Gigantism and Its Implications for the History of Life.

PubMed

Vermeij, Geerat J

2016-01-01

Gigantism-very large body size-is an ecologically important trait associated with competitive superiority. Although it has been studied in particular cases, the general conditions for the evolution and maintenance of gigantism remain obscure. I compiled sizes and dates for the largest species in 3 terrestrial and 7 marine trophic and habitat categories of animals from throughout the Phanerozoic. The largest species (global giants) in all categories are of post-Paleozoic age. Gigantism at this level appeared tens to hundreds of millions of years after mass extinctions and long after the origins of clades in which it evolved. Marine gigantism correlates with high planktic or seafloor productivity, but on land the correspondence between productivity and gigantism is weak at best. All global giants are aerobically active animals, not gentle giants with low metabolic demands. Oxygen concentration in the atmosphere correlates with gigantism in the Paleozoic but not thereafter, likely because of the elaboration of efficient gas-exchange systems in clades containing giants. Although temperature and habitat size are important in the evolution of very large size in some cases, the most important (and rare) enabling circumstance is a highly developed ecological infrastructure in which essential resources are abundant and effectively recycled and reused, permitting activity levels to increase and setting the stage for gigantic animals to evolve. Gigantism as a hallmark of competitive superiority appears to have lost its luster on land after the Mesozoic in favor of alternative means of achieving dominance, especially including social organization and coordinated food-gathering.

Pituitary gigantism.

PubMed Central

Lu, P W; Silink, M; Johnston, I; Cowell, C T; Jimenez, M

1992-01-01

A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment. Images Figure 1 PMID:1520009

Gigantism of the foot: our experience in seven cases.

PubMed

Turra, S; Santini, S; Cagnoni, G; Jacopetti, T

1998-01-01

We report our experience in seven patients with congenital gigantism of the foot with the following diagnoses: neurofibromatosis (two), fibrolipomatosis (two), Proteus syndrome (two), and idiopathic localized gigantism (one). Our purpose is to introduce a new classification of foot gigantism, based on the concept of "neuroinduction." In our experience, intraoperative examination and subsequent histologic examination show consistently pathologic findings in the plantar nerve and its terminal branches in the foot affected by gigantism. Limited surgical treatment was used in five patients. To prevent forefoot enlargement and recurrence of deformity, we suggest complete ray resection. We evaluated our results using radiographs, functional status, and cosmetic considerations.

Gigantism and Its Implications for the History of Life

PubMed Central

Vermeij, Geerat J.

2016-01-01

Gigantism—very large body size—is an ecologically important trait associated with competitive superiority. Although it has been studied in particular cases, the general conditions for the evolution and maintenance of gigantism remain obscure. I compiled sizes and dates for the largest species in 3 terrestrial and 7 marine trophic and habitat categories of animals from throughout the Phanerozoic. The largest species (global giants) in all categories are of post-Paleozoic age. Gigantism at this level appeared tens to hundreds of millions of years after mass extinctions and long after the origins of clades in which it evolved. Marine gigantism correlates with high planktic or seafloor productivity, but on land the correspondence between productivity and gigantism is weak at best. All global giants are aerobically active animals, not gentle giants with low metabolic demands. Oxygen concentration in the atmosphere correlates with gigantism in the Paleozoic but not thereafter, likely because of the elaboration of efficient gas-exchange systems in clades containing giants. Although temperature and habitat size are important in the evolution of very large size in some cases, the most important (and rare) enabling circumstance is a highly developed ecological infrastructure in which essential resources are abundant and effectively recycled and reused, permitting activity levels to increase and setting the stage for gigantic animals to evolve. Gigantism as a hallmark of competitive superiority appears to have lost its luster on land after the Mesozoic in favor of alternative means of achieving dominance, especially including social organization and coordinated food-gathering. PMID:26771527

Pituitary gigantism: update on molecular biology and management.

PubMed

Lodish, Maya B; Trivellin, Giampaolo; Stratakis, Constantine A

2016-02-01

To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions. Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein gene, multiple endocrine neoplasia types 1 and 4, McCune Albright syndrome, Carney complex, and the paraganglioma, pheochromocytoma, and pituitary adenoma association because of succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging. Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach, and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone.

Dwarfism and gigantism in historical picture postcards.

PubMed Central

Enderle, A

1998-01-01

A collection of 893 historical picture postcards from 1900 to 1935, depicting dwarfs and giants, was analysed from medical and psychosocial viewpoints. In conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis was more difficult because of heterogeneity. The most common conditions depicted were pituitary dwarfism and achondroplasia. Most of those with gigantism had pituitary gigantism and acromegaly. Brothers and sisters or parents and their children provided evidence of mendelian inheritance of some of these disorders. The cards suggest that being put on show provided, at least in some cases, social benefits. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9764085

Late paleozoic fusulinoidean gigantism driven by atmospheric hyperoxia.

PubMed

Payne, Jonathan L; Groves, John R; Jost, Adam B; Nguyen, Thienan; Moffitt, Sarah E; Hill, Tessa M; Skotheim, Jan M

2012-09-01

Atmospheric hyperoxia, with pO(2) in excess of 30%, has long been hypothesized to account for late Paleozoic (360-250 million years ago) gigantism in numerous higher taxa. However, this hypothesis has not been evaluated statistically because comprehensive size data have not been compiled previously at sufficient temporal resolution to permit quantitative analysis. In this study, we test the hyperoxia-gigantism hypothesis by examining the fossil record of fusulinoidean foraminifers, a dramatic example of protistan gigantism with some individuals exceeding 10 cm in length and exceeding their relatives by six orders of magnitude in biovolume. We assembled and examined comprehensive regional and global, species-level datasets containing 270 and 1823 species, respectively. A statistical model of size evolution forced by atmospheric pO(2) is conclusively favored over alternative models based on random walks or a constant tendency toward size increase. Moreover, the ratios of volume to surface area in the largest fusulinoideans are consistent in magnitude and trend with a mathematical model based on oxygen transport limitation. We further validate the hyperoxia-gigantism model through an examination of modern foraminiferal species living along a measured gradient in oxygen concentration. These findings provide the first quantitative confirmation of a direct connection between Paleozoic gigantism and atmospheric hyperoxia. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Evolution of Gigantism in Amphiumid Salamanders

PubMed Central

Bonett, Ronald M.; Chippindale, Paul T.; Moler, Paul E.; Van Devender, R. Wayne; Wake, David B.

2009-01-01

The Amphiumidae contains three species of elongate, permanently aquatic salamanders with four diminutive limbs that append one, two, or three toes. Two of the species, Amphiuma means and A. tridactylum, are among the largest salamanders in the world, reaching lengths of more than one meter, whereas the third species (A. pholeter), extinct amphiumids, and closely related salamander families are relatively small. Amphiuma means and A. tridactylum are widespread species and live in a wide range of lowland aquatic habitats on the Coastal Plain of the southeastern United States, whereas A. pholeter is restricted to very specialized organic muck habitats and is syntopic with A. means. Here we present analyses of sequences of mitochondrial and nuclear loci from across the distribution of the three taxa to assess lineage diversity, relationships, and relative timing of divergence in amphiumid salamanders. In addition we analyze the evolution of gigantism in the clade. Our analyses indicate three lineages that have diverged since the late Miocene, that correspond to the three currently recognized species, but the two gigantic species are not each other's closest relatives. Given that the most closely related salamander families and fossil amphiumids from the Upper Cretaceous and Paleocene are relatively small, our results suggest at least two extreme changes in body size within the Amphuimidae. Gigantic body size either evolved once as the ancestral condition of modern amphiumas, with a subsequent strong size reduction in A. pholeter, or gigantism independently evolved twice in the modern species, A. means and A. tridactylum. These patterns are concordant with differences in habitat breadth and range size among lineages, and have implications for reproductive isolation and diversification of amphiumid salamanders. PMID:19461997

Mammary gigantism and D-penicillamine.

PubMed

Finer, N; Emery, P; Hicks, B H

1984-09-01

Mammary gigantism is a rare complication of D-penicillamine treatment. We report a further case with pathological and endocrine details together with a review of the seven cases previously reported and possible mechanisms.

Dissociation of somatic growth from segmentation drives gigantism in snakes.

PubMed

Head, Jason J; David Polly, P

2007-06-22

Body size is significantly correlated with number of vertebrae (pleomerism) in multiple vertebrate lineages, indicating that change in number of body segments produced during somitogenesis is an important factor in evolutionary change in body size, but the role of segmentation in the evolution of extreme sizes, including gigantism, has not been examined. We explored the relationship between body size and vertebral count in basal snakes that exhibit gigantism. Boids, pythonids and the typhlopid genera, Typhlops and Rhinotyphlops, possess a positive relationship between body size and vertebral count, confirming the importance of pleomerism; however, giant taxa possessed fewer than expected vertebrae, indicating that a separate process underlies the evolution of gigantism in snakes. The lack of correlation between body size and vertebral number in giant taxa demonstrates dissociation of segment production in early development from somatic growth during maturation, indicating that gigantism is achieved by modifying development at a different stage from that normally selected for changes in body size.

Macrodystrophia Lipomatosa: An Unusual Cause of Localized Gigantism.

PubMed

Maheswari, S Uma; Sampath, V; Ramesh, A; Manoharan, K

2016-01-01

Macrodystrophia lipomatosa (MDL) is a rare congenital form of localized gigantism characterized by progressive overgrowth of all mesenchymal elements with a disproportionate increase in fibro adipose tissue. Here we report a case of 20 years old male who presented with history of painless gradual enlargement of entire left upper limb since childhood. Magnetic resonance imaging and histopathology confirmed the diagnosis of macrodystrophia lipomatosa. This condition has to be differentiated from other causes of localized gigantism, since these conditions differ in their course, prognosis, complications and treatment.

Macrodystrophia Lipomatosa: An Unusual Cause of Localized Gigantism

PubMed Central

Maheswari, S Uma; Sampath, V; Ramesh, A; Manoharan, K

2016-01-01

Macrodystrophia lipomatosa (MDL) is a rare congenital form of localized gigantism characterized by progressive overgrowth of all mesenchymal elements with a disproportionate increase in fibro adipose tissue. Here we report a case of 20 years old male who presented with history of painless gradual enlargement of entire left upper limb since childhood. Magnetic resonance imaging and histopathology confirmed the diagnosis of macrodystrophia lipomatosa. This condition has to be differentiated from other causes of localized gigantism, since these conditions differ in their course, prognosis, complications and treatment. PMID:27293271

Why might they be giants? Towards an understanding of polar gigantism.

PubMed

Moran, Amy L; Woods, H Arthur

2012-06-15

Beginning with the earliest expeditions to the poles, over 100 years ago, scientists have compiled an impressive list of polar taxa whose body sizes are unusually large. This phenomenon has become known as 'polar gigantism'. In the intervening years, biologists have proposed a multitude of hypotheses to explain polar gigantism. These hypotheses run the gamut from invoking release from physical and physiological constraints, to systematic changes in developmental trajectories, to community-level outcomes of broader ecological and evolutionary processes. Here we review polar gigantism and emphasize two main problems. The first is to determine the true strength and generality of this pattern: how prevalent is polar gigantism across taxonomic units? Despite many published descriptions of polar giants, we still have a poor grasp of whether these species are unusual outliers or represent more systematic shifts in distributions of body size. Indeed, current data indicate that some groups show gigantism at the poles whereas others show nanism. The second problem is to identify underlying mechanisms or processes that could drive taxa, or even just allow them, to evolve especially large body size. The contenders are diverse and no clear winner has yet emerged. Distinguishing among the contenders will require better sampling of taxa in both temperate and polar waters and sustained efforts by comparative physiologists and evolutionary ecologists in a strongly comparative framework.

Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

PubMed

Skyllouriotis, M L; Marx, M; Bittner, R E; Skyllouriotis, P; Gross, M; Wimmer, M

1997-07-01

We report a 20-year-old man with gigantism syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, and severe psychomotor retardation since childhood. Histochemical and biochemical analysis of skeletal muscle biopsy revealed myoadenylate deaminase deficiency; molecular genetic analysis confirmed the diagnosis of primary (inherited) myoadenylate deaminase deficiency. Plasma, urine, and muscle carnitine concentrations were reduced. L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. The combination of inherited myoadenylate deaminase deficiency, gigantism syndrome and carnitine deficiency has not previously been described.

Treatment of pituitary gigantism with the growth hormone receptor antagonist pegvisomant.

PubMed

Goldenberg, Naila; Racine, Michael S; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel

2008-08-01

Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. This was a descriptive case series of up to 3.5 yr duration. The study was conducted at a university hospital. Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. The intervention was administration of pegvisomant. Plasma IGF-I and growth velocity were measured. In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory.

Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

PubMed

Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

1994-11-01

The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

First observations of Gigantic Jets from Monsoon Thunderstorms over India

NASA Astrophysics Data System (ADS)

Singh, Rajesh; Maurya, Ajeet; Chanrion, Olivier; Neubert, Torsten; Cummer, Steven; Mlynarczyk, Janusz; Bór, József; Siingh, Devendraa; Cohen, Morris; Kumar, Sushil

2016-04-01

Gigantic Jets are electric discharges from thunderstorm cloud tops to the bottom of the ionosphere at ~80 km altitude. After their first discovery in 2001, relatively few observations have been reported. Most of these are from satellites at large distances and a few tens from the ground at higher spatial resolution. Here we report the first Gigantic Jets observed in India from two thunderstorm systems that developed over the land surface from monsoon activity, each storm producing two Gigantic Jets. The jets were recorded by a video camera system at standard video rate (20 ms exposure) at a few hundred km distance. ELF measurements suggest that the jets are of the usual negative polarity and that they develop in less than 40 ms, which is faster than most jets reported in the past. The jets originate from the leading edge of a slowly drifting convective cloud complex close to the highest regions of the clouds and carry ~25 Coulomb of charge to the ionosphere. One jet has a markedly horizontal displacement that we suggest is caused by a combination of close-range cloud electric fields at inception, and longer-range cloud fields at larger distances during full development. The Gigantic Jets are amongst the few that have been observed over land.

Multiple origins of gigantism in stem baleen whales

NASA Astrophysics Data System (ADS)

Tsai, Cheng-Hsiu; Kohno, Naoki

2016-12-01

Living baleen whales (Mysticeti) include the world's largest animals to have ever lived—blue whales ( Balaenoptera musculus) can reach more than 30 m. However, the gigantism in baleen whales remains little explored. Here, we compiled all published stem mysticetes from the Eocene and Oligocene and then mapped the estimated body size onto different phylogenies that suggest distinct evolutionary histories of baleen whales. By assembling all known stem baleen whales, we present three novel findings in early mysticete evolution. Results show that, regardless of different phylogenetic scenarios, large body size (more than 5-m long) evolved multiple times independently in their early evolutionary history. For example, the earliest known aetiocetid ( Fucaia buelli, 33-31 Ma) was small in size, about 2 m, and a later aetiocetid ( Morawanocetus-like animal, 26-23 Ma) can reach 8-m long—almost four times the size of Fucaia buelli—suggesting an independent gigantism in the aetiocetid lineage. In addition, our reconstruction of ancestral state demonstrates that the baleen whales originated from small body size (less than 5 m) rather than large body size as previously acknowledged. Moreover, reconstructing the evolution of body size in stem baleen whales suggests that the initial pulse of mysticete gigantism started at least back to the Paleogene and in turn should help to understand the origin, pattern, and process of the extreme gigantism in the crown baleen whales. This study illustrates that Cope's rule is insufficient to explain the evolution of body size in a group that comprises the largest animals in the history of life, although currently the lack of exact ancestor-descendant relationships remains to fully reveal the evolutionary history of body size.

An evolutionary cascade model for sauropod dinosaur gigantism--overview, update and tests.

PubMed

Sander, P Martin

2013-01-01

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism"). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

Treatment of Pituitary Gigantism with the Growth Hormone Receptor Antagonist Pegvisomant

PubMed Central

Goldenberg, Naila; Racine, Michael S.; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel

2008-01-01

Context: Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. Objective: The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. Design: This was a descriptive case series of up to 3.5 yr duration. Setting: The study was conducted at a university hospital. Patients: Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. Intervention: The intervention was administration of pegvisomant. Main Outcome Measures: Plasma IGF-I and growth velocity were measured. Results: In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Conclusions: Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory. PMID:18492755

Multiple origins of gigantism in stem baleen whales.

PubMed

Tsai, Cheng-Hsiu; Kohno, Naoki

2016-12-01

Living baleen whales (Mysticeti) include the world's largest animals to have ever lived-blue whales (Balaenoptera musculus) can reach more than 30 m. However, the gigantism in baleen whales remains little explored. Here, we compiled all published stem mysticetes from the Eocene and Oligocene and then mapped the estimated body size onto different phylogenies that suggest distinct evolutionary histories of baleen whales. By assembling all known stem baleen whales, we present three novel findings in early mysticete evolution. Results show that, regardless of different phylogenetic scenarios, large body size (more than 5-m long) evolved multiple times independently in their early evolutionary history. For example, the earliest known aetiocetid (Fucaia buelli, 33-31 Ma) was small in size, about 2 m, and a later aetiocetid (Morawanocetus-like animal, 26-23 Ma) can reach 8-m long-almost four times the size of Fucaia buelli-suggesting an independent gigantism in the aetiocetid lineage. In addition, our reconstruction of ancestral state demonstrates that the baleen whales originated from small body size (less than 5 m) rather than large body size as previously acknowledged. Moreover, reconstructing the evolution of body size in stem baleen whales suggests that the initial pulse of mysticete gigantism started at least back to the Paleogene and in turn should help to understand the origin, pattern, and process of the extreme gigantism in the crown baleen whales. This study illustrates that Cope's rule is insufficient to explain the evolution of body size in a group that comprises the largest animals in the history of life, although currently the lack of exact ancestor-descendant relationships remains to fully reveal the evolutionary history of body size.

An Evolutionary Cascade Model for Sauropod Dinosaur Gigantism - Overview, Update and Tests

PubMed Central

Sander, P. Martin

2013-01-01

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades (“Reproduction”, “Feeding”, “Head and neck”, “Avian-style lung”, and “Metabolism”). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait “Very high body mass”. Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size. PMID:24205267

Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation.

PubMed

Trivellin, Giampaolo; Daly, Adrian F; Faucz, Fabio R; Yuan, Bo; Rostomyan, Liliya; Larco, Darwin O; Schernthaner-Reiter, Marie Helene; Szarek, Eva; Leal, Letícia F; Caberg, Jean-Hubert; Castermans, Emilie; Villa, Chiara; Dimopoulos, Aggeliki; Chittiboina, Prashant; Xekouki, Paraskevi; Shah, Nalini; Metzger, Daniel; Lysy, Philippe A; Ferrante, Emanuele; Strebkova, Natalia; Mazerkina, Nadia; Zatelli, Maria Chiara; Lodish, Maya; Horvath, Anelia; de Alexandre, Rodrigo Bertollo; Manning, Allison D; Levy, Isaac; Keil, Margaret F; Sierra, Maria de la Luz; Palmeira, Leonor; Coppieters, Wouter; Georges, Michel; Naves, Luciana A; Jamar, Mauricette; Bours, Vincent; Wu, T John; Choong, Catherine S; Bertherat, Jerome; Chanson, Philippe; Kamenický, Peter; Farrell, William E; Barlier, Anne; Quezado, Martha; Bjelobaba, Ivana; Stojilkovic, Stanko S; Wess, Jurgen; Costanzi, Stefano; Liu, Pengfei; Lupski, James R; Beckers, Albert; Stratakis, Constantine A

2014-12-18

Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells. We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Gigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation

PubMed Central

Trivellin, G.; Daly, A.F.; Faucz, F.R.; Yuan, B.; Rostomyan, L.; Larco, D.O.; Schernthaner-Reiter, M.H.; Szarek, E.; Leal, L.F.; Caberg, J.-H.; Castermans, E.; Villa, C.; Dimopoulos, A.; Chittiboina, P.; Xekouki, P.; Shah, N.; Metzger, D.; Lysy, P.A.; Ferrante, E.; Strebkova, N.; Mazerkina, N.; Zatelli, M.C.; Lodish, M.; Horvath, A.; de Alexandre, R. Bertollo; Manning, A.D.; Levy, I.; Keil, M.F.; de la Luz Sierra, M.; Palmeira, L.; Coppieters, W.; Georges, M.; Naves, L.A.; Jamar, M.; Bours, V.; Wu, T.J.; Choong, C.S.; Bertherat, J.; Chanson, P.; Kamenický, P.; Farrell, W.E.; Barlier, A.; Quezado, M.; Bjelobaba, I.; Stojilkovic, S.S.; Wess, J.; Costanzi, S.; Liu, P.; Lupski, J.R.; Beckers, A.; Stratakis, C.A.

2015-01-01

BACKGROUND Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. METHODS We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. RESULTS We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein–coupled receptor, was overexpressed in patients’ pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone–producing cells. CONCLUSIONS We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.) PMID:25470569

Neurofibromatosis with unilateral lower limb gigantism.

PubMed

Sabbioni, Giacomo; Rani, Nicola; Devescovi, Valentina

2010-05-01

The case of a 3-year-old child diagnosed with Type 1 neurofibromatosis is presented, showing pigmented birthmarks and gigantism of the left lower limb associated with the presence of multiple neurofibromas. Increased bone growth appears to be the direct or indirect consequence of a still undefined paracrine effect of nerve tumor cells.

Fungal cell gigantism during mammalian infection.

PubMed

Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

2010-06-17

The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

Fungal Cell Gigantism during Mammalian Infection

PubMed Central

Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D.; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

2010-01-01

The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 µm in diameter and capsules resistant to stripping with γ-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20–50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens. PMID:20585557

[Gigantism with low serum level of growth hormone: a case report].

PubMed

Ran, X; Zhang, L; Xiong, P; Zhao, T; Tong, N; Li, X

2001-12-01

Gigantism with low or normal basal concentrations of growth hormone (GH) is a rare condition, possibly due to abnormal GH secretory patterns, enhanced tissue sensitivity to GH, or the existence of an unidentified growth promoting factor. Here we report an 11 year-old female case of gigantism with a normal pituitary gland. Her height was 181 cm, body weight 77 kg, and bone age 11.1 years. Her basal serum GH levels were lower than 1 ng/ml. The levels of T3, T4, FT3, FT4, TSH, E2, LH, FSH, PRL, PTC and ACTH were normal. Serum GH response to insulin-induced hypoglycemia or arginine stimulation tests was blunted. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-1 and the existence of an unidentified growth promoting factor or biologically active anti-GH receptor antibodies may cause clinical gigantism.

Gigantic Thrombus of the Left Atrium in Mitral Stenosis

PubMed Central

Hodzic, Enisa; Granov, Nermir

2017-01-01

Introduction Excess dilatation of the left atrium >65 mm is known in the literature as gigantic atrium. This dilation is most commonly encountered in the mitral insufficiency of rheumatic etiology, but also in severe prolapses of the mitral valve, permanent atrial fibrillation, and at the left right shunt with cardiac insufficiency. Case report In this paper is presented a case study of echocardiographically verified giant thrombus in left atrium in a 50 years old female patient aged 50 hospitalized because of tiredness, choking, heartburn and urinary tract symptoms. The patient had rheumatic fever at age of 18 years. At age of 35, she was diagnosed with mitral stenosis. In permanent atrial fibrillation with anamnestic data on the previous cerebrovascular stroke (CVI) and the repeated transitional ischemic seizures. Echocardiographic examination confirmed severe mitral stenosis with moderate aortic insufficiency and gigantic left atrium (LA) with gigantic thrombus. Invasive diagnostics were indicated and performed, followed by an acute cardiac surgery including left atrial thrombectomy and implantation of the mechanical aortic and mitral valve. The surgical course was without complications. Conclusion On eleven postoperative day, after mobilization, the patient experiences stroke with motor aphasia. She was clinically recovering from stroke consequences, and remains cardiollogically stable. PMID:29416208

Video, LMA and ULF observations of a negative gigantic jet in North Texas

NASA Astrophysics Data System (ADS)

Bruning, E. C.; Cummer, S.; Palivec, K.; Lyons, W. A.; Chmielewski, V.; MacGorman, D. R.

2017-12-01

On 8 September 2016 at 0125:38 UTC video of a negative gigantic jet was captured from Hawley, TX. VHF Lightning Mapping Arrays in West Texas and Oklahoma also observed the parent flash (duration of about 1 s) and, for the first time, mapped dozens of points along ascending negative leaders, lasting about 50 ms, which extended well above cloud top to about 35 km MSL altitude. A few well-located VHF sources were also detected near 50 km. Together, the video and VHF observations provide additional confirmation of the altitude at which the leader-to-streamer transition takes place in gigantic jet discharges. ULF magnetic field data from the Duke iCMC network show a current excursion associated with the onset of the upward movement of negative charge and leaders in the VHF. As the gigantic jet reached its full height, current spiked to 80 kA, followed by several hundred milliseconds of continuing current of 10-20 kA. Total charge moment change was about 6000 C km. The storm complex produced predominantly negative large charge moment change events, which is characteristic of storms that produce negative gigantic jets.

PITUITARY GIGANTISM--EXPERIENCE OF A SINGLE CENTER FROM WESTERN INDIA.

PubMed

Patt, Hiren P; Bothra, Nikita; Goel, Atul H; Kasaliwal, Rajeev; Lila, Anurag R; Bandgar, Tushar R; Shah, Nalini S

2015-06-01

Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism. We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014. Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time. Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Discharge processes, electric field, and electron energy in ISUAL-recorded gigantic jets

NASA Astrophysics Data System (ADS)

Kuo, Cheng-Ling; Chou, J. K.; Tsai, L. Y.; Chen, A. B.; Su, H. T.; Hsu, R. R.; Cummer, S. A.; Frey, H. U.; Mende, S. B.; Takahashi, Y.; Lee, L. C.

2009-04-01

This article reports the first high time resolution measurements of gigantic jets from the Imager of Sprites and Upper Atmospheric Lightning (ISUAL) experiment. The velocity of the upward propagating fully developed jet stage of the gigantic jets was ˜107 m s-1, which is similar to that observed for downward sprite streamers. Analysis of spectral ratios for the fully developed jet emissions gives a reduced E field of 400-655 Td and average electron energy of 8.5-12.3 eV. These values are higher than those in the sprites but are similar to those predicted by streamer models, which implies the existence of streamer tips in fully developed jets. The gigantic jets studied here all contained two distinct photometric peaks. The first peak is from the fully developed jet, which steadily propagates from the cloud top (˜20 km) to the lower ionosphere at ˜90 km. We suggest that the second photometric peak, which occurs ˜1 ms after the first peak, is from a current wave or potential wave-enhanced emissions that originate at an altitude of ˜50 km and extend toward the cloud top. We propose that the fully developed jet serves as an extension of the local ionosphere and produces a lowered ionosphere boundary. As the attachment processes remove the charges, the boundary of the local ionosphere moves up. The current in the channel persists and its contact point with the ionosphere moves upward, which produces the upward surging trailing jets. Imager and photometer data indicate that the lightning activity associated with the gigantic jets likely is in-cloud, and thus the initiation of the gigantic jets is not directly associated with cloud-to-ground discharges.

Tyrannosauroid integument reveals conflicting patterns of gigantism and feather evolution.

PubMed

Bell, Phil R; Campione, Nicolás E; Persons, W Scott; Currie, Philip J; Larson, Peter L; Tanke, Darren H; Bakker, Robert T

2017-06-01

Recent evidence for feathers in theropods has led to speculations that the largest tyrannosaurids, including Tyrannosaurus rex , were extensively feathered. We describe fossil integument from Tyrannosaurus and other tyrannosaurids ( Albertosaurus, Daspletosaurus, Gorgosaurus and Tarbosaurus ), confirming that these large-bodied forms possessed scaly, reptilian-like skin. Body size evolution in tyrannosauroids reveals two independent occurrences of gigantism; specifically, the large sizes in Yutyrannus and tyrannosaurids were independently derived. These new findings demonstrate that extensive feather coverings observed in some early tyrannosauroids were lost by the Albian, basal to Tyrannosauridae. This loss is unrelated to palaeoclimate but possibly tied to the evolution of gigantism, although other mechanisms exist. © 2017 The Author(s).

Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

PubMed

Bondanelli, Marta; Bonadonna, Stefania; Ambrosio, Maria Rosaria; Doga, Mauro; Gola, Monica; Onofri, Alessandro; Zatelli, Maria Chiara; Giustina, Andrea; degli Uberti, Ettore C

2005-09-01

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P<.05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity<1) was detected in 2 of 6 patients with gigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (P<.05) higher in patients with gigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in

Observations of Seven Blue/Gigantic Jets above One Storm over the Atlantic Ocean

NASA Astrophysics Data System (ADS)

Liu, N.; Spiva, N.; Dwyer, J. R.; Rassoul, H.; Free, D. L.; Cummer, S. A.

2013-12-01

Blue/gigantic jets are electrical discharges developing from thundercloud tops and propagating to the upper atmosphere [e.g., Pasko et al., Nature, 416, 152, 2002; Su et al., Nature, 423, 973, 2003]. Not just producing an impressive display, gigantic jets establish a direct path of electrical contact between the upper troposphere and the lower ionosphere, capable of transferring a large amount of charge between them [Cummer et al., Nat. Geosci., 2, 617, 2009]. It has been suggested that they may play an important role in the earth's electrical environment [e. g., Pasko, Nature, 423, 927, 2003]. Upward discharges from thunderstorms like blue/gigantic jets are believed to originate from lightning leaders escaping from thunderclouds when the cloud's charges of different polarities are not balanced [Krehbiel et al., Nat. Geosci., 1, 233, 2008; Riousset et al., JGR, 115, A00E10, 2010]. On the evening of August 2, 2013, 4 gigantic jets, 2 blue jets and 1 blue starter were recorded within 26 min above a storm over the Atlantic Ocean by a low light level camera from the campus of Florida Institute of Technology. The events were also captured by two all-sky cameras: one again from the Florida Tech campus and the other from a nearby location. According to the NLDN data, positive intra-cloud flashes preceded all events except one gigantic jet. The distance between the observation site to the locations of the NLDN lightning discharges varies from 77 to 82 km. Optical signatures of intra-cloud discharge activities accompanied the events are clearly visible in the videos. The duration of each jet varies from about 300 ms to 1.2 s, and the 1.2 s duration is probably the longest that has been reported to date for jets. Rebrightening of gigantic jet structures occurs for at least two of the events. The upper terminal altitude of the 4 gigantic jets is greater than 76-81 km, the 2 blue jets reach about 48 and 51 km altitude, respectively, and the blue starter reaches 24 km altitude

Gigantism associated with slipped capital femoral epiphysis.

PubMed

Unnikrishnan, A G; Agrawal, N K; Reddy, D V S; Kumar, R; Singh, S K

2003-08-01

The etiology of slipped capital femoral epiphysis (SCFE) is unknown, though hormonal as well as mechanical factors have been implicated. We report a case of gigantism who presented with SCFE. This case provides an insight into the genesis of SCFE, which in this case was related to growth hormone excess and sex-hormone deficiency.

Starvation reveals the cause of infection-induced castration and gigantism

PubMed Central

Cressler, Clayton E.; Nelson, William A.; Day, Troy; McCauley, Edward

2014-01-01

Parasites often induce life-history changes in their hosts. In many cases, these infection-induced life-history changes are driven by changes in the pattern of energy allocation and utilization within the host. Because these processes will affect both host and parasite fitness, it can be challenging to determine who benefits from them. Determining the causes and consequences of infection-induced life-history changes requires the ability to experimentally manipulate life history and a framework for connecting life history to host and parasite fitness. Here, we combine a novel starvation manipulation with energy budget models to provide new insights into castration and gigantism in the Daphnia magna–Pasteuria ramosa host–parasite system. Our results show that starvation primarily affects investment in reproduction, and increasing starvation stress reduces gigantism and parasite fitness without affecting castration. These results are consistent with an energetic structure where the parasite uses growth energy as a resource. This finding gives us new understanding of the role of castration and gigantism in this system, and how life-history variation will affect infection outcome and epidemiological dynamics. The approach of combining targeted life-history manipulations with energy budget models can be adapted to understand life-history changes in other disease systems. PMID:25143034

Starvation reveals the cause of infection-induced castration and gigantism.

PubMed

Cressler, Clayton E; Nelson, William A; Day, Troy; McCauley, Edward

2014-10-07

Parasites often induce life-history changes in their hosts. In many cases, these infection-induced life-history changes are driven by changes in the pattern of energy allocation and utilization within the host. Because these processes will affect both host and parasite fitness, it can be challenging to determine who benefits from them. Determining the causes and consequences of infection-induced life-history changes requires the ability to experimentally manipulate life history and a framework for connecting life history to host and parasite fitness. Here, we combine a novel starvation manipulation with energy budget models to provide new insights into castration and gigantism in the Daphnia magna-Pasteuria ramosa host-parasite system. Our results show that starvation primarily affects investment in reproduction, and increasing starvation stress reduces gigantism and parasite fitness without affecting castration. These results are consistent with an energetic structure where the parasite uses growth energy as a resource. This finding gives us new understanding of the role of castration and gigantism in this system, and how life-history variation will affect infection outcome and epidemiological dynamics. The approach of combining targeted life-history manipulations with energy budget models can be adapted to understand life-history changes in other disease systems.

Increased Population Risk of AIP‐Related Acromegaly and Gigantism in Ireland

PubMed Central

Radian, Serban; Diekmann, Yoan; Gabrovska, Plamena; Holland, Brendan; Bradley, Lisa; Wallace, Helen; Stals, Karen; Bussell, Anna‐Marie; McGurren, Karen; Cuesta, Martin; Ryan, Anthony W.; Herincs, Maria; Hernández‐Ramírez, Laura C.; Holland, Aidan; Samuels, Jade; Aflorei, Elena Daniela; Barry, Sayka; Dénes, Judit; Pernicova, Ida; Stiles, Craig E.; Trivellin, Giampaolo; McCloskey, Ronan; Ajzensztejn, Michal; Abid, Noina; Akker, Scott A.; Mercado, Moises; Cohen, Mark; Thakker, Rajesh V.; Baldeweg, Stephanie; Barkan, Ariel; Musat, Madalina; Levy, Miles; Orme, Stephen M.; Unterländer, Martina; Burger, Joachim; Kumar, Ajith V.; Ellard, Sian; McPartlin, Joseph; McManus, Ross; Linden, Gerard J.; Atkinson, Brew; Balding, David J.; Agha, Amar; Thompson, Chris J.; Hunter, Steven J.; Thomas, Mark G.; Morrison, Patrick J.

2016-01-01

ABSTRACT The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027–0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011–0.0047) and zero in ROI (0–0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non‐Irish patients (0–2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275–5,000) years. tMRCA‐based simulations predicted 432 (90–5,175) current carriers, including 86 affected (18–1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP‐related disease. PMID:27650164

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

PubMed

Radian, Serban; Diekmann, Yoan; Gabrovska, Plamena; Holland, Brendan; Bradley, Lisa; Wallace, Helen; Stals, Karen; Bussell, Anna-Marie; McGurren, Karen; Cuesta, Martin; Ryan, Anthony W; Herincs, Maria; Hernández-Ramírez, Laura C; Holland, Aidan; Samuels, Jade; Aflorei, Elena Daniela; Barry, Sayka; Dénes, Judit; Pernicova, Ida; Stiles, Craig E; Trivellin, Giampaolo; McCloskey, Ronan; Ajzensztejn, Michal; Abid, Noina; Akker, Scott A; Mercado, Moises; Cohen, Mark; Thakker, Rajesh V; Baldeweg, Stephanie; Barkan, Ariel; Musat, Madalina; Levy, Miles; Orme, Stephen M; Unterländer, Martina; Burger, Joachim; Kumar, Ajith V; Ellard, Sian; McPartlin, Joseph; McManus, Ross; Linden, Gerard J; Atkinson, Brew; Balding, David J; Agha, Amar; Thompson, Chris J; Hunter, Steven J; Thomas, Mark G; Morrison, Patrick J; Korbonits, Márta

2017-01-01

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304 * (or p.R304 * ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304 * carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304 * prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) for 20% penetrance. In conclusion, R304 * is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease. © 2016 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

The acromegaly--gigantism syndrome. Report of four cases treated surgically.

PubMed

Zampieri, P; Scanarini, M; Sicolo, N; Andrioli, G; Mingrino, S

1983-12-01

Four cases of growth-hormone-secreting pituitary adenoma, with associated aspects of acromegaly and gigantism, are reported in patients aged 12-26. All of the patients had macroadenomas and were treated surgically, three by the transsphenoidal approach and one with a transfrontal craniotomy. Histologic examination revealed eosinophilic adenomas in three of the cases and a mixed eosinophilic--chromophobe adenoma in one, all with cellular irregularities (mitosis and cellular and nuclear polymorphism), local invasivity, or both. Because surgical treatment did not produce complete normalization of growth hormone levels, radiotherapy followed the operations in all four cases. In our opinion, the treatment of acromegalic gigantism poses more therapeutic problems than that of simple acromegaly, with combined treatment (surgical, radiation, and medical) often being necessary.

Independent evolution of baleen whale gigantism linked to Plio-Pleistocene ocean dynamics.

PubMed

Slater, Graham J; Goldbogen, Jeremy A; Pyenson, Nicholas D

2017-05-31

Vertebrates have evolved to gigantic sizes repeatedly over the past 250 Myr, reaching their extreme in today's baleen whales (Mysticeti). Hypotheses for the evolution of exceptionally large size in mysticetes range from niche partitioning to predator avoidance, but there has been no quantitative examination of body size evolutionary dynamics in this clade and it remains unclear when, why or how gigantism evolved. By fitting phylogenetic macroevolutionary models to a dataset consisting of living and extinct species, we show that mysticetes underwent a clade-wide shift in their mode of body size evolution during the Plio-Pleistocene. This transition, from Brownian motion-like dynamics to a trended random walk towards larger size, is temporally linked to the onset of seasonally intensified upwelling along coastal ecosystems. High prey densities resulting from wind-driven upwelling, rather than abundant resources alone, are the primary determinant of efficient foraging in extant mysticetes and Late Pliocene changes in ocean dynamics may have provided an ecological pathway to gigantism in multiple independent lineages. © 2017 The Author(s).

Independent evolution of baleen whale gigantism linked to Plio-Pleistocene ocean dynamics

PubMed Central

Goldbogen, Jeremy A.

2017-01-01

Vertebrates have evolved to gigantic sizes repeatedly over the past 250 Myr, reaching their extreme in today's baleen whales (Mysticeti). Hypotheses for the evolution of exceptionally large size in mysticetes range from niche partitioning to predator avoidance, but there has been no quantitative examination of body size evolutionary dynamics in this clade and it remains unclear when, why or how gigantism evolved. By fitting phylogenetic macroevolutionary models to a dataset consisting of living and extinct species, we show that mysticetes underwent a clade-wide shift in their mode of body size evolution during the Plio-Pleistocene. This transition, from Brownian motion-like dynamics to a trended random walk towards larger size, is temporally linked to the onset of seasonally intensified upwelling along coastal ecosystems. High prey densities resulting from wind-driven upwelling, rather than abundant resources alone, are the primary determinant of efficient foraging in extant mysticetes and Late Pliocene changes in ocean dynamics may have provided an ecological pathway to gigantism in multiple independent lineages. PMID:28539520

Current Opinion in Endocrinology, Diabetes, and Obesity “Pituitary gigantism: Update on Molecular Biology and Management”

PubMed Central

Lodish, Maya B.; Trivellin, Giampaolo; Stratakis, Constantine A.

2016-01-01

Purpose of review To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions. Recent findings Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene, multiple endocrine neoplasia types 1 and 4, McCune Albright Syndrome, Carney Complex, and the paraganglioma, pheochromocytoma and pituitary adenoma association (3PA) due to succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging. Summary Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach (partial or total hypophysectomy), and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone. PMID:26574647

Oxygen hypothesis of polar gigantism not supported by performance of Antarctic pycnogonids in hypoxia

PubMed Central

Woods, H. Arthur; Moran, Amy L.; Arango, Claudia P.; Mullen, Lindy; Shields, Chris

2008-01-01

Compared to temperate and tropical relatives, some high-latitude marine species are large-bodied, a phenomenon known as polar gigantism. A leading hypothesis on the physiological basis of gigantism posits that, in polar water, high oxygen availability coupled to low metabolic rates relieves constraints on oxygen transport and allows the evolution of large body size. Here, we test the oxygen hypothesis using Antarctic pycnogonids, which have been evolving in very cold conditions (−1.8–0°C) for several million years and contain spectacular examples of gigantism. Pycnogonids from 12 species, spanning three orders of magnitude in body mass, were collected from McMurdo Sound, Antarctica. Individual sea spiders were forced into activity and their performance was measured at different experimental levels of dissolved oxygen (DO). The oxygen hypothesis predicts that, all else being equal, large pycnogonids should perform disproportionately poorly in hypoxia, an outcome that would appear as a statistically significant interaction between body size and oxygen level. In fact, although we found large effects of DO on performance, and substantial interspecific variability in oxygen sensitivity, there was no evidence for size×DO interactions. These data do not support the oxygen hypothesis of Antarctic pycnogonid gigantism and suggest that explanations must be sought in other ecological or evolutionary processes. PMID:19129117

Oxygen hypothesis of polar gigantism not supported by performance of Antarctic pycnogonids in hypoxia.

PubMed

Woods, H Arthur; Moran, Amy L; Arango, Claudia P; Mullen, Lindy; Shields, Chris

2009-03-22

Compared to temperate and tropical relatives, some high-latitude marine species are large-bodied, a phenomenon known as polar gigantism. A leading hypothesis on the physiological basis of gigantism posits that, in polar water, high oxygen availability coupled to low metabolic rates relieves constraints on oxygen transport and allows the evolution of large body size. Here, we test the oxygen hypothesis using Antarctic pycnogonids, which have been evolving in very cold conditions (-1.8-0 degrees C) for several million years and contain spectacular examples of gigantism. Pycnogonids from 12 species, spanning three orders of magnitude in body mass, were collected from McMurdo Sound, Antarctica. Individual sea spiders were forced into activity and their performance was measured at different experimental levels of dissolved oxygen (DO). The oxygen hypothesis predicts that, all else being equal, large pycnogonids should perform disproportionately poorly in hypoxia, an outcome that would appear as a statistically significant interaction between body size and oxygen level. In fact, although we found large effects of DO on performance, and substantial interspecific variability in oxygen sensitivity, there was no evidence for sizexDO interactions. These data do not support the oxygen hypothesis of Antarctic pycnogonid gigantism and suggest that explanations must be sought in other ecological or evolutionary processes.

Evolution of gigantism in nine-spined sticklebacks.

PubMed

Herczeg, Gábor; Gonda, Abigél; Merilä, Juha

2009-12-01

The relaxation of predation and interspecific competition are hypothesized to allow evolution toward "optimal" body size in island environments, resulting in the gigantism of small organisms. We tested this hypothesis by studying a small teleost (nine-spined stickleback, Pungitius pungitius) from four marine and five lake (diverse fish community) and nine pond (impoverished fish community) populations. In line with theory, pond fish tended to be larger than their marine or lake conspecifics, sometimes reaching giant sizes. In two geographically independent cases when predatory fish had been introduced into ponds, fish were smaller than those in nearby ponds lacking predators. Pond fish were also smaller when found in sympatry with three-spined stickleback (Gasterosteus aculeatus) than those in ponds lacking competitors. Size-at-age analyses demonstrated that larger size in ponds was achieved by both increased growth rates and extended longevity of pond fish. Results from a common garden experiment indicate that the growth differences had a genetic basis: pond fish developed two to three times higher body mass than marine fish during 36 weeks of growth under similar conditions. Hence, reduced risk of predation and interspecific competition appear to be chief forces driving insular body size evolution toward gigantism.

Defects in codoped NiO with gigantic dielectric response

NASA Astrophysics Data System (ADS)

Wu, Ping; Ligatchev, Valeri; Yu, Zhi Gen; Zheng, Jianwei; Sullivan, Michael B.; Zeng, Yingzhi

2009-06-01

We combine first-principles, statistical, and phenomenological methods to investigate the electronic and dielectric properties of NiO and clarify the nature of the gigantic dielectric response in codoped NiO. Unlike previous models which are dependent on grain-boundary effects, our model based on small polaron hopping in homogeneous material predicts the dielectric permittivity (104-5) for heavily Li- and MD -codoped NiO (MD=Ti,Al,Si) . Furthermore, we reproduce the experimental trends in dielectric properties as a function of the dopants nature and their concentrations, as well as the reported activation energies for the relaxation in Li- and Ti-codoped NiO (0.308 eV or 0.153 eV depending on the Fermi-level position). In this study, we demonstrate that small polaron hopping on dopant levels is the dominant mechanism for the gigantic dielectric response in these codoped NiO.

Pituitary gigantism: a case report.

PubMed

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

To present a rare case of gigantism. A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

Pituitary Gigantism: A Case Report

PubMed Central

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P.; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-01-01

Objective: To present a rare case of gigantism. Case Report: A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment. PMID:23565401

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

PubMed

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Prolactin-secreting pituitary adenoma in a man with gigantism: a case report.

PubMed

Peillon, F; Philippon, J; Brandi, A M; Fohanno, D; Laplane, D; Dubois, M P; Decourt, J

1979-12-01

A prolactin-secreting pituitary adenoma was removed trans-sphenoidally from a 37 years old man with gigantism (218 cm). Serum levels of prolactin (PRL) were elevated pre-operatively and decreased after administration of L-Dopa with no increase after TRH as is usually observed in PRL-secreting adenomas. Growth hormone (GH) and somatomedin serum levels were normal with no modification of GH after insulin hypoglycemia, oral glucose loading or L-Dopa. Morphological examination of the tumour demonstrated the presence of lactotrophs by light and electron microscopy and by immunofluorescense staining. No somatotrophs were found. In this unique case, the relationship between a PRL-secreting adenoma and gigantism is discussed.

Assessment of Unusual Gigantic Jets observed during the Monsoon season: First observations from Indian Subcontinent.

PubMed

Singh, Rajesh; Maurya, Ajeet K; Chanrion, Olivier; Neubert, Torsten; Cummer, Steven A; Mlynarczyk, Janusz; Cohen, Morris B; Siingh, Devendraa; Kumar, Sushil

2017-11-27

Gigantic Jets are electric discharges from thunderstorm cloud tops to the bottom of ionosphere at ~90 km altitude and electrically connect the troposphere and lower ionosphere. Since their first report in 2002, sporadic observations have been reported from ground and space based observations. Here we report first observations of Gigantic Jets in Indian subcontinent over the Indo-Gangetic plains during the monsoon season. Two storms each produced two jets with characteristics not documented so far. Jets propagated ~37 km up remarkably in ~5 ms with velocity of ~7.4 × 10 6 ms -1 and disappeared within ~40-80 ms, which is faster compared to jets reported earlier. The electromagnetic signatures show that they are of negative polarity, transporting net negative charge of ~17-23 C to the lower ionosphere. One jet had an unusual form observed for the first time, which emerged from the leading edge of a slowly drifting complex convective cloud close to the highest regions at ~17 km altitude. A horizontal displacement of ~10 km developed at ~50 km altitude before connecting to the lower ionosphere. Modeling of these Gigantic jets suggests that Gigantic Jets may bend when initiated at the edge of clouds with misaligned vertical charge distribution.

Spontaneous remission of acromegaly or gigantism due to subclinical apoplexy of pituitary growth hormone adenoma.

PubMed

Wang, Xian-Ling; Dou, Jing-Tao; Lü, Zhao-Hui; Zhong, Wen-Wen; Ba, Jian-Ming; Jin, Du; Lu, Ju-Ming; Pan, Chang-Yu; Mu, Yi-Ming

2011-11-01

Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.

Management of type 2 diabetes mellitus associated with pituitary gigantism.

PubMed

Ali, Omar; Banerjee, Swati; Kelly, Daniel F; Lee, Phillip D K

2007-01-01

Pituitary gigantism, a condition of endogenous growth hormone (GH) hypersecretion prior to epiphyseal closure, is a rare condition. In the adult condition of GH excess, acromegaly, the occurrence of type 2 diabetes mellitus (T2DM) and diabetic ketoacidosis (DKA) have been reported, with resolution following normalization of GH levels. We report the case of a 16-year-old male with pituitary gigantism due to a large invasive suprasellar adenoma who presented with T2DM and DKA. Despite surgical de-bulking, radiotherapy and medical treatment with cabergoline and pegvisomant, GH and insulin-like growth factor-I (IGF-I) levels remained elevated. However, the T2DM and recurrent DKA were successfully managed with metformin and low-dose glargine insulin, respectively. We review the pathophysiology of T2DM and DKA in growth hormone excess and available treatment options.

Hereditary pituitary hyperplasia with infantile gigantism.

PubMed

Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

2011-12-01

We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

A rare association of localized gigantism with tuberous sclerosis.

PubMed

Reddy, B S; Sheriff, M O; Garg, B R; Ratnakar, C

1992-10-01

An unusual association of localized gigantism with hypertrophy of the long bones and soft tissues in the left lower limb in an 18-year-old male with tuberous sclerosis (TS) is reported. The significance of this association is discussed from the point of view of its common neural crest origin during embryogenesis.

Syndrome of fetal gigantism, renal hamartomas, and nephroblastomatosis with Wilms' tumor.

PubMed

Perlman, M; Levin, M; Wittels, B

1975-04-01

A new case of the fetal gigantism-renal hamartomas-nephroblastomatosis syndrome is described, in which a Wilms' tumor occurred. It is considered that this observation provides strong evidence for the interrelationship between renal dysplasia and renal neoplasia.

Hereditary Pituitary Hyperplasia with Infantile Gigantism

PubMed Central

Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

2011-01-01

Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

A gigantic nothosaur (Reptilia: Sauropterygia) from the Middle Triassic of SW China and its implication for the Triassic biotic recovery

NASA Astrophysics Data System (ADS)

Liu, Jun; Hu, Shi-Xue; Rieppel, Olivier; Jiang, Da-Yong; Benton, Michael J.; Kelley, Neil P.; Aitchison, Jonathan C.; Zhou, Chang-Yong; Wen, Wen; Huang, Jin-Yuan; Xie, Tao; Lv, Tao

2014-11-01

The presence of gigantic apex predators in the eastern Panthalassic and western Tethyan oceans suggests that complex ecosystems in the sea had become re-established in these regions at least by the early Middle Triassic, after the Permian-Triassic mass extinction (PTME). However, it is not clear whether oceanic ecosystem recovery from the PTME was globally synchronous because of the apparent lack of such predators in the eastern Tethyan/western Panthalassic region prior to the Late Triassic. Here we report a gigantic nothosaur from the lower Middle Triassic of Luoping in southwest China (eastern Tethyan ocean), which possesses the largest known lower jaw among Triassic sauropterygians. Phylogenetic analysis suggests parallel evolution of gigantism in Triassic sauropterygians. Discovery of this gigantic apex predator, together with associated diverse marine reptiles and the complex food web, indicates global recovery of shallow marine ecosystems from PTME by the early Middle Triassic.

A gigantic nothosaur (Reptilia: Sauropterygia) from the Middle Triassic of SW China and its implication for the Triassic biotic recovery.

PubMed

Liu, Jun; Hu, Shi-Xue; Rieppel, Olivier; Jiang, Da-Yong; Benton, Michael J; Kelley, Neil P; Aitchison, Jonathan C; Zhou, Chang-Yong; Wen, Wen; Huang, Jin-Yuan; Xie, Tao; Lv, Tao

2014-11-27

The presence of gigantic apex predators in the eastern Panthalassic and western Tethyan oceans suggests that complex ecosystems in the sea had become re-established in these regions at least by the early Middle Triassic, after the Permian-Triassic mass extinction (PTME). However, it is not clear whether oceanic ecosystem recovery from the PTME was globally synchronous because of the apparent lack of such predators in the eastern Tethyan/western Panthalassic region prior to the Late Triassic. Here we report a gigantic nothosaur from the lower Middle Triassic of Luoping in southwest China (eastern Tethyan ocean), which possesses the largest known lower jaw among Triassic sauropterygians. Phylogenetic analysis suggests parallel evolution of gigantism in Triassic sauropterygians. Discovery of this gigantic apex predator, together with associated diverse marine reptiles and the complex food web, indicates global recovery of shallow marine ecosystems from PTME by the early Middle Triassic.

A gigantic nothosaur (Reptilia: Sauropterygia) from the Middle Triassic of SW China and its implication for the Triassic biotic recovery

PubMed Central

Liu, Jun; Hu, Shi-xue; Rieppel, Olivier; Jiang, Da-yong; Benton, Michael J.; Kelley, Neil P.; Aitchison, Jonathan C.; Zhou, Chang-yong; Wen, Wen; Huang, Jin-yuan; Xie, Tao; Lv, Tao

2014-01-01

The presence of gigantic apex predators in the eastern Panthalassic and western Tethyan oceans suggests that complex ecosystems in the sea had become re-established in these regions at least by the early Middle Triassic, after the Permian-Triassic mass extinction (PTME). However, it is not clear whether oceanic ecosystem recovery from the PTME was globally synchronous because of the apparent lack of such predators in the eastern Tethyan/western Panthalassic region prior to the Late Triassic. Here we report a gigantic nothosaur from the lower Middle Triassic of Luoping in southwest China (eastern Tethyan ocean), which possesses the largest known lower jaw among Triassic sauropterygians. Phylogenetic analysis suggests parallel evolution of gigantism in Triassic sauropterygians. Discovery of this gigantic apex predator, together with associated diverse marine reptiles and the complex food web, indicates global recovery of shallow marine ecosystems from PTME by the early Middle Triassic. PMID:25429609

Regional endothermy as a trigger for gigantism in some extinct macropredatory sharks.

