Pretest Pathology
Background: Diagnosis of ventriculoperitoneal (VP) shunt pathology remains a dilemma in patients with nonspecific constitutional signs and symptoms. Eosinophilia has been described in association with shunt infection and malfunction. Our purpose was to further define the relationship of eosinophilia and shunt pathology and to determine other predictors of VP shunt infection and malfunction.
pretest Pathology
Results: Of 12 patients with shunt infection and 69 with shunt malfunction, 2 and 11, respectively, had eosinophilia defined as > or =5%. The presence of eosinophilia had a 96% positive predictive value for shunt pathology and raised the pretest probability of pathology from 84% to a post test probability of 96%. The combination of fever history and ventricular fluid neutrophils >10% had a 99% specificity for shunt infection, had a 93 and 95% positive and negative predictive value, respectively, and raised the pretest probability of infection from 12% to a posttest probability of 92%.
Conclusions: In patients suspected of having a VP shunt malfunction, the presence of > or =5% eosinophils in the ventricular fluid indicates shunt pathology. The combination of fever and ventricular fluid neutrophils > 10% is predictive of shunt infection.
Context: Effective pathology practice increasingly requires familiarity with concepts in medical informatics that may cover a broad range of topics, for example, traditional clinical information systems, desktop and Internet computer applications, and effective protocols for computer security. To address this need, the University of Pittsburgh (Pittsburgh, Pa) includes a full-time, 3-week rotation in pathology informatics as a required component of pathology residency training.
Design: We assess the efficacy of the rotation in communicating these concepts using a short-answer examination administered at the end of the rotation. Because the increasing use of computers and the Internet in education and general communications prior to residency training has the potential to communicate key concepts that might not need additional coverage in the rotation, we have also evaluated incoming residents' informatics knowledge using a similar pretest.
Data sources: This article lists 128 questions that cover a range of topics in pathology informatics at a level appropriate for residency training. These questions were used for pretests and posttests in the pathology informatics rotation in the Pathology Residency Program at the University of Pittsburgh for the years 2000 through 2002. With slight modification, the questions are organized here into 15 topic categories within pathology informatics. The answers provided are brief and are meant to orient the reader to the question and suggest the level of detail appropriate in an answer from a pathology resident.
Results: A previously published evaluation of the test results revealed that pretest scores did not increase during the 3-year evaluation period, and self-assessed computer skill level correlated with pretest scores, but all pretest scores were low. Posttest scores increased substantially, and posttest scores did not correlate with the self-assessed computer skill level recorded at pretest time.
Conclusions: Even residents who rated themselves high in computer skills lacked many concepts important in pathology informatics, and posttest scores showed that residents with both high and low self-assessed skill levels learned pathology informatics concepts effectively.
When you come for a pathology test, our collection staff will ask you to tell them your full name and date of birth and will ask you to spell your full name. This is a critical part of the patient identification process and ensures that we select the correct patient file to record your results.
Approximately 35% of patients with amyotrophic lateral sclerosis (ALS) exhibit mild cognitive deficits in executive functions, language and fluency, without dementia. The precise pathology of these extramotor symptoms has remained unknown. This study aimed to determine the pathological correlate of cognitive impairment in patients with non-demented ALS.
All patients with cognitive impairment had TDP-43 pathology in extramotor brain regions (positive predictive value of 100%). The ECAS also predicted TDP-43 pathology with 100% specificity in brain regions associated with executive, language and fluency domains. We also detected a subgroup with no cognitive dysfunction, despite having substantial TDP-43 pathology, so called mismatch cases.
Cognitive impairment as detected by the ECAS is a valid predictor of TDP-43 pathology in non-demented ALS. The profile of mild cognitive deficits specifically predicts regional cerebral involvement. These findings highlight the utility of the ECAS in accurately assessing the pathological burden of disease.
