A 52-year-old man presented with a 3-week history of progressive right-sided numbness. Numbness began in his right hand and foot, ascending over 1–2 weeks to involve the entire right side (face, arm, chest and leg). He also reported a 1-day history of bilateral blurred vision in his right hemifields. His past medical history, medications and family history were non-contributory. He worked at a car wash, drank alcohol socially and denied smoking or other substance use.

Neurological examination was notable for a subtle downward drift of the right arm without pronation, decreased pinprick sensation over the right hemibody and impaired vibration sensation up to the right medial malleolus. Reflexes were symmetrical, with no Babinski sign. Coordination testing showed ataxia on right finger-to-nose.

The patient later admitted to noticing a large, painless, left testicular mass 1–2 months prior to his neurological presentation. Urology consultation confirmed a severely enlarged, firm, non-tender left testicle, with a thickened spermatic cord. Scrotal ultrasound revealed a heterogeneous mass (10.6 × 8.4 × 7.7 cm), replacing the left testis and involving the epididymal head, consistent with a testicular neoplasm.

Initial computed tomography (CT) head and neck angiogram showed a parenchymal lucency in the left posterior limb of the internal capsule, without hemorrhage or enhancement. Magnetic resonance imaging (MRI) of the spine showed possible punctate enhancement at C3–4 and C6–7, deemed artifactual. CT chest, abdomen and pelvis revealed the testicular mass and large para-aortic and left retrocrural lymph nodes, consistent with metastatic disease. Serum tumor markers showed elevated lactate dehydrogenase (606 U/L) and β-subunit of human chorionic gonadotropin (99 IU/L), with normal alpha-fetoprotein (< 2.7 ug/L).

His initial MRI head scan (Figure 1) showed a 3.0 × 4.1 × 3.2 cm lesion centered in the left posterior limb of the internal capsule, extending to the corona radiata, with mild mass effect, T1 hypointense, T2/fluid attenuated inversion recovery hyperintense, with peripheral enhancement of variable thickness and trace restricted diffusion at the margin.

Figure 1. MRI findings at admission (A–D) and lesion evolution over time on T1 with gadolinium (E–H). (A) T1 + Gadolinium: peripheral enhancement. (B) T2: lesion hyperintensity. (C) Diffusion-weighted imaging: restricted diffusion peripherally. (D) Apparent diffusion coefficient map: corresponding low signal peripherally. (E) Admission. (F) 1 month post-admission (clinical nadir). (G) 2 months post-admission (after immunotherapy). (H) 6 months post-admission (outpatient follow-up).

The patient underwent a radical left orchiectomy, and pathology confirmed a seminoma. He then started PEB (cisplatin, etoposide, bleomycin) chemotherapy. Serial MRI head scans tracked the brain lesion arising from the periventricular white matter (Figure 1), initially thought to be a metastatic lesion. Three weeks after his first scan, a repeat scan showed a stable lesion size, with interval improvement in restricted diffusion and peripheral enhancement. However, over the next month, he became progressively hemiplegic, with only flickers of movement (Medical Research Council muscle strength 0–1). His visual disturbances also progressed, and neuro-ophthalmological assessment showed a right homonymous hemianopia.

Given the clinical worsening, the differential diagnosis was expanded to include an inflammatory process. Lumbar puncture revealed elevated cerebrospinal fluid (CSF) protein (464 mg/dL) with zero white blood cells, negative cytology and no oligoclonal bands. This was followed by serum and CSF antibody testing at London Health Sciences Centre, negative for intracellular (anti-amphiphysin, anti-CV2, anti-GAD65, anti-Hu, anti-Ma2, anti-recoverin, anti-Ri, anti-SOX1, anti-titin, anti-Yo and anti-Zic4) and cell surface (anti-myelin oligodendrocyte glycoprotein (MOG) [serum only], anti-aquaporin-4 (AQP4) [serum only], anti-AMPAR, anti-CASPR2, anti-dipeptidyl-peptidase-like protein 6 (DPPX), anti—gamma-aminobutyric acid (GABA)-B, anti-LGI1, anti-NMDAR and anti-Tr) antigens as demonstrated by immunoblot or cell-based assays. Screening by tissue indirect immunofluorescence assay (TIIF) was also negative in serum and CSF for anti—glial fibrillary acid protein (GFAP), anti—GABA(A)R, anti-mGluR1, anti-mGluR5, anti-NIF, anti-neurochondrin, anti-ANNA-3, anti-MAP1B (PCA-2), anti-AP3B2, anti-PDE10A, anti-KLHL11, anti-ITPR1 and anti-GRAF.

