Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease.

Importance: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly lethal disease. Rapid, accurate diagnosis is imperative for epidemiological surveillance and public health activities to exclude treatable differentials and facilitate supportive care. In 2017, the International CJD Surveillance Network diagnostic criteria were revised to incorporate cortical ribboning on magnetic resonance imaging and the real-time quaking-induced conversion (RT-QuIC) assay, developments that require multicenter evaluation. Objective: To evaluate the accuracy of revised diagnostic criteria through the retrospective diagnosis of autopsy-confirmed cases (referred to as in-life diagnosis). Design, Setting, and Participants: This diagnostic study used a 3-year clinicopathological series using all cases of autopsy-confirmed sCJD and a noncase group with alternative neuropathological diagnoses from national surveillance centers in the United Kingdom, France, Germany, and Italy. Data were collected from January 2017 to December 2019 and analyzed from January 2020 to November 2021. Main Outcomes and Measures: Sensitivity and specificity of revised diagnostic criteria and diagnostic investigations. Secondary analyses assessing sCJD subgroups by genotype, pathological classification, disease duration, and age. Results: A total of 501 sCJD cases and 146 noncases were included. Noncase diagnoses included neurodegenerative diseases, autoimmune encephalitis, and cerebral insults such as anoxia. Participants in the sCJD cases cohort were younger (mean [SD] age, 68.8 [9.8] years vs 72.8 [10.9] years; P < .001) and had longer median (IQR) disease duration (118 [74.8-222.3] days vs 85 [51.5-205.5] days; P = .002); sex ratios were equivalent (253 [50.5%] male cases vs 74 [50.7%] male noncases). Sensitivity of revised criteria in in-life diagnosis (450 of 488 [92.2%] diagnoses; 95% CI, 89.5%-94.4%) was increased compared with prior criteria (378 of 488 [77.5%] diagnoses; 95% CI, 73.5%-81.1%; P < .001), while specificity (101 of 125 [80.8%] diagnoses; 95% CI, 72.8%-87.3%) was unchanged (102 of 125 [81.6%] diagnoses; 95% CI, 73.7%-88.0%; P > .99). Among 223 cases and 52 noncases with the full panel of investigations performed, sensitivity of revised criteria (97.8%; 95% CI, 94.9%-99.3%) was increased compared with prior criteria (76.2%; 95% CI, 70.1%-81.7%; P < .001) while specificity was unchanged (67.3%; 95% CI, 52.9%-79.7% vs 69.2%; 95% CI, 54.9%-81.3%; P > .99). In 455 cases and 111 noncases, cortical ribboning was 67.9% sensitive (95% CI, 63.4%-72.2%) and 86.5% specific (95% CI, 78.7%-92.2%). In 274 cases and 77 noncases, RT-QuIC was 91.6% sensitive (95% CI, 87.7%-94.6%) and 100% specific (95% CI, 96.2%-100%). Investigation sensitivity varied with genetic and pathological features, disease duration, and age. Conclusions and Relevance: This diagnostic study demonstrated significantly improved sensitivity of revised sCJD diagnostic criteria with unaltered specificity. The revision has enhanced diagnostic accuracy for clinical care and surveillance.

Construct Validity of the Upper-Limb Interlimb Coordination Test in Stroke.

BACKGROUND: Coordination impairments are under-evaluated in patients with stroke due to the lack of validated assessments resulting in an unclear relationship between coordination deficits and functional limitations. OBJECTIVE: Determine the construct validity of the new clinical upper-limb (UL) Interlimb Coordination test (ILC2) in individuals with chronic stroke. METHODS: Thirteen individuals with stroke, ≥40 years, with ≥30° isolated supination of the more-affected (MAff) arm, who could understand instructions and 13 healthy controls of similar age participated in a cross-sectional study. Participants performed synchronous bilateral anti-phase forearm rotations for 10 seconds in 4 conditions: self-paced internally-paced (IP1), fast internally-paced (IP2), slow externally-paced (EP1), and fast externally-paced (EP2). Primary (continuous relative phase-CRP, cross-correlation, lag) and secondary outcome measures (UL and trunk kinematics) were compared between groups. RESULTS: Participants with stroke made slower UL movements than controls in all conditions, except EP1. Cross-correlation coefficients were lower (i.e., closer to 0) in stroke in IP1, but CRP and lag were similar between groups. In IP1 and matched-speed conditions (IP1 for healthy and IP2 for stroke), stroke participants used compensatory trunk and shoulder movements. The synchronicity sub-scale and total scores of ILC2 were related to temporal coordination in IP2. Interlimb Coordination test total score was related to greater shoulder rotation of the MAff arm. Interlimb Coordination test scores were not related to clinical scores. CONCLUSION: Interlimb Coordination test is a valid clinical measure that may be used to objectively assess UL interlimb coordination in individuals with chronic stroke. Further reliability testing is needed to determine the clinical utility of the scale.