PubMed

Ferrón, Humberto G

2017-01-01

Otodontids include some of the largest macropredatory sharks that ever lived, the most extreme case being Otodus (Megaselachus) megalodon. The reasons underlying their gigantism, distribution patterns and extinction have been classically linked with climatic factors and the evolution, radiation and migrations of cetaceans during the Paleogene. However, most of these previous proposals are based on the idea of otodontids as ectothermic sharks regardless of the ecological, energetic and body size constraints that this implies. Interestingly, a few recent studies have suggested the possible existence of endothermy in these sharks thus opening the door to a series of new interpretations. Accordingly, this work proposes that regional endothermy was present in otodontids and some closely related taxa (cretoxyrhinids), playing an important role in the evolution of gigantism and in allowing an active mode of live. The existence of regional endothermy in these groups is supported here by three different approaches including isotopic-based approximations, swimming speed inferences and the application of a novel methodology for assessing energetic budget and cost of swimming in extinct taxa. In addition, this finding has wider implications. It calls into question some previous paleotemperature estimates based partially on these taxa, suggests that the existing hypothesis about the evolution of regional endothermy in fishes requires modification, and provides key evidence for understanding the evolution of gigantism in active macropredators.

Regional endothermy as a trigger for gigantism in some extinct macropredatory sharks

PubMed Central

2017-01-01

Otodontids include some of the largest macropredatory sharks that ever lived, the most extreme case being Otodus (Megaselachus) megalodon. The reasons underlying their gigantism, distribution patterns and extinction have been classically linked with climatic factors and the evolution, radiation and migrations of cetaceans during the Paleogene. However, most of these previous proposals are based on the idea of otodontids as ectothermic sharks regardless of the ecological, energetic and body size constraints that this implies. Interestingly, a few recent studies have suggested the possible existence of endothermy in these sharks thus opening the door to a series of new interpretations. Accordingly, this work proposes that regional endothermy was present in otodontids and some closely related taxa (cretoxyrhinids), playing an important role in the evolution of gigantism and in allowing an active mode of live. The existence of regional endothermy in these groups is supported here by three different approaches including isotopic-based approximations, swimming speed inferences and the application of a novel methodology for assessing energetic budget and cost of swimming in extinct taxa. In addition, this finding has wider implications. It calls into question some previous paleotemperature estimates based partially on these taxa, suggests that the existing hypothesis about the evolution of regional endothermy in fishes requires modification, and provides key evidence for understanding the evolution of gigantism in active macropredators. PMID:28938002

Gigantic jets between a thundercloud and the ionosphere.

PubMed

Su, H T; Hsu, R R; Chen, A B; Wang, Y C; Hsiao, W S; Lai, W C; Lee, L C; Sato, M; Fukunishi, H

2003-06-26

Transient luminous events in the atmosphere, such as lighting-induced sprites and upwardly discharging blue jets, were discovered recently in the region between thunderclouds and the ionosphere. In the conventional picture, the main components of Earth's global electric circuit include thunderstorms, the conducting ionosphere, the downward fair-weather currents and the conducting Earth. Thunderstorms serve as one of the generators that drive current upward from cloud tops to the ionosphere, where the electric potential is hundreds of kilovolts higher than Earth's surface. It has not been clear, however, whether all the important components of the global circuit have even been identified. Here we report observations of five gigantic jets that establish a direct link between a thundercloud (altitude approximately 16 km) and the ionosphere at 90 km elevation. Extremely-low-frequency radio waves in four events were detected, while no cloud-to-ground lightning was observed to trigger these events. Our result indicates that the extremely-low-frequency waves were generated by negative cloud-to-ionosphere discharges, which would reduce the electrical potential between ionosphere and ground. Therefore, the conventional picture of the global electric circuit needs to be modified to include the contributions of gigantic jets and possibly sprites.

Von recklinghausen neurofibromatosis-pachydermatocele causing lower limb gigantism: a case report.

PubMed

Rekha, Arcot; Gopalan, T R

2006-03-01

Gigantism of the lower limb can occur because of plexiform neurofibromas. This condition is seen with café au lait patches and multiple neurofibromatosis in this case of von Recklinghausen neurofibromatosis. We report our patient and review literature of this uncommon condition.

[Digital gigantism of the foot: a clinical study of 12 cases].

PubMed

Wang, Hai-hua; Tian, Guang-lei; Zhu, Yin; Zhang, You-le; Zhao, Jun-hui; Tian, Wen

2008-03-15

To summarize the clinical characteristic and outcome of digital gigantism of the foot. Retrospectively analyze the clinical documents of cases of digital gigantism of the foot. Twelve 12 cases with 13 feet in this study included 8 male and 4 female with an average 4.6-years-old. All the deformities were found at birth. Multiple toes involved were more than single toe, and tibial toe involved more than fibular. Forefoot was enlarged. All the phalanges involved and partial metatarsal bones were enlarged. Marked increase in subcutaneous fat was found in all cases in the operation which infiltrated interossei and articular capsules. The appearance of the nerves and its branches in the foot were normal and fat infiltrating was not discovered. The operation types included debulking, epiphyseal arrest, amputation, nerve stripping and anastomosis. Seven cases were followed up with mean periods 25.6 months. Functional evaluation according to a criterion formulated by author revealed a result of 2 excellent, 2 good and 3 fair. Digital gigantism of the foot is an uncommon congenital deformity of the foot characterized by overgrowth of both the soft-tissue and the osseous elements of the enlarged toe and forefoot. Surgical treatment is the unique method, and the goal is to reduce the size of the foot to allow fitting regular shoes and walking readily. There are several types of operations which to be chosen. The indication, the timing of operative intervention and the selection of operation type should be paid more attention.

Gigantic negative magnetoresistance in the bulk of a disordered topological insulator

NASA Astrophysics Data System (ADS)

Breunig, Oliver; Wang, Zhiwei; Taskin, A. A.; Lux, Jonathan; Rosch, Achim; Ando, Yoichi

2017-05-01

With the recent discovery of Weyl semimetals, the phenomenon of negative magnetoresistance (MR) is attracting renewed interest. Large negative MR is usually related to magnetism, but the chiral anomaly in Weyl semimetals is a rare exception. Here we report a mechanism for large negative MR which is also unrelated to magnetism but is related to disorder. In the nearly bulk-insulating topological insulator TlBi0.15Sb0.85Te2, we observed gigantic negative MR reaching 98% in 14 T at 10 K, which is unprecedented in a nonmagnetic system. Supported by numerical simulations, we argue that this phenomenon is likely due to the Zeeman effect on a barely percolating current path formed in the disordered bulk. Since disorder can also lead to non-saturating linear MR in Ag2+δSe, the present finding suggests that disorder engineering in narrow-gap systems is useful for realizing gigantic MR in both positive and negative directions.

GaAs-oxide interface states - Gigantic photoionization via Auger-like process

NASA Technical Reports Server (NTRS)

Lagowski, J.; Kazior, T. E.; Gatos, H. C.; Walukiewicz, W.; Siejka, J.

1981-01-01

Spectral and transient responses of photostimulated current in MOS structures were employed for the study of GaAs-anodic oxide interface states. Discrete deep traps at 0.7 and 0.85 eV below the conduction band were found with concentrations of 5 x 10 to the 12th/sq cm and 7 x 10 to the 11th/sq cm, respectively. These traps coincide with interface states induced on clean GaAs surfaces by oxygen and/or metal adatoms (submonolayer coverage). In contrast to surfaces with low oxygen coverage, the GaAs-thick oxide interfaces exhibited a high density (about 10 to the 14th/sq cm) of shallow donors and acceptors. Photoexcitation of these donor-acceptor pairs led to a gigantic photoionization of deep interface states with rates 1000 times greater than direct transitions into the conduction band. The gigantic photoionization is explained on the basis of energy transfer from excited donor-acceptor pairs to deep states.

Sotos syndrome: An interesting disorder with gigantism.

PubMed

Nalini, A; Biswas, Arundhati

2008-07-01

We report the case of a 16-year-old boy diagnosed to have Sotos syndrome, with rare association of bilateral primary optic atrophy and epilepsy. He presented with accelerated linear growth, facial gestalt, distinctive facial features, seizures and progressive diminution of vision in both eyes. He had features of gigantism from early childhood. An MRI showed that brain and endocrine functions were normal. This case is of interest, as we have to be aware of this not so rare disorder. In addition to the classic features, there were two unusual associations with Sotos syndrome in the patient.

Central neurocytoma presenting with gigantism: case report.

PubMed

Araki, Y; Sakai, N; Andoh, T; Yoshimura, S; Yamada, H

1992-08-01

We report a case of central neurocytoma presenting with gigantism. The patient was a 19-year-old man with a 2-year history of rapid growth. Computed tomography revealed a round, slightly enhancing calcified tumor in the septal region. This lesion was resected, and postoperative radiotherapy was given. The preoperative serum growth hormone level was 20.7 ng/mL, and postoperatively this fell to 0.9 ng/mL. Pituitary dysfunction was not noted either before or after the operation. A low level of production of growth hormone releasing factor was detected when tumor cells obtained during surgery were cultured.

Sotos syndrome: An interesting disorder with gigantism

PubMed Central

Nalini, A.; Biswas, Arundhati

2008-01-01

We report the case of a 16-year-old boy diagnosed to have Sotos syndrome, with rare association of bilateral primary optic atrophy and epilepsy. He presented with accelerated linear growth, facial gestalt, distinctive facial features, seizures and progressive diminution of vision in both eyes. He had features of gigantism from early childhood. An MRI showed that brain and endocrine functions were normal. This case is of interest, as we have to be aware of this not so rare disorder. In addition to the classic features, there were two unusual associations with Sotos syndrome in the patient. PMID:19893668

Transsphenoidal microsurgery in the treatment of acromegaly and gigantism.

PubMed

Arafah, B U; Brodkey, J S; Kaufman, B; Velasco, M; Manni, A; Pearson, O H

1980-03-01

Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal.

Proteus syndrome: A rare cause of gigantic limb.

PubMed

Chakrabarti, Nandini; Chattopadhyay, Chandan; Bhuban, Majhi; Pal, Salil Kumar

2014-04-01

A congenital disorder with variable manifestations, including partial gigantism of the hands and feet with hypertrophy of soles, nevi, hemihypertrophy, gynecomastia, macrocephaly and other skull abnormalities, and abdominal lipomatosis. The cause is unknown, although a genetic origin, generally of autosomal-dominant transmission, has been conjectured. Symptoms can be treated, but there is no known cure. We present the case of a young male with grotesque overgrowth of the right lower limb, splenomegaly and multiple nevi. Angiography revealed venous malformation within the limb. The findings are in conformity to the criteria for the Proteus syndrome.

Ecological explanations to island gigantism: dietary niche divergence, predation, and size in an endemic lizard.

PubMed

Runemark, Anna; Sagonas, Kostas; Svensson, Erik I

2015-08-01

Although rapid evolution of body size on islands has long been known, the ecological mechanisms behind this island phenomenon remain poorly understood. Diet is an important selective pressure for morphological divergence. Here we investigate if selection for novel diets has contributed to the multiple independent cases of island gigantism in the Skyros wall lizard (Podarcis gaigeae) and if diet, predation, or both factors best explain island gigantism. We combined data on body size, shape, bite force, and realized and available diets to address this. Several lines of evidence suggest that diet has contributed to the island gigantism. The larger islet lizards have relatively wider heads and higher bite performance in relation to mainland lizards than would be expected from size differences alone. The proportions of consumed and available hard prey are higher on islets than mainland localities, and lizard body size is significantly correlated with the proportion of hard prey. Furthermore, the main axis of divergence in head shape is significantly correlated with dietary divergence. Finally, a model with only diet and one including diet and predation regime explain body size divergence equally well. Our results suggest that diet is an important ecological factor behind insular body size divergence, but could be consistent with an additional role for predation.

Cope's Rule and Romer's theory: patterns of diversity and gigantism in eurypterids and Palaeozoic vertebrates

PubMed Central

Lamsdell, James C.; Braddy, Simon J.

2010-01-01

Gigantism is widespread among Palaeozoic arthropods, yet causal mechanisms, particularly the role of (abiotic) environmental factors versus (biotic) competition, remain unknown. The eurypterids (Arthropoda: Chelicerata) include the largest arthropods; gigantic predatory pterygotids (Eurypterina) during the Siluro-Devonian and bizarre sweep-feeding hibbertopterids (Stylonurina) from the Carboniferous to end-Permian. Analysis of family-level originations and extinctions among eurypterids and Palaeozoic vertebrates show that the diversity of Eurypterina waned during the Devonian, while the Placodermi radiated, yet Stylonurina remained relatively unaffected; adopting a sweep-feeding strategy they maintained their large body size by avoiding competition, and persisted throughout the Late Palaeozoic while the predatory nektonic Eurypterina (including the giant pterygotids) declined during the Devonian, possibly out-competed by other predators including jawed vertebrates. PMID:19828493

Gigantism Precedes Filter Feeding in Baleen Whale Evolution.

PubMed

Fordyce, R Ewan; Marx, Felix G

2018-05-21

Baleen whales (Mysticeti) are the largest animals on Earth, thanks to their ability to filter huge volumes of small prey from seawater. Mysticetes appeared during the Late Eocene, but evidence of their early evolution remains both sparse and controversial [1, 2], with several models competing to explain the origin of baleen-based bulk feeding [3-6]. Here, we describe a virtually complete skull of Llanocetus denticrenatus, the second-oldest (ca. 34 Ma) mysticete known. The new material represents the same individual as the type and only specimen, a fragmentary mandible. Phylogenetic analysis groups Llanocetus with the oldest mysticete, Mystacodon selenensis [2], into the basal family Llanocetidae. Llanocetus is gigantic (body length ∼8 m) compared to other early mysticetes [7-9]. The broad rostrum has sharp, widely spaced teeth with marked dental abrasion and attrition, suggesting biting and occlusal shearing. As in extant mysticetes, the palate bears many sulci, commonly interpreted as osteological correlates of baleen [3]. Unexpectedly, these sulci converge on the upper alveoli, suggesting a peri-dental blood supply to well-developed gums, rather than to inter-alveolar racks of baleen. We interpret Llanocetus as a raptorial or suction feeder, revealing that whales evolved gigantism well before the emergence of filter feeding. Rather than driving the origin of mysticetes, baleen and filtering most likely only arose after an initial phase of suction-assisted raptorial feeding [2, 4, 5]. This scenario differs strikingly from that proposed for odontocetes, whose defining adaptation-echolocation-was present even in their earliest representatives [10]. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Gigantic keloïds after chicken-pox. A case report].

PubMed

Gathse, A; Ibara, J R; Obengui; Moyen, G

2003-01-01

Keloïds are tumors which appear after a lesion or spontaneously. They are frequent on black skin. We report a gigantic keloïd case appeared after chicken-pox on a 29 year-old black girl who had viral infection when she was 6 years old. The tumors increased after chirurgical treatment and became very unaesthetic. This observation specific by its clinical presentation relates the treatment difficulties of these tumors in our area.

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism.

PubMed

Jennings, A M; Robinson, A; Kandler, R H; Betts, R P; Ryder, R E; Cullen, D R

1993-07-01

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiological assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (> 10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.

The evolution of island gigantism and body size variation in tortoises and turtles

PubMed Central

Jaffe, Alexander L.; Slater, Graham J.; Alfaro, Michael E.

2011-01-01

Extant chelonians (turtles and tortoises) span almost four orders of magnitude of body size, including the startling examples of gigantism seen in the tortoises of the Galapagos and Seychelles islands. However, the evolutionary determinants of size diversity in chelonians are poorly understood. We present a comparative analysis of body size evolution in turtles and tortoises within a phylogenetic framework. Our results reveal a pronounced relationship between habitat and optimal body size in chelonians. We found strong evidence for separate, larger optimal body sizes for sea turtles and island tortoises, the latter showing support for the rule of island gigantism in non-mammalian amniotes. Optimal sizes for freshwater and mainland terrestrial turtles are similar and smaller, although the range of body size variation in these forms is qualitatively greater. The greater number of potential niches in freshwater and terrestrial environments may mean that body size relationships are more complicated in these habitats. PMID:21270022

Pituitary gigantism in a 31 month old girl: endocrine studies and successful response to hypophysectomy.

PubMed

Espiner, E A; Carter, T A; Abbott, G D; Wrightson, P

1981-01-01

A case of pituitary gigantism occurring in a 31 month old female child is reported. Growth records indicate that the disorder began early in the second yr of life. Apart from her size and history of excessive sweating, there were no characteristic clinical features of endocrinopathy. Elevated and autonomous secretion of GH (60-109 microgram/l) and prolactin were corrected by the removal of an eosinophilic pituitary adenoma. In the subsequent 6 yr, despite the presence of immunoreactive GH (4.6-17.3 microgram/l), plasma somatomedin was subnormal and the patient showed growth failure which responded normally to exogenous GH therapy. This case, which appears to be the youngest example of verified pituitary gigantism on record, illustrates that a successful outcome can be achieved by surgical ablative therapy.

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed

Arisaka, O; Hall, R; Hughes, I A

1983-10-08

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism.

Hereditary Gigantism-the biblical giant Goliath and his brothers

PubMed Central

Donnelly, Deirdre E; Morrison, Patrick J

2014-01-01

The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members’ battles with David and his relatives. PMID:25075136

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed Central

Arisaka, O; Hall, R; Hughes, I A

1983-01-01

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism. PMID:6311318

Hereditary Gigantism-the biblical giant Goliath and his brothers.

PubMed

Donnelly, Deirdre E; Morrison, Patrick J

2014-05-01

The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members' battles with David and his relatives.

Vínculos observacionais para o processo-S em estrelas gigantes de Bário

NASA Astrophysics Data System (ADS)

Smiljanic, R. H. S.; Porto de Mello, G. F.; da Silva, L.

2003-08-01

Estrelas de bário são gigantes vermelhas de tipo GK que apresentam excessos atmosféricos dos elementos do processo-s. Tais excessos são esperados em estrelas na fase de pulsos térmicos do AGB (TP-AGB). As estrelas de bário são, no entanto, menos massivas e menos luminosas que as estrelas do AGB, assim, não poderiam ter se auto-enriquecido. Seu enriquecimento teria origem em uma estrela companheira, inicialmente mais massiva, que evolui pelo TP-AGB, se auto-enriquece com os elementos do processo-s e transfere material contaminado para a atmosfera da atual estrela de bário. A companheira evolui então para anã branca deixando de ser observada diretamente. As estrelas de bário são, portanto, úteis como testes observacionais para teorias de nucleossíntese pelo processo-s, convecção e perda de massa. Análises detalhadas de abundância com dados de alta qualidade para estes objetos são ainda escassas na literatura. Neste trabalho construímos modelos de atmosferas e, procedendo a uma análise diferencial, determinamos parâmetros atmosféricos e evolutivos de uma amostra de dez gigantes de bário e quatro normais. Determinamos seus padrões de abundância para Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Y, Zr, Ba, La, Ce, Nd, Sm, Eu e Gd, concluindo que algumas estrelas classificadas na literatura como gigantes de bário são na verdade gigantes normais. Comparamos dois padrões médios de abundância, para estrelas com grandes excessos e estrelas com excessos moderados, com modelos teóricos de enriquecimento pelo processo-s. Os dois grupos de estrelas são ajustados pelos mesmos parâmetros de exposição de nêutrons. Tal resultado sugere que a ocorrência do fenômeno de bário com diferentes intensidades não se deve a diferentes exposições de nêutrons. Discutimos ainda efeitos nucleossintéticos, ligados ao processo-s, sugeridos na literatura para os elementos Cu, Mn, V e Sc.

Gigantism caused by growth hormone secreting pituitary adenoma.

PubMed

Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

2014-06-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

Gigantism caused by growth hormone secreting pituitary adenoma

PubMed Central

Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi

2014-01-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

CT of the "Tegernsee Giant": juvenile gigantism and polyostotic fibrous dysplasia.

PubMed

Vogl, T J; Nerlich, A; Dresel, S H; Bergman, C

1994-01-01

We report the radiological findings in the unusual case of the Bavarian "Tegernsee Giant." With conventional radiography, CT, and histologic examination, we succeeded in diagnosing two disorders: The Tegernsee Giant suffered from (a) juvenile gigantism caused by a growth hormone-secreting tumor of the pituitary gland and (b) a polyostotic form of fibrous dysplasia of the skull and multiple bones particularly on the left side of the body.

Formación y evolución de planetas gigantes

NASA Astrophysics Data System (ADS)

Benvenuto, O. G.; Brunini, A.

Presentamos el estado actual del trabajo que estamos realizando en el estudio de la formación de planetas gigantes. Detallamos los algoritmos numéricos necesarios para realizar este tipo de cálculo. Presentamos algunos resultados de la formación de objetos con masas de hasta una docena de veces la del planeta Júpiter, resaltando las principales caracteríticas. Finalmente detallamos los problemas que pensamos abordar en un futuro cercano en este tema de investigación.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent.

PubMed

Kuo, Sheng-Fong; Chuang, Wen-Yu; Ng, Sohching; Chen, Chih-Hung; Chang, Chen-Nen; Chou, Chi-Hsiang; Weng, Wei-Chieh; Yeh, Chih-Hua; Lin, Jen-Der

2013-01-01

Hyperglycemia is seldom described in young patients with pituitary gigantism. Here, we describe the case of a 17-year-old Taiwanese boy who developed depressive mood disorder and diabetic ketoacidosis (DKA) at the presentation of pituitary gigantism. The boy complained of lethargy and dysphoric mood in June 2008. He presented at the emergency department with epigastralgia and dyspnea in January 2009. Results of laboratory tests suggested type 1 diabetes mellitus with DKA. However, serum C-peptide level was normal on follow-up. Although he had no obvious features of acral enlargement, a high level of insulin-like growth factor 1 was detected, and a 75 g oral glucose suppression test showed no suppression of serum growth hormone levels. A pituitary macroadenoma was found on subsequent magnetic resonance imaging. The pituitary adenoma was surgically removed, followed by gamma-knife radiosurgery, and Sandostatin long-acting release treatment. He was then administered metformin, 500 mg twice daily, and to date, his serum glycohemoglobin has been <7%.

High-detail snapshots of rare gigantic jet lightning

NASA Astrophysics Data System (ADS)

Schultz, Colin

2011-08-01

In the ionosphere, more than 80 kilometers above Earth's surface, incoming radiation reacts with the thin air to produce highly charged ions, inducing an electric potential between the ionosphere and the surface. This charge difference is dissipated by a slow leak from the ionosphere during calm weather and reinvigorated by a charge built up near the surface during a thunderstorm. In 2001, however, researchers discovered gigantic jets (GJs), powerful lightning that arcs from tropospheric clouds up to the ionosphere, suggesting there may be an alternate path by which charge is redistributed. GJs are transient species, and little is known about how much charge they can carry, how they form, or how common they are. In a step toward answering these questions, Lu et al. report on two GJs that occurred near very high frequency (VHF) lightning detection systems, which track the development of lightning in three spatial dimensions, giving an indication of the generation mechanism. The researchers also measured the charge transfer in the two GJs through remote sensing of magnetic fields. They found that both jets originated from the development of otherwise normal intracloud lightning. The dissipation of the cloud's positively charged upper layer allowed the negative lightning channel to break through and travel up out of the top of the cloud to the ionosphere. The first jet, which occurred off the coast of Florida, leapt up to 80 kilometers, depositing 110 coulombs of negative charge in 370 milliseconds. The second jet, observed in Oklahoma, traveled up to 90 kilometers, raising only 10-20 coulombs in 300 milliseconds. Each new observation of gigantic jets such as these can provide valuable information toward understanding this novel atmospheric behavior. (Geophysical Research Letters, doi:10.1029/2011GL047662, 2011)

Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.

PubMed

Rostomyan, Liliya; Daly, Adrian F; Petrossians, Patrick; Nachev, Emil; Lila, Anurag R; Lecoq, Anne-Lise; Lecumberri, Beatriz; Trivellin, Giampaolo; Salvatori, Roberto; Moraitis, Andreas G; Holdaway, Ian; Kranenburg-van Klaveren, Dianne J; Chiara Zatelli, Maria; Palacios, Nuria; Nozieres, Cecile; Zacharin, Margaret; Ebeling, Tapani; Ojaniemi, Marja; Rozhinskaya, Liudmila; Verrua, Elisa; Jaffrain-Rea, Marie-Lise; Filipponi, Silvia; Gusakova, Daria; Pronin, Vyacheslav; Bertherat, Jerome; Belaya, Zhanna; Ilovayskaya, Irena; Sahnoun-Fathallah, Mona; Sievers, Caroline; Stalla, Gunter K; Castermans, Emilie; Caberg, Jean-Hubert; Sorkina, Ekaterina; Auriemma, Renata Simona; Mittal, Sachin; Kareva, Maria; Lysy, Philippe A; Emy, Philippe; De Menis, Ernesto; Choong, Catherine S; Mantovani, Giovanna; Bours, Vincent; De Herder, Wouter; Brue, Thierry; Barlier, Anne; Neggers, Sebastian J C M M; Zacharieva, Sabina; Chanson, Philippe; Shah, Nalini Samir; Stratakis, Constantine A; Naves, Luciana A; Beckers, Albert

2015-10-01

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2 s.d. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) - occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases. © 2015 Society for Endocrinology.

The Oldest Recorded Case of Acromegaly and Gigantism in Iran.

PubMed

Najjari, Mohsen

2015-10-01

Here we commemorate the character and academic authority of Prof. Zabiholah Gorban (1903-2006), the founder of Shiraz medical school. No doubt, in the scope of history of contemporary medicine, he has been efficient and effective. With respect to this fact, his article on a rare case described in Acta anatomica published in Iran in 1966, entitled (Observations on a giant skeleton) is browsed and reviewed. A case named Siah Khan with combined acromegaly and gigantism that appears to have letters to say still after nearly half a century.

Macrodystrophia lipomatosa: a reconstructive approach to gigantism of the foot.

PubMed

Watt, Andrew J; Chung, Kevin C

2004-01-01

Localized gigantism poses a challenging surgical dilemma, and it may be treated with amputation. This case report documents the application of a reconstructive approach to a severe case of pedal macrodystrophia lipomatosa in a 1-year-old girl. A series of 3 surgeries were designed to reduce the length, width, height, and overall bulk of the congenitally enlarged foot. The 3 procedures debulked the foot for normal ambulation and same-size shoe wear for both feet. The resulting functional and aesthetic improvements achieved through reconstructive treatment provided a desirable alternative to amputation.

A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche?

PubMed

Iwatani, N; Kodama, M; Seto, H

1992-06-01

We describe a female child with pituitary gigantism and precocious adrenarche. From two years of age she showed unusual overgrowth, and at 5 years old she was 133.5 cm (+ 5.5 SD) tall and weighed 40.5 kg. Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test. In addition, the concentrations of serum dehydroepiandrosterone (DHA) and its sulfate (DHAS) were increased to adult levels, moving in accordance with changes in ACTH, which suggested that these androgens were secreted from the adrenal glands functionally. These androgens seemed to be responsible for her partial precocity. Prior reports have suggested that GH and/or PRL overproduction might have played a role in the induction of adrenarche. Also, in previous reports of 9 gigantism patients under 10 years old, the manifestation of precocious adrenarche was suggested in 8. Further investigation of the influence of GH and PRL on adrenal androgen production in children with pituitary gigantism is required. On the other hand, in short children with normal GH secretion, attention should be paid to whether or not the GH therapy in early childhood induces precocious adrenarche.

An orphan G-protein-coupled receptor causes human gigantism and/or acromegaly: Molecular biology and clinical correlations.

PubMed

Trivellin, Giampaolo; Hernández-Ramírez, Laura C; Swan, Jeremy; Stratakis, Constantine A

2018-04-01

X-linked acrogigantism (X-LAG) is a recently described form of familial or sporadic pituitary gigantism characterized by very early onset GH and IGF-1 excess, accelerated growth velocity, gigantism and/or acromegaloid features. Germline or somatic microduplications of the Xq26.3 chromosomal region, invariably involving the GPR101 gene, constitute the genetic defect leading to X-LAG. GPR101 encodes a class A G protein-coupled receptor that activates the 3',5'-cyclic adenosine monophosphate signaling pathway. Highly expressed in the central nervous system, the main physiological function and ligand of GPR101 remain unknown, but it seems to play a role in the normal development of the GHRH-GH axis. Early recognition of X-LAG cases is imperative because these patients require clinical management that differs from that of other patients with acromegaly or gigantism. Medical treatment with pegvisomant seems to be the best approach, since X-LAG tumors are resistant to the treatment with somatostatin analogues and dopamine agonists; surgical cure requires near-total hypophysectomy. Currently, the efforts of our research focus on the identification of GPR101 ligands; in addition, the long-term follow-up of X-LAG patients is of extreme interest as this is expected to lead to better understanding of GPR101 effects on human pathophysiology. Copyright © 2018. Published by Elsevier Ltd.

Gate-tunable gigantic lattice deformation in VO{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okuyama, D., E-mail: okuyama@riken.jp, E-mail: nakano@imr.tohoku.ac.jp, E-mail: iwasa@ap.t.u-tokyo.ac.jp; Hatano, T.; Nakano, M., E-mail: okuyama@riken.jp, E-mail: nakano@imr.tohoku.ac.jp, E-mail: iwasa@ap.t.u-tokyo.ac.jp

2014-01-13

We examined the impact of electric field on crystal lattice of vanadium dioxide (VO{sub 2}) in a field-effect transistor geometry by in-situ synchrotron x-ray diffraction measurements. Whereas the c-axis lattice parameter of VO{sub 2} decreases through the thermally induced insulator-to-metal phase transition, the gate-induced metallization was found to result in a significant increase of the c-axis length by almost 1% from that of the thermally stabilized insulating state. We also found that this gate-induced gigantic lattice deformation occurs even at the thermally stabilized metallic state, enabling dynamic control of c-axis lattice parameter by more than 1% at room temperature.

Pyodermia chronica glutealis complicated by acromegalic gigantism.

PubMed

Nishijima, S; Kasahara, M; Suzuki, K; Kondoh, M; Tsubura, A

1998-04-01

We report a case of pyodermia chronica glutealis complicated by acromegalic gigantism associated with hyperprolactinemia. The serum prolactin, growth hormone, adrenocorticotropic hormone, and 11-deoxycortisol levels were elevated, but the estradiol and dehydroepiandrosterone-sulphate levels were within normal limits. However, the testosterone level was very low. Histopathologically, we found sinus tracts and scarring in a specimen from the buttocks. We could not immunohistochemically detect clear androgen, growth hormone, or prolactin receptors at any site. The patient was a man with a height of 197 cm and weight of 140 kg, he had clinical features of active acromegaly such as excessive sweating and increased thickness of soft tissue. He was also diagnosed with diabetes mellitus. Under such conditions, bacteria could easily grow and lesions might have been aggravated by the heavy pressure from his weight, a possible causes of his pyodermia chronica glutealis.

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

PubMed

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

Gigantic Rolling Wave Captured on the Sun

NASA Image and Video Library

2017-12-08

A coronal mass ejection (CME) erupted from just around the edge of the sun on May 1, 2013, in a gigantic rolling wave. CMEs can shoot over a billion tons of particles into space at over a million miles per hour. This CME occurred on the sun’s limb and is not headed toward Earth. The video (seen here: bit.ly/103whUl), taken in extreme ultraviolet light by NASA’s Solar Dynamics Observatory (SDO), covers about two and a half hours. Credit: NASA/Goddard/SDO NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache.

PubMed

Otsuka, Fumio; Mizobuchi, Satoshi; Ogura, Toshio; Sato, Kenji; Yokoyama, Masataka; Makino, Hirofumi

2004-10-01

We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

A gigantic coronal jet ejected from a compact active region in a coronal hole

NASA Technical Reports Server (NTRS)

Shibata, K.; Nitta, N.; Strong, K. T.; Matsumoto, R.; Yokoyama, T.; Hirayama, T.; Hudson, H.; Ogawara, Y.

1994-01-01

A gigantic coronal jet greater than 3 x 10(exp 5) km long (nearly half the solar radius) has been found with the soft X-ray telescope (SXT) on board the solar X-ray satellite, Yohkoh. The jet was ejected on 1992 January 11 from an 'anemone-type' active region (AR) appearing in a coronal hole and is one of the largest coronal X-ray jets observed so far by SXT. This gigantic jet is the best observed example of many other smaller X-ray jets, because the spatial structures of both the jet and the AR located at its base are more easily resolved. The range of apparent translational velocities of the bulk of the jet was between 90 and 240 km s(exp -1), with the corresponding kinetic energy estimated to be of order of 10(exp 28) ergs. A detailed analysis reveals that the jet was associated with a loop brightening (a small flare) that occurred in the active region. Several features of this observation suggest and are consistent with a magnetic reconnection mechanism for the production of such a 'jet-loop-brightening' event.

Gigantic Dzyaloshinskii-Moriya interaction in the MnBi ultrathin films

NASA Astrophysics Data System (ADS)

Yu, Jie-Xiang; Zang, Jiadong; Zang's Team

The magnetic skyrmion, a swirling-like spin texture with nontrivial topology, is driven by strong Dzyaloshinskii-Moriya (DM) interaction originated from the spin-orbit coupling in inversion symmetry breaking systems. Here, based on first-principles calculations, we predict a new material, MnBi ultrathin film, with gigantic DM interactions. The ratio of the DM interaction to the Heisenberg exchange is about 0.3, exceeding any values reported so far. Its high Curie temperature, high coercivity, and large perpendicular magnetoanisotropy make MnBi a good candidate for future spintronics studies. Topologically nontrivial spin textures are emergent in this system. We expect further experimental efforts will be devoted into this systems.

Gigantic Jet Environments: A Meteorological Evaluation Using Reanalysis Data Sets

NASA Astrophysics Data System (ADS)

Splitt, M. E.; Lazarus, S. M.

2017-12-01

The meteorological conditions of gigantic jet (GJ) producing thunderstorms tend to be connected to maritime tropical environments. In particular, they have an affinity toward tropical disturbances including those with moderate values of upper tropospheric environmental wind shear. Wind shear related effects (including turbulence) in association with deep convection in these environments have been proposed as mechanisms for the arrangement of GJ favorable charge structures. This study focuses on a climatological evaluation in an effort to assess whether the proposed ingredients are consistent with observed GJ event regions. The Climate System Forecast System - Version 2 (CFSR V2) is used here to test for the proposed GJ conditions.

A Gray-purple Mass on the Floor of the Mouth: Gigantic Mucogingival Pyogenic Granuloma in a Teenage Patient.

PubMed

Brunet-LLobet, Lluís; Miranda-Rius, Jaume; Lahor-Soler, Eduard; Mrina, Ombeni; Nadal, Alfons

2014-01-01

Pyogenic granuloma is defined as a benign neoplasm of vascular phenotype. This case describes the clinical and histopathological features of a gigantic mucogingival pyogenic granuloma, in a 14-year-old healthy black boy. This exophytic gray-purple mass, related to a toothpick injury, had more than twelve-month evolution on the anterior mandible involving lingual area besides to the floor of the mouth pressing the right salivary duct. Conservative excision was performed, followed by uncomplicated healing with no recurrence in two years. The histopathological examination reported a pyogenic granuloma (lobular capillary haemangioma). The authors provide a discussion of the presurgical differential diagnosis of the lesion. This case report presents an extremely uncommon location of a gigantic pyogenic granuloma, involving mucogingival complex and affecting the salivary outflow. This clinical manuscript may shed light on the controversies about possible mechanisms inducing oral pyogenic granuloma.

Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886).

PubMed

de Herder, Wouter W

2009-01-01

In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism.

The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies.

PubMed

Neri, G; Martini-Neri, M E; Katz, B E; Opitz, J M

1984-09-01

We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed.

The parasitic castration and gigantism of Lymnaea truncatula infected with the larval stages of Fasciola hepatica.

PubMed

Wilson, R A; Denison, J

1980-01-01

The shells of Lymnaea truncatula infected with the larval stages of Fasciola hepatica were significantly longer than those of comparable uninfected controls. The dry mass (tissue, shell + parasite) of the same infected snails, 56 days after infection, was approximately twice that of the controls (tissue + shell). The increased mass of infected snails was not due to a disproportionate increase in shell weight relative to tissues. Infected snails maintained at 20 degrees C had virtually ceased egg production by 21 days post-infection whereas control snails continued to lay eggs steadily for the duration of the experiment. The dry mass of snail tissue plus the cumulative dry weight of eggs produced was taken as an indication of the ability of control snails to generate biomass. Similarly the tissue mass plus cumulative egg weight and parasite weight was taken as an indication of the ability of the infected snails to generate biomass. The control and infected snails were not significantly different in this respect indicating that the gigantism of infected snails could be the result of a switch in nutrient supply from reproduction to somatic tissue growth and parasite growth. Castration was brought about 17-21 days after infection as a result of the direct consumption of the ovotestis by a proportion of the redial population. In a separate experiment it was demonstrated that a population of infected snails maintained at 20 degrees C survived as long as a similar group of control snails. The findings with this host-parasite system are discussed in relation to possible mechanisms causing castration and gigantism in other digene-snail interactions, and in relation to parasitic castration in other groups. It is concluded that the observed gigantism of infected snails is more likely to have a nutritional rather than endocrine origin.

A Gray-purple Mass on the Floor of the Mouth: Gigantic Mucogingival Pyogenic Granuloma in a Teenage Patient

PubMed Central

Brunet-LLobet, Lluís; Miranda-Rius, Jaume; Lahor-Soler, Eduard; Mrina, Ombeni; Nadal, Alfons

2014-01-01

Pyogenic granuloma is defined as a benign neoplasm of vascular phenotype. This case describes the clinical and histopathological features of a gigantic mucogingival pyogenic granuloma, in a 14-year-old healthy black boy. This exophytic gray-purple mass, related to a toothpick injury, had more than twelve-month evolution on the anterior mandible involving lingual area besides to the floor of the mouth pressing the right salivary duct. Conservative excision was performed, followed by uncomplicated healing with no recurrence in two years. The histopathological examination reported a pyogenic granuloma (lobular capillary haemangioma). The authors provide a discussion of the presurgical differential diagnosis of the lesion. This case report presents an extremely uncommon location of a gigantic pyogenic granuloma, involving mucogingival complex and affecting the salivary outflow. This clinical manuscript may shed light on the controversies about possible mechanisms inducing oral pyogenic granuloma. PMID:24987485

Are sick individuals weak competitors? Competitive ability of snails parasitized by a gigantism-inducing trematode.

PubMed

Seppälä, Otto; Karvonen, Anssi; Kuosa, Marja; Haataja, Maarit; Jokela, Jukka

2013-01-01

Parasitized individuals are often expected to be poor competitors because they are weakened by infections. Many trematode species, however, although extensively exploiting their mollusc hosts, also induce gigantism (increased host size) by diverting host resources towards growth instead of reproduction. In such systems, alternatively to reduced competitive ability due to negative effects of parasitism on host performance, larger size could allow more efficient resource acquisition and thus increase the relative competitive ability of host individuals. We addressed this hypothesis by testing the effect of a trematode parasite Diplostomum pseudospathaceum on the competitive ability of its snail host Lymnaea stagnalis. We experimentally examined the growth of snails kept in pairs in relation to their infection status and intensity of resource competition (i.e. food availability). We found that parasitized snails grew faster and their reproduction was reduced compared to unparasitized individuals indicating parasite-induced gigantism. However, growth of the snails was faster when competing with parasitized individuals compared to unparasitized snails indicating reduced competitive ability due to parasitism. The latter effect, however, was relatively weak suggesting that the effects of the parasite on snail physiology may partly override each other in determining competitive ability.

Are Sick Individuals Weak Competitors? Competitive Ability of Snails Parasitized by a Gigantism-Inducing Trematode

PubMed Central

Seppälä, Otto; Karvonen, Anssi; Kuosa, Marja; Haataja, Maarit; Jokela, Jukka

2013-01-01

Parasitized individuals are often expected to be poor competitors because they are weakened by infections. Many trematode species, however, although extensively exploiting their mollusc hosts, also induce gigantism (increased host size) by diverting host resources towards growth instead of reproduction. In such systems, alternatively to reduced competitive ability due to negative effects of parasitism on host performance, larger size could allow more efficient resource acquisition and thus increase the relative competitive ability of host individuals. We addressed this hypothesis by testing the effect of a trematode parasite Diplostomum pseudospathaceum on the competitive ability of its snail host Lymnaea stagnalis. We experimentally examined the growth of snails kept in pairs in relation to their infection status and intensity of resource competition (i.e. food availability). We found that parasitized snails grew faster and their reproduction was reduced compared to unparasitized individuals indicating parasite-induced gigantism. However, growth of the snails was faster when competing with parasitized individuals compared to unparasitized snails indicating reduced competitive ability due to parasitism. The latter effect, however, was relatively weak suggesting that the effects of the parasite on snail physiology may partly override each other in determining competitive ability. PMID:24205383

Breast vasculitis in association with breast gigantism in a pregnant patient with systemic lupus erythematosus.

PubMed Central

Propper, D J; Reid, D M; Stankler, L; Eastmond, C J

1991-01-01

A 24 year old woman with systemic lupus erythematosus (SLE) developed widespread necrotic skin ulceration and gigantism of both breasts during an exacerbation of SLE in the last trimester of her second pregnancy. Over the remainder of the pregnancy the ulceration was only controlled by high dose corticosteroids. After parturition, however, it was possible to reduce the steroid dose without recurrence of the ulceration. Images PMID:1888201

Can oxygen set thermal limits in an insect and drive gigantism?

PubMed

Verberk, Wilco C E P; Bilton, David T

2011-01-01

Thermal limits may arise through a mismatch between oxygen supply and demand in a range of animal taxa. Whilst this oxygen limitation hypothesis is supported by data from a range of marine fish and invertebrates, its generality remains contentious. In particular, it is unclear whether oxygen limitation determines thermal extremes in tracheated arthropods, where oxygen limitation may be unlikely due to the efficiency and plasticity of tracheal systems in supplying oxygen directly to metabolically active tissues. Although terrestrial taxa with open tracheal systems may not be prone to oxygen limitation, species may be affected during other life-history stages, particularly if these rely on diffusion into closed tracheal systems. Furthermore, a central role for oxygen limitation in insects is envisaged within a parallel line of research focussing on insect gigantism in the late Palaeozoic. Here we examine thermal maxima in the aquatic life stages of an insect at normoxia, hypoxia (14 kPa) and hyperoxia (36 kPa). We demonstrate that upper thermal limits do indeed respond to external oxygen supply in the aquatic life stages of the stonefly Dinocras cephalotes, suggesting that the critical thermal limits of such aquatic larvae are set by oxygen limitation. This could result from impeded oxygen delivery, or limited oxygen regulatory capacity, both of which have implications for our understanding of the limits to insect body size and how these are influenced by atmospheric oxygen levels. These findings extend the generality of the hypothesis of oxygen limitation of thermal tolerance, suggest that oxygen constraints on body size may be stronger in aquatic environments, and that oxygen toxicity may have actively selected for gigantism in the aquatic stages of Carboniferous arthropods.

Coexisting diseases modifying each other’s presentation - lack of growth failure in Turner syndrome due to the associated pituitary gigantism.

PubMed

Dragović, Tamara; Đuran, Zorana; Jelić, Svetlana; Marinković, Dejan; Kiković, Saša; Kuzmić-Janković, Snežana; Hajduković, Zoran

2016-10-01

Turner syndrome presents with one of the most frequent chromosomal aberrations in female, typically presented with growth retardation, ovarian insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism is an extremely rare condition resulting from an excessive growth hormone (GH) secretion that occurs during childhood before the fusion of epiphyseal growth plates. The major clinical feature of gigantism is growth acceleration, although these patients also suffer from hypogonadism and soft tissue hypertrophy. We presented a girl with mosaic Turner syndrome, delayed puberty and normal linear growth for the sex and age, due to the simultaneous GH hypersecretion by pituitary tumor. In the presented case all the typical phenotypic stigmata related to Turner syndrome were missing. Due to excessive pituitary GH secretion during the period while the epiphyseal growth plates of the long bones are still open, characteristic stagnation in longitudinal growth has not been demonstrated. The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16. Physical examination of children presenting with delayed puberty but without growth arrest must include an overall hormonal and genetic testing even in the cases when typical clinical presentations of genetic disorder are absent. To the best of our knowledge, this is the first reported case of simultaneous presence of Turner syndrome and gigantism in the literature.

Gigantic Rolling Wave Captured on the Sun [hd video

NASA Image and Video Library

2017-12-08

A corona mass ejection (CME) erupted from just around the edge of the sun on May 1, 2013, in a gigantic rolling wave. CMEs can shoot over a billion tons of particles into space at over a million miles per hour. This CME occurred on the sun’s limb and is not headed toward Earth. The video, taken in extreme ultraviolet light by NASA’s Solar Dynamics Observatory (SDO), covers about two and a half hours. Credit: NASA/Goddard/SDO NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Galls and gall makers in plants from the Pé-de-Gigante Cerrado Reserve, Santa Rita do Passa Quatro, SP, Brazil.

PubMed

Urso-Guimarães, M V; Scareli-Santos, C

2006-02-01

Thirty-six morphologically different types of galls were obtained in leaves, leaflets, veins, petioles, stems, tendrils and flower buds from twenty-five species of plants in the Pé-de-Gigante Reserve, municipality of Santa Rita do Passa Quatro, state of São Paulo, Brazil. The host plant species belong to the closely related families Anacardiaceae, Annonaceae, Asteraceae, Bignoniaceae, Caryocaraceae, Erythroxylaceae, Fabaceae, Malpighiaceae, Melastomataceae, Myrtaceae, Ochnaceae, Polygalaceae, Sapindaceae, Sapotaceae, and Smilacaceae. The most common gall makers included Cecidomyiidae (Diptera), Pteromalidae (Hymenoptera) and Diaspididae (Sternorrhyncha-Hemiptera). This is the first report of galls found in the following plant genera: Gochnatia (Asteraceae), Distictela (Bignoniaceae), Banisteriopsis (Malpighiaceae), Ouratea (Ochnaceae), and Bredemeyera (Polygalaceae). The results of this work contribute to the body of knowledge about the relationship among host plants, gall makers, and the gall morphology of Pé-de-Gigante Cerrado Reserve.

Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl.

PubMed

Rix, M; Laurberg, P; Hoejberg, A S; Brock-Jacobsen, B

2005-08-01

The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

Can Oxygen Set Thermal Limits in an Insect and Drive Gigantism?

PubMed Central

Verberk, Wilco C. E. P.; Bilton, David T.

2011-01-01

Background Thermal limits may arise through a mismatch between oxygen supply and demand in a range of animal taxa. Whilst this oxygen limitation hypothesis is supported by data from a range of marine fish and invertebrates, its generality remains contentious. In particular, it is unclear whether oxygen limitation determines thermal extremes in tracheated arthropods, where oxygen limitation may be unlikely due to the efficiency and plasticity of tracheal systems in supplying oxygen directly to metabolically active tissues. Although terrestrial taxa with open tracheal systems may not be prone to oxygen limitation, species may be affected during other life-history stages, particularly if these rely on diffusion into closed tracheal systems. Furthermore, a central role for oxygen limitation in insects is envisaged within a parallel line of research focussing on insect gigantism in the late Palaeozoic. Methodology/Principal Findings Here we examine thermal maxima in the aquatic life stages of an insect at normoxia, hypoxia (14 kPa) and hyperoxia (36 kPa). We demonstrate that upper thermal limits do indeed respond to external oxygen supply in the aquatic life stages of the stonefly Dinocras cephalotes, suggesting that the critical thermal limits of such aquatic larvae are set by oxygen limitation. This could result from impeded oxygen delivery, or limited oxygen regulatory capacity, both of which have implications for our understanding of the limits to insect body size and how these are influenced by atmospheric oxygen levels. Conclusions/Significance These findings extend the generality of the hypothesis of oxygen limitation of thermal tolerance, suggest that oxygen constraints on body size may be stronger in aquatic environments, and that oxygen toxicity may have actively selected for gigantism in the aquatic stages of Carboniferous arthropods. PMID:21818347

Cerebral aneurysm

MedlinePlus Videos and Cool Tools

The tissue of the brain is supplied by a network of cerebral arteries. If the wall of a cerebral artery becomes weakened, a portion of the wall may balloon out forming an aneurysm. A cerebral aneurysm may enlarge until it bursts, sending blood ...

Gigantic Jets and the Tropical Paradigm: A Satellite Perspective

NASA Astrophysics Data System (ADS)

Lazarus, S. M.; Splitt, M. E.

2017-12-01

While not exclusively oceanic, gigantic jets (GJ) appear to have a preference for the tropical environment. In particular, a number of GJs have been observed in conjunction with tropical disturbances (i.e., weak tropical storms, depressions, and remnant lows). Given the remote aspect of TC convection and general lack of radar coverage, we explore this subset of events via analysis of their infrared and water vapor satellite presentations. The satellite perspective is relevant given that storm top mixing (dilution) of charge associated with storm-scale turbulence in this portion of the storm is thought to be connected to GJs. The thunderstorm overshoot, upper level divergence / outflow are examined in an effort to better understand the tropical paradigm. Specifically, an analysis of cloud top temperature, anvil expansion rates and asymmetries as well as placement of the GJ events with respect to the large (storm) scale circulation will be conducted.

Exploring the Molecular Growth of Two Gigantic Half‐Closed Polyoxometalate Clusters {Mo180} and {Mo130Ce6}

PubMed Central

Xuan, Weimin; Pow, Robert; Long, De‐Liang

2017-01-01

Abstract Understanding the process of the self‐assembly of gigantic polyoxometalates and their subsequent molecular growth, by the addition of capping moieties onto the oxo‐frameworks, is critical for the development of the designed assembly of complex high‐nuclearity cluster species, yet such processes remain far from being understood. Herein we describe the molecular growth from {Mo150} and {Mo120Ce6} to afford two half‐closed gigantic molybdenum blue clusters {Mo180} (1) and {Mo130Ce6} (2), respectively. Compound 1 features a hat‐shaped structure with the parent wheel‐shaped {Mo150} being capped by a {Mo30} unit on one side. Similarly, 2 exhibits an elliptical lanthanide‐doped wheel {Mo120Ce6} that is sealed by a {Mo10} unit on one side. Moreover, the observation of the parent uncapped {Mo150} and {Mo120Ce6} clusters as minor products during the synthesis of 1 and 2 strongly suggests that the molecular growth process can be initialized from {Mo150} and {Mo120Ce6} in solution, respectively. PMID:28508585

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

The small but clear gravity signal above the natural cave 'Grotta Gigante' (Trieste, Italy)

NASA Astrophysics Data System (ADS)

Braitenberg, Carla; Sampietro, Daniele; Zuliani, David; Barbagallo, Alfio; Fabris, Paolo; Fabbri, Julius; Rossi, Lorenzo; Handi Mansi, Ahmed

2014-05-01

Gravity observations are a powerful means for detecting underground mass changes. The Italian and Slovenian Karst has a number of explored caves, several are also touristic due to their size (e.g. Grotta Gigante in Italy; Skocjianske Jame and Postojnska Jama in Slovenia). Just a few years ago another big cave was discovered by chance close to Trieste when drilling a tunnel for a motor-highway, which shows that more caves are expected to be discovered in coming years. We have acquired the gravity field above the Grotta Gigante cave, a cave roughly 100 m high and 200 m long with a traditional spring-gravity meter (Lacoste&Romberg) and height measurements made with GPS and total station. The GPS was made with two different teams and processing algorithms, to cross-check accuracy and error estimate. Some stations had to be surveyed with a classical instrument due to the vegetation which concealed the satellite positioning signal. Here we present the results of the positioning acquisitions and the gravity field. The cave produces a signal of 1.5 mGal, with a clear elongated concentric symmetry. The survey shows that a systematic coverage of the Karst would have the benefit to recover the position of all of the greater existing caves. This will have a large impact on civil and environmental purposes, since it will for example allow to plan the urban development at a safety distance from subsurface caves.

Gigantic Surface Lifetime of an Intrinsic Topological Insulator

DOE PAGES

Neupane, Madhab; Xu, Su-Yang; Ishida, Yukiaki; ...

