It is not surprising that weakness in various patterns and degrees is a feature of almost all neuropathies. The degree of weakness is proportional to the number of axons or motor neurons affected. Polyneuropathies that are the result of axonal damage are characterized foremost by a relatively symmetric distribution of weakness that is, moreover, distal because the pathologic changes begin in the far distal parts of the largest and longest nerves and advance along the affected fibers toward their nerve cell bodies (dying-back neuropathy, or “distal axonopathy”). The muscles of the feet and legs are typically affected earlier and more severely than those of the hands and forearms. In milder forms of axonal disease, only the feet and lower legs are involved. Truncal and cranial muscles are usually the last to yield, and then only in severe cases. This represents the “length-dependent” pattern that is typical of axonal degeneration. The nutritional, metabolic, and toxic neuropathies assume this predominantly distal “axonal” pattern. An exception is porphyria, an axonal process in which there may be mainly proximal weakness. By contrast, in demyelinating polyneuropathies, the multifocal nature of lesions and blockage of electrical conduction often leads to weakness of proximal limb and facial muscles before or at the same time as distal parts are affected.
Another pattern of neuropathic weakness is one in which all the muscles of the limbs, trunk, and neck are involved almost simultaneously, often including respiratory paralysis, therefore making it impossible to determine if the axons or myelin, or both, have been damaged. The best characterized of these processes is the Guillain-Barré syndrome (GBS). Less common causes of generalized paralysis include diphtheria, tick paralysis, and certain toxic polyneuropathies. Fatalities, when they occur, are usually a result of respiratory failure.
A predominantly bibrachial paralysis is an unusual presentation of neuropathic disease but may occur in the inflammatory-demyelinating polyneuropathies, as well as in Sjögren syndrome, chronic immune or paraneoplastic neuropathies, lead neuropathy, Tangier disease, and in a familial type of brachial neuritis. (A more frequent cause of bibrachial palsy is disease of the motor neurons themselves namely, motor system disease, or a lesion placed centrally in the cervical cord that damages these same neurons.) Paraparesis is not typical of the generalized polyneuropathies, but it is observed with infections and inflammations of the cauda equina, as occurs with Lyme disease, cytomegalovirus, herpes simplex, and with neoplastic infiltration of the nerve roots. Bifacial and other cranial nerve paralyses are likely to occur in GBS, neoplastic invasion, with connective tissue diseases, HIV and herpes virus infection, sarcoidosis, Lyme disease, or one of the rare metabolic neuropathies (e.g., Refsum, Bassen-Kornzweig, Tangier, and Riley-Day). These are discussed in Chap. 44 on diseases of the cranial nerves and in respective chapters on infections and metabolic diseases of the nervous system.