Dopamine Transporter SPECT Research Articles

Determination of Parkinson Disease Laterality After Deep Brain Stimulation Using 123I FP-CIT SPECT.

Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS. Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS. At baseline, 11, 6, and 2 among 19 patients had left-side-dominant, right-side-dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline (r = 0.542, P = 0.02), 6 months (r = 0.579, P = 0.01), and 1 year after DBS (r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 (P = 0.045), 0.982 (P < 0.001), and 1.000 (P < 0.001) at baseline and 6 and 12 months after DBS, respectively. The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.

Clinical Phenotypes in Corticobasal Syndrome with or without Amyloidosis Biomarkers.

Corticobasal syndrome (CBS) is a neuropathologically heterogeneous entity. The use of cerebrospinal fluid and amyloid biomarkers enables detection of underlying Alzheimer's disease (AD) pathology. We thus compared clinical, eye movement, and 18FDG-PET imaging characteristics in CBS in two groups of patients divided according to their amyloid biomarkers profile. Fourteen patients presenting with CBS and amyloidosis (CBS-A+) were compared with 16 CBS patients without amyloidosis (CBS-A-). The two groups showed similar motor abnormalities (parkinsonism, dystonia) and global cognitive functions. Unlike CBS-A+ patients who displayed more posterior cortical abnormalities, CBS-A- patients demonstrated more anterior cortical and brain stem dysfunctions on the basis of neuropsychological testing, study of saccade velocities and brain hypometabolism areas on 18FDG-PET. Interestingly, Dopamine Transporter SPECT imaging showed similar levels of dopaminergic degeneration in both groups. These findings confirm common and distinct brain abnormalities between the different neurodegenerative diseases that result in CBS. We demonstrate the importance of a multidisciplinary approach to improve diagnosis in vivo in particular on oculomotor examination.

&lt;p&gt;Voxel-Based Morphometry Analysis of Structural MRI for Differentiation Between Dementia with Lewy Bodies and Alzheimer’s Disease [Letter]&lt;/p&gt;

Voxel-Based Morphometry Analysis of Structural MRI for Differentiation Between Dementia with Lewy Bodies and Alzheimer's Disease [Letter] Shohei Inui, 1, 2 Keita Sakurai, 1 Yoshio Hashizume 3 1Department of Radiology, Teikyo University School of Medicine, Tokyo, Japan; 2Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 3Choju Medical Institute, Fukushimura Hospital, Aichi, JapanCorrespondence: Keita SakuraiDepartment of Radiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, JapanTel +81-3-3964-1211Email ksak666@yahoo.co.jp We read the article entitled “Differentiation Between Dementia With Lewy Bodies And Alzheimer’s Disease Using Voxel-Based Morphometry Of Structural MRI: A Multicenter Study” by Matsuda et al with great interest.1 The authors recruited 239 patients with dementia with Lewy bodies (DLB) and 385 patients with Alzheimer’s disease (AD), and evaluated the utility of Voxel-Based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD®) for their differentiation. They also emphasized the value of dorsal brainstem (DBS) atrophy in addition to medial temporal lobe (MTL) atrophy. As the authors noted, to differentiate AD from DLB is important in the clinical setting to select appropriate pharmacotherapy. Considering the difficulty of using indicative biomarkers including dopamine transporter SPECT in all patients, it is beneficial to reinforce the supportive feature MRI using voxel-based morphometry for the differential diagnosis.

Hyposmia as a marker of (non-)motor disease severity in Parkinson\u2019s disease

The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.

Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics.