2015-09-09

We report that the interaction between light and novel two-dimensional electronic states holds promise to realize new fundamental physics and optical devices. Here, we use pump-probe photoemission spectroscopy to study the optically excited Dirac surface states in the bulk-insulating topological insulator Bi 2Te 2Se and reveal optical properties that are in sharp contrast to those of bulk-metallic topological insulators. We observe a gigantic optical lifetime exceeding 4 μs (1 μs=10 more » $${-}$$6 s) for the surface states in Bi 2Te 2Se, whereas the lifetime in most topological insulators, such as Bi2Se3, has been limited to a few picoseconds (1 ps=10 $${-}$$12 s). Moreover, we discover a surface photovoltage, a shift of the chemical potential of the Dirac surface states, as large as 100 mV. Lastly, our results demonstrate a rare platform to study charge excitation and relaxation in energy and momentum space in a two-dimensional system.« less

Cerebral Palsy (For Parents)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Parents / Cerebral Palsy What's in this ... Ahead Print en español Parálisis cerebral What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder that affects ...

Giants among larges: how gigantism impacts giant virus entry into amoebae.

PubMed

Rodrigues, Rodrigo Araújo Lima; Abrahão, Jônatas Santos; Drumond, Betânia Paiva; Kroon, Erna Geessien

2016-06-01

The proposed order Megavirales comprises the nucleocytoplasmic large DNA viruses (NCLDV), infecting a wide range of hosts. Over time, they co-evolved with different host cells, developing various strategies to penetrate them. Mimiviruses and other giant viruses enter cells through phagocytosis, while Marseillevirus and other large viruses explore endocytosis and macropinocytosis. These differing strategies might reflect the evolution of those viruses. Various scenarios have been proposed for the origin and evolution of these viruses, presenting one of the most enigmatic issues to surround these microorganisms. In this context, we believe that giant viruses evolved independently by massive gene/size gain, exploring the phagocytic pathway of entry into amoebas. In response to gigantism, hosts developed mechanisms to evade these parasites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polyostotic fibrous dysplasia with gigantism and huge pelvic tumor: a rare case of McCune-Albright syndrome.

PubMed

Sakayama, Kenshi; Sugawara, Yoshifumi; Kidani, Teruki; Fujibuchi, Taketsugu; Kito, Katsumi; Tanji, Nozomu; Nakamura, Atsushi

2011-06-01

We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

Cerebral Palsy (For Teens)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Teens / Cerebral Palsy What's in this ... do just what everyone else does. What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder of the ...

Ependimoma myxopapilar sacro gigante con osteolisis

PubMed Central

Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

2014-01-01

Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

Pituitary gigantism: a retrospective case series.

PubMed

Creo, Ana L; Lteif, Aida N

2016-05-01

Pituitary gigantism (PG) is a rare pediatric disease with poorly defined long-term outcomes. Our aim is to describe the longitudinal clinical course in PG patients using a single-center, retrospective cohort study. Patients younger than 19 years diagnosed with PG were identified. Thirteen cases were confirmed based on histopathology of a GH secreting adenoma or hyperplasia and a height >2 SD for age and gender. Laboratory studies, initial pathology, and imaging were abstracted. Average age at diagnosis was 13 years with an average initial tumor size of 7.4×3.8 mm. Initial transsphenoidal surgery was curative in 3/12 patients. Four of the nine patients who failed the initial surgery required a repeat procedure. Octreotide successfully normalized GH levels in 1/6 patients with disease refractory to surgery (1/6). Two out of five patients received pegvisomant after failing octreotide but only one patient responded to treatment. Five patients were ultimately treated with radiosurgery or radiation patients were followed for an average of 10 years. PG is difficult to treat. In most patients, the initial transsphenoidal surgery failed to normalize GH levels. If the initial surgery was unsuccessful, repeat surgery was unlikely to control GH secretion. Treatment with octreotide or pegvisomant was successful in less than half the patients failing surgery. Radiosurgery was curative, but is not an optimal treatment for pediatric patients. Despite the small sample, our study suggests that the treatment outcome of pediatric PG may be different than adults.

Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

PubMed

Zimmerman, D; Young, W F; Ebersold, M J; Scheithauer, B W; Kovacs, K; Horvath, E; Whitaker, M D; Eberhardt, N L; Downs, T R; Frohman, L A

1993-01-01

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.

What lies beneath: sub-articular long bone shape scaling in eutherian mammals and saurischian dinosaurs suggests different locomotor adaptations for gigantism.

PubMed

Bonnan, Matthew F; Wilhite, D Ray; Masters, Simon L; Yates, Adam M; Gardner, Christine K; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load.

What Lies Beneath: Sub-Articular Long Bone Shape Scaling in Eutherian Mammals and Saurischian Dinosaurs Suggests Different Locomotor Adaptations for Gigantism

PubMed Central

Bonnan, Matthew F.; Wilhite, D. Ray; Masters, Simon L.; Yates, Adam M.; Gardner, Christine K.; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load. PMID:24130690

Cerebral ischemia and neuroregeneration

PubMed Central

Lee, Reggie H. C.; Lee, Michelle H. H.; Wu, Celeste Y. C.; Couto e Silva, Alexandre; Possoit, Harlee E.; Hsieh, Tsung-Han; Minagar, Alireza; Lin, Hung Wen

2018-01-01

Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia. PMID:29623912

Ultrafast gigantic photo-response in charge-ordered organic salt (EDO-TTF)2PF6 on 10-fs time scales

DOE Office of Scientific and Technical Information (OSTI.GOV)

Itatani, J.; Rini, M.; Cavalleri, A.

2008-08-01

The initial dynamics of photo-induced phase transition in charge-ordered organic salt (EDO-TTF){sub 2}PF{sub 6} was investigated using 10-fs near-infrared laser pulses. We observed sub-20-fs gigantic photo-responses (|{Delta}R/R|>100%) due to intra-molecular vibration and a clear signature of a structural bottleneck ({approx}50 fs) for the first time.

[Congenital cardiopathy in a patient with Sotos syndrome. Description of a case].

PubMed

Di Marco, G; Levantesi, G; Parisi, G; Chiarelli, A

1989-05-01

The number of cases of Sotos syndrome or cerebral gigantism described in the literature total more than 200. For 6 of these, cardiac malformations were described. The authors report a case of Sotos syndrome in which malformative alterations of the aortic and mitral valves were simultaneously present.

Controlled Growth of Gigantic Swirls in a Laboratory Magnetosphere

NASA Astrophysics Data System (ADS)

Worstell, M. W.; Mauel, M. E.; Roberts, T. M.

2012-10-01

Space and laboratory plasma confined by a strong magnetic field have remarkable properties. Low frequency mixing of the plasma occurs through the interchange of long plasma-filled tubes aligned with the magnetic field. The plasma dynamics becomes two-dimensional because these tubes can only move radially or circulate around the poles of the magnetic dipole. Studies of turbulent interchange dynamics made using the Collisionless Terella Experiment (CTX) show that turbulence appears as chaotic time-varying modes with broad global mode structures that interact nonlinearly and form an inverse cascade.footnotetextB.A. Grierson, M.W. Worstell, M.E. Mauel, Phys. Plasmas 16 055902 (2009) When we drive vortex mixing through the application of electrostatic bias to multiple probes, we break the rotational symmetry of the plasma and small vortex tubes are seen to drive larger ``gigantic'' swirls. Statistical analysis of the time-evolving spectra and measurement of the bicoherence of the turbulence show an increase of three wave coupling during non-axisymmetric electrostatic drive of the probe array.

Gigantism and comparative life-history parameters of tyrannosaurid dinosaurs.

PubMed

Erickson, Gregory M; Makovicky, Peter J; Currie, Philip J; Norell, Mark A; Yerby, Scott A; Brochu, Christopher A

2004-08-12

How evolutionary changes in body size are brought about by variance in developmental timing and/or growth rates (also known as heterochrony) is a topic of considerable interest in evolutionary biology. In particular, extreme size change leading to gigantism occurred within the dinosaurs on multiple occasions. Whether this change was brought about by accelerated growth, delayed maturity or a combination of both processes is unknown. A better understanding of relationships between non-avian dinosaur groups and the newfound capacity to reconstruct their growth curves make it possible to address these questions quantitatively. Here we study growth patterns within the Tyrannosauridae, the best known group of large carnivorous dinosaurs, and determine the developmental means by which Tyrannosaurus rex, weighing 5,000 kg and more, grew to be one of the most enormous terrestrial carnivorous animals ever. T. rex had a maximal growth rate of 2.1 kg d(-1), reached skeletal maturity in two decades and lived for up to 28 years. T. rex's great stature was primarily attained by accelerating growth rates beyond that of its closest relatives.

Cerebral Palsy

MedlinePlus

Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

[Etiology of cerebral palsy].

PubMed

Jaisle, F

1996-01-01

The "perinatal asphyxia" is regarded to be one of the causes of cerebral palsy, though in the very most of the children with cerebral palsy there is found no hypoxia during labour. It should be mentioned, that the definition of "perinatal" and "asphyxia" neither are unic nor concret. And also there is no correlation between nonreassuring fetal heart rate patterns and acidosis in fetal blood with the incidence of cerebral palsy. Numerous studies in pregnant animals failed in proving an acute intrapartal hypoxia to be the origin of the cerebral palsy. Myers (1975) describes four patterns of anatomic brain damage after different injuries. Only his so called oligo-acidotic hypoxia, which is protracted and lasts over a longer time is leading to brain injury, which can be regarded in analogy to the injury of children with cerebral palsy. Summarising the update publications about the causes of cerebral palsy and the studies in pregnant animals there is no evidence that hypoxia during labour may be the cause of cerebral palsy. There is a great probability of a pre(and post-)natal origin of brain injury (for instance a periventricular leucomalacia found after birth) which leads to cerebral palsy. Short after labour signs of a so called "asphyxia" may occur in addition to this preexisting injury and misrepresent the cause of cerebral palsy. Finally the prepartal injury may cause both: Cerebral palsy and hypoxia.

Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm.

PubMed

Vijay, Anantha; Santhanam, R; Katusic, Zvonimir S

2006-10-01

Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.

Cerebral Atrophy

MedlinePlus

... Alzheimer’s disease, Pick’s disease, and fronto-temporal dementia cerebral palsy , in which lesions (damaged areas) may impair motor ... Alzheimer’s disease, Pick’s disease, and fronto-temporal dementia cerebral palsy , in which lesions (damaged areas) may impair motor ...

Cerebral and non-cerebral coenurosis: on the genotypic and phenotypic diversity of Taenia multiceps.

PubMed

Christodoulopoulos, Georgios; Dinkel, Anke; Romig, Thomas; Ebi, Dennis; Mackenstedt, Ute; Loos-Frank, Brigitte

2016-12-01

We characterised the causative agents of cerebral and non-cerebral coenurosis in livestock by determining the mitochondrial genotypes and morphological phenotypes of 52 Taenia multiceps isolates from a wide geographical range in Europe, Africa, and western Asia. Three studies were conducted: (1) a morphological comparison of the rostellar hooks of cerebral and non-cerebral cysts of sheep and goats, (2) a morphological comparison of adult worms experimentally produced in dogs, and (3) a molecular analysis of three partial mitochondrial genes (nad1, cox1, and 12S rRNA) of the same isolates. No significant morphological or genetic differences were associated with the species of the intermediate host. Adult parasites originating from cerebral and non-cerebral cysts differed morphologically, e.g. the shape of the small hooks and the distribution of the testes in the mature proglottids. The phylogenetic analysis of the mitochondrial haplotypes produced three distinct clusters: one cluster including both cerebral isolates from Greece and non-cerebral isolates from tropical and subtropical countries, and two clusters including cerebral isolates from Greece. The majority of the non-cerebral specimens clustered together but did not form a monophyletic group. No monophyletic groups were observed based on geography, although specimens from the same region tended to cluster. The clustering indicates high intraspecific diversity. The phylogenetic analysis suggests that all variants of T. multiceps can cause cerebral coenurosis in sheep (which may be the ancestral phenotype), and some variants, predominantly from one genetic cluster, acquired the additional capacity to produce non-cerebral forms in goats and more rarely in sheep.

Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

PubMed

Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

2016-02-01

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome

PubMed Central

Naves, Luciana A.; Daly, Adrian F.; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Jreige, Armindo; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S.; Stratakis, Constantine A.; Lupski, James R.

2017-01-01

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome. PMID:26607152

Cerebral Palsy. Fact Sheet = La Paralisis Cerebral. Hojas Informativas Sobre Discapacidades.

ERIC Educational Resources Information Center

National Information Center for Children and Youth with Disabilities, Washington, DC.

This fact sheet on cerebral palsy is written in both English and Spanish. First, it provides a definition of cerebral palsy and considers various causes (e.g., an insufficient amount of oxygen reaching the fetal or newborn brain). The fact sheet then offers incidence figures and explains characteristics of the three main types of cerebral palsy:…

A Gigantic, Exceptionally Complete Titanosaurian Sauropod Dinosaur from Southern Patagonia, Argentina

PubMed Central

Lacovara, Kenneth J.; Lamanna, Matthew C.; Ibiricu, Lucio M.; Poole, Jason C.; Schroeter, Elena R.; Ullmann, Paul V.; Voegele, Kristyn K.; Boles, Zachary M.; Carter, Aja M.; Fowler, Emma K.; Egerton, Victoria M.; Moyer, Alison E.; Coughenour, Christopher L.; Schein, Jason P.; Harris, Jerald D.; Martínez, Rubén D.; Novas, Fernando E.

2014-01-01

Titanosaurian sauropod dinosaurs were the most diverse and abundant large-bodied herbivores in the southern continents during the final 30 million years of the Mesozoic Era. Several titanosaur species are regarded as the most massive land-living animals yet discovered; nevertheless, nearly all of these giant titanosaurs are known only from very incomplete fossils, hindering a detailed understanding of their anatomy. Here we describe a new and gigantic titanosaur, Dreadnoughtus schrani, from Upper Cretaceous sediments in southern Patagonia, Argentina. Represented by approximately 70% of the postcranial skeleton, plus craniodental remains, Dreadnoughtus is the most complete giant titanosaur yet discovered, and provides new insight into the morphology and evolutionary history of these colossal animals. Furthermore, despite its estimated mass of about 59.3 metric tons, the bone histology of the Dreadnoughtus type specimen reveals that this individual was still growing at the time of death. PMID:25186586

Hyperventilation, cerebral perfusion, and syncope.

PubMed

Immink, R V; Pott, F C; Secher, N H; van Lieshout, J J

2014-04-01

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

Myocardial infarction with Moyamoya disease and pituitary gigantism in a young female patient.

PubMed

Ahn, Y K; Jeong, M H; Bom, H S; Park, J C; Kim, J K; Chung, D J; Chung, M Y; Cho, J G; Kang, J C

1999-08-01

Myocardial infarction is very rare in young female patients with systemic vascular disorders. Moyamoya disease is a cerebrovascular disease associated with an abnormal vascular network. This report presents a 19-year-old female patient who suffered from chest pain and exertional dyspnea for 2 months prior to admission. She had a history of Moyamoya disease and pituitary gigantism since childhood. Her ejection fraction on echocardiogram was 20% and a perfusion defect with partial reversibility in the anterior wall was demonstrated on stress single photon emission computed tomography (SPECT). Diagnostic coronary angiogram revealed critical stenosis in the middle left anterior descending artery, which was treated by coronary stenting. Her subjective symptoms were relieved and the perfusion defect seen on SPECT decreased after coronary intervention.

Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.

PubMed

Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O'Donnell, Martha

2012-07-01

Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.

GaAs-oxide interface states - A gigantic photoionization effect and its implications to the origin of these states

NASA Technical Reports Server (NTRS)

Lagowski, J.; Walukiewicz, W.; Kazior, T. E.; Gatos, H. C.; Siejka, J.

1981-01-01

Gigantic photoionization was discovered on GaAs-oxide interfaces leading to the discharge of deep surface states with rates exceeding 1000 times those of photoionization transitions to the conduction band. It exhibits a peak similar to acceptor-donor transitions and is explained as due to energy transfer from photo-excited donor-acceptor pairs to deep surface states. This new process indicates the presence of significant concentrations of shallow donor and acceptor levels not recognized in previous interface models.

Cerebral palsy - resources

MedlinePlus

Resources - cerebral palsy ... The following organizations are good resources for information on cerebral palsy : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope- ...

Cerebral arteriovenous malformation

MedlinePlus

AVM - cerebral; Arteriovenous hemangioma; Stroke - AVM; Hemorrhagic stroke - AVM ... The cause of cerebral AVM is unknown. An AVM occurs when arteries in the brain connect directly to nearby veins without having the ...

Management of pituitary gigantism. The role of bromocriptine and radiotherapy.

PubMed

Ritzén, E M; Wettrell, G; Davies, G; Grant, D B

1985-09-01

True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in two boys, aged 13 years (case I) and 7 1/2 years (case II). Both had shown increased growth rates since early childhood (from 4 years and 1 1/2 years, respectively), but no skeletal acromegalic features were noted. However, both showed increased sweating and both had advanced pubic hair relative to testis volume. No other pituitary dysfunction was recorded. Case I underwent transsphenoidal surgery with only incomplete and temporary suppression of GH and PRL levels. However, in both patients bromocriptine administration promptly suppressed PRL levels. Following combined irradiation and bromocriptine treatment, GH also gradually normalized over a period of 2 years. Both boys are still on treatment, and both showed an increase in plasma GH concentrations when the dose of bromocriptine was reduced or discontinued, indicating that even 3 1/2-5 years after irradiation therapy (and during continuous treatment with bromocriptine) the disease was controlled but not cured. However, in these two boys bromocriptine has proved effective in controlling the PRL/GH oversecretion.

Aging and Cerebral Palsy.

ERIC Educational Resources Information Center

Networker, 1993

1993-01-01

This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

Gigantic transverse voltage induced via off-diagonal thermoelectric effect in CaxCoO2 thin films

NASA Astrophysics Data System (ADS)

Takahashi, Kouhei; Kanno, Tsutomu; Sakai, Akihiro; Adachi, Hideaki; Yamada, Yuka

2010-07-01

Gigantic transverse voltages exceeding several tens volt have been observed in CaxCoO2 thin films with tilted c-axis orientation upon illumination of nanosecond laser pulses. The voltage signals were highly anisotropic within the film surface showing close relation with the c-axis tilt direction. The magnitude and the decay time of the voltage strongly depended on the film thickness. These results confirm that the large laser-induced voltage originates from a phenomenon termed the off-diagonal thermoelectric effect, by which a film out-of-plane temperature gradient leads to generation of a film in-plane voltage.

[Cerebral protection].

PubMed

Cattaneo, A D

1993-09-01

Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral

Molecular design of TiO2 for gigantic red shift via sublattice substitution.

PubMed

Shao, Guosheng; Deng, Quanrong; Wan, Lin; Guo, Meilan; Xia, Xiaohong; Gao, Yun

2010-11-01

The effects of 3d transition metal doping in TiO2 phases have been simulated in detail. The results of modelling indicate that Mn has the biggest potential among 3d transition metals, for the reduction of energy gap and the introduction of effective intermediate bands to allow multi-band optical absorption. On the basis of theoretical formulation, we have incorporated considerable amount of Mn in nano-crystalline TiO2 materials. Mn doped samples demonstrate significant red shift in the optical absorption edge, with a secondary absorption edge corresponding to theoretically predicted intermediate bands/states. The gigantic red shift achievable in Mn-doped TiO2 is expected to extend the useful TiO2 functionalities well beyond the UV threshold via the optical absorption of both visible and infrared photon irradiance.

Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

PubMed

Sanborn, Matthew R; Edsell, Mark E; Kim, Meeri N; Mesquita, Rickson; Putt, Mary E; Imray, Chris; Yow, Heng; Wilson, Mark H; Yodh, Arjun G; Grocott, Mike; Martin, Daniel S

2015-06-01

Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Cerebral monitoring during cardiopulmonary bypass in children.

PubMed

Kern, F H; Schell, R M; Greeley, W J

1993-07-01

Although cerebral monitoring during CPB remains primarily investigational, recent data support its clinical utility. In particular, it is cerebral metabolic monitoring that provides meaningful information in terms of preparing the brain for dhCPB and dhCA. Cerebral blood flow or cerebral blood flow velocity monitoring is less beneficial due to the presence of luxuriant cerebral blood flow at deep hypothermic temperatures. Conventional temperature monitoring can be improved upon by adding jugular venous oxygen saturation monitoring to satisfy the primary goal of cerebral protection--uniform cerebral cooling and metabolic suppression. Although online measures of cerebral cellular metabolism are not widely available, early experience with near infrared technology suggests that it is a feasible and reliable monitor of cerebral metabolic activity and is likely to represent an important noninvasive continuous monitor in the near future. CMRO2 recovery data have suggested that cerebral metabolic suppression is more severe the longer the period of dhCA. Cerebral protection strategies, such as intermittent cerebral perfusion have demonstrated less metabolic suppression of dhCA in animal models and are currently undergoing clinical evaluation in our institution. Finally, the postoperative period remains a high-risk period for neurologic injury because temperatures are normothermic, cardiac output is reduced, cerebral autoregulation is impaired, and management strategies, such as hyperventilation, are commonly used to increase pulmonary blood flow with little knowledge on its effects on cerebral perfusion.

Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

PubMed Central

Yuen, Natalie; Anderson, Steven E.; Glaser, Nicole; Tancredi, Daniel J.; O'Donnell, Martha E.

2008-01-01

OBJECTIVE— Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport. RESEARCH DESIGN AND METHODS— Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment protocols. CBF was determined by magnetic resonance (MR) perfusion–weighted imaging before and during treatment, and CE was assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion–weighted imaging. RESULTS— CBF was significantly reduced in DKA and was responsive to alterations in pCO2. ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin alone. CONCLUSIONS— These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell swelling. PMID:18633109

Revisiting cerebral thromboangiitis obliterans.

PubMed

Hurelbrink, Carrie B; Barnett, Yael; Buckland, Michael E; Wilkinson, Mark; Leicester, Jon; Anderson, Craig; Brennan, Jeffrey; Barnett, Michael

2012-06-15

We describe a 56-year-old patient with progressive cognitive decline in the context of heavy tobacco use and migraine, and imaging evidence of an occlusive terminal cerebral vasculopathy. The results of brain biopsy recapitulated the pathological features described by Lindenberg and Spatz in their classic 1939 treatise on cerebral thromboangiitis obliterans, or cerebral Buerger's disease. Although the condition is associated with heavy smoking, the identification of a hypercoagulable state in our patient suggests a multifactorial pathogenesis. The diagnosis of cerebral thromboangiitis obliterans in life is facilitated by modern neuroimaging and should prompt immediate cessation of smoking and a search for an underlying prothrombotic tendency. Copyright © 2012 Elsevier B.V. All rights reserved.

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism

PubMed Central

Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G

2017-01-01

Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability. PMID:28634279

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

PubMed

Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G; Korbonits, Márta

2017-09-01

Mutations in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP -region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability. © 2017 The authors.

Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

PubMed

Pichiorri, Floriana; Vicenzini, Edoardo; Gilio, Francesca; Giacomelli, Elena; Frasca, Vittorio; Cambieri, Chiara; Ceccanti, Marco; Di Piero, Vittorio; Inghilleri, Maurizio

2012-08-01

To determine whether intermittent theta burst stimulation influences cerebral hemodynamics, we investigated changes induced by intermittent theta burst stimulation on the middle cerebral artery cerebral blood flow velocity and vasomotor reactivity to carbon dioxide (CO(2)) in healthy participants. The middle cerebral artery flow velocity and vasomotor reactivity were monitored by continuous transcranial Doppler sonography. Changes in cortical excitability were tested by transcranial magnetic stimulation. In 11 healthy participants, before and immediately after delivering intermittent theta burst stimulation, we tested cortical excitability measured by the resting motor threshold and motor evoked potential amplitude over the stimulated hemisphere and vasomotor reactivity to CO(2) bilaterally. The blood flow velocity was monitored in both middle cerebral arteries throughout the experimental session. In a separate session, we tested the effects of sham stimulation under the same experimental conditions. Whereas the resting motor threshold remained unchanged before and after stimulation, motor evoked potential amplitudes increased significantly (P = .04). During and after stimulation, middle cerebral artery blood flow velocities also remained bilaterally unchanged, whereas vasomotor reactivity to CO(2) increased bilaterally (P = .04). The sham stimulation left all variables unchanged. The expected intermittent theta burst stimulation-induced changes in cortical excitability were not accompanied by changes in cerebral blood flow velocities; however, the bilateral increased vasomotor reactivity suggests that intermittent theta burst stimulation influences the cerebral microcirculation, possibly involving subcortical structures. These findings provide useful information on hemodynamic phenomena accompanying intermittent theta burst stimulation, which should be considered in research aimed at developing this noninvasive, low-intensity stimulation technique for safe

Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene.

PubMed

Burton, F H; Hasel, K W; Bloom, F E; Sutcliffe, J G

1991-03-07

Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering.

Gigantism due to growth hormone excess in a boy with optic glioma.

PubMed

Drimmie, F M; MacLennan, A C; Nicoll, J A; Simpson, E; McNeill, E; Donaldson, M D

2000-10-01

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.

Biology of the sauropod dinosaurs: the evolution of gigantism

PubMed Central

Sander, P Martin; Christian, Andreas; Clauss, Marcus; Fechner, Regina; Gee, Carole T; Griebeler, Eva-Maria; Gunga, Hanns-Christian; Hummel, Jürgen; Mallison, Heinrich; Perry, Steven F; Preuschoft, Holger; Rauhut, Oliver W M; Remes, Kristian; Tütken, Thomas; Wings, Oliver; Witzel, Ulrich

2011-01-01

The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism. We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores. The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates. The

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism.

PubMed

Thawani, Jayesh P; Bailey, Robert L; Burns, Carrie M; Lee, John Y K

2014-01-01

Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes.

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism

PubMed Central

Thawani, Jayesh P.; Bailey, Robert L.; Burns, Carrie M.; Lee, John Y. K.

2014-01-01

Background: Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. Case Description: A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. Conclusions: While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes. PMID:25396071

Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

PubMed

Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

2016-07-01

We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

Initial experience of a novel sheath guide for transbrachial coil embolization of cerebral aneurysms in the anterior cerebral circulation.

PubMed

Iwata, Tomonori; Mori, Takahisa; Tajiri, Hiroyuki; Miyazaki, Yuichi; Nakazaki, Masahito; Mizokami, Koji

2013-03-01

The transfemoral approach is a common technique for coil embolization of cerebral aneurysms in the anterior cerebral circulation. However, it is difficult to advance a guiding catheter into the carotid artery via the femoral route in patients with a tortuous aortic arch, an unfavorable supra-aortic takeoff, aortic diseases, or occlusion of the femoral artery. To report our initial experiences of coil embolization of cerebral aneurysms in the anterior cerebral circulation with a novel sheath guide for transbrachial carotid cannulation. A sheath guide designed specifically for transbrachial carotid cannulation was developed; transbrachial coil embolization for cerebral aneurysms began in May 2011. Included for analysis were patients who underwent transbrachial coil embolization for cerebral aneurysms in the anterior cerebral circulation from May 2011 to January 2012. Adjuvant techniques, angiographic results, procedural success, and periprocedural complications were investigated. Ten patients underwent transbrachial coil embolization of cerebral aneurysms in the anterior cerebral circulation. All procedures were successful using the brachial route. No periprocedural complications occurred. Patients were permitted to get seated immediately after coil embolization even during hemostasis. The sheath guide specifically designed for transbrachial carotid cannulation was useful for coil embolization of cerebral aneurysms in the anterior cerebral circulation.

Therapeutic interventions in cerebral palsy.

PubMed

Patel, Dilip R

2005-11-01

Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

Cerebral Palsy Litigation

PubMed Central

Sartwelle, Thomas P.

2015-01-01

The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds’ labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule—the Daubert doctrine that excludes “junk science” from the courtroom—as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring’s 40-year masquerade as science. PMID:25183322

Cerebral amyloid angiopathy increases susceptibility to infarction after focal cerebral ischemia in Tg2576 mice.

PubMed

Milner, Eric; Zhou, Meng-Liang; Johnson, Andrew W; Vellimana, Ananth K; Greenberg, Jacob K; Holtzman, David M; Han, Byung Hee; Zipfel, Gregory J

2014-10-01

We and others have shown that soluble amyloid β-peptide (Aβ) and cerebral amyloid angiopathy (CAA) cause significant cerebrovascular dysfunction in mutant amyloid precursor protein (APP) mice, and that these deficits are greater in aged APP mice having CAA compared with young APP mice lacking CAA. Amyloid β-peptide in young APP mice also increases infarction after focal cerebral ischemia, but the impact of CAA on ischemic brain injury is unknown. To determine this, we assessed cerebrovascular reactivity, cerebral blood flow (CBF), and extent of infarction and neurological deficits after transient middle cerebral artery occlusion in aged APP mice having extensive CAA versus young APP mice lacking CAA (and aged-matched littermate controls). We found that aged APP mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater CBF compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion. These data indicate CAA induces a more severe form of cerebrovascular dysfunction than amyloid β-peptide alone, leading to intra- and postischemic CBF deficits that ultimately exacerbate cerebral infarction. Our results shed mechanistic light on human studies identifying CAA as an independent risk factor for ischemic brain injury. © 2014 American Heart Association, Inc.

Gigantic transverse x-ray magnetic circular dichroism in ultrathin Co in Au/Co/Au(001)

NASA Astrophysics Data System (ADS)

Koide, T.; Mamiya, K.; Asakura, D.; Osatune, Y.; Fujimori, A.; Suzuki, Y.; Katayama, T.; Yuasa, S.

2014-04-01

Transverse-geometry x-ray magnetic circular dichroism (TXMCD) measurements on Au/Co-staircase/Au(001) reveal the orbital origin of intrinsic in-plane magnetic anisotropy A gigantic TXMCD was successfully observed at the Co L3,2 edges for Co thickness (tC0) in the 2-monolayer regime. A TXMCD-sum-rule analysis shows a remarkable enhancement of an orbital-moment anisotropy (Δmorb) and of an in-plane magnetic dipole moment (m||T). Both Δmorb and m||T exhibit close similarity in tCo dependence, reflecting the in-plane magnetic anisotropy These observations evidence that extremely strong, intrinsic, in-plane magnetic anisotropy originates from the anisotropic orbital part of the wave function, dominating the dipole-dipole-interaction-derived, extrinsic, in-plane magnetic anisotropy.

A novel germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene in an Italian family with gigantism.

PubMed

Urbani, C; Russo, D; Raggi, F; Lombardi, M; Sardella, C; Scattina, I; Lupi, I; Manetti, L; Tomisti, L; Marcocci, C; Martino, E; Bogazzi, F

2014-10-01

Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives. Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations. The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix. We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

PubMed

Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

2017-07-28

A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GH<2.5μg/L and IGF-1< lower limit of normal). Reductions in the median GH and IGF-1 levels observed at month 3 were maintained up to month 12; the median percent change from baseline to month 12 in GH and IGF-1 levels were -74.71% and -59.33%, respectively. Twenty-nine patients completed the 12-month core phase, 1 withdrew consent, and 3 discontinued treatment due to adverse events (AEs; diabetes mellitus, hyperglycemia, liver function abnormality, n=1 each). Almost all patients (97%; 32/33) experienced AEs; the most common AEs were nasopharyngitis (48.5%), hyperglycemia (42.4%), diabetes mellitus (24.2%), constipation (18.2%), and hypoglycemia (15.2%). Serious AEs were reported in 7 patients with the most common being hyperglycemia (n=2). Long-acting pasireotide demonstrated clinically relevant efficacy and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities.

PubMed

Mammis, Antonios; Eloy, Jean Anderson; Liu, James K

2010-10-01

Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.

Effects of hyperbaric oxygen on intracranial pressure and cerebral blood flow in experimental cerebral oedema1

PubMed Central

Miller, J. D.; Ledingham, I. McA.; Jennett, W. B.

1970-01-01

Increased intracranial pressure was induced in anaesthetized dogs by application of liquid nitrogen to the dura mater. Intracranial pressure and cerebral blood flow were measured, together with arterial blood pressure and arterial and cerebral venous blood gases. Carbon dioxide was administered intermittently to test the responsiveness of the cerebral circulation, and hyperbaric oxygen was delivered at intervals in a walk-in hyperbaric chamber, pressurized to two atmospheres absolute. Hyperbaric oxygen caused a 30% reduction of intracranial pressure and a 19% reduction of cerebral blood flow in the absence of changes in arterial PCO2 or blood pressure, but only as long as administration of carbon dioxide caused an increase in both intracranial pressure and cerebral blood flow. When carbon dioxide failed to influence intracranial pressure or cerebral blood flow then hyperbaric oxygen had no effect. This unresponsive state was reached at high levels of intracranial pressure. Images PMID:5497875

[A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

PubMed

Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

2009-08-01

A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

Familial Sotos syndrome (cerebral gigantism): craniofacial and psychological characteristics.

PubMed

Bale, A E; Drum, M A; Parry, D M; Mulvihill, J J

1985-04-01

Most reported cases of Sotos syndrome are sporadic, but autosomal dominant and recessive inheritance patterns have been suggested. Ascertainment of a two-generation family through a 7-year-old proposita with a learning disability allowed the relatively unbiased study of two affected relatives. Developmental delay was not pronounced in the patient's mother or sister; craniofacial characteristics at variance with the characteristic description included acrocephaly and maxillary prominence. Steepness of the anterior cranial base angle and protrusion of the middle and lower face, shown in all three patients by cephalometric radiographs, deserve further evaluation as diagnostic criteria.

Spinal deformity in patients with Sotos syndrome (cerebral gigantism).

PubMed

Tsirikos, Athanasios I; Demosthenous, Nestor; McMaster, Michael J

2009-04-01

Retrospective review of a case series. To present the clinical characteristics and progression of spinal deformity in patients with Sotos syndrome. There is limited information on the development of spinal deformity and the need for treatment in this condition. The medical records and spinal radiographs of 5 consecutive patients were reviewed. All patients were followed to skeletal maturity (mean follow-up: 6.6 y). The mean age at diagnosis of spinal deformity was 11.9 years (range: 5.8 to 14.5) with 4 patients presenting in adolescence. The type of deformity was not uniform. Two patients presented in adolescence with relatively small and nonprogressive thoracolumbar and lumbar scoliosis, which required observation but no treatment until the end of spinal growth. Three patients underwent spinal deformity correction at a mean age of 11.7 years (range: 6 to 15.4). The first patient developed a double structural thoracic and lumbar scoliosis and underwent a posterior spinal arthrodesis extending from T3 to L4. Five years later, she developed marked degenerative changes at the L4/L5 level causing symptomatic bilateral lateral recess stenosis and affecting the L5 nerve roots. She underwent spinal decompression at L4/L5 and L5/S1 levels followed by extension of the fusion to the sacrum. The second patient developed a severe thoracic kyphosis and underwent a posterior spinal arthrodesis. The remaining patient presented at the age of 5.9 years with a severe thoracic kyphoscoliosis and underwent a 2-stage antero-posterior spinal arthrodesis. The development of spinal deformity is a common finding in children with Sotos syndrome and in our series it occurred in adolescence in 4 out of 5 patients. There is significant variability on the pattern of spine deformity, ranging from a scoliosis through kyphoscoliosis to a pure kyphosis, and also the age at presentation and need for treatment.

Cerebral Palsy (For Kids)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Kids / Cerebral Palsy What's in this ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

[The cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy].

PubMed

Jin, De-xin; Chen, Xiu-yun; Huang, He; Zhang, Xu

2006-12-01

To investigate the cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The blood flow velocity of cerebral arteries was measured by using transcranial Doppler ultrasound (TCD) in 6 cases with CADASIL and a quite number of age and sex matched control subjects. All patients (4 were symptomatic and 2 asymptomatic), being an established CADASIL family with the diagnosis confirmed by clinical characteristics, neuroimaging, pathology and molecular genetics, had abnormal mark signals on MR imagining and no history of hypertension, diabetes, heart disease and migraine. A routinely TCD detection, including peak-systolic velocity (Vp), end-diastolic velocity (Vd), mean velocity (Vm) and pulsatility index (PI), was carried out on the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA) and vertebral arteries (VA) as well as the basilar artery (BA). A comparison between the cases and controls was made. Then, the changes of flow velocity in middle cerebral arteries (MCA) of the patients with CADASIL were observed before and after breathholding tests. In addition, brain CT perfusion imaging (CTP) was carried out in all the cases by using 16-slice spiral CT. The appearances of frequency spectrum were nearly normal in all the cases and there was no abnormality between the two sides on velocity (P > 0.05). As compared with the controls, the bilateral Vp, Vd and Vm in ACA and PCA were decreased obviously (P < 0.05). The velocity parameters of MCA with the exception of left Vm and right PI showed changes (P < 0.05) and there were no changes of PI in the bilateral ACA, PCA and Left MCA (P > 0.05). Moreover, there were marked changes in MCA (including Vm, Vd and PI) of all the cases as compared with the controls after breathholding (P < 0.01). Brain perfusion imaging showing the regional cerebral blood flow and regional cerebral blood volume in frontal

Molecular pathophysiology of cerebral edema

PubMed Central

Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

Symptomatic Cerebral Vasospasm and Delayed Cerebral Ischemia Following Transsphenoidal Resection of a Craniopharyngioma.

PubMed

Ricarte, Irapuá Ferreira; Funchal, Bruno F; Miranda Alves, Maramélia A; Gomes, Daniela L; Valiente, Raul A; Carvalho, Flávio A; Silva, Gisele S

2015-09-01

Vasospasm has been rarely described as a complication associated with craniopharyngioma surgery. Herein we describe a patient who developed symptomatic vasospasm and delayed cerebral ischemia after transsphenoidal surgery for a craniopharyngioma. A 67-year-old woman became drowsy 2 weeks after a transsphenoidal resection of a craniopharyngioma. A head computed tomography (CT) was unremarkable except for postoperative findings. Electroencephalogram and laboratory studies were within the normal limits. A repeated CT scan 48 hours after the initial symptoms showed bilateral infarcts in the territory of the anterior cerebral arteries (ACA). Transcranial Doppler (TCD) showed increased blood flow velocities in both anterior cerebral arteries (169 cm/second in the left ACA and 145 cm/second in the right ACA) and right middle cerebral artery (164 cm/second) compatible with vasospasm. A CT angiography confirmed the findings. She was treated with induced hypertension and her level of consciousness improved. TCD velocities normalized after 2 weeks. Cerebral vasospasm should be considered in the differential diagnosis of patients with altered neurologic status in the postoperative period following a craniopharyngioma resection. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion.

PubMed

Spray, S; Johansson, S E; Radziwon-Balicka, A; Haanes, K A; Warfvinge, K; Povlsen, G K; Kelly, P A T; Edvinsson, L

2017-08-01

Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature. © 2016 Scandinavian Physiological Society. Published by John Wiley

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement.

PubMed

Tanaka, Akiko; Estrera, Anthony L

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field-and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution.

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement

PubMed Central

Tanaka, Akiko

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field—and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution. PMID:29682460

Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

PubMed

Anniko, M; Ritzén, E M

1986-01-01

True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

Biology of the sauropod dinosaurs: the evolution of gigantism.

PubMed

Sander, P Martin; Christian, Andreas; Clauss, Marcus; Fechner, Regina; Gee, Carole T; Griebeler, Eva-Maria; Gunga, Hanns-Christian; Hummel, Jürgen; Mallison, Heinrich; Perry, Steven F; Preuschoft, Holger; Rauhut, Oliver W M; Remes, Kristian; Tütken, Thomas; Wings, Oliver; Witzel, Ulrich

2011-02-01

The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism. We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores. The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates. The

Caffeine induced changes in cerebral circulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathew, R.J.; Wilson, W.H.

1985-09-01

While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the TTXenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differencesmore » between the three sets of cerebral blood flow values.« less

What makes children with cerebral palsy vulnerable to malnutrition? Findings from the Bangladesh cerebral palsy register (BCPR).

PubMed

Jahan, Israt; Muhit, Mohammad; Karim, Tasneem; Smithers-Sheedy, Hayley; Novak, Iona; Jones, Cheryl; Badawi, Nadia; Khandaker, Gulam

2018-04-16

To assess the nutritional status and underlying risk factors for malnutrition among children with cerebral palsy in rural Bangladesh. We used data from the Bangladesh Cerebral Palsy Register; a prospective population based surveillance of children with cerebral palsy aged 0-18 years in a rural subdistrict of Bangladesh (i.e., Shahjadpur). Socio-demographic, clinical and anthropometric measurements were collected using Bangladesh Cerebral Palsy Register record form. Z scores were calculated using World Health Organization Anthro and World Health Organization AnthroPlus software. A total of 726 children with cerebral palsy were registered into the Bangladesh Cerebral Palsy Register (mean age 7.6 years, standard deviation 4.5, 38.1% female) between January 2015 and December 2016. More than two-third of children were underweight (70.0%) and stunted (73.1%). Mean z score for weight for age, height for age and weight for height were -2.8 (standard deviation 1.8), -3.1 (standard deviation 2.2) and -1.2 (standard deviation 2.3) respectively. Moderate to severe undernutrition (i.e., both underweight and stunting) were significantly associated with age, monthly family income, gross motor functional classification system and neurological type of cerebral palsy. The burden of undernutrition is high among children with cerebral palsy in rural Bangladesh which is augmented by both poverty and clinical severity. Enhancing clinical nutritional services for children with cerebral palsy should be a public health priority in Bangladesh. Implications for Rehabilitation Population-based surveillance data on nutritional status of children with cerebral palsy in Bangladesh indicates substantially high burden of malnutrition among children with CP in rural Bangladesh. Children with severe form of cerebral palsy, for example, higher Gross Motor Function Classification System (GMFCS) level, tri/quadriplegic cerebral palsy presents the highest proportion of severe malnutrition; hence, these

Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid Angiopathy.

PubMed

Honda, Kazuhiro

2016-08-01

An impairment of amyloid-β (Aβ) clearance has been suggested in Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is considered an important amyloid clearance pathway. This study examined the effect of reduced arterial pulsation that could cause an impairment in cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a surrogate marker for cerebral amyloid angiopathy (CAA). Patients who lost depiction of either side of the carotid artery or the middle cerebral artery on magnetic resonance angiography were studied. Those who showed acute cerebral infarction or a previous cortical cerebral infarction were excluded. The number of CMBs was counted on the occluded and non-occluded sides of the brain in each subject. The number of subjects who showed more CMBs on the occluded side of the brain was compared with the number of subjects who showed more CMBs on the non-occluded side of the brain. Twenty-eight patients were studied. The extent of lacunar infarction and white matter lesions was not different, irrespective of the occluded vessels or the distribution of CMBs. The prevalence of CMBs was not different between the occluded and non-occluded sides of the brain. In this cross-sectional study, reduction of arterial pulsation was not associated with a higher prevalence of CAA. Therefore, reduced arterial pulsation alone may not be enough to promote CAA.

[Advances in genetic research of cerebral palsy].

PubMed

Wang, Fang-Fang; Luo, Rong; Qu, Yi; Mu, De-Zhi

2017-09-01

Cerebral palsy is a group of syndromes caused by non-progressive brain injury in the fetus or infant and can cause disabilities in childhood. Etiology of cerebral palsy has always been a hot topic for clinical scientists. More and more studies have shown that genetic factors are closely associated with the development of cerebral palsy. With the development and application of various molecular and biological techniques such as chromosome microarray analysis, genome-wide association study, and whole exome sequencing, new achievements have been made in the genetic research of cerebral palsy. Chromosome abnormalities, copy number variations, susceptibility genes, and single gene mutation associated with the development of cerebral palsy have been identified, which provides new opportunities for the research on the pathogenesis of cerebral palsy. This article reviews the advances in the genetic research on cerebral palsy in recent years.

Human versus Robots in the Discovery and Crystallization of Gigantic Polyoxometalates.

PubMed

Duros, Vasilios; Grizou, Jonathan; Xuan, Weimin; Hosni, Zied; Long, De-Liang; Miras, Haralampos N; Cronin, Leroy

2017-08-28

The discovery of new gigantic molecules formed by self-assembly and crystal growth is challenging as it combines two contingent events; first is the formation of a new molecule, and second its crystallization. Herein, we construct a workflow that can be followed manually or by a robot to probe the envelope of both events and employ it for a new polyoxometalate cluster, Na 6 [Mo 120 Ce 6 O 366 H 12 (H 2 O) 78 ]⋅200 H 2 O (1) which has a trigonal-ring type architecture (yield 4.3 % based on Mo). Its synthesis and crystallization was probed using an active machine-learning algorithm developed by us to explore the crystallization space, the algorithm results were compared with those obtained by human experimenters. The algorithm-based search is able to cover ca. 9 times more crystallization space than a random search and ca. 6 times more than humans and increases the crystallization prediction accuracy to 82.4±0.7 % over 77.1±0.9 % from human experimenters. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs.

PubMed

Duebener, Lennart F; Hagino, Ikuo; Schmitt, Katharina; Sakamoto, Takahiko; Stamm, Christof; Zurakowski, David; Schäfers, Hans-Joachim; Jonas, Richard A

2003-04-01

Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue

Cerebral Lateralization and Aggression.

ERIC Educational Resources Information Center

Hillbrand, Marc; And Others

1994-01-01

A resurgence of interest in the relationship between cerebral lateralization (the functional asymmetry of the cerebral cortex) and aggression has occurred. Most recent studies have found that individuals with abnormal patterns of lateralization are overrepresented among violent individuals. Intervening variables (such as drug and alcohol abuse)…

Puerarin Attenuates Cerebral Damage by Improving Cerebral Microcirculation in Spontaneously Hypertensive Rats

PubMed Central

Wu, Xu-Dong; Wang, Chen; Zhang, Zhen-Ying; Fu, Yan; Liu, Feng-Ying; Liu, Xiu-Hua

2014-01-01

Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [3H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole

A Gigantic Jet Observed Over an Mesoscale Convective System in Midlatitude Region

NASA Astrophysics Data System (ADS)

Yang, Jing; Sato, Mitsuteru; Liu, Ningyu; Lu, Gaopeng; Wang, Yu; Wang, Zhichao

2018-01-01

Gigantic jets (GJs) are mostly observed over summer tropical or tropical-like thunderstorms. This study reports observation of a GJ over a mesoscale convective system (MCS) in the midlatitude region in eastern China. The GJ is observed over a relatively weak radar reflectivity region ahead of the leading line, and the maximum radar echo top along the GJ azimuth was lower than the tropopause in the same region, significantly different from past studies that indicate summer GJs are usually associated with convective surges or overshooting tops. Also different from most of previous observations showing GJ-producing summer thunderstorms only produced GJ type of transient luminous events during their life cycles, two sprites were also captured in a time window of 15 min containing the GJ, indicating that the MCS provides favorable conditions not only for the GJ but also for the sprites. The balloon-borne soundings of the MCS show that there were large wind shears in the middle and upper levels of the thundercloud, which may have played important roles for the GJ production.

On the shoulders of giants: Harvey Cushing's experience with acromegaly and gigantism at the Johns Hopkins Hospital, 1896-1912.

PubMed

Pendleton, Courtney; Adams, Hadie; Salvatori, Roberto; Wand, Gary; Quiñones-Hinojosa, Alfredo

2011-03-01

A review of Dr. Cushing's surgical cases at Johns Hopkins Hospital revealed new information about his early operative experience with acromegaly. Although in 1912 Cushing published selective case studies regarding this work, a review of all his operations for acromegaly during his early years has never been reported. We uncovered 37 patients who Cushing treated with surgical intervention directed at the pituitary gland. Of these, nine patients who presented with symptoms of acromegaly, and one with symptoms of gigantism were selected for further review. Two patients underwent transfrontal 'omega incision' approaches, and the remaining eight underwent transsphenoidal approaches. Of the 10 patients, 6 were male. The mean age was 38.0 years. The mean hospital stay was 39.4 days. There was one inpatient death during primary interventions (10%) and three patients were deceased at the time of last follow-up (33%). The mean time to death, calculated from the date of the primary surgical intervention, and including inpatient and outpatient deaths, was 11.3 months. The mean time to last follow-up, calculated from the day of discharge, was 59.3 months. At the time of last follow-up, two patients reported resolution of headache; four patients reported continued visual deficits, and two patients reported ongoing changes in mental status. This review analyzes the outcomes for 10 patients who underwent surgical intervention for acromegaly or gigantism, and offers an explanation for Cushing's transition from the transfrontal "omega incision" to the transsphenoidal approach while practicing at the Johns Hopkins Hospital.

Deep Invasive Fungal Infection of the Hand in a Child Mimicking a Local Gigantism.

PubMed

Chatterjee, Anirban; Chatterjee, Shamita

2018-04-01

Subcutaneous and deep fungal infections in the hand are rare among children. These are usually found in immunocompromised adults or in persons engaged in soil handling activities, due to direct exposure, especially in the tropics. Delay in diagnosis is usual because pyogenic and other granulomatous infections are considered first. The authors present the case of a healthy, immunocompetent 2½-year-old child who presented with progressive swelling of the right hand mimicking a localized gigantism of the entire hand. Multiple operative drainage procedures done previously had failed to resolve the condition. A biopsy established the presence of fungal hyphae, thus confirming the diagnosis of deep fungal infection of the hand and guided proper therapeutic intervention. A strong index of suspicion needs to be maintained in cases not responding to conventional antibacterial therapy, and both microbiologic and histopathologic samples need to be obtained to establish the diagnosis.

Cerebral Hypoperfusion Precedes Nausea During Centrifugation

NASA Technical Reports Server (NTRS)

Serrador, Jorge M.; Schlegel, Todd T.; Black, F. Owen; Wood, Scott J.

2004-01-01

Nausea and motion sickness are important operational concerns for aviators and astronauts. Understanding underlying mechanisms associated with motion sickness may lead to new treatments. The goal of this work was to determine if cerebral blood flow changes precede the development of nausea in motion sick susceptible subjects. Cerebral flow velocity in the middle cerebral artery (transcranial Doppler), blood pressure (Finapres) and end-tidal CO2 were measured while subjects were rotated on a centrifuge (250 degrees/sec). Following 5 min of rotation, subjects were translated 0.504 m off-center, creating a +lGx centripetal acceleration in the nasal-occipital plane. Ten subjects completed the protocol without symptoms while 5 developed nausea (4 while 6ff-center and 1 while rotating on-center). Prior to nausea, subjects had significant increases in blood pressure (+13plus or minus 3 mmHg, P less than 0.05) and cerebrovascular resistance (+46 plus or minus 17%, P less than 0.05) and decreases in cerebral flow velocity both in the second (-13 plus or minus 4%) and last minute (-22 plus or minus 5%) before symptoms (P less than 0.05). In comparison, controls demonstrated no change in blood pressure or cerebrovascular resistance in the last minute of off-center rotation and only a 7 plus or minus 2% decrease in cerebral flow velocity. All subjects had significant hypocapnia (-3.8 plus or minus 0.4 mmHg, P less than 0.05), however this hypocapnia could not fully explain the cerebral hypoperfusion associated with the development of nausea. These data indicate that reductions in cerebral blood flow precede the development of nausea. Further work is necessary to determine what role cerebral hypoperfusion plays in motion sickness and whether cerebral hypoperfusion can be used to predict the development of nausea in susceptible individuals.

Decreased steady-state cerebral blood flow velocity and altered dynamic cerebral autoregulation during 5-h sustained 15% O2 hypoxia.

PubMed

Nishimura, Naoko; Iwasaki, Ken-ichi; Ogawa, Yojiro; Aoki, Ken

2010-05-01

Effects of hypoxia on cerebral circulation are important for occupational, high-altitude, and aviation medicine. Increased risk of fainting might be attributable to altered cerebral circulation by hypoxia. Dynamic cerebral autoregulation is reportedly impaired immediately by mild hypoxia. However, continuous exposure to hypoxia causes hyperventilation, resulting in hypocapnia. This hypocapnia is hypothesized to restore impaired dynamic cerebral autoregulation with reduced steady-state cerebral blood flow (CBF). However, no studies have examined hourly changes in alterations of dynamic cerebral autoregulation and steady-state CBF during sustained hypoxia. We therefore examined cerebral circulation during 5-h exposure to 15% O2 hypoxia and 21% O2 in 13 healthy volunteers in a sitting position. Waveforms of blood pressure and CBF velocity in the middle cerebral artery were measured using finger plethysmography and transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis. As expected, steady-state CBF velocity decreased significantly from 2 to 5 h of hypoxia, accompanying 2- to 3-Torr decreases in end-tidal CO2 (ETCO2). Furthermore, transfer function gain and coherence in the very-low-frequency range increased significantly at the beginning of hypoxia, indicating impaired dynamic cerebral autoregulation. However, contrary to the proposed hypothesis, indexes of dynamic cerebral autoregulation showed no significant restoration despite ETCO2 reductions, resulting in persistent higher values of very-low-frequency power of CBF velocity variability during hypoxia (214+/-40% at 5 h of hypoxia vs. control) without significant increases in blood pressure variability. These results suggest that sustained mild hypoxia reduces steady-state CBF and continuously impairs dynamic cerebral autoregulation, implying an increased risk of shortage of oxygen supply to the brain.

Comparable Cerebral Blood Flow in Both Hemispheres During Regional Cerebral Perfusion in Infant Aortic Arch Surgery.

