Head‐to‐head comparison of 18F‐FP‐CIT and 123I‐FP‐CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study

¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head‐to‐head comparisons between ¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT. Therefore, in this study, ¹²³I‐FP‐CIT SPECT/CT was compared with ¹⁸F‐FP‐CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT. Visual analysis showed that the striatal uptake of both radiotracers was decreased in the PD group, whereas striatal uptake was intact in the ET group. The SBR between ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on ¹⁸F‐FP‐CIT PET/CT were higher than those on ¹²³I‐FP‐CIT SPECT/CT (2.19 ± .87 and 1.22 ± .49, respectively; p < .01). The PCRs in these two modalities were correlated with each other (r = .71, p < .01). The mean PCRs on ¹⁸F‐FP‐CIT PET/CT were not significantly higher than those on ¹²³I‐FP‐CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both ¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT was decreased in the PD group when compared with the ET controls. Visual analyses using both methods did not affect the diagnostic accuracy in this study. However, semiquantitative analysis indicated a better contrast of ¹⁸F‐FP‐CIT PET/CT relative to ¹²³I‐FP‐CIT SPECT/CT.     

Structural connectivity differences in motor network between tremor‐dominant and nontremor Parkinson's disease

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor‐dominant and nontremor PD phenotypes (TD‐PD and NT‐PD, respectively) using probabilistic tractography‐based network analysis. A total of 63 PD patients (35 TD‐PD patients and 28 NT‐PD patients) and 30 healthy controls underwent a 3 T MRI. Next, probabilistic tractography‐based network analysis was performed to assess structural connectivity in cerebello‐thalamo‐basal ganglia‐cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single‐photon emission computed tomography (DAT‐SPECT) with ¹²³I‐ioflupane was used to assess dopaminergic striatal depletion in all PD patients. Both PD phenotypes showed nodal abnormalities in the substantia nigra, in agreement with DAT‐SPECT evaluation. In addition, NT‐PD patients displayed connectivity alterations in nigro‐pallidal and fronto‐striatal pathways, compared with both controls and TD‐PD patients, in which the same motor connections seemed to be relatively spared. Of note, in NT‐PD group, rigidity‐bradykinesia score correlated with fronto‐striatal connectivity abnormalities. These findings demonstrate that structural connectivity alterations occur in the cortico‐basal ganglia circuit of NT‐PD patients, but not in TD‐PD patients, suggesting that these anatomical differences may underlie different motor phenotypes of PD. Hum Brain Mapp 38:4716–4729, 2017. © 2017 Wiley Periodicals, Inc.     

Ictal Single Photon Emission Computed Tomography in Occipital Lobe Seizures

Summary: Purpose: Ictal single photon emission computed tomography (SPECT) has been evaluated as an adjunctive localizing technique in temporal lobe epilepsies and, to a lesser degree, in some extratemporal epilepsies. The purpose of this study was to determine whether occipital lobe seizures are associated with distinctive ictal cerebral blood perfusion (rCP) patterns.
Methods : SPECT was used with the tracer ^99mTc HMPAO to image ictal rCP in 6 patients in whom clinical, EEG, and imaging data indicated occipital lobe seizures.
Results : Two patterns of rCP were seen. Four patients had hyperperfusion that was restricted to the occipital lobe, and two patients had hyperperfusion of the occipital lobe and the ipsilateral mesial temporal lobe, with hypoperfusion of the lateral temporal lobe. The latter 2 patients had clinical and surface EEG evidence of temporal lobe involvement in the seizure discharge.
Conclusions : Ictal rCP patterns in occipital lobe seizures are distinct from those in temporal lobe seizures and may vary according to whether or not ipsilateral temporal lobe structures are involved in the ictal discharge.     

Brain Single Photon Emission Computed Tomography Imaging in Landau-Kleffner Syndrome

Summary: Five right–handed children with Landau-Kleffner syndrome (LKS) who had disease onset between the ages of 3 and 9 years were studied with EEG and single-photon emission computed tomography (SPECT) before and, in four cases, after 6 months of corticosteroid treatment. EEG findings included both focal and generalized spikes as well as spike-wave discharges with bilateral temporal predominance. These increased markedly during sleep in 1 child, and continuous spike-and-wave complexes appeared during slow-wave sleep in another patient. Neuropsychological testing demonstrated verbal auditory agnosia. Magnetic resonance imaging (MRI) was performed in 4 children and was normal. Brain SPECT imaging demonstrated abnormal perfusion in the left temporal lobe in all patients. The response to corticosteroid therapy was mixed. Our findings reinforce the concept that LKS is a functional disease affecting the language-dominant brain areas. We conclude that SPECT imaging may be of diagnostic assistance in the evaluation of this syndrome of unknown etiology.     

Residual striatal dopaminergic nerve terminals in very long‐standing Parkinson's disease: A single photon emission computed tomography imaging study

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long‐standing PD has not yet been specifically explored. Therefore, we performed [¹²³I]‐FP‐CIT single photon emission computed tomography (SPECT) in 15 patients with very long‐standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [¹²³I]‐FP‐CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD. © 2010 Movement Disorder Society     

Teaching program for the movement disorder society‐sponsored revision of the Unified Parkinson's Disease Rating Scale: (MDS‐UPDRS)

To accompany the newly developed Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), we developed a teaching program. The DVD‐based program covers the four parts of the scale with visual and verbal instructions for uniform application. For the motor section (Part III), all items except rigidity are shown with an example of each rating option (0–4) as agreed upon by a panel of experts. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.99 and 0.72. The teaching program also provides a full patient examination with rating answers provided and four full MDS‐UPDRS cases for a Certificate Program exercise of Part III. This training program is in English, but as non‐English official translations of the MDS‐UPDRS are developed, the program can be potentially modified into different languages. © 2010 Movement Disorder Society     

