Recent Advancement and Clinical Implications of 18FDG-PET in Parkinson's Disease, Atypical Parkinsonisms, and Other Movement Disorders.

PURPOSE OF REVIEW: The molecular imaging field has been very instrumental in identifying the multiple network interactions that compose the human brain. The cerebral glucose metabolism is associated with neural function. 18F-fluoro-deoxyglucose-PET (FDG-PET) studies reflect brain metabolism in a pattern-specific manner. This article reviews FDG-PET studies in Parkinson's disease (PD), atypical parkinsonism (AP), Huntington's disease (HD), and dystonia. RECENT FINDINGS: The metabolic pattern of PD, disease progression, non-motor symptoms such as fatigue, depression, apathy, impulse control disorders, and cognitive impairment, and the risk of progression to dementia have been identified with FDG-PET studies. In prodromal PD, the REM sleep behavior disorder-related covariance pattern has been described. In AP, FDG-PET studies have demonstrated to be superior to D2/D3 SPECT in differentiating PD from AP. The metabolic patterns of HD and dystonia have also been described. FDG-PET studies are an excellent tool to identify patterns of brain metabolism.

Diagnostic Utility of [11C]DTBZ Positron Emission Tomography In Clinically Uncertain Parkinsonism: Experience of a Single Tertiary Center.

BACKGROUND: The use of single-photon emission computed tomography and positron emission tomography (PET) has proven to be helpful in differentiating Parkinson's disease (PD) from other movement disorders with a sensitivity of up to 95%. OBJECTIVE: The objective of this study was to determine the accuracy of [11C]DTBZ PET imaging in patients with clinically uncertain parkinsonism from a tertiary referral center in Mexico City. MATERIALS AND METHODS: Patients who underwent [11C]DTBZ PET brain scan due to clinically uncertain parkinsonism where divided into two groups: PD or non-PD. A scan was considered positive when visual assessment revealed a decrease in [11C]DTBZ uptake typical for PD; a scan was considered negative when visual assessment showed no decrease in [11C]DTBZ uptake or showed a decrease in tracer uptake in a non-PD pattern. Sensitivity, specificity, and positive and negative predictive values were calculated using a 2 × 2 table, with a 95% confidence interval. RESULTS: A total of 39 patients were included in the study. 14 PET studies were deemed positive and 25 PET studies were deemed negative; 12 true positives and 23 true negatives were found. This yielded a sensitivity of 92.9% (95% CI, 66.1-99.8), specificity of 92% (95% CI, 74-99), PPV of 86.7% (95% CI, 63.1-96.1), and NPV of 95.8% (95% CI, 79.1-98.4). CONCLUSIONS: The [11C]DTBZ PET has an excellent accuracy for differentiating idiopathic PD from other disorders.

SPG11-related parkinsonism: Clinical profile, molecular imaging and l-dopa response.

BACKGROUND: Molecular imaging has proven to be a powerful tool to elucidate degenerated paths in a wide variety of neurological diseases and has not been systematically studied in hereditary spastic paraplegias. OBJECTIVES: To investigate dopaminergic degeneration in a cohort of 22 patients with hereditary spastic paraplegia attributed to SPG11 mutations and evaluate treatment response to l-dopa. METHODS: Patients and controls underwent single-photon emission computed tomography imaging utilizing 99m Tc-TRODAT-1 tracer. A single-blind trial with 600 mg of l-dopa was performed comparing UPDRS scores. RESULTS: Reduced dopamine transporter density was universal among patients. Nigral degeneration was symmetrical and correlated with disease duration and motor and cognitive handicap. No statistically significant benefit could be demonstrated with l-dopa intake during the trial. CONCLUSION: Disruption of presynaptic dopaminergic pathways is a widespread phenomenon in patients with SPG11 mutations, even in the absence of parkinsonism. Unresponsiveness to treatment could be related to postsynaptic damage that needs to be further investigated.

A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging.

Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.

Cineradiographic analysis of respiratory movements in a mouse model for early Parkinson's disease.

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system known to cause a typical pattern of motor symptoms. In its later stages, PD is known to cause respiratory alterations including shortening of operational volumes and reduced velocity of respiratory-muscle contraction. It has been proposed that such changes are secondary to changes in posture and osteoarticular degeneration, leading to an alteration in the spinal axis that in turn could affect breathing mechanics. In this study, we examined respiratory movements by using cineradiography on a murine (C57BL/6J) model of mild hemi-PD. Under surgical anesthesia, PD mice received an injection of 6-OHDA solution to the right striatum, and were compared to control mice, which received an injection of saline solution. Two weeks after surgery, all mice had their respiratory movements recorded by video X-ray without any restraint. Behavioral tests were performed to assess the severity of the 6-OHDA lesion. As a result, behavioral tests confirmed mild motor impairments in PD mice as compared to controls. Parameters of respiratory function showed mild alterations in the PD group, suggestive of a restrictive-type respiratory disorder. These results suggest that respiratory alterations in PD may emerge simultaneously to other motor symptoms, and not as a consequence of the latter.

Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of scans without evidence of dopaminergic deficit (SWEDDs).

UNLABELLED: The clinical diagnosis of Parkinson's disease (PD) is susceptible to misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo imaging techniques assessing the presynaptic dopamine transporter (DAT) have emerged as a useful tool in PD diagnosis, improving its accuracy. OBJECTIVE: It was to illustrate the clinical usefulness of a brain single-photon emission computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans without evidence of dopaminergic deficit (SWEDDs) in this context. CASES: We described four representative patients with clinically unclear parkinsonian syndromes who underwent [(99m)Tc]-TRODAT-1 SPECT and reviewed the clinical implications. CONCLUSION: DAT-SPECT is an important, cost-effective, technique for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD cases present clinical and paraclinical peculiarities that may retrospectively identify them as essential/dystonic tremor. The lack of histopathological data limits further conclusions.

Evaluation of patients with Clinically Unclear Parkinsonian Syndromes submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1.

Despite its relatively high prevalence Parkinson's Disease (PD) is still misdiagnosed in approximately 25% of cases. In this study our aim was to evaluate patients with Clinically Unclear Parkinsonian Syndromes (CUPS) submitted to brain SPECT imaging using the technetium-99m labeled Dopamine Transporter (DAT) tracer TRODAT-1. We recruited 15 subjects with CUPS and matched them with 13 patients with probable PD and 13 healthy control subjects (HCS). A SPECT with TRODAT-1 was performed at the baseline evaluation and patients from the CUPS were followed-up for 2-years to ensure or not PD diagnosis ("gold-standard"). The mean+/-SD results from Right and Left striatum Binding Potential (BP) were, respectively, 1.08+/-0.20 and 1.04+/-0.16 in the HCS group, 0.47+/-0.16 and 0.53+/-0.17 in the PD group, and 0.68+/-0.11 and 0.84+/-0.17 in the CUPS group. The rate of disagreement between baseline SPECT in the CUPS group as compared to the "gold standard" diagnosis (clinical diagnosis of PD on follow-up) was of 20%. The sensitivity of the SPECT with TRODAT-1 was 100%, while specificity was 70%. In conclusion, our data provided further information about the role of the technetium-99m labeled tracer TRODAT-1 as a biomarker of DAT reduction that can also be used in the diagnosis of patients with CUPS.

Molecular imaging studies in Parkinson disease: reducing diagnostic uncertainty.

BACKGROUND: The diagnosis of Parkinson disease (PD) is based on clinical criteria but misdiagnosis is as high as 25% of cases as confirmed by anatomic-pathologic studies. Since the introduction of in vivo molecular imaging techniques using Single-Photon Emission Computed Tomography and Positron Emission Tomography, the diagnosis of PD became more reliable by assessing dopaminergic and even nondopaminergic systems. REVIEW SUMMARY: The purpose of this article is to critically review the current data on molecular neuroimaging focusing on the nigrostriatal circuitry and providing useful information on the role of these new imaging techniques in the management of clinically unclear cases of PD. CONCLUSIONS: Patients with essential tremor, psychogenic Parkinsonism or drug-induced Parkinsonism can be differentiated from PD in doubtful situations using molecular imaging techniques evaluating striatal dopamine transporters (DAT). However, in patients with vascular Parkinsonism, atypical Parkinsonism and Parkinsonism associated with dementia DAT scans have less diagnostic usefulness. Scans with non-DAT tracers (ie, D2 dopamine receptors) are necessary together with long-term clinical follow-up, and rescans to improve diagnostic accuracy.

An imaging study of parkinsonism among African-Caribbean and Indian London communities.

We previously reported on 131 parkinsonian patients of African-Caribbean and Indian origin attending movement disorders clinics in six London Hospitals, of whom approximately 20% manifested atypical parkinsonism with a late-onset, akinetic-rigid predominant syndrome, postural instability and minimal resting tremor refractory to levodopa therapy and dopamine agonists (see Hu et al., Neurology 2000;54[Suppl.3]: A188 and Hu et al., Mov Disord 2000;15[Suppl.3]:S212). To better elucidate the phenotype of these atypical patients (18)FDG/(18)F-dopa positron emission tomography (PET) were performed in a subgroup to look for cortical and striatal metabolic changes suggestive of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or dementia with Lewy bodies. Magnetic resonance imaging (MRI) rating of cerebral vascular lesion load, putaminal atrophy, and neuropsychological testing were also performed. Discriminant function analysis of (18)F-dopa/(18)FDG striatal metabolism in 43 patients failed to separate atypical ethnic minority from typical Caucasian Parkinson's disease (PD) patients. Additionally, atypical Indian and African-Caribbean patients did not show cortical reductions in glucose metabolism suggestive of PSP, CBD, or DLB. Cerebral vascular lesion load rated in these patients did not differ between atypical and typical PD groups, and none of the atypical patients had MRI changes suggestive of MSA or PSP. Our results suggest the atypical parkinsonian phenotype seen in African-Caribbean and Indian patients represents a levodopa-refractory form of PD separate from MSA or PSP in most patients.