The splenial angle: a novel radiological index for idiopathic normal pressure hydrocephalus.

OBJECTIVES: To evaluate the utility of the splenial angle (SA), an axial angular index of lateral ventriculomegaly measured on diffusion tensor MRI color fractional anisotropy maps, in differentiating NPH from Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls (HC), and post-shunt changes in NPH, compared to Evans' index and callosal angle. METHODS: Evans' index, callosal angle, and SA were measured on brain MRI of 76 subjects comprising equal numbers of age- and sex-matched subjects from each cohort of NPH, AD, PD, and HC by two raters. Receiver operating characteristics (ROC) and multivariable analysis were used to assess the screening performance of each measure in differentiating and predicting NPH from non-NPH groups respectively. Temporal changes in the measures on 1-year follow-up MRI in 11 NPH patients (with or without ventriculoperitoneal shunting) were also assessed. RESULTS: Inter-rater and intra-rater reliability were excellent for all measurements (intraclass correlation coefficients > 0.9). Pairwise comparison showed that SA was statistically different between NPH and AD/PD/HC subjects (p < 0.0001). SA performed the best in predicting NPH, with an area under the ROC curve of > 0.98, and was the only measure left in the final model of the multivariable analysis. Significant (p < 0.01) change in SA was seen at follow-up MRI of NPH patients who were shunted compared to those who were not. CONCLUSIONS: The SA is readily measured on axial DTI color FA maps compared to the callosal angle and shows superior performance differentiating NPH from neurodegenerative disorders and sensitivity to ventricular changes in NPH after surgical intervention. KEY POINTS: • The splenial angle is a novel simple angular radiological index proposed for idiopathic normal pressure hydrocephalus, measured in the ubiquitous axial plane on DTI color fractional anisotropy maps. • The splenial angle quantitates the compression and stretching of the posterior callosal commissural fibers alongside the distended lateral ventricles in idiopathic normal pressure hydrocephalus (NPH) using tools readily accessible in clinical practice and shows excellent test-retest reliability. • Splenial angle outperforms Evans' index and callosal angle in predicting NPH from healthy, Parkinson's disease, and Alzheimer's disease subjects on ROC analysis with an area under the curve of > 0.98 and is sensitive to morphological ventricular changes in NPH patients after ventricular shunting.

Callosal angle in idiopathic normal pressure hydrocephalus: small angular mal-rotations of the coronal plane affect measurement reliability.

PURPOSE: The callosal angle (CA) is a useful biomarker in the diagnosis and management of idiopathic normal pressure hydrocephalus (NPH). Used incorrectly, CA measurements are variable, affecting its reliability as a clinical tool. Our objectives are to evaluate (i) reproducibility of established CA measurements between trained raters and (ii) impact of minor angular mal-rotations of the true coronal plane on CA measurements. METHODS: CAs were measured by two independent raters on three-dimensional isovolumetric T1-weighted brain MRI of NPH patients and healthy controls using the established true coronal plane reformatted orthogonal to the plane containing the anterior-posterior commissural (AC-PC) line at the level of the posterior commissure. CA changes were subsequently evaluated when the coronal plane was mal-rotated by ± 5° and ± 10° in anterior-posterior and clockwise-anticlockwise directions. Inter-rater reliability of CA measurements was assessed using the intraclass correlation coefficient (ICC). RESULTS: On the true coronal plane, inter-rater ICC was excellent (0.973) for NPH patients and good (0.875) for controls. On mal-rotated coronal plane setups, ICC for CA was worse in controls (0.484-0.886) than NPH (0.879-0.981) groups and in clockwise-anticlockwise (0.484-0.956) than anterior-posterior (0.503-0.981) mal-rotations. CA changes secondary to mal-rotations from the true coronal plane were significant in NPH patients (P < 0.0001 to 0.0378) but not in controls (P > 0.1). CONCLUSION: This is the first demonstration of how small angular mal-rotations of the coronal plane used for CA measurement affect its value and inter-rater reliability, highlighting the importance of a standardized protocol when measuring the CA in NPH workup.

[An experience applying the transtheoretical model to assist a highly educated case to quit smoking].

Although smokers who are highly educated understand the risks involved in smoking, they tend to be highly influenced by the opinions of others and thus subject to severe social pressures. This is a case report on the application of the transtheoretical model of behavioral change to a an individual with a PhD in biotechnology who had been smoking for 20 years. The effects of the developed smoking cessation intervention were investigated and data were collected through personal meetings, telephone interviews, and e-mail during a smoking cessation counseling program that lasted from October 18th, 2012, to April 15th, 2013. The results of the assessment indicated that the main problem encountered by the case when quitting was a lack of confidence in attempting to quit smoking after experiencing previous failed attempts. In this report, strategies related to the transtheoretical model were used and counseling was provided during the smoking cessation process. Individualized strategic methods were developed to be effective in highly educated people who smoke in order to achieve successfully cessation of smoking. This report serves as a reference for using the transtheoretical model of behavioral change in developing smoking cessation programs.

