Age-matched Normal Control Subjects Research Articles

Mechanical versus bioprosthetic valves in chronic dialysis: a systematic review and meta-analysis.

Background:Many patients with end-stage kidney disease (ESKD) have valvular heart disease requiring surgery. The optimal prosthetic valve is not established in this population. We performed a systematic review and meta-analysis to assess outcomes of patients with dialysis-dependent ESKD who received mechanical or bioprosthetic valves.Methods:We searched Cochrane Central, Medline and Embase from inception to January 2020. We performed screening, full-text assessment, risk of bias and data collection, independently and in duplicate. Data were pooled using a random-effects model.Results:We identified 28 observational studies (n = 9857 patients, including 6680 with mechanical valves and 3717 with bioprosthetic valves) with a median follow-up of 3.45 years. Twenty-two studies were at high risk of bias and 1 was at critical risk of bias from confounding. Certainty in evidence was very low for all outcomes except bleeding. Mechanical valves were associated with reduced mortality at 30 days (relative risk [RR] 0.79, 95% confidence interval [CI] 0.65–0.97, I2 = 0, absolute effect 27 fewer deaths per 1000) and at 6 or more years (mean 9.7 yr, RR 0.83, 95% CI 0.72–0.96, I2 = 79%, absolute effect 145 fewer deaths per 1000), but increased bleeding (incidence rate ratio [IRR] 2.46, 95% CI 1.41–4.27, I2 = 59%, absolute effect 91 more events per 1000) and stroke (IRR 1.63, 95% CI 1.21–2.20, I2 = 0%, absolute effect 25 more events per 1000).Conclusion:Mechanical valves were associated with reduced mortality, but increased rate of bleeding and stroke. Given very low certainty for evidence of mortality and stroke outcomes, patients and clinicians may choose prosthetic valves based on factors such as bleeding risk and valve longevity.Study registration:PROSPERO no. CRD42017081863

Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer\u2019s disease

BackgroundMitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF.MethodsThirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed.ResultsThe [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR.ConclusionsOur results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

Unilateral Cleft Lip Nasal Deformity: Foundation-Based Approach to Primary Rhinoplasty.

Cleft lip results in disruption of the nasal foundation and collapse of tip structures. Most approaches to primary rhinoplasty focus on correction of lower lateral cartilages; however, recurrent deformity is common, and secondary revision is frequently required. The authors describe an alternate approach that focuses on the foundation to "upright the nose," without any nasal tip dissection. This study assessed changes with surgery and with growth. Secondary goals were to compare methods of sidewall reconstruction and septoplasty and to identify predictors of relapse. Consecutive patients undergoing repair (n = 102) were assessed. Images were captured preoperatively, postoperatively, and at 5 years of age (when available) using three-dimensional stereophotogrammetry. Standard anthropometric and contemporary shape-based analysis (volume ratio, dorsal deviation, and alar-cheek definition) was performed to assess longitudinal changes. Images of age-matched normal control subjects were used for comparison. Significant changes in anthropometric and morphometric measurements occurred following surgery. Postoperative form was similar to controls immediately after surgery and at 5 years. Nasal corrections were satisfactory, and only two patients have elected to undergo revision. When subjects were grouped according to cleft type, we found the same trends. When comparing different methods of nasal sidewall reconstruction or septoplasty, we found no differences. Alveolar cleft width was a significant predictor of worse preoperative and postoperative form. Significant nasal correction can be achieved by means of reconstruction of nasal foundation, without nasal tip dissection. Preservation of tissue planes may allow for easier secondary revision, if necessary. Therapeutic, IV.

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer's disease.

Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer's disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [11C]PBB3 and [11C]DPA713. Twenty patients with early AD and 20 age-matched normal control (NC) subjects underwent a series of PET measurements with [11C]PBB3 for tau aggregation and [11C]DPA713 for microglial activation (neuroinflammation). Inter- and intrasubject comparisons were performed regarding the levels of [11C]PBB3 binding potential (BPND) and [11C]DPA713 BPND in the light of cognitive functions using statistical parametric mapping (SPM) and regions of interest (ROIs) method. The [11C]PBB3 BPND was greater in the temporo-parietal regions of AD patents than NC subjects, and a similar increasing pattern of [11C]DPA713 BPND was observed in the same patients. Correlation analyses within the AD group showed a positive direct correlation between [11C]PBB3 BPND and [11C]DPA713 BPND in the parahippocampus. Pass analysis revealed that cognitive impairment was more likely linked to the level of the parahippocampal [11C]PBB3 BPND than that of [11C]DPA713 BPND. The pattern of abnormal tau deposition was very similar to that of neuroinflammation in patients with early-stage AD. Specifically, the direct positive correlation of tau pathology with neuroinflammation in the parahippocampus suggests that neuronal damage in this region is closely associated with microglial activation. Consistently, tau aggregation in this region matters more than neuroinflammation regarding the cognitive deterioration in AD.

Changes in Timing of Swallow Events in Parkinson's Disease.

The prevalence of Parkinson's disease (PD) increases as the population ages. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. To maximize the benefit of swallowing therapy, protocol design should be based on an understanding of the physiologic swallowing deficits present in the PD population. The aim of this study was to compare the timing of swallow events in a cohort of patients with PD with that in normal age-matched control subjects to characterize variations in the coordination of structural displacement and bolus movement that may contribute to dysphagia. This retrospective study included 68 adults with diagnoses of PD. Liquid bolus swallows during modified barium swallow studies were analyzed and compared with those from an age- and sex-matched cohort of 48 adults without PD. Patients with PD were significantly slower in initiating and completing airway closure. Hyoid elevation was prolonged in this patient population. Patients with PD demonstrate slower initiation of airway closure and a delay in relaxation of hyoid elevation during swallow. Delays increased with larger boluses. These findings may be related to impaired pharyngeal sensation and increased muscular rigidity. The results of this study will be helpful in guiding swallow therapy for patients with PD.

A Preliminary Study of Left Ventricular Rotational Mechanics in Children with Noncompaction Cardiomyopathy: Do They Influence Ventricular Function?

Current diagnostic criteria for noncompaction cardiomyopathy (NCC) lack specificity, and the disease lacks prognostic indicators. Reverse apical rotation (RAR) with abnormal rotation of the cardiac apex in the same clockwise direction as the base has been described in adults with NCC. The aim of this study was to test the hypothesis that RAR might differentiate between symptomatic NCC and benign hypertrabeculations and might be associated with ventricular dysfunction. Echocardiograms from 28 children with NCC without cardiac malformations were prospectively compared with those from 29 age-matched normal control subjects. A chart review was performed to identify the patients' histories and clinical characteristics. Speckle-tracking was used to measure longitudinal strain, circumferential strain, and rotation. RAR occurred in 39% of patients with NCC. History of left ventricular (LV) dysfunction or arrhythmia was universal in, but not exclusive to, patients with RAR. Patients with RAR had lower LV longitudinal strain but similar ejection fractions compared with patients without RAR (median, -15.6% [interquartile range, -12.9% to -19.3%] vs -19% [interquartile range, -14.5% to -21.9%], P < .01; 53% [interquartile range, 43% to 68%] vs 61% [interquartile range, 58% to 67%], P = .08). Only a pattern of contraction with RAR, early arrest of twisting by mid-systole, and premature untwisting was associated with lower ejection fraction (46%; interquartile range, 43% to 52%; P=.006). RAR is not a sensitive but is a specific indicator of complications in children with NCC. Therefore, RAR may have prognostic rather than diagnostic value. Premature untwisting of the left ventricle during ejection may be an even more worrisome indicator of LV dysfunction.

Dynamic changes of oligomeric amyloid \u03b2 levels in plasma induced by spiked synthetic A\u03b242

BackgroundA reliable blood-based assay is required to properly diagnose and monitor Alzheimer’s disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-β oligomers (AβOs) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect AβOs.MethodsTo characterize Aβ in the blood, plasma was spiked with synthetic amyloid-β (Aβ) and incubated over time. Then, the MDS was used to monitor the dynamic changes of AβO levels in the plasma.ResultsIncreasing concentrations of AβOs were observed in the plasma of patients with AD but not in the plasma of normal control subjects. The plasma from patients with AD (n = 27) was differentiated from that of the age-matched normal control subjects (n = 144) with a sensitivity of 83.3% and a specificity of 90.0%.ConclusionsSynthetic Aβ spiked into the blood plasma of patients with AD, but that of not elderly normal control subjects, induced dynamic changes in the formation of AβOs over time. AβOs were detected by the MDS, which is a useful blood-based assay with high sensitivity and specificity for AD diagnosis.

