Introduction

A principle in neurological diagnosis is that anatomical localization is derived from a careful physical examination and the etiology of a condition is usually suggested by the clinical history of the evolution of complaints, buttressed by, and often confirmed by, laboratory data including imaging techniques and clinical neurophysiological testing. As pain is ultimately mediated by the peripheral and central nervous systems, this principle is equally valid for Pain Medicine. While the history and associated laboratory, imaging techniques and neurophysiological testing usually gives the etiology, an important corollary is that different etiologies tend to predominate in different parts of the body subserved by different portions of the nervous system, e.g. plexus versus nerve with the plexus obviously being proximal to the nerve. In addition, the plexus is surrounded by different non-neurological structures than the nerve, giving a different gamut of possible tissues from which pathological process may arise or be affected in a painful process. Ascribing the locus of a pathological process to the femoral nerve when it actually is in the lumbosacral plexus carries with it the hazard of not investigating the retroperitoneal space which may be the site of numerous pathological processes, some serious such as malignancy and some even life threatening such as acute hemorrhage.

Yet, in spite of potentially disastrous consequences, for much of medicine’s history, since the association between diabetes mellitus and neurological complications was first made in 1798, when John Rollo mentioned neurological complications in his book Cases of Diabetes Mellitus, there has been misidentification of the lesion site in diabetes mellitus as femoral nerve rather than lumbosacral plexus in clinical settings in which many other conditions might be present.

A brief history of misconceptions about femoral neuropathy is in order. Descriptions of diabetic neuropathy as early as 1890 recognized cases in which there was asymmetrical lower extremity pain and weakness. [1]-[4] This concept persisted through the 18th, 19th and 20th century until at least 1976. Then it became recognized that what had previously been called femoral neuropathy was much more frequently a lumbar plexopathy. Asbury clarified the issue advocating the term proximal diabetic neuropathy in view of the ambiguities associated with the earlier term diabetic amyotrophy. [5] This syndrome "goes by a bewildering variety of names" stated Donaghy.[6] These include diabetic amyotrophy, diabetic lumbosacral plexopathy, diabetic polyradiculopathy, proximal diabetic neuropathy, ischemic mononeuropathy multiplex associated with diabetes mellitus, Bruns-Garland syndrome, and diabetic lumbosacral radiculoplexus neuropathy. [7] [8] “It is also misleadingly referred to as diabetic femoral neuropathy. The simple and descriptive term proximal diabetic neuropathy is preferred”. [5]

Unfortunately the association of the relatively uncommon femoral neuropathy with diabetes mellitus has persisted when, in fact, diabetes is much more commonly associated with a lumbar plexopathy. The long history of this erroneous association only terminated with the advent of modern meticulous Electrodiagnostic methods and should serve as a cautionary note also not to neglect the multiple possible causes of true femoral neuropathy. [9]

While the femoral nerve may be involved in the retroperitoneal space and even be the most prominently involved portion of the lumbosacral plexus, there are obviously other sites at which the femoral nerve may be involved. Lumbosacral plexopathy and femoral neuropathy share certain etiologies but the demographics and sites of involvement of the two anatomical areas vary. In addition, diabetes mellitus is commonly seen in the two populations. Recourse to tables 1 and 2 will give some insight into the different disorders affecting the two areas with their relative prevalence. It should be noted that femoral neuropathy is a relatively rare condition explaining why so many of the entities listed are characterized as rare.

Table 1- Causes of Lumbosacral Plexopathy

• Malignant Invasion-frequent
• Primary tumors-rare
• Postradiation syndrome-infrequent
• Retroperitoneal Hemorrhage-frequent
• Retroperitoneal abscess-relatively rare
• Diabetic Lumbosacral plexopathy-common
• Nondiabetic Lumbosacral plexopathy-rare
• Injections-rare
• Obstetrical Injuries-relatively uncommon
• Ischemia-rare
• Trauma-relatively uncommon
• Aneurysms-rare
• Viral Infections including Herpes-relatively uncommon

