Alternative Clinical Diagnosis Research Articles

On gaps of clinical diagnosis of dementia subtypes: A study of Alzheimer's disease and Lewy body disease.

Alzheimer's disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation of these subtypes could be difficult. However, it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectra and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these factors. We studied data of 1,920 participants recorded by the National Alzheimer's Coordinating Center from 2005 to 2019. Selection criteria included autopsy-based neuropathological assessments for AD and LBD, and the initial visit with Clinical Dementia Rating (CDR) stage of normal, mild cognitive impairment, or mild dementia. Longitudinally, we analyzed the first visit at each subsequent CDR stage. This analysis included positive predictive values, specificity, sensitivity and false negative rates of clinical diagnosis, as well as disparities by sex, race, age, and education. If autopsy-confirmed AD and/or LBD was missed in the clinic, the alternative clinical diagnosis was analyzed. In our findings, clinical diagnosis of AD+LBD had poor sensitivities. Over 61% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had a low sensitivity at the early dementia stage and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 32% had concurrent LBD neuropathology at autopsy. Among participants diagnosed as LBD, 32% to 54% revealed concurrent autopsy-confirmed AD pathology. When three subtypes were missed by clinicians, "No cognitive impairment" and "primary progressive aphasia or behavioral variant frontotemporal dementia" were the leading primary etiologic clinical diagnoses. With increasing dementia stages, the clinical diagnosis accuracy of black participants became significantly worse than other races, and diagnosis quality significantly improved for males but not females. These findings demonstrate that clinical diagnosis of AD, LBD, and AD+LBD are inaccurate and suffer from significant disparities on race and sex. They provide important implications for clinical management, anticipatory guidance, trial enrollment and applicability of potential therapies for AD, and promote research into better biomarker-based assessment of LBD pathology.

Pump-free microfluidic chip based laryngeal squamous cell carcinoma-related microRNAs detection through the combination of surface-enhanced Raman scattering techniques and catalytic hairpin assembly amplification

MicroRNA (miRNA), as one of the ideal target biomarker analytes, plays an essential role in biological processes; thus, the development of rapidly sensitive detection methods is imperative. Herein, we proposed a pump-free surface-enhanced Raman scatting (SERS) microfluidic chip for the rapid and ultrasensitive detection of miR-106b and miR-196b, laryngeal squamous cell carcinoma (LSCC)-related miRNAs. Ag–Au core-shell nanorods (Ag-AuNRs) were applied to prepare SERS tags by modifying Raman reporters and hairpin DNAs. The capture probes were synthesized by labeling hairpin DNAs onto the magnetic beads (MBs) surface. In the presence of targets, the catalytic hairpin assembly (CHA) reactions between SERS tags and capture probes could be triggered, causing the aggregation of Ag-AuNRs. The tiny magnets installed under the rectangular chamber could magnetically gather the CHA products, leading to the further aggregation of Ag-AuNRs. Thus, this strategy could achieve the double aggregation of Ag-AuNRs, resulting in the significant amplification of the SERS signal. The proposed strategy achieved simultaneous and sensitive detection of miR-106b and miR-196b, with limits of detection low to aM level. The whole detection process could be completed within 5 min. Moreover, this microfluidic chip exhibited excellent reproducibility, stability, and specificity. The high accuracy of this SERS microfluidic chip was proved by practical analysis in LSCC patients’ serum. The results demonstrated that SERS could be a promising alternative clinical diagnosis tool and exhibited potential application for the dynamic monitoring of cancer staging.

On gaps of clinical diagnosis of dementia subtypes: A study of Alzheimer's disease and Lewy body disease

