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Background:

Alzheimer disease and cerebrovascular disease affect elderly persons through alterations in brain structure and metabolism that produce cognitive decline. Understanding how each disease contributes to dementia is essential from both a pathophysiologic and diagnostic perspective.

Objective:

To elucidate how baseline cognitive function (episodic memory and executive function) and brain anatomy (white matter hyperintensities and hippocampal volume) are associated with baseline (positron emission tomography-1 [PET1]) and longitudinal (PET2) glucose metabolism in 38 subjects older than 55 years ranging from normal cognition, cognitive impairment without dementia, and dementia.

Design:

Cross-sectional regression analyses across subjects.

Setting:

Multicenter, university-based study of subcortical vascular dementia.

Main Outcome Measures:

Regional cerebral glucose metabolism was the primary outcome, with the major hypotheses that memory and hippocampal volume are related to temporoparietal hypometabolism while executive function and white matter hyperintensities correlate with frontal lobe hypometabolism.

Results:

Low baseline hippocampal volume predicted longitudinal development (PET2) of medial temporal hypometabolism. Lower memory was associated with parietal and cingulate hypometabolism at PET1, which increased at the 2-year-follow-up (PET2). Executive function was associated with frontal and temporoparietal hypometabolism at PET1 but only with frontal hypometabolism at follow-up. White matter hyperintensities predicted hypometabolism over time in the frontoparietal regions, predicting a rate of metabolic change (PET1−PET2/time).

Conclusions:

Low baseline episodic memory and hippocampal volume predict the metabolic alterations associated with Alzheimer disease, whereas elevated baseline white matter hyperintensities predict a different pattern of metabolic decline that is plausibly associated with cerebrovascular disease.

Inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. How missense mutations in this abundant, ubiquitously expressed, multifunctional protein lead to the degeneration of disparate tissues is unclear. VCP participates in diverse cellular functions by associating with an expanding collection of substrates and cofactors that dictate its functionality. In this issue of the JCI, Wang and colleagues have further expanded the VCP interactome by identifying neurofibromin-1 (NF1) as a novel VCP interactor in the CNS. IBMPFD-associated mutations disrupt binding of VCP to NF1, resulting in reduced synaptogenesis. Thus, aberrant interactions between VCP and NF1 may explain the dementia phenotype and cognitive delay observed in patients with IBMPFD and neurofibromatosis type 1.

The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.

Hymenoptera, the insect order that includes sawflies, bees, wasps, and ants, exhibits an incredible diversity of phenotypes, with over 145,000 species described in a corpus of textual knowledge since Carolus Linnaeus. In the absence of specialized training, often spanning decades, however, these articles can be challenging to decipher. Much of the vocabulary is domain-specific (e.g., Hymenoptera biology), historically without a comprehensive glossary, and contains much homonymous and synonymous terminology. The Hymenoptera Anatomy Ontology was developed to surmount this challenge and to aid future communication related to hymenopteran anatomy, as well as provide support for domain experts so they may actively benefit from the anatomy ontology development. As part of HAO development, an active learning, dictionary-based, natural language recognition tool was implemented to facilitate Hymenoptera anatomy term discovery in literature. We present this tool, referred to as the ‘Proofer’, as part of an iterative approach to growing phenotype-relevant ontologies, regardless of domain. The process of ontology development results in a critical mass of terms that is applied as a filter to the source collection of articles in order to reveal term occurrence and biases in natural language species descriptions. Our results indicate that taxonomists use domain-specific terminology that follows taxonomic specialization, particularly at superfamily and family level groupings and that the developed Proofer tool is effective for term discovery, facilitating ontology construction.

Objective. Speech recognition promises to reduce information entry costs for clinical information systems. It is most likely to be accepted across an organization if physicians can dictate without concerning themselves with real-time recognition and editing; assistants can then edit and process the computer-generated document. Our objective was to evaluate the use of speech-recognition technology in a randomized controlled trial using our institutional infrastructure.

