Lumbosacral Plexopathy

Etiology

A firm understanding of anatomy is indispensable in understanding the etiology and pathophysiology of LS plexopathy. The LS 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. 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 four anterior rami of the lumbar nerve roots travel down the psoas muscle and divide into an anterior and posterior branch. These branches later give rise to individual nerves. The femoral nerve is made up of the posterior branches of L2-L4, while the obturator nerves make up of the anterior branches of L2-L4. Other nerves 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 is primarily comprised of anterior and posterior branches of the lumbosacral trunk, as well as the S1 and S2 anterior rami.
• Sacral Plexus: It includes the superior gluteal (L4-S1), inferior gluteal (L5-S2), posterior femoral cutaneous of the thigh (S1-S3), and pudendal nerve (S1-S4). LS plexus receives its blood supply by five lumbar arterial branches of the abdominal aorta. Furthermore, the deep circumflex iliac artery, iliolumbar, and gluteal branches of the internal iliac artery also supply the plexus.[6] Illustrations of the lumbosacral neural anatomy appear in these referenced PubMed articles.[3][7]

Since LS plexus is present near to abdominal and pelvic organs, various pathologies and injuries contribute to LS plexopathy. These include (but not limited to):

• Direct trauma
  • Posterior hip dislocation
  • Sacral fracture
  • After lumbar plexus block
• Metabolic, inflammatory, and autoimmune causes: [8][9] 
  • Diabetes mellitus (DM) - more likely in those with type II DM
  • Amyloidosis
  • Sarcoidosis 
• Infections and local abscess.[10]
  • Vertebral osteomyelitis
  • Chronic infections (e.g. Tuberculosis, fungal infections)
  • Other infections: Lyme disease, HIV/AIDS, Herpes zoster (HZ)
  • Psoas abscess
• Radiation therapy of the abdominal and pelvic malignancies.
• Pregnancy-related
  • Mostly occur in the third trimester and after delivery due to birth trauma.[11] 
• Postoperative plexopathy
  • Scar tissue formation and hematomas may occur following gynecological and other pelvic surgeries.[12]
• Damage to the vasculature innervating the LS plexus
  • Femoral vessel catheterization
  • Ischemia from direct compression due to arterial pseudoaneurysms, aortic dissection, retroperitoneal hematoma, etc.).[13]

Epidemiology

Due to the diverse etiologies, the age of presentation and prevalence varies. However, the median age for diagnosis of LS plexopathy is around 65 years for all causes. LS plexopathy is more common in women due to the predisposing risk factors of pregnancy and gynecological cancers.

The incidence of diabetic amyotrophy is 4.2 per 100,000 annually[1] and occurs in 0.8 percent of people with diabetes mellitus (DM).[14] The median duration of DM is four years with a median hemoglobin A1c of 7.5% at the time of diagnosis of diabetic amyotrophy.[9][15] 

For neoplastic cases of LS plexopathy, L4-S1 segment is commonly affected (>50% of cases) followed by L1-L4 segment (31%), and pan-plexopathy (about 10%).[16] In 73% of cases, a local compression or invasion of an abdominopelvic malignancy was present. LS plexopathy occurs within one year of diagnosis in over one-third of patients with primary tumors. In 15% of cases, LS plexopathy resulted in the diagnosis of cancer.[17][18]

LS plexopathy occurs in roughly 0.7% of cases following a traumatic pelvic fracture. Incidence increases to 2% following a sacral fracture.[19] 

LS plexopathy occurs in an estimated 1 in 2000-6400 deliveries.[20] 

The incidence of retroperitoneal hematoma following femoral artery catheter is only 0.5%. About 20% of these patients develop underlying femoral neuropathy, while 9% develop LS plexopathy.[21]

Pathophysiology

The pathophysiology of LS plexopathy varies based on the etiology:

