Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
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Case Report

Volume 15, Number 12, December 2024, pages 387-395

Exploring Overlap Syndromes: An Atypical Case of Multiple Sclerosis With Anti-Sjogren’s Syndrome Type B Antibody

Figures

↓  Figure 1. MRI brain with and without contrast. On axial T2-weighted FLAIR, there are two small periventricular white matter intensities along the bodies of the lateral ventricles (a, b, red arrows) and within the right para-midline pons (c, red arrow). On axial DWI (d), there is a small area of mild restricted diffusion in the right para-midline pons, measuring 1.4 × 1.0 cm (red arrow), with corresponding signal (red arrow) on ADC (e) and contrast enhancement on post-contrast MPRAGE (f, red arrow). Post-contrast MPRAGE imaging also shows bilateral enhancement of cranial nerves III (g, blue arrows), V (h, green arrows), and VI (f, pink arrow, unilateral only shown). MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery; DWI: diffusion-weighted imaging; ADC: apparent diffusion coefficient; MPRAGE: magnetization-prepared rapid gradient echo.
Figure 1.
↓  Figure 2. MRI lumbar spine with contrast. On sagittal (a) and axial (b, d) T1-weighted post-contrast images, there is subtle enhancement of the cauda equina nerve roots (red arrows), with corresponding T2 axial (c, e) views. The upper dashed line on panel A corresponds to axial slices (b) and (c), whereas the lower dashed line corresponds to axial slices (d) and (e). MRI: magnetic resonance imaging.
Figure 2.
↓  Figure 3. MRI thoracic spine with contrast. Axial (a) and sagittal (b) T1 MRI post-contrast images of the thoracic spine show subtle enhancement of the thoracic nerve roots (red arrows). MRI: magnetic resonance imaging.
Figure 3.