Design. Clinical note dictations from physicians in two specialty divisions were randomized to either a standard transcription process or a speech-recognition process. Secretaries and transcriptionists also were assigned randomly to each of these processes.

Measurements. The duration of each dictation was measured. The amount of time spent processing a dictation to yield a finished document also was measured. Secretarial and transcriptionist productivity, defined as hours of secretary work per minute of dictation processed, was determined for speech recognition and standard transcription.

Results. Secretaries in the endocrinology division were 87.3% (confidence interval, 83.3%, 92.3%) as productive with the speech-recognition technology as implemented in this study as they were using standard transcription. Psychiatry transcriptionists and secretaries were similarly less productive. Author, secretary, and type of clinical note were significant (p < 0.05) predictors of productivity.

Conclusion. When implemented in an organization with an existing document-processing infrastructure (which included training and interfaces of the speech-recognition editor with the existing document entry application), speech recognition did not improve the productivity of secretaries or transcriptionists.

Total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH) presents many challenges to the reconstructive surgeon. The complex femoral and acetabular anatomy makes standard reconstruction technically challenging. Acetabular coverage can be improved by medialization of the component or augmentation of the deficient areas with bone graft. Femoral shortening osteotomies are considered in cases of severe dysplasia and frankly dislocated hips. Each patient’s unique anatomy dictates what options of reconstruction are available. The functional outcomes of THA in DDH are generally excellent, though higher rates of mechanical failure have been reported in this group. This article reviews the anatomy, classification, technical considerations, and outcomes of THA in patients with DDH.

BACKGROUND AND PURPOSE

Brain volumetry is widely used for evaluating tissue degeneration; however, the parcellation methods are rarely validated and use arbitrary planes to mark boundaries of brain regions. The goal of this study was to develop, validate, and apply an MR imaging tracing method for the parcellation of 3 major gyri of the frontal lobe, which uses only local landmarks intrinsic to the structures of interest, without the need for global reorientation or the use of dividing planes or lines.

METHODS

Studies were performed on 25 subjects—healthy controls and subjects diagnosed with Lewy body dementia and Alzheimer disease—with significant variation in the underlying gyral anatomy and state of atrophy. The protocol was evaluated by using multiple observers tracing scans of subjects diagnosed with neurodegenerative disease and those aging normally, and the results were compared by spatial overlap agreement. To confirm the results, observers marked the same locations in different brains. We illustrated the variabilities of the key boundaries that pose the greatest challenge to defining consistent parcellations across subjects.

RESULTS

The resulting gyral volumes were evaluated, and their consistency across raters was used as an additional assessment of the validity of our marking method. The agreement on a scale of 0–1 was found to be 0.83 spatial and 0.90 volumetric for the same rater and 0.85 spatial and 0.90 volumetric for 2 different raters. The results revealed that the protocol remained consistent across different neurodegenerative conditions.

CONCLUSION

Our method provides a simple and reliable way for the volumetric evaluation of frontal lobe neurodegeneration and can be used as a resource for larger comparative studies as well as a validation procedure of automated algorithms.

The reason why patients with dementia fall more often and sustain more fractures than patients without dementia remains unclear. Therefore, the relationship between dementia and gait velocity as a marker for mobility and falls in a cohort of frail elderly (mean age of 77.3 years) inpatients was assessed. Patients with dementia were expected to walk slower than patients without dementia. A trend was indeed observed: absolute gait velocity of 0.59 m/s in patients with dementia (n = 63) versus 0.65 m/s in patients without dementia (n = 62; p = 0.19). After adjustment for parkinsonism and walking aids, however, patients with dementia walked 0.44 m/s faster than patients without dementia (p = 0.02). Probable explanations are frontal lobe disinhibition and lack of insight, causing patients with dementia to walk relatively too fast in the context of their frailty. Therefore, the high risk of falls in dementia may be partially explained by the loss of control of gait velocity.

