Striking Bilateral Cerebellar Hypermetabolism on ¹⁸F FDG-PET in a Patient of Sudden Onset Gait Ataxia with Absence of Paraneoplastic Antibody and Other Localizing Imaging Indicator

Introduction

The pattern of ¹⁸F-Fluorodeoxyglucose (¹⁸F FDG) uptake is rather characteristic in certain neurodegenerative disorders and can pick up onset of disease at times ahead of anatomic changes on computed tomography (CT) and magnetic resonance imaging (MRI), for example, in dementia-like disorders and provides a better diagnostic accuracy and better triage of patient care.[1] A standard protocol is to get an MRI done first followed by ¹⁸F FDG-positron emission tomography-CT (¹⁸F FDG-PET/CT) to increase both sensitivity and specificity.[2] In this report, we present a patient who had a history of giddiness and gait ataxia with negative MRI who was found out to have strikingly increased bilateral cerebellar hypermetabolism in ¹⁸F FDG-PET.

Case Report

A 69-year-old gentleman, known hypertensive and no addiction or seizure history presented with complains of giddiness, gait ataxia, vomiting, and slurring of speech. Clinically, he was oriented to time, place and person. He had bilateral horizontal gaze nystagmus, scanning speech, and positive finger-nose and heel-to-shin test. Routine blood investigations were within normal limits and unremarkable brain MRI. With suspicion of paraneoplastic etiology, ¹⁸F FDG-PET/CT scan was considered which revealed striking hyper-metabolism in bilateral cerebellar hemispheres [Figure 1], and lesser but positive in pons, mid-brain and bilateral medial temporal cortices [Figure 2]. No abnormal focus of hypermetabolism was noted in the rest of the whole-body survey. Further assessment with statistical parametric mapping software, NeuroQ comparing with normal counterpart of same age and gender was done which showed hypermetabolism in bilateral cerebellar hemispheres (standard deviation SD: +25.59), Vermis (SD: +14.5), mid brain (SD: +12.14), pons (SD: +14.8), right posterior medial temporal cortex (SD: +9.6), left posterior medial temporal cortex (SD: +13.47), and left inferolateral posterior temporal cortex (SD: +6.7). No significant areas of hypometabolism were noted in the remainder [Figure 3]. Semi-quantitative SUV_max values showed significant hypermetabolism in cerebellum and aforementioned areas in comparison to cerebrum (SUV_max 36.8 in left cerebellum, SUV_max 14.1 in midbrain, SUV_max 13.1 in pons, and SUV_max 10.85 in left medial temporal cortex versus SUV_max 10 in left parietal cerebral cortex).

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Figure 1 Anteroposterior (a) and lateral view (b) of maximum intensity projection of ¹⁸F-Fluorodeoxyglucose positron emission tomography (¹⁸F FDG PET) showing striking hypermetabolism in the bilateral cerebellum and also in brainstem. Axial fusion view of ¹⁸F FDG-PET/computed tomography (c) showing similar finding of cerebellar hypermetabolism. Axial T1 (d) and T2 (e) weighted magnetic resonance imaging sequences show no significant anatomical abnormality except mega cisterna magna

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Figure 2 Axial view of fused ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F FDG-PET/CT), CT only and ¹⁸F FDG-PET respectively showing brain at various levels: (a) – mid brain (marked with blue arrow); (b) – bilateral medial temporal cortices (left medial temporal cortex marked with green arrow); and (c) – cerebellum (left cerebellum marked with red arrow) and pons (marked with yellow arrow)

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Figure 3 Statistical parametric mapping of hypermetabolic areas in brain with the help of NeuroQ software showing significant hypermetabolism in cerebellum, vermis, and pons

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The CT component of PET/CT showed no particular anatomical abnormality. Cerebrospinal fluid (CSF) routine assessment revealed elevated proteins (600.4 mg/dl). Normal pattern was noted in oligoclonal band, CSF and thus, ruled out multiple sclerosis. Heavy metal panel showed slightly raised selenium (260 µg/L), nickel (1.22 µg/L) and zinc (207.54 µg/L) which was managed medically. Vitamin B12 and folic acid levels were within normal limits. Paraneoplastic antibody panel (anti-Hu, anti-Yo, anti-Ri, NMDA, CASPR-2 etc) was negative.

