Diagnosis of Multiple System Atrophy-Parkinsonian Type [MSA-P] from Atypical Parkinsonism with Dual Tracer (FDG + DOPA) PET/MRI Brain

Abstract

Objective:

This case report demonstrates the potential of dual tracer imaging (fluorodeoxyglucose + dihydroxyphenylalanine (FDG + DOPA)) positron emission tomography/magnetic resonance imaging (PET/MRI) brain in diagnosing and distinguishing the patients with multiple system atrophy-Parkinsonian type (MSA-P) from atypical Parkinsonism.

Methods:

A 65-year-old male presented with postural instability, urinary symptom in form of urgency, hesitancy, precipitancy followed by incontinence, slowness of all activity of daily living (ADL) with stiffness of all limbs, slurred speech and difficulty in swallowing for four years. It was clinically suspected as atypical Parkinson’s disease. The DOPA PET/MRI revealed asymmetric reduced patchy uptake in bilateral striatum qualitatively and quantitatively more prominently in bilateral putamen (right> left—maximum standardised uptake value (SUVmax): putamen left 2.18; right 1.91; caudate nucleus left 2.71; right 2.62). Bilateral putamen is atrophic with heterogeneous signal changes. Midbrain Pons ratio measures 0.6 (reported threshold of 0.52).

Results:

All of these features when put together help us to point it towards the MSA-P which was further confirmed by 18F-FDG study which showed regional FDG hypometabolism in bilateral putamen with relative sparing bilateral caudate, palladium and thalamus.

Conclusion:

Dual tracer PET/MRI will be the key to reliable uses in the diagnosis of clinically suspected neurodegenerative disorder and accurate prediction of therapeutic intervention.

Objective

The aim of this study was to demonstrate the clinical utility of dual-tracer imaging (fluorodeoxyglucose + dihydroxyphenylalanine (FDG + DOPA)) positron emission tomography magnetic resonance imaging (PET/MRI) brain in the diagnosis and management of multiple system atrophy-Parkinsonian type (MSA-P) and differentiation from other atypical parkinsonian syndromes (APS).

Introduction

MSA-P manifests with parkinsonian motor symptoms and additional features such as cortical dysfunction (e.g., cognitive deficits, apraxia), pseudobulbar signs and cerebellar or pyramidal involvement.^[1] Fluorodopa (F-DOPA) PET serves as an indicator of dopaminergic neuron loss within the substantia nigra.^[2,3] In contrast, FDG PET/MRI identifies metabolic deficits that may emerge before structural brain atrophy is detectable on conventional imaging.^[4] The topography of hypometabolism aids in differentiating different APS, such as corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) or MSA.^[5,6]

This case report illustrates the clinical utility of dual-tracer (FDG and DOPA) PET/MRI brain imaging in diagnosing MSA‑P and differentiating it from other APS.

Case Presentation

A 65-year-old male presented with postural instability for the past four years. The patient developed progressive urinary dysfunction (urgency, hesitancy, followed by incontinence) over the last three years. Tremulousness of the bilateral upper limbs, slowness of daily activities and generalised limb stiffness were present for the last three years. Slurred speech was noted over the same period. He developed rapid eye movement (REM) sleep behaviour disorder (acting out dreams) and dysphagia (choking on both solids and liquids) over the last two years.

On examination (O/E):

1	HMF[MMSE]	25/30
2	Cranial nerve 3rd/4th/6th	Extraocular movements—full, no nystagmus, VOR—normal, pursuits—broken, saccades—slow
3	Motor examination	UL—cogwheel rigidity, LL—lead pipe rigidity Power -4+/5 all four limbs
4	Reflex	DTR—2+, Planter—B/L Flexor
5	Sensory examination	Exteroceptive sensation and proprioceptive sensation—normal
6	Cerebellar examination	FNF—absent, dysdiadochokinesia—absent, knee—heel test—absent
7	Extrapyramidal examination	Hypomimia, bradykinesia, speech—soft, hypophonic, micrographia, blink rate- reduced [<14/min], axial rigidity, B/L cog wheel rigidity of wrist hands, B/L lead pipe rigidity lower limbs and upper limbs, Myerson sign—present, tremor—resting tremor.
8	Gait	Start hesitation, shuffling and festinating, decreased arm swing on both sides, freezing while turning+ trembling place while turning+, turning en bloc,
9	Autonomic nervous system examination	Base line blood pressure (BP)—140/90 mm Hg, HR—80 bpm BP 3 minutes after standing—110/60 mm Hg
10	Romberg sign	Negative