Evaluation of Compressed SENSE on Image Quality and Reduction of MRI Acquisition Time: A Clinical Validation Study.

RATIONALE AND OBJECTIVES: To evaluate the effect of compressed SENSE (CS) in clinical settings on scan time reduction and image quality. MATERIALS AND METHODS: Ninety-five magnetic resonance imaging (MRI) scans from different anatomical regions were acquired, consisting of a standard protocol sequence (SS) and sequence accelerated with CS. Anonymized paired sequences were randomly displayed and rated by six blinded subspecialty radiologists. Side-by-side evaluation on perceived sharpness, perceived signal-to-noise-ratio (SNR), lesion conspicuity, and artifacts were compared and scored on a five-point Likert scale, and individual image quality was evaluated on a four-point Likert scale. RESULTS: CS reduced overall scan time by 32% while maintaining acceptable MRI quality for all regions. The largest time savings were seen in the spine (mean = 68 seconds, 44% reduction) followed by the brain (mean = 86 seconds, 37% reduction). The sequence with maximum time savings was intracranial 3D-time-of-flight magnetic resonance angiography (202 seconds, 56% reduction). CS was mildly inferior to SS on perceived sharpness, perceived SNR, and lesion conspicuity (mean scores = 2.32-2.96, P < .001 [1: SS superior; 3: equivalent; 5: CS superior]). CS was equivalent to SS for joint and body scans on overall image quality (CS = 3.02-3.37, SS = 3.04-3.68, P > .05, [1: lowest quality and 4: highest quality]). The overall image quality of CS was slightly less for brain and spine scans (mean CS = 2.79-3.05, mean SS = 3.13-3.43, P = .021) but still diagnostic. Good overall clinical acceptance for CS (88%) was noted with full clinical acceptance for body scans (100%) and high acceptance for other regions (68%-95%). CONCLUSION: CS significantly reduced MR acquisition time while maintaining acceptable image quality. The implementation of CS may improve departmental workflows and enhance patient care.

Microstructure of Brain Nuclei in Early Parkinson's Disease: Longitudinal Diffusion Kurtosis Imaging.

BACKGROUND: Diffusion kurtosis imaging provides in vivo measurement of microstructural tissue characteristics and could help guide management of Parkinson's disease. OBJECTIVE: To investigate longitudinal diffusion kurtosis imaging changes on magnetic resonance imaging in the deep grey nuclei in people with early Parkinson's disease over two years, and whether they correlate with disease progression. METHODS: We conducted a longitudinal case-control study of early Parkinson's disease. 262 people (Parkinson's disease: n = 185, aged 67.5±9.1 years; 43% female; healthy controls: n = 77, aged 66.6±8.1 years; 53% female) underwent diffusion kurtosis imaging and clinical assessment at baseline and two-year timepoints. We automatically segmented five nuclei, comparing the mean kurtosis and other diffusion kurtosis imaging indices between groups and over time using repeated-measures analysis of variance, and Pearson correlation with the two-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III. RESULTS: At baseline, mean kurtosis was higher in Parkinson's disease than controls in the substantia nigra, putamen, thalamus and globus pallidus when adjusting for age, sex, and levodopa equivalent daily dose (p < 0.027). These differences grew over two years, with mean kurtosis increasing for the Parkinson's disease group while remaining stable for the control group; evident in significant "group ×time" interaction effects for the putamen, thalamus and globus pallidus (ηp2= 0.08-0.11, p < 0.015). However, we did not detect significant correlations between increasing mean kurtosis and declining motor function in the Parkinson's disease group. CONCLUSION: Diffusion kurtosis imaging of specific grey matter structures shows abnormal microstructure in PD at baseline and abnormal progression in PD over two years.

Quantitative iron-neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification.

Background: Neuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case-control PD cohort, we evaluated the diagnostic accuracy of quantitative iron-neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association. Methods: PD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin-iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity. Results: In total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p < 0.0001) and smaller sizes after thresholding for low susceptibility (p < 0.0001) on QSM and (b) lower contrast range (p < 0.0001) and smaller sizes after thresholding for high-signal voxels (p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r | <0.6, p < 0.0001), respectively. A composite quantitative neuromelanin-iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI. Conclusion: Quantitative neuromelanin-iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.

Parkinson's Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1.

