IgG4-Related Hypertrophic Pachymeningitis at the Falx Cerebrii with Brain Parenchymal Invasion: A Case Report

doi:10.1016/j.wneu.2015.03.035

World Neurosurgery

Volume 84, Issue 2, August 2015, Pages 591.e7-591.e10

https://doi.org/10.1016/j.wneu.2015.03.035 Get rights and content

Background

Hypertrophic pachymeningitis has been described as a manifestation of a number of conditions, like infection and neoplasms such as dural carcinomatosis or lymphomas. IgG4-related hypertrophic pachymeningitis is a new entity identified during the past decade and most reports described pachymeningeal involvement only.

Case Description

We present a 58-year-old woman with isolated IgG4 hypertrophic pachymeningitis at the falx cerebrii that exhibited cerebral parenchymal invasion. She initially presented with left lower limb weakness. Magnetic resonance imaging of brain showed a contrast enhancing lesion located at the falx and that eroded into the right frontal lobe. Subsequent excisional biopsy confirmed the lesion with brain parenchyma invasion. The pathologic diagnosis was IgG4-related disease. She had no evidence of extracranial involvement.

Conclusions

Overall, this is an uncommon condition that may exhibit parenchymal invasion. Surgical biopsy would serve to establish a definitive diagnosis, and prompt comprehensive management of what is essentially a systemic and treatable condition.

Introduction

Abnormal thickening of dura is a common radiologic finding frequently seen in conditions like meningioma, dural carcinomatosis, lymphoma, intracranial hypotension, and tuberculosis. Other rare causes included systematic autoimmune diseases, fungal infection, cysticerosis, syphilis, and idiopathic hypertrophic pachymeningitis. As its name implies, idiopathic hypertrophic pachymeningitis is diagnosed when there is no other identifiable cause, and histologically the dura mater has nonspecific fibrosing inflammatory changes. IgG4-related disease was first described in patients with sclerosing pancreatitis and thereafter, it was found to be responsible for many previously unexplained inflammations in other organs like lung and kidney 2, 3. With the increase in awareness of IgG4-related disease, IgG4-related hypertrophic pachymeningitis was first described in 2009 (1). It is a relatively new entity under the category of hypertrophic pachymeningitis and is a differential diagnosis for dura thickening. The hallmark of the disease is the presence of sclerosing fibrosis with lymphoplamocytic infiltrate that consists of an increased number of IgG4-positive plasma cell. Most previous reports on IgG4-related hypertrophic pachymeningitis described pachymeningeal involvement only without brain parenchyma invasion. Here, we present a patient with isolated IgG4 hypertrophic pachymeningitis at the falx cerebrii that exhibited cerebral parenchymal invasion.

Section snippets

History and Physical Examination

Our patient was a 58-year-old woman who had a history of appendicectomy more than 10 years ago. She presented with 1-week's history of left lower limb weakness. Otherwise, she had no headache, vomiting, seizure, or other constitutional symptoms. On physical examination, she was fully alert with no cranial nerves deficits. The motor power of the left lower limb was grade 3 out of 5 (Medical Research Council grading); other limbs were normal. There was no enlarged parotid gland, palpable cervical

Discussion

IgG4-related disease was first identified as a cause of autoimmune sclerosing pancreatitis 3, 13. It was not until the past decade that extrapancreatic involvements of the salivary gland, biliary system, and skin were recognized. IgG4-related hypertrophic pachymeningitis is rare. Lu et al. (10) reviewed 33 cases reported since 2009. These included extensive involvement of the venous sinuses, convexity, falx cerebrii, and the skull base. The radiologic features commonly resembled those of

Conclusions

IgG4-related hypertrophic pachymeningitis is an uncommon condition that may exhibit parenchymal invasion and cause focal neurological deficit. It can closely resemble other meningeal lesions. An initial therapeutic trial using steroids may improve symptoms, but unlike the situation with lymphoma, radiologic resolution may not occur. Surgical biopsy would serve to establish a definitive diagnosis and prompt the comprehensive management of what is essentially a treatable systemic condition.