Exploring resting-state EEG complexity before migraine attacks.

Objective Entropy-based approaches to understanding the temporal dynamics of complexity have revealed novel insights into various brain activities. Herein, electroencephalogram complexity before migraine attacks was examined using an inherent fuzzy entropy approach, allowing the development of an electroencephalogram-based classification model to recognize the difference between interictal and preictal phases. Methods Forty patients with migraine without aura and 40 age-matched normal control subjects were recruited, and the resting-state electroencephalogram signals of their prefrontal and occipital areas were prospectively collected. The migraine phases were defined based on the headache diary, and the preictal phase was defined as within 72 hours before a migraine attack. Results The electroencephalogram complexity of patients in the preictal phase, which resembled that of normal control subjects, was significantly higher than that of patients in the interictal phase in the prefrontal area (FDR-adjusted p < 0.05) but not in the occipital area. The measurement of test-retest reliability (n = 8) using the intra-class correlation coefficient was good with r1 = 0.73 ( p = 0.01). Furthermore, the classification model, support vector machine, showed the highest accuracy (76 ± 4%) for classifying interictal and preictal phases using the prefrontal electroencephalogram complexity. Conclusion Entropy-based analytical methods identified enhancement or "normalization" of frontal electroencephalogram complexity during the preictal phase compared with the interictal phase. This classification model, using this complexity feature, may have the potential to provide a preictal alert to migraine without aura patients.

Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy

Objective To observe the peripapillary choroidal thicknesses (pCT) and subfoveal choroidal thicknesses (SFCT) of nonarteritic anterior ischemic optic neuropathy (NAION). Methods Fortyfour Chinese patients with unilateral NAION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. pCT and SFCT were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NAION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NAION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and the mean deviation(MD) of Humphrey static perimetry in NAION eyes were analyzed. Results The pCT at the nasal, nasal inferior and temporal inferior quadrants in NAION eyes with optic disc edema were significantly thicker than that of normal subjects (t=3.152, 3.166, 2.808; P 0.05). No significant correlation between choroidal thickness (r=-0.220,-0.140, 0.110), SFCT (r=0.096,-0.148,-0.131) and logMAR BCVA, perimetry MD and RNFL was found in eyes affected by NAION (P>0.05). Conclusions The peripapillary choroidal thicknesses increase in some quadrants in NAION eyes with optic disc edema. However, the choroidal thickness of NAION eyes is the same in age and refractive error-matched normal subjects. Key words: Non-arteritic anterior ischemic optic neuropathy; Choroidal thickness; Optical coherence tomography

Spinal cord anteroposterior atrophy in HAM/TSP: Magnetic resonance imaging and neuropathological analyses

To evaluate the spinal cord atrophy that occurs in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, spinal cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP spinal cords demonstrated more severe atrophy in the anteroposterior direction than those of controls. The spinal cord atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating spinal cord atrophy in the anteroposterior direction using MRI. In pathological analysis, atrophy and pathological changes were prominent in areas of the spinal cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of atrophy in the anteroposterior direction.

Differentiated Effective Connectivity Patterns of the Executive Control Network in Progressive MCI: A Potential Biomarker for Predicting AD

