Diagnosis Of Parkinsonian Syndromes Research Articles

A replication study, systematic review and meta-analysis of automated image-based diagnosis in parkinsonism

Differential diagnosis of parkinsonism early upon symptom onset is often challenging for clinicians and stressful for patients. Several neuroimaging methods have been previously evaluated; however specific routines remain to be established. The aim of this study was to systematically assess the diagnostic accuracy of a previously developed 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) based automated algorithm in the diagnosis of parkinsonian syndromes, including unpublished data from a prospective cohort. A series of 35 patients prospectively recruited in a movement disorder clinic in Stockholm were assessed, followed by systematic literature review and meta-analysis. In our cohort, automated image-based classification method showed excellent sensitivity and specificity for Parkinson Disease (PD) vs. atypical parkinsonian syndromes (APS), in line with the results of the meta-analysis (pooled sensitivity and specificity 0.84; 95% CI 0.79–0.88 and 0.96; 95% CI 0.91 –0.98, respectively). In conclusion, FDG-PET automated analysis has an excellent potential to distinguish between PD and APS early in the disease course and may be a valuable tool in clinical routine as well as in research applications.

Parkinson Disease: Epidemiology, Pathology, and Clinical Diagnosis

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

Parkinson Disease: Epidemiology, Pathology, and Clinical Diagnosis

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

Case Report: Bupropion Reduces the [123I]FP-CIT Binding to Striatal Dopamine Transporter

The diagnosis of parkinsonian syndromes in patients with severe depression may be challenging due to overlapping clinical phenomena, especially regarding psychomotor and affective symptoms. [123I]FP-CIT-SPECT is a useful method to detect degenerative parkinsonian disorders. However, some drugs may influence the tracer binding and thus alter the result. We present a case of 56-year-old female inpatient with difficult-to-treat late-onset depression. Since the current major depressive episode (MDE) was accompanied by psychotic features including delusions and hallucinations as well as hypokinesia, stooped posture and hypomimia, underlying degenerative parkinsonism was suspected. The pathologic [123I]FP-CIT-SPECT scan under ongoing antidepressant therapy with bupropion 300 mg/die (serum level of bupropion 43 ng/ml and hydroxybupropion 2,332 ng/ml) showed reduced [123I]FP-CIT binding throughout the striatum. The scan normalized upon a wash-out phase of four half-time periods (serum level of bupropion was 0.4 ng/ml and for hydroxybupropion 80.5 ng/ml). Our report should serve as a cautionary note for use of [123I]FP-CIT in depressed patients, particularly in those treated with drugs interfering with the dopamine transporter. Furthermore, our case argues for a need of consultation of a movement disorder specialist prior to dopamine transporter imaging.

Pearls and Pitfalls of Quantitative Software Analysis of Dopamine Transporter SPECT.

Dopamine transporter SPECT with I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (I-ioflupane) aids in the diagnosis of parkinsonian syndrome by demonstrating loss of striatal dopamine transporters, proportional to nigrostriatal dopaminergic neuronal loss. Quantitative software analysis (QSA) is a helpful adjunct to visual interpretation. An atlas of pearls and pitfalls of QSA is presented. Examples include correction for head tilt/orientation, scaling artifacts, and detection of balanced loss of activity. Additional examples are provided where QSA can potentially fail such as patient variation and vascular disease.

Role of University of Pennsylvania Smell Identification Test (UPSIT) in Diagnosis of Parkinsonian Syndromes in a Real World Setting (1921)

Role of University of Pennsylvania Smell Identification Test (UPSIT) in Diagnosis of Parkinsonian Syndromes in a Real World Setting (1921)

Quantitative MRI markers in Parkinson's disease and parkinsonian syndromes.

