Paraneoplastic encephalomyeloradiculits with multiple autoantibodies against ITPR-1, GFAP and MOG: case report and literature review

Abstract

Background Recently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies. Case presentation and literature review A 44-year old caucasian woman with a flu-like prodrome presented with meningism, progressive cerebellar signs and autonomic symptoms, areflexia, quadriplegia and respiratory insufficiency. MRI showed diffuse bilateral T2w-hyperintense brain lesions in the cortex, white matter, the corpus callosum as well as a longitudinal lesion of the medulla oblongata and the entire spinal cord. Anti-ITPR1, anti-GFAP and anti-MOG antibodies were detected in cerebrospinal fluid along with lymphocytic pleocytosis. Borderline tumor of the ovary was diagnosed. Thus, the disease of the patient was deemed to be paraneoplastic. The patient was treated by surgical removal of tumor, steroids, immunoglobulins, plasma exchange and rituximab. Four months after presentation, the patient was still tetraplegic, reacted with mimic expressions to pain or touch and could phonate solitary vowels. An extensive literature research was performed. Conclusion Our case and the literature review illustrate that multiple glial and neuronal autoantibodies can co-occur, that points to a paraneoplastic etiology, above all ovarian teratoma or thymoma. Clinical manifestation can be a mixture of typically associated syndromes, e.g. ataxia associated with anti-ITPR1 antibodies, encephalomyelitis with anti-GFAPα antibodies and longitudinal extensive myelitis with anti-MOG antibodies.

Coexistence of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G and Neuronal or Glial Antibodies in the Central Nervous System: A Systematic Review

“…Fifty-three relevant studies were identified after title and abstract screening. After reading the full texts and reviewing the references of the retrieved articles, 35 studies were finally included in the qualitative synthesis, of which 14 were retrospective studies [ 11 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] and 21 were case reports [ 12 , 13 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. A total of 113 patients (46 males and 67 females) were reported to show the coexistence of MOG-IgG and neuronal or glial antibodies in these 35 studies.…”

Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature

“…In addition to the cases summarized above, five further patients with ITPR1-IgG/anti-Sj detected only in the CSF have been reported (2 × seronegative [ 29 , 30 ], 2 × no serum available [ 18 ], 1 × no information provided [ 18 ]). However, as all previously published ITPR1-IgG/anti-Sj-positive patients had serum antibodies to ITPR1, and the specificity of the recombinant assays used to detect ITPR1-IgG/anti-Sj has not been formally evaluated for CSF, the clinical significance of this finding is unknown.…”

“…However, as all previously published ITPR1-IgG/anti-Sj-positive patients had serum antibodies to ITPR1, and the specificity of the recombinant assays used to detect ITPR1-IgG/anti-Sj has not been formally evaluated for CSF, the clinical significance of this finding is unknown. Moreover, co-existing CSF IgG antibodies to N -methyl d -aspartate receptors (NMDAR) (2×) and glial fibrillary astrocytic protein (GFAP) (3×) [ 16 , 29 , 30 ] were reportedly present in the CSF of some of these patients. CSF GFAP-IgG and CSF NMDAR-IgG can also cause autoimmune encephalomyelitis or encephalitis, respectively, rendering it impossible to attribute these patients’ clinical and paraclinical features to either of these antibodies with sufficient certainty.…”

“…CSF GFAP-IgG and CSF NMDAR-IgG can also cause autoimmune encephalomyelitis or encephalitis, respectively, rendering it impossible to attribute these patients’ clinical and paraclinical features to either of these antibodies with sufficient certainty. In one of these patients [ 30 ], ITPR1-IgG was negative in the CSF on three occasions, including at disease onset, but reportedly temporarily positive once, and negative in the serum in four matched serum samples, ITPR1-specific binding of the patient’s IgG to brain tissue was not demonstrated, and the associated tumour did not express ITPR1, which in summary casts doubts on the diagnosis. Accordingly, these cases were not included in this literature review.…”

Autoimmune diseases and cancers overlapping with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A systematic review

“…MOGAD was perceived primarily as a monophasic CNS inflammatory disease, but further observations showed that a relapsing course occur in 28–60% of patients, and in up to 83% of cases with long-term observation, especially those with persistent positive MOG-IgG status. 99,143 Some evidence of subclinical disease activity and progression has been shown to be present in some of the patients with MOGAD. 2 Patients with anti-NMDAR-EN tend to have more severe neurologic presentations, and poor long-term functional outcomes, and the mortality rate has been reported between 5% and 7%.…”