Incidental Detection of Meningioma in Suspected Parkinsonism Patients - A Case Series on ¹⁸F-DOPA PET/MRI

INTRODUCTION

Fluorine-18-l-dihydroxyphenylalanine (¹⁸F-DOPA) is a very special radioisotope that can be utilised for Parkinson's disease diagnosis as well as for tumour imaging. The neutral amino acid DOPA is similar to the natural dopamine precursor L-DOPA. It enters the brain and the peripheral tissues' endogenous L-DOPA catecholamine metabolic pathway. It can be labelled with 18F for positron emission tomography (PET) imaging, and it was first used to evaluate the striatal dopaminergic system's integrity in Parkinson's disease patients. The management of several additional diseases, including pancreatic cell hyperplasia, brain tumours, and neuroendocrine tumours, has greatly benefited from the recent development and application of hybrid PET/computed tomography scanners. These pathologic entities exhibit elevated absorption of 18F-DOPA due to enhanced L-DOPA decarboxylase activity. Due to its limited accessibility, the role of 18F-DOPA has not been fully established despite these potentially promising applications in severe clinical fields. In this case report, we are going to study the incidental detection of meningioma in a patient with suspected Parkinsonism.^[1,2]

CASE SERIES

Case 1

A 64-year-old female, left-handed patient has come to the nuclear medicine department with clinical suspicion of Parkinsonism for an 18F-DOPA PET/magnetic resonance imaging (MRI) scan on May 16, 2024, referred by the neurology department. The patient first came to the neurology department with complaints of increased frequency of episodes of falls for the past 3–4 months, which were mainly left-sided and associated with dizziness. Patient had no H/O seizure, headache, vomiting, loss of consciousness, or head injury. On 18F-DOPA PET/MRI scan, 18F-DOPA PET study shows asymmetric decreased DOPA uptake in bilateral putamen (SUV max: Rt. anterior putamen-1.30, Lt. anterior putamen-1.61, Rt. posterior putamen-1.10, and Lt. posterior putamen-1.37) and caudate nucleus (Rt. Caudate-1.71 and Lt. caudate-1.74) (R > L) which suggested deranged presynaptic striatal integrity and MRI showing no apparent volume loss in the brainstem, putamen, and cerebellum. Overall findings suggested the possibility of idiopathic Parkinson's disease. DOPA avid, homogenously enhancing circumscribed, extra axial dura-based mass measuring ~ 3.5 (AP) × 3.0 (TR) × 3.8 (CC) cm with overlying dural enhancement and dural tail was also seen in the left frontal region, suggestive of meningioma indenting and effacing the underlying parenchyma. It shows a signal drop on ADC with no susceptibility changes, and increased DOPA uptake (SUVmax 1.71). There was evidence of mild oedema in the underlying parenchyma. The patient then underwent left frontotemporal osteoplastic craniotomy and Simpson's Grade I excision of left frontal convexity meningioma on May 17, 2024. The tumour was greyish pink, firm, fibrous, and well-defined with vascular areas and an arachnoid plane all around the frontal cortex. The histological specimen confirmed the diagnosis of meningioma. Postoperatively, the patient was managed conservatively with intravenous medication and other supportive care. When the patient was stable, she was discharged with subsequent follow-up in the neurology and neurosurgery outpatient department. There was no improvement in the symptoms; therefore, the patient was put on antiparkinsonian therapy and showed a response [Fig 1].

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Fig 1:

A 64-year-old female with increased frequency of left-sided falls and suspected Parkinson’s disease underwent Fluorine-18-ldihydroxyphenylalanine positron emission tomography/magnetic resonance imaging (18F-DOPA PET/MRI). (a) Axial PET and (b) fused axial PET/MRI images show asymmetrically decreased DOPA uptake in the bilateral putamen and caudate nucleus (yellow arrows in a and b), more pronounced on the right (R > L), suggesting deranged presynaptic striatal integrity, (c) axial T2 image demonstrate preserved volume of the basal ganglia (blue arrows), (d) susceptibility-weighted imaging (SWI) shows loss of the swallow tail sign (orange arrows), (e) axial T1 Magnetization-Prepared Rapid Gradient-Echo (MPRAGE) images demonstrate preserved volume of the basal ganglia (blue arrows), (f) Sagittal T1 MPRAGE image shows a normal midbrain-to-pons ratio (0.58). These findings support idiopathic Parkinson’s disease. (g) Axial PET and (h) fused axial PET/MRI reveal an incidental DOPA-avid meningioma (red arrows in g and h) in the left frontal region (SUVmax 1.71). (i) Axial T2, (j) sagittal T1 MPRAGE, (k) axial T1 MPRAGE post-contrast, and (l) sagittal T1 MPRAGE post-contrast images show the lesion (red arrow in i-l) indenting and effacing the underlying parenchyma with mild surrounding edema. PET: Positron emission tomography; MRI: Magnetic resonance imaging

