Neoplastic Lumbosacral Plexopathy

Lumbosacral plexus involvement occurs most commonly due to intra-abdominal tumor extension (73% of cases); it occurs less commonly with growth from metastases, lymph nodes, or bone structures. A tumor can invade the plexus directly or track along the connective tissue or epineurium of nerve trunks.

A study by Capek et al indicated that different types of pelvic neoplasms can lead to lumbosacral plexopathy via the same route, using “splanchnic nerves as conduits” and spreading “from the end organ to the lumbosacral plexus.” They added that these tumors can produce muscle and bone “metastases” by continuing their spread via osseous and muscle nerve branches.[6]

Citing pelvic cancer as a source of lumbosacral plexopathy, Jacobs et al modeled the neoplasm’s perineural progression, assessing one patient with prostate cancer and another with cervical cancer. The investigators used consecutive magnetic resonance imaging (MRI) scans, as well as an existing mathematic model of glioblastoma multiforme, to determine average pelvic cancer growth rates of 60.7 mm/year in one patient and 129 mm/year in the other.[7]

The most prevalent types of tumors are colorectal tumors (20%), sarcomas (16%), breast tumors (11%), lymphoma (9%), and cervical tumors (9%).[8] Other tumors, including multiple myeloma, account for another 37% of cases. The most common distant metastatic lesions are caused by breast cancer. In one study, the lumbosacral plexus was involved in 50 of 2261 cases of cervical cancer; however, it was involved in 38 of the 74 patients (51%) in the subgroup with proven retroperitoneal metastatic disease.

A case study by Murthy et al described a woman aged 77 years in whom lumbosacral plexopathy was caused by intraneural clear cell adenocarcinoma of Müllerian origin. According to the investigators, the case demonstrates the need for clinicians to be aware of the potential for gynecologic malignancies to spread perineurally.[9]

The lower (sacral) plexus is involved most frequently (approximately 50%) in NLS caused by pelvic tumor, followed by upper plexus involvement (more than 30%) and panplexopathy (18%).[10] Bilateral plexopathy occurs in 25% of cases and is usually caused by breast cancer metastases. Lower plexus involvement occurs generally with colorectal and cervical neoplasms. Involvement of the sacral sympathetic nerves is less common (10%).

Malignant psoas syndrome (MPS) was first described in 1990 by Stevens and refers to severe and difficult pain due to proximal lumbosacral plexopathy, painful fixed flexion of the ipsilateral hip, and radiologic or pathologic evidence of malignant involvement of the ipsilateral psoas major muscle.[11]

Frequency

United States

The incidence of neoplastic lumbosacral plexopathy is 0.71%.

Mortality/Morbidity

Significant morbidity from neoplastic lumbosacral plexopathy occurs due to associated pain, weakness, and sensory deficits.[12] One study noted median survival of 5.5 months after diagnosis. In patients with prostate cancer,[13] symptoms may persist for years and survival may be longer.

Race

No known correlation is recognized between the incidence of neoplastic lumbosacral plexopathy and race.

Sex

One study noted a male-to-female ratio for neoplastic lumbosacral plexopathy of 1.3:1, although the investigation involved just a small number of patients.

Age

In one study, age at the time of presentation of neoplastic lumbosacral plexopathy ranged from 19-80 years, with a median age of 65.5 years.

Patients with neoplastic lumbosacral plexopathy (NLP) present most frequently (93%) with pain located in regional areas, such as the low back, buttock, hip, and thigh. Features of this pain include the following:

• The pain may be of unilateral onset, being confined to one side, in 90% of cases.
• The pain is usually constant, dull, aching, or pressurelike, but it is rarely burning. Cramping may be present in a radicular pattern.
• The pain may worsen at night, and patients generally have difficulty finding a comfortable position.
• Involvement of the iliopsoas muscle leads patients to rest with their legs and hips in flexion.
• Pain exacerbation may occur with prolonged ambulation or sitting.
• The pain may also radiate down the leg as a result of epidural involvement from the tumor.
• Eventually, such pain manifests in all patients with NLP and is the most prominent symptom. An absence of pain should prompt consideration of other diagnoses.
• The presence of autonomic symptoms is less frequent; one of these, the "hot and dry foot," occurs because of the involvement of the sympathetic components of the plexus. ^[14] A clear difference in temperature of the affected limb may be reported.
• When the disease process manifests first with pain, it lasts from 1 week to 13 months, with a median duration of 3 months, before other neurologic symptoms appear.

Weakness and sensory loss complaints eventually develop in most patients.[12] Sensory loss occurs in 50-75% of patients and is more severe with greater motor impairment, potentially adding significantly to the degree of disability for the patient.

Muscle weakness occurs in most patients and is progressive and diffuse. Unilateral weakness and gait abnormalities are common.

Incontinence and impotence generally imply bilateral plexus involvement; they occur in about 10% of NLP patients.

In a retrospective study of nine patients with NLP resulting from the perineural spread of tumors from pelvic malignancies, Lee et al found that six patients developed pain in the perianal or inguinal area prior to pain in the extremities. Five patients experienced neurogenic bladder or bowel symptoms.[15]

The most common clinical findings in neoplastic lumbosacral plexopathy include muscle weakness (86%), sensory loss (73%), reflex impairment (64%), and leg edema (47%).

Diffuse, asymmetrical motor deficits involving more than 1 nerve root develop; associated gait abnormalities are noted.

With lumbar plexus involvement, weakness usually occurs in the thigh muscles, producing weakness when the patient rises from a seated position or negotiates steps.

Involvement of the lumbosacral trunk is associated with a foot drop and numbness of the dorsum of the foot.

In patients with sacral involvement, weakness of foot flexion and hamstrings occurs.

Sensory deficits are almost exclusively unilateral and can range from mild to severe. The location of sensory deficits in specific dermatomes offers clues to the nerve root or specific nerve involvement.

Patellar tendon reflex may be impaired with upper plexopathy, and ankle reflex impairment may be noted with lower plexopathy.

Peripheral edema is seen more commonly with panplexopathy (80%) than with upper (41%) or lower plexopathy (37%).

Rectal mass is found more often with lower plexopathy (43%) than with upper plexopathy (25%) or panplexopathy (15%).

A positive straight leg raise test is most common with panplexopathy (83%).

Pain exacerbation may occur with the Valsalva maneuver.

Tumor invasion, either local or metastatic, can lead to lumbosacral plexopathy.

Results of lab studies depend on the type of cancer and the extent of involvement. Erythrocyte sedimentation rate (ESR), complete blood cell (CBC) count, alkaline phosphatase, protein electrophoresis, prostate specific antigen (PSA), and other cancer-specific labs may be abnormal, depending on the clinical situation. Uremia and hydronephrosis may be an issue with ureter obstruction, especially in patients with gynecologic malignancy.

Cerebrospinal fluid (CSF) studies may reveal elevated protein with negative cytologic findings.

The clinical diagnosis of neoplastic lumbosacral plexopathy (NLP) is confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scanning of the affected areas. MRI is preferred because it is more sensitive and provides better detail than CT scanning.[4]

MRI is more accurate in soft tissues. Hydroureter or hydronephrosis are common findings at the time of diagnosis. Diagnosis can be difficult if the scan does not show a mass lesion, but repeating the study in another 4-6 weeks often reveals pathology that was not initially apparent. Increased T2 intensity within nerve trunks, with or without enhancement, has been shown with NLP.[23]

MR neurography uses 3T MR images and improved coils to provide a clear depiction of the lumbosacral plexus and its peripheral branches. This technology can confirm a diagnosis of lumbosacral plexopathy or provide anatomic information if surgical intervention is required.[24]

CT scanning of the abdomen and pelvis is probably the most valuable in diagnosis and gives more information on bony structures. Tumor, bony erosion, and lymphadenopathy are seen in 78% of cases. Clinical findings and CT scan levels do not always demonstrate positive correlation.

