Diabetic Lumbosacral Plexopathy

The underlying pathogenesis of diabetic lumbosacral plexopathy and the site of the lesion are not clearly understood and remain subjects of controversy.[7, 17] The condition is most likely caused by inflammatory, immune-mediated vascular radiculoplexopathy.[18, 19, 20, 21] Most authors now favor an immune vasculopathy as the cause of diabetic amyotrophy. Studies suggest a role for immunomodulating agents in certain types of diabetic neuropathy, including diabetic amyotrophy.[22]

A study by Kotov et al of 445 patients with diabetes mellitus found that diabetic asymmetrical proximal neuropathy was present in 7.9% of this group and that the rate of occurrence was higher in patients with type 2 diabetes mellitus, in those with poorly controlled glycemia, and in patients who had had diabetes for over 5 years.[23]

In the United States, the overall prevalence of diabetic lumbosacral plexopathy among individuals with diabetes is 0.08%, although the condition occurs more frequently in persons with type 2 diabetes (1.1%) than in those with the type 1 disease (0.3%).

In a study of the population of Olmstead County, Minn., Ng et al found the rate of DM in persons with lumbosacral radiculoplexus neuropathy to be 66.1%, compared with 19.8% in controls.[24]

Morbidity related to diabetic lumbosacral plexopathy is mainly secondary to pain, proximal muscle wasting, and weakness, causing difficulty getting up from a chair and climbing stairs.

No race or sex predilection exists for diabetic lumbosacral plexopathy; however, the condition occurs most commonly in patients aged 50 years or older. In a series of 12 cases reported by Casey and Harrison, no patient was younger than 50 years, and 10 patients were older than 60 years.[25] In a large series of 105 patients with diabetic amyotrophy reported by Bastron and Thomas, the age of onset ranged from 36 to 83 years; symptoms progressed over an average of 6.2 months, with 9.5% of patients having painless muscle weakness.[26] Diabetic lumbosacral plexopathy is rare in children; only 3 cases of the condition in children aged 13-16 years have been reported in the literature.

Good functional recovery within 12-24 months is expected in 60% of patients with diabetic lumbosacral plexopathy, although mild weakness, discomfort, and stiffness often persist for years. Occasional relapses can occur.

The patient should be educated in the importance of good glycemic control in conjunction with proper diet and exercise.[27] During rehabilitation, in order to improve functional recovery, the patient should be taught exercises to regain strength in the affected muscle groups.

Several findings commonly are reported in patients with diabetic lumbosacral plexopathy. These include asymmetrical pain in the hip, buttock, or thigh and proximal weakness in the quadriceps, hip adductors, and iliopsoas muscles. Diabetic lumbosacral plexopathy often occurs in conjunction with significant recent weight loss (commonly 10-40 pounds) and is associated with poor glycemic control.[28]

Patients may have underlying distal symmetrical polyneuropathy (DSPN). Gradual onset with bilateral presentation is typical in individuals with DSPN; patients are usually insulin dependent. However, patients without DSPN most often have a sudden, unilateral onset. This symptom is sometimes the initial presenting feature of diabetes mellitus.[29]

Gupta et al reported on the occurrence of cervical-radiculoplexus neuropathy in a man aged 53 years with type 2 diabetes, in whom the cranial and phrenic nerves were concomitantly involved and in whom the neuropathy developed in a stepwise, monophasic course.[30]

Proximal lower limb muscle weakness and wasting are characteristic features of diabetic lumbosacral plexopathy; the patient has particular difficulty getting up from a squatting position. Minimal sensory loss is observed, and the knee-jerk reflex is absent, with commonly preserved ankle jerks; however, ankle jerks may also be absent with underlying DSPN.

Features observed in the physical examination may be localized in the lumbosacral plexus or the upper lumbar roots.

In evaluating suspected diabetic lumbosacral plexopathy, neural and electrophysiologic studies are generally helpful. Laboratory tests used to diagnose or assess control of diabetes mellitus (eg, fasting blood glucose, hemoglobin A1C) should be performed. Imaging studies may help in differentiating other causes.

Go to Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathy; and Electrophysiology for more information on these topics.

In addition to tests performed to evaluate or diagnose diabetes, lumbar puncture results may show elevated cerebrospinal fluid (CSF) proteins, sometimes more than 1 g.[13] Additional laboratory studies to rule out other causes of neuropathy, as well as cancer and bleeding diathesis, are also important.

