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Table of Contents    
CASE REPORT
Year : 2021  |  Volume : 69  |  Issue : 2  |  Page : 484-486

A Case of Possible IgG4-Related Disease with Bilateral Optic Neuropathy and Bilateral Hippocampal Bleed


1 Department of Neurology, Ramaiah Institute of Neurosciences, Ramaiah Medical College and Hospitals, Bangalore, Karnataka, India
2 Department of Medicine, Ramaiah Institute of Neurosciences, Ramaiah Medical College and Hospitals, Bangalore, Karnataka, India

Date of Submission02-Jan-2020
Date of Decision02-Mar-2020
Date of Acceptance23-Sep-2020
Date of Web Publication24-Apr-2021

Correspondence Address:
Dr. Anish Mehta
Department of Neurology, Ramaiah Institute of Neurosciences, Ramaiah Medical College and Hospitals, Bangalore - 560 054, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.314517

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 » Abstract 


IgG4-related disease (IgG4-RD) is a multisystem inflammatory disorder. The diagnosis requires consideration of clinical, radiographic, serological, and pathological evidence. Neurological involvement by IgG4-RD is relatively uncommon and is being increasingly recognized and reported with hypertrophic pachymeningitis and hypophysitis as the most frequent manifestations. IgG4-related involvement of brain parenchyma is rare, but isolated case reports exist. Here, we report a case of a young boy who presented to us with bilateral optic neuropathy and bilateral hippocampal bleed-related neurological involvement in a possible IgG4-RD, a rare entity.


Keywords: IgG4-related disease, hippocampal bleed, optic neuropathy
Key Message: In this report, we describe a case of brain parenchymal involvement in a possible IgG 4-related disease in the form of bilateral optic neuropathy with bilateral hippocampal bleed, which is a rare entity.


How to cite this article:
Gogineni S, Mehta A, Shah AG, Kumar S, Nagappa H H, Pradeep R, Javali M, Acharya P, Srinivasa R. A Case of Possible IgG4-Related Disease with Bilateral Optic Neuropathy and Bilateral Hippocampal Bleed. Neurol India 2021;69:484-6

How to cite this URL:
Gogineni S, Mehta A, Shah AG, Kumar S, Nagappa H H, Pradeep R, Javali M, Acharya P, Srinivasa R. A Case of Possible IgG4-Related Disease with Bilateral Optic Neuropathy and Bilateral Hippocampal Bleed. Neurol India [serial online] 2021 [cited 2021 May 9];69:484-6. Available from: https://www.neurologyindia.com/text.asp?2021/69/2/484/314517




IgG4-related disease (IgG4-RD) is an immune-mediated fibro inflammatory condition that is capable of affecting multiple organs.[1] Parenchymal brain involvement is rare and very few case reports have been reported in literature. Here, we report a case of a young boy who presented with bilateral optic neuropathy and bilateral hippocampal bleed-related neurological involvement diagnosed to have possible IgG4-RD, which is a rare entity.


 » Case History Top


The 18-year-old boy presented to emergency with pain abdomen, vomiting, and painless diminution of vision in the right eye of 20 days duration and shortness of breath of three days duration. On examination, he was icteric with multiple small discrete firms painless cervical and axillary lymphadenopathy. Neurological examination showed he was conscious, obeying commands, the right eye showed relative afferent pupillary defect, visual acuity on the right side showed hand movements only, whereas on the left side, the vision was normal. Fundus was normal in both eyes. There were no other long tract signs. The respiratory system showed bilateral decreased breath sounds in the basal areas (left more than right), abdomen examination showed tenderness in the epigastric and umbilical region with no organomegaly, and the cardiovascular system examination was normal.

On evaluation, his routine blood tests are shown in [Table 1] and [Table 2]. Human immunodeficiency virus, Hepatitis B surface antigen, Venereal Disease Research Laboratory (VDRL) tests were nonreactive. Chest X-Ray was suggestive of bilateral pleural effusion (left more than right) with bilateral bronchopneumonia. Ultrasound abdomen showed acute pancreatitis with multiple pseudocysts. CT abdomen (plain + contrast) suggested intrapancreatic, retroperitoneal and intraperitoneal pseudo cysts extending into the liver with multiple renal infarcts [Figure 1]a and [Figure 1]b. CT Thorax showed bilateral lower lobe consolidation left more than right with bilateral pleural effusion (left more than right) [Figure 1]c. Pleural fluid analysis showed transudative picture with glucose of 77, protein of 1.6 g, chloride of 96.1, LDH 996 u/L, pleural fluid for ADA was normal, and AFB was negative. Bronchoscopy with broncho alveolar lavage analysis was negative for AFB and malignant cells. Magnetic resonance imaging (MRI) of the brain (plain + contrast) with orbital cuts showed bilateral T1, T2, and FLAIR hyperintensities in bilateral hippocampi with patchy gadolinium enhancement and blooming on susceptibility-weighted imaging suggestive of bilateral hippocampal bleed [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f with normal orbits. Visual evoked potential studies showed absent p100 waveform in the right eye and prolongation of p100 latency (137 ms) in the left eye. Lumbar puncture for cerebrospinal fluid analysis was normal with negative for viral markers and malignant cells. Connective tissue workup including antinuclear antibody (ANA-IF) (ANA profile), perinuclear–antineutrophil cytoplasmic antibodies and cytoplasmic–antineutrophil cytoplasmic antibodies were negative. Angiotensin converting enzyme levels were normal. He was advised for a PET whole body CT and a lymph node biopsy; however, he did not give consent for the same due to financial constraints.
Table 1: Routine blood investigations (Complete blood count, liver, and renal function tests)