Positron emission tomography (PET) scanning can aid in the detection of active malignancy in the plexus region.[25] However, the sensitivity or specificity of PET scanning in the diagnosis of tumor plexopathy is not yet clear.

Bone scanning reveals pelvic, sacral, or vertebral uptake in 60% of patients with NLP.

Myelography can be abnormal with malignant plexopathy (in 28-45% of cases).

Routine spinal and pelvic roentgenograms reveal bone destruction in 50% of patients with NLP.

In aforementioned study by Lee and colleagues, of nine patients with NLP resulting from the perineural spread of tumors from pelvic malignancies, six patients displayed abnormal signal intensity on 18F-fluorodeoxyglucose (18F-FDG) PET/CT scanning.[15]

See the list below:

• Electrodiagnostic testing (electromyography [EMG], nerve conduction studies [NCSs]) reveals abnormalities in almost all patients with neoplastic lumbosacral plexopathy.[5]

  • Typical changes include acute and chronic denervation of the lumbosacral plexus. The findings are observed more extensively than would be suspected clinically. Side-to-side comparisons are helpful.

  • Myokymic discharges are not observed.

  • In the segments involved, decreased amplitudes of the evoked motor responses with normal or borderline nerve conduction velocities are noted.

Physical Therapy

For physical rehabilitation, the likely progression of neurologic weakness needs to be considered. If the patient is noted to have associated weakness after acute pain has subsided, one may recommend active range-of-motion (AROM) exercises, with advancement to low-resistance exercises. Assistive devices, such as a cane, walker, or wheelchair, may be required for ambulation in patients with weakness of the hip extensors, abductors, or quadriceps, with or without loss of joint position sense. Use of an ankle-foot orthosis (AFO) and, in rare cases, a knee-ankle-foot orthosis (KAFO) may be beneficial for mobility.

Occupational Therapy

The occupational therapist should assess activities of daily living (ADL) and prescribe appropriate adaptive equipment. In particular, be aware that standing-transfer safety may be impaired in cases in which involvement is more distal than proximal. With more proximal involvement, sit-to-stand transfers also may be affected. Equipment may be used specifically to facilitate dressing and bathing activities involving the lower extremity.

Medical or surgical treatment of the carcinoma, when possible, is the first treatment of choice.

Intra-arterial chemotherapy regionally has limited use in patients with pelvic pain and intractable pain due to plexopathy.

The most commonly used treatment with such plexopathy involves radiation treatment. Subjective improvement has been noted in 85% of patients with regard to symptoms. Objective improvement, including neurologic improvement and reduction in measurable tumor size, has been noted in 48% of patients. However, the average response duration has been found to be only 4 months.

Pain management is an important issue and may require an analgesic ladder approach, including agents specifically for the management of neuropathic pain.

Neuropathic pain may respond to nerve stimulation, antidepressants, and antiepileptics.

Plexopathy-associated complications, such as contractures, deep venous thrombosis, immobility, and compressive neuropathies, should be anticipated, and early treatment should be provided.

Lymphedema in the lower extremities may be an issue and can be particularly difficult to treat. Treatment should focus on improving the swelling, thus improving pain and function. Initial intervention may include wrapping with nonelastic wrapping, elevation, appropriate retrograde massage techniques, ROM exercises, and education. With improvement in edema, compressive garments should be considered, although these may have to be of a custom type.

Patients with more severe and recalcitrant pain may respond to the use of epidural catheter drug delivery and/or neurostimulatory/neuroablative surgical approaches. Cordotomies have been reported to have good outcomes in Europe. However, pain relief has been noted to be transient. Such ablative procedures carry the risk of sensory and motor deficits. The mortality rate has been significant at 5%.