Convergent validity of the developmental coordination disorder checklist using soft neurological signs.

AIMS: To investigate the convergent validity of a new questionnaire, the Developmental Coordination Disorder Checklist (DCDC), we examined the relationship between the DCDC score and Soft Neurological Signs (SNS) which highly correlated with the Movement Assessment Battery for Children (MABC), which is widely applied to assess fine and gross motor skills. METHODS: The patients were 70 elementary school children without intellectual disabilities who were referred to our clinic, examined for SNS, and whose parents completed the DCDC. The DCDC consists of 16 items that focus on three factors: fine motor, gross motor, and catch and throw. We used a previously described method to assess SNS, which included five tasks: (1) standing on one leg with closed eyes, (2) finger opposition test, (3) diadochokinesis, (4) associated movements during diadochokinesis, and (5) motor persistence (laterally fixed gaze). RESULTS: DCDC scores and SNS were strongly and positively correlated, with higher DCDC scores (indicating greater coordination problems) associated with a higher number of positive SNS. CONCLUSIONS: DCDC scores have been proven to be strongly correlated with SNS, and these data suggest that DCDC has good convergent validity.

Validation and comparison of prognostic scales in Chinese patients with ischemic stroke: a prospective study from CATIS.

BACKGROUND: : Various tools are currently available to quantify the risks of adverse clinical outcomes after an ischemic stroke. This study aimed to validate and compare prognostic scales among Chinese patients with ischemic stroke. METHODS: : We compared three stroke prognostic scales (Stroke Prognostication using Age and the National Institutes of Health Stroke Scale-100 [SPAN-100], Totaled Health Risks in Vascular Events [THRIVE], and Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) in 3870 Chinese patients with ischemic stroke from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The 2-year primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3). RESULTS: : Among all the scales, the ASTRAL score had the best accuracy for predicting 2-year prognosis in Chinese patients with ischemic stroke. The C-statistic of the ASTRAL score for the 2-year primary outcome was 0.79 (95% confidence interval [CI]: 0.78-0.80), and the Hosmer-Lemeshow goodness-of-fit test showed that the ASTRAL score fitted Chinese patients with ischemic stroke well (χ2 = 9.83, P = 0.277). The incidences of the primary outcome in the <5%, 5%-9.9%, 10%-19.9%, and ≥20% risk groups based on the ASTRAL scores were 3.93%, 7.55%, 14.29%, and 41.81%, respectively (odds ratio: 1.23; 95% CI: 1.21-1.26; P < 0.001). CONCLUSION: : The ASTRAL score had higher efficacy than the SPAN-100 and THRIVE scores in predicting 2-year adverse outcomes among Chinese patients with ischemic stroke, suggesting that it could be a valuable risk assessment tool for the 2-year prognosis of such patients.

Clinical Utility of CAT Administered PROMIS Measures to Track Change for Pediatric Chronic Pain.

