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.

Higher dopamine transporter density in Parkinson's disease patients with depression.

RATIONALE: Depression is a frequent non-motor symptom in Parkinson's disease (PD) with increasing rates with the progression of the disease. Molecular imaging studies have shown a reduction of dopamine transporter (DAT) density in depressed PD patients (dPD); however, DAT role in the pathophysiology of PD depression is not clear since clinical matching was inappropriate and DAT reduction could be attributed to PD severity. OBJECTIVES: To further examine the role of DAT in PD depression, this study compared thoroughly matched depressed vs. non-depressed PD patients (ndPD). MATERIALS AND METHODS: Twenty PD patients (n = 10 ndPD; n = 10 dPD) matched for age and disease severity were submitted to brain SPECT imaging with [(99m)Tc]-TRODAT-1, a DAT radioligand. DAT-binding potential was calculated using regions of interest bilaterally drawn in the striatum, caudate, and putamen. Depression was defined according to Beck Depression Inventory (BDI; cut-off >18). RESULTS: Mean BDI scores were higher in dPD (25.0 +/- 5.6) than in ndPD patients (8.0 +/- 1.9, p < 0.0001). DAT density was greater on dPD especially in the left caudate (dPD 0.87 +/- 0.19 vs. ndDP 0.69 +/- 0.18, p = 0.02) and right putamen (dPD 0.37 +/- 0.07 vs. ndPD 0.28 +/- 0.13, p = 0.03) than in ndPD patients. CONCLUSION: Our results suggest that in vivo DAT density is increased in dPD patients as compared to ndPD, suggesting that DAT is implicated in the pathophysiology of PD depression.

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.

Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study.

OBJECTIVES: To evaluate patients with "clinically established" psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism. PATIENTS AND METHODS: Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n=5) and healthy control subjects (n=5). RESULTS: The mean age (years-old) at first evaluation in the PsyP group was 37.4+/-3.7, and the mean disease duration (years) was 3.9+/-1.2. DAT BPs (means+/-standard deviations) on right/left caudate were, respectively, 0.69+/-0.18 and 0.70+/-0.18 in the PD group versus 1.17+/-0.06 and 1.12+/-0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48+/-0.10 and 0.45+/-0.06 in the PD group versus 1.10+/-0.10 and 1.21+/-0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (< or =0.70) for controls, implying pre-synaptic dopaminergic deficit. CONCLUSIONS: Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.

A study on the action of two calcium channel blockers (verapamil and flunarizine) upon an experimental model of tardive dyskinesia in rats

A discinesia tardia (DT) é complicaçäo decorrente do uso prolongado de neurolépticos. Até o presente, nenhum tratamento provou ser eficaz na DT. Evidências indiretas apontam para a açäo de drogas bloqueadoras de canais de cálcio (BCC) em algumas vias neurais. A açäo de duas dessas drogas, varapamil e flunarizina, foi testada em modelo experimental de DT em rato, neste estudo. O haloperidol foi administrado por 21 dias e induçäo de movimentos estereotipados era obtida no 24§ dia, com a injeçäo de apomorfina. As drogas BCC foram administradas por uma vez no 28§ dia (experimento agudo) e por 8 dias, após o 25§ dia (experimento crônico). A flunarizina näo induziu modificaçäo no padräo de estereotipia dos animais, mas o verapamil levou a aumento no experimento agudo e a diminuiçäo no experimento crônico. Estes achados indicam que as drogas BCC podem ter alguma açäo sobre a DT e que ensaios clínicos devem ser feitos para se comprovar se tal açäo ocorre no homem

Rural or urban living and Parkinson's disease

Although the precise etiology of Parkinson's disease (PD) is as yet unknown, it appears that certain environmental factors are involved. Prior living in a rural area has been implicated as a possible risk factor for PD, particularly in the early onset type. We evaluated the role of previous living conditions in the clinical correlates and outcome characteristics of 118 PD patients. All of them were seen from January 1987 to October 1992. The Rural Group (RG) comprised 71 patients (60.2 per cent) who had lived in the rural area for at least 10 years (Mainly in early phase of life) and the Urban Group (UG) consisted of 47 patients (39.8 per cent) who had lived their entire life in an urban environment. The average age at the beginning of the symptoms was 58.8 in the RG and 54.1 in the UG. The mixed form of the disease (tremor, rigidity and akinesia) was the most frequent in both groups. A minimum 6- month follow-up period was undertaken with 63 patients (average 20 months) and no difference in response to treatment or in progression of the illness was detected between the two groups. Our data show that the previous living environment does not appear to be a determining factor in either the clinical or outcome characteristics of PD.

Idiophatic dystonia: clinical profile of 76 brazilian patients

A distonia pode ser classificada de acordo com a idade de início (infância, adolescência e idade adulta), distribuiçäo corporal dos movimentos anormais (focal, segmentar, unilateral, multifocal e generalizada) e etiologia (idiopática e sintomática). Dentre 122 pacientes com o diagnóstico de síndrome distónica, estudamos 76 com quadros idiopáticos (62,3% do total). Havia 48 pacientes do sexo feminino e 28 do sexo masculino. O quadro mais frequentemente observado foi a da distonia focal iniciada na idade adulta (37 pacientes). Havia 6 pacientes com distonia generalizada e o início desse quadro foi mais frequente abaixo dos 20 anos de idade. Quadros focais e segmentares predominaram e foram mais comumentemente iniciados na idade adulta. Tremor postural das mäos foi observado em 15 pacientes (19,7%). De todas as formas de distonia, o torcicolo espasmódico foi a que prevaleceu. Com a exceçäo da cäimbra do escriväo (com mais homens que mulheres acometidas) e da distonia generalizada (a mesma proporçäo entre os sexos), o sexo feminino predominou sobre o masculino. Nossos dados säo semelhantes aos de outras séries que estudaram o quadro clínico da distonia idiopática. Assim, diferenças raciais, ambientais e sócio-econômicas näo parecem ser determinantes no padräo de manifestaçäo da distonia idiopática