IgG4-related Hypertrophic Pachymeningitis Research Articles

IgG4-related hypertrophic pachymeningitis with cerebral venous thrombosis.

IgG4-related hypertrophic pachymeningitis with cerebral venous thrombosis.

IgG4-related Hypertrophic Pachymeningitis with Serum ANCA Positivity.

IgG4-related Hypertrophic Pachymeningitis with Serum ANCA Positivity.

Immunoglobulin G4-Related Hypertrophic Pachymeningitis Presenting with Multiple Lower Cranial Nerve Palsies

Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ condition that infrequently exhibits neurological involvement. Here, we describe a case of IgG4-related hypertrophic pachymeningitis with multiple lower cranial nerve palsies. A 65-year-old man presented with a 5-month history of hoarseness and dysphagia. A neurologic examination revealed multiple lower cranial nerve palsies. Brain magnetic resonance imaging indicated diffuse dural involvement along the left tentorium and temporal fossa. Serum IgG and IgG4 levels were found to be elevated. Ethmoid polyp biopsy revealed chronic inflammation with moderate lymphoplasmacytic and some eosinophilic infiltration. Up to 60 IgG4-positive cells were observed per high-power field, and the measured IgG4/IgG ratio was approximately 10% to 20%. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography indicated abnormally high FDG uptake in the left posterior fossa, tentorium, and left temporal fossa, with additional involvement of the lung, iliac artery, and renal artery. Based on these findings, we diagnosed the patient with IgG4-related hypertrophic pachymeningitis and successfully treated the condition with steroids and rituximab. IgG4-RD should be differentiated from distinct conditions presenting with multiple cranial nerve palsies accompanied by pachymeningitis.

Les sous-classes d’IgG dans le LCR présentent-elles un réel intérêt ?

AbstractSerum total IgG measurement is a common lab act in medical biology. More specialized, serum IgG subclasses measurement plays a key role in IgG4-Re- lated Disease but is also useful for second-line diagnosis in humoral immune deficiencies. In the cerebrospinal fluid (CSF), an index is used as an indicator of the relative amount of CSF IgG compared to serum. Any increase in the index reflects IgG production in the central nervous system. Regarding IgG subclasses in the CSF, medical laboratories are now getting demands, actually to find out if there is any IgG4 subclass. These IgG4 in CSF could be associated with IgG4-related hypertrophic pachymeningitis but without appropriate studies corroborating this, their measurement should be done only when tissue biopsy cannot be performed. Quantitative measurement on serum is validated with nephelometry and turbidimetry assays. Each laboratory has to validate the assays on CSF before giving results. In this mini review, we present the indications of total IgG and IgG subclasses on serum as well as the benefit of IgG subclasses in CSF and the techniques available in a medical laboratory.

The Spectrum of Intracranial Hypertrophic Pachymeningitis at an Eastern Indian Tertiary Care Center.

Hypertrophic pachymeningitis (HP) is a treatable, rare inflammatory disease, either primary or secondary to systemic causes. To characterize the etiology, clinical manifestations, and treatment outcomes of HP patients and determine the factors influencing the radiological resolution of the pachymeningeal enhancement and recurrence of symptoms within the follow-up period. We collected data for this prospective observational study between March 1, 2021 and May 31, 2022, at the Bangur Institute of Neurosciences, Kolkata, and the patients were followed for a 6-month period. Demographic, clinical, laboratory, and treatment-related data were collected. A univariate logistic regression model was used for comparison between patients with and without radiological resolution of pachymeningitis and between patients with and without symptom recurrence. Among 44 patients, the male: female ratio was 1.2:1. The median age at disease onset was 35.5 (28.5-49.5) years. The etiologies were idiopathic (56.8%), tuberculosis (22.8%), immunoglobulin G subtype 4 (IgG4) disease (9.2%), other infections (6.8%), and neoplastic (4.4%). Headache was the most common presentation (95.4%), followed by cranial neuropathies (68.2%). Optic and oculomotor neuropathies were the most common. In terms of radiological features, 27.27, 29.54, and 43.18% of patients had diffuse, focal regular, and focal irregular enhancement, respectively. Temporal (50%), followed by cavernous sinus (38.63%) enhancement, was the most common. Recurrence occurred in 36 and 50% of idiopathic and IgG4-related HP cases, respectively. Mycophenolate mofetil was added to their steroid regimen with no further recurrences. The cohort had a marked absence of (antineutrophil cytoplasmic antibodies) ANCA-associated HP. The severity of clinical manifestations or distribution of pachymeningitis did not differ significantly among the etiological groups. The presence of idiopathic etiology and focal regular enhancement had a significantly higher chance of radiological resolution. The response to therapy was satisfactory. Recurrence was significantly related to shorter steroid courses (<median duration of 5.2 months).

