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The diagnosis of central nervous system tumours has been transformed in recent years from a microscopic morphology-based process to one dominated by the identification of somatic genetic alterations in tumour cells. This switch requires implementing radically different methods, for which appropriate training and financial resources must be allocated. The Canadian Association of Neuropathologists (CANP) has followed a process based on the scientific literature and consensus to develop recommendations for molecular testing of tumours of the brain and spinal cord, aiming to balance the need for treatment-determinant accurate diagnosis and the current limitations inherent in the transition to a new paradigm. The Professional Affairs Committee was charged with this task. A draft was discussed during the CANP general assembly, along with presentations from groups who had implemented molecular technologies, as well as others who relied on external laboratories. The Professional Affairs Committee summarised the consensus and submitted their recommendation to the CANP’s Executive Committee. A final report was posted on the CANP website for a month to allow all members to comment. The recommendations below apply to intrinsic tumours of the central nervous system and do not include metastatic disease or tumours impinging upon the nervous system from outside. These recommendations should be considered clinically relevant, as the results have direct consequences on the patient’s treatment, either through the use of targeted therapies or the trial-proven best application of radiation and/or chemotherapy.
Patients with temporal lobe epilepsy (TLE) commonly show memory deficits on neuropsychological tests. The BVMT-R is a widely used test of visual learning and memory that involves accurately reproducing an array of figures in the correct special location. The present study examined performance processes of visual memory in presurgical patients with TLE, including item (i.e., accuracy) and associative memory (i.e., location), which have been shown to be dissociable in studies of visual memory in other neurologic populations.
Participants and Methods:
Participants included nine patients with left TLE (67% female; 67% left-handed; mean age = 46.15 years, range = 24-55; mean education = 14.8 years, range = 9-18) and six patients with right TLE (17% female; 33% left-handed; mean age = 57.64 years, range = 22-62; mean education = 15.52 years, range 11-18). Mean duration of epilepsy was 19 years. Participants had an average of two failed anti-seizure medications prior to surgery. TLE groups were compared to 22 healthy controls (36% female; 14% left-handed; mean age = 33.68 years, range = 2253; mean education = 17.66 years, range = 1620). All participants completed comprehensive neuropsychological testing at a large Northeastern medical center. The BVMT-R was scored using standard and novel scoring paradigms. All data were retrospectively reviewed from archival datasets.
Results:
MANCOVA results indicated a significant multivariate main effect for group membership and standard BVMT-R scoring after controlling for level of education, Wilks’ A = 0.59, F(4, 64) = 4.91, p = .002. The multivariate partial eta squared (np2) of .58 indicated a strong relationship between group membership and both immediate and delayed recall, with the control group performing better overall. The TLE groups did not perform significantly different from each other. A significant multivariate main effect for group and novel BVMT-R scoring was found (also controlling for education), Wilks’ A = 0.42, F(8, 58) = 3.97, p = .001. Overall, the control group demonstrated better item learning with no significant difference between TLE groups observed. Both the control (M = (16.5, SD = 2.04) and left TLE (M = 12.33, SD = 4.03) showed stronger associative learning compared to the right TLE group (M = 10.2, SD = 4.27). For item and location delayed recall, controls (M = 4.82, SD = 1.62) had more accurate recall compared to left TLE (M = 1.56, SD = 2.04) with a trend toward better performance compared to the right TLE patients (M = 2.6, SD = 1.82); the TLE groups performed similarly. No difference was observed for associative delayed recall between the three groups.
Conclusions:
Patients with right TLE showed worse associative learning compared to left TLE, while performance was generally comparable to their right TLE counterparts on other novel BVMT-R scoring paradigms. Unsurprisingly, patients with TLE performed worse on BVMT-R using standard scoring procedures, though no lateralizing effect was observed. While these findings suggest that associative visual learning weakness may be characteristic of right TLE, findings should be interpreted cautiously the given small sample size and demographic considerations (i.e., uneven gender distribution, lack of data on ethnicity/race).
