Transcript Hypertrophic Pachymeningitis

IgG4-related Infundibulohypophysitis and Hypertrophic
Pachymeningitis in a Patient with
Panhypopituitarism
EE-02
Excerpta Extraordinaire
Sana Ali, MD; R Sharma, MD; E G Stein, MD, PhD.
contact: [email protected]
Disclosure
No potential conflicts to disclose
Join us for our oral excerpta extraordinaire (E-10)
showcasing a case of idiopathic hypertrophic
pachymeningitis of the cervical spine
Monday, May 23, 2016: 2:00-2:05 pm
Purpose
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Outline a case of IgG4-related infundibulohypophysitis and hypertrophic pachymeningitis
and elucidate radiographic findings
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Brief overview of IgG4-related disease and its
manifestations with a special emphasis on
central nervous system (CNS) involvement
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Review of other entities that can cause
hypertrophic pachymeningitis
Case Report
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54-year-old female with rheumatoid arthritis,
hypertension, Chiari I malformation, diabetes
mellitus type II and hypothyroidism was admitted
for worsening headaches, diplopia, nausea and
vomiting. The headaches were exacerbated
during Valsalva-type maneuvers.
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Patient subsequently also diagnosed with
panhypopituitarism.
Imaging Findings
Magnetic resonance imaging (MRI) of the brain with intravenous gadolinium contrast.
Coronal (a) and sagittal (b) post-contrast T1 images demonstrate an enlarged,
thickened and markedly enhancing pituitary gland and stalk (arrows). Findings are
most compatible with infundibulo-hypophysitis of infectious or inflammatory origin.
(Additionally seen is downward tonsillar herniation consistent with known Chiari I.)
a
b
Imaging Findings
MRI of the brain with intravenous gadolinium contrast. Axial post-contrast T1 image
(a) demonstrates marked thickening and enhancement of the tentorium and posterior
falx with effacement of the perimesencephalic cisterns and midbrain compression.
Axial post-contrast FLAIR images (b and c) demonstrate pachymeningeal
hyperintensity (arrows). Findings are most compatible with pachymeningitis of
infectious or inflammatory origin.
a
b
c
Hospital Course & Assessment
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Hospital Course: surgical biopsy of dural lesion, high
dose steroids and medical management for
panhypopituitarism (diabetes insipidus)
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Serum IgG elevated
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Pathology: No organisms detected. Dense
fibroconnective tissue with mixed inflammatory infiltrate
and multinucleated giant cells, focally positive for IgG4
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Constellation of findings consistent with IgG4-related
infundibulo-hypophysitis and hypertrophic
pachymeningitis
Post-Treatment Imaging Findings
MRI of the brain with intravenous gadolinium contrast. Axial post-contrast T1 images
before (a and c) and after (b and d) treatment with high-dose steroids demonstrate
interval decrease in dural thickening and almost complete resolution of pituitary gland
and stalk thickening and enlargement (arrows).
a
b
Before treatment
c
10 days after treatment
d
Before treatment
10 days after treatment
IgG4-related Disease
General Overview of IgG4-related
Disease
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Immunoglobulin G4 (IgG4)-related disease is an immunemediated systemic condition that includes a group of
disorders that were previously thought to be distinct, but with
shared pathologic, serologic, and clinical features
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Recognized as a systemic disease in 2003
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Pancreas is the most commonly involved organ
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Pituitary gland and meninges are the most commonly involved
organs in the CNS
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Marked response to corticosteroid therapy
IgG4-related Disease Spectrum
Head & Neck
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Hypertrophic pachymeningitis
Autoimmune hypophysitis
Orbital pseudotumor
Mikulicz syndrome (Sjogren
type I)
Kuttner’s tumor (chronic
sclerosing sialoadenitis)
Riedel’s thyroiditis
Hashimoto’s thyroiditis
Biliary & Endocrine
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GU & Vascular
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Chest
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Pulmonary pseudotumor
Interstitial pneumonia
Autoimmune pancreatitis
Sclerosing cholangitis
Liver pseudotumor
Retroperitoneal fibrosis
Sclerosing mesenteritis
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Tubulointerstitial nephritis
Prostatitis, testicular
involvement
Cutaneous pseudolymphoma
Inflammatory aortic aneurysm
Lymphadenopathy
Diagnostic Criteria
Kamisawa, et al. proposed three major diagnostic criteria:
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Clinical – characteristic diffuse or localized swelling/masses in
one or more organs
Serologic – elevated IgG4 concentrations (≥135 mg/dl)
Histopathologic – marked lymphoplasmacytic infiltration and
storiform fibrosis, as well as IgG4-positive plasma cells
Diagnosis considered definite if all three criteria are met, probable if first and
third are met, and possible if first and second criteria are met. (Umehara, et al.)