Lumbar spine and pelvic radiographs should be performed to evaluate for other causes of the plexopathy. Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the lumbosacral spine and pelvis may be indicated in some cases to rule out mass lesions.[14]

A study by Matsuda et al of a patient with diabetic lumbosacral radiculoplexus neuropathy found that on T2-weighted MRI scans of the skeletal muscles, high signal intensities could be seen in the bilateral hamstrings and the adductor magnus and right tensor fasciae latae, as well as in the extensor muscles of the lower legs.[31] Another study, which used short tau inversion recovery (STIR) MRI sequences to examine 17 patients with lower limb neuropathies, found that MRI-assessed amyotrophy was significantly greater in patients with severe, chronic, or proximal neuropathy.[32]

A case study by McCormack et al of a patient with diabetes and lumbar disc disease reported on the use of magnetic resonance neurography (MRN) to help distinguish diabetic lumbosacral radiculoplexus neuropathy from radiculopathy. MRI showed that structural changes in the lumbar spine were insufficient to cause the patient’s presenting symptom, ie, acute pain onset in the lower left extremity’s L5-S1 distribution. MRN of the lumbosacral plexus, however, demonstrated that the bilateral sciatic and femoral nerves were inflamed, indicating the presence of radiculoplexus neuropathy.[33]

Biopsies are rarely indicated in patients with diabetic lumbosacral plexopathy, and systematic studies are lacking in the literature. Early in the disease course, epineurial and perivascular inflammation around the small vessels may be caused by infiltration by mononuclear cells, with or without polymorphonuclear cells. Endoneurium and subperineurial space immunoglobulin-M (IgM) deposition should be expected. Activated complement (C5b-9) deposition in the endothelium of small vessels is also common. Reduced numbers of myelinated and unmyelinated axons may be observed, and differential fascicular loss of axons is also characteristic.

In an autopsy study of a patient with diabetic lumbosacral radiculoplexus neuropathy, Younger found that small blood vessels of the epineurium of the sciatic nerve were surrounded by perivascular chronic inflammation.[34] In another case report, by Tracy et al, a superficial peroneal nerve biopsy revealed evidence of active axonal degeneration, microvasculitis, and ischemic injury in a patient with diabetic lumbosacral radiculoplexus neuropathy.[35]

Electromyography (EMG) and nerve conduction studies (NCS) should be performed.[15, 16] In patients without distal symmetrical polyneuropathy (DSPN), needle EMG usually shows positive sharp waves and fibrillation potentials in the iliopsoas, hip adductors, and quadriceps, but other muscles may also be involved.

In patients with underlying DSPN, in addition to the above findings, sural sensory nerve action potential (SNAP) is usually absent, and amplitudes in peroneal and tibial compound motor action potential (CMAP) are reduced.

Femoral nerve motor conduction studies may show asymmetrical amplitudes, and paraspinal muscle needle EMG may show fibrillations and positive sharp waves, but the results are usually within the reference range.

Most patients are able to avoid inpatient care for diabetic lumbosacral plexopathy. Good glycemic control through the adjustment of diabetes medication (eg, oral agents, insulin) is of paramount importance. Education on proper diet and exercise is also essential. However, because of the sudden onset of functional loss, some patients with the condition may need to be transferred to a subacute rehabilitation facility or a convalescent home for several months, until they recover strength.

A literature review by Kazamel and Dyck suggested that in evaluating patients with diabetes, clinicians should be aware that different types of diabetic neuropathy produce different patterns of abnormal sensation and arise from different pathophysiologic mechanisms.[36]

Go to Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathy; and Electrophysiology for more information on these topics.

No surgical intervention is needed for diabetic lumbosacral plexopathy.

Consider consultation with an endocrinologist (eg, with a diabetologist) to assist with the management of diabetes mellitus.

Neurologic recovery is slow for patients with diabetic lumbosacral plexopathy. A physical therapist (PT) can assist in improving a patient's functional mobility (eg, transfers, ambulation). The PT instructs the patient in the use of assistive devices when necessary. A therapeutic exercise and range-of-motion program supervised by the PT is helpful in maintaining and improving lower extremity prime-mover muscle function and avoiding major lower extremity joint contractures.

These patients may derive further benefit from a course of outpatient physical therapy, achieving their maximum potential in terms of functional mobility and lower extremity strength.

An occupational therapist can recommend appropriate adaptive equipment (eg, a reacher, an elevated toilet seat, a tub bench) based on the degree of proximal weakness the patient is experiencing, so that the patient can be independent in activities of daily living and perform self-care tasks in a seated position.

Good glycemic control through the adjustment of diabetes medication (eg, oral agents, insulin) is of paramount importance. Education on proper diet and exercise is also essential.

Medical management includes neuromodulator medications for chronic neuropathic pain management such as anticonvulsant medications (gabapentin or pregabalin) and selective norepinephrine reuptake inhibitors (such as duloxetine). Anecdotal experience indicates that topical counter-irritant medications such as menthol and wintergreen are also valuable as comfort measures.

