Generalized peripheral neuropathy
Anita Craig and James K. Richardson
Introduction
Peripheral nerve disorders are common in the elderly and have significant impact on their function and quality of life. It is also important to recognize the impact of underlying peripheral neuropathy (PN) when rehabilitating the elderly for other conditions. Approximately 10% of Americans over the age of 60 have PN as a result of diabetes and another 10% have PN due to other causes, with a prevalence of PN of about 20% in the older American population (Richardson & Ashton-Miller, 1996). The prevalence of PN in the elderly requiring rehabilitation is undoubtedly much higher. This chapter will address recognition and treatment strategies to successfully rehabilitate elderly patients with functionally significant generalized PN.
Causes of peripheral neuropathy in the elderly
PN can be caused by a number of conditions that are especially common in the older population. Certainly the most common cause is diabetic PN (George & Twomey, 1986), but other etiologies such as alcoholism, renal disease, thyroid disease and neoplasm are commonly encountered (Box 32.1). In patients referred for subspecialty evaluation of PN, an underlying cause cannot be determined in 10–23% of cases (Wolfe & Barohn, 1998) and idiopathic PN is more common in older populations, even when comparing those younger than 80 to those greater than 80 years old (Verghese et al., 2001).
A number of pharmaceutical agents can cause neuropathies. Many agents used in the treatment of cancer can induce severe neuropathies and those neuropathies can be a treatment-limiting side-effect. General chemotherapy-induced adverse effects are more common in the elderly; however, in the limited studies that have evaluated common therapeutic agents, pacititaxel and cisplatin-based chemotherapy, elderly patients do not have a greater risk for developing PN, nor do they demonstrate greater severity of PN. However, given the greater number of elderly patients undergoing cancer treatment, chemotherapy-induced PN is an important entity, occurring in up to 30–40% of patients undergoing chemotherapy. Onset of PN may be acute or subacute, and may present days to months after initiation of treatment. Sometimes signs and symptoms appear or progress for up to 2 months after cessation of the agent, the so called ‘coasting phenomenon’ (Guitiérrez-Guitiérrez et al., 2010). Reduction in dose, slower infusion rates, or longer periods between doses may bring improvement, however sometimes cessation of treatment is required. Often symptoms of PN will improve, but in some cases recovery can be incomplete. A number of other non-chemotherapeutic drugs can cause PN. Because the elderly tend to be on multiple pharmaceuticals it is important to scrutinize the medication list of any elderly patient presenting with signs of PN (Box 32.2).
Recognizing a generalized peripheral neuropathy
PNs can be characterized by the type of nerve fibers affected, whether they affect the nerve axon or the myelin, and the pattern of distribution of the affected nerves. The majority of PNs are diffuse and symmetrical in distribution; however, many vasculitic disorders present with asymmetrical or multifocal neuropathies (Craig & Richardson, 2003). Neuropathies affecting somatic or autonomic small fibers can be difficult to diagnose as they can present with profound neuropathic pain but have relatively normal physical and electrodiagnostic examinations (Hoitsma et al., 2004).
Neuropathic processes generally affect the nerve in a length-dependent manner, with longer nerves being more susceptible. Because lower extremities are longer than upper extremities and because sensory nerves are longer than motor nerves (as a result of the former’s intraspinal dendritic processes), distal lower extremity sensory function is the first and most severely affected in diffuse PN, followed by distal lower extremity motor function, distal upper extremity sensory function, and lastly distal upper extremity motor function. In addition, nerves that are more vulnerable to compressive neuropathies, such as the median and peroneal (fibular) nerves, are more susceptible to injury in those already compromised by PN.
Patients’ historical presentations can be quite variable, due to individual insight into their PN symptoms, as well as rapidity and acuity of onset. Many patients are acutely aware of their numbness and pain, whereas others note only vague sensory abnormalities such as a sensation of walking on pillows or simply that they have to be more careful with activities involving balance. When pain or numbness is apparent to the patient, it is generally noted to be most profound in the forefoot and lessen proximally. In the upper extremities, if symptoms are present they too will follow in a distal to proximal gradient. Often, however, upper extremity symptoms will manifest as difficulty performing fine motor tasks such as buttoning or picking up small objects without using visual feedback. Loss of motor strength is often not present, but in more severe disease foot drop or loss of hand dexterity may develop. Balance problems are often present, with insidious need to touch something when walking on uneven surfaces or in low lighting, as well as difficulty climbing stairs without the use of a railing. In predominantly small fiber neuropathies severe pain can be a prominent feature. Autonomic symptoms may be present, including increased or decreased sweating, dry eyes, erectile dysfunction, gastroparesis and skin temperature changes. Cardiovascular involvement limits activity tolerance and increases risk of sudden death and myocardial ischemia (Boulton et al., 2005). Clinically significant orthostatic hypotension is of particular concern in older patients given the association between postural hypotension and falls.
