Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson's disease.

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Independent effect of cardiometabolic syndromes and depression on dementia in Parkinson's disease: A 12-year longitudinal follow-up study of a nationwide cohort.

BACKGROUND: We aimed to investigate the incidence rate of Parkinson's disease dementia (PDD) according to age and disease duration by sex. Furthermore, we explored the effect of each cardiometabolic syndrome and depression on the incidence of PDD. METHODS: Using data from the Korean National Health Insurance Service, 79,622 patients with de novo Parkinson's disease (PD) aged ≥40 years between January 2002 and December 2010 were followed to December 2019. We analyzed the incidence of PDD according to age at PD diagnosis and disease duration. To determine cardiometabolic syndromes and depression that affected PDD, we used Fine and Gray competing regression after controlling for age and sex. RESULTS: During the 12.5-year follow-up period, the incidence of PDD increased with age at PD diagnosis (0.81-45.31 per 1000 person-years among those aged 40-44 and over 80 years, respectively) and longer disease duration (22.68 per 1000 person-years in 1-2 years to 34.16 per 1000 person-years in 15-16 years). Hypertension (subdistribution hazard ratio [SHR] = 1.11; 95% confidence interval [CI] 1.07-1.16), diabetes (SHR = 1.09; 95% CI 1.05-1.14), dyslipidemia (SHR = 1.15; 95% CI 1.11-1.20), and depression (SHR = 1.36; 95% CI 1.30-1.41) independently increased the risk for PDD. CONCLUSIONS: Our findings provide insights into cardiometabolic syndromes as modifiable risk factors for incident PDD. Furthermore, our results will help in designing public health policies with respect to controlling cardiometabolic syndromes and depression to prevent incident PDD in patients with PD.

Sex differences in gastrointestinal dysfunction among patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Sex differences in gastrointestinal dysfunction have not been systematically analyzed in patients with Parkinson's disease (PD). This study was aimed to investigate the sex differences in gastrointestinal dysfunctions among the patients with PD using a multicenter trial dataset. METHODS: We analyzed the baseline data of prospectively enrolled set of patients with gastrointestinal dysfunctions. Possible sex differences in gastrointestinal symptoms assessed on the Nepean Dyspepsia Index-Korean Version (NDI-K), gastrointestinal symptom diary, and Bristol stool scale were analyzed in association with clinical PD severity and antiparkinsonian drug dosages by multiple linear regression models. We also performed post hoc analysis of the dyspepsia symptom sub-items, adjusting for multiple comparisons. RESULTS: Sixty-six of the 144 participants were female (45.8%). There were no differences in age, PD duration, Hoehn and Yahr stage, and daily dopaminergic medication dosages between sexes. NDI-K symptom and dyspepsia scores were correlated with the activity of daily living in females but not in males. In the multiple regression analysis controlling for all possible variables, female patients were shown to have worse gastrointestinal symptoms than males. When we performed post hoc analysis of the dyspepsia symptoms, inability to finish a regular meal and nausea were significantly worse in female patients. Gastrointestinal symptom diary supported that female patients more frequently complained of early fullness and bloating in the upper abdomen after meals than males, and burning pain in upper abdomen was more severe in female patients. CONCLUSION: Gastrointestinal dysfunctions may differentially affect female and male PD patients.

A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Independent effects of amyloid and vascular markers on long-term functional outcomes: An 8-year longitudinal study of subcortical vascular cognitive impairment.

BACKGROUND AND PURPOSE: Subcortical vascular cognitive impairment (SVCI) is characterized by the presence of cerebral small vessel disease (CSVD) markers. Some SVCI patients also show Alzheimer's disease and cerebral amyloid angiopathy markers. However, the effects of these imaging markers on long-term clinical outcomes have not yet been established. The present study, therefore, aimed to determine how these imaging markers influence functional disability and/or mortality. METHODS: We recruited 194 participants with SVCI from the memory clinic and followed them up. All participants underwent brain magnetic resonance imaging at baseline, and 177 (91.2%) participants underwent beta-amyloid (Aß) positron emission tomography. We examined the occurrence of ischemic or hemorrhagic strokes. We also evaluated functional disability and mortality using the modified Rankin scale. To determine the effects of imaging markers on functional disability or mortality, we used Fine and Gray competing regression or Cox regression analysis. RESULTS: During a 8.6-year follow-up period, 46 of 194 patients (23.7%) experienced a stroke, 110 patients (56.7%) developed functional disabilities and 75 (38.6%) died. Aß positivity (subdistribution hazard ratio [SHR] = 2.73), greater white matter hyperintensity (WMH) volume (SHR = 3.11) and ≥3 microbleeds (SHR = 2.29) at baseline were independent predictors of functional disability regardless of the occurrence of stroke. Greater WMH volume (hazard ratio = 2.07) was an independent predictor of mortality. CONCLUSIONS: Our findings suggest that diverse imaging markers may predict long-term functional disability and mortality in patients with SVCI, which in turn may provide clinicians with a more insightful understanding of the long-term outcomes of SVCI.