In Parkinson's disease and parkinsonian disorders, the differential diagnosis is still challenging. We aim to review current developments in MRI quantitative markers and their potential in a clinical and neuroscientific setting. There have been efforts to improve MRI acquisition methods and to explore new promising biomarkers. In parallel, technological advances in data analysis (i.e. deep learning) open new ways to use these biomarkers. The MRI markers may differ according to the brain structure investigated. Even if the newly adopted acquisition protocols served mainly the development of brainstem-related biomarkers (neuromelanin MRI, nigrosome sensitive MRI), more established markers (e.g. morphometric values) in basal ganglia, cortex and cerebellum demonstrate their relevance especially to differential diagnosis in parkinsonian syndromes. We provide an overview on recent advances in MRI quantitative markers of Parkinson's disease that we divide for didactic purposes in three anatomical levels - cortical/cerebellum structures, basal ganglia and brainstem. We show the complementarity of new biomarkers sensitive to brain tissue properties to established morphometrics.

A novel device for estimating olfactory threshold for differential diagnosis of parkinsonian syndrome: A pilot study

A novel device for estimating olfactory threshold for differential diagnosis of parkinsonian syndrome: A pilot study

A Smart Tool for the Diagnosis of Parkinsonian Syndromes using Wireless Watches

Early detection and diagnosis of Parkinson disease will provide a good chance for patients to take early actions and prevent its further development. In this paper, a smart tool for the diagnosis of Parkinsonian syndromes is designed and developed using low—cost Texas Instruments eZ430-Chronos wireless watches. With this smart tool, Parkinson Bradykinesia is detected based on the cycle of a human gait, with the watch worn on the foot, and Parkinson Tremor shaking is detected and differed by frequency 0 to 8 Hz on the arm in real-time with a developed statistical diagnosis chart. It can be used in small clinics as well as home environment due to its low-cost and easy-use property.

Clinical utility of DaTscan™ (123I-Ioflupane Injection) in the diagnosis of Parkinsonian Syndromes.

The diagnosis of movement disorders including Parkinsonian syndromes and essential tremor is mainly clinical. The most common diagnostic errors for Parkinson's disease include misdiagnoses such as Parkinson plus syndromes and cases of essential tremor. In this article, we discuss the clinical utility of DaTscan™ (123I-Ioflupane injection) and its diagnostic value in Parkinson's disease and the other Parkinsonian syndromes. Single photon emission computed tomography with 123I-Ioflupane can be useful to assist in the diagnosis of uncertain cases of Parkinsonism. An accurate diagnosis can aid clinicians in making correct decisions that are related to the overall management and treatment of Parkinson's disease, avoiding common therapeutic errors.

Paraneoplastic stiff person syndrome associated with colon cancer misdiagnosed as idiopathic Parkinson’s disease worsened after capecitabine therapy

ObjectivesTo refresh clinical diagnostic dilemmas in patients presenting with symptoms resembling to those of parkinsonism, to report rare association of colon cancer and paraneoplastic stiff person syndrome (SPS), and to draw attention on the possible correlation of capecitabine therapy with worsening of paraneoplastic SPS.MethodsCase report of the patient with paraneoplastic SPS due to colon cancer that was misdiagnosed as idiopathic Parkinson’s disease (iPD), whose symptoms worsened after beginning adjuvant capecitabine chemotherapy.ResultsWe describe a 55-year-old woman with subacute onset of symmetrical stiffness and rigidity of the truncal and proximal lower limb muscles that caused lower body bradykinesia, gait difficulties, and postural instability. Diagnose of iPD was made and levodopa treatment was initiated but failed to provide beneficial effect. Six months later, colon cancer was discovered and the patient underwent surgical procedure and chemotherapy with capecitabine thereafter. Aggravation of stiffness, rigidity, and low back pain was observed after the first chemotherapy cycle and capecitabine was discontinued. Furthermore, levodopa was slowly discontinued and low dose of diazepam was administered which resulted in partial resolution of the patient’s symptoms.ConclusionParaneoplastic SPS is rare disorder with clinical features resembling those of parkinsonian syndrome and making the correct diagnosis remains a challenge. The diagnosis of parkinsonian syndrome should be re-examined if subsequent examinations discover an associated malignant process. Although it remains unclear whether the patients with history of SPS are at the greater risk for symptoms deterioration after administration of capecitabine, clinicians should be aware of capecitabine side effects because recognition and appropriate management can prevent serious adverse outcomes.

