Version May 2024
INTRODUCTION — Lumbosacral radiculoplexus neuropathy (LRPN) refers to a group of peripheral nerve disorders characterized by anatomic location involving the lumbosacral plexus and spinal roots. The condition typically causes progressive proximal leg pain and weakness. LRPN often occurs in patients with type 2 diabetes mellitus and is commonly called diabetic amyotrophy.
This topic will review diabetic amyotrophy and idiopathic LRPN. Other conditions affecting the lumbosacral roots, plexus, and nerves are discussed separately. (See "Overview of lower extremity peripheral nerve syndromes" and "Lumbosacral plexus syndromes".)
An overview of other types of neuropathy associated with diabetes is reviewed elsewhere. (See "Epidemiology and classification of diabetic neuropathy".)
TERMINOLOGY — LRPN is typically categorized as either idiopathic or associated with diabetes mellitus. Early descriptions of the syndrome identified the presence of proximal lower extremity signs and symptoms as evidence of spinal root or cord involvement, unlike more common distal presentations of peripheral polyneuropathy [1]. Several terms have been used to describe the condition, highlighting an evolving understanding of the neuroanatomic correlation to the clinical features [2].
Terms used for LRPN associated with diabetes mellitus include [1,3-11]:
●Diabetic amyotrophy
●Bruns-Garland syndrome
●Diabetic myelopathy
●Diabetic lumbosacral plexopathy
●Proximal diabetic neuropathy
●Diabetic polyradiculopathy
●Diabetic LRPN
Idiopathic LRPN may also be called [12-14]:
●Idiopathic lumbosacral plexopathy
●Lumbosacral plexitis
●Idiopathic lumbosacral neuropathy
PATHOPHYSIOLOGY — Idiopathic LRPN and diabetic amyotrophy are not pure lumbosacral plexopathies because they also affect both the more proximal lumbosacral nerve roots and distal peripheral nerves [2,11].
Several pathophysiologic hypotheses have been raised (eg, ischemic, metabolic [hyperglycemia], and/or inflammatory) to account for diabetic amyotrophy [2,4,11,15-17]. The most likely cause is ischemic injury from a nonsystemic microvasculitis [2,11,18]. In a series of 33 patients with diabetic amyotrophy, nerve biopsy specimens showed features suggestive of microvasculitis including multifocal fiber loss, perineurial thickening, neovascularization, and abortive regeneration of nerve fibers forming microfasciculi [11]. Teased fibers showed increased axonal degeneration, empty nerve strands, and segmental demyelination. Half of the biopsies showed inflammatory cells disrupting vessel walls. Another study similarly found transmural infiltration of polymorphonuclear leukocytes and immunoglobulin M deposits in epineurial vessels suggestive of a small vessel vasculitis [17].
There is also some pathologic evidence that a nonsystemic microvasculitis may be responsible for idiopathic LRPN [2,19]. Six patients with a painful lumbosacral plexopathy felt unrelated to systemic vasculitis or diabetes were assessed in a small series as having idiopathic LRPN with sural nerve biopsy showing axonal degeneration and epineurial infiltration with mononuclear inflammatory cells [20].
EPIDEMIOLOGY — The combined incidence of diabetic amyotrophy and idiopathic LRPN has been estimated at 4.2 per 100,000 per year in a North American, primarily White, population [21]. The median age at presentation is approximately 65 to 70 years old, but cases in adults from 35 to 80 years old have also been reported [11,19,21].
LRPN is attributed to diabetes mellitus in approximately two-thirds of cases and is idiopathic in the remaining third [21,22].
●Diabetic amyotrophy is less common than other neurologic complications of diabetes, affecting approximately 1 percent of patients [23]. It typically occurs in patients with type 2 diabetes mellitus that has been somewhat recently diagnosed. In a small study of 33 patients with diabetic amyotrophy, the median duration of diabetes was four years (range 0 to 36) [11]. Diabetic amyotrophy was the presenting feature of diabetes in 21 percent. For some patients, symptom onset may coincide with intentional weight loss, a new exercise regimen, or improved glycemic control [24-26].