On physical examination, there is a loss of sensory function in a distal-to-proximal gradient. Multiple sensory modalities should be assessed. Vibratory sensation is particularly sensitive for large fiber neuropathies. This is best evaluated with a 128 Hz tuning fork maximally struck and placed at the base of the great toe, the malleolus, and the tibial tuberosity. Accuracy of the test may be improved by first familiarizing the patient with the vibratory stimulus at the clavicle. The number of seconds that the patient can perceive the vibration at each location is recorded. In PN the number of seconds that the vibration is felt increases proximally. If the patient is able to perceive the vibration for greater than 10 seconds at the great toe, PN is absent; if the sensation is present for less than 10 seconds at the malleolus, PN is likely to be present. Proprioception is also a good assessment of large fiber sensory function. This is tested by assessing the patient’s ability to perceive 8–10 small (1 cm) movements at the great toe. The inability to identify correctly at least 8–10 movements has been correlated with decreased ankle inversion/eversion proprioception (Vanden Bosch et al., 1995). Light touch using a 10-guage monofilament and pinprick will also reveal sensory loss in a distal to proximal gradient. In a patient with a purely small fiber neuropathy pinprick sensation may be decreased with relatively spared vibratory sensation.
Muscle stretch reflexes are affected, with Achilles tendon reflexes almost uniformly lost in PN, and the patellar and internal hamstring reflexes to a lesser degree. The Achilles reflexes can be obtained either with direct percussion or by the planter strike technique, which may be more reliably obtained in the older population (O’Keefe et al., 1994). Absence of Achilles tendon reflex, with or without facilitation, the inability to perceive at least 8–10 great toe movements, and the loss of vibratory sensation within 8 seconds are predictive of electrodiagnostically significant PN in older populations (Richardson, 2002).
Deficits of motor function can be seen in a distal to proximal gradient as well. Early motor strength loss may be recognized by easy fatigability; therefore, detection of subtle weakness may be improved by testing a muscle with multiple resistance maneuvers (McComas et al., 1995). The intrinsic musculature of the foot is commonly atrophied in PN, which cause changes in the architecture of the foot, with extension of the metatarsophalangeal joints in extension and interphalangeal joints in flexion (hammer toes). Toes move minimally or only in a stiff gross manner. In more advanced PN the anterior compartment, and to a lesser degree the posterior compartment, leg muscles weaken and atrophy. When PN has progressed to this point usually the intrinsic muscles of the hand become involved. Gross motor function is also affected. Patients may have a positive Romberg’s sign, wherein the patient is stable standing with feet together when eyes are open, but unstable with eyes closed. This suggests a deficit in somatosensory input and an excessive reliance upon vision for balance. A positive Romberg sign suggests a relatively severe PN; however, many patients with functionally significant PN demonstrate a negative Romberg’s sign. A more sensitive test of balance impairment due to PN is the assessment of unipedal stance time. If the patient can balance on one foot for 10 seconds or more (the best of three tries on the foot of their choice), functionally significant PN is not likely to be present. If the patient can balance on one foot for only 3–4 seconds or less, then the PN is functionally significant. It should be noted that the unipedal stance test is not used to identify PN, but rather to determine the extent of loss of balance caused by the PN once it has been identified by the other elements of the clinical examination (Hurvitz et al., 2000). Table 32.1 lists clinical characteristics of a patient with functionally significant PN.
Table 32.1
Clinical findings in functionally significant peripheral neuropathy
Test or Condition | PN Functionally Significant |
Vibratory sensation with 128 Hz tuning fork | Obvious gradient Perceived at malleolus<5–6 seconds |
Foot deformity and callouses | Present |
Achilles reflex | Absent |
Position sense at the great toe | <8 out of 10 correct responses |
Unipedal stance | <5 seconds on each of three attempts |
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