Patient Reported Outcomes (PROs) are utilized in clinical registries and trials, necessitating development of benchmarks to enhance interpretability. This study aimed to 1) examine if PROMIS measures administered via computer adaptive testing (CAT) were responsive to change, and 2) highlight one method of assessing clinically significant change for youth seen in a tertiary pain clinic. Clinically significant change was achieved if patients had significantly reliable pre-to-post-changes greater than Reliable Change Index (RCI) value and reported decreased symptoms by at least one severity level (e.g., moderate to mild). Participants were 328 youth (8-17 years old) seen in a tertiary pediatric pain management clinic. Small to moderate effect sizes were noted across PROMIS measures (except Peer Relations). Reliable magnitudes of change were estimated for this sample as approximately 6 point reduction for Pain Interference and Mobility, 9 for Fatigue, and 11 for Anxiety and Depression. Depending on the measure, 10 to 24% were categorized as improved, 3 to 6% as deteriorated, and 68 to 81% were either not clinically elevated at baseline or remained unchanged at 3 months. Overall, PROMIS CAT measures demonstrated responsiveness to change over time. Estimation of clinically significant change offers preliminary yet rigorous benchmarks for evaluating treatment response and sets the stage for understanding treatment effects. PERSPECTIVE: This study assesses responsiveness of CAT administered PROMIS measures and highlights one methodological approach of presenting clinical significance for assessing treatment outcomes in pediatric chronic pain. These benchmarks will allow clinicians and researchers to evaluate treatment response utilizing PROs while allowing for a deeper understanding of treatment effects.

Consistently High Agreement Between Independent Raters of Niemann-Pick Type C1 Clinical Severity Scale in Phase 2/3 Trial.

BACKGROUND: Niemann-Pick disease, type C1 (NPC1) is a rare neurodegenerative genetic disorder characterized by impaired intracellular transport of cholesterol and other lipids. The Niemann-Pick Disease, type C1 Severity Scale (NPC-SS) was developed to quantify neurological progression of NPC; it is used to monitor the natural history of disease progression and assess response to treatment. The objective of the study was to examine the interrater reliability of the NPC-SS in a phase 2/3 trial. METHODS: Study data were from a multicenter, prospective, randomized, double-blind trial of adrabetadex in 56 subjects with NPC1. Clinical data recorded at each study site were distributed to two independent blinded central raters to generate a severity score. A composite four-item score was utilized as the primary clinical study end point, whereas a five-item focused score has been utilized in other NPC1 trials. Interrater reliability was assessed using two-way mixed models for instrument stability, Cohen kappa, weighted kappa, and percent agreement for the four- and five-item scores. RESULTS: The frequency distribution and mean (S.D.) of the NPC-SS domain assessments by the raters were almost identical. Evaluation at the patient visit level showed wide variability between visits; however, weighted kappa calculation provided a lower variability between visits. The average kappa coefficients ranged between 0.69 and 0.89, indicating good to very good agreement between raters. CONCLUSIONS: These results support the NPC-SS, including derived four- and five-item composite scores, as reliable measures for use in a clinical trial setting.

Gold Standard for Diagnosis of DPN.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. It often causes symmetrical paresthesia, loss of sensation, and hyperalgesia. Without early intervention, it might lead to diabetic foot ulceration, gangrene, and subsequent amputation in people with diabetes. DPN is an insidious disease and often underdiagnosed. This paper reviews the current national and international prevalence of DPN, screening methods for early DPN, including quantitative sensory measurement, neurological function scoring system, confocal microscopy, and high-frequency ultrasound, and summarizes the related research progress, clinical application, and development prospects of these methods in recent years.

General movement assessment is correlated with neonatal behavior neurological assessment/cerebral magnetic resonance imaging in preterm infants.

ABSTRACT: To explore the relationship between general movements (GMs) and neonatal behavior neurological assessment (NBNA)/cerebral magnetic resonance imaging (MRI) in preterm infants.Forty preterm infants were examined with GMs assessment before gestational age of 40 weeks; NBNA was performed at the age of 40 weeks; cerebral MRI was performed at the age of 42 weeks.Our experiment showed that preterm infants with poor GMs scores are more likely to have low NBNA scores (P = .001); preterm infants with abnormal cerebral MRI are more likely to have low NBNA scores (P = .002); preterm infants with poor GMs scores are more likely to have abnormal cerebral MRI (P = .012).GM assessment is correlated with NBNA and MRI results in preterm infants for neurological development.

