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BACKGROUND: Spillover of effect, whether positive or negative, from intervention to control group patients invalidates the Stable Unit Treatment Variable Assumption (SUTVA). SUTVA is critical to valid causal inference from randomized concurrent controlled trials (RCCT). Spillover of infection prevention is an important population level effect mediating herd immunity. This herd effect, being additional to any individual level effect, is subsumed within the overall effect size (ES) estimate derived by contrast-based techniques from RCCT's. This herd effect would manifest only as increased dispersion among the control group infection incidence rates above background. METHODS AND RESULTS: The objective here is to explore aspects of spillover and how this might be visualized and diagnosed. I use, for illustration, data from 190 RCCT's abstracted in 13 Cochrane reviews of various antimicrobial versus non-antimicrobial based interventions to prevent pneumonia in ICU patients. Spillover has long been postulated in this context. Arm-based techniques enable three approaches to identify increased dispersion, not available from contrast-based techniques, which enable the diagnosis of spillover within antimicrobial versus non-antimicrobial based infection prevention RCCT's. These three approaches are benchmarking the pneumonia incidence rates versus a clinically relevant range, comparing the dispersion in pneumonia incidence among the control versus the intervention groups and thirdly, visualizing the incidence dispersion within summary receiver operator characteristic (SROC) plots. By these criteria there is harmful spillover effects to concurrent control group patients. CONCLUSIONS: Arm-based versus contrast-based techniques lead to contrary inferences from the aggregated RCCT's of antimicrobial based interventions despite similar summary ES estimates. Moreover, the inferred relationship between underlying control group risk and ES is 'flipped'.

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Purpose: This study aims to propose a diagnostic algorithm for autoimmune epilepsy in a retrospective cohort and investigate its clinical utility. Methods: We reviewed 60 patients with focal epilepsy with a suspected autoimmune etiology according to board-certified neurologists and epileptologists. To assess the involvement of the autoimmune etiology, we used the patients' sera or cerebrospinal fluid (CSF) samples to screen for antineuronal antibodies using rat brain immunohistochemistry. Positive samples were analyzed for known antineuronal antibodies. The algorithm applied to assess the data of all patients consisted of two steps: evaluation of clinical features suggesting autoimmune epilepsy and evaluation using laboratory and imaging findings (abnormal CSF findings, hypermetabolism on fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging abnormalities, and bilateral epileptiform discharges on electroencephalography). Patients were screened during the first step and classified into five groups according to the number of abnormal laboratory findings. The significant cutoff point of the algorithm was assessed using a receiver-operating characteristic curve analysis. Results: Fourteen of the 60 patients (23.3%) were seropositive for antineuronal antibodies using rat brain immunohistochemistry. Ten patients had antibodies related to autoimmune epilepsy/encephalitis. The cutoff analysis of the number of abnormal laboratory and imaging findings showed that the best cutoff point was two abnormal findings, which yielded a sensitivity of 78.6%, a specificity of 76.1%, and an area under the curve of 0.81. Conclusion: The proposed algorithm could help predict the underlying autoimmune etiology of epilepsy before antineuronal antibody test results are available.