This study investigated the potential of deep convolutional neural networks (CNN) for automatic classification of FP-CIT SPECT in multi-site or multi-camera settings with variable image characteristics. The study included FP-CIT SPECT of 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls, and 438 Parkinson's disease patients. SPECT images were smoothed with an isotropic 18-mm Gaussian kernel resulting in 3 different PPMI settings: (i) original (unsmoothed), (ii) smoothed, and (iii) mixed setting comprising all original and all smoothed images. A deep CNN with 2,872,642 parameters was trained, validated, and tested separately for each setting using 10 random splits with 60/20/20% allocation to training/validation/test sample. The putaminal specific binding ratio (SBR) was computed using a standard anatomical ROI predefined in MNI space (AAL atlas) or using the hottest voxels (HV) analysis. Both SBR measures were trained (ROC analysis, Youden criterion) using the same random splits as for the CNN. CNN and SBR trained in the mixed PPMI setting were also tested in an independent sample from clinical routine patient care (149 with non-neurodegenerative and 149 with neurodegenerative parkinsonian syndrome). Both SBR measures performed worse in the mixed PPMI setting compared to the pure PPMI settings (e.g., AAL-SBR accuracy = 0.900 ± 0.029 in the mixed setting versus 0.957 ± 0.017 and 0.952 ± 0.015 in original and smoothed setting, both p < 0.01). In contrast, the CNN showed similar accuracy in all PPMI settings (0.967 ± 0.018, 0.972 ± 0.014, and 0.955 ± 0.009 in mixed, original, and smoothed setting). Similar results were obtained in the clinical sample. After training in the mixed PPMI setting, only the CNN provided acceptable performance in the clinical sample. These findings provide proof of concept that a deep CNN can be trained to be robust with respect to variable site-, camera-, or scan-specific image characteristics without a large loss of diagnostic accuracy compared with mono-site/mono-camera settings. We hypothesize that a single CNN can be used to support the interpretation of FP-CIT SPECT at many different sites using different acquisition hardware and/or reconstruction software with only minor harmonization of acquisition and reconstruction protocols.

Revision of Diagnosis in Early Parkinsonism with Abnormal Dopamine Transporter Imaging.

In patients with early parkinsonism, misdiagnosis may occur in >30% of cases. This can have detrimental consequences clinically and in clinical trials. Dopamine transporter (DAT) SPECT imaging can help improve diagnostic accuracy. To describe characteristics of individuals initially diagnosed with idiopathic Parkinson's disease (iPD) and with abnormal DAT SPECT imaging who had a change in diagnosis on follow-up. Data were obtained from the biomarker study Parkinson's Progression Markers Initiative (PPMI). PPMI is a multicenter, observational study that enrolled 423 individuals with a diagnosis of iPD of ≤2 years duration and with abnormal DAT SPECT imaging. Participants were assessed at least annually, and diagnosis was documented by the site neurologist. Characteristics of those that had a change in diagnosis were compared to those with stable diagnosis. 390 subjects were included. Eight (2%) had a change in diagnosis. The diagnosis was changed to multiple system atrophy in 5 cases, dementia with Lewy bodies in 2, and corticobasal degeneration in 1. Revision of diagnosis occurred 2-5.2 years from enrollment. Mean motor score was higher (26.9 vs 20.6; p = 0.01), DAT binding lower (1.056 vs 1.406; p = 0.01), genetic risk score lower (-0.016 vs -0.022; p = 0.0470), and olfaction score higher (28.75 vs 22.05; p = 0.03) in those whose diagnosis changed compared to those who did not. Diagnosis remained stable in most individuals with early parkinsonism diagnosed with iPD and with abnormal DAT imaging. A small number had a revision in diagnosis. Clinical and biomarker abnormalities were greater at baseline in those whose diagnosis changed.

Quantifying the Severity of Parkinson Disease by Use of Dopaminergic Neuroimaging.

OBJECTIVE. Parkinson disease is characterized by dopaminergic neuron loss in the substantia nigra pars compacta resulting in presynaptic nigrostriatal dopamine dysfunction. The purpose of this study was to search for an optimal image biomarker to quantify the severity of Parkinson disease by comparing neuromelanin MRI and dopamine transporter SPECT. SUBJECTS AND METHODS. Forty patients with Parkinson disease (Hoehn and Yahr [HY] stage 1, four patients; stage 2, 18 patients; stage 3, eight patients; stage 4, six patients; stage 5, four patients) who underwent neuromelanin MRI and dopamine transporter SPECT were included. The signal-to-noise ratio (SNR) in the substantia nigra pars compacta on neuromelanin MR images and the striatal specific binding ratio (SBR) on dopamine transporter SPECT images were calculated on the basis of the value of each background region. The Mann-Whitney U test was used to test the significance of difference between the early-stage group (HY stages 1 and 2) and the advanced-stage group (HY stages 3-5) for each SNR and SBR. ROC analysis was used to compare intergroup discriminating performance. The correlation of each SNR and SBR with clinical rating scale was assessed. RESULTS. Both SNR and SBR were significantly greater in the early-stage group than in the advanced-stage group (p < 0.05). The ROC AUCs for differentiating the two groups were 0.73 for SNR and 0.89 for SBR. The coefficients of correlation were -0.47 for SNR versus HY stage and -0.67 for SBR versus HY stage. CONCLUSION. Dopaminergic neuroimaging, particularly dopamine transporter SPECT, is a potentially useful imaging biomarker of the severity of Parkinson disease.

