Quantification of white matter abnormalities in neurodegenerative disease

Degeneration of white matter fibre tracts occurs in several neurodegenerative disorders and results in various histological abnormalities including loss of axons, vacuolation, gliosis, axonal varicosities and spheroids, corpora amylacea, extracellular protein deposits, and glial inclusions (GI). This chapter describes quantitative studies that have been carried out on white matter pathology in a variety of neurodegenerative disease. First, in Alzheimer’s disease (AD), axonal loss quantified in histological sections stained with toluidine blue, occurs in several white matter fibre tracts including the optic nerve, olfactory tract, and corpus callosum. Second, in Creutzfeldt-Jakob disease (CJD), sections of cerebral cortex stained with haematoxylin and eosin (H/E) or immunolabelled with antibodies against the disease form of prion protein (PrPsc), reveal extensive vacuolation, gliosis of white matter, and deposition of PrPsc deposits. Third, GI immunolabelled with antibodies against various pathological proteins including tau, -synuclein, TDP-43, and FUS, have been recorded in white matter of a number of disorders including frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and neuronal intermediate filament inclusion disease (NIFID). Axonal varicosities have also been observed in NIFID. There are two important questions regarding white matter pathology that need further investigation: (1) what is the relative importance of white and gray matter pathologies in different disorders and (2) do white matter abnormalities precede or are they the consequence of gray matter pathology?

Spatial patterns of neuronal cytoplasmic inclusions in the tauopathies: A comparative study of five disorders

The tauopathies are a major molecular group of neurodegenerative disorders characterised by the deposition of abnormal cellular aggregates of the microtubule associated protein (MAP) tau in the form of neuronal cytoplasmic inclusions (NCI). Recent research suggests that cell to cell propagation of pathogenic tau may be involved in the neurodegeneration of these disorders. If pathogenic tau spreads along anatomical pathways it may give rise to specific spatial patterns of the NCI in brain tissue. To test this hypothesis, the spatial patterns of NCI in cerebral cortical regions were compared in tissue sections taken from five major tauopathies: (1) argyrophilic grain disease (AGD), (2) Alzheimer's disease (AD), (3) corticobasal degeneration (CBD), (4) Pick's disease (PiD), and (5) progressive supranuclear palsy (PSP). In the cerebral cortex of these disorders, NCI were frequently aggregated into clusters and the clusters were regularly distributed parallel to the pia mater. In a significant proportion of regions, the mean size of the regularly distributed clusters of NCI was in the range 400 – 800 m, measured parallel to the pia mater, approximating to the dimension of cell columns associated with the cortico-cortical anatomical pathways. Hence, the data suggest that cortical NCI in the tauopathies exhibit a spatial pattern in the cortex which could result from the spread of pathogenic tau along anatomical pathways. Treatments designed to protect the cortex from tau propagation may therefore be applicable across several different disorders within this molecular group.

A qualitative study of the impact of an educational intervention on older parents of adults with disabilities engaged in the phenomenon of future-care planning

This phenomenological study describes the impact of an educational intervention on the day-to-day experiences of older parent caregivers of adults with developmental disabilities who were engaged in the process of future-care planning. Qualitative strategies of individual and focus group interviewing were used with a purposive sample of older caregivers. Participants were members of an existing parent support group. Twenty-three caregivers representing 18 families were queried before and after the education program. The disabilities represented were mental retardation, cerebral palsy and autism. Parents whose children live at or away from home were included. The intervention was conducted on five Saturdays over a two month period; the duration of the study was five months. Findings used typical words of the respondents from their individual and focus group interviews to describe feelings, attitudes and experiences in making future-care plans. Data from verbatim transcriptions and researcher's field notes were coded, analyzed, sorted into themes, and subjected to interpretive analysis. Respondents showed a positive change in attitudes and actions after participating in the education program, regardless of their initial stage in care planning. Fears were replaced by hope and determination; hesitation and ineptitude by feelings of competence and confidence; and procrastination and delay by purposeful actions. Other key findings: use of a planning document greatly aided caregivers; barriers to planning were often intrinsic and amenable to education; residential plans were the most difficult aspect of planning; listening to the experiences of other parent caregivers was helpful; and making burial plans for their offspring was one aspect of planning parents wished to do themselves. ^

Functional near infrared spectroscopy study of language, joint attention and motor skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Associação entre comprometimento motor, mobilidade e qualidade de vida em crianças com paralisia cerebral espástica, nível I, II e III do Gross Motor Function Classification System