IgG4-related Hypophysitis
72-year-old male presenting with general fatigue and weakness. Patient found to have diabetes
insipidus and hypopituitarism with an elevated serum IgG4. Sagittal T1 post-contrast MRI prior
to steroid therapy (A) shows an enlarged pituitary stalk (arrow) consistent with hypophysitis.
Sagittal T1 post-contrast MRI after steroid therapy (B) reveals interval decrease in pituitary stalk
size. This patient had biopsy proven IgG4-related disease of additional renal nodules.
Harano et al. Clin Med Insights Case Rep. 2015;8:23-6
Hypertrophic Pachymeningitis
Hypertrophic Pachymeningitis:
Overview
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Hypertrophic pachymeningitis (HP) refers to localized or
diffuse thickening of the cranial or spinal cord dura mater
due to inflammation
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Often resultant progressive neurological deficits
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Headache
Vision loss
Cranial nerve palsies
Seizures
Hearing loss
Clinical management heavily relies on ability to
differentiate primary or idiopathic hypertrophic
pachymeningitis from secondary causes
Hypertrophic Pachymeningitis:
Imaging Findings
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Low T1 and T2 signal intensity with peripheral contrast
enhancement
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Dural thickening/dural mass
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Falco-tentorial, medial and basifrontal, frontal/temporal convexities
Sinus thrombosis (venous congestion)
White matter changes
Biopsy is gold standard for definitive diagnosis
Hypertrophic Pachymeningitis:
Etiology
Causes of Hypertrophic Pachymeningitis
Primary or Idiopathic (diagnosis of exclusion)
Secondary
Infectious – TB, fungal, Lyme disease, syphilis, eosinophilic
meningitis due to parasitic disease
Systemic autoimmune/vasculitis – Sarcoidosis,
granulomatosis with polyangiitis (GPA), Rheumatoid arthritis,
Behcet’s disease, Sjogren syndrome, temporal arteritis,
mixed connective tissue disorder, orbital pseudotumor, IgG4related disease, inflammatory bowel disease
Others – dural carcinomatosis, meningioma, lymphoma, etc.
Adapted from Dash et al Journal of Neurological Sciences. 250 (2015); 51-60.
GPA-associated Pachymeningitis
Biopsy proven focal GPAassociated hypertrophic
pachymeningitis. Axial nonenhanced CT (a) shows an
anterior falcine hyperdense ovoid
nodule. Axial FLAIR (b), axial
post-contrast T1 (c) and DWI (d)
reveal a peripherally enhancing
ovoid nodule (arrow) with
adjacent leptomeningeal
enhancement and FLAIR
hyperintensity over the frontal
lobes. No associated restricted
diffusion.
a
b
c
d
Sarcoid Leptomeningitis
As with many conditions that can infiltrate or inflame the pachymeninges, Sarcoid can
also cause a leptomeningitis as in this patient with pathologically proven sarcoidosis.
