INTRODUCTION — Lumbosacral plexopathies represent a distinct group of disorders of the peripheral nervous system due in part to their anatomic location, rarity, and wide array of etiologies (table 1). The most common causes of lumbosacral plexopathy are diabetic amyotrophy and the clinically similar condition of idiopathic (nondiabetic) lumbosacral radiculoplexus neuropathy (LRPN).
This topic will review diabetic amyotrophy and idiopathic LRPN. Other conditions affecting the lumbosacral plexus are discussed separately. (See "Lumbosacral plexus syndromes".)
The types of neuropathy associated with diabetes are reviewed elsewhere. (See "Epidemiology and classification of diabetic neuropathy".)
BACKGROUND — Diabetic amyotrophy [1] is also known as Bruns-Garland syndrome [1-3], diabetic myelopathy [4], proximal diabetic neuropathy [5], diabetic polyradiculopathy [6], diabetic motor neuropathy [7], diabetic radiculoplexopathy [8], diabetic lumbosacral plexopathy [9], and diabetic LRPN [10].
Diabetic amyotrophy is not a pure lumbosacral plexopathy because it also affects the lumbosacral nerve roots and peripheral nerves [10,11]. The extensive list of monikers for this condition reflects the debate regarding its neuroanatomic localization [11].
Additional debate has been waged regarding which pathophysiologic mechanisms (eg, ischemic, metabolic [hyperglycemia], and/or inflammatory) are responsible for diabetic amyotrophy [3,10-14]. However, the most likely cause is ischemic injury from a nonsystemic microvasculitis [10,11,15]. There is also evidence that a nonsystemic microvasculitis is responsible for idiopathic LRPN [11,16]. In a series of 33 patients with diabetic amyotrophy, nerve biopsy specimens showed features of multifocal fiber loss, perineurial thickening, neovascularization, and abortive regeneration of nerve fibers forming microfasciculi [10]. Teased fibers showed increased axonal degeneration, empty nerve strands, and segmental demyelination. Half of the biopsies showed inflammatory cells disrupting vessel walls. These findings are all supportive of an ischemic process due to microvasculitis.
EPIDEMIOLOGY — LRPN is associated with diabetes mellitus in approximately two-thirds of cases and is idiopathic in the remaining third [17,18]. Other conditions also associated with the development of LRPN include autoimmune disorders, prior stroke, and elevated body mass index [18]. The incidence has been estimated at 4.2 per 100,000 per year in a North American, primarily White, population [17].
CLINICAL FEATURES
Diabetic amyotrophy — Diabetic amyotrophy typically occurs in patients with type 2 diabetes mellitus that has been recently diagnosed or has been under fairly good control. Compared with other neurologic complications of diabetes, amyotrophy is relatively uncommon, affecting approximately 1 percent of patients [19].
Typical lower extremity presentation — The traditional features include the acute, asymmetric, focal onset of pain followed by weakness involving the proximal leg, with associated autonomic failure and weight loss [1-3,6,20]. Progression occurs over months and is followed by partial to full recovery in most patients. However, onset in the distal leg is not uncommon [10,11]. Furthermore, the condition becomes more widespread and symmetric with time. In nearly all cases, the symptoms and signs progress to affect the contralateral limb and the distal legs.
These points are illustrated by a prospectively studied series of 33 patients with diabetic amyotrophy. The following clinical observations were noted [10,11]:
●The median age of the patients was 65 years (range 35 to 80), and the median duration of diabetes was 4 years (range 0 to 36). All but one patient had type 2 diabetes. These patients tended to lack evidence of other diabetic end-organ damage such as retinopathy or nephropathy.
●Diabetic amyotrophy was the presenting feature of diabetes in 21 percent.
●The most severe symptom at onset was pain in 82 percent and weakness in 18 percent.
●The distribution of symptoms and signs at presentation was proximal (hip, thigh, buttock, or back) in 64 percent of patients and distal (foot or leg) in the remaining 36 percent.
●The onset was unilateral in 88 percent of patients. However, bilateral involvement eventually was present in 97 percent; spread to the contralateral limb occurred over a median time of approximately three months.
●Most patients in the series had proximal and distal sensory loss, and approximately one-half developed new autonomic symptoms such as orthostatic hypotension, urinary dysfunction, constipation, diarrhea, tachycardia, and sexual dysfunction.