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OBJECTIVE: Many patients attending the emergency room (ER) with vertigo, leave without a diagnosis. We assessed whether the three tools could improve ER diagnosis of vertigo. METHODS: A prospective observational study was undertaken on 539 patients presenting to ER with vertigo. We used three tools: a structured-history and examination, nystagmus video-oculography (VOG) in all patients, additional video head-impulse testing (vHIT) for acute-vestibular-syndrome (AVS). RESULTS: In the intervention-group (n = 424), case-history classified AVS in 34.9%, episodic spontaneous-vertigo (ESV 32.1%), and episodic positional-vertigo (EPV 22.6%). In AVS, we employed "Quantitative-HINTS plus" (Head-Impulse, Nystagmus and Test-of-Skew quantified by vHIT and VOG, audiometry) to identify vestibular-neuritis (VN) and stroke (41.2 and 31.1%). vHIT gain ≤ 0.72, catch-up saccade amplitude > 1.4○, saccade-frequency > 154%, and unidirectional horizontal-nystagmus, separated stroke from VN with 93.1% sensitivity and 88.5% specificity. In ESV, 66.2 and 14% were diagnosed with vestibular migraine and Meniere's Disease by using history and audiometry. Horizontal-nystagmus velocity was lower in migraine 0.4 ± 1.6○/s than Meniere's 5.7 ± 5.5○/s (p < 0.01). In EPV, benign positional vertigo (BPV) was identified in 82.3% using VOG. Paroxysmal positional-nystagmus lasting < 60 s separated BPV from non-BPV with 90% sensitivity and 100% specificity. In the control group of ER patients undergoing management-as-usual (n = 115), diagnoses included BPV (38.3%) and non-specific vertigo (41.7%). Unblinded assessors reached a final diagnosis in 90.6 and 30.4% of the intervention and control groups. Blinded assessors provided with the data gathered from each group reached a diagnosis in 86.3 and 41.1%. CONCLUSION: Three tools: a structured-assessment, vHIT and VOG doubled the rate of diagnosis in the ER.

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Ayurveda has a holistic and person-centric approach towards health and disease, which in turn necessitates consideration of several factors in the process of a diagnostic workup. This concept of personalised diagnosis brings about a high level of variability among the clinicians with respect to their assessment methods and disease diagnosis. Developing and validating diagnostic tools for diseases enumerated in the Ayurvedic classical textbooks can help in standardising the clinical approach, even when attempting to arrive at a patient specific diagnosis. However, diagnostic research is a very less explored area in Ayurveda and there are no established standards for developing and evaluating diagnostic tools. This paper reviews the methodology for the development and validation of diagnostic tools, available in published literature and proposes to integrate this in the field of Ayurveda. The search was conducted on online databases including PubMed, Science Direct, Scopus, and Google scholar, with keywords - ayurvedic diagnosis, diagnostic tool development, validity, reliability, and diagnostic test assessment. The articles were screened based on their comprehensiveness, relevance, and feasibility, and the methodology elaborated in the selected articles was organized into a framework that can be adopted in Ayurveda. We have also tried to examine the methodological challenges of integrating the fundamentals of ayurvedic diagnosis within the current methods of diagnostic research and explored possible solutions. The proposed tool development process involves both qualitative and quantitative components, which may be carried out in three phases that include setting the diagnostic criteria, tool development and validation, and diagnostic test assessment.

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BACKGROUND AND PURPOSE: The aim of this study was to evaluate the quality of smartphone videos (SVs) of neurologic events in adult epilepsy outpatients. The use of home video recording in patients with neurological disease states is increasing. Experts interpretation of outpatient smartphone videos of seizures and neurological events has demonstrated similar diagnostic accuracy to inpatient video-electroencephalography (EEG) monitoring. METHODS: A prospective, multicenter cohort study was conducted to evaluate SV quality in patients with paroxysmal neurologic events from August 15, 2015 through August 31, 2018. Epileptic seizures (ESs), psychogenic nonepileptic attacks (PNEAs), and physiologic nonepileptic events (PhysNEEs) were confirmed by video-EEG monitoring. Experts and senior neurology residents blindly viewed cloud-based SVs without clinical information. Quality ratings with regard to technical and operator-driven metrics were provided in responses to a survey. RESULTS: Forty-four patients (31 women, age 45.1 years [r = 20-82]) were included and 530 SVs were viewed by a mean of seven experts and six residents; one video per patient was reviewed for a mean of 133.8 s (r = 9-543). In all, 30 patients had PNEAs, 11 had ESs, and three had PhysNEEs. Quality was suitable in 70.8% of SVs (375/530 total views), with 36/44 (81.8%) patient SVs rated as adequate by the majority of reviewers. Accuracy improved with the presence of convulsive features from 72.4% to 98.2% in ESs and from 71.1% to 95.7% in PNEAs. An accurate diagnosis was given by all reviewers (100%) in 11/44 SVs (all PNEAs). Audio was rated as good by 86.2% of reviewers for these SVs compared with 75.4% for the remaining SVs (p = 0.01). Lighting was better in SVs associated with high accuracy (p = 0.06), but clarity was not (p = 0.59). Poor video quality yielded unknown diagnoses in 24.2% of the SVs reviewed. Features hindering diagnosis were limited interactivity, restricted field of view and short video duration. CONCLUSIONS: Smartphone video quality is adequate for clinical interpretation in the majority of patients with paroxysmal neurologic events. Quality can be optimized by encouraging interactivity with the patient, adequate duration of the SV, and enlarged field of view during videography. Quality limitations were primarily operational though accuracy remained for SV review of ESs and PNEAs.

