Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death

This study expands our understanding of the organization of the human caudal pons, providing a morphologic characterization of the medial superior olivary nucleus, component of the superior olivary complex, that plays an important role in the processing of acoustic information. We examined victims of sudden unexplained fetal and infant death and controls (n=75), from 25 gestational weeks to 8 months of postnatal age, by complete autopsy and in-depth autonomic nervous system histological examination, particularly of the medial superior olivary nucleus, the focus of this study. Peculiar cytoarchitectural features of the medial superior olivary nucleus were found in sudden death cases, such as hypoplasia/agenesis and immature hypercellularity, frequently related to dysgenesis of contiguous structures involved in respiratory rhythm-generating circuit, in particular to hypoplasia of the retrotrapezoid and the facial nuclei. We propose the involvement of this nucleus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities. Besides, we highlight the fundamental role of the maternal smoking in pregnancy as etiological factor in the dysmorphic neuroanatomical development of the medial superior olivary nucleus

Unexplained stillbirth versus SIDS: common congenital diseases of the autonomic nervous system--pathology and nosology

Objective: To contribute to a more balanced assessment of the morphological substrates underlying unexplained perinatal death and SIDS. Methods: In-depth histological, immunohistochemical and genetic examinations were performed on the autonomic nervous and cardiac conduction systems in 95 unexpected perinatal deaths, 140 SIDS and 78 controls (44 infants and 34 perinatal death victims). Results: The study revealed the localization and the nature of a variety of specific congenital abnormalities of the autonomic nervous system, central and peripheral, and of the cardiac conduction system that represent the morphological substrates of the pathophysiological mechanism of sudden fetal death and SIDS. Conclusions: The observation of similar anomalies of the autonomic nervous and the cardiac conduction systems in both unexplained perinatal deaths and SIDS indicates their common congenital nature. Therefore, the definitions of these deaths, currently nosographically distinct, should be unified. \ua9 2010 Elsevier Ireland Ltd. All rights reserved

Feto-Placental Atherosclerotic Lesions in Intrauterine Fetal Demise: Role of Parental Cigarette Smoking

The atherogenic effect of cigarette smoking is already recognizable in coronary arteries of fetuses in the last gestational weeks. In this study we analyzed the atherogenic effect of mother’s and father’s smoking habit on coronary arteries and even on adnexa of 30 human fresh fetuses died from 32 to 41 gestational weeks. In 12 cases only the mothers of the victims were cigarette smokers, in 7 cases only the fathers were smokers, whereas in 11 cases nobody smoked

Unexpected sudden death related to medullary brain lesions

Sudden infant death syndrome (SIDS) "gray zone" or borderline cases are defined as those cases in which it is difficult to establish whether the pathological findings are sufficiently severe to have caused the death. Examination of the brainstem in 103 cases of SIDS disclosed five SIDS "gray zone" cases in which only further investigations of serial sections successfully identified anatomico-pathological findings that likely represent the morphological substrates for a sudden reflexogenic death. A complete autopsy was performed, including close examination of the brainstem and cardiac conduction system, according to our guidelines. Our five cases are consistent with the triple-risk model of SIDS, a hypothesis postulating an underlying biological vulnerability to exogenous stressors or triggering factors in a critical developmental period. Inflammatory infiltrates (cases 1 and 2), necrotic focus of the solitary tract (case 3), hemangioendothelioma (case 4) and mild pneumonia (case 5) alone might or might not have accounted for the sudden deaths, if it had not been for the location and/or concomitant presence of brainstem abnormalities that could have had a triggering role in causing the sudden death of these babies

Severe intra- and periventricular hemorrhage: role of arteriolosclerosis related to maternal smoke

The authors aimed to describe the atherosclerotic lesions of the cerebral arterioles, as a substrate of their rupture and bleeding for ests. The study was performed on brain of 9 caucasian fetal victims of intra- and periventricular hemorrhage, all grade IV, and 9 control cases. In the 9 victims of hemorrhage the arteriolar wall structure was altered, focally transformed into a deposit of amorphous eosinophilic material. Such changes often affected the full-thickness of the wall, causing rupture and hemorrhage. In 8 of these cases and in 2 victims of the control group the mothers were heavy cigarette smokers (15-20 cigarettes/day) before and during pregnancy. The authors conclude that intra- and periventricular haemorrhage can be ascribed to the toxic effects of prenatal absorption of nicotine