●Idiopathic LRPN occurs in patients who do not have diabetes mellitus. Mild glucose intolerance has been reported in some patients with idiopathic LRPN [19]; however, such patients do not typically go on to develop diabetes mellitus. In a retrospective series of 42 patients with LRPN and two or more years of follow-up, diabetes developed in only two (5 percent) [19]. Other conditions also associated with the development of idiopathic LRPN include autoimmune disorders, prior stroke, and elevated body mass index [22].
CLINICAL FEATURES — The clinical features of both diabetic and idiopathic LRPN typically include an acute, asymmetric, focal onset of lower extremity pain followed by weakness with associated autonomic failure and weight loss [1-4,7,19,27-29].
Typical lower extremity presentation — The traditional features of LRPN include pain and weakness involving proximal leg muscles [1,3,4,7,27].
●Pain and weakness – Symptoms typically begin with an acute onset of asymmetric or unilateral leg pain followed by progressive weakness. In one series, 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 [2,11].
LRPN symptoms typically become more widespread and symmetric over weeks to months. In nearly all cases, the symptoms and signs progress to affect the contralateral limb and the distal legs. In one series, symptoms were initially unilateral in 88 percent, but 97 percent had developed bilateral involvement by a median time of approximately three months [11]. The clinical examination frequently shows muscle atrophy and lower extremity hyporeflexia. Most patients needed ambulatory aids at some point during the illness, and approximately one-half required wheelchair assistance.
Symptoms may progress for six months or longer before improving gradually, with at least partial recovery occurring in most patients [24]. (See 'Prognosis' below.)
●Other features – Many patients with LRPN report clinical symptoms that reflect autonomic and sensory nerve involvement in the condition. Approximately one-half of patients develop new autonomic symptoms including [11,30]:
•Orthostatic hypotension
•Tachycardia
•Urinary and/or sexual dysfunction
•Constipation or diarrhea
Sensory nerve impairment is common on electrodiagnostic testing, and some patients report proximal and distal lower extremity sensory loss, but this is typically less severe than weakness or pain.
Unintentional weight loss is common in patients with diabetic amyotrophy or idiopathic LRPN. Weight loss of >10 pounds has been reported to occur in up to 85 percent of patients in some series [2].
Cervical and thoracic involvement — Upper limb and thoracic symptoms have also been observed as part of the syndrome of diabetic amyotrophy [7,11]. 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 [2,11]. Other patients have pain or weakness involving the chest or abdominal wall, suggesting a thoracic radiculopathy [7,11]. Most patients who develop upper limb and thoracic symptoms also have some 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 most frequent symptoms at evaluation were weakness, pain, and numbness occurring in 99, 81, and 66 percent, respectively [31]. Involvement of one or more trunks of the brachial plexus was more common than pan plexopathy. Some patients had isolated or superimposed involvement of the phrenic, long thoracic, axillary, suprascapular, or anterior interosseus nerves. 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. Weight loss of >10 pounds occurred in 35 percent. Nearly 80 percent of patients had type 2 diabetes mellitus at baseline and most of the other patients had impaired fasting glucose, gestational diabetes, or steroid-induced diabetes.
DIAGNOSTIC EVALUATION — The diagnosis of LRPN should be considered in patients with acute onset lumbosacral pain and progressive proximal lower extremity weakness.
Diagnosis — The diagnosis of diabetic amyotrophy is made in patients with suggestive clinical features and known or newly diagnosed diabetes mellitus after diagnostic testing has excluded other causes of symptoms. For patients who do not have diabetes mellitus, the diagnosis of idiopathic LRPN is made in patients with suggestive clinical features and supportive diagnostic testing.