Intravenous human immunoglobulin (IVIg) may hasten recovery in patients with diabetic lumbosacral plexopathy, although this treatment has not yet been proven in controlled studies and remains controversial.[37, 38, 39] Other immunosuppressive agents, such as cyclophosphamide and methylprednisolone, are also thought to improve recovery. Kilfoyle et al studied treatment with pulsed methylprednisolone at 500 mg for 2 days every 2 weeks (instituted within 3 months of symptom onset) and noted significant improvement in pain and weakness in the majority of patients.[40]

Another study, by Dyck et al, suggested that methylprednisolone is effective against diabetic lumbosacral radiculoplexus neuropathy. The double-blind, placebo-controlled study involved 75 patients with the condition, who were randomized to a 12-week regimen of intravenous methylprednisolone or placebo.[41] Although the study’s primary outcome (time to improvement of neuropathy impairment score) was not significantly different between the 2 groups, patients treated with methylprednisolone reported significantly greater symptom improvement, particularly with regard to measures of pain and positive sensory symptoms.

However, a 2009 Cochrane review concluded that no evidence from randomized trials supported a recommendation for immunotherapy’s use in the treatment in diabetic amyotrophy.[42] In 2012 and 2017, updates to the review reported that supportive evidence was still lacking.[43, 44]

Class Summary

The administration of human immunoglobulins may improve the clinical and immunologic aspects of the disease. Blood products may decrease autoantibody production and increase solubilization and removal of immune complexes.

Immunoglobulins (Gamimune, Gammagard S/D, Sandimmune)

Immunoglobulin neutralizes circulating myelin antibodies through anti-idiotypic antibodies. In addition, it down-regulates proinflammatory cytokines, including interferon (IFN)-gamma; blocks Fc receptors on macrophages; suppresses inducer T-cells and B-cells and augments suppressor T-cells; blocks complement cascade; promotes remyelination; and may increase cerebrospinal fluid (CSF) levels of immunoglobulin (Ig) G (10%).

Class Summary

Immunosuppressive agents such as cyclophosphamide, methylprednisolone, and prednisone may improve recovery.

Cyclophosphamide

Cyclophosphamide is a cyclic polypeptide that suppresses some humoral activity. It is chemically related to nitrogen mustards and is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none–type reaction. When used in autoimmune diseases, the mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

Azathioprine (Imuran)

Azathioprine is an imidazolyl derivative of 6-mercaptopurine. It antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It works primarily on T cells and suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production.

Methylprednisolone (Medrol, Solu-Medrol)

Methylprednisolone is an immunosuppressant that decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Prednisolone

Prednisone is an immunosuppressant that can be used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Class Summary

These drugs have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin.

Amitriptyline

Amitriptyline is an oral analgesic for certain types of chronic pain. The usual adult dose ranges from 30-150 mg/d.

Nortriptyline (Pamelor)

Nortriptyline has demonstrated effectiveness in the treatment of chronic pain via inhibition of the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane. As a result, this drug increases the synaptic concentration of these neurotransmitters in the central nervous system (CNS). In addition, pharmacodynamic effects, such as the desensitization of adenyl cyclase and the down-regulation of beta-adrenergic receptors and serotonin receptors, appear to play a role in its mechanisms of action.

Doxepin (Silenor)

This agent inhibits histamine and acetylcholine activity and has proven useful in the treatment of various forms of depression associated with chronic and neuropathic pain.

Desipramine (Norpramin)

Desipramine may increase the synaptic concentration of norepinephrine in the CNS by inhibiting reuptake by presynaptic neuronal membrane. The drug may have effects in the desensitization of adenyl cyclase and in the downregulation of beta-adrenergic receptors and serotonin receptors.

Class Summary

These agents are used for neuropathic pain.

Gabapentin (Neurontin)

Gabapentin has anticonvulsant properties and antineuralgic effects; however, its exact mechanism of action is unknown. The drug is structurally related to gamma-aminobutyric acid (GABA) but does not interact with GABA receptors. Titration to effect can take place over several days (300 mg on day 1, 300 mg bid on day 2, and 300 mg tid on day 3).

Pregabalin (Lyrica)

Pregabalin is a structural derivative of GABA. The mechanism of action is unknown. It binds with high affinity to the alpha2-delta site (a calcium channel subunit). It is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

Class Summary

Class of medications that act as antidepressants and reduce neuropathic pain by preventing re-uptake of serotonin-norepinephrine, thereby increasing brain levels of these mood-elevating agents.

Duloxetine (Cymbalta, Irenka)

Neuropathic analgesic medication for off-label use-management of neuropathic pain from diabetic polyradiculopathy. Duloxetine (Cymbalta) is FDA-approved for the following diagnoses: major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and, in adults, chronic musculoskeletal pain.