Schooling transforms child development yet fades into the background in research on prosocial behavior. Mass education, however, was central to the concerns of founding theorists such as Durkheim, Dewey, and Piaget. Putting on a sociological lens makes it easier to see how schools continue to play an active role in prosocial development, and how the concerns of these founding researchers resonate today. To situate the active role of school contexts in prosocial behavior, this chapter first examines schools as social systems, structuring children’s social networks, imposing roles and norms of behavior, and impacting the timing of development. The chapter then examines classroom, pedagogical, and peer prosocial behaviors, and their connection to classic theoretical work in the field. After reviewing these forms of prosocial behavior, the chapter closes by examining the links between prosocial behavior and student outcomes and implications and future directions for theory, research, and practice.
Cytomegalovirus (CMV) is among the most common of intrauterine infections against which we have no effective preventative or therapeutic options. The developing nervous system is a frequent target of CMV and while most injuries are subclinical, severe insults leading to microcephaly and migration defects are well known. A 20-week gestational age fetus was found to have several abnormalities on prenatal ultrasound, the most prominent of which was a large echogenic focus in one cerebral hemisphere. Congenital CMV infection was identified by amniocentesis and maternal serology. The pregnancy was ended by early induction of labour for a 368g stillborn infant. Postmortem examination revealed massive intracerebral hemorrhage as the correlate for the sonographic finding. The microscopic examination of the brain was also striking for extensive polymicrogyria, a high burden of CMV and abundant angiocentric CMV pathology. Catastrophic intracerebral hemorrhage has not been previously reported in association with congenital CMV infection. The present case expands the range of potential injuries the developing brain is subject to in the setting of CMV infection and raises the possibility of a direct vascular injury.
Learning Objectives
Consider intracerebral hemorrhage in the range of potential outcomes in congenital CMV infection
Describe how polymicrogyria may result from an insult during proliferation and migration
Discuss possible mechanisms of injury to the developing brain by CMV
Many patients with epilepsy do not achieve adequate pharmacologic control of their seizures and must consider surgical options. Many such patients undergo temporal lobectomy and experience a marked reduction in the frequency and severity of their seizures. However, many are less fortunate. One suspected factor for the latter group is the limited ability of clinical imaging to delineate subtle epileptogenic abnormalities, leading to subtotal resection of lesional tissue. A long range goal in this field is to increase the sensitivity and specificity of detecting such abnormalities by “training” MRI with pathology, feature analysis and machine learning. A key component of this is the ability to segment histopathology to facilitate its mapping to co-registered MRI. A foundational step in this process is to determine whether or not algorithms are capable of detecting the architectural abnormalities in cortical dysplasia on the basis of these segmentations. In brief, reliable semi-automated segmentations were developed to extract a number of features including neuron size, clustering, eccentricity, field-fraction and polarity. Feature analyses using t-Distributed Stochastic Neighbor Embedding (t-SNE) plots demonstrate a non-random association between selected features and diagnostic categories. These results indicate that automated algorithms are capable of distinguishing dysplastic from normal cortex on the basis of semi-automated segmentations.
Learning Objectives
Describe the value of segmentation in image analysis
Define the role of feature analysis such as t-SNE in high dimensionality histopathology data
A 20-year-old male presented with evidence of gigantism/acromegaly. Endocrinological investigations identified elevated growth hormone levels and a failed glucose tolerance test. Imaging revealed a macroadenoma expanding the sella with encroachment on the optic chiasm and cavernous sinuses. Trans-sphenoidal resection was undertaken and a gross total removal was achieved. Histopathological features were typical of a densely granulated somatotroph adenoma with abundant growth hormone expression, scattered prolactin expression and sparse examples of fibrous bodies. Unexpectedly, the adenoma not only expressed PIT-1 but also SF-1 transcription factors. This finding suggests that the adenoma may have been pluripotent. The prognostic significance of this finding is uncertain although the patient is stable from an endocrinological and imaging perspective approximately one-year post-op. A pituitary adenoma of this nature has not been previously reported. The recent literature on atypical transcription factor expression patterns and revisions to the classification of pituitary adenomas will be reviewed.
