Summary Since the discovery of the first clinically relevant antineuronal antibody specific for a paraneoplastic aetiology in 1985, the number of such reactivities has grown at a rate of about one per year. Clinicians can now diagnose a paraneoplastic syndrome much more easily. This ability is especially important because, typically, the neurological symptoms occur before the cancer is diagnosed. Early tumour diagnosis is essential, because effective treatment of the cancer still seems to be the most efficient treatment option for the neurological symptoms. Immunomodulatory therapy should, nevertheless, be initiated as early as possible and seems especially helpful for peripheral syndromes and limbic encephalitis. The recent fundamental advances in understanding of the autoimmune pathology of these disorders, especially the role of cytotoxic T cells, should eventually lead to more effective treatment options.

Paraneoplastic neurological syndromes: an update on diagnosis, pathogenesis, and therapy

Background. Paclitaxel-induced peripheral neuropathy (PN) may be severeand dose-limiting at initial doses ≥ 275 mg/M2, but itsneurotoxicity at doses ≤ 250 mg/M2 has been incompletelycharacterized. The purposes of this study were to characterize and quantifypaclitaxel-induced PN and to determine the utility of quantitative sensorytesting (QST). Methods. We prospectively examined clinically and by QST 37women with metastatic breast cancer, treated with paclitaxel (200–250mg/m2) (average number of cycles = 7.3 over an average of 20.1weeks). QST included thermal threshold (TT) and vibration threshold (VT).Results. Paresthesias appeared in 31 (84%) patients after an averageof 1.7 cycles and an average cumulative dose of 371.5 mg/M2. Symptomsoccurred after the first or second dose in 26 (84%) patients and thenstabilized in 10 (32%), improved in 13 (42%) despite continuedtreatment, resolved completely in 6 (19%), and were progressive in 2(7%). Paclitaxel was discontinued in only 1 (3%) patientbecause of neurotoxicity and no patient required dose reduction because ofPN. Thirty-six (97%) developed signs of PN. The most sensitive QSTwas great toe VT but QST did not predict or identify subclinical PN in anypatient. Neurologic syndromes other than PN developed in 12 (32%)patients, and 7 were due to metastatic cancer. Conclusions. 1)Paclitaxel-induced PN is mostly sensory, and begins after the first orsecond dose. At these doses the neuropathy is mild, and rarelydose-limiting. 2) QST quantified the neuropathy but was less sensitive thanthe clinical examination. 3) Knowledge of the features of paclitaxel's PNallows it to be differentiated from other neurologic syndromes which maysignal tumor progression.

Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing.

Objective—When to suspect a paraneoplastic disorder is a puzzling problem that has not recently been studied in a large series of patients referred for peripheral neuropathy. Methods—From 422 consecutive patients with peripheral neuropathy, 26 were analysed who concomitantly had carcinoma but no tumorous infiltration, drug toxicity, or cachexia. Their clinical, pathological, and electrophysiological data were analysed according to the presence of anti-onconeural antibodies, the latency between presentation and cancer diagnosis, and the incidence of carcinoma in the corresponding types of neuropathy of the population of 422 patients. Results—Seven patients (group I) had anti-onconeural antibodies (six anti-Hu, one anti-CV2) and 19 did not (groups IIA and B). In group I, subacute sensory neuropathy (SSN) was the most frequent but other neuropathies including demyelinating neuropathies were present. Patients in group II A had a short latency (mean 7.88 months), and a rapidly and usually severe neuropathy which corresponded in 11/14 to an established inflammatory disorder including neuropathy with encephalomyelitis, mononeuritis multiplex, and acute or chronic inflammatory demyelinating polyneuropathy (CIDP). Patients in group IIB had a long latency (mean 8.4 years) and a very chronic disorder corresponding in four of five to an axonal noninflammatory polyneuropathy. In this population, the incidence of carcinoma occurring with a short latency was 47% in sensory neuronopathy, 1.7% in GuillainBarre syndrome, 10% in mononeuritis multiplex and CIDP, and 4.5% in axonal polyneuropathy. Conclusions—Paraneoplastic neuropathies associated with carcinoma are heterogeneous disorders. Neuropathies occurring with a long latency with tumours probably resulted from a coincidental association. Neuropathies which occurred within a few years of the tumour evolved rapidly and corresponded mostly to inflammatory disorders. As dysimmune neuropathies are probably paraneoplastic in a limited number of cases, patients with these disorders should probably not be investigated systematically for carcinoma in the absence of antionconeural antibodies, except when the neuropathy is associated with encephalomyelitis and probably with vasculitis. Questions remain concerning CIDP. (J Neurol Neurosurg Psychiatry 1999;67:7‐14)

https://jnnp.bmj.com/content/jnnp/67/1/7.full.pdf

Carcinoma associated paraneoplastic peripheral neuropathies in patients with and without anti-onconeural antibodies

Spectrum of paraneoplastic neurologic disorders in women with breast and gynecologic cancer.

Patients with cancer experience many acute and chronic pain syndromes, the identification of which may be helpful in the assessment and treatment of pain. Syndromes are defined by the relationship with the cancer, the pain pathophysiology, and the clinical characteristics of the pain. The most common pain syndromes are directly related to the tumor; bone pain syndromes are most common. Neuropathic pain syndromes may involve cancer-related injury at any level of the peripheral nervous system. Treatment-related pain syndromes may follow any type of antineoplastic therapy. This article reviews the phenomenology of common acute and chronic cancer pain syndromes.

Cancer Pain Syndromes

Paraneoplastic sensorimotor neuropathy occurs in association with many different types of cancer. The clinical findings are heterogeneous, and the pathogenesis is unknown. We have encountered 9 women with breast cancer and shared neurological features that suggest a distinct paraneoplastic syndrome. The syndrome is characterized by upper and lower extremity paresthesias and numbness, itching, muscle weakness and cramps, and in some, radicular symptoms and signs. Serum and CSF inflammatory changes suggested an immune pathogenesis but none had detectable antibodies directed at nervous system elements. Six patients presented with neuropathy 2 months to 8 years before the discovery of the breast cancer. In 7 the neoplastic disease was localized to the breast and axillary lymph nodes. The neurologic course was chronic in all, and while symptoms were annoying, disability was minimal until late. One improved transiently with plasmapheresis, and three had mild transient improvement with treatment of the cancer. Recognition of this paraneoplastic syndrome may forewarn the physician of an underlying breast malignancy.

Kendra Peterson

Papers

Paraneoplastic sensorimotor neuropathy associated with breast cancer.