Unravelling the Neural Basis of Spatial Delusions After Stroke.

OBJECTIVE: Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology. METHODS: In a prospective, cumulative, case-control study, we screened 400 patients with acute right-hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion-track and network-mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model, including clinical, behavioral, and neuroimaging data. Finally, we performed a nested cross-validation of the model with a support-vector machine analysis. RESULTS: The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%), and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included 2 distinct streams, connecting right fronto-thalamic and right occipitotemporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto-parietal regions, age, and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80 [0.75-0.85]). INTERPRETATION: Our results localize the anatomic circuits that may have a role in the abnormal spatial-emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke. ANN NEUROL 2021;89:1181-1194.

Cerebrovascular Complications of Anemia.

PURPOSE OF THE REVIEW: Anemia has been called the fifth cardiovascular risk factor. It is one of the most prevalent pathologies worldwide. In this article, we aimed to perform a narrative review of the main cerebrovascular complications of anemia and its influence on stroke prognosis. RECENT FINDINGS: Both hypoproliferative anemia (thalassemia, iron deficiency anemia, etc.) and hyperproliferative anemia (sickle cell disease, paroxysmal nocturnal hemoglobinuria, hereditary spherocytosis, etc.) are associated to cerebrovascular disease ranging from transient ischemic attack to ischemic stroke and hemorrhagic stroke with both intraparenchymal hemorrhage and subarachnoid hemorrhage or cerebral venous thrombosis. Anemia is associated to a worse prognosis in patients with cerebrovascular disease In some cases, like sickle cell disease, pathophysiological mechanisms and therapeutic guidelines are well established, while in others, due to their rarity, there are still lack of robust data. More studies are needed to clarify how the prognosis of stroke patients with anemia could be improved.

First and Second Dissociation Enthalpies in Bi-Component Crystals Consisting of Maleic Acid and L-Phenylalanine.

The energetics of the stepwise dissociation of a A:B2 bi-component crystal, according to A:B2(cr) → A:B(cr) + B(cr) and A:B(cr) → A(cr) + B(cr), was investigated using MA:Phe2 and MA:Phe (MA = maleic acid; Phe = L-phenylalanine) as model systems. The enthalpy changes associated with these sequential processes and with the overall dissociation reaction A:B2(cr) → A(cr) + 2B(cr) were determined by solution calorimetry. It was found that they are all positive, indicating that there is a lattice enthalpy gain when MA:Phe2 is formed, either from the individual precursors or by adding Phe to MA:Phe. Single-crystal X-ray diffraction (SCXRD) analysis showed that MA:Phe2 is best described as a protic salt containing a maleate anion (MA-) and two non-equivalent L-phenylalanine units, both linked to MA- by NH···O hydrogen bonds (H-bond): one of these units is protonated (HPhe+) and the other zwitterionic (Phe±). Only MA- and HPhe+ molecules are present in the MA:Phe lattice. In this case, however, NH···O and OH···O H-bonds are formed between each MA- unit and two HPhe+ molecules. Despite these structural differences, the enthalpy cost for the removal of the zwitterionic Phe± unit from the MA:Phe2 lattice to yield MA:Phe is only 0.9 ± 0.4 kJ mol-1 higher than that for the dissociation of MA:Phe, which requires a proton transfer from HPhe+ to MA- and the rearrangement of L-phenylalanine to the zwitterionic, Phe±, form. Finally, a comparison of the dissociation energetics and structures of MA:Phe and of the previously reported glycine maleate (MA:Gly) analogue indicated that parameters, such as the packing coefficient, density, hydrogen bonds formed, or fusion temperature, are not necessarily good descriptors of dissociation enthalpy or lattice enthalpy trends when bi-component crystals with different molecular composition are being compared, even if the stoichiometry is the same.

Mapping delusions of space onto a structural disconnectome that decouples familiarity and place networks.

Interpretation of space is an important determinant of human behaviour. Delusions of space, or reduplicative paramnesias, are a particularly disturbing form of spatial disorientation characterized by the patients' strong belief of place reduplication, transformation or mislocation. Their occurrence following focal brain damage provides a unique opportunity to unveil the structural-functional basis of space misinterpretations. First, we identified reports of lesion-associated reduplicative paramnesias with brain images available through a systematic review of the literature (n = 24). Each lesion was matched with 4 stroke controls and the sample was randomly split in an exploratory (n = 60) and in a validation (n = 60) dataset. Second, we used 178 7T tractographies to compute structural disconnectome maps and analysed lesion topography and disconnection patterns. Delusions of space were significantly associated with structural disconnection of right ventrolateral prefrontal and right temporal regions, and this finding was replicated in the validation sample. Third, we performed a functional meta-analysis of syndrome-related terms. We demonstrated that the structural disconnectomes of delusions of space were spatially correlated with the functional meta-analytic maps of familiarity and place, and replicated the previous evidence that the lesion topography maps are spatially correlated with belief-related functional networks. No association was found with control terms. These results reveal that structural disconnection putatively mediates functional changes associated with reduplicative paramnesias and provide a possible neural basis for the content specificity for places that characterizes these delusional beliefs.

High-resolution identification of mercury in particles in mouse kidney after acute lethal exposure.

Contamination of the food chain by mercury is a major concern of Public Health of our day. Kidney and nervous system are the major targets of mercury toxicity in mammals. We show here that the detailed subcellular in vivo topography of microparticles of mercury in tissues can be achieved by scanning electron microscopy (SEM) coupled with X-ray elemental microanalysis (XRM). SEM-XRM offered the fine topography of mercury in the kidney of BALB/c mice that were submitted to an intraperitoneal lethal injection of mercuric chloride (HgCl2). All of the renal mercury was seen inside blood vessels located in both cortex and medulla of the mouse kidney. This blood-born mercury was organised in spheroid particles of less than 50 nm in diameter (31.4 +/- 14.1 nm). They were seen attached either to aggregates of plasma proteins or to the surface of blood cells. No evidence of internalisation of mercury by blood, endothelial or kidney cells was found. The average kidney density of mercury microspheres was 1920 +/- 1320 particles per mm2. We propose SEM-XRM as an elective approach to further investigations, at the subcellular level, on the quantitative dynamics of mercury particles in the tissues.