Autoimmune Encephalitis Pattern on PET-MRI in a Patient with Amyotrophic Lateral Sclerosis

Introduction

Amyotrophic lateral sclerosis (ALS) is an idiopathic, progressive, fatal primary motor neuron disorder. As per current evidence the etiology of ALS is multifactorial and potentially includes a range of genetic and environmental factors such as oxidative stresses, current/prior neuroinfection/inflammation, glutamate toxicity, mitochondrial dysfunction, and malignancy. Because the natural course of ALS is generally irreversible, early diagnosis, and treatment assumes great importance, more so when it can be attributed to a potentially treatable etiology. Fluorodeoxyglucose positron emission tomography-magnetic resonance imaging (FDG PET-MRI) has proven to be valuable in detecting patterns of autoimmune encephalitis, which are not usually evident in conventional MRI. We report a unique autoimmune encephalitis pattern on imaging (MR-PET) in a patient with ALS which has not been described before.

Case Report

A 55-year-old woman presented with gradually progressive quadriparesis from 2 years. She had a positive history of fasciculations and muscle atrophy of arms. There was no history of autonomic symptoms or cognition or behavioral/psychiatric abnormalities. Neurological examination showed both upper and lower motor neuron signs. Needle electromyography (EMG) showed a chronic neurogenic pattern with re-innervation signifying anterior horn cell loss, following which a diagnosis of ALS was made.

Considering the possibility of a paraneoplastic etiology, the patient was referred for ¹⁸F-FDG whole-body PET-MRI. Whole body images (skull top to mid-thigh) in all five-bed positions were acquired followed by dedicated brain MRI in 3D mode 60 min after intravenous injection of 8.97 mCi of ¹⁸F-FDG on a simultaneous Siemens mMR Biograph scanner. The MRI brain showed features of ALS, i.e., motor cortex mineralization while the whole-body scan demonstrated diffuse muscle atrophy [Figure 1]. PET showed bi-frontal FDG hypermetabolism [Figure 2] with occipital-temporal hypometabolism [Figure 3], suggesting an autoimmune pattern. A serum autoimmune antibody panel was not done as the patient defaulted.

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Figure 1 Coronal whole-body T1 magnetic resonance image showing fatty infiltration and atrophy of shoulder, pelvic girdle muscles, upper thigh, and para spinal muscles; signifying diffuse muscle atrophy

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Figure 2 Z score values for areas with significant hypermetabolism (frontal)

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Figure 3 Z score values for areas with significant hypometabolism (parieto-occipital)

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Discussion

Charcot coined the term ALS from its pathology; amyotrophy (muscle loss) and lateral sclerosis (involvement of the lateral corticospinal tracts). ALS is a progressive motor neuron disorder characterized by loss of motor function without sensory loss. The incidence is estimated at approximately 1.4/100,000 people with higher rates of affection of individuals between the ages of 39 and 80 years and with a male preponderance ratio of 1.7:1.[1] Despite being a rare disease, the cumulative lifetime risk of ALS ranges from 1 in 300 to 1 in 400.[2] Few patients also have frontotemporal dementia, with impairment of executive function, thus contesting the historical consensus that ALS is a pure motor disorder.[3]

It is diagnosed clinically and also utilizes the aid of adjunctive tests like EMG. Radiological (MRI) features include cerebral atrophy, mineralization of motor cortex on T2* images [Figure 4], and T2W hyper-intense signal along the corticospinal tracts. Molecular (PET) imaging demonstrates hypometabolism in the motor cortex and frontotemporal regions.[4]

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Figure 4 Axial susceptibility weighted imaging MR image shows mineralization of motor cortex as evidenced by hypointensity along the central sulcus

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Autoimmune encephalitis is an inflammatory disorder of the brain having a variable spectrum of clinical presentations, ranging from mild cognitive impairment to more severe forms of encephalopathy and refractory seizures with neurologic dysfunction, and is frequently a challenging diagnosis. It is usually attributed to the presence of antibodies against intracellular antigens, certain synaptic/ion channel receptors, or a few cell-surface proteins.[5] Conventional brain MRIs are usually normal in suspected autoimmune encephalitis and pathological FDG hypo/hypermetabolism or a combination of both with a specific gradient (anteroposterior/superoinferior) [Figure 5] can aid in the diagnosis of AE as well as necessitate further workup for the offending antibody/antigen.[6] Few studies found FDG-PET imaging to be more sensitive than MRI in detecting increased FDG metabolism in otherwise normal-appearing parenchyma, obtaining a good correlation between these specific FDG-PET patterns and clinical presentation/severity.[78]

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Figure 5 Axial positron emission tomography image of brain showing bifrontal hyper metabolism with occipito-temporal hypometabolism

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Autoimmunity and neuroinflammation have been intricately associated with the etiopathogenesis of ALS in few studies as evidenced by elevated circulating CD+ 4 T lymphocytes, chemo/cytokines, and abnormalities of complement proteins.[910] Moreover, patients with autoimmune disorders have been reported to be at increased risk of developing ALS which could suggest a shared genetic architecture between these two conditions.[11]

FDG PET-MR imaging findings depicting an obvious autoimmune pattern have not been described previously in an ALS patient. The imaging findings described above can ascribe autoimmunity as one of several etiologies of ALS. The current case is unique for the reasons stated below.

First, there is sparse literature exploring the metabolic/molecular neuroimaging findings in ALS, which could aid in determining if there is a causal association between ALS and autoimmune disorders thereby establishing a potentially treatable etiology of ALS to modify certain prevention/treatment strategies.[12]

Second, studies can be done on whether a co-existing autoimmune encephalitic pattern on imaging can influence the natural history of ALS/course of treatment.

Third, it raises the question of whether FDG-PET imaging can be routinely done in patients of ALS with cognitive disturbances to aid in detecting/ruling out potential auto-immune causes of ALS, be it specific antibody-related/seronegative variants. Utilizing novel imaging techniques such as PET-MR and whole-body imaging might reveal a higher incidence of potentially treatable varieties of ALS than hitherto suspected.

In conclusion, we have described a rare occurrence of autoimmune encephalitic pattern in a patient with ALS. Characteristic findings of each entity were demonstrated on whole-body MR-PET scan. It is not definitely known whether the association between autoimmunity and motor neuron disease is causative or not. Further studies exploring the possible causative role of autoimmunity and inflammation in motor neuron disease can be conducted.