Longitudinal network changes and phenoconversion risk in isolated REM sleep behavior disorder.

Isolated rapid eye movement sleep behavior disorder is a prodrome of α-synucleinopathies. Using positron emission tomography, we assessed changes in Parkinson's disease-related motor and cognitive metabolic networks and caudate/putamen dopaminergic input in a 4-year longitudinal imaging study of 13 male subjects with this disorder. We also correlated times to phenoconversion with baseline network expression in an independent validation sample.

Disordered network structure and function in dystonia: pathological connectivity vs. adaptive responses.

Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations.

Functional brain networks in the evaluation of patients with neurodegenerative disorders.

Network analytical tools are increasingly being applied to brain imaging maps of resting metabolic activity (PET) or blood oxygenation-dependent signals (functional MRI) to characterize the abnormal neural circuitry that underlies brain diseases. This approach is particularly valuable for the study of neurodegenerative disorders, which are characterized by stereotyped spread of pathology along discrete neural pathways. Identification and validation of disease-specific brain networks facilitate the quantitative assessment of pathway changes over time and during the course of treatment.

Stereotyped Relationship Between Motor and Cognitive Metabolic Networks in Parkinson's Disease.

Background: Idiopathic Parkinson's disease (iPD) is associated with two distinct brain networks, PD-related pattern (PDRP) and PD-related cognitive pattern (PDCP), which correlate respectively with motor and cognitive symptoms. The relationship between the two networks in individual patients is unclear.

Objective: To determine whether a consistent relationship exists between these networks, we measured the difference between PDRP and PDCP expression, termed delta, on an individual basis in independent populations of patients with iPD (n = 356), patients with idiopathic REM sleep behavioral disorder (iRBD) (n = 21), patients with genotypic PD (gPD) carrying GBA1 variants (n = 12) or the LRRK2-G2019S mutation (n = 14), patients with atypical parkinsonian syndromes (n = 238), and healthy control subjects (n = 95) from the United States, Slovenia, India, and South Korea.

Adaptive and pathological connectivity responses in Parkinson's disease brain networks.

Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, whether the connectivity patterns in these networks differ with disease progression compared to the beneficial adaptations that may also occur over time. To distinguish the 2 responses, we focused on assortativity, the tendency for network connections to link nodes with similar properties.

Cognition-Related Functional Topographies in Parkinson's Disease: Localized Loss of the Ventral Default Mode Network.

Cognitive dysfunction in Parkinson's disease (PD) is associated with increased expression of the PD cognition-related pattern (PDCP), which overlaps with the normal default mode network (DMN). Here, we sought to determine the degree to which the former network represents loss of the latter as a manifestation of the disease process. To address this, we first analyzed metabolic images (fluorodeoxyglucose positron emission tomography [PET]) from a large PD sample with varying cognitive performance.

Diplopia in Parkinson's disease: Indication of a cortical phenotype with cognitive dysfunction?

Background: Visual disturbances are increasingly recognized as common non-motor symptoms in Parkinson's disease (PD). In PD patients, intermittent diplopia has been found to be associated with the presence of visual hallucinations and the Parkinson's psychosis spectrum. Here, we investigated whether diplopia in PD is associated with other non-motor traits and cognitive impairment.

Neuropathological correlation supports automated image-based differential diagnosis in parkinsonism.

Purpose: Up to 25% of patients diagnosed as idiopathic Parkinson's disease (IPD) have an atypical parkinsonian syndrome (APS). We had previously validated an automated image-based algorithm to discriminate between IPD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). While the algorithm was accurate with respect to the final clinical diagnosis after long-term expert follow-up, its relationship to the initial referral diagnosis and to the neuropathological gold standard is not known.

Dynamic F-FPCIT PET: Quantification of Parkinson's disease metabolic networks and nigrostriatal dopaminergic dysfunction in a single imaging session.

Previous multi-center imaging studies with F-FDG PET have established the presence of Parkinson's disease motor- and cognition-related metabolic patterns termed PDRP and PDCP in patients with this disorder. Given that in PD cerebral perfusion and glucose metabolism are typically coupled in the absence of medication, we determined whether subject expression of these disease networks can be quantified in early-phase images from dynamic F-FPCIT PET scans acquired to assess striatal dopamine transporter (DAT) binding. We studied a cohort of early-stage PD patients and age-matched healthy control subjects who underwent F-FPCIT at baseline; scans were repeated 4 years later in a smaller subset of patients.

Metabolic Network Abnormalities in Drug-Naïve Parkinson's Disease.

Background: An ideal imaging biomarker for a neurodegenerative disorder should be able to measure abnormalities in the earliest stages of the disease.

