Ageing-related tau astrogliopathy severely affecting the substantia nigra.

AIMS: Astrocytic tau pathology is a major feature of tauopathies and ageing-related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement. We aimed to identify cases with prominent astrocytic tau pathology in the SN. METHODS: We use the term nigral tau-astrogliopathy (NITAG) to describe cases showing an unusually high density of ARTAG with less neuronal tau pathology in the SN. We collected clinical information and studied the distribution of tau pathology, morphological features and immunostaining profiles in three cases. RESULTS: Three cases, all males with parkinsonism, were identified with the following clinicopathological diagnoses: (i) atypical parkinsonism with tau pathology reminiscent to that in postencephalitic parkinsonism (69-year-old); (ii) multiple system atrophy (73-year-old); (iii) traumatic encephalopathy syndrome/chronic traumatic encephalopathy (84-year-old). Double-labelling immunofluorescence confirmed co-localization of GFAP and phosphorylated tau in affected astrocytes. Staining profiles of NITAG revealed immunopositivity for various phosphorylated tau antibodies. Some astrocytic tau lesions were also seen in other brainstem regions and cerebral grey matter. CONCLUSIONS: We propose NITAG is a rare neuropathological feature, and not a distinct disease entity, in the frame of multiple system ARTAG, represented by abundant tau-positive astrocytes in various brain regions but having the highest density in the SN. The concept of NITAG allows the stratification of cases with various background pathologies to understand its relevance and contribution to neuronal dysfunction.

Is the Phenotype Designation by PSP-MDS Criteria Stable Throughout the Disease Course and Consistent With Tau Distribution?

INTRODUCTION: The MDS-PSP criteria have shown high sensitivity for the PSP diagnosis, but do not discriminate the phenotype diversity. Our purpose was to search for anatomopathological differences among PSP phenotypes resulting from the application of the MDS-PSP criteria comparing with the previous ones. METHODS: Thirty-four PSP cases from a single brain bank were retrospectively classified according to the criteria used by Respondek et al. in 2014 and the PSP-MDS criteria at 3 years (MDS-3y), 6 years (MDS-6y) and at the last clinical evaluation before death (MDS-last). Semiquantitative measurement of total, cortical and subcortical tau load was compared. For comparative analysis, PSP-Richardson syndrome and PSP postural instability were grouped (PSP-RS/PI) as well as the PSP atypical cortical phenotypes (PSP-Cx). RESULTS: Applying the Respondek's criteria, PSP phenotypes were distributed as follow: 55.9% PSP-RS/PI, 26.5% PSP-Cx, 11.8% PSP-Parkinsonism (PSP-P), and 5.9% PSP-Cerebellum. PSP-RS/PI and PSP-Cx had a higher total tau load than PSP-P; PSP-Cx showed a higher cortical tau load than PSP-RS/PI and PSP-P; and PSP-RS/PI had a higher subcortical tau load than PSP-P. Applying the MDS-3y, MDS-6y and MDS-last criteria; the PSP-RS/PI group increased (67.6, 70.6 and 70.6% respectively) whereas the PSP-Cx group decreased (8.8, and 8.8 and 11.8%). Then, only differences in total and subcortical tau burden between PSP-RS/PI and PSP-P were observed. INTERPRETATION: After the retrospective application of the new MDS-PSP criteria, total and subcortical tau load is higher in PSP-RS/PI than in PSP-P whereas no other differences in tau load between phenotypes were found, as a consequence of the loss of phenotypic diversity.

Linfoma primario del sistema nervioso central de localización inhabitual: un reto diagnóstico / Primary central nervous system lymphoma in a unusual site: a diagnostic challenge

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Bases fisiopatológicas de los síntomas no motores de la enfermedad de Parkinson / Pathophysiological bases of the non-motor symptoms in Parkinson’s disease

Introducción. Los sustratos neuroanatómicos y neuroquímicos de la mayoría de los síntomas no motores (SNM) de la enfermedad de Parkinson (EP) no se conocen en profundidad. Objetivo. Revisar los conocimientos actuales sobre la fisiopatología de los distintos SNM de la EP sobre la base de estudios recientes. Desarrollo. En la mayoría de los SNM, la base fisiopatológica es compleja. Además del papel de la disfunción dopaminérgica, se piensa que la degeneración de sistemas celulares no dopaminérgicos (noradrenérgicos, serotoninérgicos y colinérgicos) subyace al desarrollo de la mayoría de los SNM y esta hipótesis puede aplicarse a la demencia, la depresión, los trastornos del sueño y los trastornos vegetativos. La demencia, además, se debe fundamentalmente a diferentes alteraciones que se producen en la corteza cerebral. En el trastorno del espectro impulsivo-compulsivo influye de forma crucial la disfunción del estriado ventral y de las proyecciones mesolímbicas. La pérdida de olfato parece deberse a la degeneración neuronal del bulbo olfatorio, y el dolor tiene una base patogénica muy variada y puede ser musculoesquelético, distónico, radicular o central. Conclusiones. A pesar de que se ha producido un gran avance en la investigación sobre la fisiopatología de los SNM de la EP son necesarios nuevos estudios comparativos clinicomorfológicos y patobioquímicos para esclarecer las bases fisiopatológicas de la EP y proporcionar una base más amplia para futuras estrategias terapéuticas de los SNM (AU)

Introduction. The neuro-anatomical and neurochemical substrates underlying most of the non-motor symptoms (NMS) of Parkinson’s disease (PD) are not understood in depth. Aim. To review the current knowledge on the pathophysiology of the different NMS of PD based on recent studies. Development. In most of the NMS the pathophysiological foundation is complex. In addition to the dopaminergic dysfunction, the degeneration of non-dopaminergic (i.e. noradrenergic, serotoninergic and cholinergic) cellular systems is thought to underlie the development of most of the NMS and can be applied in dementia, depression, sleep disorders andvegetative disorders. Dementia, moreover, is essentially caused by different alterations that take place with the cerebral cortex. Dysfunction of the ventral striatum and of the mesolimbic projections exerts a crucial influence in impulsivecompulsive spectrum disorder. Loss of the sense of smell appears to be due to the neuronal degeneration of the olfactory bulb and the pain has an extremely varied pathogenetic basis and may be musculoskeletal, dystonic, radicular or central. Conclusions. Despite the fact that a huge amount of progress has been made in research on the pathophysiology of the NMS of PD, further clinicopathological and pathobiochemical comparative studies are needed to explain the pathophysiological bases of PD and to provide a broader foundation for future therapeutic strategies to treat NMS (AU)