PubMed

Rüffer, André; Tischer, Philip; Münch, Frank; Purbojo, Ariawan; Toka, Okan; Rascher, Wolfgang; Cesnjevar, Robert Anton; Jüngert, Jörg

2017-01-01

Cerebral protection during aortic arch repair can be provided by regional cerebral perfusion (RCP) through the innominate artery. This study addresses the question of an adequate bilateral blood flow in both hemispheres during RCP. Fourteen infants (median age 11 days [range, 3 to 108]; median weight, 3.6 kg [range, 2.8 to 6.0 kg]) undergoing RCP (flow rate 54 to 60 mL · kg -1 · min -1 ) were prospectively included. Using combined transfontanellar/transtemporal two- and three-dimensional power/color Doppler sonography, cerebral blood flow intensity in the main cerebral vessels was displayed. Mean time average velocities were measured with combined pulse-wave Doppler in the basilar artery, and both sides of the internal carotid, anterior, and medial cerebral arteries. In addition, bifrontal regional cerebral oximetry (rSO 2 ) was assessed. Comparing both hemispheres, measurements were performed at target temperature (28°C) during full-flow total body perfusion (TBP) and RCP. A regular circle of Willis with near-symmetric blood flow intensity to both hemispheres was visualized in all infants during both RCP and TBP. In the left internal carotid artery, blood flow direction was mixed (retrograde, n = 5; antegrade, n = 8) during TBP and retrograde during RCP. Comparison between sides showed comparable cerebral time average velocities and rSO 2 , except for higher time average velocities in the right internal carotid artery (TBP p = 0.019, RCP p = 0.09). Unilateral comparison between perfusion methods revealed significantly higher rSO 2 in the right hemisphere during TBP (82% ± 9%) compared with RCP (74% ± 11%, p = 0.036). Bilateral assessment of cerebral rSO 2 and time average velocity in the main great cerebral vessels suggests that RCP is associated with near-symmetric blood flow intensity to both hemispheres. Further neurodevelopmental studies are necessary to verify RCP for neuroprotection during aortic arch repair. Copyright © 2017 The Society of

Fulminant cerebral infarction of anterior and posterior cerebral circulation after ascending type of facial necrotizing fasciitis.

PubMed

Lee, Jun Ho; Choi, Hui-Chul; Kim, Chulho; Sohn, Jong Hee; Kim, Heung Cheol

2014-01-01

Necrotizing fasciitis is a soft tissue infection that is characterized by extensive necrosis of the subcutaneous fat, neurovascular structures, and fascia. Cerebral infarction after facial necrotizing fasciitis has been rarely reported. A 61-year-old woman with diabetes was admitted with painful swelling of her right cheek. One day later, she was stuporous and quadriplegic. A computed tomographic scan of her face revealed right facial infection in the periorbital soft tissue, parotid, buccal muscle, and maxillary sinusitis. A computed tomographic scan of the brain revealed cerebral infarction in the right hemisphere, left frontal area, and both cerebellum. Four days later, she died from cerebral edema and septic shock. Involvement of the cerebral vasculature, such as the carotid or vertebral artery by necrotizing fasciitis, can cause cerebral infarction. Facial necrotizing fasciitis should be treated early with surgical treatment and the appropriate antibiotic therapy. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Impact of extracranial contamination on regional cerebral oxygen saturation: a comparison of three cerebral oximetry technologies.

PubMed

Davie, Sophie N; Grocott, Hilary P

2012-04-01

Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to estimate regional cerebral oxygen saturation. Although NIRS cerebral oximetry is being increasingly used in many clinical settings, interdevice technologic differences suggest potential variation in the ability to accurately acquire brain oxygenation signals. The primary objective of this study was to determine if NIRS-derived regional cerebral oxygen saturation measurements accurately account for oxygen saturation contamination from extracranial tissue. Twelve healthy volunteers had each of three NIRS devices (FORE-SIGHT [CAS Medical Systems Inc; Brandford, CT], INVOS 5100C-PB [Covidien; Boulder, CO], and EQUANOX Classic 7600 [Nonin Medical Inc; Plymouth, MN]) randomly applied to the forehead. After this, a circumferential pneumatic head cuff was positioned such that when inflated, hypoxia-ischemia would be produced in the extracranial scalp tissue beneath the NIRS cerebral oximeters. Comparisons among the three devices were made of the NIRS measurements before and following hypoxia-ischemia produced in the scalp tissue with inflation of the head cuff. The induction of extracranial hypoxia-ischemia resulted in a significant reduction in regional cerebral oxygen saturation measurements in all three NIRS devices studied. At 5 min postinflation of the pneumatic head cuff, the INVOS demonstrated a 16.6 ± 9.6% (mean ± SD) decrease from its baseline (P = 0.0001), the FORE-SIGHT an 11.8 ± 5.3% decrease from its baseline (P < 0.0001), and the EQUANOX a 6.8 ± 6.0% reduction from baseline (P = 0.0025). Extracranial contamination appears to significantly affect NIRS measurements of cerebral oxygen saturation. Although the clinical implications of these apparent inaccuracies require further study, they suggest that the oxygen saturation measurements provided by cerebral oximetry do not solely reflect that of the brain alone.

The clinical presentation and biochemical diagnosis of acromegaly and gigantism.

PubMed

Jialal, I; Nathoo, B C; Joubert, S; Asmal, A C; Pillay, N L

1982-04-24

Over a 5-year period 14 patients with acromegaly and gigantism were seen at the endocrine clinic of King Edward VIII Hospital: 9 were Blacks and 5 Indians; 8 of the patients were women. The mean age of the patients was 46 years. Surprisingly, only 2 patients complained of acral overgrowth. Symptomatology was varied and not characteristic of the condition. On examination all patients had unequivocal signs of soft-tissue and bony overgrowth, 64% had visual abnormalities and 50% hypertension. Radiologically, 88% showed an enlarged pituitary fossa. On biochemical investigation, the fasting levels of growth hormone (GH) were increased in 12 patients and during oral glucose tolerance tests, the GH levels in these 12 patients were not suppressed. One patient in whom the fasting GH level was not increased had progressed to the stage of panhypopituitarism, in the remaining patient challenge with thyrotrophin-releasing hormone (TRH) led to increased GH levels and L-dopa challenge resulted in a paradoxical decrease in GH levels. Seven patients with increased GH levels who were challenged with L-dopa showed the typical decrease in GH levels found in this condition; in 5 of these patients, challenged with TRH, GH levels increased. The findings emphasize that despite the ease of clinical diagnosis, appropriate biochemical investigations are necessary to confirm the exact status of the disease, which is rare in the population studied.

Body mass index in ambulatory cerebral palsy patients.

PubMed

Feeley, Brian T; Gollapudi, Kiran; Otsuka, Norman Y

2007-05-01

Malnutrition is a common problem in children with cerebral palsy. Although malnutrition is often recognized in patients with severe cerebral palsy, it can be unrecognized in less severely affected patients. The consequences of malnutrition are serious, and include decreased muscle strength, poor immune status, and depressed cerebral functioning. Low body mass index has been used as a marker for malnutrition. The purpose of this study was to determine which patients in an ambulatory cerebral palsy patient population were at risk for low body mass index. A retrospective chart review was performed on 75 patients. Age, sex, height, weight, type of cerebral palsy, and functional status [gross motor functional classification system (GMFCS) level] was recorded from the chart. Descriptive statistics with bivariate and multivariate regression analyses were performed. Thirty-eight boys and 37 girls with an average age of 8.11 years were included in the study. Unique to our patient population, all cerebral palsy patients were independent ambulators. Patients with quadriplegic cerebral palsy had a significantly lower body mass index than those with diplegic and hemiplegic cerebral palsy. Patients with a GMFCS III had significantly lower body mass index than those with GMFCS I and II. When multivariate regression analysis to control for age and sex was performed, low body mass index remained associated with quadriplegic cerebral palsy and GMFCS III. Malnutrition is a common health problem in patients with cerebral palsy, leading to significant morbidity in multiple organ systems. We found that in an ambulatory cerebral palsy population, patients with lower functional status or quadriplegia had significantly lower body mass index, suggesting that even highly functioning ambulatory cerebral palsy patients are at risk for malnutrition.

Cerebral Microcirculation during Experimental Normovolaemic Anemia

PubMed Central

Bellapart, Judith; Cuthbertson, Kylie; Dunster, Kimble; Diab, Sara; Platts, David G.; Raffel, O. Christopher; Gabrielian, Levon; Barnett, Adrian; Paratz, Jenifer; Boots, Rob; Fraser, John F.

2016-01-01

Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia. Experimental studies suggest that anemia leads to cerebral hypoxia and increased rates of infarction, but the lack of clinical equipoise, when testing the cerebral effects of transfusion among critically injured patients, supports the need of experimental studies. The aim of this study was to quantify cerebral microcirculation and the potential presence of axonal damage in an experimental model exposed to normovolaemic anemia, with the intention of describing possible limitations within management practices in critically ill patients. Under non-recovered anesthesia, six Merino sheep were instrumented using an intracardiac transeptal catheter to inject coded microspheres into the left atrium to ensure systemic and non-chaotic distribution. Cytometric analyses quantified cerebral microcirculation at specific regions of the brain. Amyloid precursor protein staining was used as an indicator of axonal damage. Animals were exposed to normovolaemic anemia by blood extractions from the indwelling arterial catheter with simultaneous fluid replacement through a venous central catheter. Simultaneous data recording from cerebral tissue oxygenation, intracranial pressure, and cardiac output was monitored. A regression model was used to examine the effects of anemia on microcirculation with a mixed model to control for repeated measures. Homogeneous and normal cerebral microcirculation with no evidence of axonal damage was present in all cerebral regions, with no temporal variability, concluding that acute normovolaemic anemia does not result in short-term effects on cerebral microcirculation in the ovine brain. PMID:26869986

Mineralocorticoid receptor activation causes cerebral vessel remodeling and exacerbates the damage caused by cerebral ischemia.

PubMed

Dorrance, Anne M; Rupp, Nikki C; Nogueira, Edson F

2006-03-01

Mineralocorticoid receptor antagonists protect against ischemic cerebrovascular disease; this appears to be caused by changes in cerebral vessel structure that would promote blood flow. Therefore, we hypothesized that mineralocorticoid receptor activation with deoxycorticosterone acetate would cause deleterious remodeling of the cerebral vasculature and exacerbate the damage caused by cerebral ischemia. Six-week-old male Wistar rats were treated with deoxycorticosterone acetate (200 mg/kg) for 6 weeks. At 12 weeks of age, the deoxycorticosterone acetate-treated rats had elevated systolic blood pressure compared with age-matched controls (157+/-5.9 versus 124+/-3.1 mm Hg deoxycorticosterone acetate versus control; P<0.05). The area of ischemic damage resulting from middle cerebral artery occlusion was greater in the deoxycorticosterone acetate-treated rats than control (63.5+/-3.72 versus 46.6+/-5.52% of the hemisphere infarcted, deoxycorticosterone acetate versus control; P<0.05). Middle cerebral artery structure was assessed using a pressurized arteriograph under calcium-free conditions. Over a range of intralumenal pressures, the lumen and ODs of the middle cerebral arteries were smaller in the deoxycorticosterone acetate-treated rats than the control rats (P<0.05). There was also an increase in the wall thickness and wall:lumen ratio in the vessels from deoxycorticosterone acetate-treated rats (P<0.05). The vessels from the deoxycorticosterone acetate-treated rats were stiffer than those from control rats as evidenced by a leftward shift in the stress/strain curve. These novel data suggest that mineralocorticoid receptor activation without salt loading and nephrectomy is sufficient to elicit deleterious effects on the cerebral vasculature that lead to inward hypertrophic remodeling and an increase in the ischemic damage in the event of a stroke.

Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine.

PubMed

Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N; Long, De-Liang; McBurney, Roy T; Cronin, Leroy

2014-04-28

The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical 'real-space' search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo(2)O(2)S(2)](2+)-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo(10)(C5)}; 2, {Mo(14)(C4)4(C5)2}; 3, {Mo(60)(C4)10}; 4, {Mo(48)(C4)6}; 5, {Mo(34)(C4)4}; 6, {Mo(18)(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.

A gigantic new dinosaur from Argentina and the evolution of the sauropod hind foot.

PubMed

González Riga, Bernardo J; Lamanna, Matthew C; Ortiz David, Leonardo D; Calvo, Jorge O; Coria, Juan P

2016-01-18

Titanosauria is an exceptionally diverse, globally-distributed clade of sauropod dinosaurs that includes the largest known land animals. Knowledge of titanosaurian pedal structure is critical to understanding the stance and locomotion of these enormous herbivores and, by extension, gigantic terrestrial vertebrates as a whole. However, completely preserved pedes are extremely rare among Titanosauria, especially as regards the truly giant members of the group. Here we describe Notocolossus gonzalezparejasi gen. et sp. nov. from the Upper Cretaceous of Mendoza Province, Argentina. With a powerfully-constructed humerus 1.76 m in length, Notocolossus is one of the largest known dinosaurs. Furthermore, the complete pes of the new taxon exhibits a strikingly compact, homogeneous metatarsus--seemingly adapted for bearing extraordinary weight--and truncated unguals, morphologies that are otherwise unknown in Sauropoda. The pes underwent a near-progressive reduction in the number of phalanges along the line to derived titanosaurs, eventually resulting in the reduced hind foot of these sauropods.

A Paleocene penguin from New Zealand substantiates multiple origins of gigantism in fossil Sphenisciformes.

PubMed

Mayr, Gerald; Scofield, R Paul; De Pietri, Vanesa L; Tennyson, Alan J D

2017-12-12

One of the notable features of penguin evolution is the occurrence of very large species in the early Cenozoic, whose body size greatly exceeded that of the largest extant penguins. Here we describe a new giant species from the late Paleocene of New Zealand that documents the very early evolution of large body size in penguins. Kumimanu biceae, n. gen. et sp. is larger than all other fossil penguins that have substantial skeletal portions preserved. Several plesiomorphic features place the new species outside a clade including all post-Paleocene giant penguins. It is phylogenetically separated from giant Eocene and Oligocene penguin species by various smaller taxa, which indicates multiple origins of giant size in penguin evolution. That a penguin rivaling the largest previously known species existed in the Paleocene suggests that gigantism in penguins arose shortly after these birds became flightless divers. Our study therefore strengthens previous suggestions that the absence of very large penguins today is likely due to the Oligo-Miocene radiation of marine mammals.

Intraspecific competition and high food availability are associated with insular gigantism in a lizard.

PubMed

Pafilis, Panayiotis; Meiri, Shai; Foufopoulos, Johannes; Valakos, Efstratios

2009-09-01

Resource availability, competition, and predation commonly drive body size evolution. We assess the impact of high food availability and the consequent increased intraspecific competition, as expressed by tail injuries and cannibalism, on body size in Skyros wall lizards (Podarcis gaigeae). Lizard populations on islets surrounding Skyros (Aegean Sea) all have fewer predators and competitors than on Skyros but differ in the numbers of nesting seabirds. We predicted the following: (1) the presence of breeding seabirds (providing nutrients) will increase lizard population densities; (2) dense lizard populations will experience stronger intraspecific competition; and (3) such aggression, will be associated with larger average body size. We found a positive correlation between seabird and lizard densities. Cannibalism and tail injuries were considerably higher in dense populations. Increases in cannibalism and tail loss were associated with large body sizes. Adult cannibalism on juveniles may select for rapid growth, fuelled by high food abundance, setting thus the stage for the evolution of gigantism.

A gigantic new dinosaur from Argentina and the evolution of the sauropod hind foot

PubMed Central

González Riga, Bernardo J.; Lamanna, Matthew C.; Ortiz David, Leonardo D.; Calvo, Jorge O.; Coria, Juan P.

2016-01-01

Titanosauria is an exceptionally diverse, globally-distributed clade of sauropod dinosaurs that includes the largest known land animals. Knowledge of titanosaurian pedal structure is critical to understanding the stance and locomotion of these enormous herbivores and, by extension, gigantic terrestrial vertebrates as a whole. However, completely preserved pedes are extremely rare among Titanosauria, especially as regards the truly giant members of the group. Here we describe Notocolossus gonzalezparejasi gen. et sp. nov. from the Upper Cretaceous of Mendoza Province, Argentina. With a powerfully-constructed humerus 1.76 m in length, Notocolossus is one of the largest known dinosaurs. Furthermore, the complete pes of the new taxon exhibits a strikingly compact, homogeneous metatarsus—seemingly adapted for bearing extraordinary weight—and truncated unguals, morphologies that are otherwise unknown in Sauropoda. The pes underwent a near-progressive reduction in the number of phalanges along the line to derived titanosaurs, eventually resulting in the reduced hind foot of these sauropods. PMID:26777391

Respiratory evolution facilitated the origin of pterosaur flight and aerial gigantism.

PubMed

Claessens, Leon P A M; O'Connor, Patrick M; Unwin, David M

2009-01-01

Pterosaurs, enigmatic extinct Mesozoic reptiles, were the first vertebrates to achieve true flapping flight. Various lines of evidence provide strong support for highly efficient wing design, control, and flight capabilities. However, little is known of the pulmonary system that powered flight in pterosaurs. We investigated the structure and function of the pterosaurian breathing apparatus through a broad scale comparative study of respiratory structure and function in living and extinct archosaurs, using computer-assisted tomographic (CT) scanning of pterosaur and bird skeletal remains, cineradiographic (X-ray film) studies of the skeletal breathing pump in extant birds and alligators, and study of skeletal structure in historic fossil specimens. In this report we present various lines of skeletal evidence that indicate that pterosaurs had a highly effective flow-through respiratory system, capable of sustaining powered flight, predating the appearance of an analogous breathing system in birds by approximately seventy million years. Convergent evolution of gigantism in several Cretaceous pterosaur lineages was made possible through body density reduction by expansion of the pulmonary air sac system throughout the trunk and the distal limb girdle skeleton, highlighting the importance of respiratory adaptations in pterosaur evolution, and the dramatic effect of the release of physical constraints on morphological diversification and evolutionary radiation.

Respiratory Evolution Facilitated the Origin of Pterosaur Flight and Aerial Gigantism

PubMed Central

Claessens, Leon P. A. M.; O'Connor, Patrick M.; Unwin, David M.

2009-01-01

Pterosaurs, enigmatic extinct Mesozoic reptiles, were the first vertebrates to achieve true flapping flight. Various lines of evidence provide strong support for highly efficient wing design, control, and flight capabilities. However, little is known of the pulmonary system that powered flight in pterosaurs. We investigated the structure and function of the pterosaurian breathing apparatus through a broad scale comparative study of respiratory structure and function in living and extinct archosaurs, using computer-assisted tomographic (CT) scanning of pterosaur and bird skeletal remains, cineradiographic (X-ray film) studies of the skeletal breathing pump in extant birds and alligators, and study of skeletal structure in historic fossil specimens. In this report we present various lines of skeletal evidence that indicate that pterosaurs had a highly effective flow-through respiratory system, capable of sustaining powered flight, predating the appearance of an analogous breathing system in birds by approximately seventy million years. Convergent evolution of gigantism in several Cretaceous pterosaur lineages was made possible through body density reduction by expansion of the pulmonary air sac system throughout the trunk and the distal limb girdle skeleton, highlighting the importance of respiratory adaptations in pterosaur evolution, and the dramatic effect of the release of physical constraints on morphological diversification and evolutionary radiation. PMID:19223979

Velocidades radiales Coravel y fotometría UBV de gigantes rojas del cúmulo abierto Melotte71

NASA Astrophysics Data System (ADS)

Mermilliod, J. C.; Clariá, J. J.; Andersen, J.; Mayor, M.

Se presentan velocidades radiales determinadas con el espectrovelocímetro CORAVEL y fotometría UBV de 24 gigantes rojas del cúmulo abierto de edad-intermedia Melotte71. Las observaciones realizadas en La Silla y Cerro Tololo permiten confirmar la pertenencia al cúmulo de 16 estrellas, de las cuales 8 constituyen nuevas binarias espectroscópicas cuyos períodos oscilan entre 74 y 1627 días. La velocidad radial media es +57.17 ± 0.47 km/s. El mejor ajuste con una isócrona teórica se obtiene para log t (edad) = 9.00 y Z = 0.008, no obstante existir algunas discrepancias respecto de la ubicación predicha y observada del ``clump".

Non operative management of cerebral abscess

NASA Astrophysics Data System (ADS)

Batubara, C. A.

2018-03-01

Cerebral abscess is a focal intracerebral infection that begins as a localized area of cerebritis and develops into a collection of pus surrounded by a well-vascularized capsule. Patients typically present with varying combinations of aheadache, progressive neurologic deficits, seizures, and evidence of infection. Computed Tomography and Magnetic Resonance Imagingare the most important diagnostic tools in diagnosing cerebral abscess. The treatment of cerebral abscess has been a challenge. Small cerebralabscesses (< 2.5 cm) have been treated empirically with antibiotics. Elevation of intracranial pressure and threatening herniation can be managed by the use of intravenous mannitol (or hypertonic saline) and dexamethasone. Acute seizures should be terminated with the administration of intravenous benzodiazepines or by intravenous fosphenytoin. Anticonvulsants prophylaxis must be initiated immediately and continued at least one year due to high risk in the cerebral abscesses. Easier detection of underlying conditions, monitoring of the therapeutic progress, and recognition of complications have probably contributed to the improved prognosis.

A reappraisal of retrograde cerebral perfusion.

PubMed

Ueda, Yuichi

2013-05-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients.

LTR Retrotransposons Contribute to Genomic Gigantism in Plethodontid Salamanders

PubMed Central

Sun, Cheng; Shepard, Donald B.; Chong, Rebecca A.; López Arriaza, José; Hall, Kathryn; Castoe, Todd A.; Feschotte, Cédric; Pollock, David D.; Mueller, Rachel Lockridge

2012-01-01

Among vertebrates, most of the largest genomes are found within the salamanders, a clade of amphibians that includes 613 species. Salamander genome sizes range from ∼14 to ∼120 Gb. Because genome size is correlated with nucleus and cell sizes, as well as other traits, morphological evolution in salamanders has been profoundly affected by genomic gigantism. However, the molecular mechanisms driving genomic expansion in this clade remain largely unknown. Here, we present the first comparative analysis of transposable element (TE) content in salamanders. Using high-throughput sequencing, we generated genomic shotgun data for six species from the Plethodontidae, the largest family of salamanders. We then developed a pipeline to mine TE sequences from shotgun data in taxa with limited genomic resources, such as salamanders. Our summaries of overall TE abundance and diversity for each species demonstrate that TEs make up a substantial portion of salamander genomes, and that all of the major known types of TEs are represented in salamanders. The most abundant TE superfamilies found in the genomes of our six focal species are similar, despite substantial variation in genome size. However, our results demonstrate a major difference between salamanders and other vertebrates: salamander genomes contain much larger amounts of long terminal repeat (LTR) retrotransposons, primarily Ty3/gypsy elements. Thus, the extreme increase in genome size that occurred in salamanders was likely accompanied by a shift in TE landscape. These results suggest that increased proliferation of LTR retrotransposons was a major molecular mechanism contributing to genomic expansion in salamanders. PMID:22200636

Cerebellar malformations alter regional cerebral development.

PubMed

Bolduc, Marie-Eve; Du Plessis, Adre J; Evans, Alan; Guizard, Nicolas; Zhang, Xun; Robertson, Richard L; Limperopoulos, Catherine

2011-12-01

The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p < 0.001), subgenual white matter (p = 0.03), midtemporal white matter (p = 0.02), and inferior occipital grey matter (p = 0.03) volumes than typically developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

PubMed Central

2010-01-01

Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

PubMed

Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

2010-10-19

Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.

Optoacoustic mapping of cerebral blood oxygenation in humans

NASA Astrophysics Data System (ADS)

Petrov, Yuriy; Prough, Donald S.; Petrov, Irene Y.; Richardson, C. Joan; Fonseca, Rafael A.; Robertson, Claudia S.; Esenaliev, Rinat O.

2017-03-01

Noninvasive, transcranial mapping, monitoring, and imaging are highly important for detection and management of cerebral abnormalities and neuroscience research. Mapping, imaging, and monitoring of cerebral blood oxygenation are necessary for diagnostics and management of patients with traumatic brain injury, stroke, and other neurological conditions. We proposed to use optoacoustic technology for noninvasive, transcranial monitoring and imaging. In this work, we developed optoacoustic systems for mapping of cerebral blood oxygenation in humans and tested them in adults and neonates. The systems provide noninvasive, transcranial optoacoustic measurements in the transmission (forward) and reflection (backward) modes in the near infrared spectral range. Novel, ultra-sensitive probes were built for detection of optoacoustic signals and measurement of blood oxygenation in neonates and adults. Cerebral oxygenation was measured at different lateral sites from the superior sagittal sinus (SSS), a large central cerebral vein, located immediately beneath the midline of the human skull. In neonates, cerebral oxygenation was measured through open anterior and posterior fontanelles. Optoacoustic signal detection at different locations allowed for mapping of cerebral blood oxygenation. Our future studies will be focused on 3D mapping of cerebral blood oxygenation.

Cerebral intolerance during flow arrested carotid angioplasty.

PubMed

St Louis, Myron; Park, Brian D; Dahn, Michael; Bozeman, Patricia

2012-01-01

The use of flow arrest as a means of providing cerebral protection during carotid angioplasty offers the advantages of improved efficiency of debris removal and the ability to provide protection under unfavorable (tortuous) anatomic circumstances. However, in contrast to the filtration methods of cerebral protection, this modality requires complete interruption of antegrade carotid artery flow during balloon angioplasty and stent deployment. We report our experience with 9 patients undergoing carotid angioplasty with the Mo.Ma device, which utilizes common and external carotid artery balloon occlusion during the angioplasty procedure. We assessed the clinical outcomes and intraprocedural hemodynamic data. The average duration of carotid occlusion was 8.3 minutes. Of the 9 patients, 2 patients (22%) experienced cerebral intolerance. No stroke occurred in this patient cohort. There appeared to be a poor relationship between procedure intolerance and the presence of significant contralateral stenosis or low carotid back pressure. Furthermore, the incidence of postangioplasty hypotension was not clearly related to cerebral intolerance. Carotid angioplasty with stenting can be safely conducted with flow arrest as an alternative to filter-type cerebral protection devices. However, because cerebral intolerance is not an infrequent occurrence with this approach, clinicians must be cognizant of management strategies for transient cerebral intolerance.

Neuroevolutional Approach to Cerebral Palsy and Speech.

ERIC Educational Resources Information Center

Mysak, Edward D.

Intended for cerebral palsy specialists, the book emphasizes the contribution that a neuroevolutional approach to therapy can make to habilitation goals of the child with cerebral palsy and applies the basic principles of the Bobath approach to therapy. The first section discusses cerebral palsy as a reflection of disturbed neuro-ontogenisis and…

A reappraisal of retrograde cerebral perfusion

PubMed Central

2013-01-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

Cerebral palsy

MedlinePlus

... Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Cerebral palsy URL of this page: //medlineplus.gov/ency/article/ ...

Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

PubMed

Chi, O Z; Barsoum, S; Vega-Cotto, N M; Jacinto, E; Liu, X; Mellender, S J; Weiss, H R

2016-03-01

Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Characteristics and generation of secondary jets and secondary gigantic jets

NASA Astrophysics Data System (ADS)

Lee, Li-Jou; Huang, Sung-Ming; Chou, Jung-Kung; Kuo, Cheng-Ling; Chen, Alfred B.; Su, Han-Tzong; Hsu, Rue-Rou; Frey, Harald U.; Takahashi, Yukihiro; Lee, Lou-Chuang

2012-06-01

Secondary transient luminous events (TLEs) recorded by the ISUAL-FORMOSAT2 mission can either be secondary jets or secondary gigantic jets (GJs), depending on their terminal altitudes. The secondary jets emerge from the cloud top beneath the preceding sprites and extend upward to the base of the sprites at ˜50 km. The secondary jets likely are negative electric discharges with vertically straight luminous columns, morphologically resembling the trailing jet of the type-I GJs. The number of luminous columns in a secondary jet seems to be affected by the size of the effective capacitor plate formed near the base of the preceding sprites and the charge distribution left behind by the sprite-inducing positive cloud-to-ground discharges. The secondary GJs originate from the cloud top under the shielding area of the preceding sprites, and develop upward to reach the lower ionosphere at ˜90 km. The observed morphology of the secondary GJs can either be the curvy shifted secondary GJs extending outside the region occupied by the preceding sprites or the straight pop-through secondary GJs developing through the center of the preceding circular sprites. A key factor in determining the terminal height of the secondary TLEs appears to be the local ionosphere boundary height that established by the preceding sprites. The abundance and the distribution of the negative charge in the thundercloud following the sprite-inducing positive cloud-to-ground discharges may play important role in the generation of the secondary TLEs.

Transcranial Doppler of the middle cerebral artery indicates regional gray matter cerebral perfusion.

PubMed

Pasha, Evan P; Tarumi, Takashi; Haley, Andreana P; Tanaka, Hirofumi

2017-11-30

We determined if transcranial color-coded Doppler derived hemodynamics are associated with MRI-based cerebral blood flow (CBF) in regions clinically important to dementia in healthy middle-aged adults. In 30 subjects (18m/12f; age  =  52  ±  1 years), blood flow velocity (BFV) and cerebrovascular conductance (CVC) were measured with transcranial color-coded Doppler (TCCD) at the middle cerebral artery (MCA) and cerebral blood flow (CBF) was assessed with arterial spin labeled perfusion MRI. BFV and CVC were associated with hippocampus (r  =  0.58 and r  =  0.61, both p  <  0.01) and occipitoparietal (r  =  0.50 and r  =  0.58, both p  <  0.01) CBF. CVC was further associated with posterior cingulate CBF (r  =  0.58 p  <  0.01). Independent of age and sex, BFV and CVC were associated with hippocampus (r  =  0.59 and r  =  0.55, both p  <  0.003) and occipitoparietal (r  =  0.50 and r  =  0.57, both p  <  0.01) CBF. CVC was independently associated with posterior cingulate CBF (r  =  0.38, p  =  0.049). TCCD-measured BFV and CVC of the MCA are indicators of cerebral perfusion to clinically valuable brain regions in healthy middle-aged adults. TCCD may not be a good indicator of blood flow to cerebral white matter.

Pituitary tumor with gigantism, acromegaly and preclinical Cushing's disease diagnosed from the 10th row.

PubMed

Tourtelot, John B; Vesely, David L

2013-08-01

A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.

Surgical trauma induces overgrowth in lower limb gigantism: regulation with use of rapamycin is promising.

PubMed

Pinto, Rohan Sebastian; Harrison, William David; Graham, Kenneth; Nayagam, Durai

2018-01-04

We describe an unclassified overgrowth syndrome characterised by unregulated growth of dermal fibroblasts in the lower limbs of a 35-year-old woman. A PIK3CA gene mutation resulted in lower limb gigantism. Below the waist, she weighed 117 kg with each leg measuring over 100 cm in circumference. Her total adiposity was 50% accounted for by her legs mainly. Liposuction and surgical debulking were performed to reduce the size of the limbs but had exacerbated the overgrowth in her lower limbs. Systemic sepsis from an infected foot ulcer necessitated treatment by an above-knee amputation. Postoperatively, the stump increased in size by 19 kg. A trial of rapamycin to reverse the growth of the stump has shown promise. We discuss the clinical and genetic features of this previously unclassified disorder and the orthopaedic considerations involved. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Study on Cerebral Embolism in Mitral Stenosis

PubMed Central

Kwon, Osun; Kim, Myung Hwan; Kim, Kwon Sam; Bae, Jong Hoa; Kim, Myung Shick; Song, Jung Sang

1986-01-01

To evaluate the significance of episodes of cerebral embolism in patients with mitral valve disease in Korea, 128 patients with echocardiographic diagnosis of mitral valve disease were examined. Among these, 82 patients had predominant mitral stenosis. The clinical features of 82 patients with mitral stenosis have been reviewed to elucidate the factors favoring cerebral embolism which occurred in 19 patients, i.e., incidence of 23.2%.Atrial fibrillation was present in 16 of 19 patients with cerebral embolism (84.2%). Cerebral embolic episodes occurred in 16 of 47 patients with atrial fibrillation (34.0%).The mean age (55.3 ± 12.1 years) of patients without cerebral embolism was significantly older than that (43.2 ± 14.6 years) of patients without cerebral embolism (P<0.005).There was no significant relationship between the incidence of embolism and sex, left atrial thrombi, left atrium/aortic root diameter, mitral valvular orifice area, mitral valvular vegetation or calcification, left ventricular enddiastolic dimension or left ventricular posterior wall thickness. Cerebral embolism is common in patients with mitral stenosis in our country. The presence of atrial fibrillation and low cardiac output increase the attack of cerebral emboli whereas the severity of mitral stenosis, as judged by valve area, may not correlate with the occurrence of emboli. The best treatment for cerebral embolism is prevention. Therefore, we believe that more vigorous treatment of patients with mitral valve disease who are old or associated with atrial fibrillation as well as previous embolic history is indicated. PMID:15759378

Duplicated middle cerebral artery

PubMed Central

Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

2009-01-01

Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion. PMID:22140405

Cerebral specialization. [greater performance efficiency for certain mental abilities or processes by one cerebral hemisphere over another

NASA Technical Reports Server (NTRS)

Morris, Robin D.; Hopkins, William D.; Rumbaugh, Duane M.

1991-01-01

The concept of greater performance efficiency for certain mental abilities or processes in one cerebral hemisphere rather than the other is referred to as 'cerebral lateralization'. The experimental paradigm for lateralization research involves the study of patients with one damaged hemisphere, which prevents their performance of a certain task or function; this approach, however, presents many difficulties in extrapolating to brain function in normal patients. Attention is presently given to gender differences in lateralization, cerebral asymmetries in other species, and the evolutionary bases of hemispheric specialization.

Cerebral Palsy

MedlinePlus

... her strength. Recommend on Facebook Tweet Share Compartir Cerebral palsy (CP) is a group of disorders that affect a ... ability to move and maintain balance and posture. CP is the most common motor disability in childhood. ...

Effects of ischemic stroke on dynamics of cerebral autoregulation

NASA Astrophysics Data System (ADS)

Chen, Zhi; Ivanov, Plamen Ch; Hu, Kun; Stanley, Eugene; Novak, Vera

2004-03-01

Cerebral vasoregulation involves several complex mechanisms adapting blood flow to fluctuations of systemic blood pressure (BP). Autonomic BP and metabolic vasoregulation are impaired after stroke and cerebral blood flow depends on systemic BP. To probe the mechanisms of cerebral autoregulation we study levels of nonlinear synchronization between cerebral blood flow velocity (BFV) and peripheral BP. We quantify the instantaneous phase of each signal employing analytic signal approach and Hilbert transform. As a marker of synchronization, we introduce a measure of cross-correlation between the instantaneous phase increments of the BFV and BP signals at different time lags. We have studied 12 subjects with minor chronic ischemic stroke and 11 matched normotensive controls (age<65years). BFV and BP of these subjects are continuously recorded during supine baseline, head-up tilt, hyperventilation and CO2 rebreathing. For control subjects we find significant synchronization between cerebral BFV and peripheral BP only for short time lags of up to 5-6 seconds, suggesting a rapid return to a steady cerebral blood flow after initial blood pressure perturbations. In contrast, for stroke subjects BFV/BP we find enhanced synchronization over longer time lags of up to 20 seconds, suggesting entrainment of cerebral blood flow velocity by slow vasomotor rhythms. These findings suggest that cerebral vasoregulation is impaired and cerebral blood flow follows the fluctuations of systemic BP in a synchronous manner. Our analysis shows that cerebral autoregulation is impaired in 10 out of the 12 stroke subjects, which is typically difficult to diagnose with conventional methods. Thus, our novel synchronization approach offers a new tool sensitive for evaluation of changes in the dynamics of cerebral autoregulation under stroke.

Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia.

PubMed

Xu, Lili; Hu, Zhiyong; Shen, Jianjun; McQuillan, Patrick M

2015-04-01

Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (p<0.05). Ginkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine

PubMed Central

Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N.; Long, De-Liang; McBurney, Roy T.; Cronin, Leroy

2014-01-01

The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical ‘real-space’ search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo2O2S2]2+-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo10(C5)}; 2, {Mo14(C4)4(C5)2}; 3, {Mo60(C4)10}; 4, {Mo48(C4)6}; 5, {Mo34(C4)4}; 6, {Mo18(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations. PMID:24770632

The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. 1984.

PubMed

Neri, Giovanni; Martini-Neri, Maria Enrica; Katz, Ben E; Opitz, John M

2013-11-01

The ensuing paper by Professor Giovanni Neri and colleagues was originally published in 1984, American Journal of Medical Genetics 19:195–207. The original article described a new family with a condition that the authors designated as the Perlman syndrome. This disorder, while uncommon, is an important multiple congenital anomaly and dysplasia syndrome; the causative gene was recently identified. This paper is a seminal work and is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al. [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed. © 2013 Wiley Periodicals, Inc.

Lower limb gigantism, lymphedema, and painful varicosities following a thigh vascular access graft.

PubMed

Thompson, Michael; Mathuram Thiyagarajan, Umasankar; Akoh, Jacob A

2014-07-01

Prosthetic arteriovenous grafts (AVGs) are associated with greater morbidity than autogenous arteriovenous fistulas (AVFs), but their use is indicated when AVF formation is not possible. This report adds to the literature a case of lower limb gigantism, painful varicosities, and lymphedema following long-term use of AVG in the upper thigh. The patient's past medical history included renal transplantation on the same side well before the AVG was inserted and right leg deep vein thrombosis. Suspicion of AVG thrombosis was excluded by Doppler ultrasound, which demonstrated an access flow of 1700 mL/min. A computed tomography (CT) scan of the abdomen and pelvis did not identify the cause of her symptoms. Whereas functional incompetence of the iliac vein valve might be responsible for the varicosities, the extent of hypertrophy in this case raises the suspicion of lymphatic blockage possibly secondary to groin dissection undertaken at the time of graft insertion, in addition to the previous dissection at the time of transplantation. This case highlights the need for minimal groin dissection during AVG insertion, particularly in patients with a history of previous abdominopelvic surgery. © 2014 International Society for Hemodialysis.

Changes in intracranial pressure gradients between the cerebral hemispheres in patients with intracerebral hematomas in one cerebral hemisphere.

PubMed

Qiu, Wusi; Jiang, Qizhou; Xiao, Guoming; Wang, Weiming; Shen, Hong

2014-01-01

Intracranial-pressure (ICP) monitoring is useful for patients with increased ICP following hemorrhagic stroke. In this study, the changes in pressure gradients between the two cerebral hemispheres were investigated after hemorrhagic stroke of one side, and after a craniotomy. Twenty-four patients with acute cerebral hemorrhages and intracerebral hematomas who exhibited mass effect and midline shift to the contralateral side on computed tomography were selected for this study. After admission, both sides of the cranium were drilled, and optical fiber sensors were implanted to monitor the brain parenchyma pressure (BPP) in both cerebral hemispheres. All patients underwent surgical hematoma evacuations. The preoperative and postoperative BPP data from both cerebral hemispheres were collected at various time points and compared pairwise. There were statistically significant differences (P < 0.01) in the preoperative BPP values between the two hemispheres at three different time points. Differences in the BPP values between the two hemispheres at the time of surgery, and 24 and 48 h after surgery, were not statistically significant (P > 0.05). The posteroperative BPPs of both hemispheres were statistically significantly lower than preoperative recordings. BPP sensors should be applied to the injured cerebral hemisphere, because this becomes the source of increased ICP. Hematoma evacuation surgery effectively decreases ICP and eliminates pressure gradients between the two cerebral hemispheres, consequently enabling brain shift correction.

Cerebral glucose deficiency versus oxygen deficiency in neonatal encephalopathy.

PubMed

Rudolph, A M

2018-04-24

Hypoxic-ischemic encephalopathy (HIE) in newborn infants is generally considered to result from decreased arterial oxygen content or cerebral blood flow. Cerebral injury similar to that of HIE has been noted with hypoglycemia. Studies in fetal lambs have shown that ventilation with 3% oxygen did not change cerebral blood flow, but ventilation with 100% oxygen resulted in marked reduction in cerebral blood flow, glucose delivery and glucose consumption. Blood glucose concentration falls markedly after birth; this, associated with the fall in cerebral blood flow, greatly reduces glucose supply to the brain. In preterm infants, blood glucose levels tend to be very low. Also persistent patency of the ductus arteriosus may reduce cerebral flow in diastole, thus exaggerating the decrease in glucose supply. I propose that glycopenic-ischemic encephalopathy is a more appropriate term for the cerebral insult. We should consider more aggressive management of the low blood glucose concentrations in the neonate, and particularly in preterm infants. Administration of high levels of oxygen in inspired air should be avoided to reduce the enhancement of cerebral vasoconstriction and decreased flow that normally occurs after birth.

Human cerebral autoregulation before, during and after spaceflight.

PubMed

Iwasaki, Ken-ichi; Levine, Benjamin D; Zhang, Rong; Zuckerman, Julie H; Pawelczyk, James A; Diedrich, André; Ertl, Andrew C; Cox, James F; Cooke, William H; Giller, Cole A; Ray, Chester A; Lane, Lynda D; Buckey, Jay C; Baisch, Friedhelm J; Eckberg, Dwain L; Robertson, David; Biaggioni, Italo; Blomqvist, C Gunnar

2007-03-15

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased

Neurofibromatosis, gigantism, elephantiasis neuromatosa and recurrent massive subperiosteal hematoma: a new case report and review of 7 case reports from the literature.

PubMed

Steenbrugge, F; Poffyn, B; Uyttendaele, D; Verdonk, R; Verstraete, K

2001-04-01

The authors report the case of a 13-year-old patient with neurofibromatosis (NF-I), who suffered blunt trauma to the left tibia in 1993. The diagnosis of subperiosteal hematoma was made. Treatment consisted of temporary rest. There was a recurrence in 1996, and the subperiosteal hematoma was drained. In 1997, a shortening osteotomy of the left tibia was performed. However, massive gigantism with elephantiasis of the left leg remained, causing a serious functional and cosmetic problem. In 1999, the leg was amputated above the knee. The literature is reviewed and 7 case reports are compared. The pathogenesis of subperiosteal hematoma is discussed.

[The Cerebral Function Monitor. Description, functioning and interpretation principles].

PubMed

Roujas, F; Bertrand, C; Hrouda, P; Laborit, G; Lang, G; Rivet, P

1979-01-01

The Monitor of Cerebral Function enables continuous monitoring of the cerebral electrical activity and this over long periods due to the slow recording speeds. The cerebral electrical signals picked up by the electrodes attached to the scalp are registered in the form of a curve which fluctuates to a greater or lesser extent depending on the recording speed. The examination of the height of the curve with respect to zero and its amplitude indicates the voltage of the cerebral activity and yields information regarding polymorphism. It is thus possible to monitor variations in cerebral activity over a prolonged period during anaesthesia as well as during the revival phase with the Monitor of Cerebral Function, the electroencephalogram being reserved as an aid to precise diagnosis and for localization and close scruting of the anomalies.

Five-year follow-up of a 13-year-old boy with a pituitary adenoma causing gigantism--effect of octreotide therapy.

PubMed

Schoof, Ellen; Dörr, Helmuth G; Kiess, Wieland; Lüdecke, Dieter K; Freitag, Eduard; Zindel, Volker; Rascher, Wolfgang; Dötsch, Jörg

2004-01-01

In children, there is little experience with octreotide therapy for pituitary tumors, especially growth hormone (GH) producing adenomas. We report on a 13-year-old boy with gigantism due to a GH-producing pituitary adenoma caused by a Gsalpha mutation on the basis of McCune-Albright syndrome. At the age of 6.5 years a GH- and prolactin-producing pituitary adenoma was diagnosed. The adenoma was surgically removed. Immediately thereafter, the small adenoma residuum was treated with octreotide (2 x 100 microg/day s.c.). During therapy with octreotide, the growth rate dropped to normal values; however, rose again after 2 years of treatment. The insulin-like growth factor I (IGF-I) levels remained above the 95th percentile, the GH level mostly >2 microg/l. After 5 years of octreotide therapy, GH (6.9 microg/l), IGF-I (620 microg/l), IGF-binding protein 3 (5.4 mg/l), and prolactin (17.0 ng/ml) levels were still elevated. The growth velocity was +2.4 SDS (standard deviation score), the pubertal status was mature, and the bone age was 14.3 years (prospective final height 208 cm). A magnetic resonance imaging scan showed an unchanged residual 4-mm rim of adenoma at the pituitary site. Side effects from octreotide therapy were not reported by the patient or his family. The therapy was changed to the long-acting release octreotide analog octreotide-LAR. After 1 year of treatment with octreotide-LAR, the GH level was 1.0 microg/l, and the prospective final height dropped by 10 cm. This case demonstrates that combined surgical and medical treatment can influence the prognosis of childhood gigantism; however, the prognosis of this rare condition remains uncertain. Copyright 2004 S. Karger AG, Basel

Decreased cerebral perfusion in Duchenne muscular dystrophy patients.

PubMed

Doorenweerd, Nathalie; Dumas, Eve M; Ghariq, Eidrees; Schmid, Sophie; Straathof, Chiara S M; Roest, Arno A W; Wokke, Beatrijs H; van Zwet, Erik W; Webb, Andrew G; Hendriksen, Jos G M; van Buchem, Mark A; Verschuuren, Jan J G M; Asllani, Iris; Niks, Erik H; van Osch, Matthias J P; Kan, Hermien E

2017-01-01

Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume. Copyright © 2016 Elsevier B.V. All rights reserved.

Time-of-Flight MR Angiography for Detection of Cerebral Hyperperfusion Syndrome after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Moyamoya Disease.

PubMed

Sato, K; Yamada, M; Kuroda, H; Yamamoto, D; Asano, Y; Inoue, Y; Fujii, K; Kumabe, T

2016-07-01

Cerebral hyperperfusion syndrome is a potential complication of superficial temporal artery-MCA anastomosis for Moyamoya disease. In this study, we evaluated whether TOF-MRA could assess cerebral hyperperfusion syndrome after superficial temporal artery-MCA anastomosis for this disease. This retrospective study included patients with Moyamoya disease who underwent superficial temporal artery-MCA single anastomosis. TOF-MRA and SPECT were performed before and 1-6 days after anastomosis. Bilateral ROIs on the source image of TOF-MRA were manually placed directly on the parietal branch of the superficial temporal artery just after branching the frontal branch of the superficial temporal artery and on the contralateral superficial temporal artery on the same axial image, respectively. The change ratio of the maximum signal intensity of the superficial temporal artery on TOF-MRA was calculated by using the following formula: (Postoperative Ipsilateral/Postoperative Contralateral)/(Preoperative Ipsilateral/Preoperative Contralateral). Of 23 patients (26 sides) who underwent the operation, 5 sides showed cerebral hyperperfusion syndrome postoperatively. There was a significant difference in the change ratio of signal intensity on TOF-MRA observed between the cerebral hyperperfusion syndrome and non-cerebral hyperperfusion syndrome groups (cerebral hyperperfusion syndrome group: 1.88 ± 0.32; non-cerebral hyperperfusion syndrome group: 1.03 ± 0.20; P = .0009). The minimum ratio value for the cerebral hyperperfusion syndrome group was 1.63, and the maximum ratio value for the non-cerebral hyperperfusion syndrome group was 1.30. Thus, no overlap was observed between the 2 groups for the change ratio of signal intensity on TOF-MRA. Diagnosis of cerebral hyperperfusion syndrome is indicated by an increase in the change ratio of signal intensity on TOF-MRA by more than approximately 1.5 times the preoperative levels. © 2016 by American Journal of Neuroradiology.

Reversible cerebral vasoconstriction syndrome: a comprehensive update.

PubMed

Mehdi, Ali; Hajj-Ali, Rula A

2014-09-01

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological syndrome characterized by recurrent thunderclap headache, with or without neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS affects patients in various racial and ethnic groups and in all age groups, although most commonly in the fourth decade of life. Many conditions and exposures have been linked to RCVS, including vasoactive drugs and the peripartum period. Disturbance of the cerebral vascular tone is thought to contribute to the disease's pathophysiology. RCVS generally follows a monophasic course. Associated strokes and cerebral hemorrhages are not uncommon. In this review we will attempt to provide a comprehensive overview of RCVS, with emphasis on the controversies in the field and the newest findings in the reported literature.

Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review

PubMed Central

Shekhar, Shashank; Liu, Ruen; Travis, Olivia K; Roman, Richard J; Fan, Fan

2017-01-01

Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function. PMID:29333537

Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

PubMed

Deschamps, Alain; Hall, Richard; Grocott, Hilary; Mazer, C David; Choi, Peter T; Turgeon, Alexis F; de Medicis, Etienne; Bussières, Jean S; Hudson, Christopher; Syed, Summer; Seal, Doug; Herd, Stuart; Lambert, Jean; Denault, André; Deschamps, Alain; Mutch, Alan; Turgeon, Alexis; Denault, Andre; Todd, Andrea; Jerath, Angela; Fayad, Ashraf; Finnegan, Barry; Kent, Blaine; Kennedy, Brent; Cuthbertson, Brian H; Kavanagh, Brian; Warriner, Brian; MacAdams, Charles; Lehmann, Christian; Fudorow, Christine; Hudson, Christopher; McCartney, Colin; McIsaac, Dan; Dubois, Daniel; Campbell, David; Mazer, David; Neilpovitz, David; Rosen, David; Cheng, Davy; Drapeau, Dennis; Dillane, Derek; Tran, Diem; Mckeen, Dolores; Wijeysundera, Duminda; Jacobsohn, Eric; Couture, Etienne; de Medicis, Etienne; Alam, Fahad; Abdallah, Faraj; Ralley, Fiona E; Chung, Frances; Lellouche, Francois; Dobson, Gary; Germain, Genevieve; Djaiani, George; Gilron, Ian; Hare, Gregory; Bryson, Gregory; Clarke, Hance; McDonald, Heather; Roman-Smith, Helen; Grocott, Hilary; Yang, Homer; Douketis, James; Paul, James; Beaubien, Jean; Bussières, Jean; Pridham, Jeremy; Armstrong, J N; Parlow, Joel; Murkin, John; Gamble, Jonathan; Duttchen, Kaylene; Karkouti, Keyvan; Turner, Kim; Baghirzada, Leyla; Szabo, Linda; Lalu, Manoj; Wasowicz, Marcin; Bautista, Michael; Jacka, Michael; Murphy, Michael; Schmidt, Michael; Verret, Michaël; Perrault, Michel-Antoine; Beaudet, Nicolas; Buckley, Norman; Choi, Peter; MacDougall, Peter; Jones, Philip; Drolet, Pierre; Beaulieu, Pierre; Taneja, Ravi; Martin, Rene; Hall, Richard; George, Ronald; Chun, Rosa; McMullen, Sarah; Beattie, Scott; Sampson, Sonia; Choi, Stephen; Kowalski, Stephen; McCluskey, Stuart; Syed, Summer; Boet, Sylvain; Ramsay, Tim; Saha, Tarit; Mutter, Thomas; Chowdhury, Tumul; Uppal, Vishal; Mckay, William

2016-04-01

Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.

[Acetabuloplasty in cerebral palsy patients].

PubMed

Schejbalová, A; Chládek, P

2007-12-01

Acetabuloplasty as an isolated surgical procedure is one of the options allowing for hip joint realignment in cerebral palsy patients. Also, it is often involved in combined techniques used for hip joint reconstruction. In the years 2004-2005, 20 cerebral palsy patients, aged from 4 to 13 years, were indicated for acetabuloplasty. The group included children with varying degrees of locomotor disability, ranging from inability even to crawl to ability to move without support (stages 2 to 7 on the Vojta scale). Clinical and X-ray findings were evaluated at 2 and 6 months after surgical treatment and then every 6 months of follow- up. The X-ray finding was described by means of CE angle (Wiberg) values and hip migration percentage. Of 21 hips (in 20 patients) treated by acetabuloplasty in our modification during the two years, one developed recurrent dorsal dislocation which was possible to deal with by conservative treatment. All hips pre-operatively categorized as group B or group C were post-operatively assessed as group A hips. Subsequent migration of the acetabulum occurred within a year in two patients with distinct original asymmetry. Surgery on bones comprising the hip joint in cerebral palsy patients is indicated according to the degree of lateral migration and changes in hip joint geometry involving the proximal femur or pelvis, or in combination with open reduction. Acetabuloplasty is indicated as an isolated procedure or as part of combined techniques leading to a better coverage of the hip joint. It is recommended for children up to 10 years of age, but also older ones, in whom the flexibility of child bones enables us to do without internal osteosynthesis. Acetabuloplasty is indicated as an isolated surgical procedure for hip joint subluxation in cerebral palsy children. It has no adverse effects on hip abductors that, in cerebral palsy patients, are 85 % insufficient. It improves hip joint symmetry and helps to avoid more demanding reconstructive or

Cerebral oxygenation in the beach chair position for shoulder surgery in regional anesthesia: impact on cerebral blood flow and neurobehavioral outcome.