Parkinson's disease (PD) is a debilitating movement disorder characterised by the loss of dopaminergic neurons in the substantia nigra. As neuroprotective agents mitigating the rate of neurodegeneration are unavailable, the current therapies largely focus only on symptomatic relief. Here, we identified stress-inducible phosphoprotein 1 (STIP1) as a putative neuroprotective factor targeted by PD-specific autoantibodies. STIP1 is a co-chaperone with reported neuroprotective capacities in mouse Alzheimer's disease and stroke models. With human dopaminergic neurons derived from induced pluripotent stem cells, STIP1 was found to alleviate staurosporine-induced neurotoxicity. A case-control study involving 50 PD patients (average age = 62.94 ± 8.48, Hoehn and Yahr >2 = 55%) and 50 age-matched healthy controls (HCs) (average age = 63.1 ± 8) further revealed high levels of STIP1 autoantibodies in 20% of PD patients compared to 10% of HCs. Using an overlapping peptide library covering the STIP1 protein, we identified four PD-specific B cell epitopes that were not recognised in HCs. All of these epitopes were located within regions crucial for STIP1's chaperone function or prion protein association. Our clinical and neuro-immunological studies highlight the potential of the STIP1 co-chaperone as an endogenous neuroprotective agent in PD and suggest the possible involvement of autoimmune mechanisms via the production of autoantibodies in a subset of individuals.

Plasma Neurofilament Light Concentration Is Associated with Diffusion-Tensor MRI-Based Measures of Neurodegeneration in Early Parkinson's Disease.

BACKGROUND: Neurofilament light is a marker of axonal degeneration, whose measurement from peripheral blood was recently made possible by new assays. OBJECTIVE: We aimed to determine whether plasma neurofilament light chain (NfL) concentration reflects brain white matter integrity in patients with early Parkinson's disease (PD). METHODS: 137 early PD patients and 51 healthy controls were included. Plasma NfL levels were measured using ultrasensitive single molecule array. 3T MRI including diffusion tensor imaging was acquired for voxelwise analysis of association between NfL and both fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts and subcortical nuclei. RESULTS: A pattern of brain microstructural changes consistent with neurodegeneration was associated with increased plasma NfL in most of the frontal lobe and right internal capsule, with decreased FA and increased MD. The same clusters were also associated with poorer global cognition. A significant cluster in the left putamen was associated with increased NfL, with a significantly greater effect in PD than controls. CONCLUSION: Plasma NfL may be associated with brain microstructure, as measured using diffusion tensor imaging, in patients with early PD. Higher plasma NfL was associated with a frontal pattern of neurodegeneration that also correlates with cognitive performance in our cohort. This may support a future role for plasma NfL as an accessible biomarker for neurodegeneration and cognitive dysfunction in PD.

Corrigendum: Increased Activation of Default Mode Network in Early Parkinson's With Excessive Daytime Sleepiness.

[This corrects the article DOI: 10.3389/fnins.2019.01334.].

Increased Activation of Default Mode Network in Early Parkinson's With Excessive Daytime Sleepiness.

BACKGROUND AND OBJECTIVES: The underlying neuropathology of excessive daytime sleepiness (EDS) remains elusive in Parkinson's disease (PD). We aim to investigate neural network changes that underlie EDS in PD. METHODS: Early PD patients comprising eighty-one patients without EDS (EDS-) and seventeen patients with EDS (EDS+) received a resting state functional MRI scan and the Epworth Sleepiness Scale (ESS). Connectivities within the default mode network (DMN), motor and basal ganglia networks were compared between the EDS+ and EDS- groups. Correlations between network connectivity and the severity of EDS were investigated through linear regression. RESULTS: EDS+ patients displayed a trend of increased network connectivity of the posterior DMN (pDMN). A significant positive correlation was found between connectivity of the ventromedial prefrontal cortex in the pDMN and ESS. CONCLUSION: EDS+ patients are likely to display increased activation in the DMN, suggesting neural compensation in early PD or impaired attentiveness due to mechanisms such as mind-wandering.

Neuropsychiatry--an emerging field.

Neuropsychiatry is an emerging field at the intersection of neurology and psychiatry, driven by the unprecedented advances in neuroscience. The arbitrary demarcation between neurology and psychiatry, which largely existed only in the last century and a half, has become less tenable. We discuss the definition and scope of this emerging field. We also review the development of clinical neuropsychiatry in Singapore in the context of historical developments and recent changes in the field from other countries. At a more practical level, we discuss a few of the clinical settings in which neuropsychiatry operates, in particular, the stigma associated with psychiatric disorders locally, and the significant number of patients with psychiatric or psychosomatic symptoms presenting to neurology and general practice clinics. The stigma may be ameliorated by better understanding of the neurobiological basis of psychiatry. We see the future of neuropsychiatry in Singapore, as in other developed countries, as one approach to understand and manage complex brain disorders. We advocate training for both psychiatry and neurology residents in their counterpart fields, which will lead to greater understanding of both fields, and enhance collaboration in clinical care and research.