Tables

↓  Table 1. Serum and CSF Evaluation
 
Evaluations Value (normal range)
aAbnormal results. Ig: immunoglobulin; Ab: antibody; CSF: cerebrospinal fluid; IFA: immunofluorescence assay; ANNA: anti-neuronal nuclear antibody; PCA: Purkinje cell antibody; DNER: delta/notch-like EGF-related receptor; AGNA/SOX1: anti-glial nuclear antibody/anti-SRY (sex determining region Y)-box 1; CRMP5/CV2: collapsin response mediator protein 5 (also known as “CV2”); MPO: myeloperoxidase; PR3: proteinase 3; C-ANCA: cytoplasmic antineutrophil cytoplasmic antibodies; P-ANCA: perinuclear antineutrophil cytoplasmic antibodies; MOG: myelin oligodendrocyte glycoprotein; SSA: Sjogren’s syndrome type A (also known as anti-Ro); SSB: Sjogren’s syndrome type B (also known as anti-La); CCP: cyclic citrullinated peptide; Rnp: ribonucleoprotein; CSF: cerebrospinal fluid; RBC: red blood cell; WBC: white blood cell; VDRL: venereal disease research laboratory test; GAD65: glutamic acid decarboxylase 65; AI: antibody index; EU: endotoxin units; APL-U: IgA phospholipid units; GPL-U: IgG phospholipid units; MPL-U: IgM phospholipid units.
Serum evaluation
  IgA level 259.45 (84.5 - 499 mg/dL)
  IgG level 764.35 (610.3 - 1,616 mg/dL)
  IgM level 155.25 (35 - 242 mg/dL)
  Tissue IFA observation No fluorescence observed
  ANNA1 (HU) Ab, IFA Negative
  ANN2 (R1) Ab, IFA Negative
  ANNA3 Ab, IFA Negative
  PCA1 (YO) Ab, IFA Negative
  PCA2 Ab, IFA Negative
  PCA TR (DNER) Ab, IFA Negative
  AGNA/SOX1 Ab, IFA Negative
  AMPHIPHYSIN Ab, IFA Negative
  CRMP5/CV2 Ab, IFA Negative
  Aquaporin 4 Ab (IgG) Negative
  Anti-MPO Ab < 0.2 (0.0 - 0.9 U)
  Anti-PR3 Ab < 0.2 (0.0 - 0.9 U)
  C-ANCA < 1:20
  P-ANCA < 1:20
  Atypical P-ANCA < 1:20
  Lyme total Ab Negative
  MOG Ab, serum Negative
  Sjogren’s Ab (SSA) < 0.2 (0.0 - 0.9 AI)
  Sjogren’s Ab (SSB) 2.7, 2.8 (0.0 - 0.9 AI)a
  Ribosomal P Ab < 0.2 (0.0 - 0.9 AI)
  Salivary protein 1 IgG Ab 2.6 (< 20 EU/mL)
  Salivary protein 1 IgA Ab 2.0 (< 20 EU/mL)
  Salivary protein 1 IgM Ab 74.2 (< 20 EU/mL)a
  Carbonic anhydrase VI IgG Ab > 160.0 (< 20 EU/mL)a
  Carbonic anhydrase VI IgA Ab 87.0 (< 20 EU/mL)a
  Carbonic anhydrase VI IgM Ab 17.2 (< 20 EU/mL)
  Parotid specific protein IgG Ab 18.2 (< 20 EU/mL)
  Parotid specific protein IgA Ab 27.4 (< 20 EU/mL)a
  Parotid specific protein IgM Ab 22.0 (< 20 EU/mL; borderline: 20 - 25 EU/mL)
  Cyclic citrullinated peptide (CCP) Ab IgG < 16 (< 20)
  Lupus anticoagulant Not detected
  Rheumatoid factor < 14 (< 14 IU/mL)
  Cardiolipin Ab, IgA < 2.0 (< 20 APL-U/mL)
  Cardiolipin Ab, IgG < 2.0 (< 20 GPL-U/mL)
  Cardiolipin Ab, IgM < 2.0 (< 20 MPL-U/mL)
  Beta-2 glycoprotein I Ab, IgM < 2.0 (< 20 U/mL)
  Beta-2 glycoprotein I Ab, IgA < 2.0 (< 20 U/mL)
  Beta-2 glycoprotein I Ab, IgG < 2.0 (< 20 U/mL)
  Antinuclear Ab, IFA Negative
  Anti-DNA (Ds) Ab 3 (0-9 IU/mL)
  Rnp Ab < 0.2 (0.0 - 0.9 AI)
  Smith Ab < 0.2 (0.0 - 0.9 AI)
  Scleroderma (Scl-70) Ab < 0.2 (0.0 - 0.9 AI)
  Oligoclonal bands, serum 0
CSF evaluation Value (normal range)
  Protein 24 (15 - 45 mg/dL)
  Glucose 71 (40 - 75 mg/dL)
  RBC count 3,100 (0/mm3)a
  WBC count 8 (0 - 5/mm3)a
  Neutrophils 34%
  Lymphocytes 59%
  Monocytes 6%
  Eosinophils 1%
  Cryptococcus gattii neoformans DNA CSF Not detected
  Cytomegalovirus DNA CSF Not detected
  Enterovirus RNA CSF Not detected
  Escherichia coli K1 DNA CSF Not detected
  Haemophilus influenzae DNA CSF Not detected
  Herpes simplex virus 1 DNA CSF Not detected
  Herpes simplex virus 2 DNA CSF Not detected
  Herpes virus 6 DNA CSF Not detected
  Parechovirus A RNA CSF Not detected
  Listeria monocytogenes DNA CSF Not detected
  Neisseria meningitidis DNA CSF Not detected
  Streptococcus agalactiae DNA CSF Not detected
  Streptococcus pneumoniae DNA CSF Not detected
  Varicella zoster virus DNA CSF Not detected
  VDRL, CSF Non-reactive
  CRMP5/CV2 AB, IFA, CSF Negative
  GAD65 antibody, IFA, CSF Negative
  Aquaporin 4 Ab (IgG), CSF Negative
  MOG Ab, CSF Negative
  Oligoclonal bands, CSF 5 CSF-specific bands
  Flow cytometry analysis No immunophenotypically abnormal T or B cells detected
  Cytology Negative for malignancy

 

↓  Table 2. Longitudinal Disease Course
 
Time point Clinical findings Laboratory data Imaging findings Treatment
CSF: cerebrospinal fluid; MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery; IV: intravenous; SSB: Sjogren’s syndrome B.
Hospital admission (initial presentation) Left face and hemibody paresthesias CSF: mild leukocytosis, 5 CSF-specific oligoclonal bands MRI brain: T2 FLAIR hyperintensity in the bilateral periventricular regions and right pons; cranial nerve enhancement 5-day course of high-dose IV methylprednisolone
Abnormal gait with left leg dragging Serum: positive anti-SSB antibody; no serum oligoclonal bands MRI spine: enhancement in the cauda equina and thoracic nerve roots
Weakness in left hip and knee
Absent lower extremity reflexes
Hospital discharge (8 days post-admission) Mild improvement in strength No new laboratory findings No new imaging findings Discharged with follow-up to neuroimmunology and rheumatology
Persistent left-sided paresthesias
2 months post-discharge Improved motor exam Serum: elevated salivary protein 1 IgM, elevated carbonic anhydrase VI IgG and IgM antibodies, elevated parotid specific protein IgA antibody MRI brain: persistent enhancement of cranial nerves 3-day course of high-dose oral prednisone
Residual numbness Ofatumumab 20 mg monthly