PubMed

Aguirre, José A; Märzendorfer, Olivia; Brada, Muriel; Saporito, Andrea; Borgeat, Alain; Bühler, Philipp

2016-12-01

Beach chair position is considered a potential risk factor for central neurological events particularly if combined with low blood pressure. The aim of this study was to assess the impact of regional anesthesia on cerebral blood flow and neurobehavioral outcome. This is a prospective, assessor-blinded observational study evaluating patients in the beach chair position undergoing shoulder surgery under regional anesthesia. University hospital operating room. Forty patients with American Society of Anesthesiologists classes I-II physical status scheduled for elective shoulder surgery. Cerebral saturation and blood flow of the middle cerebral artery were measured prior to anesthesia and continued after beach chair positioning until discharge to the postanesthesia care unit. The anesthesiologist was blinded for these values. Controlled hypotension with systolic blood pressure≤100mm Hg was maintained during surgery. Neurobehavioral tests and values of regional cerebral saturation, bispectral index, the mean maximal blood flow of the middle cerebral artery, and invasive blood pressure were measured prior to regional anesthesia, and measurements were repeated after placement of the patient on the beach chair position and every 20 minutes thereafter until discharge to postanesthesia care unit. The neurobehavioral tests were repeated the day after surgery. The incidence of cerebral desaturation events was 5%. All patients had a significant blood pressure drop 5 minutes after beach chair positioning, measured at the heart as well as the acoustic meatus levels, when compared with baseline values (P<.05). There was no decrease in either the regional cerebral saturation (P=.136) or the maximal blood flow of the middle cerebral artery (P=.212) at the same time points. Some neurocognitive tests showed an impairment 24 hours after surgery (P<.001 for 2 of 3 tests). Beach chair position in patients undergoing regional anesthesia for shoulder surgery had no major impact on

Cerebral infarction in association with Ecstasy abuse.

PubMed

Manchanda, S; Connolly, M J

1993-11-01

A previously fit 35 year old man presented with a right hemiparesis and dysphasia 36 hours after abuse of Ecstasy (3,4-methylenedioxymethamphetamine). Computerized axial tomography scan demonstrated an extensive acute left cerebral infarction and carotid digital subtraction angiogram, 2 days after admission, revealed left middle cerebral artery occlusion. There were no other known risk factors and all other investigations were negative. The patient made a partial recovery. We propose an association between Ecstasy abuse and cerebral infarction.

Neuroblastoma in a patient with Sotos' syndrome.

PubMed Central

Nance, M A; Neglia, J P; Talwar, D; Berry, S A

1990-01-01

Sotos' syndrome, or cerebral gigantism, is a disorder of growth regulation. Tumours have occasionally been reported in children with Sotos' syndrome, but it is uncertain whether this is a coincidence, or whether it is aetiologically related to the underlying disorder of growth. We report a 15 month old child with a paraspinal neuroblastoma and Sotos' syndrome and suggest that children with this condition may be at higher risk for developing tumours than the general population. Images PMID:2319581

Acute effect of coffee drinking on dynamic cerebral autoregulation.

PubMed

Sasaki, Hiroyuki; Hirasawa, Ai; Washio, Takuro; Ogoh, Shigehiko

2016-05-01

Drinking coffee causes caffeine-induced physiological alterations such as increases in arterial blood pressure, sympathetic nerve activity, cerebral vasoconstriction, etc., and these physiological alterations may be associated with a reduced risk of cerebral vascular disease. However, the effect of coffee drinking on dynamic cerebral blood flow (CBF) regulation remains unclear. The aim of this study was to test our hypothesis that coffee drinking enhances dynamic cerebral autoregulation. Twelve healthy young subjects participated in the present study. After a 5 min baseline measurement in a semi-recumbent position on the hospital bed, each subject drank water (CON) as a placebo condition or coffee beverage (Coffee INT). Arterial blood pressure and middle cerebral artery blood velocity (MCAv) were measured continuously throughout the experiment. At 30 min after the intake of either water or coffee, dynamic cerebral autoregulation was examined using a thigh cuffs occlusion and release technique. Each condition was randomly performed on a different day. Under Coffee INT condition, mean arterial blood pressure was increased (P = 0.01) and mean MCAv was decreased (P = 0.01) from the baseline. The rate of regulation (RoR), as an index of dynamic cerebral autoregulation, during coffee condition was significantly higher than that during CON (P = 0.0009). The findings of the present study suggest that coffee drinking augments dynamic CBF regulation with cerebral vasoconstriction. This phenomenon may be associated with a reduction in the risk of cerebral vascular disease.

Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction

PubMed Central

Neumann, Jake T.; Cohan, Charles H.; Dave, Kunjan R.; Wright, Clinton B.; Perez-Pinzon, Miguel A.

2018-01-01

Cardiopulmonary arrest is one of the leading causes of death and disability, primarily occurring in the aged population. Numerous global cerebral ischemia animal models induce neuronal damage similar to cardiac arrest. These global cerebral ischemia models range from vessel occlusion to total cessation of cardiac function, both of which have allowed for the investigation of this multifaceted disease and detection of numerous agents that are neuroprotective. Synapses endure a variety of alterations after global cerebral ischemia from the resulting excitotoxicity and have been a major target for neuroprotection; however, neuroprotective agents have proven unsuccessful in clinical trials, as neurological outcomes have not displayed significant improvements in patients. A majority of these neuroprotective agents have specific neuronal targets, where the success of future neuroprotective agents may depend on non-specific targets and numerous cognitive improvements. This review focuses on the different models of global cerebral ischemia, neuronal synaptic alterations, synaptic neuroprotection and behavioral tests that can be used to determine deficits in cognitive function after global cerebral ischemia. PMID:23170794

System of gigantic valleys northwest of Tharsis, Mars: Latent catastrophic flooding, northwest watershed, and implications for northern plains ocean

USGS Publications Warehouse

Dohm, J.M.; Anderson, R.C.; Baker, V.R.; Ferris, J.C.; Hare, T.M.; Strom, R.G.; Rudd, L.P.; Rice, J. W.; Casavant, R.R.; Scott, D.H.

2000-01-01

Mars Orbiter Laser Altimeter (MOLA) reveals a system of gigantic valleys to the northwest of the huge martian shield volcano, Arsia Mons, in the western hemisphere of Mars. These newly identified northwestern slope valleys (NSVs) potentially signify previously undocumented martian catastrophic floods and may corroborate the northern ocean hypotheses. These features, which generally correspond spatially to gravity lows, were previously obscurred in Mariner and Viking Orbiter imagery by veneers of materials, including volcanic lava flows and air fall deposits. Geologic investigations of the Tharsis region suggest that the NSVs were mainly carved prior to the construction of Arsia Mons and its associated Late Hesperian and Amazonian age lava flows, concurrent with the early development of the outflow channels that debouch into Chryse Planitia.

Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

PubMed

Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

2013-03-01

Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P < 0.05). However, there was a negative correlation between radioactivity counts per unit volume detected on the SPECT rheoencephalogram and lactic acid concentration in the homolateral internal carotid artery and vein. In summary, this study found abnormal CBF in metabolism and utilization of brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity.

PubMed

Liu, Jie; Tseng, Benjamin Y; Khan, Muhammad Ayaz; Tarumi, Takashi; Hill, Candace; Mirshams, Niki; Hodics, Timea M; Hynan, Linda S; Zhang, Rong

2016-06-01

Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug-induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the 'over-' rather than the 'less-reactive' CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure. This study measured the individual variability of static cerebral autoregulation (CA) and determined its associations with brain white matter hyperintensity (WMH) in older adults. Twenty-seven healthy older adults (13 females, 66 ± 6 years) underwent assessment of CA during steady-state changes in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside (SNP) and phenylephrine. Cerebral blood flow (CBF) was measured using colour-coded duplex ultrasonography at the internal carotid (ICA) and vertebral arteries (VA). CA was quantified by a linear regression slope (CA slope) between percentage changes in cerebrovascular resistance (CVR = MAP/CBF) and MAP relative to baseline values. Periventricular and deep WMH volumes were measured with T2-weighted magnetic resonance imaging. MAP was reduced by -11 ± 7% during SNP, and increased by 21 ± 8% during phenylephrine infusion. CA demonstrated large individual variability with the CA slopes ranging from 0.37 to 2.20 at the ICA and from 0.17 to 3.18 at the

Genomic gigantism: DNA loss is slow in mountain grasshoppers.

PubMed

Bensasson, D; Petrov, D A; Zhang, D X; Hartl, D L; Hewitt, G M

2001-02-01

Several studies have shown DNA loss to be inversely correlated with genome size in animals. These studies include a comparison between Drosophila and the cricket, Laupala, but there has been no assessment of DNA loss in insects with very large genomes. Podisma pedestris, the brown mountain grasshopper, has a genome over 100 times as large as that of Drosophila and 10 times as large as that of Laupala. We used 58 paralogous nuclear pseudogenes of mitochondrial origin to study the characteristics of insertion, deletion, and point substitution in P. pedestris and Italopodisma. In animals, these pseudogenes are "dead on arrival"; they are abundant in many different eukaryotes, and their mitochondrial origin simplifies the identification of point substitutions accumulated in nuclear pseudogene lineages. There appears to be a mononucleotide repeat within the 643-bp pseudogene sequence studied that acts as a strong hot spot for insertions or deletions (indels). Because the data for other insect species did not contain such an unusual region, hot spots were excluded from species comparisons. The rate of DNA loss relative to point substitution appears to be considerably and significantly lower in the grasshoppers studied than in Drosophila or Laupala. This suggests that the inverse correlation between genome size and the rate of DNA loss can be extended to comparisons between insects with large or gigantic genomes (i.e., Laupala and Podisma). The low rate of DNA loss implies that in grasshoppers, the accumulation of point mutations is a more potent force for obscuring ancient pseudogenes than their loss through indel accumulation, whereas the reverse is true for Drosophila. The main factor contributing to the difference in the rates of DNA loss estimated for grasshoppers, crickets, and Drosophila appears to be deletion size. Large deletions are relatively rare in Podisma and Italopodisma.

Cerebral infarction in association with Ecstasy abuse.

PubMed Central

Manchanda, S.; Connolly, M. J.

1993-01-01

A previously fit 35 year old man presented with a right hemiparesis and dysphasia 36 hours after abuse of Ecstasy (3,4-methylenedioxymethamphetamine). Computerized axial tomography scan demonstrated an extensive acute left cerebral infarction and carotid digital subtraction angiogram, 2 days after admission, revealed left middle cerebral artery occlusion. There were no other known risk factors and all other investigations were negative. The patient made a partial recovery. We propose an association between Ecstasy abuse and cerebral infarction. PMID:7904748

Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux.

PubMed

Grüne, Frank; Kazmaier, Stephan; Sonntag, Hans; Stolker, Robert Jan; Weyland, Andreas

2014-02-01

Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Measurements were performed under fentanyl-midazolam anesthesia in a randomized sequence aiming at partial pressures of carbon dioxide of 30 and 50 mmHg. Endpoints were CBF, blood flow velocity in the middle cerebral artery, and cerebral metabolic rates for oxygen, glucose, and lactate. Global CBF was measured using a modified Kety-Schmidt technique with argon as inert gas tracer. CBF velocity of the middle cerebral artery was recorded by transcranial Doppler sonography. Data were presented as mean (SD). Two-sided paired t tests and one-way ANOVA for repeated measures were used for statistical analysis. Moderate hyperventilation significantly decreased CBF by 60%, blood flow velocity by 41%, cerebral oxygen delivery by 58%, and partial pressure of oxygen of the jugular venous bulb by 45%. Cerebral metabolic rates for oxygen and glucose remained unchanged; however, net cerebral lactate efflux significantly increased from -0.38 (2.18) to -2.41(2.43) µmol min 100 g. Moderate hyperventilation, when compared with moderate hypoventilation, in patients with cardiovascular disease undergoing intravenous anesthesia increased net cerebral lactate efflux and markedly reduced CBF and partial pressure of oxygen of the jugular venous bulb, suggesting partial impairment of cerebral aerobic metabolism at clinically relevant levels of hypocapnia.

Cerebral Effect of Intratracheal Aerosolized Surfactant Versus Bolus Therapy in Preterm Lambs.

PubMed

Rey-Santano, Carmen; Mielgo, Victoria E; López-de-Heredia-y-Goya, Jon; Murgia, Xabier; Valls-i-Soler, Adolfo

2016-04-01

Aerosolization has been proposed as a useful alternative to rapid intratracheal instillation for the delivery of exogenous surfactant in neonatal respiratory distress syndrome. However, there is a lack of information regarding the likely safety of this new therapeutic approach for the neonatal brain. We aimed to compare the cerebral effects of aerosolized versus bolus surfactant administration in premature lambs with respiratory distress syndrome. Prospective randomized study. BioCruces Institute Animal Research Facility. Fourteen intensively monitored and mechanically ventilated preterm lambs. Preterm lambs were randomly assigned to receive intratracheal aerosolized surfactant or bolus surfactant. Brain hemodynamics (cerebral and regional cerebral blood flow) and cerebral oxygen metabolism (cerebral oxygen delivery, cerebral metabolic rate of oxygen, and oxygen extraction fraction) were measured every 30 minutes for 6 hours. We also performed cerebral biochemical and histological analysis. In preterm lambs with respiratory distress syndrome, cerebral blood flow, regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate of oxygen increased significantly in the bolus surfactant group during the first 5 minutes, without changes in cerebral oxygen extraction fraction. By 60 minutes, all parameters had decreased in both groups, cerebral blood flow and regional cerebral blood flow (in inner and cerebellum brainstem regions) remaining higher in the bolus surfactant than in the aerosolized surfactant group. Overall, the impact of aerosol surfactant was not significantly different to that of bolus surfactant in terms of cerebral necrosis, edema, inflammation, hemorrhage, infarct, apoptosis, or oxidative stress. In preterm lambs with severe respiratory distress syndrome, aerosol surfactant administration seems to be as safe as bolus administration, showing more stable cerebral hemodynamics and cerebral oxygen metabolism to the same dose of

[Insomnia and cerebral hypoperfusion].

PubMed

Káposzta, Zoltán; Rácz, Klára

2007-11-18

Insomnia is defined as difficulty with the initiation, maintenance, duration, or quality of sleep that results in the impairment of daytime functioning, despite adequate opportunity and circumstances for sleep. In most countries approximately every third inhabitant has insomnia. Insomnia can be classified as primary and secondary. The pathogenesis of primary insomnia is unknown, but available evidence suggests a state of hyperarousal. Insomnia secondary to other causes is more common than primary insomnia. Cerebral hypoperfusion can be the cause of insomnia in some cases. In such patients the cerebral blood flow should be improved using parenteral vascular therapy. If insomnia persists despite treatment, then therapy for primary insomnia should be instituted using benzodiazepine-receptor agonists such as Zolpidem, Zopiclone, or Zaleplon. In those cases Midazolam cannot be used for the treatment of insomnia due to its marked negative effect on cerebral blood flow. In Hungary there is a need to organize multidisciplinary Insomnia Clinics because insomnia is more than a disease, it is a public health problem in this century.

Pediatric Cerebral Palsy in Botswana: Etiology, Outcomes, and Comorbidities

PubMed Central

Bearden, David R.; Monokwane, Baphaleng; Khurana, Esha; Baier, James; Baranov, Esther; Westmoreland, Kate; Mazhani, Loeto; Steenhoff, Andrew P.

2016-01-01

BACKGROUND Cerebral palsy is the most common cause of motor dysfunction in children worldwide and is often accompanied by multiple comorbidities. Although cerebral palsy has been studied extensively in high-resource settings, there are few published studies on cerebral palsy etiology, outcomes and comorbidities in low-resource settings. METHODS Children with cerebral palsy were prospectively enrolled from inpatient and outpatient settings at a referral center in Gaborone, Botswana, in a cross-sectional study conducted from 2013 to 2014. Cerebral palsy etiology, outcomes, and comorbidities were determined through caregiver interviews, review of medical records, and direct physical examination. RESULTS Sixty-eight children with cerebral palsy were enrolled. Subjects were 41% male, with a median age of 4 years (interquartile range = 2 to 7). The most common etiologies for cerebral palsy in our cohort were intrapartum hypoxic events (18%), postnatal infections (15%), prematurity (15%), focal ischemic strokes (10%), and prenatal infections (10%). Severe motor impairment was common, with the most severe category present in 41%. The predominant comorbidities were cognitive impairment (84%), epilepsy (77%), and visual impairment (46%). CONCLUSIONS Cerebral palsy in Botswana has different etiologies and is associated with poorer outcomes and higher prevalence of comorbidities than what has been reported in high-resource settings. Further studies are necessary to determine optimal preventative and treatment strategies in this population. PMID:27114082

Noninvasive optoacoustic monitoring of cerebral venous blood oxygenation in newborns

NASA Astrophysics Data System (ADS)

Petrov, Irene Y.; Wynne, Karon E.; Petrov, Yuriy; Esenaliev, Rinat O.; Richardson, C. Joan; Prough, Donald S.

2012-02-01

Cerebral ischemia after birth and during labor is a major cause of death and severe complications such as cerebral palsy. In the USA alone, cerebral palsy results in permanent disability of 10,000 newborns per year and approximately 500,000 of the total population. Currently, no technology is capable of direct monitoring of cerebral oxygenation in newborns. This study proposes the use of an optoacoustic technique for noninvasive cerebral ischemia monitoring by probing the superior sagittal sinus (SSS), a large central cerebral vein. We developed and built a multi-wavelength, near-infrared optoacoustic system suitable for noninvasive monitoring of cerebral ischemia in newborns with normal weight (NBW), low birth-weight (LBW, 1500 - 2499 g) and very low birth-weight (VLBW, < 1500 g). The system was capable of detecting SSS signals through the open anterior and posterior fontanelles as well as through the skull. We tested the system in NBW, LBW, and VLBW newborns (weight range: from 675 g to 3,000 g) admitted to the neonatal intensive care unit. We performed single and continuous measurements of the SSS blood oxygenation. The data acquisition, processing and analysis software developed by our group provided real-time, absolute SSS blood oxygenation measurements. The SSS blood oxygenation ranged from 60% to 80%. Optoacoustic monitoring of the SSS blood oxygenation provides valuable information because adequate cerebral oxygenation would suggest that no therapy was necessary; conversely, evidence of cerebral ischemia would prompt therapy to increase cerebral blood flow.

Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury.

PubMed

Gupta, Ram; Singh, Manjeet; Sharma, Ajay

2003-08-01

The present study is designed to investigate the effect of dietary flavanoid rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced cerebral injury. Global cerebral ischaemia was induced by occluding right and left common carotid arteries for 10min followed by reperfusion for 24h. Cerebral infarct size was estimated using triphenyltetrazolium chloride staining. Elevated plus maze was employed to estimate short-term memory. Degree of motor incoordination was evaluated using inclined beam-walking test and lateral push test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was employed as an index of oxidative stress. Global cerebral ischaemia followed by reperfusion produced a significant impairment in short-term memory and motor coordination and produced a notable increase in mitochondrial TBARS. Administration of rutin and garlic oil before global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. Administration of sodium selenite either before or after global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. The protective effect of rutin, sodium selenite and garlic oil was accompanied by a marked decrease in mitochondrial TBARS. On the basis of these results, it may be suggested that rutin and garlic oil administrated before cerebral ischaemia may scavenge reactive oxygen species and consequently attenuate global cerebral ischaemia and reperfusion-induced cerebral injury. Sodium selenite administrated before and after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

Association of Lead Levels and Cerebral Palsy

PubMed Central

Bansal, Neha; Aggarwal, Anju; Faridi, M. M. A.; Sharma, Tusha; Baneerjee, B. D.

2017-01-01

Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001). Among children with cerebral palsy, 19 (55.88%) children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children. PMID:28491920

The importance of bilateral monitoring of cerebral oxygenation (NIRS): Clinical case of asymmetry during cardiopulmonary bypass secondary to previous cerebral infarction.

PubMed

Matcan, S; Sanabria Carretero, P; Gómez Rojo, M; Castro Parga, L; Reinoso-Barbero, F

2018-03-01

Cerebral oximetry based on near infrared spectroscopy (NIRS) technology is used to determine cerebral tissue oxygenation. We hereby present the clinical case of a 12-month old child with right hemiparesis secondary to prior left middle cerebral artery stroke 8 months ago. The child underwent surgical enlargement of the right ventricular outflow tract (RVOT) with cardiopulmonary bypass. During cardiopulmonary bypass, asymmetric NIRS results were detected between both hemispheres. The utilization of multimodal neuromonitoring (NIRS-BIS) allowed acting on both perfusion pressure and anesthetic depth to balance out the supply and demand of cerebral oxygen consumption. No new neurological sequelae were observed postoperatively. We consider bilateral NIRS monitoring necessary in order to detect asymmetries between cerebral hemispheres. Although asymmetries were not present at baseline, they can arise intraoperatively and its monitoring thus allows the detection and treatment of cerebral ischemia-hypoxia in the healthy hemisphere, which if undetected and untreated would lead to additional neurological damage. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Fludrocortisone therapy in cerebral salt wasting.

PubMed

Taplin, Craig E; Cowell, Christopher T; Silink, Martin; Ambler, Geoffrey R

2006-12-01

Cerebral salt wasting is an increasingly recognized condition in pediatrics and is characterized by inappropriate natriuresis and volume contraction in the presence of cerebral pathology. Diagnosis can be difficult and therapy challenging. A few single case reports of the successful use of fludrocortisone exist. We report 4 patients with cerebral salt wasting, all of whom presented with hyponatremia in the presence of known intracerebral pathology. All had clinically significant hyponatremia, and 3 had hyponatremic seizures. Two of the patients also satisfied clinical criteria for diabetes insipidus. They all were treated with regimens using increased sodium and fluid administration but experienced ongoing salt wasting. Fludrocortisone was instituted in all 4 patients and in 3 resulted in rapid improvement in net sodium balance, enabling the weaning of hypertonic fluids and stabilization of serum electrolytes. In 3 patients, fludrocortisone treatment was complicated by hypokalemia, and in 1 patient by hypertension, which necessitated a dose reduction or brief cessation of therapy. Duration of therapy was 4 to 125 days. Cerebral salt wasting presents considerable management challenges; however, fludrocortisone therapy can be an effective adjunct to treatment.

Somatosensory discrimination deficits following pediatric cerebral malaria.

PubMed

Dugbartey, A T; Spellacy, F J; Dugbartey, M T

1998-09-01

Pathologic studies of central nervous system damage in human falciparum malaria indicate primary localization in the cerebral white matter. We report a sensory-perceptual investigation of 20 Ghanaian children with a recent history of cerebral malaria who were age-, gender-, and education-matched with 20 healthy control subjects. Somatosensory examinations failed to show any evidence of hemianesthesia, pseudohemianesthesia, or extinction to double simultaneous tactile stimulation. While unilateral upper limb testing revealed intact unimanual tactile roughness discrimination, bimanual tactile discrimination, however, was significantly impaired in the cerebral malaria group. A strong negative correlation (r = -0.72) between coma duration and the bimanual tactile roughness discrimination test was also found. An inefficiency in the integrity of callosal fibers appear to account for our findings, although alternative subcortical mechanisms known to be involved in information transfer across the cerebral hemispheres may be compromised as well.

Unusual AIP mutation and phenocopy in the family of a young patient with acromegalic gigantism.

PubMed

Imran, Syed Ali; Aldahmani, Khaled A; Penney, Lynette; Croul, Sidney E; Clarke, David B; Collier, David M; Iacovazzo, Donato; Korbonits, Márta

2018-01-01

Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein ( AIP ) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy. Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions.Unusual, previously not described AIP variant with loss of the stop codon.Phenocopy may occur in families with a disease-causing germline mutation.

Unusual AIP mutation and phenocopy in the family of a young patient with acromegalic gigantism

PubMed Central

Aldahmani, Khaled A; Penney, Lynette; Croul, Sidney E; Clarke, David B; Collier, David M; Iacovazzo, Donato; Korbonits, Márta

2018-01-01

Summary Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy. Learning points: Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions. Unusual, previously not described AIP variant with loss of the stop codon. Phenocopy may occur in families with a disease-causing germline mutation. PMID:29472986

Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral artery infarction.

PubMed

Nielsen, T H; Schalén, W; Ståhl, N; Toft, P; Reinstrup, P; Nordström, C H

2014-08-01

The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.

Genetic drift and mutational hazard in the evolution of salamander genomic gigantism.

PubMed

Mohlhenrich, Erik Roger; Mueller, Rachel Lockridge

2016-12-01

Salamanders have the largest nuclear genomes among tetrapods and, excepting lungfishes, among vertebrates as a whole. Lynch and Conery (2003) have proposed the mutational-hazard hypothesis to explain variation in genome size and complexity. Under this hypothesis, noncoding DNA imposes a selective cost by increasing the target for degenerative mutations (i.e., the mutational hazard). Expansion of noncoding DNA, and thus genome size, is driven by increased levels of genetic drift and/or decreased mutation rates; the former determines the efficiency with which purifying selection can remove excess DNA, whereas the latter determines the level of mutational hazard. Here, we test the hypothesis that salamanders have experienced stronger long-term, persistent genetic drift than frogs, a related clade with more typically sized vertebrate genomes. To test this hypothesis, we compared dN/dS and Kr/Kc values of protein-coding genes between these clades. Our results do not support this hypothesis; we find that salamanders have not experienced stronger genetic drift than frogs. Additionally, we find evidence consistent with a lower nucleotide substitution rate in salamanders. This result, along with previous work showing lower rates of small deletion and ectopic recombination in salamanders, suggests that a lower mutational hazard may contribute to genomic gigantism in this clade. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

External carotid compression: a novel technique to improve cerebral perfusion during selective antegrade cerebral perfusion for aortic arch surgery.

PubMed

Grocott, Hilary P; Ambrose, Emma; Moon, Mike

2016-10-01

Selective antegrade cerebral perfusion (SACP) involving cannulation of either the axillary or innominate artery is a commonly used technique for maintaining cerebral blood flow (CBF) during the use of hypothermic cardiac arrest (HCA) for operations on the aortic arch. Nevertheless, asymmetrical CBF with hypoperfusion of the left cerebral hemisphere is a common occurrence during SACP. The purpose of this report is to describe an adjunctive maneuver to improve left hemispheric CBF during SACP by applying extrinsic compression to the left carotid artery. A 77-yr-old male patient with a history of aortic valve replacement presented for emergent surgical repair of an acute type A aortic dissection of a previously known ascending aortic aneurysm. His intraoperative course included cannulation of the right axillary artery, which was used as the aortic inflow during cardiopulmonary bypass and also allowed for subsequent SACP during HCA. After the onset of HCA, the innominate artery was clamped at its origin to allow for SACP. Shortly thereafter, however, the left-sided cerebral oxygen saturation (SrO2) began to decrease. Augmenting the PaO2, PaCO2 and both SACP pressure and flow failed to increase left hemispheric SrO2. Following the use of ultrasound guidance to confirm the absence of atherosclerotic disease in the carotid artery, external pressure was applied partially compressing the artery. With the carotid compression, the left cerebral saturation abruptly increased, suggesting pressurization of the left cerebral hemispheric circulation and augmentation of CBF. Direct ultrasound visualization and cautious partial compression of the left carotid artery may address asymmetrical CBF that occurs with SACP during HCA for aortic arch surgery. This strategy may lead to improved symmetry of CBF and corresponding cerebral oximetry measurements during aortic arch surgery.

Cerebral Metabolic Alterations in Rats With Diabetic Ketoacidosis

PubMed Central

Glaser, Nicole; Yuen, Natalie; Anderson, Steven E.; Tancredi, Daniel J.; O'Donnell, Martha E.

2010-01-01

OBJECTIVE Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND METHODS We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 × 2 factorial study design. RESULTS Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference −0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (−0.32 ± 0.10, P = 0.003, and −0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. CONCLUSIONS These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment—consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline. PMID:20028943

[Analysis of 58 neonatal cases with cerebral infarction].

PubMed

Li, Zhi-hua; Chen, Chao

2013-01-01

Cerebral infarction (CI) is one of severe diseases of central nervous system in neonates, and some infants with CI could have poor prognosis in the long term. This study aimed to analyze the clinical data and prognosis of all neonatal cases with cerebral infarction in recent years and to help future clinical work. Totally 58 neonatal cases with CI admitted to NICU of the hospital from January 1999 to December 2010 were included in this study. We analyzed all clinical data and prognosis by retrospective analysis. Fifty-two term babies and six preterm babies were included. There were altogether 51 cases with asphyxia and 7 with hemorrhagic cerebral infarction. Perinatal hypoxia-ischemia was the most common high-risk factor and it accounted for 46.6%. Seizure was the most frequent initial symptom and the most common clinical manifestation (accounted for 77.6%), and it was followed by intermittent cyanosis, apnea and lethargy. Cerebral CT scan and magnetic resonance imaging were major methods to help to make the diagnosis and they also had close relation with prognosis. Diffusion weighted imaging was very helpful to diagnose infarction in early stage. Left middle cerebral artery was the most common artery to be involved. Supportive therapy and symptomatic treatment were the main methods in the acute stage of neonatal cerebral infarction. Those babies with poor prognosis mostly had large infarction involving cerebral hemisphere, thalamus and basal ganglia. Neonatal cerebral infarction was a severe brain injury affecting long tern nervous system prognosis. Perinatal hypoxia was the most common high-risk factor and seizure was the most frequent initial symptom. Diffusion weighted imaging was valuable to diagnose infarction in early stage. Most of infants with poor prognosis had large infarction involving hemisphere, thalamus and basal ganglia. Early diagnosis with brain imaging would be helpful for rehabilitation therapy and improving prognosis.

Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia

PubMed Central

Jones, Phill B.; Shin, Hwa Kyoung; Boas, David A.; Hyman, Bradley T.; Moskowitz, Michael A.; Ayata, Cenk; Dunn, Andrew K.

2009-01-01

Real-time investigation of cerebral blood flow (CBF), and oxy- and deoxyhemoglobin concentration (HbO, HbR) dynamics has been difficult until recently due to limited spatial and temporal resolution of techniques like laser Doppler flowmetry and magnetic resonance imaging (MRI). The combination of laser speckle flowmetry (LSF) and multispectral reflectance imaging (MSRI) yields high-resolution spatiotemporal maps of hemodynamic and metabolic changes in response to functional cortical activation. During acute focal cerebral ischemia, changes in HbO and HbR are much larger than in functional activation, resulting in the failure of the Beer-Lambert approximation to yield accurate results. We describe the use of simultaneous LSF and MSRI, using a nonlinear Monte Carlo fitting technique, to record rapid changes in CBF, HbO, HbR, and cerebral metabolic rate of oxygen (CMRO2) during acute focal cerebral ischemia induced by distal middle cerebral artery occlusion (dMCAO) and reperfusion. This technique captures CBF and CMRO2 changes during hemodynamic and metabolic events with high temporal and spatial resolution through the intact skull and demonstrates the utility of simultaneous LSF and MSRI in mouse models of cerebrovascular disease. PMID:19021335

Cerebral vasculopathy in children with sickle cell anemia.

PubMed

Fasano, Ross M; Meier, Emily R; Hulbert, Monica L

2015-01-01

Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Multiple organ gigantism caused by mutation in VmPPD gene in blackgram (Vigna mungo)

PubMed Central

Naito, Ken; Takahashi, Yu; Chaitieng, Bubpa; Hirano, Kumi; Kaga, Akito; Takagi, Kyoko; Ogiso-Tanaka, Eri; Thavarasook, Charaspon; Ishimoto, Masao; Tomooka, Norihiko

2017-01-01

Seed size is one of the most important traits in leguminous crops. We obtained a recessive mutant of blackgram that had greatly enlarged leaves, stems and seeds. The mutant produced 100% bigger leaves, 50% more biomass and 70% larger seeds though it produced 40% less number of seeds. We designated the mutant as multiple-organ-gigantism (mog) and found the mog phenotype was due to increase in cell numbers but not in cell size. We also found the mog mutant showed a rippled leaf (rl) phenotype, which was probably caused by a pleiotropic effect of the mutation. We performed a map-based cloning and successfully identified an 8 bp deletion in the coding sequence of VmPPD gene, an orthologue of Arabidopsis PEAPOD (PPD) that regulates arrest of cell divisions in meristematic cells. We found no other mutations in the neighboring genes between the mutant and the wild type. We also knocked down GmPPD genes and reproduced both the mog and rl phenotypes in soybean. Controlling PPD genes to produce the mog phenotype is highly valuable for breeding since larger seed size could directly increase the commercial values of grain legumes. PMID:28588392

Multiple organ gigantism caused by mutation in VmPPD gene in blackgram (Vigna mungo).

PubMed

Naito, Ken; Takahashi, Yu; Chaitieng, Bubpa; Hirano, Kumi; Kaga, Akito; Takagi, Kyoko; Ogiso-Tanaka, Eri; Thavarasook, Charaspon; Ishimoto, Masao; Tomooka, Norihiko

2017-03-01

Seed size is one of the most important traits in leguminous crops. We obtained a recessive mutant of blackgram that had greatly enlarged leaves, stems and seeds. The mutant produced 100% bigger leaves, 50% more biomass and 70% larger seeds though it produced 40% less number of seeds. We designated the mutant as multiple-organ-gigantism ( mog ) and found the mog phenotype was due to increase in cell numbers but not in cell size. We also found the mog mutant showed a rippled leaf ( rl ) phenotype, which was probably caused by a pleiotropic effect of the mutation. We performed a map-based cloning and successfully identified an 8 bp deletion in the coding sequence of VmPPD gene, an orthologue of Arabidopsis PEAPOD ( PPD ) that regulates arrest of cell divisions in meristematic cells . We found no other mutations in the neighboring genes between the mutant and the wild type. We also knocked down GmPPD genes and reproduced both the mog and rl phenotypes in soybean. Controlling PPD genes to produce the mog phenotype is highly valuable for breeding since larger seed size could directly increase the commercial values of grain legumes.

Earth’s oldest ‘Bobbit worm’ – gigantism in a Devonian eunicidan polychaete

PubMed Central

Eriksson, Mats E.; Parry, Luke A.; Rudkin, David M.

2017-01-01

Whilst the fossil record of polychaete worms extends to the early Cambrian, much data on this group derive from microfossils known as scolecodonts. These are sclerotized jaw elements, which generally range from 0.1–2 mm in size, and which, in contrast to the soft-body anatomy, have good preservation potential and a continuous fossil record. Here we describe a new eunicidan polychaete, Websteroprion armstrongi gen. et sp. nov., based primarily on monospecific bedding plane assemblages from the Lower-Middle Devonian Kwataboahegan Formation of Ontario, Canada. The specimens are preserved mainly as three-dimensional moulds in the calcareous host rock, with only parts of the original sclerotized jaw walls occasionally present. This new taxon has a unique morphology and is characterized by an unexpected combination of features seen in several different Palaeozoic polychaete families. Websteroprion armstrongi was a raptorial feeder and possessed the largest jaws recorded in polychaetes from the fossil record, with maxillae reaching over one centimetre in length. Total body length of the species is estimated to have reached over one metre, which is comparable to that of extant ‘giant eunicid’ species colloquially referred to as ‘Bobbit worms’. This demonstrates that polychaete gigantism was already a phenomenon in the Palaeozoic, some 400 million years ago. PMID:28220886

Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

PubMed Central

Pozzoli, Uberto; Elgar, Greg; Cagliani, Rachele; Riva, Laura; Comi, Giacomo P.; Bresolin, Nereo; Bardoni, Alessandra; Sironi, Manuela

2003-01-01

The human DMD gene is the largest known to date, spanning > 2000 kb on the X chromosome. The gene size is mainly accounted for by huge intronic regions. We sequenced 190 kb of Fugu rubripes (pufferfish) genomic DNA corresponding to the complete dystrophin gene (FrDMD) and provide the first report of gene structure and sequence comparison among dystrophin genomic sequences from different vertebrate organisms. Almost all intron positions and phases are conserved between FrDMD and its mammalian counterparts, and the predicted protein product of the Fugu gene displays 55% identity and 71% similarity to human dystrophin. In analogy to the human gene, FrDMD presents several-fold longer than average intronic regions. Analysis of intron sequences of the human and murine genes revealed that they are extremely conserved in size and that a similar fraction of total intron length is represented by repetitive elements; moreover, our data indicate that intron expansion through repeat accumulation in the two orthologs is the result of independent insertional events. The hypothesis that intron length might be functionally relevant to the DMD gene regulation is proposed and substantiated by the finding that dystrophin intron gigantism is common to the three vertebrate genes. [Supplemental material is available online at www.genome.org.] PMID:12727896

Cerebral Palsy: General Information. Fact Sheet Number 2 = La Paralisis Cerebral: Informacion General. Fact Sheet Number 18.

ERIC Educational Resources Information Center

Interstate Research Associates, McLean, VA.

This fact sheet on cerebral palsy is offered in both English and Spanish. First, it provides a definition and considers various causes (e.g., an insufficient amount of oxygen reaching the fetal or newborn brain). The fact sheet then offers incidence figures and explains characteristics of the three main types of cerebral palsy: spastic, athetoid,…

Prevalence of cerebral palsy in Uganda: a population-based study.

PubMed

Kakooza-Mwesige, Angelina; Andrews, Carin; Peterson, Stefan; Wabwire Mangen, Fred; Eliasson, Ann Christin; Forssberg, Hans

2017-12-01

Few population-based studies of cerebral palsy have been done in low-income and middle-income countries. We aimed to examine cerebral palsy prevalence and subtypes, functional impairments, and presumed time of injury in children in Uganda. In this population-based study, we used a nested, three-stage, cross-sectional method (Iganga-Mayuge Health and Demographic Surveillance System [HDSS]) to screen for cerebral palsy in children aged 2-17 years in a rural eastern Uganda district. A specialist team confirmed the diagnosis and determined the subtype, motor function (according to the Gross Motor Function Classification System [GMFCS]), and possible time of brain injury for each child. Triangulation and interviews with key village informants were used to identify additional cases of suspected cerebral palsy. We estimated crude and adjusted cerebral palsy prevalence. We did χ 2 analyses to examine differences between the group screened at stage 1 and the entire population and regression analyses to investigate associations between the number of cases and age, GMFCS level, subtype, and time of injury. We used data from the March 1, 2015, to June 30, 2015, surveillance round of the Iganga-Mayuge HDSS. 31 756 children were screened for cerebral palsy, which was confirmed in 86 (19%) of 442 children who screened positive in the first screening stage. The crude cerebral palsy prevalence was 2·7 (95% CI 2·2-3·3) per 1000 children, and prevalence increased to 2·9 (2·4-3·6) per 1000 children after adjustment for attrition. The prevalence was lower in older (8-17 years) than in younger (<8 years) children. Triangulation added 11 children to the cohort. Spastic unilateral cerebral palsy was the most common subtype (45 [46%] of 97 children) followed by bilateral cerebral palsy (39 [40%] of 97 children). 14 (27%) of 51 children aged 2-7 years had severe cerebral palsy (GMFCS levels 4-5) compared with only five (12%) of 42 children aged 8-17 years. Few children (two [2%] of

Cerebral aneurysms: Formation, progression and developmental chronology

PubMed Central

Etminan, Nima; Buchholz, Bruce A.; Dreier, Rita; Bruckner, Peter; Torner, James C.; Steiger, Hans-Jakob; Hänggi, Daniel; Macdonald, R. Loch

2015-01-01

The prevalence of unruptured intracranial aneurysms (UAIs) in the general population is up to 3%. Existing epidemiological data suggests that only a small fraction of UIAs progress towards rupture over the lifetime of an individual, but the surrogates for subsequent rupture and the natural history of UIAs are discussed very controversially at present. In case of rupture of an UIA, the case-fatality is up to 50%, which therefore continues to stimulate interest in the pathogenesis of cerebral aneurysm formation and progression. Actual data on the chronological development of cerebral aneurysm has been especially difficult to obtain and, until recently, the existing knowledge in this respect is mainly derived from animal or mathematical models or short-term observational studies. Here, we highlight the current data on cerebral aneurysm formation and progression as well as a novel approach to investigate the developmental chronology of cerebral aneurysms. PMID:24323717

The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.

PubMed

Marumo, Toshiyuki; Eto, Kei; Wake, Hiroaki; Omura, Tomohiro; Nabekura, Junichi

2010-11-01

20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Investigating cerebral oedema using poroelasticity.

PubMed

Vardakis, John C; Chou, Dean; Tully, Brett J; Hung, Chang C; Lee, Tsong H; Tsui, Po-Hsiang; Ventikos, Yiannis

2016-01-01

Cerebral oedema can be classified as the tangible swelling produced by expansion of the interstitial fluid volume. Hydrocephalus can be succinctly described as the abnormal accumulation of cerebrospinal fluid (CSF) within the brain which ultimately leads to oedema within specific sites of parenchymal tissue. Using hydrocephalus as a test bed, one is able to account for the necessary mechanisms involved in the interaction between oedema formation and cerebral fluid production, transport and drainage. The current state of knowledge about integrative cerebral dynamics and transport phenomena indicates that poroelastic theory may provide a suitable framework to better understand various diseases. In this work, Multiple-Network Poroelastic Theory (MPET) is used to develop a novel spatio-temporal model of fluid regulation and tissue displacement within the various scales of the cerebral environment. The model is applied through two formats, a one-dimensional finite difference - Computational Fluid Dynamics (CFD) coupling framework, as well as a two-dimensional Finite Element Method (FEM) formulation. These are used to investigate the role of endoscopic fourth ventriculostomy in alleviating oedema formation due to fourth ventricle outlet obstruction (1D coupled model) in addition to observing the capability of the FEM template in capturing important characteristics allied to oedema formation, like for instance in the periventricular region (2D model). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Microsurgery Simulator of Cerebral Aneurysm Clipping with Interactive Cerebral Deformation Featuring a Virtual Arachnoid.

PubMed

Shono, Naoyuki; Kin, Taichi; Nomura, Seiji; Miyawaki, Satoru; Saito, Toki; Imai, Hideaki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2018-05-01

A virtual reality simulator for aneurysmal clipping surgery is an attractive research target for neurosurgeons. Brain deformation is one of the most important functionalities necessary for an accurate clipping simulator and is vastly affected by the status of the supporting tissue, such as the arachnoid membrane. However, no virtual reality simulator implementing the supporting tissue of the brain has yet been developed. To develop a virtual reality clipping simulator possessing interactive brain deforming capability closely dependent on arachnoid dissection and apply it to clinical cases. Three-dimensional computer graphics models of cerebral tissue and surrounding structures were extracted from medical images. We developed a new method for modifiable cerebral tissue complex deformation by incorporating a nonmedical image-derived virtual arachnoid/trabecula in a process called multitissue integrated interactive deformation (MTIID). MTIID made it possible for cerebral tissue complexes to selectively deform at the site of dissection. Simulations for 8 cases of actual clipping surgery were performed before surgery and evaluated for their usefulness in surgical approach planning. Preoperatively, each operative field was precisely reproduced and visualized with the virtual brain retraction defined by users. The clear visualization of the optimal approach to treating the aneurysm via an appropriate arachnoid incision was possible with MTIID. A virtual clipping simulator mainly focusing on supporting tissues and less on physical properties seemed to be useful in the surgical simulation of cerebral aneurysm clipping. To our knowledge, this article is the first to report brain deformation based on supporting tissues.

Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?

PubMed Central

De Silva, T. Michael; Miller, Alyson A.

2016-01-01

Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors. PMID:27014073

Cerebral blood flow regulation during cognitive tasks

PubMed Central

Sorond, Farzaneh A.; Schnyer, D.M.; Serrador, J.M.; Milberg, W.P.; Lipsitz, L.A.

2008-01-01

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 ± 1.5 years; 15 old, 74 ± 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. PMID:18387547

Crossed aphasia following cerebral infarction in a right-handed patient with atypical cerebral language dominance.

PubMed

Tan, Xiaoping; Guo, Yang; Dun, Saihong; Sun, Hongzan

2018-05-18

Crossed aphasia (CA), usually referred to as an acquired language disturbance, is caused by a lesion in the cerebral hemisphere ipsilateral to the dominant hand, and the exact mechanism is not clear. The development of handedness is influenced by education and training and the impact of habitualization, while language is more susceptible to the impact of speech habits, and it is not absolutely accurate to judge cerebral language dominance by the degree of hand preference. We describe a case of CA after right hemispheric stroke in a right-handed patient with atypical language dominance and attempt to analyze the mechanism of CA based on functional imaging methods, including arterial spin labeling (ASL) and positron emission tomography/magnetic resonance imaging (PET-MRI). Brain MRI at 24 h after admission showed a large cerebral infarction in the right cerebral hemisphere, including the posteroinferior part of Broca's area in the right frontal lobe, the right temporal lobe, and the right occipital lobe. The patient exhibited a non-fluent aphasia on a standard language test (the Aphasia Battery of Chinese [ABC]) performed on the 7th day after onset. Thus, atypical language dominance was suspected. One week after admission, ASL imaging showed high perfusion in the infarct core zone and low perfusion in the left cerebellar hemisphere. Two months later, PET/MRI demonstrated low metabolism in the posterior frontal lobe, temporal lobe, temporal occipital junction area, and the right basal ganglia. The findings suggest that the patient has right-sided cerebral language dominance, or that both hemispheres have linguistic functions. Not all patients show linguistic capabilities on the side opposite hand preference. The language dominance should be predicted by a combination of clinical manifestations and functional imaging techniques.

Racial, Ethnic, and Socioeconomic Disparities in the Prevalence of Cerebral Palsy

PubMed Central

Xing, Guibo; Fuentes-Afflick, Elena; Danielson, Beate; Smith, Lloyd H.; Gilbert, William M.

2011-01-01

OBJECTIVE: Racial and ethnic disparities in cerebral palsy have been documented, but the underlying mechanism is poorly understood. We determined whether low birth weight accounts for ethnic disparities in the prevalence of cerebral palsy and whether socioeconomic factors impact cerebral palsy within racial and ethnic groups. METHODS: In a retrospective cohort of 6.2 million births in California between 1991 and 2001, we compared maternal and infant characteristics among 8397 infants with cerebral palsy who qualified for services from the California Department of Health Services and unaffected infants. RESULTS: Overall, black infants were 29% more likely to have cerebral palsy than white infants (relative risk: 1.29 [95% confidence interval: 1.19–1.39]). However, black infants who were very low or moderately low birth weight were 21% to 29% less likely to have cerebral palsy than white infants of comparable birth weight. After we adjusted for birth weight, there was no difference in the risk of cerebral palsy between black and white infants. In multivariate analyses, women of all ethnicities who did not receive any prenatal care were twice as likely to have infants with cerebral palsy relative to women with an early onset of prenatal care. Maternal education was associated with cerebral palsy in a dose-response fashion among white and Hispanic women. Hispanic adolescent mothers (aged <18 years) had increased risk of having a child with cerebral palsy. CONCLUSIONS: The increased risk of cerebral palsy among black infants is primarily related to their higher risk of low birth weight. Understanding how educational attainment and use of prenatal care impact the risk of cerebral palsy may inform new prevention strategies. PMID:21339278

Cerebral oxygenation during intermittent hypoxemia and bradycardia in preterm infants.

PubMed

Schmid, Manuel B; Hopfner, Reinhard J; Lenhof, Susanne; Hummler, Helmut D; Fuchs, Hans

2015-01-01

Episodes of hypoxemia and bradycardia frequently occur with apnea of prematurity in preterm infants. Little is known about the impact of different event types on the brain. To describe the influence of hypoxemia and bradycardia, either isolated or in combination, on cerebral oxygenation. In 16 preterm infants with intermittent hypoxemia and/or bradycardia, cerebral tissue oxygen saturation (StO2, as measured by near-infrared spectroscopy), heart rate and pulse oximetric saturation (SpO2) were recorded simultaneously for 16 h. Events were classified as isolated bradycardia (type 1), isolated hypoxemia (type 2) or combined (simultaneous, type 3; bradycardia first, type 4; hypoxemia first, type 5). Primary outcome was a score representing the area below baseline for cerebral StO2 desaturation during an event. Secondary outcomes were duration and depth of cerebral desaturation. Patients had a median (range) gestational age of 25.9 (22.6-30.4) weeks and a postnatal age of 32.5 (7-58) days. The median (quartiles) number of events was 49 (34-58). Isolated hypoxemias were the most frequent events (24; 9-36) and isolated bradycardias the least common (0; 0-1). Cerebral StO2 baseline was not different between event types. Cerebral desaturation score, duration of event and depth of cerebral desaturation were smallest for isolated bradycardias and largest for combined events, especially for those starting with hypoxemia followed by bradycardia. Regardless of event type, 12/16 infants maintained cerebral StO2 >60% despite severe SpO2 desaturations. Isolated bradycardias had the lowest impact on cerebral desaturation, and combined events had the highest. Most infants preserved cerebral oxygenation >60% during events. © 2014 S. Karger AG, Basel.

Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

PubMed

Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

2017-12-01

Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

Cerebral metabolic intermediate response following severe canine intrauterine growth retardation.

PubMed

Kliegman, R M

1986-07-01

The effect of intrauterine growth retardation and neonatal hypoglycemia on cerebral metabolic intermediates were determined in newborn dogs subjected to 5 days of maternal canine starvation (MCS) before birth. Birth weight was reduced 23% (232 +/- 6 versus 300 +/- 10 g). Circulating blood glucose was reduced after 3 h of neonatal fasting in MCS pups (2.7 +/- 0.4 +/- versus 5.7 +/- 1.1 mM). Cerebral cortical levels of glucose were also reduced at this time. Cerebral glucose-6-phosphate was not altered; nonetheless fructose-6-phosphate was lower in MCS pups at 6 and 9 h, while fructose 1,6-diphosphate appeared elevated at 3 h. These data suggest that cerebral glycolytic activity may be increased by increased activity of phosphofructokinase. Cerebral glutamine appeared reduced in fasting MCS pups at 3, 6, and 8 h of age. A considerable disturbance of the adenine nucleotide pool was noted between 3-9 h in MCS pups; while the cerebral energy reserve was diminished in MCS pups between 3-24 h. The data of reduced cerebral energy status and reserve suggest that cerebral energy production was diminished. Although glucose levels were low at 3 h, subsequent recovery was not immediate as adenine-nucleotides remained low beyond the period of hypoglycemia. The combined effects of intrauterine growth retardation and transient neonatal hypoglycemia appear to result in reduced cerebral oxidative metabolism; this occurs despite an apparent enhanced utilization of alternate fuels.

Cerebral Vascular Injury in Traumatic Brain Injury.

PubMed

Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

2016-01-01

Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. Published by Elsevier Inc.

Cerebral hemodynamics before and after shunting in normal pressure hydrocephalus.

PubMed

Bakker, S L M; Boon, A J W; Wijnhoud, A D; Dippel, D W J; Delwel, E J; Koudstaal, P J

2002-09-01

To study the relationship between cerebral hemodynamics and clinical performance in normal pressure hydrocephalus (NPH), before and after surgery. Ten patients were studied prospectively before and 3 months after shunt surgery by means of transcranial Doppler (TCD). Clinical performance was scored by means of an NPH scale and the modified Rankin scale. Peak systolic and mean cerebral blood flow velocity (MCV) were lower and cerebrovascular CO2 reactivity was higher after shunt surgery. The three patients with clinical improvement had higher preoperative end diastolic cerebral blood flow velocity and MCV. All postoperative cerebral blood flow velocities were higher in patients with clinical improvement. Our data suggest that higher cerebral blood flow velocity before surgery in patients with NPH is related to clinical improvement after shunt surgery. Cerebral hemodynamic parameters may develop into predictors of successful shunt surgery in patients with normal pressure hydrocephalus.

Early optical detection of cerebral edema in vivo.

PubMed

Gill, Amandip S; Rajneesh, Kiran F; Owen, Christopher M; Yeh, James; Hsu, Mike; Binder, Devin K

2011-02-01

Cerebral edema is a significant cause of morbidity and mortality in diverse disease states. Currently, the means to detect progressive cerebral edema in vivo includes the use of intracranial pressure (ICP) monitors and/or serial radiological studies. However, ICP measurements exhibit a high degree of variability, and ICP monitors detect edema only after it becomes sufficient to significantly raise ICP. The authors report the development of 2 distinct minimally invasive fiberoptic near-infrared (NIR) techniques able to directly detect early cerebral edema. Cytotoxic brain edema was induced in adult CD1 mice via water intoxication by intraperitoneal water administration (30% body weight intraperitoneally). An implantable dual-fiberoptic probe was stereotactically placed into the cerebral cortex and connected to optical source and detector hardware. Optical sources consisted of either broadband halogen illumination or a single-wavelength NIR laser diode, and the detector was a sensitive NIR spectrometer or optical power meter. In one subset of animals, a left-sided craniectomy was performed to obtain cortical biopsies for water-content determination to verify cerebral edema. In another subset of animals, an ICP transducer was placed on the contralateral cortex, which was synchronized to a computer and time stamped. Using either broadband illumination with NIR spectroscopy or single-wavelength laser diode illumination with optical power meter detection, the authors detected a reduction in NIR optical reflectance during early cerebral edema. The time intervals between water injection (Time Point 0), optical trigger (defined as a 2-SD change in optical reflectance from baseline), and defined threshold ICP values of 10, 15 and 20 mm Hg were calculated. Reduction in NIR reflectance occurred significantly earlier than any of the ICP thresholds (p < 0.001). Saline-injected control mice exhibited a steady baseline optical signal. There was a significant correlation between

Acute posterior multifocal placoid pigment epitheliopathy associated with cerebral vasculitis.