IgG4-related hypertrophic pachymeningitis with tumor-like intracranial and intracerebral lesions

ObjectiveIgG4-related hypertrophic pachymeningitis is a rare fibroinflammatory disorder that may cause localized or diffused thickening of the dura mater. Misinterpretations of the clinical and imaging findings are common. Clinical manifestations depend on the location of the inflammatory lesion and on compression of neural structures leading to functional deficits. A dural biopsy is commonly needed for a definitive diagnosis. Immunomodulatory therapy is considered the therapy of choice.MethodsFour patients with IgG4-related hypertrophic pachymeningitis were identified over a 5-year period. Patient-related characteristics including age, preoperative workup, signs and symptoms of patients, and diagnostic procedures were evaluated. Furthermore, the surgical treatment and 5-year follow-up outcomes were analyzed.ResultsThere were two adults and two adolescents (mean age 32 years; range 15 to 67 years). Two patients were male, and two were female. No history of disease was known in any of the patients. Clinical symptoms were epilepsy (n = 2), ataxia and nausea (n = 1), and facial nerve palsy (n = 1). MR imaging studies showed contrast enhancing lesions in the temporal region in two patients, and in the cerebellar region in the other two patients. Subtotal resection was performed in two instances and a biopsy via a suboccipital retrosigmoid approach was obtained in the other two patients. Histochemical and immunohistochemical investigations revealed an IgG 4 disease in all of these patients. Immunomodulatorry therapy led to clinical stability during follow-up of 5 years in all four cases.ConclusionThe diagnosis of IgG4-related hypertrophic pachymeningitis is challenging, but is of great relevance as treatment differs significantly from other forms of pachymeningitis and a specific therapeutic approach may avoid long-term neurological complications. Our series contributes to a better clinical characterization of this rare disease.

Chiari decompression for syringomyelia in the setting of IgG4-related hypertrophic pachymeningitis: A case-based update

Hypertrophic pachymeningitis can lead to clinical brainstem and cervical spinal cord compression leading to neurologic deficits. IgG4-related hypertrophic pachymeningitis (IgG4-RHP) is one recently recognized etiology of previously idiopathic cases. A 34-year-old right-handed female presented with slowly progressive neurologic symptoms and worsening radiographic syringomyelia. She successfully underwent Chiari decompression and excision of her pachymeningitis with improvement in her radiographic findings. Extensive clinical workup has led to a diagnosis of IgG4-RHP and treatment with steroids. IgG4-RHP is a rare cause of spinal cord compression and on our review of the literature this is the first description of significant syringomyelia associated with this condition. This remains a challenging entity to treat and neurology and rheumatology referrals should be placed early to investigate IgG4-RHP as an etiology for idiopathic cases. Treatment of this disease is likely to evolve with further research.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases

BackgroundIgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.Case presentationTwo ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave’s disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.ConclusionsA high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

Hypertrophic pachymeningitis, IgG4-related disease: case report

ABSTRACT The IgG4-related disease (IgG4-RD) is a systemic disease recently characterized as an inflammatory condition generally related to the increase in serum IgG4 levels, a subclass of immunoglobulins (IgG) which corresponds to less than 6% of the total serum IgG, with singular histopathological features. The involvement of the central nervous system is rare and may be isolated or associated with other organs, mimicking tumors. Commonly, it involves the hypophysis, presenting hypophysitis as the main manifestation, but it can also affect the dura mater, presenting as IgG4-related hypertrophic pachymeningitis (IgG4-RHP). Neurological manifestations occur as a result of mass effect, typically due to vascular or nervous structures compression, resulting in functional deficits according to the anatomical site of the lesion. The main histopathological features are dense lymphoplasmacytic infiltrate, fibrosis arranged, at least focally, in a storiform pattern, and obliterative phlebitis, associated with increased numbers of IgG4+ plasma cells or an increased IgG4/IgG ratio in tissue. In this disease, the serum IgG4 levels are usually increased. The objective of this article is to report the case of a 37-year-old male patient who presented a pulsatile headache associated with diplopia and blurred vision. After radiological, histopathological and immunohistochemical studies, the diagnosis of IgG4-RHP was confirmed, besides presenting a literature review about IgG4-RD and IgG4-RHP.

