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      I 123‐FP‐CIT (DaTSCAN) SPECT beyond the Most Common Causes of Parkinsonism: A Systematic Review

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          Abstract

          Background

          As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane ( 123I) single‐photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic tool has been a matter of debate for years. The performance of DaTSCAN is generally recommended in the follow‐up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug‐induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms.

          Objectives

          We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms.

          Methods

          The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms “DaTSCAN”, “ioflupane”, “DaT‐SPECT”, “123I‐FP‐CIT SPECT”, “dopamine transporter imaging”, and “[123I] FP‐CIT SPECT”. Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia‐parkinsonism, essential tremor, and parkinsonism due to non‐degenerative causes were excluded.

          Results

          The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X‐associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti‐IgLON5 disease, ring chromosome 20 syndrome, chorea‐acanthocytosis, and neuronal ceroid lipofuscinosis).

          Conclusions

          This review highlights the need to determine in the future the utility and cost‐effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases.

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          Most cited references69

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          MDS clinical diagnostic criteria for Parkinson's disease.

          This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.
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            The diagnosis of Parkinson's disease.

            The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic accuracy for the disease and other forms of parkinsonism in community-based samples of patients taking antiparkinsonian medication confirmed a diagnosis of parkinsonism in only 74% of patients and clinically probable Parkinson's disease in 53% of patients. Clinicopathological studies based on brain bank material from the UK and Canada have shown that clinicians diagnose the disease incorrectly in about 25% of patients. In these studies, the most common reasons for misdiagnosis were presence of essential tremor, vascular parkinsonism, and atypical parkinsonian syndromes. Infrequent diagnostic errors included Alzheimer's disease, dementia with Lewy bodies, and drug-induced parkinsonism. Increasing knowledge of the heterogeneous clinical presentation of the various parkinsonisms has resulted in improved diagnostic accuracy of the various parkinsonian syndromes in specialised movement-disorder units. Also genetic testing and various other ancillary tests, such as olfactory testing, MRI, and dopamine-transporter single-photon-emission computed-tomography imaging, help with clinical diagnostic decisions.
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              Neuronal ceroid lipofuscinoses.

              The neuronal ceroid lipofuscinoses (NCL) are severe neurodegenerative lysosomal storage disorders of childhood, characterized by accumulation of autofluorescent ceroid lipopigments in most cells. NCLs are caused by mutations in at least ten recessively inherited human genes, eight of which have been characterized. The NCL genes encode soluble and transmembrane proteins, localized to the endoplasmic reticulum (ER) or the endosomal/lysosomal organelles. The precise function of most of the NCL proteins has remained elusive, although they are anticipated to carry pivotal roles in the central nervous system. Common clinical features in NCL, including retinopathy, motor abnormalities, epilepsia and dementia, also suggest that the proteins may be functionally linked. All subtypes of NCLs present with selective neurodegeneration in the cerebral and cerebellar cortices. Animal models have provided valuable data about the pathological characteristics of NCL and revealed that early glial activation precedes neuron loss in the thalamocortical system. The mouse models have also been efficiently utilized for the evaluation of therapeutic strategies. The tools generated by the accomplishments in genomics have further substantiated global analyses and these have initially provided new insights into the NCL field. This review summarizes the current knowledge of the NCL proteins, basic characteristics of each disease and studies of pathogenetic mechanisms in animal models of these diseases.
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                Author and article information

                Contributors
                (View ORCID Profile)
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                Journal
                Movement Disorders Clinical Practice
                Movement Disord Clin Pract
                Wiley
                2330-1619
                2330-1619
                June 2024
                May 2024
                June 2024
                : 11
                : 6
                : 613-625
                Affiliations
                [1 ] Department of Neurology La Princesa University Hospital Madrid Spain
                [2 ] Department of R&D HT Médica Madrid Spain
                [3 ] Department of Radiology HT Médica, San Juan de Dios Hospital Córdoba Spain
                [4 ] Faculty of Medicine Autonomous University of Madrid Madrid Spain
                Article
                10.1002/mdc3.14055
                38693679
                11df4a10-7850-4c4b-b510-472c3c5787cb
                © 2024

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