Nurr1‐Based Therapies for Parkinson's Disease

Previous studies have documented that orphan nuclear receptor Nurr1 (also known as NR4A2) plays important roles in the midbrain dopamine (DA) neuron development, differentiation, and survival. Furthermore, it has been reported that the defects in Nurr1 are associated with Parkinson's disease (PD). Thus, Nurr1 might be a potential therapeutic target for PD. Emerging evidence from in vitro and in vivo studies has recently demonstrated that Nurr1‐activating compounds and Nurr1 gene therapy are able not only to enhance DA neurotransmission but also to protect DA neurons from cell injury induced by environmental toxin or microglia‐mediated neuroinflammation. Moreover, modulators that interact with Nurr1 or regulate its function, such as retinoid X receptor, cyclic AMP‐responsive element‐binding protein, glial cell line‐derived neurotrophic factor, and Wnt/β‐catenin pathway, have the potential to enhance the effects of Nurr1‐based therapies in PD. This review highlights the recent progress in preclinical studies of Nurr1‐based therapies and discusses the outlook of this emerging therapy as a promising new generation of PD medication.     

A within‐subject comparison of 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]fluoro‐L‐dopa in Parkinson's disease

Progression of Parkinson's disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6‐[¹⁸F]fluoro‐m‐tyrosine is not a substrate for catechol‐O‐methyltransferase and therefore has a more favorable uptake‐to‐background ratio than 6‐[¹⁸F]fluoro‐L ‐dopa. The objective of this study was to evaluate 6‐[¹⁸F]fluoro‐m‐tyrosine relative to 6‐[¹⁸F]fluoro‐L ‐dopa with partial catechol‐O‐methyltransferase inhibition as a biomarker for clinical status in Parkinson's disease. Twelve patients with early‐stage Parkinson's disease, off medication, underwent Unified Parkinson Disease Rating Scale scoring, brain magnetic resonance imaging, and 3‐dimensional dynamic positron emission tomography using equivalent doses of 6‐[¹⁸F]fluoro‐m‐tyrosine and 6‐[¹⁸F]fluoro‐L ‐dopa with tolcapone, a catechol‐O‐methyltransferase inhibitor. Images were realigned within subject, after which the tissue‐derived uptake rate constant was generated for volumes of interest encompassing the caudate nucleus, putamen, and subregions of the putamen. We computed both bivariate (Pearson) and partial (covariate of age) correlations between clinical subscores and tissue‐derived uptake rate constant. Tissue‐derived uptake rate constant values were correlated between the radiopharmaceuticals (r = 0.8). Motor subscores were inversely correlated with the contralateral putamen 6‐[¹⁸F]fluoro‐m‐tyrosine tissue‐derived uptake rate constant (|r| > 0.72, P < .005) but not significantly with the 6‐[¹⁸F]fluoro‐L ‐dopa tissue‐derived uptake rate constant. The uptake rate constants for both radiopharmaceuticals were also inversely correlated with activities of daily living subscores, but the magnitude of correlation coefficients was greater for 6‐[¹⁸F]fluoro‐m‐tyrosine. In this design, 6‐[¹⁸F]fluoro‐m‐tyrosine uptake better reflected clinical status than did 6‐[¹⁸F]fluoro‐L ‐dopa uptake. We attribute this finding to 6‐[¹⁸F]fluoro‐m‐tyrosine's higher affinity for the target, L ‐aromatic amino acid decarboxylase, and the absence of other major determinants of the uptake rate constant. These results also imply that L ‐aromatic amino acid decarboxylase activity is a major determinant of clinical status. © 2011 Movement Disorder Society     

SCOPA‐cognition cutoff value for detection of Parkinson's disease dementia

The SCOPA‐Cognition is a reliable and valid test to evaluate cognitive functioning in Parkinson's disease and is widely used in clinical and research settings. Recently, the Movement Disorder Society introduced criteria for Parkinson's disease dementia. The objective of the present study was to use these criteria to determine SCOPA‐Cognition cutoffs for maximum accuracy, screening, and diagnosing of Parkinson's disease dementia. A total of 282 patients with Parkinson's disease were assessed with the SCOPA‐Cognition and the Movement Disorder Society's Parkinson's disease dementia criteria. From the 275 patients with a complete assessment of the dementia criteria, 12% (n = 32) fulfilled the criteria. Data from 268 patients with complete assessments of both the dementia criteria and the SCOPA‐Cognition were used to determine cutoffs for maximum accuracy, screening, and diagnosing of Parkinson's disease dementia. The area under the curve was 0.91 (95% confidence interval, 0.85–0.97), showing a strong association between the dementia criteria and the SCOPA‐Cognition. The cutoff for maximum accuracy was 22/23, based on the highest sum of sensitivity (0.80) and specificity (0.87), with positive and negative predictive values of 0.43 and 0.97, respectively. The optimal screening cutoff was 24/25, and the optimal diagnostic cutoff was 17/18. Using the recently published Parkinson's disease dementia criteria as a reference, the current study presents SCOPA‐Cognition cutoffs for maximum accuracy, screening, and diagnosing of Parkinson's disease dementia. The availability of SCOPA‐Cognition cutoffs for Parkinson's disease dementia may contribute to the scale's usefulness and promote its further use in both clinical and research settings. © 2011 Movement Disorder Society