[123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson's disease
Lorberboym M, Treves TA, Melamed E, Lampl Y, Hellmann M, Djaldetti R;
Commented by , 25 Jul 2006
Background
In patients who develop Parkinsonism under neuroleptic treatment, it can be difficult to judge if symptoms are due to dopamine receptor blockade alone or combined with an underlying, co-existent nigrostriatal dysfunction. It has been reported that imaging of dopamin transporter (DaT) receptors using (123I)-FP/CIT SPECT helps to differentiate between pre-synaptic versus post-synaptic dysfunction in nigrostriatal dopaminergic transmission.
Objectives
The objectives of this study were to evaluate DaT binding in patients in whom parkinsonian symptoms developed during treatment with dopamin receptor blocking agents in order to assess whether these symptoms were induced by blockade of dopamine receptors or by an underlying nigrostriatal degeneration, and to correlate the parkinsonian signs and symptoms with the SPECT imaging.
Methods
This was a cross-sectional study in which the clinical characteristics and striatal binding of FP-CIT was evalauted in patients who developed Drug-Induced Parkinsonism (DIP). A total of 20 patients who developed parkinsonism while on neuroleptic agents and 10 age-matched controls were enrolled.
Neurological assessment was performed with the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS). FP-CIT binding of the entire striatum, caudate, and putamen was calculated. Patients were divided into two subgroups according to SPECT results.
Results
There were 9 patients who had normal scans and 11 who showed significantly diminished striatal binding, suggesting degeneration of the nigrostriatal system. Subanalyses of the abnormal scans revealed significantly diminished binding in the caudate and putamen. There were no differences in clinical features between patients with normal and abnormal scans.
Symptoms included asymmetric tremor, bradykinesia, and rigidity in both groups. Freezing of gait was present in two patients with normal scans. These results indicate that DIP is clinically indistinguishable from PD. The authors concluded that brain imaging with FP-CIT helps to determine whether DIP is entirely drug-induced or an exacarbation of subclinical PD.
Professor Emre's comments
Dopamine transporter receptors are located on the presynaptic dopaminergic nigrostriatal terminals. Their imaging using FP-CIT provides a fair assessment of the integrity of nigrostriatal dopaminergic system. FP-CIT uptake is normal in patients with intact dopaminergic innervation whereas it is reduced when there is a loss of dopaminergic terminals.
It was suggested that one of the important uses of this method is to differentiate loss of presynaptic dopaminergic terminals, i.e.degeneration of the nigrostriatal system from dysfunction of the post-synaptic receptors, e.g. due to dopaminergic receptor blockade (ref. 1, ref. 2).
One of the dilemmas in patients who develop parkinsonism under neuroleptic treatment is to decide if extrapyramidal symptoms are entirely due to a blockade of post-synaptic dopaminergic receptors or if co-existent, sub-clinical nigrostriatal pathology contributes to the signs of parkinsonism.
Features such as symmetrical motor involvement, lack of tremor and lack of response to dopaminergic medication are believed to be suggestive of drug-induced parkinsonism (ref. 3).
This study demonstrated that clinical features of patients with normal FP-CIT scans (suggesting normal nigrostriatal dopaminergic function) are not distinguishable from those with abnormal scans (suggesting co-existent nigrostriatal pathology), thus clinical evaluation alone does not seem to help for this differentiation.
The results also revealed that about half of the patients with seemingly drug-induced parkinsonism showed evidence of co-existent nigrostriatal dysfunction. Overall these results confirm and extend the previous assumptions that some patients with drug-induced parkinsonism have subclinical nigral pathology which becomes clinically evident when an additional dopaminergic receptor blockade occurs, and that imaging of dopamine transporter receptors with SPECT can help to identify such patients.
These findings have important therapeutic implications as patients with abnormal scans can confidently be treated with dopaminergic medication whereas witdrawal of neuroleptics or swithing to an atypical neuroleptic may suffice for those with normal scans.
References
1. Tolosa E, Coelho M, Gallardo M. DAT imaging in drug-induced and psychogenic parkinsonism. Movement Disorders 2003; 18 Suppl 7; 28-33
2. Booij J, Speelman JD, Horstink MW, Wolters EC. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. European Journal of Nuclear Medicine 2001; 28 (3); 266-272
3. Hausner RS. Neuroleptic-induced parkinsonism and Parkinson's disease: differential diagnosis and treatment. Journal of Clinical Psychiatry 1983; 44 (1); 13-16