IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition characterized by tumefactive lesions, lymphoplasmacytic infiltration, and storiform fibrosis. Although involvement of various organs, including the gastrointestinal tract, is well documented (1, 2), central nervous system (CNS) manifestations—primarily IgG4-related hypertrophic pachymeningitis (IgG4-RHP)—are rare. Notably, isolated CNS involvement is increasingly recognized, with approximately 30% to 50% of patients lacking systemic manifestations at diagnosis (3).

The clinical presentation varies according to the site of dural inflammation, most commonly manifesting as headaches, cranial nerve palsies, and visual disturbances (4). Diagnosis requires a multimodal approach that integrates elevated serum IgG4 levels, characteristic dural thickening on magnetic resonance imaging (MRI), and histopathological confirmation of IgG4-positive plasma cell infiltration with storiform fibrosis (5).

High-dose glucocorticoids remain the first-line therapy; however, relapse during tapering represents a significant clinical challenge. In refractory cases, B-cell depletion therapy has become the standard second-line option (6). More recently, the therapeutic landscape has expanded with the approval of the anti-CD19 antibody inebilizumab, offering a new targeted strategy for preventing disease flares (7).

In this report, we describe a complex case of IgG4-RHP presenting with visual impairment, marked dural thickening, and concomitant white matter lesions. A distinctive feature of this case was the transdiaphragmatic herniation of the rectus gyrus into the sella turcica—a rare neuroradiological finding that highlights the potential for severe mechanical complications in IgG4-RHP and underscores the importance of early diagnostic recognition and intervention.

A 54-year-old Japanese man presented with right-sided visual impairment and visual field loss. His medical history included hypertension, and he was a former smoker. Six months before presentation, he developed blurred vision in the right eye, which persisted despite treatment at a local clinic. Four months later, a gradual visual field defect appeared in the temporal region of the right eye.

On physical examination, the patient was alert and oriented. Aside from visual symptoms, no focal motor or sensory deficits or other cranial nerve abnormalities were identified. There was swelling of the right cervical lymph nodes, blindness in the upper quadrant of the right eye on the ear side, an enlarged scotoma in the left eye (Figure 1A), and markedly reduced visual acuity of 0.02 in the right eye.

Blood tests revealed elevated levels of C-reactive protein (2.5 mg/dL; reference range, <0.3 mg/dL), IgG (2068 mg/dL; reference range, 870–1700 mg/dL), and IgG4 (429 mg/dL; reference range, <135 mg/dL). Tumor markers, including carcinoembryonic antigen, carbohydrate antigen 19-9, prostate-specific antigen, and serum soluble interleukin-2 receptor, were all within normal limits. Serologic tests for collagen vascular diseases—such as anti-nuclear antibody, Sjögren’s syndrome antigen A/B antibodies, and proteinase 3-specific and myeloperoxidase-specific antineutrophil cytoplasmic antibodies—were also negative. The angiotensin-converting enzyme level was unremarkable, and no pituitary dysfunction was detected.

To screen for systemic IgG4-RD, non-contrast computed tomography (CT) of the chest including the neck and of the abdomen including the pelvis was performed. This revealed hilar lymphadenopathy (Figure 1B) but no other organ involvement, such as pancreatitis or retroperitoneal fibrosis. Head MRI showed widespread signal changes in the frontal white matter. Gadolinium-enhanced MRI demonstrated a subdural mass lesion extensively involving the bilateral frontotemporal regions. Bilateral compression was present, causing the rectus gyrus to be abnormally displaced downward with transdiaphragmatic herniation into the sella turcica (Figures 1C–E). Despite the bitemporal lesions, electroencephalography was not performed because the patient exhibited no clinical seizures. Lumbar puncture was not performed because of the risk of tonsillar herniation, and cerebrospinal fluid could not be obtained during biopsy because of severe adhesion between the subdural lesion and the cerebral cortices, with absence of visible subarachnoid spaces.

A biopsy was performed via a small frontal craniotomy. The lesion appeared whitish, continuous with the overlying dura mater, firmly adherent to the underlying cerebral cortices, elastic-hard in consistency, and relatively avascular. Microscopically, the resected specimens demonstrated markedly thickened dura mater with infiltration by inflammatory cells, approximately half of which stained positively for IgG4 (Figure 2).

The patient was diagnosed with IgG4-related hypertrophic pachymeningitis and treated with intravenous methylprednisolone (1000 mg for 3 days). Oral prednisolone was then initiated at 1 mg/kg (60 mg), tapered by 10 mg per week to 20 mg, and subsequently reduced by 5 mg per month.

