The diabetic state can also affect single nerves (mononeuropathy), multiple nerves (mononeuropathy multiplex), or groups of nerve roots. These asymmetrical or focal neuropathies have a relatively rapid onset, and complete recovery is usual. This contrasts with chronic distal symmetrical neuropathy, where there is usually no improvement in symptoms 5 years after onset (36). Unlike chronic distal symmetrical neuropathy they are often unrelated to the presence of other diabetic complications (9,15,16). Asymmetrical neuropathies are more common in men and tend to predominantly affect older patients (52). A careful history is therefore mandatory in order to identify any associated symptoms that might point to another cause for the neuropathy. A vascular etiology has been suggested by virtue of the rapid onset of symptoms and the focal nature of the neuropathic syndromes (53).
Proximal Motor Neuropathy (Femoral Neuropathy, Amyotrophy, and Plexopathy)
The syndrome of progressive asymmetrical proximal leg weakness and atrophy was first described by Garland (54), who coined the term "diabetic amyotrophy." This condition has also been named as "proximal motor neuropathy," "femoral neuropathy" or "plexopathy." The patient presents with severe pain, which is felt deep in the thigh, but can sometimes be of burning quality and extend lower than the knee. The pain is usually continuous and often causes insomnia and depression (55). Both type 1 and type 2 patients more than the age of 50 are affected (54-57). There is an associated weight loss, which can sometimes be very severe, and can raise the possibility of an occult malignancy.
On examination there is profound wasting of the quadriceps with marked weakness in these muscle groups, although hip flexors and hip abductors can also be affected (58). Thigh adductors, glutei, and hamstring muscles may also be involved. The knee jerk is usually reduced or absent. The profound weakness can lead to difficulty from getting out of a low chair or climbing stairs. Sensory loss is unusual, and if present indicates a coexistent distal sensory neuropathy.
It is important to carefully exclude other causes of quadriceps wasting, such as nerve root and cauda equina lesions, and the possibility of occult malignancy causing proximal myopathy syndromes such as polymyocytis. Magnetic resonance imaging (MRI) of the lumbo-sacral spine is now mandatory in order to exclude focal nerve root intrapment and other pathologies. An erythrocyte sedimentation rate, an X-ray of the lumbar/sacral spine, a chest X-ray, and ultrasound of the abdomen may also be required. CSF protein is often elevated. Electrophysiological studies may demonstrate increased femoral nerve latency and active denervation of affected muscles.
The cause of diabetic proximal motor neuropathy is not known. It tends to occur within the background of diabetic distal symmetrical neuropathy (59). It has been suggested that the combination of focal features superimposed on diffuse peripheral neuropathy may suggest vascular damage to the femoral nerve roots, as a cause of this condition (60).
As in distal symmetrical neuropathy there is scarcity of prospective studies that have looked at the natural history of proximal motor neuropathy. Coppack and Watkins (55) have reported that pain usually starts to settle after about 3 months, and usually settles by 1 year, while the knee jerk is restored in 50% of the patients after 2 years. Recurrence on the other side is a rare event. Management is largely symptomatic and supportive. Patients should be encouraged and reassured that this condition is likely to resolve. There is still controversy as to whether the use of insulin therapy influences the natural history of this syndrome as there are no controlled trials. Some patients benefit from physiotherapy that involves extension exercises aimed at strengthening the quadriceps. The management of pain in proximal motor neuropathy is similar to that of chronic or acute distal symmetrical neuropathies (see Chapter 21).
Chronic Inflammatory Demyelinating Polyradiculopathy
Chronic inflammatory demyelinating polyradiculopathy (CIDP) occurs more commonly among patients with diabetes, creating diagnostic and management challenges (61). Patients with diabetes may develop clinical and electrodiagnostic features similar to that of CIDP (62). Clearly, it is vital to recognize these patients as unlike diabetic polyneuropathy, CIDP is treatable (63). One should particularly be alerted when an unusually severe, rapid, and progressive polyneuropathy develops in a diabetic patient.
Nerve conduction studies show features of demyelination. The presence of 3 of the following criteria for demyelination is required: partial motor nerve conduction block, reduced motor nerve conduction velocity, prolonged distal motor latencies, and prolonged F-wave latencies (64). Although, electrophysiological parameters are important, these alone cannot be entirely relied on to differentiate CIDP from diabetic polyneuropathy (65).