Independent effect of neurogenic orthostatic hypotension on mild cognitive impairment in Parkinson's disease.

PURPOSE: Orthostatic hypotension (OH) is an associative or causative factor of cognitive impairment in Parkinson's disease (PD). However, the association between mild cognitive impairment (MCI) and neurogenic OH directly associated with the presence of alpha-synuclein in PD remains unclear. We aimed to evaluate the relationship between MCI and neurogenic OH in patients with de novo PD. We also investigated the patterns of neuropsychological performance according to neurogenic OH. METHODS: A total of 456 patients with PD-normal cognition (PD-NC, n = 204) or PD-MCI (n = 252) were recruited from multiple centers in Korea. All patients underwent comprehensive neuropsychological tests and tilt-table tests to evaluate cognitive function and neurogenic OH. We used logistic regression analysis and multivariate analysis of covariance to determine the association between MCI and neurogenic OH and the pattern of neuropsychological performance according to neurogenic OH. RESULTS: Neurogenic OH (odds ratio = 3.66, 95% confidence interval 2.06 to 6.47) was independently associated with MCI in patients with de novo PD, regardless of orthostatic symptoms, while nonneurogenic OH was not. Patients with PD with neurogenic OH exhibited worse performance in frontal-executive function and visual memory function than those without neurogenic OH. CONCLUSION: Our findings provide insight into neurogenic OH as an important clinical factor with cognitive impairment in individuals with PD and vice versa. Therefore, the evaluation of cognitive function is necessary in PD patients with neurogenic OH.

Harmonisation of PET imaging features with different amyloid ligands using machine learning-based classifier.

PURPOSE: In this study, we used machine learning to develop a new method derived from a ligand-independent amyloid (Aß) positron emission tomography (PET) classifier to harmonise different Aß ligands. METHODS: We obtained 107 paired 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) PET images at the Samsung Medical Centre. To apply the method to FMM ligand, we transferred the previously developed FBB PET classifier to test similar features from the FMM PET images for application to FMM, which in turn developed a ligand-independent Aß PET classifier. We explored the concordance rates of our classifier in detecting cortical and striatal Aß positivity. We investigated the correlation of machine learning-based cortical tracer uptake (ML-CTU) values quantified by the classifier between FBB and FMM. RESULTS: This classifier achieved high classification accuracy (area under the curve = 0.958) even with different Aß PET ligands. In addition, the concordance rate of FBB and FMM using the classifier (87.5%) was good to excellent, which seemed to be higher than that in visual assessment (82.7%) and lower than that in standardised uptake value ratio cut-off categorisation (93.3%). FBB and FMM ML-CTU values were highly correlated with each other (R = 0.903). CONCLUSION: Our findings suggested that our novel classifier may harmonise FBB and FMM ligands in the clinical setting which in turn facilitate the biomarker-guided diagnosis and trials of anti-Aß treatment in the research field.

Risk Factors of Outcomes of COVID-19 Patients in Korea: Focus on Early Symptoms.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea. METHODS: In this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables. RESULTS: Logistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic. CONCLUSION: COVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups.

Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study.

OBJECTIVES: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptom-related quality of life in patients with Parkinson's disease on stable dopaminergic medications. METHODS: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point. RESULTS: The gastrointestinal symptom-related quality-of-life score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drug-related serious adverse events throughout the trial. CONCLUSIONS: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms. (Clinical trial identifier: NCT02775591.) © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Behavioural and trait changes in parkinsonian patients with impulse control disorder after switching from dopamine agonist to levodopa therapy: results of REIN-PD trial.