Frontotemporal dementia (FTD) is a clinical term encompassing dementia characterized by the presence of two major phenotypes: 1) behavioral and personality disorder, and 2) language disorder, which includes primary progressive aphasia and semantic dementia. Recently, the gene for familial frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U) linked to chromosome 17 was cloned. In the present study, 62 unrelated patients from the Washington University Alzheimer's Disease Research Center and the Midwest Consortium for FTD with clinically diagnosed FTD and/or neuropathologically characterized cases of FTLD-U with or without motor neuron disease (MND) were screened for mutations in the progranulin gene (GRN; also PGRN). We discovered two pathogenic mutations in four families: 1) a single-base substitution within the 3′ splice acceptor site of intron 6/exon 7 (g.5913A>G [IVS6–2A>G]) causing skipping of exon 7 and premature termination of the coding sequence (PTC); and 2) a missense mutation in exon 1 (g.4068C>A) introducing a charged amino acid in the hydrophobic core of the signal peptide at residue 9 (p.A9D). Functional analysis in mutation carriers for the splice acceptor site mutation revealed a 50% decrease in GRN mRNA and protein levels, supporting haploinsufficiency. In contrast, there was no significant difference in the total GRN mRNA between cases and controls carrying the p.A9D mutation. Further, subcellular fractionation and confocal microscopy indicate that although the mutant protein is expressed, it is not secreted, and appears to be trapped within an intracellular compartment, possibly resulting in a functional haploinsufficiency.

The purpose of this study was to evaluate the effect of neurotrophin 3 (NT-3) enhanced nerve regeneration on the reinnervation of a target muscle. Muscle fibers can be classified according to their mechanical properties and myosin heavy chain (MHC) isoform composition. MHC1 containing slow-type and MHC2a or 2b fast-type fibers are normally distributed in a mosaic pattern, their phenotype dictated by motor innervation. After denervation, all fibers switch to fast-type MHC2b expression and also undergo atrophy resulting in loss of muscle mass. After regeneration, discrimination between fast and slow fibers returns, but the distribution and fiber size change according to the level of reinnervation.

In this study, rat gastrocnemius muscles (ipsilateral and contralateral to the side of nerve injury) were collected up to 8 mo after nerve repair, with or without local delivery of NT-3. The phenotype changes of MHC1, 2a, and 2b were analyzed by immunohistochemistry, and fiber type proportion, diameter, and grouping were assessed by computerized image analysis. At 8 mo, the local delivery of NT-3 resulted in significant improvement in gastrocnemius muscle weight compared with controls (NT-3 group 47%, controls 39% weight of contralateral normal muscle; P < 0.05). NT-3 delivery resulted in a significant increase in the proportion (NT-3 43.3%, controls 35.7%; P < 0.05) and diameter (NT-3 87.8 μm, controls 70.8 μm; P < 0.05) of fast type 2b fibers after reinnervation. This effect was specific to type 2b fibers; no normalization was seen in other fiber types.

This study indicates that NT-3–enhanced axonal regeneration has a beneficial effect on the motor target organ. Also, NT-3 may be specifically affecting a subset of motoneurons that determine type 2b muscle fiber phenotype. As NT-3 was topically applied to cut nerves, our data suggest a discriminating effect of the neurotrophin on neuro–muscular interaction. These results would imply that muscle fibers may be differentially responsive to other neurotrophic factors and indicate the potential clinical role of NT-3 in the prevention of muscle atrophy after nerve injury.

Objectives To estimate survival after a diagnosis of dementia in primary care, compared with people without dementia, and to determine incidence of dementia.

Design Cohort study using data from The Health Improvement Network (THIN), a primary care database.

Setting 353 general practices in the United Kingdom providing data to THIN.

Participants All adults aged 60 years or over with a first ever code for dementia from 1990 to 2007 (n=22 529); random sample of five participants without dementia for every participant with dementia matched on practice and time period (n=112 645).

Main outcome measures Median survival by age and sex; mortality rates; incidence of dementia by age, sex, and deprivation.

