Lumbosacral Plexopathy

Etiology

Anatomical Overview

The lumbosacral plexus is a combination of lumbar and sacral plexuses and encompasses the anterior rami of the L1 through S4 nerve roots of the peripheral nervous system, with a small contribution from T12 as well. The lumbar plexus lies above the pelvic brim and forms from L1 through L4 nerve roots, while the S1 through S4 nerve roots make up the sacral plexus, which lies below the pelvic brim. 

Lumbar plexus

The lumbar plexus is formed by the anterior rami of the first 4 lumbar nerves, which descend through the psoas muscle and bifurcate into anterior and posterior divisions. These divisions subsequently branch out to form the individual nerves of the plexus. Specifically, the femoral nerve originates from the posterior divisions of the L2 to L4 nerve roots, whereas the obturator nerves are derived from their anterior counterparts. Additional components of the lumbar plexus include the iliohypogastric nerve (T12-L1), ilioinguinal nerve (L1), genitofemoral nerve (L1-L2), and lateral femoral cutaneous nerve of the thigh (L2-L3). The sciatic nerve, a major nerve of the lower limb, incorporates fibers from both the anterior and posterior divisions of the lumbosacral trunk, along with the S1 and S2 anterior rami.

Sacral plexus

The sacral plexus is primarily composed of the superior gluteal (L4-S1), inferior gluteal (L5-S2), posterior femoral cutaneous of the thigh (S1-S3), and pudendal nerve (S1-S4). The vascular supply to the lumbosacral plexus is provided by 5 lumbar arterial branches from the abdominal aorta, complemented by the deep circumflex iliac artery, the iliolumbar artery, and the gluteal branches of the internal iliac artery. This anatomical configuration is extensively documented and illustrated in several studies.[3][6][7]

Lumbosacral Plexopathy Etiologies

Since the lumbosacral plexus is present near abdominal and pelvic organs, various pathologies and injuries contribute to lumbosacral plexopathy, including:

• Direct trauma
• Posterior hip dislocation
• Sacral fracture
• After lumbar plexus block

• Metabolic, inflammatory, and autoimmune causes [8][9][10]
• Diabetes (more likely in those with type II diabetes, ie, diabetic amyotrophy) [11]
• Amyloidosis
• Sarcoidosis 
• Post Sars CoV-2 infection (has been reported for brachial, but clinically has been seen in the lumbosacral plexus) [12]

• Infections and local abscess [13]
• Vertebral osteomyelitis
• Chronic infections (eg, tuberculosis, fungal infections)
• Other infections, eg, Lyme disease, HIV/AIDS, herpes zoster, COVID-19
• Psoas abscess with extension (Please see StatPearls' companion resource, "Psoas Syndrome", for further information on psoas abscess) 

• Radiation therapy of the abdominal and pelvic malignancies [14][15]

• Pregnancy-related causes (mostly occur in the third trimester and after delivery due to birth trauma) [16] 

• Femoral vessel catheterization
• Ischemia from direct compression (eg, arterial pseudoaneurysms, aortic dissection, and retroperitoneal hematoma) [17]

• Psoas muscle metastatic disease (endometrioid adenocarcinoma) mimicking a psoas abscess with resultant lumbosacral plexopathy [18]

  Damage to the vasculature innervating the lumbosacral plexus
• Postoperative plexopathy (scar tissue formation and hematomas may occur following gynecological and other pelvic surgeries) [19]

• Cocaine with rhabdomyolysis [20]

• Toxicities from antineoplastic drugs (ie, ladiratuzumab vedotin) [21]

Epidemiology

Lumbosacral plexopathy presents a complex epidemiological profile due to its varied etiologies, influencing both the age of onset and overall prevalence. Typically, the median age at diagnosis across all causes is approximately 65 years. Women are disproportionately affected by lumbosacral plexopathy, largely attributed to risk factors, eg, pregnancy and gynecological cancers. Diabetic amyotrophy specifically shows an incidence rate of 4.2 per 100,000 annually [1], affecting 0.8% of individuals diagnosed with diabetes mellitus.[22] Among these patients, the median duration of diabetes before the onset of amyotrophy is 4 years, with a median hemoglobin A1c value of 7.5% at diagnosis.[9][23]

