Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.</p> <p>We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin.</p> <p>Methods/Design</p> <p>We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain.</p> <p>Discussion</p> <p>As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process.</p> <p>Trial registration</p> <p><b>(ITRSCC) NCT00368199</b></p

A predictive tool for an effective use of ¹⁸F-FDG PET in assessing activity of sarcoidosis

<p>Abstract</p> <p>Background</p> <p>¹⁸F-FDG PET/CT (PET) is useful in assessing inflammatory activity in sarcoidosis. However, no appropriate indications are available. The aim of this study was to develop a prediction rule that can be used to identify symptomatic sarcoidosis patients who have a high probability of PET-positivity.</p> <p>Methods</p> <p>We retrospectively analyzed a cohort of sarcoidosis patients with non organ specific persistent disabling symptoms (n = 95). Results of soluble interleukin-2 receptor (sIL-2R) assessment and high-resolution computed tomography (HRCT) were included in the predefined model. HRCT scans were classified using a semi-quantitative scoring system and PET findings as positive or negative, respectively. A prediction model was derived based on logistic regression analysis. We quantified the model’s performance using measures of discrimination and calibration. Finally, we constructed a prediction rule that should be easily applicable in clinical practice.</p> <p>Results</p> <p>The prediction rule showed good calibration and good overall performance (goodness-of-fit test, p = 0.78, Brier score 20.1%) and discriminated between patients with positive and negative PET findings (area under the receiver-operating characteristic curve, 0.83). If a positive predictive value for the presence of inflammatory activity of ≥90% is considered acceptable for clinical decision-making without referral to PET, PET would be indicated in only 29.5% of the patients. Using a positive predictive value of 98%, about half of the patients (46.3%) would require referral to PET.</p> <p>Conclusions</p> <p>The derived and internally validated clinical prediction rule, based on sIL-2R levels and HRCT scoring results, appeared to be useful to identify sarcoidosis patients with a high probability of inflammatory activity. Using this rule may enable a more effective use of PET scan for assessment of inflammatory activity in sarcoidosis.</p

The predictive value of transcranial duplex sonography for the clinical diagnosis in undiagnosed parkinsonian syndromes: comparison with SPECT scans

<p>Abstract</p> <p>Background</p> <p>Transcranial duplex sonography (TCD) of the substantia nigra has emerged as a promising, non-invasive tool to diagnose idiopathic Parkinson's disease (IPD). However, its diagnostic accuracy in patients with undefined parkinsonism remains to be determined.</p> <p>In this study we determined the predictive value of TCD for the clinical diagnosis in undiagnosed parkinsonian syndromes. Additionally we compared the predictive value of TCD with that of presynaptic and postsynaptic single photon emission computer tomography (SPECT) scans.</p> <p>Methods</p> <p>We studied 82 patients with an unclassified parkinsonian syndrome. All 82 patients were subjected to a TCD, 59 of them underwent a presynaptic SPECT scans and 32 underwent a postsynaptic SPECT scan.</p> <p>We determined the diagnostic accuracy of TCD and SPECT scans in differentiating:</p> <p>1) IPD patients from patients without nigrostriatal degeneration and 2) IPD patients from patients with atypical parkinsonian syndromes (APS).</p> <p>To compare the diagnostic accuracy of TCD and SPECT scans, we used the clinical diagnosis after follow-up according to generally accepted clinical criteria as the gold standard. This clinical diagnosis was determined by a movement disorder specialist.</p> <p>3) Finally, we ascertained the predictive value of the TCD for the SPECT result.</p> <p>Results</p> <p>The clinical diagnoses after follow-up resulted in 51 cases of IPD, 7 patients with APS and 17 patients without nigrostriatal degeneration. In total 7 patients remained undiagnosed.</p> <p>1) The accuracy of TCD, assessed by sensitivity and specificity, to differentiate IPD patients from patients without nigrostriatal degeneration was 50% and 82% respectively.</p> <p>For the presynaptic SPECT scans sensitivity was 97% and specificity 100%.</p> <p>2) In differentiating IPD patients from APS patients, the sensitivity and specificity of TCD was 50% and 43% respectively. For presynaptic SPECT scans this was 97% and 0%. For the postsynaptic SPECT scans the sensitivity was 75% and the specificity 81%.</p> <p>3) The positive predictive value (PPV) of an abnormal TCD for an abnormal presynaptic SPECT scan was 88%.</p> <p>Conclusion</p> <p>Presynaptic SPECT scanning has a higher predictive value for the clinical diagnosis than TCD. However, since the PPV of an abnormal TCD for parkinsonism with nigrostriatal degeneration is high, TCD might be used as screening tool, before ordering a presynaptic SPECT.</p