In ALS brains, TDP-43 pathology can be widespread in cases of ALS-related/FTD and some have suggested a sequential spread.8 A non-specific association was found between the presence of cognitive impairment (yes/no) as measured by a dementia screening tool, the Mini Mental State Examination and moderate to severe TDP-43 pathology.9 Using more detailed neuropsychology, Prudlo and colleagues divided the patients with ALS into three clinical groups: ALS with no cognitive impairment, ALS with cognitive impairment and ALS-FTD. A significant difference was demonstrated in the severity of pathologically misfolded TDP-43 inclusions, between patients with ALS-FTD and the combined non-demented clinical groups (ALS with or without cognitive impairment); however, there was no difference between the two non-demented groups: ALS with cognitive impairment and ALS with no cognitive impairment.10 An association between the cognitive profile in patients with non-demented ALS with cognitive impairment and TDP-43 has not been shown previously. Furthermore, the association between specific cognitive functions (executive, language and fluency) tested during life using the same cognitive tool and the distribution of postmortem TDP-43 pathology over several distinct brain regions has never been demonstrated. Studies are limited as cohorts have been assessed by different cognitive tests not designed for ALS or physical disability. The introduction of, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) enables a more cohesive approach. This standardised tool assesses ALS-related cognitive deficits (verbal fluency, executive and language functions) and is sensitive to milder cognitive impairments.1 11 Using the ECAS, we have been able to demonstrate an association between the presence of cognitive impairment and synaptic loss in the prefrontal cortex of patients with ALS.7 Here we are the first to examine the relationship between the profile of cognitive impairment as detected by the ECAS in non-demented ALS and the localised distribution of TDP-43.
The aim was to determine the pathological correlate of cognitive impairment in patients with non-demented ALS. Our hypotheses are that (1) the specific profile of cognitive impairment in patients with non-demented ALS (executive, fluency and language dysfunction) is associated with TDP-43 pathology in corresponding brain regions identified a priori and (2) the ECAS assessed in vivo is a good predictor of TDP-43 pathology postmortem.
Subdomain cognitive dysfunction detected by the ECAS relates to specific regional distribution of TDP-43 pathology. (A) Pathological TDP-43 staining, demonstrating characteristic cytoplasmic aggregation and nuclear clearance of TDP-43. Images are taken at 20 magnification, illustrating mild, moderate and severe scoring of pathology. (B) Sensitivity and specificity analysis assessing the utility of ECAS subdomains in predicting TDP-43 pathology in corresponding brain regions, demonstrating high positive predictive value. Values are percentage with 95% CIs. ECAS, Edinburgh Cognitive and Behavioural Amytrophic lateral sclerosis Screen.
To determine whether cognitive impairment as detected by the ECAS was a good predictor of extramotor pathology in ALS we first assessed whether patients with impaired ECAS scores exhibited extramotor pathology assessed by TDP-43 aggregation in postmortem tissue.
Three out of 27 patients met criteria for ALSbi; one of these had a NEK1 mutation, one had a SOD1 mutation and one was a sporadic case. The brain areas thought to predominantly be associated with behavioural dysfunction are (1) the orbitofrontal cortex (BA11/12), (2) ventral anterior cingulate (BA24) and (3) medial prefrontal cortex (BA6). There was no TDP-43 present in the case with SOD1 mutation, in keeping with previous literature; however, the remaining two cases did have TDP-43 inclusions in two or more of these brain regions (table 4). 7 out of our cohort of 27 patients met criteria for ALSci. All 7 of these patients exhibited TDP-43 pathology in extramotor brain regions (table 4). Therefore, in every case exhibiting ALSci, there was evidence of extramotor TDP-43 pathology. There were six false negatives, whereby TDP-43 pathology in extramotor brain regions was not accompanied by an impairment in the ECAS.24 These data taken together were used to assess the diagnostic accuracy of ECAS in predicting TDP-43 pathology in extramotor brain regions resulting in a diagnostic accuracy of 66.67% (95% CI 46.04 to 83.48), with a sensitivity of 43.75% (95% CI 19.75 to 70.12) and a specificity of 100% (95% CI 71.51 to 100).
Three of the 27 patients demonstrated mild executive dysfunction when tested (one with pure executive dysfunction and two with a combined executive, language and fluency dysfunction) and all three had corresponding TDP-43 pathology at postmortem in the brain areas associated with executive functions (BA6, BA11, BA24, BA46 and BA9). Furthermore eight of the 27 patients demonstrated mild language impairment (BA44, BA41, BA20 and BA39) when tested with ECAS (six with pure language dysfunction and two with a combined executive, language and fluency dysfunction), all of whom had TDP-43 pathology in corresponding brain areas at postmortem. Four of the 27 patients demonstrated mild fluency dysfunction when tested with ECAS (two with pure fluency dysfunction and two with a combined executive, language and fluency dysfunction) and all four had corresponding TDP-43 pathology at postmortem in the brain areas associated with fluency (BA9, BA44 and BA41). There were no cases where cognitive impairment was present in the absence of TDP-43 pathology; however, there was a small subgroup (n=6) of patients who had TDP-43 pathology with no cognitive impairment (false negatives). These results taken together gave rise to the ECAS accurately predicting TDP-43 pathology with a positive predictive value of 100% and 100% specificity in executive function, language and fluency domains (figure 1B). 041b061a72