References (13)

V. Deshpande et al.
Consensus statement on the pathology of IgG4-related disease
Mod Pathol
(2012)
H.E. Moss et al.
IgG4-related inflammatory pseudotumor of the central nervous system responsive to mycophenolate mkofetil
J Neurol Sci
(2012)
S.K. Chan et al.
IgG4-related sclerosing pachymeningitis: a previously unrecognized form of central nervous system involvement in IgG-4 related sclerosing disease
Am J Surg Pathol
(2009)
H. Hamano et al.
High serum IgG4 concentrations in patients with sclerosing pancreatitis
N Engl J Med
(2001)
J.W. Hyun et al.
Steroid-resistant relapsing IgG4-related pachymeningitis treated with methotrexate
JAMA Neurol
(2014)
A. Iguchi et al.
A case of MPO- and PR3-ANCA-positive hypertrophic cranial pachymeningitis with elevated serum IgG4
Mod Rheumatol
(2013)

There are more references available in the full text version of this article.

Cited by (24)

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case
2021, Clinical Neurology and Neurosurgery
Citation Excerpt :
Rituximab is a monoclonal antibody against CD20 antigen on plasma cells that may act therapeutically in patients refractory to steroids. While rituximab is less toxic than immune-suppressants, it is more expensive [1]. A prospective pilot investigation of 30 IgG4-related disease patients revealed a response rate of 97 % to rituximab treatment [37].
Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients’ serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community.
MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder.
MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment.
IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.
Inflammatory Demyelinating Pseudotumor With Liver Dysfunction: IgG4 Related Disease With Primary Biliary Cholangitis
2020, American Journal of the Medical Sciences
Citation Excerpt :
If necessary, surgical operation should be performed to improve condition or obtain pathological specimens for diagnosis. Although several cases of IgG4-RD involving brain parenchyma have been reported,22-24 only 1 case reported sufficient evidence of brain parenchyma involvement. This is the first report where lesions in the brain parenchyma were attributed to IgG4-RD while liver dysfunction was caused by PBC, which were all confirmed by pathology.
Immunoglobulin G4 related disease (IgG4-RD) is a recently recognized immune-mediated disease which is far from understanding. A case of inflammatory demyelinating pseudotumor had been confirmed as IgG4-RD according to pathology features and clinical context. Combined with liver dysfunction, IgG4 related sclerotic cholangitis was suspected. However, primary biliary cholangitis was finally diagnosed by immune marks and histopathological findings. This is the first report in which mass lesions in the brain parenchyma were caused by IgG4-RD while liver dysfunction was due to primary biliary cholangitis. The clinical features of IgG4-RD are miscellaneous, and the accumulation of case reports might enrich clinicians experience and broaden their horizons about this condition.
Clinical presentation, treatment and outcome of IgG4-related pachymeningitis: From a national case registry and literature review
2019, Seminars in Arthritis and Rheumatism
Pachymeningitis is rare, either idiopathic or secondary to inflammatory disorders, after tumoral, surgical or infectious causes have been excluded. The fibroinflammatory IgG4-related disease is one of the etiologies of pachymeningitis with only few cases reported yet. From a single referral regional center, we evaluated the frequency of IgG4-related disease as the cause of inflammatory pachymeningitis in 10% of cases. From a National case registry of IgG4-related disease the pachymeningitis frequency was 4.1%. We report eight new cases with cranial, spinal or both involvements and a literature review of 46 pathological proven cases. We observed that IgG4-related pachymeningitis is in most cases not associated to extra-neurological manifestations of the disease. Only 27% of spinal and 40% of cranial IgG4-related pachymeningitis are associated with other disease localizations. First line treatment strategies included surgery and steroids. The use of immunosuppressants or rituximab was necessary in 18% of spinal and 54% of cranial localizations. Some patients remained with sequellae and clinical and/or radiological improvement can be difficult to obtain.