●The majority of patients needed ambulatory aids, and approximately one-half required wheelchair assistance at some point during the illness.
●Weight loss of >10 pounds was recorded in 85 percent.
In the same series, the following laboratory findings were reported [11]:
●The median glycated hemoglobin (A1C) was 7.5 percent (range 5.1 to 12.9 percent).
●The median fasting plasma glucose was 145 mg/dL (8 mmol/L), with a range of 75 to 225 mg/dL (4.2 to 12.5 mmol/L).
●The cerebrospinal fluid protein was typically elevated to a median 90 mg/dL (5 mmol/L), with a range of 44 to 214 mg/dL (2.4 to 11.9 mmol/L).
Cervical and thoracic involvement — Upper limb and thoracic involvement has also been observed as part of the syndrome of diabetic amyotrophy [6,10]. Some have pain or weakness involving the chest or abdominal wall, suggesting a thoracic radiculopathy, while others have symptoms consistent with a brachial plexopathy [6,10]. Arm involvement occurs in up to one-third of patients and may be in the form of mononeuropathies of the ulnar and median nerves, or may affect more proximal sites in the brachial plexus [10,11]. Most upper limb symptoms occur in association with lumbosacral plexus involvement.
In one retrospective series of 85 patients diagnosed with diabetic cervical radiculoplexus neuropathy who presented with pain, paraesthesia, or weakness involving the cervical nerve roots, brachial plexus, or upper extremity nerves, the following observations were made [21]:
●The median age was 62 years (range 32 to 83 years).
●The most common symptom at onset was pain in 62 percent. The most frequent symptoms at evaluation were weakness, pain, and numbness in 99, 81, and 66 percent, respectively. Onset was unilateral in 81 percent, with eventual involvement of the contralateral side in 35 percent. Autonomic symptoms, such as orthostatic dizziness and changes in sweating, were noted in 15 percent.
●Involvement of the upper, middle, and lower brachial plexus was approximately equal, with each occurring in 50 to 60 percent, and pan plexopathy was present in 30 percent. Involvement of lumbosacral and thoracic regions was noted in 24 and 19 percent, respectively. Some patients had isolated or superimposed involvement of the phrenic, long thoracic, axillary, suprascapular, or anterior interosseus nerves.
●Type 2 and type 1 diabetes mellitus were present in 79 and 7 present, respectively. Most of the remaining patients had impaired fasting glucose, gestational diabetes, or steroid-induced diabetes.
●Among 28 patients who had lumbar puncture, the most common cerebrospinal fluid abnormality was elevated protein.
●Neurophysiologic testing showed a predominantly axonal neuropathy; nerve biopsy, obtained in 11 patients, was interpreted as showing mainly ischemic injury from microvasculitis.
●Weight loss >10 pounds was recorded in 35 percent.
These findings are similar in many respects to those described above for diabetic amyotrophy with lower limb involvement.
Idiopathic lumbosacral radiculoplexus neuropathy — Idiopathic LRPN (also known as idiopathic lumbosacral plexopathy and lumbosacral plexitis) is similar to diabetic amyotrophy with respect to its pathophysiology, clinical features, prognosis, and management [11,16].
Like diabetic amyotrophy, patients with idiopathic LRPN present with severe, debilitating pain in one proximal lower limb, typically followed by weakness of the ipsilateral limb and eventual spread to the contralateral limb within weeks to months [11,16,22,23]. As in diabetic amyotrophy, weight loss and autonomic symptoms occur as well.
Despite the similarities between diabetic amyotrophy and LRPN, patients with LRPN typically do not go on to develop diabetes. In a retrospective series of 42 patients with LRPN and two or more years of follow-up, diabetes developed in only two (5 percent) [16]. Nevertheless, there may be a low level of diabetic impairment or glucose intolerance in some patients with LRPN, as the median glycated hemoglobin in this cohort was 5.5 percent (range 4.3 to 7.1 percent) [16].
Other laboratory features of idiopathic LRPN are essentially identical to diabetic amyotrophy, including cerebrospinal fluid protein elevation in some to a median 67 mg/dL (0.67 g/L), with a range of 18 to 283 mg/dL (0.18 to 2.83 g/L) [16].