Discussion

This case demonstrates how FDOPA and FDG PET/MRI can enhance differentiation of MSA-P from other APS. In our patient, the asymmetric reduction in DOPA uptake (right > left) within bilateral putamen and relative preservation of caudate nucleus uptake, along with midbrain-pons ratio of 0.6, pointed towards MSA-P. Previous studies demonstrate that MSA-P typically shows bilateral, symmetric or mildly asymmetric reduction in putaminal uptake, associated with putaminal atrophy and hypointensity on MRI [Figure 1].^[5]

Figure 1.

Note: HMF, Higher Mental Functions; MMSE, Mini-Mental State Examination; VOR, Vestibulo-Ocular Reflex; DTR, Deep Tendon Reflexes; FNF, Finger–Nose–Finger Test; B/L, Bilateral.

A comparative pattern of dual tracer PET/MRI in atypical Parkinsonism is summarised in Table 1. Compared to other reports, our findings align with FDOPA PET indicating presynaptic dopaminergic loss,^[2,3] while FDG PET highlights cortical metabolic changes. Our case’s isolated bilateral putaminal hypometabolism without diffuse cortical involvement is characteristic of MSA-P,^[5,6] whereas CBD exhibits asymmetric cortical hypometabolism involving frontal and parietal lobes.^[5]

The combination of early-onset autonomic symptoms, REM sleep behaviour disorder and asymmetric striatal FDOPA uptake strongly supports MSA-P.^[5,6] Preservation of thalamic and caudate metabolism helped differentiate it from PSP and DLB. Table 2 highlights key PET/MRI differentiators across atypical Parkinsonian syndromes. Midbrain-to-pons ratio of 0.6 was above the PSP threshold (<0.52), effectively ruling out PSP despite some overlapping clinical features. Unlike idiopathic Parkinson’s disease (IPD), where early cortical involvement is minimal,^[5] MSA-P shows distinct striatal metabolic patterns. Incorporating dual-tracer imaging enhances diagnostic confidence, as demonstrated by Meyer et al. and Zhao et al.^[5,6] Our case shows how FDG and DOPA PET/MRI complement clinical assessment, allowing early diagnosis, prognostication and optimal management planning.

Table 1.

Pattern of dual tracer (FDG + DOPA) PET/MRI brain in atypical Parkinsonism

1	Reduced and patchy DOPA uptake in bilateral striatum (putamen and caudate nucleus) 18F-FDG study hypometabolism in bilateral frontal, parietal and temporal lobes and bilateral cerebellum Midbrain/ pons ratio measures 0.51(borderline	MSA-C
2	Decreased DOPA uptake qualitatively and quantitatively in bilateral putamen and caudate nucleus. Midbrain/pons ratio is noted (0.47) with positive humming bird sign	PSP
3	FDG hypometabolism of bilateral temporal lobes including hippocampus, the frontal and parietal lobes and occipital lobe. Cingulate of island sign	CBD
4	FDG hypometabolism of bilateral temporal lobes including hippocampus, the frontal and parietal lobes including precuneus and posterior cingulate gyrus with atrophy	AD
5	Bilateral frontal, anterior temporal hypometabolism with atrophy	FTD
6	F-DOPA asymmetrical decreased uptake in bilateral putamen and caudate nucleus (R>L) Normal tracer uptake in bilateral basal ganglia	IPD

Notes: FDG + DOPA, fluorodeoxyglucose + dihydroxyphenylalanine; PET/MRI, positron emission tomography magnetic resonance imaging; MSA-C, multiple system atrophy—cerebellar type; AD, Alzheimer’s disease; FTD, frontotemporal dementia; IPD, idiopathic Parkinson’s disease; PSP, progressive supranuclear palsy; CBD, corticobasal degeneration.