Combined assessment of midbrain hyperechogenicity, hyposmia and motor asymmetry improves diagnostic accuracy in early Parkinson’s disease

Evaluation of: Busse K, Heilmann R, Kleinschmidt S et al. Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson’s disease. J. Neurol. Neurosurg. Psychiatr. 83(4), 441–447 (2012).The differential diagnosis of Parkinsonian syndromes can be challenging, particularly in early disease stages, when overlapping clinical signs and symptoms may lead to erroneous classification. However, an early differentiation between Parkinson’s disease (PD) and other diseases causing Parkinsonism is crucial for prognostic and therapeutic reasons and is essential for clinical research. In a recent study, Busse et al. investigated the diagnostic utility of a set of tests to improve diagnostic differentiation between PD, essential tremor and other Parkinsonian disorders. The authors studied a total of 632 patients divided into a retrospective (n = 517) and a prospective (n = 115) group. Diagnostic anchors were based on clinical criteria. Combining midbrain hyperechogenicity, hyposmia and motor asymmetry increased specificity and positive predictive value for diagnosis of PD up to 98% at the expense of sensitivity, whereas two features provided 91% sensitivity with 77% specificity. The results of this study further support the diagnostic utility of transcranial sonography in diagnosing PD.

Transcranial sonography in Parkinson's disease

Transcranial sonography has become a useful tool in the differential diagnosis of parkinsonian syndromes. This is a non-invasive, low cost procedure. The main finding on transcranial sonography in patients with idiopathic Parkinson's disease is an increased echogenicity of the mesencephalic substantia nigra region. This hyperechogenicity is present in more than 90% of cases, and reflects a dysfunction in the dopaminergic nigrostriatal pathway. This study discussed how the hyperechogenicity of the substantia nigra may facilitate the differential diagnosis of parkinsonian syndromes.

Interobserver agreement in the visual and semi-quantitative analysis of the 123I-FP-CIT SPECT images in the diagnosis of Parkinsonian syndrome

Aims Using 123I-FP-CIT SPECT images makes it possible to identify presynaptic deterioration of the dopaminergic pathway by studying the dopamine transporter (DAT). A correct analysis of the SPECT images contributes to an adequate interpretation and diagnosis of movement disorders. Aims: 1. To compare visual and semiquantitative analysis of 123I-FP-CIT SPECT images in patients with movement disorders. 2. To evaluate interobserver agreement in visual and semiquantitative analysis. 3. To obtain a cut-off in the semiquantitative analysis to discriminate primary Parkinsonism Syndrome (PS) from non-primary PS. Methods A 123I-FP-CIT SPECT was performed in 32 patients with movement disorders suggestive of primary PS. Visual and semiquantitative images analyses were performed independently by two nuclear medicine physicians. Visual analysis was based on the visual interpretation. Semiquantitative analysis was calculated as specific uptake (caudate, putamen and striatum) versus non-specific uptake (occipital). Sensitivity, specificity, PPV, and NPV were calculated. Data were compared using ANOVA test followed by Bonferroni post hoc test. Interobserver agreement of the visual and semiquantitative analysis was assessed by intraclass correlation coefficient and Kappa statistics, respectively. ROC curve was generated with semiquantitative data. Results Visual analysis showed 86% sensitivity and 100–88% specificity for the differential diagnosis of primary PS from non-primary PS. Semiquantitative analysis showed a gradual hypouptake proportional to the disease severity obtained in the visual analysis. Semiquantitative analysis did not provide any additional information to the visual analysis. Intraclass correlation coefficient and Kappa statistics showed 0.92 and 0.80 values, respectively. The cut-off value to differentiate primary PS from non-primary PS was 1.9 on the putamen index.