Neoplastic cases of lumbosacral plexopathy predominantly involve the L4 to S1 segments in over 50% of cases, with the L1 to L4 segments affected in 31%, and panplexopathy in approximately 10% of cases.[24] In 73% of these cases, the plexopathy is associated with local compression or invasion by an abdominopelvic malignancy. Notably, lumbosacral plexopathy manifests within a year of diagnosing primary tumors in over one-third of the affected patients, and in 15% of these cases, the plexopathy itself leads to the cancer diagnosis.[25][26]

Traumatic incidents also contribute to lumbosacral plexopathy incidence, with about 0.7% following traumatic pelvic fractures, and increasing to 2% following postsacral fractures.[27] Additionally, lumbosacral plexopathy occurs in approximately 1 in 2000 to 6400 deliveries.[28] Furthermore, the incidence of retroperitoneal hematoma following femoral artery catheterization stands at only 0.5%. However, about 20% of these cases develop subsequent femoral neuropathy, and 9% progress to lumbosacral plexopathy.[29]

Pathophysiology

The pathophysiology of lumbosacral plexopathy varies based on the following etiologies:

• Trauma (ie, injury or traction on the plexus)
• Tumor, eg, infiltration by the tumor or metastasis, intraneural lymphomatosis, the perineural spread of prostate cancer
• Radiation (endothelial damage leading to chronic inflammatory cell migration and a state of fibrosis, followed by an irreversible state of microvascular injury and ischemic damage)
• Hematoma due to compression of the nerve plexus
• Diabetic and nondiabetic lumbosacral plexopathy caused by inflammatory or microvascular changes
• Vascular endoleak complication after an endovascular aneurysm repair [30]

Histopathology

In cases of malignancy extending to and causing plexopathy, the histopathology of the malignancy would be determined by biopsy, potentially receptor tested, and treated based on the oncologic standard of care for that case.

Toxicokinetics

Antineoplastic, specifically ladiratuzumab vedotin, has been shown to have an affiliation. Additionally, cocaine has been documented, especially with concomitant rhabdomyolysis, to have an association.

History and Physical

A comprehensive clinical history and meticulous physical examination are essential for diagnosing lumbosacral plexopathy. Typically, patients report low back pain that radiates to 1 side, often exacerbated in a supine position. However, bilateral lumbosacral plexopathy has been reported in sarcoidosis as well as pregnancy.[31]

Clinical History

The clinical presentation can vary secondary to the underlying etiology. Patients with diabetic lumbosacral plexopathy usually experience unilateral pain in the proximal thigh, accompanied by numbness, paresthesias, or dysesthesias in the lower limbs, predominantly on 1 side. Conversely, lumbosacral plexopathy resulting from radiotherapy often manifests without pain. Furthermore, the symptom onset can range from acute (eg, motor vehicular collisions) to chronic, as seen after radiotherapy.

In severe cases, muscle weakness and atrophy may be noted. While sphincter dysfunction is uncommon, its presence could indicate cauda equina syndrome.[32] Systemic symptoms, eg, fever, chills, night sweats, fatigue, and weight loss, may indicate underlying malignancy or infection. Pertinent history may include exposure to factors, including road traffic accidents, abdominopelvic neoplasms, radiotherapy, abdominal surgery, diabetes mellitus, bleeding disorders, or recent pregnancy, which can guide the identification of the etiology of lumbosacral plexopathy.

Physical Examination

Physical examination findings vary; mild cases may appear normal, whereas trauma cases might show bruises. The straight leg raise test is often positive in over half the patients. Asymmetric lower limb muscle weakness and correspondingly diminished or absent deep tendon reflexes may be noted, with the knee jerk reflex commonly impacted in lumbar plexopathy and the ankle jerk reflex in sacral plexopathy. Muscle weakness involving hip flexion, knee extension, or adduction could indicate damage to the lumbar plexus. During a physical exam, acute or chronic foot drop is the most common initial sign of ALS.[33]

Sensory loss may follow a dermatomal pattern for proximal lumbosacral plexopathy involving nerve roots or a nerve distribution pattern. Sensory alterations in the medial thigh, anterior thigh, and medial leg suggest lumbar plexus involvement, whereas changes in the posterior thigh, dorsum of the foot, and perineum point to sacral plexus involvement. Spinal point tenderness is notable in cases of sacral fracture or infection. During examination, a rectal exam is advisable to assess rectal tone. Although rare, saddle anesthesia and bowel or bladder incontinence may also occur, complicating differentiation from cauda equina and conus medullaris syndromes. The inguinal region should be palpated for potential hematomas.

