Milica Jecmenica-Lukic

Regional patterns of brain tissue loss associated with depression in Parkinson disease

Objective: To investigate, using MRI and voxel-based morphometry (VBM), whether specific patterns of gray matter (GM) and white matter (WM) loss are associated with depression in patients with Parkinson disease (PD). Methods: Forty patients with PD and 26 healthy subjects were studied. Patients were diagnosed with depression using DSM-IV criteria. The Hamilton Depression Rating Scale (HDRS) was administered to patients. The topographic distribution of brain tissue loss in patients with PD and controls was assessed using VBM as implemented in Statistical Parametric Mapping (SPM5). Results: Twenty-four patients with PD were diagnosed as nondepressed (PD-NDep) and 16 as having depression (PD-Dep). Patient groups were similar in terms of clinical findings, except for the HDRS score (p < 0.001). Compared to controls, patients with PD showed common GM loss in the right anterior cingulate (AC) cortex and insula, and in the left middle frontal and angular gyri (p < 0.001). No regions of WM loss common to PD-NDep and PD-Dep patients relative to healthy controls were found. PD-Dep vs PD-NDep patients showed WM loss in the right AC bundle and inferior orbitofrontal (OF) region (p < 0.001). In patients with PD, HDRS score correlated with WM loss in the right inferior OF region (r = −0.51, p < 0.05). Conclusions: Tissue loss in several WM regions within the cortical-limbic network occurs in PD-Dep vs PD-NDep patients. Such pattern of brain atrophy overlaps with key regions involved in major depressive disorders, suggesting an increased vulnerability of this neural circuit in PD. This may partially account for the high prevalence of depression in PD.

Pattern of brain tissue loss associated with freezing of gait in Parkinson disease

Objective: To investigate whether a specific pattern of gray matter (GM) tissue loss is associated with freezing of gait (FOG) in patients with Parkinson disease (PD). Methods: Seventeen patients with PD with FOG (PD-FOG), 20 patients with PD with no FOG (PD-noFOG), and 34 healthy control subjects were recruited. PD-FOG and PD-noFOG patients were matched on an individual basis for age, disease duration, and Hoehn and Yahr stage. Patients were also administered a comprehensive neuropsychological battery focused on executive functions. The extent and distribution of GM atrophy were assessed using voxel-based morphometry. Results: In patients with PD, the severity of FOG correlated with frontal executive deficits. Compared with healthy control subjects, PD-FOG patients showed a distributed pattern of GM atrophy including the dorsolateral prefrontal, medial, and lateral temporal, inferior parietal, and occipital cortices. PD-noFOG patients showed only small regions of GM atrophy in the bilateral frontal and temporal cortex. The left inferior frontal gyrus, left precentral gyrus, and left inferior parietal gyrus were more atrophic in PD-FOG patients relative to both healthy control subjects and PD-noFOG patients. In PD-FOG patients, the severity of FOG was associated with GM volumes of the frontal and parietal cortices bilaterally. Conclusions: GM frontal and parietal atrophy occur in PD-FOG patients. FOG in PD seems to share with executive dysfunction and perception deficits a common pattern of structural damage to the frontal and parietal cortices.

Premotor signs and symptoms of multiple system atrophy

Diagnostic criteria for multiple system atrophy are focused on motor manifestations of the disease, in particular ataxia and parkinsonism, but these criteria often cannot detect the early stages. Non-motor symptoms and signs of multiple system atrophy often precede the onset of classic motor manifestations, and this prodromal phase is estimated to last from several months to years. Autonomic failure, sleep problems, and respiratory disturbances are well known symptoms of established multiple system atrophy and, when presenting early and preceding ataxia or parkinsonism, should be regarded as evidence of premotor multiple system atrophy. An early and accurate diagnosis is becoming increasingly important as new neuroprotective agents are developed.

Suicide and suicidal ideation in Parkinson's disease

Little is known about the prevalence and correlates of suicidal behavior in Parkinsons disease (PD). In the first part of the study, we followed a cohort of 102 consecutive PD patients for 8 years and found that the suicide-specific mortality was 5.3 (95% CI 2.1-12.7) times higher than expected. In the second part, we tested 128 PD patients for death and suicidal ideation and administered an extensive neurological, neuropsychological and psychiatric battery. Current death and/or suicidal ideation was registered in 22.7%. On univariate logistic regression analysis, psychiatric symptoms (depression, but also anxiety and hopelessness), but not the PD-related variables, were associated with such ideation. On multivariate logistic regression analysis this association held for major depression (odds ratio=4.6; 95% CI 2.2-9.4; p<0.001), psychosis (odds ratio=19.2; 95% CI 1.4-27.3; p=0.026), and increasing score of the Beck Hopelessness Scale (odds ratio=1.2; 95% CI 1.0-1.4; p=0.008). In conclusion, the suicide risk in PD may not be as high as it is expected, but it is certainly not trivial. According to our data almost a quarter of PD patients had death and/or suicidal ideation, that may significantly influence their quality of life.