Differenzialdiagnose der Parkinson-Syndrome mittels MRT

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in clinical neurology. Despite published consensus operational criteria for the diagnosis of Parkinson's disease (PD) and the various atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration (CBD), the clinical separation of APDs from PD carries a high rate of misdiagnosis. However, the early differentiation between APD and PD, each characterized by a very different natural history, is crucial for determining the prognosis and choosing a treatment strategy. Despite limitations the various modern magnetic resonance imaging (MRI) techniques have undoubtedly added to the differential diagnosis of neurodegenerative parkinsonism. In clinical practice conventional MRI with visual assessment of T2 and T1-weighted imaging is a well established method for the exclusion of symptomatic parkinsonism due to other pathologies and may also point to the diagnosis of APD. Furthermore, advances in MRI techniques, such as diffusion-weighted imaging (DWI), have enabled abnormalities in the basal ganglia and infratentorial brain structures in APD to be quantitatively illustrated.

Interobserver reproducibility of the interpretation of I-123 FP-CIT single-photon emission computed tomography

I-123 ioflupane (FP-CIT) single-photon emission computed tomography is a recognized tool in the diagnosis of Parkinsonian syndromes. In practice, data interpretation relies on visual and semiquantitative analyses. Good interobserver reproducibility is a prerequisite before claiming the robustness of a technique. This study aimed at evaluating interobserver reproducibility of this approach. Thirty nuclear medicine physicians participated in the study. Data included FP-CIT images and semiquantitative measurements of 12 cases, covering a wide spectrum of scintigraphic patterns and for which a 'true' clinical diagnosis based on long-term follow-up was available. Interobserver agreement was defined, for each case, as the highest percentage reached among the three proposed answers with complete agreement arbitrarily set at 80% or more. Variability in an individual observer's sensitivity to assess data as normal, equivocal or abnormal was scored using a three-point scale. Response rate was 99.7%. Among the three possible answers,'normal' accounted for 41.2% of the total, 'abnormal' for 49.8% and 'equivocal' for 8.1%. The mean interobserver agreement was 76% (range: 37-100%), with complete agreement being reached only in five cases. The interpretation proposed by most observers accorded to clinical diagnosis in 75% of the cases. Abnormalities of the central nervous system were encountered in all the cases with disagreement between the observer's interpretation and clinical diagnoses. An important variability in the observers' sensitivity was seen. In the particular setting of this preliminary study evaluating the reproducibility of FP-CIT single-photon emission computed tomography interpretation in a group of nuclear medicine physicians with various experiences, interobserver agreement was suboptimal. Collegial discussion and standardized interpretation criteria could contribute to an improved reproducibility.