Table 2 -Causes of Femoral Neuropathy

1. Retroperitoneal and Iliacus Compartment Hemorrhage
   1. Spontaneous-rare
   2. Associated with anticoagulants, eg heparin, coumadin- relatively common
   3. Traumatic iliacus muscle avulsion-rare
   4. Hemophilia and other coagulinopathies-rare
   5. Traumatic pseudoaneurysm and iliacus hematoma-rare
2. Iliacus abscess-rare
3. Abdominal aortic aneurysm and pseudoaneurysm-rare
4. Trauma, stretch or compression-relatively common
5. Idiopathic-rare (some may have been diabetic)
6. Tumors, enlarged lymph nodes, complications of radiation, chemotherapeutic injection-rare
7. Diabetes mellitus (usually as part of a lumbar plexopathy)-rare as isolated lesion, common as plexopathy
8. Pregnancy and delivery-relatively common
9. Iatrogenic

   1. Hip arthroplasty-relatively common

   2. Neural blockade and tourniquet use-rare

   3. Abdominal hysterectomy including retractor injury-relatively common

   4. Renal transplants and other urological and pelvic surgery-relatively common

   5. Lithotomy position for delivery and operation, including vaginal hysterectomy-relatively common

   6. Inguinal and femoral herniorrhaphies-infrequent to rare

Anatomy of the Lumbosacral Plexus

The lumbosacral plexus is comprised of two distinct portions: the lumbar plexus and the sacral plexus, each innervating a different part of the lower limb. [Figure] The lumbar plexus is formed by the ventral primary rami of L1-4 with contributions from the ventral rami of L4 and T12. The lumbar plexus separates into anterior and posterior divisions. The anterior one forms the obturator nerve that innervates the medial thigh, while the posterior division forms the femoral nerve innervating the anterior and medial thigh. The anatomy of the femoral nerve is detailed below. All cutaneous and muscular branches of the plexus are limited to the thigh except for the saphenous nerve, a continuation of the femoral nerve that supplies the medial leg. The caudally located sacral plexus is formed from the ventral primary rami of L5-S4, and separates into anterior and posterior divisions. The anterior division forms the tibial nerve and innervates the posterior thigh and leg. The posterior division forms the gluteal nerve, inferior gluteal, and peroneal nerve. All these innervate the posterior hip and anterolateral leg. The lumbar plexus is linked to the sacral plexus by the lumbosacral trunk that contains the some fibers from the 4th and all of those from the 5th lumbar ventral root. The trunk passes over the sacral ala adjacent to the sacroiliac joints.

The sacral plexus is formed from the union of the lumbosacral trunk with the ventral rami of the 1st through 4th sacral nerves. The plexus lies on the posterior and posterior lateral wall of the pelvis. The sacral ventral roots divide into ventral and dorsal branches analogous to the lumbar plexus division. The lateral sciatic nerve trunk gives rise to the common peroneal nerve and is formed by union of dorsal ranches of the lumbosacral trunk (L4, L5) and the dorsal branches of the ventral rami of S1 and S2. The medial trunk of the sciatic nerve forms the tibial nerve arises from the ventral portions of the ventral rami of L4 to S2. Other nerves formed are the superior and inferior gluteal, pudendal and the posterior cutaneous nerve of the thigh.

Clinical Manifestations of Lumbosacral Plexus Dysfunction

Neurologic signs consist of motor deficit with flaccid paralysis, associated with sensory deficits to all types of stimulation in the territory of the damaged nerve roots. Careful examination reveals motor and sensory deficits extending beyond a single nerve root or individual nerve.
Pain may be a prominent feature of lumbosacral plexus disorders. Characteristically, in diabetic proximal neuropathy, (itself a poor term, but better than previous terms-see above for the multiplicity of terms employed historically) a prominent feature is pain that is often severe and located in the back, hips, and thighs; occasionally, pain is mild or even absent.

The pain is usually excruciating in severity and after a period of days to weeks resolves, only to leave severe weakness in its wake. The condition may develop in long-standing diabetics during periods of poor metabolic control and weight loss, but it can also occur in mild and well controlled diabetics or be the presenting feature of diabetes. The clinical features are variable, and the onset may be gradual or sudden. The patient may have systemic symptoms of anorexia, malaise, and weight loss. The usual motor findings are unilateral wasting and weakness of the proximal legs and hip girdle, but distal muscles may also be affected. The quadriceps group is often the most affected muscles. The weakness varies from mild to so severe as to render the patient wheelchair-bound. All these symptoms and signs are usually, but not always, asymmetrical. Patients frequently have coexisting sensorimotor polyneuropathy.[5][6][7]