Results The median survival of people with dementia diagnosed at age 60-69 was 6.7 (interquartile range 3.1-10.8) years, falling to 1.9 (0.7-3.6) years for those diagnosed at age 90 or over. Adjusted mortality rates were highest in the first year after diagnosis (relative risk 3.68, 95% confidence interval 3.44 to 3.94). This dropped to 2.49 (2.29 to 2.71) in the second year. The incidence of recorded dementia remained stable over time (3-4/1000 person years at risk). The incidence was higher in women and in younger age groups (60-79 years) living in deprived areas.

Conclusions Median survival was much lower than in screened populations. These clinically relevant estimates can assist patients and carers, clinicians, and policy makers when planning support for this population. The high risk of death in the first year after diagnosis may reflect diagnoses made at times of crisis or late in the disease trajectory. Late recording of diagnoses of dementia in primary care may result in missed opportunities for potential early interventions.

Background:

The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population.

Methods:

A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia.

Results:

A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7.

Conclusion:

Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia.

GLOSSARY

= Alzheimer disease;

= area under the curve;

= confidence interval;

= cognitive impairment no dementia;

= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;

= European Australasian Stroke Prevention in Reversible Ischemia Trial;

= European Australasian Stroke Prevention in Reversible Ischemia Trial, cognitive substudy;

= hazard ratio;

= lacunar infarct;

= mild cognitive impairment;

= modified Rankin scale;

= no cognitive impairment;

= Oxfordshire Community Stroke Project;

= partial anterior circulation infarct;

= posterior circulation infarct;

= receiver operating curve;

= total anterior circulation infarct;

= vascular dementia;

= Wechsler Adult Intelligence Scale–Revised;

= Wechsler Memory Scale–Revised.

Mutations in progranulin (PGRN) are associated with frontotemporal dementia with or without parkinsonism. We describe the prominent phenotypic variability within and among eight kindreds evaluated at Mayo Clinic Rochester and/or Mayo Clinic Jacksonville in whom mutations in PGRN were found. All available clinical, genetic, neuroimaging and neuropathologic data was reviewed. Age of onset ranged from 49 to 88 years and disease duration ranged from 1 to 14 years. Clinical diagnoses included frontotemporal dementia (FTD), primary progressive aphasia, FTD with parkinsonism, parkinsonism, corticobasal syndrome, Alzheimer’s disease, amnestic mild cognitive impairment, and others. One kindred exhibited maximal right cerebral hemispheric atrophy in all four affected individuals, while another had maximal left hemisphere involvement in all three of the affected. Neuropathologic examination of 13 subjects revealed frontotemporal lobar degeneration with ubiquitin-positive inclusions plus neuronal intranuclear inclusions in all cases. Age of onset, clinical phenotypes and MRI findings associated with most PGRN mutations varied significantly both within and among kindreds. Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals.

Vascular and neurodegenerative disease commonly co-occur in older persons. We review findings from the Rush Religious Orders Study and Memory and Aging Project. Both studies enroll subjects without diagnosed dementia, perform annual evaluations and obtain autopsies proximate to death. We found that macroscopic infarcts are common, lower the threshold for cognitive impairment, and often coexist with Alzheimer’s disease (AD) pathology. We also found that vascular pathology may be associated with memory impairment and may be difficult to distinguish from clinical AD. Finally, because dementia in older persons often results from mixed pathology and the clinical phenotypes overlap, some risk factors may increase risk for clinical AD through an increase in vascular pathology.

BACKGROUND

Older adults with dementia may have diminished capacity to make medical treatment decisions.

OBJECTIVE

To examine rates and neuropsychological predictors of treatment decision making, or consent capacity, among older adults with dementia over 9 months.

DESIGN

Consent capacity was assessed initially and 9 months later in subjects with and without dementia using a longitudinal repeated measures design.

PARTICIPANTS

Fifty-three older adults with dementia and 53 similarly aged adults without dementia.