The Combination of DAT-SPECT, Structural and Diffusion MRI Predicts Clinical Progression in Parkinson’s Disease

There is an increasing interest in identifying non-invasive biomarkers of disease severity and prognosis in idiopathic Parkinson’s disease (PD). Dopamine-transporter SPECT (DAT-SPECT), diffusion tensor imaging (DTI), and structural magnetic resonance imaging (sMRI) provide unique information about the brain’s neurotransmitter and microstructural properties. In this study, we evaluate the relative and combined capability of these imaging modalities to predict symptom severity and clinical progression in de novo PD patients. To this end, we used MRI, SPECT, and clinical data of de novo drug-naïve PD patients (n = 205, mean age 61 ± 10) and age-, sex-matched healthy controls (n = 105, mean age 58 ± 12) acquired at baseline. Moreover, we employed clinical data acquired at 1 year follow-up for PD patients with or without L-Dopa treatment in order to predict the progression symptoms severity. Voxel-based group comparisons and covariance analyses were applied to characterize baseline disease-related alterations for DAT-SPECT, DTI, and sMRI. Cortical and subcortical alterations in de novo PD patients were found in all evaluated imaging modalities, in line with previously reported midbrain-striato-cortical network alterations. The combination of these imaging alterations was reliably linked to clinical severity and disease progression at 1 year follow-up in this patient population, providing evidence for the potential use of these modalities as imaging biomarkers for disease severity and prognosis that can be integrated into clinical trials.

SUCCESSFUL USE OF ELECTROCONVULSIVE THERAPY FOR THE TREATMENT OF NEUROPSYCHIATRIC MANIFESTATIONS OF DEMENTIA WITH LEWY BODIES

Introduction Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative disorders. DLB is characterized by progressive cognitive decline, executive dysfunction, visual hallucinations, fluctuating cognition, and Parkinsonism. Up to 65% of patients with Lewy Body Dementia have depression. Psychiatrists frequently treat individuals with DLB given prominent neuropsychiatric manifestations, including depression, hallucinations, delusions, agitation, and fluctuating cognition. Individuals with DLB require a comprehensive but specific treatment approach given sensitivity to both antipsychotic medications and anticholinergic side effects of other medications. Electroconvulsive therapy (ECT) is often omitted from the treatment model for DLB because of limited evidence. We highlight the use of electroconvulsive therapy (ECT) in a case of DLB. Methods We provide a case report and literature review on the use of ECT for the treatment of DLB. A 67-year-old male veteran with depression, 10-year history of REM sleep behavior disorder, bradykinesia, three-year history of cognitive impairment, and visual hallucinations was admitted for depressed mood and disturbing visual hallucinations featuring a saw blade swinging around his head and somatic delusion of a water hose traversing his body. At night he moved to avoid being hit by the blade. His wife reported word-finding difficulty, memory problems, and having to manage their finances. Four years prior to presentation, he stopped working as a pastor due to inability to write sermons. On admission, his MOCA was 19/30 and QIDS was 22. Medication trials including paroxetine, sertraline, escitalopram, vilazodone, bupropion, mirtazapine, venlafaxine, quetiapine, aripiprazole, alprazolam, buspirone, and lorazepam failed to address his depression and hallucinations. Results Brain MRI was unremarkable, with mild microvascular ischemic changes in periventricular white matter. Iodine-123 dopamine transporter SPECT (DAT-scan) imaging showed abnormal uptake consistent with a Parkinsonian syndrome (supporting the diagnosis of DLB). Considering past medication failures, patient consented for an acute course of ECT. He received eight right unilateral (RUL) ultra-brief pulse treatments utilizing Mecta Spectrum over the course of three weeks without any major side effects. For muscle relaxation he received succinylcholine; methohexital and remifentanil were given for anesthesia. Over his acute course of treatment, charge was progressively increased from six, to eight, to ten times the seizure threshold. At the end of his acute course of eight ECT treatments, his MOCA improved from 19/30 to 23/30 and QIDS improved from 22 to 12. Following the course of ECT, his visual hallucinations disappeared, and he was more interactive, engaged, and less depressed. The patient's improvement is congruent with other case reports in the literature showing clinical improvement following ECT for symptoms related to DLB. A table with a literature review describing the use of ECT for DLB will be presented. Conclusions DLB presents frequently to psychiatrists secondary to prominent psychiatric manifestations of the illness such as mood and behavioral disturbances. The treatment of psychiatric symptoms in DLB is often challenging due to the sensitivity of antidopaminergic medications on motor symptoms. ECT is a feasible alternative to treat neuropsychiatric manifestations of DLB; however, infrequently considered due to fear of complications and stigma. Modifications to the treatment such us holding dopamine agonists the morning of ECT to avoid delirium, decreasing the frequency of ECT to twice per week to minimize cognitive effects, and close monitoring of the patient's cognitive function are measures that can be implemented to optimize ECT in this population. No double-blinded randomized control trials exist in this area; comparing standard treatment to ECT would help further delineate the role of ECT in treating patients with DLB. This research was funded by None.