There are no tests to confirm the diagnosis of LRPN. Diagnostic testing is performed to support the clinical diagnosis and to exclude alternative diagnoses. Testing typically includes screening laboratory testing, neuroimaging of the lumbar spine and lumbosacral plexus, and electrodiagnostic evaluation.
Differential diagnosis — The differential diagnosis of LRPN includes other conditions that may also cause a lumbosacral plexopathy. These include neoplasms, inflammatory conditions such as sarcoidosis, infections (eg, cytomegalovirus, human immunodeficiency virus [HIV], Lyme disease), retroperitoneal hematomas, and systemic vasculitides (table 1). (See "Lumbosacral plexus syndromes" and "Lumbosacral plexus syndromes", section on 'Specific disorders'.)
For patients with diabetes mellitus, the differential diagnosis also includes other forms of diabetic neuropathy. These conditions are typically identified by the distribution and extent of neuropathic symptoms. Other forms of diabetic neuropathy are described in greater detail separately. (See "Epidemiology and classification of diabetic neuropathy".)
Laboratory investigations — We perform limited screening laboratory tests for the evaluation of possible diabetic amyotrophy or idiopathic LRPN to assess glycemic status and to exclude alternative causes of symptoms. These typically include:
●Complete blood count with differential
●Prothrombin time, international normalized ratio (INR), and activated partial thromboplastin time
●Fasting blood glucose and hemoglobin A1C levels
●Erythrocyte sedimentation rate and C-reactive protein levels
We perform additional laboratory testing including specific infectious agents (eg, Borrelia species or cytomegalovirus) for selected patients with risk factors or additional clinical features suggestive of a specific infectious cause. For patients with symptoms or screening laboratory evidence suggestive of a systemic inflammatory condition, we perform additional laboratory testing to assess for systemic vasculitides. (See "Overview of and approach to the vasculitides in adults".)
We reserve lumbar puncture for cerebrospinal fluid (CSF) analysis for patients with additional features suggestive of a myelopathy or when initial laboratory, imaging, and electrodiagnostic testing are nondiagnostic. CSF analysis in patients with LRPN may show an elevated protein level at 60 to 90 mg/dL; levels >250 mg/dL are uncommon [2,19].
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) in a small series of patients with diabetic amyotrophy [2]. The median glycated hemoglobin (A1C) was 7.5 percent (range 5.1 to 12.9 percent).
Neuroimaging — We typically perform neuroimaging of the lumbar spine and lumbosacral plexus for patients with features of LRPN to exclude compressive or infiltrative etiologies. We also perform cervical and thoracic spinal neuroimaging for patients with atypical clinical features such as insidious onset of symptoms or the presence of myelopathic signs such as hyperreflexia or spasticity. Neuroimaging may be helpful both to support the diagnosis of LRPN and to exclude alternative possibilities.
We prefer magnetic resonance imaging (MRI) with gadolinium contrast as the imaging method of choice for LRPN. For patients unable to undergo MRI, computed tomography (CT) of the lumbar spine and lumbosacral plexus with contrast may be performed as a less sensitive alternative.
Neuroimaging does not provide definitive visualization of pathology in diabetic amyotrophy or idiopathic LRPN but may show findings that support the diagnosis. MRI findings in LRPN include slightly to moderately increased T2 signal, gadolinium enhancement, or enlargement of the nerve roots, plexus, and peripheral nerves (image 1 and image 2) [31-34]. Other techniques, including magnetic resonance neurography with diffusion tensor imaging, may also be used to help identify lesions due to diabetic amyotrophy [35].
Electrodiagnostic studies — Electrodiagnostic evaluation including a nerve conduction study (NCS) and electromyography (EMG) is typically performed for all patients with diabetic amyotrophy and idiopathic LRPN to define the extent of and localize the nerve involvement as well as to exclude alternative diagnostic possibilities.