AbstractBackgroundAlzheimer’s disease (AD) and Lewy body disease (LBD) are most common dementias, and can occur concurrently (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation could be difficult. Yet it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectrums and demographic variables. We aimed to compare clinical diagnosis and post‐mortem autopsy‐confirmed pathological results to assess the clinical subtype diagnosis quality across these factors.MethodParticipants were selected from the National Alzheimer’s Coordinating Center dataset, with autopsy‐confirmed AD and/or LBD results, and initial visits with Clinical Dementia Rating (CDR) of 0, 0.5, or 1.0. We analyzed the clinical AD and/or LBD diagnosis in first visits at each CDR stage. This analysis included precision (PPV), sensitivity and specificity of the clinical diagnosis, and disparities in these metrics by sex, race/ethnicity, age and education. If autopsy‐confirmed AD, LBD, or AD+LBD was missed in the clinic, the alternative clinical diagnosis was analyzed.Result1887 qualified participants (Table 1) from September 1, 2005 to August 20, 2019 were included. Clinical AD+LBD diagnosis had poor sensitivity from 3% (CDR 0.5) to 6% (CDR 2.0). Over 60% of participants with autopsy‐confirmed AD+LBD were diagnosed clinically as AD (Table 2). Clinical AD diagnosis had low sensitivities at early dementia stage (57%) and low specificities at all stages (Table 3). Among participants clinically diagnosed as AD, over 33% had autopsy‐confirmed concurrent LBD neuropathology. Clinical LBD diagnosis had poor PPVs from mild cognitive impairment (22%) to severe dementia (20%). Within participants clinically diagnosed as LBD, 32% to 54% revealed autopsy‐confirmed AD+LBD pathology. When clinicians missed these three subtypes, “No cognitive impairment”, “Undecided” and “Primary progressive aphasia or behavioral variant frontotemporal dementia” were the leading alternative clinical diagnosis. With increasing dementia stages, the difference in clinical diagnosis accuracy significantly increased between White and Black/African‐American participants, and diagnosis quality significantly improved for males but not for females.ConclusionOur findings demonstrates that the clinical diagnosis of AD, LBD and AD+LBD are inaccurate and harbor significant disparities based on race and sex at all dementia stages.

Plasma and CSF Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: A Cross-Sectional and Longitudinal Study.

Background: Neurofilament light chain (NfL) is a validated biofluid marker of neuroaxonal damage with great potential for monitoring patients with neurodegenerative diseases. We aimed to further validate the clinical utility of plasma (p) vs. CSF (c) NfL for distinguishing patients with Amyotrophic Lateral Sclerosis (ALS) from ALS mimics. We also assessed the association of biomarker values with clinical variables and survival and established the longitudinal changes of pNfL during the disease course.Methods: We studied 231 prospectively enrolled patients with suspected ALS who underwent a standardized protocol including neurological examination, electromyography, brain MRI, and lumbar puncture. Patients who received an alternative clinical diagnosis were considered ALS mimics. We classified the patients based on the disease progression rate (DPR) into fast (DPR > 1), intermediate (DPR 0.5–1), and slow progressors (DPR < 0.5). All patients were screened for the most frequent ALS-associated genes. Plasma and CSF samples were retrospectively analyzed; NfL concentrations were measured with the SIMOA platform using a commercial kit.Results: ALS patients (n = 171) showed significantly higher pNfL (p < 0.0001) and cNfL (p < 0.0001) values compared to ALS mimics (n = 60). Both cNfL and pNfL demonstrated a good diagnostic value in discriminating the two groups, although cNfL performed slightly better (cNfL: AUC 0.924 ± 0.022, sensitivity 86.8%, specificity 92.4; pNfL: AUC 0.873 ± 0.036, sensitivity 84.7%, specificity 83.3%). Fast progressors showed higher cNfL and pNfL as compared to intermediate (p = 0.026 and p = 0.001) and slow progressors (both p < 0.001). Accordingly, ALS patients with higher baseline cNfL and pNfL levels had a shorter survival (highest tertile of cNfL vs. lowest tertile, HR 4.58, p = 0.005; highest tertile of pNfL vs. lowest tertile, HR 2.59, p = 0.015). Moreover, there were positive associations between cNfL and pNfL levels and the number of body regions displaying UMN signs (rho = 0.325, p < 0.0001; rho = 0.308, p = 0.001). Finally, longitudinal analyses in 57 patients showed stable levels of pNfL during the disease course.Conclusion: Both cNfL and pNfL have excellent diagnostic and prognostic performance for symptomatic patients with ALS. The stable longitudinal trajectory of pNfL supports its use as a marker of drug effect in clinical trials.

Customised next-generation sequencing multigene panel to screen a large cohort of individuals with chromatin-related disorder

BackgroundThe regulation of the chromatin state by epigenetic mechanisms plays a central role in gene expression, cell function, and maintenance of cell identity. Hereditary disorders of chromatin regulation are a...

