Peripheral neuropathies II: Clinical syndromes

Distal symmetrical neuropathy

accounts for 75% of diabetic neuropathies. It occurs more commonly in diabetics with poor glycaemic control and its frequency can be reduced (but not abolished) by tight control. This is predominantly sensory, with parallel autonomic involvement. Some patients have painful paraesthesiae; others simply have numbness. The sensory loss combined with poor circulation can lead to foot ulcers and, on occasion, neuropathic arthropathies (Charcot’s joints). Treatment is improved glycaemic control and symptomatic support.

Asymmetrical proximal neuropathy

has a whole range of synonyms, including diabetic amyotrophy or lumbosacral radiculoplexopathy. This presents with asymmetrical painful proximal weakness of the proximal muscles in the legs. It usually occurs in patients with non-insulin-dependent diabetes who have poor glycaemic control and have lost weight. Most patients improve once started on insulin with improved control.

Autonomic neuropathy

can occur in association with sensory neuropathy or in relative isolation. The whole range of autonomic failure occurs with postural hypotension, a resting tachycardia, delayed gastric emptying with nausea and vomiting, intermittent diarrhoea and constipation, loss of bladder tone with retention and overflow, impotence and disordered sweating. Treatment is symptomatic (p. 114).

Mononeuropathies and radiculopathies

Isolated peripheral nerve lesions, particularly carpal tunnel, are more common in diabetics. Isolated thoracic radiculopathies also occur and can mimic intra-abdominal disease.

Nutritional deficiencies

Patients with nutritional deficiencies (Box 1, p. 103) often have more than one vitamin deficiency. This can be associated with other problems such as alcoholism, in which the major factor is nutritional deficiency. The clinical presentation is of a painful, predominantly sensory distal symmetrical axonal neuropathy. Treatment is with appropriate vitamins. Vitamin B12 deficiency is more complicated because there is often an associated myelopathy (subacute combined degeneration of the cord). In the full syndrome, there is a progressive paraparesis, with loss of proprioception, prominent distal paraesthesiae and associated dementia. Vitamin B12 measurement and the demonstration of antiparietal cell antibodies and malabsorption of vitamin B12 give a diagnosis.

Toxic neuropathies

Most toxic neuropathies produce a sensorimotor distal symmetrical peripheral neuropathy. Exceptions include lead, which produces a predominantly motor neuropathy. Other signs may point to a particular toxin, for example alopecia in thallium poisoning.

Neuropathies associated with neoplasias

Neoplasia can involve the peripheral nerves directly, by nerve invasion or malignant meningitis, or indirectly as a paraneoplastic phenomenon. Direct involvement of the nerves occurs more commonly in lymphoma. Paraneoplastic neuropathies are usually symmetrical distal sensorimotor axonal neuropathies. They occur in about 1% of cancer patients. The whole range of neuropathies are seen as a paraneoplastic phenomenon, though are much rarer.

Infective neuropathies

Leprosy is estimated to affect 12 million people in the developing world. The pattern of peripheral nerve involvement depends on the type of leprosy. In tuberculoid leprosy, where the host reaction predominates with few organisms (paucibacillary), there is marked nerve thickening and a mononeuritis multiplex presentation. In lepromatous leprosy, with poor host reaction and high number of organisms (multibacillary), there is superficial sensory neuritis, particularly affecting the cooler parts of the body. Typically there are areas of anaesthetic depigmented skin. Intermediate patterns are seen. Treatment is with dapsone and rifampicin. Steroids may also be required to prevent host-mediated tissue damage. Lyme disease, caused by Borrelia burgdorferi, is endemic in parts of the USA. Early involvement can affect the facial nerve, radiculopathies or a lymphocytic meningitis. Later, patients can present with a distal symmetrical neuropathy.

AIDS

Several different patterns of neuropathies are associated with HIV infection and AIDS. These are discussed on page 101.

Inherited neuropathies

These neuropathies present as distal symmetrical neuropathies. They are very insidious in onset and there are usually relatively minor symptoms with much more marked signs. In particular, positive sensory symptoms such as paraesthesiae are unusual. Signs such as pes cavus, indicating that abnormalities were present before fusion of the bony epiphyses, may also be found.

Charcot–Marie–Tooth (CMT) disease is the most commonly inherited neuropathy. This was previously referred to as hereditary motor and sensory neuropathy (HMSN). The classification is primarily into the demyelinating form (CMT type 1) and the axonal form (CMT type 2). CMT 1 usually presents before age 30 years and is associated with peripheral nerve hypertrophy. CMT 2 can present later and patients are usually less severely affected. In both forms of CMT there is a preferential atrophy of the peroneal muscles to produce the ‘inverted champagne bottle’ legs (Fig. 1). The genetic basis for some of these has been elucidated (Table 2). There are some forms of CMT 1 and all forms of CMT 2 in which the genetic basis has not been established. Interestingly, a much rarer condition of hereditary liability to pressure palsies has been found to be due to different mutations in the same gene as CMT 1a.

Fig. 1 Distal wasting typical of Charcot–Marie–Tooth disease.

Rarer hereditary neuropathies

The genetic basis for most forms of familial amyloid polyneuropathies has been determined. These sensorimotor axonal neuropathies with autonomic involvement result from mutations in transthyretin or gelosolin, which result in deposition of amyloid in several tissues, including peripheral nerve. DNA analysis is now the diagnostic method of choice in these patients.