Afebrile seizures associated with minor infections: comparison with febrile seizures and unprovoked seizures.

This study aimed to demonstrate that afebrile seizures provoked by minor infections constitute a distinct epilepsy syndrome different from febrile seizures and unprovoked afebrile seizures. Of the children who were admitted to hospitals for their first seizure, 1170 had febrile seizures, 286 had provoked seizures, and 125 had unprovoked afebrile seizures. Children with provoked seizures were afebrile at the time of seizure but manifested definite symptoms or signs of minor infection, for example, cough, coryza, vomiting or diarrhea, normal metabolic and cerebrospinal fluid investigations, and no obvious cause for their seizures. The average follow-up was 6.1 years. The Kaplan-Meier estimate of risk at 5 years for subsequent unprovoked afebrile seizures after a first febrile seizure, provoked seizure, or unprovoked afebrile seizure was 1.6%, 5.7%, and 65.7% respectively. All differences were statistically significant (P < 0.0014). In conclusion, afebrile seizures provoked by minor illnesses constitute a distinct type of situation-related seizures, which have not been previously described. Children with provoked seizures have a much lower risk of subsequent unprovoked afebrile seizures than patients with the first afebrile seizure. Careful inquiry for symptoms of minor infections when children present with their first afebrile seizure will help determine the risk for subsequent seizures and the need for antiepileptic drugs.

Absence of A673T amyloid-ß precursor protein variant in Alzheimer's disease and other neurological diseases.

The rare variant A673T in the amyloid-ß precursor protein (APP) gene has been shown to reduce the risk of cognitive impairment. We genotyped the variant in 8721 Asian individuals comprising 552 with Alzheimer's disease and vascular dementia, 790 with Parkinson's disease, and 7379 controls. The A673T variant was absent in all of the subjects. Our finding suggests that the A673T protective variant is not relevant in our Asian population. Studies in other ethnic populations would clarify whether this variant is specific to specific races/ethnicities.

Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Health-related quality of life, emotional and behavioral problems in mild to moderate prematures at (pre-)school age.

BACKGROUND: There is a gap in the knowledge of longterm outcome of mild to moderate prematures compared to the extreme prematures or very low birth weight infants. AIM: Determine health-related quality of life (HRQoL) and prevalence of emotional and behavioral problems in (pre-)school age children born at 32 to 36 weeks' gestation. STUDY DESIGN: A descriptive cohort study in a non-Neonatal Intensive Care Unit. Patient characteristics, diagnoses, treatment and social economic status (SES) were analyzed. Study tools were the TNO-AZL Preschool Quality of Life (TAPQoL) and Child Behavior Checklist (CBCL). SUBJECTS: 362 children born between 32 and 36 weeks' gestation who had a follow-up evaluation at 2-5 years of age. OUTCOME MEASURE: Health-related quality of life and the occurrence of emotional and behavioral problems. RESULTS: Main characteristics (mean±SD) were: gestation 34.7±1 weeks and birth weight 2360±444 g. Most families were two-parent middle-class households with parents employed at their educational level. Questionnaire response rate was 62.7%. The 12-item TAPQoL showed significantly lower scores for stomach and liveliness, while scores for behavior, communication and sleep were significantly higher compared to the general population. The TAPQoL subscale score for lung problems was significantly lower for children who had received continuous positive airway pressure (CPAP). CBCL scores were within the validated normal range although the study-population scored higher on emotionally reactive, somatic complaints and attention problems compared to their full-term peers. CONCLUSION: Children born at 32 to 36 weeks' gestational age do not experience an overall lower HR-QoL at 2 to 5 years of age. CPAP results in lower HRQoL scores for lung problems. The overall occurrence of behavioral and emotional problems does not differ from the general term-born pediatric population. Several subitems need further attention.

Risk factors for peripheral intravenous catheter infection in hospitalized patients: a prospective study of 3165 patients.

We conducted a prospective study of 6538 polyurethane peripheral intravenous (IV) catheters in 3165 hospitalized adult patients using semiquantitative culture techniques. We found that extending the scheduled catheter replacement interval from 48 to 72 hours to 72 to 96 hours was not a risk factor for local catheter infection, but that catheter insertion by personnel other than IV therapists and the use of continuous infusion to maintain catheter patency were 2 independent risk factors for infection.