OBJECTIVE: In this multicentre open-label trial, we compared behavioural and neuropsychiatric symptoms in Parkinson's disease (PD) patients with impulse control disorders (ICD) treated with dopamine agonists before and 12 weeks after substituting dopamine agonists with an equivalent dose of levodopa/carbidopa slow-release formulation. METHODS: Baseline characteristics of 50 PD patients with ICD were compared with those of 60 medicated and 40 drug-naive PD control groups. Neuropsychiatric trait changes in the PD-ICD group were investigated 12 weeks after the intervention. ICD behaviours were assessed via modified Minnesota Impulsive Disorders Interview (mMIDI), whereas parkinsonian severity and neuropsychiatric characters were systematically assessed with the Unified PD Rating Scale (UPDRS) and a predefined neuropsychological assessment battery. RESULTS: At baseline, ICD patients showed higher scores in the Neuropsychiatric Inventory and anxiety, anger and obsessive-compulsive traits compared with both PD control groups. In contrast, the three PD groups showed indifference in the impulsivity scales. At 12 weeks post intervention, ICD behaviours significantly improved (p<0.001, Δ modified MIDI score=‒5.27 ± 5.75) along with the UPDRS II daily activity scores (p=0.02, Δ=‒2.07 ± 4.53). Behavioural disinhibition tended to improve (p=0.06), although no significant changes were observed in the Neuropsychiatric Inventory and personality trait scores. Dopamine agonist withdrawal syndrome developed in 5.3% of the PD-ICD group. CONCLUSIONS: This study provides class IV evidence suggesting that switching from dopamine agonists to levodopa/carbidopa slow-release formulations alleviated ICD behaviours in PD patients leading to improvement in daily activities whereas neuropsychiatric traits associated with ICD persisted after the 12-week therapy. TRIAL REGISTRATION NUMBER: NCT01683253.

Neuropsychiatric Traits Associated with Refractory Impulse Control Disorder in Parkinson's Disease.

INTRODUCTION: Impulse control disorder (ICD) in Parkinson's disease (PD) is a critical nonmotor symptom with personality or neuropsychiatric traits contributing to ICD. OBJECTIVE: This study aimed to identify predictive traits for persistent or paradoxical aggravation of ICD after dopamine agonist substitution therapy for ICD in PD. METHODS: We conducted a case-control study using a database of a multicenter intervention trial for ICD in PD. The poor-outcome group was defined by showing paradoxical increases in ICD behaviors after the substitution of dopamine agonists with levodopa. We analyzed the pre-intervention personality traits associated with the poor outcome and also evaluated the risk traits for refractory ICD using a receiver-operating characteristic (ROC) curve analysis. RESULTS: The poor-outcome group showed higher levels of anger expression (p =0.007) and obsessive-compulsive traits (p =0.009) compared with the good-outcome group at the pre-intervention state. In the ROC curve analysis, the Obsessive-Compulsive Inventory showed the highest area under the curve with 80.0% sensitivity and 74.3% specificity in discriminating against the poor-outcome group. CONCLUSIONS: Our results suggest that assessment of obsessive compulsiveness may be useful for predicting the refractoriness of ICD behaviors in planning an interventional treatment for ICD in PD.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep.

BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. METHODS: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days. RESULTS: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD.

PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer's Disease.

An in depth study of PSEN1 mutation p.Thr116Ile (c.335C>T) is presented from two Korean families with autosomal dominant inheritance. Clinical manifestation of our patients included memory loss, attention deficits, visuospatial dysfunction, agnosia, aphasia, apraxia, and personality changes, which occurred in their 30s. PSEN1 Thr116Ile was initially discovered in an Italian patient and two French families with early onset Alzheimer's disease (EOAD) with similar age of onset. To verify the possible pathogenic mechanisms of mutation, in silico predictions and 3D modeling were performed. Structure predictions revealed significant aberrations in first hydrophilic loop (HL-I loop). The hydrophobic isoleucine could alter the loop orientation through increased hydrophobic contacts with the surrounding amino acids. Mutation could destroy a possible hydrogen bond between tyrosine 115 and threonine 116, which may affect the loop conformation. HL-I was confirmed as a conservative region of PSEN1, which may be critical in PSEN1 functions. An additional pathogenic mutation, PSEN1 Thr116Asn, was also found for the same residue, where the patient presented young onset AD (YOND). Other mutations in HL-I loop, such as Tyr115His and Glu120Asp, were described in patients with YOND, supporting the critical role of HL-I loop in PSEN1 activity.

Free fatty acid as an outcome predictor of atrial fibrillation-associated stroke.