Natural history of perinatal coronary atherosclerosis

The metabolic rate of the arterial wall depends on the process of filtration of nutrient substances, as capillaries are largely absent in the wall. Therefore, by altering the filtration process, the deposition of lipids favors yet further deposition, creating a vicious circle. In these conditions, the morphological picture is characterized by the accumulation of passive lipid deposits that predominate over the cell defense reactions. The reaction of the smooth muscle cells (SMCs) of the tunica media is considered to be secondary to the above process, contributing to the phagocytic and intimal thickening processes. Thus, the myocytic reaction is not attributed a significant weight in the birth of the atherosclerotic process. Results of our research on the harmful effects of cigarette smoke, in particular, on the arterial wall have contributed to better delineate the morpho-functional picture of onset and development of atherosclerosis. In the fetal arteries, the reaction powers of the SMCs are especially marked. In these conditions, our observations have demonstrated that surprisingly, in fetuses of smoking mothers, the very first defense reaction is morphological alteration of the architecture of the tunica media. In absence of morphologically apparent lesions of the endothelium and subendothelial connective tissue, the early morphologically observable alteration is the appearance of columns of cells running down from the muscular tunica and perpendicularly infiltrating the intima, as if attempting to block penetration of the molecules of the gaseous products circulating in the blood. These histopathological alterations are associated with marked changes in the biological homeostasis of the SMCs. Our molecular biology studies have, in fact, revealed that the first biological reaction in these cells caused by the gaseous products of nicotine combustion is intense activation of the c-fos proto-oncogene. This gene belongs to the family of “Immediate Early Genes”, so defined because of their characteristically rapid activation in response to various injuries, due to the fact that they do not require protein synthesis. In addition, the SMCs are transformed from the contractile or quiescent phenotype, characterized by the presence of α-actin, into the synthetic or activated type, showing loss of the contractile function and a switch in actin expression from the α- to the β-form, a protein usually expressed by fibroblasts. Activated SMCs, or myofibroblasts, start to produce collagen, elastin and extracellular matrix material and reacquire the primordial characteristic of ameboid movement, enabling them to leave the media, which appears subverted and thinned, and to move through the intima towards the lumen. The biological evolution of the lesions is characterized by the maintenance of a delicate balance between cell proliferation and apoptosis of the SMCs and the beginning of cytogenetic alterations, in particular trisomy of chromosome 7, so that the atherosclerotic process resembles that of a benign tumor. These observations have allowed us to interpret the atherosclerotic process not, as previously believed, as the consequence of a passive accumulation of lipid materials, first in the intima and then in the media of an arterial wall lacking the ability to react. The atherosclerosis is the expression of the reaction of myofibroblasts to the action of harmful agents. During evolution of the condition, if there is continual deposition of lipid substances, these will predominate and foster an overwhelming monocytic infiltration. Our observations of atherosclerotic lesions in victims of non-smoking mothers have led us to believe that yet other risk factors may play a role contributing to trigger arterial wall alterations. Since most of the subjects of our studies lived in large industrialized cities, we can hypothesize that air pollution could also exert an atherogenic effect

Is robot-assisted gait training intensity a determinant of functional recovery early after stroke? A pragmatic observational study of clinical care

Gait rehabilitation is a critical factor in functional recovery after a stroke. The aim of this pragmatic observational study was to identify the optimal dose and timing of robot-assisted gait training (RAGT) that can lead to a favourable outcome in a sample of subacute stroke survivors. Subacute patients with stroke who underwent a RAGT within a multidisciplinary rehabilitation program were enrolled. A set of clinical (i.e. age, type of stroke and time since stroke) and rehabilitation stay outcomes (length of stay and RAGT number of sessions) were recorded to evaluate their impact on functional outcome measures by functional independence measure (FIM) or functional ambulation category (FAC). We included 236 patients (62.73 ± 11.82 year old); 38.44% were females, and 59.32% were ischaemic stroke patients. Patients that received at least 14 RAGT sessions, had 15.83% more chance to be responders compared to those that receive less sessions (P = 0.006). Similarly, younger patients (≤60 years) were more prone to be responders (+15.1%). Lastly, an early rehabilitation (<6 weeks) was found to be more efficient (+21.09%) in determining responsiveness (P < 0.001). Becoming newly independent for gait, that refers to a FAC score ≥4, was related with age and RAGT sessions (P = 0.001). In conclusion, a younger age (≤60 years), an early rehabilitation (<6 weeks since stroke) and a higher RAGT dose (at least 14 sessions) were related to a favourable outcome in patients with subacute stroke

