Radiation-induced lumbar plexopathy

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The lumbosacral nerves
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Lumbar plexus and its branches
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Dissection of pelvis showing sacral and pudendal plexuses
Anatomical terms of neuroanatomy

Radiation-induced lumbar plexopathy (RILP) or radiation-induced lumbosacral plexopathy (RILSP) is nerve damage in the pelvis and lower spine area caused by therapeutic radiation treatments. RILP is a rare side effect of external beam radiation therapy [1] [2] [3] and both interstitial and intracavity brachytherapy radiation implants. [4] [5]

Contents

In general terms, such nerve damage may present in stages, earlier as demyelination and later as complications of chronic radiation fibrosis. RILP occurs as a result of radiation therapy administered to treat lymphoma or cancers within the abdomen or pelvic area such as cervical, ovarian, bladder, colon, kidney, pancreatic, prostate, testicular, colorectal, colon, rectal or anal cancer. [6] [7] The lumbosacral plexus area is radiosensitive and radiation plexopathy can occur after exposure to mean or maximum radiation levels of 50-60 Gray [6] with a significant rate difference noted within that range. [8]

Signs and symptoms

Lumbosacral plexopathy is characterized by any of the following symptoms; usually bi-lateral and symmetrical, though unilateral is known. [7]

Symptoms are typically a step-wise progression with periods of stability in between, [1] [3] weakness often appearing years later. [7] Weakness frequently presents in the lower leg muscle groups. [7] Symptoms are usually irreversible. [9]

Initial onset of symptoms may occur as early as 2 [7] to 3 [10] [1] months after radiotherapy. The median onset is approximately 5 years, [7] but can be highly variable, 2-3 decades after radiation therapy. [7] One case study recorded the initial onset occurring 36 years post treatment. [11]

Cause

The treatment's ionizing radiation is an activation mechanism for apoptosis (cell death) within the targeted cancer, [12] but it can also impact nearby healthy radiosensitive tissues, like the lumbosacral plexus. The occurrence and severity of RILP is related to the magnitude of ionizing radiation [9] and the radiosensitivity of peripheral nerves may be further aggravated when combined with chemotherapy, like taxanes and platinum drugs, during treatment. [13]

Pathophysiology

The pathophysiological process behind radiation's RILP nerve damage has been discussed since the 1960s [9] and is still without a precise definition. [1] [12] Consensus does exist on a progression of RILP symptoms, with a stepping (a time delay) between two periods of plexopathy onset, the first from radiation injury and the later from fibrosis. Proposed mechanisms of the early nerve damage include microvascular damage (ischemia) supplying the myelin, [1] radiation damage of the myelin, [14] and oxygen free radical cell damage. [1] [14] The delayed nerve damage is attributed to compression neuropathy [1] and a late fibro-atrophic ischemia from retractile fibrosis. [1] [14]

Diagnosis

The more common source of lumbar plexopathy is a direct or secondary [2] tumor involvement of the plexus with MRI being the typical confirmation tool. [14] Tumors typically present with enhancement of nerve roots and T2-weighted hyperintensity. [2] The differential consideration of RILP requires taking a medical history and neurologic examination. [14]

RILP's neurological symptoms can mimic other nerve disorders. People may present with pure lower motor neuron syndrome, a symptom of amyotrophic lateral sclerosis (ALS). [4] [15] RILP may also be misdiagnosed as leptomeningeal metastasis often showing nodular MRI enhancement of the cauda equina nerve roots or having increased CSF protein content. [4]

Other differential diagnoses to consider are Chronic Inflammatory Demyelinating Polyradiculoneuropathy, neoplastic lumbosacral plexopathy, paraneoplastic neuronopathy, diabetic lumbosacral plexopathy, degenerative disk disease (osteoporosis of the spine), Osteoarthritis of the spine, Lumbar Spinal Stenosis, post-infectious plexopathy, carcinomatous meningitis (CM), mononeuritis multiplex, and chemotherapy-induced plexopathy. [1]