Implementation\xa0of a genomic medicine multi-disciplinary team approach for rare disease\xa0in the clinical setting: a prospective exome sequencing\xa0case series

BackgroundA multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit. Here we describe the results of establishing a genomic medicine multi-disciplinary team (GM-MDT) for case selection, processing, interpretation and return of results.MethodsWe report a consecutive case series of 132 patients (involving 10 medical specialties with 43.2% cases having a neurological disorder) undergoing exome sequencing over a 10-month period following the establishment of the GM-MDT in a UK NHS tertiary referral hospital. The costs of running the MDT are also reported.ResultsIn total 76 cases underwent exome sequencing following triage by the GM-MDT with a clinically reportable molecular diagnosis in 24 (31.6%). GM-MDT composition, operation and rationale for whether to proceed to sequencing are described, together with the health economics (cost per case for the GM-MDT was £399.61), the utility and informativeness of exome sequencing for molecular diagnosis in a range of traits, the impact of choice of sequencing strategy on molecular diagnostic rates and challenge of defining pathogenic variants. In 5 cases (6.6%), an alternative clinical diagnosis was indicated by sequencing results. Examples were also found where findings from initial genetic testing were reconsidered in the light of exome sequencing including TP63 and PRKAG2 (detection of a partial exon deletion and a mosaic missense pathogenic variant respectively); together with tissue-specific mosaicism involving a cytogenetic abnormality following a normal prenatal array comparative genomic hybridization.ConclusionsThis consecutive case series describes the results and experience of a multidisciplinary team format that was found to promote engagement across specialties and facilitate return of results to the responsible clinicians.

PB1993 EFFICACY OF ANTI-NEUTROPHIL ANTIBODIES TESTING IN PREDICTING CLINICAL OUTCOMES AND SPONTANEOUS RESOLUTION OF NEUTROPENIA IN CHILDREN: A SINGLE CENTER EXPERIENCE

Background: Autoimmune neutropenia (AIN) is common form of neutropenia in children. AIN presents with absolute neutrophil count (ANC) of less than 0.5 x 109/L, but mild infection and spontaneous resolution. AIN is caused by anti-neutrophil antibodies (ANA). Detection of ANA is usually helpful in the diagnosis of AIN, but is controversy about the exclusion of congenital neutropenia or the prediction of outcome. Aims: The purpose of this study was to demonstrate the efficacy of the ANA testing for predicting clinical outcomes and spontaneous resolution of neutropenia in children with neutropenia. Methods: We reviewed the records of 62 patients with neutropenia of less than 1.5 x 109/L who were tested for ANA (positive or negative) in Department of Pediatrics, Pusan National University Children's Hospital, from February 2013 to January 2018. Patients with ANC > 1.5 x 109/L at presentation, alternative clinical diagnosis such as marrow failure or malignancy, and patients who were lost to follow-up were excluded. Blood samples for immunoglobulin G (IgG) and immunoglobulin M (IgM) ANA were tested by immunofluorescent flow cytometric technique. Results: For total of 62 pediatric patients with neutropenia, the mean age was 18.69 months (range, 3-96 months), 31 of the patients were boys and 31 was girl. All 62 patients had neutropenia, the mean ANC was 0.38 x 109/L (range, 0-1.39 x 109/L). Positive ANA were detected in 18 cases (29.0%) and absent in 44 (71.0%). Fifteen of 18 patients (83.3%) in ANA positive and 23 of 44 patients (52.3%) in ANA negative showed recovery from neutropenia, statistically significant (P = 0.022). The median age at recovery for those with resolving neutropenia was 26.8 months for the ANA positive and 20.48 months for ANA negative patients, respectively. The frequency of admission to the tertiary hospital with recurrent fevers and infections after the ANA testing (2.52, range, 0–23) in ANA negative was significantly higher than those (0.72, range, 0–3) in ANA positive (P = 0.008). Summary/Conclusion: Our study documents that ANA testing in children with neutropenia is helpful in establishing the diagnosis of AIN and effective in predicting clinical prognosis and spontaneous resolution of neutropenia. We also recommend that you consider to the results of ANA testing when treat of neutropenic children with recurrent fever and infection.

Accuracy of a Novel Histoplasmosis Enzyme Immunoassay to Evaluate Suspicious Lung Nodules.

Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from a highly endemic region. A total of 152 serum samples from patients presenting with pulmonary nodules ≤30 mm in maximum diameter were analyzed for histoplasmosis antibodies by immunodiffusion and EIA IgG and IgM tests. Serology and FDG-PET/CT scan diagnostic test characteristics were estimated and compared. Cancer prevalence was 55% (n = 83). Thirty-nine (26%) individuals were positive for IgG histoplasmosis antibodies. Twelve samples were IgM antibody positive. Immunodiffusion serology was similar to IgM antibody results with 13 positive tests. Diagnostic likelihood ratios for benign disease were 0.62, 0.33, and 0.28 for FDG-PET/CT, IgG, and IgM antibodies, respectively. When both IgG and IgM were positive (n = 8), no nodules were cancerous and six were FDG-PET/CT avid. A positive EIA test for both IgM and IgG strongly suggested histoplasmosis etiology and benign granuloma for 12% of benign nodules arising from a highly endemic region. Presence of either IgG or IgM histoplasma antibodies was associated with benign disease. The EIA test was more sensitive in assessing histoplasma exposure than immunodiffusion serology. A new CLIA-certified histoplasmosis antibody EIA test measures histoplasmosis exposure, offers a possible alternative clinical diagnosis for benign IPNs, and may improve IPN evaluation while avoiding harmful invasive biopsies.

Clinicopathological correlations in behavioural variant frontotemporal dementia.

Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system. Patients with FTLD were distributed between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive supranuclear palsy, eight Pick's disease, three frontotemporal dementia with parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one with motor neuron disease, 27 type B including 21 with motor neuron disease, eight type C with right temporal lobe presentations, and 11 unclassifiable including eight with motor neuron disease), FTLD-FUS (eight patients), and one patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy-nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least 'possible' bvFTD diagnostic criteria at first presentation. The frequency of the six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP, suggesting that these features alone cannot be used to separate patients by major molecular class. Voxel-based morphometry revealed that nearly all pathological subgroups and even individual patients share atrophy in anterior cingulate, frontoinsula, striatum, and amygdala, indicating that degeneration of these regions is intimately linked to the behavioural syndrome produced by these diverse aetiologies. In addition to these unifying features, symptom profiles also differed among pathological subtypes, suggesting distinct anatomical vulnerabilities and informing a clinician's prediction of pathological diagnosis. Data-driven classification into one of the 10 most common pathological diagnoses was most accurate (up to 60.2%) when using a combination of known predictive factors (genetic mutations, motor features, or striking atrophy patterns) and the results of a discriminant function analysis that incorporated clinical, neuroimaging, and neuropsychological data.

Patterns of pediatric venous disease.

The spectrum of chronic venous disease (CVD) is well documented in adults; clinical guidelines standardize diagnosis and treatment. There is a paucity of data published commenting on pediatric CVD exclusive of Klippel-Trénaunay syndrome (KTS) and post-thrombotic syndrome. This study aimed to define patterns of pediatric venous disease. All venous reflux studies performed on patients<18 years of age between January 2012 and June 2014 were reviewed. Study indication, patient history, clinical examination, and duplex ultrasound results were queried and described. Venous reflux parameters were compared using one-way analysis of variance. Twenty patients were evaluated. All presented through the vascular surgery or multidisciplinary venous clinic at a tertiary academic medical center. Indications for referral included swelling (n= 10), varicose veins (n= 9), and rubor/acrocyanosis (n= 3); two patients carried a diagnosis of KTS. Mean age at study was 13 years (range, 5-17 years). Clinical examination revealed the following: dependent rubor(n= 3); edema (n= 9); and varicose veins or venous abnormality concerning for venous malformation (n= 9). There were no stigmata of chronic inflammation, hyperpigmentation, or ulceration; 90% of patients (n= 18) demonstrated venous reflux by duplex ultrasound interrogation. Mean right great saphenous vein (GSV) diameter was 0.49 cm (range, 0.31-0.66 cm); mean left GSV diameter was 0.55 cm (range, 0.24-0.93 cm). Adjunctive studies were often used (including magnetic resonance venography and lymphoscintigraphy). Despite the presence of venous reflux on imaging, an alternate diagnosis was made in 8 of 18 children (44%), including postural orthostatic hypotension syndrome (n= 2), vascular malformation (n= 2), lymphedema (n= 2), complex regional pain syndrome (n= 1), and acrocyanosis of disuse (n= 1). An additional case of KTS was identified. Three cases referred for varicose veins were diagnosed with venous malformation. Maximum GSV diameter and venous reflux time were compared across patients with isolated CVD, KTS, or an alternate diagnosis (as before). Whereas there was no significant difference in maximum GSV diameter, superficial venous reflux time was significantly increased in the patients with primary CVD and KTS (P= .0394). The differential diagnosis for pediatric lower extremity edema and varicosities is broad; workup often requires adjunctive studies to secure the appropriate diagnosis. Often there is venous reflux present despite an alternative clinical diagnosis. Superficial venous reflux time may aid in the diagnosis of primary CVD. Whereas the clinical significance of pediatric venous reflux remains unclear, ongoing work to expand on venous parameters in healthy pediatric controls is warranted, as is additional follow-up to assess the natural history of pediatric venous disease.