Sudden unexpected death of a term fetus in an anticardiolipin-positive mother

A term male fetus suddenly and unexpectedly died in utero at the 40th week of gestation. The mother had a regular and unremarkable pregnancy except for an anticardiolipin antibodies positivity. The histological examination of the cardiac conduction system showed islands of conduction tissue in the central fibrous body, known as persistent fetal dispersion. The brainstem examination revealed a severe bilateral hypoplasia of the arcuate nucleus. This morphological finding has been described in more than 35% of our stillborn as well as sudden infant death syndrome (SIDS) cases, independently from the presence of anticardiolipin antibodies. Some authors have given emphasis to the possible lethal association of maternal autoantibodies and QT prolongation. Our findings emphasize the need of an accurate postmortem examination including the study of brainstem and cardiac conduction system in every case of unexpected late intrauterine death, following the same standardized autopsy protocol adopted in SIDS cases

Involvement of somatostatin in breathing control before and after birth, and in perinatal and infant sudden unexplained death

The distribution of the somatostatin was studied by immunohistochemistry on serial sections of the 56 brain stems from subjects aged from 30 gestational weeks to 12 postnatal months, dying of both known and unknown causes. The unexplained deaths included 13 sudden intrauterine deaths, 4 sudden neonatal deaths and 24 sudden infant deaths. We observed intense somatostatin positivity in the cell bodies and fibres of many brainstem nuclei prevalently involved in the respiratory activity (parabrachial/K\uf6lliker-Fuse complex, locus coeruleus, hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii nucleus, ambiguus nucleus, and reticular formation) in stillbirths. Only in 8 foetuses with unexplained death the hypoglossus nucleus was somatostatin-negative. In the postnatal deaths, the immunopositivity was prevalently limited to the ventrolateral and ventral subnuclei of the tractus solitarii nucleus. In 13 sudden infant death victims and in one case of death due to pneumonia, somatostatin-positivity was also present in the hypoglossus nucleus. We concluded that: 1) the somatostatin is an important foetal breathing-inhibitor, but it becomes important for the physiological control of respiration immediately after delivery; 2) functional alterations of the hypoglossal nucleus can occur in both sudden perinatal and infant deaths and contribute to the induction of both fatal breathing movements in foetuses and abnormal ventilatory control in infants leading to irreversible apneic phenomena

Early atherosclerotic lesions of the cardiac conduction system arteries in infants

INTRODUCTION : Although several studies have described initial atherosclerotic lesions of the coronary arteries, already detectable in infancy and even during the intrauterine life, little, if any, attention has been given to the possible involvement of the cardiac conduction system arteries. In particular, to the best of our knowledge, none has considered the lesions of the cardiac conduction arteries as an initial stage of atherosclerosis. METHODS: The cardiac conduction system of 70 infants dying suddenly and unexpectedly was removed in two blocks for paraffin embedding and serially cut. RESULTS: The histological study of the cardiac conduction arteries of the 70 cases examined showed a normal structure in 55 cases (78.57%). In 15 cases (21.43%), there was a thickening of the sinoatrial node and/or atrioventricular artery associated with a thickening of varying severity in coronary artery walls. The lesions were marked by thickening and deposits of amorphous material and mainly lipids in the intima, as well as fragmentation of the elastic fiber system. A significant correlation was evident between early atherosclerotic lesions and both formula feeding and parental cigarette smoking (P<.05, chi(2) test). CONCLUSIONS: The combination of both the considered risk factors seems to increase the early atherogenic effect of each noxa because the coronary lesions were more diffused in formula-fed infants whose parents both smoked