Dopamine transporter imaging for the diagnosis of multiple system atrophy cerebellar type

IntroductionThe added value of dopamine transporter SPECT (DAT-SPECT) for the diagnosis of “possible” multiple system atrophy of the cerebellar type (MSA-C) remains unknown. MethodsWe reviewed retrospectively the charts of 128 consecutive patients with a clinical diagnosis of MSA-C who were seen between 2007 and 2016 at the French Reference Center for MSA. The main objective was to evaluate the proportion of patients for whom the diagnosis of “possible” MSA-C was made because of a positive DAT-SPECT. ResultsSeventy-eight MSA-C patients had at least one DAT-SPECT. Fifty-nine of them were considered for the final analysis. In these, 22 had “possible” MSA-C and 23 “probable” MSA-C before DAT-SPECT, while 14 did not reach diagnosis criteria at that time. In those with “possible” MSA-C, DAT-SPECT was positive in 64%. In patients with “probable” MSA-C, 83% showed nigrostriatal denervation. Six out of 14 (43%) received a diagnosis of “possible” MSA-C because of positive DAT-SPECT. These patients had mean disease duration of 2.3 years at the time of DAT-SPECT compared to 3.5 years of the entire cohort of MSA-C patients with DAT-SPECT. Of the eight remaining, one had positive DAT-SPECT but also pons atrophy on magnetic resonance imaging, and seven progressed to “probable” MSA based on clinical features. ConclusionOur results suggest that DAT-SPECT significantly contributes to the diagnosis of “possible” MSA-C (43% of patients not reaching consensus diagnosis criteria before DAT-SPECT). DAT-SPECT seems especially useful in patients with shorter disease duration, while a negative result does not exclude a diagnosis of MSA.

Dopamine Transporter SPECT with I-123 labelled FP-CIT (DaTSCANTM)

The aim of the S1 guideline is to assist in establishing the indication and in performing, interpreting and reporting SPECT investigations of the dopamine transporter (DAT) with DaTSCANTM. Compared to the preceding version dated from 2007 the current update considers relevant new publications, the guidelines of the European (EANM) and Society of Nuclear Medicine (SNM), and the current version of the S3 guideline of the German Society of Neurology on "Idiopathic Parkinsonsian Syndrome". In addition new technical developments are incorporated.

Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder

REM sleep behavior disorder (RBD) is strongly associated with development of Parkinson’s Disease and other α-synuclein-related disorders. Dopamine transporter (DAT) binding deficit predicts conversion to α-synuclein-related disorders in individuals with RBD. In turn, identifying which individuals with RBD have the highest likelihood of having abnormal DAT binding would be useful. The objective of this analysis was to examine if there are basic clinical predictors of DAT deficit in RBD. Participants referred for inclusion in the RBD cohort of the Parkinson Progression Markers Initiative were included. Assessments at the screening visit including DAT SPECT imaging, physical examination, cognitive function screen, and questionnaire-based non-motor assessment. The group with DAT binding deficit (n = 49) was compared to those without (n = 26). There were no significant differences in demographic or clinical features between the two groups. When recruiting RBD cohorts enriched for high risk of neurodegenerative disorders, our data support the need for objective biomarker assessments.

Individual parkinsonian motor signs and striatal dopamine transporter deficiency: a study with [I-123]FP-CIT SPECT

IntroductionTotal parkinsonian motor symptom severity correlates with presynaptic striatal dopamine function in patients with Parkinson’s disease. There is a lack of studies that have investigated the associations between parkinsonian motor signs and striatal dopaminergic deficiency in patients with parkinsonism of an unknown origin. Identification of specific motor signs associated with the highest likelihood of striatal dopamine deficiency could aid the differential diagnostics of parkinsonian and tremor syndromes.MethodsIn this cross-sectional clinical and imaging study, detailed motor examinations were performed for 221 patients with parkinsonism or tremor of an unknown origin immediately before dopamine transporter (DAT) [I-123]FP-CIT SPECT imaging. Region-of-interest and voxel-based methods were used to investigate striatal DAT deficiency in relation to individual motor signs.ResultsUpper extremity rigidity and facial expression were the only motor signs that differentiated patients with normal and abnormal striatal DAT function. The presence of any upper extremity rigidity showed the highest likelihood of DAT deficiency (OR 4.79, 95% CI 1.56–14.75, P = 0.006) followed by reduced facial expression (OR 2.14, 95% CI 1.14–4.00, P = 0.018). In patients with DAT deficits, reduced facial expression was associated with DAT deficiency specifically in the caudate nucleus, and increased upper extremity rigidity was associated with DAT loss in the dorsal putamen (FWE-corrected P < 0.05).ConclusionsIncreased upper extremity muscle tone and hypomimia are independently associated with a higher likelihood of striatal hypodopaminergic imaging finding. This information can be used as a factor when the clinical need of auxiliary investigations, such as DAT SPECT, is considered for patients with parkinsonism.

The applicability of 123I-FP-CIT SPECT dopamine transporter imaging in clinical practice

The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer's disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.

Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4).

Background:α-synuclein is a lead Parkinson’s disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC).Objective:To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study.Methods:Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded.Results:The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred.Conclusion:Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.

High prevalence of parkinsonism in patients with MCI or mild Alzheimer's disease

IntroductionThe objective of this study was to examine the prevalence of the coexistence of parkinsonism in patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD). MethodsOutpatients were evaluated with Mini–Mental State Examination, Clinical Dementia Rating Scale, NIA-AA criteria, MRI, and 123I-IMP SPECT (3D-SSP). Parkinsonism in patients diagnosed with MCI (Mini–Mental State Examination ≥24, n = 63) or mild AD (Mini–Mental State Examination 20–23, n = 43) was examined using the Unified Parkinson's Disease Rating Scale–III and 123I-FP-CIT dopamine transporter SPECT. ResultsOne hundred six patients (60–97 years) were enrolled. Fifty-six patients (52.8%) were diagnosed as having concomitant parkinsonism with rigidity and resting tremor and dopamine transporter reduction in the basal ganglia. The mean (SD) age (n = 56) was 80.6 (6.1) years, significantly older than patients without parkinsonism [77.6 (7.0) years, n = 50] (P < .05). The mean (SD) UPDRS–III score was 5.8 (2.4). ConclusionThe prevalence rate of the coexistence of mild parkinsonism in MCI or mild AD may be higher than previously recognized.

Author response: Teaching NeuroImages: A rare case of giant perivascular spaces in the midbrain manifesting as atypical parkinsonism.

