Evaluation of the Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes in China.

Background: Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China. Methods: An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored. Results: The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria. Conclusion: The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.

"Non-classical" paraneoplastic neurological syndromes associated with well-characterized antineuronal antibodies as compared to "classical" syndromes - More frequent than expected.

OBJECTIVES: Paraneoplastic neurological syndromes (PNSs) are rare disorders in association with cancer and sub-divided into "classical" and "non-classical" syndromes according to a 2004 consensus paper proposed by a panel of PNS experts. "Classical" PNSs are regarded to account for the vast majority of cases. However, systematic reports on clinical PNS manifestations are rare. Therefore, we analyzed the spectrum of PNS in our clinic. METHODS: We retrospectively investigated medical records from consecutive patients diagnosed with definite PNS and serological evidence of well-characterized onconeural antibodies (anti-Hu, Yo, Ri, CV2/CRMP5, Ma1, Ma2, and amphiphysin) analyzed between 1991 and 2014 in our clinic. RESULTS: Of the 50 patients identified with onconeural antibody-positive PNS, 28 patients (56.0%) had "classical" PNS, and 22 (44.0%) "non-classical" PNS. Subacute cerebellar degeneration was the most frequent "classical" syndrome, brainstem encephalitis and subacute sensorimotor neuronopathy the most frequent "non-classical" syndromes. Anti-Hu antibodies were most frequent in both groups. 86.1% of patients developed neurological symptoms before the cancer was known. No differences between "classical" and "non-classical" syndromes were detected with respect to age, tumor entities and median time to diagnosis. However, whereas most patients with "classical" syndromes were females, there was no gender predominance in patients with "non-classical" PNS and the latter had significantly more frequent peripheral neurological syndromes. CONCLUSIONS: The so-called "non-classical" PNSs in association with well-characterized onconeural antibodies were more common in our patient population than expected. Therefore, in neurological disorders of unclear etiology with a subacute onset and atypical presentation further diagnostic work-up including investigation of onconeural antibodies is necessary.

[Lambert-Eaton myasthenic syndrome, an immune pathology of neuromuscular junctions]. / Pathologie dysimmunitaire de la jonction neuro-musculaire : le syndrome de Lambert-Eaton.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder affecting neuromuscular junctions. LEMS has served as a model of paraneoplastic neurological syndromes and antitumoral immunity, shedding light on the pathological role of autoantibodies directed against synaptic targets. Autoantibodies associated with LEMS are directed against voltage-gated calcium channels (VGCC) present on nerve terminals of neuromuscular synapses. Anti-VGGC antibodies play a direct pathological role in LEMS by blocking VGCC and calcium entry during depolarisation. Nearly half of patients with LEMS have small-cell lung cancer (SCLC), which also expresses VGCC. Diagnosis of LEMS frequently permits early detection and treatment of SCLC Knowledge of this syndrome has led to the discovery of a broad range of cancerous and non cancerous antibody-mediated neurological syndromes, and led to the concept of autoimmune synaptopathies.

Anti-SOX1 antibodies in patients with paraneoplastic and non-paraneoplastic neuropathy.

Anti-SOX1 antibodies have been described to be positive in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and, in a lower amount, in patients with anti-Hu positive paraneoplastic neurological syndromes, and with SCLC alone, respectively. We found 5/32 patients with paraneoplastic neuropathy and, surprisingly, 4/22 patients with neuropathy of unknown origin positive for anti-SOX1 antibodies, whereas no patient with inflammatory neuropathy and no healthy controls showed any reactivity (p=0.007). All patients with neuropathy of unknown origin where followed up for four years without diagnosis of a tumour so far. Anti-SOX1 antibodies are associated with paraneoplastic neuropathies and may define another group of non-paraneoplastic, immune-mediated neuropathies.

[Paraneoplastic neurological syndromes with reference to anti-neuronal autoantibodies].

Paraneoplastic neurological syndromes (PNS) are thought to be caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and nervous system. There are several clinical phenotypes in combinations with the neurological syndromes, origin of cancer and the specific autoantibodies. In most patients, the neurological disorder develops before the cancer becomes clinically overt together with autoantibodies. As these antibodies are associated with a restricted range of cancers, the presence of the antibodies requires physicians in charge to search the underlying cancers. The early cancer treatment and active immunotherapy tended to ameliorate the neurological symptoms, especially in those harboring antibodies against cell surface antigens like NMDAR. VGKC, VGCC. The group of PNS having antibodies against intracellular antigens might be caused via cytotoxic T cell activation.

[Paraneoplastic neurological syndromes]. / Syndromes neurologiques paranéoplasiques.

The classic paraneoplastic neurological syndromes include Lambert-Eaton myasthenic syndrome, limbic encephalitis, sensory neuronopathy, intestinal pseudo-obstruction, subacute cerebellar degeneration, encephalomyelitis, and dermatomyositis. Approximately ten onconeural antibodies that recognize cancer and the nervous system have been described in paraneoplastic neurological syndromes. These antibodies appear to be important diagnostic tools, even though they may not always be present. Deciding whether a given neurological picture is definitely or possibly paraneoplastic depends on the clinical syndrome, any association with onconeural antibodies, and the time elapsed between onset of neurological symptoms and the discovery of the cancer. Diagnosis of a classic paraneoplastic neurological syndrome or the discovery of onconeural antibodies mandates an active and persistent search for cancer, using new techniques such as fluorodeoxyglucose positron emission tomography. In patients with one of these syndromes, the best treatment of the neurological disease is often the diagnosis and early treatment of the cancer.

Paraneoplastic neurologic syndromes.

Cancer can affect the nervous system through many metastatic and nonmetastatic mechanisms, including side effects of cancer treatment, infections, coagulopathy, and metabolic or nutritional deficits. Paraneoplastic neurologic disorders (PND) are an extensive group of syndromes that cannot be explained by any of these complications and may affect any part of the nervous system. PND often develop before the presence of a cancer is known and their recognition may lead to the tumor diagnosis.

Paraneoplastic syndromes of the spinal cord, nerve, and muscle.

Cancer can affect the peripheral nervous system by non-metastatic, sometimes immune-mediated mechanisms. Recognition of these paraneoplastic syndromes is important because it can lead to the detection of the tumor, and also helps to avoid unnecessary studies to determine the cause of the neurologic symptoms in patients with cancer. Many paraneoplastic syndromes of the peripheral nervous system are not associated with serum antibodies that serve as markers of paraneoplasia. For this group of disorders the diagnosis depends on the clinician's index of suspicion and conventional electrophysiologic and laboratory tests. Treatment of the tumor, immunotherapy, or both may improve some of these syndromes. This review focuses on paraneoplastic syndromes of the spinal cord, peripheral nerve, and muscle.