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OBJECTIVE: To report the sensitivity and the ability to precisely localize ulnar neuropathies at the elbow (UNE) of different severity by ultrasonography (US) and compare it to standard 10-cm nerve conduction studies (NCSs), and 2-cm short-segment NCSs (SSNCSs) across the elbow. METHODS: In a group of consecutive UNE patients, a prospective and blinded study was performed. The evaluation included clinical examination, electrodiagnostic (EDx) and US studies. We compared US and NCSs for sensitivity and the ability to precisely localize the UNE of different clinical severity. RESULTS: We studied 202 affected arms of 197 UNE patients. Clinically very mild UNE was diagnosed in seven, mild in 43, moderate in 99 and severe in 53 arms. The sensitivities of SSNCSs were 14%, 67%, 93% and 100%, of 10-cm NCSs, 29%, 44%, 80% and 96%, and of US 14%, 47%, 59% and 89%, respectively. Precise UNE localization was possible using SSNCSs in 29%, 56%, 78% and 85%, and using US in 29%, 44%, 70% and 98%, respectively. CONCLUSION: The present study demonstrated that NCSs are more sensitive than US for the diagnosis of UNE of all clinical grades of severity. US was more efficient in localizing clinically severe, and SSNCSs in localizing mild or moderate UNE. SIGNIFICANCE: We recommend SSNCSs as the first confirmatory test in UNE across all grades of severity.

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BACKGROUND: In patients suffering from Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) disease severity is assessed by Medical Research Counsil (MRC) Scale or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. However, none of these methods is appropriate to objectively assess muscle weakness or to detect very small subclinical changes. More objective and quantitative measures are needed in order to evaluate treatment efficiency or to detect subclinical affection of upper limps for early diagnosis. The goal of our study was to objectively quantify muscular weakness in CIDP patients with the non-invasive Quantitative Motor (Q-Motor) test of Grip Force Assessment (QGFA) as well as the Involuntary Movement Assessment (QIMA) and to search for differences between typical and atypical CIDP variants. In addition, we hypothesized that Q-Motor findings correlate with disease severity scales such as MRC or INCAT score. METHODS: In this cross-sectional exploratory proof-of-concept study subjects with confirmed diagnosis of typical or atypical CIDP were examined and compared to healthy controls (HC). For Q-Motor tests all subjects had to lift a device (250 g and 500 g) equipped with an electromagnetic sensor that measured grip force (GF) and three-dimensional changes in position and orientation. The measures "grip force variability" (GFV), "position index" (PI) and "orientation index" (OI) were provided to assess involuntary movements due to muscular weakness. RESULTS: 33 patients with CIDP and 28 HC were included. All measures were significantly elevated in CIDP patients for both devices in the right and left hand compared to healthy controls. Subgroup analysis revealed no differences between typical and atypical CIDP variants. INCAT score only weakly correlated with OI and PI. However, there was a stronger correlation between MRC and QIMA parameters in both hands. CONCLUSION: Q-Motor assessments were capable to objectively assess muscular weakness in CIDP. In particular, QIMA measures detected subclinical generalized muscle weakness even in patients with milder disability. Sensitivity and rater-independence of Q-Motor assessments support a further exploration of QIMA measures as potential endpoints for future clinical trials in CIDP.