Evaluation

Neuroimaging, specifically magnetic resonance imaging (MRI) of the lumbosacral spine, and electrodiagnostic studies, eg, nerve conduction study and electromyography, are essential in the confirmation of the diagnosis of lumbosacral plexopathy. 

Imaging Studie

MRI with gadolinium contrast is the best test for the evaluation of the lumbosacral plexus. When contraindications to MRI (eg, a noncompatible pacemaker) are identified, a computed tomography (CT) scan with contrast can be utilized.[34][35] MR neurography is a useful modality compared to traditional MRI in lumbosacral plexopathy evaluation. Neurography helps identify extraspinal injuries responsible for neuropathic leg pain.[35] Recently, high-resolution ultrasounds have also been shown to be an excellent alternative for dynamic evaluation and visualization of the nerve architecture, and can be used as an affordable first step for diagnosticians trained in ultrasound imaging.[36]

In cases of malignancy, differentiating direct compression from metastatic disease can be challenging. Thus, advanced imaging is often needed.[37] MRI is often ordered for the initial evaluation of neoplasm-associated lumbosacral plexopathy. Positron emission tomography (PET) is used to determine the full extent of malignancy.[26] PET scans also help in staging the disease, subsequent treatment, and prognosis.

Electrodiagnostic Studies

Electrodiagnostic studies, eg, electromyography (EMG), help differentiate lumbosacral plexopathy from other types of neuropathy or radiculopathies. Electromyography helps in the localization of neurological injury. EMG can also help differentiate malignancy from radiation-induced plexopathy.[38][39] Myokymic discharges occur in cases of radiation-induced plexopathy but do not occur in cases of neoplasm. Myokymia is the spontaneous burst of an individual motor unit. These bursts occur several times per second and rhythmically. Denervation of the paraspinal muscles is commonly seen in radiculopathy and helps to differentiate from lumbosacral plexopathy.[2] Magnetic nerve root stimulation can aid in the diagnosis of patients with contraindications to EMG (eg, bleeding disorders). The use of magnetic root stimulation for a more extensive analysis of nerve root damage has been reported in challenging cases of lumbosacral plexopathy.[40] 

Laboratory Investigations

Recommended blood tests to identify the etiology in patients with lumbosacral plexopathy should include a complete blood count with an erythrocyte sedimentation rate, C-reactive protein, coagulation studies, autoantibodies testing (eg, antinuclear antibodies, antineutrophil cytoplasmic antibodies, anti-Sjögren-syndrome-related antigen A, and anti-Ro/anti-La antibodies), and hemoglobin A1c. Furthermore, serum protein electrophoresis, angiotensin-converting enzyme levels, human immunodeficiency virus (HIV), Lyme antibodies, rapid plasma reagin, and Epstein-Barr virus serology may be indicated for specific cases.[41]

Additional Diagnostic Studies

If the cause of lumbosacral plexopathy is still not identified despite the above investigations, it indicates the need for a lumbar puncture. When malignancy is found, a biopsy of pelvic organs, as well as a biopsy of the suspected affected nerve root, is needed. Sciatic nerve fascicular biopsies aid in diagnosis for complex cases and cases of suspected malignancy present in the sciatic nerve distribution.[42]

Biopsy

Biopsy may be indicated in indeterminate masses compressing or metastasizing to the lumbosacral plexus. This may also be for aspiration for organisms for culture and sensitivity in the case of infectious etiology, or histopathology in the cases of malignancy. Although intramuscular metastasis is rare, sporadic cases have been documented.

Treatment / Management

The treatment of lumbosacral plexopathy primarily comprises therapy tailored to the specific underlying cause and symptomatic relief.

Supportive Treatments

Supportive therapies typically involve the administration of analgesics and muscle relaxants, including non-steroidal anti-inflammatory drugs (NSAIDs), pregabalin, gabapentin, duloxetine, amitriptyline, and opioids. For patients experiencing foot drop, ankle-foot orthoses may be beneficial. In cases of infection, appropriate antibiotics and antifungals are necessary.

