Cardiac 123 I-meta-iodo-benzyl-guanine in a patient with bipolar affective disorder,musical hallucinations and Parkinsonism

To the Editor,

A 51-year-old businesswoman with a 30-year history of type-1 bipolar affective disorder presented with a 2-year history of musical hallucinations and decline in occupational function. Family history included vascular dementia and stroke. Regular medications were venlafaxine 225 mg, sodium valproate 900 mg and risperidone 1 mg. On admission, affect was restricted, but there were no other psychotic features. Mild executive dysfunction was evident on bedside cognitive testing with ACE-R 92/100. Physical examination revealed a stiff gait with retropulsion, tongue tremor, dysfluent and decrementing finger-taps, asymmetric rigidity of the right upper limb and non-habituating glabellar and palmo-mental reflexes. There was no rest tremor, and eye movements were normal. Bloods were unremarkable, but computed tomography (CT) of the brain showed cerebral atrophy with predilection for the frontal and left temporal lobes.

The parkinsonism did not resolve with the withdrawal of risperidone, and 6 months later, the patient proceeded to cardiac ¹²³I-meta-iodo-benzyl-guanine (MIBG) to refine a differential diagnosis that included both synucleinopathies (Parkinson disease, dementia with Lewy bodies) and tauopathies (Parkinson-plus, Alzheimer disease, fronto-temporal dementia).

Diminished cardiac activity was demonstrated on both early (Figure 1(A)) and late (Figure 1(B)) phase ¹²³I-MIBG imaging with a low cardiac-to-mediastinal uptake ratio indicative of significant sympathetic cardiac denervation. A normal study (Figure 1(C) and (D)) is included for comparison. The result was consistent with the presence of Lewy body pathology, and a probable diagnosis of Parkinson disease was made.

Figure 1.

123I-MIBG scintigraphy demonstrating diminished cardiac activity (black arrows) in the index patient on both (A) early and (B) late phase imaging. The cardiac silhouette (white arrows) is more clearly visible in the (C) early and (D) late phase images of a normal study, which is included for comparison.

¹²³I-MIBG is a radioactive analogue of the adrenergic blocker guanethidine that is actively taken up by postganglionic sympathetic nerve endings and incorporated into presynaptic vesicles. While originally developed to assess postganglionic sympathetic nerve dysfunction in heart disease,¹²³I-MIBG is also used to detect early Lewy body disease, which is known to affect postganglionic sympathetic cardiac neurons before affecting the neurons of the central nervous system.

In clinical practice, cardiac ¹²³I-MIBG can help resolve differential diagnoses distinguished by the presence or absence of Lewy bodies. A meta-analysis of 19 studies comprising 1972 patients with parkinsonism showed that ¹²³I-MIBG detects Parkinson disease with sensitivity of 88% and discriminates between Parkinson disease and non-Lewy body parkinsonism with specificity of 85% (Treglia et al., 2012). Another meta-analysis of eight studies comprising 346 patients with dementia showed pooled sensitivity of 98% and specificity of 94% in distinguishing dementia with Lewy bodies from other forms of dementia (Treglia and Cason, 2012). False positives may be generated by complicated diabetes mellitus, treatment with tricyclic antidepressants and incidental Lewy body disease, while false negatives may be caused by very early disease and some rarer forms of Parkinson disease.