NCS and EMG abnormalities in LRPN involve the lumbar and sacral roots, the lumbosacral plexus, and the lower extremity peripheral nerves. Findings generally reflect axonal degeneration more than segmental demyelination [2,31]. In cases with upper limb symptoms, abnormalities are found in the cervical nerve roots, brachial plexus, or upper extremity nerves [31]. Although findings are initially more prominent in proximal muscles, distal and bilateral involvement is likely to develop in the first few months after disease onset.
●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 [11,19].
●Needle EMG shows fibrillation potentials, decreased motor unit recruitment, and chronic findings of focal nerve injury such as long-duration, high-amplitude motor unit action potentials. EMG abnormalities may also be seen beyond the lumbosacral or brachial plexuses in the paraspinal muscles [7,31].
Regardless of the presence of diabetic amyotrophy, patients with diabetes often have electrodiagnostic evidence of other common neuropathies, including a sensorimotor polyneuropathy, compression mononeuropathies such as median, ulnar, or common peroneal (fibular) neuropathies, or thoracic radiculopathies. (See "Epidemiology and classification of diabetic neuropathy".)
TREATMENT — Management of diabetic amyotrophy and idiopathic LRPN is supportive and symptomatic. No treatments are proven to be effective to improve outcomes or hasten recovery.
Symptomatic management — Symptomatic management of diabetic amyotrophy and idiopathic LRPN typically includes pharmacotherapy for neuropathic pain and physical and occupational therapies for weakness.
●Pain – Data on the optimal management of pain in LRPN are scant, based largely on clinical experience with other forms of diabetic neuropathy. We suggest using an antidepressant (eg, amitriptyline, duloxetine, venlafaxine) or gabapentinoid antiseizure medication (eg, gabapentin, pregabalin). For patients with partial response to the initial medication selection, we use combination therapy by adding an additional agent from a different pharmacologic class. Effective pharmacotherapy is typically weaned after clinical recovery when pain resolves. Some patients with persisting symptoms may require long-term pharmacotherapy.
We generally avoid opioid analgesics for symptomatic pain management of most patients with diabetic amyotrophy or idiopathic LRPN due to the potential for tolerance, addiction, and overdose. These agents have not been found to be effective for long-term or chronic neuropathic pain. For selected patients with disabling pain who do not respond to other therapies, opioids may be used for short-term pain relief. (See "Management of diabetic neuropathy", section on 'Not recommended' and "Pharmacologic management of chronic non-cancer pain in adults", section on 'Opioids'.)
The approach to pain management and selection of therapy for diabetic neuropathy are discussed in greater detail separately. (See "Management of diabetic neuropathy", section on 'Pain management'.)
●Weakness – Supportive care for weakness associated with LRPN consists of physical and occupational therapies for exercise, gait training, and assessing the need for ambulatory aids (eg, orthoses, cane, wheelchair). Assistive devices are frequently temporary measures to promote mobility, exercise, and fall prevention during the acute symptomatic period. However, some patients with LRPN may have persistent weakness requiring long-term use of ambulatory aids. (See 'Prognosis' below.)
No proven role of immunomodulatory treatment — The results from some [15,27,36-38] but not all [10] retrospective studies in patients with diabetic amyotrophy suggest that some immunomodulatory treatments used early in the disease course were associated with clinical improvement. These regimens included such therapies as oral prednisone, intravenous methylprednisolone, intravenous immune globulin (IVIG), cyclophosphamide, and plasma exchange. However, a randomized trial found that pulse methylprednisolone therapy was not beneficial compared with placebo for functional improvement in diabetic amyotrophy [39]. In addition, a 2017 systematic review found no evidence from published randomized trials to support the use of immunotherapy for diabetic amyotrophy [40].
Some small retrospective studies of patients with idiopathic LRPN reported functional improvement with immunomodulatory therapies such as IVIG or glucocorticoids [19,20,41-43]. However, these data are limited by small numbers, no control groups to compare active treatment with the natural history of recovery, and multiple different agents used. A 2013 systematic review found no evidence from randomized trials to support the use of immunotherapy for idiopathic LRPN [13].