8:00 AM Abstract No. 9 - Computed tomography characteristics associated with post-retrieval alleviation of clinical symptoms accompanying inferior vena cava filter strut penetration

Purpose: To investigate the relationship between inferior vena cava (IVC) filter strut penetration with clinical symptoms preand post-retrieval. Materials and Methods: Retrospective analysis was performed of patients who underwent IVC filter retrieval over a 10 year period. Filter penetration associated symptoms included any patient complaint which could potentially be explained by filter penetration (i.e. abdominal and/or back pain) which was not consistent with an alternative clinical diagnosis. Chart review for alleviation of symptoms up to 30 days post-retrieval was then performed. IVC filter penetration was graded on pre-retrieval computed tomography (CT) according to increasing depth of strut penetration (grade 0-2) and evidence of contact with adjacent structures (grade 3). Results: 49 filter retrievals with pre-retrieval CT were included in our analysis, with a mean dwell time of 232 days. There was no significant difference in filter dwell time between low grade (grade 0 or 1) and high grade (grade 2 or 3) penetration or filter type. Of 21 patients with low grade penetration (grade 0, n 1⁄4 12; grade 1, n 1⁄4 9) and 19 patients with grade 2 penetration, there were no filter penetration associated symptoms. There were 9 patients with grade 3 penetration, with 4 cases of penetration associated symptoms (abdominal pain, n 1⁄4 3; back pain, n 1⁄4 1) which all had complete resolution of symptoms following filter retrieval. These 4 cases with symptomatic resolution had evidence of fat stranding on CT, while the remaining 45 cases did not (sensitivity 100% [95% CI: 39100%]; specificity 100% [95% CI: 90-100%]). Two cases of high grade penetration (without fat stranding) had symptoms which were highly consistent with an alternative clinical diagnosis, and neither had alleviation of symptoms with retrieval (back pain with chronic compression fractures; nausea with heavy non-steroidal anti-inflammatory drug use alleviated with decrease in dosage). Conclusion: Patients with high grade filter strut penetration and associated symptoms not consistent with an alternative diagnosis have a high likelihood of symptom alleviation after filter retrieval, particularly in patients with evidence of fat stranding on pre-retrieval CT. JVIR ’ Distinguished Abstracts S11

Abstract W P246: Diagnostic Value of Lobar Hemorrhages for Cerebral Amyloid Angiopathy in Hospital and Community-based Individuals: A Pathological Correlation Study

Objectives: To determine and compare the accuracy of the Boston criteria for the diagnosis of cerebral amyloid angiopathy (CAA) applied to: 1) a large hospital-based cohort; 2) a cohort of community-dwelling individuals. Methods: Among patients seen at a single academic medical center and participants enrolled in the Framingham Heart Study (FHS) we identified all individuals having had brain MRI (including hemosiderin-specific sequences) and pathological assessment of CAA at age ≥55. CAA was defined as Vonsattel degree ≥2, except in non-autopsy studies, where any vascular amloyid deposition was considered diagnostic of CAA. We excluded cases with: 1) non-lobar ICH; 2) alternative clinical diagnosis for the lobar hemorrhage/es; 3) CAA-negative studies based on small brain biopsy samples (greater diameter &lt;1 cm) or clot evacuations with none or rare vessels identified; 4) autopsy studies not grading CAA. We determined sensitivity and specificity of “possible CAA” (1 lobar hemorrhage) and “probable CAA” (&gt;1 strictly lobar hemorrhage) in both cohorts. Results: The study included 143 cases: 96 from the hospital cohort (mean age at time of MRI 74.1±8.2 years, 47.9% women, 47.9% autopsy studies, 54.2% cases with any lobar microbleed, 44.8% with any lobar ICH) and 47 from FHS (mean age at time of MRI 83.4±10.9 years, 48.9% women, 100% autopsy studies, 17% cases with any lobar microbleed, no lobar ICH cases). Hospital cohort: CAA prevalence was 72.6%. Specificity/sensitivity of “possible CAA” and “probable CAA” were 78.2%/33.3% and 92%/57.7%. Community cohort: CAA prevalence was 47%. Specificity/sensitivity of “probable CAA” were 88%/3%. Discussion: Specificity of detection of multiple lobar hemorrhages on MRI (“probable CAA”) for moderate-severe CAA is similarly high in both hospital and community cohorts. This increases the opportunity to identify individuals with CAA for observational studies and emerging anti-amyloid therapeutic trials. In view of its poor sensitivity, “probable CAA” diagnosis represents an inadequate screening tool for exclusion of CAA in both populations.

