Alzheimer's disease (AD) represents the most frequent progressive neuropsychiatric disorder worldwide leading to dementia. We systematically investigated the presence and extent of the AD‐related ...cytoskeletal pathology in serial thick tissue sections through all subcortical brain nuclei that send efferent projections to the transentorhinal and entorhinal regions in three individuals with Braak and Braak AD stage 0 cortical cytoskeletal pathology and fourteen individuals with Braak and Braak AD stage I cortical cytoskeletal pathology by means of immunostainings with the anti‐tau antibody AT8. These investigations revealed consistent AT8 immunoreactive tau cytoskeletal pathology in a subset of these subcortical nuclei in the Braak and Braak AD stage 0 individuals and in all of these subcortical nuclei in the Braak and Braak AD stage I individuals. The widespread affection of the subcortical nuclei in Braak and Braak AD stage I shows that the extent of the early subcortical tau cytoskeletal pathology has been considerably underestimated previously. In addition, our novel findings support the concept that subcortical nuclei become already affected during an early ‘pre‐cortical’ evolutional phase before the first AD‐related cytoskeletal changes occur in the mediobasal temporal lobe (i.e. allocortical transentorhinal and entorhinal regions). The very early involved subcortical brain regions may represent the origin of the AD‐related tau cytoskeletal pathology, from where the neuronal cytoskeletal pathology takes an ascending course toward the secondarily affected allocortex and spreads transneuronally along anatomical pathways in predictable sequences.
The substantia nigra is not the induction site in the brain of the neurodegenerative process underlying Parkinson disease (PD). Instead, the results of this semi-quantitative study of 30 autopsy ...cases with incidental Lewy body pathology indicate that PD in the brain commences with the formation of the very first immunoreactive Lewy neurites and Lewy bodies in non-catecholaminergic neurons of the dorsal glossopharyngeus-vagus complex, in projection neurons of the intermediate reticular zone, and in specific nerve cell types of the gain setting system (coeruleus-subcoeruleus complex, caudal raphe nuclei, gigantocellular reticular nucleus), olfactory bulb, olfactory tract, and/or anterior olfactory nucleus in the absence of nigral involvement. The topographical parcellation of the nuclear grays described here is based upon known architectonic analyses of the human brainstem and takes into consideration the pigmentation properties of a few highly susceptible nerve cell types involved in PD. In this sample and in all 58 age- and gender-matched controls, Lewy bodies and Lewy neurites do not occur in any of the known prosencephalic predilection sites (i.e. hippocampal formation, temporal mesocortex, proneocortical cingulate areas, amygdala, basal nucleus of Meynert, interstitial nucleus of the diagonal band of Broca, hypothalamic tuberomamillary nucleus).
Clinical signs frequently recognized in early phases of sporadic Parkinson's disease (PD) may include autonomic dysfunctions and the experience of pain. Early disease-related lesions that may account ...for these symptoms are presently unknown or incompletely known. In this study, immunocytochemistry for alpha-synuclein was used to investigate the first relay stations of the pain system as well as parasympathetic and sympathetic pre- and postganglionic nerve cells in the lower brainstem, spinal cord, and coeliac ganglion in 100 microm polyethylene glycol embedded sections from six autopsy individuals, whose brains were staged for PD-associated synucleinopathy. Immunoreactive inclusions were found for the first time in spinal cord lamina I neurons. Lower portions of the spinal cord downwards of the fourth thoracic segment appeared to be predominantly affected, whereas the spinal trigeminal nucleus was virtually intact. Additional involvement was seen in parasympathetic preganglionic projection neurons of the vagal nerve, in sympathetic preganglionic neurons of the spinal cord, and in postganglionic neurons of the coeliac ganglion. The known interconnectivities between all of these components offer a possible explanation for their particular vulnerability. Lamina I neurons (pain system) directly project upon sympathetic relay centers, and these, in turn, exert influence on the parasympathetic regulation of the enteric nervous system. This constellation indicates that physical contacts between vulnerable regions play a key role in the pathogenesis of PD.
Compared with bupivacaine, acute myotoxicity of ropivacaine is less severe. Thus, in this study we compared the long term myotoxic effects of both drugs in a clinically relevant setting. Femoral ...nerve catheters were inserted in anesthetized pigs, and either 20 mL of bupivacaine (5 mg/mL) or ropivacaine (7.5 mg/mL) was injected. Subsequently, bupivacaine (2.5 mg/mL) and ropivacaine (3.75 mg/mL) were continuously infused (8 mL/h) over 6 h. Control animals were treated with corresponding volumes of normal saline. After 7 and 28 days, respectively, muscle samples were dissected at the former injection sites, and histological patterns of muscle damage were blindly scored (0 = no damage to 3 = marked lesions/myonecrosis) and compared. No morphological tissue changes were detected in control animals. In the observed period, both local anesthetics induced morphologically identical patterns of calcific myonecrosis, formation of scar tissue, and a marked rate of fiber regeneration. However, bupivacaine’s effects were constantly more pronounced than those of ropivacaine. These data show that both drugs induce irreversible skeletal muscle damage in a clinically relevant model, and confirm the exceeding rate of myotoxicity of bupivacaine. However, the clinical impact of these long term myotoxic effects still has to be assessed.
