Involvement of precerebellar nuclei in multiple system atrophy

Abstract

In this semiquantitative study based on 26 post-mortem cases, we describe the involvement of precerebellar nuclei in multiple system atrophy (MSA), a progressive degenerative disorder of the human central nervous system characterized by abnormal, argyrophilic and alpha-synuclein immunopositive intracellular inclusions within selectively vulnerable oligodendrocytes and nerve cells. The Campbell-Switzer silver-pyridine technique with alpha-synuclein immunoreactions using 100-microm thick sections is recommended over more conventional methods, thereby permitting visualization of the pertinent lesions in greater detail and facilitating post-mortem diagnosis of MSA specimens. Affected oligodendrocytes occur in specific fibre tracts and grey matters, with most pathology being observed in projections from the precerebellar nuclei to the cerebellum (ponto-cerebellar, olivo-cerebellar, reticulo-cerebellar tracts) and in descending/ascending fibre tracts of the motor system (cortico-pontine, cortico-bulbar, cortico-spinal, spino-reticular, spino-olivary, spino-cerebellar tracts). Three types of abnormal intraneuronal aggregations occur: (i) a loosely woven network within the cell nucleus; (ii) a latticework accumulating in peripheral portions of the cell body; and (iii) irregularly outlined patches of compact, intensely argyrophilic material usually located within deposits of lipofuscin granules. Counter-staining for the presence of extraneuronal lipofuscin can aid neuropathologists in the recognition of lost existent neurones in MSA. Neurones with inclusion bodies occur in the inferior olivary nuclear complex, lateral reticular nucleus, external cuneate nucleus, conterminal nucleus, interfascicular nucleus, nucleus of Roller, dorsal paramedian reticular nucleus, subventricular nucleus, arcuate nucleus, pontobulbar body and pontine grey. The lateral reticular nucleus and accessory nuclei of the inferior olive sustain the most damage and reveal prominent neuronal loss, followed by the pontobulbar body and arcuate nucleus. The uniformly bilateral damage and, in some cases, even obliteration of the nuclei studied, supply additional evidence for the pathoanatomical substrata of the cerebellar dysfunction that reportedly emerges in the clinical course of MSA.

Quantitative pathological changes in the cerebellum of multiple system atrophy

“…αSynu cleinimmunoreactive GCIs have been observed in white and grey matter regions, which provide these inputs to the cerebellum in MSA, e.g. the pontocer ebellar and reticulocerebellar tracts [13], and in the present study they were also observed in cerebellar white matter. This pathology has also been observed in motor tracts providing both the input and output pathways of the cerebellum, e.g., the corticopontine, cortical bulbar, corticospinal, and spinoreticular tracts.…”

“…This pathology has also been observed in motor tracts providing both the input and output pathways of the cerebellum, e.g., the corticopontine, cortical bulbar, corticospinal, and spinoreticular tracts. In addition, significant densities of inclusions have been observed in precerebellar nuclei such as the inferior olivary nucleus [8], lateral reticular nucle us, interfascicular nucleus, and the nucleus of Roller in MSA [13].…”

Neurochemical and Structural Organization of the Principal Nucleus of the Inferior Olive in the Human

“…This observation is consistent with the finding of NPNFP expression in the IOpr and the link between NPNFP expression and the loss of neurons in the cerebral cortex (Hof et al, 1990;Bussiere et al, 2003). Cerebellar or brainstem damage, specifically to the central tegmental tract, results in a specific type of degeneration in the olive, ''hypertrophic olivary degeneration,'' (Weber, 1942;Gautier and Blackwood, 1961;Goto et al, 1988;Braak et al, 2003;Rü b et al, 2005;Aladdin et al, 2008;Valente et al, 2008). There is also degeneration of IO neurons in several neurological disorders, for example spinocerebellar ataxias and Joubert syndrome (Braak et al, 2003;Rü b et al, 2005;Valente et al, 2008;Popescu et al, 2009).…”

The Central Vestibular Complex in Dolphins and Humans: Functional Implications of Deiters’ Nucleus

“…The brains were fixed in 10% formalin, embedded either in paraffin or celloidin, serially sectioned coronally at a thickness of 20 or 30 m and stained for cells (cresyl violet), fibers (Heidenhain-Woelcke), or impregnated with protargol silver stain (Bodian), respectively [Dailly, 1972;Schwerdtfeger et al, 1984]. These slides were compared to a microslide control series of the human brainstem cut at a thickness of 100 m and stained with aldehydefuchsin-Darrow red from the control case collection of the Dr. Senckenbergische Anatomie, Frankfurt a.M. [Braak et al, 2003]. The control individual was without any record of neuropsychiatric diseases.…”