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

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.

Clinical and electrophysiological features of peripheral neuropathy in older patients with lung carcinoma

Background/Aim. Peripheral nervous system affection in people with lung cancer is commonly associated with paraneoplastic neuropathy. However, clinical studies evaluating the frequency, clinical, and electrophysiological characteristics of peripheral neuropathies which are not related to onconeuronal antibodies, in this, on average, older population of patients, are very rare. The aim of this study was to define the frequency, as well as clinical and electrophysiological characteristics of idiopathic neuropathies in patients suffering from lung cancer in early stages of the diseases. Methods. Clinical and electrophysiological data of 105 elderly subjects (age 63.4 ? 7.8 years) suffering from lung carcinoma who underwent extensive neurological and electrophysiological evaluation (nerve conduction studies) between 2013?2018 were estimated. Exclusion criteria were ?classical? paraneoplastic neurological syndromes with onconeuronal antibodies present, as well as patients with typical known causes of peripheral neuropathy (e.g. diabetes, alcoholism, chronic renal insufficiency, vitamin deficiencies, etc.). Results. There were 19.1% patients with clinically manifest neuropathies, with additional 37.1% patients with only electrophysiological abnormalities. The most frequent pathophysiological pattern was axonal pathology (71.2%) with predominantly distal and symmetrical distribution (86.4%). Conclusion. Patients with lung cancer in the early stages of the disease show a high incidence of clinically minor damage of the nerves, according to the pattern of chronic sensomotor distal neuropathy, with predominance of axonal damage. These findings underline the importance of a detailed clinical and electrophysiological evaluation in this category of patients who are without the typical etiological factors for peripheral neuropathies since, during cancer therapy, patients undergo a series of treatments with additional risk for the development/aggravation of neuropathy.

A 59-Year-Old Man with Progressive Difficulties with Balance and Weight Loss

Paraneoplastic peripheral neuropathies are rare but important to consider in the evaluation of subacute peripheral neuropathy. The clinical and electrophysiological pattern as well as antibody evaluation is essential order to identify a specific paraneoplastic neuropathy. A positive paraneoplastic antibody in the cerebral spinal fluid is not required to make the diagnosis, but is helpful to consider if the serum antibodies are negative. This chapter emphasizes the importance of differential diagnosis and work up. Treatment options are described. Immunotherapy is also an important consideration.

Peripheral neuropathy

Disorders of peripheral nerves are one of the most common neurological problems today and include the increasing number of people with diabetes worldwide and those with inherited neuropathy, toxic neuropathy, carpal tunnel syndrome, inflammatory neuropathy, radiculopathies, and, increasingly, traumatic nerve injuries. Neuropathic pain is a growing problem without solution. In this chapter, ten landmark papers in peripheral nerve disorders have been selected, covering Bell’s palsy, Charcot-Marie-Tooth disease, carpal tunnel syndrome, paraneoplastic neuropathy, neurophysiology, familial amyloid polyneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, toxic neuropathy, diabetic neuropathy, and Guillain–Barré syndrome. These important papers set the stage for many subsequent advances in the field but may be forgotten now, so they are brought to the reader’s attention.