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Case 2

A 76-year-old male patient suffered from left-hand tremor and forgetfulness of recent memory for 1 year. The patient was referred for 18F-DOPA PET/MRI for the diagnosis of Parkinson's disease. 18F-DOPA PET study shows asymmetric decreased DOPA uptake in bilateral putamen (SUVmax: Rt. anterior putamen - 2.00, Lt. anterior putamen - 2.12, Rt. posterior putamen - 1.35, and Lt. posterior putamen - 1.58) and caudate nucleus (Rt. Caudate-1.86 and Lt. caudate - 2.21. suggesting that the basal ganglia on the right side are more affected than the left. A gradient decrease of DOPA uptake was also noted: in the caudate nucleus > anterior putamen > posterior putamen.

Reduced DOPA uptake in bilateral basal ganglia (Rt > Lt) supports deranged presynaptic striatal integrity and MRI showing no apparent volume loss in the brainstem, putamen, and cerebellum, which suggested the possibility of idiopathic Parkinson's disease PD with possible PD dementia. Incidentally, we also found DOPA avid (SUV max 2.03) homogenously enhancing dura-based mass measuring 2 cm × 1.04 cm × 1.19 cm with a dural tail in the left posterior frontal region: morphologically, meningioma indenting the underlying brain parenchyma with no associated oedema. Prominent sulcal spaces and ventricular system suggest bilateral cortical atrophy. The neurologist and neurosurgeon decided not to perform the surgery for meningioma, and the patient was put on antiparkinsonian therapy. On follow-up, we found that the patient was responding to antiparkinsonian therapy [Fig 2].

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Fig 2:

A 76-year-old male with left-hand tremor and recent memory impairment for 1 year, suspected of Parkinson’s disease, underwent Fluorine-18-l-dihydroxyphenylalanine positron emission tomography/magnetic resonance imaging (18F-DOPA PET/MRI). (a) Axial PET and (b) fused axial PET/MRI images show asymmetrically decreased DOPA uptake in the bilateral putamen and caudate nucleus (yellow arrows in a and b), more pronounced on the right (R > L), suggesting deranged presynaptic striatal integrity,(c) axial T2 image demonstrate no apparent volume loss in the putamen and caudate nucleus (blue arrows), (d) Susceptibility-weighted imaging (SWI) shows loss of the swallow tail sign (orange arrows), (e) axial T1 Magnetization-Prepared Rapid Gradient-Echo (MPRAGE) images demonstrate no apparent volume loss in the putamen and caudate nucleus (blue arrows), (f) sagittal T1 MPRAGE image demonstrates a normal midbrain-to-pons ratio (0.53). These findings are supportive of idiopathic Parkinson’s disease. (g) Axial PET and (h) fused axial PET/MRI show increased DOPA uptake in an incidental meningioma (SUVmax 2.03) (red arrows in g and h), (i) axial T2 demonstrate a meningioma in the left posterior frontal region (red arrow), (j) coronal T2 FLAIR image shows prominent sulci and bilateral periventricular white matter hyperintensities, suggesting cerebral atrophy with ischemic changes, (k) axial T1 MPRAGE post-contrast, and (l) sagittal T1 MPRAGE post-contrast images demonstrate a meningioma in the left posterior frontal region (red arrows in k and l). PET: Positron emission tomography; MRI: Magnetic resonance imaging

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DISCUSSION

18F-DOPA is a versatile PET agent that evaluates presynaptic dopaminergic integrity by measuring the absorption of a dopamine precursor. The increased absorption of 18F-FDOPA is associated with the L-amino acid transporter (LAT). The expression and activity of the aromatic L-amino acid decarboxylase (AADC), which changes 18F-FDOPA into 18F-dopamine, as well as the amount of 18F-dopamine in synaptic vesicles through vesicular monoamine transporters, are likely more important factors in the tracer's retention. The activity of the AADC and the density of catecholaminergic terminals are both reflected in the uptake of 18F-DOPA in the striatal nuclei. Therefore, the number of surviving dopaminergic cells will affect measurements of 18F-DOPA uptake in the striatum of PD patients. 18F-DOPA can be helpful in cases where there is clinical doubt for people with Parkinson's disease, such as movement difficulties, and has been demonstrated to reflect the monoaminergic abnormalities in PD accurately. The prolonged retention of 18F-FDOPA in tumours that release serotonin and catecholamines is likely explained by the LAT's role in transporting amino acids, which are subsequently used for protein synthesis in malignancies.^[2,3]

