Paraneoplastic Neuropathies: What's New Since the 2004 Recommended Diagnostic Criteria

Abstract

The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded. The antibodies associated with PNS are commonly classified as onconeural (intracellular) and neuronal surface antibodies (NSAbs). Since 2004, the number of antibodies and the associated tumors has increased. Knowledge has grown on the mechanisms underlying the neuropathies observed in lymphoma, paraproteinemia, and multiple myeloma. Moreover, other unrevealed mechanisms underpin sensorimotor neuropathies and late-stage neuropathies, where patients in advanced stages of cancer—often associated with weight loss—experience some mild sensorimotor neuropathy, without concomitant use of neurotoxic drugs. The spectrum of paraneoplastic neuropathies has increased to encompass motor neuropathies, small fiber neuropathies, and autonomic and nerve hyperexcitability syndromes. In addition, also focal neuropathies, as cranial nerves, plexopathies, and mononeuropathies, are considered in some cases to be of paraneoplastic origin. A key differential diagnosis for paraneoplastic neuropathy, during the course of cancer disease (the rare occurrence of a PNS), is chemotherapy-induced peripheral neuropathy (CIPN). Today, novel complications that also involve the peripheral nervous system are emerging from novel anti-cancer therapies, as targeted and immune checkpoint inhibitor (ICH) treatment. Therapeutic options are categorized into causal and symptomatic. Causal treatments anecdotally mention tumor removal. Immunomodulation is sometimes performed for immune-mediated conditions but is still far from constituting evidence. Symptomatic treatment must always be considered, consisting of both drug therapy (e.g., pain) and attempts to treat disability and neuropathic pain.

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

“…Neurodegeneration is a recognised feature of paraneoplastic disease. It cannot be overemphasised how important the newly described association of increased blood Nf levels in this context might be (Mizenko et al, 2021; Zoccarato et al, 2021). This is because a challenge for neuro‐immunology remains the limited number of validated paraneoplastic antibodies, but frequently a high clinical suspicion of an association remains in individuals who do not harbour any of the known paraneoplastic antibodies.…”

Sigma Antagonists for Treatment of Neuropathic Pain Syndromes in Cancer Patients: A Narrative Review

“…Subacute sensory neuronopathy is the most common type of peripheral paraneoplastic neurological syndrome [43]. Other syndromes include sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathy, autonomic neuropathy, focal nerve lesions, and plexus nerve lesions [43]. Paraneoplastic neuropathy is associated with onconeural or intracellular antibodies or neuronal surface antibodies [43].…”

“…Other syndromes include sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathy, autonomic neuropathy, focal nerve lesions, and plexus nerve lesions [43]. Paraneoplastic neuropathy is associated with onconeural or intracellular antibodies or neuronal surface antibodies [43]. In late-stage cancer, patients may experience sensory-motor neuropathy, a relatively mild condition distinct from CIPN [43].…”

“…Paraneoplastic neuropathy is associated with onconeural or intracellular antibodies or neuronal surface antibodies [43]. In late-stage cancer, patients may experience sensory-motor neuropathy, a relatively mild condition distinct from CIPN [43]. There are multiple mechanisms underlying these various paraneoplastic neuropathies, including the autoimmune hypothesis that maintains that the body's immune response to cancer mounts a defense using antibodies against neural antigens [43].…”

Case Report: Hematologic Recovery Following Stereotactic Ablative Radiotherapy in a Patient With Early-Stage Non-Small Cell Lung Cancer and Paraneoplastic Myelofibrosis

“…Small cohort studies have reported the incidence of paraneoplastic syndromes to be 11%–16% in lung cancer patients ( 2 – 4 ). Paraneoplastic disorders are diagnoses of exclusion; however, diagnostic criteria have been developed for some syndromes with available specialized testing ( 5 , 6 ). These syndromes occur due to two main mechanisms: the generation of physiologic antibodies directed against a tumor epitope that cross reacts with normal tissue (neurologic paraneoplastic syndromes) and abhorrent production of a functional soluble factor ectopically produced by tumor cells (endocrine paraneoplastic syndromes) ( 7 ).…”