Amyotrophic lateral sclerosis and myasthenia gravis: association or chance occurrence?

Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1.1.2009. For each patient, detailed clinical information is collected by caring physicians, including comorbidities. From 1.1.2009 to 31.12.2014, 671 patients were diagnosed with ALS; five patients (0.75%) were also affected by MG. Considering Western Countries incidence rates the occurrence of both the diseases should be a really exceptional event (7.5/10⁹), compared to our findings (1.87/10⁷) (p < 0.01). Patients with ALS and MG had more frequently a bulbar onset and a fast progressive course. These cases of ALS after MG raise the possibility of potential shared immunological dysfunctions, which may be expression of common pathogenic mechanisms, as well as of shared disease-course modulating events.     

Interhemispheric Connectivity Characterizes Cortical Reorganization in Motor-Related Networks After Cerebellar Lesions

Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30–40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general.     

Low Apparent Survival and Heterogeneous Movement Patterns of Invasive Blue Catfish in a Coastal River

Blue Catfish Ictalurus furcatus were purposefully introduced into freshwater tributaries to Chesapeake Bay in the past, and populations have subsequently spread to new areas, negatively impacting native communities and causing concern for resource managers. To aid development of management strategies, we implemented a multiyear (2012–2015) tagging study of invasive Blue Catfish in a 40-km stretch of the Potomac River to estimate survival and assess movement patterns. Blue Catfish (N = 1,237) were captured by electrofishing and double-tagged to allow us to estimate tag retention rates; we used reward tags to increase reporting rates. Recaptured fish (N = 104; 8.4% return rate) were at large for between 2 and 1,208 d. Tag retention rates were 0.88 (SE = 0.045) after 1 year and declined to 0.31 (SE = 0.107) after 2.7 years. The mean minimum distance moved by fish was 24.1 km (range = 0.0–112.6 km). Most (63%) fish displayed downriver movements, but distance moved was unrelated to fish size or days at large. Greater distances were observed among fish that moved downriver (34.4 km) than those that moved upriver (6.7 km). These results suggest high variability in movement behaviors for Blue Catfish inhabiting the tidal Potomac River from freshwater reaches to estuarine habitats. We estimated an annual apparent survival rate of 0.56 (SE = 0.057; Brownie tag-return model) across the study period. This survival rate is lower than survival rates reported from their native range. Long-distance movements of Blue Catfish in the Potomac River indicate that robust, large-scale control measures will be needed to reduce population abundance and minimize negative impacts of this species on native communities.

Received May 2, 2017; accepted September 12, 2017     

Multi-View Ensemble Classification of Brain Connectivity Images for Neurodegeneration Type Discrimination

Brain connectivity analyses using voxels as features are not robust enough for single-patient classification because of the inter-subject anatomical and functional variability. To construct more robust features, voxels can be aggregated into clusters that are maximally coherent across subjects. Moreover, combining multi-modal neuroimaging and multi-view data integration techniques allows generating multiple independent connectivity features for the same patient. Structural and functional connectivity features were extracted from multi-modal MRI images with a clustering technique, and used for the multi-view classification of different phenotypes of neurodegeneration by an ensemble learning method (random forest). Two different multi-view models (intermediate and late data integration) were trained on, and tested for the classification of, individual whole-brain default-mode network (DMN) and fractional anisotropy (FA) maps, from 41 amyotrophic lateral sclerosis (ALS) patients, 37 Parkinson’s disease (PD) patients and 43 healthy control (HC) subjects. Both multi-view data models exhibited ensemble classification accuracies significantly above chance. In ALS patients, multi-view models exhibited the best performances (intermediate: 82.9%, late: 80.5% correct classification) and were more discriminative than each single-view model. In PD patients and controls, multi-view models’ performances were lower (PD: 59.5%, 62.2%; HC: 56.8%, 59.1%) but higher than at least one single-view model. Training the models only on patients, produced more than 85% patients correctly discriminated as ALS or PD type and maximal performances for multi-view models. These results highlight the potentials of mining complementary information from the integration of multiple data views in the classification of connectivity patterns from multi-modal brain images in the study of neurodegenerative diseases.     

Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree

AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was found between imaging vascularity and pathological grade(P = 0.035). Post-transplantation recurrence rate was 14.55%(24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients(12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients(58.3%), intrahepatic in 7 patients(29.2%) and both intrahepatic and extrahepatic in 3 patients(12.5%). Two patients had a variation in imaging characteristics between the primary HCC(hypervascular) and the intrahepatic recurrent HCC(hypovascular), while 1 patient had a variation of histopathological characteristics(from moderate to poor differentiation), however no association was found between imaging and histopathological variations.CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.     

Rituximab therapy for primary glomerulonephritis: Report on two cases

The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient(hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function(he became dialysis independent with serum creatinine going back to 1.6 mg/d L) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids.     

Disconnectome of the migraine brain: a “connectopathy” model

BackgroundIn the past decades a plethora of studies has been conducted to explore resting-state functional connectivity (RS-FC) of the brain networks in migraine with conflicting results probably due to the variability and susceptibility of signal fluctuations across the course of RS-FC scan. On the other hand, the structural substrates enabling the functional communications among the brain connectome, characterized by higher stability and reproducibility, have not been widely investigated in migraine by means of graph analysis approach. We hypothesize a rearrangement of the brain connectome with an increase of both strength and density of connections between cortical areas specifically involved in pain perception, processing and modulation in migraine patients. Moreover, such connectome rearrangement, inducing an imbalance between the competing parameters of network efficiency and segregation, may underpin a mismatch between energy resources and demand representing the neuronal correlate of the energetically dysfunctional migraine brain.MethodsWe investigated, using diffusion-weighted MRI imaging tractography-based graph analysis, the graph-topological indices of the brain “connectome”, a set of grey matter regions (nodes) structurally connected by white matter paths (edges) in 94 patients with migraine without aura compared to 91 healthy controls.ResultsWe observed in migraine patients compared to healthy controls: i) higher local and global network efficiency (p < 0.001) and ii) higher local and global clustering coefficient (p < 0.001). Moreover, we found changes in the hubs topology in migraine patients with: i) posterior cingulate cortex and inferior parietal lobule (encompassing the so-called neurolimbic-pain network) assuming the hub role and ii) fronto-orbital cortex, involved in emotional aspects, and visual areas, involved in migraine pathophysiology, losing the hub role. Finally, we found higher connection (edges) probability between cortical nodes involved in pain perception and modulation as well as in cognitive and affective attribution of pain experiences, in migraine patients when compared to healthy controls (p < 0.001). No correlations were found between imaging and clinical parameters of disease severity.ConclusionThe imbalance between the need of investing resources to promote network efficiency and the need of minimizing the metabolic cost of wiring probably represents the mechanism underlying migraine patients’ susceptibility to triggers. Such changes in connectome topography suggest an intriguing pathophysiological model of migraine as brain “connectopathy”.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01315-6.