MEASUREMENTS

A standardized measure MacArthur Competence Assessment Tool-Treatment of 4 legal standards for capacity (Understanding, Appreciation, Reasoning, and Expressing a Choice) and a neuropsychological battery.

RESULTS

In the dementia group, 9.4% had impaired capacity initially, and 26.4% had impaired capacity at 9 months. Mean scores in the dementia group were impaired relative to controls initially and at 9 months for Understanding (initial t=2.49, P=.01; 9-month t=3.22, P<.01) and Reasoning (initial t=2.18, P=.03; 9-month t=4.77, P<.01). Declining capacity over 9 months was attributable to a further reduction in Reasoning (group × time F=9.44, P=.003). Discriminant function analysis revealed that initial scores on naming, delayed Logical Memory, and Trails B were associated with impaired capacity at 9 months.

CONCLUSIONS

Some patients with mild-to-moderate dementia develop a clinically relevant impairment of consent capacity within a year. Consent capacity in adults with mild-to-moderate dementia should be reassessed periodically to ensure that it is adequate for each specific informed consent situation. Interventions that maximize Understanding and Reasoning by supporting naming, memory, and flexibility may help to optimize capacity in this patient group.

Background

Subclinical vascular or degenerative lesions occur in the brain before the clinical expression of dementia. Those lesions in a brain that just experienced a stroke may have lower thresholds for early epileptic seizures. Therefore, epileptic seizures may be a marker of subclinical brain lesions, which may lead to dementia.

Objective

To test the hypothesis that patients with stroke who have epileptic seizures without dementia have an increased risk of new‐onset dementia.

Methods

169 consecutive patients with stroke without pre‐existing dementia recruited in the Lille Stroke/Dementia Study were investigated (90 men; 150 ischaemic strokes; median age 73 years). Pre‐stroke cognitive functions were evaluated with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), with a cut‐off of 104 for the diagnosis of dementia. The patients were followed up over a 3‐year period. Dementia was diagnosed with International Classification of Diseases, 10th revision criteria in survivors who underwent neurological visits, and with the IQCODE score in those who could not. The relationship between epileptic seizures and new‐onset dementia was studied within 3 years, using life‐table methods.

Results

9 patients (5.3%; 95% CI 2.9 to 8.7%) had early seizures. Epileptic seizures were independent predictors of new‐onset dementia within 3 years after stroke (HR 3.81; 95% CI 1.13 to 12.82), with increasing age (HR 1.04; 95% CI 1.01 to 1.08), IQCODE scores at admission (HR 1.08; 95% CI 1.02 to 1.13) and diabetes mellitus (HR 3.52; 95% CI 1.46 to 8.47).

Conclusion

Patients with stroke who have epileptic seizures may be at increased risk of dementia. Whether cognitive follow‐up should be systematically performed in those patients remains to be validated.

Objective

The aim of this study is to investigate whether a combination of the Korean version of the mini-mental state examination (K-MMSE) and the Korean dementia screening questionnaire (KDSQ) is better than the use of test alone when differentiating patients with dementia from those without dementia in Korea.

Methods

The subjects (patients without dementia, 1120; patients with dementia, 908) were recruited from the Clinical Research Center for Dementia of South Korea. K-MMSE and KDSQ were used. Diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, fourth Edition. The weighted sum rule derived from logistic regression analysis was used for the combination of K-MMSE and KDSQ.

Results

On comparing the Area Under the Curve for each test using the method of Hanley and McNeil, the weighted sum was significantly greater than KDSQ or K-MMSE, and K-MMSE was significantly greater than KDSQ.

Conclusion

This study shows that when differentiating patients with dementia from those without dementia in Korea, a combination of K-MMSE and KDSQ achieved using the weighted sum method is better than either test performed alone. Further epidemiological studies in community-based settings are required before our results can be generalized to nonclinical samples.

Objectives

We compared the attitudes about dementia screening among older adults with and without an experience of dementia caregiving.

Design

A cross-sectional study.

Setting

Primary care clinics in Indianapolis, Indiana.

