1. Excerpta Extraordinaire
IgG4-related Infundibulo-hypophysitis and Hypertrophic Pachymeningitis in a Patient with Panhypopituitarism
EE-02
Excerpta Extraordinaire
Lopez, Dayibi
Sana Ali, MD; R Sharma, MD; E G Stein, MD, PhD.
contact:

2. 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

3. Purpose
Outline a case of IgG4-related infundibulo-hypophysitis and hypertrophic pachymeningitis and elucidate radiographic findings
Brief overview of IgG4-related disease and its manifestations with a special emphasis on central nervous system (CNS) involvement
Review of other entities that can cause hypertrophic pachymeningitis

4. Case Report
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.
Patient subsequently also diagnosed with panhypopituitarism.

5. 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
4/8/15

6. 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
4/8/15

7. Hospital Course & Assessment
Hospital Course: surgical biopsy of dural lesion, high dose steroids and medical management for panhypopituitarism (diabetes insipidus)
Serum IgG elevated
Pathology: No organisms detected. Dense fibroconnective tissue with mixed inflammatory infiltrate and multinucleated giant cells, focally positive for IgG4
Constellation of findings consistent with IgG4-related infundibulo-hypophysitis and hypertrophic pachymeningitis

8. 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 c d
Before treatment
10 days after treatment
/8/15
/18/15

9. IgG4-related Disease

10. General Overview of IgG4-related Disease
Immunoglobulin G4 (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
Recognized as a systemic disease in 2003
Pancreas is the most commonly involved organ
Pituitary gland and meninges are the most commonly involved organs in the CNS
Marked response to corticosteroid therapy
Recognized as a systemic disease in 2003 when extra-pancreatic manifestations were identified in patients with autoimmune pancreatitis.

11. IgG4-related Disease Spectrum
Head & Neck
Biliary & Endocrine
Hypertrophic pachymeningitis
Autoimmune hypophysitis
Orbital pseudotumor
Mikulicz syndrome (Sjogren type I)
Kuttner’s tumor (chronic sclerosing sialoadenitis)
Riedel’s thyroiditis
Hashimoto’s thyroiditis
Autoimmune pancreatitis
Sclerosing cholangitis
Liver pseudotumor
Retroperitoneal fibrosis
Sclerosing mesenteritis
GU & Vascular
Tubulointerstitial nephritis
Prostatitis, testicular involvement
Cutaneous pseudolymphoma
Inflammatory aortic aneurysm
Lymphadenopathy
Chest
Pulmonary pseudotumor
Interstitial pneumonia

12. Diagnostic Criteria
Kamisawa, et al. proposed three major diagnostic criteria:
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.)

13. 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

14. Hypertrophic Pachymeningitis

15. Hypertrophic Pachymeningitis: Overview
Hypertrophic pachymeningitis (HP) refers to localized or diffuse thickening of the cranial or spinal cord dura mater due to inflammation
Often resultant progressive neurological deficits
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

16. Hypertrophic Pachymeningitis: Imaging Findings
Low T1 and T2 signal intensity with peripheral contrast enhancement
Dural thickening/dural mass
Falco-tentorial, medial and basifrontal, frontal/temporal convexities
Sinus thrombosis (venous congestion)
White matter changes
Biopsy is gold standard for definitive diagnosis

17. 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, IgG4-related disease, inflammatory bowel disease
Others – dural carcinomatosis, meningioma, lymphoma, etc.
Adapted from Dash et al Journal of Neurological Sciences. 250 (2015);

18. GPA-associated Pachymeningitisb c d
Biopsy proven focal GPA- associated hypertrophic pachymeningitis. Axial non- enhanced 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.

19. 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
NEW

20. 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 c d
At presentation
Post-chemotherapy
5/24/2010
6/1/

21. Infectious Pachymeningitis
Diffuse hypertrophic pachymeningitis in a patient with known tuberculosis. Axial post-contrast T1 image (a) demonstrates uniform tentorial enhancement. Axial post-contrast 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);

22. 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

23. 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

24. Summary
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.
Clinical management heavily relies on ability to differentiate idiopathic hypertrophic pachymeningitis from secondary causes.

25. References
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.
Ezzeldin M, Shawagfeh A, Schnadig V, Smith RG, Fang X. Hypertrophic spinal pachymeningitis: idiopathic vs. IgG4-related. J Neurol Sci. 2014;347(1-2):
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.
Hufnagel M, Henneke P, Schmitt-graeff A. IgG4-related disease. N Engl J Med. 2012;366(17):
Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38(10):982-4.
Leporati P, Fonte R, Chiovato L. IgG4-related disease. N Engl J Med. 2012;366(17):1645.
Martínez-de-alegría A, Baleato-gonzález S, García-figueiras R, et al. IgG4-related Disease from Head to Toe. Radiographics. 2015;35(7):
Niks EH, De baets MH, Verschuuren JJ. IgG4-related disease. N Engl J Med. 2012;366(17):
Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):
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. 2014;55(5):300-2.
Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), Mod Rheumatol. 2012;22(1):21-30.
Vaglio A, Zwerina J. IgG4-related disease. N Engl J Med. 2012;366(17):1646.
Wallace ZS, Carruthers MN, Khosroshahi A, et al. IgG4-related disease and hypertrophic pachymeningitis. Medicine (Baltimore). 2013;92(4):
Weinstein A. IgG4-related disease. N Engl J Med. 2012;366(17):1645.