Mild Cognitive Impairment in Early Parkinson's Disease Using the Movement Disorder Society Task Force Criteria: Cross-Sectional Study in Hoehn and Yahr Stage 1

Background: Mild cognitive impairment (MCI) in Parkinsons disease (PD) is common and confers a higher risk for developing dementia. Methods: In this cross-sectional study of MCI in PD conducted at a university hospital, a comprehensive neuropsychological battery covering five domains (attention/working memory, executive, verbal, and visual memory, language, and visuospatial) was administered to 111 nondemented PD patients in Hoehn and Yahr stage 1 and to 105 healthy matched control subjects (HC). MCI was diagnosed according to level 2 of the Movement Disorder Society Task Force criteria. Results: Criteria for MCI associated with PD (PD-MCI) were fulfilled by 24% of PD patients in the initial stage of the disease at the z cutoff scores of -1.5 SD in contrast to 7% of HC fulfilling criteria for MCI. Memory and visuospatial domains were the most commonly affected at -1.5 SD. PD-MCI patients mostly had a multiple-domain MCI subtype (78%). They presented a more severe bradykinesia and higher mood and apathy scores in comparison with cognitively normal PD patients. Basic motor scores predicted performance on some cognitive tests and specific cognitive-motor relationships emerged. Conclusions: MCI, predominantly of a multiple-domain subtype, was quite prevalent even in the initial stage of PD.

Brain structural and functional signatures of impulsive–compulsive behaviours in Parkinson’s disease

This study assessed brain structural and functional alterations in patients with Parkinson’s disease and impulsive–compulsive behaviours (PD-ICB) compared with controls and PD no-ICB cases. Eighty-five PD patients (35 PD-ICB) and 50 controls were recruited. All subjects underwent three-dimensional T1-weighted, diffusion tensor (DT), and resting state functional magnetic resonance imaging (RS fMRI). We assessed cortical thickness with surface-based morphometry, subcortical volumes using FIRST, DT MRI metrics using region of interest and tractography approaches, and RS fMRI using a model free approach. Compared with controls, both PD groups showed a pattern of brain structural alterations in the basal ganglia (more evident in PD no-ICB patients), sensorimotor and associative systems. Compared with PD no-ICB, PD-ICB cases showed left precentral and superior frontal cortical thinning, and motor and extramotor white matter tract damage. Compared with controls, all patients had an increased functional connectivity within the visual network. Additionally, PD no-ICB showed increased functional connectivity of bilateral precentral and postcentral gyri within the sensorimotor network compared with controls and PD-ICB. Severity and duration of PD-ICB modulated the functional connectivity between sensorimotor, visual and cognitive networks. Relative to PD no-ICB, PD-ICB patients were characterised by a more severe involvement of frontal, meso-limbic and motor circuits. These data suggest ICB in PD as the result of a disconnection between sensorimotor, associative and cognitive networks with increasing motor impairment, psychiatric symptoms, and ICB duration. These findings may have important implications in understanding the neural substrates underlying ICB in PD.

Finger tapping analysis in patients with Parkinson’s disease and atypical parkinsonism

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinsons disease (PD), progressive supranuclear palsy-Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of -0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (-0.21°/cycle, p=0.032), and particularly from PD (-0.56°/cycle, p=0.001), and MSA-P patients (-1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.

The Pathophysiology of Fatigue in Parkinson's Disease and its Pragmatic Management

Fatigue is 1 of the most common and most disabling symptoms among patients with Parkinsons disease (PD) and has a significant impact on their quality of life. Yet the pathophysiology of fatigue is poorly understood, while its treatment is “limited to an empirical approach based on plausible hypotheses.”

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study

Objectives In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson’s syndrome (PSP-RS). Methods Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. Results Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. Conclusions This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course.

The utility of FDG-PET in the differential diagnosis of Parkinsonism

Abstract Introduction: Differential diagnosis of parkinsonian disorders can be difficult on clinical grounds, especially in the early stage. Recent advancements in 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging reveals different patterns of regional glucose metabolism in idiopathic Parkinson’s disease (IPD) and atypical parkinsonian syndromes, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), which may help differentiating between these conditions. Purpose: To assess the utility of FDG-PET imaging in differential diagnosis of Parkinsonism in clinical practice. Methods: FDG-PET was performed in 72 patients with parkinsonism (age 34–80 years) referred to our center by movement disorder specialists. FDG-PET diagnosis was obtained by visual assessment of individual scans combined with voxel-based statistical parametric mapping analysis. FDG-PET diagnosis assigned at the time of imaging was compared with the final clinical diagnosis made by the movement disorder specialists after ≥2 years follow-up. Results: FDG-PET findings were consistent with IPD in 27, MSA in 18, PSP in 19 and CBS in 2 patients. The final clinical diagnosis was IPD in 29, MSA in 20, PSP in 21 and CBS in 2 patients. Concordance between the FDG-PET and clinical diagnoses was 92% in the overall sample (IPD 93%, MSA 90%, PSP 91% and CBS 100%). The diagnostic accuracy of FDG-PET was 93% for IPD and MSA and 97% for PSP. Conclusion: FDG-PET may help differentiate between IPD, MSA, PSP and CBS among patients presenting with parkinsonian symptoms, which is important for patient counselling and making early decisions about treatment.