• Trauma - direct injury or traction on the plexus
• Tumor - direct infiltration by the tumor or metastasis, intra-neural lymphomatosis, the perineural spread of prostate cancer
• Radiation - This leads to 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 - Direct compression
• Diabetic and non-diabetic LS plexopathies - caused by inflammatory or microvascular changes

History and Physical

A detailed clinical history and physical examination are crucial for the diagnosis of LS plexopathy. Patients typically present with low back pain radiating to one side. Pain may be positional, worse in a supine position. Patients with diabetic LS plexopathy (diabetic amyotrophy) typically complain of unilateral pain in the proximal thigh. Pain may be associated with numbness, paresthesias, or dysesthesias of the lower limbs. These symptoms are usually unilateral. LS plexopathy secondary to radiotherapy is usually painless. The duration of symptoms may vary from very acute (after road traffic accident) to chronic (after radiotherapy). In severe cases, muscle weakness and atrophy may occur. Sphincter disturbances are rare and their presence should suspect cauda equine syndrome.[22] Fever, chills, night sweats, fatigue, and weight loss may suggest malignancy or infection. A history of a road traffic accident, abdominopelvic neoplasm, radiotherapy, abdominal surgery, diabetes mellitus, bleeding disorders, or recent pregnancy hints towards LS plexopathy and narrows down the etiology. 

Physical examination may be normal in mild cases. Bruises may be seen in cases of trauma. A straight leg raise test is positive in more than half of the patients. Asymmetric lower limb muscle weakness may be seen with asymmetrically absent or reduced deep tendon reflexes. Knee jerk reflex is affected in lumbar plexopathy and ankle jerk is affected in sacral plexopathy. Muscle weakness in hip flexion, knee extension, or adduction suggests a possible injury to the lumbar plexus. Sensory loss may be present in a dermatomal pattern in cases of proximal LS plexopathy involving the roots, or in the nerve distribution. Sensory changes to the medial thigh, anterior thigh, and medial leg can suggest lumbar plexus involvement; posterior thigh, dorsum of the foot, and perineum are likely related to sacral plexus involvement. Spinal point tenderness may be present, especially in cases of sacral fracture or infection. A rectal exam should be performed to assess rectal tone. Saddle anesthesia and bowel or bladder incontinence are rare and may be present, making it difficult to differentiate from cauda equina and conus medullaris syndromes. The inguinal region should also be palpated for suspected hematomas.

Evaluation

Neuroimaging, preferably, magnetic resonance imaging (MRI) of the LS spine and electrodiagnostic studies (nerve conduction study and electromyography) are important in confirmation of the diagnosis of LS plexopathy. 

Imaging

MRI with gadolinium contrast is the best test for the evaluation of the LS plexus. When there are contraindications to MRI (e.g., a noncompatible pacemaker), a computed tomography (CT) scan with contrast can be utilized.[23][24] MR neurography is a useful modality compared to traditional MRI in LS plexopathy evaluation. Neurography helps identify extraspinal injuries responsible for neuropathic leg pain.[24]

In cases of malignancy, it can be challenging to differentiate direct compression from metastatic disease. Thus advanced imaging is often needed.[25] MRI is often ordered for the initial evaluation of neoplasm-associated LS plexopathy. Positron emission tomography (PET) is to determine the full extent of malignancy.[18] It also helps in the staging of the disease and subsequent treatment and prognosis.

Electrodiagnostic Studies

Electrodiagnostic studies such as electromyography (EMG) are useful to 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.[26][27] 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 LS plexopathy.[2] Magnetic nerve root stimulation can aid in the diagnosis of patients with contraindications to EMG (e.g. bleeding disorders). There are cases reported with the use of magnetic root stimulation for a more extensive analysis of nerve root damage under challenging cases of lumbosacral plexopathy.[28] 

