The biventer cervicis nerve-muscle preparation of adult hens: effects of phenyl saligenin phosphate administration

A biventer cervicis nerve-muscle preparation was used to assess in vitro neuromuscular function in adult white leghorn hens with clinical signs of delayed neuropathy induced by phenyl saligenin phosphate (PSP). Denervation of fast-twitch muscle fibers 13-15 days after PSP was indicated by higher excitability thresholds and by discontinuities of the strength-duration curves. Nerve degeneration was also indicated by significantly elevated rheobase values for all three experimental groups (2, 6 and 10 mg/kg PSP, im) and by shorter chronaxie for preparations from hens receiving 6 and 10 mg/kg. Chronaxie values for preparations from hens given 2 mg/kg PSP were longer than controls, indicating only partial denervation. Biventer cervicis muscle from all PSP-treated hens was 100-1000x more sensitive to acetylcholine (ACh) than muscle from untreated hens, a response typical of denervated slow-tonic muscle. Tension development in response to ACh was 20-45x greater than control in muscle of PSP-treated hens. The greatest sensitivity and tension development in response to ACh was encountered in muscles from hens given 10 mg/kg PSP. Denervation was also indicated histologically by the extensive degeneration and loss of larger myelinated nerve fibers. This study indicates that alteration in neuromuscular function and morphology occurs in the neck region of chickens during OPIDN and that deficits in nerves innervating both fast-twitch and slow-tonic muscles can be differentiated by nerve stimulation and by denervation hypersensitivity to ACh.     

Nerve conduction and ATP concentrations in sciatic-tibial and medial plantar nerves of hens given phenyl saligenin phosphate

To assess the relationship of nerve conduction and adenosine triphosphate (ATP) status in organophosphorus-induced delayed neuropathy (OPIDN), we evaluated both in adult hen peripheral nerves following exposure to a single 2.5 mg/kg dose of phenyl saligenin phosphate (PSP). ATP concentrations were determined at days 2, 4, 7, and 14 post-dosing, from five segments (n = 5 per group) representing the entire length of the sciatic-tibial and medial plantar nerve. Initial effects of PSP dosing were seen in the most distal segment at day 2, when a transient ATP concentration increase (388 +/- 79 pmol/ml/mg versus control value of 215 +/- 23, P < 0.05) was noted. Subsequently, ATP concentration in this distal segment returned to normal. In the most proximal nerve segment, ATP concentrations were decreased on day 7, and further decreased on day 14 post-dosing (P < 0.05). Changes in ATP concentration and nerve conduction velocity begin at post-dosing day 2, and were found prior to development of clinical neuropathy and axonopathic lesions. These results suggest that alterations in sciatic-tibial and medial plantar nerve conduction associated with sciatic-tibial and medial plantar nerve ATP concentration are early events in the development of OPIDN.     

Modification of phenyl saligenin phosphate-induced delayed effects by calcium channel blockers: in vivo and in vitro electrophysiological assessment

Effects of organophosphorus esters (OPs) inducing delayed neuropathy in the adult hen have traditionally been evaluated by assessment of morphology and function of nerve and muscle in the rear limbs of animals exposed. In this study, organophosphorus-induced delayed neuropathy (OPIDN), including neuromuscular function and histology, were studied in vivo using sciatic nerve, tibial nerve and gastrocnemius muscle in anesthetized hens that had been administered phenyl saligenin phosphate (PSP), 2.5 mg/kg by intramuscular injection. In addition, OPIDN was examined in vitro using the biventer cervicis nerve and muscle of the same adult hens. Both nerve-muscle preparations were used for construction of strength duration curves (SDC) on days 4-5, 7-8, and 15-16 after PSP; the biventer cervicis preparation was also used 21-22, 37 and 64 days after PSP administration. Histological examination was done at these same time periods. SDC revealed significant increases in excitability thresholds for preparations from hens receiving PSP only compared to preparations from control hens, or compared to preparations from hens treated with PSP and either nifedipine (1 mg/kg intramuscularly for 5 days), or verapamil (7 mg/kg intramuscularly for 4 days), with treatment beginning 24 hours before administration of PSP. Ataxia, which appeared 7-10 days after hens were given PSP, was less pronounced in hens given PSP plus either calcium channel blocker than in hens given PSP alone. Whether treatment was initiated before or after PSP, verapamil, a phenylalkylamine, reduced sensitivity of the biventer cervicis muscle to acetylcholine-induced stimulation. The dihydropyridine, nifedipine, was less effective at reducing muscle sensitivity to acetylcholine post-exposure than when used as a pretreatment. Lesions were extensive in the biventer cervicis nerve after PSP administration and modification by treatment with calcium channel blockers was evident.     

Neuropathological abnormalities in developmental dysphasia

The brain of a 7-year-old girl with developmental dysphasia who died of complications of infectious mononucleosis was examined grossly and histologically. The neuropathological studies revealed atypical symmetry of the plana temporale and a dysplastic gyrus on the inferior surface of the left frontal cortex along the inferior surface of the sylvian fissure. These anomalies are likely related to midgestation, the period of neuronal migration from the germinal matrix to the cerebral cortex, and are consistent with a neurodevelopmental cause of developmental dysphasia.     