Mild cognitive impairment (MCI) is often a transitional state between normal aging and Alzheimer's disease (AD). When observed longitudinally, some MCI patients convert to AD, while a considerable portion either remains MCI or revert to a normal functioning state. This divergence has provided some enlightenment on a potential biomarker to be represented in the resting state brain activities of MCI patients with different post-hoc labels. Recent studies have shown impaired executive functions, other than typically explicated memory impairment with AD/MCI patients. This observation raises the question that whether or not the executive control network (ECN) was impaired, which pivotally supports the central executive functions. Given the fact that effective connectivity is a sufficient index in detecting resting brain abnormalities in AD/MCI, the current study specifically asks a question whether the effective connectivity patterns are differentiated in MCI patients with different post-hoc labels. We divided the MCI subjects into three groups depending on their progressive state obtained longitudinally: 1) 15 MCI-R subjects: MCI reverted to the normal functioning state and stabilized to the normal state in 24 months; 2) 35 MCI-S subjects: MCI patients maintained this disease in a stable state for 24 months; 3) 22 MCI-P subjects: MCI progressed to AD and stabilized to AD in 24 months, and 4) 39 age-matched normal control subjects (NC). We conducted a Granger causality analysis after identifying the core nodes of ECN in all of the subjects using Independent Component Analysis. Our findings revealed that different MCI groups presented different effective connectivity patterns within the ECN compared to the NC group. Specifically, (1) dorsolateral prefrontal cortex (dLPFC) and medial prefrontal cortex (mPFC) were the core nodes in the ECN network that exhibited different connecting patterns; (2) an effective connection circuit "R.dLPFC→ right caudate→ left thalamus→R.dLPFC" in the ECN showed different levels of damage; and (3) there were four pathways between the R.dLPFC and L.LP, and these four pathways were also different. Our results would help to understand the potential central mechanism of MCI patients. The differentiated effective connectivity of ECN may serve as a potential biomarker for early detection of AD, which may also provide a reference for clinical researchers to manipulate active but distinctive interventions for MCI patients who have different risks.

Correlation between Dopamine Transporter Degradation and Striatocortical Network Alteration in Parkinson's Disease.

The association between dopamine neuron loss and functional change in the striatocortical network was analyzed in 31 patients with Parkinson’s disease (PD) [mean disease duration 4.03 ± 4.20 years; Hoehn and Yahr (HY) stage 2.2 ± 1.2] and 37 age-matched normal control subjects. We performed 99mTc-TRODAT-1 SPECT/CT imaging to detect neuron losses and resting-state functional magnetic resonance imaging to detect functional changes. Mean striatal dopamine transporter binding ratios were determined by region of interest analysis. The functional connectivity correlation coefficient (fc-cc) was determined in six striatal subregions, and interactions between these binding ratios and the striatocortical fc-cc values were analyzed. The PD patients had significant functional network alterations in all striatal subregions. Lower striatal dopamine transporter binding correlated significantly with lower fc-cc values in the superior medial frontal (SMF) lobe and superior frontal lobe and higher fc-cc values in the cerebellum and parahippocampus. The difference in fc-cc between the ventral inferior striatum and SMF lobe was significantly correlated with increased disease duration (r = –0.533, P = 0.004), higher HY stage (r = –0.431, P = 0.020), and lower activities of daily living score (r = 0.369, P = 0.049). The correlation of frontostriatal network changes with clinical manifestations suggests that fc-cc may serve as a surrogate marker of disease progression.

Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy.

BackgroundNon-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case–control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients.MethodsForty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed.ResultsThe peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P < 0.05). There was no significant difference in the choroidal thicknesses between the unaffected fellow eyes of NA-AION patients and normal eyes of healthy controls; or between the NA-AION eyes with resolved optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05).ConclusionsIncrease in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is abnormal in Chinese patients with NA-AION compared with normal subjects with similar age and refractive error status.

Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease.

HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset.Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset.Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age.Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD.Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset.

Achondroplasia: Really rhizomelic?

Achondroplasia is the most common form of short limb dwarfism in humans. The shortening of the limb lengths in achondroplasia is widely described as "rhizomelic." While this appearance may be convincing clinically, the description is not necessarily true or helpful radiologically. The aims of this study, were therefore, to determine whether rhizomelic shortening is a true feature of achondroplasia at diagnosis in infancy. Humeral, radial, femoral, and tibial diaphyseal lengths were recorded by two independent observers from 22 skeletal surveys of infants with achondroplasia and compared with 150 normal age-matched control subjects. Upper and lower limb bone length ratios (radial/humeral and tibial/femoral lengths, respectively) in both groups were compared using an unpaired t-test. Mean upper limb length ratios were statistically higher within the achondroplasia group at 0.87 ± 0.04 (n = 22, mean age 70 ± 94 days) compared to normal controls at 0.79 ± 0.02 (n = 150, mean age 113 days ± 88 days; P < 0.0001). Lower limb length ratios were not significantly different between groups (0.84 ± 0.04 vs. 0.83 ± 0.02, P = 0.46). There was good inter-observer agreement of limb length measurements, with an average measurement difference of 0.1 ± 1.4 mm. In conclusion, infants with achondroplasia demonstrate statistically significant rhizomelic shortening within the upper limbs, but not lower limbs at diagnosis, compared to normal controls. The term "rhizomelic shortening" in relation to achondroplasia should be reserved when describing upper limb proportions. © 2016 Wiley Periodicals, Inc.