Objective: We investigated metabolic network changes in two independent cohorts of drug-naïve Parkinson's disease (PD) patients who have not been exposed to dopaminergic medication.

Methods: We scanned 85 de novo, drug-naïve PD patients and 85 age-matched healthy control subjects from Italy (n = 96) and the United States (n = 74) with [ F]-fluorodeoxyglucose PET.

LRRK2 and GBA Variants Exert Distinct Influences on Parkinson's Disease-Specific Metabolic Networks.

The natural history of idiopathic Parkinson's disease (PD) varies considerably across patients. While PD is generally sporadic, there are known genetic influences: the two most common, mutations in the LRRK2 or GBA1 gene, are associated with slower and more aggressive progression, respectively. Here, we applied graph theory to metabolic brain imaging to understand the effects of genotype on the organization of previously established PD-specific networks.

Network imaging biomarkers: insights and clinical applications in Parkinson's disease.

Parkinson's disease presents several practical challenges: it can be difficult to distinguish from atypical parkinsonian syndromes, clinical ratings can be insensitive as markers of disease progression, and its non-motor manifestations are not readily assessed in animal models. These challenges, along with others, are beginning to be addressed by innovative imaging methods to characterise Parkinson's disease-specific functional networks across the whole brain and measure their expression in each patient. These signatures can help improve differential diagnosis, guide selection of patients for clinical trials, and quantify treatment responses and placebo effects in individual patients.

Relationships between activity and well-being in people with parkinson's disease.

Objectives: The complex symptomatology of Parkinson' disease (PD) usually goes along with reduced physical activity. Previous studies have indicated positive effects of activating therapies on patients' well-being. This study, therefore, examined how activity in daily life is related to patients' subjective condition.

Restless legs syndrome is a relevant comorbidity in patients with inflammatory bowel disease.

Background And Aims: In patients with inflammatory bowel disease (IBD), restless legs syndrome (RLS) may occur as an extraintestinal disease manifestation. Iron deficiency (ID) or folate deficiency/vitamin B deficiency (FD/VBD) has previously been described to cause RLS. Here, we determined the prevalence and severity of RLS in IBD patients and evaluated the effect of iron and/or folic acid/vitamin B supplementation.

Assessment of thrombus length in acute ischemic stroke by post-contrast magnetic resonance angiography.

Objectives: Post-contrast magnetic resonance angiography (PC-MRA) enables visualization of vessel segments distal to an intra-arterial thrombus in acute ischemic stroke. We hypothesized that PC-MRA also allows clot length measurement in different intracranial vessels.

Methods: Patients with MRI-confirmed ischemic stroke and intracranial artery occlusion within 24 hours of symptom onset were prospectively evaluated.

Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia.

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts.

Characterization of diplopia in non-demented patients with Parkinson's disease.

Introduction: Although diplopia is considered a frequent symptom of Parkinson's disease (PD), little is known about its clinical manifestation, associated mechanisms and treatment. Here we characterized binocular diplopia in non-demented PD patients in an interdisciplinary setting.

Methods: PD patients were prospectively screened for diplopia, visual hallucinations, problems with spatial perception, contrast sensitivity, presence of blurred vision, and history of ophthalmological comorbidities via interview.

Theory of mind performance in Parkinson's disease is associated with motor and cognitive functions, but not with symptom lateralization.

Next to the typical motor signs, Parkinson's disease (PD) goes along with neuropsychiatric symptoms, amongst others affecting social cognition. Particularly, Theory of Mind (ToM) impairments have mostly been associated with right hemispherical brain dysfunction, so that it might prevail in patients with left dominant PD. Fourty-four PD patients, twenty-four with left and twenty with right dominant motor symptoms, engaged in the Reading the Mind in the Eyes (RME) and the Faux Pas Detection Test (FPD) to assess affective and cognitive ToM.

Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life.

Purpose: Inflammatory bowel disease has been associated with neurological symptoms including restless legs syndrome. Here, we investigated the impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, mood, cognition, and quality of life.

Methods: Two groups of inflammatory bowel disease patients, with and without restless legs syndrome, were prospectively evaluated for sleep disorders, fatigue, daytime sleepiness, depression, anxiety, and health-related quality of life.

The single intake of levodopa modulates implicit learning in drug naïve, de novo patients with idiopathic Parkinson's disease.

Although dopamine is known to aggravate implicit learning, the exact impact on behaviour when feedback is unavailable remains unclear. Previous studies revealed that non-rewarded learning habits are affected in long-term dopaminergic treated patients with Parkinson's disease (PD). We studied the influence of a onetime levodopa intake on implicit learning in de novo, untreated PD patients.