The LATs enable the steady flow of amino acids required for cellular development, metabolism, and signalling, in addition to their function in neurosecretion. However, compared to other bigger amino acids like leucine, which is a significant activator of mechanistic target of rapamycin kinase and permits continuous protein synthesis, cell cycle progression, and inhibiting autophagy induction, these transporters have a reduced affinity for L-DOPA. Because they are essential for growth, migration, and invasiveness, these nutrient transporters are not unique to NETs and can be overexpressed in a range of tumour types.^[2]

High levels of LAT1 expression have been reported in meningiomas. As a result, these tumours may exhibit elevated FDOPA uptake.^[4] Furthermore, there have been reports of increased uptake of other amino acid PET tracers in meningiomas.^[5-7] For example, a group of 10 meningiomas demonstrated increased uptake of - [^11C] methyl-Ltryptophan (AMT)^[4] and somatostatin radiolabelled analogues.^[8]

These two cases are unique in the sense that both these patients show the versatility of 18F-DOPA as a radionuclide, which can be used for both tumour imaging and for imaging the presynaptic pathway to diagnose Parkinson's disease. Both patients, when undergoing 18F-DOPA PET/MRI, had idiopathic Parkinson's disease (IPD) with coexisting meningioma, in which we got decreased 18F-DOPA uptake in the basal ganglia with no apparent volume loss in the putamen and caudate, and the midbrain/pons ratio was normal. There was a loss of swallow tail sign, a sensitive biomarker for IPD^[9], and concurrently, we found DOPA uptake in the meningioma. In these cases, PD and meningioma are not correlated. Patient's symptoms were a result of Parkinson's disease, and not because of meningioma, as in the first case, the patient was having episodes of left-sided falls. On the PET/MRI scan, we found a meningioma in the left frontal region. We decreased DOPA uptake right > left, which justifies the patient's symptom on the contralateral side of the affected basal ganglia. Furthermore, the patient's symptoms did not improve after surgery, and the patient responded to anti-Parkinsonian therapy. In the second case, this patient also had left-sided symptoms, and on PET/MRI, decreased DOPA uptake in Rt basal ganglia (contralateral side) > Lt. basal ganglia were found with meningioma on the left side. This patient was given antiparkinsonian therapy, and the patient's symptoms improved. Therefore, in both cases, meningioma was an incidental finding, and the reason for the patient's symptoms was Parkinson's disease.

Some research articles have reported tumour-induced Parkinsonian syndrome. It is extremely uncommon for people with intracranial tumours to develop Parkinsonian syndrome (only 0.3% of cases in a published series). Patients with tumour-induced Parkinsonian syndrome also need to be evaluated for the potential of a merely accidental link. The postoperative phase following tumour removal is critical to the eventual recurrence of symptoms. Meningiomas are the most prevalent histotype, especially those located in the frontal or parietal falx, the sphenoid ridge (from the dorsal face of the sphenoid), and the frontal or temporal skull base. These tumours are most described as producing Parkinsonian symptoms when they have a supratentorial localisation. Actually, the only thing that may have concealed it was the striatal damage. Patients who have tumour-induced Parkinsonism have an unclear reaction to levodopa/carbidopa and bromocriptine.^[9,10] The pathogenetic mechanism in the case of a high-frontal meningioma may have been the compression of the connections between the basal nuclei and the supplementary motor area, which resulted in a noticeable movement abnormality without substantially compressing the basal ganglia structures. Parkinsonian symptoms can, of course, also result from space-occupying lesions that are in the supplementary motor region. These individuals typically have a very good prognosis compared to those who have Parkinson's disease, and the vast majority of them recover completely. However, in our cases, both patients responded to antiparkinsonian therapy positively, and the symptoms of the first patient did not improve after surgery. Therefore, one should be careful while interpreting the 18F-DOPA study, as haemangioma, ischaemic brain lesion, infarction, scar tissue, abscess, sarcoidosis, irradiated areas, and many other nonneoplastic processes are among the numerous nontumoral locations and processes in the brain that exhibit uptake of all radiolabelled amino acids. Amino acids are also necessary for active inflammatory cells, and the elevated perfusion of infections may further enhance amino acid absorption. Furthermore, it is critical to be mindful of the possibility of false-positive and false-negative situations in a variety of clinical contexts.^[10,11]

Integrating 18F-DOPA PET with MRI in both our cases not only helps to classify IPD from atypical Parkinsonism better while detecting coexisting brain pathologies, but also, in a single session, provides a better preoperative evaluation tool for surgery planning.

CONCLUSION

This case series demonstrates how 18F-DOPA PET/MRI may concurrently assess dopaminergic impairment and identify incidental cerebral diseases. Reduced striatal uptake in both patients was indicative of idiopathic Parkinson’s disease, and the coinciding meningiomas were an accidental discovery rather than the source of symptoms. These results show the additional clinical utility of hybrid imaging in thorough neurological assessment and management and highlight the significance of carefully interpreting imaging results to prevent misattribution of clinical symptoms.