Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson’s disease

doi:10.1016/S0987-7053(01)00273-8

Neurophysiologie Clinique/Clinical Neurophysiology

Volume 31, Issue 5, September 2001, Pages 321-340

https://doi.org/10.1016/S0987-7053(01)00273-8 Get rights and content

Abstract

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) provide the means to studying in vivo the neurochemical, hemodynamic or metabolic consequences of the degeneration of the nigrostriatal dopaminergic system in Parkinson’s disease (PD). The extent of striatal dopaminergic denervation can be quantified with radiotracers as 〚¹⁸F〛FDopa for PET and 〚¹²³I〛tropanes for SPECT. There are other radiotracers such as 〚¹¹C〛Dopa and meta-tyrosines as well as PET tracers for uptake sites. Striatal uptake of 〚¹⁸F〛FDopa and 〚¹²³I〛tropanes is markedly decreased in PD, more in the putamen than in the caudate nucleus, and inversely correlates with the severity of motor signs and with duration of disease. PET and SPECT make possible the assessment by noninvasive means of the changes in dopamine receptor density, the effect of neuronal transplants or neuroprotective treatments in PD patients, or the nigrostriatal dopaminergic function in at-risk subjects. Activation studies using cerebral blood flow and metabolism measurements during a motor task reveal an impaired ability to activate the supplementary motor area and dorsolateral prefrontal cortex in PD. This functional disability is reversed by the use of dopaminergic medication or by surgical treatment by pallidotomy or deep brain stimulation. The differential diagnosis between PD and multiple system atrophy, progressive supranuclear palsy or corticobasal degeneration is not yet clearly established by PET and SPECT, even though these syndromes have some particular neurochemical and metabolic profiles. On the other hand, PET and SPECT are useful for distinguishing PD from Dopa-responsive dystonia, or for assessing the integrity of the nigrostriatal dopaminergic pathway in atypical cases of postural tremor or iatrogenic parkinsonian syndromes.

Résumé

La tomographie par émission de positons (TEP) et la tomographie par émission de simples photons (TESP) constituent un moyen privilégié d’exploration des conséquences neurochimiques, hémodynamiques, ou métaboliques de la dégénérescence de la voie dopaminergique nigrostriée à l’origine de la maladie de Parkinson. Celle-ci peut être visualisée en utilisant comme traceurs la 〚¹⁸F〛FDopa en TEP et les 〚¹²³I〛tropanes en TESP. D’autres traceurs peuvent être employés, comme la 〚¹¹C〛Dopa et les meta-tyrosines et d’autres marqueurs des sites de recapture. La fixation striatale de la 〚¹⁸F〛FDopa et des 〚¹²³I〛tropanes est fortement diminuée dans la maladie de Parkisnon, de façon plus marquée dans le putamen que dans le noyau caudé, et est inversement corrélée à la sévérité des signes moteurs et à la durée d’évolution. Il est possible d’explorer de façon non invasive les anomalies de densité des récepteurs dopaminergiques ou l’effet des greffes neuronales ou de traitements neuropretecteurs chez les patients parkinsoniens, ou encore la phase présymptomatique de la maladie chez les personnes à risque. La perte des projections dopaminergiques striatales dans la maladie de Parkinson entraîne des modifications importantes du métabolisme et du débit sanguin cérébral lors de la réalisation de séquences motrices. Les études d’activation indiquent en effet un défaut d’activation de l’aire motrice supplémentaire et du cortex préfrontal dorsolatéral, qui peut être réversible sous traitement dopaminergique ou traitement chirurgical par pallidotomie ou stimulation cérébrale profonde. L’intérêt de la TEP ou de la TESP n’est pas encore démontré pour le diagnostic différentiel entre la maladie de Parkinson et l’atrophie multisystématisée, la paralysie supranucléaire progressive, et la dégénérescence corticobasale, bien que ces syndromes aient dans un certain nombre de cas un profil métabolique et neurochimique particulier. En revanche, la TEP et la TESP permettent de distinguer la dystonie Dopa-sensible de la maladie de Parkinson, ou de vérifier l’intégrité de la voie dopaminergique nigrostriée dans les formes atypiques de tremblements de posture, ou de syndromes parkinsoniens secondaires à un traitement neuroleptique.

Section snippets

PET and SPECT methods

PET and SPECT are nuclear medicine techniques in which temporal changes in the concentrations of radioactive tracers are recorded in brain and other target organs. PET and SPECT have different physical principles and performances. PET studies are carried out by administering a tracer labelled with a positron-emitting isotope with a short half-life (T_1/2) generated by a cyclotron. The spatial resolution of commercially available PET tomographs is currently of 4 mm, which can be improved with

Studies on neurotransmitters

Numerous PET and SPECT studies have investigated the nigrostriatal dopaminergic degeneration in PD patients 14, 16. Both pre- and post-synaptic dopaminergic functions can be measured (table I). Pre-synaptic aspects are mostly studied with 〚¹⁸F〛-Fluoro-Dopa (〚¹⁸F〛FDopa), a substrate for Dopa-decarboxylase in catecholaminergic neurons. 〚¹⁸F〛FDopa striatal uptake rate is correlated to cellular density of substantia nigra dopaminergic neurons and to striatal dopamine concentrations 〚145〛. Tracers

Studies on cerebral blood flow and metabolism

Radiotracers used for cerebral blood flow measurement are 〚¹⁵O〛H₂O or 〚¹⁵O〛CO₂ for PET, and 〚^99mTc〛HMPAO or 〚¹³³Xe〛 for SPECT. Glucose metabolism is studied with PET and 〚¹⁸F〛-Fluoro-deoxyglucose (FDG), an extension of the 〚¹⁴C〛-1-deoxyglucose (〚¹⁴C〛-DG) autoradiographic method used in the original rat model 〚147〛. A number of PET and SPECT studies have investigated functional regional cerebral blood flow and metabolism consequences of nigrostriatal dopaminergic degeneration in PD, either in

Differential diagnosis

While the majority (60–80%) of cases of parkinsonism can be diagnosed as PD, several differential diagnoses are possible. Here we review the literature on PET and SPECT studies on the differential diagnosis of PD, in particular ‘Parkinson plus’ syndromes, Dopa-responsive dystonia, tremor and toxic and iatrogenic parkinsonian syndromes.