PubMed

Weinstein, J M; Bresnick, G H; Bell, C L; Roschmann, R A; Brooks, B R; Strother, C M

1988-09-01

Acute multifocal posterior placoid pigment epitheliopathy (APMPPE) is an unusual self-limited retinal disorder that has been associated with various systemic complications. To our knowledge, three prior cases associated with cerebral vasculitis have been described. This article describes a patient with APMPPE and angiographically documented cerebral vasculitis who was notable because of (a) the presence of two different cerebral ischemic events, occurring 1 month apart, and (b) the long latency (3 months) between the onset of ocular symptoms and the second cerebral ischemic event. Recognition of the association between APMPPE and cerebral vasculitis may permit early treatment of CNS involvement and prevention of morbidity.

Improved hemodynamic parameters in middle cerebral artery infarction after decompressive craniectomy.

PubMed

Amorim, Robson Luis; de Andrade, Almir Ferreira; Gattás, Gabriel S; Paiva, Wellingson Silva; Menezes, Marcos; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

2014-05-01

Decompressive craniectomy (DC) reduces mortality and improves functional outcome in patients with malignant middle cerebral artery infarction. However, little is known regarding the impact of DC on cerebral hemodynamics. Therefore, our goal was to study the hemodynamic changes that may occur in patients with malignant middle cerebral artery infarction after DC and to assess their relationship with outcomes. Twenty-seven patients with malignant middle cerebral artery infarction who were treated with DC were studied. The perfusion CT hemodynamic parameters, mean transit time, cerebral blood flow, and cerebral blood volume were evaluated preoperatively and within the first 24 hours after DC. There was a global trend toward improved cerebral hemodynamics after DC. Preoperative and postoperative absolute mean transit times were associated with mortality at 6 months, and the ratio of post- and preoperative cerebral blood flow was significantly higher in patients with favorable outcomes than those with unfavorable outcomes. Patients who underwent surgery 48 hours after stroke, those with midline brain shift>10 mm, and those who were >55 years showed no significant improvement in any perfusion CT parameters. DC improves cerebral hemodynamics in patients with malignant middle cerebral artery infarction, and the level of improvement is related to outcome. However, some patients did not seem to experience any additional hemodynamic benefit, suggesting that perfusion CT may play a role as a prognostic tool in patients undergoing DC after ischemic stroke.

Cerebral blood flow autoregulation is impaired in schizophrenia: A pilot study.

PubMed

Ku, Hsiao-Lun; Wang, Jiunn-Kae; Lee, Hsin-Chien; Lane, Timothy Joseph; Liu, I-Chao; Chen, Yung-Chan; Lee, Yao-Tung; Lin, I-Cheng; Lin, Chia-Pei; Hu, Chaur-Jong; Chi, Nai-Fang

2017-10-01

Patients with schizophrenia have a higher risk of cardiovascular diseases and higher mortality from them than does the general population; however, the underlying mechanism remains unclear. Impaired cerebral autoregulation is associated with cerebrovascular diseases and their mortality. Increased or decreased cerebral blood flow in different brain regions has been reported in patients with schizophrenia, which implies impaired cerebral autoregulation. This study investigated the cerebral autoregulation in 21 patients with schizophrenia and 23 age- and sex-matched healthy controls. None of the participants had a history of cardiovascular diseases, hypertension, or diabetes. All participants underwent 10-min blood pressure and cerebral blood flow recording through finger plethysmography and Doppler ultrasonography, respectively. Cerebral autoregulation was assessed by analyzing two autoregulation indices: the mean blood pressure and cerebral blood flow correlation coefficient (Mx), and the phase shift between the waveforms of blood pressure and cerebral blood flow determined using transfer function analysis. Compared with the controls, the patients had a significantly higher Mx (0.257 vs. 0.399, p=0.036) and lower phase shift (44.3° vs. 38.7° in the 0.07-0.20Hz frequency band, p=0.019), which indicated impaired maintenance of constant cerebral blood flow and a delayed cerebrovascular autoregulatory response. Impaired cerebral autoregulation may be caused by schizophrenia and may not be an artifact of coexisting medical conditions. The mechanism underlying impaired cerebral autoregulation in schizophrenia and its probable role in the development of cerebrovascular diseases require further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebral Arterial Gas Embolism During Upper Endoscopy.

PubMed

Eoh, Eun J; Derrick, Bruce; Moon, Richard

2015-09-15

Arterial gas embolism can be caused by direct entry of gas into systemic arteries or indirectly by venous-to-arterial shunting. Although arterial gas embolism is rare, most documented cases are iatrogenic, resulting from the entry of gas during procedures that involve direct vascular cannulation or intracavitary air insufflation. Of the 18 identified case reports of air embolism during endoscopy, 11 cases describe findings of cerebral arterial gas embolism during upper endoscopy. Only 1 of these occurred during endoscopic balloon dilation of an esophageal stricture. We report a rare case of cerebral arterial gas embolism in a 64-year-old woman, which occurred during endoscopic dilation of an esophageal stricture and was subsequently treated with hyperbaric oxygen therapy. In this case report, we explore the possible etiologies, clinical workup, and therapeutic management of cerebral artery gas embolisms. Hyperbaric oxygen therapy is the treatment of choice for cerebral arterial gas embolism, with earlier treatments resulting in better outcomes.

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

Magnetic resonance features of cerebral malaria.

PubMed

Yadav, P; Sharma, R; Kumar, S; Kumar, U

2008-06-01

Cerebral malaria is a major health hazard, with a high incidence of mortality. The disease is endemic in many developing countries, but with a greater increase in tourism, occasional cases may be detected in countries where the disease in not prevalent. Early diagnosis and evaluation of cerebral involvement in malaria utilizing modern imaging modalities have an impact on the treatment and clinical outcome. To evaluate the magnetic resonance (MR) features of patients with cerebral malaria presenting with altered sensorium. We present the findings in three patients with cerebral malaria presenting with altered sensorium. MR imaging using a 1.5-Tesla unit was carried out. The sequences performed were 5-mm-thick T1-weighted, T2-weighted, fluid-attenuated inversion-recovery (FLAIR), and T2-weighted gradient-echo axial sequences, and sagittal and coronal FLAIR. Diffusion-weighted imaging was performed with b values of 0 and 1000 s/mm(2), and apparent diffusion coefficient (ADC) maps were obtained. Focal hyperintensities in the bilateral periventricular white matter, corpus callosum, occipital subcortex, and bilateral thalami were noticed on T2-weighted and FLAIR sequences. The lesions were more marked in the splenium of the corpus callosum. No enhancement on postcontrast T1-weighted MR images was observed. There was no evidence of restricted diffusion on the diffusion-weighted sequence and ADC map. MR is a sensitive imaging modality, with a role in the assessment of cerebral lesions in malaria. Focal white matter and corpus callosal lesions without any restricted diffusion were the key findings in our patients.

The history of cerebral PET scanning

PubMed Central

Portnow, Leah H.; Vaillancourt, David E.; Okun, Michael S.

2013-01-01

Objective: To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Background: Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post–World War II period provided the necessary infrastructure for the first cerebral PET scan. Methods: A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at www.sfn.org. A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. Results: The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Conclusions: Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders. PMID:23460618

Explicit and implicit motor learning in children with unilateral cerebral palsy.

PubMed

van der Kamp, John; Steenbergen, Bert; Masters, Rich S W

2017-07-30

The current study aimed to investigate the capacity for explicit and implicit learning in children with unilateral cerebral palsy. Children with left and right unilateral cerebral palsy and typically developing children shuffled disks toward a target. A prism-adaptation design was implemented, consisting of pre-exposure, prism exposure, and post-exposure phases. Half of the participants were instructed about the function of the prism glasses, while the other half were not. For each trial, the distance between the target and the shuffled disk was determined. Explicit learning was indicated by the rate of adaptation during the prism exposure phase, whereas implicit learning was indicated by the magnitude of the negative after-effect at the start of the post-exposure phase. Results No significant effects were revealed between typically developing participants and participants with unilateral cerebral palsy. Comparison of participants with left and right unilateral cerebral palsy demonstrated that participants with right unilateral cerebral palsy had a significantly lower rate of adaptation than participants with left unilateral cerebral palsy, but only when no instructions were provided. The magnitude of the negative after-effects did not differ significantly between participants with right and left unilateral cerebral palsy. The capacity for explicit motor learning is reduced among individuals with right unilateral cerebral palsy when accumulation of declarative knowledge is unguided (i.e., discovery learning). In contrast, the capacity for implicit learning appears to remain intact among individuals with left as well as right unilateral cerebral palsy. Implications for rehabilitation Implicit motor learning interventions are recommended for individuals with cerebral palsy, particularly for individuals with right unilateral cerebral palsy Explicit motor learning interventions for individual with cerebral palsy - if used - best consist of singular verbal instruction.

Bundle of measures for external cerebral ventricular drainage-associated ventriculitis.

PubMed

Chatzi, Maria; Karvouniaris, Marios; Makris, Demosthenes; Tsimitrea, Eleni; Gatos, Charalampos; Tasiou, Anastasia; Mantzarlis, Kostas; Fountas, Kostas N; Zakynthinos, Epaminondas

2014-01-01

To assess the prevalence and outcome of external cerebral ventricular drainage-associated ventriculitis in neurocritical patients before and after the implementation of a bundle of external cerebral ventricular drainage-associated ventriculitis control measures. Clinical prospective case series. University Hospital of Larissa, Greece. Consecutive patients were recruited from the ICU of the hospital. Patient inclusion criteria included presence of external ventricular drainage and ICU stay more than 48 hours. The bundle of external cerebral ventricular drainage-associated ventriculitis control measures included 1) reeducation of ICU personnel on issues of infection control related to external cerebral ventricular drainage, 2) meticulous intraventricular catheter handling, 3) cerebrospinal fluid sampling only when clinically necessary, and 4) routine replacement of the drainage catheter on the seventh drainage day if the catheter was still necessary. The bundle was applied after an initial period (preintervention) where standard policy for external cerebral ventricular drainage-associated ventriculitis was established. External cerebral ventricular drainage-associated ventriculitis prevalence, external cerebral ventricular drainage-associated ventriculitis events per 1,000 drainage days (drain-associated infection rate), length of ICU stay, Glasgow Outcome Scale at 6 months, and risk factors for external cerebral ventricular drainage-associated ventriculitis. Eighty-two patients entered the study in the preintervention period and 57 patients during the intervention period. During the preintervention and intervention period, external cerebral ventricular drainage-associated ventriculitis prevalence was 28% and 10.5% (p = 0.02) and drain-associated infection rate was 18 and 7.1, respectively (p = 0.0001); mean (95% CI) length of ICU stay in patients who presented external cerebral ventricular drainage-associated ventriculitis was 44.4 days (36.4-52.4 d), whereas mean

Cerebral amyloid angiopathy, cerebral microbleeds and implications for anticoagulation decisions: The need for a balanced approach.

PubMed

Charidimou, Andreas; Shoamanesh, Ashkan; Al-Shahi Salman, Rustam; Cordonnier, Charlotte; Perry, Luke A; Sheth, Kevin N; Biffi, Alessandro; Rosand, Jonathan; Viswanathan, Anand

2018-02-01

Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Does cerebral oxygen delivery limit incremental exercise performance?

PubMed Central

Olin, J. Tod; Dimmen, Andrew C.; Polaner, David M.; Kayser, Bengt; Roach, Robert C.

2011-01-01

Previous studies have suggested that a reduction in cerebral oxygen delivery may limit motor drive, particularly in hypoxic conditions, where oxygen transport is impaired. We hypothesized that raising end-tidal Pco2 (PetCO2) during incremental exercise would increase cerebral blood flow (CBF) and oxygen delivery, thereby improving peak power output (Wpeak). Amateur cyclists performed two ramped exercise tests (25 W/min) in a counterbalanced order to compare the normal, poikilocapnic response against a clamped condition, in which PetCO2 was held at 50 Torr throughout exercise. Tests were performed in normoxia (barometric pressure = 630 mmHg, 1,650 m) and hypoxia (barometric pressure = 425 mmHg, 4,875 m) in a hypobaric chamber. An additional trial in hypoxia investigated effects of clamping at a lower PetCO2 (40 Torr) from ∼75 to 100% Wpeak to reduce potential influences of respiratory acidosis and muscle fatigue imposed by clamping PetCO2 at 50 Torr. Metabolic gases, ventilation, middle cerebral artery CBF velocity (transcranial Doppler), forehead pulse oximetry, and cerebral (prefrontal) and muscle (vastus lateralis) hemoglobin oxygenation (near infrared spectroscopy) were monitored across trials. Clamping PetCO2 at 50 Torr in both normoxia (n = 9) and hypoxia (n = 11) elevated CBF velocity (∼40%) and improved cerebral hemoglobin oxygenation (∼15%), but decreased Wpeak (6%) and peak oxygen consumption (11%). Clamping at 40 Torr near maximal effort in hypoxia (n = 6) also improved cerebral oxygenation (∼15%), but again limited Wpeak (5%). These findings demonstrate that increasing mass cerebral oxygen delivery via CO2-mediated vasodilation does not improve incremental exercise performance, at least when accompanied by respiratory acidosis. PMID:21921244

Cerebral salt-wasting syndrome due to hemorrhagic brain infarction: a case report.

PubMed

Tanaka, Tomotaka; Uno, Hisakazu; Miyashita, Kotaro; Nagatsuka, Kazuyuki

2014-07-23

Cerebral salt-wasting syndrome is a condition featuring hyponatremia and dehydration caused by head injury, operation on the brain, subarachnoid hemorrhage, brain tumor and so on. However, there are a few reports of cerebral salt-wasting syndrome caused by cerebral infarction. We describe a patient with cerebral infarction who developed cerebral salt-wasting syndrome in the course of hemorrhagic transformation. A 79-year-old Japanese woman with hypertension and arrhythmia was admitted to our hospital for mild consciousness disturbance, conjugate deviation to right, left unilateral spatial neglect and left hemiparesis. Magnetic resonance imaging revealed a broad ischemic change in right middle cerebral arterial territory. She was diagnosed as cardiogenic cerebral embolism because atrial fibrillation was detected on electrocardiogram on admission. She showed hyponatremia accompanied by polyuria complicated at the same time with the development of hemorrhagic transformation on day 14 after admission. Based on her hypovolemic hyponatremia, she was evaluated as not having syndrome of inappropriate secretion of antidiuretic hormone but cerebral salt-wasting syndrome. She fortunately recovered with proper fluid replacement and electrolyte management. This is a rare case of cerebral infarction and cerebral salt-wasting syndrome in the course of hemorrhagic transformation. It may be difficult to distinguish cerebral salt-wasting syndrome from syndrome of inappropriate antidiuretic hormone, however, an accurate assessment is needed to reveal the diagnosis of cerebral salt-wasting syndrome because the recommended fluid management is opposite in the two conditions.

Cerebral blood flow in humans following resuscitation from cardiac arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohan, S.L.; Mun, S.K.; Petite, J.

1989-06-01

Cerebral blood flow was measured by xenon-133 washout in 13 patients 6-46 hours after being resuscitated from cardiac arrest. Patients regaining consciousness had relatively normal cerebral blood flow before regaining consciousness, but all patients who died without regaining consciousness had increased cerebral blood flow that appeared within 24 hours after resuscitation (except in one patient in whom the first measurement was delayed until 28 hours after resuscitation, by which time cerebral blood flow was increased). The cause of the delayed-onset increase in cerebral blood flow is not known, but the increase may have adverse effects on brain function and maymore » indicate the onset of irreversible brain damage.« less

The MM-CGI Cerebral Palsy: modification and pretesting of an instrument to measure anticipatory grief in parents whose child has cerebral palsy.

PubMed

Al-Gamal, Ekhlas; Long, Tony

2014-07-01

To establish the potential of a modified version of the MM-CGI Childhood Cancer to assess anticipatory grief in parents of children with cerebral palsy, to amend the existing scale for use with the specific patient group, to test the psychometric properties of the modified version (MM-CGI Cerebral Palsy) and to review the clinical potential of the new scale. Parents of children with cerebral palsy may experience reactions similar to parents of children with other enduring or life-limiting conditions, and anticipatory grief may be one such psychological reaction. While the burden of caring is sometimes balanced by positive perceptions of the child, which enhance coping ability, for many parents the outcome is damage to their physical and mental health and impaired family functioning. A cross-sectional, descriptive, correlational design. The MM-CGI Cerebral Palsy was administered in structured interviews with 204 parents. Standardised measures of caregivers' depression, stress and perceived social support were also administered. Mothers and fathers were recruited from healthcare centres and schools for special education. Cronbach's alpha was used to assess internal consistency, and Pearson's product-moment correlation was used to assess construct validity. The subscales were each found to measure a single dimension of anticipatory grief, and significant correlations were established with existing instruments. The instrument demonstrated excellent internal consistency reliability and good construct validity. The MM-CGI Cerebral Palsy could be useful for diagnosing anticipatory grief among parents of children with cerebral palsy. This preliminary work moves the programme on to testing in intervention studies. In the absence of an existing measure for the assessment of anticipatory grief, specifically in parents of children with cerebral palsy, the MM-CGI Cerebral Palsy could prove to be an effective assessment tool for clinicians and researchers. © 2013 John Wiley

Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.

PubMed

Clozel, J P; Kuhn, H; Hefti, F

1989-12-01

Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.

Hemodilution increases cerebral blood flow in acute ischemic stroke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorstrup, S.; Andersen, A.; Juhler, M.

1989-07-01

We measured cerebral blood flow in 10 consecutive, but selected, patients with acute ischemic stroke (less than 48 hours after onset) before and after hemodilution. Cerebral blood flow was measured by xenon-133 inhalation and emission tomography, and only patients with focal hypoperfusion in clinically relevant areas were included. Hemodilution was done according to the hematocrit level: for a hematocrit greater than or equal to 42%, 500 ml whole blood was drawn and replaced by the same volume of dextran 40; for a hematocrit between 37% and 42%, only 250 ml whole blood was drawn and replaced by 500 cc ofmore » dextran 40. Mean hematocrit was reduced by 16%, from 46 +/- 5% (SD) to 39 +/- 5% (SD) (p less than 0.001). Cerebral blood flow increased in both hemispheres by an average of 20.9% (p less than 0.001). Regional cerebral blood flow increased in the ischemic areas in all cases, on an average of 21.4 +/- 12.0% (SD) (p less than 0.001). In three patients, a significant redistribution of flow in favor of the hypoperfused areas was observed, and in six patients, the fractional cerebral blood flow increase in the hypoperfused areas was of the same magnitude as in the remainder of the brain. In the last patient, cerebral blood flow increased relatively less in the ischemic areas. Our findings show that cerebral blood flow increases in the ischemic areas after hemodilution therapy in stroke patients. The marked regional cerebral blood flow increase seen in some patients could imply an improved oxygen delivery to the ischemic tissue.« less

Identification of proteins regulated by curcumin in cerebral ischemia.

PubMed

Shah, Fawad-Ali; Gim, Sang-Ah; Sung, Jin-Hee; Jeon, Seong-Jun; Kim, Myeong-Ok; Koh, Phil-Ok

2016-03-01

Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral ketone body metabolism.

PubMed

Morris, A A M

2005-01-01

Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

Cerebral hemodynamic changes in stroke during sleep-disordered breathing.

PubMed

Pizza, Fabio; Biallas, Martin; Kallweit, Ulf; Wolf, Martin; Bassetti, Claudio L

2012-07-01

Sleep-disordered breathing (SDB) negatively impacts stroke outcome. Near-infrared spectroscopy showed the acute cerebral hemodynamic effects of SDB. Eleven patients (7 men, age 61±13 years) with acute/subacute middle cerebral artery stroke (National Institutes of Health Stroke Scale score 10±7) and SDB (apnea-hypopnea index 32±28/hour) were assessed with nocturnal polysomnography and bilateral near-infrared spectroscopy recording. Cerebral oxygenation and hemoglobin concentration changes during obstructive and central apneas were analyzed. During SDB, near-infrared spectroscopy showed asymmetrical patterns of cerebral oxygenation and hemoglobin concentrations with changes significantly larger on the unaffected compared with the affected hemisphere. Brain tissue hypoxia was more severe during obstructive compared with central apneas. Profound cerebral deoxygenation effects of SDB occurred in acute/subacute stroke. These changes may contribute to poor outcome, arising in the possibility of a potential benefit of SDB treatment in stroke management.

Cerebral hematocrit decreases with hemodynamic compromise in carotid artery occlusion: a PET study.

PubMed

Yamauchi, H; Fukuyama, H; Nagahama, Y; Katsumi, Y; Okazawa, H

1998-01-01

This study investigated whether in patients with internal carotid artery occlusion the regional cerebral hematocrit correlates with cerebral hemodynamics or metabolic state and, if so, how the regional cerebral hematocrit changes in the hemodynamically compromised region. We used positron emission tomography to study seven patients with unilateral internal carotid artery occlusion and no cortical infarction in the chronic stage. The distributions of red blood cell and plasma volumes were assessed using oxygen-15-labeled carbon monoxide and copper-62-labeled human serum albumin-dithiosemicarbazone tracers, respectively. The calculated hematocrit value was compared with the hemodynamic and metabolic parameters measured with the oxygen-15 steady-state technique. In the cerebral cortex, the value of the cerebral hematocrit varied but was correlated with the hemodynamic and metabolic status. Stepwise regression analysis revealed that the large vessel hematocrit, the cerebral metabolic rate of oxygen, and the cerebral blood flow or the oxygen extraction fraction accounted for a significant proportion of variance of the cerebral hematocrit. The oxygen extraction fraction and the cerebral metabolic rate of oxygen negatively correlated with the cerebral hematocrit, whereas the cerebral blood flow correlated positively: patients with reduced blood supply relative to metabolic demand (decreased blood flow with increased oxygen extraction fraction) showed low hematocrit values. In carotid artery occlusion in the chronic stage, regional cerebral hematocrit may vary according to cerebral hemodynamics and metabolic status. Regional cerebral hematocrit may decrease with hemodynamic compromise unless oxygen metabolism concomitantly decreases.

Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

ERIC Educational Resources Information Center

Towbin, Abraham

1978-01-01

Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

Coupling between arterial pressure, cerebral blood velocity, and cerebral tissue oxygenation with spontaneous and forced oscillations.

PubMed

Rickards, Caroline A; Sprick, Justin D; Colby, Hannah B; Kay, Victoria L; Tzeng, Yu-Chieh

2015-04-01

We tested the hypothesis that transmission of arterial pressure to brain tissue oxygenation is low under conditions of arterial pressure instability. Two experimental models of hemodynamic instability were used in healthy human volunteers; (1) oscillatory lower body negative pressure (OLBNP) (N = 8; 5 male, 3 female), and; (2) maximal LBNP to presyncope (N = 21; 13 male, 8 female). Mean arterial pressure (MAP), middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2) were measured non-invasively. For the OLBNP protocol, between 0 and -60 mmHg negative pressure was applied for 20 cycles at 0.05 Hz, then 20 cycles at 0.1 Hz. For the maximal LBNP protocol, progressive 5 min stages of chamber decompression were applied until the onset of presyncope. Spectral power of MAP, mean MCAv, and ScO2 were calculated within the VLF (0.04-0.07 Hz), and LF (0.07-0.2 Hz) ranges, and cross-spectral coherence was calculated for MAP-mean MCAv, MAP-ScO2, and mean MCAv-ScO2 at baseline, during each OLBNP protocol, and at the level prior to pre-syncope during maximal LBNP (sub-max). The key findings are (1) both 0.1 Hz OLBNP and sub-max LBNP elicited increases in LF power for MAP, mean MCAv, and ScO2 (p ≤ 0.08); (2) 0.05 Hz OLBNP increased VLF power in MAP and ScO2 only (p ≤ 0.06); (3) coherence between MAP-mean MCAv was consistently higher (≥0.71) compared with MAP-ScO2, and mean MCAv-ScO2 (≤0.43) during both OLBNP protocols, and sub-max LBNP (p ≤ 0.04). These data indicate high linearity between pressure and cerebral blood flow variations, but reduced linearity between cerebral tissue oxygenation and both arterial pressure and cerebral blood flow. Measuring arterial pressure variability may not always provide adequate information about the downstream effects on cerebral tissue oxygenation, the key end-point of interest for neuronal viability.

[Research on brain white matter network in cerebral palsy infant].

PubMed

Li, Jun; Yang, Cheng; Wang, Yuanjun; Nie, Shengdong

2017-10-01

Present study used diffusion tensor image and tractography to construct brain white matter networks of 15 cerebral palsy infants and 30 healthy infants that matched for age and gender. After white matter network analysis, we found that both cerebral palsy and healthy infants had a small-world topology in white matter network, but cerebral palsy infants exhibited abnormal topological organization: increased shortest path length but decreased normalize clustering coefficient, global efficiency and local efficiency. Furthermore, we also found that white matter network hub regions were located in the left cuneus, precuneus, and left posterior cingulate gyrus. However, some abnormal nodes existed in the frontal, temporal, occipital and parietal lobes of cerebral palsy infants. These results indicated that the white matter networks for cerebral palsy infants were disrupted, which was consistent with previous studies about the abnormal brain white matter areas. This work could help us further study the pathogenesis of cerebral palsy infants.

Nonlinear assessment of cerebral autoregulation from spontaneous blood pressure and cerebral blood flow fluctuations.

PubMed

Hu, Kun; Peng, C K; Czosnyka, Marek; Zhao, Peng; Novak, Vera

2008-03-01

Cerebral autoregulation (CA) is an most important mechanism responsible for the relatively constant blood flow supply to brain when cerebral perfusion pressure varies. Its assessment in nonacute cases has been relied on the quantification of the relationship between noninvasive beat-to-beat blood pressure (BP) and blood flow velocity (BFV). To overcome the nonstationary nature of physiological signals such as BP and BFV, a computational method called multimodal pressure-flow (MMPF) analysis was recently developed to study the nonlinear BP-BFV relationship during the Valsalva maneuver (VM). The present study aimed to determine (i) whether this method can estimate autoregulation from spontaneous BP and BFV fluctuations during baseline rest conditions; (ii) whether there is any difference between the MMPF measures of autoregulation based on intra-arterial BP (ABP) and based on cerebral perfusion pressure (CPP); and (iii) whether the MMPF method provides reproducible and reliable measure for noninvasive assessment of autoregulation. To achieve these aims, we analyzed data from existing databases including: (i) ABP and BFV of 12 healthy control, 10 hypertensive, and 10 stroke subjects during baseline resting conditions and during the Valsalva maneuver, and (ii) ABP, CPP, and BFV of 30 patients with traumatic brain injury (TBI) who were being paralyzed, sedated, and ventilated. We showed that autoregulation in healthy control subjects can be characterized by specific phase shifts between BP and BFV oscillations during the Valsalva maneuver, and the BP-BFV phase shifts were reduced in hypertensive and stroke subjects (P < 0.01), indicating impaired autoregulation. Similar results were found during baseline condition from spontaneous BP and BFV oscillations. The BP-BFV phase shifts obtained during baseline and during VM were highly correlated (R > 0.8, P < 0.0001), showing no statistical difference (paired-t test P > 0.47). In TBI patients there were strong correlations

Nonlinear Assessment of Cerebral Autoregulation from Spontaneous Blood Pressure and Cerebral Blood Flow Fluctuations

PubMed Central

Peng, C. K.; Czosnyka, Marek; Zhao, Peng

2009-01-01

Cerebral autoregulation (CA) is an most important mechanism responsible for the relatively constant blood flow supply to brain when cerebral perfusion pressure varies. Its assessment in nonacute cases has been relied on the quantification of the relationship between noninvasive beat-to-beat blood pressure (BP) and blood flow velocity (BFV). To overcome the nonstationary nature of physiological signals such as BP and BFV, a computational method called multimodal pressure-flow (MMPF) analysis was recently developed to study the nonlinear BP–BFV relationship during the Valsalva maneuver (VM). The present study aimed to determine (i) whether this method can estimate autoregulation from spontaneous BP and BFV fluctuations during baseline rest conditions; (ii) whether there is any difference between the MMPF measures of autoregulation based on intra-arterial BP (ABP) and based on cerebral perfusion pressure (CPP); and (iii) whether the MMPF method provides reproducible and reliable measure for noninvasive assessment of autoregulation. To achieve these aims, we analyzed data from existing databases including: (i) ABP and BFV of 12 healthy control, 10 hypertensive, and 10 stroke subjects during baseline resting conditions and during the Valsalva maneuver, and (ii) ABP, CPP, and BFV of 30 patients with traumatic brain injury (TBI) who were being paralyzed, sedated, and ventilated. We showed that autoregulation in healthy control subjects can be characterized by specific phase shifts between BP and BFV oscillations during the Valsalva maneuver, and the BP–BFV phase shifts were reduced in hypertensive and stroke subjects (P < 0.01), indicating impaired autoregulation. Similar results were found during baseline condition from spontaneous BP and BFV oscillations. The BP–BFV phase shifts obtained during baseline and during VM were highly correlated (R > 0.8, P < 0.0001), showing no statistical difference (paired-t test P > 0.47). In TBI patients there were strong

Cerebral near-infrared spectroscopy insensitively detects low cerebral venous oxygen saturations after stage 1 palliation.

PubMed

Rescoe, Erin; Tang, Xiaoqi; Perry, Dorothy Alison; Sleeper, Lynn A; DiNardo, James A; Kussman, Barry D; Kheir, John N

2017-09-01

Measurement of cerebral venous oxyhemoglobin saturation (ScvO 2 ) is considered a gold standard in assessing the adequacy of tissue oxygen delivery (DO 2 ) after the stage 1 palliation (S1P), with SvO 2  <30% often representing severely compromised DO 2 . Regional oxygenation index (rSO 2 ) based on near-infrared resonance spectroscopy (NIRS) frequently is used to screen for compromised DO 2 , although its sensitivity to detect severe abnormalities in SvO 2 is uncertain. ScvO 2 was measured by co-oximetry from the internal jugular vein as clinically indicated in 73 neonates after S1P. These values were compared with cerebral rSO 2 (FORE-SIGHT; CASMED) via mixed effects model linear regression, Bland-Altman analysis, and sensitivity analysis. Because NIRS devices measure a composite of arterial and venous blood, we calculated an rSO 2 -based ScvO 2 designed to remove arterial contamination from the rSO 2 signal: rSO 2 -based ScvO 2  = (rSO 2 - arterial oxygen saturation × 0.3)/0.7. Among 520 time-matched pairs of ScvO 2 and cerebral rSO 2 , the slope of the relationship between rSO 2 and ScvO 2 (after we adjusted for effects of hemoglobin) was 0.37 ± 0.04 with only modest correlation (r 2  = 0.39), and mean bias of +8.26. When ScvO 2 was <30%, cerebral rSO 2 was <30 in less than 1%, <40 less than 1%, and <50 in 45.7% of data points; specificity of rSO 2 in the same range is >99%. Correction of rSO 2 for arterial contamination significantly decreased mean bias (+3.03) and improved the sensitivity of rSO 2 to detect ScvO 2  <30 to 6.5% for rSO 2  <30, 29% for rSO 2  <40, and 77.4% for rSO 2  <50. Cerebral rSO 2 in isolation should not be used to detect low ScvO 2 , because its sensitivity is low, although correction of rSO 2 for arterial contamination may improve sensitivity. Cerebral rSO 2 of 50 or greater should not be considered reassuring, though values below 30 are specific for low ScvO 2 . Copyright © 2017 The American Association for Thoracic

Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities.

PubMed

Umemura, Toshitaka; Kawamura, Takahiko; Hotta, Nigishi

2017-03-01

Diabetes patients have more than double the risk of ischemic stroke compared with non-diabetic individuals, and its neuroimaging characteristics have important clinical implications. To understand the pathophysiology of ischemic stroke in diabetes, it is important to focus not only on the stroke subtype, but also on the size and location of the occlusive vessels. Specifically, ischemic stroke in diabetes patients might be attributed to both large and small vessels, and intracranial internal carotid artery disease and small infarcts of the posterior circulation often occur. An additional feature is that asymptomatic lacunar infarctions are often seen in the basal ganglia and brain stem on brain magnetic resonance imaging. In particular, cerebral small vessel disease (SVD), including lacunar infarctions, white matter lesions and cerebral microbleeds, has been shown to be associated not only with stroke incidence, but also with the development and progression of dementia and diabetic microangiopathy. However, the pathogenesis of cerebral SVD is not fully understood. In addition, data on the association between neuroimaging findings of the cerebral SVD and diabetes are limited. Recently, the clinical importance of the link between cerebral SVD and retinal microvascular abnormalities has been a topic of considerable interest. Several clinical studies have shown that retinal microvascular abnormalities are closely related to cerebral SVD, suggesting that retinal microvascular abnormalities might be pathophysiologically linked to ischemic cerebral SVD. We review the literature relating to the pathophysiology and neuroimaging of cerebrovascular disease in diabetes, and discuss the problems based on the concept of cerebral large and small vessel disease. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Familial risk of cerebral palsy: population based cohort study.

PubMed

Tollånes, Mette C; Wilcox, Allen J; Lie, Rolv T; Moster, Dag

2014-07-15

To investigate risks of recurrence of cerebral palsy in family members with various degrees of relatedness to elucidate patterns of hereditability. Population based cohort study. Data from the Medical Birth Registry of Norway, linked to the Norwegian social insurance scheme to identify cases of cerebral palsy and to databases of Statistics Norway to identify relatives. 2,036,741 Norwegians born during 1967-2002, 3649 of whom had a diagnosis of cerebral palsy; 22,558 pairs of twins, 1,851,144 pairs of first degree relatives, 1,699,856 pairs of second degree relatives, and 5,165,968 pairs of third degree relatives were identified. Cerebral palsy. If one twin had cerebral palsy, the relative risk of recurrence of cerebral palsy was 15.6 (95% confidence interval 9.8 to 25) in the other twin. In families with an affected singleton child, risk was increased 9.2 (6.4 to 13)-fold in a subsequent full sibling and 3.0 (1.1 to 8.6)-fold in a half sibling. Affected parents were also at increased risk of having an affected child (6.5 (1.6 to 26)-fold). No evidence was found of differential transmission through mothers or fathers, although the study had limited power to detect such differences. For people with an affected first cousin, only weak evidence existed for an increased risk (1.5 (0.9 to 2.7)-fold). Risks in siblings or cousins were independent of sex of the index case. After exclusion of preterm births (an important risk factor for cerebral palsy), familial risks remained and were often stronger. People born into families in which someone already has cerebral palsy are themselves at elevated risk, depending on their degree of relatedness. Elevated risk may extend even to third degree relatives (first cousins). The patterns of risk suggest multifactorial inheritance, in which multiple genes interact with each other and with environmental factors. These data offer additional evidence that the underlying causes of cerebral palsy extend beyond the clinical management of

A Mixed-Ligand Approach for a Gigantic and Hollow Heterometallic Cage {Ni64 RE96 } for Gas Separation and Magnetic Cooling Applications.

PubMed

Chen, Wei-Peng; Liao, Pei-Qin; Yu, Youzhu; Zheng, Zhiping; Chen, Xiao-Ming; Zheng, Yan-Zhen

2016-08-01

Nanosized aggregations of metal ions shielded by organic ligands possessing both exquisite structural aesthetics and intriguing properties are fundamentally interesting. Three isostructural gigantic transition-metal-rare-earth heterometallic coordination cages are reported, abbreviated as {Ni64 RE96 } (RE=Gd, Dy, and Y) and obtained by a mixed-ligand approach, each possessing a cuboidal framework made of 160 metal ions and a nanosized spherical cavity in the center. Along with the structural novelty, these hollow cages show highly selective adsorptions for CO2 over CH4 or N2 at ambient temperatures. Moreover, the gadolinium analogue exhibits large magnetocaloric effect at ultralow temperatures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Safety of Pregnancy After Cerebral Venous Thrombosis: Results of the ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis)-2 PREGNANCY Study.

PubMed

Aguiar de Sousa, Diana; Canhão, Patrícia; Crassard, Isabelle; Coutinho, Jonathan; Arauz, Antonio; Conforto, Adriana; Béjot, Yannick; Giroud, Maurice; Ferro, José M

2017-11-01

Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis. Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies. A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous). In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent. © 2017 American Heart Association, Inc.

Mobility Experiences of Adolescents with Cerebral Palsy

ERIC Educational Resources Information Center

Palisano, Robert J.; Shimmell, Lorie J.; Stewart, Debra; Lawless, John J.; Rosenbaum, Peter L.; Russell, Dianne J.

2009-01-01

The purpose of this study was to describe how youth with cerebral palsy experience mobility in their daily lives using a phenomenological approach. The participants were 10 youth with cerebral palsy, 17 to 20 years of age, selected using purposeful sampling with maximum variation strategies. A total of 14 interviews were completed. Transcripts…

Application of non-invasive cerebral electrical impedance measurement on brain edema in patients with cerebral infarction.

PubMed

He, Lan Ying; Wang, Jian; Luo, Yong; Dong, Wei Wei; Liu, Li Xu

2010-09-01

To investigate the change of brain edema in patients with cerebral infarction by non-invasive cerebral electrical impedance (CEI) measurements. An invariable secure current at a frequency of 50 kHz and an intensity of 0.1 mA was given into a person's brain. CEI values of the bilateral hemisphere of 200 healthy volunteers and 107 patients with cerebral infarction were measured by non-invasive brain edema monitor. The results of perturbative index (PI) converted from CEI were compared with the volumes of brain edema, which were calculated by an image analysing system according to magnetic resonance imaging or computed tomography. (1) In the healthy volunteers, PI values in the left and right hemisphere were 7.98 +/- 0.95 and 8.02 +/- 0.71 respectively, and there was no significant difference between the two sides (p>0.05). Age, gender and different measuring times did not obviously affect PI values (p>0.05). (2) In the cerebral infarction group, CEI measurements were more sensitive to the volumes of lesion, which were more than 20 ml. The positive ratio of PI was higher when the volumes of infarction were >20 ml (80.0%): the ratio of PI was 75.9% when the volumes of infarction were 20-50 ml and it was 83.3% when the volumes of lesion were more than 50 ml. PI was lower when the volumes were less than 20 ml. (3) PI of the infarction side increased obviously 3-5 days after onset; the difference of two sides was the most significant. There was a positive correlation between PI of the infarction side and volume of infarction. PI may be a sensitive parameter for non-invasive monitoring of the change of brain edema in patients with cerebral infarction. CEI is a valuable method for the early detection of brain edema.

Dramatically accelerated growth and extraordinary gigantism of transgenic mud loach Misgurnus mizolepis.

PubMed

Nam, Y K; Noh, J K; Cho, Y S; Cho, H J; Cho, K N; Kim, C G; Kim, D S

2001-08-01

Transgenic mud loaches (Misgurnus mizolepis), in which the entire transgene originated from the same species, have been generated by microinjecting the mud loach growth hormone (mlGH) gene fused to the mud loach beta-actin promoter. Out of 4,100 eggs injected, 7.5% fish derived from the injected eggs showed dramatically accelerated growth, with a maximum of 35-fold faster growth than their non-transgenic siblings. Many fast-growing transgenic individuals showed extraordinary gigantism: their body weight and total length (largest fish attained to 413 g and 41.5 cm) were larger and longer than even those of 12-year-old normal broodstock (maximum size reached to 89 g and 28 cm). Of 46 transgenic founders tested, 30 individuals transmitted the transgene to next generation with a wide range of germ-line transmission frequencies ranging from 2% to 33%. The growth performance of the subsequent generation (F1) was also dramatically accelerated up to 35-fold, although the levels of enhanced growth were variable among transgenic lines. Three transgenic germ-lines up to F4 were established, showing the expected Mendelian inheritance of the transgene. Expression of GH mRNA in many tissues was detected by RT-PCR analyses. The time required to attain marketable size (10 g) in these transgenic lines was only 30-50 days after fertilization, while at least 6 months in non-transgenic fish. Besides growth enhancement, significantly improved feed-conversion efficiency up to 1.9-fold was also observed.

Gigantism associated with a pituitary tumour secreting growth hormone and prolactin and cured by transsphenoidal hypophysectomy.

PubMed

Favre, L; Rogers, L M; Cobb, C A; Rabin, D

1979-06-01

An 18-year old male is reported who presented with a history of a growtn spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by L-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported.

Unusual Association: Cerebral Arteriovenous Malformation and Chiari Type I Malformation.

PubMed

Ogul, Hayri; Kantarci, Mecit

2017-06-01

Cerebral arteriovenous malformation (AVM) is a common type of cerebral vascular malformation. The imaging findings are enlarged vessels, thrombosed sinuses, and hemorrhage or gliosis on adjacent brain parenchyma. Magnetic resonance (MR) imaging can be used safely for diagnosis. Chiari type I malformation is characterized by a caudal descent of the cerebellar tonsil. Coincidence of cerebral AVM and Chiari type I malformation is very rare. In this paper, the authors report MR imaging findings of a patient with coincidence of cerebral AVM and Chiari type I malformation.

Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds in humans.

PubMed

Miyatani, F; Kuriyama, N; Watanabe, I; Nomura, R; Nakano, K; Matsui, D; Ozaki, E; Koyama, T; Nishigaki, M; Yamamoto, T; Mizuno, T; Tamura, A; Akazawa, K; Takada, A; Takeda, K; Yamada, K; Nakagawa, M; Ihara, M; Kanamura, N; Friedland, R P; Watanabe, Y

2015-10-01

Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Retinal vascular changes are a marker for cerebral vascular diseases

PubMed Central

Moss, Heather E.

2016-01-01

The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

[Mental impairment in children with cerebral palsy: diagnosis and treatment].

PubMed

Nemkova, S A

2018-01-01

The article covers the problems of diagnosis and treatment of mental impairment in children with cerebral palsy. Mental disorders in cerebral palsy include cognitive impairment (disorders of perception, memory, attention, motor-visual coordination, intelligence and speech), border disorders (cerebral/asthenic, neurosis-like, psychopathic-like syndromes) and personality disorders (accentuation of character, mental infantilism). Diagnosis of mental disorders in patients with cerebral palsy is a challenging task, due to various combinations of them with physical, speech and sensory disorders, which requires a differentiated approach. Current trends in comprehensive system of rehabilitation, including medical and social, and psychological-pedagogical correction of cognitive, emotional and behavioral disorders, in cerebral palsy are reviewed. Experience of using cortexin, which compensates for cognitive impairment and improves social adaptation, is discussed.

Local estrogenic/androgenic balance in the cerebral vasculature

PubMed Central

Krause, Diana N.; Duckles, Sue P.; Gonzales, Rayna J.

2011-01-01

Reproductive effects of sex steroids are well-known, however it is increasingly apparent that these hormones have important actions on non-reproductive tissues such as the vasculature. The latter effects can be relevant throughout the lifespan, not just limited to reproductive years, and are not necessarily restricted to one sex or the other. Our work has established that cerebral blood vessels are a non-reproductive target tissue for sex steroids. We have found that estrogen and androgens alter vascular tone, endothelial function, oxidative stress and inflammatory responses in cerebral vessels. Often the actions of estrogen and androgens oppose each other. Moreover, it is clear that cerebral vessels are directly targeted by sex steroids as they express specific receptors for these hormones. Interestingly, cerebral blood vessels also express enzymes that metabolize sex steroids. These findings suggest that local synthesis of 17β-estradiol and dihydrotestosterone can occur within the vessel wall. One of the enzymes present, aromatase, converts testosterone to 17β-estradiol, which would alter the local balance of androgenic and estrogenic influences. Thus cerebral vessels are affected by circulating sex hormones as well as locally synthesized sex steroids. The presence of vascular endocrine effector mechanisms has important implications for male-female differences in cerebrovascular function and disease. Moreover, the cerebral circulation is a target for gonadal hormones as well as anabolic steroids and therapeutic drugs used to manipulate sex steroid actions. The long-term consequences of these influences have yet to be determined. PMID:21535417

Protective effect of cilazapril on the cerebral circulation.

PubMed

Véniant, M; Clozel, J P; Kuhn, H; Clozel, M

1992-01-01

The goal of an antihypertensive treatment is to prevent "end-organ" damage. Cerebral vascular complications are among the most important because they are life threatening and can occur even at an early stage of the disease. Recently, it has been shown that cilazapril can decrease the mortality of stroke-prone rats, suggesting a decrease in the incidence of strokes, which occur spontaneously in these animals. The present article reviews the different functional and morphological changes that may explain the cerebral protective effects of cilazapril, such as the normalization of cerebral vascular reserve, decrease in the media, increase in the external diameter, and normalization of the mechanics and endothelial function of cerebral arterioles. In addition, the inhibition by cilazapril of injury-induced proliferation of smooth muscle cells and the infiltration of the endothelium by macrophages could prevent the development of atherosclerosis.

Platelet Factor 4 Mediates Inflammation in Cerebral Malaria

PubMed Central

Srivastava, Kalyan; Cockburn, Ian A.; Swaim, AnneMarie; Thompson, Laura E.; Tripathi, Abhai; Fletcher, Craig A.; Shirk, Erin M.; Sun, Henry; Kowalska, M. Anna; Fox-Talbot, Karen; Sullivan, David; Zavala, Fidel; Morrell, Craig N.

2008-01-01

Summary Cerebral malaria is a major complication of Plasmodium falciparum infection in children. The pathogenesis of cerebral malaria involves vascular inflammation, immune stimulation and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria. Plasmodium infected red blood cells (RBC) activated platelets independent of vascular effects, resulting in increased plasma PF4. PF4 or CXCR3 null mice had less ECM, decreased brain T-cell recruitment, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium infected RBC can activate platelets and platelet derived PF4 then contributes to immune activation and T-cell trafficking as part of the pathogenesis of ECM. PMID:18692777

T2’-Imaging to Assess Cerebral Oxygen Extraction Fraction in Carotid Occlusive Disease: Influence of Cerebral Autoregulation and Cerebral Blood Volume

PubMed Central

Deichmann, Ralf; Pfeilschifter, Waltraud; Hattingen, Elke; Singer, Oliver C.; Wagner, Marlies

2016-01-01

Purpose Quantitative T2'-mapping detects regional changes of the relation of oxygenated and deoxygenated hemoglobin (Hb) by using their different magnetic properties in gradient echo imaging and might therefore be a surrogate marker of increased oxygen extraction fraction (OEF) in cerebral hypoperfusion. Since elevations of cerebral blood volume (CBV) with consecutive accumulation of Hb might also increase the fraction of deoxygenated Hb and, through this, decrease the T2’-values in these patients we evaluated the relationship between T2’-values and CBV in patients with unilateral high-grade large-artery stenosis. Materials and Methods Data from 16 patients (13 male, 3 female; mean age 53 years) with unilateral symptomatic or asymptomatic high-grade internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis/occlusion were analyzed. MRI included perfusion-weighted imaging and high-resolution T2’-mapping. Representative relative (r)CBV-values were analyzed in areas of decreased T2’ with different degrees of perfusion delay and compared to corresponding contralateral areas. Results No significant elevations in cerebral rCBV were detected within areas with significantly decreased T2’-values. In contrast, rCBV was significantly decreased (p<0.05) in regions with severe perfusion delay and decreased T2’. Furthermore, no significant correlation between T2’- and rCBV-values was found. Conclusions rCBV is not significantly increased in areas of decreased T2’ and in areas of restricted perfusion in patients with unilateral high-grade stenosis. Therefore, T2’ should only be influenced by changes of oxygen metabolism, regarding our patient collective especially by an increase of the OEF. T2’-mapping is suitable to detect altered oxygen consumption in chronic cerebrovascular disease. PMID:27560515

Cerebral gas embolism due to upper gastrointestinal endoscopy.

PubMed

ter Laan, Mark; Totte, Erik; van Hulst, Rob A; van der Linde, Klaas; van der Kamp, Wim; Pierie, Jean-Pierre E

2009-07-01

Cerebral gas embolism as a result of upper gastrointestinal endoscopy is a rare complication and bares a high morbidity. A patient is presented who underwent an upper endoscopy for evaluation of a gastric-mediastinal fistula after subtotal oesophagectomy and gastric tube reconstruction because of oesophageal cancer. During the procedure, cerebral gas emboli developed resulting in an acute left-sided hemiparesis. After hyperbaric oxygen therapy, the patient recovered almost completely. The aetiology and treatment is discussed based on the reviewed literature. Once cerebral gas emboli are recognized, patient outcome can be improved by hyperbaric oxygen therapy.

Mental Imagery Abilities in Adolescents with Spastic Diplegic Cerebral Palsy

ERIC Educational Resources Information Center

Courbois, Yanick; Coello, Yann; Bouchart, Isabelle

2004-01-01

Four visual imagery tasks were presented to three groups of adolescents with or without spastic diplegic cerebral palsy. The first group was composed of six adolescents with cerebral palsy who had associated visual-perceptual deficits (CP-PD), the second group was composed of five adolescents with cerebral palsy and no associated visual-perceptual…

New Hope for Children with Cerebral Palsy.

ERIC Educational Resources Information Center

Obringer, S. John

This paper explains the use of a unique experimental therapy for students with a type of cerebral palsy specifically called Botox. Botulinum Toxin Type A has been tried on a sizable number of students with cerebral palsy in clinical settings to reduce spastic and dystonic movements. By injecting Botox into overly tight heel cords, a normal or near…

Effect of nicergoline on cerebral blood flow

PubMed Central

Iliff, L. D.; Boulay, G. H. Du; Marshall, John; Russell, R. W. Ross; Symon, Lindsay

1977-01-01

Cerebral blood flow (CBF) was measured before and after intravenous injection of the cerebral vasodilator nicergoline in 13 patients with cerebrovascular disease. CBF increased in seven. The possibility that the effect of the drug in the remainder may have been masked by a fall of CBF which occurs during sequential measurement of patients at rest is discussed. PMID:925694

Cerebral oximetry: a replacement for pulse oximetry?

PubMed

Frost, Elizabeth A M

2012-10-01

Cerebral oximetry has been around for some 3 decades but has had a somewhat checkered history regarding application and reliability. More recently several monitors have been approved in the United States and elsewhere and the technique is emerging as a useful tool for assessing not only adequate cerebral oxygenation but also tissue oxygenation and perfusion in other organs.

Relationship between relative cerebral blood flow, relative cerebral blood volume, and relative cerebral metabolic rate of oxygen in the preterm neonatal brain.

PubMed

Nourhashemi, Mina; Kongolo, Guy; Mahmoudzadeh, Mahdi; Goudjil, Sabrina; Wallois, Fabrice

2017-04-01

The mechanisms responsible for coupling between relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic rate of oxygen ([Formula: see text]), an important function of the microcirculation in preterm infants, remain unclear. Identification of a causal relationship between rCBF-rCBV and [Formula: see text] in preterms may, therefore, help to elucidate the principles of cortical hemodynamics during development. We simultaneously recorded rCBF and rCBV and estimated [Formula: see text] by two independent acquisition systems: diffuse correlation spectroscopy and near-infrared spectroscopy, respectively, in 10 preterms aged between 28 and 35 weeks of gestational age. Transfer entropy was calculated in order to determine the directionality between rCBF-rCBV and [Formula: see text]. The surrogate method was applied to determine statistical significance. The results show that rCBV and [Formula: see text] have a predominant driving influence on rCBF at the resting state in the preterm neonatal brain. Statistical analysis robustly detected the correct directionality of rCBV on rCBF and [Formula: see text] on rCBF. This study helps to clarify the early organization of the rCBV-rCBF and [Formula: see text] inter-relationship in the immature cortex.

MRI of plaque characteristics and relationship with downstream perfusion and cerebral infarction in patients with symptomatic middle cerebral artery stenosis.

PubMed

Lu, Shan-Shan; Ge, Song; Su, Chun-Qiu; Xie, Jun; Mao, Jian; Shi, Hai-Bin; Hong, Xun-Ning

2017-10-30

Intracranial plaque characteristics are associated with stroke events. Differences in plaque features may explain the disconnect between stenosis severity and the presence of ischemic stroke. To investigate the relationship between plaque characteristics and downstream perfusion changes, and their contribution to the occurrence of cerebral infarction beyond luminal stenosis. Case control. Forty-six patients with symptomatic middle cerebral artery (MCA) stenosis (with acute cerebral infarction, n = 30; without acute cerebral infarction, n = 16). 3.0T with 3D turbo spin echo sequence (3D-SPACE). Luminal stenosis grade, plaque features including lesion T 2 and T 1 hyperintense components, plaque enhancement grade, and plaque distribution were assessed. Brain perfusion was evaluated on mean transient time maps based on the Alberta Stroke Program Early CT score (MTT-ASPECTS). Plaque features, grade of luminal stenosis, and MTT-ASPECTS were compared between two groups. The association between plaque features and MTT-ASPECTS were assessed using Spearman's correlation analysis. Multivariate logistic regression and receiver operating characteristic (ROC) curves were constructed to assess the effect of significant variables alone and their combination in determining the occurrence of cerebral infarction. Stronger enhanced plaques were associated with downstream lower MTT-ASPECTS (P = 0.010). Plaque enhancement grade (P = 0.039, odds ratio [OR] 5.9, 95% confidence interval [CI] 1.1-32) and MTT-ASPECTS (P = 0.003, OR 2.6, 95% CI 1.4-4.7) were associated with a recent cerebral infarction, whereas luminal stenosis grade was not (P = 0.128). The combination of MTT-ASPECTS and plaque enhancement grade provided incremental information beyond luminal stenosis grade alone. The area under the receiver operating characteristic curve (AUC) improved from 0.535 to 0.921 (P < 0.05). Strongly enhanced plaques are associated with a higher likelihood of downstream

Maternal Infections During Pregnancy and Cerebral Palsy in the Child

PubMed Central

Bear, Joshua J.; Wu, Yvonne W.