Most experts recommend CSF analysis in order to demonstrate the typical findings in this condition: increased protein and a normal or only slightly elevated cell count (63). However, spinal taps are not mandatory (63).
The diagnostic value of nerve biopsy, usually of the sural nerve has been debated recently. Some authorities assert that nerve biopsy is of no value (66), whereas others consider it essential for the diagnosis and management of upto 60% patients with CIDP (67). The diagnostic yield of sural nerve biopsies may be limited as the most prominent abnormalities may lie in the proximal segments of the nerve roots or in the motor nerves, which are areas not accessible to biopsy. Typical appearances include segmental demyelination and remyelination, anion bulbs, and inflammatory infiltrates, but these may also be found in diabetic polyneuropathy (68). A defining feature of CIDP not found in diabetic polyneuropathy is the presence of macrophages in biopsy specimens in association with demyelination (68).
Treatments for CIDP include intravenous immunoglobulin, plasma exchange, and corti-costeroids (63). Therapy should be started early in order to prevent continuing demyelina-tion and also as it results in rapid and significant reversal of neurological disability (69,70).
The most common cranial mononeuropathy is the third cranial nerve palsy. The patient presents with pain in the orbit, or sometimes with a frontal headache (53,71). There is typically ptosis and ophthalmoplegia, although the pupil is usually spared (72,73). Recovery occurs usually over three months. The clinical onset and time-scale for recovery, and the focal nature of the lesions on the third cranial nerve, on postmortem studies suggested an ischaemic etiology (53,74). It is important to exclude any other cause of third cranial nerve palsy (aneurysm or tumour) by computed tomography or MRI scanning, where the diagnosis is in doubt. Fourth, sixth, and seventh cranial nerve palsies have also been described in diabetic subjects, but the association with diabetes is not as strong as that with third cranial nerve palsy.
Truncal radiculopathy is well recognized to occur in diabetes. It is characterized by an acute onset pain in a dermatomal distribution over the thorax or the abdomen (75). The pain is usually asymmetrical, and can cause local bulging of the muscle (76). There may be patchy sensory loss detected by pin prick and light touch examination. It is important to exclude other causes of nerve root compression and occasionally, MRI of the spine may be required. Some patients presenting with abdominal pain have undergone unnecessary investigations, such as barium enema, colonoscopy, and even laparo-tomy, when the diagnosis could easily have been made by careful clinical history and examination. Recovery is usually the rule within several months, although symptoms can sometimes persist for a few years.
A number of nerves are vulnerable to pressure damage in diabetes. In the Rochester Diabetic Neuropathy Study, which was a population-based epidemiological study, Dyck et al. (77), found electrophysiological evidence of median nerve lesions at the wrist in about 30% of diabetic subjects, although the typical symptoms of carpel tunnel syndrome occurred in less than 10%. The patient typically has pain and paraesthesia in the hands, which sometimes radiate to the forearm and are particularly marked at night. In severe cases clinical examination may reveal a reduction in sensation in the median territory in the hands, and wasting of the muscle bulk in the thenar eminence. The clinical diagnosis is easily confirmed by median nerve conduction studies and treatment involves surgical decompression at the carpel tunnel in the wrist. There is generally good response to surgery, although painful symptoms appear to relapse more commonly than in the nondiabetic population (78).
The ulnar nerve is also vulnerable to pressure damage at the elbow in the ulnar groove. This results in wasting of the dorsal interossei, particularly the first dorsal interossius. This is easily confirmed by ulnar electrophysiological studies which localize the lesion to the elbow. Rarely, the patients may present with wrist drop because of radial nerve palsy after prolonged sitting (with pressure on the radial nerve in the back of the arms) while unconscious during hypoglycaemia or asleep after an alcohol binge.
In the lower limbs the common peroneal (lateral popliteal) is the most commonly affected nerve. The compression is at the level of the head of the fibula and causes foot drop. Unfortunately, complete recovery is not usual. The lateral cutaneous nerve of the thigh is occasionally also affected with entrapment neuropathy in diabetes. Phrenic nerve involvement in association with diabetes has also been described, although the possibility of a pressure lesion could not be excluded (79).
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