Participants

Eighty one subjects with dementia caregiving experience (CG) and a random sample of 125 subjects without dementia caregiving experience (NCG).

Measurements

Attitudes of dementia screening, including acceptance of dementia screening and its perceived harms and benefits, as determined by the PRISM-PC questionnaire.

Results

After adjusting for age, race, gender, and education and in comparison to NCG, CGs had a lower dementia screening acceptance mean score (53.9 vs. 60.6; p < 0.05) and a higher perceived suffering score (61.6 vs. 55.9, p < 0.05). However, there were no differences in perceived benefits of dementia screening (72.8 vs. 69.0; p > 0.05), perceived stigma (32.9 vs. 37.5; p > 0.05), and perceived negative impact on independence (47.6 vs. 54.0; p > 0.05). The top three barriers to screening identified by both groups were emotional suffering by the family (86% of CGs and 75% of NCGs), loss of driving privileges (75% of CGs and 78% of NCGs), and becoming depressed (64% of CGs and 43% of NCGs).

Conclusion

The experience of being a dementia caregiver may influence one's own attitude about accepting dementia screening for oneself.

Epidemiologic studies on dementia generally have 2 major interacting objectives: descriptive, where rates of dementia and Alzheimer Disease (AD) are calculated for communities and selected populations, and analytic, which attempt to explain the observed phenotypic variations in communities and populations by identifying disease risk factors. The public health benefits derived from descriptive studies are exemplified by the recent published review of the global prevalence of dementia under the auspices of Alzheimer Disease International. This review emphasized the enormous and growing burden associated with dementia particularly for countries in the developing world and outlined strategies to influence policy making, planning, and healthcare allocation. One interesting feature of descriptive studies on dementia is that although the few epidemiologic studies conducted in Africa suggest that rates of dementia and AD are relatively low, rates of AD and dementia have been reported to be relatively high for African Americans. The Indianapolis-Ibadan Dementia Project has reported that the incidence rates for AD and dementia in Yoruba are less than half the incidence rates for AD and dementia in African Americans. Analytic studies are now underway to identify risk factors that may account for these rate differences. The risk factor model being applied, attempts to identify not only putative genetic and environmental factors but also their interactions. So far the major findings have included: apolipoprotein E e4, a major risk factor for AD in most populations, is also a risk factor for AD in African Americans but not for Yoruba; African Americans are at higher risk not only for AD, but also for diseases associated with increased cardiovascular risk such as hypertension, diabetes, and metabolic syndrome; African Americans have higher rates of hypercholesterolemia than Yoruba: there is an interaction between apolipoprotein E e4, cholesterol, and AD risk in both Yoruba and African Americans. We eventually hope to create a risk factor model that will not only account for the dementia rate differences between Yoruba and African Americans, but also help explain dementia rates in other developing and developed countries.

After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin,E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described ‘dementia praecox’ and the ‘ schizophrenias’, were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82–120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137–147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia.

The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi—92% of studies reviewed, basal ganglia—68% of studies reviewed, corpus callosum—63% of studies reviewed, and thalamus—42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed).

The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated.

Future studies will likely benefit from: (1) studying more homogeneous patient groups so that the relationship between MRI findings and clinical symptoms become more meaningful; (2) studying at risk populations such as family members of patients diagnosed with schizophrenia and subjects diagnosed with schizotypal personality disorder in order to define which abnormalities are specific to schizophrenia spectrum disorders, which are the result of epiphenomena such as medication effects and chronic institutionalization, and which are needed for the development of frank psychosis; (3) examining shape differences not detectable from measuring volume alone; (4) applying newer methods such as diffusion tensor imaging to investigate abnormalities in brain connectivity and white matter fiber tracts; and, (5) using methods that analyze brain function (fMRI) and structure simultaneously.