Digital endpoints for self-administered home-based functional assessment in pediatric Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia is an inherited, progressive, neurodegenerative disease that typically begins in childhood. Disease severity is commonly assessed with rating scales, such as the modified Friedreich's Ataxia Rating Scale, which are usually administered in the clinic by a neurology specialist. OBJECTIVE: This study evaluated the utility of home-based, self-administered digital endpoints in children with Friedreich's ataxia and unaffected controls and their relationship to standard clinical rating scales. METHODS: In a cross-sectional study with 25 participants (13 with Friedreich's ataxia and 12 unaffected controls, aged 6-15 years), home-based digital endpoints that reflect activities of daily living were recorded over 1 week. Domains analyzed were hand motor function with a digitized drawing, automated analysis of speech with a recorded oral diadochokinesis test, and gait and balance with wearable sensors. RESULTS: Hand-drawing and speech tests were easy to conduct and generated high-quality data. The sensor-based gait and balance tests suffered from technical limitations in this study setup. Several parameters discriminated between groups or correlated strongly with modified Friedreich's Ataxia Rating Scale total score and activities of daily living total score in the Friedreich's ataxia group. Hand-drawing parameters also strongly correlated with standard 9-hole peg test scores. INTERPRETATION: Deploying digital endpoints in home settings is feasible in this population, results in meaningful and robust data collection, and may allow for frequent sampling over longer periods of time to track disease progression. Care must be taken when training participants, and investigators should consider the complexity of the tasks and equipment used.

Validity and Reliability of the Neuromuscular Gross Motor Outcome.

BACKGROUND: Approved treatments in spinal muscular atrophy (SMA) have resulted in unprecedented gains for many individuals. Use of available outcomes, typically developed for a specific type of SMA, do not cover the range of progression, often resulting in a battery of functional testing being completed at visits. Our objective was to validate the Neuromuscular Gross Motor Outcome (GRO) as a tool to quantify function in SMA across the span of abilities. METHODS: Patients with genetically confirmed SMA completed functional testing at each visit including the Neuromuscular GRO and other appropriate gross motor outcomes. RESULTS: We enrolled 91 patients with SMA types 1 to 3 between 8 days and 32.1 years. The GRO utilizes a 0- to 2-point scale with scores in our cohort ranging from 1 to 95 points with no floor or ceiling effect. GRO scores were significantly different across functional categories (P < 0.001) and treatment status (P = 0.01) and correlated to other functional assessments (P ≤ 0.001). All patients were measured using the GRO, whereas traditional outcomes were only appropriate on 36% to 59% of our cohort. CONCLUSION: The Neuromuscular GRO quantifies function across the span of age and abilities included in our cohort, allowing for continuous longitudinal monitoring on one scale to reduce the burden of testing in our heterogeneous clinic population.

Neurally adjusted ventilatory assist as a weaning mode for adults with invasive mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Prolonged ventilatory support is associated with poor clinical outcomes. Partial support modes, especially pressure support ventilation, are frequently used in clinical practice but are associated with patient-ventilation asynchrony and deliver fixed levels of assist. Neurally adjusted ventilatory assist (NAVA), a mode of partial ventilatory assist that reduces patient-ventilator asynchrony, may be an alternative for weaning. However, the effects of NAVA on weaning outcomes in clinical practice are unclear. METHODS: We searched PubMed, Embase, Medline, and Cochrane Library from 2007 to December 2020. Randomized controlled trials and crossover trials that compared NAVA and other modes were identified in this study. The primary outcome was weaning success which was defined as the absence of ventilatory support for more than 48 h. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with accompanying 95% confidence interval (CI) were expressed. RESULTS: Seven studies (n = 693 patients) were included. Regarding the primary outcome, patients weaned with NAVA had a higher success rate compared with other partial support modes (OR = 1.93; 95% CI 1.12 to 3.32; P = 0.02). For the secondary outcomes, NAVA may reduce duration of mechanical ventilation (MD = - 2.63; 95% CI - 4.22 to - 1.03; P = 0.001) and hospital mortality (OR = 0.58; 95% CI 0.40 to 0.84; P = 0.004) and prolongs ventilator-free days (MD = 3.48; 95% CI 0.97 to 6.00; P = 0.007) when compared with other modes. CONCLUSIONS: Our study suggests that the NAVA mode may improve the rate of weaning success compared with other partial support modes for difficult to wean patients.

Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity.

BACKGROUND AND OBJECTIVE: There is no agreement on the gold standard for detection and grading of chemotherapy-induced peripheral neurotoxicity (CIPN) in clinical trials. The objective is to perform an observational prospective study to assess and compare patient-based and physician-based methods for detection and grading of CIPN. METHODS: Consecutive patients, aged 18 years or older, candidates for neurotoxic chemotherapy, were enrolled in the United States, European Union, or Australia. A trained investigator performed physician-based scales (Total Neuropathy Score-clinical [TNSc], used to calculate Total Neuropathy Score-nurse [TNSn]) and supervised the patient-completed questionnaire (Functional Assessment of Cancer Treatment/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX]). Evaluations were performed before and at the end of chemotherapy. On participants without neuropathy at baseline, we assessed the association between TNSc, TNSn, and FACT/GOG-NTX. Considering a previously established minimal clinically important difference (MCID) for FACT/GOG-NTX, we identified participants with and without a clinically important deterioration according to this scale. Then, we calculated the MCID for TNSc and TNSn as the difference in the mean change score of these scales between the 2 groups. RESULTS: Data from 254 participants were available: 180 (71%) had normal neurologic status at baseline. At the end of the study, 88% of participants developed any grade of neuropathy. TNSc, TNSn, and FACT/GOG-NTX showed good responsiveness (standardized mean change from baseline to end of chemotherapy >1 for all scales). On the 153 participants without neuropathy at baseline and treated with a known neurotoxic chemotherapy regimen, we verified a moderate correlation in both TNSc and TNSn scores with FACT/GOG-NTX (Spearman correlation index r = 0.6). On the same sample, considering as clinically important a change in the FACT/GOG-NTX score of at least 3.3 points, the MCID was 3.7 for TNSc and 2.8 for the TNSn. CONCLUSIONS: MCID for TNSc and TNSn were calculated and the TNSn can be considered a reliable alternative objective clinical assessment if a more extended neurologic examination is not possible. The FACT/GOG-NTX score can be reduced to 7 items and these items correlate well with the TNSc and TNSn. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a patient-completed questionnaire and nurse-assessed scale correlate with a physician-assessed scale.

Hyperventilation maneuver during EEG in children with epilepsy after the COVID-19 pandemic. Is a routine procedure necessary?

OBJECTIVE: Hyperventilation (HV) is one of the main and basic activation methods during ambulatory electroencephalogram (EEG), unless medical reasons contraindicate it. During the COVID-19 pandemic, with the high risk of human-to-human infection, local guidelines and recommendations have been developed that suggest not to perform the HV maneuver routinely. Our objective was to characterize patients who present positive HV in an epilepsy center. METHODS: We analyzed retrospectively all the ambulatory EEGs performed during one year in our specialized ambulatory child and adolescent epilepsy center, and describe patients with positive maneuver. RESULTS: A total of 305 EEGs were performed. Patients under 3 years and 11 months were excluded as well as all patients that did not fill up the criteria for epilepsy diagnosis. From the 252 EEGs that were included in the study, 194 EEGs (77%) were classified as abnormal and 58 (23%) as normal. From these same 252 EEGs, 150 EEG finished correctly the HV maneuver. Physiological slowing response was found in 54 EEGs (36%), no changes (negative) in 83 (55%), and abnormal response (positive) in 13 EEGs (9%). The 13 HV-positive EEGs showed 4 patients with an increase of epileptiform activity, 3 patients experienced an increase of basal preregistered abnormal slowing, and 6 EEGs showed trigger of bilaterally synchronous and symmetric 2-4 Hz spike-and-slow wave discharges and absences. None of these last 6 patients needed more than 3 minutes to elicit the paroxysmal discharge. SIGNIFICANCE: Based on these findings and according with other studies, the low positivity and high specificity of the HV maneuver support the idea that HV could be excluded during the COVID-19 pandemic situation, and also reevaluate whether it could be changed to a complementary maneuver, restricted only for cases where absence epilepsy is suspected. Larger studies will be needed to reaffirm this proposal.

External validation of the Epilepsy Surgery Grading Scale in a Japanese cohort of patients with epilepsy.