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case

BackgroundDural 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. MethodsMRI (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. ResultsMRI 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. ConclusionsIHSP 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.

Imaging features, clinicopathological analysis and diagnostic strategy of IgG4-related hypertrophic pachymeningitis.

This study was conducted to summarize the clinical, magnetic resonance imaging (MRI) and pathological features of IgG4-realated hypertrophic pachymeningitis (IgG4-RHP) and its differential diagnosis from similar diseases. Data of IgG4-RHP patients admitted to Department of Neurology, Neurosurgery and Infection, the First Affiliated Hospital of Medical School of Zhejiang University from January 1, 2015 to July 31, 2019 were collected and their clinical symptoms, laboratory examinations, imaging and pathological features were investigated. At the same time, the clinicopathological and imaging findings of other dura thickening diseases diagnosed in our hospital were compared and analyzed. The clinical symptoms of 4 IgG4-RHP patients include chronic headache and cranial nerves injury, etc. Levels of serum IgG4 and cerebrospinal fluid (CSF) IgG4 increased in all patients. Focal enhancement of dura mater could be seen on plain and enhanced cranial MRI. Pathological results were consistent with IgG4-RHP symptoms. Among other diseases that cause dural thickening, the content of serum C-reactive protein in patients with Rosai-Dorfman disease declined. Patients with intracranial hypotension syndrome often have postural headache. Patients with tuberculous meningitis can have previous pulmonary tuberculosis. The diagnosis of patients with atypical meningioma depends on the results of operation and pathology. Patients with central nervous system leukemia can be diagnosed with reference to the results of laboratory results. The clinicopathological and imaging manifestations of IgG4-RHP are summarized in this study. Meanwhile, the clinical data of several other diseases with similar imaging characteristics are analyzed in order to clarify the diagnostic strategy of IgG4-RHP and provide help for the next treatment.

Hypertrophic Pachymeningitis in Chinese Patients: Presentation, Radiological Findings, and Clinical Course.

Background Hypertrophic pachymeningitis (HP) is generally regarded as a rare inflammatory disease, which results in a diffuse thickening of the dura mater. We retrospectively collected data from patients with HP. Methods A total of 16 patients with HP were included in our study. The clinical features, laboratory evaluation, imaging findings, treatment, and outcome were reviewed. Results Of the 16 cases, half were male, with a mean age of 52.6 ± 13.2 years. The mean duration from onset to diagnosis was 8.6 months. The most frequent presenting symptoms in HP cases were a recurrently chronic headache (81.3%) and multiple cranial nerve injury (50%). Antineutrophil cytoplasmic antibody- (ANCA-) related HP was found in 5 cases and IgG4-related HP in 1 case. The intracranial pressure was elevated in 4 cases. The cerebrospinal fluid (CSF) had lymphocytosis in 5 cases and increased protein in 12 cases. Immunoglobulins (IgG, IgA, and IgM) and protein showed linear relationships in the CSF. On magnetic resonance imaging (MRI), localized or diffuse dura maters were thickened in all cases. HP combined with subacute subdural hemorrhage or hypertrophic spinal pachymeningitis was also observed in individual cases. Biopsy of the dura mater in one case showed amounts of inflammatory cells infiltrating, with an increased percentage of IgG4-positive plasma cells. Of all cases referring to glucocorticoid treatment, the symptoms have improved significantly in 10 cases. In other 6 cases, mycophenolate mofetil or azathioprine was added. All patients showed clinical improvement at the follow-up visits. Conclusion The clinical characters of HP are chronic onset, recurrently chronic headache, and multiple cranial nerves paralysis. Inflammatory changes in CSF caused by intrathecal synthesis of immunoglobulin, characteristic dural enhancement on MRI, and pathologic biopsy are all helpful for diagnosis. The addition of immunosuppressant, especially mycophenolate mofetil, is a good choice for steroid-resistance HP.