After review by neuro-oncology and the tumor board, paraneoplastic tumefactive demyelination (TD) was favored as the most likely diagnosis, supported by the neuroimaging findings. Brain biopsy was considered, but ultimately deferred, as clinical and imaging evolution were felt to be consistent with TD. The patient received intravenous methylprednisolone (IVMP) 1 g for 5 days, followed by intravenous immunoglobulin (IVIG) 2 g/kg over 5 days. Following immunotherapy, his neurological symptoms stabilized and slightly improved, with MRI scans showing progressive improvement in the peripheral enhancement, diffusion restriction and overall size of the lesion (Figure 1).

He was discharged to an inpatient rehabilitation hospital 3 months after his initial presentation. At his neuro-oncology follow-up, 6 months after onset, he had made significant motor recovery (strength 4 + /5 in a pyramidal distribution) but required support for walking and assistance with bathing. His follow-up MRI scan showed mild volume loss in the region of the lesion, with Wallerian degeneration involving the left cerebral peduncle and pons.

Paraneoplastic TD associated with testicular seminoma is a rare but recognized entity. It has also been reported in association with ovarian and thyroid malignancies. ^{Reference Jurkiewicz, Kotulska, Nowak, Malczyk, Borkowska and Bilska1,Reference Panagiotis, Hakim and Lidia2} A case series by Shiraishi et al. details six pathologically confirmed cases, and one additional case, all associated with seminoma. ^{Reference Shiraishi, Umemura, Nakayama, Yamada, Shijo and Hashimoto3} Consistent with this series, our patient was a middle-aged male whose neurological presentation coincided with the discovery of seminoma. The brain lesion was large, located deep within white matter structures and evolved over time with imaging characteristics typical of TD. Antibodies were negative in our patient, as in most cases in the Shiraishi series, although one case was positive for anti-amphiphysin antibodies. A recent publication reports a case with positive anti-LUZP4 antibodies. ^{Reference Little, Shipley, Rock, Berger and Xu4} Antibody negative cases may reflect either the presence of undiscovered antibodies or humoral-independent, often T cell–driven mechanisms of immune pathogenesis.

A major diagnostic challenge in such patients is differentiating TD from metastatic disease. Neuroimaging features are critical. While TD lesions are typically >2 cm, T2/FLAIR hyperintense and T1 hypointense, their enhancement patterns, edema and mass effect can vary. Key features favoring TD over malignancy include open-ring enhancement, a T2-hypointense rim, milder mass effect and edema, and evolving high apparent diffusion coefficient centrally with restricted diffusion peripherally. Additional modalities such as magnetic resondance spectroscopy and perfusion may also be used to further distinguish the etiology. ^{Reference Nakayama, Naganawa and Ouyang5,Reference Suh, Kim, Jung, Choi and Kim6}

Neuroimaging in our patient revealed specific lesion characteristics: deep white matter involvement, T2/FLAIR hyperintensity, initial peripheral enhancement, and improving restricted diffusion (Figure 1). These findings pointed toward paraneoplastic TD. His positive and sustained response immunotherapy and lack of recrudescence several months later despite the absence of maintenance immunosuppression further supported this diagnosis.

Management involves treating the underlying malignancy and the demyelinating event. In the literature, high-dose IVMP is the first-line treatment for paraneoplastic TD. For steroid-refractory cases, IVIG or plasma exchange (PLEX) was used as second-line therapy. ^{Reference Algahtani, Shirah and Alassiri7,Reference Hardy and Chataway8} Our patient showed improvement after IVMP and IVIG, with sustained functional gains supporting that a steroid taper may not be necessary after tumor-directed therapy. Shiraishi’s case required IVIG after steroids failed to produce significant improvement. In their case series, prognosis was deemed “poor” in one patient, “partial” in four and “good” in two. ^{Reference Shiraishi, Umemura, Nakayama, Yamada, Shijo and Hashimoto3} Our patient’s recovery was significant, from hemiplegia to 4+ on right hip flexion and knee flexion at his latest follow-up, a year after onset.

This case illustrates paraneoplastic TD, a rare manifestation of testicular seminoma that can be challenging to differentiate from metastatic disease. Neuroimaging is crucial for accurate diagnosis, potentially avoiding the need for brain biopsy. Management requires treatment of the underlying seminoma, alongside immunotherapy for the demyelinating event.