This paper addresses the question, how the variations of the deep phenotype in disorders of sex development (DSD) are appropriately described. This is a relevant question, because extensive phenotypic variability occurs in gonads and sex ducts. With the advance of video endoscopy and laparoscopy, fresh insight in gonadal and sex duct anatomy is emerging. So far, an attempt to standardize the diagnostic approach and, in particular, how to document these findings has not been published. We propose a standardized examination schedule for these procedures. It consists of 5 pictures of relevant anatomic features. For laparoscopy, it includes two pictures each of gonads and sex ducts on either side and an image of the retrovesical space. For endoscopy, the examination of the ureteric orifices, the posterior urethra, and the urogenital sinus derivates is recommended. Adherence of a standardized schedule and image storing enhances patient autonomy, because they can carry their examination for a second opinion without need for repeated examination. Physicians and scientists create a structured image library that facilitates the comparison of clinical outcomes, research on genotype phenotype associations and may lead to better classifications.

With increasing efforts to develop and utilize mouse models of a variety of neuro-developmental diseases, there is an urgent need for sensitive neuroimaging methods that enable in vivo analysis of subtle alterations in brain anatomy and function in mice. Previous studies have shown that the brains of Fibroblast Growth Factor 17 null mutants (Fgf17−/−) have anatomical abnormalities in the inferior colliculus (IC)–the auditory midbrain–and minor foliation defects in the cerebellum. In addition, changes in the expression domains of several cortical patterning genes were detected, without overt changes in forebrain morphology. Recently, it has also been reported that Fgf17−/− mutants have abnormal vocalization and social behaviors, phenotypes that could reflect molecular changes in the cortex and/or altered auditory processing / perception in these mice. We used manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) to analyze the anatomical phenotype of Fgf17−/− mutants in more detail than achieved previously, detecting changes in IC, cerebellum, olfactory bulb, hypothalamus and frontal cortex. We also used MEMRI to characterize sound-evoked activity patterns, demonstrating a significant reduction of the active IC volume in Fgf17−/− mice. Furthermore, tone-specific (16- and 40-kHz) activity patterns in the IC of Fgf17−/− mice were observed to be largely overlapping, in contrast to the normal pattern, separated along the dorsal-ventral axis. These results demonstrate that Fgf17 plays important roles in both the anatomical and functional development of the auditory midbrain, and show the utility of MEMRI for in vivo analyses of mutant mice with subtle brain defects.

Dissecting surgical specimens from the upper aerodigestive tract is often difficult because of their complicated anatomy. The local environment dictates the routes of tumour spread and surgical margins at risk, and these features differ for various subsites within this part of the body. The examination of surgical specimens of the upper aerodigestive tract should disclose whether postoperative adjuvant treatment is needed and allow the evaluation of preoperatively performed diagnostic imaging. The aim of this article is to provide a concise guideline for the dissection of specimens from this part of the body.

Summary

Physical characteristics of water (O2 solubility and capacitance) dictate that cardiovascular and ventilatory performance be controlled primarily by the need for oxygen uptake rather than carbon dioxide excretion, making O2 receptors more important in fish than in terrestrial vertebrates. An understanding of the anatomy and physiology of mechanoreception and O2 chemoreception in fishes is important, because water breathing is the primitive template upon which the forces of evolution have modified into the various cardioventilatory modalities we see in extant terrestrial species. Key to these changes are the O2-sensitive chemoreceptors and mechanoreceptors, their mechanisms and central pathways.

Skull base tumors, in addition to blood supply from the external carotid artery, frequently receive a portion of their blood supply from the cavernous portion of the internal carotid artery, especially when the cavernous sinus is invaded by tumor. Preoperative embolization routinely includes obliteration of the supply to the tumor from the external carotid system. However, a variety of strategies are available that enable preoperative embolization of supply from the internal carotid artery as well. These include direct catheterization of cavernous branches of the internal carotid artery, temporary occlusion of the internal carotid artery during external carotid embolization, embolization of the internal carotid artery supply during temporary or permanent occlusion of the internal carotid artery, and internal carotid artery sacrifice. The angiographic anatomy in any particular case dictates these options.

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