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OBJECTIVE: The high degree of clinical overlap between atypical parkinsonian syndromes (APS) and Parkinson's disease (PD) makes diagnosis challenging. We aimed to identify novel diagnostic protein biomarkers of APS using multiplex proximity extension assay (PEA) testing. METHODS: Cerebrospinal fluid (CSF) samples from two independent cohorts, each consisting of APS and PD cases, and controls, were analysed for neurofilament light chain (NF-L) and Olink Neurology and Inflammation PEA biomarker panels. Whole-cohort comparisons of biomarker concentrations were made between APS (n=114), PD (n=37) and control (n=34) groups using logistic regression analyses that included gender, age and disease duration as covariates. RESULTS: APS versus controls analyses revealed 11 CSF markers with significantly different levels in cases and controls (p<0.002). Four of these markers also reached significance (p<0.05) in APS versus PD analyses. Disease-specific analyses revealed lower group levels of FGF-5, FGF-19 and SPOCK1 in multiple system atrophy compared with progressive supranuclear palsy and corticobasal syndrome. Receiver operating characteristic curve analyses suggested that the diagnostic accuracy of NF-L was superior to the significant PEA biomarkers in distinguishing APS, PD and controls. The biological processes regulated by the significant proteins include cell differentiation and immune cell migration. Delta and notch-like epidermal growth factor-related receptor (DNER) had the strongest effect size in APS versus controls and APS versus PD analyses. DNER is highly expressed in substantia nigra and is an activator of the NOTCH1 pathway which has been implicated in the aetiology of other neurodegenerative disorders including Alzheimer's disease. CONCLUSIONS: PEA testing has identified potential novel diagnostic biomarkers of APS.

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Although the 3-m timed up-and-go test (TUG) is reliable for evaluating mobility, TUG time is insufficient to evaluate mild gait disturbance; we, therefore aimed to investigate other measurements with instrumented TUG (iTUG) using a free smartphone application. Our inclusion criterion in this study is only that participants can walk without any assistance. This study included three heterogeneous groups; patients who underwent a tap test or shunt surgery, 29 inpatients hospitalized for other reasons, and 87 day-care users. After the tap test, 28 were diagnosed with tap-positive idiopathic normal-pressure hydrocephalus (iNPH) and 8 were diagnosed with tap-negative. Additionally, 18 patients were assessed iTUG before and after shunt surgery. During iTUG, time and 3-dimensional (3D) acceleration were automatically recorded every 0.01 s. A volume of the 95% confidence ellipsoid (95%CE) of all plots for 3D acceleration was calculated. Additionally, an iTUG score was defined as (95%CE volume) 0.8 / 1.9 - 1.9 × (time) + 60. The measurement reliability was evaluated using intraclass correlations and Bland-Altman plots. The participants with mild gait disturbance who accomplished within 13.5 s on the iTUG time had the 95%CE volumes for 3D acceleration of ≥70 m3/s6 and iTUG scores of ≥50. The mean iTUG time was shortened and the mean 95%CE volumes and iTUG scores were increased after the tap test among 28 patients with tap-positive iNPH and after shunt surgery among 18 patients with definite iNPH. Conversely, the mean iTUG score among 8 patients with tap-negative was decreased after the tap test. The intraclass correlations for the time, 95%CE volume and iTUG score were 0.97, 0.80 and 0.90, respectively. Not only the iTUG time but also the 95%CE volume was important for evaluating mobility. Therefore, the novel iTUG score consisting both is useful for the quantitative assessment of mobility.