Amide proton transfer MR imaging at 3. 0 T of the basal ganglia in Parkinson's disease

Objective To explore the feasibility of amide proton transfer (APT) MR imaging for the detection of basal ganglia abnormalities in patients with Parkinson's disease (PD). Methods Twenty-seven patients with PD and twenty-three age-matched normal control subjects underwent cerebral APT and structural MR imaging. The magnetic resonance ratio asymmetry (MTRasym) values at 3.5 ppm of bilateral globus pallidus, putamen and caudate were measured on APT images. MTRasym (3.5 ppm) values of cerebral structures between PD patients and control subjects were compared with independent-samples t test. Paired-samples t test was used to compare the difference of MTRasym (3.5 ppm) between the side of onset and contralateral side in patients with PD. The difference of MTRasym (3.5 ppm) among normal controls, early-stage PD, and advanced-stage PD patients was assessed with one-way analysis of variance. Results Compared to normal controls, MTRasym (3.5 ppm) values of globus pallidus, putamen and caudate were significantly increased in PD patients ((0.89±0.12)% vs (0.57±0.16)%, (1.05±0.11)% vs (0.82±0.15)%, (1.15±0.13)% vs (0.78±0.19)%; t=3.311, 2.562, 3.277 respectively, all P values <0.05). Significant differences in MTRasym (3.5 ppm) values of these cerebral structures were observed among normal controls, early-stage PD and advanced-stage PD patients. And MTRasym (3.5 ppm) values in globus pallidus, putamen and caudate were significantly higher in early-stage PD patients than normal controls. In PD patients, even not statistically significant, MTRasym (3.5 ppm) values of sides of onset were slightly lower than contralateral sides. Conclusions APT MR imaging can sensitively identify the difference of MTRasym (3.5 ppm) in the basal ganglia between PD patients and normal controls. APT might be a useful tool to evaluate abnormal metabolite in basal ganglia of PD patients. Key words: Parkinson disease; Basal ganglia; Magnetic resonance imaging; Amide proton transfer

OSA Syndrome and Posttraumatic Stress Disorder: Clinical Outcomes and Impact of Positive Airway Pressure Therapy

We sought to determine the impact of OSA syndrome (OSAS) on symptoms and quality of life (QoL) among patients with posttraumatic stress disorder (PTSD). In addition, we assessed adherence and response to positive airway pressure (PAP) therapy in this population. This was a case-controlled observational cohort study at the Sleep Disorders Center of an academic military medical center. Two hundred consecutive patients with PTSD underwent sleep evaluations. Patients with PTSD with and without OSAS were compared with 50 consecutive age-matched patients with OSAS without PTSD and 50 age-matched normal control subjects. Polysomnographic data, sleep-related symptoms and QoL measures, and objective PAP usage were obtained. Among patients with PTSD, more than one-half (56.6%) received a diagnosis of OSAS. Patients with PTSD and OSAS had lower QoL and more somnolence compared with the other groups. Patients with PTSD demonstrated significantly lower adherence and response to PAP therapy. Resolution of sleepiness occurred in 82% of patients with OSAS alone, compared with 62.5% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS (P < .001). Similarly, posttreatment Functional Outcomes of Sleep Questionnaire ≥ 17.9 was achieved in 72% of patients with OSAS, compared with only 56.3% of patients with PTSD and OSA who were PAP adherent and 26.2% who were nonadherent (P < .03). In patients with PTSD, comorbid OSAS is associated with worsened symptoms, QoL, and adherence and response to PAP. Given the negative impact on outcomes, the possibility of OSAS should be considered carefully in patients with PTSD. Close follow-up is needed to optimize PAP adherence and efficacy in this at-risk population.

Elevation of the Plasma Aβ40/Aβ42 Ratio as a Diagnostic Marker of Sporadic Early-Onset Alzheimer's Disease.

