Clinical Applications of [¹²³I]FP-CIT SPECT Imaging

Dopamine transporter (DAT) imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) is commonly used in routine clinical studies to exclude or detect a loss of striatal DATs in individual patients with a movement disorder or dementia. In this chapter, we describe the clinical applications of [123I]FP-CIT SPECT imaging. To facilitate the interpretation of [123I]FP-CIT SPECT images, we first describe the results of [123I]FP-CIT SPECT studies in healthy controls. Thereafter, we describe the typical findings when applying this technique in movement disorders and dementia characterised by a loss of striatal DATs (e.g. Parkinson's disease and dementia with Lewy bodies). We will also describe the possibilities to analyse [123I]FP-CIT SPECT scans in the setting of routine clinical practice. Finally, we briefly discuss the characterisation of extrastriatal [123I]FP-CIT binding and its potential role in future studies.</p

Clinical Applications of [¹²³I]FP-CIT SPECT Imaging

Dopamine transporter (DAT) imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) is commonly used in routine clinical studies to exclude or detect a loss of striatal DATs in individual patients with a movement disorder or dementia. In this chapter, we describe the clinical applications of [123I]FP-CIT SPECT imaging. To facilitate the interpretation of [123I]FP-CIT SPECT images, we first describe the results of [123I]FP-CIT SPECT studies in healthy controls. Thereafter, we describe the typical findings when applying this technique in movement disorders and dementia characterised by a loss of striatal DATs (e.g. Parkinson's disease and dementia with Lewy bodies). We will also describe the possibilities to analyse [123I]FP-CIT SPECT scans in the setting of routine clinical practice. Finally, we briefly discuss the characterisation of extrastriatal [123I]FP-CIT binding and its potential role in future studies.</p

Abnormal susceptibility to distracters hinders perception in early stage Parkinson's disease: a controlled study

BACKGROUND: One of the perceptual abnormalities observed in Parkinson's disease (PD) is a deficit in the suppression of reflexive saccades that are automatically triggered by the onset of a peripheral target. Impairment of substantia nigra function is thought to lead to this reduced ability to suppress reflexive saccades. METHODS: The present study examined whether this perceptual deficit is also present in early stage PD when using hardly noticeable task-irrelevant stimuli. Eleven non-demented de novo, untreated PD patients (mean age 57 yr, range 44 – 70) participated in the study as well as 12 age-matched controls. Performance on an 'oculomotor capture' task, in which in half of the trials an irrelevant stimulus with sudden onset was added to the display, was compared between patients and controls. Analysis of variance (ANOVA) was performed with group (patients/controls) and age (< 61 yrs/≥ 61 yrs) as independent factors and type of trial (control/distracter) as repeated measurements factor. The factor sex was used as covariate. RESULTS: With respect to Reaction Time (RT), a significant interaction between group and condition was found. RTs increased under the 'irrelevant stimulus' condition in both groups, the patients exhibiting a significantly larger increase in RTs than the control group. Also, a significant interaction effect between group and condition for number of correct responses was found. The number of correct responses was reduced in the onset distracter condition, the reduction being larger in the patients. In the patient group, contrary to the control group, a higher age was associated with fewer correct responses at baseline and in the onset distracter condition, suggesting that perceptual functions in PD are highly susceptible to the effects of ageing. The increased reaction times and larger number of incorrect responses of the PD patients in the onset distracter condition may be related to impairments of substantia nigra function and lower brain stem. CONCLUSION: The capture task seems to be a sensitive instrument to detect early perceptual deficits in PD. The magnitude of the observed deficits suggests that perceptual functions in early stage PD are so substantially impaired that this may interfere with daily activities

Effects of augmented visual feedback during balance training in Parkinson's disease: A pilot randomized clinical trial

AbstractBackgroundBalance training has been demonstrated to improve postural control in patients with Parkinson's disease (PD). The objective of this pilot randomized clinical trial was to investigate whether a balance training program using augmented visual feedback is feasible, safe, and more effective than conventional balance training in improving postural control in patients with PD.MethodsThirty-three patients with idiopathic PD participated in a five-week training program consisting of ten group treatment sessions of 60 min. Participants were randomly allocated to (1) an experimental group who trained on workstations consisting of interactive balance games with explicit augmented visual feedback (VFT), or (2) a control group receiving conventional training. Standing balance, gait, and health status were assessed at entry, at six weeks, and at twelve weeks follow-up.ResultsSixteen patients were allocated to the control group and seventeen to the experimental group. The program was feasible to apply and took place without adverse events. Change scores for all balance measures favored VFT, but the change in the primary outcome measure, i.e. the Functional Reach test, did not differ between groups (t(28) = -0.116, p = .908). No other differences between groups were statistically significant.ConclusionsVFT proved to be a feasible and safe approach to balance therapy for patients with PD. In this proof-of-concept study VFT was not superior over conventional balance training although observed trends mostly favored VFT. These trends approached clinical relevance only in few cases: increasing the training load and further optimization of VFT may strengthen this effect.Trial registrationControlled Trials, ISRCTN47046299

Differential insular cortex sub-regional atrophy in neurodegenerative diseases: a systematic review and meta-analysis

The insular cortex is proposed to function as a central brain hub characterized by wide-spread connections and diverse functional roles. As a result, its centrality in the brain confers high metabolic demands predisposing it to dysfunction in disease. However, the functional profile and vulnerability to degeneration varies across the insular sub-regions. The aim of this systematic review and meta-analysis is to summarize and quantitatively analyze the relationship between insular cortex sub-regional atrophy, studied by voxel based morphometry, with cognitive and neuropsychiatric deficits in frontotemporal dementia (FTD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). We systematically searched through Pubmed and Embase and identified 519 studies that fit our criteria. A total of 41 studies (n = 2261 subjects) fulfilled the inclusion criteria for the meta-analysis. The peak insular coordinates were pooled and analyzed using Anatomic Likelihood Estimation. Our results showed greater left anterior insular cortex atrophy in FTD whereas the right anterior dorsal insular cortex showed larger clusters of atrophy in AD and PD/DLB. Yet contrast analyses did not reveal significant differences between disease groups. Functional analysis showed t

Bi-allelic <i>NIT1 </i>variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage

Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C&gt;T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C&gt;T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.</p

Bi-allelic <i>NIT1 </i>variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage

Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C&gt;T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C&gt;T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.</p

Prodromal Markers in Parkinson's Disease:Limitations in Longitudinal Studies and Lessons Learned

A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies