenous injection of a paramagnetic contrast agent. Regional cerebral blood volume (CBV), blood flow (rCBF), and mean transit time (MTT) were obtained with the block-Circulant Singular Value Decomposition (cSVD) for frontal, temporal, parietal, occipital, and cerebellar lobes, bilaterally. Perfusion parameters were separately obtained for both gray and white matter in each lobe. Subjects with schizophrenia showed no significant differences in perfusion parameters when compared with controls. Interestingly, inverse correlations between age at onset and occipital, frontal and cerebellar MTT and between length of illness and frontal CBV were found. Preserved cerebral and cerebellar perfusion in our chronic population may in part be due to the effects of antipsychotic treatment which may have normalized blood volume and flow. Hypoperfusion in relation to chronicity, particularly in the frontal lobe, has been observed in accordance with earlier studies using positron emission tomography.

Pneumolabyrinth and positional vertigo after stapedectomy.

Pneumolabyrinth due to late complications of stapes surgery is a rare entity. Symptoms may include various degrees of hearing loss, tinnitus and dizziness. We report the case of a 67-year-old patient who developed a unique pneumolabyrinth variant affecting the vestibule, cochlea and semicircular canals 28 years after stapedectomy. The patient presented with intractable paroxysmal positional vertigo of the lateral semicircular canal. The pneumolabyrinth was visualized by means of high resolution computed tomography. Exploratory tympanotomy findings were consistent with a perilymphatic fistula. One year after surgical treatment the subject was free of vertigo spells. Pathogenetic mechanisms are discussed.

The impact of schizophrenia on frontal perfusion parameters: a DSC-MRI study.

We performed a dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) analysis to study the role of the demographic/clinical information on perfusion parameters between patients with schizophrenia and normal control subjects. 39 schizophrenia patients and 27 normal controls were studied with a Siemens 1.5T magnet. PWI images were obtained following intravenous injection of paramagnetic contrast agent (gadolinium-DTPA). For each perfusion parameter, i.e. relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT) and time-to-peak (TTP), the best predictor model was computed in left and right frontal cortex following a stepwise strategy. First of all, a linear model, including all the sociodemographic information and clinical variables as predictors was computed. At each step, the least significant predictor was excluded and a new linear model was evaluated until all predictors were excluded. Then, the best predictor model was selected based on the F statistic value and on the p value. The models for the rCBF and the rCBV both in the left and right frontal cortex were estimated independently from each other, and the best models contained the same predictors, i.e. clinical state, age, and length of illness. No significant models were obtained for the MTT and the TTP. This study showed a decrease in rCBF and rCBV frontal cortex values in subject affected by schizophrenia. Future DSC-MRI studies should further investigate the role of cerebral perfusion for the pathophysiology of the disease by recruiting first-episode patients and by considering cerebellar, parietal and temporal regions.

Adult-onset migraine-related ophthalmoplegia and omolateral fetal-type posterior cerebral artery.

A 33-year-old woman with a long history of typical migraine without aura developed a pupillary-involving right third nerve palsy, after a typical migraine attack. The right pupil was 5 mm and showed delayed direct and consensual photomotor responses; the left pupil was 3 mm and reactive. Pupillary reaction to convergence was slow on the right eye. Ptosis, impaired elevation of the eye and weakened adduction were noted in the right eye. CT scan of the brain showed no abnormalities, whereas a CT digital cerebral angiography revealed a fetal-type right posterior cerebral artery (PCA). MRI disclosed thickening and contrast-enhancement of the cisternal portion of the right oculomotor nerve. A lumbar puncture, performed 5 days after the onset of ocular symptoms, yielded acellular cerebrospinal fluid (CSF) with normal protein and glucose levels. Ptosis and diplopia recovered within a week, whereas blurred vision, anisocoria and accommodation deficit subsided after 10 weeks.

Induced endolymphatic flow from the endolymphatic sac to the cochlea in Ménière's disease.

OBJECTIVE: The aim of the present study was to verify whether drugs injected into the endolymphatic sac (ES) can reach the cochlea and possibly treat inner ear disorders. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center, Otolaryngology Department, University of Verona. SUBJECTS AND METHODS: Patients with Ménière's disease (MD) who were candidates for ES decompression were selected. Nineteen subjects received dexamethasone (DEX) via injection into the ES. To objectively define whether substances administered into the ES could reach the cochlea, we added gadolinium (GD) in three patients. All subjects had intraoperative electrocorticogram recordings and an audiologic follow-up. The three subjects who underwent injection of the DEX-GD solution were followed-up with magnetic resonance imaging. The audiological data are presented during a follow-up period of 12 months. RESULTS: Intraoperative electrocochleography recordings revealed no changes in two patients and summating potentials and compound action potential latency and wave-form modifications in all the other subjects. GD distribution was observed from 48 hours to one week after ES injection into the cochlea of the three subjects injected with DEX-GD. GD-related enhancement of inner ear structures lasted more than two weeks in all subjects. Pure tone average results showed hearing improvement of at least 20 dB HL in 42 percent of patients (8 of 19) at the 12-month follow-up. Statistically significant differences emerged between the mean pure tone average of the ES procedure subjects at one and 12 months after surgery (P = 0.0096). CONCLUSION: This novel approach might reveal new prospects for treating viral, metabolic, autoimmune, and genetic disorders of the cochlea.

EEG-fMRI as an useful tool to detect epileptic foci associated with secondary bilateral synchrony.

INTRODUCTION: Tailoring the epileptic cortex is the key issue in the pre-surgical work-up of patients with pharmacoresistant focal epilepsy. Not always, however, the conventional MRI and the scalp EEG are able to provide the information needed to address this issue since the imaging may be normal (criptogenetic epilepsy) and the EEG, even ictal, poorly localizing. PATIENT AND METHODS: We present a case of focal criptogenetic epilepsy with speech arrest seizures and bilateral synchronous spike and wave scalp EEG pattern (secondary bilateral synchrony). The patient underwent an EEG-fMRI continuous co-registration. RESULTS: The EEG-fMRI showed a clear cut activation of a BOLD signal during the epileptic discharge over the left Supplementary Motor Area (SMA) and, on lesser degree, over the homolateral motor strip. DISCUSSION: Knowledge and expertise about this technique has greatly increased over the last few years making it an useful tool for localizing purposes specially in patients with ambiguous scalp EEG and normal MRI just like the one we presented.