In routine neurologic examination, many injuries of lumbosacral plexus are misdiagnosed as injuries of femoral nerve, and many sacral plexus injuries as injuries of sciatic or common peroneal nerve.[10][11] In cases in which post surgical injury is suspected, clinical suspicion is important in determining which findings are due to the guarding associated with pain since pain is a major limiting factor in routine neurologic assessment in these cases and actual uscle weakness.At least 75% of patients with lumbosacral plexus metastases present with pain, usually unilateral and affecting the low back, hip, and thigh.[12]-[15]

Nearly all patients with malignant invasion of the lumbosacral plexus eventually develop local or radicular pain that progressively worsens, is usually unrelenting despite narcotics, and is characteristically worse at night. Most patients subsequently develop weakness and sensory symptoms after a lag period of weeks to months. Bladder dysfunction is uncommon. Examination reveals weakness, sensory loss, and diminished muscle stretch reflexes in a pattern reflecting involvement of more than 1 nerve root. Approximately 50% of patients have sacral or sciatic notch tenderness or a positive straight-leg raising test that may cause confusion with lumbar disc pathology. [13] Patients may develop a "hot dry foot" from involvement of the sympathetic fibers.[16]-[18]

Another group of patients, mainly with rectal tumors, presents with perineal pain, sensory loss, and early bowel or bladder sphincter involvement, reflecting selective tumor involvement of the coccygeal plexus. [12][13] Rarely a benign space occupying process will affect the lumbosacral plexus. Some of the identified causes include pelvic hydatid cyst, dermoid cyst of the omentum and leiomyoma of the uterus [19]-[21] Acute lumbosacral plexopathy may occur during or shortly after radiation therapy for pelvic tumors.
Radiation-induced lumbosacral plexopathy usually presents as bilateral but asymmetric leg weakness. The weakness may involve any muscles innervated by L2 through S1, but it often has L5-S1 predominance. Atrophy, fasiculations, and loss of tendon reflexes accompany the weakness. Pain eventually occurs in approximately one-half of patients, but it is usually not early or severe. Approximately one-third of patients have early and prominent numbness and paresthesias. Radiation induced lumbosacral plexopathy may be difficult to differentiate on clinical grounds from recurrent malignancies. [15][22][23] Bladder or bowel symptoms are unusual, and, if present, they are often attributable to radiation-induced proctitis or bladder fibrosis.

In a study of 85 cancer patients with lumbosacral plexopathy and documented pelvic tumor by CT or biopsy, three clinical syndromes were delineated: lower (L4-S1), 51%; upper (L1-L4), 31%; and pan-plexopathy (L1-S3), 18%. Seventy percent of patients had the insidious onset of pelvic or radicular leg pain, followed weeks to months later by sensory symptoms and weakness. The quintet of leg pain, weakness, edema, rectal mass, and hydronephrosis suggests plexopathy due to cancer. CT showed pelvic tumor in 96%.Stewart [9] has stated that there are 4 possible syndromes of invasion of the plexus due to malignancy:

1. Involvement of the lumbar plexus.
2. Involvement of the sacral plexus.
3. Bilateral involvement of the most caudal fibers of the sacral plexus.
4. Involvement of the entire lumbosacral plexus.[9][12]

Insidious low back pain or pelvic pain, sometimes with radiation into the leg is often the first manifestation. Inevitably there is severe pain with sensory and motor findings occurring. Bladder and bowel dysfunction occurs with large intrapelvic tumors or localized erosion into the cauda equina.

The differential diagnosis of lesions of the lower motor neuron in the leg requires extensive testing of motor power, tone and presence or absence of atrophy of all muscles and muscle groups, deep tendon reflex at the knee and ankle, and sensory testing in all dermatomes of the lower extremity. A plantar response, crossed adductor reflex and cremasteric reflex should be sought to rule out upper motor neuron pathology involving more proximal locations in the spinal cord or above.

