Here we present a case report of cranial nerve (CN) V (trigeminal nerve) involvement in multiple sclerosis (MS) at initial presentation. A 53-year-old African American male who initially sought medical assistance due to episodes of intermittent left facial pain. The discomfort, characterized by a burning, throbbing sensation in the cheek that occasionally spread to the forehead and neck, prevented him from adopting a flat sleeping position. His painful episodes, recurring up to 10 times daily, would typically last between 30 and 45 seconds. There was no history of facial trauma, and his initial physical examination and blood work were negative for any significant abnormality. Given symptoms localized to the trigeminal nerve distribution, trigeminal neuralgia (TN) was the primary concern. Subsequent magnetic resonance imaging (MRI) and a cerebrospinal fluid (CSF) analysis revealed abnormalities confirming multiple sclerosis (MS). No external compression to the left-sided facial or trigeminal nerve or vascular abnormality such as vascular loops involving trigeminal nerve was identified on contrast-enhanced MRI brain.

Magnetic resonance imaging demonstrated several T2/fluid attenuated inversion recovery sequence (FLAIR) hyperintense supra and infratentorial demyelinating plaques in bilateral periventricular and subcortical white matter, callososeptal interface (Figure 1A and Figure 1B), and cervicothoracic spinal cord (not shown). None of these lesions demonstrated abnormal enhancement. However, abnormal enhancement and restricted diffusion was noted at the root entry zone (REZ) and cisternal segment of trigeminal nerve extending to the Meckel’s cave (Gasserian ganglion) (Figure 2A and Figure 2B). These findings were consistent with active inflammation of the left trigeminal nerve, presumed secondary to MS.

The patient’s therapeutic regimen began with Avonex (interferon beta-1a), transitioning to Gilenya (sphingosine 1-phosphate receptor modulator), and finally to Aubagio (Teriflunomide, a pyrimidine synthesis inhibitor). Unfortunately, persistent facial pain proved resistant to previous treatments, which included intravenous (IV) methylprednisolone, Lyrica (Pregabalin), Gabapentin, Amitriptyline, and Vimpat (Lacosamide). Carbamazepine demonstrated efficacy but was discontinued due to side effects like skin rashes and fever. Nine years into his disease, the patient underwent CyberKnife treatment for left-sided TN, resulting in a marked improvement in his facial pain and insomnia.

Following several years after the initial diagnosis, the patient experienced various MS-related symptoms in a relapsing and remitting pattern. These symptoms included left shoulder pain, gait imbalance, internuclear ophthalmoplegia, and bladder spasticity typical for MS flare and remittance. Despite the variety of symptoms, MRI scans demonstrated stable persistent enhancement of left trigeminal nerve and stable burden of demyelinating plaques.

In MS, initial presentation, severity, and progression of disease can vary among individuals. Magnetic resonance imaging (MRI) is the primary imaging modality used to evaluate MS. Isolated CN involvement is a less common phenomenon and reported in 10.4% of MS patients within a 5-year period, with 7.3% of these patients presenting this involvement as their initial symptom [1],[2]. However, it is important to note that not all individuals with MS experience TN. The prevalence of TN in MS ranges from 1.1% to 4.5% [1],[2]. Signal abnormality in trigeminal nerve has been reported to 3–6% of patients [3],[4]. Involvement of intrapontine fasciculi, principal, sensory spinal, and motor nuclei, and the trigeminal nerve itself has been reported [5].

Here, we presented a care report of trigeminal nerve involvement as an initial presentation of MS. Radiologists must carefully analyze brain MRI scans to identify signal changes in areas associated with CNs to rule out involvement with MS [1],[6]. Dedicated imaging including axial T2, FLAIR, and contrast-enhanced T1 sequences for MS evaluation and dual excitation acquisitions, such as constructive interference of steady state (CISS) and T2-weighted turbo-spin-echo techniques, such as sampling perfection with application optimized contrasts (SPACE) [4] should be performed to visualize specific CNs, such as CN II, V, VII, and VIII. Radiologists must also consider and differentiate MS from other conditions that may mimic CN involvement, such as tumors, infections, or other inflammatory conditions [6]. In such difficult cases with atypical clinical and radiological presentation diagnosis of MS is uncertain, McDonald criteria serve as valuable tool by providing standardize framework for evaluating clinical, radiological, and laboratory evidence.

Trigeminal nerve involvement is rare but potential initial presentation in MS. Therefore, patients presenting with isolated CN lesions should be thoroughly evaluated for early detection, effective treatment, and improved prognosis of MS. Radiologists must work closely with neurologists to correlate imaging findings with the clinical presentation to ensures accurate interpretation and assessment of CN involvement in the context of MS.