Table 2.

Comparative summary of characteristic FDG and DOPA PET/MRI findings across different atypical parkinsonian syndromes to aid in differential diagnosis

Syndrome	FDG PET findings	DOPA PET findings	Key differentiating features
MSA-P	Hypometabolism in bilateral putamen; relative sparing of caudate, thalamus, cortex	Asymmetric or symmetric reduced DOPA uptake in bilateral putamen (R>L or symmetric)	Early autonomic dysfunction, RBD, cerebellar atrophy (MSA-C subtype), normal midbrain volume
PSP	Hypometabolism in bilateral frontal cortex, thalamus, midbrain; ‘hummingbird sign’ on MRI	Decreased DOPA uptake diffusely in caudate and putamen; midbrain/Pons ratio <0.52	Early postural instability, vertical gaze palsy, early frontal cognitive dysfunction
CBD	Asymmetric hypometabolism in parietal, frontal cortex (especially sensorimotor areas); ‘cingulate island’ preserved	Asymmetric DOPA reduction (contralateral to more affected side)	Asymmetric rigidity, apraxia, cortical sensory loss
DLB	Hypometabolism in occipital cortex (posterior cingulate sign spared); parietal and temporal involvement	Relatively preserved DOPA uptake early; decline later	Prominent early cognitive decline, hallucinations, fluctuating cognition
IPD	Usually no cortical hypometabolism early; normal FDG PET	Asymmetric DOPA uptake reduction in putamen (posterior putamen more affected)	Good levodopa response, slow disease progression, absent early autonomic failure
MSA-C	Hypometabolism in cerebellum, pons, with bilateral putaminal changes	Reduced DOPA uptake in putamen; cerebellar atrophy evident	Cerebellar ataxia prominent early, gait and coordination dysfunction

Notes: FDG and DOPA, fluorodeoxyglucose and dihydroxyphenylalanine; PET/MRI, positron emission tomography/magnetic resonance imaging; MSA-C, multiple system atrophy—cerebellar type; MSA-P, multiple system atrophy-Parkinsonian type; IPD, idiopathic Parkinson’s disease; PSP, progressive supranuclear palsy; CBD, corticobasal degeneration; DLB, dementia with Lewy bodies; REM, rapid eye movement; RBD, REM sleep behaviour disorder.

Taken together, these observations strongly point to MSA‑P. This diagnosis was supported by 18F‑FDG PET/MRI, which revealed pronounced hypometabolism confined to the bilateral putamina, with relative preservation of the caudate nuclei, pallidia and thalami. FDOPA PET/MRI further demonstrated presynaptic dopaminergic denervation, effectively excluding Alzheimer’s disease (AD).^[7,8]. By contrast, APS often show diffuse cortical hypometabolism on FDG PET/MRI,^[9,10] whereas our case displayed a primarily striatal metabolic defect, facilitating accurate differentiation. A diagnostic approach integrating clinical and imaging findings is illustrated in Figure 2.

Figure 2.

Diagnostic pathway integrating clinical features with dual-tracer PET/MRI findings for accurate differentiation of atypical parkinsonism

Conclusion

This case highlights the value of dual-tracer imaging with FDOPA and FDG PET/MRI in guiding clinical evaluation of suspected MSA‑P. The presence of mild cognitive deficits on FDG PET/MRI may serve as a prognostic marker for future cognitive decline or dementia. Early and precise diagnosis through this imaging approach supports tailored therapeutic planning and underscores the importance of incorporating cognitive rehabilitation into the management of APS.