Laboratory Investigations

Recommended blood tests to identify the etiology in patients with LS plexopathy should include a complete blood count with an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), coagulation studies, autoantibodies testing (antinuclear antibodies (ANA), Antineutrophil cytoplasmic antibodies (ANCA), Anti-Sjögren's-syndrome-related antigen A, anti-Ro/anti-La antibodies, etc.) and hemoglobin A1c. Furthermore, serum protein electrophoresis (SPEP), angiotensin-converting enzyme (ACE) levels, human immunodeficiency virus (HIV), Lyme antibodies, rapid plasma reagin (RPR), and Epstein-Barr virus (EBV) serology may be indicated for specific cases.[29]

Other Investigations

If the cause of LS 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 difficult cases; for cases of suspected malignancy present in the distribution of the sciatic nerve.[30]

Treatment / Management

Treatment for LS plexopathy depends upon the underlying etiology. Symptomatic management with analgesics and muscle relaxants is given. Analgesics include non-steroidal anti-inflammatory drugs (NSAIDs), pregabalin, gabapentin, duloxetine, amitriptyline, and opioids. Ankle-foot orthoses (AFOs) can be used for the foot drop. Appropriate antibiotics and antifungals are required for the infection.

Diabetic amyotrophy is a transient condition that usually resolves with good glycemic control. Neuropathic pain treatments are advised for symptomatic management.[4][31] In severe unremitting cases, steroids, intravenous immunoglobulin (IVIG), cyclophosphamide, and even plasma exchange may be tried.[29](B3)

In cases of malignancy, the primary tumor should be removed and accordingly managed. In severe symptomatic cases, a dorsal rhizotomy may be considered. Rhizotomy was shown to cause a significant reduction in pain and opioid usage in this population. This treatment method is primarily used for terminal patients.[32]

Radiation plexopathy can often present without pain, only weakness and sensory changes. Unlike other types of plexopathy, it is usually bilateral and can occur even years after radiation.[33] There are no known treatments for radiation-induced plexopathy. Physiotherapy and rehabilitation are the mainstays of treatment. Further radiotherapy sessions should be discontinued.(B2)

Surgical nerve repair techniques and nerve grafting have helped improve muscle function in pelvic fractures. One small study of 10 patients experiencing traumatic lumbosacral plexopathy, who underwent nerve grafting showed significant improvement of muscle function at 38 months follow-up.[34][35](B3)

Retroperitoneal hematoma is usually conservatively managed with blood transfusions and bed rest. Surgery is advised in cases of worsening hematoma or worsening neurological function.[36](B3)

Differential Diagnosis

• Cauda equina syndrome
• Conus medullaris syndrome
• Hereditary sensory and motor neuropathy (also called Charcot-Marie-Tooth disease)
• Lumbosacral radiculopathy
• Mononeuropathies (e.g. Femoral neuropathy, sciatic neuropathy, common femoral neuropathy)
• Polyneuropathy (e.g. diabetic neuropathy, chronic inflammatory demyelinating neuropathy (CIDP), drug-related neuropathy)
• Spinal canal stenosis
• Spinal cord tumors

Prognosis

Prognosis depends upon the underlying etiology, its response to treatment, and the timing of therapeutic intervention. Prognosis is good for patients with LS plexopathy secondary to pregnancy, retroperitoneal hematoma, and diabetic amyotrophy. The majority of patients with pregnancy-related LS plexopathy have a complete resolution of their symptoms two to six months following delivery.[11][37] 

Progressive neurological deterioration is common in patients with lumbosacral plexopathy secondary to malignancy. Prognosis is abysmal in neoplastic instances, with a mean survival of six months. Lymphoma has demonstrated to be the most responsive tumor to therapy.[16] At 42 month follow-up, 86% of patients diagnosed with LS plexopathy secondary to malignancy had died.

Traumatic LS plexopathies are generally considered to have an unfavorable prognosis but a case-series of 72 patients with traumatic LS plexopathies demonstrated that more than two-thirds (about 70%) of patients recovered spontaneously within 18 months.[38]

Complications

• Progressive neurological deterioration
• Intractable pain
• Bedsores
• Recurrent infections
• Joint contractures