DIAGNOSIS — The diagnosis of diabetic amyotrophy is based mainly upon the presence of suggestive clinical features in a patient with known or newly diagnosed diabetes mellitus, and appropriate laboratory investigations, particularly electrodiagnostic studies. In select cases, neuroimaging may be useful to exclude other peripheral and central nervous system etiologies as a cause of the neurologic symptoms and signs.
In patients who do not have diabetes, idiopathic LRPN is the primary consideration in the differential diagnosis. (See 'Idiopathic lumbosacral radiculoplexus neuropathy' above.)
Cytomegalovirus and HIV can rarely cause a lumbosacral radiculoneuropathy that is similar to diabetic amyotrophy electrophysiologically. (See "Lumbosacral plexus syndromes", section on 'Specific disorders' and "Lumbosacral plexus syndromes", section on 'Infectious, inflammatory, and infiltrative causes'.)
The sections below will review the evaluation of patients with suspected diabetic amyotrophy or idiopathic LRPN. A detailed discussion of the evaluation of lumbosacral plexopathy is presented separately. (See "Lumbosacral plexus syndromes", section on 'Diagnostic evaluation'.)
Laboratory investigations — Suggested routine blood tests for the evaluation of possible diabetic amyotrophy and idiopathic LRPN are a complete blood count, coagulation profile, fasting blood glucose, hemoglobin A1C, and sedimentation rate. A glucose tolerance test may be informative for select patients with impaired fasting glucose. (See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults" and "Type 2 diabetes mellitus: Prevalence and risk factors", section on 'Abnormal glucose metabolism'.)
Electrodiagnostic studies — In patients with diabetic amyotrophy or idiopathic lumbosacral radiculoneuropathy, electrodiagnostic study findings generally reflect axonal degeneration more than segmental demyelination [11,21]. Abnormalities typically involve the lumbar and sacral roots, the lumbosacral plexus, and the lower extremity peripheral nerves. In cases with upper limb symptoms, abnormalities are found in the cervical nerve roots, brachial plexus, or upper extremity nerves [21].
●Nerve conduction studies show markedly reduced amplitudes of the compound muscle action potentials and sensory nerve action potentials, while conduction velocities show only mild slowing [10,16].
●Needle electromyography (EMG) shows fibrillation potentials, decreased motor unit recruitment, and long-duration, high-amplitude motor unit action potentials. Paraspinal muscles are often involved [6,21]; this finding demonstrates that pathology must exist outside of the lumbosacral and brachial plexuses.
Although the above findings are initially more prominent in proximal muscles, distal and bilateral involvement is likely to develop in the first few months after disease onset.
Regardless of the presence of diabetic amyotrophy, patients with diabetes often have electrodiagnostic evidence of other neuropathies, including the following:
●A mild, primarily axonal, length-dependent sensorimotor polyneuropathy
●Mononeuropathies at typical sites of compression, such as ulnar neuropathies at the elbow or median neuropathies at the wrist manifesting as slowed nerve conduction velocity or conduction block at the ulnar groove or carpal tunnel, respectively
●Thoracic radiculopathies, manifesting as increased fibrillation potentials and positive sharp waves in the corresponding thoracic paraspinous musculature on needle examination
Neuroimaging — Magnetic resonance imaging (MRI) has superseded computed tomography (CT) as the imaging method of choice for plexus evaluation. It is useful to rule out other causes of neurologic impairment, such as structural lesions of the lumbosacral plexus, brachial plexus, or spinal cord. Neuroimaging does not provide definitive visualization of pathology in diabetic amyotrophy or idiopathic radiculoplexus neuropathy, but MRI may reveal slightly to moderately increased T2 signal, gadolinium enhancement, or enlargement of the nerve roots, plexus, and peripheral nerves (image 1 and image 2) [21,24-26]. Magnetic resonance neurography with diffusion tensor imaging has also been shown to identify lesions due to diabetic amyotrophy [27].
PROGNOSIS — While clinical improvement is the rule with diabetic amyotrophy, most patients will not recover completely. Foot drop and, at times, lingering neuropathic pain can persist for years. In the series of 33 patients with diabetic amyotrophy cited earlier, 48 percent required wheelchair assistance at some point during the illness [11]. At a mean follow-up of two years, 9 percent needed a wheelchair and only 6 percent felt they had recovered completely. In another study that reported two patients with diabetic amyotrophy who progressed to fulminant quadriparesis, one patient remained wheelchair bound and severely disabled at 42 months, while the other made a good recovery with mild residual truncal and proximal leg weakness [28].