The Epilepsy Surgery Grading Scale (ESGS) is a simple method to predict the likelihood of a patient with epilepsy proceeding to surgery and achieving seizure freedom. Usefulness of the ESGS has been confirmed in established epilepsy centres in the United States and Belgium for adult patients with drug-resistant focal epilepsy undergoing presurgical evaluation. However, the applicability of the ESGS has not yet been evaluated in a wider range of epilepsy patients that may reflect the general spectrum of epilepsy. The present study validated the ESGS in a Japanese epilepsy centre in which admission-based comprehensive epilepsy studies were indicated beyond presurgical evaluation. This single-centre retrospective study included adult patients with epilepsy admitted to the Epilepsy Monitoring Unit from 2010 to June 2019. Patients were classified as ESGS Grade 1 (most favorable), Grade 2 (intermediate), and Grade 3 (least favourable). Patients were grouped into three cohorts: all patients, patients with drug-resistant focal epilepsy, and patients who underwent resective epilepsy surgery. We assessed progression to surgery and seizure freedom at one year after surgery. Of the 1,158 total admissions, 670 patients met the inclusion criteria and formed the total cohort. Of these, 435 (64.9%) had drug-resistant focal epilepsy and 78 (11.6%) proceeded to resective surgery. Overall, progression to surgery was observed in 41.3%, 16.6%, and 4.8% of patients with Grade 1, 2, and 3, respectively. In the surgical cohort, seizure freedom was observed in 85.2%, 65.2%, and 31.3% of patients with Grade 1, 2, and 3, respectively. Our results indicate that the ESGS is effective in predicting whether a patient proceeds to epilepsy surgery and achieves seizure freedom even in the general population of epilepsy patients, regardless of type or resistance to antiepileptic drugs.

Evaluation of the 6-item Identify Chronic Migraine screener in a large medical group.

OBJECTIVE: To evaluate the sensitivity and specificity of the 6-item Identify Chronic Migraine screener (ID-CM[6]), designed to improve the detection of chronic migraine (CM). BACKGROUND: CM is often undertreated and underdiagnosed. Survey-based studies have found that approximately 75-80% of people meeting criteria for CM do not report having received an accurate diagnosis. METHODS: This study used claims data of patients enrolled in a large medical group who had at least one medical claim with an International Classification of Diseases 9th/10th revision diagnostic code for migraine in the 12-month prescreening period. The Identify Chronic Migraine survey was administered by e-mail, in-person, or over the telephone to all enrolled patients. A Semi-Structured Diagnostic Interview (SSDI) was administered by telephone by a trained physician. The ID-CM(6) and SSDI classifications of CM status were compared to evaluate sensitivity and specificity of the ID-CM(6) screening tool. RESULTS: The analysis of the ID-CM(6) screening tool included 109 patients, with 65/109 (59.6%) positive for CM based on the SSDI. The mean (standard deviation) age of the patient sample was 49 (15) years and 100/109 (91.7%) were female. Using the SSDI as the diagnostic gold standard, the ID-CM(6) had a sensitivity of 70.8% (46/65) and a specificity of 93.2% (41/44). CONCLUSION: The ID-CM(6) demonstrated acceptable sensitivity and good specificity in determining CM status. The results of this analysis support the real-world utility of the ID-CM(6) as a simple and useful tool to identify patients with CM.

Additional validation study and French cross-cultural adaptation of the Pediatric Stroke Outcome Measure-Summary of Impressions (PSOM-SOI).

