Anti-Collapsing Response-Mediating Protein-5 Antibody-Positive Paraneoplastic Perioptic Neuritis without Typical Neurological Symptoms.

A 68-year-old male presented with blurred vision in both eyes. Ophthalmoscopy revealed bilateral prominent disc swelling and vitritis. No systematic neurological symptoms were observed. Magnetic resonance imaging revealed bilateral meningeal enhancement of the optic nerve. Small cell carcinoma was found, and antibodies against collapsing response-mediating protein-5 (CRMP-5) were detected in the serum. Ophthalmological manifestations disappeared during a decrease in tumour size with treatment for the malignancy. This case report describes this rare case of anti-CRMP-5 antibody-positive paraneoplastic perioptic neuritis without neurological symptoms, showing that prompt diagnosis and timely treatment of the underlying tumour are crucial to prevent increased levels of autoantibodies and irreversible damage to the nervous system.

Lung Cancer Wherein Durvalumab Induced Both Anti-CRMP-5 Antibody-related Paraneoplastic Neurological Syndromes and Neurological Adverse Events.

A 68-year-old man with small-cell lung cancer developed anti-collapsin response-mediator protein (CRMP)-5 antibody-related paraneoplastic neurological syndrome (PNS) presenting with ataxia and chorea during treatment with durvalumab. As a result of steroid therapy, anti-CRMP-5 antibodies became negative, hyperintense lesions on brain magnetic resonance imaging disappeared, and neurological symptoms improved. After resuming durvalumab, he became unable to walk due to neurological adverse events (nAEs). There have been no reported cases manifesting PNSs and nAEs as a result of the same immune checkpoint inhibitors (ICIs) administered at different times. Resuming ICIs in patients diagnosed with PNSs should be performed with prudence.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes.

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.

A Longitudinal, Observational Analysis of Neuronal Injury Biomarkers in a Case Report of a Patient With Paraneoplastic Anti-CRMP5 Antibody-Associated Transverse Myelitis.

Biomarkers are needed to guide therapeutic decision making in autoimmune and paraneoplastic neurologic disorders. Here, we describe a case of paraneoplastic collapsing response-mediator protein-5 (CRMP5)-associated transverse myelitis (TM) where plasma neurofilament light (NfL) chain and glial fibrillary protein (GFAP) levels were observed over a 14-month clinical course, correlating with radiographical and clinical outcome measures in response to treatment. Blood and CSF samples obtained at diagnosis as well as 7 and 14 months into treatment. At the time of initial diagnosis, both plasma NfL (782.62 pg/ml) and GFAP (283.26 pg/ml) were significantly elevated. Initial treatment was with IV steroids and plasma exchange (PLEX) followed by neuroendocrine tumor removal, chemotherapy, and radiation. After initial improvement with chemotherapy, the patient experienced clinical worsening and transient elevation of plasma NfL (103.27 pg/ml and GFAP (211.58 pg/ml) levels. Whole body positron emission tomography PET scan did not demonstrate recurrence of malignancy. Repeat PLEX and rituximab induction resulted in improvements in patient function, neurologic exam, and plasma biomarker levels. To our knowledge, this is the first described longitudinal, prospective analysis of neuronal injury biomarkers and association of clinical treatment outcomes in CRMP5 myelitis. Our findings suggest that clinical improvement correlates with NfL and GFAP concentrations.

CRMP5 Antibodies-Diagnostic Challenges.

CRMP5-associated paraneoplastic neurological syndromes (PNS) are rare, and only few studies describe larger cohorts of patients with CRMP5 antibodies. We have included 24 patients with CRMP5 antibodies and compared clinical findings with diagnostic findings from two different line assays (Ravo and Euroimmun), staining of cerebellar sections and results of a newly developed cell-based assay for detection of CRMP5 antibodies, CRMP5-CBA. We found that peripheral neuropathy and cerebellar ataxia together with lung cancer were the most common diagnoses associated with CRMP5 antibodies. CRMP5-CBA was easy to perform, identified all relevant cases for CRMP5-associated PNS and is therefore a valuable add-on for verification of CRMP5 positivity in diagnosis of PNS.

Spontaneous Regression of Small Cell Lung Carcinoma and Associated Hemichorea.

The spontaneous regression (SR) of cancer is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and this phenomenon is rare in the case of small cell lung carcinoma (SCLC). We herein report an 83-year-old woman who presented with left-sided hemichorea associated with anti-SOX1 (SOX1-Ab) and -CV2/CRMP5 (CV2/CRMP5-Ab) antibodies with SR following a 7-year interval free of disease progression of SCLC. Hemichorea can present with the coexistence of anti-SOX1 and CV2/CRMP5-Ab with SR after a long interval free of SCLC. The immune response associated with these onco-neural antibodies may become independent of the original tumor trigger and remain active for many years.

[A case of paraneoplastic myelopathy associated with anti-CV2/CRMP5 antibodies with small-cell lung cancer].

A 66-year-old woman with small-cell lung cancer and cancer-associated retinopathy with anti-recoverin antibodies presented with subacute paraplegia associated with recurrence of lung cancer. Although a spinal cord MRI did not show any visible lesion, the neurological symptoms and cerebrospinal fluid findings indicated myelitis. Anti-CV2/CRMP5 antibodies were also positive and the patient was diagnosed with paraneoplastic myelopathy. After medication with prednisolone, her neurological symptoms improved and she survived over three years without recurrence of neurological symptoms. In general, paraneoplastic myelopathy is refractory against immunotherapy but in this case, immunotherapy was successful and resulted in long-term survival. We recommend examining anti-neuronal antibodies and choose and continue the appropriate immunotherapy.

Antibody Testing in Atypical Optic Neuritis.

Optic neuritis (ON) is a common manifestation of central nervous system demyelinating disorders such as multiple sclerosis (MS). The last two decades have seen increasing recognition of atypical optic neuritis syndromes, driven in large part by characterization of demyelinating diseases associated with antibodies to aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). Given their increased importance in the workup of ON, familiarity with serological tests for ON has become essential for ophthalmologists. This review will discuss technological aspects, performance, and clinical implications of serological tests for atypical ON.

Paraneoplastic autoimmunity and small-cell lung cancer: Neurological and serological accompaniments.

Paraneoplastic neurological autoimmunity is often associated with small-cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC-predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%; the median age at diagnosis was 64 years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti-neuronal nuclear antibody-type 1, voltage-gated calcium channel (VGCC)-N-type, VGCC-P/Q-type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR); while the most common in patients without neurological manifestations were: GAD65, muscle-AChR, and VGCC-P/Q-type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody-positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited-stage disease at diagnosis.