PROGNOSIS — Patients with diabetic amyotrophy and idiopathic LRPN typically improve within months after symptom onset. However, most patients will not recover completely [2,12,19]. Foot drop and, at times, lingering neuropathic pain commonly persist. In the series of patients with diabetic amyotrophy, 48 percent required wheelchair assistance at some point during the illness [2]. 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 nonambulatory and severely disabled at 42 months, while the other made a good recovery with mild residual truncal and proximal leg weakness [44].
Diabetic amyotrophy and idiopathic LRPN are typically a monophasic condition. Recurrent attacks have been reported to occur uncommonly, although the frequency is uncertain [2,45,46].
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 AND RECOMMENDATIONS
●Definition – LRPN refers to a group of peripheral nerve disorders characterized by anatomic location involving lumbosacral plexus and spinal roots. LRPN is often associated with type 2 diabetes mellitus, in which case it is commonly known as diabetic amyotrophy. (See 'Introduction' above and 'Terminology' above.)
●Clinical features – The clinical features of both diabetic and idiopathic LRPN typically include the acute, asymmetric, focal onset of lower extremity pain followed by progressive weakness involving the proximal leg, with associated autonomic failure and weight loss. Some patients also have upper limb and thoracic symptoms. Symptoms may progress for six months or longer before improving. (See 'Clinical features' above.)
●Diagnosis – The diagnosis of diabetic amyotrophy is made in patients with suggestive clinical features and known or newly diagnosed diabetes mellitus, after diagnostic testing has excluded other causes to symptoms. For patients who do not have diabetes mellitus, the diagnosis of idiopathic LRPN is made in patients with suggestive clinical features and supportive diagnostic testing. (See 'Diagnosis' above.)
●Diagnostic testing – We perform diagnostic testing for patients with the clinical diagnosis of diabetic amyotrophy or idiopathic LRPN to support the clinical diagnosis and to exclude alternative causes of symptoms. (See 'Diagnostic evaluation' above.)
•Screening laboratory tests consist of a complete blood count with differential, coagulation studies (prothrombin time, international normalized ratio [INR], and activated partial thromboplastin time), fasting blood glucose and hemoglobin A1c levels, erythrocyte sedimentation rate, and C-reactive protein levels. (See 'Laboratory investigations' above.)
•We typically perform MRI with gadolinium contrast of the lumbar spine and lumbosacral plexus as the imaging of choice for patients with clinical features suggestive of LRPN. CT is a less sensitive alternative option. Imaging of the thoracic and/or cervical cord is also performed when clinical features suggest a spinal localization. (See 'Neuroimaging' above.)
•Electrodiagnostic evaluation includes nerve conduction studies (NCS) and electromyography (EMG); electrodiagnostic testing can also help to define the extent of and localize the nerve involvement. (See 'Electrodiagnostic studies' above.)
●Treatment – Management of diabetic amyotrophy and idiopathic LRPN is symptomatic. We suggest an antidepressant (eg, amitriptyline, duloxetine, venlafaxine) or gabapentinoid antiseizure medication (eg, gabapentin, pregabalin) based on data for other forms of diabetic neuropathy (Grade 2C). Supportive care for weakness associated with LRPN consists of physical and occupational therapies for exercise, gait training, and assessing the need for ambulatory aids (eg, orthoses, cane, wheelchair). (See 'Symptomatic management' above.)
No immunomodulatory treatments have been proven to be effective to improve outcomes or hasten recovery. (See 'No proven role of immunomodulatory treatment' above.)
●Prognosis – Patients with diabetic amyotrophy and idiopathic LRPN typically improve slowly over several months. However, most patients will not recover completely. Recurrence is uncommon. (See 'Prognosis' above.)
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