Often in a lumbosacral plexus lesion, the quadriceps group may bear the brunt of the injury but involvement of the iliopsoas muscle and hip adductors clearly labels the lesion beyond the expected findings for a femoral neuropathy and places the lesion more proximally in the plexus. Extension of the sensory abnormality outside the area of the anterior thigh may also offer strong evidence of plexus involvement. However, the elucidation of the true site of the lesion within the plexus or nerves may require extensive Electrodiagnostic testing as some involvement may not be discernible clinically. With post surgical and traumatic conditions there may be multiple nerve involvement of individual nerves, e.g. the femoral and obturator nerves, further confounding the situation.

Etiological Considerations

Malignant infiltration

Tumors, which are locally invasive or distant metastases, may impinge upon the lumbosacral plexus. Tumors arising in pelvic structures, abdominal or retroperitoneal spaces are frequent invaders of the lumbosacral plexus. This includes prostatic tumors, cervical tumors, kidney tumors, bladder tumors retroperitoneal lymph nodes and bony masses. Metastatic lesions may invade the plexus directly or indirectly by metastases to the spine and retroperitoneal nodes. As many as 15% patients with malignant tumors initially present as lumbosacral metastases. [12]-[15][24]-[35] Rarely a benign space occupying process will affect the lumbosacral plexus. Pelvic hydatid cyst, dermoid cyst of the greater omentum, leiomyoma of the uterus and primary nerve sheath tumors have been described.[19]-[21][36]

Radiation Plexopathy

Postradiation plexopathy is relatively uncommon but must be differentiated from recurrent malignancy but recurrent malignancy is much more common. Differentiation depends mostly on imaging studies. Intervals of one month to many years between treatment and onset of symptoms are common with a median of 5 years.[12][15] [26]-[31] There is usually painless weakness in the legs as a first symptom with less frequent occurrence of sensory symptoms that may be absent completely. Late onset pain, usually of lesser intensity than in malignant recurrent invasion may occur. Many of those afflicted are young men treated for testicular cancer or women treated for uterine or ovarian cancer with radiation and while there is a suggestion of dose-related involvement, the association is not clear.[32]

Retroperitoneal Hemorrhage and Abscesses

Retroperitoneal hemorrhage is usually a complication of anticoagulation and may cause compression of the lumbar plexus, the entire lumbosacral plexus or the femoral nerve (see below under femoral neuropathy). Less common causes are hemophilia, DIC syndrome (Disseminated intravascular coagulinopathy), and thrombocytopenia or rarely rupture of an abdominal aortic aneurysm.[37]-[44] Ischemia may also present as lumbosacral plexopathy and rarely as a complication of dialysis via the femoral vein. [38]-[43], [45]-[50] Retroperitoneal abscess may arise from infection in the vertebral bodies, perinephric areas or gastrointestinal tract. Involvement of the plexus within the psoas muscle is the usual site of involvement. HIV immunosuppression has produced rectal abscess with resulting pelvic cellulites and involvement of the plexus. Numerous organisms such as tuberculosis, syphilis and schistosmiasis (a recurrent syndrome) have been recognized. Non-infectious inflammation has been recognized in sarcoid and a painful lumbosacral plexopathy with elevated sedimentation rate in 6 patients with plexopathy; 3 had diabetes but no relief with diabetic control. Four of the five had relief with immunosuppressive drugs. Vaccination has also been reported in temporal association with plexitis.[51]-[55]

Trauma

Direct injury to the lumbosacral plexus may result from pelvic fractures, gunshot wounds, and penetrating injuries by other objects and in the neonatal period by forcible breech extractions. [56]-[61]

Pregnancy and Complications of Delivery

Weakness in a leg following delivery is an uncommon but recognized complication of pregnancy. Differential diagnosis includes peroneal palsy from stirrups and lumbar discopathy. This may, when a true lumbosacral plexopathy be due to prolonged labor, cephalopelvic disproportion and the use of forceps. Obviously these conditions often coexist with pressure induced by the fetal head or the forceps or both at fault. Another possibility is damage to the lumbar nerve roots by epidural analgesia.[62]-[66]

Diabetic Radiculoplexopathy

Reference has been made above to the confusing terminology surrounding this entity and its usually erroneous identification as a “diabetic femoral neuropathy”. The vast majority of diabetics who develop a proximal syndrome of pain and weakness have a diffuse involvement of the lumbosacral plexus by modern electodiagnostic techniques. The pathophysiology of this disorder is not clear. One postmortem study showed possible multiple infarcts in the lumbosacral plexus and proximal obturator and femoral nerves. Others have postulated a toxic effect of metabolites peculiar to diabetics. Electromyographic evidence implicates the spinal nerves, hence the designation radiculoplexopathy.[67][68] Small vessel disease has been implicated because of a report in diabetic women undergoing renal transplants when the iliac artery was used to supply the kidney giving rise to ischemic changes (presumably) in the plexus. Non-diabetic patients did not encounter similar difficulties.[69]