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BACKGROUND: The 2017 revision of the McDonald criteria highlights the usefulness of cerebrospinal fluid (CSF) immunoglobulin G (IgG) analysis to diagnose multiple sclerosis (MS). The objective of this study was to assess the diagnostic performances of CSF IgG analysis in the absence of a gold standard. METHODS: All patients who underwent CSF IgG analysis for events suggestive of MS in Nancy University Hospital (France) from 2008 to 2011 were retrospectively included. A latent class analysis with Bayesian approach was used to infer MS prevalence (latent variable) as well as the diagnostic properties of the 2005 and 2010 McDonald criteria and CSF IgG analysis (observed variables). RESULTS: Data from 673 patients were analysed. For CSF IgG analysis, the Bayesian latent class analysis estimated sensitivity of 0.93 (95% CrI 0.89-0.96) and specificity of 0.81 (95% CrI 0.77-0.85). The true prevalence estimate was 36% (95% CrI 0.33-0.40). Sensitivity and specificity estimates for patients with events suggestive of remitting-onset MS were similar to those for the whole sample-0.92 (95% CrI 0.85-0.96) and 0.80 (95% CrI 0.76-0.84), respectively-but higher for patients with signs of progressive-onset MS-0.95 (95% CrI 0.84-0.99) and 0.88 (95% CrI 0.78-0.94), respectively. CONCLUSIONS: In the absence of a gold standard, latent class analysis indicates good diagnostic properties of CSF IgG analysis for MS. This test could thus be useful, especially for patients who tested negative for the 2005 and 2010 McDonald criteria. These findings deserve to be confirmed prospectively.

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In this case report we compare two patients presenting with similar symptoms of a brainstem syndrome including ataxia, dysarthria, and diplopia. Their MRIs showed hyperintense FLAIR signal changes with patchy areas of contrast enhancement within the brainstem particularly the pons and cerebellum. The broad differential diagnosis of this brainstem pathology included rhomboencephalitis, neurosarcoidosis, lymphoma, vasculitis, infection, and paraneoplastic or autoimmune process. Patient 1 had an extensive work up including CSF cytology, MRI brain spectroscopy, full body CT, cerebral angiogram, and ultimately brainstem biopsy. None of these studies were diagnostic of a specific etiology and total cost was $176,069. After months of declining medical condition without a clear diagnosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was considered and the patient began steroid therapy resulting in clinical and radiographic improvement. Patient 2 had serum and CSF studies that were negative for infectious, paraneoplastic, and other inflammatory processes. The team diagnosed CLIPPERS and initiated steroid therapy within days resulting in dramatic clinical and radiographic resolution. The workup cost $12,905. Comparison of these cases shows how early awareness of CLIPPERS and a directed diagnostic work up can limit invasive diagnostic testing, expedite initiation of effective therapy, improve patient outcomes, and reduce cost.

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INTRODUCTION: We studied, using a data-driven approach, how different combinations of diagnostic tests contribute to the differential diagnosis of dementia. METHODS: In this multicenter study, we included 356 patients with Alzheimer's disease, 87 frontotemporal dementia, 61 dementia with Lewy bodies, 38 vascular dementia, and 302 controls. We used a classifier to assess accuracy for individual performance and combinations of cognitive tests, cerebrospinal fluid biomarkers, and automated magnetic resonance imaging features for pairwise differentiation between dementia types. RESULTS: Cognitive tests had good performance in separating any type of dementia from controls. Cerebrospinal fluid optimally contributed to identifying Alzheimer's disease, whereas magnetic resonance imaging features aided in separating vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Combining diagnostic tests increased the accuracy, with balanced accuracies ranging from 78% to 97%. DISCUSSION: Different diagnostic tests have their distinct roles in differential diagnostics of dementias. Our results indicate that combining different diagnostic tests may increase the accuracy further.