Shift work effects on serial PEF measurements for occupational asthma

Diurnal variation (DV) affects lung function but the changes are thought to be related to sleep patterns rather than time of day. When diagnosing occupational asthma (OA), serial peak expiratory flow (PEF) measurements are the recommended first line investigation, but could be confounded by shift work. The aim of the study was to investigate the effects of shift work on PEF measurements used for diagnosing OA. PEF records containing more than one shift pattern with ≥ 4 days per shift were identified. OA diagnosis was based on an Oasys-2 score ≥ 2.51 and non-OA on having an alternative clinical diagnosis and Oasys-2 score <2.51. The mean area between curves (ABC) score, mean PEF DV and cross-shift PEF changes were calculated for each shift. Records from 123 workers with OA and 69 without OA satisfied inclusion criteria. In the OA group, PEF declined more on afternoon and night shifts than days (P < 0.001). The ABC score was lower in the OA group on night (P < 0.05) and afternoon shifts (P < 0.05) as compared with days, without significant differences in DV. Among those without OA, cross-shift PEF increased more on day shifts (mean + 25 l/min) than afternoon or night shifts (+1 l/min) (P < 0.001). The sensitivity for the ABC score and DV were good and similar across shifts, but specificity was reduced using DV (DV mean 39%; ABC 98%). PEF responses between work and rest show small differences according to shift type. The ABC score has a high sensitivity and specificity for all shifts; differences in DV have lower specificity.

Impact of 123I-FP-CIT (DaTSCAN) SPECT on the diagnosis and management of patients with dementia with Lewy bodies

To assess the impact of imaging the presynaptic dopaminergic terminal using DaTSCAN single-photon emission computed tomography (SPECT) on the clinical diagnosis and subsequent management of patients with possible dementia with Lewy bodies (DLB), who were referred for imaging. A retrospective case note study was undertaken, involving a series of consecutive patients who had undergone DaTSCAN SPECT 12-24 months earlier. Case notes of 80 patients were reviewed. DaTSCAN imaging results were abnormal (indicating DLB) in 20 (25%) and normal (suggesting an alternative diagnosis or absence of disease) in 60 (75%) patients. Of the 20 patients with an abnormal scan, 18 had a postscan working clinical diagnosis of DLB (90%), one had diagnosis of vascular dementia (5%) and another had no recorded outcome (5%). Fifty-eight out of the 60 patients with a normal DaTSCAN image result had an alternative clinical diagnosis of DLB (95%). Consequently, DaTSCAN findings were concordant with the outcome clinical diagnosis in 76 out of the 80 (95%) cases. Subsequent to DaTSCAN SPECT, scan findings and diagnoses were discussed with patients and/or their carers in 94% of cases and subsequent treatment options discussed in 93% of cases. It would seem that DaTSCAN imaging has a marked influence on the working clinical diagnosis and subsequent management of patients with suspected DLB.

S160 The effect of shift work on serial peak expiratory flow measurements used to diagnose occupational asthma

We investigated the effects of shift work on Peak Expiratory Flow (PEF) measurements used for diagnosing occupational asthma (OA). In a clinic database of workers investigated for OA, 123 workers...