2016-01-01

INTRODUCTION Chorioamnionitis is a risk factor for cerebral palsy. The relationship between extra-amniotic infections and cerebral palsy is less well studied. We examined maternal intra- and extra-amniotic infections and risk of cerebral palsy in the child. METHODS Among a retrospective cohort of six million Californian births, 1991–2001, we analyzed administrative maternal and newborn hospital discharge abstracts linked to records of all children receiving services for cerebral palsy at the California Department of Developmental Services. We identified maternal hospital diagnoses of intra-amniotic (chorioamnionitis) and extra-amniotic (other genitourinary and respiratory) infections occurring up to twelve months before delivery. Using multivariable logistic regression, we determined the independent association between maternal infections and cerebral palsy, adjusting for infant sex, maternal age, race, education, socioeconomic status, and obesity. RESULTS 5.5% of mothers had a hospital discharge diagnosis of at least one of the following: chorioamnionitis (2.0%), other genitourinary (3.1%), and respiratory infection (0.6%). An infection diagnosis was more common in mothers of the 8,473 infants with cerebral palsy than in mothers of unaffected children (13.7% vs. 5.5%, P<0.001). All three types of maternal infections (chorioamnionitis, OR 3.1, 95% CI 2.9–3.4; other genitourinary infection, OR 1.4, 95% CI 1.3–1.6; and respiratory infection, OR 1.9, 95% CI 1.5–2.2) were associated with cerebral palsy in multivariable analyses. Maternal extra-amniotic infections, whether diagnosed during prenatal or birth hospitalizations, conferred an increased risk of cerebral palsy. CONCLUSIONS Maternal extra-amniotic infections diagnosed in the hospital during pregnancy are associated with a modestly increased risk of cerebral palsy in the child. PMID:26857522

Modelling the effects of cerebral microvasculature morphology on oxygen transport.

PubMed

Park, Chang Sub; Payne, Stephen J

2016-01-01

The cerebral microvasculature plays a vital role in adequately supplying blood to the brain. Determining the health of the cerebral microvasculature is important during pathological conditions, such as stroke and dementia. Recent studies have shown the complex relationship between cerebral metabolic rate and transit time distribution, the transit times of all the possible pathways available dependent on network topology. In this paper, we extend a recently developed technique to solve for residue function, the amount of tracer left in the vasculature at any time, and transit time distribution in an existing model of the cerebral microvasculature to calculate cerebral metabolism. We present the mathematical theory needed to solve for oxygen concentration followed by results of the simulations. It is found that oxygen extraction fraction, the fraction of oxygen removed from the blood in the capillary network by the tissue, and cerebral metabolic rate are dependent on both mean and heterogeneity of the transit time distribution. For changes in cerebral blood flow, a positive correlation can be observed between mean transit time and oxygen extraction fraction, and a negative correlation between mean transit time and metabolic rate of oxygen. A negative correlation can also be observed between transit time heterogeneity and the metabolic rate of oxygen for a constant cerebral blood flow. A sensitivity analysis on the mean and heterogeneity of the transit time distribution was able to quantify their respective contributions to oxygen extraction fraction and metabolic rate of oxygen. Mean transit time has a greater contribution than the heterogeneity for oxygen extraction fraction. This is found to be opposite for metabolic rate of oxygen. These results provide information on the role of the cerebral microvasculature and its effects on flow and metabolism. They thus open up the possibility of obtaining additional valuable clinical information for diagnosing and treating

Is Vasomotion in Cerebral Arteries Impaired in Alzheimer's Disease?

PubMed

Di Marco, Luigi Yuri; Farkas, Eszter; Martin, Chris; Venneri, Annalena; Frangi, Alejandro F

2015-01-01

A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer's disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion- the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain- is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation.

Cerebral Palsy Checklist: Babies & Preschoolers (Birth to age 5)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy Checklist: Babies & Preschoolers KidsHealth / For Parents / Cerebral Palsy Checklist: Babies & Preschoolers What's in this article? Step ...

Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model.

PubMed

Midulla, P S; Gandsas, A; Sadeghi, A M; Mezrow, C K; Yerlioglu, M E; Wang, W; Wolfe, D; Ergin, M A; Griepp, R B

1994-09-01

Retrograde cerebral perfusion (RCP) is a new method of cerebral protection that has been touted as an improvement over hypothermic circulatory arrest (HCA). However, RCP has been used clinically for durations and at temperatures that are "safe" for HCA alone. This study was designed to compare RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe" limits, in order to determine unequivocally whether RCP provides better cerebral protection than HCA. Four groups of six Yorkshire pigs (20 to 30 kg) were randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. Arterial, mixed venous and cerebral venous oxygen, glucose and lactate contents; quantitative EEG; were monitored at baseline (37 degrees C); at the end of cooling cardiopulmonary bypass (20 degrees C); during rewarming (30 degrees C); and at two and four hours post intervention. Animals were recovered and were evaluated daily using a quantitative behavioral score (0 to 9). Mean behavioral score was lower in the HCA group than in the other three groups at seven days (HCA 5.8 +/- 1.1; RCP 8.5 +/- 0.2; ACP 9.0 +/- 0.0; HCA-HP 8.5 +/- 0.2, p < 0.05). Recovery of QEEG was better in the ACP group than in all others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCA-HP (HCA 15 +/- 4; RCP 27 +/- 3; ACP 78 +/- 5; HCA-HP 19 +/- 3, p < 0.001). However, histopathological evidence of ischemic injury was present in 5 of 6 HCA animals and also in 4 of 6 of the HCP-HP group, but only in 1 of 6 RCP animals and in none of the ACP group. This study demonstrates that ACP affords the best cerebral protection by all outcome measures, but RCP provides clear improvement compared to HCA.

Intracerebral Hemorrhage Caused by Cerebral Hyperperfusion after Superficial Temporal Artery to Middle Cerebral Artery Bypass for Atherosclerotic Occlusive Cerebrovascular Disease

PubMed Central

Matano, Fumihiro; Murai, Yasuo; Mizunari, Takayuki; Adachi, Koji; Kobayashi, Shiro; Morita, Akio

Few papers have reported detailed accounts of intracerebral hemorrhage caused by cerebral hyperperfusion after superficial temporal artery to middle cerebral artery bypass (STA-MCA) bypass for atherosclerotic occlusive cerebrovascular disease. We report a case of vasogenic edema and subsequent intracerebral hemorrhage caused by the cerebral hyperperfusion syndrome (CHS) after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease disease without intense postoperative blood pressure control. A 63-year-old man with repeating left hemiparesis underwent magnetic resonance angiography (MRA), which revealed right internal carotid artery (ICA) occlusion. We performed a double bypass superficial temporal artery (STA)–middle cerebral artery (MCA) bypass surgery for the M2 and M3 branches. While the patient’s postoperative course was relatively uneventful, he suffered generalized convulsions, and computed tomography revealed a low area in the right frontal lobe on Day 4 after surgery. We considered this lesion to be pure vasogenic edema caused by cerebral hyperperfusion after revascularization. Intravenous drip infusion of a free radical scavenger (edaravone) and efforts to reduce systolic blood pressure to <120 mmHg were continued. The patient experienced severe left hemiparesis and disturbance of consciousness on Day 8 after surgery, due to intracerebral hemorrhage in the right frontal lobe at the site of the earlier vasogenic edema. Brain edema associated with cerebral hyperperfusion after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease should be recognized as a risk factor for intracerebral hemorrhage. The development of brain edema associated with CHS after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease requires not only intensive control of blood pressure, but also consideration of sedation therapy with propofol. PMID:28664022

Pathophysiology of dysarthria in cerebral palsy.

PubMed Central

Neilson, P D; O'Dwyer, N J

1981-01-01

Electromyograms were recorded with hooked-wire electrodes from sixteen lip, tongue and jaw muscles in six normal and seven cerebral palsied adult subjects during a variety of speech and non-speech tasks. The recorded patterns of muscle activity fail to support a number of theories concerning the pathophysiology of dysarthria in cerebral palsy. There was no indication of weakness in individual articulator muscles. There was no evidence of uncontrolled sustained background activity or of abnormal tonic stretch reflex responses in lip or tongue muscles. Primitive or pathological reflexes could not be elicited by orofacial stimulation. No imbalance between positive and negative oral responses was observed. The view that random involuntary movement disrupts essentially normal voluntary control in athetosis was not supported. Each cerebral palsied subject displayed an idiosyncratic pattern of abnormal muscle activity which was reproduced across repetitions of the same phrase, indicating a consistent defect in motor programming. PMID:7334387

Cerebral vasomotor reactivity in neurodegenerative diseases.

PubMed

Smoliński, Łukasz; Członkowska, Anna

Small-caliber cerebral vessels change their diameters in response to alterations of key metabolite concentrations such as carbon dioxide or oxygen. This phenomenon, termed the cerebral vasomotor reactivity (CVMR), is the basis for blood flow regulation in the brain in accordance with its metabolic status. Typically, CVMR is determined as the amount of change in cerebral blood flow in response to a vasodilating stimulus, which can be measured by various neuroimaging methods or by transcranial Doppler. It has been shown that CVMR is impaired in cerebrovascular diseases, but there is also evidence of a similar dysfunction in neurodegenerative disorders. Here, we review studies that have investigated CVMR in the common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Moreover, we discuss potential neurodegenerative mechanisms responsible for the impairment of CVMR. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Cerebral Palsy Checklist: Teens & Young Adult (13 to 21)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy Checklist: Teens & Young Adults KidsHealth / For Parents / Cerebral Palsy Checklist: Teens & Young Adults What's in this article? ...

Bilateral cerebral hemispheric infarction associated with sildenafil citrate (Viagra) use.

PubMed

Kim, K-K; Kim, D G; Ku, Y H; Lee, Y J; Kim, W-C; Kim, O J; Kim, H S

2008-03-01

Sildenafil citrate (Viagra) is one of the frequently prescribed drugs for men with erectile dysfunction. We describe a 52-year-old man with bilateral middle cerebral artery (MCA) territory infarction after sildenafil use. He ingested 100 mg of sildenafil and about 1 h later, he complained of chest discomfort, palpitation and dizziness followed by mental obtundation, global aphasia and left hemiparesis. Brain magnetic resonance imaging documented acute bilateral hemispheric infarction, and cerebral angiography showed occluded bilateral MCA. Despite significant bilateral MCA stenosis and cerebral infarction, systemic hypotension persisted for a day. We presume that cerebral infarction was caused by cardioembolism with sildenafil use.

Autoregulation of cerebral blood circulation under orthostatic tests

NASA Technical Reports Server (NTRS)

Gayevyy, M. D.; Maltsev, V. G.; Pogorelyy, V. E.

1980-01-01

Autoregulation of cerebral blood flow (ACBF) under orthostatic tests (OT) was estimated in acute experiments on rabbits and cats under local anesthesia according to changes of perfusion pressure (PP) in carotid arteries, cerebral blood flow, pressure in the venous system of the brain, and resistance of cerebral vessels. The OT were conducted by turning a special table with the animal fastened to it from a horizontal to a vertical (head up or head down) position at 40 to 80 deg. In most experiments ACBF correlated with the changes of PP. Different variations of ACBF and its possible mechanisms are discussed.

Effect of antihypertensive treatment on focal cerebral infarction.

PubMed

Fujii, K; Weno, B L; Baumbach, G L; Heistad, D D

1992-06-01

The goal of the current study was to determine whether treatment of hypertension reduces cerebral infarction after occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHRSPs). Three-month-old SHRSPs received untreated drinking water or drinking water containing cilazapril, an angiotensin converting enzyme inhibitor, or hydralazine and hydrochlorothiazide. After 3 months of treatment, the left middle cerebral artery was occluded and neurological deficit was evaluated. Infarct volume was measured 3 days after occlusion using computer imaging techniques from brain slices. Cilazapril and hydralazine with hydrochlorothiazide were equally effective in reducing systolic blood pressure in SHRSPs. One day after occlusion of the middle cerebral artery, neurological deficit was decreased by both cilazapril and hydralazine with hydrochlorothiazide compared with untreated SHRSPs, and the deficit 3 days after occlusion was decreased significantly only by cilazapril. Infarct volume was 178 +/- 7 mm3 (mean +/- SEM) in untreated SHRSPs, and it was significantly reduced to 117 +/- 15 mm3 by hydralazine with hydrochlorothiazide and to 101 +/- 17 mm3 by cilazapril. Infarct volume in Wistar-Kyoto rats was 27 +/- 16 mm3. Thus, reduction in arterial pressure by hydralazine with hydrochlorothiazide or an angiotensin converting enzyme inhibitor is protective against focal cerebral ischemia in SHRSPs.

The Effects of Obesity on the Cerebral Vasculature

PubMed Central

Dorrance, Anne M; Matin, Nusrat; Pires, Paulo W

2016-01-01

The incidence of obesity in the population is increasing at an alarming rate, with this comes an increased risk of insulin resistance (IR). Obesity and IR increase an individual’s risk of having a stroke and they have been linked to several forms of dementia. Stroke and dementia are associated with, or exacerbated by, reduced cerebral blood flow, which has recently been described in obese patients. In this review we will discuss the effects of obesity on cerebral artery function and structure. Regarding their function, we will focus on the endothelium and nitric oxide (NO) dependent dilation. NO dependent dilation is impaired in cerebral arteries from obese rats, and the majority of evidence suggests this is a result of increased oxidative stress. We will also describe the limited studies showing that inward cerebral artery remodeling occurs in models of obesity, and that the remodeling is associated with an increase in the damage caused by cerebral ischemia. We will also discuss some of the more paradoxical findings associated with stroke and obesity, including the evidence that obesity is a positive factor for stroke survival. Finally we will discuss the evidence that links these changes in vascular structure and function to cognitive decline and dementia. PMID:24846235

Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao Canxiang; Yang Qingwu; Lv Fenglin

Inflammatory reaction plays an important role in cerebral ischemia-reperfusion injury, however, its mechanism is still unclear. Our study aims to explore the function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia-reperfusion. We made middle cerebral artery ischemia-reperfusion model in mice with line embolism method. Compared with C3H/OuJ mice, scores of cerebral water content, cerebral infarct size and neurologic impairment in C3H/Hej mice were obviously lower after 6 h ischemia and 24 h reperfusion. Light microscopic and electron microscopic results showed that cerebral ischemia-reperfusion injury in C3H/Hej mice was less serious than that in C3H/OuJ mice. TNF-{alpha} andmore » IL-6 contents in C3H/HeJ mice were obviously lower than that in C3H/OuJ mice with ELISA. The results showed that TLR4 participates in the process of cerebral ischemia-reperfusion injury probably through decrease of inflammatory cytokines. TLR4 may become a new target for prevention of cerebral ischemia-reperfusion injury. Our study suggests that TLR4 is one of the mechanisms of cerebral ischemia-reperfusion injury besides its important role in innate immunity.« less

Effect of age on cerebral blood flow during hypothermic cardiopulmonary bypass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brusino, F.G.; Reves, J.G.; Smith, L.R.

1989-04-01

Cerebral blood flow was measured in 20 patients by xenon 133 clearance methodology during nonpulsatile hypothermic cardiopulmonary bypass to determine the effect of age on regional cerebral blood flow during these conditions. Measurements of cerebral blood flow at varying perfusion pressures were made in patients arbitrarily divided into two age groups at nearly identical nasopharyngeal temperature, hematocrit value, and carbon dioxide tension and with equal cardiopulmonary bypass flows of 1.6 L/min/m2. The range of mean arterial pressure was 30 to 110 mm Hg for group I (less than or equal to 50 years of age) and 20 to 90 mmmore » Hg for group II (greater than or equal to 65 years of age). There was no significant difference (p = 0.32) between the mean arterial pressure in group I (54 +/- 28 mm Hg) and that in group II (43 +/- 21 mm Hg). The range of cerebral blood flow was 14.8 to 29.2 ml/100 gm/min for group I and 13.8 to 37.5 ml/100 gm/min for group II. There was no significant difference (p = 0.37) between the mean cerebral blood flow in group I (21.5 +/- 4.6 ml/100 gm/min) and group II (24.3 +/- 8.1 ml/100 gm/min). There was a poor correlation between mean arterial pressure and cerebral blood flow in both groups: group I, r = 0.16 (p = 0.67); group II, r = 0.5 (p = 0.12). In 12 patients, a second cerebral blood flow measurements was taken to determine the effect of mean arterial pressure on cerebral blood flow in the individual patient. Changes in mean arterial pressure did not correlate with changes in cerebral blood flow (p less than 0.90). We conclude that age does not alter cerebral blood flow and that cerebral blood flow autoregulation is preserved in elderly patients during nonpulsatile hypothermic cardiopulmonary bypass.« less

Dynamic cerebral autoregulation in stroke patients with a central sympathetic deficit.

PubMed

Gierthmühlen, J; Allardt, A; Sawade, M; Baron, R; Wasner, G

2011-05-01

To investigate the functional role of the sympathetic innervation on cerebral autoregulation. Seventeen patients with infarction of the dorsolateral medulla oblongata affecting central sympathetic pathways (Wallenberg's syndrome) and 21 healthy controls were included in the study. Cerebral blood flow velocity (CBFV) in the medial cerebral artery was investigated using transcranial Doppler ultrasound during decrease in cerebral perfusion pressure induced by leg-cuff test and tilt table. Upon leg-cuff test, changes of cerebral blood flow and mean arterial blood pressure as well as autoregulatory index did not differ between patients or controls. No differences were found in changes of CBFV, mean arterial blood pressure and heart rate between patients or controls during the tilt table test. We suggest that the sympathetic nervous system does not have an influence on cerebral autoregulation after decrease in perfusion pressure under normotonous conditions. © 2010 John Wiley & Sons A/S.

Increasing rates of cerebral palsy across the severity spectrum in north-east England 1964-1993. The North of England Collaborative Cerebral Palsy Survey.

PubMed

Colver, A F; Gibson, M; Hey, E N; Jarvis, S N; Mackie, P C; Richmond, S

2000-07-01

To report epidemiological trends in cerebral palsy including analyses by severity. Descriptive longitudinal study in north-east England. Every child with suspected cerebral palsy was examined by a developmental paediatrician to confirm the diagnosis. Severity of impact of disability was derived from a parent completed questionnaire already developed and validated for this purpose. All children with cerebral palsy, not associated with any known postneonatal insult, born 1964-1993 to mothers resident at the time of birth in the study area. Cerebral palsy rates by year, birth weight, and severity. Severity of 30% and above defines the more reliably ascertained cases; children who died before assessment at around 6 years of age are included in the most severe group (70% and above). 584 cases of cerebral palsy were ascertained, yielding a rate that rose from 1.68 per 1000 neonatal survivors during 1964-1968 to 2.45 during 1989-1993 (rise = 0.77; 95% confidence interval 0.2-1.3). For the more reliably ascertained cases there was a twofold increase in rate from 0.98 to 1.96 (rise = 0.98; 95% confidence interval 0.5-1.4). By birth weight, increases in rates were from 29.8 to 74.2 per 1000 neonatal survivors < 1500 g and from 3.9 to 11.5 for those 1500-2499 g. Newborns < 2500 g now contribute one half of all cases of cerebral palsy and just over half of the most severe cases, whereas in the first decade of this study they contributed one third of all cases and only one sixth of the most severe (chi(2) and chi(2) for trend p < 0.001). The rate of cerebral palsy has risen in spite of falling perinatal and neonatal mortality rates, a rise that is even more pronounced when the mildest and least reliably ascertained are excluded. The effect of modern care seems to be that many babies < 2500 g who would have died in the perinatal period now survive with severe cerebral palsy. A global measure of severity should be included in registers of cerebral palsy to determine a minimum

Pediatric Cerebral Palsy in Africa: Where Are We?

PubMed

Donald, Kirsten A; Kakooza, Angelina M; Wammanda, Robinson D; Mallewa, Macpherson; Samia, Pauline; Babakir, Haydar; Bearden, David; Majnemer, Annette; Fehlings, Darcy; Shevell, Michael; Chugani, Harry; Wilmshurst, Jo M

2015-07-01

Cerebral palsy is the most common cause of physical disability in children worldwide. However, little is reported on this condition in the African context. Doctors from 22 countries in Africa, and representatives from a further 5 countries outside Africa, met to discuss the challenges in the evaluation and management of children with cerebral palsy in Africa and to propose service needs and further research. Basic care is limited by the poor availability of diagnostic facilities or medical personnel with experience and expertise in managing cerebral palsy, exacerbated by lack of available interventions such as medications, surgical procedures, or even regular therapy input. Relevant guidelines are lacking. In order to guide services for children with existing disabilities, to effectively target the main etiologies and to develop preventive strategies for the continent, research priorities must include multicenter collaborative studies looking at the prevalence, risk factors, and treatment of cerebral palsy. © The Author(s) 2014.

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy.

PubMed

Nomura, J-I; Uwano, I; Sasaki, M; Kudo, K; Yamashita, F; Ito, K; Fujiwara, S; Kobayashi, M; Ogasawara, K

2017-12-01

Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy. Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images. Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98

Cerebral venous circulatory system evaluation by ultrasonography.

PubMed

Zavoreo, Iris; Basić-Kes, Vanja; Zadro-Matovina, Lucija; Lisak, Marijana; Corić, Lejla; Cvjeticanin, Timon; Ciliga, Dubravka; Bobić, Tatjana Trost

2013-06-01

Venous system can be classified as pulmonary veins, systemic veins and venous sinuses that are present only within the skull. Cerebral venous system is divided into two main parts, the superficial and the deep system. The main assignment of veins is to carry away deoxygenated blood and other maleficient materials from the tissues towards the heart. Veins have thinner walls and larger lumina than arteries. Between 60% and 70% of the total blood volume is found in veins. The major factors that influence venous function are the respiratory cycle, venous tone, the function of the right heart, gravity, and the muscle pump. Venous system, in general, can be presented by selective venography, Doppler sonography, computed tomography (CT) venography and magnetic resonance (MR) venography, and cerebral venous system can be displayed by selective venography, cerebral CT venography, cerebral MR venography, and specialized extracranial and transcranial Doppler sonography. The aim of this paper is to show the possibilities of intracranial and extracranial ultrasound evaluation of the head and neck venous circulation and chronic cerebrospinal venous insufficiency as one of the most common pathologies evaluated as part of neurodegenerative processes in the central nervous system.

Genomic analysis identifies masqueraders of full-term cerebral palsy.

PubMed

Takezawa, Yusuke; Kikuchi, Atsuo; Haginoya, Kazuhiro; Niihori, Tetsuya; Numata-Uematsu, Yurika; Inui, Takehiko; Yamamura-Suzuki, Saeko; Miyabayashi, Takuya; Anzai, Mai; Suzuki-Muromoto, Sato; Okubo, Yukimune; Endo, Wakaba; Togashi, Noriko; Kobayashi, Yasuko; Onuma, Akira; Funayama, Ryo; Shirota, Matsuyuki; Nakayama, Keiko; Aoki, Yoko; Kure, Shigeo

2018-05-01

Cerebral palsy is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested genetic diseases can be misdiagnosed as cerebral palsy. We hypothesized that two simple criteria, that is, full-term births and nonspecific brain MRI findings, are keys to extracting masqueraders among cerebral palsy cases due to the following: (1) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of cerebral palsy and (2) brain MRI assessment is essential for excluding environmental causes and other particular disorders. A total of 107 patients-all full-term births-without specific findings on brain MRI were identified among 897 patients diagnosed with cerebral palsy who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole-exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines. Pathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1 , CYP2U1 , SPAST , GNAO1 , CACNA1A , AMPD2 , STXBP1 , and SCN2A . Five identified variants had previously been reported. No pathogenic copy number variations were identified. The AMPD2 missense variant and the splice-site variants in CTNNB1 and AMPD2 were validated by in vitro functional experiments. The high rate of detecting causative genetic variants (52.9%) suggests that patients diagnosed with cerebral palsy in full-term births without specific MRI findings may include genetic diseases masquerading as cerebral palsy.

Younger age of menopause in women with cerebral aneurysms.

PubMed

Ding, Christine; Toll, Valerie; Ouyang, Bichun; Chen, Michael

2013-07-01

The incidence of subarachnoid hemorrhage in women surges following menopause. Estrogen fluctuations have been implicated in cerebral aneurysm formation, growth and rupture and are thought to explain the well-known gender disparity. The aim of this study was to examine the association between age at menopause, which can determine lifetime estrogen exposure, and the presence of cerebral aneurysms. A retrospective case-control study was conducted by interviewing postmenopausal women with intradural cerebral aneurysms about their basic medical and gynecologic histories. This information was compared with the same data points collected from 4682 women contacted through random digit phone dialing in the National Institute of Child Health and Human Development-sponsored Contraceptive and Reproductive Experiences Study published in 2002. Among 76 consecutive postmenopausal women with cerebral aneurysms who were treated by a single physician and interviewed, multivariate logistic regression showed that later menopause age (OR 0.79, CI 0.63 to 0.996, p=0.046) was significantly associated with a lower aneurysm incidence. Premature menopause (<40 years) was seen in 26% of cases and 19% of controls (p=0.15). Each categorical increase in menopause age (<40, 40-44, 45-49, 50-54, ≥55 years) decreased the likelihood by 21%. Despite a trend towards earlier mean age at menopause in the case group, the difference was not statistically significant. There is a trend showing that an earlier age at menopause is associated with the presence of a cerebral aneurysm. This suggests that loss of estrogen earlier in a woman's life may contribute to the pathogenesis of cerebral aneurysm. These data may identify a risk factor for cerebral aneurysm pathogenesis and also a potential target for future therapies.

Multiple small hemorrhagic infarcts in cerebral air embolism: a case report.

PubMed

Togo, Masaya; Hoshi, Taku; Matsuoka, Ryosuke; Imai, Yukihiro; Kohara, Nobuo

2017-11-16

Cerebral air embolism is a rare cause of cerebral infarction. In cerebral air embolism, T2 star-weighted imaging shows numerous spotty hypointense signals. Previous reports have suggested that these signals represent air in the brain and are gradually diminished and absorbed. We experienced two cases of cerebral air embolism, and in one of them, we conducted an autopsy. Case 1 was a 76-year-old Japanese man with lung cancer and emphysema. A spasmodic cough induced massive cerebral and cardiac air embolisms and the patient died because of cerebral herniation. T2 star-weighted imaging of brain magnetic resonance imaging showed multiple spotty low signals. Brain autopsy showed numerous spotty hemorrhagic infarcts in the area of T2 star-weighted imaging signals. Case 2 was an 85-year-old Japanese man with emphysema who suffered from acute stroke. Similar spotty T2 star-weighted imaging signals were observed and remained unchanged 2 months after the onset. These findings indicate that T2 star-weighted imaging in cerebral air embolism partially represents micro-hemorrhagic infarction caused by air bubbles that have migrated into the brain.

[Cerebral actinomycosis pseudotumor: a case report].

PubMed

Battikh, R; M'Sadek, F; Bougrine, F; Madhi, W; Ben Abdelhafidh, N; Bouziani, A; Yedeas, M; Othmani, S

2011-03-01

Cerebral actinomycosis is rare and difficult to diagnose. We report a case of a 45-year-old man hospitalized for seizures associated with fever and left hemiparesis. The white cell count and C-reactive protein were elevated. HIV serology was negative. Blood cultures remained sterile. The CT scan revealed hyperdense nodular lesions in the occipital area, with annular contrast uptake and peripheral edema causing a mass effect, suggestive of brain metastasis. The pathology examination of a surgical specimen disclosed cerebral actinomycosis. A dental origin of the infection was suspected. Hemiparesis remained after a 12-month antibiotic regimen associated with dental care and short-term corticosteroid therapy. Actinomycosis should be discussed as a possible diagnosis for all cerebral lesions, particularly in patients with a potential dental infection. Histology is required for positive diagnosis. Antibiotic therapy alone is generally sufficient; surgery is often performed for diagnostic purposes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Cerebral ischaemia: A neuroradiological study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bories, J.

1985-01-01

After a brief clinical and pathophysiological approach, the papers presented in this book are devoted to CT and angiography. Concerning CT, a particular study has been made of cerebral arterial territories on cuts parallel to the orbito-meatal line: these are very important in making the differential diagnosis from some tumors. Also concerning CT, a paper has been devoted to cerebral ''lacunae.'' The term ''lacuna'' as far as CT imaging is concerned, should be reserved only for those hypodense areas corresponding to small cavities containing fluid, which are sequelae of infarcts in the territory of penetrating arteries. Before this sequellar statemore » come all the evolutive states of a small deep infarct. The angiographic study specifies the indications of angiography in the study of cerebral ischemia, and the techniques to be used. It shows the main etiologic aspects. Because of the important place of vascular surgery today, it seemed necessary to show also the main post operative angiographic aspects. After CT and angiography, some pages are reserved to more modern techniques. Finally, some pages are devoted to certain particular associations and etiologies: childhood, cardiopathies, migraine, oral contraception and end with venous infarction.« less

Effects of blockade of cerebral lymphatic drainage on regional cerebral blood flow and brain edema after subarachnoid hemorrhage.

PubMed

Sun, Bao-Liang; Xia, Zuo-Li; Wang, Jing-Ru; Yuan, Hui; Li, Wen-Xia; Chen, Yu-She; Yang, Ming-Feng; Zhang, Su-Ming

2006-01-01

The study was designed to observe the influence of blockade of cerebral lymphatic drainage on the regional cerebral blood flow (rCBF) and brain edema after experimental subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and SAH plus cervical lymphatic blockade (SAH + CLB) groups. Autologous arterial hemolysate was injected into rat's cisterna magna to induce SAH. The rCBF was recorded continuously by a laser Doppler flowmeter. Intracranial pressure (ICP) was also monitored. After 24 hours and 72 hours of SAH, the rats were sacrificed and the brain was harvested for water content detection. It was found that there was no obvious change of rCBF and brain water content during the experiment in non-SAH group. An immediate and persistent drop in rCBF was found in SAH group. The drop in rCBF was more obvious in SAH + CLB group. CLB also worsened the SAH-induced increase in ICP. The brain water content 24 hours and 72 hours after induction of SAH in SAH group increased significantly. CLB led to a further increase of brain water content. In conclusion, blockade of cerebral lymphatic drainage pathway deteriorates the secondary cerebral ischemia and brain edema after SAH.

Reversible Cerebral Vasoconstriction Syndrome in Pediatrics: A Case Series and Review.

PubMed

Coffino, Samantha W; Fryer, Robert H

2017-06-01

Reversible cerebral vasoconstriction syndrome is a transient vasculopathy associated with severe headaches and stroke. In most cases of reversible cerebral vasoconstriction syndrome, there is a precipitating event or trigger, such as pregnancy, serotonin agonist treatment or illicit drug use. The authors present 2 pediatric cases of reversible cerebral vasoconstriction syndrome and review the previous 11 pediatric cases in the literature. In many instances, the clinical and radiographic features are similar in both pediatric and adult cases. In the pediatric group, reported potential triggers include trauma (1/13), exercise (2/13), water to the face (3/13), hypertension (3/13), and medication or substance use (4/13). One surprising difference is that 11 out of 13 pediatric patients with reversible cerebral vasoconstriction syndrome are male while most cases in adults are female. Many of the pediatric patients with reversible cerebral vasoconstriction syndrome were treated with a calcium channel blocker and the overall outcome of pediatric reversible cerebral vasoconstriction syndrome was good, with most patients experiencing a full recovery.

Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

PubMed

Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

2013-12-15

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (p<0.01) and reduce cerebral infarct volume of focal cerebral ischemia rats remarkably (p<0.05-0.01). Meanwhile, each group could alleviate cerebral water content and cerebral index (p<0.05-0.01) and regulate oxidative stress of focal cerebral ischemia rats obviously (p<0.05-0.01). Activities of middle group corresponded with that treated with positive control drug. The results obtained here showed that Dragon's blood dropping pills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Effectiveness of sugammadex for cerebral ischemia/reperfusion injury.

PubMed

Ozbilgin, Sule; Yılmaz, Osman; Ergur, Bekir Ugur; Hancı, Volkan; Ozbal, Seda; Yurtlu, Serhan; Gunenc, Sakize Ferim; Kuvaki, Bahar; Kucuk, Burcu Ataseven; Sisman, Ali Rıza

2016-06-01

Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats. Copyright © 2016. Published by Elsevier Taiwan.

Patterns of human local cerebral glucose metabolism during epileptic seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

1982-10-01

Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy.

PubMed

Harada, Yukinori; Hara, Yuuta

2017-01-01

Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

Cerebral blood flow in patients with congestive heart failure treated with captopril.

PubMed

Paulson, O B; Jarden, J O; Godtfredsen, J; Vorstrup, S

1984-05-31

The effect of captopril on cerebral blood flow was studied in five patients with severe congestive heart failure and in five control subjects. Cerebral blood flow was measured by inhalation of 133xenon and registration of its uptake and washout from the brain by single photon emission computer tomography. In addition, cerebral (internal jugular) venous oxygen tension was determined in the controls. The measurements were made before and 15, 60, and 180 minutes after a single oral dose of captopril (6.25 mg in patients with congestive heart failure and 25 mg in controls). Despite a marked decrease in blood pressure, cerebral blood flow increased slightly in the patients with severe congestive heart failure. When a correction was applied to take account of a change in arterial carbon dioxide tension, however, cerebral blood flow was unchanged after captopril administration even in patients with the greatest decrease in blood pressure, in whom a decrease in cerebral blood flow might have been expected. In the controls, blood pressure was little affected by captopril, whereas a slight, but not statistically significant, decrease in cerebral blood flow was observed. The cerebral venous oxygen tension decreased concomitantly.

Influence of voluntary control of masticatory side and rhythm on cerebral hemodynamics.

PubMed

Hasegawa, Yoko; Ono, Takahiro; Sakagami, Joe; Hori, Kazuhiro; Maeda, Yoshinobu; Hamasaki, Toshimitsu; Nokubi, Takashi

2011-02-01

The aim of this study was to investigate the influence on cerebral hemodynamics of voluntary control of masticatory side and rhythm during gum chewing. Blood flow velocity in the middle cerebral artery was measured using transcranial Doppler ultrasonography to evaluate cerebral circulation in healthy volunteers. Heart rate and masseter muscle activity were recorded simultaneously. Volunteers performed three tasks: (1) free gum chewing, (2) gum chewing in which mastication was limited to the right side, and (3) gum chewing in which mastication was limited to the right side and rhythm was set at 1.0 Hz. Changes in cerebral circulation during pre-task, on-task, and post-task periods were analyzed using random effects model, and differences in cerebral circulation and muscle activity between tasks were analyzed using the Friedman test. In all tasks, on-task cerebral circulation was greater than pre-task. Muscle activity and masticatory rhythm varied between tasks, whereas the rate of increase in cerebral circulation did not differ significantly among tasks. These results suggest that cerebral circulation is activated during gum chewing, irrespective of voluntary control of masticatory side and rhythm.

Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology

PubMed Central

Dehaes, Mathieu; Cheng, Henry H.; Buckley, Erin M.; Lin, Pei-Yi; Ferradal, Silvina; Williams, Kathryn; Vyas, Rutvi; Hagan, Katherine; Wigmore, Daniel; McDavitt, Erica; Soul, Janet S.; Franceschini, Maria Angela; Newburger, Jane W.; Ellen Grant, P.

2015-01-01

Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi), cerebral oxygen metabolism (CMRO2i) and SO2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO2i and CBFi, which returned to baseline when stable. However, SO2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO2 alone. PMID:26713191

Functional stability of cerebral circulatory system

NASA Technical Reports Server (NTRS)

Moskalenko, Y. Y.

1980-01-01

The functional stability of the cerebral circulation system seems to be based on the active mechanisms and on those stemming from specific of the biophysical structure of the system under study. This latter parameter has some relevant criteria for its quantitative estimation. The data obtained suggest that the essential part of the mechanism for active responses of cerebral vessels which maintains the functional stability of this portion of the vascular system, consists of a neurogenic component involving central nervous structures localized, for instance, in the medulla oblongata.

Electrical Cerebral Stimulation Modifies Inhibitory Systems

NASA Astrophysics Data System (ADS)

Cuéllar-Herrera, M.; Rocha, L.

2003-09-01

Electrical stimulation of the nervous tissue has been proposed as a method to treat some neurological disorders, such as epilepsy. Epileptic seizures result from excessive, synchronous, abnormal firing patterns of neurons that are located predominantly in the cerebral cortex. Many people with epilepsy continue presenting seizures even though they are under regimens of antiepileptic medications. An alternative therapy for treatment resistant epilepsy is cerebral electrical stimulation. The present study is focused to review the effects of different types of electrical stimulation and specifically changes in amino acids.

Association factor analysis between osteoporosis with cerebral artery disease: The STROBE study.

PubMed

Jin, Eun-Sun; Jeong, Je Hoon; Lee, Bora; Im, Soo Bin

2017-03-01

The purpose of this study was to determine the clinical association factors between osteoporosis and cerebral artery disease in Korean population. Two hundred nineteen postmenopausal women and men undergoing cerebral computed tomography angiography were enrolled in this study to evaluate the cerebral artery disease by cross-sectional study. Cerebral artery disease was diagnosed if there was narrowing of 50% higher diameter in one or more cerebral vessel artery or presence of vascular calcification. History of osteoporotic fracture was assessed using medical record, and radiographic data such as simple radiography, MRI, and bone scan. Bone mineral density was checked by dual-energy x-ray absorptiometry. We reviewed clinical characteristics in all patients and also performed subgroup analysis for total or extracranial/ intracranial cerebral artery disease group retrospectively. We performed statistical analysis by means of chi-square test or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon's rank sum test for continuous variables. We also used univariate and multivariate logistic regression analyses were conducted to assess the factors associated with the prevalence of cerebral artery disease. A two-tailed p-value of less than 0.05 was considered as statistically significant. All statistical analyses were performed using R (version 3.1.3; The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 14.0; SPSS, Inc, Chicago, Ill, USA). Of the 219 patients, 142 had cerebral artery disease. All vertebral fracture was observed in 29 (13.24%) patients. There was significant difference in hip fracture according to the presence or absence of cerebral artery disease. In logistic regression analysis, osteoporotic hip fracture was significantly associated with extracranial cerebral artery disease after adjusting for multiple risk factors. Females with osteoporotic hip fracture were associated with total calcified cerebral artery

Cerebral malaria in children: using the retina to study the brain

PubMed Central

Beare, Nicholas A. V.; Taylor, Terrie E.; Barrera, Valentina; White, Valerie A.; Hiscott, Paul; Molyneux, Malcolm E.; Dhillon, Baljean; Harding, Simon P.

2014-01-01

Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria. The retina is an attractive source of potential surrogate markers for paediatric cerebral malaria because, in this condition, the retina seems to sustain microvascular damage similar to that of the brain. In paediatric cerebral malaria a combination of retinal signs correlates, in fatal cases, with the severity of brain pathology, and has diagnostic and prognostic significance. Unlike the brain, the retina is accessible to high-resolution, non-invasive imaging. We aimed to determine the extent to which paediatric malarial retinopathy reflects cerebrovascular damage by reviewing the literature to compare retinal and cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We then compared retina and brain in terms of anatomical and physiological features that could help to account for similarities and differences in vascular pathology. These comparisons address the question of whether it is biologically plausible to draw conclusions about unseen cerebral vascular pathogenesis from the visible retinal vasculature in retinopathy-positive paediatric cerebral malaria. Our work addresses an important cause of death and neurodisability in sub-Saharan Africa. We critically appraise evidence for associations between retina and brain neurovasculature in health and disease, and in the process we develop new hypotheses about why these vascular beds are susceptible to sequestration of parasitized erythrocytes. PMID:24578549

Research of Sleep Disorders in Patients with Acute Cerebral Infarction.

PubMed

Chen, Xiaofang; Bi, Hongye; Zhang, Meiyun; Liu, Haiyan; Wang, Xueying; Zu, Ruonan

2015-11-01

The purpose of this study is to investigate the incidence of sleep disorders (SD), characteristic of cerebral infarction patients with different parts affected. The research selected 101 patients with a first occurrence of acute cerebral infarction as the experimental group, and 86 patients without cerebral infarction as controls. Polysomnography, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and US National Stroke Scale were assessed. Compared with control group, the incidence of SD was higher in experimental group (P < .05), and the incidence of SD in women was more frequent in experimental group (P < .05). There was no significant difference in the types of SD patients with acute cerebral infarction. In addition, the sleep quality of cerebral infarction patients with different parts affected was different: the sleep quality of left hemisphere infarction patients was poor compared with the right one, and the sleep quality of anterior circulation patients was poor compared with posterior circulation patients. Patients with thalamus infarction had a longer sleep time and a shorter sleep latency and stage 2 of non-rapid eye movement sleep compared with non-thalamus infarction group. The prevalence of SD was relatively high in acute cerebral infarction patients, and the detailed classification of acute cerebral infarction may provide a more effective therapeutic method and therefore relieve patients' pain and supply a better quality of sleep. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise.

PubMed

Madsen, P L; Sperling, B K; Warming, T; Schmidt, J F; Secher, N H; Wildschiødtz, G; Holm, S; Lassen, N A

1993-01-01

Results obtained by the 133Xe clearance method with external detectors and by transcranial Doppler sonography (TCD) suggest that dynamic exercise causes an increase of global average cerebral blood flow (CBF). These data are contradicted by earlier data obtained during less-well-defined conditions. To investigate this controversy, we applied the Kety-Schmidt technique to measure the global average levels of CBF and cerebral metabolic rate of oxygen (CMRO2) during rest and dynamic exercise. Simultaneously with the determination of CBF and CMRO2, we used TCD to determine mean maximal flow velocity in the middle cerebral artery (MCA Vmean). For values of CBF and MCA Vmean a correction for an observed small drop in arterial PCO2 was carried out. Baseline values for global CBF and CMRO2 were 50.7 and 3.63 ml.100 g-1.min-1, respectively. The same values were found during dynamic exercise, whereas a 22% (P < 0.0001) increase in MCA Vmean was observed. Hence, the exercise-induced increase in MCA Vmean is not a reflection of a proportional increase in CBF.

Diabetic microangiopathy: impact of impaired cerebral vasoreactivity and delayed angiogenesis after permanent middle cerebral artery occlusion on stroke damage and cerebral repair in mice.

PubMed

Poittevin, Marine; Bonnin, Philippe; Pimpie, Cynthia; Rivière, Léa; Sebrié, Catherine; Dohan, Anthony; Pocard, Marc; Charriaut-Marlangue, Christiane; Kubis, Nathalie

2015-03-01

Diabetes increases the risk of stroke by three, increases related mortality, and delays recovery. We aimed to characterize functional and structural alterations in cerebral microvasculature before and after experimental cerebral ischemia in a mouse model of type 1 diabetes. We hypothesized that preexisting brain microvascular disease in patients with diabetes might partly explain increased stroke severity and impact on outcome. Diabetes was induced in 4-week-old C57Bl/6J mice by intraperitoneal injections of streptozotocin (60 mg/kg). After 8 weeks of diabetes, the vasoreactivity of the neurovascular network to CO2 was abolished and was not reversed by nitric oxide (NO) donor administration; endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) mRNA, phospho-eNOS protein, nNOS, and phospho-nNOS protein were significantly decreased; angiogenic and vessel maturation factors (vascular endothelial growth factor a [VEGFa], angiopoietin 1 (Ang1), Ang2, transforming growth factor-β [TGF-β], and platelet-derived growth factor-β [PDGF-β]) and blood-brain barrier (BBB) occludin and zona occludens 1 (ZO-1) expression were significantly decreased; and microvessel density was increased without changes in ultrastructural imaging. After permanent focal cerebral ischemia induction, infarct volume and neurological deficit were significantly increased at D1 and D7, and neuronal death (TUNEL+ / NeuN+ cells) and BBB permeability (extravasation of Evans blue) at D1. At D7, CD31+ / Ki67+ double-immunolabeled cells and VEGFa and Ang2 expression were significantly increased, indicating delayed angiogenesis. We show that cerebral microangiopathy thus partly explains stroke severity in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

PubMed

Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Probabilistic atlas based labeling of the cerebral vessel tree

NASA Astrophysics Data System (ADS)

Van de Giessen, Martijn; Janssen, Jasper P.; Brouwer, Patrick A.; Reiber, Johan H. C.; Lelieveldt, Boudewijn P. F.; Dijkstra, Jouke

2015-03-01

Preoperative imaging of the cerebral vessel tree is essential for planning therapy on intracranial stenoses and aneurysms. Usually, a magnetic resonance angiography (MRA) or computed tomography angiography (CTA) is acquired from which the cerebral vessel tree is segmented. Accurate analysis is helped by the labeling of the cerebral vessels, but labeling is non-trivial due to anatomical topological variability and missing branches due to acquisition issues. In recent literature, labeling the cerebral vasculature around the Circle of Willis has mainly been approached as a graph-based problem. The most successful method, however, requires the definition of all possible permutations of missing vessels, which limits application to subsets of the tree and ignores spatial information about the vessel locations. This research aims to perform labeling using probabilistic atlases that model spatial vessel and label likelihoods. A cerebral vessel tree is aligned to a probabilistic atlas and subsequently each vessel is labeled by computing the maximum label likelihood per segment from label-specific atlases. The proposed method was validated on 25 segmented cerebral vessel trees. Labeling accuracies were close to 100% for large vessels, but dropped to 50-60% for small vessels that were only present in less than 50% of the set. With this work we showed that using solely spatial information of the vessel labels, vessel segments from stable vessels (>50% presence) were reliably classified. This spatial information will form the basis for a future labeling strategy with a very loose topological model.

Autonomic neural control of dynamic cerebral autoregulation in humans

NASA Technical Reports Server (NTRS)

Zhang, Rong; Zuckerman, Julie H.; Iwasaki, Kenichi; Wilson, Thad E.; Crandall, Craig G.; Levine, Benjamin D.

2002-01-01

BACKGROUND: The purpose of the present study was to determine the role of autonomic neural control of dynamic cerebral autoregulation in humans. METHODS AND RESULTS: We measured arterial pressure and cerebral blood flow (CBF) velocity in 12 healthy subjects (aged 29+/-6 years) before and after ganglion blockade with trimethaphan. CBF velocity was measured in the middle cerebral artery using transcranial Doppler. The magnitude of spontaneous changes in mean blood pressure and CBF velocity were quantified by spectral analysis. The transfer function gain, phase, and coherence between these variables were estimated to quantify dynamic cerebral autoregulation. After ganglion blockade, systolic and pulse pressure decreased significantly by 13% and 26%, respectively. CBF velocity decreased by 6% (P<0.05). In the very low frequency range (0.02 to 0.07 Hz), mean blood pressure variability decreased significantly (by 82%), while CBF velocity variability persisted. Thus, transfer function gain increased by 81%. In addition, the phase lead of CBF velocity to arterial pressure diminished. These changes in transfer function gain and phase persisted despite restoration of arterial pressure by infusion of phenylephrine and normalization of mean blood pressure variability by oscillatory lower body negative pressure. CONCLUSIONS: These data suggest that dynamic cerebral autoregulation is altered by ganglion blockade. We speculate that autonomic neural control of the cerebral circulation is tonically active and likely plays a significant role in the regulation of beat-to-beat CBF in humans.

Nutritional status of children with cerebral palsy in Turkey.

PubMed

Tüzün, Emine Handan; Güven, Duygu Korkem; Eker, Levent; Elbasan, Bülent; Bülbül, Selda Fatma

2013-03-01

The aim of this study was to assess the nutritional status, and provide information regarding anthropometric measurements of cerebral-palsied children living in the city of Ankara, Turkey. A total of 447 children with cerebral palsy (CP) were participated in this cross-sectional study. Participants were assessed for functional motor impairment by the gross motor function classification system (GMFCS). Assesment of nutritional status was based on the triceps skinfold thickness (TSF), arm fat area (AFA) estimates derived from TSF and mid-upper arm circumference measurements. TSF and AFA Z-scores were computed using reference data. Cerebral-palsied children had lower TSF and AFA Z-scores compared to reference data from healthy children. The prevalence of underweight and overweight among boys was 8.3 and 9.5%, respectively, whereas it was 19.0 and 0.5% for girls. Underweight was more prevalent in the low functioning children than in moderate functioning children. The findings of this study indicate that cerebral-palsied children face nutritional challenges. Underweight is more prevalent than overweight among cerebral-palsied children. To optimize the outcomes of rehabilitation and prevention efforts, an understanding of the heterogeneity of nutritional status among children with CP is required.

Size Matters: Cerebral Volume Influences Sex Differences in Neuroanatomy

PubMed Central

Towler, Stephen; Welcome, Suzanne; Halderman, Laura K.; Otto, Ron; Eckert, Mark A.; Chiarello, Christine

2008-01-01

Biological and behavioral differences between the sexes range from obvious to subtle or nonexistent. Neuroanatomical differences are particularly controversial, perhaps due to the implication that they might account for behavioral differences. In this sample of 200 men and women, large effect sizes (Cohen's d > 0.8) were found for sex differences in total cerebral gray and white matter, cerebellum, and gray matter proportion (women had a higher proportion of gray matter). The only one of these sex differences that survived adjustment for the effect of cerebral volume was gray matter proportion. Individual differences in cerebral volume accounted for 21% of the difference in gray matter proportion, while sex accounted for an additional 4%. The relative size of the corpus callosum was 5% larger in women, but this difference was completely explained by a negative relationship between relative callosal size and cerebral volume. In agreement with Jancke et al., individuals with higher cerebral volume tended to have smaller corpora callosa. There were few sex differences in the size of structures in Broca's and Wernicke's area. We conclude that individual differences in brain volume, in both men and women, account for apparent sex differences in relative size. PMID:18440950

Effect of sumatriptan on cerebral blood flow in the baboon model.

PubMed

Oliver, D W; Dormehl, I C; Hugo, N

1994-08-01

Changes in cerebral blood flow are implicated to be important in the pathophysiology of migraine. Furthermore, serotonin (5-HT) is known to be the most important substance in the etiology of migraine. Sumatriptan (CAS 103628-46-2), a 5-HTID receptor agonist was recently introduced in the treatment of migraine. In the present study a baboon model was used to investigate the changes in cerebral blood flow due to anaesthesia and pharmacological interventions using 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) and single photon emission computed tomography (SPECT). The effect of sumatriptan on cerebral blood flow was investigated after 10 min and again after 23 min, with the animal under anaesthesia, i.e. induction with ketamine and maintenance on thiopental. Sumatriptan did not alter the cerebral blood flow during the 10 min procedure. However, sumatriptan reversed the increased cerebral blood flow due to the prolonged anaesthesia (23 min), lowering the cerebral blood flow by more than 20%. No significant changes in the biochemical parameters (blood pressure, heart rate, pO2 and pCO2) were observed. These results also suggest that sumatriptan reverses the increased cerebral blood flow most likely via 5-HTID receptor stimulation.

Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly.

PubMed

Choi, Hyo Jung; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Baek, Hye Won; Lee, Jun Ho; Kim, Hyun Jung; Han, Ji Young; Yoon, Eun Jin; Kim, Yu Kyeong; Woo, Jong Inn; Lee, Dong Young

2016-08-01

Although many preclinical studies have suggested the possible linkage between dyslipidemia and cerebral amyloid deposition, the association between serum lipid measures and cerebral amyloid-beta (Aβ) deposition in human brain is still poorly known. We aimed to investigate the association in cognitively normal (CN) elderly individuals. Cross-sectional study. University hospital dementia clinic. 59 CN elderly. The study measures included comprehensive clinical and neuropsychological assessment based on the CERAD protocol, magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B positron emission tomography scans, and quantification for serum lipid biomarkers. Multiple linear regression analyses showed that a higher serum triglycerides level was associated with heavier global cerebral Aβ deposition even after controlling age, sex, and apolipoprotein E ε4 genotype. Serum apolipoprotein B also showed significant positive association with global cerebral Aβ deposition, but the significance disappeared after controlling serum triglycerides level. No association was found between other lipid measures and global cerebral Aβ deposition. The findings suggest that serum triglycerides are closely associated with cerebral amyloidosis, although population-based prospective studies are needed to provide further evidence of the causative effect of triglycerides on cerebral amyloidosis. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Growth-hormone-induced signal transducer and activator of transcription 5 signaling causes gigantism, inflammation, and premature death but protects mice from aggressive liver cancer.