The testing to resolve a RILP diagnosis involves blood serum analysis, X-rays, EMG, MRI and cerebrospinal fluid analysis. [2] [1] [14]

Prevention

Since RILP's neurological changes are typically irreversible and a curative strategy has yet to be defined, prevention is the best approach. [1] Treating the primary cancer remains an obvious requirement, but lower levels of lumbar plexus radiation dosing will minimize or eliminate RILP. [1] [14]

One method to reduce the lumbosacral plexus' dosing is to include it with other at-risk organs that get spared from radiation. [16] [17]

Key to prevention is resolving the lack of clinical evidence between radiation treatments and the onset of neurological problems. That relationship is hidden by RILP's low toxicity rate, the lack of a large monitored population size and the lack of data pooling across multiple institutions. [1] [18]

Management

Treatment of RILP is primarily supportive [14] with mental, [2] [9] physiological [2] [1] [9] [14] and social aspects [9] and consideration of any aggravating (synergistic) neurological factors. [1] [9]

To prevent compounding existing RILP symptoms and to minimize further progression

The effect on the person with the condition, depends upon the type of impairment. Handicaps may include physical challenges, bowel and/or bladder dysfunction and may occur in multiple settings of work and home. [9] Physical and occupational therapy are important elements in maintaining mobility and use of the lower extremities, along with assistive aides such as Ankle-Foot-Orthotics (AFOs), cane, walkers, etc. [2] [9] [14] Sensory reeducation techniques may be necessary for balance [2] and lymphedema management may be required. [9]

Pharmaceuticals that may be effective for RILP's neuropathic pain are

Non-pharmaceutical RILP considerations are

Functional impairment and residual pain can lead to social isolation. [9] Cancer support groups are valuable resources to learn about the syndrome and therapeutic options, and are a means to voice emotions related to having cancer and surviving it. [9] [1] [14]

Outcomes

With increasing cancer treatment survival rates, the quality of life for its survivors has become a public health priority. [1] The effects of RILP can be debilitating. With no effective treatment to control radiation damage's progressive nature, limb dysfunction is the likely result. [9]

Radiation damage's outcome is related to its initial onset time.

Epidemiology

An exact occurrence rate has not been established. Literature on the topic is sparse. [20] Clinical occurrences of RILP are rare, affecting between 0.3 and 1.3% of those treated with abdominal or pelvic radiation. [2] The incidence rate is variable, dependent upon the irradiated zone, dosage level and method of delivery. For example, when alternate dosing levels were compared, higher rates were observed, from 12 to 23%, the higher RILP rates occurring with higher dosages. [20]

History

As of 1977 lumbosacral neuropathy arising from radiation therapy had been rarely reported. One of the earliest cases was in 1948. [6] [10] [21]

The incidence rate of peripheral neuropathy has been demonstrated to decrease when lower therapeutic radiation dosing levels are used. [20] [1] A similar nerve injury, Radiation-induced Brachial Plexopathy (RIBP), may occur secondary to breast radiation therapy. [22] Studies on RIBP have observed the brachial plexus' radiosensitivity. Injury was observed after dosages of 40 Gy in 20 fractions and RIBP significantly increased with doses greater than 2 Gy per fraction. [20] RIBP is more common than lumbosacral radiculoplexopathy [4] and has a clinical history with reduced dosing levels. RIBP occurrence rates were in the 60% range in the 1960s when 60 Gray treatments were applied in 5 Gray fractions; RIBP occurrences in the 2010s approach 1% with 50 Gray treatments applied in 3 Gy fractions. [1]

RILP occurrence rates are estimated at 0.3% to 1.3%, though the actual rate is likely higher. The soft tissue damage leading to RILP is more commonly seen with exposure levels over 50 Gy, though has occurred with as little as 30 Gy. [23] A major step toward reducing RILP occurrences is by limiting the lumbosacral plexus' dosing level when treating pelvic malignancies, limiting the mean dose to < 45 Gy. One approach to reduced levels, the plexus' mapping with other organs at risk, was clinically evaluated during the 2010s. [16] [17]