Bupivacaine causes muscle damage. However, the myotoxic potency of ropivacaine is still unexplored. Therefore, we performed this study to compare the effects of bupivacaine and ropivacaine on ...skeletal muscle tissue in equipotent concentrations. Femoral nerve catheters were inserted into anesthetized minipigs, and 20 mL of either bupivacaine (5 mg/mL) or ropivacaine (7.5 mg/mL) was injected. Subsequently, bupivacaine (2.5 mg/mL) and ropivacaine (3.75 mg/mL) were continuously infused over 6 h. Control animals were treated with corresponding volumes of normal saline. Finally, muscle samples were dissected at injection sites. After processing and staining, histological patterns of muscle damage were blindly examined, scored (0 = no damage to 3 = myonecrosis), and statistically analyzed. After normal saline, only interstitial edema was found. Bupivacaine treatment caused severe tissue damage (score, 2.3 ± 0.7), whereas ropivacaine induced fiber injury of a significantly smaller extent (score, 1.3 ± 0.8). Furthermore, bupivacaine, but not ropivacaine, induced apoptosis in muscle fibers. In summary, both drugs induce muscle damage with similar histological patterns. Compared with bupivacaine, which induces both necrosis and apoptosis, the tissue damage caused by ropivacaine is significantly less severe. We conclude that ropivacaine’s myotoxic potential is more moderate in comparison with that of bupivacaine.
Summary Pituitary carcinomas are exceedingly rare. At present, the sole diagnostic criterion is metastatic spread, either craniospinal or systemic. There is no agreement on a histologic, ...immunohistochemical, and/or ultrastructural definition. We report a clinically and morphologically well-documented example of pituitary thyrotropin cell carcinoma in a man with multiple endocrine neoplasia type 1 syndrome. The tumor produced thyrotropin, α -subunit, and prolactin and, through electron microscopy, was found to consist solely of Thyrotroph cells. Over a protracted course, craniospinal and systemic metastases were noted. The primary and metastatic deposits of this aggressive tumor were studied. To our knowledge, this tumor is the first reported case of thyrotropin cell carcinoma occurring in association with the multiple endocrine neoplasia type 1 syndrome. The literature regarding thyrotropin carcinomas is reviewed. Based on the study of several biopsies during disease progression, we believe that the carcinoma originated de novo without an intermediary adenoma phase.
Fabry Disease With Concomitant Lewy Body Disease Del Tredici, Kelly; Ludolph, Albert C; Feldengut, Simone ...
Journal of neuropathology and experimental neurology,
2020-April-01, Letnik:
79, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal ...storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3 age-matched individuals were examined. Inclusion body pathology was semiquantitatively evaluated. Although Lewy neurites/bodies were not present in the 50-year-old individual or in controls, severe neuronal loss in the substantia nigra pars compacta and LP corresponding to neuropathological stage 4 of Parkinson disease was seen in the 58-year-old FD patient. Major cerebrovascular lesions and/or additional pathologies were absent in this individual. We conclude that Lewy body disease with parkinsonism can occur within the context of FD. Further studies determining the frequencies of both inclusion pathologies in large autopsy-controlled FD cohorts could help clarify the implications of both lesions for disease pathogenesis, potential spreading mechanisms, and therapeutic interventions.
Early identification of Acanthamoeba in cerebrospinal fluid is mandatory to prevent fatal granulomatous amebic encephalitis. In the case presented here amebic trophozoites were detected in a routine ...cerebrospinal fluid sample. The antibiotic treatment and the apparently low virulence of this isolate were responsible for the benign progression of the infection.
Ontogeny of the Human Amygdala ULFIG, NORBERT; SETZER, MATTHIAS; BOHL, JÜRGEN
Annals of the New York Academy of Sciences,
April 2003, Letnik:
985, Številka:
1
Journal Article
Recenzirano
: Data on the fetal development of the human amygdala is reviewed with special reference to major ontogenetic events. In the fifth gestational month, the inferior portion of the amygdala reveals ...cell‐dense columns merging with the ganglionic eminence (proliferative zone) in Nissl‐stained sections. These columns contain vimentin‐positive fibers and can therefore be regarded as migrational routes. In the sixth and seventh months, distinct reorganization of the cytoarchitectonics takes place. The sequential occurrence of afferens can be visualized using anti‐GAP‐43; moreover, outgrowing axons appear to reach the periphery of the ganglionic eminence. The latter may thus represent an intermediate target for growing axons using anti‐calbindin and anti‐calretinin. Migrating and immature amygdaloid neurons can be shown in the fifth month. From the eighth month onwards, various nonpyramidal neurons and pyramidal neurons are immunolabeled. Transient expression of calretinin in pyramidal neurons is observed. When punctate calbindin and calretinin immunostaining in the fifth and eighth months is compared, distinct redistribution is observed. On the whole, it is apparent that the amygdala has reached a high degree of maturity in the eighth month. At this developmental stage, AKAP79, being enriched in postsynaptic densities, shows a characteristic nuclear‐specific distribution pattern. The latter largely corresponds to the expression pattern of NMDAR1. Thus, AKAP79 may have a preference for anchoring enzymes to glutamate receptors. The aforementioned results provide a basis for investigations on subtle changes in pathologically altered material, such as hemorrhage, in the ganglionic eminence of preterm infants.
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