Etiology-Specific Therapies

Diabetic amyotrophy, often transient, generally improves with effective glycemic control. Neuropathic pain management strategies are recommended for symptomatic relief in these patients.[4][43] Treatment options that may be considered in persistent, severe cases include steroids, intravenous immunoglobulin (IVIG), cyclophosphamide, and plasma exchange.[41](B3)

In malignancy-associated lumbosacral plexopathy, excision or appropriate management of the primary tumor is critical. For severe symptomatic cases, dorsal rhizotomy may be performed, which has been shown to significantly reduce pain and decrease opioid dependence in terminally ill patients.[44]

Radiation-induced plexopathy, often manifesting as painless weakness and sensory changes, usually occurs bilaterally and can appear years following radiation exposure.[45] No effective treatments for radiation-induced plexopathy have been established; thus, physiotherapy and rehabilitation are emphasized, and any further radiotherapy should be avoided.(B2)

Surgical intervention, eg, nerve repair techniques and nerve grafting, has shown promising results in improving muscle function following pelvic fractures. A small study involving 10 patients with traumatic lumbosacral plexopathy reported significant muscle function improvement at a 38-month followup after undergoing nerve grafting.[46][47](B3)

For patients with a retroperitoneal hematoma, conservative management typically includes blood transfusions and bed rest. Surgical intervention may be necessary if the hematoma worsens or if neurological function deteriorates.[48](B3)

Differential Diagnosis

Differential diagnoses that should also be considered when evaluating lumbosacral plexopathy include:

• Cauda equina syndrome
• Conus medullaris syndrome
• Hereditary sensory and motor neuropathy (also called Charcot-Marie-Tooth disease)
• Lumbosacral radiculopathy
• Mononeuropathies (eg, Femoral neuropathy, sciatic neuropathy, and common femoral neuropathy)
• Polyneuropathy (eg, diabetic neuropathy, chronic inflammatory demyelinating neuropathy, and drug-related neuropathy)
• Spinal canal stenosis
• Spinal cord tumors
• Malingering
• Somatization disorder
• Vascular Arterial Insufficiency

Toxicity and Adverse Effect Management

Toxicity and adverse effect management depend upon the treatments required. In cases of toxicity secondary to antineoplastic treatment, it may or may not be possible to discontinue or change the regimen. A risk-benefit decision may need to be made with the patient regarding chemotherapy and radiation therapy. Numerous chemicals have been shown to cause toxic neuropathies and myopathies. In cases where cocaine is felt to be a possible etiology, cessation should be encouraged. An addiction medicine program or Cocaine Anon should be considered.

Any biopsy or abscess drainage risks are standard for those procedures and should be done in facilities with adequate equipment and personnel to manage complications. Any specific medications used should have their adverse effect profiles reviewed (ie, serotonergic, sedative, anticholinergic effects), monitored, and dose adjusted as needed.

If opiates are used, a competent adult should be trained in Narcan, usually by watching the online video, and Narcan should be prescribed, and everyone should know where it is and when to use it. In cases of end-of-life and hospice, shared decision-making should be used regarding when Narcan should no longer be used.

Prognosis

Prognosis depends upon the underlying etiology, its response to treatment, and the timing of therapeutic intervention. Prognosis is good for patients with lumbosacral plexopathy secondary to pregnancy, retroperitoneal hematoma, and diabetic amyotrophy. The majority of patients with pregnancy-related lumbosacral plexopathy have a complete resolution of their symptoms 2 to 6 months following delivery.[16][49] 

Progressive neurological deterioration is common in patients with lumbosacral plexopathy secondary to malignancy. Prognosis is abysmal in neoplastic instances, with a mean survival of 6 months. Lymphoma has been demonstrated to be the most responsive tumor to therapy.[24] At 42-month follow-up, 86% of patients diagnosed with lumbosacral plexopathy secondary to malignancy had died.

Traumatic lumbosacral plexopathies are generally considered to have an unfavorable prognosis, but a case series of 72 patients with traumatic lumbosacral plexopathies demonstrated that more than two-thirds (about 70%) of patients recovered spontaneously within 18 months.[50]

Complications

Complications associated with lumbosacral plexopathy include:

• Progressive neurological deterioration
• Intractable pain, eg, chronic pain syndrome 
• Bedsores
• Recurrent infections
• Joint contractures
• Depression
• Arterial vascular insufficiency
• Reflex sympathetic dystrophy