Neuropathological findings in Sneddon's syndrome

The authors report the neuropathologic findings in a case of Sneddon's syndrome. There were multiple small, predominantly cortical, infarcts, with focal hyperplasia and fibrotic occlusion of arterial vessels in the superficial white matter, cortex, and leptomeninges. A very occasional arterial thrombus was seen. These findings suggest that Sneddon's syndrome is caused by a noninflammatory arteriopathy affecting superficial cerebral vessels.     

Neuropathological findings in benign tremulous Parkinsonism

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non‐tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD. Patients with verified benign tremulous PD had less severe neuronal loss in the substantia nigra than controls (χ²: P = .003). Twelve of these had been correctly diagnosed with PD at their first neurological evaluation, whereas the other 4 were originally thought to have another tremor disorder. The only consistent distinguishing feature of the 5 pathologically disproved cases, who may have had either essential tremor with associated rest tremor or dystonic tremor, was a failure to develop unequivocal bradykinesia within a decade of onset of tremor at rest. Our findings support the existence of a distinct subgroup of benign tremulous PD. The slower rate of clinical progression correlates with less severe nigral cell loss at postmortem, although many of these patients transgress the benign tremulous parkinsonism definition by the final third of their disease course and develop the common features of advanced PD. © 2012 Movement Disorder Society     

Neuropathological findings in Dandy Walker Variant

Objective: Dandy-Walker malformation is a congenital malformation that is characterized by hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of the posterior fossa. The aim of the study is to describe the morphological and morphometric alterations of neurons (in various regions of the brain) in a case of Dandy-Walker Variant.

Methods: By Golgi method and routine techniques, the alterations in the brain of a 23 years old case of Dandy-Walker Variant who died accidentally were studied. Furthermore, a detailed morphometric analysis of neuronal parameters and a statistical comparison with an age-matched control were applied.

Results: In the cerebellum the morphological study, apart from gliosis, revealed reduction of the size of cell body and poverty of dendritic arborization with loss of dendritic branches and spines. In the cerebral cortex and the hippocampus the most prominent findings were the tortuous configuration of the apical dendrites of the pyramidal neurons, the focal swellings of the axons and the dendrites and significant gliosis.

Conclusion: Although the gross anatomical examination of the brain demonstrated only mild neurodevelopmental anomalies (except the key features of the syndrome), the microscopic examination revealed significant morphological alterations of neurons and dendrites.     

Neuropathological stageing of Alzheimer-related changes

Summary Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre- (transentorhinal stages I–II). The two forms of limbic stages (stages III–IV) were marked by a conspicuous affection of layer Pre- in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V–VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.Supported by the Deutsche Forschungsgemeinschaft     

阿尔茨海默病神经病理标志物的研究进展

阿尔茨海默病(Alzheimer's disease,AD)是一种缓慢进展的原发性退行性脑变性疾病,多起病于老年期,潜隐起病,缓慢不可逆进展,临床上以认知损害为主.     

Neuropathological aspects of infantile spasms

A review of the neuropathological findings in 50 personal autopsy cases and in the available literature (214 confirmed cases) of infantile spasms demonstrates that this type of early infantile epilepsy occurs in a wide range of cerebral lesions caused by various noxae during different stages of brain development. With regard to morphology and the presumed time of occurrence of the CNS lesions, four groups can be distinguished: (1) embryofetal lesions, including a) cerebral malformations or developmental disorders-agyria-pachygyria (lissencephaly), micrencephaly, micropolygyrias, (hemi)megalencephaly, agenesis of corpus callosum, tuberous sclerosis, heterotopias, cortical microdysplasias, b) metabolic disorders (leukodystrophies, neurolipidoses, spongy dystrophies, Leigh and Alpers diseases, aminoacidopathies); (2) perinatal and postnatal encephalopathies, e.g. polycystic brain, diffuse and lobar sclerosis, ulegyrias, white matter and basal ganglia scars, status marmoratus, hippocampal sclerosis, and cerebellar atrophy; (3) combined embryofetal (developmental) and perinatal or postnatal brain lesions, particularly association of microdysplasias with secondary anoxic or vascular changes; (4) acute vascular and inflammatory brain injuries; (5) cases without definite brain pathology. Evaluation of the available data indicates that embryo-fetal lesions alone or accompanied and/or superimposed by perinatal or postnatal lesions account for about 61% of the cases confirmed by autopsy, in which infantile spasms can be regarded as fetal epilepsies, while a smaller group is featured by perinatal or postnatal lesions occurring in early age, i.e. affecting the immature brain. Similar lesions are observed in cases showing transition of West syndrome to Lennox syndrome. Negative pathology findings in a small number of cases do not necessarily implicate negative pathobiology.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropathological classification of Huntington's disease

In postmortem brain specimens from 163 clinically diagnosed cases of Huntington's disease (HD) the striatum exhibited marked variation in the severity of neuropathological involvement. A system for grading this severity was established by macroscopic and microscopic criteria, resulting in five grades (0-4) designated in ascending order of severity. The grade correlates closely with the extent of clinical disability as assessed by a rating scale. In five cases of clinically diagnosed HD there were no discernible neuropathological abnormalities (grade 0), suggesting that the anatomical changes lag behind the development of clinical abnormalities. In eight cases, neuropathological changes could only be recognized microscopically (grade 1). The earliest changes were seen in the medial paraventricular portions of the caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. Counts of neurons in the CN reveal that 50% are lost in grade 1 and that 95% are lost in grade 4; astrocytes are greatly increased in grades 2-4. These studies indicate that analyses of the CN in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1-2, these regions would reflect early cellular and biochemical changes in HD.