 

↓  Table 3. A Case-Based Literature Review of MS and SS Overlaps and Diagnostic Dilemmas
 
Case Patient Case presentation Suspected initial diagnosis Diagnostic dilemmas and changes Final diagnosis Key takeaways
F: female; BLE: bilateral lower extremity; MS: multiple sclerosis; SSB: Sjogren’s syndrome B; SS: Sjogren’s syndrome; MRI: magnetic resonance imaging; CNS: central nervous system; UCTD: undifferentiated connective tissue disease; IFN: interferon; PBC: primary biliary cholangitis; BUE: bilateral upper extremity; N/A: not available.
Our case F, 39 years Patient presented with left face and hemibody paresthesias, abnormal gait with left leg dragging, weakness in left hip and knee, and absent BLE reflexes. MS Serum studies revealed a positive Sjogren’s anti-SSB antibody, despite no history of systemic or sicca symptoms. MS and SS overlap It is important to consider autoimmune overlap conditions in cases where there are atypical neurologic symptoms, as the co-occurrence of MS and SS can impact treatment strategies.
Mohamednour et al, 2020 [10] F, 58 years Patient with a 3-year history of MS presented with polyarthralgia, sicca symptoms, and Raynaud’s. MS Initial MRI of the brain and spine were reported as normal with few “nonspecific white matter areas”, complicating the diagnosis. SS CNS involvement in SS can closely resemble MS, complicating the diagnosis. Peripheral neuropathy and vasculitis are key differentiators. Early neurophysiological testing is crucial, and effective immunosuppression with shared decision-making can achieve successful outcomes.
Jung et al, 2000 [11] F, 45 years Patient with a 4-year history of dry eyes and mouth presented with BLE weakness, voiding difficulty, decreased visual acuity, BLE spasticity and hyperesthesia, and diffuse hyperreflexia. MS Erythematous skin lesions soon developed in the periauricular area and BLE. Skin and salivary gland biopsies both showed lymphocytic infiltration. SS SS should be considered as a differential diagnosis of a patient presenting with a syndrome that resembles MS because of the similarity in clinical manifestations and laboratory findings of both diseases.
Thong et al, 2002 [12] F, 40 years Patient with a history of a lacunar stroke with no residual deficits presented with acute urinary retention and diminished sensation below T5 spinal level, followed by a year of episodes of ataxia and upper limb dysmetria, retrobulbar neuritis, and pseudobulbar palsy. UCTD Five years after initial neurologic symptoms, the patient presented with pseudobulbar palsy and endorsed 1 year of sicca symptoms. Schirmer test was positive, and anti-Ro antibody was elevated. SS Patients with MS-like diseases should be carefully evaluated for other system autoimmune conditions as the treatment and prognosis differ from MS. Particularly, sicca symptoms should be sought as they often go unnoticed by patients.
De Santi et al, 2005 [13] F, 48 years Patient with a 29-year history of MS treated well with IFN-beta 1a for 5 years presented with xerophthalmia and xerostomia with dysphagia. MS N/A MS and SS overlap SS can develop long after the onset of MS, even during successful IFN-beta treatment. This case highlights the need to monitor MS patients for SS, as symptoms may arise unexpectedly, complicating diagnosis and management.
Guzel et al, 2022 [14] F, 51 years Patient with a history of PBC and Hashimoto thyroiditis presented with numbness and weakness in the left upper and lower extremities; further questioning revealed symptoms of dry eyes and mouth. MS and SS overlap N/A MS and SS overlap This case highlights the rare coexistence of four autoimmune diseases, emphasizing the importance of considering multiple overlapping autoimmune disorders in complex presentations.
Liu et al, 2014 [15] F, 75 years Patient presented with recurring numbness and sensory changes in BUE and BLE with zonesthesia in the waist. MS Patient had subsequent worsening of paresthesias and swelling of the parotid gland; oral and ocular sicca syndromes were suspected from history taking and confirmed by Schirmer test and labial salivary gland biopsies SS SS should be considered in the differential diagnosis of patients presenting with MS-like neurological symptoms, as it can mimic MS both clinically and neuroradiologically.