OBJECTIVE: We investigated whether baseline plasma free fatty acid (FFA) concentration is associated with any (ischemic/hemorrhagic) stroke, ischemic stroke/systemic embolism (ISSE), or ischemic stroke among stroke survivors with atrial fibrillation (A-fib). Moreover, we compared the outcome predictability of FFA with previously adopted models, including the CHADS2 and CHA2 DS2 -VASc scoring systems. METHODS: We analyzed data from 279 stroke patients with A-fib and investigated the association between plasma FFA concentration and outcomes using Cox regression models with competing risk analyses. RESULTS: Median follow-up period was 17.5 months. During the study period, any stroke, ISSE, and ischemic stroke occurred in 22, 21, and 17 patients, respectively. The cumulative risk for any stroke, ISSE, and ischemic stroke were 5.1%, 4.7%, and 4.2% at the end of the first year and 14.8%, 12.1%, and 10.8% at the end of the third year, respectively. After adjusting covariates (model 1), baseline FFA concentration was associated with recurrence of any stroke (hazard ratio [HR] = 1.774, 95% confidence interval [CI] = 1.124-2.801, per 1mEq/l increment of FFA). FFA showed a trend association with ISSE (HR = 1.569, 95% CI = 0.950-2.592) and ischemic stroke (HR = 1.630, 95% CI = 0.967-2.746). In adjusted models including CHADS2 or CHA2 DS2 -VASc score as a covariate, (models 2 and 3) FFA was still shown to be an independent predictor of any stroke and ischemic stroke. There was a significant or trend association between FFA and ISSE. INTERPRETATION: FFA may be a potential biomarker that predicts outcome events in stroke with A-fib along with the CHADS2 and CHA2 DS2 -VASc scoring systems.

Free Fatty Acid Is Associated with Thrombogenicity in Cardioembolic Stroke.

BACKGROUND: Recently, the role of free fatty acids (FFAs) in thromboembolism has re-emerged in the context of cardioembolic stroke. Therefore, we attempted to determine the role of FFAs in embolic risk in various potential sources of cardioembolism (PSCE). We hypothesized that if elevated FFA levels in stroke patients are associated with thrombogenesis, then patients with a well-known high risk of embolic sources would have high FFA levels. METHODS: Data collected from 2 hospital-based stroke registries were analyzed to investigate the association between FFA and PSCE. RESULTS: A total of 2,770 acute stroke patients, including 539 with cardioembolic stroke, were selected for analysis. FFA was an independent predictor for cardioembolism (OR 2.755, 95% CI 2.221-3.417, p < 0.001). Among the PSCE, FFA levels were significantly associated with high risk of atrial fibrillation (AF), valvular heart disease, congestive heart failure with low ejection fraction, left atrial thrombus, left ventricular thrombus, left atrial smoke, and ventricular wall motion abnormality. FFA levels increased with the number of PSCE per patient without interaction with the presence of AF. CONCLUSIONS: Among acute stroke patients, FFA levels increased in groups with higher risk of cardioembolic stroke irrespective of the presence of AF. These results suggest that enhanced thrombogenicity could be the main mechanism to explain the elevated FFA levels in patients with cardioembolic stroke.

Thalamic involvement in paroxysmal kinesigenic dyskinesia: a combined structural and diffusion tensor MRI analysis.

Alteration of basal ganglia-thalamocortical circuit has been hypothesized to play a role in the pathophysiology underlying paroxysmal kinesigenic dyskinesia (PKD). We investigated macrostructural and microstructural changes in PKD patients using structural and diffusion tensor magnetic resonance imaging (MRI) analyses. Twenty-five patients with idiopathic PKD and 25 control subjects were prospectively studied on a 3T magnetic resonance (MR) scanner. Cortical thickness analysis was used to evaluate cortical gray matter (GM) changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical GM structures, respectively. Tract-based spatial statistics (TBSS) was used to evaluate white matter integrity changes in a whole-brain manner, and region-of-interest (ROI) analysis of diffusion tensor metrics was performed in subcortical GM structures. Compared to controls, PKD patients exhibited a reduction in volume of bilateral thalami and regional shape deformation mainly localized to the anterior and medial aspects of bilateral thalami. TBSS revealed an increase in fractional anisotropy (FA) of bilateral thalami and right anterior thalamic radiation in patients relative to controls. ROI analysis also showed an increase in FA of bilateral thalami in patients compared to controls. We have shown evidence for thalamic abnormalities of volume reduction, regional shape deformation, and increased FA in patients with PKD. Our novel findings of concomitant macrostructural and microstructural abnormalities in the thalamus lend further support to previous observations indicating causal relationship between a preferential lesion in the thalamus and development of PKD, thus providing neuroanatomical basis for the involvement of thalamus within the basal ganglia-thalamocortical pathway in PKD.

Altered thalamocortical functional connectivity in idiopathic generalized epilepsy.

OBJECTIVE: Aberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed-based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics. METHODS: Forty-nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic-clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel-based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between-group comparison of thalamocortical FC was then carried out using resting-state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables. RESULTS: Neuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE. SIGNIFICANCE: Our results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long-standing burden of the disease.