We appreciate the comments of Dr. Shakya Bhattacharjee on our Teaching NeuroImage.1 Certainly, the present case raises concern about the final reason for this parkinsonism. We did not carry out dopamine transporter (DaT) SPECT scan because we did not think it would be of substantial help to understand the nature of our patient's parkinsonism. DaT SPECT is a useful tool, but is not the gold standard for parkinsonism diagnosis.2,3 DaT scan can also be abnormal in secondary parkinsonisms, such as vascular or mass-related parkinsonism.3,4 In any case, there are at least 3 published cases with parkinsonism associated to dilated Virchow-Robin spaces and abnormal DaT scan.5,6 Another case, with reviewed and updated information, including DaT status of several cases, was published last year.7

Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation

BackgroundDystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally.Case presentationA 19-year-old girl with congenital mild dysmorphic facial features, cochlear implants for infant-onset deafness, and mild cognitive and emotional disability, presented with an adolescent-onset, severe generalized dystonia. Brain MRI and multiple single gene sequencing were inconclusive. Due to life-threatening dystonia, we implanted a neurostimulation device, targeting the postero-ventral internal pallidum bilaterally. The Burke-Fahn-Marsden Dystonia Rating Scale motor/disability scores improved from 87/25 to 21/13 at 2.5 months postoperatively, 26/14 at 3 years, and 30/14 at 4 years. Subsequent whole exome sequencing identified heterozygosity for the ACTB p.Arg183Trp variant. Brain imaging included 123I-ioflupane single photon emission computed tomography (Dopamine Transporter-SPECT), SPECT with 123I-epidepride (binds to dopamine type 2-receptors) and 18 Fluoro-Deoxy-Glucose (FDG)–PET. Both Epidepride-SPECT and FDG-PET showed reduced tracer uptake in the striatum bilaterally, particularly in the putamen. DaT-SPECT was slightly abnormal.ConclusionsIn this patient with dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest migration and proliferation (facial dysmorphogenesis), hair cell stereocilia function (infant-onset deafness), and altered synaptic activity patterns associated with pubertal changes in striatal function (adolescent-onset dystonia). The temporal differences in developmental onset are likely due to varying degrees of susceptibility and of compensatory upregulation of other actin variants in the affected structures.

Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count.

In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement. We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method. The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD. The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.

123I-FP-CIT SPECT Accurately Distinguishes Parkinsonian From Cerebellar Variant of Multiple System Atrophy.

Dopamine transporter SPECT imaging is a valuable tool to estimate the integrity of presynaptic dopaminergic pathways in degenerative parkinsonisms. Evidence about SPECT differential pattern between parkinsonian and cerebellar forms of multiple system atrophy (MSA-P and MSA-C) is lacking. We aimed at assessing whether MSA-P and MSA-C variants have a distinct semiquantitative I-FP-CIT SPECT pattern. We studied a unicentric 13-year (2003-2016) retrospective cohort of subjects with possible or probable MSA and scanned with the same acquisition and reconstruction SPECT protocol. Age-dependent semiquantitative reference limits for striatal volumes of interest, asymmetry indices, and caudate/putamen ratio were previously established with a percentile approach on a cohort of subjects with nondegenerative conditions and normal visual scan. Thirty-four subjects with clinical MSA (28 MSA-P and 6 MSA-C) were identified (mean age, 68.2 ± 10.1 years; male/female ratio 1.00; disease duration, 2.5 ± 2.2 years; Movement Disorders Society Unified Parkinson's Disease Rating Scale III score, 33.8 ± 12.4). The MSA-P subjects exhibited lower uptake values for all volumes of interest, for example, striatal uptake on the more affected side (1.10 ± 0.51) compared with MSA-C (2.30 ± 0.41, P = 0.0005), as well as significantly higher asymmetry indices % (24.7 ± 24.8 vs 6.3 ± 4.5, P = 0.028) and caudate/putamen ratio (2.26 ± 1.23 vs 1.13 ± 0.17, P = 0.00148). The MSA-P and MSA-C subjects exhibited significantly distinct semiquantitative SPECT pattern with severe uptake impairment and high asymmetry for MSA-P and borderline uptake values for MSA-C. Clinical distinction of these 2 phenotypical entities is necessary in order to evaluate SPECT potential to discriminate between degenerative parkinsonisms.