The future

As reviewed above, PET and SPECT techniques have already provided important contributions to the diagnosis and to a better understanding of the pathophysiology of PD and related syndromes. During the next few years, PET activation methods should be used to investigate the mechanism of action of deep brain stimulation, particularly on frontostriatal motor and non-motor circuits. Studies using dopaminergic presynaptic ligands will be developed to assess the long-term neuroprotective effect of

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ReviewContributions of PET and SPECT to the understanding of the pathophysiology of Parkinson’s diseaseContribution de la tomographie par émission de positons et de la tomographie par émission de simples photons à la compréhension de la physiopathologie de la maladie de Parkinson.

Abstract

Résumé

Section snippets

PET and SPECT methods

Studies on neurotransmitters

Studies on cerebral blood flow and metabolism

Differential diagnosis

The future

Trends Neurosci

Eur J Pharmacol

J Neurol Sci

Lancet

Behav Brain Res

Neuropsychologia

Trends Neurosci

Life Sci

Neurosci Lett

The biochemistry of Parkinson's disease

Effect of age on D2-dopamine receptors in normal human brain measured by positron emission tomography and 11C-Raclopride

Arch Neurol

Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease

Brain

Brain muscarinic receptors in progresive supranuclear palsy and Parkinson's disease: a positron emission tomographic study

J Neurol Neurosurg Psychiatry

〚123I〛-β-CIT and SPECT in essential tremor and Parkinson's disease

J Neural Transm

Dopa-responsive dystonia: A clinical and molecular genetic study

Ann Neurol

Loss of striatal 〚76Br〛bromospiperone binding sites demonstrated by positron emission tomography in progressive supranuclear palsy

J Cereb Blood Flow Metab

Accurate differentiation of parkinsonism and essential tremor using visual assessment of 〚123I〛-FP-CIT SPECT imaging: The 〚123I〛-FP-CIT study group

Mov Disord

Positron emission tomography study in porgressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations

Arch Neurol

Does frontal cortex hypometabolism in progressive supranuclear palsy result from subcortical dysfunction?

Eu

J Neurol

Corticobasal degeneration: decreased and asymmetrical glucose consumption as studied with PET

Mov Disord

Imaging the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Eur J Nucl M

PET studies in progressive supranuclear palsy

J Neural Transm Suppl

PET and SPECT studies in Parkinson's disease

Bailliere's Clinical Neurology

The early diagnosis of Parkinson's disease

Ann Neurol

Differing patterns of striatal 18F-Dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

Ann Neurol

The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET

Brain

Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-Raclopride and positron emission tomography

Ann Neurol

A comparison of the abnormal patterns of cerebral activation associated with neuropathic and essential tremor

Neurology

Isolated tremor and disruption of the nigrostriatal dopaminergic system: An 18F-dopa PET study

Neurology

Relief of akinesia by apomorphine and cerebral metabolic changes in Parkinson's disease

Mov Disord

Fréquence et profil clinique des formes familiales de maladie de Parkinson. Enquête portant sur 428 cas-index recrutés dans un service de neurologie

Rev Neurol (Paris)

〚18F〛-Dopa PET study in patients with juvenile-onset Parkinson’s disease and parkin gene mutations

Neurology

Measurement of dopaminergic degeneration in Parkinson's disease with 〚123I〛ß-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy

J Neural Transm

Dopamine D2 receptor imaging with SPECT. Studies in different neuropsychiatric disorders

J Cereb Blood Flow Metab

Striatal dopamine D2-receptor blockade by typical and atypical neuroleptics

Lancet

D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side-effects. A SPECT study

J Cereb Blood Flow

Nigral dysfunction in drug-induced parkinsonism: an 18F-Dopa PET study

Neurology

The differential diagnosis of Parkinson's disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data

J Neurol Neurosurg Psychiatry

Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease

Nature

Age-dependant decline of nigrostriatal dopaminergic function: A positron emission tomographic study of grandparents and their children

Ann Neurol

Review
Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson’s diseaseContribution de la tomographie par émission de positons et de la tomographie par émission de simples photons à la compréhension de la physiopathologie de la maladie de Parkinson.

〚¹²³I〛-β-CIT and SPECT in essential tremor and Parkinson's disease

Accurate differentiation of parkinsonism and essential tremor using visual assessment of 〚¹²³I〛-FP-CIT SPECT imaging: The 〚¹²³I〛-FP-CIT study group

Differing patterns of striatal ¹⁸F-Dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

〚¹⁸F〛-Dopa PET study in patients with juvenile-onset Parkinson’s disease and parkin gene mutations

Measurement of dopaminergic degeneration in Parkinson's disease with 〚¹²³I〛ß-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy

Nigral dysfunction in drug-induced parkinsonism: an ¹⁸F-Dopa PET study