The patient was then administered plasma exchange therapy (4 cycles) under the provisional diagnosis of autoimmune encephalitis. However, no significant improvement was noted. Further blood culture was considered to rule out systemic infection, which showed no growth of organism. Electroencephalogram revealed no epileptiform activity. Medical management was initiated with prednisolone 40 mg once-a-day which was gradually tapered to 5 mg once-a-day and then weaned off. The patient did not observe any significant response with the treatment and diagnosis is still yet unknown. At post-6 months of ¹⁸F FDG-PET, he expired out of respiratory illness (pneumonia).

Discussion

Cerebellar hypermetabolism is rather a rare clinical finding and has been associated with some diseases in the literature. Cerebellar hypermetabolism was associated with paraneoplastic syndrome secondary to a malignancy in some reports[3456789] also known as paraneoplastic cerebellar degeneration (PCD), which is a subset of broader entity of autoimmune encephalitis. The cases in abovementioned reports had normal MRI findings, cerebellar hypermetabolism (unilateral or bilateral) with positive cerebellar signs. These patients underwent further evaluation with autoimmune antibody panel which showed positive anti-Yo in 2 cases[34] which are more commonly associated with cerebellar demyelination.[10] Our patient was negative for autoimmune antibodies in paraneoplastic antibody panel (anti-Hu, anti-Yo, anti-Ri, NMDA, and CASPR-2) and did not show any abnormal focus in whole-body survey in ¹⁸F FDG-PET.

Another cause of cerebellar hypermetabolism that is mentioned in the literature is associated with neurodegenerative disorders. Nagasaka et al. demonstrated a case of Creutzfeldt-Jakob disease with hypermetabolism in right frontoparietal cortex (abnormal high intensity areas in the frontoparietal cortex on diffusion weighted MRI) and left cerebellum, reporting it as crossed cerebellar hypermetabolism.[11] Meadowcroft et al. demonstrate an increase in glucose utilization within the cerebellum, primary olfactory cortex, and the ventral striatum in Alzheimer’s disease.[12] Other causes of cerebellar hypermetabolism are primary cerebellar neoplasia or secondaries to cerebellum, meningeal carcinomatosis,[13] toxin induced, post vaccinations, and infections (viral and prion).[1415]

One case of neurosarcoidosis was reported with similar pattern of diffuse hypermetabolism in bilateral diffuse cerebellar hemispheres and no anatomical delineation on either MRI or CT, there were related lymphadenopathy which on further evaluation turned out to be sarcoidosis and responded to steroids.[16] There was no such finding in the whole-body survey of ¹⁸F FDG-PET in our case and patient was unresponsive to steroids as well.

Although a definitive diagnosis could not be established, the striking and isolated cerebellar hypermetabolism on ¹⁸F FDG-PET in the absence of MRI abnormalities or seropositive paraneoplastic markers represents a rare and diagnostically challenging presentation. Prior studies have described cerebellar hypermetabolism in association with PCD, autoimmune encephalitis, and neurodegenerative disorders, but often with positive serology or MRI correlation.[3451112]

Conclusion

We herein reported a unique case of classical cerebellar signs with predominant bilateral cerebellar hypermetabolism in ¹⁸F FDG-PET and no definite anatomical correlation. The case emphasizes the potential of FDG-PET to detect functional abnormalities in suspected neuroimmunological conditions when other modalities remain noncontributory.[12] Highlighting such atypical findings contributes to clinical awareness and may prompt comprehensive investigation in future patients with similar presentations.