The objective of this study was to verify the association between some mobility items of the International Classification Functionality (ICF), with the evaluations Gross Motor Function Measure (GMFM-88), 1-minute walk test (1MWT) and if the motor impairment influences the quality of life in children with Cerebral Palsy (PC), by using the Paediatric Quality of Life Inventory (PedsQL 4.0 versions for children and parents). The study included 22 children with cerebral palsy spastic, classified in levels I, II, and III on the Gross Motor Function Classification System (GMFCS), with age group of 9.9 years old. Among those who have participated, seven of them were level I, eight of them were level II and seven of them were level III. All of the children and teenagers were rated by using check list ICF (mobility item), GMFM-88, 1-minute walk test and PedsQL 4.0 questionnaires for children and parents. It was observed a strong correlation between GMFM-88 with check list ICF (mobility item), but moderate correlation between GMFM-88 and 1-minute walk test (1MWT). It was also moderate the correlation between the walking test and the check list ICF (mobility item). The correlation between PedsQl 4.0 questionnaires for children and parents was weak, as well as the correlation of both with GMFM, ICF (mobility item) and the walking test. The lack of interrelation between physical function tests and quality of life, indicates that, regardless of the severity of the motor impairment and the difficulty with mobility, children and teenagers suffering of PC spastic, functional level I, II and III GMFCS and their parents have a varied opinion regarding the perception of well being and life satisfaction.

Origem do plexo lombossacral e seus nervos em quatis (Nasua nasua, LINNAEUS, 1766)

The objective of this research is to study the origin of the lumbosacral plexus and its nerves in coatis (Nasua nasua). Six adult specimens, three males and three females, were used in this research. The animals were donated by IBAMA / GO or were collected when found dead by the edges of highways in Southeast Goiás. The specimens were fixed in aqueous 10% formaldehyde solution and preserved in the same solution. The observations reveal that the lumbosacral plexus of the coati has a structure with few intercommunications between its components. There are no typical handle formations, but the roots or its branches converge to form the nerves that are driven to the pelvic limb. The components of the Lumbosacral Plexus are ventral branches of L4 to S3. The Lumbosacral plexus generates several short nerves destined to pelvic structures and, at the same time, three long nerves: femoral, obturator and sciatic, all destined to the hind limb.

Visual signs and symptoms of corticobasal degeneration

Corticobasal degeneration is a rare, progressive neurodegenerative disease and a member of the 'parkinsonian' group of disorders, which also includes Parkinson's disease, progressive supranuclear palsy, dementia with Lewy bodies and multiple system atrophy. The most common initial symptom is limb clumsiness, usually affecting one side of the body, with or without accompanying rigidity or tremor. Subsequently, the disease affects gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Corticobasal degeneration can be difficult to distinguish from other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid clinical diagnosis. Typical ocular features include increased latency of saccadic eye movements ipsilateral to the side exhibiting apraxia, impaired smooth pursuit movements and visuo-spatial dysfunction, especially involving spatial rather than object-based tasks. Less typical features include reduction in saccadic velocity, vertical gaze palsy, visual hallucinations, sleep disturbance and an impaired electroretinogram. Aspects of primary vision such as visual acuity and colour vision are usually unaffected. Management of the condition to deal with problems of walking, movement, daily tasks and speech problems is an important aspect of the disease.

Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

Aim: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). Method: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. Results: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. Interpretation: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

(Table 1) Distribution of upper Campanian-lower Maestrichtian calcareous nannofossils at DSDP Hole 71-511

Calcareous nannofossils from upper Campanian-lower Maestrichtian Deep Sea Drilling Project Leg 71 Cores 511-23 and 511-24 are described and correlated with assemblages of similar age from piston and drill cores on the Falkland Plateau, South Atlantic Ocean. The Leg 71 cores partially fill a drilling gap of at least 20 meters left within a thick (50 m) carbonate section first drilled by DSDP Leg 36 at Site 327. Cores 511-23 and 511-24 both fall within the upper portion of the Biscutum coronum Zone of Wind and demonstrate an overlap in the range of Monomarginatus quaternarius with the ranges of M. pectinatus, Misceomarginatus pleniporus, and Biscutum coronum across the Campanian/ Maestrichtian boundary. Resolution of the sequence of highest occurrence datums for the latter species must await the recovery of a more complete section. Comparison of the Site 511 assemblages with those from Mas Orcadas Core 07-75-44 to the north confirms earlier speculation that the Falkland Plateau served as an important boundary between major water masses during the Late Cretaceous.