Polycystic subdural hygroma associated with immunoglobulin G4-related intracranial hypertrophic pachymeningitis: a case report

BackgroundRecent studies have examined hypertrophic pachymeningitis as an IgG4-RD. However, there are no reports of immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis with polycystic subdural hygroma.Case presentationA 56-year-old man presented to the hospital with complaints of a persistent, pulsatile, occipital headache and general malaise. Magnetic resonance imaging of the brain revealed hypertrophic pachymeningitis with polycystic subdural hygroma and hematoma. Based on the dural biopsy findings and exclusion of other diseases, the patient was diagnosed with immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis. IgG4-related diseases may cause subdural hygroma more commonly than other diseases that cause hypertrophic pachymeningitis.ConclusionsThis is the first case report discussing polycystic subdural hygroma and hematoma with IgG4-related hypertrophic pachymeningitis.

Hypertrophic pachymeningitis an unusual manifestation of systemic lupus erythematosus: A case report

Hypertrophic pachymeningitis is a rare inflammatory disease of the dura matter characterised by localized or diffuse thickening of the dura mater with fibrosis. Hypertrophic pachymeningitis is often secondary to infections, carcinomatosis or inflammatory diseases. It may also be idiopathic. We report a case of pachymeningitis which was A 45-year-old female presented with left-extremity focal seizure. MRI revealed diffuse pachymeningeal thickening showing intense post contrast enhancement involving falx cerebri and along bilateral fronto-parietal convexities. These findings suggest either Neurosarcoidosis, Behcet’s disease, SLE,Idiopathic hypertrophic pachymeningitis or IgG4 related hypertrophic pachymeningitis.

Glossopharyngeal/vagus nerve disorder due to IgG4-related hypertrophic pachymeningitis.

Glossopharyngeal/vagus nerve disorder due to IgG4-related hypertrophic pachymeningitis.

IgG4-Related Hypertrophic Pachymeningitis Mimicking Cerebral Venous Thrombosis

Immunoglobulin G4-related hypertrophic pachymeningitis (IgG4-RHP) is an increasingly recognized manifestation of IgG4-related disease (IgG4-RD), which is a fibroinflammatory condition that can affect virtually any organ. The three hallmark histopathological features of IgG4-RD are lymphoplasmacytic infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. We report a case of biopsy-confirmed IgG4-RHP that was initially misdiagnosed as cerebral venous thrombosis. Key Words: IgG4-related hypertrophic pachymeningitis, Intracranial thrombosis, Histopathology

IgG4-Related Mastoiditis, Hypertrophic Pachymeningitis and Inflammatory Pseudotumor: A Case Report and Review of the Literature

IgG4-Related Mastoiditis, Hypertrophic Pachymeningitis and Inflammatory Pseudotumor: A Case Report and Review of the Literature

Author response: Teaching NeuroImages: Idiopathic hypertrophic pachymeningitis.

As discussed by Dr. Budhram, immunoglobulin G4 (IgG4)–related disease (RD) must be considered in patients with hypertrophic pachymeningitis (HP) as it accounts for a high proportion of cases originally thought to be idiopathic.1 IgG4-related HP is pathologically characterized by a lymphoplasmacytic infiltration of IgG4-positive plasma cells.2 The patient we presented had normal IgG4 levels in both serum and CSF.1 Dural biopsy was consistent with a chronic lymphohistiocytic pachymeningitis without substantial plasma cell infiltrate to suggest IgG4-RD. In addition, immunohistochemistry performed on the dural biopsy specimen was IgG4-negative. Our case highlights the steroid responsiveness of idiopathic HP and the excellent response to immunotherapy with methotrexate.1 We agree with Dr. Budhram that immunostaining of dural specimens should be done in patients with HP, as this may help guide treatment for steroid-refractory HP when IgG4 disease can be identified.

Overlap of idiopathic and IgG4-related hypertrophic pachymeningitis: Case Series (P2.385)

Overlap of idiopathic and IgG4-related hypertrophic pachymeningitis: Case Series (P2.385)

IgG4-related hypertrophic pachymeningitis coexpressing antineutrophil cytoplasmic antibodies.

IgG4-related hypertrophic pachymeningitis coexpressing antineutrophil cytoplasmic antibodies.