Occasional relief of chronic pain has been achieved with plexus dissection and neurolysis. A study by Son et al indicated that in patients with terminal pelvic cancer, selective dorsal root rhizotomy can relieve intractable pain from neoplastic lumbosacral plexopathy. The study involved six patients who underwent the procedure, with their pain ratings and daily narcotic use found to have decreased postoperatively.[26]

Pain is a significant issue in most patients and studies have shown that pain is often poorly controlled in these patients. A multidisciplinary approach is needed. Consider early consultation with pain service, given the patient's short life expectancy following diagnosis. These patients may benefit from opiate analgesics, continuous infusion pumps, and procedures such as local and regional blocks, sympathectomy, and rhizotomy.

Nonpharmacologic measures, such as transcutaneous electrical nerve stimulation (TENS) or Anodyne therapy, may be used for neuropathic pain.

Tricyclic antidepressants, such as amitriptyline (10-100 mg qhs), may be helpful at low doses. Antiepileptics, such as gabapentin (300-3600 mg/d in 3-4 divided doses) also can be tried. Opiates, especially methadone and steroids, can be considered as well. Mexiletine, a class 1b antiarrhythmic, at 200 mg bid, has been used for the management of significant neuropathic pain due to neoplastic plexus infiltration.[27] Low- (0.1 g/kg/d) and higher-dose (0.2-2 g/kg/d) intravenous immunoglobulin therapy has, in limited cases, been successfully used for idiopathic brachial and lumbosacral plexopathy. However, its effectiveness in neoplastic plexopathy is unproven. A single dose (500 mg or 1 g) of intravenous magnesium sulfate has been used with success in a small sample of patients with neuropathic pain due to neoplastic plexopathy.[28]

Class Summary

These agents have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin.

Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain.

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.

Morphine sulfate (Astramorph, MS Contin, MSIR)

Generally used for short-term, acute pain, moderate to severe in nature, as well as for chronic pain (eg, that associated with cancer). Morphine sulfate is available in immediate (3-4 h duration) and extended-release preparation (12 h). Switch over to long-acting preparations (MS Contin) once the pain is controlled with short-acting preparation (MS IR). Morphine can produce drug dependence and has the potential to be abused. Tolerance may develop with repeat exposure. Abrupt cessation of the drug or a sudden reduction in dose with prolonged use may result in withdrawal symptoms. Physical dependence is not of paramount importance in terminally ill patients.

Methadone (Dolophine)

Used in the management of severe pain. Methadone inhibits ascending pain pathways, diminishing the perception of and response to pain.

Class Summary

These agents inhibit events involved in muscle contraction.

Methocarbamol (Robaxin)

Reduces nerve impulse transmission from the spinal cord to skeletal muscle.

Class Summary

Antiepileptics are used to manage severe muscle spasms and to provide sedation in neuralgia.

Pregabalin (Lyrica)

Structural derivative of GABA. The mechanism of action is unknown. Pregabalin binds with high affinity to the alpha2 -delta site (a calcium channel subunit). In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Pregabalin is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as an adjunctive therapy in partial-onset seizures.

Gabapentin (Neurontin)

Has anticonvulsant properties and antineuralgic effects; however, the exact mechanism of action is unknown. Gabapentin is structurally related to GABA but does not interact with GABA receptors.

See the list below:

• Neoplastic lumbosacral plexopathy (NLP) progresses much faster than does radiation-related plexopathy, and the patient survival rate is limited. Median survival is 5.5 months from the time of diagnosis, with a range of 1-34 months. In one study, at 1-month follow-up visit, only 15-17% of patients demonstrated improvement in pain or weakness, and 28% showed improvement in CT scan findings. Over half of the patients (59%) demonstrated gradual worsening of neurologic deficits.

• In another study, 13 patients who underwent palliative irradiation for NLP had median survival of 185 days, with a range of 47-636 days.[29]