Biodistribution of technetium-99m pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na99mTc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na99mTc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gama counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. Results: Significant reduction in mean %ATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in %ATI/g was observed between the two groups. Conclusion: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na99mTc

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Purpose: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. Methods: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25μCi). After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI/g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). Results: On the 9th day after the administration of the 2nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g) compared (p<0.5) to pre-treatment weight (353.66± 22.8). The % ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. Conclusion: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study

Rede Social Pessoal de Cuidadores Informais de Adultos com Necessidades Especiais

Objetivo. Devido ao aumento da esperança de vida, os adultos com necessidades especiais vivem mais tempo, sendo os seus principais cuidadores, geralmente familiares, também mais envelhecidos. Tal situação representa novas necessidades específicas de apoio, sendo inúmeros os desafios colocados ao Serviço Social no sentido de garantir o bem-estar da pessoa com incapacidade e dos seus cuidadores. Assim, este estudo tem como objetivo realizar um levantamento das necessidades de apoio e a caraterização da rede social pessoal de apoio do cuidador informal de adultos com necessidades especiais. Participantes. A amostra é constituída por 40 cuidadores informais de adultos com necessidades especiais, integrados na resposta social “Centro de Atividades Ocupacionais-CAO” da Associação de Paralisia Cerebral de Coimbra, de ambos os sexos com idade igual ou superior a 40 anos. Material e métodos. Foi utilizado o Instrumento de Avaliação da Rede Social Pessoal e um questionário para caracterização sociodemográfica e sociofamiliar dos cuidadores, assim como para avaliação de necessidades. Resultados. Aproximadamente um terço dos cuidadores relatou a experiência de níveis moderados de sobrecarga associada à prestação de cuidados, enquanto mais de metade relatou a experiência de níveis elevados e muito elevados dessa sobrecarga; o apoio financeiro foi referido como a forma de apoio mais necessária no presente, ainda que o apoio em residência tenha sido percecionado por cerca de um terço dos cuidadores como a forma de apoio mais necessária no futuro; enquanto mais de metade considerou o apoio domiciliário e de unidade residencial (institucional). Estes cuidadores familiares referiram a "incerteza" e a "esperança" como os sentimentos mais frequentemente experienciados em relação ao futuro das suas vidas. No que respeita às redes sociais, as relações familiares são centrais a nível estrutural; em termos de caraterísticas funcionais da rede, foram observados valores mais elevados para as dimensões de reciprocidade do apoio e satisfação com a rede social. Implicações. Este estudo sublinha a importância da avaliação das necessidades de apoio dos cuidadores familiares de adultos com necessidades especiais. A sua implementação sistemática pode auxiliar a tomada de decisão baseada na evidência empírica para as intervenções do Serviço Social, tais como na planificação e gestão de respostas e serviços sociais, a par do reconhecimento e ativação dos recursos das próprias famílias, de forma a promover a eficiência dos recursos e eficácia das intervenções, focadas no bem-estar do cidadão com deficiência e das suas famílias. / Aim. The general increase in human life expectancy has resulted in greater rates of survival for adults with special care needs, as well as for their ageing family caregivers. This situation poses different and specific support needs, which represent a major challenge in social work interventions aimed at ensuring the well-being of disabled persons and their caregivers. Therefore, this study was aimed to describe the needs for support and the perceived social support network of family caregivers of adults with special care needs. Participants. The sample for this study comprised 40 family caregivers of disabled adults with special care needs, of both genders and aged 40 years old at minimum, who attended a long-term care facility at Coimbra Cerebral Palsy Association. Material and methods. Participants were administered a self-report questionnaire on socio-economic, family and caregiving needs, along with the Instrument for Assessing Personal Social Networks. Results. Nearly one third a family caregivers experienced moderate caregiving burden, while more than half experienced high or very high levels of caregiving burden; financial support was perceived as the most needed form of support in the present, but residential home care was identified as the most needed form of support in the future; while more than a half considered home-based support and residential support viable options for their disabled family members with special care needs. These family caregivers reported "uncertainty" and "hope" as the most common feelings towards their family life in the future. On the topic of social networks, family relations were found to be crucial at the structural level; in terms of functional characteristics of the network, elevated scores were observed for reciprocity of support and satisfaction with the social network. Implications. This study highlights the importance of increasing the specificity of the assessments of needs for support in family caregivers of disabled adults with special care needs. The systematic conduction of these assessments may assist evidence-based decision making in social work interventions, such as for planning and managing social services, acknowledging and activating the families' own resources, and ultimately promote the efficacy and effectiveness 57 interventions aimed at improving the well-being of disabled citizens and their families.