Occasional patients have recurrent attacks of diabetic amyotrophy [11], although the precise rate of recurrence is uncertain.
Idiopathic LRPN is also associated with long-term morbidity with residual pain, weakness, and sensory symptoms predominating [16,29]. Like diabetic amyotrophy, recurrent bouts have been reported [11,30,31].
TREATMENT — No treatments are proven to be effective for diabetic amyotrophy or for the clinically similar condition of idiopathic LRPN.
The results from some [12,20,32,33] but not all [9] retrospective studies suggested that treatments employing immune suppression were associated with clinical improvement in diabetic amyotrophy. These regimens included such therapies as oral prednisone, intravenous methylprednisolone, intravenous immune globulin, cyclophosphamide, and plasma exchange. However, a 2017 systematic review found no published randomized controlled trials evaluating immunotherapy for diabetic amyotrophy [34]. A blinded, randomized controlled study presented only in abstract form found that pulse methylprednisolone therapy was not beneficial compared with placebo for functional improvement in diabetic amyotrophy [35].
Several small retrospective studies reported that immunomodulatory therapies were helpful in the recovery of LRPN [16,36-38]; a 2013 systematic review found no randomized controlled trials evaluating immunotherapy for LRPN [39].
Symptomatic management — Symptomatic management of diabetic amyotrophy and idiopathic LRPN should be approached from a multidisciplinary standpoint. Although data are scant, clinical experience suggests that the concurrent use of narcotic analgesics and agents for neuropathic pain is beneficial in the initial phase. Neuropathic pain treatments include tricyclic antidepressants (eg, amitriptyline), gabapentin, pregabalin, duloxetine, and venlafaxine. (See "Management of diabetic neuropathy", section on 'Pain management'.)
Antidepressants may be helpful to combat the emotional component of the illness. Physical and occupational therapy with emphasis on exercise, gait training, and equipment/orthotic needs should round out the therapeutic regimen. Patient education and reassurance are a necessity.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neuropathy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Nerve damage caused by diabetes (The Basics)")
●Beyond the Basics topics (see "Patient education: Diabetic neuropathy (Beyond the Basics)")
SUMMARY
●Diabetic amyotrophy is not a pure lumbosacral plexopathy because it also affects the lumbosacral nerve roots and lower extremity peripheral nerves. In addition, it may involve cervical nerve roots, brachial plexus, or upper extremity nerves. The most likely cause of diabetic amyotrophy and the clinically similar condition of idiopathic lumbosacral radiculoplexus neuropathy (LRPN) is ischemic injury from a nonsystemic microvasculitis. (See 'Background' above.)
●Diabetic amyotrophy typically occurs in patients with type 2 diabetes mellitus. The traditional features include the acute, asymmetric, focal onset of pain followed by weakness involving the proximal leg, with associated autonomic failure and weight loss. Progression occurs over months and is followed by partial recovery in most patients. However, onset in the distal leg is not uncommon. Furthermore, the condition becomes more widespread and symmetric with time. In nearly all cases, the symptoms and signs progress to affect the contralateral limb and the distal legs. (See 'Clinical features' above.)
●Upper limb and thoracic involvement has also been observed as part of the syndrome of diabetic amyotrophy. Symptoms and signs reflect involvement of cervical or thoracic nerve roots, brachial plexus, or upper extremity nerves. (See 'Cervical and thoracic involvement' above.)
●Idiopathic LRPN is similar to diabetic amyotrophy with respect to its pathophysiology, clinical features, prognosis, and management. (See 'Idiopathic lumbosacral radiculoplexus neuropathy' above.)
●The diagnosis of diabetic amyotrophy is mainly based upon the presence of suggestive clinical features in a patient with known or newly diagnosed diabetes mellitus. Appropriate laboratory investigations, particularly electrodiagnostic studies, and neuroimaging in select patients, are useful to exclude other peripheral and central nervous system etiologies as a cause of the neurologic symptoms and signs. In patients who do not have diabetes, idiopathic LRPN is the primary consideration in the differential diagnosis. (See 'Diagnosis' above.)
●While clinical improvement is the rule with diabetic amyotrophy and idiopathic LRPN, most patients do not recover completely. (See 'Prognosis' above.)
●No treatments are proven to be effective for diabetic amyotrophy or for idiopathic LRPN. (See 'Treatment' above.)