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Objective: To objectively measure color vision dysfunction in idiopathic Parkinson's disease (iPD) using an easily administered, essentially free, modified Stroop test. Methods: Sixty-one iPD patients and 26 age-matched controls (HC) were enrolled after IRB approval and performed congruent (CST) and incongruent (IST) modified Stroop tests consisting of 40 words in 10 colors arranged in a 5 x 8 grid. The scorer was blinded to participant diagnosis. Errors on IST were defined as type 1 (written word reported rather than color) or type 2 (color reported different from the written word or its color). Results: The iPD group and the control group completed testing with similar CST performance. On the IST, 75.4% of iPD patients had type 2 errors (p = 0.001, OR 4.907, 95%CI 1.838-13.097) compared to 38.5% HC, with a positive predictive value of 82%. The mean number of type 2 errors was also higher in the iPD group, even with MoCA scores as a covariate in the analysis. Type 1 errors were not significantly different between the groups. A univariate logistic regression model with age, gender, MoCA, normalized IST completion time and the presence/absence of type 2 errors also resulted in type 2 errors as the only significant factor in the equation (p = 0.026). Conclusions: The modified Stroop test incorporated into the clinical evaluation of a patient may provide a quick and inexpensive objective measure of a non-motor feature of iPD, which could help in the clinical diagnosis of iPD in conjunction with the motor assessments currently used by neurologists.

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BACKGROUND: Survival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer's disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD. METHODS: We included 616 patients (50% female; age 67 ± 8 years; mean Mini Mental State Examination score 22 ± 3) with dementia due to AD from the Amsterdam Dementia Cohort. Information on mortality was obtained from the Dutch Municipal Register. We used age- and sex-adjusted Cox proportional hazards analysis to study associations of baseline demographics, comorbidity, neuropsychology, magnetic resonance imaging (MRI) (medial temporal lobe, global cortical and parietal atrophy, and measures of small vessel disease), and cerebrospinal fluid (CSF) (ß-amyloid 1-42, total tau, and tau phosphorylated at threonine 181 [p-tau]) with mortality (outcome). In addition, we built a multivariate model using forward selection. RESULTS: After an average of 4.9 ± 2.0 years, 213 (35%) patients had died. Age- and sex-adjusted Cox models showed that older age (HR 1.29 [95% CI 1.12-1.48]), male sex (HR 1.60 [95% CI 1.22-2.11]), worse scores on cognitive functioning (HR 1.14 [95% CI 1.01-1.30] to 1.31 [95% CI 1.13-1.52]), and more global and hippocampal atrophy on MRI (HR 1.18 [95% CI 1.01-1.37] and HR 1.18 [95% CI 1.02-1.37]) were associated with increased risk of mortality. There were no associations with comorbidity, level of activities of daily living, apolipoprotein E (APOE) ε4 status, or duration of disease. Using forward selection, the multivariate model included a panel of age, sex, cognitive tests, atrophy of the medial temporal lobe, and CSF p-tau. CONCLUSIONS: In this relatively young sample of patients with AD, disease-related determinants were associated with an increased risk of mortality, whereas neither comorbidity nor APOE genotype had any prognostic value.

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INTRODUCTION: Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression. METHODS: We included 674 patients with SCD (46% female, 64 ± 9 years, Mini-Mental State Examination 28 ± 2) from three memory clinic cohorts. A multivariate model based on the Disease State Index classifier incorporated the available baseline tests to predict progression to MCI or dementia over time. We developed and internally validated the model in one cohort and externally validated it in the other cohorts. RESULTS: After 2.9 ± 2.0 years, 151(22%) patients showed clinical progression. Overall performance of the classifier when combining cognitive tests, magnetic resonance imagining, and cerebrospinal fluid showed a balanced accuracy of 74.0 ± 5.5, with high negative predictive value (93.3 ± 2.8). DISCUSSION: We found that a combination of diagnostic tests helps to identify individuals at risk of progression. The classifier had particularly good accuracy in identifying patients who remained stable.