Axial non-contrast chest CT (a and b) demonstrates bilateral upper lobe parenchymal
pulmonary disease. Axial post-contrast T1 images (c and d) demonstrate classic
bilateral frontal leptomeningeal enhancement.
a
b
c
d
Lymphoma-associated
Pachymeningitis
Lymphoma-associated pachymeningitis and clival infiltration in a patient with CNS
lymphoma. Sagittal and axial post-contrast T1 images at presentation (a and c) and
after intrathecal methotrexate (b and d). Interval resolution of patchy irregular
enhancement in the clivus (arrowhead) and resolution of diffuse thickened
pachymeningeal enhancement (arrows).
a
b
At presentation
c
Post-chemotherapy
d
At presentation
Post-chemotherapy
Infectious Pachymeningitis
Diffuse hypertrophic pachymeningitis in a patient with known tuberculosis. Axial postcontrast T1 image (a) demonstrates uniform tentorial enhancement. Axial postcontrast image (b) two years later in the same patient demonstrates interval
resolution of previously seen dural enhancement.
Dash et al Journal of Neurological Sciences. 250 (2015); 51-60.
Metastatic Pachymeningitis
Metastatic pachymeningitis in a patient with prostate cancer. Axial non-contrast head
CT image in bone windows (a) demonstrates extensive blastic and lytic osseous
lesions. Axial post-contrast (b) head CT demonstrates enhancing nodular soft tissue
masses along the dura. Axial T1 post-contrast (c and d) images demonstrate bilateral
heterogeneously enhancing lobulated dural-based masses and diffuse dural
enhancement. There is additional heterogeneous enhancement of the left temporal
calvarium and scalp (arrow) consistent with transcalvarial metastases.
a
b
c
d
Idiopathic Pachymeningitis
Biopsy proven idiopathic intra-cranial and cervical pachymeningitis. MR sagittal T1 (a), T2 (b)
and post-contrast T1 (c) images demonstrate mass-like nodular enhancing dural thickening both
anteriorly and posteriorly (arrows) extending into the cervical spine.
a
b
c
Summary
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IgG4-related disease is an immune-mediated systemic
condition that includes a group of disorders that were
previously thought to be distinct, but with shared
pathologic, serologic, and clinical features.

Many cases of HP that were originally thought to be
idiopathic have been found to be IgG4-related.
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Clinical management heavily relies on ability to
differentiate idiopathic hypertrophic pachymeningitis from
secondary causes.
References
1. Dash GK, Thomas B, Nair M, Radhakrishnan A. Clinico-radiological spectrum and outcome in
idiopathic hypertrophic pachymeningitis. J Neurol Sci. 2015;350(1-2):51-60.
2. Ezzeldin M, Shawagfeh A, Schnadig V, Smith RG, Fang X. Hypertrophic spinal pachymeningitis:
idiopathic vs. IgG4-related. J Neurol Sci. 2014;347(1-2):398-400.
3. Harano Y, Honda K, Akiyama Y, Kotajima L, Arioka H. A Case of IgG4-Related Hypophysitis
Presented with Hypopituitarism and Diabetes Insipidus. Clin Med Insights Case Rep. 2015;8:23-6.
4. Hufnagel M, Henneke P, Schmitt-graeff A. IgG4-related disease. N Engl J Med. 2012;366(17):16434.
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Head to Toe. Radiographics. 2015;35(7):2007-25.
8. Niks EH, De baets MH, Verschuuren JJ. IgG4-related disease. N Engl J Med. 2012;366(17):1644-5.
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10. Takeuchi S, Osada H, Seno S, Nawashiro H. IgG4-Related Intracranial Hypertrophic
Pachymeningitis : A Case Report and Review of the Literature. J Korean Neurosurg Soc.
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11. Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease
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13. Wallace ZS, Carruthers MN, Khosroshahi A, et al. IgG4-related disease and hypertrophic
pachymeningitis. Medicine (Baltimore). 2013;92(4):206-16.
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