Three months after treatment initiation (Day 103), the serum IgG4 level had decreased from 429 to 70.3 mg/dL, with an intermediate value of 166 mg/dL on Day 33 (Figure 3). The patient was receiving oral prednisolone at 14 mg/day, with a tapering target of 10 mg/day. Given the chronic nature of the disease, maintenance therapy with inebilizumab is under consideration for future management. Peripheral vision had also improved, although a scotoma remained in the right visual field, while the left-sided scotoma had diminished (Figure 1F). Follow-up chest CT demonstrated a marked reduction in the size of the previously noted hilar lymphadenopathy (Figure 1G). Cranial MRI showed regression of the frontal white matter lesions and thinning of the previously thickened dura mater on gadolinium-enhanced imaging. Although the dural thickening improved after 3 months (Figures 1H, I), follow-up cerebrospinal fluid sampling has not been performed to date because the herniation of the rectus gyrus into the sella turcica persisted.

According to the 2020 revised comprehensive diagnostic criteria for IgG4-RD (8), this case was definitively diagnosed on the basis of systemic involvement (cervical and hilar lymph node enlargement), dural thickening, marked elevation of serum IgG4, and biopsy findings demonstrating dural fibrosis with infiltration of IgG4-positive plasma cells. Although the patient presented primarily with neurological symptoms, the identification of hilar lymphadenopathy via systemic CT screening was instrumental in supporting the diagnosis of a multiorgan fibroinflammatory process. Notably, the marked regression of these lymph nodes following glucocorticoid therapy confirmed their involvement in the systemic pathology of IgG4-RD. This underscores the importance of comprehensive systemic screening because identification of subclinical organ involvement can provide critical diagnostic confirmation even in cases that initially appear to represent isolated CNS disease.

Ten cases of IgG4-RHP with significant white matter lesions have been reported to date, including the present case (Table 1) (9–17). As detailed in Table 1, therapeutic strategies in these cases largely depended on lesion morphology. Cases presenting with focal mass lesions were predominantly managed with surgical resection, often because of an initial suspicion of neoplasms such as meningioma; in these instances, additional steroid therapy was typically not required following successful excision. By contrast, patients with diffuse dural thickening, including the present case, were treated with high-dose glucocorticoids and consistently demonstrated a favorable response. This clinical course supports the hypothesis that the associated white matter lesions represented reversible vasogenic edema caused by impaired venous or lymphatic drainage due to dural inflammation and mechanical compression, rather than permanent ischemic injury (3). Whereas dural biopsy was essential for definitive histological diagnosis, therapeutic surgical resection of the white matter lesions was not indicated because these changes were secondary and reversible, responding appropriately to medical therapy.

Although B-cell depletion therapies such as rituximab or the recently approved inebilizumab were not used in the reviewed cases—likely because of adequate responses to first-line therapy or the timing of the reports—they are now strongly recommended for patients with refractory disease, with frequent relapses, or requiring steroid-sparing regimens to prevent long-term morbidity. The right-sided quadrant hemianopsia and the enlarged left-sided scotoma in this patient can be explained by compression of the optic chiasm. Consistent with prior reports, the patient responded well to steroid therapy, showing marked clinical and radiological improvement.

In addition, MRI demonstrated herniation of the rectus gyrus into the sella turcica without evidence of hypopituitarism. Although cases of rectus gyrus herniation have been described in association with empty sella following pituitary surgery (18, 19), no prior reports have documented transdiaphragmatic herniation caused by chronic downward displacement from dural thickening. Notably, although the dural mass decreased substantially after treatment, the herniated rectus gyrus remained displaced at the 3-month follow-up. This finding suggests that chronic mechanical deformation may result in persistent anatomical alterations even after the underlying inflammatory process has been controlled.

While glucocorticoids provided an effective initial response, intravenous methylprednisolone pulse therapy was selected for induction to rapidly alleviate the critical mass effect threatening visual function, in accordance with international consensus recommendations for organ-threatening IgG4-RD (6, 8). Nevertheless, the risk of relapse remains a major concern in the management of IgG4-RD. The recent approval of inebilizumab in Japan (2025) offers a new targeted strategy to maintain remission and reduce steroid dependency. Given the severity of the neurological manifestations and the structural changes observed in this case, long-term maintenance therapy with such B-cell–targeted agents may be considered to prevent disease flares and irreversible damage. This case therefore represents a rare presentation of IgG4-related hypertrophic pachymeningitis characterized by massive dural thickening, extensive white matter lesions, and rectus gyrus herniation. The combination of these findings—particularly chronic herniation into the sella turcica—has not been previously reported. Our observations underscore the clinical importance of recognizing such atypical manifestations and serve as a crucial reminder for neurologists to include IgG4-RD in the differential diagnosis of hypertrophic pachymeningitis, thus ensuring early intervention to prevent irreversible neurological sequelae.