Failure Of Gallium-68 Citrate Scan To Detect Large, Enhancing Central Nervous System Tuberculomas: A Cautionary Tale

doi:10.21203/rs.3.rs-4610855/v1

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Case Report

Failure Of Gallium-68 Citrate Scan To Detect Large, Enhancing Central Nervous System Tuberculomas: A Cautionary Tale

https://doi.org/10.21203/rs.3.rs-4610855/v1

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Background

Gallium-68 citrate is an emerging diagnostic tool for the evaluation of infections. Its performance in brain infections, specifically central nervous system (CNS) tuberculosis, is unknown. The available diagnostics for CNS tuberculosis are imprecise.

Case Presentation

We report a patient with large, active, enhancing, microbiologically confirmed tuberculomas in the right frontal lobe who underwent Gallium-68 PET CT. It did not show any tracer uptake in the tuberculous lesions.

Conclusions

We report caution in the use of Gallium-68 PET CT for CNS TB, especially with concomitant steroid use.

Gallium-68 PET CT

Central nervous system tuberculosis

Brain infections

Tuberculosis (TB) of the central nervous system (CNS) is the most severe form of disease with high rates of disability and mortality. Imaging plays a key role in supporting the diagnosis of CNS TB and in the evaluation of extrapulmonary involvement. The available microbiological diagnostics are poorly sensitive. Magnetic Resonance Imaging (MRI) brain is the preferred modality for detecting meningeal and parenchymal disease. Nuclear imaging with various radioactive probes has shown mixed results. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is poorly sensitive to intracranial and intraspinal lesions in relation to the MRI in view of high metabolic uptake throughout the brain. However, it is useful for evaluating extra neural involvement [1, 2].

Though Gallium-67 (Ga-67) citrate has been used to detect cranial and cerebral pathologies, evidence for the utility of Gallium-68 (Ga-68) citrate for brain infections is scarce [3]. In vivo animal studies have shown an appreciable tumour-to-brain ratio to the Ga- 68 isotype [4]. Compared with FDG-PET, it showed a better definition for intracerebral lesions [5]. Ga-68 could be a useful adjunct in the diagnosis and follow-up of CNS TB patients. However, currently, no data exists in the literature. Here, we present a case where a Ga-68 citrate scan showed no avidity in the active intracranial tuberculous lesions.

A 47-year-old gentleman from North India with no comorbid illnesses presented with intermittent low-grade fever and holocranial headache for 3 months and altered sensorium for a week with no neurological deficit. He was evaluated at a local medical facility and was diagnosed to have rifampicin-susceptible tuberculous meningitis based on TrueNat MTB/Rif (Molbio Diagnostics, Verna, India) in the cerebrospinal fluid. He was initiated on anti-tuberculous therapy (ATT) with rifampicin, streptomycin, levofloxacin and ethambutol since his liver enzymes were elevated at baseline. After 2 months of therapy, he developed unsteadiness while walking, progressive over the next 4 months. He then presented to our centre with the above complaints. Magnetic Resonance Imaging (MRI) of the Brain and Spine with Gadolinium contrast revealed multiple ring-enhancing lesions with perilesional edema in the right supratentorial and infra-tentorial compartments with basal cistern lesions (Fig. 1a and 1b). In addition, spine imaging revealed extramedullary compressive tuberculomas at the thoracic spinal level (T1 to T12 levels). He was then initiated on appropriate weight-based anti-mycobacterial therapy with isoniazid, rifampicin, pyrazinamide, ethambutol and pyridoxine along with dexamethasone at 0.4mg per kg per day. After 45 days of appropriate anti-TB therapy and steroids, he had a worsening imbalance and was given infliximab (5 mg per kg) for a severe paradoxical reaction. Around 45 days of infliximab, he developed worsening left-sided spastic hemiparesis and was readmitted. Neurological examination revealed significant gait ataxia, with cerebellar findings predominantly involving the lower limbs and trunk and impaired dorsal column sensations.

The baseline laboratory investigations were normal. The C-reactive protein was 4.76 mg/L (Reference normal: < 6 mg/L). Given the subacute development of a new onset hemiparesis, a repeat contrast-enhanced MRI brain and spine was done. There was a significant increase in the enhancement as well as the perilesional edema with new lesions in the right frontal, parietal, temporal, and occipital lobe lesions, with some of the lesions compressing the brainstem and causing uncal herniation (Fig. 2a and 2b). The spine imaging did not show any progression or regression of prior lesions. At this time, he was on tapering dexamethasone of 4 mg per day. A Gallium-68 citrate scan of the brain was performed at this point to evaluate activity in the lesions. However, this did not reveal any uptake in the brain (Fig. 2c and 2d).