Clivus Inflammatory Pseudotumor Associated with Immunoglobulin G4-Related Disease
2018, World Neurosurgery
Immunoglobulin G4 (IgG4)-related disease is a more recently recognized syndrome. It is characterized by increasing IgG4-positive plasma cells and lymphocyte infiltration. Reports of intracranial pseudotumors associated with IgG4-related disease are very rare. We report a rare case of clivus pseudotumor associated with IgG4-related disease mimicking meningioma.
A 50-year-old man presented with abducens paralysis of the right eye. Brain magnetic resonance imaging revealed a uniformly enhanced mass located in the right upper clivus area, and meningioma was highly suspected. The tumor was totally resected via a retrosigmoid approach craniotomy, which achieved sufficient decompression of the right abducens nerve. Postoperative pathology revealed IgG4-related disease with IgG4 strongly positive on immunohistochemical staining. The patient had no history of autoimmune disease. Postoperative laboratory data revealed no elevation of either IgG (6.94 g/L) or IgG4 (0.131 g/L). Follow-up contrast MRI showed the lesion had disappeared.
Although several cases of intrasellar hypophysitis have been reported, reports of intracranial pseudotumors associated with IgG4-related disease are rare. Special attention is required when the differential diagnosis includes meningioma. Preoperative diagnosis is very important because inflammatory pseudotumors associated with IgG4-related disease could be treated with steroid therapy, avoiding surgery.
IgG4-related disease of the central and peripheral nervous systems
2018, The Lancet Neurology
IgG4-related disease can involve nearly any organ system, including the central and peripheral nervous systems. The pathology findings are consistent from organ to organ, but careful clinicopathological correlation is necessary to establish the diagnosis. Many non-neurological and neurological inflammatory conditions, previously regarded as idiopathic in nature, are now recognised to fall within the spectrum of IgG4-related disease. The condition is highly treatable, but probably remains substantially under-recognised. In this Review, we offer an important and timely update on the current and emerging aspects of this neurological disease. Following a short overview of IgG4-related disease, we describe the current understanding of neurological findings, pathophysiology, approaches to diagnosis, and treatment of IgG4-related disease affecting the central and peripheral nervous systems.
Neurologic Features of Immunoglobulin G4–Related Disease
2017, Rheumatic Disease Clinics of North America
Citation Excerpt :
The substance of the brain and the spinal cord are rarely involved by IgG4-RD. The authors are aware of only 1 case with satisfactory evidence of brain parenchyma involvement.40 Otherwise, there are 2 reports of IgG4-related pachymeningitis in which the inflammation extends to involve the underlying brain parenchyma.16,41 In those 2 cases, although the substance of the brain itself was not biopsied, the proximity of the parenchymal lesions and their concomitant resolution with their associated pachymeningitis after glucocorticoid therapy supports the notion of IgG4-RD pathologic complications.

View all citing articles on Scopus

: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

View full text

Case ReportIgG4-Related Hypertrophic Pachymeningitis at the Falx Cerebrii with Brain Parenchymal Invasion: A Case Report

Background

Case Description

Conclusions

Introduction

Section snippets

History and Physical Examination

Discussion

Conclusions

Mod Pathol

J Neurol Sci

IgG4-related sclerosing pachymeningitis: a previously unrecognized form of central nervous system involvement in IgG-4 related sclerosing disease

Am J Surg Pathol

High serum IgG4 concentrations in patients with sclerosing pancreatitis

N Engl J Med

Steroid-resistant relapsing IgG4-related pachymeningitis treated with methotrexate

JAMA Neurol

A case of MPO- and PR3-ANCA-positive hypertrophic cranial pachymeningitis with elevated serum IgG4

Mod Rheumatol

Case Report
IgG4-Related Hypertrophic Pachymeningitis at the Falx Cerebrii with Brain Parenchymal Invasion: A Case Report