Chapter 52 - Neuromuscular complications

Abstract

Neuromuscular complications are common in patients with cancer. Their occurrence depends on several factors, such as the type of malignancy, tumor type, time course of the malignancy, and different types of treatment, such as surgery, radiotherapy, chemotherapy, or combinations of these. Miscellaneous other conditions, such as metabolic, paraneoplastic, and infectious causes of neuromuscular dysfunction, occur. In addition, tumor cachexia is important, with loss of muscle mass a frequent sign in cancer. The peripheral nervous system consists of cranial nerves, nerve roots, the nerve plexus, peripheral nerves (either as focal mononeuropathies or polyneuropathies), neuromuscular transmission, and muscle. Conventionally, motor neuron disease and variants are also considered in this context. The distribution of symptoms and signs varies. Focal and asymmetrical symptoms and signs point to a focal lesion, which may be caused by the tumor or its metastases, and also by treatment such as surgery or radiotherapy. The most common distribution is bilateral and symmetrical, as in neuropathies and myopathies, and most neuromuscular transmission disorders. Pain is often caused by lesions of the neuromuscular system, and can be a localizing sign; pain strategies against neuropathic pain are needed. The neurologist seeing patients with neuromuscular symptoms in a neuro-oncological setting has several roles: the precise localization of the focal lesion of the peripheral nervous system, the extent of tumor burden on the peripheral nervous system, and, sometimes, the initial detection of a tumor in paraneoplastic syndromes. If patients develop symptoms during treatment, estimation of the extent of neurotoxicity, which can be a dose-limiting factor for chemotherapy and also some biological medications, is an issue. Cranial nerve symptoms and signs, occurring either alone or multiple, are frequent in oncology patients. Peripheral nerve lesions occur at several sites inside the skull, at their exit from the skull, and in the neck or thorax region. Nerve roots are frequently affected in patients with cancer. In the majority, this is due to vertebral column metastasis, less often by meningeal involvement. The cervical and brachial plexi are the sites of local metastasis or infiltration from adjacent tumors such as lung cancer, breast cancer, or lymphoma. Local recurrence of tumors, less frequently sequelae of radiotherapy, can cause dysfunction of the sacral plexus, whereas the lumbar plexus is less frequently involved. Individual peripheral nerves can be damaged at several sites. The most frequent type of lesion is therapy related (surgery, pressure, malpositioning); neoplastic, toxic, and other causes are rare. Several types of polyneuropathy exist: paraneoplastic neuropathies can appear before the onset of cancer or may lead to the detection of cancer. The most frequent types of neuropathy in patients with cancer are chemotherapy-induced neuropathies, which may be a dose-limiting factor for treatment. Other causes of neuropathy, such as metabolic derangements, infections, or direct neoplastic involvements, are infrequent. Myasthenia gravis can be considered to be a paraneoplastic syndrome for thymoma only. Lambert–Eaton myasthenic syndrome is a presynaptic disorder affecting the cholinergic motor and autonomic synapses. About half of the cases are paraneoplastic, most frequently associated with small-cell lung cancer. Myopathies occur at various stages of tumor disease. They may be the presenting sign of a tumor disease like inflammatory myopathies, such as dermatomyositis or polymyositis, or appear during tumor treatment, such as metabolic or toxic myopathy, or in the late stages of cancer, such as cachexia. In clinical practice, direct involvement of the peripheral nervous system by cancer is as important as systemic effects on the peripheral nerve structures. For some conditions, such as tumor cachexia, neuropathies in advanced cancer, or in terminally ill patients, similar mechanisms can be suspected, which also occur in severe systemic non-neoplastic diseases such as chronic infections; a common pathway of pathogenesis can be suspected.