Computed tomographic pulmonary angiography: Utility in acute pulmonary embolism in providing additional information and making alternative clinical diagnosis

To evaluate the role of computed tomographic (CT) pulmonary angiography (CT-PA) in detecting additional information that may help in making an alternative clinical diagnosis in patients referred to CT for a suspected acute pulmonary embolism (PE). 50 patients (34 males, 16 females) in the age group of 18-72 years (mean 42.3 years), having high clinical suspicion of PE, underwent CTPA over a 2 year period. Chest x-ray, arterial blood gas (ABG) analysis, echocardiography were done in all patients. All patients underwent at least one other imaging examination besides CTPA: ventilation perfusion scan, Doppler ultrasound or compression ultrasound (for DVT). All patients were followed for 3 months after completion of the diagnostic work up at baseline. The final diagnosis was achieved by a combination of clinical, imaging, and laboratory analysis, after adequate imaging, laboratory tests, and follow up. CTPA helped correctly identify 29 of 30 patients with PE. In the remaining 20 patients (with no evidence of PE), CT-PA provided additional information (that suggested or confirmed alternate clinical diagnosis) in 15 patients (75%): pleural effusion (n=8), mediastinal or hilar lymphadenopathy (6), pneumonia/airspace consolidation (5), atelectasis/collapse (2), aspergilloma (1), malignancy (1), and others (2). CT-PA is highly specific and sensitive for diagnosis of PE. In addition, in a majority of patients who do not have PE, it also provides important ancillary additional information and helps in making an alternative clinical diagnosis.

Painful digital infarction in a male smoker treated as Buerger's disease

A 40-year-old male smoker presented with a 3-week history of painful digital infarction involving the hands. Histology was unhelpful, showing lichen simplex chronicus. A provisional diagnosis of a vasculitic disease was made. Treatment included aspirin, azathioprine, iloprost, methylprednisolone, nifedipine and prednisolone. After failure of these treatments an alternative clinical diagnosis of Buerger's disease was made. Treatment was to advise the patient of the importance of continuing to abstain from smoking, to perform bilateral video-assisted thoracoscopic sympathectomies and to commence folate supplementation. This led to marked improvement of his symptoms and healing of the digital infarction.

Is FDG‐PET a useful tool in clinical practice for diagnosing corticobasal ganglionic degeneration?

Seven consecutive patients were suspected to suffer from corticobasal ganglionic degeneration (CBGD) and were studied with ([18])F-fluorodeoxyglucose (FDG) PET imaging of the brain. At the time of their FDG-PET scan, 4 of 7 patients fulfilled the clinical criteria of CBGD as proposed by Lang and associates [In Calne DB, 1994; Neurodegenerative disease. Philadelphia: Saunders]. For 2 of these 4 patients, however, an alternative clinical diagnosis was also considered. Three of the seven patients underwent an FDG-PET scan when their clinical features were not yet developed sufficiently to confirm a clinical diagnosis of CBGD. Simple visual analysis of the FDG-PET scans was carried out. All 7 patients showed an asymmetrical pattern of glucose metabolism that was demonstrated in previous studies to be characteristic in patients who had a clinical diagnosis of CBGD. The PET results helped to confirm the clinical suspicion of CBGD in 2 patients and to rule out other diagnoses in 2 other patients. For 3 patients with no sufficient symptoms to diagnose CBGD, the pattern of glucose metabolism was characteristically asymmetrical. A probable diagnosis of CBGD was made in these patients. Our results suggest that routine visual inspection of a cerebral FDG-PET scan is a useful tool to confirm suspicion of the clinical diagnosis of probable CBGD, to differentiate from other hypokinetic-rigid syndromes, and to support a diagnosis CBGD in patients who do not (yet) sufficiently fulfill the clinical criteria.

Treating Myofascial Pain

Neuropathic pain invariably affects the musculoskeletal system, causing muscle contracture and shortening: “Myofascial Pain”. Spondylosis, the universal outcome of age, wear and tear, is probably the most common cause of neuropathic pain. By irritating nerve roots, spondylosis can lead to peripheral neuropathy and muscle shortening. Many myofascial syndromes (from Achilles Tendonitis to Tennis Elbow) caused by muscle shortening of spondylotic origin are customarily misconstrued as mundane local conditions. The spondylosis and muscle-shortening model can explain many musculoskeletal pain problems for which there is no alternative clinical diagnosis; it also enables these disparate syndromes to be grouped under one aetiological classification. Intramuscular stimulation effectively relieves pain by releasing muscle, which in turn relieves paraspinal muscle shortening and pressure on nerve roots, as well as stimulating the production of platelet-derived growth factor to promote healing.