Clinical evidence of the cause-and-effect for prevention and the management of radiation induced polyneuropathy is limited. [9]

In 2011 the Radiation Oncology Institute (ROI) announced the National Radiation Oncology Registry (NROR). ROI and Massachusetts General Hospital would initially focus the NROR on prostate cancer, collecting efficacy and side effect information (like radiation induced neuropathy, RILP) from people treated with radiotherapy. [24] In 2013 the American Society for Radiation Oncology (ASTRO) joined the effort [25] and the number of data collection sites increased to 30 for a 1-year pilot project. Pitfalls of medical data collection arose with only 14 sites being able to provide data and all those requiring significant manual entry efforts. [26] The first NROR project conclusion was that future registries would need to cope with Big data analytics. In 2015 ASTRO, the National Cancer Institute and the American Association of Physicists in Medicine sponsored a Big Data Workshop at the National Institutes of Health.

Research

Experimental approaches for RILP treatment and management include:

See also

Related Research Articles

<span class="mw-page-title-main">Radiation therapy</span> Therapy using ionizing radiation, usually to treat cancer

Radiation therapy or radiotherapy is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.

Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves. Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy.

<span class="mw-page-title-main">Peripheral neuropathy</span> Nervous system disease affecting nerves beyond the brain and spinal cord

Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerves are affected. Neuropathies affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute or chronic, and may be reversible or permanent.

<span class="mw-page-title-main">Glioblastoma</span> Aggressive type of brain cancer

Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness.

<span class="mw-page-title-main">Proton therapy</span> Medical Procedure

In medicine, proton therapy, or proton radiotherapy, is a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often to treat cancer. The chief advantage of proton therapy over other types of external beam radiotherapy is that the dose of protons is deposited over a narrow range of depth; hence in minimal entry, exit, or scattered radiation dose to healthy nearby tissues.

<span class="mw-page-title-main">Radiosurgery</span> Surgical Specialty

Radiosurgery is surgery using radiation, that is, the destruction of precisely selected areas of tissue using ionizing radiation rather than excision with a blade. Like other forms of radiation therapy, it is usually used to treat cancer. Radiosurgery was originally defined by the Swedish neurosurgeon Lars Leksell as "a single high dose fraction of radiation, stereotactically directed to an intracranial region of interest".

<span class="mw-page-title-main">Malignant peripheral nerve sheath tumor</span> Medical condition

A malignant peripheral nerve sheath tumor (MPNST) is a form of cancer of the connective tissue surrounding nerves. Given its origin and behavior it is classified as a sarcoma. About half the cases are diagnosed in people with neurofibromatosis; the lifetime risk for an MPNST in patients with neurofibromatosis type 1 is 8–13%. MPNST with rhabdomyoblastomatous component are called malignant triton tumors.

<span class="mw-page-title-main">Neuritis</span> Inflammation of a nerve or generally any part of the nervous system

Neuritis, from the Greek νεῦρον), is inflammation of a nerve or the general inflammation of the peripheral nervous system. Inflammation, and frequently concomitant demyelination, cause impaired transmission of neural signals and leads to aberrant nerve function. Neuritis is often conflated with neuropathy, a broad term describing any disease process which affects the peripheral nervous system. However, neuropathies may be due to either inflammatory or non-inflammatory causes, and the term encompasses any form of damage, degeneration, or dysfunction, while neuritis refers specifically to the inflammatory process.

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Proximal diabetic neuropathy, also known as diabetic amyotrophy, is a complication of diabetes mellitus that affects the nerves that supply the thighs, hips, buttocks and/or lower legs. Proximal diabetic neuropathy is a type of diabetic neuropathy characterized by muscle wasting, weakness, pain, or changes in sensation/numbness of the leg. It is caused by damage to the nerves of the lumbosacral plexus.

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<span class="mw-page-title-main">Nerve compression syndrome</span> Human disease

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References

PD-icon.svgThis article incorporates text in the public domain from the 20th edition of Gray's Anatomy (1918)

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