Parkinson's disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons.

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.

The long term myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blocks.

UNLABELLED: 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. IMPLICATIONS: In a period of 4 wk after peripheral nerve block, both long-acting local anesthetics, bupivacaine and ropivacaine, produced calcific myonecrosis suggestive of irreversible skeletal muscle damage. In comparison with ropivacaine, however, the extent of bupivacaine-induced muscle lesions was significantly larger.

The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades.

UNLABELLED: 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. IMPLICATIONS: After continuous peripheral nerve blockades, the long-acting local anesthetics bupivacaine and ropivacaine both induce fiber necrosis in porcine skeletal muscle tissue. In comparison with ropivacaine, bupivacaine causes tissue damage of a significantly larger extent and additionally induces apoptosis in skeletal muscle cells.

Where does parkinson disease pathology begin in the brain?

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).