Thickening of the somatosensory cortex in migraine without aura.

OBJECTIVE: We aimed to explore cortical thickness abnormalities in a homogeneous group of patients with migraine without aura and to delineate possible relationships between cortical thickness changes and clinical variables. METHODS: Fifty-six female migraine patients without aura and T2-visible white matter hyperintensities and 34 female controls were scanned on a 3T magnetic resonance imager. Cortical thickness was estimated and compared between patients and controls using a whole-brain vertex-by-vertex analysis. Correlation analysis was conducted between cortical thickness of significant clusters and clinical variables. RESULTS: Compared to controls, migraine patients had cortical thickening in left rostral middle frontal gyrus and bilateral post-central gyri. Region-of-interest analysis revealed cortical thickening of bilateral post-central gyri in migraine patients relative to controls. The average thickness of bilateral post-central gyri positively correlated with disease duration as well as estimated lifetime headache frequency. CONCLUSIONS: We have provided evidence for interictal cortical abnormalities of thickened prefrontal cortex and somatosensory cortex in female migraine patients without aura. Our findings of greater thickening of the somatosensory cortex in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time may lead to structural changes of the somatosensory cortex through increased noxious afferent input within the trigemino-thalamo-cortical pathway in migraine.

Nonmotor Symptoms and Cognitive Decline in de novo Parkinson's Disease.

BACKGROUND: Cognitive impairments are common in Parkinson's disease (PD). Despite its clinical importance, the development of dementia is still difficult to predict. In this study, we investigated the possible associations between non-motor symptoms and the risk of developing dementia within a 2-year observation period in PD. METHODS: A total of 80 patients with PD participated in this study. Nonmotor symptoms (the Nonmotor Symptoms Questionnaire), PD status (Unified Parkinson's Disease Rating Scale), depression (Geriatric d Depression Scale or Montgomery-Asberg Depression Scale), stereopsis and severity of nonmotor symptoms (Non-motor symptoms scale) were assessed. Global cognitive function (Mini-Mental State Examination) were evaluated at baseline and 2 years later. RESULTS: Presence of depression, vivid dreaming, REM sleep behavior disorders, hyposmia, abnormal stereopsis, non-smoking and postural instability/ gait disturbance phenotype were associated with a significantly more rapid decline of Mini-Mental State Examination. Logistic regression analyses demonstrated that depression (odds ratio=13.895), abnormal stereopsis (odds ratio=10.729), vivid dreaming (odds ratio=4.16), REM sleep behavior disorders (odds ratio=5.353) and hyposmia (odds ratio=4.911) were significant independent predictors of dementia risk within 2 years. Postural instability/ gait disturbance phenotype and age >62 years were also independent predictors of dementia risk (odd ratio=38.333, odds ratio=10.625). CONCLUSIONS: We suggest that depression, vivid dreaming, REM sleep behavior disorders, hyposmia and abnormal stereopsis are closely associated with cognitive decline, and that presence of these nonmotor symptoms predict the subsequent development of Parkinson's disease dementia.

Lesions on DWI and the Outcome in Hyperacute Posterior Circulation Stroke.

BACKGROUND: few studies have addressed the association between the characteristics of ischemic lesions detected by diffusion-weighted imaging (dWi) and the clinical outcome in patients with hyperacute posterior circulation ischemic stroke. this study demonstrates a relationship between the findings assessed by dWi and the outcome in patients with hyperacute posterior circulation ischemic stroke. METHODS: We reviewed data from 118 patients who had posterior circulation ischemic stroke within six hours from the onset of their symptoms. the clinical outcome included early neurological deterioration (end) and a favorable outcome at three months after the onset of symptoms. using dWi, the lesion volume and the number and location of injured anatomical regions were analyzed to evaluate whether the results correlated with the clinical outcome measures. RESULTS: the number of injured anatomical regions assessed by dWi was associated with the initial and delayed neurological status. Both the total volume and the number of injured anatomical regions associated with end and a favorable outcome. analysis of the location of the injured regions determined that only a pontine lesion independently associated with end. interestingly, four out of five patients who underwent decompressive craniectomy exhibited a large infarction volume but minor symptoms. CONCLUSIONS: in patients with hyperacute posterior circulation ischemic strokes, the lesions assessed by dWi were associated with the clinical outcome, regardless of the initial neurological status. dWi is an effective initial imaging tool for assessing the extent of lesions and clinical outcomes in patients with hyperacute posterior circulation ischemic stroke.