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Table 2: Test values of serum amylase, lipase, and IgG4 levels at admission and after 6 weeks with reference range

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Figure 1: CT abdomen (Plain + Contrast) and CT thorax plain. (a): Right renal wedge-shaped infarct. (b) Multiple pancreatic pseudocysts. (c) Bilateral Pleural effusion (left > right)

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Figure 2: MRI brain (plain and Contrast). (a) T1-weighted sagittal image showing bilateral hippocampal hyperintensity. (b) T2-weighted axial image showing bilateral hippocampal hyperintensity. (c) SWI axial image showing bilateral hippocampal blooming. (d and e) Contrast brain coronal and axial images showing bilateral hippocampal patchy enhancement. (f) Contrast sagittal image showing normal orbits

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In view of multiple system involvement that is pancreatitis with multiple pseudo cysts, bilateral pleural effusion, generalized lymphadenopathy, multiple renal infarcts, and bilateral optic neuropathy clinical possibilities of infections/inflammatory/vasculitis/malignancy were considered and was appropriately investigated for the same. Serum IgG4 levels were sent which showed elevated IgG4 levels 277 mg/dL (<135 mg/dL). Lymph node/renal biopsy were advised. However, the patient did not give consent for the same. Hence, we made a diagnosis of possible IgG4-RD. The patient was started on injectable steroids (1 g infusion for three days followed by oral steroids – 1 mg/kg/body weight tapered over 8 weeks). Patient showed clinical and serological improvement in the form that vision improved to 6/18 in the right eye, abdominal and respiratory symptoms improved, with near normalcy of the serological values on follow-up after six weeks, and is on maintenance dose of 0.5 mg/kg/body weight.


 » Discussion Top


IgG4-RD is a systemic, immune-mediated fibro-inflammatory disease of unknown cause, involving a wide variety of organs.[1] Clinically, enlargement of the affected organ(s) may be accompanied by high serum levels of IgG4, and the histology shows the classic triad—infiltration of IgG4-bearing plasma cells, storiform fibrosis, and obliterative phlebitis.[2] IgG4-RD is an antigen-driven process, the antigen (or antigens) initiating the process remains unknown.

Two major interactions between cells of the B-lymphocyte lineage and CD4+ T-lymphocytes appear to drive the pathophysiology of IgG4-RD.

IgG4-related inflammation can infiltrate directly into the substance of the central or peripheral nervous system, or neurological structures can be compressed by the mass effect of nearby diseased non-neurological organs. Most common neurological involvement in IgG4-RD is the dura mater (pachymeninges) and the pituitary gland and stalk (hypophysitis). Brain tissue is rarely involved by IgG4-RD, but isolated case reports exist.

The comprehensive clinical diagnostic criteria for IgG4-RD includes:

  1. Clinical examination showing characteristic diffuse or localized swelling or masses in single or multiple organs
  2. Elevated serum IgG4 RD concentration >135 mg/dL
  3. Histopathologic examination showing


    1. Marked lymphocytic and plasmacytic infiltration and fibrosis
    2. Infiltration of IgG4 + plasma cells: ratio of IgG4+/IgG + cells >40% and >10 IgG4 + plasma cells/hpf combination of 1 + 2 + 3 = definite IgG4-RD 1 + 3 = Probable IgG4 RD 1 + 2 = Possible IgG4 RD


Lui PC et al. reported an intraventricular IgG4-RD mass lesion, proven by biopsy to be IgG4-RD. Regev et al. reported biopsy-proven involvement of the brain parenchyma in a patient with systemic manifestations of IgG4-RD.[3] Li LF et al. reported two cases of IgG4-related pachymeningitis in which the underlying brain parenchyma was suggested to also be involved with IgG4-RD based on radiographic findings, however were not biopsy proven.[4]

Treatment is systemic steroids 0.6 mg/kg/day for 2–3 months followed by maintenance of 2.5–5 mg/day for 6–12 months followed by tapering dose. If nonresponsive to steroid-sparing agents like rituximab, 1 gm infusion 2 weeks apart every 6 months can be given.

In our case, patient had neurological involvement in the form of bilateral optic neuropathy with bilateral hippocampal bleed in a possible IgG4-RD; the cause of this association is largely unknown, however, as the venous drainage of hippocampus is by vein of Rosenthal; we hypothesize that possibly there could have been involvement of the same secondary to obliterative phlebitis causing bilateral hippocampal bleed, and the optic neuropathy could be secondary to vasculopathy-/immune-mediated inflammatory response.

To the best of our knowledge, we could not find this association of neurological involvement in the literature so far.


 » Conclusion Top


IgG4-RD is a rare condition that can affect multiple organs. Limited data is available regarding central nervous system involvement in IgG4-RD because of its rarity. Early diagnosis of this rare entity and treatment with systemic steroids can decrease the morbidity and mortality and improve the quality of life in these patients. To the best of our knowledge, we could not find this association in the literature so far, showing dramatic response with steroids.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366:539-51.  Back to cited text no. 1
    
2.
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012;22:21-30.  Back to cited text no. 2
    
3.
Regev K, Nussbaum T, Cagnano E, Giladi N, Karni A. Central nervous system manifestation of IgG4-related disease. JAMA Neurol 2014;71:767-70.  Back to cited text no. 3
    
4.
Li LF, Tse PY, Tsang FC, Lo RC, Lui WM, Leung GK. IgG4-related hypertrophic pachymeningitis at the falx cerebri with brain parenchymal invasion: A case report. World Neurosurg 2015;84:591e7-10.  Back to cited text no. 4
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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