Amyloid neuropathies

Abstract

Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis.

Figure 1

Examples of normal and reduced sural sensory responses obtained with surface electrodes by stimulating the nerve proximally in the calf and recording distally in the ankle. Reduced sural sensory responses are seen in many different neuropathies, including those due to amyloid.

Figure 2

Examples of normal and reduced peroneal motor responses obtained with surface electrodes by recording the extensor digitorum brevis muscle in the dorsum of the foot. In the reduced response (Fig. 2b) only a distal stimulation is performed because the response is very small. In the normal response (Fig. 2a) the peroneal nerve was stimulated at three different sites in the leg. Reduced motor responses may be seen in moderate to severe neuropathy.

Figure 3

Quantitative sudomotor axon test demonstrating normal sweat volume in the forearm (top trace), diminished sweating in the proximal and distal leg (middle traces), and near absent sweating in the foot. This is consistent with a length dependent neuropathic process.

Figure 4

(a) Normal hemodynamic responses to standardized Valsalva maneuver (forced exhalation to a pressure of 40 mmHg for 15 seconds). Blood pressure (red trace) falls due to decreased venous return, but soon begins to recover due to autonomically mediated compensatory responses including increased heart rate (top trace). (b) In the patient with autonomic neuropathy, heart rate does not increase during Valsalva maneuver and blood pressure drops precipitously.

Figure 5

(a) Normal heart rate variability (green trace) in response to paced deep breathing (blue trace). This reflex is mediated by the vagus nerve. (b) This figure demonstrates near absent heart rate variability in a patient with autonomic neuropathy.

Figure 6

Hemodynamic responses to upright tilt in a patient with autonomic neuropathy demonstrate orthostatic hypotension and lack of compensatory tachycardia.