There is a great variability in the appearance of plexopathy in the diabetic. It may range from a severe insulin-dependent diabetic to a mild non-insulin-dependent diabetic, occasionally appearing as the initial manifestation of previously unrecognized diabetes. There may be sudden or gradual onset with severe pain in the back, hips and thighs although rarely there is little or no pain. Relentless pain, often worse at night and at rest (differentiating it from radiculopathy which is usually better at rest) is a common feature. Asymmetry is the rule in both pain and weakness.The weakness is generally progressive and often continues, and in fact becoming more prominent, after the pain subsides. Recovery is incomplete to at least a mild degree in 60% of patients and recovery may take from 3 to 18 months. [70][71]

Idiopathic Lumbosacral Plexopathies

Rarely a syndrome resembling diabetic plexopathy occurs in the absence of diabetes mellitus. There is no age predilection and children have also been reported with this syndrome. Acute or insidious onset of severe pain followed by weakness occurs. Electromyography shows widespread involvement of the plexus but, unlike diabetic plexopathy, there is sparing of the paraspinal muscles. [72] Relapses are not unknown and the pain, followed by the weakness resolves within weeks to months. Incomplete recovery occasionally is found. Treatment with intravenous IVIG has sometimes been found to be efficacious, even in relapses.[73]-[80] Reference has been made previously to a painful lumbosacral plexopathy with elevated erythrocyte sedimentation rate responsive to immunosuppressive therapy that may as well have been classified with the idiopathic group as in the inflammatory group.[54] Heroin addicts have also been reported to have intense pain and relatively mild weakness, usually with good resolution. Rhabdomyolysis with a compartment-elevated pressure is usually imputed as the likely pathophysiology.[81]-[84] Injections, intravenous administration of chemotherapeutic agent and viral infections.

Injections, intravenous administration of chemotherapeutic agents, and viral infections have all been implicated in the production of lumbosacral plexitis. The viral infections are usually herpes zoster although genital herpes may produce a syndrome of urinary retention, constipation and sacral pain. A lax anal sphincter, sensory abnormalities in the sacral dermatomes and variable reflex loss has been reported.

Miscellaneous Conditions

A variety of conditions have been reported to cause lumbosacral plexopathy including stem cell transplants, kidney transplantation (among other surgeries in the retroperitoneal space), total knee arthroplasty, gastric bypass surgery and regional paracervical block.[85]-[89]

Diagnosis and Investigations

Frequently the diagnosis is suggested by the circumstances in which the pain and weakness, sensory loss or perversion arose. However, often the patient is in such severe pain that clinical examination is difficult and even in the best of circumstances electodiagnostic evaluation is indicated to differentiate among plexopathy, neuropathy or multiple nerve lesions in order to direct investigation to the proper anatomical location. Needle evaluation usually is of more value than nerve conduction velocities except in the case of a suspected generalized neuropathy. Proximal nerve conduction studies such as the F-wave are of limited value in localization. [65][90][91] Imaging of the affected area may consist of plain x-rays of the spine, pelvis and sacrum for bony destruction, tumor or infection. CT scanning or MRI of the retroperitoneal space, spine or pelvis.[29][92][93]

Conclusions

The diagnosis and treatment of lumbosacral plexopathy depends on a firm grasp of the anatomical location of the lesion, which usually requires electrophysiological confirmation. Confusion with individual or complex multiple nerve dysfunctions can be avoided by careful history taking, physical examination, electrophysiological testing and imaging of appropriate potential pathological sites. The differential diagnosis varies between femoral neuropathy and lumbosacral plexopathy. (See Tables 1 and 2). Relief of pain is mandatory, especially during the early stages of the acute plexopathies when pain is usually the predominant complaint. Long-term pain may require invasive measures. The diagnosis of diabetic femoral neuropathy is rarely indicated and a careful search for evidence of a lumbosacral plexopathy should precede this rare diagnosis.