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Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) and to investigate their clinical value in a large memory clinic cohort. Methods: We included 2,934 patients (age 67 ± 9 years; 1,391 [47%] female; MMSE 24 ± 5) from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline). We analyzed the effect of age, APOE e4 and diagnosis on visual ratings using linear regression analyses. Subsequently, we compared diagnostic and predictive value in three age-groups (<65 years, 65-75 years, and >75 years). Results: Linear regression analyses showed main effects of age and diagnosis and an interaction age*diagnosis for MTA, PA, and GCA. For MTA the interaction effect indicated steeper age effects in MCI and AD than in controls. PA and GCA increased with age in MCI and controls, while AD patients have a high score, regardless of age. For WMH we found a main effect of age, but not of diagnosis. For MTA, GCA and PA, diagnostic value was best in patients <65 years (optimal cut-off: ≥1). PA and GCA only discriminated in patients <65 years and MTA in patients <75 years. WMH did not discriminate at all. Taking into account APOE did not affect the identified optimal cut-offs. When we used these scales to predict progression in MCI using Cox proportional hazard models, only MTA (cut-off ≥2) had any predictive value, restricted to patients >75 years. Conclusion: Visual ratings of atrophy and WMH were differently affected by age and diagnosis, requiring an age-specific approach in clinical practice. Their diagnostic value seems strongest in younger patients.

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There is a need for quantitative, precise assessment of small fiber peripheral nerve function. We tested a customized camera device and protocol designed to quantify secretions of individual sweat glands (SGs). Testing was performed on 178 healthy controls and 20 neuropathy subjects. Sweating was stimulated on a 2.25 cm2 skin area by iontophoresis of pilocarpine. The camera imaged sweat from 50 to 400 sweat ducts. We calculated secretion rate of individual SGs, total sweat volume, and number of secreting SGs at four body sites. Neuropathy subjects were tested at the two distal sites to demonstrate the device's capability to detect abnormal sudomotor function. Normal ranges were calculated for each body site. Neuropathy subjects had lower sweat rates per SG, lower total sweat, and lower SG density. The normal values decreased with advancing age, were lower in females, and differed between body sites. There was good agreement with repeat testing. The device provides reliable, precise quantitative measures of sweat secretion from single SGs for characterization of sudomotor nerve function in healthy control subjects and in subjects with known peripheral neuropathy. The test combines the capabilities of existing tests of sudomotor function while providing additional capabilities.

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Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity.

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INTRODUCTION: Changes in cerebrospinal fluid (CSF) tau and amyloid ß (Aß)42 accompany development of Alzheimer's brain pathology. Robust tau and Aß42 immunoassays were developed to establish a tau/Aß42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects. METHODS: A CSF tau/Aß42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET. Performance was assessed using an independent validation cohort. RESULTS: A tau/Aß42 = 0.215 cutoff provided 94.8% sensitivity and 77.7% specificity. Concordance with PET visual reads was estimated at 86.9% in a ∼50% PET positive population. In the validation cohort, the cutoff demonstrated 78.4% sensitivity and 84.9% specificity to distinguish the AD and HC populations. DISCUSSION: A tau/Aß42 cutoff with acceptable sensitivity and specificity distinguished HC from mild-to-moderate AD subjects and maximized concordance to brain amyloidosis. The defined cutoff demonstrated that CSF analysis may be useful as a surrogate to imaging assessment of AD pathology.

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Aphasia has a large impact on the quality of life and adds significantly to the costs of stroke care. Early recognition of aphasia in stroke patients is important for prognostication and well-timed treatment planning. We aimed to identify available screening tests for differentiating between aphasic and non-aphasic stroke patients, and to evaluate test accuracy, reliability, and feasibility. We searched PubMed, EMbase, Web of Science, and PsycINFO for published studies on screening tests aimed at assessing aphasia in stroke patients. The reference lists of the selected articles were scanned, and several experts were contacted to detect additional references. Of each screening test, we estimated the sensitivity, specificity, likelihood ratio of a positive test, likelihood ratio of a negative test, and diagnostic odds ratio (DOR), and rated the degree of bias of the validation method. We included ten studies evaluating eight screening tests. There was a large variation across studies regarding sample size, patient characteristics, and reference tests used for validation. Many papers failed to report on the consecutiveness of patient inclusion, time between aphasia onset and administration of the screening test, and blinding. Of the three studies that were rated as having an intermediate or low risk of bias, the DOR was highest for the Language Screening Test and ScreeLing. Several screening tools for aphasia in stroke are available, but many tests have not been verified properly. Methodologically sound validation studies of aphasia screening tests are needed to determine their usefulness in clinical practice.

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