Although plasma amyloid-β (Aβ) levels have been evaluated as a possible diagnostic marker of Alzheimer's disease (AD), the findings are inconsistent. The present study aimed to validate plasma levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio as biomarkers of AD in subjects with early-onset AD (EOAD) without familial AD genetic mutations. Patients with sporadic EOAD (sEOAD) were prospectively recruited by nine neurology clinics. Plasma levels of Aβ40 and Aβ42 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in 100 sEOAD (50-69 year-old) and 46 age-matched normal control subjects (50-72 year-old). Cerebrospinal fluid (CSF) was obtained from 32 sEOAD subjects and 25 controls. The integrity of the blood-brain barrier was assessed using the CSF/plasma albumin ratio. The plasma levels of Aβ42 were significantly lower, while the Aβ40/Aβ42 ratio was significantly higher in sEOAD patients than in controls. The levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio did not differ in relation to the APOEɛ4 allele. The CSF/plasma albumin ratio was comparable between the two groups, and the plasma parameters of Aβ proteins were not significantly associated. A multivariate analysis revealed that an increased Aβ40/Aβ42 ratio is valuable for the discrimination of sEOAD from controls (β=0.344, p=0.000). The area under the ROC curve for the Aβ40/Aβ42 ratio was 0.76, and a cut-off ratio of 5.87 was suggested to have 70% sensitivity and 68% specificity. The plasma Aβ40/Aβ42 ratio had moderate validity for the discrimination of sEOAD patients from age-matched controls.

Damage to the Optic Radiation in Patients With Mild Traumatic Brain Injury.

There are known limitations of conventional computed tomography and magnetic resonance imaging in detecting neural injury in patients with mild traumatic brain injury (TBI). Diffusion tensor imaging (DTI) provides a method to further assess cerebral injury in this patient population. We report 2 patients with mild TBI who showed injury of the optic radiation (OR) as demonstrated by DTI. Two patients who complained of visual field loss after mild TBI and 9 age-matched normal control subjects were recruited for this study. Peripheral field defects were detected with automated perimetry in both patients. Regarding the configuration of OR, the total volume of OR was decreased in the right OR of both patients compared with controls; in contrast, the left ORs were divided into 2 parts in both patients. The voxel numbers of both ORs in both patients were more than 2 standard deviations lower than that of normal control subjects. The apparent diffusion coefficient value of the right OR in patient 2 was more than 2 standard deviations higher than that of normal controls. We demonstrated injury of the OR using DTI in 2 patients who showed visual field defects after mild TBI.

Subjective Discomfort Symptoms Are Related to Low Corneal Temperature in Patients With Evaporative Dry Eye.

To measure the corneal temperature in patients with dry eye (DE) and to correlate the values with subjective discomfort symptoms. Twenty-four patients with DE (scored as DEWS severity grade 2 to 3) and 15 age-matched normal control subjects were enrolled. Subjective symptoms of discomfort were scored with an Ocular Surface Disease Index questionnaire, and a 100-mm horizontal visual analog scale (VAS) technique was used to measure symptom intensity. Schirmer I test, tear film breakup time (TFBUT), and Oxford grade scoring were performed in all subjects. Dynamic infrared noncontact thermal imaging (Tomey TG 1000) was used to measure the central corneal temperature (CCT). After training, subjects were asked to maintain their eyes forcedly open and to signal the discomfort onset time (DOT). The temperature was measured at eye opening (T0) and every second during 10 seconds of sustained eye opening (T10). The first discomfort sensation onset time (DOT) was also recorded. Temperature values were correlated with the clinical tests, Ocular Surface Disease Index, VAS, and DOT, and data were statistically evaluated (significance P < 0.05). The corneal temperature immediately after eye opening was significantly lower in patients with DE than in controls, in correlation to the subject age, VAS, and TFBUT. A 3-phase cooling profile in patients with DE and a point of highest decrease (HD) in both groups were identified. DOT occurred earlier in patients with DE than in controls (5.9 vs. 15.9 seconds) and was strongly correlated to the VAS, TFBUT, and CCT-HD. Subjective sensation of discomfort occurred earlier in patients with DE than in controls, in correlation to low corneal temperatures and enhanced tear evaporation.