PubMed

Friedbichler, Katrin; Themanns, Madeleine; Mueller, Kristina M; Schlederer, Michaela; Kornfeld, Jan-Wilhelm; Terracciano, Luigi M; Kozlov, Andrey V; Haindl, Susanne; Kenner, Lukas; Kolbe, Thomas; Mueller, Mathias; Snibson, Kenneth J; Heim, Markus H; Moriggl, Richard

2012-03-01

Persistently high levels of growth hormone (GH) can cause liver cancer. GH activates multiple signal-transduction pathways, among them janus kinase (JAK) 2-signal transducer and activator of transcription (STAT) 5 (signal transducer and activator of transcription 5). Both hyperactivation and deletion of STAT5 in hepatocytes have been implicated in the development of hepatocellular carcinoma (HCC); nevertheless, the role of STAT5 in the development of HCC as a result of high GH levels remains enigmatic. Thus, we crossed a mouse model of gigantism and inflammatory liver cancer caused by hyperactivated GH signaling (GH(tg) ) to mice with hepatic deletion of STAT5 (STAT5(Δhep) ). Unlike GH(tg) mice, GH(tg) STAT5(Δhep) animals did not display gigantism. Moreover, the premature mortality, which was associated with chronic inflammation, as well as the pathologic alterations of hepatocytes observed in GH(tg) mice, were not observed in GH(tg) animals lacking STAT5. Strikingly, loss of hepatic STAT5 proteins led to enhanced HCC development in GH(tg) mice. Despite reduced chronic inflammation, GH(tg) STAT5(Δhep) mice displayed earlier and more advanced HCC than GH(tg) animals. This may be attributed to the combination of increased peripheral lipolysis, hepatic lipid synthesis, loss of hepatoprotective mediators accompanied by aberrant activation of tumor-promoting c-JUN and STAT3 signaling cascades, and accumulation of DNA damage secondary to loss of cell-cycle control. Thus, HCC was never observed in STAT5(Δhep) mice. As a result of their hepatoprotective functions, STAT5 proteins prevent progressive fatty liver disease and the formation of aggressive HCC in the setting of hyperactivated GH signaling. At the same time, they play a key role in controlling systemic inflammation and regulating organ and body size. Copyright © 2011 American Association for the Study of Liver Diseases.

High-precision chronology for Central American maize diversification from El Gigante rockshelter, Honduras.

PubMed

Kennett, Douglas J; Thakar, Heather B; VanDerwarker, Amber M; Webster, David L; Culleton, Brendan J; Harper, Thomas K; Kistler, Logan; Scheffler, Timothy E; Hirth, Kenneth

2017-08-22

The first steps toward maize ( Zea mays subspecies mays ) domestication occurred in the Balsas region of Mexico by ∼9,000 calendar years B.P. (cal B.P.), but it remains unclear when maize was productive enough to be a staple grain in the Americas. Molecular and microbotanical data provide a partial picture of the timing and nature of morphological change, with genetic data indicating that alleles for some domestication traits were not yet fixed by 5,300 cal B.P. in the highlands of Mexico. Here, we report 88 radiocarbon dates on the botanical remains from El Gigante rockshelter (Honduras) to establish a Bayesian chronology over the past ∼11,000 y spanning the transition to maize-based food production. Botanical remains are remarkably well preserved and include over 10,000 maize macrofossils. We directly dated 37 maize cobs to establish the appearance and local change of maize at the site. Cobs are common in deposits dating between 4,340 and 4,020 cal B.P., and again between 2,350 and 980 cal B.P. The earliest cobs appear robustly domesticated, having 10-14 rows, suggesting strong selection for increased yield. The later cobs are comparable to these earliest ones, but show clear emergence of diverse traits, including increased cob width, rachis segment length, and cupule width. Our results indicate that domesticated landraces of maize productive enough to be a staple grain existed in Central America by 4,300 cal B.P.

High-precision chronology for Central American maize diversification from El Gigante rockshelter, Honduras

PubMed Central

Kennett, Douglas J.; Thakar, Heather B.; VanDerwarker, Amber M.; Webster, David L.; Culleton, Brendan J.; Harper, Thomas K.; Kistler, Logan; Scheffler, Timothy E.; Hirth, Kenneth

2017-01-01

The first steps toward maize (Zea mays subspecies mays) domestication occurred in the Balsas region of Mexico by ∼9,000 calendar years B.P. (cal B.P.), but it remains unclear when maize was productive enough to be a staple grain in the Americas. Molecular and microbotanical data provide a partial picture of the timing and nature of morphological change, with genetic data indicating that alleles for some domestication traits were not yet fixed by 5,300 cal B.P. in the highlands of Mexico. Here, we report 88 radiocarbon dates on the botanical remains from El Gigante rockshelter (Honduras) to establish a Bayesian chronology over the past ∼11,000 y spanning the transition to maize-based food production. Botanical remains are remarkably well preserved and include over 10,000 maize macrofossils. We directly dated 37 maize cobs to establish the appearance and local change of maize at the site. Cobs are common in deposits dating between 4,340 and 4,020 cal B.P., and again between 2,350 and 980 cal B.P. The earliest cobs appear robustly domesticated, having 10–14 rows, suggesting strong selection for increased yield. The later cobs are comparable to these earliest ones, but show clear emergence of diverse traits, including increased cob width, rachis segment length, and cupule width. Our results indicate that domesticated landraces of maize productive enough to be a staple grain existed in Central America by 4,300 cal B.P. PMID:28784803

Protective role of brain water channel AQP4 in murine cerebral malaria

PubMed Central

Promeneur, Dominique; Lunde, Lisa Kristina; Amiry-Moghaddam, Mahmood; Agre, Peter

2013-01-01

Tragically common among children in sub-Saharan Africa, cerebral malaria is characterized by rapid progression to coma and death. In this study, we used a model of cerebral malaria appearing in C57BL/6 WT mice after infection with the rodent malaria parasite Plasmodium berghei ANKA. Expression and cellular localization of the brain water channel aquaporin-4 (AQP4) was investigated during the neurological syndrome. Semiquantitative real-time PCR comparing uninfected and infected mice showed a reduction of brain AQP4 transcript in cerebral malaria, and immunoblots revealed reduction of brain AQP4 protein. Reduction of brain AQP4 protein was confirmed in cerebral malaria by quantitative immunogold EM; however, polarized distribution of AQP4 at the perivascular and subpial astrocyte membranes was not altered. To further examine the role of AQP4 in cerebral malaria, WT mice and littermates genetically deficient in AQP4 were infected with P. berghei. Upon development of cerebral malaria, WT and AQP4-null mice exhibited similar increases in width of perivascular astroglial end-feet in brain. Nevertheless, the AQP4-null mice exhibited more severe signs of cerebral malaria with greater brain edema, although disruption of the blood–brain barrier was similar in both groups. In longitudinal studies, cerebral malaria appeared nearly 1 d earlier in the AQP4-null mice, and reduced survival was noted when chloroquine rescue was attempted. We conclude that the water channel AQP4 confers partial protection against cerebral malaria. PMID:23277579

Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke.

PubMed

Xiao, Ming; Li, Qiang; Feng, Hua; Zhang, Le; Chen, Yujie

2017-01-01

During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke.

Cerebral candidiasis in a 4-year-old boy after intestinal surgery.

PubMed

Zhang, Shu-Cheng

2015-03-01

Cerebral candidiasis is a devastating disease which contributes to a high mortality. Most of the cerebral candidiasis are never microbiologically or radiologically confirmed. In this case, a 4-year-old boy who developed cerebral candidiasis was successfully rescued and presented. The diagnosis of cerebral candidiasis was established based on both microbiologic and radiologic examinations. The pathogen was revealed to be Candida albicans by cerebrospinal fluid and central venous catheter cultures, and the cerebral involvement was recorded by series head magnetic resonance imaging (MRI) with an appearance of special encephalitis demonstrated. The imaging studies played a critical role throughout the diagnosis and treatment. Familiarity with the imaging findings in the appropriate clinical setting may result in a heightened level of awareness of this infection and, consequently, in earlier diagnosis and treatment. © The Author(s) 2014.

The impact of a highly visible display of cerebral perfusion pressure on outcome in individuals with cerebral aneurysms.

PubMed

Kirkness, Catherine J; Burr, Robert L; Cain, Kevin C; Newell, David W; Mitchell, Pamela H

2008-01-01

Nurses' ability to rapidly detect decreases in cerebral perfusion pressure (CPP), which may contribute to secondary brain injury, may be limited by poor visibility of CPP displays. To evaluate the impact of a highly visible CPP display on the functional outcome in individuals with cerebral aneurysms. Patients with cerebral aneurysms (n = 100) who underwent continuous CPP monitoring were enrolled and randomized to beds with or without the additional CPP display. Six-month outcome was assessed. Functional outcome was not significantly different between control and intervention groups after controlling for initial neurologic condition (odds ratio .904, 95% confidence interval 0.317 to 2.573). However, greater time below CPP thresholds (55 to 70 mm Hg) was significantly associated with poorer outcome (P = .005 to .010). Although the enhanced CPP display was not associated with significantly better outcome, longer periods of CPP below set levels were associated with poorer outcome.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

PubMed

Boucetta, Soufiane; Montplaisir, Jacques; Zadra, Antonio; Lachapelle, Francis; Soucy, Jean-Paul; Gravel, Paul; Dang-Vu, Thien Thanh

2017-10-01

Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep

Postoperative Cerebral Vasospasm Following Transsphenoidal Pituitary Adenoma Surgery.

PubMed

Eseonu, Chikezie I; ReFaey, Karim; Geocadin, Romergryko G; Quinones-Hinojosa, Alfredo

2016-08-01

Cerebral vasospasm following a transsphenoidal resection of a pituitary adenoma is a devastating occurrence that can lead to delayed cerebral ischemia and poor neurologic outcome if not diagnosed and treated in a timely manner. The etiology of this condition is not well understood but can lead to significant arterial vasospasm that causes severe ischemic insults. In this paper, we identify common presenting symptoms and essential management strategies to treat this harmful disease. A retrospective case report and literature review of presentation, treatment, and outcome of cerebral vasospasm following transsphenoidal surgery. We present 1 case and review 12 known cases in the literature on vasospasm following transsphenoidal surgery. Mean age was 48 (±13.8) years. There were 46.2% male patients. Factors associated with vasospasm, such as cerebral spinal fluid leaks following surgery, were seen in 38.5% of cases, and postoperative subarachnoid hemorrhage (SAH) was seen in 84.6% of cases. Hemiparesis was the presenting symptom of delayed cerebral ischemia in 61.5% of cases. For management, maintaining at least a euvolemic volume status was used in 76.9%, induced hypertension was used in 61.5%, and nimodipine was administered in 46.2% of cases. Patients returned to their neurologic baseline in 61.5% of cases, had new permanent deficits in 7.7% of cases, and died in 30.8% of cases. Cerebral vasospasm following transsphenoidal surgery is a dangerous disease that can lead to a high likelihood of mortality if not identified and treated. Early postoperative events, such as peritumoral subarachnoid hemorrhage and hemiparesis, may be factors associated with post-transsphenoidal surgery vasospasm. Effective treatment options used in patients that regained complete neurologic recovery were by inducing hypertension, maintaining euvolemia, and administering nimodipine. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral oxygen delivery is reduced in newborns with congenital heart disease.

PubMed

Lim, Jessie Mei; Kingdom, Theodore; Saini, Brahmdeep; Chau, Vann; Post, Martin; Blaser, Susan; Macgowan, Christopher; Miller, Steven P; Seed, Mike

2016-10-01

To investigate preoperative cerebral hemodynamics in newborns with congenital heart disease. We hypothesized that cerebral blood flow and oxygen delivery would be decreased in newborns with congenital heart disease compared with controls. Using a "feed-and-sleep" approach to performing neonatal magnetic resonance imaging, we measured cerebral blood flow by using a slice prescription perpendicular to the right and left internal carotid arteries and basilar artery at the level of the clivus. We calculated brain volume by segmenting a 3-dimensional steady-state free procession acquisition of the whole brain, allowing quantification of cerebral blood flow indexed to brain volume. Cerebral oxygen delivery was calculated as the product of cerebral blood flow and preductal systemic arterial oxygen content obtained via a combination of conventional pulse oximetry and laboratory analysis of venous blood samples for hemoglobin concentration. A complete set of measurements were obtained in 32 newborns with heart disease and 31 controls. There was no difference in gestational age between the heart disease and control groups. There was no difference in cerebral blood flow compared with controls (103.5 ± 34.0 vs 119.7 ± 40.4 mL/min), whereas cerebral oxygen delivery was significantly lower in the congenital heart disease subjects (1881 ± 625.7 vs 2712 ± 915.7 mLO2/min). Ten newborns with congenital heart disease had diffuse excessive high signal intensity in their white matter and 2 had white matter injury whereas another 5 had both. Newborns with unrepaired cyanotic congenital heart disease have decreased cerebral oxygen delivery due to arterial desaturation. If brain growth and development are adversely affected through oxygen conformance, our findings could have clinical implications in terms of timing of surgical repair. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

PubMed

Aravamuthan, Bhooma R; Waugh, Jeff L

2016-01-01

Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain

Biaxial Response of Passive Human Cerebral Arteries

PubMed Central

Monson, Kenneth L.; Barbaro, Nicholas M.; Manley, Geoffrey T.

2008-01-01

The cerebral circulation is fundamental to the health and maintenance of brain tissue, but injury and disease may result in dysfunction of the vessels. Characterization of cerebral vessel mechanical response is an important step toward a more complete understanding of injury mechanisms and disease development in these vessels, paving the way for improved prevention and treatment. We recently reported a large series of uniaxial tests on fresh human cerebral vessels, but the multi-axial behavior of these vessels has not been previously described. Twelve arteries were obtained from the surface of the temporal lobe of patients undergoing surgery and were subjected to various combinations of axial stretch and pressure around typical physiological conditions before being stretched to failure. Axial and circumferential responses were compared, and measured data were fit to a four parameter, Fung-type hyperelastic constitutive model. Artery behavior was nonlinear and anisotropic, with considerably greater resistance to deformation in the axial direction than around the circumference. Results from axial failure tests of pressurized vessels resulted in a small shift in stress-stretch response compared to previously reported data from unpressurized specimens. These results further define the biaxial response of the cerebral arteries and provide data required for more rigorous study of head injury mechanisms and development of cerebrovascular disease. PMID:18855141

Cerebral palsy litigation: change course or abandon ship.

PubMed

Sartwelle, Thomas P; Johnston, James C

2015-06-01

The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds' labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule-the Daubert doctrine that excludes "junk science" from the courtroom-as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring's 40-year masquerade as science. © The Author(s) 2014.

Remote ischaemic preconditioning and prevention of cerebral injury.

PubMed

Rehni, Ashish K; Shri, Richa; Singh, Manjeet

2007-03-01

Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hr was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Glibenclamide (5 mg/kg, iv) a KATP channel blocker and caffeine (7 mg/kg, iv) an adenosine receptor blocker attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning may be due to activation of adenosine receptors and consequent activation of KATP channels in mice.

Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury.

PubMed

Carteron, Laurent; Solari, Daria; Patet, Camille; Quintard, Hervé; Miroz, John-Paul; Bloch, Jocelyne; Daniel, Roy T; Hirt, Lorenz; Eckert, Philippe; Magistretti, Pierre J; Oddo, Mauro

2018-06-19

Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Prospective study (clinicaltrials.gov NCT01573507). Academic ICU. Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral microdialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdialysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

The Role of Oxidative Stress in Cerebral Aneurysm Formation and Rupture

PubMed Central

Starke, Robert M.; Chalouhi, Nohra; Ali, Muhammad S.; Jabbour, Pascal M.; Tjoumakaris, Stavropoula I.; Gonzalez, L. Fernando; Rosenwasser, Robert H.; Koch, Walter J.; Dumont, Aaron S.

2013-01-01

Oxidative stress is known to contribute to the progression of cerebrovascular disease. Additionally, oxidative stress may be increased by, but also augment inflammation, a key contributor to cerebral aneurysm development and rupture. Oxidative stress can induce important processes leading to cerebral aneurysm formation including direct endothelial injury as well as smooth muscle cell phenotypic switching to an inflammatory phenotype and ultimately apoptosis. Oxidative stress leads to recruitment and invasion of inflammatory cells through upregulation of chemotactic cytokines and adhesion molecules. Matrix metalloproteinases can be activated by free radicals leading to vessel wall remodeling and breakdown. Free radicals mediate lipid peroxidation leading to atherosclerosis and contribute to hemodynamic stress and hypertensive pathology, all integral elements of cerebral aneurysm development. Preliminary studies suggest that therapies targeted at oxidative stress may provide a future beneficial treatment for cerebral aneurysms, but further studies are indicated to define the role of free radicals in cerebral aneurysm formation and rupture. The goal of this review is to assess the role of oxidative stress in cerebral aneurysm pathogenesis. PMID:23713738

Plateau Waves of Intracranial Pressure and Partial Pressure of Cerebral Oxygen.

PubMed

Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

2016-01-01

This study investigates 55 intracranial pressure (ICP) plateau waves recorded in 20 patients after severe traumatic brain injury (TBI) with a focus on a moving correlation coefficient between mean arterial pressure (ABP) and ICP, called PRx, which serves as a marker of cerebrovascular reactivity, and a moving correlation coefficient between ABP and cerebral partial pressure of oxygen (pbtO2), called ORx, which serves as a marker for cerebral oxygen reactivity. ICP and ICPamplitude increased significantly during the plateau waves, whereas CPP and pbtO2 decreased significantly. ABP, ABP amplitude, and heart rate remained unchanged. In 73 % of plateau waves PRx increased during the wave. ORx showed an increase during and a decrease after the plateau waves, which was not statistically significant. Our data show profound cerebral vasoparalysis on top of the wave and, to a lesser extent, impairment of cerebral oxygen reactivity. The different behavior of the indices may be due to the different latencies of the cerebral blood flow and oxygen level control mechanisms. While cerebrovascular reactivity is a rapidly reacting mechanism, cerebral oxygen reactivity is slower.

Cerebral responses to exercise and the influence of heat stress in human fatigue.

PubMed

Robertson, Caroline V; Marino, Frank E

2017-01-01

There are a number of mechanisms thought to be responsible for the onset of fatigue during exercise-induced hyperthermia. A greater understanding of the way in which fatigue develops during exercise could be gleaned from the studies which have examined the maintenance of cerebral blood flow through the process of cerebral autoregulation. Given that cerebral blood flow is a measure of the cerebral haemodynamics, and might reflect a level of brain activation, it is useful to understand the implications of this response during exercise and in the development of fatigue. It is known that cerebral blood flow is significantly altered under certain conditions such as altitude and exacerbated during exercise induced - hyperthermia. In this brief review we consider the processes of cerebral autoregulation predominantly through the measurement of cerebral blood flow and contrast these responses between exercise undertaken in normothermic versus heat stress conditions in order to draw some conclusions about the role cerebral blood flow might play in determining fatigue. Copyright © 2016. Published by Elsevier Ltd.

Cerebral blood flow asymmetries in headache-free migraineurs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, S.R.; Welch, K.M.; Ewing, J.R.

1987-11-01

Regional cerebral blood flow (rCBF) asymmetries were studied in controls and patients with common and classic/complicated migraine using /sup 133/Xe inhalation with 8 homologously situated external collimators over each cerebral hemisphere. Migraine patients as a group more frequently had posterior rCBF asymmetries than controls (p less than 0.03). Although there were no differences in the number of anterior rCBF asymmetries, migraine patients had 2 or more asymmetric probe pairs more often than controls (p less than 0.02). The posterior rCBF asymmetries, consistent with the site of activation of many migraine attacks, may be related to more labile control of themore » cerebral circulation.« less

[Trismus, pseudobulbar syndrome and cerebral deep venous thrombosis].

PubMed

Alecu, C; De Bray, J M; Penisson-Besnier, I; Pasco-Papon, A; Dubas, F

2001-03-01

We report a case of cerebral deep venous thrombosis that manifested clinically by a pseudobulbar syndrome with major trismus, abnormal movements and static cerebellar syndrome. To our knowledge, only three other cases of deep cerebral venous thrombosis associated with cerebellar or pseudobulbar syndrome have been published since 1985. The relatively good prognosis in our patient could be explained by the partially intact internal cerebral veins as well as use of early anticoagulant therapy. There was a spontaneous hyperdensity of the falx cerebri and the tentorium cerebelli on the brain CT scan, an aspect highly contributive to diagnosis. This hyperdensity of the falx cerebri was found in 19 out of 22 cases of deep venous thrombosis detailed in the literature.

Pathogenesis, diagnosis and treatment of cerebral fat embolism.

PubMed

Zhou, Yihua; Yuan, Ying; Huang, Chahua; Hu, Lihua; Cheng, Xiaoshu

2015-01-01

In this study, we analyzed two cases of pure cerebral fat embolism and reviewed related literatures to explore the pathogenesis, clinical manifestations, diagnosis and treatment of cerebral fat embolism, improve the treatment efficiency and reduce the misdiagnosis rate. In our cases, patients fully returned to consciousness at the different times with good prognosis, normal vital signs and without obvious sequelae. For patients with the limb fractures, who developed coma without chest distress, dyspnea or other pulmonary symptoms 12 or 24 h post injury, cerebral fat embolism should be highly suspected, except for those with intracranial lesions, such as delayed traumatic intracerebral hemorrhage, etc. The early diagnosis and comprehensive treatment can improve prognosis.

Is Vasomotion in Cerebral Arteries Impaired in Alzheimer’s Disease?

PubMed Central

Di Marco, Luigi Yuri; Farkas, Eszter; Martin, Chris; Venneri, Annalena; Frangi, Alejandro F.

2015-01-01

Abstract A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer’s disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion— the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain— is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation. PMID:25720414

The relationship between cardiac output and dynamic cerebral autoregulation in humans.

PubMed

Deegan, B M; Devine, E R; Geraghty, M C; Jones, E; Ólaighin, G; Serrador, J M

2010-11-01

Cerebral autoregulation adjusts cerebrovascular resistance in the face of changing perfusion pressures to maintain relatively constant flow. Results from several studies suggest that cardiac output may also play a role. We tested the hypothesis that cerebral blood flow would autoregulate independent of changes in cardiac output. Transient systemic hypotension was induced by thigh-cuff deflation in 19 healthy volunteers (7 women) in both supine and seated positions. Mean arterial pressure (Finapres), cerebral blood flow (transcranial Doppler) in the anterior (ACA) and middle cerebral artery (MCA), beat-by-beat cardiac output (echocardiography), and end-tidal Pco(2) were measured. Autoregulation was assessed using the autoregulatory index (ARI) defined by Tiecks et al. (Tiecks FP, Lam AM, Aaslid R, Newell DW. Stroke 26: 1014-1019, 1995). Cerebral autoregulation was better in the supine position in both the ACA [supine ARI: 5.0 ± 0.21 (mean ± SE), seated ARI: 3.9 ± 0.4, P = 0.01] and MCA (supine ARI: 5.0 ± 0.2, seated ARI: 3.8 ± 0.3, P = 0.004). In contrast, cardiac output responses were not different between positions and did not correlate with cerebral blood flow ARIs. In addition, women had better autoregulation in the ACA (P = 0.046), but not the MCA, despite having the same cardiac output response. These data demonstrate cardiac output does not appear to affect the dynamic cerebral autoregulatory response to sudden hypotension in healthy controls, regardless of posture. These results also highlight the importance of considering sex when studying cerebral autoregulation.

The development of cerebral amyloid angiopathy in cerebral vessels. A review with illustrations based upon own investigated post mortem cases.

PubMed

Mendel, T A; Wierzba-Bobrowicz, T; Lewandowska, E; Stępień, T; Szpak, G M

2013-12-01

The process of β-amyloid accumulation in cerebral vessels is presented. Cerebral amyloid angiopathy (CAA) was confirmed during an autopsy. It was diagnosed according to the Boston criteria. Cerebral amyloid angiopathy can involve all kinds of cerebral vessels (cortical and leptomeningeal arterioles, capillaries and veins). The development of CAA is a progressive process. β-amyloid appears first in the tunica media, surrounding smooth muscle cells, and in the adventitia. β-amyloid is progressively accumulated, causing a gradual loss of smooth muscle cells in the vessel wall and finally replacing them. Then, the detachment and delamination of the outer part of the tunica media results in the "double barrel" appearance, fibrinoid necrosis, and microaneurysm formation. Microbleeding with perivascular deposition of erythrocytes and blood breakdown products can also occur. β-amyloid can also be deposited in the surrounding of the affected vessels of the brain parenchyma, known as "dysphoric CAA". Ultrastructurally, when deposits of amyloid fibers were localized in or outside the arteriolar wall, the degenerating vascular smooth muscle cells were observed. In the Institute of Psychiatry and Neurology the study was carried out in a group of 48 patients who died due to intracerebral hemorrhage caused by sporadic CAA.

Bone age in cerebral palsy

PubMed Central

Miranda, Eduardo Régis de Alencar Bona; Palmieri, Maurício D'arc; de Assumpção, Rodrigo Montezuma César; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patrícia Maria de Moraes Barros

2013-01-01

Objective To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status. Methods 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle. Results In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54). Conclusion There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series. PMID:24453693

Cerebral aneurysms: relations between geometry, hemodynamics and aneurysm location in the cerebral vasculature

NASA Astrophysics Data System (ADS)

Passerini, Tiziano; Veneziani, Alessandro; Sangalli, Laura; Secchi, Piercesare; Vantini, Simone

2010-11-01

In cerebral blood circulation, the interplay of arterial geometrical features and flow dynamics is thought to play a significant role in the development of aneurysms. In the framework of the Aneurisk project, patient-specific morphology reconstructions were conducted with the open-source software VMTK (www.vmtk.org) on a set of computational angiography images provided by Ospedale Niguarda (Milano, Italy). Computational fluid dynamics (CFD) simulations were performed with a software based on the library LifeV (www.lifev.org). The joint statistical analysis of geometries and simulations highlights the possible association of certain spatial patterns of radius, curvature and shear load along the Internal Carotid Artery (ICA) with the presence, position and previous event of rupture of an aneurysm in the entire cerebral vasculature. Moreover, some possible landmarks are identified to be monitored for the assessment of a Potential Rupture Risk Index.

Plantar flexor muscle weakness and fatigue in spastic cerebral palsy patients.

PubMed

Neyroud, Daria; Armand, Stéphane; De Coulon, Geraldo; Sarah R Dias Da Silva; Maffiuletti, Nicola A; Kayser, Bengt; Place, Nicolas

2017-02-01

Patients with cerebral palsy develop an important muscle weakness which might affect the aetiology and extent of exercise-induced neuromuscular fatigue. This study evaluated the aetiology and extent of plantar flexor neuromuscular fatigue in patients with cerebral palsy. Ten patients with cerebral palsy and 10 age- and sex-matched healthy individuals (∼20 years old, 6 females) performed four 30-s maximal isometric plantar flexions interspaced by a resting period of 2-3s to elicit a resting twitch. Maximal voluntary contraction force, voluntary activation level and peak twitch were quantified before and immediately after the fatiguing task. Before fatigue, patients with cerebral palsy were weaker than healthy individuals (341±134N vs. 858±151N, p<0.05) and presented lower voluntary activation (73±19% vs. 90±9%, p<0.05) and peak twitch (100±28N vs. 199±33N, p<0.05). Maximal voluntary contraction force was not significantly reduced in patients with cerebral palsy following the fatiguing task (-10±23%, p>0.05), whereas it decreased by 30±12% (p<0.05) in healthy individuals. Plantar flexor muscles of patients with cerebral palsy were weaker than their healthy peers but showed greater fatigue resistance. Cerebral palsy is a widely defined pathology that is known to result in muscle weakness. The extent and origin of muscle weakness were the topic of several previous investigations; however some discrepant results were reported in the literature regarding how it might affect the development of exercise-induced neuromuscular fatigue. Importantly, most of the studies interested in the assessment of fatigue in patients with cerebral palsy did so with general questionnaires and reported increased levels of fatigue. Yet, exercise-induced neuromuscular fatigue was quantified in just a few studies and it was found that young patients with cerebral palsy might be more fatigue resistant that their peers. Thus, it appears that (i) conflicting results exist regarding

Changes in serum interleukin-33 levels in patients with acute cerebral infarction.

PubMed

Liu, Jingyao; Xing, Yingqi; Gao, Ying; Zhou, Chunkui

2014-02-01

Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hypopituitarism in children with cerebral palsy.

PubMed

Uday, Suma; Shaw, Nick; Krone, Ruth; Kirk, Jeremy

2017-06-01

Poor growth and delayed puberty in children with cerebral palsy is frequently felt to be related to malnutrition. Although growth hormone deficiency is commonly described in these children, multiple pituitary hormone deficiency (MPHD) has not been previously reported. We present a series of four children with cerebral palsy who were born before 29 weeks gestation who were referred to the regional endocrinology service, three for delayed puberty and one for short stature, in whom investigations identified MPHD. All patients had a height well below -2 standard deviation score (2nd centile) at presentation and three who had MRI scans had an ectopic posterior pituitary gland. We therefore recommend that the possibility of MPHD should be considered in all children with cerebral palsy and poor growth or delayed puberty. Early diagnosis and treatment is essential to maximise growth and prevent associated morbidity and mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Detection and quantification of microRNA in cerebral microdialysate.

PubMed

Bache, Søren; Rasmussen, Rune; Rossing, Maria; Hammer, Niels Risør; Juhler, Marianne; Friis-Hansen, Lennart; Nielsen, Finn Cilius; Møller, Kirsten

2015-05-07

Secondary brain injury accounts for a major part of the morbidity and mortality in patients with spontaneous aneurysmal subarachnoid hemorrhage (SAH), but the pathogenesis and pathophysiology remain controversial. MicroRNAs (miRNAs) are important posttranscriptional regulators of complementary mRNA targets and have been implicated in the pathophysiology of other types of acute brain injury. Cerebral microdialysis is a promising tool to investigate these mechanisms. We hypothesized that miRNAs would be present in human cerebral microdialysate. RNA was extracted and miRNA profiles were established using high throughput real-time quantification PCR on the following material: 1) Microdialysate sampled in vitro from A) a solution of total RNA extracted from human brain, B) cerebrospinal fluid (CSF) from a neurologically healthy patient, and C) a patient with SAH; and 2) cerebral microdialysate and CSF sampled in vivo from two patients with SAH. MiRNAs were categorized according to their relative recovery (RR) and a pathway analysis was performed for miRNAs exhibiting a high RR in vivo. Seventy-one of the 160 miRNAs detected in CSF were also found in in vivo microdialysate from SAH patients. Furthermore specific miRNAs consistently exhibited either a high or low RR in both in vitro and in vivo microdialysate. Analysis of repeatability showed lower analytical variation in microdialysate than in CSF. MiRNAs are detectable in cerebral microdialysate; a large group of miRNAs consistently showed a high RR in cerebral microdialysate. Measurement of cerebral interstitial miRNA concentrations may aid in the investigation of secondary brain injury in neurocritical conditions.

Cerebral Folate Deficiency

ERIC Educational Resources Information Center

Gordon, Neil

2009-01-01

Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

[Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

PubMed

Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

2017-01-01

To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

Cerebral versus systemic hemodynamics during graded orthostatic stress in humans

NASA Technical Reports Server (NTRS)

Levine, B. D.; Giller, C. A.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.

1994-01-01

BACKGROUND: Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hemodynamic collapse. Recent research in patients with neurocardiogenic syncope has suggested that cerebral vasoconstriction may occur during orthostatic hypotension, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. However, the regulation of cerebral blood flow (CBF) in such patients may be quite different from that of healthy individuals, particularly when assessed during the rapidly changing hemodynamic conditions associated with neurocardiogenic syncope. To be able to interpret the pathophysiological significance of these observations, a clear understanding of the normal responses of the cerebral circulation to orthostatic stress must be obtained, particularly in the context of the known changes in systemic and regional distributions of blood flow and vascular resistance during orthostasis. Therefore, the specific aim of this study was to examine the changes that occur in the cerebral circulation during graded reductions in central blood volume in the absence of systemic hypotension in healthy humans. We hypothesized that cerebral vasoconstriction would occur and CBF would decrease due to activation of the sympathetic nervous system. We further hypothesized, however, that the magnitude of this change would be small compared with changes in systemic or skeletal muscle vascular resistance in healthy subjects with intact autoregulation and would be unlikely to cause syncope without concomitant hypotension. METHODS AND RESULTS: To test this hypothesis, we studied 13 healthy men (age, 27 +/- 7 years) during progressive lower body negative pressure (LBNP). We measured systemic flow (Qc is cardiac output; C2H2 rebreathing), regional forearm flow (FBF; venous occlusion plethysmography), and blood pressure (BP; Finapres) and calculated systemic (SVR) and forearm (FVR) vascular resistances. Changes in brain blood flow were

Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition.

PubMed

Mao, Lun-Lin; Hao, Dong-Lin; Mao, Xiao-Wei; Xu, Yuan-Feng; Huang, Ting-Ting; Wu, Bo-Na; Wang, Li-Hui

2015-08-18

PTEN is a dual specificity phosphatase and is implicated in inflammation and apoptosis of cerebral ischemia and reperfusion (I/R) injury. Bisperoxovanadium (Bpv), a specific inhibitor of PTEN's phosphatase activity, has demonstrated powerful neuroprotective properties. We investigated the neuroprotective roles of Bpv in the rat model of middle cerebral artery occlusion (MCAO) cerebral I/R injury, and explored the modulation of inflammatory mediators and PI3K/Akt/GSK-3β pathways by Bpv. Our results showed that treatment with Bpv (0.2 mg/kg/day) significantly decreased neurological deficit scores at 7 days after MCAO and infarct volume at 4 days after MCAO. The IL-10 concentration was increased and TNF-α concentration was decreased in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO by Bpv. Furthermore, Bpv (0.2 mg/kg/day) treatment significantly reduced PTEN mRNA and protein levels and increased PI3K, Akt and p-GSK-3β proteins expression in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO. In conclusions, Bpv treatment demonstrates neuroprotective effects on cerebral ischemia and reperfusion injury of ischemic stroke rats and is associated with its modulation of inflammatory mediator production and up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3β. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Khalaf, Ahmed M.; Hashim, Mahmoud A.; Alsharabati, Mohammed; Fallon, Kenneth; Cure, Joel K.; Pappas, Peter; Mineishi, Shin; Saad, Ayman

2017-01-01

Patient: Male, 44 Final Diagnosis: Cerebral toxoplasmosis after HSCT Symptoms: Hemiparesis • muscle weakness Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. Case Report: We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. Conclusions: Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions. PMID:28280256

[Raman spectra of monkey cerebral cortex tissue].

PubMed

Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

2010-01-01

Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

Cerebral oximetry in cardiac and major vascular surgery.

PubMed

Fischer, G W; Silvay, G

2010-01-01

We describe the development and current applications of cerebral oximetry (based on near-infrared reflectance spectroscopy) that can be used during cardiac and major vascular surgery to determined brain tissue oxygen saturation. There are presently three cerebral oximetry devices with FDA approval in the United States to measure and monitor cerebral tissue oxygen saturation. 1. INVOS (Somanetics Corporation, Troy, MI - recently COVIDIEN, Boulder, CO); FORE-SIGHT (CAS Medical Systems, Inc. Branford, CT); EQUANOX (Nonin Medical Inc.Minnesota, MN). All devices are portable, non-invasive and easy to use in operating room and intensive care unit. The data provided in these communication may provided information for improvement of perioperative neuromonitoring techniques, and may be crucial in the design of future clinical trials.

[Electrophysiological markers of middle cerebral artery blood flow velocity in healthy subjects].

PubMed

Fokin, V F; Ponomareva, N V; Kuntsevich, G I

2013-01-01

to determine electrophysiological markers of middle cerebral artery blood flow velocity (BFV). transcranial Doppler registration of middle cerebral artery BFV and direct current (DC) potentials recording from surface of head were performed in 30 healthy volunteers. Analysis of correlation between the BFV and DC potentials was used. significant correlation between BFV and DC potential characteristics was observed. The highest correlation was found between BFV in middle cerebral artery and the difference of DC potentials between central and temporal areas of head (r = 0,55; p = 0,003). These areas coincide with the location of middle cerebral artery and the correlation observed may be connected with streaming potential generated by the blood flow in middle cerebral artery. If electrode placement did not coincide with blood current, DC potentials and BFV were not correlated. it is assumed that electrical field created BFV in middle cerebral artery may contribute to the generation of DC potentials registered from the head.

Cerebral hemodynamics with intra-aortic balloon pump: business as usual?

PubMed

Caldas, J R; Panerai, R B; Bor-Seng-Shu, E; Almeida, J P; Ferreira, G S R; Camara, L; Nogueira, R C; Oliveira, M L; Jatene, F B; Robinson, T G; Hajjar, L A

2017-06-22

Intra-aortic balloon pump (IABP) is commonly used as mechanical support after cardiac surgery or cardiac shock. Although its benefits for cardiac function have been well documented, its effects on cerebral circulation are still controversial. We hypothesized that transfer function analysis (TFA) and continuous estimates of dynamic cerebral autoregulation (CA) provide consistent results in the assessment of cerebral autoregulation in patients with IABP. Continuous recordings of blood pressure (BP, intra-arterial line), end-tidal CO 2 , heart rate and cerebral blood flow velocity (CBFV, transcranial Doppler) were obtained (i) 5 min with IABP ratio 1:3, (ii) 5 min, starting 1 min with the IABP-ON, and continuing for another 4 min without pump assistance (IABP-OFF). Autoregulation index (ARI) was estimated from the CBFV response to a step change in BP derived by TFA and as a function of time using an autoregressive moving-average model during removal of the device (ARI t ). Critical closing pressure and resistance area-product were also obtained. ARI with IABP-ON (4.3  ±  1.2) were not different from corresponding values at IABP-OFF (4.7  ±  1.4, p  =  0.42). Removal of the balloon had no effect on ARI t , CBFV, BP, cerebral critical closing pressure or resistance area-product. IABP does not disturb cerebral hemodynamics. TFA and continuous estimates of dynamic CA can be used to assess cerebral hemodynamics in patients with IABP. These findings have important implications for the design of studies of critically ill patients requiring the use of different invasive support devices.

Performance of Aspergillus PCR in cerebrospinal fluid for the diagnosis of cerebral aspergillosis.

PubMed

Imbert, S; Brossas, J-Y; Palous, M; Joly, I; Meyer, I; Fekkar, A

2017-11-01

Cerebral aspergillosis is a rare but often fatal form of invasive aspergillosis that remains difficult to diagnose. The literature has shown the value of Aspergillus PCR in blood-derived samples for the diagnosis of invasive aspergillosis but provides far less information for cerebrospinal fluid (CSF) in cerebral aspergillosis. Here, we evaluated the usefulness of an Aspergillus PCR assay performed on CSF for the diagnosis of cerebral aspergillosis. This retrospective study involved 72 patients with suspected cerebral aspergillosis for a total of 88 CSF samples in whom CSF Aspergillus PCR was performed. Seventeen patients had proven/probable invasive aspergillosis according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, including 12 cases of proven/probable cerebral aspergillosis. Aspergillus PCR in CSF was positive in nine of the twelve patients with cerebral aspergillosis, i.e. 75% sensitivity. In contrast, CSF culture was positive for Aspergillus in only two patients. In the non-cerebral aspergillosis group (60 patients), PCR was positive in one patient, i.e. 98.3% specificity. In this particular population of high-risk patients with suspicion of cerebral aspergillosis, the disease incidence was 16.7%. Therefore, the positive and negative predictive values of PCR were 90% and 95.2%, respectively. The results of this study indicate that Aspergillus PCR in CSF is an interesting tool that may eliminate the need for cerebral biopsy in patients with suspected cerebral aspergillosis. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences

PubMed Central

Cipolla, Marilyn J

2013-01-01

The adaptation of the cerebral circulation to pregnancy is unique from other vascular beds. Most notably, the growth and vasodilatory response to high levels of circulating growth factors and cytokines that promote substantial hemodynamic changes in other vascular beds is limited in the cerebral circulation. This is accomplished through several mechanisms, including downregulation of key receptors and transcription factors, and production of circulating factors that counteract the vasodilatory effects of vascular endothelial growth factor (VEGF) and placental growth factor. Pregnancy both prevents and reverses hypertensive inward remodeling of cerebral arteries, possibly through downregulation of the angiotensin type 1 receptor. The blood–brain barrier (BBB) importantly adapts to pregnancy by preventing the passage of seizure provoking serum into the brain and limiting the permeability effects of VEGF that is more highly expressed in cerebral vasculature during pregnancy. While the adaptation of the cerebral circulation to pregnancy provides for relatively normal cerebral blood flow and BBB properties in the face of substantial cardiovascular changes and high levels of circulating factors, under pathologic conditions, these adaptations appear to promote greater brain injury, including edema formation during acute hypertension, and greater sensitivity to bacterial endotoxin. PMID:23321787

De novo point mutations in patients diagnosed with ataxic cerebral palsy

PubMed Central

Parolin Schnekenberg, Ricardo; Perkins, Emma M.; Miller, Jack W.; Davies, Wayne I. L.; D’Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A.; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O’Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis

2015-01-01

Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. PMID:25981959

Effect of Intracranial Stenosis Revascularization on Dynamic and Static Cerebral Autoregulation.

PubMed

Ortega-Gutierrez, Santiago; Samaniego, Edgar A; Huang, Amy; Masurkar, Arjun; Zheng-Lin, Binbin; Derdeyn, Colin P; Hasan, David; Marshall, Randolph; Petersen, Nils

2018-06-01

Severe intracranial stenosis might lead to acute cerebral ischemia. It is imperative to better assess patients who may benefit from immediate reperfusion and blood pressure management to prevent injury to peri-infarct tissue. We assessed cerebral autoregulation using static and dynamic methods in an 81-year-old woman suffering acute cerebral ischemia from severe intracranial stenosis in the petrous segment of the left internal carotid artery (LICA). Static cerebral autoregulation, which is evaluated by magnetic resonance imaging and magnetic resonance perfusion studies showed a progression of infarcts and a large perfusion-diffusion mismatch in the entire LICA territory between the second and third days after onset despite maximized medical therapy. Dynamic methods, including transfer function analysis and mean velocity index, demonstrated an increasingly impaired dynamic cerebral autoregulation (DCA) on the affected side between these days. Revascularization through acute intracranial stenting resulted in improved perfusion in the LICA territory and normalization of both dynamic and static cerebral autoregulation. Thus, DCA, a noninvasive bedside method, may be useful in helping to identify and select patients with large-vessel flow-failure syndromes that would benefit from immediate revascularization of intracranial atherosclerotic disease.

Intrinsic Cholinergic Mechanisms Regulating Cerebral Blood Flow as a Target for Organophosphate Action

DTIC Science & Technology

1988-10-01

autoregulation, render the cerebral circulation dependent upon systemic circulation exposing brain to ischernic damage or edema in shock or stress...Thus, sharp reductions of arterial pressure, as might occur in hemorrhagic or traumatic shock, will render the cerebral circulation vulnerable to...autoregulated range, rendering local areas of the brain vulnerable to cerebral edema and breakdown of the blood brain barrier. -2- 8. Cerebral blood

The systemic pathology of cerebral malaria in African children

PubMed Central

Milner, Danny A.; Whitten, Richard O.; Kamiza, Steve; Carr, Richard; Liomba, George; Dzamalala, Charles; Seydel, Karl B.; Molyneux, Malcolm E.; Taylor, Terrie E.

2014-01-01

Pediatric cerebral malaria carries a high mortality rate in sub-Saharan Africa. We present our systematic analysis of the descriptive and quantitative histopathology of all organs sampled from a series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and control patients (without coma, or without malaria infection) who were clinically well characterized prior to death. We found brain swelling in all cerebral malaria patients and the majority of controls. The histopathology in patients with sequestration of parasites in the brain demonstrated two patterns: (a) the “classic” appearance (i.e., ring hemorrhages, dense sequestration, and extra-erythrocytic pigment) which was associated with evidence of systemic activation of coagulation and (b) the “sequestration only” appearance associated with shorter duration of illness and higher total burden of parasites in all organs including the spleen. Sequestration of parasites was most intense in the gastrointestinal tract in all parasitemic patients (those with cerebral malarial and those without). PMID:25191643

Gender characteristics of cerebral hemodynamics during complex cognitive functioning.

PubMed

Misteli, Maria; Duschek, Stefan; Richter, André; Grimm, Simone; Rezk, Markus; Kraehenmann, Rainer; Boeker, Heinz; Seifritz, Erich; Schuepbach, Daniel

2011-06-01

Functional Transcranial Doppler sonography (fTCD) has been applied to assess peak mean cerebral blood flow velocity (MFV) with a high temporal resolution during cognitive activation. Yet, little attention has been devoted to gender-related alterations of MFV, including spectral analysis. In healthy subjects, fTCD was used to investigate a series of cerebral hemodynamic parameters in the middle cerebral arteries (MCA) during the Trail Making Tests (TMT), a means of selective attention and complex cognitive functioning. In females, there was a frequency peak at 0.375 Hz in both MCA, and we observed a dynamic shift in hemispheric dominance during that condition. Further, after the start phase, there was an MFV decline during complex functioning for the entire sample. These novel results suggest condition-specific features of cerebral hemodynamics in females, and it adds to the notion that gender is a fundamental confounder of brain physiology. Copyright © 2011 Elsevier Inc. All rights reserved.

Health-related physical fitness for children with cerebral palsy

PubMed Central

Maltais, Désirée B.; Wiart, Lesley; Fowler, Eileen; Verschuren, Olaf; Damiano, Diane L.

2014-01-01

Low levels of physical activity are a global health concern for all children. Children with cerebral palsy have even lower physical activity levels than their typically developing peers. Low levels of physical activity, and thus an increased risk for related chronic diseases, are associated with deficits in health-related physical fitness. Recent research has provided therapists with the resources to effectively perform physical fitness testing and physical activity training in clinical settings with children who have cerebral palsy, although most testing and training data to date pertains to those who walk. Nevertheless, based on the present evidence, all children with cerebral palsy should engage, to the extent they are able, in aerobic, anaerobic and muscle strengthening activities. Future research is required to determine the best ways to evaluate health-related physical fitness in non-ambulatory children with cerebral palsy and foster long-term changes in physical activity behavior in all children with this condition. PMID:24820339

Cerebral collaterals and collateral therapeutics for acute ischemic stroke.

PubMed

Winship, Ian R

2015-04-01

Cerebral collaterals are vascular redundancies in the cerebral circulation that can partially maintain blood flow to ischemic tissue when primary conduits are blocked. After occlusion of a cerebral artery, anastomoses connecting the distal segments of the MCA with distal branches of the ACA and PCA (known as leptomeningeal or pial collaterals) allow for partially maintained blood flow in the ischemic penumbra and delay or prevent cell death. However, collateral circulation varies dramatically between individuals, and collateral extent is significant predictor of stroke severity and recanalization rate. Collateral therapeutics attempt to harness these vascular redundancies by enhancing blood flow through pial collaterals to reduce ischemia and brain damage after cerebral arterial occlusion. While therapies to enhance collateral flow remain relatively nascent neuroprotective strategies, experimental therapies including inhaled NO, transient suprarenal aortic occlusion, and electrical stimulation of the parasympathetic sphenopalatine ganglion show promise as collateral therapeutics with the potential to improve treatment of acute ischemic stroke. © 2014 John Wiley & Sons Ltd.

Non-invasive assessment of cerebral oxygen metabolism following surgery of congenital heart disease.

PubMed

Neunhoeffer, Felix; Sandner, Katharina; Wiest, Milena; Haller, Christoph; Renk, Hanna; Kumpf, Matthias; Schlensak, Christian; Hofbeck, Michael

2017-07-01

Cerebral protection is a major issue in the treatment of infants with complex congenital heart disease. We tested a new device combining tissue spectrometry and laser Doppler flowmetry for non-invasive determination of cerebral oxygen metabolism following cardiac surgery in infants. We prospectively measured regional cerebral oxygen saturation cSO 2 and microperfusion (rcFlow) in 43 infants 12-24 h following corrective ( n  = 30) or palliative surgery ( n  = 13) of congenital heart defects. For comparison, cerebral blood flow (CBF) was determined by colour duplex sonography of the extracranial cerebral arteries. Cerebral fractional tissue oxygen extraction, approximated cerebral metabolic rate of oxygen (aCMRO 2 ) and cerebral metabolic rate of oxygen (CMRO 2 ) were calculated. cSO 2 was lower [54.6% (35.7-64.0) vs 59.7% (44.5-81.7); P  < 0.01] after neonatal palliation, while rcFlow [69.7 AU (42.5-165.3) vs 77.0 AU (41.2-168.1); P  = 0.06] and cerebral fractional tissue oxygen extraction [0.34 (0.24-0.82) vs 0.38 (0.17-0.55); P  = 0.63] showed a trend towards lower values. We found a positive correlation between aCMRO 2 and CMRO 2 ( r  = 0.27; P  = 0.03). aCMRO 2 was significantly lower after neonatal palliation [4.0 AU (2.1-6.3) vs 4.9 AU (2.2-15.6); P  = 0.02]. According to our experience, combined photospectrometry and laser Doppler flowmetry enable non-invasive assessment of cerebral oxygen metabolism. The method promises new insights into perioperative cerebral perfusion following palliation or corrective surgery in infancy. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia.

PubMed

Kim, S W; Chung, S J; Oh, Y-S; Yoon, J H; Sunwoo, M K; Hong, J Y; Kim, J-S; Lee, P H

2015-09-01

The burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia. The study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial. The frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds. This study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral

Sex Determination and Polyploid Gigantism in the Dwarf Surfclam (Mulinia Lateralis Say)

PubMed Central

Guo, X.; Allen-Jr., S. K.

1994-01-01

Mulinia lateralis, the dwarf surfclam, is a suitable model for bivalve genetics because it is hardy and has a short generation time. In this study, gynogenetic and triploid. M. lateralis were successfully induced. For gynogenesis, eggs were fertilized with sperm irradiated with ultraviolet light and subsequently treated with cytochalasin B to block the release of the second polar body (PB2). Triploidy was induced by blocking PB2 in normally fertilized eggs. The survival of gynogenetic diploids was very low, only 0.7% to 8 days post-fertilization (PF), compared with 15.2% in the triploid groups and 27.5% in the normal diploid control. Larvae in all groups metamorphosed at 8-10 days PF, and there was no significant post-larval mortality. At sexual maturation (2-3 months PF), all gynogenetic diploids were female, and there was no significant difference (P > 0.05) in sex ratio between diploids and triploids. These results suggested that the dwarf surfclam may have an XX-female, XY-male sex determination with Y-domination. Compared with diploids, triploids had a relative fecundity of 59% for females and 80% for males. Eggs produced by triploid females were 53% larger (P < 0.001) in volume than those from diploid females. In both length and weight measurements at three months PF, the gynogenetic diploids were not significantly (P > 0.33) different from normal diploid females, suggesting that inbreeding depression was minimal in meiosis II gynogens. Triploid clams were significantly larger (P < 0.001) than normal diploids. We hypothesize that the increased body-size in triploids was caused by a polyploid gigantism due to the increased cell volume and a lack of cell-number compensation. PMID:7896101

Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

PubMed

Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

2018-04-01

Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity.

PubMed

Bragin, Denis E; Statom, Gloria L; Yonas, Howard; Dai, Xingping; Nemoto, Edwin M

2014-12-01

The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity. Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy. University laboratory. Male Sprague-Dawley rats. At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (Δ intracranial pressure/Δ mean arterial pressure) and induced cerebrovascular reactivity (Δ cerebral blood flow/Δ mean arterial pressure). At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on

Neuroimaging findings in children with retinopathy-confirmed cerebral malaria.

PubMed

Potchen, Michael J; Birbeck, Gretchen L; Demarco, J Kevin; Kampondeni, Sam D; Beare, Nicholas; Molyneux, Malcolm E; Taylor, Terrie E

2010-04-01

To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria. In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT. All children had ophthalmological examination to confirm the presence of the retinopathy specific for cerebral malaria. Independent interpretation of CT images was provided by two neuroradiologists. Acute brain CT findings in three children included diffuse oedema with obstructive hydrocephalus (2), acute cerebral infarctions in multiple large vessel distributions with secondary oedema and herniation (1), and oedema of thalamic grey matter (1). One child who was reportedly normal prior to admission had parenchymal atrophy suggestive of pre-existing CNS injury. Among 56 survivors (9-84 months old), 15 had adverse neurologic outcomes-11/15 had a follow-up head CT, 3/15 died and 1/15 refused CT. Follow-up head CTs obtained 7-18 months after the acute infection revealed focal and multifocal lobar atrophy correlating to regions affected by focal seizures during the acute infection (5/11). Other findings were communicating hydrocephalus (2/11), vermian atrophy (1/11) and normal studies (3/11). The identification of pre-existing imaging abnormalities in acute cerebral malaria suggests that population-based studies are required to establish the rate and nature of incidental imaging abnormalities in Malawi. Children with focal seizures during acute cerebral malaria developed focal cortical atrophy in these regions at follow-up. Longitudinal studies are needed to further elucidate mechanisms of CNS injury and death in this common fatal disease. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome.

PubMed

Swanson, Larry W; Sporns, Olaf; Hahn, Joel D

2016-10-04

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure-function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network's modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system.

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome

PubMed Central

Swanson, Larry W.; Sporns, Olaf; Hahn, Joel D.

2016-01-01

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure–function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network’s modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system. PMID:27647882

Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine.

PubMed

Tibussek, Daniel; Natesirinilkul, Rungrote; Sun, Lisa R; Wasserman, Bruce A; Brandão, Leonardo R; deVeber, Gabrielle

2016-02-01

We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended. Copyright © 2016 by the American Academy of Pediatrics.