23. Single photon emission computed tomography (SPECT) and DaTSCAN in diagnosis of parkinsonian syndromes

23. Single photon emission computed tomography (SPECT) and DaTSCAN in diagnosis of parkinsonian syndromes

IBZM SPECT and FDG PET in the differential diagnosis of Parkinsonian syndromes

Summary Aim: Both IBZM SPECT and FDG PET may be used for differentiation between Parkinson's disease (PD) and atypical neurodegenerative parkinsonian syndromes (APS). However, there are only very limited data of both modalities in the same subjects. The present study compared both modalities with respect to inter-rater agreement in 30 patients with neurodegenerative parkinsonian syndromes (PS) confirmed by FP-CIT SPECT. Methods: IBZM SPECT and FDG PET were categorized as PD or APS by visual inspection of standardized report pages and statistical parametric maps (SPMs). Categorization was performed independently by five readers. Inter-rater agreement was quantified using Cohen's kappa κ. Results: IBZM SPECT resulted in PD and APS in 11 and 19 cases, respectively (majoritarian categorization). Inter-rater agreement was κ = 0.64 ± 0.10. FDG PET resulted in PD and APS in 12 and 18 cases, respectively (majoritarian categorization). Inter-rater agreement was κ = 0.68 ± 0.07. Majoritarian diagnosis disagreed between IBZM SPECT and FDG PET in 13 cases (43%). Semi-quantitative analysis of IBZM SPECT using the striatum-to-reference distribution volume ratio was in good agreement with visual categorization (area under ROC curve 0.92). Conclusion: In neurodegenerative PS, inter-rater agreement of visual analysis is substantial in both IBZM SPECT and FDG PET. Furthermore, (I) visual analysis of IBZM SPECT is reliable if adequate standardized image display is used, (II) visual analysis of FDG SPMs allows unique categorization as either PD or APS in most subjects, and (III) IBZM SPECT and FDG PET are discordant in a significant fraction of cases.

Anal sphincter EMG in the diagnosis of parkinsonian syndromes

The role of electromyography (EMG) recorded from the external anal sphincter (EAS) in the diagnosis of atypical parkinsonian syndromes is a matter for continuous debate. Most studies addressing this issue are retrospective. In this study, we prospectively investigated six patients with Parkinson's Disease (IPD), 14 patients with multiple system atrophy (MSA) and eight with progressive supranuclear palsy (PSP) using EMG of the EAS, motor-evoked potential (MEP) to the EAS and EMG of m. gastrocnemius and nerve conduction velocity measured at the sural nerve. Patients were followed up for 2 years to secure correct diagnosis. The mean duration of motor unit potentials (MUPs) recorded from the EAS was significantly longer in patients with MSA and PSP compared with MUPs recorded from patients with PD (P < 0.005 for both). There were no signs of diffuse loss of motor neurons or peripheral neuropathy. MEP revealed signs of supranuclear affection in patients with MSA, whereas in patients with PSP the mechanism is a focal loss of motor neurons in Onuf's nucleus. Abnormal EMG of the EAS is strongly suggestive of atypical parkinsonism and the pathophysiology may be different in patients with MSA and PSP.

Avaliação da doença de Parkinson pela ressonância magnética

OBJETIVO: Avaliar a doença de Parkinson pela ressonância magnética. MATERIAIS E MÉTODOS: De outubro de 1999 a outubro de 2002, foram estudados 42 pacientes com parkinsonismo, por meio de um aparelho de ressonância magnética de 1,5 T. Os pacientes foram divididos em dois grupos: grupo com doença de Parkinson (n = 26) e grupo com síndrome parkinsoniana atípica (n = 16), sendo os resultados comparados com um grupo controle (n = 18). Foram avaliadas as seguintes variáveis: espessura da pars compacta do mesencéfalo, grau de hipointensidade de sinal no putâmen, grau de atrofia cerebral, lesões no mesencéfalo, lesões na substância branca e a presença de lesão na borda póstero-lateral do putâmen. A análise estatística dos dados foi realizada, com a utilização do programa SPSS. RESULTADOS: A média de idade foi de 58,2 anos nos grupos com doença de Parkinson e controle, e 60,5 anos no grupo com síndrome parkinsoniana atípica. Os pacientes com doença de Parkinson e síndrome parkinsoniana atípica apresentaram redução da espessura da pars compacta e maior grau de hipointensidade de sinal no putâmen. O grau de atrofia cerebral foi maior nos pacientes com síndrome parkinsoniana atípica. As lesões no mesencéfalo e na substância branca foram semelhantes entre os grupos. O sinal hiperintenso na borda póstero-lateral do putâmen foi um achado pouco freqüente na população estudada, mas sugestivo de atrofia de múltiplos sistemas. CONCLUSÃO: Desta forma, a ressonância magnética detectou alterações morfológicas cerebrais que podem auxiliar no diagnóstico por imagem das síndromes parkinsonianas.