BACKGROUND: The Pediatric Stroke Outcome Measure-Summary of Impressions (PSOM-SOI) measures neurological function across right and left sensorimotor domains (Item A), language production (Item B), language comprehension (Item C), and cognition/behaviour (Item D). OBJECTIVE: This study was a cross-cultural adaptation into French of the PSOM-SOI and an assessment of its reliability and limitations of use. MATERIAL AND METHODS: The translation and adaptation of the PSOM-SOI was followed by the assessment of its reliability in a cohort of 69 children with diagnosed acute neonatal arterial ischemic stroke. Three independent raters retrospectively scored the PSOM-SOI based on data from in-person neurological examination and results of standardized tests performed at age 7 in the cohort database. Comparison 1 (C1) involved a less experienced rater and an experienced rater and comparison 2 (C2) involved 2 experienced raters. Inter-rater reliability (IRR) was measured with Kappa coefficients. RESULTS: The cross-cultural adaptation was easily performed, and no rater had difficulties using the French PSOM-SOI. The IRR was better in C1 than C2. For Item A, the agreement in C1 (κ=0.47) and C2 (κ=0.44) was moderate. The C1 agreement was substantial for Items B (κ=0.71) and C (κ=0.70); the C2 agreement was fair for Item B (κ=0.23) and slight for Item C (κ=0.16). For Item D, the agreement was moderate in C1 (κ=0.52) and fair in C2 (κ=0.35). In all but one comparison, agreement or minor disagreement (≤0.5 points) was obtained for more than 90% of the item scores. Regarding the total score, agreement for normal function (≤0.5) versus abnormal function (>0.5) was achieved for 90% in C1 and 67% in C2. CONCLUSION: The IRR of the French PSOM-SOI gave variable results depending on the item and rater's experience, but the extent of disagreements was minor for individual items and total score. Additional prospective validation studies using the French PSOM-Short Neurological Exam to score the PSOM-SOI are needed. A dichotomised total score (cut-off≤0.5) could be used to define normal function versus poor outcome.

Cerebrospinal fluid biomarker profiling in corticobasal degeneration: Application of the AT(N) and other classification systems.

INTRODUCTION: Total tau (τT), phosphorylated tau (τP-181) and amyloid beta (Aß42) are cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). There is no consensus on the interpretation criteria of these biomarkers. The aim of this study was to apply three different sets of criteria for CSF AD biomarker interpretation in a cohort of corticobasal degeneration (CBD) patients. METHOD: SForty patients fulfilling diagnostic criteria for "probable CBD" were included. The AT(N), BIOMARKAPD/ABSI and the τP-181/Aß42 ratio criteria were applied. RESULTS: The AT(N) criteria categorized 50% of "probable CBD" patients as AD, and 62.5% as harboring amyloid pathology. The BIOMARKAPD/ABSI and τP- 181/Aß42 criteria categorized ~40% of "probable CBD" patients as AD. DISCUSSION: Use of different interpretation criteria for CSF AD biomarkers produces diverse results. AD pathology is common in patients fulfilling "probable" CBD criteria. CBD diagnostic criteria may have suboptimal positive predictive value. A consensus regarding interpretation criteria of CSF AD biomarkers is pivotal.

Development of a Comprehensive Outcome Measure for Motor Coordination; Step 1: Three-Phase Content Validity Process.

BACKGROUND: Motor coordination, the ability to produce context-dependent organized movements in spatial and temporal domains, is impaired after neurological injuries. Outcome measures assessing coordination mostly quantify endpoint performance variables (ie, temporal qualities of whole arm movement) but not movement quality (ie, trunk and arm joint displacements). OBJECTIVE: To develop an outcome measure to assess coordination of multiple body segments at both endpoint trajectory and movement quality levels, based on observational kinematics, in adults with neurological injuries. METHODS: A 3-phase study was used to develop the Comprehensive Coordination Scale (CCS): instrument development, Delphi process, and focus group meeting. The CCS was constructed from common tests used in clinical practice and research. Rating scales for different behavioral elements were developed to guide analysis. For content validation, 8 experts (ie, neurological clinicians/researchers) answered questionnaires about relevance, comprehension, and feasibility of each test and rating scale. A focus group conducted with 6 of 8 experts obtained consensus on rating scale and instruction wording, and identified gaps. Three additional experts reviewed the revised CCS content to obtain a final version. RESULTS: Experts identified a gap regarding assessment of hand/finger coordination. The CCS final version is composed of 6 complementary tests of coordination: finger-to-nose, arm-trunk, finger, lower extremity, and 2- and 4-limb interlimb coordination. Constructs include spatial and temporal variables totaling 69 points. Higher scores indicate better performance. CONCLUSIONS: The CCS may be an important, understandable and feasible outcome measure to assess spatial and temporal coordination. CCS measurement properties are presented in the companion article.