Learning Objectives
Appreciate the rarity of dual transcription factor expression in pituitary adenomas
Rationalize the use of transcription factor characterization in the revised WHO classification of pituitary adenomas
Post-mortem examination of the nervous system is a complex task that culminates in “brain cutting”. It relies on expertise in neuroanatomy, clinical neurosciences, neuroimaging and experience in order to recognise the most subtle abnormalities. Like any specialist examination in medicine, it warrants formal training, a standardised approach and optimal conditions. Revelations of aberrant tissue retention practices of a select few pathologists (e.g. Goudge, Liverpool and Alder Hey inquiries) and a motivated sociopolitical climate led some Canadian jurisdictions to impose broad restrictions on tissue retention. This raised concerns that nervous system examinations for diagnosis, education and research were at risk by limiting examinations to the fresh or incompletely fixed state. Professional experience indicates that cutting an unfixed or partly fixed brain is inferior.
Methods:
To add objectivity and further insight we sought the expert opinion of a group of qualified specialists. Canadian neuropathologists were surveyed for their opinion on the relative merits of examining brains in the fresh or fully fixed state.
Results:
A total of 14 out of 46 Canadian neuropathologists responded (30%). In the pervasive opinion of respondents, cutting and sampling a brain prior to full fixation leads to a loss of diagnostic accuracy, biosafety and academic deliverables.
Conclusions:
Brain cutting in the fresh state is significantly impaired along multiple dimensions of relevance to a pathologist’s professional roles and obligations.
Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions.
Methods:
We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry.
Results:
Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON.
Conclusion:
NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.
Engaging in paid employment after claiming retirement benefits may be an important avenue for individuals to work longer as life expectancies rise. After separating from one's career employer, individuals may engage in paid work to stay active or to supplement their current level of retirement savings or both. Individuals who choose not to work after claiming may be expressing their preference to stay retired, perhaps because their retirement income is sufficient. However, the decision to work after claiming may be driven by the lack of retirement planning and insufficient savings, while the lack of post-claiming work may reflect the inability to find adequate employment opportunities. We use administrative records merged with panel data from several surveys of public employees in North Carolina to study the decision to engage in paid work after claiming retirement benefits. More than 60% of active workers plan to work after claiming benefits, while only around 42% of the same sample of individuals have engaged in post-claiming paid work in the first few years after leaving public sector employment. Despite this gap, stated work plans are strongly predictive of actual post-claiming work behavior. Our final analysis uses self-reported measures to gauge the financial well-being of our sample in the early years after leaving career employment.
This study examines the distribution options of 85 large public retirement plans covering general state employees, teachers, and local government employees. The interest rates used to price annuities vary considerably across the plans. As a result, retirees with the same monthly benefit if a single life benefit is chosen will have substantially different monthly benefits if they select a joint and survivor annuity. We examine the impact of variation in the pricing of annuity options using both cross-plan differences in interest rates and the change in the choice of annuity options in one plan after the price of options changes due to new assumed interest rates and mortality rates.
Choices regarding the disposition of wealth at retirement can have substantial implications for retirement income security. We analyze the factors determining annuity payout option choices within the context of a public sector defined pension plan with no default annuity option. Using combined administrative records and survey data, we explore the role of individual and household characteristics as well as risk preferences, time preferences, and financial literacy. We also document retiree well-being and satisfaction with retirement decision making. The evidence is consistent with predictions over which households might benefit most from each annuity option. Comparing retirees who chose different types of annuities, we find that these groups of retirees report very different levels of well-being in retirement. All retirees report lower levels of retirement income security over time, with strong differences among those who chose different types of annuities.