Brain Correlates of Persistent Postural-Perceptual Dizziness: A Review of Neuroimaging Studies.

Persistent postural-perceptual dizziness (PPPD), defined in 2017, is a vestibular disorder characterized by chronic dizziness that is exacerbated by upright posture and exposure to complex visual stimuli. This review focused on recent neuroimaging studies that explored the pathophysiological mechanisms underlying PPPD and three conditions that predated it. The emerging picture is that local activity and functional connectivity in multimodal vestibular cortical areas are decreased in PPPD, which is potentially related to structural abnormalities (e.g., reductions in cortical folding and grey-matter volume). Additionally, connectivity between the prefrontal cortex, which regulates attentional and emotional responses, and primary visual and motor regions appears to be increased in PPPD. These results complement physiological and psychological data identifying hypervigilant postural control and visual dependence in patients with PPPD, supporting the hypothesis that PPPD arises from shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks that overweigh visual over vestibular inputs and increase the effects of anxiety-related mechanisms on locomotor control and spatial orientation

Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task.

Different lines of research suggest that anxiety-related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self-motion. Twenty-four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self-motion (vertical motion), and (2) trials simulating self-motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion-introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto-insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo-vestibular and anxiety-related systems during simulated vertical self-motion. Hum Brain Mapp 38:715-726, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.Italian University Ministry. Grant Number: PRIN grant 2010MEFNF7_002 ; Italian Space Agency. Grant Number: COREA grant 2013-084-R.0This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/hbm.2341

Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice

Altered Insular and Occipital Responses to Simulated Vertical Self-Motion in Patients with Persistent Postural-Perceptual Dizziness.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a common functional vestibular disorder characterized by persistent symptoms of non-vertiginous dizziness and unsteadiness that are exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Recent physiologic and neuroimaging data suggest that greater reliance on visual cues for postural control (as opposed to vestibular cues-a phenomenon termed visual dependence) and dysfunction in central visuo-vestibular networks may be important pathophysiologic mechanisms underlying PPPD. Dysfunctions are thought to involve insular regions that encode recognition of the visual effects of motion in the gravitational field. METHODS: We tested for altered activity in vestibular and visual cortices during self-motion simulation obtained via a visual virtual-reality rollercoaster stimulation using functional magnetic resonance imaging in 15 patients with PPPD and 15 healthy controls (HCs). We compared between groups differences in brain responses to simulated displacements in vertical vs horizontal directions and correlated the difference in directional responses with dizziness handicap in patients with PPPD. RESULTS: HCs showed increased activity in the anterior bank of the central insular sulcus during vertical relative to horizontal motion, which was not seen in patients with PPPD. However, for the same comparison, dizziness handicap correlated positively with activity in the visual cortex (V1, V2, and V3) in patients with PPPD. CONCLUSION: We provide novel insight into the pathophysiologic mechanisms underlying PPPD, including functional alterations in brain processes that affect balance control and reweighting of space-motion inputs to favor visual cues. For patients with PPPD, difficulties using visual data to discern the effects of gravity on self-motion may adversely affect balance control, particularly for individuals who simultaneously rely too heavily on visual stimuli. In addition, increased activity in the visual cortex, which correlated with severity of dizziness handicap, may be a neural correlate of visual dependence

Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp−Parrish−Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients

exaggerated insect bite like reaction in patients affected by oncohaematological diseases

Sir,Patients affected by chronic B-cell lymphatic leukaemia(CBLL) and, more rarely, other oncohaematologicaldiseases may present with papules, plaques, nodules andvesico-bullous lesions on exposed areas (1–3). Theselesions are usually considered an exaggerated reaction toinsect bites, although the patients not always had ahistory (except for the seasonal presentation of cuta-neous findings), the clinical picture, and response totreatment suggestive of insect bite (3, 4). This phenom-enon has been described in about 40 patients affected bylymphoproliferative disorders, 95% of whom had CBLL(1–7). Weed (1) first gave the definition of 'exaggerateddelayed hypersensitivity to mosquito bites' and reportedthis condition only in patients affected with CBLL.Later, Houston & Keene (2) described a case ofexaggerated insect bite-like reaction also in a patientwith lymphocytic lymphoma. In 1986, Rosen et al. (3)studied 10 patients and suggested that the cutaneouslesions could be linked, in some way, to the onco-haematological conditions, without explaining the exactpathway.Five patients affected by different B lymphoprolifera-tive disorders, who presented with pruritic papules,nodules and vesico-bullous lesions on exposedareas during spring and summer time, are reported.We discuss an immuno-allergic mechanism, involvingboth allergic reaction to insect bite and the impair-ment of the immune response in oncohaematologicalpatients.CASE REPORTSFrom 1995 to 2001, three patients affected by CBLL andtwo by non-Hodgkin B-cell lymphomas attended ourdepartment with polymorphous, erythematous cuta-neous papules and plaques, some of them evolving intobullous lesions. During spring-summer all the patientsdeveloped very itchy lesions, plaques (Fig. 1) andsometimes bullae, mainly localized on upper and/orlower limbs and on the face. Three patients referred tohave been bitten by mosquitoes, the other two deniedthis occurrence. At the time of the clinical examination,all the patients were living in or close to the area ofPavia, Italy, where seasonal infestations of mosquitoes(Aedes) are particularly widespread. All the patientsunderwent a 4-mm punch biopsy, necessary for ahistopathologic evaluation; a direct immunofluores-cence test was carried out for four patients, to excludeautoimmune bullous diseases.At the time of the eruption, one patient was ontreatment with VACOP-B protocol (adriblastina, cyclo-phosphamide, etoposide, vincristine, bleomycin, predni-sone), two patients with chlorambucil and one withcyclophosphamide. An 87-year-old patient was notunder treatment. Blood analysis revealed peripheraleosinophilia in three patients out of five. Stool analysissearching for parasites was carried out in those threepatients and proved negative. IgE was in the normalrange in all the patients. Serum protein electrophoresisrevealed that total immunoglobulins were in the normalrange or little lower in all the patients, while all of thempresented a different degree of decrease of IgG, IgMand/or IgA in sera. The other clinical and serologicalfindings were unremarkable or consistent with theirhaematological condition.The histopathology was characterized by a variety offindings, all of which were consistent with an arthropodbite reaction. In particular, a wedge-shaped, superficialor superficial-deep perivascular and often also inter-stitial infiltrate was present. It was mainly composed ofeosinophils in association with lymphocytes and rarelyneutrophils. The density or the depth of the infiltratevaried from case to case, also according to the age of thelesion. An oedema of the subpapillary dermis wasalways evident. One patient presented a subepidermalvesicle. In another patient spongiosis could be seen an

Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients

Background Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia. Design and Methods We studied 605 patients with essential thrombocythemia (follow-up 4596 person-years) with the aim of defining prognostic factors for thrombosis, myelofibrosis, and leukemia during follow-up. Results Sixty-six patients (11%) developed thrombosis with a 10-year risk of 14%. Age >60 years ( p 60 years ( p =0.02) was significantly correlated with the development of leukemia. Cytotoxic treatment did not imply a higher risk of leukemia. At the time of the analysis, 64 of the 605 patients (10.6%) had died. The 10-year probability of survival was 88%, with a median survival of 22.3 years. Age >60 years ( p <0.001) and history of thrombosis ( p =0.001) were independent risk factors for survival. Conclusions The findings from this study on a large series of patients treated according to current clinical practice provide reassurance that essential thrombocythemia is an indolent disorder and affected patients have a long survival. The main risk is thrombosis, while myelofibrosis and leukemia are rare and late complications