He was then restarted on high-dose dexamethasone at 0.4 mg per kg per day, which is being tapered over 12 weeks. Anti-TB therapy was continued. At a follow-up visit 10 weeks later, his weakness has improved, and he is functionally independent for all activities of daily living.

In our patient, the Gallium-68 citrate scan failed to show uptake in the active cerebral tuberculomas. This is the first report of performance of Ga-68 citrate PET CT for CNS tuberculoma. FDG PET has been useful in assessing extra neural disease and response of the inflammatory granulomatous lesions to treatment. However, it is of limited value in CNS tuberculosis perse in view of high physiologic uptake in the brain. Ga-68 citrate PET CT could be a useful adjunct for evaluating activity in the CNS TB lesions, in the place of FDG PET. However, in our patient it did not show any uptake despite the presence of large enhancing granulomatous lesions in the MRI. Whether this reflects the performance of Ga-68 scan in CNS TB lesions or modified by the concomitant use of high dose steroids is unclear.

The effect of steroids on Ga-67 citrate uptake was demonstrated by Alan D Waxman et al. [6] in intracerebral tumours. Steroids when given above replacement doses, reduced the sensitivity of Ga -67 in detecting primary and metastatic brain tumours than technetium glucoheptonate. Uptake of Ga -67 in the brain is due to a non-transferrin-mediated mechanism [7]. Poor uptake of Gallium isotopes on steroid therapy could be due to its interaction with the blood-brain barrier (BBB) in two ways. Firstly, by reducing the permeability of tight junctions. Secondly, as a strong inducer of P-glycoprotein expression in BBB [8]. But this may not explain the discordant results where Gadolinium enhanced the lesions whereas Ga68 citrate failed to do so. The exact mechanism of differential uptakes in various radiopharmaceuticals needs to be studied further.

Ga-67 citrate has been in clinical use since the 1970s and shown to be more sensitive than routine chest radiography for the detection of both lung parenchymal involvement and adenopathy in tuberculosis. It also facilitates the choice of biopsy sites [9]. Recently developed Ga-68 citrate, unlike Ga-67 citrate, has a shorter half-life (66 hours), leading to a dosimetric advantage and early procedure completion [10]. It has shown excellent performance in the diagnosis of bone and prosthetic joint infections and endovascular infections [11, 12].

Ga-68 citrate may perform better than FDG PET in specific settings such as small lesions with low glycolytic activity and pathologies nearby or within the organs with high physiologic uptake sites like the brain, heart, liver, and kidney [13]. Ga-68 citrate scan is a potential alternative modality to FDG PET to measure intracranial disease activity; however, clinicians should practice caution while interpreting results in patients on concurrent steroids.

Since ours is a case report, we emphasise cautious interpretation of our findings. This report will spur further research in this important area. As we await further evidence, we suggest against routine use of Gallium − 68 citrate PET CT scan in CNS tuberculosis for clinical purposes.

CNS- Central Nervous System

TB- Tuberculosis

MRI- Magnetic Resonance Imaging

FDG PET -18F Fluoro Deoxy Glucose Positron Emission Tomography (FDG PET)

Ga- Gallium

ATT- Anti Tuberculous Therapy

BBB- Blood Brain Barrier

Ethical approval and consent to participate

The patient provided written informed consent to participation.

Consent for publication

The patient provided written consent for publication of the case

Availability of data and materials

All relevant data has been presented in the manuscript, and further inquiries can be made to the corresponding author.

Competing Interests

The authors have no competing interests to declare.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

AMconceptualised the study. SSK and AKN wrote the original draft. HAV and JH provided the radiological assessment and images. JH provided the critical review. All authors reviewed and approved the final manuscript and agreed to the submission for publication.

Acknowledgement

The authors also thank Dr. Minnu Ann Mohan, Dr. Mithun Mohan George, and Dr. Nishi Somarkutty for their technical assistance and proof reading the article.

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No competing interests reported.

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You are reading this latest preprint version

Failure Of Gallium-68 Citrate Scan To Detect Large, Enhancing Central Nervous System Tuberculomas: A Cautionary Tale

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Abstract

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Background

Case Presentation

Discussion and Conclusions

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